Department of Medicine
Cardiology; Critical Care Medicine; Molecular and Cellular Biology; Stem Cells
My clinical expertise is in the management of patients with cardiovascular diseases. I use echocardiography, stress testing and nuclear imaging to identify disorders in heart muscle, valvular and vascular function. I have specialized training in the diagnosis and management of patients with cardiac muscle disease (cardiomyopathy) due to decreased contractile function (systolic dysfunction) and diastolic function.
My lab‘s research is focused on identifying novel therapies for the treatment of cardiomyopathy using several approaches. Currently, we are focused on identifying novel growth factors and pathways involved in the differentiation of cardiac and vascular tissues from pluripotent stem cells. This model system allows study of biological steps that occur in the formation and development of the human cardiovascular system. The growth factors and signaling pathways governing this process highlight undiscovered approaches to treatment of heart disease in adults. Our goal is to apply the identified growth factors and pathways as therapies in translational models of heart disease.
Currently we employ high-throughput analysis of stem cell derived cardiovascular precursors (identified by expression of Neuropilin-1) using transcriptional profiling to identify changes in gene expression that occur as stem cells differentiate to the earliest precursors of the human heart and blood vessels. From this dataset we are able to identify the transcriptional mechanism controlling the differentiation process, that represents a master control mechanism governing formation of the heart and vessels. We are applying similar approaches to understand how stem cells from adults with heart and vascular diseases differentiate to cardiac and vascular tissues, and determine if a common mechanism controlling heart and vascular cell formation exists between the developing heart and the adult heart. We employ cardiac stem cell, mesenchymal stem cell, and cancer stem cell models for our adult studies.
In parallel projects, we are focused on understanding the mechanisms that control the growth of early cardiovascular precursor cells derived from stem cells. Expansion of cardiovascular precursor cells is important to understand how these cells grow in development, and provide a means to expand these cells to large quantities for uses in tissue engineering and cell therapy applications.
FInally, a developing project involves understanding the interactions of capillary endothelium and cardiac myocytes using both in vitro and in vivo models. In the setting of heart failure, several endothelial cell derived proteins are abnormally expressed, indicating an under appreciated role for the secretory function of capillary endothelium in the pathogenesis of heart failure.