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| Brian Popko, Ph.D.
Professor Department of Neurology Committee on Neurobiology |
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My laboratory takes a molecular genetic approach to obtain a better understanding of the normal function, as well as dysfunction, of the nervous system. Over the past decade, as the DNA sequence of the human and mouse genomes has become known, the techniques associated with the identification and isolation of mutant genes in the mammalian genome have been dramatically improved. Furthermore, remarkable advances have been made in the development of quantitative approaches toward the molecular analysis of complex biological systems. Moreover, our ability to manipulate the mouse genome has become increasingly sophisticated, such that intricate mouse models can be generated. The research interest of my laboratory exploits these recent advances and includes the following general areas of inquiry. 1. Mouse models: The detailed analyses of spontaneous mouse mutants, as well as the generation of transgenic models of disease, have proven to be extremely valuable tools in understanding of human disorders. These efforts have resulted in the identification of genes responsible for human genetic disorders, and the generation of authentic models of human diseases. Additionally, the “phenocopying” of particular traits of a syndrome have proven to be very useful. Mouse models of Alzheimer’s disease, Creutzfeldt-Jakob disease, Parkinson’s disease, amyotrophic lateral sclerosis and multiple sclerosis have all proven extremely informative in our current understanding of these disorders, as well as in the design of therapeutic approaches. Our laboratory is focusing considerable effort on the generation and analysis of mouse models of neurological disorders with the expectation that they will continue to provide important insight. 2. Molecular profiling: Microarray techniques have been developed over
the past few years that allow for the simultaneous monitoring of the expression
of tens of thousands of genes in a particular tissue or cell. These
approaches are useful in uncovering the molecular causes and consequences
of human disorders. We are exploiting microarray technology to examine
the molecular profile displayed by various neurological disorders.
By comparing these data with similar analyses of the mouse models generated
above, we should be able to begin to distinguish disease causing events
from the effects of these disorders at the molecular level.
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| References | |||
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Marcus, J., Dupree JL and Popko B. Myelin-Associated Glycoprotein and Myelin Galactolipids Stabilize Developing Axo-Glial Interactions. J. Cell Biol. 156:567-577, 2002. Gao X, Gillig TA, Ye P, D’Ercole AJ, Matsushima GK, Popko B. Interferon-gamma
protects against cuprizone-induced demyelination. Molec Cell Neurosci.
16:338-349, 2000.
Dupree, JL, Girault, J-A, Popko B: Axo-glial interactions regulate the localization of axonal paranodal proteins. J. Cell Biol. 147:145-152, 1999. Fujita N, Kemper A, Dupree J, Nakayasu H, Maeda N, Suzuki K, Suzuki K, Popko B: The cytoplasmic domain of the large myelin-associated glycoprotein isoform is needed for proper CNS but not PNS myelination. J Neurosci 18:1970-1978, 1998. Dupree J, Coetzee T, Blight A, Suzuki K, Popko B: Myelin galactolipids are essential for proper node of Ranvier formation in the CNS. J Neurosci 18:1642-1649, 1998. Coetzee T, Suzuki K, Popko B: New perspectives on the function of myelin galactolipids. Trends Neurosci 21:126-130 1998. Coetzee T, Fujita N, Dupree J, Shi R , Blight A, Suzuki K, Suzuki K, Popko B: Myelination in the absence of galactocerebroside and sulfatide: Normal structure with abnormal function and regional instability. Cell 86:209-219, 1996. Rath EM, Kelly D, Bouldin TW, Popko B: Impaired peripheral nerve regeneration in a mutant strain of mice (Enr) with a Schwann cell defect. J Neurosci 15:7226-7237, 1995.
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Last updated 08/20/02 |
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