Feltri Research Overview

Our research focuses on adhesion between myelinating cells, axons and the extracellular matrix and the signals that promote myelination. 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 the extensions contacting axons and the RhoGTPAse interactome in Schwann cells. By these techniques we have identified novel molecules important for myelination and for the support of axons by glial cells. We have recently discovered that mechanical forces generated by the extracellular matrix and other cells are also essential for correct myelination, and we are actively pursuing the molecular mechanisms by which mechanical signals are transduced in myelin-forming glia.  

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 applying our experience on conditional mutagenesis to ask if there is cell autonomy in the pathogenesis of Krabbe disease.

Faculty and Staff

Dr. M. Laura Feltri

Professor of Biochemistry & Neurology

Dr. Feltri is currently Professor of Biochemistry and Neurology at the Hunter James Kelly Research Institute in the State University of New York at Buffalo.  Before 2011 she was 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.

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.

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

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

Michael Weaver

PhD student, HJKRI, Feltri Lab

  • 2015-present: MD/PhD student, Hunter James Kelly Research Institute, Department of Neuroscience, University at Buffalo. “The role of mechanotransduction in peripheral nerve development and regeneration.”
  • 2014-2015: Research Specialist, Princeton University. “The effect of high glucose levels on ECM assembly and mRNA splicing in diabetic nephropathy. Design of a high-throughput screen for detecting inhibitors of ECM fibril assembly. Analysis of wound healing markers in post-mastectomy breast reconstruction patients. Investigation of primary human fibroblasts harboring a novel mutation in fibronectin.”
  • 2011 – 2014: BA, Molecular Biology and Biochemistry, Rutgers University. “Extracellular matrix-mediated inhibition of Glioblastoma tumor cell detachment and dispersal.”

Students

Irene Yu, Medical Student

Arsalan Haghdel, Undergraduate student, Biomedical Sciences

Thomas Rush, Undergraduate Student, Biochemistry

Oliver Sampson, Undergraduate Student, Biomedical Engineering

Past Members

  • Kathleen Catignas, PhD Student
  • Yoonchan Hwang, Undergraduate student & Research Technician
  • 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