Daniel Greif MD

Assistant Professor of Medicine (Cardiology)

Research Interests

Vascular biology; Vascular smooth muscle; Vessel wall; Developmental biology; Clonal analysis; Lineage analysis; Pulmonary artery hypertension; Aorta; Intracranial hemorrhage; Atherosclerosis.

Research Summary

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. Our research spans from cultured cells to mouse models to human samples. We aim to gain critical insights into the pathogenesis of diverse cardiovascular pathologies and leverage these insights into novel therapeutics for human disease.

Extensive Research Description

My laboratory investigates blood vessel morphogenesis, the maintenance of the adult blood vessel and diseases of the vasculature. To this end, we utilize fundamental biochemical, genetic and developmental biological approaches. We initially investigated the origins of the smooth muscle and adventitial cells of the pulmonary artery and have delineated with cellular resolution the patterns of cell differentiation, proliferation, recruitment and migration in the developing pulmonary arterial wall. Furthermore, we have initiated a genetic dissection of the molecular processes and signals that underlie blood vessel formation and have demonstrated a role of the platelet derived growth factor pathway in this process.

Our ongoing and planned studies of vessel development, maintenance and disease use similar fundamental approaches. For instance, 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. In addition, little is known about the maintenance of blood vessels, and we are embarking on a study to evaluate 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 pulmonary artery hypertension, atherosclerosis, supravalvular aortic stenosis, restenosis and intracranial hemorrhage. Finally, we are studying clinical samples obtained from patients with vascular diseases and relating them to our findings in animal models.

Current Research Projects:

  • Excess smooth muscle in pulmonary hypertension: cellular origins and recruitment and the role of pluripotency factors.
  • Aortic wall development and disease (atherosclerosis, supravalvular aortic stenosis): progenitor cell specification, migration and differentiation.
  • Mural cell TGF-beta signaling and blood brain barrier formation: implications for intracerebral hemorrhage.

Selected Publications

  • Greif, DM*, Eichmann A*. (2014). Vascular biology: Brain vessels squeezed to death. Nature, 508:50 (Corresponding authors).
  • Sheikh, AQ, Lighthouse, JK, Greif, DM*. (2014). Recapitulation of developing artery muscularization in pulmonary hypertension. Cell Reports, 6:809 (*Corresponding author).
  • Seidelman, S, Lighthouse, JK, Greif, DM*. (2014). Development and pathologies of the arterial wall. Cellular and Molecular Life Sciences, 71:1977 (*Corresponding author).
  • Kim, J, Kang, Y, Kojima, Y, Lighthouse, JK, Hu, X, Aldred, MA, McLean, DL, Park, H, Comhair, SA, Greif, DM, Erzurum, SC, Chun, HJ. (2013). A Novel Endothelial Apelin-FGF Link Mediated by MicroRNAs 424 and 503 is Disrupted in Pulmonary Arterial Hypertension. Nature Medicine, 19:74.
  • Greif, DM*, Kumar, M, Lighthouse, JK, Hum, J, An, A, Ding, L, Red-horse, K, Espinoza, FH, Olson, L, Offermanns, S, Krasnow, MA*. (2012); Radial construction of an arterial wall. Developmental Cell, 23:482 (*Corresponding authors).
  • Greif, DM. Invited chapter - Vascular embryology and angiogenesis. In: Vascular Medicine, A Companion to Braunwald’s Heart Disease, 2nd edition, eds. M.A. Creager, J.A. Beckman, and J. Loscalzo, Elsevier Inc., Philadelphia, PA, (2012).
  • London, NR, Zhu, W, Bozza, FA, Smith, MC, Greif, DM, Sorensen, LK, Chen, L, Kaminoh, Y, Chan, AC, Passi, SF, Day, CW, Barnard, DL, Zimmerman, GA, Krasnow, MA, Li, DY. (2010). Targeting Robo4-dependent slit signaling to survive the cytokine storm in sepsis and influenza. Science Translational Medicine, 2 23ra19:1-10.
  • Dudzinski, DM, Igarashi, J, Greif, D, Michel, T. (2006). The regulation and pharmacology of endothelial nitric oxide synthase. Annual Review of Pharmacology and Toxicology, 46:235-76.
  • Banerjee, SS, Lin, Z, Atkins, GB, Greif, DM, Rao, RM, Feinberg, MW, Chen, Z, Simon, DI, Luscinskas, FW, Michel, TM, Garcia-Cardena, G, Gimbrone, MA, Jain, MK. (2004). KLF2 is a novel transcriptional regulator of proinflammatory activation. The Journal of Experimental Medicine, 199:1305.
  • Greif, DM, Sacks, DB, Michel, T. (2004). Calmodulin phosphorylation and modulation of endothelial nitric oxide synthase catalysis. Proceedings of the National Academy of Sciences, 101: 1165-1170.


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