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Cell and Molecular Biology Graduate Group


E. John Wherry

E. John Wherry
Assistant Professor
Immunology Program
The Wistar Institute

Microbiology, Virology, and Parasitology Program


Address

Office:
The Wistar Institute
3601 Spruce Street
Room 251
Philadelphia, PA 19104

Office Tel: 215-495-6825
Lab Tel: 215-495-6826
Fax: 215-495-6817
E-mail: jwherry@wistar.org

Education

Pennsylvania State University: BS (Science), 1994.

Thomas Jefferson University: PhD (Immunology), 2000.

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.

Description of Research

The aim 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 to lymphocytic choriomeningitis virus has demonstrated that during chronic infection virus-specific CD8 T cells gradually lose the ability to perform effector functions (IFN-γ, TNF-α, cytotoxicity, etc) and fail to acquire key memory T cell properties such as homeostatic proliferation and antigen-independent maintenance. Similar defects in effector functions have reported during human chronic infections. We are using cellular and genomic approaches to dissect the molecular pathways involved regulating these defects in function and memory T cell differentiation during persisting infections. 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. Our gene expression analyses have, and will continue to, identify dysregulated cellular pathways that will be further investigated for their mechanistic contribution to altered T cell differentiation and effector function. Lastly, using foundation provided by these studies, we are investigating therapeutic interventions (e.g., therapeutic vaccination) designed to target specific pathways in virus-specific T cells, overcome functional defects, and restore effective antiviral immunity during chronic infections.

Selected Publications

Sarkar S, Teichgräber V, Kalia V, Polley A, Masopust D, Harrington LE, Ahmed R, Wherry EJ. Strength of stimulus and clonal competition impact the rate of memory CD8 T cell differentiation. J Immunol. 2007 Nov 15;179(10):6704-14.

Wherry EJ, Ha SJ, Kaech SM, Haining WN, Sarkar S, Kalia V, Subramaniam S, Blattman JN, Barber DL, Ahmed R. Molecular signature of CD8+ T cell exhaustion during chronic viral infection. Immunity. 2007 Oct;27(4):670-84. Epub 2007 Oct 18. Erratum in: Immunity. 2007 Nov;27(5):824.

Kaech SM, Wherry EJ. Heterogeneity and cell-fate decisions in effector and memory CD8+ T cell differentiation during viral infection. Immunity. 2007 Sep;27(3):393-405. Review.

Shin H, Wherry EJ. CD8 T cell dysfunction during chronic viral infection. Curr Opin Immunol. 2007 Aug;19(4):408-15. Epub 2007 Jul 25. Review.

Shin H, Blackburn SD, Blattman JN, Wherry EJ. Viral antigen and extensive division maintain virus-specific CD8 T cells during chronic infection. J Exp Med. 2007 Apr 16;204(4):941-9. Epub 2007 Apr 9.

PubMed Search
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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

Velma Decman- Postdoctoral Fellow
Charlie Kao- Postdoctoral Fellow
Alison Crawford- Postdoctoral Fellow
Douglas Dolfi- Postdoctoral Fellow
Mohammed Ali- Technician
Antonio Polley- Technician
Shawn Blackburn- Graduate Student
Haina Shin- Graduate Student
Brian Laidlaw- Undergraduate Student
Maanasi Samunt- Undergraduate Student


last updated 7/2008
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