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Dax-Fu

Dax Fu

Research Interests

Zinc physiology with a focus on structure, function and regulation of zinc transporters.

Zinc transporters regulate subcellular zinc distributions to ensure proper metalation of numerous zinc enzymes and signaling molecules. Fluctuations of cytosolic zinc concentration constitute the basis for zinc signaling, but also challenge zinc homeostasis with broad disease implications. Our research is focusing on ZnT8, a pancreatic zinc transporter that mediates zinc enrichment in insulin secretory granules. ZnT8 is a major autoantigen in type-1 diabetes. A nonsynonymous variant of ZnT8 is also a validated risk factor contributing to the susceptibility of type-2 diabetes. We are investigating molecular mechanisms underlying the disease risk. Enabling technologies have been developed to study the structure and dynamic of ZnT8 at the molecular level, and its physiological roles in regulating insulin processing and secretion in beta cells. Research findings are being translated to new diagnostic tools and therapeutic interventions for early detection and treatments of diabetes.

Steven Claypool PhD, MA

Steven Claypool

Research Interests

Phospholipids are the building blocks of biological membranes which enable cells to separate biochemical pathways, establish specialized functions that can respond when appropriate, and adapt to constantly fluctuating metabolic conditions. My laboratory’s research focus is on the underappreciated contribution of the mitochondrion to cellular phospholipid metabolism. In addition to being the sole producer of the canonical mitochondrial lipid, cardiolipin (CL), the mitochondrion hosts one of the two major pathways in a cell for the production of phosphatidylethanolamine (PE). Ablation of the mitochondrial capacity to synthesize either CL or PE is embryonically lethal in mice. Moreover, in the yeast Saccharomyces cerevisiae, the combined absence of CL and PE is synthetically lethal. Using a combination of yeast and mammalian cell culture models, my lab currently has three major ongoing projects centered on different aspects of mitochondrial phospholipid metabolism in health and disease. The research objectives of our current projects are:

  1. To fill in the numerous structural and cell biological gaps in our understanding of the mitochondrial phosphatidylethanolamine biosynthetic pathway.
  2. To determine the physiological function(s) of TAZ-based CL remodeling.
  3. To understand how CL can influence the structure/function of a membrane protein, the ADP/ATP carrier, at a molecular level.

The long term goal of our basic research is to understand lipid assembly and remodeling pathways in the mitochondrion and relate deficits in these processes to human disease.

Publications

Bibliography

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