University at Buffalo, The State University of New York

Feltri Laboratory

We seek to understand how cell-cell and cell-extracellular matrix interactions contribute to cell shape and polarity within a developing tissue. We apply these biological questions to the development of the nervous system and to the process of myelination, with the goal to translate basic findings into a cure for demyelinating diseases.

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Feltri Research Overview

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Our research focuses on adhesion and signaling molecules that mediate contact between myelinating cells and axons or the extracellular matrix. One of our major efforts has been the study of laminin receptors on Schwann cells, the myelinating peripheral glia. By generating and comparing animal models of demyelinating neuropathies to patient's biopsies, we and others have determined that laminins are required for 'radial sorting' of axons in early development. Radial axonal sorting is a pre-requisite for myelination and is arrested in human laminins and dystroglycan-glycosyltransferases deficiencies. Using conditional mutagenesis we have determined that integrins, dystroglycan and RhoGTPAses are required for radial sorting because they induce cytoskeletal rearrangements that allow the generation of glial extensions that contact and wrap axons.

More recently, we have adapted innovative sub-fractionation and proteomic techniques to profile these extensions contacting axons and the RhoGTPAse interactome in Schwann cells. Laminin receptors are also important for myelin and nodes of Ranvier to achieve the correct length, thickness, architecture and stability. Patients lacking laminins have abnormally thick and instable myelin, short internodes and immature nodes of Ranvier. We first determined that laminin 211, dystroglycan and certain integrins are required to form myelin of normal cytoarchitecture, and now we are seeking to understand why perturbing laminin function leads to myelin instability and demyelination.

Using genetic, cell biology and biochemistry we are testing the hypothesis that laminin receptors influence growth factors and signaling molecules to prevent demyelination. These studies also lead us to discover that some of the signaling molecules under scrutiny are more important in the central nervous system, where they inhibit oligodendrocyte myelination. Thus they represent potential molecular targets to promote remyelination in demyelinating disease such as Multiple Sclerosis of Leukodystrophies.

Since our arrival at the HJKRI we are also applying our experience on conditional mutagenesis to ask if there is cell autonomy in the pathogenesis of Krabbe disease.

HJKRI Lawrence Wrabetz profile picture

Faculty and Staff

Dr. M. Laura Feltri
Professor of Biochemistry & Neurology

 

Dr. Feltri is currently Professor of Biochemistry at the Hunter James Kelly Research Institute in the State University of New York at Buffalo, the Head of the Unit of NeuroGlia in the San Raffaele Scientific Institute of Milano, and adjunct Associate Professor in the Department of Neurology at the University of Pennsylvania...

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Yannick Poitelon

Research Assistant Professor, Department of Biochemistry

Post Doctoral Research Scientist, HJKRI, Feltri Lab

  • 2016 - present: Hunter James Kelly Research Institute, University at Buffalo, NY, USA, Research Assistant Professor
  • 2011 - present: Hunter James Kelly Research Institute, University at Buffalo, NY, USA, Postdoctoral Research Scientist
  • 2010 - 2011: DIBIT - Neuroglia Unit, San Raffaele Institute, Milan, Italy, Postdoctoral fellow
  • 2008: Vascular Biology Unit, Instituto de Biomedicina de Valencia, Spain, Training
  • 2005 - 2009: PhD in Medical Genetic, Aix-Marseilles University, France, "Exploration of animal and cellular models of AR-CMT2A"
  • 2004 - 2005: Master in Human Pathology, Aix-Marseille University, France. "Pathophysiological mechanisms of Lamin A/C associated Charcot-Marie-Tooth disease"
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    Leandro Marziali

    Post Doctoral Research Scientist, HJKRI, Feltri Lab

  • 2016 - present: Postdoctoral Research Scientist in the Feltri laboratory at the Hunter James Kelly Research Institute for studying the role of p38gamma on myelination and oligodendrocyte maturation.
  • 2016: received PhD in neuroscience.
  • 2010 - 2016: Laboratory of Dra. Juana Pasquini at the School of Pharmacy and Biochemistry of the University of Buenos Aires (IQUIFIB-CONICET). PhD project involving the study of the combined effects of Transferrin and Thyroid Hormone on CNS myelination and oligodendrocyte maturation.
  • 2009: University of Buenos Aires, Buenos Aires, Argentina. Biochemistry major.
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    Kathleen Catignas

  • 2011 - present: Hunter James Kelly Research Institute, SUNY Buffalo, Department of Biochemistry. PhD student under Dr. M. Laura Feltri, investigating the integrins at the Schwann cell-axon interface during peripheral nerve development.
  • 2007 - 2011: University of North Carolina @ Greensboro. Lab instructor. Member of Dennis LaJeunesse lab, studying the role of DH31-expressing enteroendocrine cells in the Drosophila midgut.
  • 2002 - 2007: Florida State University. Biology major with a concentration in Cellular/Molecular Biology. Florida Bright Futures Scholar. 2007 Undergraduate Teaching Assistant. Directed Individual Study in Drosophila genetics with Dr. Wu-Min Deng.
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    Nadav Weinstock

    MD-PhD student, HJKRI, Feltri Lab

  • 2012 - present: MD/PhD student, University at Buffalo School of Medicine
  • 2008 - 2012: BS, Biological Sciences, University at Buffalo
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    Gustavo Della Flora Nunes

    PhD student, HJKRI, Feltri Lab

  • 2015 – present: Hunter James Kelly Research Institute, SUNY Buffalo, Department of Biochemistry. PhD student under Dr. M. Laura Feltri
  • 2014-2015: Master in Neuroscience, Federal University of Rio Grande do Sul, Brazil. “Animal model of autism by prenatal exposure to valproic acid: analysis of excitatory and inhibitory synapses”.
  • 2009-2013: BS, Biomedical Sciences, Federal University of Rio Grande do Sul, Brazil
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    Joseph Gawron

    Research Technician, HJKRI, Feltri Lab

  • 2016-present: Research Technician, Hunter James Kelly Research Institute, University at Buffalo
  • 2013-2015: MS in Biotechnology, University at Buffalo. “Silencing and Overexpression of the Ubiquitin-Conjugating Enzyme E2B in Murine Erythroleukemia Cells”
  • 2009-2013: BS, Biology, Canisius College, Buffalo, New York
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    Yoonchan Hwang

    Research Technician III, HJKRI, Feltri lab

  • 2014- present: Research Technician III in the Feltri laboratory at the Hunter James Kelly Research Institute for studying the role of p38gamma on myelination and oligodendrocyte maturation.
  • 2014: BS, Biological Science, University at Buffalo
  • 2013-2014: Laboratory of Dr. Michael C. Yu, Biological Science, University at Buffalo. The projects involve arginine methylation in protein-protein interactions in the TRAMP complex and splicesomal proteins in S. cerevisiae.


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    Students

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    Irene Yu, Medical Student Arsalan Haghdel, Undergraduate student, Biomedical Sciences Thomas Rush, Undergraduate Student, Biochemistry

    Past Members

    • Kevin Espino, Undergraduate
    • Scott Ferguson, Undergraduate
    • Gustavo Della Flora Nunes, Undergraduate
    • Marta Pellegatta, PhD Student
    • Dominique Ameroso, Master student & Research Technician
    • Kansho Abiko, Undergraduate
    • Monica Ghidinelli, PhD Student
    • Marilena Palmisano, PhD Student
    • Kenneth Minorczyk, Undergraduate

    Selected Publications

    • Poitelon Y, Lopez-Anido C, Catignas K, Berti C, Palmisano M, Williamson C, Ameroso D, Abiko K, Hwang Y, Gregorieff A, Wrana JL, Asmani M, Zhao R, Sim FJ, Wrabetz L, Svaren J, Feltri ML.YAP and TAZ control peripheral myelination and the expression of laminin receptors in Schwann cells. . Nat Neurosci. 2016 Jul; 19(7):879-87.
    • Poitelon Y, Bogni S, Matafora V, Della-Flora Nunes G, Hurley E, Ghidinelli M, Katzenellenbogen BS, Taveggia C, Silvestri N, Bachi A, Sannino A, Wrabetz L, Feltri ML. Spatial mapping of juxtacrine axo-glial interactions identifies novel molecules in peripheral myelination. . Nat Commun. 2015 Sep 18;6:8303.
    • Colombelli C, Palmisano M, Eshed-Eisenbach Y, Zambroni D, Pavoni E, Ferri C, Saccucci S, Nicole S, Soininen R, McKee KK, Yurchenco PD, Peles E, Wrabetz L, Feltri ML. Perlecan is recruited by dystroglycan to nodes of Ranvier and binds the clustering molecule gliomedin. . J Cell Biol. 2015 Feb 2;208(3):313-29.
    • Pellegatta M, De Arcangelis A, D'Urso A, Nodari A, Zambroni D, Ghidinelli M, Matafora V, Williamson C, Georges-Labouesse E, Kreidberg J, Mayer U, McKee KK, Yurchenco PD, Quattrini A, Wrabetz L, Feltri ML. ?6?1 and ?7?1 Integrins are Required in Schwann Cells to Sort Axons. J Neurosci. 2013 Nov 13;33(46):17995-8007.
    • Berti C, Bartesaghi L, Ghidinelli M, Zambroni D, Figlia G, Chen ZL, Quattrini A, Wrabetz L, Feltri ML. Non-redundant function of dystroglycan and ?1 integrins in radial sorting of axons. Development. 2011 Sep;138(18):4025-37.
    • Court FA, Zambroni D, Pavoni E, Colombelli C, Baragli C, Figlia G, Sorokin L, Ching W, Salzer JL, Wrabetz L, Feltri ML. MMP2-9 cleavage of dystroglycan alters the size and molecular composition of Schwann cell domains. J Neurosci. 2011 Aug 24;31(34):12208-17.
    • Taveggia C, Feltri ML, Wrabetz L. Signals to promote myelin formation and repair. Nat Rev Neurol. 2010 May;6(5):276-87.
    • Court FA, Hewitt JE, Davies K, Patton BL, Uncini A, Wrabetz L, Feltri ML. A laminin-2, dystroglycan, utrophin axis is required for compartmentalization and elongation of myelin segments. J Neurosci. 2009 Mar 25;29(12):3908-19.
    • Nodari A, Zambroni D, Quattrini A, Court FA, D'Urso A, Recchia A, Tybulewicz VL, Wrabetz L, Feltri ML. Beta1 integrin activates Rac1 in Schwann cells to generate radial lamellae during axonal sorting and myelination. J Cell Biol. 2007 Jun 18;177(6):1063-75. PubMed PMID: 17576799; PubMed Central PMCID: PMC2064366.

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