The research in my laboratory is concerned with development, physiology and diseases of the pancreas. Our specific interests include: (1) the molecular pathways directing the specification and differentiation of endocrine pancreatic cells; (2) endocrine regulation of animal growth and body metabolism; and (3) the molecular mechanisms underlying pancreatic beta cell death in diabetes and pancreatic cancers. We are actively working on two research projects.
The first is functional characterization of regulatory factor X (RFX) domain-containing 1 (RFXDC1). Rfxdc1 is a novel gene whose transcript and protein are restricted to the islets of Langerhans of the pancreas. Knockdown of RFXDC1 function during zebrafish embryonic development by morpholino antisense oligos causes abnormal pancreatic formation. We hypothesized that RFXDC1 may function as a transcriptional regulator or coregulator during development of the pancreas. We are now trying to generate a knockout mouse model to study the physiological function of Rfxdc1.
The second project is investigating the molecular mechanisms of pancreatic beta cell apoptosis in diabetes. We are particularly interested in understanding the causal relationship between endoplasmic reticulum (ER) stress and beta cell death and survival. SEL1L is an ER membrane protein and is highly expressed in the pancreas. It has been shown by other investigators that SEL1L forms a highly conserved protein quality control complex with other proteins on the ER membrane to facilitate degradation of misfolded or unassembled proteins in the ER, which otherwise will aggravate and become cytotoxic. We have generated Sel1L-deficient mouse embryos and are learning to understand the in vivo functions of SEL1L by characterizing the phenotypes of these embryos.