Research and Press Releases

Common Type of Fiber May Trigger Bowel Inflammation

mouse colon stained blue

Inulin, a type of fiber found in certain plant-based foods and fiber supplements, causes inflammation in the gut and exacerbates inflammatory bowel disease in a preclinical model, according to a new study by Weill Cornell Medicine investigators. The surprising findings could pave the way for therapeutic diets that may help ease symptoms and promote gut health. 

The study, published March 20 in the Journal of Experimental Medicine, shows that inulin, which is found in foods like garlic, leeks and sunchoke, as well as commonly used fiber supplements and foods with added fiber, stimulates microbes in the gut to release bile acids that increase the production of molecules that promote intestinal inflammation. One such protein, called IL-33, causes immune cells called group 2 innate lymphoid cells (ILC2s) to become activated, triggering an excessive immune response similar to an allergic reaction. That excessive immune response then exacerbates intestinal damage and symptoms in an animal model of inflammatory bowel disease. 

Dr. Arifuzzaman and Dr. Artis in the lab

Dr. Mohammad Arifuzzaman (left) and Dr. David Artis (right).



Dietary fiber, including inulin, is considered an essential part of a healthy diet for most people. Gut microbes turn inulin and other types of dietary fiber into short-chain fatty acids that turn on immune cells called regulatory T cells, which help reduce inflammation and have other beneficial effects throughout the body. This led to a remarkable rise in use of dietary fiber as an additive in both foods and supplements, and purified inulin or inulin-rich chicory root is often the main source of the fiber.

“Inulin is now everywhere, from clinical trials to prebiotic sodas,” said lead author Dr. Mohammad Arifuzzaman, a postdoctoral associate at Weill Cornell Medicine. He and his colleagues expected that inulin would also have protective effects in inflammatory bowel disease. But they found just the opposite. 

Feeding inulin to mice in the context of a model of inflammatory bowel disease increased the production of certain bile acids by specific groups of gut bacteria. The increased bile acids boosted the production of an inflammatory protein called IL-5 by ILC2s. The ILC2s also failed to produce a tissue-protecting protein called amphiregulin. In response to these changes, the immune system promotes the production of immune cells called eosinophils, which further ramp up inflammation and tissue damage. Previously, a 2022 study by the same team of investigators showed that this flood of eosinophils may help protect against parasite infections. However, in the inflammatory bowel disease model, this chain reaction exacerbated intestinal inflammation, weight loss and other symptoms like diarrhea. 

In translational patient-based studies, the team also analyzed human tissue, blood and stool samples from Weill Cornell Medicine’s Jill Roberts Institute for Research in Inflammatory Bowel Disease Live Cell Bank. This analysis revealed that patients with inflammatory bowel disease, like the mice fed inulin, had higher levels of bile acids in their blood and stool and excessive levels of eosinophils in their intestine compared with people without the condition. The results suggest that the inflammation cascade similar to that in the mice fed inulin is already primed in humans with inflammatory bowel disease, and dietary uptake of inulin may further exacerbate the disease.

These unexpected discoveries may help explain why high-fiber diets often exacerbate inflammatory bowel disease in patients. It may also help scientists develop therapeutic diets to reduce symptoms and gut damage in patients with inflammatory bowel disease or related conditions. New therapies are urgently needed for these increasingly common gut conditions. Existing biologic therapies can increase the risk of developing infections or autoimmune diseases, which cause the immune system to attack the body. 

“The present study show that not all fibers are the same in how they influence the microbiota and the body’s immune system,” said senior author Dr. David Artis, director of the Jill Roberts Institute for Research in Inflammatory Bowel Disease and director of the Friedman Center for Nutrition and Inflammation at Weill Cornell Medicine. "These findings could have broader implications for the delivery of precision nutrition to individual patients to promote their overall health based on their unique symptoms, microbiota composition and dietary needs."

Many Weill Cornell Medicine physicians and scientists maintain relationships and collaborate with external organizations to foster scientific innovation and provide expert guidance. The institution makes these disclosures public to ensure transparency. For this information, see profile for Dr. Artis.

The research reported in this story was funded in part by the National Institute of Allergy and Infectious Diseases, the National Institute of Diabetes and Digestive and Kidney Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of General Medical Sciences, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases, all part of the National Institutes of Health, through grant numbers K99AI173660, DP2HD101401, R35GM131877, DK126871, AI151599, AI095466, AI095608, AR070116, AI172027, DK132244). Additional support was provided by the Crohn’s & Colitis Foundation (grant numbers 851136, 937437, 901000); AGA Research Foundation; WCM Research Assistance for Primary Parents Initiative; The. W.M. Keck Foundation; the Howard Hughes Medical Institute; CURE for IBD; the Jill Roberts Institute for Research in IBD; Kenneth Rainin Foundation; the Sanders Family Foundation; Rosanne H. Silbermann Foundation, Linda and Glenn Greenberg; and the Allen Discovery Center Program, a Paul G. Allen Frontiers Group advised program of the Paul G. Allen Family Foundation.


Two Weill Cornell Medicine Faculty Recognized with AAI Awards

a composite image of tworesearchers

Two Weill Cornell Medicine faculty members, Dr. Gregory Sonnenberg and Dr. Melody Zeng, are recipients of prestigious awards from the American Association of Immunologists (AAI) for their accomplishments in the field of immunology.

Dr. Sonnenberg is the 2023 recipient of the AAI-BD Biosciences Investigator Award, recognizing his outstanding contributions to the field of immunology as a mid-career scientist, and Dr. Zeng is a recipient of an AAI ASPIRE Award, recognizing her work as an early-career immunologist and potential for advancing the field of immunology. The AAI has been dedicated to advancing immunology to improve health and fostering development opportunities for immunologists since it was founded in 1913.

Dr. Sonnenberg, the Henry R. Erle, MD-Roberts Family Associate Professor of Medicine is being honored for his laboratory’s research defining how the immune system controls health, immunity and inflammation in tissues lining various body surfaces, such as the gastrointestinal tract and respiratory system, and how immune system dysfunction can lead to gastrointestinal diseases, multiple sclerosis, asthma or cancer. For example, Dr. Sonnenberg and his lab discovered that immune cells called group 3 innate lymphoid cells (ILC3s) play a central role in regulating immunologic tolerance and healthy immune cell interactions with trillions of beneficial microbes in the gut, known as the microbiota. They also recently found that dysfunction of ILC3s may explain how colorectal cancer progresses and why this disease is resistant to checkpoint blockade immunotherapy.

“It is a tremendous honor to be chosen as the 2023 recipient of the AAI-BD Biosciences Investigator Award. I am also very humbled to be recognized by this important association and to be included among a list of prior recipients that are such phenomenal scientists,” said Dr. Sonnenberg, who is also a member of the Division of Gastroenterology & Hepatology and Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine. “This award also recognizes the significant contributions and dedication of talented individuals that I am lucky enough to have worked with in my lab over the years, as well as close collaborators and colleagues within our multidisciplinary network at Weill Cornell Medicine.”

Dr. Zeng, an assistant professor of immunology in pediatrics, is being recognized for her research and contribution to the growing collective evidence that the gut microbiota regulates the immune system. As a postdoctoral fellow at the University of Michigan School of Medicine, she was among the first to discover that a class of antibodies called IgG recognizes gut bacteria for maintenance of host-microbe symbiosis in the intestine. Dr. Zeng established her lab at Weill Cornell Medicine in 2019 and has continued to study the role of IgG in immune regulation by gut bacteria and its role in inflammatory and infectious disorders in early life. For example, her team recently discovered in a preclinical study that IgG antibodies transferred from mothers to infants through breast milk help shape infants’ gut bacteria and immunity against pathogenic bacteria that cause diarrheal illness.

“I am very honored and excited to be recognized along with the other recipients of this year’s AAI ASPIRE Award,” said Dr. Zeng, who is also a member of the Gale and Ira Drukier Institute for Children’s Health at Weill Cornell Medicine. “The annual AAI Meeting is a preeminent conference for immunologists, providing a platform for trainees to showcase their research and to network. It is also where I gave my first national meeting presentation as a student more than ten years ago, and it will be a sincere thrill to give a talk as an award recipient at this year’s event. This award also acknowledges the excellent training I received from my mentors, as well as the exciting research program that my amazing team works hard every day to build with tremendous support from many of my colleagues at Weill Cornell Medicine.”

The award ceremony will take place in May in Washington, D.C., at the organization’s 106th annual conference, where Drs. Sonnenberg and Zeng will present lectures about their research.


NIH Awards MERIT Grant for Inflammatory Bowel Disease Research

man in suit jacket sitting at lab hood

Dr. Gregory F. Sonnenberg, The Henry R. Erle, M.D.-Roberts Family Associate Professor of Medicine and head of basic research in Gastroenterology and Hepatology at Weill Cornell Medicine, has been awarded a $3.26 million, five-year MERIT grant from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, to investigate the underlying mechanisms of inflammatory bowel disease (IBD).

The new grant, which has the possibility of extension for five additional years, will fund research on a novel pathway that protects the intestine from damage and inflammation driven by an immune-derived factor called tumor necrosis factor (TNF).

“It’s a huge honor to be considered and nominated for a NIH MERIT award, and such a privilege to be able to move this research forward with my laboratory over an extended period of time,” Dr. Sonnenberg said.

The MERIT program, a backronym for “Method for Extending Research In Time,” gives investigators with stellar records of research accomplishment a five-year award with the possibility of extending the initial award for up to five additional years without the need to undergo another competitive peer review.

Dr. Sonnenberg’s proposal was based on research his laboratory pioneered over the past decade characterizing key immune cell pathways in the intestine. It’s one of the major mysteries in the field. “TNF is normally beneficial, but what causes this shift for it to become a major mediator of chronic inflammatory diseases?” asked Dr. Sonnenberg, who is in the Division of Gastroenterology & Hepatology in the Weill Department of Medicine and a member of the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine.

picture of Greg Sonnenberg and his lab members sitting in the lab

The Sonnenberg lab, with Dr. Greg Sonnenberg, seated second from right.

Many current therapies block TNF to reduce inflammation in chronic inflammatory diseases, including IBD, rheumatoid arthritis and psoriasis, but those treatments are only effective in a subset of patients, and even if successful, this therapy can lose efficacy over time. Dr. Sonnenberg’s team discovered that TNF-induced gut inflammation correlates with the depletion of group 3 innate lymphoid cells (ILC3s), a special class of cells abundant in the healthy intestine. “This provoked a hypothesis that these cells are keeping the TNF molecule in check and stopping it from driving tissue inflammation,” Dr. Sonnenberg said.

Experiments published last year in preclinical models confirmed that hypothesis and revealed that ILC3s are essential to protect the intestine from TNF-mediated damage and inflammation, which the team will explore further with support of this MERIT Award. Dr. Sonnenberg and his laboratory proposed a series of experiments to define the cellular and molecular signals by which ILC3s protect from TNF-induced inflammation. He also plans to investigate this pathway in both mouse models and patient-based organoids, complex human cell culture systems that model the guts of healthy individuals or patients with IBD.

Researchers cannot apply for MERIT grants directly. Dr. Sonnenberg and his laboratory originally applied for a standard “R01” grant from the NIH, which received a fundable score after peer-review and was subsequently nominated by NIH program staff for the MERIT award instead. Each year, NIAID issues about 15 new MERIT awards. The new award, which can double the length and amount of the grant, will take the investigation further, laying the groundwork for a much deeper understanding of IBD and paving the way for new therapeutic strategies.

Research reported in this newsroom story was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number R37AI174468.


Gut Fungi's Lasting Impact on Severe COVID-19 Immune Response

closeup of monitor beside patient bed with patient on a respirator

Certain gut-dwelling fungi flourish in severe cases of COVID-19, amplifying the excessive inflammation that drives this disease while also causing long-lasting changes in the immune system, according to a new study led by investigators at Weill Cornell Medicine and NewYork-Presbyterian. This discovery identifies a group of patients who may benefit from specialized, but yet-to-be determined treatments.

Dr. Iliyan Iliev

Dr. Iliyan Iliev

Utilizing patient samples and preclinical models, the research team determined that the growth of fungi in the intestinal tract, particularly strains of Candida albicans yeast, trigger an upsurge in immune cells whose actions can exacerbate lung damage. Their findings, published in Nature Immunology on Oct. 23, also elucidate that patients retain a heightened immune response and immune memory against these fungi for up to a year after the resolution of SARS-CoV-2 infection. The research reveals a new dimension of the complex pathology unleashed by severe COVID-19, according to senior author Dr. Iliyan Iliev, an associate professor of immunology in medicine in the department of medicine, co-director of the Microbiome Core Lab and a member of the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine. 

“Severe and long COVID-19 were not thought to involve fungal blooms in the intestines that, in addition to the virus, can impact patient’s immunity,” he said. 

Dr. Iliev, an immunologist who studies the microbiome and the chronic inflammatory conditions targeting the gastrointestinal tract, pivoted to COVID-19 during the pandemic. As researchers gained a better handle on the new viral infections, it became clear that, in COVID-19 as in inflammatory bowel disease, the body’s own inflammatory immune response causes harm.

Dr. Takato Kusakabe

Dr. Takato Kusakabe

To investigate this errant immune response, Dr. Iliev and Dr. Takato Kusakabe, a postdoctoral fellow and a first author in the study, worked with numerous colleagues to acquire three large clinical cohorts of COVID-19 patients and develop a mouse model to study the disease. They collaborated with members of the Weill Department of Medicine and the Department of Pathology and Laboratory Medicine at Weill Cornell Medicine, including Dr. Stephen JosefowitzDr. Mirella SalvatoreDr. Melissa Cushing, Dr. Lars Westblade, and Dr. Adolfo García-Sastre, a professor of microbiology and director of the Global Health and Emerging Pathogens Institute of the Icahn School of Medicine at Mount Sinai.

How Gut Fungi Harm the Lungs

The team first made the connection when analysis of blood samples from patients at New York-Presbyterian/Weill Cornell Medical Center diagnosed with severe COVID-19 unveiled the presence of antibodies tuned to attack fungi common to the gut. The researchers then found that populations of yeast, and one species in particular, Candida albicans, increased in the intestines of the patients during the course of severe COVID-19. 

When they looked at the patients’ immune systems, the researchers found a parallel increase in immune cells called neutrophils. In severe COVID-19, excessive numbers of neutrophils appear in the lungs, where their activity worsens the inflammatory response already damaging these organs. 

Turning to preclinical models, the investigators found that mice bearing fungi from patients with severe COVID-19 produced more neutrophils in their blood and lungs, and had signs of heightened inflammation when infected with SARS-CoV-2. However, giving them an antifungal drug reduced these effects. 

The Immune System Remembers

From within patients’ blood samples, researchers also uncovered evidence of persistent changes to the immune system they believe are related to a condition known as long COVID-19, in which symptoms linger, or new ones develop, after an infection has cleared.  

When the team examined patients’ blood up to a year afterward, they found it still contained anti-fungal antibodies. In addition, when they looked at the stem cells that give rise to neutrophils, the researchers found that these progenitors are primed to respond to fungi. They found that an immune protein called IL-6 that these fungi induce, appears to bolster both the neutrophils and the antibodies.   

Further experiments showed that blocking IL-6 in the patients or in mice dampened this immunological memory, causing the presence of neutrophils and antibodies to wane. 

While these results do not have immediate implications for treating severe or long COVID-19, they suggest new opportunities to tailor therapy, according to Dr. Iliev. For example, anti-fungal antibodies could potentially serve as a marker to identify patients who might benefit from a therapy that targets the fungi or the immunological changes they instigate. Or, assuming further research supports it, the antibodies’ presence could indicate someone might be at risk for long COVID-19. The team’s discoveries may also have relevance beyond COVID-19, said Dr. Iliev, who notes this research could open new avenues of exploration for the treatment of other infectious and inflammatory diseases.

Many Weill Cornell Medicine physicians and scientists maintain relationships and collaborate with external organizations to foster scientific innovation and provide expert guidance. The institution makes these disclosures public to ensure transparency. For this information, see the profile for Dr. Melissa Cushing.

Research reported in this newsroom story was supported by the National Institutes of Health grants P30CA016087, R01AI143861, R01AI143861-02S1, R01AI160706, R01DK130425, U19AI135972, U19AI168631, U19AI142733, DK113136, DK121977 and AI137157. Additional support was provided by the Jill Roberts Institute for Research in Inflammatory Bowel Disease, the Leona M. and Harry B. Helmsley Charitable Trust, the Irma T. Hirschl Career Scientist Award, Crohn’s and Colitis Foundation, and the Burrough Welcome Trust PATH Award. Dr. Iliev is a fellow of the CIFAR program Fungal Kingdom: Threats and Opportunities.


New Consortium Aims to Transform Understanding of How the Human Body Senses Health and Disease

 

a yellow scientific image against a black backdrop

New York, NY (November 9, 2023) - The Allen Discovery Center (ADC) for Neuroimmune Interactions at the Icahn School of Medicine at Mount Sinai hopes to revolutionize the field of medicine with a groundbreaking project to understand how the human body senses health and disease.

Spearheaded by Dr. Brian S. Kim of Mount Sinai and co-led by Dr. David Artis of Weill Cornell Medicine, this new multidisciplinary research center brings together leading experts studying the intersection of immunology and neuroscience. This pioneering effort aims to reshape our understanding of fundamental biology and human disease, with the near-term goal of changing the way we treat chronic diseases.

Headshot of a man sitting in a green chair

Dr. David Artis. Credit: John Abbott

The Allen Discover Center for Neuroimmune Interactions is funded at $10 million over four years by the Paul G. Allen Family Foundation, with a total potential for $20 million over eight years. The Allen Discovery Center program is advised by The Paul G. Allen Frontiers Group.

The motivation behind this center is rooted in the profound advances achieved in immunology and neuroscience over the past decade. These breakthroughs have unveiled the intricate communication between the immune and nervous systems. The team’s mission is to explore the role of immune cells as environmental and internal sensors influencing various aspects of human behavior and to recognize the sensory nervous system's newfound capacity to act as an immune organ.

“Together, our combined expertise aims to advance fundamental neuroimmunology, with a commitment to translating our findings into revolutionary therapies rapidly,” said Dr. Kim. “For example, many diseases arise from the immune system going awry. However, we are now finding that the nervous system communicates closely with the immune system to sense inflammation in ways we never imagined. We are also seeing how different organs communicate through this unique network. We can envision a future in which we treat psoriasis by tuning nerves in the skin, anxiety by modulating gut inflammation, and improving cancer therapy by limiting bad nerves from sprouting into the tumor.”

Physician-scientist in the lab

Dr. Brian Kim. Credit: Mount Sinai Health Syst

Dr. Kim, vice chair of research and professor of dermatology, Icahn Mount Sinai, and director of the Mark Lebwohl Center for Neuroinflammation and Sensation at Mount Sinai, pioneered the understanding of peripheral neurons as sensors of inflammation leading to FDA-approved itch therapies. He will lead this collaboration, joined by an exceptional team of investigators from Icahn Mount Sinai, Weill Cornell Medicine, NYU Langone Health, and Yale School of Medicine.

“Collaborating with The Paul G. Allen Frontiers Group to launch the Allen Discovery Center for Neuroimmune Interactions here in New York City allows us to bring together outstanding investigators from Icahn Mount Sinai, NYU Langone Health, Weill Cornell Medicine, and Yale School of Medicine, providing a tremendous opportunity to leverage cutting-edge technologies to provide new insights into how the nervous and immune systems communicate with each other to regulate immunity, inflammation, and tissue homeostasis,” said Dr. Artis, who is director of the Jill Roberts Institute for Research in Inflammatory Bowel Disease and director of the Friedman Center for Nutrition and Inflammation at Weill Cornell Medicine. “The outcome of these studies will have implications for our understanding of the pathophysiology of a number of diseases, from asthma and allergy to autoimmunity and cancer.”

About the Mount Sinai Health System

Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with more than 43,000 employees working across eight hospitals, more than 400 outpatient practices, more than 300 labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time—discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it. Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 7,400 primary and specialty care physicians; 13 joint-venture outpatient surgery centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and more than 30 affiliated community health centers. Hospitals within the System are consistently ranked by Newsweek’s® “The World’s Best Smart Hospitals, Best in State Hospitals, World Best Hospitals and Best Specialty Hospitals” and by U.S. News & World Report's® “Best Hospitals” and “Best Children’s Hospitals.” The Mount Sinai Hospital is on the U.S. News & World Report® “Best Hospitals” Honor Roll for 2023-2024.

About The Paul G. Allen Frontiers Group

The Paul G. Allen Frontiers Group, a division of the Allen Institute, is dedicated to exploring the landscape of bioscience to identify and foster ideas that will change the world. The Frontiers Group recommends funding to The Paul G. Allen Family Foundation, which then invests through award mechanisms to accelerate our understanding of biology, including: Allen Discovery Centers at partner institutions for leadership-driven, compass-guided research; and Allen Distinguished Investigators for frontier explorations with exceptional creativity and potential impact. The Paul G. Allen Frontiers Group was founded in 2016 by the late philanthropist and visionary Paul G. Allen. For more information, visit alleninstitute.org/division/frontiers-group/

About Weill Cornell Medicine

Weill Cornell Medicine is committed to excellence in patient care, scientific discovery and the education of future physicians in New York City and around the world. The doctors and scientists of Weill Cornell Medicine—faculty from Weill Cornell Medical College, Weill Cornell Graduate School of Medical Sciences, and Weill Cornell Physician Organization—are engaged in world-class clinical care and cutting-edge research that connect patients to the latest treatment innovations and prevention strategies. Located in the heart of the Upper East Side’s scientific corridor, Weill Cornell Medicine’s powerful network of collaborators extends to its parent university Cornell University; to Qatar, where Weill Cornell Medicine-Qatar offers a Cornell University medical degree; and to programs in Tanzania, Haiti, Brazil, Austria and Turkey. Weill Cornell Medicine faculty provide exemplary patient care at NewYork-Presbyterian/Weill Cornell Medical Center, NewYork-Presbyterian Westchester Behavioral Health Center, NewYork-Presbyterian Lower Manhattan Hospital, NewYork-Presbyterian Queens and NewYork-Presbyterian Brooklyn Methodist Hospital. Weill Cornell Medicine is also affiliated with Houston Methodist. For more information, visit weill.cornell.edu.


Pain-Sensing Gut Neurons Protect Against Inflammation

Neurons that sense pain protect the gut from inflammation and associated tissue damage by regulating the microbial community living in the intestines, according to a study from researchers at Weill Cornell Medicine.

The researchers, whose report appears Oct. 14 in Cell, found in a preclinical model that pain-sensing neurons in the gut secrete a molecule called substance P, which appears to protect against gut inflammation and related tissue damage by boosting the population of beneficial microbes in the gut. The researchers also found that these pain-sensing nerves are diminished in number, with significant disruptions to their pain-signaling genes, in people who have inflammatory bowel disease (IBD).

“These findings reshape our thinking about chronic inflammatory disease, and open up a whole new approach to therapeutic intervention,” said study senior author Dr. David Artis, director of the Jill Roberts Institute for Research in Inflammatory Bowel Disease, director of the Friedman Center for Nutrition and Inflammation and the Michael Kors Professor of Immunology at Weill Cornell Medicine.

a man posing for a picture

Dr. David Artis

The study’s first author, Dr. Wen Zhang, a postdoctoral researcher in the Artis laboratory, added, “Defining a previously unknown sensory function for these specific neurons in influencing the microbiota adds a new level of understanding to host-microbiota interactions.”

IBD covers two distinct disorders, Crohn’s disease and ulcerative colitis, and is believed to affect several million people in the United States. Typically it is treated with drugs that directly target elements of the immune system. Scientists now appreciate that gut-dwelling bacteria and other microbes also help regulate gut inflammation.

As Dr. Artis’s laboratory and others have shown in recent years, the nervous system, which is “wired” into most organs, appears to be yet another powerful regulator of the immune system at the body’s barrier surfaces. In the new study, Dr. Artis and his team specifically examined pain neurons that innervate—extend their nerve endings into—the gut.

a woman smiling for a portrait

Dr. Wen Zhang

These gut-innervating pain neurons, whose cell bodies sit in the lower spine, express a surface protein called TRPV1, which serves as a receptor for pain-related signals. TRPV1 can be activated by high heat, acid, and the chili-pepper compound capsaicin, for example—and the brain translates this activation into a sense of burning pain. The researchers found that silencing these TRPV1 receptors in gut nerves, or deleting TRPV1-expressing neurons, led to much worse inflammation and tissue damage in IBD mouse models, whereas activating the receptors had a protective effect.

The investigators observed that the worsened inflammation and tissue damage in TRPV1-blocked mice were associated with changes in the relative populations of different species of gut bacteria. When this altered bacterial population was transplanted into normal mice, it caused the same worsened susceptibility to inflammation and damage. By contrast, broad-spectrum antibiotic treatment could reverse this susceptibility even in TRPV1-blocked mice. This result demonstrated that TRPV1-expressing nerves protect the gut mainly by helping to maintain a healthy gut microbe population. To continue reading, click here.


Fungal Association with Tumors May Predict Worse Outcomes

The presence of some fungal species in tumors predicts—and may even help drive—worse cancer outcomes, according to a study from Weill Cornell Medicine and Duke University researchers.

The study, which appears Sept. 29 in Cell, provides a scientific framework to develop tests that delineate specific fungal species in tumors that are relevant for prediction of cancer progression and therapy. The results also point to the possibility of using antifungal treatments to augment conventional cancer treatments in some cases.

“These findings open up a lot of exciting research directions, from the development of diagnostics and treatments to studies of the detailed biological mechanisms of fungal relationships to cancers,” said senior author Dr. Iliyan Iliev, associate professor of immunology in medicine in the Division of Gastroenterology and Hepatology and a member of the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine.

a man posing for a picture

Dr. Iliyan Iliev. Credit: Jennifer Conrad

The first author of the study was Anders Dohlman, a doctoral student in biomedical engineering at Duke University.

The idea that viruses and bacteria can trigger or accelerate cancer development is now well established. However, little is known about the cancer-related roles of fungi—which, like bacteria and viruses, colonize the gut, lungs, skin and other barrier tissues, interact with the immune system, and sometimes cause disease.

In the new study, researchers catalogued fungal species and their associations with different cancers by analyzing The Cancer Genome Atlas, the largest well-annotated genomic database of human tumors.

The analysis revealed that the DNA of certain fungal species are relatively abundant in some tumor types. These species include, in gastrointestinal tumors, Candida tropicalis and Candida albicans, which causes thrush and yeast infections; in lung tumors, species of the fungal genus Blastomyces; and in breast tumors, species of the fungus Malassezia.

The researchers devised sophisticated computational methods to exclude fungal DNA likely to have originated from laboratory contamination, and were able to confirm, in particular, the presence of live Candida species in colorectal tumor samples.

Their analysis linked higher levels of Candida in gastrointestinal tumors to tumor gene activity promoting inflammation and reduced cell-to-cell adhesion—features associated with cancer’s late-stage spread to distant organs, known as metastasis. Higher Candida levels for such tumors were also directly associated with a greater rate of metastasis.

The findings, according to the researchers, suggest that high levels of particular fungi in tumor biopsies might someday be used as biomarkers, indicating, for example, a higher metastasis risk—which in turn could lead to the choice of more effective treatment. To continue reading, click here.


Discovery Reveals How the Immune System Tolerates Friendly Gut Bacteria

Immune cells called group 3 innate lymphoid cells (ILC3s) play an essential role in establishing tolerance to symbiotic microbes that dwell in the human gastrointestinal tract, according to a study led by researchers at Weill Cornell Medicine.

The discovery, reported Sept. 7 in Nature, illuminates an important aspect of gut health and mucosal immunity—one that may hold the key to better treatments for inflammatory bowel disease (IBD), colon cancer and other chronic disorders.

“As part of this study, we define a novel pathway that drives immune tolerance to microbiota in the gastrointestinal tract,” said senior author Dr. Gregory F. Sonnenberg, associate professor of microbiology and immunology in medicine and head of basic research in the Division of Gastroenterology & Hepatology, and a member of the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine. “This is a fundamental advance in our understanding of mucosal immunity and may hold the key to understanding what goes wrong when the immune system begins to inappropriately attack microbiota in diseases such as IBD.”

two men posing for a photo

Drs. Mengze Lyu and Gregory Sonnenberg

Scientists have long known that trillions of bacteria, fungi, and other microbes dwell symbiotically in the intestines of mammals. The mechanism by which the immune system normally tolerates these “beneficial” gut microbes, instead of attacking them, has not been well understood. But there is evidence that this tolerance breaks down in IBD, leading to harmful flareups of gut inflammation. Thus, a detailed understanding of gut immune tolerance could enable the development of powerful new treatments for IBD—a class of diseases that include Crohn’s disease and ulcerative colitis, which affect several million individuals in the United States alone.

In the study, Dr. Sonnenberg and colleagues, including lead author Dr. Mengze Lyu, a postdoctoral researcher in the Sonnenberg lab, used single-cell sequencing and fluorescent imaging techniques to delineate immune cells in the mesenteric lymph nodes that drain the intestines of healthy mice. They focused on cells expressing a transcription factor, RORγt, which are known to drive either inflammation or tolerance in response to microbes that colonize the intestine. The dominant immune cell types in these tissues, they found, were T cells and ILC3s. The latter are a family of immune cells that represent an innate counterpart of T cells, and work as a first line of defense in mucosal tissues such as the intestines and lungs.

In close collaboration with researchers at the University of Birmingham, UK, the scientists observed that in lymph node regions called interfollicular zones, ILC3s are in close association with a specific type of T cell, called RORγt+ regulatory T cells (Tregs), which are adapted to dial down inflammation and immune activity to promote tolerance in the gut. To continue reading, please click here.


Scientists Identify a Key Molecular Protector of Gut Health

A protein called Zbtb46, expressed by specialized immune cells, has a major role in protecting the gastrointestinal tract from excessive inflammation, according to a study from researchers at Weill Cornell Medicine.

The finding, which appears July 13 in Nature, is a significant advance in the understanding of how the gut maintains health and regulates inflammation, which could lead to better strategies for treating diseases like inflammatory bowel disease (IBD).

“We’ve known that there are related families of immune cells in the gut that can either protect from inflammation or at other times be major drivers of inflammation,” said senior author Dr. Gregory Sonnenberg, associate professor of microbiology and immunology in medicine in the Division of Gastroenterology & Hepatology, and a member of the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine. “This new finding helps us understand how these cells are regulated to optimally promote intestinal health and prevent inflammation.”

IBD, which includes Crohn’s disease and ulcerative colitis, affects several million people in the United States. These chronic inflammatory disorders target the gut, can be seriously debilitating, and treatments may not work well for some patients—mainly because scientists don’t have a complete picture of what is driving these diseases and how the sophisticated immune cell networks in the gut support tissue health.

Dr. Sonnenberg’s laboratory has been advancing the science of gut immunity with studies of recently identified immune cells called ILC3s. These “innate lymphoid cells” are related to T cells and B cells, and clearly have important roles in protecting the gut and other organs from excess inflammation. However, in the context of IBD or colorectal cancer they become altered. In general, scientists have wanted to know more about how these cells work.

a man and woman smiling for a portrait

Drs. Gregory Sonnenberg and Wenqing Zhou. Provided by Sonnenberg lab


To this end, Dr. Sonnenberg and his team, including first author Dr. Wenqing Zhou, a postdoctoral researcher in the Sonnenberg Laboratory, set out to make a detailed catalog of ILC3s and other related immune cells residing in the large intestine of mice, using relatively new single-cell sequencing techniques.

A surprise finding was that a subset of ILC3s express Zbtb46, an anti-inflammatory protein that prior studies had suggested is produced only in dendritic cells, a very different type of immune cell. The researchers showed in experiments with mice that ILC3s expressing Zbtb46 have a strong ability to restrain inflammation following gut infection. When they blocked Zbtb46 expression in ILC3s, gut infection led to signs of severe inflammation, including a rise in the numbers of other gut immune cells promoting inflammation. To read further, please click here


Toxin-producing Yeast Strains in Gut Fuel IBD

Individual Candida albicans yeast strains in the human gut are as different from each other as the humans that carry them, and some C. albicans strains may damage the gut of patients with inflammatory bowel disease (IBD), according to a new study from researchers at Weill Cornell Medicine. The findings suggest a possible way to tailor treatments to individual patients in the future.

The researchers, who report their findings March 16 in Nature, used an array of techniques to study strains, or genetic variants, of Candida from the colons of people with or without ulcerative colitis, a chronic, relapsing and remitting inflammatory disorder of the colon and rectum and one of the main forms of IBD. They found that certain strains, which they call “high-damaging,” produce a potent toxin called candidalysin that damages immune cells.

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Dr. Iliyan Iliev

“Such strains retained their “high-damaging” properties when they were removed from the patient’s gut and triggered pro-inflammatory immunity when colonized in mice, replicating certain disease hallmarks,” said senior author Dr. Iliyan Iliev, an associate professor of immunology in medicine in the Division of Gastroenterology and Hepatology and a scientist in the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine.

IBD affects approximately 3.1 million people in the United States and can greatly impair patients’ quality of life. Such patients rely on a handful of available therapies, but treatments may not always be effective. The new study has suggested one reason steroids, a commonly used treatment, may not work; treating mice with the drug to suppress intestinal inflammation failed in the presence of “high-damaging” C. albicans strains.

“Our findings suggest that C. albicans strains do not cause spontaneous intestinal inflammation in a host with intact immunity,” Dr. Iliev said. “But they do expand in the intestines when inflammation is present and can be a factor that influences response to therapy in our models and perhaps in patients.”

Most studies of the human microbiome in healthy individuals and those with IBD have focused on bacteria and viruses, but recent research by Dr. Iliev and others has illuminated the contributions of fungi to the effects of microbes on humans and mice. They have found that intestinal fungi play an important role in regulating immunity at surfaces exposed to the outside, such as the intestines and lungs, due to their potent immune-stimulating characteristics. While the collective community of fungi in the body, known as the mycobiota, has been linked to several diseases, including IBD, researchers previously had not understood the mechanisms by which the mycobiota contribute to inflammation in the gut. To continue reading article, click here.


A New and Versatile Genetic Manipulation Pipeline for Studying Nonmodel Gut Bacteria

Scientists at the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine have developed a pipeline that enables genetic manipulation of nonmodel gut bacteria. The pipeline will allow scientists to study the biological roles of these bacteria, which are increasingly recognized as key factors in health and disease, at the single-gene level.

Scientists have developed advanced genetic tools for some model gut bacteria, such as E. coli, but have lacked the necessary tools for a large group of gut bacteria called Firmicutes/Clostridia that are dominant in a healthy human gut. In the study, published Jan. 19 in Cell, the researchers have developed gene-modification techniques for multiple nonmodel gut bacteria, from more than five different phyla including Firmicutes/Clostridia.

The researchers demonstrated the potential of their new genetic tools by using them to study the role of a key gut bacterial gene in regulating colon inflammation.

"Gut bacteria play a major role in the onset and development of human diseases like inflammatory bowel disease and cancers," said Dr. Chun-Jun Guo, assistant professor of immunology in medicine in the Department of Gastroenterology and Hepatology and a scientist in the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine. “We were able not only to develop genetic manipulation tools for previously 'intractable' gut bacteria, but also to discover an interesting role for a microbial gene in the host using these tools.”

Gut bacteria have generally evolved symbiotic relationships, also known as commensal, with their animal hosts, including humans. Although scientists over the last two decades have been increasingly aware of gut microbes' importance in immune function and overall health—and in promoting disease when they are disrupted, for example by antibiotic use or poor diets—the development of genetic tools for manipulating these microbes has not kept pace. To read further, click here.


Two Weill Cornell Medicine Faculty Members Inducted into ASCI

Two Weill Cornell Medicine physician-scientists, Dr. Randy Longman and Dr. Robert Schwartz, have been elected as members of the American Society for Clinical Investigation.

The American Society for Clinical Investigation (ASCI) is one of the nation’s oldest nonprofit medical honor societies and focuses on the unique role of physician-scientists in research, clinical care and medical education. It is comprised of more than 3,000 physician-scientists serving in the upper ranks of academic medicine and industry. Members are leaders in their fields in translating innovative laboratory findings into clinical advancements. Drs. Longman and Schwartz join 93 other new members elected this year and will be officially inducted at the organization’s annual meeting in April.

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Dr. Randy Longman

Dr. Randy Longman is an associate professor of medicine in the Division of Gastroenterology and Hepatology at Weill Cornell Medicine and director of the Jill Roberts Center for Inflammatory Bowel Disease at Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medical Center. His research focuses on interactions between gut microbes and the immune system in inflammatory bowel disease (IBD). His work has identified specific strains of bacteria that are involved and how they relay signals to the immune system to activate inflammation in patients with Crohn’s disease and ulcerative colitis, the most common forms of IBD.

Dr. Longman is currently leading a clinical trial evaluating whether dietary fiber supplementation may improve the efficacy of fecal microbiota transplantation (FMT) in patients with moderate ulcerative colitis. Supported by the National Institute of Diabetes and Digestive and Kidney Diseases, the trial is based on his earlier work that identified specific microbes associated with clinical responses to FMT. Dr. Longman’s research is funded by several organizations, including the National Institutes of Health and the Crohn’s and Colitis Foundation.

“It’s very meaningful to be elected as a member of the ASCI, knowing my peers recognize my work has contributed toward moving the needle forward,” said Dr. Longman, who is also a member of the Jill Roberts Institute for Research in Inflammatory Bowel Disease. “As a physician-scientist, the most important thing for me is that my research discoveries may translate into clinical treatments that help patients.” To read further, click here.


Preclinical Study Finds Gut Fungi Influence Neuroimmunity and Behavior

A specific group of fungi residing in the intestines can protect against intestinal injury and influence social behavior, according to new preclinical research by scientists at Weill Cornell Medicine. The findings extend a growing body of work identifying a "gut-immunity-brain axis," a signaling system that may have a wide range of effects on physiology in both health and disease, influenced not only by the body's own cells but also the resident microbes.

The study, published Feb. 16 in Cell, reveals a novel set of molecular signals connecting fungi in the gut to their host’s cells throughout the body, including immune cells and neurons.

“We have made a direct link between a major immune pathway induced by fungi in the lining of the intestine and signals in the nervous system that impact animal behavior,” said senior author Dr. Iliyan Iliev, associate professor of immunology in medicine in the Division of Gastroenterology and Hepatology and a member of the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine.

Drs. Dilek ColakMelanie Johncilla and Megan Allen from Weill Cornell Medicine and Dr. Rhonda K. Yantiss from Weill Cornell Medicine and NewYork-Presbyterian also contributed to this study.

The lining of the intestine must balance conflicting needs, absorbing water and nutrients from food while acting as a barrier to prevent the vast population of microbes in the gut from invading the bloodstream. Examining this system in a mouse model, the scientists mapped the locations of different fungi within the intestine and found that a unique consortium of fungi tends to accumulate at specific sites near the gut epithelium, or lining, suggesting that these species have colonized the gut and interact closely with the nearby epithelial cells.

image of two people in front of flow cytometry

Dr. Irina Leonardi (left) and Dr. Iliyan Iliev. Photo credit: Jennifer Conrad.

Mice carrying some of these fungi enjoyed better protection against events that can disrupt the intestinal barrier, such as intestinal injury and bacterial infection. "There was fortification of those barrier functions when we added that specific fungal community to mice," Dr. Iliev said.

Improving intestinal barrier integrity wasn't the only effect of the fungi. In separate experiments, the team found that mice carrying the fungal community in their gut displayed more social behavior than animals without these fungi. To read further, click here.


Key Growth Factor Protects Gut from Inflammatory Bowel Disease

A growth factor protein produced by rare immune cells in the intestine can protect against the effects of inflammatory bowel disease (IBD), according to a new discovery from Weill Cornell Medicine researchers.

In their study, published Jan. 31 in Nature Immunology, the researchers found that the growth factor, HB-EGF, is produced in response to gut inflammation by a set of immune-regulating cells called ILC3s. These immune cells reside in many organs including the intestines, though their numbers are known to be depleted in the inflamed intestines of IBD patients.

The researchers showed in experiments in mice that this growth factor can powerfully counter the harmful effects of a key driver of intestinal inflammation called TNF. In doing so, ILC3s protect gut-lining cells when they would otherwise die and cause a breach in the intestinal barrier.

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Dr. Gregory Sonnenberg

“We’ve discovered a new cellular pathway that is essential to protect against gut inflammation. This discovery could lead to a better understanding of IBD pathogenesis and new strategies to treat this disease” said study senior author Dr. Gregory Sonnenberg, an associate professor of microbiology and immunology in medicine in the Division of Gastroenterology & Hepatology and a scientist in the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine.

IBD, a disease category including ulcerative colitis and Crohn’s disease, features chronic gut inflammation and many potential follow-on effects including arthritis and colorectal cancer. The condition appears to be quite common in the United States; a survey-based study by researchers at the Centers for Disease Control and Prevention in 2015 suggested that more than 1 percent of the U.S. population—more than three million people—were living with IBD. Current treatments help some but not all patients.

Dr. Sonnenberg and his laboratory have found in recent studies that ILC3s play a key role in protecting the gut from harmful inflammation and are depleted in human patients who have IBD or colon cancer. In the new study, the team sought a more precise understanding of how ILC3s fight against IBD’s inflammatory effects. To continue reading, click here.


Novel Immune Cell Population May Trigger Inflammation in Multiple Sclerosis and other Brain Disorders

A group of immune cells that normally protect against inflammation in the gastrointestinal tract may have the opposite effect in multiple sclerosis (MS) and other brain inflammation-related conditions, according to a new study by Weill Cornell Medicine and NewYork-Presbyterian researchers. The results suggest that countering the activity of these cells could be a new therapeutic approach for such conditions.

The researchers, who reported their finding Dec. 1 in Nature, were studying a set of immune cells called group 3 innate lymphoid cells (ILC3s), which help the immune system tolerate beneficial microbes and suppress inflammation in the intestines and other organs throughout the body. They discovered a unique subset of these ILC3s that circulate in the bloodstream and can infiltrate the brain—and, to their surprise, do not quench inflammation but instead ignite it.

The scientists called this subset inflammatory ILC3s, and found them in the central nervous system of mice with a condition modeling MS. Instead of constraining the immune response, this subset of ILC3s spurred another group of immune cells called T cells to attack myelinated nerve fibers, leading to MS-like disease symptoms. The researchers detected similar inflammatory ILC3s in the peripheral blood and cerebrospinal fluid of MS patients.

“This work has the potential to inform our understanding of, and potential treatments for, a broad variety of conditions involving T-cell infiltration of the brain,” said senior author Dr. Gregory Sonnenberg, associate professor of microbiology and immunology in medicine in the Division of Gastroenterology and Hepatology and a member of the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine.

Dr. Greg Sonnenberg and John Benji Grigg

Dr. Greg Sonnenberg (left) and John Benji Grigg


MS affects more than two million people worldwide. Other conditions that feature chronic brain inflammation afflict tens of millions more and include Alzheimer’s and Parkinson’s diseases. There is also evidence that neuroinflammation develops naturally with aging and is a major factor in age-related cognitive decline, and more recently inflammatory T-cell responses in the brain have been linked to neurological symptoms associated with SARS-CoV-2 infection.

The researchers have shown in recent work that ILC3s residing in the gut act as sentinels and immune regulators, suppressing inflammation—including inflammatory T-cell activity—and warding off cancer. In the new study, they examined the roles of ILC3s in the brain, and found, contrary to their expectation, that ILC3s are not normally present in the brain under healthy conditions but can infiltrate the brain from the bloodstream during inflammation. When they do infiltrate the central nervous system, they have pro-inflammatory rather than anti-inflammatory effects.

The researchers showed with a mouse model of MS that these inflammatory ILC3s in the brain function as antigen-presenting cells: They display bits of myelin protein, the main ingredient in the insulating layer around nerve fibers, to T cells—prompting them to attack myelin, causing the nerve damage that gives rise to disease signs. They found the inflammatory ILC3s in close association with T cells in regions of active inflammation and nerve damage in the mouse brains. To read more, click here.


Antibodies Help Keep Harmful Forms of Gut Fungi in Check

Antibody protection against harmful forms of fungi in the gut may be disrupted in some patients with Crohn’s disease—a condition caused by chronic inflammation in the bowel—according to a new study by Weill Cornell Medicine investigators.

Previous studies have shown that the immune system plays a key role in maintaining a healthy balance of gut bacteria. In the new study, published Nov. 22 in Nature Microbiology, senior author Dr. Iliyan Iliev, associate professor of immunology in medicine in the Division of Gastroenterology and Hepatology, and his team at Weill Cornell Medicine investigated if it might also play a role in managing gut fungi. Unlike bacteria, fungi can change their shape in response to environmental conditions, and certain forms are harmful to humans. In particular, a type of fungus called Candida albicans transforms from a yeast form that is not pathogenic to a form that produces long, branched structures called hyphae, which can invade tissues and cause damage.

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(From left) Dr. Iliyan Iliev and Itai Doron.

The investigators found that antibodies that are secreted in the gut help control the pathogenesis of Candida albicans in healthy individuals and that this protective mechanism may be disabled in people with Crohn’s disease, causing a harmful overgrowth of the pathogenic form of the fungus. An intestinal overabundance of Candida albicans is associated with inflammatory bowel disease and several other conditions that directly or indirectly affect the gastrointestinal tract.

“We found that antibodies secreted in the gut are involved in maintaining specific intestinal fungi such as C. albicans in its benign, so-called commensal form,” said Dr. Iliev, who is also a scientist in the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine. “This process is interrupted in patients with Crohn’s disease.” To read more, click here.


Researchers Identify Bacteria That Underlie Success of Fecal Microbiota Transplants

Circular genome map of Odoribacter splanchnicus isolated from an ulcerative colitis patient. Image courtesy of Drs. Longman and Lima.

The effectiveness of fecal microbiota transplantation (FMT) in treating ulcerative colitis depends on a small set of beneficial bacterial strains, suggests a new study from researchers at Weill Cornell Medicine and NewYork-Presbyterian.

In the study, reported Oct. 1 in Gastroenterology, the researchers sampled gut bacteria from healthy FMT donors and from FMT recipients with ulcerative colitis, identifying the bacterial strains whose transfer correlates with treatment effectiveness.

The scientists found that one of these strains was linked particularly strongly to treatment success. They showed that its protection against colitis involves several interrelated mechanisms, including the induction of an increase in anti-inflammatory T cells in the gut, and the production of anti-inflammatory, gut health-promoting molecules called short-chain fatty acids.

“Fecal microbiota transplant has been shown to be effective in several clinical trials, but ultimately we need to identify the specific microbial factors that make it work and focus on delivering those,” said senior author Dr. Randy Longman, director of the Jill Roberts Center for Inflammatory Bowel Disease at Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medical Center. “This study takes us a significant step closer to that goal.”

Scientists over the past two decades have begun to recognize the broad importance of gut-resident bacteria in regulating human health, especially immune system and gut health. Both of these are disrupted in ulcerative colitis, the most common form of inflammatory bowel disease, which affects more than two million people worldwide. To read more, click here.


Key Immune Cells Maintain Healthy Gut Bacteria to Protect Against Colorectal Cancer

Artistic rendering of a tumor growing within a colon, resulting in local alterations of resident microbiota. Artist/Image Source: Sarah Field Sonnenberg

An immune cell subset called innate lymphoid cells (ILC3s) protects against colorectal cancer, in part by helping to maintain a healthy dialogue between the immune system and gut microbes, according to a new study led by researchers at Weill Cornell Medicine and NewYork-Presbyterian. The finding opens the door to new strategies for treating this type of cancer.

The researchers, who published their findings August 17 in Cell, showed that ILC3s tend to be drastically reduced and functionally altered in people with colorectal cancer. Further, they demonstrate that experimentally disrupting the functions of ILC3s in mice leads to aggressive colon cancer and greatly reduces the effectiveness of cancer immunotherapies.

Colorectal cancer is the fourth most common cancer in the United States, with about 150,000 new cases each year and about 50,000 deaths. While early detection of these cancers or precancerous polyps with screening colonoscopies is very effective, treatments for advanced colorectal tumors remain a major challenge with limited therapeutic options. Oncologists are particularly concerned about the relative resistance of these tumors to immunotherapies—treatments that work well against some other cancers by boosting the immune system’s ability to attack malignant cells.

Dr. Greg Sonnenberg

Dr. Greg Sonnenberg

“These findings suggest new possibilities for the clinical approach to colorectal cancer, and also help explain why this type of cancer often fails to respond to immunotherapies,” said senior author Dr. Gregory Sonnenberg, an associate professor of microbiology and immunology in medicine in the Division of Gastroenterology and Hepatology and a member of the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine.

One factor impacting the resistance to immunotherapies may be the gut microbiome, the population of bacteria and other microbial species that reside in the intestines and normally aid digestion, support various metabolic functions and play a role in regulating the immune system. Colorectal cancer is associated with chronic gut inflammation and a major disruption of the normal microbiome. Further, recent studies suggest that patients’ microbiomes play a key role in controlling the outcome of cancer immunotherapies and may explain why some patients’ cancers do, or do not, respond well to treatment.

In the new study, Dr. Sonnenberg and colleagues, including lead author Dr. Jeremy Goc, a research associate in Dr. Sonnenberg’s laboratory, examined the role of ILC3s, which reside in the intestines and are known to help mediate the relationship between the immune system and gut microbes.

Among this loss of normal ILC3 activity in the gut, the authors further observed that the ability of ILC3s to regulate a specific immune cell subset called T cells was significantly disrupted. This disruption of the dialogue between ILC3s and T cells further led to a rise in inflammation in the gut that subsequently modifies the gut microbiome. These gut microbe changes in turn induce a decrease in the levels of T cells that are good at fighting tumors.

Dr. Jeremy Goc

Group 3 innate lymphoid cells normally play a key role in maintaining a healthy dialogue between the microbiome and the immune environment in the lower gut. In close collaboration with Dr. Manish Shah, the Bartlett Family Professor of Gastrointestinal Oncology director of the Gastrointestinal Oncology Program in the Division of Hematology and Medical Oncology, and member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, the research group analyzed colorectal tumors and pre-cancerous polyps from humans and mice. They found that ILC3s from cancerous tissues were relatively depleted as compared with healthy tissues and were further fundamentally altered in their functions.

“This is an exciting finding that could have broad implications for our understanding of the pathways that control the pathogenesis, progression and therapeutic responsiveness of gastrointestinal malignancies,” said study co-author Dr. Shah, who is also chief of the Solid Tumor Oncology Service and co-director of the Center for Advanced Digestive Care at NewYork-Presbyterian/Weill Cornell Medical Center.

Among this loss of normal ILC3 activity in the gut, the authors further observed that the ability of ILC3s to regulate a specific immune cell subset called T cells was significantly disrupted. This disruption of the dialogue between ILC3s and T cells further led to a rise in inflammation in the gut that subsequently modifies the gut microbiome. These gut microbe changes in turn induce a decrease in the levels of T cells that are good at fighting tumors. To read more, click here.


Study Identifies ‘Achilles heel’ of Bacteria Linked to Crohn’s Disease

The discovery of an “Achilles heel” in a type of gut bacteria that causes intestinal inflammation in patients with Crohn’s disease may lead to more targeted therapies for the difficult to treat disease, according to Weill Cornell Medicine and NewYork-Presbyterian investigators.

In a study published Feb. 3 in Cell Host and Microbe, the investigators showed that patients with Crohn’s disease have an overabundance of a type of gut bacteria called adherent-invasive Escherichia coli (AIEC), which promotes inflammation in the intestine. Their experiments revealed that a metabolite produced by the bacteria interacts with immune system cells in the lining of the intestine, triggering inflammation. Interfering with this process, by either reducing the bacteria’s food supply or eliminating a key enzyme in the process relieved gut inflammation in a mouse model of Crohn’s disease.

“The study reveals a therapeutically targetable weak point in the bacteria,” said senior author Dr. Randy Longman, associate professor of medicine in the Division of Gastroenterology and Hepatology and the Director of the Jill Roberts Center for Inflammatory Bowel Disease at Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medical Center.

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Dr. Monica Viladomiu

To find this “Achilles heel,” Dr. Longman and his colleagues, including Drs. Ellen Scherl and Chun-Jun Guo at Weill Cornell Medicine and collaborators Dr. Gretchen Diehl at Memorial Sloan Kettering and Dr. Kenneth Simpson at Cornell’s Ithaca campus, targeted a process the AIEC bacteria uses to convert a byproduct of sugar fermentation in the gut to grow. Specifically, the AIEC uses 1,2-propanediol, a byproduct of the breakdown of a type of sugar called fucose that is found in the lining of the intestines. When the AIEC converts 1,2-propanediol, it produces propionate, which the study showed interacts with a type of immune system cell called mononuclear phagocytes that are also found in the lining of the gut. This sets off a cascade of inflammation.

Next, the investigators genetically engineered AIEC bacteria to lack a key enzyme in this process called propanediol dehydratase. Without propanediol dehydratase, the bacteria do not set off a cascade of inflammation in a mouse model of Crohn’s disease. Reducing the available supply of fucose in the animal’s gut also reduced inflammation.

“Changing one metabolic pathway in one type of bacteria can have a big impact on intestinal inflammation,” said the study’s co-lead author Dr. Monica Viladomiu, a post-doctoral associate in medicine in the Division of Gastroenterology and Hepatology and in the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine. Maeva Metz, a Weill Cornell Medicine Graduate School of Medical Sciences doctoral candidate in Dr. Longman’s laboratory, is also co-lead author.

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Maeva Metz

The discovery could lead to better treatments for Crohn’s disease, a type of inflammatory bowel disease that affects more than 4 million people worldwide. Currently, patients with Crohn’s disease are often treated with antibiotics, which can kill both beneficial and harmful bacteria causing unwanted side effects. But treatments that precisely target the inflammatory cascade discovered by Dr. Longman and colleagues might help reduce inflammation while preserving beneficial bacteria.

“If we can develop small molecule drugs that inhibit propanediol dehydratase or use dietary modifications to reduce the availability of fucose, we may be able to reduce intestinal inflammation in patients with Crohn’s disease with fewer side effects,” said Dr. Longman, who is also a member of the Jill Roberts Institute for Research in Inflammatory Bowel Disease.

One of the next steps for the team will be testing potential treatments. They also plan to study the potential role of an enzyme called fucosyltransferase 2 in protecting the gut against this inflammatory cascade. Dr. Longman explained that many patients with Crohn’s disease have mutations in the gene that encodes this enzyme, rendering it nonfunctional.

“From a clinical perspective, that's interesting because it may help us stratify people for whom one intervention or another maybe more useful,” Dr. Longman said.


Fungi in the Gut Prime Immunity Against Infection


Weill Cornell Medicine Scientist Receives Pathogenesis of Infectious Disease Award

Dr. Iliyan Iliev, an associate professor of immunology in medicine in the Division of Gastroenterology and Hepatology and a scientist in the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine, has been awarded the Investigators in the Pathogenesis of Infectious Disease (PATH) award by the Burroughs Wellcome Fund.

The PATH award provides early-career scientists with $500,000 over five years to investigate the interplay between humans and pathogens, and how such encounters can lead to disease. These prestigious awards are intended to give the freedom and flexibility to pursue new avenues of inquiry, stimulating higher risk research projects that hold potential for significantly advancing understanding of how infectious diseases work and how health is maintained.

“This award is not only a great recognition, but it’s also a trust that the Burroughs Wellcome Fund has in us to go in a direction that we haven’t yet explored in our lab,” Dr. Iliev said.

The PATH award will allow Dr. Iliev to explore processes that allow fungi to breach intestinal barriers and cause systemic Candidiasis, which is the most common type of systemic fungal infection caused by a yeast called Candida albicans that is found in humans. To read more, click here.


Dr. Gregory Sonnenberg Awarded The 2020 ICIS-Luminex John R. Kettman Award For Excellence in Interferon & Cytokine Research

Above left: Lymphoid Follicle in the colon of a healthy mouse demonstrating the presence of RORgt+ILC3. The section is stained for RORgt (green), IL-7Ra (red) and CD3 (blue). Image courtesy of Dr. Gregory Sonnenberg

The Jill Roberts Institute for Research in IBD is pleased to announce that one of our esteemed faculty members, Dr. Gregory Sonnenberg, an associate professor of microbiology and immunology in medicine, was awarded the inaugural ICIS-LUMINEX John R. Kettman Award for Excellence in Interferon & Cytokine Research from the international Cytokine & Interferon Society. The award recognizes mid-level investigators who have made outstanding contributions to the field of interferon or cytokine biology. Dr. Sonnenberg was honored for his scientific contributions to the fields of immunology and microbiology, and for his success as an independent, extramurally funded investigator. To read more about Dr. Sonnenberg and other Weill Cornell Medicine awards and honors that were bestowed in October 2020, please click here.


Dr. Sonnenberg Receives ICIS-LUMINEX John R. Kettman Award for Excellence in Interferon & Cytokine Research

sonnenberg-gregory

Dr. Gregory F. Sonnenberg, Associate Professor of Microbiology & Immunology in Medicine, Division of Gastroenterology and Hepatology, WDOM, has received the inaugural ICIS-LUMINEX John R. Kettman Award for Excellence in Interferon & Cytokine Research.

The ICIS-LUMINEX John R. Kettman Award for Excellence in Interferon & Cytokine Research recognizes Dr. Sonnenberg for “establishing himself as an extramurally funded and well-respected independent investigator, and his innovative research program which continues to make seminal scientific contributions at the interface of immunology and microbiology.”

The WDOM congratulates Dr. Sonnenberg on receiving this prestigious award.


COVID-19 Research Grants Support Weill Cornell Medicine Investigators

Weill Cornell Medicine has awarded eight grants of $100,00 each to faculty for a variety of research projects on COVID-19, funded by the institution’s Board of Overseers and additional donors. The grants will support studies aimed at understanding fundamental aspects of the disease, the body’s immune response and social determinants of health that affect COVID-19 outcomes.

One of the faculty members selected as a grant recipient is Julie Magarian Blander, Ph.D., the Gladys and Roland Harriman Professor of Immunology in Medicine, who is also a faculty member of the Jill Roberts Institute for IBD. Immunologists are uniquely poised to make an impact and contribution through their investigation into COVID-19 that may have a global effect on the pandemic. Dr. Blander’s research project, A T cell Biomarker for Protective COVID-19 Immunity, is summarized in following paragraph.

Identifying patients who have recovered from COVID-19 and are immune to future infection is essential to emerging from the pandemic. To do this, scientists must develop reliable tests for immunity to the SARS-CoV-2 virus. Though testing for antibodies to the virus is common, so far it is unclear whether they protect against future infection. Dr. Blander and her team will use blood collected from Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medical Center healthcare workers who recovered from COVID-19 to find virus-fighting immune cells called CD8 T cells. They will then identify the receptor these T cells use to find and destroy cells infected with the SARS-CoV-2 virus and try to develop a test to determine if individuals with this receptor are safe from future infections. If they are successful, it could lead to new tests that identify people who are protected from COVID-19 because they have recovered from SARS-CoV-2 infection or from a previous infection with a similar virus that generates a similar immune response.

 

To read the full WCM article about all eight grant recipients, please follow the link here.


Fungus in Gut May Explain Why Some Ulcerative Colitis Patients Benefit from Fecal Transplant

Higher levels of a type of fungus in the gut are associated with better outcomes for patients with a type of inflammatory bowel disease called ulcerative colitis who are treated with gut microbes from healthy donors, according to a new study by Weill Cornell Medicine investigators.

The study, published April 15 in Cell Host & Microbe, suggests a way to determine which patients may be good candidates for the therapy, called fecal microbiota transplant (FMT), in which stool—and the healthy bacteria, fungi and other microbes it contains—are transferred from a donor to the patient.

Ulcerative colitis is a type of inflammatory bowel disease that causes chronic sores and inflammation in the colon and rectum. Prior research has shown that FMT can promote healing in the mucosal lining of the lower digestive tract, relieving ulcerative colitis symptoms in some people. Based on the new study, those patients who benefit from this therapy have higher levels of the fungus Candida in their gut prior to the procedure.

Graphic depicting association of Candida levels with response to fecal microbiota transplant in ulcerative colitis patients.

“The fecal transplant then acts to decrease the population of Candida,” said senior study author Dr. Iliyan D. Iliev, assistant professor of immunology in medicine in the Division of Gastroenterology and Hepatology and co-director of the Microbiome Core Lab at the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine. While more research is needed, the decline in Candida after FMT may help to reduce inflammation in the colon and rectum. “Altered fungus levels may also affect bacteria in the gut, altogether reducing inflammation,” said Dr. Irina Leonardi, first author of the study and a postdoctoral associate in medicine at Weill Cornell Medicine.

About 750,000 people in North America have ulcerative colitis. The disease does not always respond to medication, and while surgery can relieve symptoms, it is not curative. The current research may one day help doctors determine which patients might be candidates for FMT or other microbiome-based therapies. To read more, click here.


Scientists Identify New Pathways to Inflammation in Allergy-Linked Immune Cells

The protein interleukin-33 (shown in green) in the cell nucleus (blue) of stromal cells (red) of mucosal tissue that is embedded in visceral adipose tissue (large octagonal purple cells). Image courtesy of Dr. Tanel Mahlakõiv and Dr. David Artis, WCM.

A class of immune cells push themselves into an inflammatory state by producing large quantities of a serotonin-making enzyme, according to a study in mice led by scientists at Weill Cornell Medicine.

The study, published March 10 in Immunity, found that the inflammatory and infection-fighting abilities of the cells, called type 2 innate lymphoid cells (ILC2s), are much impaired without the enzyme. The finding suggests possibilities for new treatments targeting ILC2s, which have been linked to asthma and other allergic disorders, to suppress their activation in inflammatory disorders.

The work also hints at what could be a major mechanism of “cross-talk” between the nervous system, which uses serotonin as a signaling molecule or neurotransmitter, and the immune system.

“There’s a lot more to do in terms of understanding the biology of these innate lymphoid cells, but it’s an exciting area that offers us potential new approaches to therapeutic intervention,” said study senior author Dr. David Artis, director of the Jill Roberts Institute for Research in Inflammatory Bowel Disease, director of the Friedman Center for Nutrition and Inflammation and the Michael Kors Professor of Immunology in the Department of Medicine at Weill Cornell Medicine.

Innate lymphoid cells are a recently discovered family of white blood cells that reside in the skin, airways and other barrier tissues of the body. They appear to have important roles as first-responders against environmental pathogens, but scientists also recognize that ILCs may hold the keys to understanding common inflammatory and autoimmune conditions such as asthma and inflammatory bowel disease. To read more, click here.


Immune Cells Heal the Intestine by Controlling Iron

An iron-regulating molecule called hepcidin is produced by the immune system and restricts the growth of gut bacteria after an intestinal injury, helping to heal the lining of the intestine, according to a study by Weill Cornell Medicine, NewYork-Presbyterian and Institut Cochin investigators.

The study, published April 10 in Science, was conducted in mice and human samples and could have important implications for treating gastrointestinal diseases that damage the lining of the intestines as a result of infection, chronic inflammation or cancer. Currently, most treatments for gut-damaging conditions like inflammatory bowel disease (IBD) focus solely on reducing inflammation and do not directly address the need to promote tissue repair.

“Not being able to heal your intestine is a major problem in patients with inflammatory bowel disease and other gastrointestinal disorders,” said senior author Dr. Gregory F. Sonnenberg, associate professor of microbiology and immunology in medicine in the Division of Gastroenterology and Hepatology and a member of the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine. “There is an urgent need to better understand the pathways that promote mucosal healing and harness that knowledge to design new treatment strategies.”

Bleeding in the intestines is often one the first signs of diseases like IBD or colorectal cancer, said lead author Dr. Nicholas Bessman, a postdoctoral associate in medicine at Weill Cornell Medicine. Intestinal bleeding may further exacerbate these diseases or hamper healing by fueling overgrowth of gut bacteria. This happens because blood contains large amounts of iron, which is essential for bacterial growth. To investigate the potential role of the iron-regulator hepcidin, the team collaborated with Dr. Carole Peyssonnaux and other researchers at the Université de Paris, INSERM, Institut Cochin, and examined intestinal healing in mice with and without the hepcidin gene. To read further, please click here.

From left: Drs. Robbyn Sockolow and Gregory Sonnenberg

Dr. Nicholas J. Bessman


New Technique Allows Genome Editing of Gut Bacteria

Scientists at Weill Cornell Medicine, Stanford University and the University of California, San Francisco have adapted genome editing tools to function in a common species of intestinal bacteria. With this technological advance, they can now precisely alter the human gut microbes’ production of small molecule metabolites that can affect their host’s metabolism, immune system and nervous system. The technique has revealed a new regulator of mucosal immune function, which operates at the externally facing surfaces that line organs such as the gut and the lungs. It could also form the basis for genetically engineering the gut microbiota to promote human health or treat disease.

Humans and other animals host thriving populations of microbes on and in their bodies. In recent years, investigators have found that these bacteria, viruses and fungi, collectively called the microbiota, exert profound influence on their hosts’ metabolism and disease pathology. The intestinal microbiota are especially diverse, varying from one individual to the next and hosting microbes that produce thousands of small molecules.

“There are many studies addressing associations between the gut microbiota and human diseases,” said Dr. Chun-Jun Guo, an assistant professor of immunology in medicine in the Division of Gastroenterology and Hepatology at Weill Cornell Medicine and lead author on the new study, published Dec. 13 in Science. Because the gut microbes appear to exert their influence on the host through the various bacterial metabolites they excrete, Dr. Guo and his colleagues wanted to probe these phenomena more thoroughly and understand the underlying mechanisms. “We wanted to develop a technology that allows us to manipulate the level of these bacterial metabolites or genes in vivo so we can directly study their impacts on the host biology,” Dr. Guo said. To read more, click here.


CURE For IBD presents donation in continuing partnership with Jill Roberts Institute

Photo above: From left to right, Front row: Kassi Reicin, Kyla Reicin, Lina Krivyan, Dr. Robbyn Sockolow, Benjamin Goldmark, Patti Kaufman, Dr. Ellen Scherl, and Jill Roberts From left to right, Back row: Joe Lepler, Chris Pedicone, Dr. David Artis, Thomas Plaza, Dr. Tom Haverty

Photo below: From left to right, Front row: Dr. Robbyn Sockolow, Benjamin Goldmark, Patti Kaufman and Dr. Ellen Scherl From left to right, Back row: Dr. David Artis, Chris Pedicone, Thomas Plaza, Elizabeth Goldmark

Since 2017, the Jill Roberts Institute for Research in Inflammatory Bowel Disease (IBD) and its Director, Dr. David Artis, have partnered with Chris Pedicone, Founder and President of CURE for IBD for a fruitful collaboration between laboratory research and dedicated fundraising efforts to find a cure for inflammatory bowel disease. CURE for IBD is a volunteer non-profit organization devoted solely to funding IBD research that seeks new treatments and cures for family, friends, and others living with IBD. On February 14, 2020, the CURE for IBD team, including Benjamin Goldmark, Elizabeth Goldmark, Dr. Tom Haverty, Patti Kaufman, Lina Krivyan, Joe Lepler, Chris Pedicone, Thomas Plaza, Kassi Reicin, and Kyla Reicin, visited the Jill Roberts Institute for discussion and a tour of the laboratory facilities. At the close of their visit, CURE for IBD graciously presented the Jill Roberts Institute with a check for $50,000 to support IBD research efforts. This year included a special $2,000 donation from Benjamin Goldmark, who chose to raise funds for CURE for IBD to complete his Bar Mitzvah project and to honor a family member who lives with IBD. Dr. Artis and members of the Jill Roberts Institute extend their gratitude to CURE for IBD and celebrate this ongoing partnership that supports current and future IBD research efforts.


Gut Instincts: Researchers Discover First Clues on How Gut Health Influences Brain Health

New cellular and molecular processes underlying communication between gut microbes and brain cells have been described for the first time by scientists at Weill Cornell Medicine and Cornell’s Ithaca campus.

Over the last two decades, scientists have observed a clear link between autoimmune disorders and a variety of psychiatric conditions. For example, people with autoimmune disorders such as inflammatory bowel disease (IBD), psoriasis and multiple sclerosis may also have depleted gut microbiota and experience anxiety, depression and mood disorders. Genetic risks for autoimmune disorders and psychiatric disorders also appear to be closely related. But precisely how gut health affects brain health has been unknown.

“Our study provides new insight into the mechanisms of how the gut and brain communicate at the molecular level,” said co-senior author Dr. David Artis, director of the Jill Roberts Institute for Research in Inflammatory Bowel Disease, director of the Friedman Center for Nutrition and Inflammation and the Michael Kors Professor of Immunology at Weill Cornell Medicine. “No one yet has understood how IBD and other chronic gastrointestinal conditions influence behavior and mental health. Our study is the beginning of a new way to understand the whole picture.”

For the study, published Oct. 23 in Nature, the researchers used mouse models to learn about the changes that occur in brain cells when gut microbiota are depleted. First author Dr. Coco Chu, a postdoctoral associate in the Jill Roberts Institute for Research in Inflammatory Bowel Disease, led a multidisciplinary team of investigators from several departments across Weill Cornell Medicine, Cornell’s Ithaca campus, the Boyce Thompson Institute, Broad Institute at MIT and Harvard, and Northwell Health with specialized expertise in behavior, advanced gene sequencing techniques and the analysis of small molecules within cells.

Mice treated with antibiotics to reduce their microbial populations, or that were bred to be germ-free, showed a significantly reduced ability to learn that a threatening danger was no longer present. To understand the molecular basis of this result, the scientists sequenced RNA in immune cells called microglia that reside in the brain and discovered that altered gene expression in these cells plays a role in remodeling how brain cells connect during learning processes. These changes were not found in microglia of healthy mice. To read more, click here.


It’s all about timing—JRI Researchers identify an essential role for the circadian clock in regulating innate lymphoid cell homeostasis in the gut

Regular daily changes between light and dark has enormous impacts on behavior and physiology of humans and many other mammals (also known as circadian rhythm). Disturbance of normal circadian rhythm in humans by shifted work, sleep disorders or frequent inter-continental flights is causally associated with obesity, cardiovascular diseases and intestinal disorders such as irritable bowel syndrome or inflammatory bowel disease. In a new study published on Oct. 4th, 2019 in Science Immunology and highlighted by the journal cover image, researchers from Weill Cornell Medicine have identified that the homeostasis of group 3 innate lymphoid cells (ILC3s), one of the key immune cell populations regulating intestinal immunity and barrier function, critically requires circadian rhythm.

 

The study was led by Dr. Gregory Sonnenberg, an associate professor of microbiology and immunology in medicine in the Division of Gastroenterology and Hepatology and a member of the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine, and Dr. Fei Teng, a postdoctoral researcher in the Sonnenberg Lab. The researchers found that intestinal ILC3s in mice exhibit diurnal oscillations in genes involved in both circadian clock and classical ILC3 effector functions in response to light signals. By genetic ablation of this pathway, they also found circadian regulation is essential for survival and appropriate cytokine production of ILC3s in the presence of intestinal commensal bacteria. Lastly, the researchers identified ILC3s isolated from the inflamed intestine of patients with inflammatory bowel disease exhibited substantial alterations in expression of several circadian-related genes. This study has uncovered a previously under-appreciated role of circadian rhythm on the homeostasis of intestinal ILC3s and suggested that this pathway may serve as a novel target to boost or restore normal ILC3 responses in the context of intestinal inflammation.

 

This work is in collaboration with Dr. Manish A. Shah (NewYork-Presbyterian Hospital) and Dr. Gérard Eberl (Institut Pasteur, France) and was supported by the NIH (R01AI143842, R01AI123368, R01AI145989, and U01AI095608), the NIAID Mucosal Immunology Studies Team (MIST), the Crohn’s and Colitis Foundation of America, the Searle Scholars Program, the American Asthma Foundation Scholar Award, Pilot Project Funding from the Center for Advanced Digestive Care (CADC), an Investigators in the Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund, a Wade F.B. Thompson/Cancer Research Institute CLIP Investigator grant, the Cancer Research Institute Lloyd J. Old STAR Program, the Meyer Cancer Center Collaborative Research Initiative, and the Jill Roberts Institute (JRI) for Research in IBD.


2019 NYC IBD Day Held at Weill Cornell Medicine

Image Credits: Jennifer Conrad

On September 18, 2019, the 5th Annual New York City IBD Research Day was hosted by Weill Cornell Medicine in the Belfer Research Building. This yearly symposium is a collaborative effort of five institutions: The Jill Roberts Institute at Weill Cornell Medicine, The Immunology Institute of the Icahn School of Medicine at Mount Sinai, The Center for Basic and Translational Research on Disorders of the Digestive System at The Rockefeller University and The Skirball Institute and the Departments of Medicine and Surgery at New York University Langone Health and Columbia University, who joined the group last year. In honor of the late Lloyd F. Mayer, MD, there is a Mayer Prize given yearly. Drs. Sergio Lira and David Artis presented the Mayer Prize to their colleague, Dr. Yasmine Belkaid. Dr. Belkaid, highly esteemed for her research examining the microbiota’s ability to build a immunological response to infection in the GI tract and skin, started the day with her talk on “Regulation of Tissue Inflammation.” Dr. Belkaid also received the Lurie Prize in Biomedical Sciences in 2019 for her outstanding achievements in biomedical research. Throughout the course of the day, the attendees listened to ten presenters, who had traveled from around the globe for this event, engaging in lively Q & A conversations afterwards. Each year, two Trainees or Junior Scientists are given the opportunity to present a talk and this year Ravi Sheth and Yinhu Wang were selected. This event provides the valuable moments for junior scientists to meet and engage in meaningful dialogue with the scientists who have defined IBD research because of their innovative work. The academic institutions of the Icahn School of Medicine at Mount Sinai, The Rockefeller University, NYU Langone Health, and Weill Cornell Medicine all provided sponsorship for this event. Generous sponsorship was also received from Boehringer Ingelheim, Janssen, the NY Crohn’s Foundation, the Kenneth Rainin Foundation, Cure for IBD, Pfizer, and Regeneron and in total, these contributions made the enriching day possible.


Dr. Chun-Jun Guo Receives NIH New Innovator Award

Dr. Chun-Jun (“C.J.”) Guo, an assistant professor of immunology in medicine in the Division of Gastroenterology and Hepatology and scientist at the Jill Roberts Institute for Research In Inflammatory Bowel Disease at Weill Cornell Medicine, has won a Director’s New Innovator Award from the National Institutes of Health (NIH) for an ambitious project to detail how the hundreds of different bacterial species living in the human gut contribute to human health and disease.

The NIH Director’s New Innovator Award, part of the NIH Common Fund, was established in 2007 to support “exceptionally creative early-career investigators who propose innovative, high-impact projects.” The award provides $1.5 million up-front to scientists, plus additional funds for university overhead costs, and is intended to support research programs lasting five years. Dr. Guo is among 60 scientists nationwide to receive the prestigious award this year.

“I’m very grateful for this award,” Dr. Guo said. “It provides my lab with a unique and exciting opportunity to pursue high-risk, high-reward research that would not get funding through traditional NIH grant mechanisms.”

Dr. Guo is an expert on the genetic manipulation of gut microbes. The diverse population of microbes in the human gut—the gut “microbiome”—has become a major focus of research in the past decade, as scientists have recognized it as a factor in major illnesses including inflammatory bowel disease, arthritis, diabetes and cancer. But determining in molecular detail what the roughly 1,000 species of gut microbes do to trigger disease or help maintain human health is an enormous undertaking. To read more, click here.


Weill Cornell Investigator Receives Inaugural Cancer Research Institute STAR Award

Dr. Gregory F. Sonnenberg, an associate professor of microbiology and immunology in medicine in the Weill Department of Medicine’s Division of Gastroenterology and Hepatology and a member of the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine, has been named an awardee for the inaugural CRI Lloyd J. Old STAR (Scientists Taking Risks) Program by the Cancer Research Institute.

The STAR program recognizes immunologists who are conducting high-risk, high-reward research in tumor immunology. Dr. Sonnenberg is one of five scientists to receive the honor following an international competition. As a recipient, he will receive a $1.25 million, five-year grant, to explore disruptive and uncommon cancer research paths. The CRI Lloyd J. Old STAR Award was named after the Cancer Research Institute’s founding medical and scientific director Lloyd J. Old, who was known as the “father of modern tumor immunology.”

“This is an incredible grant from a scientist’s standpoint,” Dr. Sonnenberg said. “Traditionally, this level of funding only comes from the National Institutes of Health. The Cancer Research Institute is really trusting us to take risks and make rapid scientific advances.”

Dr. Sonnenberg’s lab focuses on the immune system and its interaction with the body’s gut microbiome, which comprises trillions of microorganisms in the gastrointestinal tract. With this grant, he plans to examine the relationship between the immune system, microbiome and cancer. To read more, click here.


Discovery May Open Up New Possibilities for Treating Allergic Inflammatory Diseases

A molecule best known for its association with migraines may be a key to new treatments for common worm infections as well as allergic inflammatory disorders such as asthma, according to a study from scientists at Weill Cornell Medicine and the National Institutes of Health (NIH).

The scientists, whose work was published July 25 in Immunity, found a subset of white blood cells that reside in the lungs of mammals and produce the molecule, called CGRP, during worm infection in mice. The researchers discovered that the effect of CGRP in this context is to restrain the main immune response against the worms, known as a type 2 immune response. In the absence of CGRP signaling, this response is stronger and the worm infection ends more quickly.

The discovery suggests that CGRP-blocking drugs, developed in recent years to treat migraines, might also be useful in treating worm infections, which affect more than a billion people globally. Just as importantly, the findings hint that future drugs enhancing CGRP signaling could be useful against common inflammatory disorders such as asthma, food allergy and atopic dermatitis, which are caused by excessive type 2 immune responses. To read more, click here.


Weill Cornell Medicine celebrates Dr. Randy Longman’s appointment as new Center Director

Photo above: The reception to honor the appointment of Dr. Randy Longman. Pictured (L to R): Dr. Randy Longman, Jill Roberts, Dr. Anthony Hollenberg, Dr. Ellen Scherl, Dr. Charles Maltz, Dr. David Cohen, Dr. Dana Lukin, Dr. Julie Blander and Dr. David Artis.

Photo below: Dr. Randy Longman speaking at the reception. Photo credit: Tina Aswani Omprakash

On June 11, 2019, the WCM Division of Gastroenterology and Hepatology hosted a reception to congratulate Dr. Randy Longman, the newly appointed Director of the Jill Roberts Center for Inflammatory Bowel Disease (JRC), and honor the Center’s Founding Director, Dr. Ellen Scherl.

The JRC is one of the premier IBD centers for patient care and clinical research, and is composed of a team of gastroenterologists, surgeons, rheumatologists and hepatologists. Dr. Randy Longman joined the JRC in 2013. His role at the Center includes directing JRC activities, providing patient care and developing clinical and translational research that Dr. Longman passionately champions as a key approach to finding new treatments for IBD patients.

Dr. Longman is also a member of the Jill Roberts Institute for Research in IBD (JRI), where he leads a basic and translational IBD research program. He also contributes to JRI research activities including the WCM Microbiome Initiative and the JRC-JRI IBD Live Cell Bank.

Dr. David Cohen, the GI Division Chief, provided opening remarks, followed by Dr. David Artis, the Director of the JRI, Dr. Fabrizio Michelassi, Chair of Surgery at WCM, Dr. Anthony Hollenberg, Chair of Medicine at WCM, and Dr. Ellen Scherl, the Founding Director of JRC who all spoke warmly about Dr. Longman’s contributions and achievements.

The reception marks a new chapter in the JRC-JRI partnership in basic, clinical and translational IBD research and care, which could have never been possible without the unwavering support and vision of Jill Roberts, who attended the reception.

To learn more about the Jill Roberts Center for IBD, please click here. 

For the WCM Press Release, please click here.


Discovery Reveals Potential New Pathway for Treating Obesity and Related Disorders

A molecule that helps prevent fat accumulation in mammals is produced within fat tissues by stem-like cells that may be therapeutic targets for obesity and related disorders, according to a new study from scientists at Weill Cornell Medicine.

Obesity has become a global pandemic in recent decades, and presently affects more than 90 million Americans and hundreds of millions of people worldwide. Obesity can be debilitating on its own, but it also increases the risk of other major diseases including cancers, heart disease, diabetes and immunological disorders.

One molecule of interest for anti-obesity strategies is the signaling protein interleukin-33 (IL-33), which, in mice, acts on immune cells within fat tissues to dampen inflammation and curb obesity during overfeeding. IL-33 is thought to have the same effect on humans, in whom lower blood levels of IL-33 have been linked to higher body weight. The principal source of beneficial IL-33 in fat tissues has been a mystery, but the investigators, in their study published May 3 in Science Immunology, identified that source as a population of immature, fat-resident cells called adipose stem and progenitor cells. To read more, click here.


Inaugural Society for Mucosal Immunology Trainee Symposium for Local Chapter NYC hosted by the JRI

The Jill Roberts Institute hosted the Inaugural Society for Mucosal Immunology Symposium for Local Chapter NYC, organized by Drs. Iliyan Iliev and Gregory Sonnenberg. The symposium was sponsored by the Society for Mucosal Immunology. The event was filled to capacity and attendees listened to presentations from junior scientists, representing local New York City institutions working in Mucosal Immunology, including Columbia University, the Icahn School of Medicine at Mt. Sinai, Memorial Sloan Kettering Cancer Center, The Rockefeller University, Rutgers University, the Skirball Institute at New York University, and Weill Cornell Medicine. Drs. Iliev and Sonnenberg were pleased to include Keynote Speakers Dr. Miriam Merad from Icahn School of Medicine at Mt. Sinai and Dr. Dan Littman from the Skirball Institute at New York University on the event program to round out the strong presentations.  It provided a valuable opportunity to the junior scientists to present their research and to speak to a large audience. Most importantly, it provided an invaluable opportunity to develop connections and future fruitful collaborations among NYC-based institutions to further advance scientific discovery in the field of mucosal immunology. We are grateful for the financial support of the Society for Mucosal Immunology, The Office of the Dean at WCM and the JRI.

 


New York Academy of Science Awards Prize to JRI’s Dr. Xin Li

Photo: Dr. Bart Lambrecht (Left) and Dr. Xin Li (right) attending the New York Academy of Sciences "Severe Asthma, Inflammation, and Lung Repair” Conference

The Jill Roberts Institute is pleased to announce that Dr. Xin Li, a Postdoctoral Associate in the Iliev Lab, has been awarded the Outstanding Presentation Prize for his presentation, Sensing Fungal Dysbiosis by Gut-Resident CX3CR1+ Mononuclear Phagocytes Aggravates Allergic Airway Disease from the New York Academy of Sciences and F1000 (Faculty 1000). The award was presented during the “Severe Asthma, Inflammation, and Lung Repair” Conference held on Friday, April 26, 2019. The director of the Jill Roberts Institute, Dr. David Artis, also presented his talk, Regulation of Chronic Inflammation, at the event, details of which can be found here: https://www.nyas.org/events/2019/severe-asthma-novel-concepts-therapeutics/. This event included outstanding immunologists that travel from around the world to New York City. One of the highlights of the event was the closing Keynote Address, Charcot-Leyden Protein Crystals: From Marker of Death to a Drug Target in Asthma, presented by Dr. Bart N. Lambrecht, who is a key leader in the field of asthma and lung research working at Ghent University. 


Researchers Discover New Pathway Regulating Intestinal Health that is Impaired in Children with IBD

Image Credit: A color enhanced image of the healthy small intestine where immune cells and epithelial cells are highlighted in green and red. Image credit: Sonnenberg Lab

Production of an essential protein for maintaining a healthy immune response in the intestine called interleukin-2 (IL-2) depends on immune cells known as innate lymphoid cells (ILCs), according to a study by Weill Cornell Medicine researchers. The study, published April 3 in Nature, is the first to identify these cells and the factors that influence them as potential new targets for treating chronic gut inflammation associated with inflammatory bowel disease or food allergies.

“We have understood for quite a while that IL-2 is important for maintaining a healthy immune response in the gut,” said senior author Dr. Gregory Sonnenberg, an associate professor of microbiology and immunology in medicine in the Division of Gastroenterology and Hepatology and a member of the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine. “Dramatic inflammation occurs when humans or mice are missing IL-2, but the specific cells that make it and the regulatory pathways controlling its production in the intestine were previously unknown.” To continue reading, click here.


CURE For IBD presents donation in continuing partnership with Jill Roberts Institute

Pictured in above image (L to R): Ron Kazel, Joe Lepler, Lina Krivyan, Drs. Ellen Scherl and David Artis, Jill Roberts, Patti Kaufman, Dr. Tom Haverty, Kyla Reicin

Since 2017, the Jill Roberts Institute for Research in Inflammatory Bowel Disease (IBD) and its Director, Dr. David Artis, have partnered with Chris Pedicone, Founder and President of CURE for IBD for a fruitful collaboration between laboratory research and dedicated fundraising efforts to find a cure for inflammatory bowel disease. CURE for IBD is a volunteer non-profit organization devoted solely to funding IBD research that seeks new treatments and cures for family, friends, and others living with IBD. On February 4, 2019, the CURE for IBD team, including Ron Kazel, Joe Lepler, Lina Krivyan, Patti Kaufman, Dr. Tom Haverty and Kyla Reicin, visited the Jill Roberts Institute for discussion and a tour of the laboratory facilities. At the close of their visit, CURE for IBD graciously presented the Jill Roberts Institute with a check for $75,000 to support IBD research efforts. Dr. Artis and members of the Jill Roberts Institute extend their gratitude to CURE for IBD and celebrate this ongoing partnership that supports current and future IBD research efforts.


Researchers Create the First Anatomical Map of Innate Lymphoid Cells in Healthy Human Tissues

Image credit: This heat map represents the low (blue) and high (red) gene expression of innate lyphoid cells in the body. Credit: Dr. Laurel Monticelli

Researchers have long known that dysfunction in the body’s innate immune system breaks the first line of defense against invading pathogens, enabling diseases to flourish unchecked. However, scientists’ ability to enhance the protective features of the innate immune system has been hampered by a lack of information about what a ‘healthy’ innate immune system looks like in different sites throughout the human body.

Now, in findings published Feb. 12 in Immunity, Weill Cornell Medicine investigators have been the first to generate an anatomical ‘map’ detailing the distribution of innate lymphoid cells in tissues from previously healthy humans. By establishing a baseline of immune activity, this study provides important insights into how the healthy immune system functions in an organ-specific way. This knowledge can be used to aid scientists in developing more effective treatments for a range of immunological diseases including infection, autoimmunity, and cancer. To read more, click here.


Researchers Identify Critical Role for Protein in Colon Inflammation

A protein induced by gut microbes is vital in healing colons that have become inflamed due to a short-term form of colitis, Weill Cornell Medicine researchers discovered in a new study. However, they also found that this molecule, called TNF-like ligand 1A (TL1A) contributes to the sustained inflammation characterized by chronic inflammatory bowel disease (IBD).

In a study published Dec. 11 in Immunity, Dr. Randy Longman, an assistant professor of medicine in the Division of Gastroenterology and Hepatology and a researcher in the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine, and his colleagues investigated colitis in mice and humans to better understand how immune cells communicate to help heal the inner-most layer of the intestinal tract, called the mucosal barrier. Developing a better understanding of the molecular factors that contribute to IBD may one day help clinicians more accurately diagnose and treat patients, Dr. Longman said. About 1.6 million people in the United States have IBD, 907,000 of whom have ulcerative colitis. To read more, click here.


Daedalus Fund Supports Eight Investigators

Photo credit: Dr. Augustine M.K. Choi, the Stephen and Suzanne Weiss Dean of Weill Cornell Medicine (second from left), and Larry Schlossman, managing director of BioPharma Alliances and Research Collaborations at Weill Cornell Medicine (first from left), join the winners of the Daedalus Fund for Innovation awards. From third from left: Dr. Shahin Rafii, Dr. Matthew Greenblatt, Dr. Lew Cantley, Dr. Julie Blander, Dr. Juan Cubillos-Ruiz, Dr. Peter Goldstein, Dr. Barbara Hempstead and Dr. Steven Lipkin.

Eight Weill Cornell Medicine faculty members have been selected for the fifth round of the Daedalus Fund for Innovation awards, a pioneering institutional program that helps advance promising applied and translational research projects and emerging technologies that have commercial potential. Awardees are chosen twice annually and are eligible for two levels of funding: $100,000 and $300,000 (the latter, subject to the satisfaction of certain specified pre-defined milestones).

The researchers — Drs. Julie Blander, Lew Cantley, Juan Cubillos-Ruiz, Peter Goldstein, Matthew Greenblatt, Barbara Hempstead, Steven Lipkin and Shahin Rafii — have each won a Daedalus award to fund proof-of-concept studies that will enhance the data package, thereby helping to upgrade their technologies and translate their early-stage discoveries into new therapeutic modalities and hopefully more effective treatments for patients. To read more, click here.


Sensing of Fungi by Gut Immune Cells Can Contribute to Airway Allergic Diseases

Common drug treatments that lead to changes in gut fungi can persistently exacerbate allergic airway diseases such as asthma, according to a study by Weill Cornell Medicine researchers.

The study, published online Nov. 29 in Cell Host & Microbe, suggests that the enormous modern prevalence of allergic airway diseases may be attributable in part to the widespread use of antimicrobials, including antifungals and other therapies that disrupt the normal balance between bacterial and fungal species in the gut.

“We were able to identify gut-resident immune cells that sense fungal community imbalance in the intestines and transmit these immune signals to the lung contributing to aggravated allergy,” said senior study author Dr. Iliyan D. Iliev, an assistant professor of immunology in medicine in the Division of Gastroenterology and Hepatology and a researcher in the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine. To read more....


Gift establishes Friedman Center for Nutrition and Inflammation

With a $7.5 million gift from the Friedman Family Foundation, endowed by Stephen and Vice Chair Overseer Barbara Friedman, Weill Cornell Medicine has established an innovative cross-campus center dedicated to improving human health through research in the complex relationship between nutrition, inflammation and the development of disease.

The Friedman Center for Nutrition and Inflammation will create new programs across Weill Cornell Medicine and Cornell’s Ithaca campus, harnessing key resources to study the interaction between diet, the immune system and the microbiome – the genetic material generated by the viruses, bacteria, fungi and parasites that live in or on the human body.

The two Cornell campuses are working together to engage other donors to match the support provided by the Friedmans and the Friedman Family Foundation with the vision of a $15 million initiative that will foster groundbreaking research and provide state-of-the-art education in nutrition, inflammation and the microbiome for medical and graduate students and clinicians.

The Friedman Center will be directed by Dr. David Artis, a world leader in immunology, inflammation and microbiome research. He is director of the Jill Roberts Institute for Research in Inflammatory Bowel Disease and the Michael Kors Professor in Immunology at Weill Cornell Medicine.

Researchers at the center will work to develop treatments and preventive strategies for illnesses including cancer, arthritis, Alzheimer’s disease, diabetes and inflammatory bowel disease – virtually every disease area represented in the Belfer Research Building, says Dr. Artis. To read more, click here.


New Faculty Recruit to the Jill Roberts Institute Will Explore How the Human Microbiota Regulates Health and Disease

Dr. Chun-Jun Guo is a newly appointed faculty member to the Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Department of Medicine at Weill Cornell Medicine. His lab is located on the 7th floor of Belfer Research Building and his research program focuses on studying the molecular mechanisms behind host-microbe interaction in the context of health and disease.

Before joining JRI-WCM, Dr. Guo was a postdoctoral scholar at Professor Michael Fischbach’s lab at Stanford working on the small molecules from the bacteria living in the human intestine, commonly known as ‘the human gut microbiota’. These molecules are highly abundant, circulatory, and few of them are well-known ligands for host receptors. However, the biology of the majority of them still remains elusive. Dr. Guo developed the first CRISPR-Cas9-based system in a gut commensal Clostridium sporogenes that is previously challenging to be genetically modified. By mutating the biosynthetic genes for a metabolite and using mouse models, Dr. Guo is able to toggle on/off the production of these abundant microbiome-derived small molecules in the host and use this tool to investigate their effects on host biology and IBD progression. To continue reading, click here...


2018 NYC IBD Day Held at New York University Langone Health

On September 12, 2018, the 4th Annual New York City IBD Research Day was hosted by New York University Langone Health in the Farkas Auditorium. This yearly symposium is a collaborative effort of four institutions: The Jill Roberts Institute at Weill Cornell Medicine, The Immunology Institute of the Icahn School of Medicine at Mount Sinai, The Center for Basic and Translational Research on Disorders of the Digestive System at The Rockefeller University and The Skirball Institute and the Departments of Medicine and Surgery at New York University Langone Health. The big announcement this year was that Columbia University will join this group of institutions, hosting the 2019 NYC IBD Day. In honor of the late Lloyd F. Mayer, MD, there is a Mayer Prize given yearly. Dr. Sergio Lira presented the Mayer Prize to his friend and colleague, Dr. Dan Littman. Throughout the course of the day, the attendees listened to ten presenters, who had traveled from around the globe for this event, engaging in lively Q & A conversations afterwards. This year, Irina Leonardi, a Postdoctoral Associate from the Jill Roberts Institute, was invited to be a speaker in the highly-regarded program. She presented a seminar entitled, “Immune Recognition of the Intestinal Mycobiota.” Generous sponsorship from The Helmsley Charitable Trust, the NY Crohn’s Foundation, the Kenneth Rainin Foundation, Cure for IBD, Pfizer, Boehringer Ingelheim, Regeneron, and Janssen made the enriching day possible.


Identifying pathways that control the location and function of immune cells in the intestine

Group 3 innate cells (red staining with green staining in the center) are found in between B cell follicles (grey staining) where immune responses take place in gut-associated lymph nodes. Picture courtesy of Dr. David Withers.

The intestinal mucosal barrier surface is constantly exposed to various stimuli such as food antigens, beneficial microbes, and infectious pathogens. Immune cells in the intestine and associated lymphoid tissues play a critical role in maintaining barrier function and intestinal homeostasis.

A new study by Dr. David Artis and his colleagues at Weill Cornell Medicine, identifies that the accumulation and function of group 3 innate lymphoid cells, a key immune cell population that limits bacterial infections in the intestine, are regulated by G protein-coupled receptor 183 (GPR183) and its ligand oxysterol produced by stromal cells. The study is co-authored by multiple investigators including Dr. Gregory F. Sonnenberg (Weill Cornell Medicine) and Dr. David Withers (University of Birmingham) and was published on June 26, 2018 in Cell Reports.

“Group 3 innate lymphoid cells are enriched in mucosal barrier surfaces and lymphoid tissues, and are a key immune cell in maintaining intestinal health against bacterial infections,” said Dr. Artis, director of the Jill Roberts Institute for Research in Inflammatory Bowel Disease and the Michael Kors Professor of Immunology at Weill Cornell Medicine. “However, the molecular mechanisms that control how group 3 innate lymphoid cells are distributed in the intestine and lymphoid tissues and how their functions are controlled during bacterial infection are not fully understood.”

For their study, Dr. Artis and his colleagues focused on a G protein-coupled receptor 183 (GPR183, also known as EBI2). GPR183 is highly expressed on lymphocytes in spleen and lymph nodes and controls cell migration to achieve efficient antibody responses and CD4+ T cell responses. Dr. Artis and his team found that group 3 innate lymphoid cells, not only in gut-draining lymph nodes but also in the intestine, highly expressed GPR183 that controls the distribution of group 3 innate lymphoid cells in these tissues. Furthermore, GPR183 ligand, 7α,25-dihydroxycholesterol was produced by gut stromal cells, supporting a role for these structural cells in controlling the location and functional potential of group 3 innate lymphoid cells.

To examine the role of GPR183 and its ligand, Dr. Artis and his team employed mice that lack the receptor and the ligand-producing enzyme CH25H and found disorganized accumulation of ILC3s in the gut-draining lymph nodes and reduced ILC3 accumulation in the intestine in the absence of GPR183 or its ligand. “Considering the regulation of lymphocytes by ILC3s in the lymphoid organs and the importance of immune cell localization in these organs, it is important to know how ILC3 localization is controlled in the lymph nodes. And our findings may provide new targets to control immune responses in the lymphoid organs,” said Dr. Coco Chu, a postdoctoral associate in Dr. Artis’ laboratory and a co-first author of the study.

“We then wanted to know if this GPR183 is essential for a protection against gastrointestinal pathogens,” said Dr. Saya Moriyama, a postdoctoral associate in Dr. Artis’ laboratory and another co-first author of the study. To examine this, Dr. Artis and his colleagues used Citrobacter rodentium infection, which is a gastrointestinal pathogen of mice that has several pathogenic similarities with clinically important human gastrointestinal pathogens. “And we found that GPR183 promotes accumulation of cytokine-producing group 3 innate lymphoid cells in the gut and is required for protection against this infection.,” she added.

GPR183 plays important roles in regulating the distribution and function of ILC3s in both lymphoid and non-lymphoid tissue so GPR183 and its oxysterol ligand-producing pathway could be potential therapeutic targets for controlling and regulating ILC3 functions in multiple infectious and inflammatory diseases.

This study was supported by grants from the National Institutes of Health (DP5OD012116, AI123368, DK110262, AI095608, AI074878, AI083480, AI095466, AI095608, AI102942, AI097333 and AI106697), the German Research Foundation (KL 2963/1-1), the Novo Nordic Foundation (14052), the Jill Roberts Institute, the Wellcome Trust (Senior Research Fellowship 110199/Z/15/Z), Cure for IBD, the Crohn’s and Colitis Foundation of America, the Searle Scholars Program, an American Asthma Foundation Scholar Award, the Burroughs Wellcome Fund. Dr. Moriyama is also the Japanese Society for the Promotion of Science Overseas Research Fellow.


Weill Cornell Medicine Opens New Microbiome Core

The Jill Roberts Institute for Research in Inflammatory Bowel Disease is now home to Weill Cornell Medicine’s new Microbiome Core, https://www.microbiome.weill.cornell.edu/,which officially opens June 1. The core’s mission is to provide researchers with the technological platforms required to perform microbiome sequencing and analysis.

A microbiome is the aggregate of microorganisms living in an environment and the human microbiome consists of microorganisms that live in the human body.

“There’s a major biomedical revolution right now in understanding how the microbiome contributes to disease, and we are excited to be a part of that,” said Dr. Randy Longman, an assistant professor of medicine and a gastroenterologist at the Jill Roberts Center for Inflammatory Bowel Disease. “Now scientists are researching how the microbiome plays a role in normal development, the function of the immune system, metabolism, and the susceptibility to diseases including allergies, arthritis, cancer, inflammatory bowel disease and more.” To continue reading...


Modified Inactivated Vaccine May Produce Immune Response as Effective as Live Vaccine

Vaccines containing inactivated versions of disease-causing germs are traditionally not as effective as live vaccines made with weakened pathogens. But new research from Weill Cornell Medicine scientists reveals how a molecule found in live vaccines produces a robust immune response, and adding it to an inactivated vaccine can create the same strong results.

These insights may provide a blueprint for engineering more potent inactivated or “dead” vaccines that can deliver strong immunity while overcoming concerns about the health risks of live vaccines.

“There has been a reluctance in the general population to get vaccinated, but vaccines are the single most effective medical intervention proven to prevent disease,” said senior author Dr. Julie Magarian Blander, a senior faculty member in the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine, who was recruited as a professor of immunology in medicine. “We have known that live vaccines provide better protection, often for life, in one dose, compared to dead vaccines that frequently require multiple doses or boosters over time.” To continue reading...


Nervous System Puts the Brakes on Inflammation

Mucus production (red) in the lung under inflammatory conditions. Picture courtesy of Dr Saya Moriyama.

Cells in the nervous system can “put the brakes” on the immune response to infections in the gut and lungs to prevent excessive inflammation, according to research by Weill Cornell Medicine scientists. This insight may one day lead to new ways to treat diseases caused by unchecked inflammation, such as asthma and inflammatory bowel disease.   

The study, published March 1 in Science, provides some clues about what might be going wrong in these diseases, which have become more common in industrialized countries, and in helminth infections, which are still a major public health problem in less-industrialized countries. It also may explain how some existing treatments for diseases like asthma work and point to new treatment strategies.

“There is a crosstalk between the nervous system and the immune system, and that plays an important role in regulating acute and chronic inflammation,” said Dr. David Artis, director of the Jill Roberts Institute for Research in Inflammatory Bowel Disease and the Michael Kors Professor of Immunology at Weill Cornell Medicine. “Those two organ systems are closely interacting and play an important role in human health and disease.” To continue reading...


Scientists Identify Immune Cells That Keep Gut Fungi Under Control

Photo above shows opportunistic fungus called candida albicans (red) engulfed by CX3CR1+ phagocytes (green) in the gut villi (blue). Photo credit: Dr. Iliyan Iliev and Dr. Irina Leonardi.

Immune cells that process food and bacterial antigens in the intestines control the intestinal population of fungi, according to a new study from Weill Cornell Medicine scientists. Defects in the fungus-fighting abilities of these cells may contribute to some cases of Crohn’s disease and other forms of inflammatory bowel disease (IBD).

The findings, published Jan. 11 in Science, illuminate a strong connection between fungi, immunity and intestinal inflammation and suggest a new, targeted treatment strategy for IBD.

“After discovering that fungi might be involved in the pathology of IBD, one of the big questions in the field has been how to identify patients who would benefit from antifungal co-therapy, and our finding suggests a way to do that,” said senior author Dr. Iliyan Iliev, an assistant professor of microbiology and immunology in medicine at Weill Cornell Medicine and a scientist at the Jill Roberts Institute for Research in Inflammatory Bowel Disease. To continue reading...


The Jill Roberts Institute plays starring role in the treatment of a young actress living with Crohn's Disease

When Analise Scarpaci was 10-years-old, she dreamed of singing and dancing on famed Broadway stages. So when she was diagnosed with a form of inflammatory bowel disease called Crohn’s disease, she wasn’t going to let that obstacle stand in her way. Thanks to her doctors at Weill Cornell Medicine and NewYork-Presbyterian, Scarpaci, now 18 and a Broadway star, is able to manage her disease and contribute to researchers’ understanding of the genetic and immunological underpinnings of IBD—all the while pursuing what she loves.


CURE For IBD presents donation to Jill Roberts Institute for research funding

Pictured in above image (L to R): Ms. Patti Kaufman, Dr. Robbyn Sockolow, Dr. David Artis, Dr. David Cohen, Mr. Chris Pedicone, and Ms. Lina Krivyan

On November 15, 2017, the Jill Roberts Institute for Research in Inflammatory Bowel Disease (IBD) and its Director, Dr. David Artis, welcomed Chris Pedicone, Founder and President of CURE for IBD for a visit and tour of the IBD research facilities at Weill Cornell Medicine. Joining the visit were Patti Kaufman, a Trustee and Fundraiser and Lina Krivyan, also a Fundraiser at CURE for IBD. CURE for IBD is a volunteer non-profit organization devoted solely to fund IBD research in order to find new treatments and cures for family, friends, and others living with IBD. This notable moment would not have been possible without Jill Roberts, a long-term supporter of IBD research and patient care at Weill Cornell Medicine. CURE for IBD presented the Jill Roberts Institute with a check for $35,000 to support IBD research efforts. Dr Artis and members of the Jill Roberts Institute extended their sincere thanks to CURE for IBD and are delighted to partner with CURE for IBD to support ongoing and future IBD research efforts at Weill Cornell Medicine. 


NYC IBD Research Day 2017

On November 2, 2017, the 3rd Annual New York City IBD Research Day was hosted by The Rockefeller University on their campus. The symposium is a yearly event coming to fruition through the collaboration of three institutions: The Jill Roberts Institute at Weill Cornell Medicine, The Immunology Institute of the Icahn School of Medicine at Mount Sinai, and The Center for Basic and Translational Research on Disorders of the Digestive System at The Rockefeller University. Dr. Bana Jabri graciously accepted the Lloyd D. Mayer, MD Award presented by her friend and colleague, Dr. Sergio Lira. The attendees listened to ten presenters, who had traveled from around the globe for this event, engaging in lively Q & A conversations afterwards. Generous sponsorship from The Helmsley Charitable Trust, the NY Crohn’s Foundation, the Kenneth Rainin Foundation, Pfizer, and Boehringer Ingelheim made the enriching day possible.


A Cellular Tango: Immune and Nerve Cells Work Together to Fight Gut Infections

Nerve cells in the gut play a crucial role in the body’s ability to marshal an immune response to infection, according to a new study from Weill Cornell Medicine scientists.

The study, published Sept. 6 in Nature, shows that the immune system and nervous system have co-evolved to respond to infectious threats. This means that scientists looking for ways to treat diseases like inflammatory bowel disease or asthma that involve an excessive immune system response may also have to address the nervous system’s role. 

“The immune system and neuronal system don’t act independently,” said senior author Dr. David Artis, director of the Jill Roberts Institute for Research in Inflammatory Bowel Disease and the Michael Kors Professor of Immunology at Weill Cornell Medicine. “They are working together.”

Continue reading...


Dr. Gregory Sonnenberg Wins Inaugural Award from the Society for Mucosal Immunology

Dr. Gregory Sonnenberg, an assistant professor of microbiology and immunology at Weill Cornell Medicine, has received the newly established Young Investigator Award from the Society for Mucosal Immunology.

The award honors investigators within 15 years of their postdoctoral training who have made significant contributions to the field of mucosal immunology, which is the study of immune responses that occur in the intestines, lungs and urogenital tract.

Dr. Sonnenberg accepted his award at the 18th International Congress of Mucosal of Immunology on July 19 in Washington, D.C. The award carries a cash prize and additional funds to support Dr. Sonnenberg’s laboratory.

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Research Uncovers Bacteria Linking Crohn’s Disease to Arthritis

Patients with Crohn’s disease, a type of inflammatory bowel disease (IBD) that causes abdominal pain and diarrhea, can also experience joint pain. In Crohn’s disease, which affects about 800,000 Americans, the immune system can attack not only the bowels, but the musculoskeletal system as well, leading to spondyloarthritis, a painful condition that affects the spine and joints. Now new research, published Feb. 8 in Science Translational Medicine, helps explain the connection between these seemingly unrelated symptoms, and could help physicians identify Crohn’s disease patients who are more likely to develop spondyloarthritis, enabling them to prescribe more effective therapies for both conditions.

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Cell Death in Gut Implicated in IBD

The natural lifecycle of cells that line the intestine is critical to preserving stable conditions in the gut, according to new research led by a Weill Cornell Medicine investigator. The findings may lead to the development of new therapies to alleviate inflammatory bowel disease (IBD) and other chronic inflammatory illnesses.

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Kenneth Rainin Foundation Awards $750,000 for Collaborative Inflammatory Bowel Disease Research Projects

OAKLAND, Calif., Feb. 14, 2017 /PRNewswire-USNewswire/ -- The Kenneth Rainin Foundation announced today that it has awarded $750,000 for Inflammatory Bowel Disease (IBD) research through its Synergy Award program. The Rainin Foundation funds scientific projects that have the potential to yield transformative discoveries and major insights into predicting and preventing IBD.

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Investigator Wins Award to Continue Study of Fungi in Inflammatory Bowel Disease

Dr. Iliyan Iliev, an assistant professor of immunology in medicine at Weill Cornell Medicine, has been awarded a one-year, $100,000 grant from the Kenneth Rainin Foundation to study the behavior of fungi in the immune system when patients with inflammatory bowel disease are administered a form of immunotherapy.  

Continue to read...


NYC IBD Research Day 2016

New York City IBD Research Day, on Nov 7, 2016, was a success.  Over 200 attendees enjoyed presentations on a variety of research presented by a multitude of lecturers from around the globe. The symposium was a one day event hosted by the Jill Roberts Institute at the Weill Cornell Medicine Belfer Research Building, in collaboration with the Immunology Institute of the Icahn School of Medicine at Mount Sinai, and the Center for Basic and Translational Research on Disorders of the Digestive System at The Rockefeller University. Dr. Richard Blumberg of Harvard Medical School was presented with the Lloyd F. Mayer, MD award.


The Fungus Among Us

NEW YORK (July 25, 2016) - By now, most of us have made peace with the fact that we are host to a complicated extended family of bacteria whose trillion-plus members give us vitamins, help us digest food, protect us from pathogens, and only rarely turn virulent on us. But what about the fungus among us?

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Disruption of Intestinal Fungi Leads to Increased Severity of Inflammatory Disease

Fungi that live in a healthy gut may be as important for good health as beneficial intestinal bacteria, according to new research conducted at Weill Cornell Medicine.

Scientists have known for quite some time that the so-called "good" gut bacteria in the intestines, known as commensal bacteria, are a key component of a healthy body. These bacteria are critical for proper digestive and immune system function. Recent discoveries, however, have indicated that other microbes, such as fungi and viruses, may also play a part in how the body handles inflammation.

Continue reading at: http://weill.cornell.edu/news/news/2016/06/disruption-of-intestinal-fung...


An Off-Switch for Allergy: Starving the Immune System Prevents Allergic Inflammation in the Lung

NEW YORK (April 4, 2016) — Starving immune cells of key nutrients stymies their ability to launch an allergic response, according to new research from a multi-institutional collaboration led by Weill Cornell Medicine investigators. The findings illuminate how nutrients help drive tissue inflammation caused by the immune system — an insight that could lead to new treatments for a wide range of inflammatory conditions from hay fever and food allergies to asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF).

Continue to read at: http://weill.cornell.edu/news/news/2016/04/an-off-switch-for-allergy-sta...


Bacteria in Immune Cells May Protect Against Chronic Inflammation

NEW YORK (March 15, 2016) — A population of bacteria inhabits human and mouse immune cells and appears to protect the body from inflammation and illness, Weill Cornell Medicine scientists discovered in a new study. The findings challenge conventional wisdom about the relationship between bacteria and the human body — and about how the microbes influence health and disease. The study, published March 15 in Immunity, focused on "good" or "commensal" bacteria that live in the human intestine and are essential for digestion and proper immune function.

Continue reading at: http://weill.cornell.edu/news/news/2016/03/bacteria-in-immune-cells-may-...


Innovative Therapeutic Approach Shows Promise in Treating Inflammatory Bowel Disease

NEW YORK (February 16, 2016) — An investigative therapy given to mice blocks the overactive immune responses that are a hallmark of inflammatory bowel disease without impairing the body's ability to fight infection, an international research team led by Weill Cornell Medicine investigators finds in a new study. The preclinical discovery may lead to more effective treatment strategies for IBD.

Continue to read at: http://weill.cornell.edu/news/news/2016/02/hed-innovative-therapeutic-ap...


Restoring "Gut Health" in Patients with Inflammatory Bowel Disease May Be a Matter of Pushing Cells to Repair Our Tissues

NEW YORK (August 04, 2015) — New insight into how the intestines repair themselves after daily attacks from microbes and other environmental triggers could lead to innovative approaches to treating inflammatory bowel disease, according to new research by Weill Cornell Medical College investigators. The findings, published Aug. 4 in PNAS, reveal a mechanism that allows the single layer of cells that line the inside of the intestines, called the gut epithelium, to signal the immune system to repair tissue damage caused by the daily onslaught of microbes and other environmental factors that the body encounters. Because a defect in that repair system underlies Crohn's disease and ulcerative colitis, the two primary forms of IBD, restoring tissue-protective repair mechanisms could reduce the diseases' hallmarks, chronic inflammation and tissue damage.

Continue reading at: http://weill.cornell.edu/news/news/2015/08/restoring-gut-health-in-patie...


Weill Cornell Investigators Discover a New Pathway that Prevents Chronic Inflammation in the Gut

New York (April 23, 2015) — An international research team led by Weill Cornell Medical College investigators has discovered an answer to why the human immune system ignores roughly 100 trillion beneficial bacteria that populate the gastrointestinal tract. The findings, published April 23 in the journal Science, advance investigators' understanding of how humans maintain a healthy gastrointestinal tract, and may provoke new ways to treat inflammatory bowel disease — including Crohn's disease and ulcerative colitis — whose origins have been mysterious and treatment difficult.

Continue reading at: http://weill.cornell.edu/news/pr/2015/04/weill-cornell-investigators-dis...


Immune Cells in "White" Body Fat Limit Obesity, Researchers Say

In the Dec. 22 issue of Nature, a research team, led by investigators at Weill Cornell Medical College, has found that an immune cell type appears to help burn fat and prevent the development of obesity. The findings suggest new ways of possibly preventing or treating obesity and obesity-related diseases in humans, says the study's senior investigator, Dr. David Artis, an immunologist who leads the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell.

Continue reading at: http://weill.cornell.edu/news/news/2014/12/immune-cells-in-white-body-fa...


JRI Investigators Featured in Weill Cornell Medicine: Inside Medicine


Jill Roberts Institute for Research in Inflammatory Bowel Disease Leads the Field

NEW YORK (April 18, 2016) — A string of high-profile research studies underscores the early successes of the Jill Roberts Institute for Research in Inflammatory Bowel Disease, where scientists are assiduously investigating the root causes of the disease. Now, with the official opening of its permanent laboratories, the Weill Cornell Medicine institute is poised to lead the way in advancing research to improve patient care. Established nearly two years ago with a generous gift to Weill Cornell Medicine from longtime benefactor Jill Roberts, the institute uses a multidisciplinary approach to drive and then translate discoveries into new preventative and treatment strategies for IBD, a group of chronic inflammatory conditions of the intestine that affects an estimated 3.5 million people worldwide.

Continue reading at weill.cornell.edu


New Jill Roberts Institute for Research in Inflammatory Bowel Disease Established at Weill Cornell Medical College

NEW YORK — Weill Cornell Medical College announced today that through the generosity of longstanding benefactor Jill Roberts and the Jill Roberts Charitable Foundation it is establishing the Jill Roberts Institute for Research in Inflammatory Bowel Disease. Dr. David Artis, one of the world's leading immunologists, was recruited from the University of Pennsylvania School of Medicine to direct the institute, which is dedicated to understanding the molecular underpinnings of inflammatory bowel disease with the goal of translating basic research breakthroughs into the most advanced therapies for patients.

Continue reading at: http://weill.cornell.edu/news/pr/2014/06/new-jill-roberts-institute-for-research-in-inflammatory-bowel-disease-established-at-weill-cornell-m.html


Weill Cornell Medicine The Jill Roberts Institute for Research in Inflammatory Bowel Disease 413 E 69th Street, 7th Floor New York, NY 10021 Phone: (646) 962-6312