Matthew Vander Heiden, MD, PhD

Basic science, cancer cell metabolism, target metabolism in cancer

Recently, there has been a resurgent interest among the scientific community to understand cancer cell metabolism. My research has focused on understanding how cancer cells convert nutrients into the cellular components needed to proliferate. We have made inroads into this basic science question by studying the form of a protein involved in glucose metabolism that is present at high levels in all cancer cells. This protein contributes to the form of metabolism carried out by tumor cells and is different from the enzyme found in many normal tissues because it can communicate with cell growth signal. These growth signals turn off activity of the enzyme. This finding demonstrated a heretofore unappreciated biochemical link between cell growth signals and regulation of a metabolic pathway. My laboratory's current efforts have been to test the hypothesis that cell growth signals reprogram metabolism to support the distinct energetic needs of proliferating cells. Unlike normal cells, which rely heavily on ATP to support housekeeping functions, proliferating cells have the additional requirement of duplicating mass. This large synthesis requirement for lipids, amino acids, and nucleotides requires an excess of carbon and reducing equivalents. Metabolic processes in proliferating cells must be reprogrammed to balance ATP production with the production of building blocks required for growth. Efforts to understand how metabolism is reprogrammed to facilitate accumulation of biomass have furthered our understanding of glucose metabolism in proliferating cells. In addition, we are using this knowledge to explore novel therapeutic approaches to target tumor cell metabolism for therapy.