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
- Identify underlying causes of IBD awarded by NIH, Principal Investigator 2022-2023.
- The American Association of Immunologist-AAI-BD Biosciences Investigator Award presented by The American Association of Immunologist (AAI), Principal Investigator 2022-2023
- Defining host-microbiota interactions during colorectal cancer and immune checkpoint blockade awarded by National Cancer Institute Principal Investigator 2020 - 2022
- Biopharma Agreement awarded by Boston Pharmaceuticals, Inc Principal Investigator 2020 - 2021
- New Proposal Created for Kayisha Brewster on 10-Jan-2020 1:19:21 PM awarded by EA Pharma Co., Ltd. Principal Investigator 2020 - 2020
- Defining host-microbe interactions in cancer and immunotherapy awarded by Cancer Research Institute, Inc. Principal Investigator 2019 - 2024
- Interleukin-2 regulation of mucosal inflammation awarded by National Institute of Allergy & Infectious Diseases Principal Investigator 2019 - 2024
- Defining a novel mechanism of mucosal healing awarded by National Institute of Allergy & Infectious Diseases Principal Investigator 2019 - 2024
- Tolerogenic and pathologic interactions between ILCs and T cells in autoimmunity awarded by National Institute of Allergy & Infectious Diseases Key Personnel 2019 - 2022
- IL-2-dependent regulation of intestinal health and inflammation awarded by Crohn''s & Colitis Foundation of America, Inc. Key Personnel 2019 - 2021
- Innate immune regulation of host-microbe interactions awarded by Burroughs Wellcome Fund Principal Investigator 2018 - 2023
- Modulating host-microbiota interactions to improve cancer immunotherapies awarded by Cancer Research Institute, Inc. Principal Investigator 2018 - 2021
- Interrogation of a Novel Immuno-Regulatory Pathway in Colitis-Associated Cancer awarded by Crohn''s & Colitis Foundation of America, Inc. Key Personnel 2017 -
- Immune Regulation of Intestinal Health and Disease awarded by National Institute of Allergy & Infectious Diseases Principal Investigator 2016 - 2021
- Harnessing the Co-Evolution of Mammals and Microbes to Engineer Novel Vaccines awarded by Searle Scholars Program Principal Investigator 2016 -
- Regulating Disparate Proinflammatory CD4+ T Cells in Asthma awarded by American Asthma Foundation Principal Investigator 2016 -
- Innate Immune Regulation of Airway Inflammation awarded by National Institute of Allergy & Infectious Diseases Co-Investigator 2016 - 2021