Jim Riley
Research Associate Professor, Dept of Pathology and Laboratory Medicine

Gene Therapy & Vaccines Program

Microbiology, Virology & Parasitology Program

Address

556 Biomedical Rsch Bldg (BRB) II/III
421 Curie Boulevard
Philadelphia, PA 19104

Office tel.: 215 573-6792
Lab tel.: 215 746-5509
Fax: 215 573-8590
E-mail: rileyj@mail.med.upenn.edu

Vanderbilt University: BS (Molecular Biology), 1989.

Emory University: PhD (Genetics and Molecular Biology), 1994.

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.

Description of Research

Our research team tries to understand the basic principles that control human T cell activation and differentiation and to use this knowledge to develop T cell-based therapies.  One major focus of the lab is to create artificial antigen presenting cells (aAPCs) that can specifically expand differential T cell subsets.  Current projects include defining the optimal co-stimulatory requirements to expand central and effector memory cells; gd T cells, natural killer cells and T regulatory cells.  Once a subset is defined and characterized in vitro, we use humanized mice to model in vivo effects of these expanded T cell populations.   For example, when human PMBCs are engrafted into these mice, a disease similar to graft v host disease (GVHD) ensues.  We have found that APCs that provide CD28 costimulation expand highly functional T regulatory cells are much more effective in blocking GVHD disease than T regulatory cells expanded in the absence of CD28 costimulation.  Similar models are in place to define the optimal T cell response against tumors and HIV. 

In addition to their replicative abilities and potent effector functions, another reason T cells are attractive for adoptive cell therapy is that they can be genetically modified with relative ease.  This enables testing of strategies to re-direct the T cells to recognize to a particular antigen via the introduction of single chain Ab immunorecptors or TCR genes.  This allows the rapid generation of a large number of antigen specific T cells.  Other projects include creating vectors that will make T cells immune to HIV-1 infection once they re-infused back into the patient, extending the replication potential of T cells and the introduction of master control genes to push the differentiation of T cells down a particular pathway.  The use of humanized mice has proven to be an invaluable tool to testing the efficacy of these gene therapy strategies. 

In collaboration with Drs. Carl June and Bruce Levine several Phase I clinical trials are underway to test the most promising T cell therapies in humans.  In addition to helping develop these therapies, we also participate in analyzing the effects of the therapies in the patients.  This bench to bedside back to bench approach is fertile ground to develop new insights into how the immune system works and how to best exploit this knowledge to fight particular diseases.

Selected Publications

Parry RV., Chemnitz JM., Frauwirth FA., Lanfranco AR., Braunstein I., Kobayashi SV., Linsley PS., Thompson CB. and Riley JL (2005). CTLA-4 and PD-1 Receptors Inhibit T Cell Activation by Distinct Mechanisms. Molecular and Cellular Biology 25(21): 9543-53

Chemnitz JM., Braunstein I., Lanfranco AR., and Riley JL (2006). B and T Lymphocyte Attenuator-Mediated Signal Transduction Provides a Potent Inhibitory Signal to Primary Human CD4 T Cells That Can Be Initiated by Multiple Phosphotyrosine Motifs The Journal of Immunology 176(11): 6603

Basu, S, Golovina T, Mikheeva, T, June, CH, and Riley JL (2008). Cutting Edge: foxp3-Mediated Induction of Pim 2 Allows Human T Regulatory Cells to Preferentially Expand in Rapamycin The Journal of Immunology 180(9): 5794-5798

Golovina TN, Mikheeva T, Suhoski MM, Aqui NA, Tai VC, Shan X, Liu R, Balcarcel RR, Fisher N, Levine BL, Carroll RG, Warner N, June CH,and Riley JL. (2008). CD28 Costimulation is Essential for Human T Regulatory Expansion and Function The Journal of Immunology in press

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, and Riley JL (2008). Control of HIV-1 immune escape by CD8 T-cells expressing enhanced T-cell receptor, Nature Medicine in press

Search PubMed for more articles

Lab

Rotation Projects

Please contact Dr. Riley concerning current rotation projects.

Lab personnel

Angel Varela-Rohena, Post doctoral Fellow
Samik Basu, MD, Post doctoral Fellow
Max Richardson, Ph.D, Post doctoral Fellow
Tatiana Mikheeva, Research Specialist
Linjie Zheng, Research Specialist
Angela Mexas, Senior Research Investigator
Andrew Medvec, Research Specialist