Y. Eugene Chen, MD, PhD  Although important advances have been made in recent years in our understanding nuclear receptors in the regulation of metabolism, development, differentiation, inflammation, growth and programmed cell death, relatively little is known about the effects of these nuclear receptors and their ligands on the regulation of vascular smooth muscle cells. The objective of our projects is to begin to define the role of these transcription factors as endogenous regulators of pro-atherogenic and anti-atherogenic genetic programs that couple perturbations in lipid metabolism to vascular cell function. In particular, we focus our initial effort on two classes of receptors: (1) the liver X receptor (LXR), and (2) the peroxisome proliferator-activated receptors (PPARs).

Salim Hayek, MD   Our research focuses on using biomarkers to predict a patient’s risk for disease, potential outcome from a treatment or intervention, or to help guide a patient’s treatment plan.  We are currently investigating the effects of the biomarker suPAR (soluble urokinase plasminogen activator receptor) on disease pathogenesis; in human studies, suPAR is highly predictive of cardiovascular outcomes and there is some evidence that the presence of suPAR itself may cause damage. We’re examining this possibility using mouse models of atherosclerosis, myocardial infarction, or hypertension, by comparing genetic overexpression or deletion of the gene. 

Cindy H. Hsu, MD, PhD   Our research focuses on the discovery and translation of novel neuroprotective therapies for cardiac arrest patients by developing clinically relevant large animal models. We validate the efficacy of candidate therapies with multimodal approaches that include blood-based brain injury biomarkers, electrophysiology, digital neuropathology, pharmacokinetics studies, high throughput sequencing analysis, and neurocognitive tests. 

Tom Kerppola, PhD  Our laboratory uses novel experimental approaches to investigate molecular mechanisms of cardiac diseases.  We have developed methods that enable visualization of protein interactions and modifications in cardiomyocytes and analysis of chromatin binding complexes in freshly isolated heart tissues.  We have identified transcription factor complexes that control cardiomyocyte hypertrophy in response to the balance of growth promoting and growth modulating stimuli.

Daniel A. Lawrence, PhD  A significant area of interest focuses on the vascular biology of the CNS and its relationship to CNS disease processes. A second area study is the development of fibrotic disease. In particular, how upregulation of the protein PAI-1 promotes the pathogenesis of thrombotic and fibrotic diseases, and on the development of novel therapeutic interventions for the treatment of thrombotic and fibrotic diseases. Our studies use combinations of biochemical, molecular, and genetic approaches.

Venkatesh Murthy, MD   Our research focus is in the use of multi-omics and advanced cardiovascular imaging to improve our understanding of cardiac and metabolic diseases. We use data from patient cohorts, clinical trials as well as large epidemiologic studies (MESA, CARDIA, Framingham) using computational methods to integrate metabolomics, proteomics and genomics with integrate imaging data from CT, MRI and echocardiography. We also develop and validate quantitative imaging biomarkers using cardiac PET and CMR imaging in both patient cohorts and clinical trials.

David J. Pinsky, MD  The predominant research focus is to elucidate the mechanisms by which blood vessels modulate their phenotype following periods of interrupted blood flow.  Efforts are underway to elucidate the signal transduction mechanisms by which endogenous and inhaled CO exert their homeostatic regulatory effects on injured blood vessels. Various animal models are used in the laboratory to understand the pathophysiological consequences of ischemia-induced microvascular dysfunction. Ultimately, the goals of the 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.

Marschall Runge, MD, PhD & Nageswara Madamanchi, PhD   The Runge laboratory is interested in understanding the role of oxidative stress in the development of atherosclerosis and hypertension which are key risk factors for myocardial infarction and stroke. The most important source of reactive oxygen species in vascular cells are the multiple forms of enzymes nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase). Genetically engineered mouse models are being used to demonstrate the key NADPH oxidases that regulate oxidative stress in the cardiovascular system in order to identify targets for the therapeutic prevention of cardiovascular disease.

Thomas Sanderson, PhD Research in the Sanderson lab is focused on understanding brain damage caused by ischemic insults during cardiac arrest, ischemic stroke, and neonatal hypoxia/ischemia. Two primary avenues of investigation are (1) the role mitochondrial dysfunction in death of neurons during post-ischemic reperfusion and (2) the development and clinical translation of neuroprotective therapies that modulates the activity of mitochondria to reduce ischemia-reperfusion injury.

Michael Wang, MD, PhD  My laboratory focuses on the causes and consequences of ischemic stroke, a leading cause of cardiovascular death and disability.  A major effort in the lab is to understand the molecular changes that occur in blood vessels of the brain in CADASIL, an inherited disorder that results from mutations in NOTCH3.  Additional lines of research include studies of effects of stroke on circadian rhythms, sleep, and autonomic function and approaches to enhance recovery after neurological injury.  We integrate investigations of human tissues, genetically modified animals, and cellular models and use physiological, molecular & cellular techniques.