Metabolic Regulation of Epigenetic Signaling
Recent studies have shown that many enzymes active in epigenetic mechanisms of genomic regulation are sensitive to the metabolic state of the cell. A major aim of the lab is to understand the mechanisms by which metabolic perturbations influence genomic signaling mediated by chromatin modifying enzymes. Long term goals of this work include: 1) the discovery of biological mechanisms underlying oncometabolite-driven cancers, 2) the development of new diagnostics for cancers driven by metabolic mutations, and 3) the identification of small molecules which inhibit epigenetic modifications through metabolic disruption.
New Acetylation-Based Signaling Mechanisms
Acetyl-CoA links metabolism and signaling by mediating protein and nucleic acid modifications known as acetylations, whose modulation is an emerging paradigm in cancer treatment. A major focus of the laboratory is applying chemical approaches to discover and characterize new enzymatic and non-enzymatic acetylation mechanisms involved in fundamental biology and disease. By expanding the pharmacological map of acetylation-based signaling mechanisms in cancer, these studies aim to uncover new avenues for therapeutic development.