E. John Wherry, PhD

faculty photo
Associate Professor of Microbiology
Department: Microbiology
Graduate Group Affiliations

Contact information
421 Curie Blvd
BRB II/III Room 354
Philadelphia, PA 19104
Office: 215-746-8141
Education:
BS (Science)
Pennsylvania State University, 1993.
PhD (Immunology)
Thomas Jefferson University, 2000.
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Description of Research Expertise

Research Interests
Memory CD8 T cell differentiation during acute and chronic infections.

Key words: Immunological memory, T cell memory, Chronic infection, T cell dysfunction, Memory T cell differentiation.

Research Summary


A major goal of the research in Dr. Wherry's laboratory is to understand the mechanisms of suboptimal CD8 T cell responses during chronic infections. Our previous work studying CD8 T cell responses during chronic viral infections has demonstrated that virus-specific CD8 T cells often lose effector functions and fail to acquire key memory T cell properties such as homeostatic proliferation (i.e. become exhausted). Using a variety of approaches including global gene expression profiling we are defining cellular pathways involved in this T cell exhaustion and normal memory T cell differentiation. Some of areas of considerable current interest for the lab include inhibitory receptors (e.g. PD-1, LAG-3), transcription factors and inflammatory pathways. T cell exhaustion is a common feature during many chronic infections and we are studying both viral and parasitic infections in mice and also will begin to extend our investigations to people infected with hepatitis C virus. In addition, we are examining how co-infection with two pathogens can impact T cell memory. Finally, in other studies in the lab we are investigating the mechanisms of T cell mediated protective immunity to influenza virus and how T cell memory changes with age.


Lab
Rotation Projects
1) Regulatory mechanisms during chronic viral infections
2) Role of inflammatory environment versus antigen in T cell exhaustion
3) Transcriptional regulation of T cell differentiation
4) Age-related changes in T cell responses
5) Molecular program of memory T cell self-renewal

Lab personnel
Mohammed Ali- Research Specialist
Bertram Bensch - Postdoctoral Fellow
Ramin Herati - Fellow
Sarah Henrickson - Fellow
Jonathan Johnnidis- Graduate Student
Makoto Kurachi - Postdoctoral Fellow
Pam Odorizzi - Graduate Student
Olesya Palko - Research Specialist
Kristen Pauken - Postdoctoral Fellow
Erietta Stelekati - Postdoctoral Fellow
Vesselin Tomov – Postdoctoral Fellow

Samantha Halter - Executive Asisstant

Selected Publications

Osborne LC, Monticelli LA, Nice TJ, Sutherland TE, Siracusa MC, Hepworth MR, Tomov VT, Kobuley D, Tran SV, Bittinger K, Bailey AG, Laughlin AL, Boucher J-L, Wherry EJ, Bushman FD, Allen JE, Virgin HW, and Artis D.: Coinfection. Virus-helminth coinfection reveals a microbiota-independent mechanism of immunomodulation. Science 345(6196): 578-82, August 2014.

Moon E.K., Wang L.C., Dolfi D.V., Wilson C.B., Ranganathan R., Sun J., Kapoor V., Scholler J., Pure E., Milone M.C., June C.H., Riley J., Wherry E.J., Albelda S.M.: Multifactorial T cell Hypofunction That is Reversible Can Limit the Efficacy of Chimeric Antibody Receptor-transduced Human T cells in Solid Tumors. Cancer Research 20(16): 4262-73, August 2014.

Turner D.L., Bickham K.L., Thome J.J., Kim C.Y., D'Ovidio F., Wherry E.J., Farber. D.L.: Lung niches for the generation and maintenance of tissue-resident memory T cells. Mucosal Immunol. 7(3): 501-10, May 2014.

Stelekati E., Shin H., Doering T.A., Dolfi D.V., Ziegler C.G., Beiting D.P., Dawson L., Liboon J., Wolski D., Ali M.A., Katsikis P.D., Shen H., Roos D.S., Haining W.N., Lauer G.M., Wherry E.J.: Bystander chronic infection negatively impacts development of CD8(+) T cell memory. Immunity 40(5): 801-13, May 2014.

Lee, J.E., Walsh, M.C., Hoehn, K.L., James, D.E., Wherry, E.J., Choi,Y.C.: Regulator of fatty acid metabolism, acetyl CoA carboxylase 1 (ACC1) controls T cell immunity. J. Immunol. 192(7): 3190-9, April 2014.

Schadler K.L., Crosby E.J., Zhou A.Y., Bhang D.H., Braunstein L., Baek K.H., Crawford D., Crawford A., Angelosanto J., Wherry E.J., Ryeom S.: Immunosurveillance by antiangiogenesis: tumor growth arrest by T cell-derived thrombospondin-1. Cancer Research 74(8): 2171-81, April 2014.

Barnett LG.., Simkins H.M., Barnett B.E., Korn L.L., Johnson A.L., Wherry E.J., Wu G.F. and Laufer T.M.: B cell antigen presentation in the initiation of follicular helper T cell and germinal center differentiation. J. Immunol. 192(8): 3607-17, April 2014.

Kurachi, M., Barnitz, R.A., Yosef, N, Ordorizzi, P.M., Dilorio, M.A., Lemieux, M.E., Yates, K.,Godec, J., Klatt, M.G., Regev, A., Wherry, E.J., Haining, W.N.: The transcription factor BATF operates as an essential differentiation checkpoint in early effector CD8+ T cells. Nat. Immunol. 15(4): 373-83, April 2014 Notes: Drs. Wherry and Haining are co-corresponding authors.

Lagor, W.R., Fields, D.W., Crawford, A., Abt, M.C., Artis, D., Wherry, E.J., Rader, D.J.: Genetic manipulation of the ApoF/Stat2 locus supports an important role for type 1 interferon signaling in atherosclerosis. Atherosclerosis 231(1): 234-41, March 2014.

Kroy D.C, Ciuffreda D., Cooperider J.H.,Tomilson M., Huack G.D., Anja K., Elias N., Freeman G.J., de Kruyf R.,Misdraji J., Kim A.Y., Lauer G.M.,Wherry E.J.: Liver environment and HCV replication affect human T-cell phenotype and expression of inhibitory receptors. Gastro 146(2): 550-61, Feb 2014.

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Last updated: 12/17/2014
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