Anna R.

Identifying Small-Molecule Inducers of the β-Cell Master Gene Pax4 in Pancreatic α-cells

Mentors: Kaihui Hu He, Morten Lundh

Type 1 diabetes is an autoimmune disease in which insulin-secreting β-cells in the pancreas die. This causes circulating glucose levels to rise, and therefore necessitates providing patients with insulin. In mouse models, turning on expression of the β-cell master gene Pax4 in pancreatic α-cells (which do not normally produce insulin) has been shown to transdifferentiate the α-cells into insulin-secreting cells. This transdifferentiation of α-cells mitigates the effects of the death of β-cells.

Anna and her mentors developed and conducted a high-throughput chemical screen, in order to identify small molecules that induce Pax4 expression in mouse pancreatic α-cells. By screening 8,960 chemical compounds with a wide variety of different structures, Anna identified 10 compounds as top hits that cause significant increases in Pax4 expression in α-cells. Identifying small molecules that turn on Pax4 expression in α-cells could lead to an increase β-cells, and thus could might be a potential future treatment of Type 1 diabetes.

 

Anna

Anna, a senior at Brookline High School, identified small molecules that may induce production of insulin, in cells in the pancreas that do not normally produce it.