.jpg "Biplab Dasgupta, Ph.D photo")
Cincinnati Children's Hospital
Cincinnati, United States
Presently I am a Professor in the division of Oncology at Cincinnati Children's Hospital. Broadly, my lab is interested in understanding the mechanisms of cancer development and progression. We work at the interface of nutrient and energy sensing, signaling and tumor metabolism to examine metabolic genes that regulate cancer development. We are also keenly interested in understanding the molecular mechanisms by which environmental factors (carcinogens, diet, stress and lifestyle) interact with genes and with each other to disrupt tissue homeostasis and regulate cancer development. The evolutionarily conserved AMPK - mTOR pathway is crucial for the homeostatic regulation of energy and nutrients and therefore plays an important role in growth, stress and therapy resistance of tumors. Using genetically engineered mouse models and high-grade brain tumor models in mice, we investigate the complex and context-dependent function of the AMPK-mTOR axis in the normal brain and brain tumors. Through network integration analysis of metabolomics and transcriptomics data, we identify metabolic susceptibility of brain tumors. For example, we showed that AMPK is a positive regulator of glycolysis in the CNS, and is a novel target in glioblastoma. We discovered that the lipogenic enzyme SCD undergoes genetic and epigenetic alterations in PTEN null tumors and is a therapeutic target in a subset of glioblastoma. We identified that ATIC is a rate limiting enzyme in the de novo purine synthesis pathway and a unique target in DIPG - a lethal pediatric brain tumor. We have also identified that the pyruvate metabolizing enzyme PDH that facilitates entry of glucose carbons to the TCA cycle is a biomarker for mitochondrial complex I inhibitor sensitivity in a subset of glioblastoma. A new research direction in my laboratory is to undestand the mechanisms by which diabetes increases risk for cancer incidence, development and progression.