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


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, including lineage and clonal analyses. 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 and disease use similar fundamental approaches. For instance, we are studying the morphogenesis of the walls of other vessels, such as the aorta, 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 will apply our approaches to study animal models of vascular diseases that involve ectopic and aberrant smooth muscle cells, such as atherosclerosis, restenosis, pulmonary artery hypertension and aneurysmal diseases. Finally, we will study clinical samples obtained from patients with vascular diseases and relate them to our findings in animal models.

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, including lineage and clonal analyses. 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 and disease use similar fundamental approaches. For instance, we are studying the morphogenesis of the walls of other vessels, such as the aorta, 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 will apply our approaches to study animal models of vascular diseases that involve ectopic and aberrant smooth muscle cells, such as atherosclerosis, restenosis, pulmonary artery hypertension and aneurysmal diseases. Finally, we will study clinical samples obtained from patients with vascular diseases and relate them to our findings in animal models.


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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