Xiaoling Li, Ph.D.
Signal Transduction Laboratory / Metabolism, Genes, and Environment Group
Building 101, Room F239A
111 T.W. Alexander Drive
Research Triangle Park, NC 27709
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/or 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 us a unique opportunity to study gene-environment interactions during the processes of disease and aging.
The mammalian genome consists of seven sirtuins, collectively known as SIRT1 to SIRT7. They are expressed in different tissues with distinct subcellular localizations. The laboratory focuses on SIRT1, the most conserved mammalian sirtuin. Using mouse and cultured cells as model systems, the group combines molecular, cellular, and genetic approaches to study the role of SIRT1 in the regulation of metabolism, stress response, reproduction, and ultimately aging.
Here are some areas of research: (1) The role of SIRT1 in transcriptional responses, particularly nuclear receptor mediated signaling; (2) The role of SIRT1 in metabolic diseases associated with aging; (3) The regulation of SIRT1's activity in response to various environmental, nutritional, and hormonal cues.
Xiaoling Li, Ph.D., heads the Metabolism, Genes, and Environment Group within the Laboratory of Signal Transduction (LST) of National Institute of Environmental Health Sciences (NIEHS). She received her Bachelor degree in Biochemistry from Peking University in China in 1994, her Master degree in Molecular Biology from Institute of Biophysics of Chinese Academy of Sciences in 1997, and her Ph.D. in Biological Chemistry from the Johns Hopkins School of Medicine in 2002. She was a Leukemia & Lymphoma Society postdoctoral fellow in the laboratory of Leonard Guarente at Massachusetts Institute of Technology before joining NIEHS in 2007.
Guo X, Kesimer M, Tolun G, Zheng X, Xu Q, Lu J, Sheehan JK, Griffith JD, Li X. The NAD(+)-dependent protein deacetylase activity of SIRT1 is regulated by its oligomeric status. Sci Rep. 2012;2:640.
Purushotham A, Xu Q, Lu J, Foley JF, Yan X, Kim DH, Kemper JK, Li X. Hepatic deletion of SIRT1 decreases hepatocyte nuclear factor 1α/farnesoid X receptor signaling and induces formation of cholesterol gallstones in mice. Mol Cell Biol. 2012;32(7):1226-36.
Guo X, Williams JG, Schug TT, Li X. DYRK1A and DYRK3 promote cell survival through phosphorylation and activation of SIRT1. J Biol Chem. 2010;285(17):13223-32.
Purushotham A, Schug TT, Xu Q, Surapureddi S, Guo X, Li X. Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation. Cell Metab. 2009;9(4):327-38.
Li X, Zhang S, Blander G, Tse JG, Krieger M, Guarente L. SIRT1 deacetylates and positively regulates the nuclear receptor LXR. Mol Cell. 2007;28(1):91-106.