Alicia S. Wellman
Institut Pasteur de Bangui
heads the Metabolism, Genes, and Environment Group and holds a secondary appointment in the NIEHS Epigenetics and Stem Cell Biology Laboratory. The long-term goal of the Metabolism, Genes, and Environment Group is to understand the signal transduction that coordinates the gene-environment interaction in biological processes associated with metabolic homeostasis, and investigate how dysregulation of this interplay contributes to pathogenesis of metabolic diseases and aging. To achieve this goal, the group focuses on a family of unique protein modification enzymes called sirtuins. Sirtuins are a highly conserved family of NAD+-dependent protein deacetylases and ADP-ribosyltransferases that target histones, transcription factors, co-factors, as well as numerous other key regulators. The NAD+-dependent activities enable sirtuins to monitor cellular energy status and modulate gene transcription, energy metabolism, and genome stability in response to environmental signals. These activities are also important for cell survival in response to various environmental stressors and are required for lifespan extension provided by calorie restriction (CR) in a number of model organisms. Therefore, sirtuins are considered to be essential genetic factors that directly link the environment to animal physiology, providing a unique opportunity to study gene-environment interactions during the processes of disease and aging.
The role of SIRT1 in transcriptional responses, particularly nuclear receptor mediated signaling The role of SIRT1 in metabolic diseases associated with aging The regulation of SIRT1’s activity in response to various environmental, nutritional, and hormonal cues
Current projects: Investigate the function of hepatic and intestinal SIRT1 in lipid metabolism Study the role of SIRT1 in age-associated metabolic diseases Understand the molecular mechanisms underlying the phosphorylation regulation of SIRT1 Identification of other signaling pathways regulated by sirtuins