E. John Wherry, PhD
Professor of Microbiology
Director, Institute for Immunology
Perelman School of Medicine
University of Pennsylvania

312 Biomedical Research Bldg II/III
421 Curie Blvd.
Philadelphia, PA 19104

TEL 215-746-8141
LAB 215-898-2873
FAX 215-746-8294

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  Research questions

  A major goal is to understand the mechanisms of T cell exhaustion during chronic infections. During chronic viral infections, 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 multiparameter flow cytometry, systems biology and global gene expression profiling and genetically modified mice we are defining cellular and transcriptional pathways involved in T cell exhaustion and normal memory T cell differentiation. Pathways such as the inhibitory receptor PD-1 identified by these approaches are now major targets for cancer immunotherapy.

  Some of areas of considerable current interest include inhibitory receptors (e.g. PD-1, LAG-3), transcription factors and inflammatory pathways. In addition, we are examining how co-infection with two pathogens can impact T cell memory.

  In addition, we are investigating the mechanisms of T follicular helper cell responses in humans following influenza vaccination, enteric viral infection and age-related changes in T cell immunity in both mice and humans.

  Rotation projects

  1. Regulatory mechanisms during chronic viral infections and cancer
  2. Mechanisms of PD-1 and other inhibitory receptors in animal models and humans
  3. Transcriptional and epigenetic regulation of T cell differentiation
  4. Defining exhaustion-specific genes for development of novel mouse strains and molecular tools
  5. Molecular program of subpopulations of exhausted and memory T cells
  6. T follicular helpers in vaccination and chronic infections
  7. Single cell gene expression and genomics in T cells
  8. Enteric, respiratory, and mucosal infections