Pavan Reddy, M.D.
Dr. Pavan Reddy received a medical degree from Osmania University, India. He then continued his training at the University of Michigan where he completed a three-year residency in internal medicine, a hematology/oncology fellowship and a one-year fellowship in blood and marrow transplantation. Following the completion of his fellowship, he joined the faculty of the University of Michigan in 2002. Dr. Reddy's research interests focus on understanding the immunobiology of graft-versus-host disease (GVHD) in the laboratory and translating the insights gained into improved treatments for patients with GVHD. Associate Division Chief (basic Research) and Co-Director, Leukemia, Lymphoma and BMT Program at the UMCCC.
Allogeneic bone marrow transplantation is the most potent form of immune therapy against a number of malignant diseases by its graft-versus-leukemia/tumor effect. However, acute graft-versus-host disease (GVHD) the major complication of allogeneic BMT is tightly linked to the Graft-versus-leukemia (GVL) effect. The immunobiology of GVHD and GVL responses are complex and cytokines are critical for regulating immune responses. My laboratory focused on understanding the role of cytokines and cellular effectors in the biology of GVHD/GVL by utilizing well-characterized mouse models of allogeneic BMT. Our laboratory specifically focuses on the following three aspects of GVHD / GVL.
- Evaluate the role of IL-18: We have previously shown that a single cytokine, interleukin-18, can modulate GVHD/GVL responses through differential mechanisms. Future studies are being planned on examining the cellular and molecular pathways that are responsible for these differential mechanisms of action by IL-18.
- Development of novel immuno-modulators: We have recently discovered that histone deacetylase inhibitors, the anti-neoplastic drugs, are a novel suppressors of the secretion of multiple pro-inflammatory cytokines and can also regulate the function of antigen presenting cells / T cella and modulate GVHD and GVL. Some of these exciting preliminary results have been published in the journal PNAS. We are in the process of dissecting the mechanisms of immune modulation by alteration of histone acetylation and the effect of such modulation on GVHD/GVL.
- Determine the role of direct and indirect antigen presentation in GVHD and GVL: We are investigating the role direct antigen presentation by GVHD target / tumor cells or by cross-presentation by host derived APCs or donor APCs in mediating GVH responses. We are also exploring the role of allo-antigen expression in these responses.
Reddy P, Sun Y, Toubai T, Durán-Strüück R, Clouthier SG, Weisiger E, Maeda Y, Tawara I, Krijanovski O, Gatza E, Liu C, Malter C, Mascagni P, Dinarello CA, Ferrara JLM. Histone deacetylase inhibition modulates indoleamine 2,3-dioxygenase dependent dendritic cell functions and regulates experimental graft-versus-host disease. Journal of Clinical Investigation 2008,;118:2562-2573.
Toubai T, Sun Y, Reddy P. GVHD pathophysiology: is acute different from chronic? Bailliere's Best Practice and Research: Clinical Hematology 2008, 21:101-117.
Paczesny S, Krijanovski O, Braun TM, Choi S, Clouthier SG, Kuick R, Misek DE, Cooke KR, Kitko CL, Weyand A, Bickley D, Jones D, Whitfield J, Reddy P, Levine JE, Hanash SM, Ferrara JL. A biomarker panel for acute graft versus host disease. Blood 2009, 113:273-278.
Toubai T, Shono Y, Nishihira J, Ibata M, Suigita J, Kato N, Ohkawara T, Tone S, Lowler KP, Ota S, Tanaka J, Asaka M, Reddy P, Imamura M. Serum macrophage migration inhibitory factor (MIF) levels after allogeneic hematopoietic stem cell transplantation. Int J Lab Hematol 2009, 31:161-168.
Khaled Y, Abidi MH, Janakiraman N, Kato K, Levine JE, Reddy P, Medina M, Peres E, Hanbali A, Mineishi S. Outcomes after auto-SCT in African Americans with multiple myeloma. Bone Marrow Transplantation 2009, 43(11):845-51.
Ferrara JL: Levine JE, Reddy P, Holler E. Graft-versus-host disease. The Lancet, 2009 May 2;373(9674):1550-61.
Khaled Y, Reddy P, Krijanovski O. Emerging drugs for acute graft-versus-host disease. Expert Opinion Emerging Drugs 2009, 14(2):219-32.
Sun Y, Chin YE, Weisiger E, Malter C, Tawara I, Toubai T, Gatza E, Mascagni P, Dinarello CA, Reddy P. Cutting edge: Negative regulation of dendritic cells through acetylation of the nonhistone protein STAT-3. Journal of Immunology, 2009 May 15;182(10):5899-903.
Khaled Y, Mellacheruvu S, Reddy P, Peres E, Mineishi S. Long-term outcomes following myeloablative allogeneic transplantation for multiple myeloma compared to autologous transplantation and the impact of graft-versus-myeloma effect. Bone Marrow Transplantation, 2009, 44(5):325-6. Letter to the Editor.
Choi S, Reddy P. Graft-versus-host disease. British Medical Journal Point of Care. 2009. Epocrates Online.