B.S. in Biology from Xavier University
Ph.D. Candidate in Department of Cell and Developmental Biology
I am interested in studying the role of Sostdc1, a secreted factor, in β cell function and glucose stimulated insulin secretion. Our lab has shown that Sostdc1 is up-regulated in the HNF6 transgenic mouse model of diabetes. My studies will determine whether absence of Sostdc1 improves β cell function and whether over-expression of Sostdc1 in islets impairs β cell function and causes diabetes.
Investigating the Role of HNF6 in Pancreas Development and Adult Function
Our lab generated transgenic mice in which Hnf6 is over-expressed under control of an islet enhancer from the Pdx1 promoter (Pdx1PB-Hnf6). Among other abdnormalities, these mice exhibit overt diabetes and reduced insulin secretion. Microarray analysis revealed a 2-fold upregulation of the Wnt/Bmp inhibitor Sostdc1. One of my projects is to evaluate whether lack of Sostdc1 improves β cell function and insulin secretion. Sostdc1 KO mice exhibit mild improvements in glucose homeostasis after 8 and 12 weeks of high fat diet feeding (HFD) and secrete more insulin in response to secretagogues. I am currently investigating whether the improvement in glucose homeostasis and changes in β cell proliferation are related to improved Wnt and Bmp signaling in Sostdc1 KO islets.
I am also investigating the interaction of Pdx1 and Hnf6 in the formation of endocrine progenitors in the developing pancreas. Both of these genes are absolutely required for the proper formation of the pancreas and both regulate expression of the endocrine marker Ngn3. I will examine whether mice doubly heterozygous for Pdx1 and Hnf6 generate appropriate numbers of endocrine progenitors during development and hormone positive cells in the adult. I will also investigate whether increased expression of Pdx1 and Hnf6 in human pancreatic ductal cells will promote endocrine differentiation.