Gregory Sonnenberg
Assistant Professor of Microbiology and Immunology in Medicine
The focus and long-term research goals of the are to interrogate the mechanisms that maintain a state of health in the human gastrointestinal tract. This is a considerable challenge given the enormous surface area of this organ in which a single layer of intestinal epithelial cells segregates an estimated 100 trillion commensal bacteria from a significant portion of our bodies total immune system. While interactions between mammalian hosts and commensal bacteria are normally beneficial, it is becoming increasingly clear the dysregulated interactions can result in chronic inflammation. Further, emerging studies in patient populations indicate that abnormal host immune responses to commensal bacteria are causally-linked to the pathogenesis and progression of numerous chronic infectious, inflammatory and metabolic diseases, including inflammatory bowel disease (IBD), HIV/AIDS, viral hepatitis, cardiovascular disease, obesity, diabetes and cancer. Ongoing research in the Sonnenberg Laboratory aims to (1) interrogate the pathways that regulate normally beneficial host interactions with commensal bacteria, (2) determine how these pathways become disrupted in chronic human diseases, and (3) identify novel therapeutic targets to prevent or limit dysregulated host-commensal bacteria relationships in human disease.
Education and Training
- Ph.D., University of Pennsylvania 2011
- B.S., State University of New York at Buffalo 2007
Grants awarded
- Harnessing the Co-Evolution of Mammals and Microbes to Engineer Novel Vaccines awarded by Searle Scholars Program Principal Investigator 2016 -
- Immune Regulation of Intestinal Health and Disease awarded by National Institute of Allergy & Infectious Diseases Principal Investigator 2016 -
- Immune Regulation of Intestinal Health and Disease awarded by National Institute of Allergy & Infectious Diseases Principal Investigator 2015 -
- CCFA Genetics Initiative Pilot Feasibility Study: Xenophagy Defects in Patients With Monogenic Inflammatory Bowel Disease awarded by Crohn's & Colitis Foundation of America, Inc. Key Personnel 2015 -
- Regulation of Host-Commensal Relationships in Human Health and Disease awarded by National Institutes of Health, Office of the Director Principal Investigator 2014 -
- Human MAIT Cells in Airway Mucosal Immune Responses to Intracellular Infections: Pilot Project #1 Innate Lymphoid Cell Regulation of Adaptive Immunity and Intestinal Homeostasis awarded by National Institute of Allergy & Infectious Diseases Principal Investigator Subaward 2014 - 2015
Selected Publications
Fung T.C., Bessman N.J., Hepworth M.R., Kumar N., Shibata N., Kobuley D., Wang K., Ziegler C.G.K., Goc J., Shima T., Umesaki Y., Sartor R.B., Sullivan K.V., Lawley T.D., Kunisawa J., Kiyono H., Sonnenberg G.F. (2016) Lymphoid tissue-resident commensal bacteria promote members of the IL-10 cytokine family to establish mutualism. Immunity [PMCID: in progress].
Withers D.R., Hepworth M.R., Wang X., Mackley E.C., Halford E.E., Dutton E.E., Marriott C.L., Brucklacher-Waldert V., Veldhoen M., Kelsen J., Baldassano R.N., Sonnenberg G.F. (2016) Transient inhibition of ROR-γt therapeutically limits intestinal inflammation by reducing TH17 cells and preserving group 3 innate lymphoid cells. Nature Medicine [PMCID: in progress].
Hepworth M.R., Fung T.C., Masur S.H., Kelsen J.R., McConnell F.M., Dubrot J., Withers D.R., Hugues S., Farrar M.A., Reith W., Eberl G., Baldassano R.N., Laufer T.M., Elson C.O., Sonnenberg G.F. (2015) Group 3 Innate lymphoid cells mediated intestinal selection of commensal bacteria-specific CD4+ T cells. Science [PMCID: in progress].
Goc J., Hepworth M.R., Sonnenberg G.F., (2015) Group 3 innate lymphoid cells: regulating host-commensal bacteria interactions in inflammation and cancer. International Immunology [PMCID: in progress].
Kelsen J.R., Dawany N., Moran C.J., Petersen B.S., Sarmady M., Sasson A., Pauly-Hubbard H., Martinez A., Maurer K., Soong J., Rappaport E., Franke A., Keller A., Winter H.S., Mamula P., Piccoli D., Artis D., Sonnenberg G.F., Daly M., Sullivan K.E., Baldassano R.N., Devoto M. (2015) Exome sequencing analysis reveals variants in primary immunodeficiency genes in patients with very early onset inflammatory bowel disease. Gastroenterology [PMCID: in progress].
Sonnenberg G.F., Artis D. (2015) Innate lymphoid cells in the initiation, regulation and resolution of inflammation Nature Medicine [PMCID: in progress].
Wagage S., Harms Pritchard G., Dawson L., Buza E.L., Sonnenberg G.F., Hunter C.A. (2015) The group 3 innate lymphoid cell defect in aryl hydrocarbon receptor deficient mice is associated with T cell hyperactivation during intestinal infection. PLoS One [PMCID:PMC4444139].
Kelsen J.R., Baldassano R.N., Artis D., Sonnenberg G.F. (2015) Maintaining intestinal health: the genetics and immunology of very early onset inflammatory bowel disease. Cellular and Molecular Gastroenterology and Hepatology [PMCID: in progress].
Mackley E.C., Houston S., Marriott C.L., Halford E.E., Lucas B., Carovic V., Filbey K.J., Maizels R.M., Hepworth M.R., Sonnenberg G.F., Miling S., Withers D.R. (2015) CCR7-dependent trafficking or RORg (+) ILCs creates a unique microenvironment within mucosal draining lymph nodes. Nature Communication. [PMC4354100].
Hepworth M.R., Sonnenberg G.F. (2014) Regulation of the adaptive immune system by innate lymphoid cells. Current Opinion in Immunology. Mar 1;27C:75-82 [PMC3979357].
Sonnenberg G.F. (2014). Regulation of intestinal health and disease by innate lymphoid cells. International Immunology. May 12. pii: dxu052 [PMC4142604].
Fung, T.C., Artis, D., Sonnenberg G.F. (2014) Anatomical localization of commensal bacteria in immune cell homeostasis and disease. Immunological Reviews. Jul;260(1):45-49 [PMC4216679].
Hepworth M.R., Monticelli L.A., Fung T.C., Ziegler C.G.K., Grunberg S., Sinha R., Mantegazza A.R., Ma H.L., Crawford A., Angelosanto J.M., Wherry E.J., Koni P.A., Bushman F.D., Elson C.O., Eberl G., Artis D., Sonnenberg G.F. (2013) Innate lymphoid cells regulate CD4+ T cell responses to intestinal commensal bacteria. Nature [PMC3699860].
Sonnenberg G.F., Mjosberg J., Spits H., Artis D. (2013) Snapshot: Innate lymphoid cells. Immunity [PMID24012419]
Sonnenberg G.F. and Artis D. (2012) Innate lymphoid cell interactions with the microbiota: implications for intestinal health and disease. Immunity. [PMC3495160].
Sonnenberg G.F., Monticelli L.A., Alenghat T., Fung T.C., Hutnick N.A., Kunisawa J., Shibata N., Grunberg S., Sinha R., Zahm A.M., Tardif M.R., Sathaliyawala T., Kubota M., Farber D.L., Collman R.G., Shaked A., Fouser L.A., Weiner D.B., Tessier P.A., Friedman J.R., Kiyono H., Bushman F.D., Chang K.M., Artis D. (2012) Innate lymphoid cells promote anatomical containment of lymphoid-resident commensal bacteria. Science [PMC3659421].
Monticelli L.A., Sonnenberg G.F., Abt M.C., Alenghat T., Ziegler C.G.K., Doering T.A., Angelosanto J.M., Laidlaw B.J., Yang C.Y., Sathaliyawala T., Kubota M., Tuner D., Diamond J.M., Goldrath A.W., Farber D.L., Collman R.G., Wherry E.J., Artis D. (2011) Innate lymphoid cells promote lung tissue homeostasis following acute influenza virus infection. Nature Immunology [PMC3320042].
Sonnenberg G.F., Fouser L.A., Artis, D. (2011) Border Patrol: regulation of immunity, inflammation and tissue homeostasis at barrier surfaces by IL-22. Nature Immunology. [PMID: 21502992].
Sonnenberg G.F., Monticelli L.A., Elloso M.M., Fouser L.A., Artis D. (2011) CD4+ lymphoid tissue-inducer cells promote innate immunity in the gut. Immunity 34:122-134. [PMC3035987].
Sonnenberg G.F., Nair M.G., Kirn T.J., Zaph C., Fouser L.A., Artis D. (2010) Pathological versus protective functions of IL-22 in airway inflammation are regulated by IL-17A. Journal of Experimental Medicine [PMC2882840].
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