Bruce D. Trapp, Ph.D.
Professor
Department of Neuroscience
Chairman
Department of Neurosciences Cleveland Clinic Foundation Lerner Research Institute / NC30
Degree: Loyola University
Phone: (614) 444-7177
Fax: (614) 444-7927
Email: trappb@ccf.org
Link to NLM PubMed publications list for Bruce D. Trapp (last 10 years)
Research Area:
Cellular and Molecular Biology of Myelination, Demyelination, and Dysmyelination.
Current Research:
The objective of our research effort is two-fold. The first is to obtain a better understanding of cellular and molecular events involved in glial cell development and myelin formation. The second is 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.
Cellular and molecular biology of myelination
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. We are currently investigating the effects of axotomy on the production and survival of oligodendrocyte progenitors and premyelinating oligodendrocytes in optic nerve. We are testing the hypothesis that alternative splicing of myelin protein genes occurs as premyelinating oligodendrocytes differentiate into myelin- forming oligodendrocytes. We are trying to determine if remyelination in the adult CNS involves the production of new oligodendrocytes in a manner which resembles that in development. We 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 and set the stage for further elucidation of their function in gene knockout or transgenic animals. We 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 P0 protein in the PNS or expressing P0 protein in the CNS.
Pathogenesis of Neurological Deficits in Multiple Sclerosis
The overall objective of these studies is to determine the cause and to therapeutically prevent irreversible neurological deficits in MS patients. MS is an inflammatory demyelinating disease of the CNS. Historically, it has been assumed that there was relative sparing of axons from the pathological consequences of inflammatory demyelination. We have recently described consistent and abundant axonal transection in MS lesions. More importantly, our data indicate that axonal transection begins at disease onset and is later accompanied by degeneration of chronically demyelinated axons. We propose that irreversible axonal loss represents the underlying pathogenic process responsible for permanent neurological deficits in MS patients and 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, and 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.
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