Researcher

    Alexandre Dubrac , Ph.D.

    alexandre.dubrac@umontral.ca
    Alexandre Dubrac
    Research Axis
    Fetomaternal and Neonatal Pathologies Axis
    Research Theme
    Mechanisms for congenital anomalies
    Address
    CHUSJ - Centre de Recherche Office 5.17.019

    Phone
    514 345-4931 7881

    Title

    • Assistant Professor, Department of Pathology and Cell Biology, University of Montreal

    Laboratory

    Organotypic control of vascular morphogenesis and quiescence

    Education

    • Postdoctoral fellow in vascular biology, Yale New Haven Heart and Vascular Center, Yale University, New Haven, CT, US (2012-2018)
    • Postdoctoral fellow tumor angiogenesis, INSERM UMR1037, Université Paul Sabatier, Toulouse, France (2009-2011)
    • PhD in angiogenèse, INSERM U1029, Université Bordeaux 1, Bordeaux, France (2005-2008)
    • MSc in cellular, molecular and developmental biology, INSERM U589, Université Paul Sabatier, Toulouse, France (2003-2004)
    • BSc in biology, Université Paul Sabatier, Toulouse, France (2002)

    Research Interests

    The laboratory is interested in the molecular mechanisms governing blood vessel morphogenesis in development and vascular diseases. Newly formed blood vessels are composed of endothelial tubes (EC) that migrate, proliferate, and become quiescent. The pericytes, surrounding the blood vessels, are also crucial for vascular quiescence and integrity. Maintaining vascular quiescence is, therefore, essential for human health, and its dysregulation will promote the onset and progression of several vascular diseases, including cancer and retinopathy. We are focusing on two main projects:

    1.  TGFβ control of the EC proliferation in proliferative retinopathy. Proliferative retinopathies are currently treated with VEGF neutralizing antibodies, with limited therapeutic success. Therefore, it is crucial to identify new targets that could improve currently available treatments. TGFβ signaling is a significant regulator of the EC proliferation and the retina and brain blood vessels morphogenesis, and we are investigating the underlying mechanisms which are still poorly understood.
    2.  Pericyte identity and function in development and proliferative retinopathy. We have recently identified a new pericyte paradigm proliferative retinopathy, whereby pathological pericytes (activated) promote pathological angiogenesis in oxygen-induced retinopathy (OIR), a mouse model that mimics some aspects of the retinopathy of prematurity (ROP). The laboratory aims to identify new molecular markers to target activated pericytes in proliferative retinopathy in order to develop new therapeutic strategies.

    Research Topics

    • Angiogenesis
    • Endothelial cell
    • Pericyte
    • Retinopathy
    • TGFβ
    • Vascular malformation

    Career Summary

    Dr. Alexandre Dubrac obtained his Ph.D. at Université de Bordeaux I, where he worked with Professor Andreas Bikfalvi on chemokines and tumor angiogenesis. Next, he joined Professor Anne Eichmann's group at the Cardiovascular Research Center at Yale University. As a postdoctoral fellow, he investigated the function of axon guidance regulators in angiogenesis and proliferative retinopathies. Among others, he has demonstrated that Slit2 and Robo1 & 2 are essential for developmental and pathological angiogenesis in the retina. Furthermore, he also studied the endothelial TGFβ/SMAD signaling in the arteriovenous malformations (AVM) of Hereditary Hemorrhagic Telangiectasias (HHT). In 2017, he was promoted as Associate Researcher at Yale University. He worked on the endothelial cell-pericyte interaction during the retinal vascular development and proliferative retinopathies. Dr. Dubrac was recruited in 2018 as a P.I. at the CHU Sainte-Justine Research Center and as an assistant professor in the Department of Pathology and Cellular Biology at the University of Montreal.

    Awards and Distinctions

    • Research scholars (junior 1), FRQS, 2019-2023
    • Scientific Development Grant, American Heart Association, 2017-2020
    • Co-chair to organize the Gordon Research Seminar, Vascular Cell Biology, Ventura, CA, USA, 2017
    • Post-doctoral fellowship, American Heart Association, 2014-2016

    Major financing

    • Canadian Institutes of Health Research (CIHR), 2019-2024
    • Canada Foundation for innovation (CFI)
    • Fonds de recherche du Québec - Santé (FRQS), 2019-2013

    Selected Publications

    1. Dubrac A*, Künzel S*, Martin K, Greif DM, Eichmann A. NCK-dependent pericyte migration promotes pathological neovascularization in ischemic retinopathy. Nat Commun. 2018 Aug 27;9(1):3463. * equal contribution. co-corresponding author.
    2. Ola R, Künzel HS, Zhang F, Genet G, Chakraborty R, Pibouin-Fragner L, Martin K, Sessa W, Dubrac A*, Eichmann A*. SMAD4 prevents arterial-venous malformations by inhibiting Casein Kinase 2. Circulation. 2018 Jul 5. pii: CIRCULATIONAHA.118.033842. * equal contribution.
    3. Zhang F, Zarkada G, Han J, Li J, Dubrac A, Ola R, Genet G, Boye K, Michon P, Künzel S, Camporez JP, Singh AK, Fong GH, Simons M, Fernández-Hernando C, Sessa WC, Shulman GI, Eichmann A. Lacteal junction zippering protects against diet-induced obesity. Science. 2018 Aug 10;361(6402):599-603.
    4. Yu P, Wilhelm K*, Dubrac A*, Tung JK*, Alves TC, Fang JS, Xie Y, Zhu J, Chen Z, De Smet F, Zhang J, Jin SW, Sun L, Sun H, Kibbey RG, Hirschi KK, Hay N, Carmeliet P, Chittenden TW, Eichmann A, Potente M, Simons M. FGF-dependent metabolic control of vascular development. Nature. 2017 May 11;545(7653):224-228. * equal contribution.
    5. Zhang F, Prahst C, Mathivet T, Pibouin-Fragner L, Genet G, Zhang J, Tong R, Ye W, Dubrac A, Eichmann A. The Robo4 cytoplasmic domain is dispensable for vascular barrier protection and inhibition of neovascularization. Nat Commun. 2016 Nov 24;7:13517.
    6. Ola R, Dubrac A, Han J, Angulo Urarte A, Zhang F, Fang JS, Larrivée B, Lee M, Genet G, Hirschi KK, Sessa WC, Vinals Canals F, Graupera M, Yan M, Young LH, Oh SP, Eichmann A. PI3Kinase inhibition improves vascular malformations in mouse models of hereditary hemorrhagic telangiectasia type 2. Nat Commun. 2016 Nov 29;7:13650.
    7. Baeyens N*, Larrivée B*, Ola R, Hayward B, Dubrac A, Huang B, Ross TD, Coon BG, Tsarfati M, Tong H, Eichmann A and Schwartz MA. Defective fluid shear stress mechanotransduction mediates hereditary hemorrhagic telangiectasia (HHT). J Cell Biol. 2016 Sep 26;214(7):807-16. * equal contribution.
    8. Dubrac A, Genet G, Ola R, Zhang F, Pibouin-Fragner L, Han J., Zhang J., Thomas JL, Chedotal A, Schwartz MA, Eichmann A. Targeting NCK-mediated endothelial cell front-rear polarity inhibits neo-vascularization. Circulation. 2016 Jan 26;133(4):409-21.
    9. Rama N*, Dubrac A*, Mathivet T, Ní Chárthaigh RA, Genet G, Cristofaro B, Pibouin-Fragner L, Ma L, Eichmann A and Chédotal A. Slit2 signaling through Robo1 and Robo2 is required for retinal neovascularization. Nature Medicine. 2015 May;21(5):483-91. * equal contribution.
    10. Aspalter IM*, Gordon E*, Dubrac A, Ragab A, Narloch J, Vizán P, Geudens I, Thomas Collins R, Franco CA, Abrahams CL, Thurston G, Fruttiger M, Ian Rosewell3, Anne Eichmann2,9,10†, Holger Gerhardt1, 6,11, †. Alk1 and Alk5 inhibition by Nrp1 controls vascular sprouting downstream of Notch. Nat Commun. 2015 Jun 17;6:7264. * equal contribution.
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Edited by Hoffmann Maude

Created on 9/18/2014
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