药学院学术报告（6月3日15:00)

报告题目：Engineering Pseudo-Axonal Scaffolds for Myelination: Implications for Development, Disease and High Throughput Screening

报 告 人：Chan, Jonah R.博士（Associate Professor of Neurology, University of California, San Francisco）

报告时间：2013年6月3日（星期一）15:00

报告地点：独墅湖校区二期云轩楼2301室

Chan, Jonah R.博士简介

l Education / Training

University of Illinois at Urbana-Champaign B.S. 1994 Biochemistry

University of Illinois at Urbana-Champaign Ph.D. 2000 Neuroscience

Stanford University Postdoctoral 2005 Neurobiology

l Positions and Employment

1992-1992 Research Intern, Department of Pathology, Northwestern University, Chicago, IL

1993-1994 Monsanto Biotechnology Research Fellow, Department of Biochemistry, University of Illinois at Urbana-Champaign, IL

1994-2000 Graduate Student, Department of Biochemistry, University of Illinois at Urbana-Champaign, IL

2000-2005 Postdoctoral Fellow, Department of Neurobiology, Stanford University, Stanford, CA

2005-2007 Assistant Professor of Cell and Neurobiology, Keck School of Medi cine, University of Southern California, Los Angeles, CA

2007-2010 Assistant Professor of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, CA

2010- Associate Professor of Neurology, University of California, San Francisco

2010- Debbie and Andy Rachleff Endowed Chair of Neurology

l Selected peer-reviewed publications

1. Bilderback, T. R., Chan, J. R., Harvey, J. J., and Glaser, M. Measurement of the Rate of Myelination Using a Fluorescent Analogue of Ceramide. J. Neurosci. Res. 49: 497-507, 1997.

2. Chan, J. R., Phillips, L. J., and Glaser, M. Glucocorticoids and Progestins Signal the Initiation and Enhance the Rate of Myelin Formation. PNAS , 95: 10459-10464, 1998.

3 . Chan, J. R. , Rodriguez-Waitkus, P. M., Ng, B. K., Liang, P., and Glaser, M. Progesterone Synthesized by Schwann cells During Myelin Formation Regulates Neuronal Gene Expression. Mol. Biol. Cell 11:2283-2295, 2000.

4. Chan, J. R., Cosgaya, J. M., Wu, Y., and Shooter, E. M. Neurotrophins are Key Mediators of the Myelination Program in the Peripheral Nervous System. PNAS , 100: 12545-12550, 2001.

5. Cosgaya, J. M.* , Chan, J. R.*, and Shooter, E. M. A Novel Role for the Neurotrophin Receptor p75^NTR as a Positive Modulator of Myelination. Science, 298: 1245-1248, 2002. *Contributed Equally. Commentary by Hempstead, B. L., and Salzer, J. L. A Glial Spin on Neurotrophins. Science, 298: 1184-1186, 2002.

6. Yamauchi, J., Chan, J. R., and Shooter, E. M. NT3 Activation of TrkC Induces Schwann Cell Migration through the c-Jun N-terminal Kinase Pathway. PNAS , 100: 14421-14426, 2003.

7. Ullian, E. M., Harris, B. T., Wu, A., Chan, J. R., and Barres, B. A. Schwann Cells and Astrocytes Induce Synapse Formation by Spinal Motor Neurons in Culture. Mol. Cell. Neurosci., 25: 241-251, 2004.

8. Wu, Y. J., Kruttgen, A., Moller, J. C., Shine, D., Chan, J. R., Shooter, E. M., and Cosgaya, J. M. NGF, BDNF, and NT3 are Sorted to Dense-Core Vesicles and Released via the Regulated Pathway in Primary Rat Cortical Neurons. J. Neurosci. Res., 75: 825-834, 2004.

9. Yamauchi, J., Chan, J. R., and Shooter, E. M., Neurotrophins Regulate Schwann Cell Migration by Activating Divergent Signaling Pathways Dependent upon Rho GTPases. PNAS, 101: 8774-8779, 2004.

10. Chan, J. R., Watkins, T. A., Cosgaya, J. M., Zhang, C. Z., Chen, L., Reichardt, L. F., Shooter, E. M., and Barres, B. A., NGF Controls Axonal Receptivity to Myelination by Schwann cells and Oligodendrocytes. Neuron, 43: 183-191, 2004. Commentary by Brophy, P. J. New Roles for an Old Molecule in Axon-Glial Interaction. Neuron, 43: 154-155, 2004.

11. Saxena, S., Howe, C. L., Steiner, P., Hi rling, H., Cosgaya, J. M., Youssef, S., Chan, J. R. Weis, J., and Kruttgen, A. Differential Endocytic Sorting of p75NTR and TrkA in Response to NGF: A Role for Late Endosomes in TrkA Trafficking. Mol. Cell. Neurosci., 28:571-587, 2005.

12. Yamauchi, J., Chan, J. R., Miyamoto, Y., Tsujimoto, G., and Shooter, E. M. The Neurotrophin-3 Receptor TrkC Directly Phosphorylates and Activates the Nucleotide Exchange Factor Dbs to Enhance Schwann Cell Migration. PNAS , 102: 5198-5203, 2005. Commentary by Hempstead, B. L. Coupling neurotrophins to cell migration through selective guanine nucleotide exchange factor activation. PNAS, 102: 5645-5646, 2005.

13. Yamauchi, J., Miyamoto, Y., Tanoue, A., Shooter, E. M., and Chan, J. R*. Ras Activation of a Rac1 Exchange Factor, Tiam1, Mediates Neurotrophin-3 Induced Schwann Cell Migration. PNAS , 102: 14889-14894, 2005.

14. Rosenberg, S. S., Ng, B. K., and Chan, J. R*. The Quest for Remyelination: A New Role for Neurotrophins and their Receptors. Brain Pathology, 16: 288-294, 2006.

15. Chan, J. R.*, Jolicoeur, C., Yamauchi, J., Elliot, J., Fawcett, J. P., Ng, B. K., and Cayouette, M.* The Polarity Protein Par-3 Directly Interacts with p75^NTR to Regulate Myelination. Science, 314: 832-836, 2006. *Co-corresponding Author. Commentary by Taveggia, C., Salzer, J. L. PARsing the events of myelination. Nat. Neurosci., 10: 17-18, 2007.

16. Lee, X., Yang, Z., Shao, Z., Rosenberg, S. S., Levesque, M., Pepinsky, R. B., Qiu, M., Miller, R. H., Chan, J. R.*, and Mi, S.* NGF regulates the expression of axonal LINGO-1 to inhibit oligodendrocyte differentiation and myelination. J. Neurosci., 27: 220-225, 2007. *Co-corresponding Author

17. Chan, J. R*. Myelination: all about Rac ’n’ roll. J. Cell Biol., 177: 953-955, 2007.

18. Ng, B. K., Chen, L., Mandemakers, W., Cosgaya, J. M., and Chan, J. R*. Anterograde Transport and Secretion of Endogenous BDNF Along Sensory Axons Promotes Schwann Cell Myelination. J. Neurosci., 27: 7597-7603, 2007.

19. Rosenberg, S. S., Powell, B. L., and Chan, J. R*. Receiving Mixed Signals: Uncoupling Oligodendrocyte Differentiation and Myelination. Cell Mol. Life Sci., 64: 3059-3068, 2007.

20. Miyamoto, Y., Yamauchi, J., Chan, J. R., Okada, A., Tomooka, Y., Hisanaga, S. I., and Tanoue, A. Cdk5 Regulates Differentiation of Oligodendrocyte Precur sor Cells through the Direct Phosphorylation of

Paxillin. J. Cell Sci., 120: 4355-4366, 2008.

21. Yamauchi, J.*, Miyamoto, Y., Chan, J. R.*, and Tanoue, A. ErbB2 Directly Activates the Exchange Factor Dock7 to Promote Schwann Cell Migration. J. Cell Biol., 181: 351-365, 2008. *Co-corresponding Author

22. Rosenberg, S. S., Kelland, E. E., Tokar, E., De La Torre, A., and Chan, J. R*. The Geometric and Spatial Constraints of the Microenvironment Induce Oligodendrocyte Differentiation. PNAS , 105:14662-14667, 2008.

23. Rosenberg, S. S., and Chan, J. R*. Modulating Myelination: Knowing When to Say Wnt. Genes Dev., 23:1487-93, 2009.

24. Hahn, A. T. and Chan, J. R*. A Collaboration Conducive to Conduction: Matching Axonal Density to Oligodendroglial Number. Eur J Neurosci, 30:2029, 2009.

25. Kim, Y., Chen, J., Chan, J. R.*, and Langen, R.* Engineering a Polarity Sensitive Biosensor for Time-Lapse Imaging of Apoptosis. Nature Methods, 7:63-73, 2010. *Co-corresponding Author

26. Chong, S. Y. C. and Chan, J. R*. Tapping into the Glial Reservoir: Cells Committed to Remain Uncommitted. J. Cell Biol., 188:305-312, 2010.

27. Kim, Y., Chen, J., Langen, R. and Chan, J. R*. Monitoring apoptosis and neuronal degeneration by real-time detection of phosphatidylserine externalization. Nature Protocols, 5:1396-1405, 2010.

28. Lewallen, K. A., Shen, Y. A., De La Torre, A. R., Ng, B. K., Meijer, D., and Chan, J. R*. Assessing the Role of N-cadherin at the Schwann Cell-Axon Interface and in the Initiation of Myelination. J Neurosci , 31:3032-3043, 2011.

29. Fancy, S. P. J., Chan, J. R., Baranzini, S. E., Franklin, R. J. M., and Rowitch, D. H. Myelin regeneration: A recapitulation of development? Ann Rev Neurosci 34:21-43, 2011.

30. Tep, C., Kim, M. L., Opincariu, L. I., Limpert, A. S., Chan, J. R., Appel, B., Carter, B. D. and Yoon, S. O. Brain-derived Neurotrophic Factor (BDNF) Induces Polarized Signaling of Small GTPase (Rac1) Protein at the Onset of Schwann Cell Myelination through Partitioning-defective 3 (Par3) Protein. J Biol Chem, 287:1600-1608, 2012.

31. Chong, S. Y., Rosenberg, S. S., Fancy, S. P., Zhao, C., Shen, Y. A., Hahn, A. T., McGee, A. W., Xu, X., Zheng, B., Zhang, L. I., Rowitch, D. H., Franklin, R. J., Lu, Q. R. and Chan, J. R*. Neurite Outgrowth Inhibitor Nogo-A establishes spatial segregation and extent of myelination during development. PNAS , 109:1299-1304, 2012. Commentary by Scholze A.R. and Barres B. A. A Nogo Signal Coordinates the Perfect Match Between Myelin and Axons. PNAS, 109:1003-1004, 2012.

32. Yamauchi, J., Miyamoto, Y., Torii, T., Takashima, S., Kondo, K., Kawahara, K., Nemoto, N., Chan, J. R*., Tsujimoto, G., and Tanoue A. Phosphorylation of Cyto hesin-1 by Fyn Regulates Initiation of Myelination and Myelin Membrane Extent during Development. Sci Signal, 2012 Sep 25;5(243):ra69.

33. Lee S, Leach MK, Redmond SA, Chong SY, Mellon SH, Tuck SJ, Feng ZQ, Corey JM, Chan JR*. A culture system to study oligodendrocyte myelination processes using engineered nanofibers. Nat Methods. 2012 Sep;9(9):917-22.

34. Redmond SA, Chan JR*. Neuroscience. Revitalizing remyelination--the answer is circulating. Science. 2012 Apr 13;336(6078):161-2.

35. Lee, S. O., Leach, M., Redmond, S.A., Chong, S. Y. C., Mellon, S., Corey, J., and Chan, J. R*. Engineering Nanofibers for Oligodendrocyte Myelination: Fiber Diameter is Sufficient to Initiate Wrapping. Nature MethodsNat Protoc. 2013 Apr;8(4):771-82

36. Yu Y, Chen Y, Kim B, Wang H, Zhao C, He X, Liu L, Liu W, Wu LM, Mao M, Chan JR , Wu J, Lu QR. Olig2 targets chromatin remodelers to enhancers to initiate oligodendrocyte differentiation. Cell . 2013 Jan 17;152(1-2):248-61.