James L. Riley

About

James L. Riley, Ph.D., is a Professor of Microbiology at the University of Pennsylvania's Perelman School of Medicine. His research focuses on the signals that control primary human T cell activation and function, with particular attention to how these manipulations can be exploited to develop T cell therapies for HIV, autoimmune disease, and cancer. Dr. Riley's lab studies how to re-direct and expand human T regulatory cells for autoimmune disease treatment, utilizing TCR and CARs to redirect Tregs, and examining how these methods influence antigen suppression and T regulatory cell stability. His work also investigates how expanding T cells in different media affects their function and engraftment potential, as well as how external signaling and environmental factors perturb metabolic pathways. Additionally, Dr. Riley's research includes designing HIV-resistant, HIV-specific T cells as part of the HIV Cure effort. As a leader of the BEAT HIV Martin Delaney Collaboratory, his lab evaluates strategies to make T cells resistant to HIV entry and integration, and develops HIV-1 specific chimeric antigen receptors to assess their ability to control HIV replication in vitro and in humanized mouse models. His basic research findings have served as the basis for numerous Phase I adoptive T cell therapy clinical trials.

Research topics

• Medicine
• Internal medicine
• Immunology
• Intensive care medicine
• Oncology
• Virology
• Cancer research

Selected publications

• Recommendations for measuring HIV reservoir size in cure-directed clinical trials

  Nature Medicine · 2020 · 136 citations

  DOI

• CAR Binders Affect CAR T-cell Tonic Signaling, Durability, and Sensitivity to Target

  Cancer Immunology Research · 2025-04-29 · 4 citations

  articleOpen accessSenior author

  Patients can develop human anti-mouse immune responses against CD19-specific chimeric antigen receptor (CAR) T cells due to the use of a murine CD19-specific single-chain variable fragment to redirect T cells. We screened a yeast display library to identify an array of fully human CD19 single-chain variable fragment binders and performed a series of studies to select the most promising fully human CAR. We observed significant differences in the ability of CARs employing these CD19 binders to be…

  PublisherOA PDFDOI

• Optimal pairing of binder and co-stimulatory domains improves dual CART cell efficacy

  Molecular Therapy · 2025-08-06 · 2 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Rab5 improves CAR T cell efficacy via reducing fratricide and maintaining surface CAR levels

  The Journal of Experimental Medicine · 2026-03-27 · 1 citations

  articleSenior author

  We show continuous tumor exposure results in a loss of chimeric antigen receptor (CAR) T cell (CART) endocytic activity due to downregulation of Rab5. Loss of endocytic activity exacerbates the effects of trogocytosis, the bidirectional transfer of tumor target antigens and CARs between malignant cells and CARTs, resulting in CART dysfunction and fratricide. Constitutive expression of Rab5 within the CARTs reduced fratricide by reducing the amount of trogocytosed antigens on the cell surface, wh…

  PublisherDOI

• CCR5-targeted allogeneic gamma–delta CD19 chimeric antigen receptor T cells for HIV-associated B cell-malignancy immunotherapy

  Nature Biomedical Engineering · 2025-10-21 · 1 citations

  article
  PublisherDOI

Recent grants

• NIH Grant P01AI080192

  NIH · $25.2M · 2015

• Molecular & Translational Immunotechnology Core

  NIH · $36.7M · 1999–2029

• Microphysiological systems for modeling autoimmunity in type 1 diabetes

  NIH · $2.3M · 2019–2024

Frequent coauthors

• Carl H. June

  Parker Institute for Cancer Immunotherapy

  330 shared

• Richard G. Carroll

  113 shared

• Bruce L. Levine

  University of Pennsylvania

  102 shared

• Bruce R. Blazar

  University of Minnesota

  58 shared

• Tatiana N. Golovina

  Fraunhofer USA Center for Molecular Biotechnology

  53 shared

• Richard V. Parry

  51 shared

• Craig B. Thompson

  45 shared

• Daniel C. St. Louis

  Henry M. Jackson Foundation

  43 shared

Labs

• Riley LabPI

Education

• PhD, Genetics and Molecular Biology

  Emory University

  1994

• BS, Molecular Biology

  Vanderbilt Health

  1989

Similar researchers at University of Pennsylvania

• John Q. Trojanowskih-296
• Daniel J Raderh-236