Former Feltri Laboratory

Feltri Research Overview

Sciatic nerve fibers were teased and immunostained of Cajal Bands and cytoskeleton.

Sciatic nerve fibers that were teased and immunostained for various components of Cajal Bands and of the cytoskeleton.

The Feltri lab research focused on adhesion between myelinating cells, axons and the extracellular matrix and the signals that promote myelination. One of their major efforts was 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.

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 tested 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.

While at the Institute for Myelin and Glia Exploration, the Feltri laboratory researchers applied their experience on conditional mutagenesis to ask if there is cell autonomy in the pathogenesis of Krabbe disease.

Dr. M. Laura Feltri

DIRECTOR, 2011 - 2023

SUNY DISTINGUISHED Professor of Biochemistry & Neurology

Dr. Feltri was a Professor of Biochemistry and Neurology at the Institute for Myelin and Glia Exploration in the State University of New York at Buffalo and Director of the Institute. 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.

Learn more on the M. Laura Feltri Legacy page