James L. Riley

faculty photo
Research Associate Professor of Microbiology
Department: Microbiology

Contact information
8-115
SCTR
Philadelphia, PA 19104-6160
Office: (215) 573-6792
Fax: (215) 573-8590
Graduate Group Affiliations
Education:
BS (Molecular Biology)
Vanderbilt University (Charles K Singleton, mentor), 1989.
Ph.D. (Genetics and Molecular Biology)
Emory University (Jeremy M. Boss, mentor), 1994.
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Description of Research Expertise

Research Interests
CD28 family of receptors, adoptive T cell therapy, lentiviral vectors for cell engineering.

Key words: T cell activation, Tumor Specific T cells, HIV specific T cells, expression profiles.

Research Summary
Research in the Riley laboratory focuses on the cell biology of and therapeutic use of primary human T cells. One major project studies the signaling pathways initiated by members of the CD28 family (CD28, ICOS, CTLA-4, PD-1 and BTLA). These receptors, despite their structural similarity, play distinct roles in modulating the immune system. No recognizable enzymatic activity has been associated with any of their cytoplasmic tails but rather these receptors are thought to recruit unique set of signal transducing molecules, which choreograph their distinct effects on T cell activation. Our approach has been to perform structure-function experiments to determine which domains within the CD28 family members cytoplasmic tails are responsible for transducing particular signals. Understanding how these pathways alter a T cell’s response to antigen stimulation on a global basis may lead to the development of novel therapeutics for HIV and cancer.

The second major project strives to develop artificial antigen presenting cells (APCs) to optimally expand T cell subsets. We have created a library of lentiviral vectors encoding costimulatory molecules, HLA alleles, cytokines and chemokines that we used to transduce a MHC deficient cell line, K562. To date, we have engineered cells to express up to eight genes, providing the platform by which to dissect the signals required to optimally activate and expand human T cell subsets. Beyond the potential of this model to understand human T cell differentiation, this project is translational in nature. We are currently developing master cell banks that will allow us to use these artificial APCs to preferentially expand desired T cell subsets for adoptive T cell immunotherapy trails.

The third major project is to develop gene therapy approaches to redirect T cells to target infectious diseases or tumors using high affinity TCRs. We have developed humanized murine models to study the specificity and effectiveness of primary human T cells transduced with lentiviral vectors expressing these high affinity TCRs. Additionally, we are studying how viruses and tumors escape from this augmented immune pressure. Moreover, we are trying to dissect the signaling pathways by which enhanced affinity TCRs direct a more pronounced T cell response.
Rotation Projects for 2009-2010
Please contact Dr. Riley concerning current rotation projects.

Lab personnel:
Angel Varela-Rohena, Ph.D. Postdoctoral Fellow
Fang Wei Ph.D. Postdoctoral Fellow
Samik Basu, MD. Postdoctoral Fellow
Max Richardson, Ph.D Postdoctoral Fellow
Caleph Wilson, Ph.D. Postdoctoral Fellow
Gabriela Plesa, Ph.D. Postdoctoral Fellow
Andrew Medvac, Research Specialist
Tatiana Mikheeva, Research Specialist
Hong Kong, Research Specialist
Lingjie Zheng, Research Specialist

Description of Itmat Expertise

The Riley laboratory studies signals that regulate T cell activation and on the application of these findings for immunotherapy of chronic infections and cancer. The lab is currently developing lentiviral vectors as a safe and effective means to engineer T cells for targeted immunotherapy.

Selected Publications

Varela-Rohena A, Molloy PE, Dunn SM, Li Y, Suhoski MM, Carroll RG, Milicic A, Mahon T, Sutton DH, Laugel B, Moysey R, Cameron BJ, Vuidepot A, Purbhoo MA, Cole DK, Phillips RE, June CH, Jakobsen BK, Sewell AK*, Riley JL*.: Control of HIV-1 immune escape by CD8 T cells expressing enhanced T-cell receptor. Nature Medicine 14(12): 1390-1395, DEC 2008.

Basu S, Golovina T, Mikheeva T, June CH, Riley JL: Cutting edge: Foxp3-mediated induction of pim 2 allows human T regulatory cells to preferentially expand in rapamycin. Journal Of Immunology 180(9): 5794-5798, MAY 2008.

June CH, Blazar BR, and Riley JL: Engineering lymphocyte subsets: tools, trials and tribulations. Nature Reviews Immunology 9(10): 704-716, OCT 2009.

Plesa G, Zheng L, Medvec A, Wilson CB, Robles-Oteiza C, Liddy N, Bennett AD, Gavarret J, Vuidepot A, Zhao Y, Blazar BR, Jakobsen BK, Riley JL.: TCR affinity and specificity requirements for human T regulatory cell function. Blood 119(15): 3420-30, April 2012.

Richardson MW, Jadlowsky J, Didigu CA, Doms RW, Riley JL.: Kruppel-like Factor 2 Modulates CCR5 Expression and Susceptibility to HIV-1 Infection. The Journal of Immunology 189(8): 3815, Oct 2012.

Martin S, Saha B, Riley JL.: The Battle over mTOR: An Emerging Theatre in Host-Pathogen Immunity. PLoS Pathogens 9: e1002894. Sep 2012.

Rech AJ*, Mick R*, Martin S*, Recio A, Aqui NA, Powell DJ, Colligon TA, Trosko JA, Leinbach LI, Pletcher CH, Tweed CK, DeMichele A, Fox KR, Domchek SM, Riley, JL* and Vonderheide RH*: CD25 blockade depletes and selectively reprograms regulatory T-cells and cooperates with immunotherapy in cancer patients Science Translational Medicine 4(134): ra62, May 2012.

James L Riley: Combination Checkpoint Blockade - Taking Melanoma Immunotherapy to the Next Level. New England Journal of Medicine 369(2): 187-9, Jul 2013.

Wei F, Zhong S, Ma Z, 1, Kong H, Medvec A, Ahmed R, Freeman G, Krogsgaard M, and Riley JL.: Strength of PD-1 Signaling Differentially Affects T Cell Effector Functions. Proceedings of the National Academy of Sciences 110(27): E2480-89, Jul 2013.

Richardson MW, Guo L, Xin F, Yang X, Riley JL.: Stabilized Human TRIM5 Alpha Protects Human T cells from HIV-1 Infection. Molecular Therapy in press, 2014.

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Last updated: 04/10/2014
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