Research & Publications
Cardiovascular disease is the number one cause of death globally. My laboratory utilizes multi-disciplinary approaches to investigate how blood vessels initially form, are maintained and go awry in disease. In addition, we study the role of alveolar myofibroblasts in lung development and fibrotic disease. Our research spans from cultured cells to mouse models to human samples. We aim to gain critical insights into the pathogenesis of diverse cardiovascular and pulmonary pathologies and leverage these insights into novel therapeutics for human disease.
Specialized Terms: Vascular biology; Vascular smooth muscle; Vessel wall; Developmental biology; Clonal analysis; Lineage analysis; Pulmonary artery hypertension; Aorta; Intracranial hemorrhage; Atherosclerosis.
Extensive Research Description
Our laboratory investigates blood vessel development and disease as well as myofibroblasts in lung development and fibrotic disease. To this end, we utilize fundamental biochemical, genetic/genomic and developmental biological approaches. We recently uncovered novel smooth muscle cell progenitors that undergo clonal expansion during diverse vascular diseases, such as pulmonary hypertension and atherosclerosis.
Our ongoing and planned studies of vessel and lung development, maintenance and disease use similar fundamental approaches. Our initial investigations focused on pulmonary artery development, and we are studying the morphogenesis of the walls of other vessels, such as the aorta and cerebral vasculature, and comparing and contrasting their morphogenesis with that of the pulmonary artery. Little is known about the maintenance of blood vessels, and we are interested in evaluating the patterns of cell turnover, proliferation and migration as well as the underlying mechanisms in the adult vessel wall. Moreover, diseases of the vasculature are thought to largely involve a recapitulation of developmental programs, and we are applying our approaches to study animal models of vascular diseases that involve ectopic and aberrant smooth muscle cells, such as atherosclerosis, supravalvular aortic stenosis, restenosis, intracranial hemorrhage and pulmonary hypertension. In addition, we have extended our studies to lung fibrosis which is an important cause of hypoxia and hence pulmonary hypertension. Furthermore, we are studying clinical samples obtained from patients with vascular and lung diseases and relating them to our findings in animal models and cultured cells. Finally, we have a strong interest in expanding our studies into single cell analysis, computational biology and human genetics/genomics.
Current Research Projects:
- Excess smooth muscle in pulmonary hypertension: cell autonomous and non-cell autonomous regulation.
- Aortic wall development and disease (atherosclerosis, supravalvular aortic stenosis): progenitor cell specification, migration and differentiation.
- Mural cell signaling and blood brain barrier formation: implications for intracerebral hemorrhage.
- Alveolar myofibroblasts in lung development and fibrotic disease
Aorta; Aortic Stenosis, Subvalvular; Cardiology; Cerebral Hemorrhage; Hypertension, Pulmonary; Pulmonary Fibrosis; Vascular Diseases; Developmental Biology; Atherosclerosis; Myofibroblasts
- Out to the tissues: the arterial side (arteries, arterioles – development, structure, functions, pathologies).Dave, JM, Saito, J, Mottola, G, Greif, DM. Invited chapter: Out to the tissues: the arterial side (arteries, arterioles – development, structure, functions, pathologies). In: Z. Gallis. The Vasculome: From Many to One. Philadelphia, PA: Elsevier Inc.; 2020, in press.
- Vascular embryology and angiogenesisNtokou, A, Kabir, I, Saddouk, FZ, Greif, DM. (2018). Invited chapter in: Vascular Medicine, A Companion to Braunwald’s Heart Disease, 3rd edition, editors M.A. Creager, J.A. Beckman, and J. Loscalzo, Elsevier Inc., Philadelphia, PA.
- Vascular embryology and angiogenesis.Greif, DM. (2012). Invited chapter in: Vascular Medicine, A Companion to Braunwald’s Heart Disease, 2nd edition, editors M.A. Creager, J.A. Beckman, and J. Loscalzo, Elsevier Inc., Philadelphia, PA.
- Specialized smooth muscle cell progenitors in pulmonary hypertensionSaddouk, FZ, Ntokou, A, Greif, DM. Invited chapter: Specialized smooth muscle cell progenitors in pulmonary hypertension. In: T. Naknishi, H. Baldwin, J. Fineman, and H. Yamagishi, editors. Molecular Mechanism of Congenital Heart Disease and Pulmonary Hypertension. Springer Nature, 2020, pp 25-30.