School of Medicine
Cancer Cell Biology
Area of interest
The Patterson laboratory has two major ongoing efforts. The first is to understand the transcriptional programs regulating endothelial cell differentiation and cell type-specific gene expression. We postulate a two-step transcriptional response that mediates endothelial cell differentiation. The first step would involve a transcriptional program that activates expression of genes required for determination of the endothelial cell lineage. The second step would determine expression of genes characteristic of, but not necessarily specific for, the endothelial cell lineage. To determine the factors involved in early steps in
endothelial cell differentiation, we are using the KDR/flk-1 promoter as a model. Using a combination of transient transfection assays, DNA-protein and protein-protein interaction experiments, and transgenic models, we have identified important cis-acting elements in the 5' flanking sequence and 1st intron of this gene, and we are in the process of determined the unique transcription factors interacting with this sequence. In an attempt to identify factors comprising the second step in the endothelial cell transcriptional response, we have been searching for transcription factors in endothelial cells that are inducible by the potent angiogenic factor VEGF. Our ultimate goal is to define the cascade of transcription factors involved in the endothelial cell differentiation process, based
on the assumption that these same factors will participate in endothelial cell phenotypic expression in cardiovascular disease.
In a second project, our laboratory is exploring the interface between mechanisms of protein folding and protein degradation, particularly as these processes relate to modulation of the stress reponse in tissues such as the ischemic myocardium and in transformed cell types. As a model, we have examined the function of a novel, highly conserved protein identified in our laboratory that we call CHIP. Our most recent experiments have demonstrated that CHIP itself is a ubiquitylation factor that determines the ubiquitylation and degradation of proteins that interact with the molecular chaperones Hsc70 and Hsp90, and thus provides protection to cells under conditions of stress. Consistent with this hypothesis, we have generated mice that are deficient in CHIP (CHIP -/-), and find that cells in these mice are susceptible to stress-induced apoptosis. Our major goals for the future will be to determine how CHIP mediates its antiapoptotic effects and to determine how this effect modifies cardiac responses to ischemia and hypertrophy.
Awards and Honors
2002 Ruth and Phillip Hettleman Prize for Artistic and Scholarly Achievement
2002 Editorial Board, Circulation Research
2003-2008 Established Investigator Award, American Heart Association
2003-2008 Burroughs Wellcome Fund Clinical Scientist Award in Translational Research
2003 Member, American Society for Clinical
2003 Henry A. Foscue Distinguished Professor of Medicine and Cardiology, University of North Carolina at Chapel Hill