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The Blaxall Lab has a long-standing interest in understanding the development, progression and regression (treatment) of heart failure. We are particularly interested in developing novel heart failure therapeutics and are pursuing several projects with therapeutic potential, including advanced screening, medicinal chemistry, and drug development. A major focus is also to understand the pathologic intercellular communication between myocyte and non-myocyte (e.g. fibroblast) cells in the heart. Based on 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 also pursuing several genes not previously associated in with heart failure.
We are investigating the ability of novel small molecules to normalize βAR – Gβγ signaling and cardiac dysfunction, targeting both the heart and the adrenal gland.
A relatively new gene, Mena, had not previously been studied in a cardiovascular context. We have demonstrated an important functional role for Mena both in heart function, conduction and signaling.
Protease activated receptors (PARs), known in part for their role in blood clotting, are highly regulated in heart failure. We have demonstrated an important functional role for PARs in the pathogenesis of heart failure in the absence of blood clotting. We have also demonstrated a key role for PARs in the pathologic intercellular communication between myocytes and non-myocytes (fibroblasts) in the heart.
Fibronectin, an important component of the extracellular matrix, plays an important role in inflammation and repair following myocardial infarction (MI). We are investigating the role of novel inhibitors of fibronectin polymerization in reducing pathologic cardiac remodeling post-MI.
We have recently discovered a key role for mixed lineage kinases in the pathologic intercellular communication between myocytes and fibroblasts (replicating the glia-neuron interaction in HIV-mediated neurodegeneration). We have identified small molecules targeting this pathway with therapeutic potential.
For these and other collaborative studies, we utilize a translational approach to investigate the functional cardiac and adrenergic-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 cardiac myocytes and tissue samples.
Burns C. Blaxall, PhD, FAHA, FACC, FAPSDirector of Translational Science, Heart InstituteCo-Director of Heart Institute Research Core & Biorepository
Phone: 513-803-4005Email: email@example.com
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