The major goal of the Kume laboratory is to understand the molecular mechanisms of cardiovascular development, with an emphasis on the formation/remodeling of blood vessels.  Lab members use a variety of methods, including the generation of transgenic and knockout mice, cell and molecular biology, biochemistry, and FACS analysis, in their studies. Mouse mutants provide useful models to study both normal cardiovascular development and developmental defects that may contribute to inherited cardiovascular defects.

The Kume laboratory focuses on the roles of two closely related Fox genes, Foxc1 and Foxc2, encoding winged helix/forkhead transcription factors. These genes show overlapping domains of RNA expression in many embryonic tissues, including endothelial cells of the heart and blood vessels.  To date, null mutations have been generated in the two genes.  Lab members have shown that embryos lacking either Foxc1 or Foxc2, and most compound heterozygotes, die with similar abnormal phenotypes, including defects in the cardiovascular system.   Moreover, compound Foxc1; Foxc2 homozygotes die earlier and with much more severe defects than single homozygotes alone.  Significantly, Kume lab members have found profound abnormalities in the early remodeling of blood vessels.  Current studies focuses on how Fox transcription factors function in response to extracellular signals and regulate downstream target genes in cardiovascular development.  

For more information about Dr. Kume visit his Vanderbilt Faculty Page

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