Past PhD Projects

We are currently focusing on developing new strategies to make allogeneic Bone Marrow Transplantation (BMT) safer and more effective. One of our focus areas in this setting is the development of strategies against graft versus host disease (GvHD), the most common complication of allogeneic transplantation. To address this problem, we are developing Withaferin-A (an immunomodulatory phytochemical) as a potential candidate against GvHD and the initial results are encouraging. We are currently investigating the effect of Withaferin-A on the Graft versus Tumor (GvT) response which is a prerequisite before any drug can be considered as a candidate for anti-GvHD prophylaxis.

Allogeneic hematopoietic stem cell transplantation (alloHSCT) is an important treatment modality for leukaemia. T-cells in the graft offer beneficial graft-versus-leukemia (GVL) action by eliminating residual cancer cells that escape radio- or chemotherapy. Nevertheless, about 40-60% patients develop a severe complication called acute GvHD, wherein the allogeneic T-cells mount an immune reaction against host tissues. Limited efficacy and high toxicities of current prophylactic and treatment regimens for GvHD, necessitate development of novel prophylactic agent for acute GvHD which preserves the GVL activity of the graft. Our study aims to screen and develop phytochemicals with potent immunosuppressive activity for GVHD prophylaxis. We have developed a murine model of acute GvHD based on complete MHC-mismatch to evaluate prophylactic efficacy of target compounds in vivo (Fig 1). The current work in the lab is focuses on evaluating in vivo prophylactic efficacy and understanding the cellular mechanism of action of prophylactic action of target compounds for GVHD prophylaxis.