Expertise

My current research goal is to understand the mechanisms by which acute myeloid leukemia stem cells (LSCs) bearing defined genetic and epigenetic mutations alter the normal bone marrow (BM) microenvironment to support the growth of leukemic but not normal hematopoiesis. In collaboration with others in the Prof. Reuben Kapur laboratory we have demonstrated that by inhibiting the activation of ROCK in KIT, BCR-ABL and Flt3-ITD expressing oncogenic cells, which are associated with leukemogenesis induced cell death. While presence of genetic changes in hematopoietic stem and progenitor (HSC/Ps) can regulate transformation in a cell autonomous manner; some of these mutations can also modulate the response of LSCs to the BM microenvironment. We are investigating the role of epigenetic regulators such as Tet2 and Dnmt3a and how mutation (or loss of function) in Tet2 and Dnmt3a co-operate with oncogenic forms of Flt3 receptor tyrosine kinase to results in frank AML. My other ambitious project is to study the role of small GTPases in the regulation of stem and progenitor cell trafficking between the bone marrow and the blood stream and their impact on hematopoietic niche functions including adhesion, homing, engraftment and mobilization of hematopoietic stem and progenitor cells. Our long term goal is to understand the mechanism that control the niche functions by which we can explore the possibilities of utilizing the mobilized HSC for stem cell transplantation and other clinical applications.

Communities
Pediatrics, Pediatrics
Degrees
PhD, Sri Krishnadevaraya University, Biochemistry, 2005
MS, Sri Krishnadevaraya University, Biochemistry, 1997
BS, University of Madras, Biochemistry, 1994