My laboratory is focused on endothelial cells and how they become disrupted in disease. We also study a normal, yet highly proliferative endothelial cell found in blood called endothelial colony forming cells (ECFCs) and how ECFCs might be used in regenerative medicine.

Project I: Cellular and Molecular Basis of Hemangioma
Hemangioma is a tumor of endothelial cells that occurs in infants. These tumors can grow rapidly, cause organ damage and disfigurement and even threaten life. A fascinating aspect is that all true hemangiomas regress, beginning after one year of age. We are elucidating the cellular and molecular mechanisms that drive this uncontrolled growth and the spontaneous regression. We discovered a “hemangioma stem cell” that can form hemangioma-like blood vessels in nude mice. Our ultimate goal is to translate our basic science research on infantile hemangiomas to safe fast-acting therapies that will stop hemangiomas from growing to a life-threatening size.

Project II: Using Blood-derived Endothelial Colony Forming Cells (ECFC) and Mesenchymal Progenitor Cells (MPC) for Tissue Vascularization
Our goal is to build vascular networks from human ECFCs and MPCs to re-build damaged tissues and organs. We and others have shown that human ECFCs can be obtained from blood and expanded in the laboratory without difficulty. We showed that ECFCs combined MPCs isolated from cord blood or adult bone marrow form extensive, perfused vascular networks in vivo in nude mice. In the future, we envision use of a patient's own ECFCs and MPCs to build vascular networks for tissue-engineering or in situ regeneration of vascular networks in ischemic tissue.

Project III: Endothelial Cell Growth and Differentiation in Semilunar Heart Valves
We are studying growth and differentiation pathways in normal cardiac valve endothelium. Valve endothelium is unique in that the endothelial cells from adult valves can recapitulate processes that occur during valve development. These pathways involve TGF-ß-mediated endothelial to mesenchymal transformation (EMT). Recently, we have identified valvular progenitor cells with endothelial/mesenchymal plasticity. Further, we are studying this plasticity in the mitral valve in the context of mitral regurgitation that develops post-myocardial infarction.