Seminar Abstract:
This seminar topic concerns fundamental issues of cell growth and development as they relate to human disease and therapeutic intervention. Efforts are directed towards understanding human cancer as a disease of uncontrolled cell growth and development. A common theme within this biology is a rewiring of metabolism to support and drive these processes. At the core of this effort lies the utilization of computational modeling and high throughput technologies. Using these tools, I have studied the effects of an alternative glycolytic pathway observed in proliferating cells that I recently identified. These efforts have enumerated several principles of glycolytic regulation in growing cells. Towards this end, I have defined and characterized a metabolic pathway that is genetically selected for and drives the development of human cancer. This pathway involves the diversion of glycolytic flux into de novo serine metabolism through phosphoglycerate dehydrogenase (PHGDH). This direction has also led to the study of problems in stem cell biology and cell fate determination that I will discuss. Together, these findings define a systems biology approach through combining these mathematical tools with an integration of genetics, biochemistry, and cell biology along with high-throughput technologies such as mass spectrometry. Investing such effort I believe has the potential to fundamentally alter our understanding of disease biology and lead to innovative therapies.