Regulation of the Human Proglucagon Gene

Identification of DNA sequences and regulatory factors important in the expression and regulation of expression of the human proglucagon gene in pancreatic islet, intestinal L cell, and select neurons of the hypothalamus. Using in vitro (transient transfection) and in vivo (transgenic) methods to characterize the human proglucagon gene. Our work has shown that sequences necessary for expression of the human proglucagon gene differ from those identified as required for expression of the better characterized rat proglucagon model, thus lessons learned form the rat proglucagon gene may not be directly applicable to our understanding of the human proglucagon gene.

Role of Glucokinase in Diabetes

We also explore the role of glucokinase, and associated proteins (e.g., glucokinase regulatory protein) in glucose metabolism in the liver and Diabetes. We use a heterozygous liver-specific knockout mouse as a model for MODY2 (maturity onset diabetes of the young 2) to characterize the molecular changes in the liver due to depleted glucokinase activity and to identify mechanism that may be used to increase enzymatic levels.

Origin and Evolution of New Vertebrate Genes

Origin and evolution of new gene function.  We have studies a number of genes that have acquired novel functions in vertebrates. An example is the lysozyme gene.  To understand the evolution of lysozyme genes we have cloned and characterized lysozyme genes from diverse vertebrate species.  Our studies of the mammalian lysozyme gene family have focused on understanding the mechanism of the change in gene function.

Collaborative Research in China

We are involved in a number of collaborations (Tsinghua University, Peking Universities, East China Normal University, and the Kunming Institute of Zoology, Chinese Academy of Sciences) on genes involved with cancer, diabetes and evolution of new physiological function.