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Lawrence                       Wrabetz

Lawrence Wrabetz MD

Department of Neurology

Director, Hunter James Kelly Research Institute; Professor of Neurology and Biochemistry

Specialty/Research Focus

Developmental Neurology; Neurology

 
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Professional Summary:

My laboratory has a longstanding interest in myelin and its diseases. Myelin surrounds large axons and permits rapid conduction of signals. It is formed by oligodendrocytes in the central nervous system, and Schwann cells in the peripheral nervous system. During development, these cells migrate with the axons that they will myelinate, and depend on those same axons for appropriate signals to survive and differentiate. Myelin-forming glia coordinately express a unique set of genes encoding myelin structural proteins, and enzymes that synthesize myelin lipids-this coordination is in large part transcriptionally-mediated. Given the unique three dimensional transformation of the cell required for myelination, many of the involved proteins include adhesion among their functions. Therefore, our projects include studies of transcriptional regulation, axonal signals to myelinating glia, the role of adhesion in myelination and the characterization of animal models of human demyelinating diseases.

Education and Training:
  • Fellowship, Neuroscience, University of Pennsylvania School of Medicine (1991)
  • Residency, Neurology, University of Pennsylvania School of Medicine (1988)
  • MD, Medicine and Surgery, University of Chicago Pritzker School of Medicine, (Honors) (1984)
  • BS, Chemistry, Marquette University, Summa Cum Laude (1980)
Employment:
  • Professor, Departments of Neurology and Biochemistry, State University of New York at Buffalo, School of Medicine and Biomedical Sciences (2011-present)
  • Director, HJKRI-Hunter James Kelly Research Institute, State University of New York at Buffalo, School of Medicine and Biomedical Sciences (2011-present)
  • Adjunct Member, Cancer Center Genetics Program, Roswell Park Cancer Institute (2011-present)
  • Head of Unit: Biology of Myelin, San Raffaele Scientific Institute, DIBIT, Italy (1995–2011)
  • Researcher, Dept. Genetics and Cell Biology, San Raffaele Scientific Institute, DIBIT, Italy (1993–2011)
  • Lecturer, Department of Neurology, University of Pennsylvania, School of Medicine (1991–1993)

Research Expertise:
  • Developmental neurology
  • Leukodystrophy
Research Centers:
  • Center of Excellence in Bioinformatics and Life Sciences
UB 2020 Strategic Strengths:
  • Molecular Recognition in Biological Systems and Bioinformatics
Grants and Sponsored Research:
  • December 2007–December 2020
    Grants and Sponsored Research(selected)
    Role: Principal Investigator
  • April 2012–March 2017
    NIH: R25 GM095459: Enabling Access to Cutting-Edge Biomedical and Behavioral Science
    Role: Co-Investigator
    $1,900,000
  • April 2010–June 2015
    Empire State Development Corporation - Krabbe Disease Research Capital Equipment
    NY
    Role: Principal Investigator
    $6,000,000
  • September 2010–December 2013
    Telethon Program Project: Modulating Neuregulin-1 signals to treat hereditary demyelinating neuropathies
    Role: Principal Investigator
    $406,100
  • October 2012–September 2013
    Empire State Development Corporation, The Research Foundation - Krabbe Disease Research Working Capital
    NY
    Role: Principal Investigator
    $980,000
  • February 2006–January 2012
    NIH: R01 NS055256 Pathogenesis of Myelin Protein Zero Neuropathies in Transgenic Mice
    Role: Principal Investigator
    $1,215,000
  • February 2009–January 2011
    Fondazione Mariani: Side by Side analysis of children and mice with Myelin Protein Zero Neuropathies to promote treatment strategies
    Role: Principal Investigator
    $186,078
  • September 2007–August 2010
    Telethon GGP07100: P0 glycoprotein trafficking and quality control in Charcot Marie Tooth 1B Neuropathy
    Role: Principal Investigator
    $487,654
See All (8 Total) >

Journal Articles:
See All (35 Total) >
Books and Book Chapters:
  • Wrabetz L, Feltri ML, Kleopa K, Scherer S. Inherited Neuropathies- Clinical, Genetic, and Biological Features. In Lazzarini, R (ed.), Myelin Biology and Disorders, Academic Press, San Diego, 2004, 905-951..
  • Wrabetz L, Feltri ML, Suter U. Animals Models of Charcot-Marie-Tooth Disease. In Lazzarini, R (ed.), Myelin Biology and Disorders, Academic Press, San Diego, 2004, 1143-1168..
  • Kirschner D, Wrabetz L, Feltri ML. P0: Gene, Protein, Function. In Lazzarini, R (ed.), Myelin Biology and Disorders, Academic Press, San Diego, 2004, 523-545..
  • Scherer SS, Feltri ML, Wrabetz L. Genetic Mutations Affecting Myelination. In Kettenmann H, Ransom BR (ed.), Neuroglia, 3rd ed. Oxford University Press, Oxford, UK, 2012, 796-806..

Presentations:
  • "Presentations: Oral Presentations/Symposia Chair by Invitation (selected):" (2013)
  • "Pathogenesis in Hereditary Demyelinating Neuropathies: Toxic Mechanisms Target Development" Richard P. Bunge Memorial Lecture in Neuroscience, University of Miami (2013)
  • "Endoplasmic Reticulum Stress and Translational Homeostasis in Myelinating Glia" Conference on Glia in Disease, University of Rochester, CTSI Symposium (2012)
  • "ER Stress in Glia and Neurodegeneration" , University of Buffalo, Molecular Basis of Neurodegenerative Disorders (2012)
  • "Preclinical Studies in Animals" Muscle Study Group Scientific Meeting (2012)
  • "Pathogenesis in CMT Neuropathy versus Krabbe Leukodystrophy" 2nd Krabbe Translational Research Network, University of Pittsburgh (2012)
  • "Toxic Mechanisms Impact Development in Hereditary Neuropathies" , Washington University School of Medicine, Department of Developmental Biology (2012)
  • "Translational Homeostasis as a Therapeutic Target in CMT1B Neuropathy" 8th Great Lakes Glia Meeting (2011)
  • "Translational Homeostasis as a Therapeutic Target in ER stress Diseases" ISN Satellite Meeting on Myelin Biology (2011)
  • "Translational Homeostasis as a Therapeutic Target in ER Stress Diseases" Translational Homeostasis as a Therapeutic Target in ER Stress Diseases (2011)
  • "Genetic Background and CMT animal models" European Neuromuscular Center, Outcome Measures in Rodent Models of CMT (2011)
  • "Translational Homeostasis as a Therapeutic Target in ER Stress Diseases" MRC Centre for Neuromuscular Diseases, University College London (2010)
  • "Schwann cell pathways in inherited demyelinating neuropathies" World Federation of Neurology-XII International Congress on Neuromuscular Diseases, World Federation of Neurology-XII International Congress, Pathogenic Mechanisms of Inherited Neuropathies (2010)
  • "Toxic Mechanisms in Hereditary Neuropathy" ISF-Legacy Heritage Fund Inaugural Meeting On New Approaches To Neurodegenerative Diseases (2010)
  • "Endoplasmic reticulum stress impedes differentiation and translational homeostasis in hereditary demyelinating neuropathy" , CSIC Institute of Neuroscience, UMH (2009)
  • "Altered translational control is pathogenetic in CMT1B mice" , Myelin Satellite to International Society for Neurochemistry (2009)
  • "P0S63del impedes the arrival of wildtype P0 glycoprotein to myelin in CMT1B mice" CMT Meeting (2009)
  • "Cell stress signals and peripheral neuropathy" , IFTZ Medizinische Universität (2008)
  • "Packing defects or cell stress modulate hereditary demyelinating neuropathy" , University of Illinois (2008)
  • Gordon Conference Myelin, Glial cell death and axonal pathology (2008)
  • "Intracellular pathogenesis and phenotype in CMT neuropathies" Glial Cells in Health & Disease: The VIIIth European Meeting, The Molecular Pathology of Myelination (2007)
  • "Inherited Neuropathies and Schwann cells" Peripheral Nerve Society Meeting (2007)
  • "MTMR2 phospholipid phosphatase, CMT4B, and membrane trafficking in Schwann cells" Second European and North American Charcot-Marie-Tooth Consortium Meeting, Cell Biology of CMT (2007)
  • "Endoplasmic reticulum stress and pathogenesis of CMT1B neuropathy" , European Neurochemical Society, : Inherited Peripheral Neuropathies and Schwann cell Biology (2007)
  • "Pathogenetic basis for phenotypic variation in CMT neuropathies" International Symposium on CMT neuropathies, German Congress for Muscle Pathology (2007)
  • "Pathological Protein Quality Control in Hereditary Neuropathy" Director’s Seminar Series, National Institute of Neurological Disorders and Stroke, NIH (2006)
  • "Pitfalls of Translational Research for Genetic Diseases—The Plus and Minus of Animal Models" Translational Research Forum, National Institute of Neurological Disorders and Stroke, NIH (2006)
  • "Transgenic Mouse Models of Phenotypic Diversity in Hereditary Demyelinating Neuropathies" , University of Torino, University of Torino (2006)
  • "Unfolded Protein Response: A Cause for demyelinating Charcot Marie Tooth Neuropathy" Interdepartmental Seminar Series, University of Bonn (2006)
  • "ER Stress Modulates Demyelinating CMT Neuropathy in Transgenic Mice" , Albert Einstein School of Medicine, Department of Neuroscience (2006)
  • "Myelin Protein Zero trafficking and quality control in Charcot-Marie-Tooth neuropathies" Myelin Gordon Conference (2006)
  • "Intracellular pathogenesis of childhood-onset hereditary neuropathies" , University of Antwerp (2006)
  • "Intracellular pathogenesis of childhood-onset hereditary neuropathies" Research advances in developmental neurosciences and paediatric neurology, Congress of the European Academy of Childhood Disability (2005)
  • "Protein Quality Control of P0 Glycoprotein in Hereditary Neuropathies" Jordi Folch-Pi Memorial Symposium, American Society for Neurochemistry, Progress on the pathogenesis of hereditary neurodegenerative disorders (2005)
  • "Gain of abnormal function and phenotypic diversity in MPZ-related neuropathies" Second Annual Symposium of the North American Charcot-Marie-Tooth Consortium, Ann Lee Beyer Plenary Lecture (2005)
  • "Protein quality control in the pathogenesis of CMT1B hereditary neuropathy" Dutch Endo-Neuro-Psycho Meeting (2005)
  • "Importance of defined genetic background to experimental design" , Charles River Laboratories European Short Course (2005)
  • "Protein Quality Control of P0 Glycoprotein in Mouse Models of Hereditary Neuropathies" , Vienna BioCenter (IBMA, IMP & Univ Vienna) and Austrian Society of Genetics (2004)
  • "Transgenic mouse models of CMT1B neuropathy reveal gain of abnormal Mpz function" First European and North American Charcot-Marie-Tooth Consortium Meeting, CMT type 1B and MPZ (2004)
  • "Genetic Nomenclature, Defined Strains and Experimental Design" , Charles River Laboratories/The Jackson laboratory Course, Setting the gold standard in genetics (2004)
  • "Genotype, phenotype and mechanism comparisons in transgenic mouse models of hereditary neuropathies" , IBRO Congress (2003)
  • "Schwann cell biology: from developmental mechanisms to pathological processes" , IBRO Congress (2003)
  • "Transgenic mouse models of hereditary neuropathy" UK Glial Club Meeting (2003)
  • "Trangenic mice model diversity in hereditary neuropathies" , European School of Medical Genetics (2002)
  • "Proteomics on transgenic optic nerve" Franco-Italian Meeting on MS (2001)
  • "Axoglial signals target the myelin basic protein promoter" INSERM, Hopital de la Salpetriere (2000)
  • "Epitope tagged-P0 glycoprotein in transgenic mice causes CMT1B-like neuropathy" , Society for Neuroscience (2000)
  • "Gain of P0 glycoprotein function: Mouse models of diverse hereditary neuropathies" , University of Edinburgh (2000)
  • "Gain of P0 function: Mouse models of hereditary neuropathies" Gordon Conference on Myelin (2000)
  • "From stem cells to glia: molecules and mechanisms" UK Glial Cell Club Meeting (2000)
  • "P0 overexpression causes congenital hypomyelination in transgenic mice" Telethon Scientific Convention (1999)
  • "A distinct axonal signal regulates MBP transcription during CNS myelinogenesis" Society for Neuroscience (1999)
  • "Regulation of MBP transcription during CNS myelinogenesis: the role of axons" British Neuroscience Association Meeting (1999)
  • "P0 gene dosage and mouse models of CMT1B" Third International Conference on Charcot-Marie-Tooth Disorders (1998)
  • "Increased P0 glycoprotein gene dosage causes a dysmyelinating peripheral neuropathy in transgenic mice" Gordon Conference on Myelin (1998)
  • "Normal PNS myelination depends on precise dosage of the P0 glycoprotein gene" Armenise-Harvard Symposium (1997)
  • "Transgenic mouse model of remyelination" Remyelination in Multiple Sclerosis, European Charcot Foundation Symposium (1996)
  • "Normal PNS myelination depends on precise dosage of the P0 glycoprotein gene" Armenise-Harvard Symposium
See All (58 Total) >

Clinical Specialties:
Clinical Offices:
Insurance Accepted:

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Contact Information

701 Ellicott Street
Hunter James Kelly Research Institute
NYS Center of Excellence Bioinformatics & Life Sciences, B4-324
Buffalo, NY 14203
Phone: (716) 881-8913
Fax: (716) 849-6651
Email: lwrabetz@buffalo.edu


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