Department of Neuroscience

Professor and Chair of the Department of Neuroscience
Department of Neuroscience
Affiliated Cleveland Clinic Foundation Lerner Research Institute
College of Medicine

PubMed articles

Phone: 614-444-7177
Fax: 614-444-7927
Research Interests: Cellular and molecular biology of myelination, demyelination and dysmyelination

My Research Lab

Current Research:
Cellular and Molecular Biology of Myelination

The objective of this research effort is:

  1. To better understand cellular and molecular events involved in glial cell development and myelin formation
  2. To understand how myelin, myelin-forming cells and axons are destroyed in autoimmune demyelinating diseases and how gene mutations cause dysmyelination

A common theme of these research programs is that novel information about the normal function of myelin-forming cells and myelin-axon interactions will help us understand the mechanisms involved in human diseases which destroy myelin or myelin-forming cells.

Pathogenesis of Neurological Deficits in Multiple Sclerosis

The overall objective of these studies is to determine the cause of irreversible neurological deficits in MS patients and to develop methods to prevent and treat these.. MS is an inflammatory demyelinating disease of the central nervous system (CNS). Historically, it has been assumed that there was relative sparing of axons from the pathological consequences of inflammatory demyelination. Dr. Trapp's team has recently described consistent and abundant axonal transection in MS lesions. More importantly, the team’s data indicate that axonal transection begins at disease onset and is later accompanied by degeneration of chronically demyelinated axons.

The researchers propose that irreversible axonal loss represents the underlying pathogenic process responsible for permanent neurological deficits in MS patients. They propose that it is also responsible for the conversion of relapsing-remitting MS to secondary progressive MS. The therapeutic correlate to this hypothesis is that anti-inflammatory and neuroprotective strategies should be applied early in the disease course and continued during periods of apparent disease quiescence.

Current studies are investigating:

  • Cellular and molecular mechanisms of myelin and oligodendrocyte destruction
  • Mechanisms responsible for axonal degeneration in MS
  • Molecules and molecular interactions that mediate entry of immune cells into MS lesions
  • Animal models of inflammatory demyelination that include axonal transection

Continuation of these studies should provide direction for therapeutic intervention, which may delay or stop progression of MS. A major objective of these studies is to obtain a better understanding of cellular and molecular events that regulate oligodendrocyte production, differentiation and CNS myelination.

Current work focuses on the production and survival of newly formed or premyelinating oligodendrocytes in the developing rodent CNS. These cells are produced in excess during development and many are removed by programmed cell death.

Researchers are currently investigating the effects of axotomy on the production and survival of oligodendrocyte progenitors and premyelinating oligodendrocytes in the optic nerve. Researchers are testing the hypothesis that alternative splicing of myelinprotein genes occurs as premyelinating oligodendrocytes differentiate into myelin- forming oligodendrocytes. They are trying to determine if remyelination in the adult CNS involves the production of new oligodendrocytes in a manner which resembles that in development.

They also investigate the molecular interactions between glial cells and axons, which results in differentiation of myelin-forming cells and maturation of axons.

Other studies concentrate on the developmental appearance and location of glial and myelin proteins in normal development. These studies set the stage for further elucidation of their function in gene knockout or transgenic animals. Researchers are currently investigating the phenotypes in mice that are:

  1. Deficient in the myelin-associated glycoprotein and/or the L1 cell adhesion molecule
  2. Overexpressing PDGF
  3. Overexpressing protein in the peripheral nervous system (PNS) or expressing myelin protein zero (P0) protein in the CNS

Education: Loyola University

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