Until recently, little detailed information was known about the
factors controlling pancreas development and islet beta cell
function. However, our understanding has increased greatly with the
identification and molecular characterization of the islet-enriched
MafA, MafB, and PDX-1 transcription factors. Gene knockouts
performed on these and other pancreas-enriched factors are helping
to elucidate the events influencing pancreatic morphogenesis.
Because of their unique expression pattern and fundamental
significance to beta cells, work here is focused on defining the
transcription factors involved in controlling the expression of
Pdx-1 and MafA. In addition, we are examining how transcriptional
factors influence beta cell formation and function. Our recent
results indicate that MafA and MafB strongly impact whether a cell
becomes a producer in the islet of the insulin (beta) or glucagon
(alpha) hormone. Both animal and cell culture models are used in
these studies, with comprehensive and diverse methods from Cre/loxP
conditional gene inactivation to mass spectrometry involved in
addressing our experimental questions.
Understanding the mechanisms involved in controlling of pancreatic islet beta-cell specific transcription will likely lead to the development of therapeutic approaches that will prevent, correct, or at least delay the decline in beta cell function observed in diabetics. In fact, considerable efforts are focused on trying to develop an unlimited source of insulin-producing beta-like cells from adult and embryonic stem cells, as a consequence of success in reversing type 1 diabetes by islet transplantation. We believe that long-term success in this endeavor will require a fundamental understanding of the regulatory factors that are required for controlling the specialized genetic programs associated with beta cells. Our hope is that successful completion of our proposed studies will provide information important for generating acceptable islet-like cells for therapeutic treatment.
The beta cell biology community here is also very interactive and supportive, with eight groups meeting weekly to discuss their most recent findings. This gives students, post-docs, and faculty a routine opportunity to obtain input from a group of experts.
The following timeline graph is generated from all co-authored publications.
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Key: MeSH Term KeywordAmino Acid Sequence Cell Compartmentation Chloramphenicol O-Acetyltransferase Chromosome Deletion Cricetinae Embryonic Development Epitopes Fungal Proteins Gene Deletion Gene Dosage Gene Expression Genes, Homeobox Glucose-6-Phosphatase HeLa Cells In Vitro Techniques LIM Domain Proteins Liver Mice, Mutant Strains Models, Biological Molecular Sequence Data Molecular Structure Multigene Family Oocytes Peptides Phosphoproteins Protein Isoforms Protein Multimerization Sequence Homology, Amino Acid Transcription Factor TFIIIA Transgenes