Issam Ben-Sahra, PhD
Assistant Professor, Biochemistry and Molecular Genetics; Feinberg School of Medicine
My current research is geared toward understanding the impact of metabolic pathways controlled by mTOR, a nutrient-sensing regulator of cell growth, on the properties of cells and tumors with specific upstream oncogenic pathways activated. I discovered that mTORC1 signaling through S6K1, controls the de novo pyrimidine synthesis pathway by promoting the phosphorylation of the rate limiting enzyme CAD in response to growth factors or oncogenic signaling. I also uncovered that mTORC1 through regulation of the metabolic enzyme MTHFD2 can stimulate metabolic flux through the mitochondrial tetrahydrofolate cycle producing one carbon unit to sustain de the novo purine synthesis pathway. As mTOR activation is common to a majority of human tumors, these studies characterizes metabolic changes common to tumor cells that differentiate them from their tissue of origin. These metabolic differences promote tumor growth but also offer unique avenues for therapeutic intervention, which will be tested in preclinical models in this study.