Cardiovascular & Blood Biology Faculty

The Beard and Carlson lab (cooperating with Brian Carlson) is focused on systems engineering approaches for understanding the biophysical and biochemical operation of physiological systems. Dan Beard is the Director of the Virtual Physiological Rat (VPR) project, previously supported as an NIH National Center for Systems Biology, working to analyze, interpret, simulate, and ultimately predict physiological function in health and disease. The scope of topics in the lab cover integrated experimental and computational projects spanning the scales of subcellular to whole organism function and include: (1) Cardiac energy metabolism. (2) Cardiovascular system dynamics. (3) Regulation of coronary blood flow. (4) Stem cell derived cardiomyocytes.

The Beard and Carlson lab (cooperating with Daniel Beard) is focused on systems engineering approaches for understanding the biophysical and biochemical operation of physiological systems. Dan Beard is the Director of the Virtual Physiological Rat (VPR) project, previously supported as an NIH National Center for Systems Biology, working to analyze, interpret, simulate, and ultimately predict physiological function in health and disease. The scope of topics in the lab cover integrated experimental and computational projects spanning the scales of subcellular to whole organism function and include: (1) Cardiac energy metabolism. (2) Cardiovascular system dynamics. (3) Regulation of coronary blood flow. (4) Stem cell derived cardiomyocytes.

The major focus of the laboratory is to determine the impact of various genetic alterations on atherosclerosis and arterial thrombosis using in vivo mouse models. We have developed models of vascular injury in the setting of atherosclerosis that allow us to identify the impact of many genes and conditions on atherothrombosis. We have recently used these mouse models to study links between obesity, diabetes and vascular endpoints. We have demonstrated that factors produced by adipocytes are capable of directly affecting atherosclerosis and arterial thrombosis. In addition, while surveying factors in the plasma that are increased in vascular inflammatory conditions, including diabetes and atherosclerosis, we have identified factors that are consistently and markedly elevated. Importantly, we have now shown that these factors serve as highly informative biomarkers since they represent specific interactions between leukocytes and endothelial cells. Additional experiments designed to determine their role in vascular and adipose inflammation are underway. To address the broader role of adipose tissue inflammation in vascular disease, we have recently developed a model of visceral fat inflammation and demonstrated that visceral, but not subcutaneous fat inflammation, is sufficient to accelerate atherosclerosis – in the absence of diabetes. Efforts are ongoing to identify the specific proatherogenic factors that are released from inflammatory visceral fat.    

The Isom laboratory focuses on understanding the molecular composition of individual sodium channel signaling complexes in excitable cells.  We are testing the hypothesis that studying the conducting and non-conducting functions of the sodium channel beta subunits may yield important insights into the molecular basis of inherited disease.  Part of our studies involve disruption of sodium channel signaling complexes in vivo and testing the consequences of such disruption on paroxysmal diseases such as cardiac arrhythmia and epilepsy.  In addition, because sodium channel beta subunits can function as cell adhesion molecules in the absence of the ion conducting pore, we are studying whether mutations in beta subunit genes may result in defects in axon guidance or cell-cell communication.  Our studies have significant clinical implications since it is already known that mutations in ion channels and their auxiliary subunits can lead to neurological or cardiovascular diseases.

The Pinsky laboratory aims to elucidate the mechanisms by which blood vessels modulate their phenotype following periods of interrupted blood flow.  Ultimately, the goals of our laboratory are to develop new insights into endogenous mechanisms of ischemic vascular injury and protection, in order to develop new therapeutic strategies targeted at the intersection of thrombotic, fibrinolytic, and inflammatory axes.

The Russell Laboratory examines the genetic determinants of heart development and the pathogenesis of human congenital heart defects. Using a zebrafish model, we are characterizing novel signaling pathways determined to be involved in cardiac outflow tract development based on the identification of genetic mutations in human patients with tetralogy of Fallot and hypoplastic left heart syndrome. In addition, we are continuing to search for additional novel disease genes using massively parallel sequencing of human patient samples.