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Your Environment. Your Health.

Metabolism, Genes, and Environment Group

Gene-Environment Interaction in Disease and Aging

Xiaoling Li, Ph.D.
Xiaoling Li, Ph.D.
Principal Investigator
Tel 984-287-3484
Fax 919-541-1898
P.O. Box 12233
Mail Drop F2-11
Durham, N.C. 27709

Research Summary

Xiaoling Li, Ph.D., 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 illustration provides an overview of the research performed by members of the Metabolism, Genes, and Environment Group.
SIRT1 is a vital metabolic sensor that directly couples the environmental signals and cellular metabolic status to the chromatin structure and gene expression, thereby modulating metabolism, reproduction, and development. Those functions of SIRT1 ultimately impact more complex biological phenomena, such as 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 Metabolism, Genes, and Environment Group 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 aging.

Major areas of research:

  • 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

Li earned 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, Ph.D., at Massachusetts Institute of Technology before joining NIEHS in 2007. She has published a number of peer-reviewed articles in leading biomedical journals.

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