ResearchI. The developmental biology of leptin and leptin receptors
II. Epigenetic programming by exposure to glucocorticoids early in life
III. Molecular mechanisms of gene regulation by thyroid hormone and corticosteroid receptors during mouse and frog brain development
IV. Neuroendocrine mechanisms of developmental plasticity
V. Structural and functional evolution of the corticotropin releasing-factor family of neuropeptides
VI. Molecular basis for hormone action in amphibian metamorphosis
I. Structural and functional evolution of the corticotropin releasing-factor family of neuropeptidesCorticotropin releasing factor (CRF) and related peptides (i.e., the urocortins) play central roles in the regulation of neuroendocrine, autonomic, immune, and behavioral responses to physical and emotional stress. The general objectives of our studies are to understand the structural and functional evolution of the CRF family of neuropeptides and the components of their signaling pathways (i.e., CRF receptors and binding protein). Our experiments exploit a powerful model organism, the South African clawed frog Xenopus laevis, for which many molecular and biochemical tools are now available for the study of physiology and development. We also take a comparative approach utilizing diverse vertebrate species and the continually expanding genomic databases. The specific goals of our current research are:
1) To understand how central CRF stress circuits are organized and regulated in response to environmental stress. For these studies we are using gene expression and comparative genomics analyses to identify evolutionarily conserved gene regulatory sequences in stress-responsive genes. We then test the functionality of these sequences using in vitro transfection assays, in vivo electroporation-mediated gene transfer, germline transgenesis and chromatin immunoprecipitation (ChIP) assay.
2) To determine how corticosteroid feedback and the CRF binding protein (BP) modulate CRF expression and action.
3) To isolate and characterize novel CRF-like peptides (i.e., CRFs and urocortins) from diverse vertebrates species. Our goal is to understand the evolution of this peptide family, and the functions that these essential stress peptides play in extant vertebrate species.
The basic components and organization of the vertebrate neuroendocrine stress axis arose early in evolution, and the structure and function of these pathways are conserved. The high degree of conservation is attributable to the central, adaptive role that this system plays in vertebrates. Comparative studies of the neuroendocrine stress system are essential to elucidate the evolutionary history and the functional organization of these pathways in extant species.
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