Pere Puigserver, PhD
Associate Professor, Department of Cell Biology, Harvard Medical School
Associate Professor, Cancer Biology, Dana-Farber Cancer Institute
DF/HCC Program AffiliationCancer Genetics
Lab WebsitePuigserver Lab
Research AbstractOur research interests are on the genetic and biochemical mechanisms underlying the control of intermediary metabolism. The precise organization and regulation in time and space of these metabolic pathways are essential to maintain nutrient and energy homeostasis in development, survival and health of an organism. Defects in this control will lead to important metabolic abnormalities detected in cancer, aging, diabetes and obesity. The ultimate goal of our research is to understand the coordination, activities and assembly of these regulatory biochemical processes and to lay the foundation for new therapies for metabolic diseases and cancer.
Our lab focuses on a fundamental biological question: How nutrient and hormonal signals are sensed to control energy and nutrient metabolism. We study how changes in these signals are sensed and provoke transcriptional responses that induce expression of gene sets linked to energy and nutrient metabolic pathways. We use mammalian cells as biological models to identify and analyze these signals, transcriptional components, metabolic gene expression and function. Moreover, we systematically analyze the significance of these findings in the energy and nutrient metabolic context of the whole organism in mouse models. Overall, the complete process is still poorly understood, but we have started to describe how transcriptional components of the PGC-1 pathway such as SIRT1 and GCN5 sense nutrient and energy signals to control glucose and lipid metabolism. In particular, we have begun to decipher how a novel acetylation code in transcriptional coactivators is sensing nutrient signals to adapt cells to maintain their physiological function. We are in the process of identifying novel components of this regulatory metabolic system by using biochemical, genetic, synthetic chemistry and systems biology approaches.