Biochemistry & Molecular Biology, Cell Biology, Cellular Mechanism of Disease
University of Michigan
Billions of years of evolution in an oxygen environment has determined that oxygen occupies a central feature of our biology. Physiological hypoxia tends to be acute in nature and has cell specific responses thought to be important in maintaining cellular homeostasis. Whereas, pathological hypoxia is chronic and is hypothesized to be a driving force in tissue damage and cancer. The major goal of our research program is to determine the molecular mechanisms by which oxygen signaling regulate homeostasis, inflammation and cancer. Regulation of hypoxia-mediated genes is dependent on the nuclear transcription factor, hypoxia inducible factor (HIF). HIF signaling is critical in the adaptive response to low oxygen levels by activating genes involved in metabolism, angiogenesis, cell survival and iron metabolism. Using the latest in cell biology and mouse transgenic technology we have developed novel animal models and cell lines to study accurately the role of oxygen sensitive transcription factors in health and disease. These studies have revealed new pathways that have not previously been associated with hypoxia, and identified HIFs as major therapeutics targets in several diseases.