Blaxall Lab
My laboratory has a long-standing interest in understanding the development, progression and regression (treatment) of heart failure, particularly as it relates to [beta]-adrenergic receptor ([beta]-AR) signaling. We have recently identified differential expression of a number of novel genes associated with both the development and regression of cardiac disease by large-scale gene expression profiling of both mouse and human heart tissue from non-failing, failing, and genetically or surgically "rescued" cardiac phenotypes. We are pursuing three main projects based largely on genes identified in these studies:
- A relatively new gene, named Mena, had not previously been studied in a cardiovascular context. Prior to our studies, Mena was known to be a cytoarchitectural gene that played a role in cell/neuron/axon migration. We have demonstrated an important functional role for Mena in cardiac structure, function and [beta]-AR signaling.
- Protease activated receptors (PARs), known in part for their role in blood clotting, were also found to be highly regulated in heart failure. We have demonstrated an important functional role for PAR expression and activity in cardiac cells in the pathogenesis of heart failure.
- Finally, [beta]-ARs are chronically desensitized and downregulated in heart failure. We are investigating the ability of novel small molecules to normalize pathologic [beta]-AR signaling and cardiac dysfunction.
For these and other collaborative studies, we utilize a translational approach to investigate the functional cardiac and [beta]-AR-related relevance of specific genes and molecules. Our investigational techniques range from in vitro biochemistry, pharmacology, cell biology and isolated adult cardiomyocyte contractility studies to high-resolution in vivo cardiac phenotyping in genetic and surgical mouse models of heart failure, coupled with validation in human heart failure cardiac myocytes and tissue samples.
Interested in learning more? Please contact: Burns_Blaxall@urmc.rochester.edu