Solutions and Goals

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Cell-surface membrane proteins provide entry points for therapeutics and biomarker discovery.

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ZnT8, a zinc-specific transporter, is specifically expressed in the pancreatic islet. Our research has identified ZnT8 as a dynamic cell-surface marker for beta cells.

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We have discovered and developed a ZnT8-targted drug delivery platform for pancreatic islets.

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We have successfully developed an islet-targeted therapy to establish efficacy and safety in a mouse model of T1D. 

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We are developing surrogate endpoints to facilitate clinical evaluation and regulatory approval.

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Our long-term goal is to eliminate the necessity for frequent insulin injections and pancreas transplants for individuals facing severe diabetes.

References

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1. Huang, Q., Merriman, C., Zhang, H., and Fu, D. (2017) Coupling of Insulin Secretion and Display of a Granule-resident Zinc Transporter ZnT8 on the Surface of Pancreatic Beta Cells. J Biol Chem 292, 4034-4043

2. Guo, Z., Kasinathan, D., Merriman, C., Nakayama, M., Li, H., Li, H., Xu, C., Wong, G. W., Yu, L., Golson, M. L., and Fu, D. (2023) Cell-Surface Autoantibody Targets Zinc Transporter-8 (ZnT8) for In Vivo beta-Cell Imaging and Islet-Specific Therapies. Diabetes 72, 184-195

3. Kasinathan, D., Guo, Z., Sarver, D. C., Wong, G. W., Yun, S., Michel, A., Yu, L., Golson, M. L., and Fu, D. (2023) Cell-surface ZnT8 antibody prevents and reverses autoimmune diabetes in mice. Diabetes In review

4. Gu, Y., Merriman, C., Guo, Z., Jia, X., Wenzlau, J., Li, H., Li, H., Rewers, M., Yu, L., and Fu, D. (2021) Novel autoantibodies to the beta-cell surface epitopes of ZnT8 in patients progressing to type-1 diabetes. J Autoimmunity 122, 102677

5. Wan, H., Merriman, C., Atkinson, M. A., Wasserfall, C. H., McGrail, K. M., Liang, Y., Fu, D., and Dai, H. (2017) Proteoliposome-based full-length ZnT8 self-antigen for type 1 diabetes diagnosis on a plasmonic platform. Proc Natl Acad Sci U S A 114, 10196-10201

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