Research Summary
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 self-antigen in type-1 diabetes, and also a major risk factor for type-2 diabetes. We are investigating molecular mechanisms driving pathophysiologic changes in pancreatic beta-cells, which are the sole provider of insulin in the human body. 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.
Lab
Lab Website: Fu Lab
Selected Publications
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Lu M and Fu D*. Structure of the zinc transport YiiP. Science, 317:1746-8 (2007). This paper was selected as a Science highlight.
Gupta S, Chai J, Cheng, J, D'Mello R, Chance* MC, and Fu* D. Visualizing the kinetic power stroke that drives proton-coupled Zn(II) transport. Nature 512(7512):101-4(2014)
Merriman C, Huang Q, Rutter GA, Fu D*. Lipid-tuned Zinc Transport Activity of Human ZnT8 Protein Correlates with Risk for Type-2 Diabetes, JBC 291(53):26950-26957. (2016) This work was selected as a JBC paper-of-the-week.
Wan H, Merriman C, Wasserfall HC, Atkinson MA, Mcgrail KM, Liang Y, Fu D*, and Dai H* A novel proteoliposome-based full-length ZnT8 self-antigen for type 1 diabetes diagnosis on a plasmonic platform. PNAS 19;114(38):10196-10201 (2017).
Huang Q, Merriman C, Zhang H, Fu D*. Coupling of Insulin Secretion and Display of a Granule-resident Zinc Transporter ZnT8 on the Surface of Pancreatic Beta Cells, JBC 292(10):4034-4043 (2017).
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