Associate Professor
Department of Molecular and Cellular Biochemistry
and Center for Molecular Neurobiology
Ph.D.: Tufts University Medical School
Post-doctoral Training: Cornell University
Medical College, Columbia University
Center for Molecular Neurobiology
The Ohio State University
134 Rightmire Hall
1060 Carmack Road
Columbus, OH 43210
Phone: 614-292-8542
Fax: 614-292-5379
E-mail: Yoon.84@osu.edu
Link to NLM & NIH PubMed publications list for Sung Ok Yoon (last 10 years)
Research Area:
- Signal transduction of apoptosis
- Mechanisms of RacGTPase/RhoGTPase regulation in vitro and in vivo
- Transgenic mice model of apoptosis using spinal cord injury/cortical axotomy as paradigms
- Transgenic mice model of RhoGTPase regulation during neuronal development and regeneration after CNS injury
- Molecular mechanisms of myelination
Research Description:
Project 1: One of the current focuses of the lab is to understand the signaling mechanisms by NGF, which can promote either neuronal survival or death, depending on the outcome of the interplay between its two distinct receptors, TrkA, a receptor tyrosine kinase, and p75, a member of the TNF receptor family. We have recently determined that p75 activates Rac GTPase upon binding NGF, which is in turn required for activation of c-jun N-terminal kinase and subsequent apoptosis. Co-activation of TrkA and 75 results in attenuation of Rac activity, suggesting that Rac is a critical component in determination of cell survival and death. We now have identified a Rho family of guanidine exchange factor that binds p75 and participates in Rac activation, and we will focus on biochemical understanding of its regulation by NGF.
Project 2: p75 is often induced after various insults and injuries in vivo. Using spinal cord injury and cortical axotomy as models, we have recently determined that p75 activation is a critical component in apoptosis in vivo. Both in the spinal cord and in the brain, p75 is activated by proNGF, a precursor form of NGF, which binds p75 selectively, and not TrkA. We now have the data that demonstrate that proNGF is secreted to cerebrospinal fluid as an active form that binds p75 in vivo. Perturbation of this binding in vivo using a neutralizing proNGF-specific antibody resulted in rescue of all the neurons that would otherwise undergo cell death. We are currently investigating the signaling mechanisms by which pro-NGF activates p75 in vivo.
Project 3: The knockout analyses of neuregulin and its receptors have indicated that they play essential roles in Schwann cell development. The role they play in oligodendrocyte development in vivo, however, has remained unclear, since such knockout animals die before CNS myelination begins. We examined the role of neuregulin signaling in the CNS, by generating transgenic mice that express a dominant-negative mutant of the ErbB2 receptor among oligodendrocytes, using a MBP promoter. The transgenic mice exhibited widespread hypomyelination, resulting from a reduction in oligodendrocyte differentiation. The number of progenitors was conversely increased in the transgenic mice. A reduction in oligodendrocyte differentiation is attributed in part to apoptosis of oligodendrocyte progenitors as they exit the cell cycle. A significant reduction in the number of p27+ oligodendrocyte precursors in the transgenic mice supports this conclusion. Together, these data suggest that for oligodendrocyte progenitors, ErbB2 signaling plays a role in governing a properly timed exit from the cell cycle during development into myelinating oligodendrocytes.
The DN-ErbB2 construct comprises two domains; one, containing the cytoplasmic domain of ErbB1 with its ATP binding site inactivated, and the other, containing the extracellular and transmembrane domains of p75. We generated two additional transgenic mice in order to define the domain responsible for the interaction with ErbB2 and subsequent hypomyelination. To our surprise, p75 extracellular and transmembrane domains were responsible for the hypomyelination phenotype, and not the ErbB1 cytoplasmic domain. p75 extracellular and transmembrane domains interacted with all three ErbB receptors. There will be two main areas of focus in the near future. (1) biochemical analyses of the interaction between p75 and ErbB receptors; and (2) analyses of the role of neurotrophins in CNS myelination.
Techniques and Models:
- Molecular biology
- Biochemistry
- Cell Biology
- Transgenic mice and in vivo analyses
- Small animal surgery
- Primary neural cultures
In May 2005, Tony Harrington was sent off as a postdoc to Johns Hopkins University by members of Dr. Yoon's lab.
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