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Associate Professor of Pharmacology
Primary Office: 2-572 Bowen Science BuildingIowa City, IA 52242
BS, Biology, LeMoyne College, Syracuse, NYPhD, Biochemistry & Molecular Biology, Louisiana State University Medical Center, New Orleans, LA
Postdoctoral Research Associate, Pediatrics, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
Oligodendroglial Cell Biology and CNS Myelination: Myelin in the central nervous system (CNS) is essential for normal nervous system development and function. Multiple sclerosis (MS) is the #1 neurological disease that afflicts young adults and results in targeted destruction of myelin, oligodendrocytes, and eventually, neurons in the CNS. Oligodendrocytes in the CNS serve to synthesize and maintain myelin sheaths, which are highly complex, multilamellar membranous structures essential to normal nervous system function. Myelination is a tightly regulated event that must occur during perinatal and early postnatal CNS development in vertebrates. Disruption of myelination during development can lead to mental retardation, movement disorders, and other neurological deficits. Our research efforts focus on gaining a better understanding of the molecular and cellular biology of oligodendrocytes and the process of myelination. Our studies consider issues of cell polarity and membrane targeting for the distribution of proteins on the oligodendroglial cell surface and myelin membrane surrounding neurons. In particular, we are studying myelin/oligodendrocyte glycoprotein (MOG), which is specifically targeted for immune attack in MS. Our structure-function analyses of MOG have revealed sequence motifs in the cytoplasmic domain of this protein that are necessary for its membrane targeting and its ability to undergo endocytosis for reuptake back into the cell. Recently, we identified stathmin, a phosphoregulatory protein affecting microtubule dynamics, as a cytosolic binding partner for MOG, and we are now investigating the significance of these interactions. Surprisingly, the human MOG gene expresses alternatively spliced mRNAs that are translated to unique isoforms lacking these targeting and endocytic motifs. These novel MOG isoforms found in human CNS may exhibit altered developmental expression and may interact with alternative cytosolic partners. Studies in these areas are ongoing. We utilize an array of techniques encompassing cell biology, molecular biology, and protein chemistry. We hope that our efforts will aid in designing improved therapies for MS and myelin- related developmental neurological disorders. MOG and stathmin colocalize at the inner face of the plasma membrane.
Alternative isoforms of myelin/oligodendrocyte glycoprotein with variable cytoplasmic domains are expressed in human brain.
2007 April. 101(2):298-312.
Mutually exclusive apicobasolateral sorting of two oligodendroglial membrane proteins, proteolipid protein and myelin/oligodendrocyte glycoprotein, in Madin-Darby canine kidney cells.
J Neurosci Res.
2001 December 15. 66(6):1140-1148.
Identification of a basolateral membrane targeting signal within the cytoplasmic domain of myelin/oligodendrocyte glycoprotein.
2001 June. 77(5):1301-1309.
Epitope specificity of demyelinating monoclonal autoantibodies directed against the human myelin oligodendrocyte glycoprotein (MOG).
1999 June 1. 97(1-2):9-15.
Investigation of myelin/oligodendrocyte glycoprotein membrane topology.
1996 November. 67(5):2219-2222.
Myelin/oligodendrocyte glycoprotein is alternatively spliced in humans but not mice.
J Neurosci Res.
1996 October 15. 46(2):271-281.
Myelin/oligodendrocyte glycoprotein (MOG) expression is associated with myelin deposition. .
1996 September. 18(1):39-48.
The N-terminal domain of the myelin oligodendrocyte glycoprotein (MOG) induces acute demyelinating experimental autoimmune encephalomyelitis in the Lewis rat. .
1995 December. 63(1):17-27.
Identification of epitopes of myelin oligodendrocyte glycoprotein for the induction of experimental allergic encephalomyelitis in SJL and Biozzi AB/H mice..
1994 November 15. 153(10):4349-4356.
Cloning and cDNA sequence analysis of myelin/oligodendrocyte glycoprotein: a novel member of the immunoglobulin gene superfamily..
Schweiz Arch Neurol Psychiatr .
Date Last Modified: 08/04/2015 -
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