The Cardiopulmonary Research Program (CRP) at the Krannert Cardiovascular Research Center studies the basic molecular underpinnings of heart and lung disorders using state-of-the-art precision medicine tools and techniques. Led by Ankit A. Desai, MD, CRP is dedicated to understanding the mechanisms and genetics of pulmonary arterial hypertension and sickle cell cardiomyopathy, complemented by Dr. Desai’s active clinical practice serving patients with pulmonary arterial hypertension and sickle cell disease for more than 15 years. The program employs genome-wide association study strategies to prioritize functional and preclinical studies of candidate genes that lead to the development of pulmonary arterial hypertension and heart failure.
Pulmonary arterial hypertension is a type of high blood pressure that impacts the arteries in the lungs and the right side of the heart when blood vessels in the lungs become narrowed, blocked or damaged. This condition over time can lead to right heart failure.
Sickle cell disease is a genetic condition and type of anemia characterized by an abnormal shape of red blood cells that become blocked in blood vessels or break down, and cause harm to multiple organs including the heart.
CPR focuses on three major cardiovascular domains:
- Genetic mechanisms of pulmonary arterial hypertension (PAH) and right heart failure, which impacts the heart’s right ventricle, with a particular focus on endothelial cell signaling
- Genetic mechanisms of inflammation-mediated ventricular tachycardia and cardiomyopathy in patients with sickle cell disease
- Novel molecular mechanisms of beta-blockers in myocardial infarction via beta-adrenergic independent signaling.
These areas reflect CPRs multi-disciplinary expertise across molecular biology, cellular signaling and animal physiology. Each domain is fundamentally grounded in omics-based platforms and studies of diverse populations and health disparities.
Current Treatment Challenges
There is a growing need to improve patient outcomes and quality of life, as more people are impacted by pulmonary arterial hypertension that could lead to increased morbidity and mortality. Pulmonary arterial hypertension largely affects women (~4:1 female to male ratio) with survival rates estimated to be around 50% at 7 years despite the addition of multiple therapies. Dr. Desai’s group is focused on addressing this dismal prognosis by better understanding the complexity of its pathogenesis. Studies are aimed at new molecular pathways that are discovered from genetic studies in patients and translating them as targets for novel therapies.
Sudden death is an increasingly reported cause of early death in patients with sickle cell disease and is considered a top five cause of death. Recent published data suggest a high prevalence of heart arrhythmias (nearly 25%) in patients with sickle cell disease, but little is known about possible links between heart arrhythmias and sudden death, highlighting a poorly characterized and potentially underrecognized health risk for these patients. Dr. Desai’s lab was one of the first labs to demonstrate increased vulnerability for the development of heart arrhythmias in “humanized” sickle mouse models. Their lab showed that targeting inflammation and a novel protein called interleukin 18 may alleviate the development of sickle cell cardiomyopathy and associated heart arrythmias. Their lab is now focused on translating these findings to patients, and exploring new therapies that may treat patients who suffer from this condition.
