The University of Utah, Salt Lake City, USA
Indian Institute of Chemical Biology, Kolkata
The world of mathematics was always fascinating to me during my school days. I wanted to pursue my higher studies in the field of mathematics. However, it was during the days of my undergraduate studies, my interests in the field of molecular biology gradually overtook my inclination towards field of mathematics. The eye-opener for me was the "central dogma" of molecular biology describing transmission of coded genetic information from DNA to protein for everyday functions of an organism. Slowly but steadily, I became interested in the field of gene expression over the years.
During those days, lot more was known about mechanisms of prokaryotic transcriptional regulation than eukaryotic one. Also, it started becoming clear that substantial number of human cancers are associated with misregulation of their cellular expression at the level of transcription. So, mechanistic understanding of transcriptional regulation in detail and deciphering the role of any given oncogenic or tumor suppressor factor(s) in that processes was a key challenge for combating various human cancers through targeted therapeutic approaches. All these further motivated me in pursuing my graduate career in the field of eukaryotic transcriptional regulation.
Therefore, I joined the laboratory of David J. Stillman at the University of Utah for my graduate thesis work to study transcriptional regulation by human counterpart of the FACT complex (composed of two subunits Spt16 and SSRP1) in yeast (yFACT). It was during the days of my graduate studies, I came to know the real "awesome power of yeast genetics" to address transcriptional regulatory mechanisms of yFACT in association with several factors including ATP-dependent chromatin remodelers (e.g. Swi/Snf complex), post-translational histone modifiers (e.g. Gcn5 for acetylation; Set1, Set2, and Dot1 for methylations etc.), and readers of these modification marks (e.g. bromo-, chromo-, and PHD-domain containing factors).
Towards studying direct analyses of transcriptional misregulation caused by cellular oncogenic proteins, I joined the pioneering laboratory of Bob Roeder at The Rockefeller University as a postdoctoral fellow to study mechanisms of transcriptional misregulationby leukemogenic MLL fusion protein complexes. The human MLL gene encodes histone H3-Lysine 4 methyl transferase and regulates expression of key HOX gene clusters during different stages of haematopoiesis. Balance translocation of N-terminus of MLL with >80 other fusion partners give rise to various acute leukemias of poor prognosis. Although over last couple of years, few studies including ours have provided important mechanistic understanding of transcriptional regulation by fusion partners as well as corresponding MLL fusion protein complexes, lot more is unknown in relation to detailed mechanistic regulation and disease specificity. Using various biochemical and cell biological approaches, we aim to further study the mechanistic role of novel interacting partners in transcriptional regulation and leukemic disease pathogenesis by MLL fusion.