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Jonathan David Powell, M.D., Ph.D.

Photo of Dr. Jonathan David Powell, M.D., Ph.D.
  • Associate Director, Bloomberg~Kimmel Institute for Cancer Immunotherapy
  • Professor of Oncology
Male

Expertise

Bone Marrow Transplant, Medical Oncology

Research Interests

Cancer Immunotherapy; Mechanisms of T cell activation and tolerance; Bone Marrow Transplantation

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Insurance Information

Maryland

410-955-8964

Outside of Maryland

410-464-6641
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International Patients

+1-410-502-7683
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Locations

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Appointment Phone: 410-955-8964
401 N. Broadway
Baltimore, MD 21231 map
Phone: 410-502-7887 | Fax: 410-614-9705

Background

Dr. Jonathan Powell is the Associate Director of the Bloomberg~Kimmel Institute for Cancer Immunotherapy at the Johns Hopkins School of Medicine in Baltimore, and a Professor of Oncology and Pharmacology. His research focuses on cancer immunotherapy, mechanisms of T cell activation and tolerance, and bone marrow transplantation. 

His team is currently engaged in understanding and targeting metabolic programming in both cancer and immune cells in order to enhance immunotherapy for cancer.

Dr. Powell received his undergraduate degree in biochemistry from Dartmouth College. He earned his M.D. and his Ph.D. degree from Emory University. He completed his residency at Johns Hopkins and performed a fellowship in hematology-oncology at Harvard Medical School and a fellowship in Immunology at the National Institutes of Health. Dr. Powell joined the Johns Hopkins faculty in 2001.

Dr. Powell is a member of the American Society of Hematology, the American Association of Immunologists and the Federation of Clinical Immunology Societies. He has published and spoken extensively on his research, as well as authored book chapters and peer reviews. Dr. Powell also serves as associate editor of the Journal of Clinical Investigation.

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Titles

  • Associate Director, Bloomberg~Kimmel Institute for Cancer Immunotherapy
  • Director of Admissions, Graduate Program in Immunology
  • Professor of Oncology
  • Professor of Pharmacology and Molecular Sciences

Departments / Divisions

Centers & Institutes

Education

Degrees

  • MD PhD, Emory University School of Medicine (1992)

Residencies

  • Johns Hopkins University School of Medicine / Oncology (1995)

Fellowships

  • National Institutes of Health / Immunology
  • Brigham and Women's Hospital / Hematology and Oncology (1996)
  • Harvard Medical School / Medicine (1996)
  • National Institutes of Health / Hematology and Oncology (1998)

Research & Publications

Research Summary

The Jonathan D. Powell laboratory is interested in understanding the biochemical and molecular pathways that govern T cell activation versus tolerance.

The 2 signal model provides the framework for the understanding of T cell responses. Signal 1 refers to T Cell Receptor (TCR) recognition while Signal 2 refers to engagement of costimulatory receptors by ligands present on activated antigen presenting cells. Using high throughput microarray analysis the lab has uncovered several novel TCR-induced genes and pathways that play critical roles in dictating the outcome of antigen recognition. They identified the Early Growth Response (EGR) family of transcription factors as playing an important role in determining the fate of TCR recognition. Egr-2 and Egr-3 null T cells induce more aggressive autoimmune disease but also are more effective in mounting anti-tumor responses. A second pathway that was revealed by their screen involves activation of the adenosine A2aR. Activating the receptor with A2aR agonists can promote tolerance and inhibit autoimmune disease. Alternatively, by employing A2aR null mice and specific antagonists, the lab is interested in blocking the ability to tumor-derived adenosine to inhibit T cell function and thus enhance the efficacy to tumor vaccines. In this regard the lab is involved in the preclinical development of A2aR antagonists as a means of enhancing tumor vaccines.

In addition to Signal 1, the lab is also interested in understanding how accessory signals derived from the environment (Signal 2) regulate T cell activation and function. Along these lines they have identified the evolutionarily conserved Serine/Threonine kinase the mammalian Target of Rapamycin (mTOR) as playing a central role in dictating the outcome of antigen recognition. By engineering mice to delete mTOR in T cells, they have determined that mTOR activation is critical for Th1, Th2 and Th17 differentiation. Furthermore, in the absence of mTOR T cells differentiate down a Foxp3+ regulatory T cell pathway. Currently, they are engineering T cell specific Rheb, Rictor and TSC2 null mice in order to dissect the upstream and downstream signaling pathways responsible for regulating T cells. In addition, by taking a proteomic approach the lab is seeking to identify novel substrates specifically involved in dictating mTOR-induced T cell differentiation. Clinically, the lab has been able to exploit their findings to develop novel regimens to promote graft acceptance and inhibit Graft Versus Host Disease. In collaboration with investigators at the NIH, they have devised a novel treatment protocol to employ non-myeloablative stem cell transplantation for the treatment of sickle cell disease.

Lab

Our laboratory is interested in understanding the biochemical and molecular pathways that govern T cell activation versus tolerance.

The 2 signal model provides the framework for our understanding of T cell responses. Signal 1 refers to T Cell Receptor (TCR) recognition while Signal 2 refers to engagement of costimulatory receptors by ligands present on activated antigen presenting cells. Using high throughput microarray analysis we have uncovered several novel TCR-induced genes and pathways that play critical roles in dictating the outcome of antigen recognition. We identified the Early Growth Response (EGR) family of transcription factors as playing an important role in determining the fate of TCR recognition. Indeed, Egr-2 and Egr-3 null T cells induce more aggressive autoimmune disease but also are more effective in mounting anti-tumor responses. A second pathway that was revealed by our screen involves activation of the adenosine A2aR. Activating the receptor with A2aR agonists can promote tolerance and inhibit autoimmune disease. Alternatively, by employing A2aR null mice and specific antagonists, the lab is interested in blocking the ability to tumor-derived adenosine to inhibit T cell function and thus enhance the efficacy to tumor vaccines. In this regard the lab is involved in the preclinical development of A2aR antagonists as a means of enhancing tumor vaccines.

In addition to Signal 1, we are also interested in understanding how accessory signals derived from the environment (Signal 2) regulate T cell activation and function. Along these lines we have identified the evolutionarily conserved Serine/Threonine kinase the mammalian Target of Rapamycin (mTOR) as playing a central role in dictating the outcome of antigen recognition. By engineering mice to delete mTOR in T cells we have determined that mTOR activation is critical for Th1, Th2 and Th17 differentiation. Furthermore, in the absence of mTOR T cells differentiate down a Foxp3+ regulatory T cell pathway. Currently, we are engineering T cell specific Rheb, Rictor and TSC2 null mice in order to dissect the upstream and downstream signaling pathways responsible for regulating T cells. In addition, by taking a proteomic approach we are seeking to identify novel substrates specifically involved in dictating mTOR-induced T cell differentiation. Clinically, we have been able to exploit our findings to develop novel regimens to promote graft acceptance and inhibit Graft Versus Host Disease. Indeed, in collaboration with investigators at the NIH we have devised a novel treatment protocol to employ non-myeloablative stem cell transplantation for the treatment of sickle cell disease.

Lab Website: Jonathan D. Powell Lab

Clinical Trial Keywords

immunotherapy

Selected Publications

View all on Pubmed

Leone, RD; Zhao, L; Englert, JM; Sun, IM; Oh, MH; Sun, IH; Arwood, ML; Bettencourt, IA; Patel, CH; Wen, J; Tam, A; Blosser, RL; Prchalova, E; Alt, J; Rais, R; Slusher, BS; Powell, JD. Glutamine blockade induces divergent metabolic programs to overcome tumor immune evasion. Science. 2019 Nov;366(6468):1013-1021

Patel, CH; Leone, RD; Horton, MR; Powell, JD. Targeting metabolism to regulate immune responses in autoimmunity and cancer. Nat Rev Drug Discov. 2019 Sep;18(9):669-688

Hess, BM; Thomas, DG; Weber, TJ; Hutchison, JR; Straub, TM; Bruckner-Lea, CJ; Powell, JD; Kabilan, S; Corley, RA. An integrated experimental-computational approach for predicting virulence in New Zealand white rabbits and humans following inhalation exposure to Bacillus anthracis spores. PLoS One. 2019 Jul;14(7):e0219160

Larimer, C; Brann, MR; Powell, JD; Marshall, MJ; Suter, JD; Addleman, RS. Rapid nondestructive measurement of bacterial cultures with 3D interferometric imaging. Sci Rep. 2019 May;9(1):8055

Vigeland, CL; Beggs, HS; Collins, SL; Chan-Li, Y; Powell, JD; Doerschuk, CM; Horton, MR. Inhibition of glutamine metabolism accelerates resolution of acute lung injury. Physiol Rep. 2019 Mar;7(5):e14019

Contact for Research Inquiries

Cancer Research Building
1650 Orleans Street
Baltimore, MD 21231 map
Phone: 410-502-7887
Fax: 410-614-9705

Academic Affiliations & Courses

Graduate Program Affiliation

Immunology Graduate Program

Courses and Syllabi

  • Genes to Society, Immunology Section
    2010
  • Graduate Course in Tumor Immunology
    2011
  • Graduate Immunology Course
    2002
  • Advanced Immunology Course on Immunometabolism
    2016
  • Principles of Immunology, 2001 – 2009
    2001 - 2009
  • Graduate Program Immunology Core, Director
    2002 - 2005
  • Immuno-pharmacology Small Group, Group Leader
    2002 - 2007
  • Discovery to Market Course, Carey School of Business
    2012 - 2013

Activities & Honors

Honors

  • V Foundation Award, 2001
  • Special Achievement Award, NIAID, NIH, 1999
  • Special Achievement Award, NIAID, NIH, 2000
  • Medical Scientist Research Scholarship, Emory University School of Medicine, 1992
  • Transfusion Medicine Research Grant, Emory University School of Medicine, 1988
  • Mead-Johnson Award for Excellence in Graduate Research, National Student Research Forum, 1988
  • James W. McGlaughlin Award for Excellence in Research in Immunology, National Student Research Forum, 1988

Memberships

  • American Society of Hematology, 1995
  • American Association of Immunologists, 2002
  • Federation of Clinical Immunology Societies, 2011

Professional Activities

  • Associate Editor, Journal of Clinical Investigation (JCI), 2017
  • Ad hoc reviewer for several NIH RO1 and PPG study sections, 2003
  • Ad hoc reviewer for the Welcome Trust (UK), Arthritis Research Campaign (UK), MRC (UK) and Austrian Science Fund (Austria), 2005
  • FDA advisory panel for immunologic devices, 2011
  • Ad hoc reviewer for the Pasteur Institute, France, 2013

Videos & Media

The Bloomberg~Kimmel Institute: Dr. Jonathan Powell

Immunotherapy: Sorting the Hype from the Hope | Lindsey Pujanandez – Science Translational Medicine

Recent News Articles and Media Coverage

Glutamine-blocking drug slows tumor growth and strengthens anti-tumor response, Science Daily, November 8, 2019

Patient Ratings & Comments

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