Protul Shrikant

Professor

My graduate training was in the field of Cellular and Molecular Immunology, wherein I investigated transcriptional and post-transcriptional mechanisms employed by cytokines to regulate ICAM-1 gene expression by primary astrocytes and microglial cells of the CNS. These investigations shed new light on the role of cytokines in inflammatory diseases like Multiple Sclerosis and AIDS dementia. During my post-doctoral training, I extend these skills to conduct in vitro and in vivo cellular immunology investigations into mechanisms regulating antigen specific CD8+ and CD4+ T cell responses that determine tolerance versus immunity by developing novel murine tumor models.  As an independent investigator, I have combined these experiences to delineate the effects of antigen and cytokines on CD8+ T cell fate.  Over the past 18 years, I have supervised and mentored over 14 graduate students and 19 post-doctoral/clinical fellows and we have collectively characterized several molecular pathways guiding CD8+ T cell responses which have been successfully targeted in murine model systems and the clinic.  The achievements from our laboratory investigations have resulted in the application of IL-21 in the treatment of RCC and Melanoma, the use of rapamycin to promote CD8+ T cell memory responses for durable immunity in cancer and the ability to ex vivo produce tumor specific resident memory T (TRM) cells for clinical benefit.  The bench to bedside to bench paradigm is actively practiced by my research group and we have produced significant impact (publications and clinic) and created a useful platform for training future scientists. In addition, I was instrumental in establishing the Immune monitoring core at RPCI and was a joint leader of the Mayo Clinic Cancer Center’s Cancer Immunology and Immunotherapy CCSG program.  Based on these experiences have taken up responsibilities for developing Cancer Immunotherapy at UACC and perform Immune Monitoring for clinician scientists at University of Arizona. Our ability to collaborate with basic and clinician scientists nationally and internationally is fundamental to our success at advancing novel basic science concepts for clinical benefit.

Degrees
  • BSc (Hons): St. Xavier's College (Mumbai)
  • MS: University of Bridgeport, CT
  • Ph.D.: University of Alabama at Birmingham
Fellowship
  • Post-doctoral Fellowship (NMSS) at University of Minnesota

Recent Publications

2016

Chaudhuri, L., R. K. Srivastava, F. Kos, and P. A. Shrikant, "Uncoupling protein 2 regulates metabolic reprogramming and fate of antigen-stimulated CD8+ T cells.", Cancer Immunol Immunother, vol. 65, issue 7, pp. 869-74, 2016 07. PMCID: PMC4919150  PMID: 27271549

2015

Huang, R-Y., C. Eppolito, S. Lele, P. Shrikant, J. Matsuzaki, and K. Odunsi, "LAG3 and PD1 co-inhibitory molecules collaborate to limit CD8+ T cell signaling and dampen antitumor immunity in a murine ovarian cancer model.", Oncotarget, vol. 6, issue 29, pp. 27359-77, 2015 Sep 29. PMCID: PMC4694995  PMID: 26318293
Matsuzaki, J., T. Tsuji, I. F. Luescher, H. Shiku, J. Mineno, S. Okamoto, L. J. Old, P. Shrikant, S. Gnjatic, and K. Odunsi, "Direct tumor recognition by a human CD4(+) T-cell subset potently mediates tumor growth inhibition and orchestrates anti-tumor immune responses.", Sci Rep, vol. 5, pp. 14896, 2015 Oct 08. PMCID: PMC4597193  PMID: 26447332
Fu, C., X. Liang, W. Cui, J. L. Ober-Blöbaum, J. Vazzana, P. A. Shrikant, K. P. Lee, B. E. Clausen, I. Mellman, and A. Jiang, "β-Catenin in dendritic cells exerts opposite functions in cross-priming and maintenance of CD8+ T cells through regulation of IL-10.", Proc Natl Acad Sci U S A, vol. 112, issue 9, pp. 2823-8, 2015 Mar 03. PMCID: PMC4352820  PMID: 25730849

2014

Liang, X., C. Fu, W. Cui, J. L. Ober-Blöbaum, S. P. Zahner, P. A. Shrikant, B. E. Clausen, R. A. Flavell, I. Mellman, and A. Jiang, "β-catenin mediates tumor-induced immunosuppression by inhibiting cross-priming of CD8⁺ T cells.", J Leukoc Biol, vol. 95, issue 1, pp. 179-90, 2014 Jan. PMID: 24023259

2013

Mukhopadhyay, A., T. Khoury, L. Stein, P. Shrikant, and A. K. Sood, "Prostate derived Ets transcription factor and Carcinoembryonic antigen related cell adhesion molecule 6 constitute a highly active oncogenic axis in breast cancer.", Oncotarget, vol. 4, issue 4, pp. 610-21, 2013 Apr. PMCID: PMC3720608  PMID: 23592399
Huntoon, K. M., L. Russell, E. Tracy, K. W. Barbour, Q. Li, P. A. Shrikant, F. G. Berger, L. Ann Garrett-Sinha, and H. Baumann, "A unique form of haptoglobin produced by murine hematopoietic cells supports B-cell survival, differentiation and immune response.", Mol Immunol, vol. 55, issue 3-4, pp. 345-54, 2013 Oct. PMCID: PMC3646973  PMID: 23548836

2012

Odunsi, K., J. Matsuzaki, J. Karbach, A. Neumann, P. Mhawech-Fauceglia, A. Miller, A. Beck, C. D. Morrison, G. Ritter, H. Godoy, et al., "Efficacy of vaccination with recombinant vaccinia and fowlpox vectors expressing NY-ESO-1 antigen in ovarian cancer and melanoma patients.", Proc Natl Acad Sci U S A, vol. 109, issue 15, pp. 5797-802, 2012 Apr 10. PMCID: PMC3326498  PMID: 22454499
Qian, F., J. Liao, J. Villella, R. Edwards, P. Kalinski, S. Lele, P. Shrikant, and K. Odunsi, "Effects of 1-methyltryptophan stereoisomers on IDO2 enzyme activity and IDO2-mediated arrest of human T cell proliferation.", Cancer Immunol Immunother, vol. 61, issue 11, pp. 2013-20, 2012 Nov. PMID: 22527253
Srivastava, R. K., A. Utley, and P. A. Shrikant, "Rapamycin: A rheostat for CD8(+) T-cell-mediated tumor therapy.", Oncoimmunology, vol. 1, issue 7, pp. 1189-1190, 2012 Oct 01. PMCID: PMC3494641  PMID: 23170275