The Jill Roberts Institute for Research in Inflammatory Bowel Disease

Gregory Sonnenberg, Ph.D.

The Henry R. Erle, M.D.-Roberts Family Associate Professor of Medicine & Head of Basic Research in Gastroenterology & Hepatology

The focus and long-term research goals of the Sonnenberg Laboratory are to interrogate the mechanisms by which the mammalian immune system controls tissue homeostasis, physiology, immunity, inflammation, and cancer at mucosal barrier surfaces of the body. This is a considerable challenge given the enormous surface area of these sites, such as the gastrointestinal tract, which is home to an estimated 10 trillion microbes (termed the microbiota) and most of our body’s total immune system. While interactions between mammalian hosts and microbiota are normally beneficial, these interactions must be tightly regulated to prevent chronic inflammation. Studies in patient populations indicate that abnormal host immune responses to microbiota are causally-linked to the pathogenesis and progression of numerous chronic disorders, including inflammatory bowel disease (IBD), HIV/AIDS, viral hepatitis, cardiovascular disease, multiple sclerosis, Alzheimer’s diseases, autism, obesity, diabetes, and cancer. Further, these interactions can influence the success or failure of clinical therapies. Ongoing research in the Sonnenberg Laboratory aims to (1) interrogate the pathways that regulate normally beneficial host interactions with microbiota; (2) determine how these pathways become disrupted in multiple chronic human diseases; and (3) identify novel preventative, therapeutic or curative approaches to target the immune system and/or microbiota to benefit human health.

One specific focus is on pathways that regulate a state of health in the mammalian gastrointestinal tract. This is a considerable challenge as this organ system has an enormous surface area that is continuously exposed to dietary antigens, trillions of normally beneficial microbes (termed the microbiota), and frequent pathogens. Therefore, the intestinal immune system must be tolerant to innocuous stimuli, while providing protection from infections. This functional dichotomy could be why the intestine contains the largest and most sophisticated compartment of the mammalian immune system with numerous organized lymphoid structures and complex cellular networks. The Sonnenberg Laboratory has been at the forefront of interrogating novel pathways regulating immunity, inflammation, and tissue health in the mammalian intestine, with a particular focus on emerging families of innate lymphoid cells, dendritic cells, and distinct consortia of microbes.

Fundamental discoveries by the Sonnenberg Lab include: (i) defining novel pathways of immune regulation that are essential to protect the gastrointestinal tract from chronic inflammation; (ii) identifying key transcriptional and regulatory pathways shaping tissue protective lymphocytes; (iii) pioneering the innate lymphoid cell family and unique consortia of microbiota, and uncovering their roles in immunity, inflammation, and cancer; (iv) developing novel therapeutic strategies to drive tissue repair, boost therapeutic efficacy, or limit inflammation without compromising protective immunity; and (v) defining that antigen presenting and IL-2 producing ILC3s are necessary and sufficient to promote microbiota specific Tregs and tolerance in the gut. Recent developments also indicate the mucosal immune system and microbiota profoundly impact the development, progression, and therapeutic responsiveness of cancer. This is an emerging area in the lab that is focused on harnessing host-microbe interactions to combat cancer and improve immunotherapies. Recent research by the Lab provoked a paradigm shift in our understanding of how host-microbiota dialogues are disrupted in colon cancer and contribute to tumor progression or therapy resistance.

We have also recently launched a pioneering translational research effort involving clinical collaborators at Weill Cornell Medicine and other research institutions to examine primary human samples from both healthy individuals and defined patient populations. Our ongoing research will further interrogate mucosal immune responses and interactions with microbiota in healthy and diseased primary human tissue samples. We anticipate that these studies will allow us to directly translate our findings in mouse models to clinically relevant information.

Talented graduate students and postdoctoral researchers are encouraged to directly contact Dr. Sonnenberg to discuss potential rotation projects and open positions in the laboratory.

 

Education and Training

  • Ph.D., University of Pennsylvania 2011
  • B.S., State University of New York at Buffalo 2007

View Recent Publications

 

Grants awarded

Contact Us

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