E. John Wherry

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

Winograd R, Byrne KT, Evans RA, Odorizzi PM, Meyer AR, Bajor DL, Clendenin C, Stanger BZ, Furth EE, Wherry EJ, Vonderheide RH.: Induction of T-cell Immunity Overcomes Complete Resistance to PD-1 and CTLA-4 Blockade and Improves Survival in Pancreatic Carcinoma. Cancer Immunology Research 3(4): 399-411, April 2015.

Schlie K, Westerback A, DeVorkin L, Hughson LR, Brandon JM, MacPherson S, Gadawski I, Townsend KN, Poon VI, Elrick MA, Côté HC, Abraham N, Wherry EJ, Mizushima N, Lum JJ: Survival of Effector CD8+ T Cells during Influenza Infection is Dependent on Autophagy. Journal of Immunology April 2015 Notes: Pub ahead of print.

Twyman-Saint Victor C, Rech AJ, Maity A, Rengan R, Pauken KE, Stelekati E, Benci JL, Xu B, Dada H, Odorizzi PM, Herati RS, Mansfield KD, Patsch D, Amaravadi RK, Schuchter LM, Ishwaran H, Mick R, Pryma DA, Xu X, Feldman MD, Gangadhar TC, Hahn SM, Wherry EJ, Vonderheide RH, Minn AJ.: Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature March 2015.

Gandhi SJ, Minn A, Vonderheide RH, Wherry EJ, Hahn SM, Maity A.: Awakening the immune system with radiation: Optimal dose and fractionation. Caner Letters March 2015.

Pauken KE, Wherry EJ.: Overcoming T cell exhaustion in infection and cancer. Trends Immunol March 2015.

Bengsch B and Wherry EJ: The importance of cooperation: partnerless NFAT induces T cell exhaustion. Immunity 42(2): 203-5, Feb 2015.

Kahan SM, Wherry EJ and Zajac AJ.: T cell exhaustion during persistent viral infections. Virology Jan 2015.

Penaloza-MacMaster P, Barber DL, Wherry EJ, Provine NM, Teigler JE, Parenteau L, Blackmore S, Borducchi EN, Larocca RA, Yates KB, Shen H, Haining WN, Sommerstein R, Pinschewer DD, Ahmed R, Barouch DH.: Vaccine-elicited CD4 T cells induce immunopathology after chronic LCMV infection. Science 347(6219): 278-82, Jan 2015.

Gaiha GD, McKim KJ, Woods M, Pertel T, Rohrbach J, Barteneva N, Chin CR, Liu D, Soghoian DZ, Cesa K, Wilton S, Waring MT, Chicoine A, Doering T, Wherry EJ, Kaufmann DE, Lichterfeld M, Brass AL, Walker BD.: Dysfunctional HIV-specific CD8+ T cell proliferation is associated with increased caspase-8 activity and mediated by necroptosis. Immunity 41(6): 1001-12, Dec 2014.

Pauken KE, Wherry EJ.: TIGIT and CD226: tipping the balance between costimulatory and coinhibitory molecules to augment the cancer immunotherapy toolkit. Cancer Cell 26(6): 785-7, Dec 2014.

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Last updated: 04/09/2015
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