E. John Wherry, PhD

faculty photo
Richard and Barbara Schiffrin President's Distinguished Professor
Department: Microbiology
Graduate Group Affiliations

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

Research Interests
T cell exhaustion, T cell Memory.

Key words: T cell exhaustion, 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 T cell exhaustion during chronic infections and cancer. Our 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 (i.e. become exhausted). Using approaches including high dimensional flow cytometry, transcriptional and epigenetic profiling and in vivo models we are defining cellular pathways involved in T cell exhaustion and normal memory T cell differentiation. Some areas of considerable current interest for the lab include inhibitory receptors (e.g. PD-1, LAG-3), transcription factors and inflammatory pathways. Blockade of inhibitory receptors such as PD-1 (i.e. checkpoint blockade) is now a major therapeutic approach in human cancer. Ongoing studies are examining the mechanisms of these blockades in preclinical models as well as in humans and are investigating the next generation of immune targets to reverse T cell exhaustion. In addition to T cell exhaustion, the laboratory has major interests in the biology of human T follicular helper cells (TFH). Our studies are interrogating the pathways controlling optimal TFH responses following human vaccination. Finally, additional interests in the lab include intestinal novovirus infection, respiratory infections and co-infections.

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

Lab personnel
Sharon Adamski - Research Specialist
Mohammed Ali - Research Specialist
John Attanasio - Lab Tech
Bertram Bensch - Postdoctoral Fellow
Ramin Herati - Infectious Disease Fellow
Sarah Henrickson - Pediatrics Fellow
Alex Huang - Oncology Fellow
Jonathan Johnnidis- Graduate Student
Makoto Kurachi - Postdoctoral Fellow
Olesya Palko - Research Specialist
Felix Quagliarello- Lab Manager
Laura McLane - Graduate Student
Kristen Pauken - Postdoctoral Fellow
Ryan Staupe - Graduate Student
Erietta Stelekati - Postdoctoral Fellow
Vesselin Tomov – Postdoctoral Fellow
Laura Vella - Pediatrics Fellow

Samantha Halter - Executive Assistant

Selected Publications

Blackburn, S.D., Shin, H., Freeman, G.J., Wherry, E.J.: Selective expansion of a subset of exhausted CD8 T cells by αPD-L1 blockade. PNAS 105(39): 15016-21, Sep 2008.

Blackburn, S.D., Shin, H., Haining, W.N., Zou, T., Workman, C.J., Polley, A., Betts, M.R., Freeman, G.J., Vignali, D.A.A., Wherry, E.J. : Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nat. Immunol. 10(1): 29-37, Jan 2009.

Doering TA, Crawford A, Angelosanto JM, Paley MA, Wherry EJ: Defining the transcriptional networks of CD8+ T cell memory versus exhaustion. Immunity 37(6): 1130-44, 2009.

Paley MA, Kroy DC, Dolfi DV, Bikoff E, Robertson EJ, Lauer GM, Reiner SL and Wherry EJ: Key role for balancing progenitor and terminal subsets of exhausted T cells during chronic infection. Science 338(6111): 1220-5, 2012.

Crawford, A., Angelosanto, J.M., Doering, T.A., Kao, C., Wherry E.J.: Molecular and transcriptional basis of CD4+ T cell dysfunction during chronic infection. Immunity 40(2): 289-302, Feb 2014.

Kurachi M, Barnitz RA, Yosef N, Odorizzi PM, Dilorio MA, Lemieux ME, Yates K, Godec J, Klatt MG, Regev A, Wherry EJ and Haining WN.: BATF operates as an essential differentiation checkpoint in early effector CD8+ T cells. Nature Immunology 15(4): 373-83, 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.

Herati RS, Reuter MA, Dolfi DV, Mansfield KD, Aung H, Badwan OZ, Kurupati RK, Kannan S, Ertl H, Schmader KE, Betts MR, Canaday DH, Wherry EJ.: Circulating CXCR5+PD-1+ response predicts influenza vaccine antibody responses in young adults but not elderly adults. Journal of Immunology 193(7): 3528-37, Oct 2014.

Chang JT, Wherry EJ and Goldrath AW.: Molecular regulation of effector and memory T cell differentiation. Nature Immunology 15(12): 1104-15, DEC 2014.

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

Pauken KE, Wherry EJ.: Overcoming T cell exhaustion in infection and cancer. Trends Immunol 36(4): 265-76, April 2015.

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 520(7547): 373-7, April 2015.

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

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: 07/09/2015
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