High throughput methods to identify beta cell modulators
Beta-cell death, and the consequent deficiency in insulin secretion, is a key feature of type 1 diabetes. For decades, the standard of care for this disease has been insulin therapy by intramuscular injection. Current approaches to develop new treatments have prioritized islet transplantation and directed stem-cell differentiation, while many technological advances have focused on glucose detection and insulin delivery. While cell-based treatments show promise, a chemical intervention capable of restoring glycemic control in type 1 diabetes would have enormous impact clinically, by enabling an in vivo pancreatic effect while avoiding the need for immunosuppression. Bridget’s group is developing phenotypic-cell based assays to find compounds that increase human beta-cell proliferation, that can protect beta cells from the inflammatory processes of diabetes progression, or that can induce beta-cell transdifferentiation, in which other cells in the pancreas take over the role of beta cells by producing insulin themselves.
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7. Fomina-Yadlin D, Kubicek S, Walpita D, Dan?ík V, Hecksher-Sørensen J, Bittker JA, Sharifnia T, Shamji A, Clemons PA, Wagner BK, and Schreiber SL. Small-molecule inducers of insulin expression in pancreatic alpha cells. Proc Natl Acad Sci USA 2010; 107:15099-15104. PMCID: PMC2930573
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9. Wagner BK*, Kitami T*, Gilbert TJ, Peck D, Ramanathan A, Schreiber SL, Golub TR, and Mootha VK. Large-scale chemical dissection of mitochondrial function. Nat Biotechnol 2008; 26:343-351 * Equal contributors. (News and Views report in same issue, 26:294-296). PMCID: PMC2715872