Anthony Young, PhD, Director
The Center for Molecular Neurobiology performs basic research and provides superior training in developmental, cellular and molecular neuroscience. Research strengths include the use of three prominent molecular genetic model systems (mice, zebra fish and Drosophila), as well as research directly applicable to humans. This is an intercollegiate program whose faculty have joint appointments in the Center as well as in departmental tenure-initiating units. They can thus contribute to the missions of their departmental units and form bridges between the Center and departments within separate colleges.
Ongoing Research Programs
- Sung Ok Yoon, PhD, studies molecular mechanisms underlying neurodegeneration and the role of GTPases in myelination.
- Michael Zhu, PhD, studies G protein and G protein-coupled receptors, Ca2+ signaling and Ca2+ channels, and the structure and function of transient receptor potential (TRP) channels.
- Chen Gu, PhD, is studying mechanisms by which voltagegated ion channels are localized to the proper subcellular compartments in neurons, and the physiological and pathological
consequences of channel targeting.
- Mariano Viapiano, PhD, has focused on functions of the extracellular matrix in the normal and diseased nervous system, on molecular mechanisms of glioma cell motility and invasion, and on extracellular matrix targets in neuropathologies.
- Jeff Kuret, PhD, and his laboratory team employ molecular, cellular and pharmacological methods to investigate Alzheimer’s disease pathogenesis. Their work focuses on the formation of characteristic lesions, including amyloid plaques, neurofibrillary tangles and granulovacuolar degeneration bodies.
- Christine Beattie, PhD, is generating zebra fish models of the motoneuron diseases spinal muscular atrophy and amyotrophic lateral sclerosis (ALS), and she is using these models to investigate molecular mechanisms of these diseases. She also uses these models to perform drugand genetic-suppressor screens.
- Tsonwin Hai, PhD, studies Eukaryotic gene expression, the stress response and signal transduction, cell death and cell cycle regulation, and molecular mechanisms of disease,
including breast cancer and diabetes.
Research Accomplishments of 2007
- Tumor-cell dispersion is the major reason for the almost invariably rapid and lethal outcome of malignant gliomas. Mariano Viapiano, PhD, and colleagues have discovered that fibulin-3 is a unique component of the glioma extracellular matrix that is absent in the normal central nervous system. Moreover, expression of fibulin-3 enhances substratedependent cell adhesion, motility and dispersion – findings that have broad implications with respect to glioma cell migration and suggest that fibulin-3 may provide a target against tumor progression.
- Understanding mechanisms that regulate the trafficking of ion channels to discrete subcellular domains is a fundamental problem of neurobiology, but Chen Gu, PhD, and colleagues have discovered that axon-dendrite targeting of the potassium channel Kv3.1 is controlled by a conditional interaction between domains located near its carboxy and amino termini. This interaction is mediated by the cytoskeletal adaptor protein ankyrin G, and alterations in this interaction among channel splice variants correlate with changes in trafficking. These findings have relevance to diseases as diverse as multiple sclerosis and epilepsy.
- Intracellular aggregation of the microtubule-associated protein tau into filamentous inclusions is a defining characteristic of Alzheimer’s disease; it has been postulated that
tau aggregation may be toxic to cells. Jeff Kuret, PhD, and colleagues have developed a method using agonist dyes to drive tau aggregation, allowing them to study the biochemistry and toxicology of tau. They find that conformational changes associated with tau aggregation are incompatible with microtubule binding, and that aggregation-associated toxicity is not acute but develops over several days.
- After spinal cord injury, oligodendrocytes undergo apoptotic death during an extended period, resulting in chronic demyelination, but the mechanism by which oligodendrocytes die is not clear. Sung-Ok Yoon, PhD, and colleagues have discovered that oligodendrocyte apoptosis is regulated oppositely by two protein kinases, JNK3 and Pin1. Cells are
normally protected against cell death by protein-protein interactions mediated by Pin1, but injury-induced expression of JNK3 leads to alterations in these interactions and to cell
death.
- Amyotrophic lateral sclerosis (ALS) is a debilitating adultonset neurodegenerative disease, and mutations in the superoxide dismutase 1 gene (SOD1) are known to produce one type of familial ALS. Although the identification of genes that suppress (or enhance) the ALS phenotype via modifier screens would mark a major advance, such screens are not plausible using transgenic mouse models. Hoping to identify genetic modifiers, Christine Beattie, PhD, and colleagues created transgenic zebra fish that express mutant or wildtype SOD1 and found that fish expressing the mutant protein exhibit abnormal swimming behavior, muscle weakness and fatigue, partial paralysis and cellular stress – all indicating that the transgenic zebra fish replicate aspects of ALS pathology and should provide a powerful screening system to identify modifier genes that affect SOD1 toxicity.
OSU Center for Molecular Neurobiology
206 Rightmire Hall
1060 Carmack Road
Columbus, OH 43210
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