Department of Neurosciences
Bruce D Trapp, Ph.D.
Staff and Department Chair
Professor, Molecular Medicine, CCLCM-CWRU
Professor, Molecular Medicine, CCLCM-CWRU
Lerner Research Institute
9500 Euclid Avenue
Cleveland, Ohio 44195
Phone: (216) 444-7177
Fax: (216) 444-7927
Our research aims are to obtain a better understanding of cellular/molecular events involved in glial cell development and myelin formation in the central and peripheral nervous systems (CNS and PNS) and to understand how myelin, myelin-forming cells, and axons are destroyed in autoimmune and inherited diseases of myelin.
New data about the normal functioning of myelin-forming cells and myelin-axon interactions will help us understand the pathogenic mechanisms involved in permanent neurological disability in human diseases of myelin.
Cellular/Molecular Biology of Myelination: Our aim is to obtain a better understanding of cellular/molecular events that regulate production and differentiation of oligodendrocytes and CNS myelination. Using transgenic mice, we study the role of myelin and myelin proteins in maintaining axonal function and survival. We also investigate the role ofCNS progenitor cells as a source of new oligodendrocytes in the adult brain.
Pathogenesis of Neurological Disability in Multiple Sclerosis (MS): In these studies, we seek to determine the causes of MS, an inflammatory demyelinating disease of the CNS, and to therapeutically preventirreversible neurological disability in MS patients. Historically, it has been assumed that axons were spared most of the pathological consequences of inflammatory demyelination. We have described axonal degeneration during demyelination and as a result of chronic demyelination. We also focus on neuronal degeneration and axonal pathology in the cerebral cortex and hippocampus of MS patients. Recent studies also focus on the therapeutic potential of progenitor cells to repair demyelinated or dysmyelinated brain.
Selected from ~230:
Yin X, Kidd GJ, Ohno N, Perkins GA, Ellisman MH, Bastian C, Brunet S, Baltan S, Trapp BD. (2016) Proteolipid protein-deficient myelin promotes axonal mitochondrial dysfunction via altered metabolic coupling. J Cell Biol 215(4):531-542. PMID: 27872255; PMCID: PMC5119941
Bai CB, Sun S, Roholt A, Benson E, Edberg D, Medicetty S, Dutta R, Kidd G, Macklin WB, Trapp B. (2016) A mouse model for testing remyelinating therapies. Exp Neurol 283(Pt A):330-340. PMID: 27384502
Chen Z, Chen JT, Johnson M, Gossman ZC, Hendrickson M, Sakaie K, Martinez-Rubio C, Gale JT, Trapp BD. (2015) Cuprizone does not induce CNS demyelination in nonhuman primates. Ann Clin Transl Neurol 2:208-13. PMID:25750925; PMCID:PMC4338961
Mahad DH, Trapp BD, Lassmann H. (2015) Pathological mechanisms in progressive multiple sclerosis. Lancet Neurol 14:183-93. PMID:25772897
Yin X, Kiryu-Seo S, Kidd GJ, Feltri ML, Wrabetz L, Trapp BD. (2015) Proteolipid protein cannot replace P0 protein as the major structural protein of peripheral nervous system myelin. Glia 63: 66-77. PMID:25066805; PMCID:PMC4237650
Chiang H, Ohno N, Hsieh YL, Mahad DJ, Kikuchi S, Komuro H, Hsieh ST, Trapp BD. (2015) Mitochondrial fission augments capsaicin-induced axonal degeneration. Acta Neuropathol 129:81-96. PMID:25322817; PMCID:PMC4282704
Chen Z, Jalabi W, Hu W, Park HJ, Gale JT, Kidd GJ, Bernatowicz R, Gossman ZC, Chen JT, Dutta R, Trapp BD. (2014) Microglial displacement of inhibitory synapses provides neuroprotection in the adult brain. Nat Commun 22: 4486-97. PMID:25047355; PMCID:PMC4109015
Ohno N, Chiang H, Mahad DJ, Kidd GJ, Liu L, Ransohoff RM, Sheng ZH, Komuro H, Trapp BD. (2014) Mitochondrial immobilization mediated by syntaphilin facilitates survival of demyelinated axons. Proc Natl Acad Sci USA 111: 9953-58, 2014. PMID:24958879; PMCID:PMC4103317
Dutta R, Trapp BD. (2014) Relapsing and progressive forms of multiple sclerosis: insights from pathology. Curr Opin Neurol 27: 271-78. PMID:24722325; PMCID:PMC4132635
Huynh JL, Garg P, Thin TH, Yoo S, Dutta R, Trapp BD, Haroutunian V, Zhu J, Donovan MJ, Sharp AJ, Casaccia P. (2014) Epigenome-wide differences in pathology-free regions of multiple sclerosis-affected brains. Nat Neurosci 17: 121-30. PMID:24270187; PMCID:PMC3934491
Koenig KA, Sakaie KE, Lowe MJ, Lin J, Stone L, Bermel RA, Beall EB, Rao SM, Trapp BD, Phillips MD. (2013) High spatial and angular resolution diffusion-weighted imaging revelas forniceal damage related to memory impairment. Magn Reson Imaging 31: 695-99. PMID:23295147
Chen JT, Easley K, Schneider C, Nakamura K, Kidd GJ, Chang A, Staugaitis SM, Fox RJ, Fisher E, Arnold JL, Trapp BD. (2013) Clinically feasible MTR is sensitive to cortical demyelination in MS. Neurology 80: 246-52. PMID:23269598; PMCID:PMC3589181
Dutta R, Chomyk AM, Chang A, Ribaudo MV, Deckard SA, Doud MK, Edberg DD, Bai B, Li M, Baranzini SE, Fox RJ, Staugaitis SM, Macklin WB, Trapp BD. (2013) Hippocampal demyelination and memory dysfunction are associated with increased levels of the neuronal microRNA miR-124 and reduced AMPA receptors. Ann Neurol 73: 637-45. PMID:23595422; PMCID:PMC3679350
Nikolakopoulou AM, Dutta R, Chen Z, Miller RH, Trapp BD. (2013) Activated microglia enhance neurogenesis via trypsinogen secretion. Proc Natl Acad Sci USA 110: 8714-19, 2013. PMID:23650361; PMCID:PMC3666689
Koenig KA, Lowe MJ, Lin J, Sakaie KE, Stone L, Bermel RA, Beall EB, Rao SM, Trapp BD, Phillips MD. (2013) Sex differences in resting-state functional connectivity in multiple sclerosis. AJNR Am J Neuroradiol 34: 2304-11, 2013. PMID:23811974
Kang Z, Wang C, Zepp J, Wu L, Sun K, Zhao J, Chandrasekharan U, DiCorelto PE, Trapp BD, Ransohoff RM, Li X. (2013) Act1 mediates IL17-induced EAE pathogenesis selectively in NG2+ cells. Nat Neurosci16: 1401-08. PMID:23995070; PMCID:PMC4106025
Chen Z, Jalabi W, Shpargel KB, Farabaugh KT, Dutta R, Yin X, Kidd GJ, Bergmann CC, Stohlman SA, Trapp BD. (2012) Lipopolysaccharide-induced microglial activation and neuroprotection against experimental brain injury is independent of hematogenous TLR4. J Neurosci 32: 11706-15, 2012. PMID:22915113; PMCID:PMC4461442
Campbell GR, Kraytsberg Y, Krishnan KJ, Ohno N, Ziabreva I, Reeve A, Trapp BD, Newcombe J, Reynolds R, Lassmann H, Khrapko T, Turnbull DM, Mahad DJ. (2012) Clonally expanded mitochondrial DNA deletions within the choroid plexus in multiple sclerosis. Acta Neuropathol 124: 209-20. PMID:22688405; PMCID:PMC3674417
Chang A, Staugaitis SM, Dutta R, Batt CE, Easley KE, Chomyk AM, Yong VW, Fox RJ, Kidd GJ, Trapp BD. (2012) Cortical remyelination: a new target for repair therapies in multiple sclerosis. Ann Neurol 72: 918-26. PMID:23076662; PMCID:PMC3535551