PRINCIPAL INVESTIGATORS

Yun Wang, M.D., Ph.D., Senior Investigator

Chief, Neural Protection and Regeneration Section

Ph.D. - 1986, Department of Pharmacology, University of Colorado Health Sciences Center

M.D. - 1979, School of Medicine, National Defense Medical Center, Taipei, Taiwan

RESEARCH INTERESTS

The Neural Protection and Regeneration (NPR) section is dedicated to studying genes and compounds with potential neuroprotective or neuroregenerative properties. We employ in vitro and in vivo models of neurodegeneration, e.g. Parkinson?s disease and stroke and drug-induced toxicity to test therapeutic strategies and study mechanisms of potentially beneficial genes or compounds. For gene function studies, we produce adeno-associated viral (AAV) vectors for gene delivery to cells of the central nervous system such as neurons and glia. We have generated numerous AAV vectors containing genes encoding neurotrophic factors or genes involved in modulating neurotransmission (e.g. neurotransmitter receptors and transporters). These AAV vectors are used to studying gene function in models of neurodegeneration and addiction. We are currently investigating the function of several novel neurotrophic factors in cell culture and rodent models of stroke and methamphetamine-induced neurotoxicity. We have ongoing experiments involving small molecules with antioxidant properties or the capacity to activate neuroprotective genes in models of Parkinson?s disease, stroke, and methamphetamine toxicity. Our hope is that the research conducted by the NPR section will lead to the development of therapies aimed at preventing neurodegeneration and promoting neuroregeneration.

Selected Publications:

1. Airavaara, M., Harvey, B.K., Voutilainen, M.H., Shen, H., Chou, J., Lindholm, P., Lindahl, M., Tuominen, R.K., Saarma, M., Wang, Y., Hoffer, B.J. CDNF protects the nigrostriatal dopamine system and promotes recovery after MPTP treatment in mice. Cell Transplant. 2011, in press.
   

2. Chou, J., Greig, N.H., Reiner, D., Hoffer, B.J., Wang, Y. Enhanced survival of dopaminergic neuronal transplants in hemi-Parkinsonian rats by the p53 inactivator PFT-alpha. Cell Transplant. 2011, in press.
   

3. Deng, P., Pang, Z.P., Lei, Z., Shikano, S., Xiong, Q., Harvey, B.K., London, B., Wang, Y., Li, M., Xu, Z. Upregulation of A-type potassium currents protects neurons against cerebral ischemia. J.Cerebral.Blood.Flow.Metab. 2011, in press.
   

4. Harvey, B.K., Airavaara, M.T., Hinzman, J., Simons, E.M., Chiocco, M.J., Howard, D.B., Shen, H., Gerhardt, G.A., Hoffer, B.J., Wang, Y. Targeted over-expression of glutamate transporter 1 (GLT-1) reduces ischemic brain injury in rat model of stroke. PLoS. One. 6, e22135, 2011.
   

5. Liu, H.S., Shen, H., Harvey, B.K., Castillo, P., Lu, H., Yang, Y., Wang, Y. Post-treatment with amphetamine enhances re-innervation of the ipsilateral side cortex in stroke rats. Neuroimage. 56, 280-289, 2011.
   

6. Shen, H., Yu, S., Wang, Y. Enhanced neurodegeneration after a high dose of methamphetamine in adenosine A3 receptor null mutant mice. Neuroscience. 2011, in press.
   

7. Shen, H., Harvey, B.K., Chiang, Y.H., Pick, C.G., Wang, Y. Methamphetamine potentiates behavioral and electrochemical responses after mild traumatic brain injury in mice. Brain Res. 1368, 248-253, 2011.
   

8. Luo, Y., Wang, Y., Kuang, S.Y., Chiang, Y.H., Hoffer, B.J. Decreased level of Nurr1 in heterozygous young adult mice leads to exacerbated acute and long-term toxicity after repeated methamphetamine exposure. PLoS. One. 5, e15193, 2010.
   

9. Li, Y., Perry, T., Kindy, M.S., Harvey, B.K., Tweedie, D., Holloway, H.W., Powers, K., Shen, H., Egan, J., Lahiri, D.K., Mattson, M.P., Hoffer, B.J., Wang, Y., Greig, N.H. GLP-1 receptor stimulation preserves primary cortical and dopaminergic neurons in cellular and rodent models of stroke and Parkinsonism. Proc. Natl. Acad. Sci U. S. A. 106, 1285-1290, 2009.
   

10. Luo, Y., Kuo, C.C., Shen, H., Chou, J., Greig, N.H., Hoffer, B.J., Wang, Y. Delayed treatment with a p53 inhibitor enhances recovery in stroke brain. Ann. Neurol. 65, 520-530, 2009.