The Sonnenberg Lab studies the pathways that regulate a state of health in the gastrointestinal tract. This is a considerable challenge as this organ 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 mucosal immune system must be tolerant to innocuous stimuli, while protecting from infections. This functional dichotomy is likely why the intestine contains the largest and most sophisticated compartment of the immune system with numerous organized lymphoid structures and complex cellular networks.
The Sonnenberg Laboratory has been at the forefront of research in this area, with a focus on emerging families of lymphocytes, antigen presenting cells (APCs), and consortia of microbes.
Our seminal contributions include: (i) in 2013 we discovered RORgt+ APCs and defined their essential role in immune tolerance; (ii) over the next decade, we expanded our understanding of a diverse RORgt+ APC family, defined how they are regulated and sense the environment, and identified key roles for RORgt+ APCs in allergy, autoimmunity, cancer, and associated immunotherapies; (iii) we established a paradigm that group 3 innate lymphoid cells (ILC3s) are genuine determinants of gut health and tissue physiology that are dysregulated in chronic diseases; and (iv) we identified novel checkpoints in the biology of cytokines, lymphocytes, APCs, and microbes that shape gut health and provide novel therapeutic opportunities.
Figure 1.
Group 3 innate lymphocytes (red and green) interacting with microbiota-specific regulatory T cells (blue, green and cyan) in lymphoid tissues.
Figure 2.
TNF-driven intestinal inflammation, where the gut epithelial cells (marked by EpCAM in green) exhibit substantial cell death (marked by cleaved caspase 3 in red)
Biography
Dr. Sonnenberg completed his doctoral research training at the University of Pennsylvania School of Medicine in 2011. In 2012 and with a NIH Director’s Award, he established the Sonnenberg Laboratory at the University of Pennsylvania. In 2014, Dr. Sonnenberg was recruited as an Assistant Professor to Weill Cornell Medicine, Cornell University. He was promoted to Associate Professor in 2018 and was appointed the Henry R. Erle, M.D.-Roberts Family Associate Professor of Medicine with tenure in 2022. In 2021, Dr. Sonnenberg became Head of Basic Research in the Gastroenterology & Hepatology at Weill Cornell Medicine and Deputy Editor-in-Chief at Mucosal Immunology, and in 2025 Associate Vice Chair for Research in Medicine.
Distinctions:
2016, Searle Scholars Award
2017, Society for Mucosal Immunology –Young Investigator Award (inaugural year)
2018 Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Disease
2019 Cancer Research Institute Lloyd J. Old STAR Award (inaugural year)
2020 International Cytokine & Interferon Society (ICIS)-Luminex John R. Kettman Award for Excellence in Interferon & Cytokine Research (inaugural year)
2023, American Association of Immunologists (AAI)-BD Biosciences Investigator Award
2023, NIH/NIAID MERIT Award (R37AI174468)
2026, Kenneth Rainin Foundation Innovator Award
Selected Publications:
Ahmed A, Joseph AM, Zhou J, Horn V, Uddin J, Lyu M, Goc J; JRI Live Cell Bank; Sockolow RE, Wing JB, Vivier E, Sakaguchi S, Sonnenberg GF. CTLA-4-expressing ILC3s restrain interleukin-23-mediated inflammation. Nature. 2024 Jun;630(8018):976-983. doi: 10.1038/s41586-024-07537-3. Epub 2024 Jun 12. PMID: 38867048.
Lyu M, Suzuki H, Kang L, Gaspal F, Zhou W, Goc J, Zhou L, Zhou J, Zhang W; JRI Live Cell Bank, Shen Z, Fox JG, Sockolow RE, Laufer TM, Fan Y, Eberl G, Withers DR, Sonnenberg GF. ILC3s select microbiota-specific regulatory T cells to establish tolerance in the gut. Nature. 2022 Sep 7. doi: 10.1038/s41586-022-05141-x. Epub ahead of print. PMID: 36071169.
Zhou W, Zhou L, Zhou J; JRI Live Cell Bank, Chu C, Zhang C, Sockolow RE, Eberl G, Sonnenberg GF. ZBTB46 defines and regulates ILC3s that protect the intestine. Nature. 2022 Jul 13. PMID: 35831503. *Highlighted in Nature Reviews Gastroenterology & Hepatology and Trends in Immunology.
Grigg JB, Shanmugavadivu A, Regen T, Parkhurst CN, Ahmed A, Joseph AM, Mazzucco M, Gronke K, Diefenbach A, Eberl G, Vartanian T, Waisman A, Sonnenberg GF. Antigen-presenting innate lymphoid cells orchestrate neuroinflammation. Nature. 2021 Dec;600(7890):707-712. doi: 10.1038/s41586-021-04136-4. Epub 2021 Dec 1. PMID: 34853467; PMCID: PMC8702489.
Goc J, Lv M, Bessman NJ, Flamar AL, Sahota S, Suzuki H, Teng F, Putzel GG; JRI Live Cell Bank, Eberl G, Withers DR, Arthur JC, Shah MA, Sonnenberg GF. Dysregulation of ILC3s unleashes progression and immunotherapy resistance in colon cancer. Cell. 2021 Sep 16;184(19):5015-5030.e16. doi: 10.1016/j.cell.2021.07.029. Epub 2021 Aug 17. PMID: 34407392; PMCID: PMC8454863.
