Cellular function and differentiation depend on an ability to read environmental cues and to execute a gene expression program that is appropriate to time, place and context. Nutrient availability is among the most important signals to which cells respond. Importantly, nutrients are not only transmitted from outside an organism, i.e., by feeding, but are also transmitted from cell to cell and from tissue to tissue. Metabolic control of gene expression is critical to the maintenance of cellular longevity. Dysregulation of the nutritional control of gene expression underlies a series of conditions including nondetection of satiety, which can lead to obesity and diabetes, and diseases such as cancer.
Our laboratory is engaged in several projects that dissect specific problems in the metabolic control of gene expression. In particular, we are interested in how changing environmental conditions lead to reversible transfer of two carbon, i.e. acetyl, and one carbon, i.e. methyl, groups to proteins and DNA, respectively. These processes are fundamentally important because two carbon transfers link carbohydrate and fat metabolism to nicotinamide adenine dinucleotide (NAD) biosynthesis and because one carbon transfers link the folate cycle and methionine biosynthesis to S-adenosyl methionine metabolism. Trainees in our group are engaged in interdisciplinary projects, performing protein purification, enzymology, structural biology, yeast and somatic cell genetics, genomics, and chemical biology.