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Jonathan D. Powell

Jonathan D. Powell

Department Affiliation: Primary: Oncology; Secondary: Pharmacology and Molecular Sciences
Degree: M.D., Ph.D., Emory University School of Medicine
Rank: Professor
Telephone Number: 410-502-7887
Fax Number: 410-614-9705
E-mail address: poweljo@jhmi.edu
School of Medicine Address: Room 443, Cancer Research Bldg., 1650 Orleans Street, Baltimore, MD 21231 

Mechanisms of T cell activation and tolerance.

Dr. Powell’s lab is interested in studying the cellular, biochemical and molecular mechanisms surrounding T cell activation, differentiation, function and tolerance. The lab has identified a critical role for mTOR signaling in determining CD4+ effector and regulatory T cell differentiation as well CD8+ effector and memory generation. Mechanistically, the lab has linked the ability of mTOR to regulate metabolic reprogramming as a means of dictating the consequences of antigen recognition. To this end the lab has interrogated these pathways in models of infectious diseases, autoimmunity, transplantation immunity and tumor immunity. Additionally, the Powell lab has contributed to increasing our understanding of how endogenous adenosine inhibits T cell function by engaging the A2aR.  Some of these studies have provided the preclinical rationale for current clinical trials investigating A2aR antagonists as a means of enhancing cancer immunotherapy.  Most recently, the lab has focused on the role of metabolic programming in regulating the activation, differentiation and function of immune cells. To this end the lab has recently helped develop a novel glutamine antagonist which not only inhibits tumor growth but directly enhances CD8+ T cell effector function.

Representative Publications:

  • Leone, R.D., Zhao, L., Englert, J.M., Sun, I.M., Oh, M.H., Sun, I.H., Arwood, M.L., Bettencourt, I.A., Patel, C.H., Wen, J., Tam, A., Blosser, R.L., Prchalova, E., Alt, J., Rais, R., Slusher, B.S., Powell, J.D. Glutamine blockade induces divergent metabolic programs to overcome tumor immune evasion. Science 366(6468):1013-1021, 2019. Pub Med Reference
  • Patel, C.H., Leone, R.D., Horton, M.R., Powell, J.D. Targeting metabolism to regulate immune responses in autoimmunity and cancer. Nat Rev Drug Discov. (9):669-688, 2019. Pub Med Reference
  • Ranek, M.J., Kokkonen-Simon, K.M., Chen, A., Dunkerly-Eyring, B.L., Vera, M.P., Oeing, C.U., Patel, C.H., Nakamura, T., Zhu, G., Bedja, D., Sasaki, M., Holewinski, R.J., Van Eyk, J.E., Powell, J.D., Lee, D.I., Kass, D.A. PKG1-modified TSC2 regulates mTORC1 activity to counter adverse cardiac stress. Nature 566(7743):264-269, 2019. Pub Med Reference
  • Leone, R.D., Sun, I.M., Oh, M.H., Sun, I.H., Wen, J., Englert, J., Powell, J.D. Inhibition of the adenosine A2a receptor modulates expression of T cell coinhibitory receptors and improves effector function for enhanced checkpoint blockade and ACT in murine cancer models. Cancer Immunol Immunother. 67(8):1271-1284, 2018.  Pub Med Reference
  • Pollizzi, K.N., Sun, I.H., Patel, C.H., Lo, Y.C., Oh, M.H., Waickman, A.T., Tam, A.J., Blosser, R.L., Wen, J., Delgoffe, G.M., Powell, J.D. Asymmetric inheritance of mTORC1 kinase activity during division dictates CD8(+) T cell differentiation. Nat Immunol. 17(6):704-711, 2016. Pub Med Reference
  • Lee, C.F., Lo, Y.C., Cheng, C.H., Furtmüller, G.J., Oh, B., Andrade-Oliveira, V., Thomas, A.G., Bowman, C.E., Slusher, B.S., Wolfgang, M.J., Brandacher, G., Powell, J.D. Preventing Allograft Rejection by Targeting Immune Metabolism. Cell Rep. 13(4):760-770, 2015.  Pub Med Reference
  • Pollizzi, K.N., Patel, C.H., Sun, I.H., Oh, M.H., Waickman, A.T., Wen, J., Delgoffe, G.M., Powell, J.D. mTORC1 and mTORC2 selectively regulate CD8⁺ T cell differentiation. J Clin Invest. 125(5):2090-2108, 2015. Pub Med Reference
  • Heikamp, E.B., Patel, C.H., Collins, S., Waickman, A., Oh, M.H., Sun, I.H., Illei, P., Sharma, A., Naray-Fejes-Toth, A., Fejes-Toth, G., Misra-Sen, J., Horton, M.R., Powell, J.D. The AGC kinase SGK1 regulates TH1 and TH2 differentiation downstream of the mTORC2 complex. Nat Immunol. 15(5):457-464, 2014. Pub Med Reference
  • Powell, J.D., Heikamp, E.B., Pollizzi, K.N., Waickman, A.T. A modified model of T-cell differentiation based on mTOR activity and metabolism. Cold Spring Harb Symp Quant Biol. 78:125-130, 2013. Pub Med Reference
  • Powell, J.D., Pollizzi, K.N., Heikamp, E.B., Horton, M.R. Regulation of immune responses by mTOR. Annu Rev Immunol. 30:39-68, 2012. Pub Med Reference
  • Delgoffe, G.M., Pollizzi, K.N, Waickman, A.T., Heikamp, E., Meyers, D.J., Horton, M.R., Xiao, B., Worley, P.F., Powell, J.D.  The kinase mTOR regulates the differentiation of helper T cells through the selective activation of signaling by mTORC1 and mTORC2.  Nature Immunology 12(4):295-303, 2011.  Pub Med Reference.
  • Delgoffe, G.M., Kole, T.P., Zheng, Y., Zarek, P.E., Matthews, K.L., Xiao, B., Worley, P.F., Kozma, S.C., Powell, J. D.  The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment.  Immunity 30(6):832-844, 2009. Pub Med Reference
  • Powell, J.D., Delgoffe, G.M.  The mammalian target of rapamycin: linking T cell differentiation, function, and metabolism. Immunity 33(3):301-11, 2010.  Pub Med Reference.
  • Hsieh, M.M, Kang, E.M., Fitzhugh, C.D., Link, M.B., Bolan, C.D., Kurlander, R., Childs, R.W., Rodgers, G.P., Powell, J.D., Tisdale, J.F.  Allogeneic hematopoietic stem-cell transplantation for sickle cell disease.  N Engl J Med. 361(24):2309-17, 2010.  Pub Med Reference.
  • Zheng, Y., Delgoffe, G.M., Meyer, C.F., Chan, W., Powell, J.D.  Anergic T cells are metabolically anergic.  J Immunol. 183(10):6095-101, 2009.  Pub Med Reference.
  • Delgoffe, G.M., Kole. T.P., Cotter, R.J., and Powell, J.D.   Enhanced interaction between Hsp90 and raptor regulates mTOR signaling upon T cell activation.  Mol Immunol. 46(13):2694-2698, 2009.   Pub Med Reference.
  • Huang, G.N., Huso, D.L., Bouyain, S., Tu, J., McCorkell, K.A., May, M.J., Zhu, Y., Lutz, M., Collins, S., Dehoff, M., Kang, S., Whartenby, K., Powell, J.D., Leahy, D., Worley, P.F.  NFAT binding and regulation of T cell activation by the cytoplasmic scaffolding Homer proteins.  Science. 319(5862):476-481, 2008.  Pub Med Reference.
  • Delgoffe, G.M., Kole, T.P., Zheng, Y., Zarek, P.E., Matthews, K.L., Xiao, B., Worley, P.F., Kozma, S.C., Powell, J. D.  The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment.  Immunity. 30(6):832-844, 2009.  Pub Med Reference
  • Zarek, P.E., Huang, C.T., Lutz, E.R., Kowalski, J., Horton, M.R., Linden, J., Drake, C.G., Powell, J.D.  A2A receptor signaling promotes peripheral tolerance by inducing T-cell anergy and the generation of adaptive regulatory T cells.  Blood 111(1):251-9, 2008.  Pub Med Reference
  • Collins, S., Wolfraim, L.A., Drake, C.G., Horton, M.R., Powell, J.D.  Cutting Edge: TCR-induced NAB2 enhances T cell function by coactivating IL-2 transcription.  J. Immuno. 177(12):8301-5, 2006.  Pub Med Reference
  • Safford, M., Collins, S., Lutz, M.A., Allen, A., Huang, C.T., Kowalski, J., Blackford, A., Horton, M.R., Drake, C., Schwartz, R.H., Powell, J.D.  Egr-2 and Egr-3 are negative regulators of T cell activation.  Nat. Immunol. 6(5):472-80, 2005.  Pub Med Reference

Other graduate program in which Dr. Powell participates:

Immunology Graduate Program