Dr. Siva Hari Prasad Gorantla
School of Life Sciences, University of Hyderabad (P.O. Central University)
Theme of my research work is understanding the molecular mechanisms involved in leukemiagenesis and identification of novel therapeutic agents in leukemia. During my doctoral and postdoctoral studies, I have extensively investigated the molecular pathogenesis of several hematological malignancies including myeloproliferative neoplasms (MPNs), Acute myeloid leukemia (AML), Chronic Eosinophilic leukemia (CEL) and Chronic Neutrophilic Leukemia (CNL) etc. Main focus of my research work involves generation of leukemia models and understanding the drug resistance mechanisms against targeted therapies.
During my studies, I established a imatinib mediated resistance in FIP1L1-PDGFRA positive chronic eosinophilic leukemia model, where F604S exchange in FIP1L1-PDGFRA stabilize the target protein level by preventing the SRC and CBL mediated ubiquitination of FIP1L1-PDGFRA. This study highlights the protein destabilization agents will be a novel therapeutic agent in CEL patients.
My studies identified another resistance mechanisms in myeloproliferative diseases against ruxolitinib, where drug resistance is mediated by generation of 45-kDa JAK2 novel variant which alters the active-conformation of JAK2 to inactive. Based on these finding we want to extent our findings to other leukaemia models and solid tumours against targeted therapies and try to identify novel therapeutic agents in these cancer models. For this purpose, we actively collaborate with clinicians and systems biologist for next generation sequencing (NGS) of both cell lines and patients’ samples.
My immediate interest lies in