Our laboratory is interested in basic research studies involving endocrine systems, including the pituitary, pancreas, and thyroid.

Growth Hormone Gene Regulation. We are interested in the mechanisms of human growth hormone (GH) and chorionic somatomammotropin (CS) gene regulation in the pituitary and placenta, respectively. We are primarily interested in enhancers and silencers, which are involved in cell-specific regulation of the GH and CS genes. We have demonstrated that a CS enhancer/silencer is controlled by members of the transcription enhancer factor (TEF) family. We have recently discovered another silencer element that is localized downstream of the GH gene. This element is interesting in that part of its functional elements are contributed by Alu repeat sequences.

Intracellular Amyloid And Cell Death. Type 2 diabetes is a disease characterized by pancreatic amyloid deposition by islet amyloid precursor protein (IAPP). Amyloid formation is associated with beta cell death and diminished insulin production. IAPP expression in cultured pancreatic cells generates amyloid within the endoplasmic reticulum (ER) followed by apoptosis. These events are preceded by ER stress responses that may be involved in mediating apoptosis. We have created human IAPP knock-in mice to establish whether amyloid formation is pathophysiologically involved in the genesis of Type 2 diabetes in animals.

Genesis of Differentiated Thyroid Cancer. We are defining the genes involved in the pathogenesis of differentiated thyroid carcinomas (follicular adenoma, FA; papillary, PTC; follicular, FTC; and undifferentiated anaplastic thyroid cancers). We are primarily interested in defining the pathways involved in the genesis of FTC, which are among the more aggressive thyroid cancers. We are studying the PAX8/PPARgamma fusion oncogene that is frequently involved in FTC and are attempting to establish linkages with this oncogene and pathways that are commonly involved in FTC tumorigenesis.