Cancer Immunology and Immunotherapy Research interests: Tumor Immunology, Dendritic cell differentiation; regulation of T cell activation by antigen-presenting cells; role of indoleamine 2,3-dioxygenase (IDO) in Immune tolerance.clinical trials of IDO inhibitors in cancer and HIV. 1120 15th Street CN 4133 Augusta, GA 30912 Office: (706) 721-8749 E-mail: msharma@georgiahealth.edu

Sharma, Madhav, Ph.D., M.B.A

1120 15th Street CN 4133 Augusta, GA 30912 Office: (706) 721-8749 E-mail: msharma@georgiahealth.eduMember, GRU Cancer Center
Senior Research Scientist
Cancer Immunology, Inflammation and Tolerance Program

1120 15th Street
CN 4133
Augusta, GA 30912
Office: (706) 721-8749
E-mail: msharma@georgiahealth.edu

IFL Link | PubMed Link

 

Professional Overview

Madhav Sharma, PhD is a member of the Cancer Immunology, Inflammation and Tolerance Program, GRU Cancer Center.  Dr. Sharma earned his Ph.D (1991) from the National Institute of Immunology, (Jawaharlal Nehru University) New Delhi, India under supervision of Dr. GP Talwar. He also holds Master of Business Administration (2007) from Augusta State University (Now Georgia Regents University).  Dr. Sharma is working as Senior Research Scientist in the Department of Pediatrics in the Medical College of Georgia at GRU.

 

Current Research

His current research focuses on tumor immunology, and molecular mechanisms of immune suppression and tolerance. Dr. Sharma works with Dr. Munn and is involved in studies of regulation of T cell activation by tolerogenic dendritic cells and regulatory T cells (Tregs) in the setting of cancer.  A major focus of the laboratory is the immunoregulatory role of tryptophan metabolism via the enzyme indoleamine 2,3-dioxygenase (IDO).  Dr. Sharma is supported by grants from the National Cancer Institute as Co-Investigator.

Active projects include:

  • Preclinical and basic-science studies of the role of IDO-expressing plasmacytoid dendritic cells (pDCs) in tumor immunology, with an emphasis on how these tolerogenic antigen-presenting cells suppress anti-tumor immune responses via IDO and downstream pathways (AhR and GCN2).
  • Mechanistic studies of strategies to enhance anti-tumor immune response using vaccines
    in combination with inhibitors of immunosuppressive pathways (IDO, PD-1 and CTLA-4).
  • Control of regulatory T cell (Treg) suppressor activity by IDO, and functional activity of CD4+ helper T cells and reprogrammed Tregs.

Key References

  • Sharma MD, Huang L, Shi H, Lee E, Wilson JM, Lemos H, Pan F, Blazer BR, Pardoll DM, Mellor AL, Munn DH.   An inherently bi-functional subset of Foxp3+ Treg/T-helper cells is controlled by the transcription factor Eos. Immunity, 38 (5) pp.998-1012 (2013)

{Preview by Rieder, and  Shevach, “ Eos, Goddess of Treg Cell Reprogramming” Immunity, 38 (5) pp.949-950 (2013).

  • Sharma MD, Hou DY, Baban B, Koni PA, He Y, Blazer BR, Mellor AL,  Munn DH.   Reprogrammed Foxp3+ Tregs provide essential help to support cross presentation CD8+ T cell priming in naïve mice. Immunity  33 (6) pp.942-954 (2010)

{Preview by  Piccirillo “ Treg’s Alter Ego: An Accessory in Tumor Killing” Immunity, 33 (6) pp.937-939 (2010)

  • Sharma MD, Hou DY, Liu Y, Koni PA, Metz R, Chandler P, Mellor AL, He Y, Munn DH*.  Indoleamine 2,3-dioxygenase controls conversion of Foxp3+ Tregs to TH17-like cells in tumor-draining lymph nodes. Blood 113:6102 – 6111 June (2009)
  • Sharma MD, Baban B, Chandler P, Hou DY, Singh N, Yagita H, Azuma M, Blazar BR, Mellor AL, Munn DH.  Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2,3-dioxygenase.  J Clin Invest  117:2570-2582 (2007)
  • Munn DH, Sharma MD, Baban B, Harding HP, Zhang Y, Ron D, Mellor AL.  GCN2 kinase in T cells mediates proliferative arrest and anergy induction in response to indoleamine 2,3‑dioxygenase.  Immunity 22:633-642 (2005)
  • Munn DH, Sharma MD, Hou D, Baban B, Lee JR, Antonia SJ, Messina JL, Chandler P, Koni PA, Mellor AL.  Expression of indoleamine 2,3-dioxygenase by plasmacytoid dendritic cells in tumor-draining lymph nodes.  J Clin Invest 114:280-190 (2004)
  • Munn DH, Sharma MD, Mellor AL.  Ligation of B7-1/B7-2 by human CD4+ T cells triggers indoleamine 2,3-dioxygenase activity in dendritic cells.  J Immunol 172:4100-4110 (2004)
  • Munn DH, Sharma MD, Lee J, Jhaver KG, Johnson TS, Keskin DB, Marshall B, Chandler P, Antonia SJ, Burgess R, Slingluff CL Jr, Mellor AL.  Potential regulatory function of human dendritic cells expressing indoleamine 2,3-dioxygenase.  Science 297:1867-1870 (2002)