Metabolic Coordination of Tumor Suppression
Our laboratory studies the mechanisms that link nutrient metabolism to cell fate decisions in stem cells and cancer cells. Cells metabolize available nutrients in order to provide the building blocks required for growth and proliferation, response to stressors, and execution of specialized cellular functions. Metabolites can also serve as signals that regulate diverse cellular processes. For example, specific metabolites are required for the function of enzymes that modify DNA and the histone proteins that guard access to DNA. In this manner, cells integrate information about their metabolic state in order to control expression of genes that determine cellular identity and function. During normal embryonic development, controlled changes in modifications on DNA and DNA-associated histone proteins allow expression of specific genes required for embryonic cells to differentiate into mature cell types. These precise modes of gene regulation are subverted in cancer, where disrupted nutrient metabolism and aberrant profiles of DNA and histone modifications accompany malignant transformation. Studying intracellular metabolic pathways can therefore yield important insights into how individual cell types support proliferation and establish cell identity in both normal development and in disease.
We study metabolic pathways in two different cellular systems: embryonic stem cells and cancer cells. We combine genetic and metabolomics approaches to investigate how normal and malignant cells rewire metabolic pathways to support growth and how these metabolic changes influence cellular programs that control self-renewal and differentiation. By studying both stem cells and cancer cells, we aim to answer fundamental questions about how cells regulate the commitment to differentiation and how failure to execute terminal differentiation can underlie diseases such as cancer.