Vijay K. Kuchroo, D.V.M., Ph.D.

Dr. Vijay Kuchroo is the Samuel L. Wasserstrom Professor of Neurology at Harvard Medical School, Senior Scientist at Brigham and Women’s Hospital, and Co-Director of the Center for Infection and Immunity, Brigham Research Institutes, Boston. Vijay Kuchroo is also an associate member of the Broad Institute and a participant in a Klarman Cell Observatory project that focuses on T cell differentiation. He is the founding Director of the Evergrande Center for Immunologic Diseases at Harvard Medical School and Brigham and Women’s Hospital.  His major research interests include autoimmune diseases – particularly the role of co-stimulation – the genetic basis of experimental autoimmune encephalomyelitis and multiple sclerosis, and cell surface molecules and regulatory factors that regulate induction of T cell tolerance and dysfunction. His laboratory has made several transgenic mice that serve as animal models for human multiple sclerosis.His laboratory also first described TIM family of genes and identified Tim-3 as an inhibitory receptor expressed on T cells, which is now being exploited for cancer immunotherapy. He was first to describe the development of a highly pathogenic Th17 cells which has been shown to induce multiple different autoimmune diseases in humans.  A paper describing development of Th17 authored by Dr. Kuchroo has been one of the highest cited papers in Immunology.

Dr. Kuchroo came to the United States in 1985 and was at the National Institutes of Health, Bethesda as Fogarty International Fellow for a year before joining the department of pathology at Harvard Medical School as a research fellow. He later joined the Center for Neurologic Diseases at Brigham and Women’s Hospital as a junior faculty member in 1992.

He obtained his degree in Veterinary Medicine from the College of veterinary medicine, Hisar, India. Subsequently, he specialized in pathology at the University of Queensland, Brisbane (Australia) where he obtained a Ph.D. in 1985. He received the Fred Z. Eager Research prize and medal for his Ph.D. research work. Based on his contributions, he was awarded the Javits Neuroscience Award by the National Institutes of Health in 2002 and the Ranbaxy prize in Medical Research from the Ranbaxy Science Foundation in 2011. He was named Distinguished Eberly lecturer in 2014, Garber Lecturer by the French Society of Immunology in 2014 and was recipient of Nobel Laureate Peter Doherty lecture/prize in 2014. In 2019, he was the recipient of the Milestones in Research Award by the National Multiple Sclerosis Society, New York. He was also awarded 2020 ICIS-Biolegend William E. Paul Award by the International Cytokine and Interferon Society for his role in discovery of Th17 cells.

Dr. Kuchroo has 25 patents and has founded 5 different biotech companies including CoStim Pharmaceuticals, Potenza Pharmaceuticals, Tizona Pharmaceuticals and Celsius pharmaceuticals.  He also serves on the scientific advisory boards and works in advisory capacity to a number of internationally recognized pharmaceutical companies including Biocon, Syngene, Sanofi, Pfizer, Novartis and Glaxo-Smith-Klein (GSK).

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ABSTRACT

“Checkpoint” moleculesand induction of anti-tumor immunity

Vijay K. Kuchroo, Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women’s Hospital, Boston, MA 02115, Broad Institute of MIT and Harvard, Cambridge, MA 02142.

Expression of co-inhibitory receptors or “check-point” molecules, such as CTLA-4 and PD-1, on effector T cells is a key mechanism for ensuring immune homeostasis. Dysregulated expression of co-inhibitory receptors on CD4+ T cells promotes autoimmunity while sustained overexpression on CD8+ T cells promotes T cell dysfunction or exhaustion, leading to impaired ability to clear chronic viral infections and cancer. Antibody blockade of both CTLA4 and PD-1 in cancer patients resulted in revival of anti-tumor immunity and inhibition of tumor growth in clinical setting. However, not all patients respond to the therapy and there is some degree of selectivity in terms of responsiveness of different tumor types.  This raises an important issue of why don’t all subjects respond to the checkpoint blockade and why are some tumor types resistant to the therapy. There may be additional checkpoint molecules that are co-expressed with CTLA4 and PD-1, suppressing anti-tumor immunity and promoting resistance.  Although analyses of selected co-inhibitory receptors has indicated some degree of co-expression of multiple checkpoint molecules on T cells, the extent of co-expression across the full landscape of known co-inhibitory receptors has not been fully examined.Using RNA and protein expression profiling at single-cell resolution of tumor infiltrating lymphocytes, weidentify a module of co-inhibitory receptors, which includes not only several known co-inhibitory receptors (CTLA4, PD-1, Tim-3, Lag-3, and TIGIT), but also a number of novel surface receptors (Chiharra et al., Nature, 2018). Studies with a number of “novel” co-inhibitory molecules and the mechanism by which they regulate anti-tumor immunity will be presented.