- Research Associate Professor of Neurology at University of Pennsylvania School of Medicine (1995 – 2014)
- Research Professor of Neurology at University of Pennsylvania School of Medicine (2014– present)
- Research Assistant Professor of Neurology at University of Pennsylvania School of Medicine (1989 – 1995)
- Associate Professor of Pediatrics at University of Pennsylvania School of Medicine (2008 – 2014)
- Professor of Pediatrics at University of Pennsylvania School of Medicine (2014– present)
Children's Hospital of Philadelphia
516D Abramson Research Center
Our lab studies factors that control the maturation of oligodendrocytes, the myelinating cells of the central nervous system, from stem cells through to myelination.
Key words: oligodendrocytes, myelin, growth factors, oxidative stress, neuroinflammation, MS, HIV, perinatal white matter injury
Description of Research
In the central nervous system, oligodendrocytes synthesize myelin as an extension of their plasma membranes. This myelin wraps axons and facilitates rapid and efficient conduction of nervous impulses as well as axonal nourishment and protection. Destruction of myelin through injury, such as birth injury leading to cerebral palsy, or disease, such as multiple sclerosis or HIV, causes loss of motor and cognitive function. Oligodendrocyte precursors and stem cells remain in the CNS following the pathology and are potentially capable of forming mature oligodendrocytes and then myelin. However, their maturation is severely limited. Reasons for this include processes such as oxidative stress and inflammation which signal to inhibitors present in the area that impede maturation. Our goal is to identify factors in the CNS that inhibit the development of mature oligodendrocytes both during development and disease. We have identified several key signaling factors that regulate developmental myelination and are increased during demyelinating disease. On-going areas of investigation in the lab include: 1) The role of white matter loss and demyelination in HIV-associated neurocognitive deficits. 2) Factors which limit myelination in perinatal white matter injury. 3) The role of lipid signaling in developmental myelination and remyelination following demyelinating disease.
Micah Romer research assistant
Bassam Zidane, graduate student
Lindsay Roth, graduate student
- Ph.D., Biology, University of Pennsylvania (1984)
- M.S., Pathology, Hahnemann University (1977)
- A.B., Biology, Vassar College (1974)
- Monnerie, H., Romer, M., Jensen, B., Millar, J., Jordan-Sciutto, K., Kim, S.F., Grinspan, J.B.: Reduced Sterol Regulatory Element-Binding Protein (SREBP) Processing through Site-1 Protease (S1P) Inhibition Alters Oligodendrocyte differentiation In Vitro. J. Neurochem. 140: 53-67, 2017.
- Jensen, B.K., Monnerie, H., Mannell, M.V., Gannon, P.J., Espinoza-Akay, C., Erickson, M.A., Bruce-Keller, A.J., Gelman, B.B., Briand, L.A., R. Pierce, R.C., Jordan-Sciutto, K.L., Grinspan, J.B.: Altered Oligodendrocyte Maturation and Myelin Maintenance: The Role of Anti-Retrovirals in HIV-Associated Neurocognitive Disorders. Journal of Neuropathology Experimental Neurology 74(11): 1093-1118, November 2015.
- Veasey, S.C., Lear, J., Zhu, Y.,Grinspan, J. B., Hare, D.J., Wang, S., Bunch,D., Lim, D.C., Doble, P.A., Robinson, S.R.: Long-term Intermittent Hypoxia Elevates Cobalt Levels in the Brain and Injures White Matter in Adult Mice. Sleep 36: 1471-1481, 2013.
- Reid, M.V., Murray, K. A., Marsh, E.D., Golden, J. A., Simmons, R.A., Grinspan, J. B.. Delayed myelination in an intrauterine growth retardation model is mediated by oxidative stress upregulating BMP4. Journal of Neuropathology Experimental Neurology. Vol 71(7) . 2012:640-653, 2012.
- Feigenson, K., Reid, M., See, J., Crenshaw, E.B. III, Grinspan, J. B.. Canonical Wnt signaling requires the BMP pathway to inhibit oligodendrocyte maturation. ASN NEURO. Vol 3. 2011:147-158.
- French, H. M., Reid, M., Mamontov, P., Simmons, R. A., Grinspan, J. B.. Oxidative stress disrupts oligodendrocyte maturation. Journal of Neuroscience Research. Vol 87. 2009:3076-3087, 2011.
- French, H. M., Reid, M., Mamontov, P., Simmons, R. A., Grinspan, J. B.: Oxidative stress disrupts oligodendrocyte maturation.Journal of Neuroscience Research 87: 3076-3087, 2009.
- Feigenson, K., Reid, M., See, J., Crenshaw E.B. III, Grinspan, J. B.. Wnt signaling is sufficient to perturb oligodendrocyte maturation.Molecular and Cellular Neuroscience. Vol 42. 2009:255-265, 2009.
- Ara, J., See, J., Mamontov, P., Hahn, A., Bannerman, P. Pleasure, D., Grinspan, J.B.. Bone morphogenetic proteins 4, 6, and7 are upregulated in mouse spinal cord during experimental autoimmune encephalomyelitis. Journal of Neuroscience Research. Vol 86. 2008:125-135, 2008
- See, J., Mamontov, P., Ahn K., Wine-Lee, L., Crenshaw III, E.B., Grinspan, J. B.. BMP mutant mice exhibit glial cell maturation defects. Molecular and Cellular Neuroscience. Vol 35. 2007:171-182, 2007.
- See, J., Zhang, X., Eraydin, N. Mun, S.B., Mamontov, P., Golden, J. Grinspan, J.B.: Oligodendrocyte maturation is inhibited by bone morphogenetic protein. Molecular and Cellular Neuroscience 26: 481-492, 2004.