Assistant Professor
Department of Physiology and Biophysics
Jacobs School of Medicine & Biomedical Sciences
Apoptosis and cell death; Cardiac pharmacology; Cardiology; Cardiovascular Disease; Inflammation; Pathophysiology; Stem Cells; Translational imaging; Translational Research
My research program is focused on investigating mechanisms of cardiac dysfunction and structural remodeling in heart disease, as well as identifying novel therapeutic interventions to prevent or reverse the deleterious consequences of acute and chronic ischemia- and/or hemodynamic overload-induced injury. These studies generally utilize non-invasive cardiovascular imaging techniques and invasive hemodynamic assessment to assess cardiac performance in vivo in preclinical experimental models, along with ex vivo analysis of myocardial tissue to examine cellular and molecular mechanisms underlying observed changes in physiological function. Using this approach, we aim to conduct impactful translational research with direct relevance to the pathophysiology and treatment of human heart disease.
Ongoing research in my laboratory is focused in two areas:
1. Novel Therapeutic Approaches to Enhance Cardiopulmonary Resuscitation and Minimize Multi-Organ Injury After Cardiac Arrest.
In an effort to improve the dismal clinical outcomes associated with sudden cardiac arrest, our research in this area is directed towards (1) improved understanding of the role of the innate immune response to systemic ischemia and reperfusion in the context of cardiac arrest and resuscitation and (2) identification of novel interventions to reduce multi-organ injury in this setting. One hypothesis to be tested is that mobilization of inflammatory leukocytes from the spleen is an integral component of the systemic inflammatory response that exacerbates multi-organ injury following resuscitation from cardiac arrest. Completion of studies to test this hypothesis and identify mechanisms underlying post-resuscitation inflammation is expected to reveal novel therapeutic opportunities, such as the use of ß2-adrenergic receptor antagonists, CCR2 inhibitors, or allogeneic mesenchymal stem cells to attenuate leukocyte mobilization, infiltration, and behavior after cardiac arrest. In addition, an ongoing collaborative effort with a small, New York State-based pharmaceutical company (Pro-Al Medico Technologies) aims to develop a novel nanoparticle formulation of thyroid hormone (T3np) for use as a resuscitative therapy to replace epinephrine as the drug of choice in advanced cardiac life support protocols.
2. Mechanisms and Reversibility of Cardiac Fibrosis and Myocardial Stiffening in Heart Failure.
Heart failure with preserved ejection fraction (HFpEF) has emerged as the most common form of heart failure, but the poor understanding of how it develops has made it difficult to devise effective treatments. Ongoing research in my laboratory aims to address this problem by examining how repetitive stretch-induced remodeling of the non-cellular components of heart muscle (i.e., the cardiac extracellular matrix; ECM) leads to persistent fibrotic collagen deposition and a sustained reduction in cardiac compliance in HFpEF. To do so, we have developed a novel porcine model of repetitive pressure overload (RPO), in which episodic mechanical stretch associated with intermittent hypertension produces a pattern of cardiac remodeling exhibited by many HFpEF patients characterized by reduced myocardial compliance and increased interstitial fibrosis in the absence of overt left ventricular hypertrophy or sustained hypertension. Ongoing and future projects utilizing this model are designed to (1) determine how repetitive stretch-induced injury activates pro-inflammatory and pro-fibrotic signaling in the heart, (2) assess whether coronary microvascular dysfunction is involved in this pattern of remodeling, and (3) evaluate novel therapeutic interventions to prevent or reverse hypertrophy-independent myocardial stiffening by targeting remodeling of the cardiac ECM. In addition, we have recently collected intriguing preliminary data from a separate porcine model that support the novel hypothesis that repetitive stretch-induced myocardial stiffening may play a mechanistic role in the development of HFpEF in patients with chronic coronary artery disease.