Burns C. Blaxall, Ph.D.
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Burns C. Blaxall, Ph.D.
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Research
- Heart failure and beta (b)-adrenergic receptor signaling.
Background
Dr. Blaxall earned his Ph.D. in Pharmacology in 1999 from the University of Colorado Health Sciences Center, followed by postdoctoral training at Duke University Medical Center in the laboratory of Dr. Walter Koch, collaborating with Drs. Howard Rockman and Robert Lefkowitz, where he defined gene expression profiles that correlate with the development, progression and rescue of mouse and human heart failure. He was recruited to the University of Rochester Medical Center in 2003. His general research interests focus on mechanisms regulating cardiac function and disease, beta-adrenergic receptors, the functional role of novel genes discovered by gene expression profiling of heart failure and their potential interactions with beta-adrenergic receptor signal transduction.
Research Overview
Our 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
Recent Publications
- Blaxall BC, Tschannen-Moran BM, Milano CA and Koch WJ. Differential gene expression and genomic patient stratification following Left Ventricular Assist Device (LVAD) support in humans. J Amer Coll Card, 41:1096-1106, 2003. (see also Editorial Comment, Bristow MR, J Amer Coll Card, 41:1107-1108).
- Blaxall BC, Spang R, Rockman HA and Koch WJ. Differential myocardial gene expression in the development and rescue of murine heart failure. Physiol Genom 15:105-114, 2003.
- Ding B, Abe J, Wei H, Aizawa T, Walsh RA, Molina CA, Zhao A, Berk BC, Blaxall BC, and Yan C. Phosphodiesterase 3A1 (PDE3A1) and inducible cAMP early repressor (ICER) mediate angiotensin II and b1-adrenergic stimulation-induced cardiomyocyte apoptosis. Circulation, in press 2005.