Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Navi Mumbai, India
National Cancer Institute, National Institutes of Health, Maryland, USA
Indian Institute of Science Education and Research (IISER) Bhopal
After finishing my masters in Biotechnology, I wanted to build my career in the biotech industry and therefore joined Torrent Research Centre in Gandhinagar, Gujarat. Soon after joining, I realized that in order to grow in the industry, one at least needs a PhD, so I acceded to the PhD program at ACTREC, Navi Mumbai under the mentorship of Dr Surekha Zingde. I was studying the tumor antigens eliciting a humoral immune response in oral cancer using proteomic technologies. In the first year of my PhD, I came up with an idea to develop a new method to identify tumor antigens and discussed it with Dr Zingde. She immediately gave the nod to start working on it as it looked promising and interestingly nobody had used it before. I was enthusiastic about it and started working on it, but within a month, a new article got published using the exact same method. It was disheartening but that was the moment, I realized that I like research. Although it was a small incident, it made me realize that I like the thrill of the chase to discover/develop something new and decided to pursue research as my career. During PhD, identification of several isoforms of tumor antigens created my interest in alternative splicing in cancer. Immediately after PhD, I joined Dr Lopa Mishra’s Laboratory at the Georgetown University Medical Centre, Washington DC and studied the role of TGF-β signaling in hepatocellular carcinoma. The training in Dr. Mishra’s lab helped me to understand the role of altered signaling pathways in cancer, which will be helpful in my career in the long run.
My ultimate goal is to contribute to cancer research by unraveling the basic mechanisms that enable cancer cells to churn out aberrant splice products. I realized that in order to understand cancer’s aberrant proteins, I need to thoroughly understand the mechanism of alternative splicing, and I need to know its regulators. Hence, I joined Dr. Shalini Obersoerffer’s Laboratory at NCI-Frederick. Dr. Oberdoerffer’s interests were more focused upon alternative pre-mRNA splicing in lymphocyte development, whereas my long-term goal was to understand aberrant alternative splicing in cancer, but I realized that Dr. Oberdoerffer’s lab could provide me with the training and technical tools to ask the right questions about the mechanism of alternative splicing in cancer cells. In Dr. Oberdoerffer’s lab, we showed a mechanistic link between DNA methylation and alternative splicing through modulation of a DNA binding protein, CTCF (Nature 2011). This finding provided a novel aspect to diverse functions of CTCF and highlighted the role of DNA binding proteins in regulation of alternative splicing in a methylation-dependent manner.
Having obtained the necessary training and expertise in cancer biology, epigenetics, and alternative splicing, I decided to pursue my long-term career goal to study the interplay between epigenetics and alternative splicing in cancer in my own laboratory at IISER Bhopal. Aberrant alternative splicing and epigenetic changes are both associated with various cancers, but epigenetic regulation of alternative splicing in cancer is largely unknown. In the first project that I undertook at IISER Bhopal, we found that the intragenic DNA methylation mediated binding of BORIS at the alternative exon of Pyruvate Kinase (PKM) is associated with cancer-specific splicing that promotes Warburg effect and breast cancer progression. As Warburg effect and hypoxia response pathway cross-talk with each other, it generated my interest in hypoxia in the context of cancer biology which then lead to the development of the proposal to address hypoxia-mediated alternative splicing in cancer. You may find more about the proposal in the research summary.
Finally, I would like to add a short note about my experience with the India Alliance Fellowship application process. Even though the entire process took several months, starting from preliminary application deadline in March 2016 to interview in November 2016, it was smooth and helped me think thoroughly about each and every aspect of the research proposal. The final interview was very professional; the selection committee was helpful and gave me enough time to explain my proposal followed by thoughtful questions on different aspects of the proposal. The India Alliance was prompt in answering all my queries from the application process to start of the Fellowship. My Grant Adviser helped me during the entire process to keep it smooth and hassle free.