Department of Medicine; Krannert Institute of Cardiology
Discovery of novel biomarkers and therapeutic targets for pulmonary hypertension, cardiomyopathy and ventricular tachycardia
I am a physician scientist who has been dedicated to understanding the genetic mechanisms of cardiomyopathy and pulmonary arterial hypertension (PAH), in particular, in relation to minority health. My research work is complimented by my clinical practice, serving patients with cardiovascular diseases for nearly 15 years. With continuous support from the NIH, the American Heart Association, and the American Thoracic Society for the last thirteen years, our lab group utilizes genome-wide strategies to prioritize functional and preclinical studies of candidate genes and pathways leading to the development of cardiomyopathy and PAH. We have established several highly novel findings and mechanisms that contribute to the development of PAH, cardiomyopathy and arrhythmias: 1) characterizing cardiomyopathy associated with sickle cell disease (SCD), a rare hemolytic anemia predominantly affecting African Americans in the US; 2) detailing evidence of electrophysiolgical remodeling of the sickle mouse heart, a highly vulnerable animal model of cardiomyopathy and ventricular tachycardia (VT) and 3) discovering interleukin-18 (IL-18), a well-known pro-inflammatory cytokine, as a novel therapeutic target and a biomarker for cardiomyopathy and VT in SCD. For the first time, the cumulative work links observations of “sudden death” and PH as top causes of death in patients with SCD with a clinical framework, specifically, VT, and via an IL-18-mediated molecular mechanism. Most recently, these observations combined with published work from many others have culminated into the development of clinical guidelines by the American Society of Hematology (ASH) that shape decision-making by patients and providers. Furthermore, with international collaborations, my lab group has recently reported: 4) evidence of common genetic variation in the largest global GWAS meta-analysis of patients with PAH and 5) survival differences among minority populations with PAH, including evidence of the contribution of genetic ancestry. These latter observations fundamentally change our understanding of the genetic landscape of PAH. With the continued support of IU, my lab members, and collaborators, I have demonstrated a record of productivity in an area of high relevance for medically under-served populations and leverage my expertise for interdisciplinary work that spans the field of genetics, molecular biology, experimental physiology, hematology, and clinical cardiology.