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 patientsâ€™ samples.
My immediate interest lies in
- Understanding the drug resistance mechanisms in leukemia models and solid tumors against targeted therapies.
- Generation of Leukemia models
- Identification of novel therapeutic agents in Leukemia
- Independent Postdoctoral Fellow, Dept. Of Haematology and Oncology, Albert-Ludwig University, Germany.
- Postdoctoral Fellow, Klinikum Rechts Der Isar, Dept. Of Haematology and Oncology, Technical University of Munich, Germany.
- Ph.D. Klinikum Rechts Der Isar, Dept. Of Haematology and Oncology, Technical University of Munich, Germany.
- Research Fellow, Dept. of Biochemistry, Hyderabad Central University, Hyderabad, India.
- Masters in Biotechnology, Calicut University, Kerala, India.
- American Society of Haematology annual meeting held in New Orleans (USA). Title: Ruxolitinib mediated paradox JAK2 hyperphosphorylation is due to protection of activation loop tyrosines from phosphatases.
- American Society of Haematology annual meeting held in New Orleans (USA). Title: JAK2 inhibitor (Ruxolitinib) resistance is mediated by the generation of 45- kDa JAK2 variant which alters the kinase domain of JAK2.
- American association of cancer research annual meeting held in Washington. Title: An F604S exchange in FIP1L1-PDGFRA modulates FIP1L1- PDGFRA protein stability in a SRC- and SHP-2 dependent manner.
- DGHO (German hematology association) annual meeting held in Berlin. Title: Identification of a novel mode of kinase inhibitor resistance: An F604S exchange in FIP1L1-PDGFRA modulates FIP1L1-PDGFRA protein stability in a SRC-dependent manner.
- American society of hematology annual meeting held in Sanfransisco. Title: JAK2V617F requires an intact SH2 domain for constitutive activation and induction of a myeloproliferative disease.
- Awarded a focus grant from Bayer Grants 4 Targets scheme for the title â€œIdentification of novel drug targets in CSF3R mutations mediated chronic Neutrophilic Leukemia (CNL) and atypical chronic myeloid Leukemia (aCML).
- Awarded with "young investigator prize" for the Title â€œIdentification of a novel mode of kinase inhibitor resistance: An F604S exchange in FIP1L1-PDGFRA modulateFIP1L1-PDGFRA protein stability in a SRC- and SHP-2 dependent mannerâ€ by German Hematology Association (DGHO)
- Awarded for â€œAbstract Achievement Award for the 2013 ASHâ€ (American association of Hematology) annual meeting held in New Orleans, USA
- Selected for "best of the Annual meeting" 2013 DGHO, Ã–GHO and SGHSSH (German, Austria and Switzerland tri nation hematology association) in Vienna.
- Awarded with "best presentation" prize in a 22nd (2013) work-shop conducted by Bio- Thera Stiftung, Uniklinikum Freiburg, Germany.
- Selected for "merit travel award" in 2011 and 2013 by EHA (EuropeanHematology Association) held in London and Sweden.
- Selected for the finalist in AACR 2010 (American association of cancer research) "Scholar- in -training award".