Xiaoyong Yang

453TET-1_DSP_Yang2

A genetically engineered cell line used for probing O-GlcNAc signaling. The enzyme (green) that catalyzes O-GlcNAc cleavage is induced by tetracycline withdrawal in HeLa Tet-Off cells. The cell nuclei (red) are stained by TO-PRO-3.

Our laboratory is interested in the nutritional and circadian regulation of metabolic homeostasis and its implications in human diseases including diabetes, obesity, cancer, and aging. The long-term goal of our research is to understand mechanisms of cell signaling that govern intermediary metabolism in response to environmental and genetic cues, and to design rational strategies to battle metabolic diseases.

Like phosphorylation, acetylation, methylation and ubiquitination, the cell uses an amino sugar, called N-acetylglucosamine (O-GlcNAc), to regulate protein function. Numerous cytoplasmic and nuclear proteins are modified by O-GlcNAc. This dynamic and reversible posttranslational modification is emerging as a key regulator of diverse cellular processes. Since O-GlcNAc levels fluctuate with the availability of glucose, free fatty acids, uridine and glutamine, it has been hypothesized that O-GlcNAc serves as a nutrient sensor. Our first goal is to elucidate how O-GlcNAc acts as a molecular switch that couples nutrient cues to cellular regulation of signal transduction, transcription and protein degradation, and how perturbations in this modification contribute to human diseases including diabetes, cancer, and aging.

The circadian clock controls approximate 24-hr behavioral and physiological cycles that prepare an organism for daily environmental changes. Our second goal is to depict molecular pathways that couple the circadian clock to metabolic physiology. There are the emerging links between circadian rhythm disorders and diabetes, obesity, cardiovascular disease, and aging. We plan to explore novel strategies for treating these interrelated diseases.

To approach these goals, a combination of cutting-edge tools are employed, including biochemistry, molecular and cellular biology, mouse genetics, genomics, proteomics, metabolomics, and physiology.

Yang_fig_1

A wheel of time. The circadian clock regulates diverse physiological processes including metabolism, reproduction, central nervous system (CNS) functions, growth and differentiation, and immune responses. A superfamily of nuclear receptors (NRs) is proposed to mediate two-way communications between molecular clocks and the physiological processes through a myriad of transcriptional circuits.

Opportunities

Positions are available for highly motivated graduate students and postdoctoral fellows who are interested in exploring the frontier of research on metabolic physiology.