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2004-11-23 0:34:00

饶毅博士简介


饶毅 博士,资深研究员 Yi Rao, Ph.D., Investigator, National Institute of Biological Sciences, Beijing. 电话(Tel):010-80726688-8501 传真(Fax):010-80726689 E-mail:raoyi@nibs.ac.cn

教育经历Education
1983年 江西医学院学士
B.S. Medical , 1978~1983,
Jiangxi Medical College, China
1991年 加州大学旧金山分校神经科学博士
Ph. D. Neuroscience,1991,
University of California at San Francisco, USA
工作经历Professional Experience
2004-present National Institute of Biological Sciences, Beijing, China(中国北京生命科学研究所工作)
1994-present started his own lab in the Department of Anatomy and Neurobiology at Washington University School of Medicine in St. Louis, Missouri.华盛顿大学医学院(圣路易斯,密苏里)解剖学与神经生物学系
1991-1994 Harvard University, with Dr. Douglas Melton in the Department of Biochemistry and Molecular Biology on embryonic induction in vertebrates(哈佛大学生物化学与分子生物学系博士后,研究脊椎动物的胚胎诱导)
研究概述:
我们主要兴趣在于两个相关而有不同的基本生物学过程: 1)神经细胞的极性(polarity)
2)细胞发育的分子机理。

为了研究这些神经生物学和发言生物学问题,我们使用多学科的综合途径, 主要包括分子生物学, 现代成像,遗传学,和生物化学。极性是神经细胞的一个基本性质。我们研究神经细胞在形态发生过程中极性形成的机理(polarity in morphogenesis)和神经细胞迁移过程中的极性(polarity in migration)。神经细胞在形态上有轴突(axons)和树突(dendrites),它们有不同的作用,树突多半接受信号,而轴突通常发送信号。如果没有神经细胞的极性,神经系统的信息传递就会紊乱。我们在分子和亚细胞水平研究神经细胞轴突和树突极性发生的机理.除了可以帮助基础理解以外,如果能知道怎样形成轴突,也许可以提示如何在损伤后帮助促进神经纤维再生。 极性在神经发育中还有一个重要作用在于神经细胞的迁移过程中。我们希望理解神经细胞迁移在空间和时间上的控制机理。包括:细胞和细胞间相互作用,细胞外分泌性信号(通常是蛋白质),细胞内信号转导通路和细胞运动基本机器(通常认为是细胞骨架的调控)。我们已经知道一些细胞可以通过分泌导向性的蛋白质来控制其它细胞的迁移方向。这些细胞外信号使细胞内分子的活性有极性分布,从而导致细胞进行有极性的运动。我们传统是用分子生物学来进行这些研究,但最近还建立生物物理学的方法(现代成像技术)来实时观察运动的细胞内部分子活性。希望基础研究的结果和具体的分子也许有助于改善脑瘤控制上。 我们对动物发育机理中细胞命运有兴趣。我们希望对干细胞,特别是全能干细胞有比较根本的理解。我们和王晓东实验室合作,用生物化学手段研究干细胞转化过程的分子基础。我们对用特种神经元形成的分子机理也感兴趣,希望以遗传和生化手段进行研究。

Research Description:
We are interested in cellular and molecular mechanisms underlying axon guidance and neuronal migration in vertebrates. We study cell-cell interactions that control neuronal migration, identify extracellular molecular cues that guide the direction of neuronal migration and investigate intracellular signal transduction mechanisms that mediate cellular responses to extracellular cues.

In the mammalian cerebellum, we have discovered cellular interactions that determine the timing and direction of the migration of cells from the external germinal layer (EGL) to the internal granule layer (IGL). An attractive signal has been found to play a role in anchoring the EGL cells in the embryonic cerebellum, whereas a repulsive is responsible for directing the postnatal EGL to migrate towards the IGL. Because EGL migration is a model for cortical migration, these findings suggest that similar mechanisms may function in neocortical development.

In the olfactory system, the interneurons in the olfactory bulb are derived from cells migrating from the anterior subventricular zone (SVZa) in the forebrain. The secreted protein Slit has been shown to be a repellent that may be involved in directing the SVZa cells towards to the olfactory bulb. It would be interesting to know whether other extracellular cues function together with Slit to direct the SVZa cells.We have started to investigate the signal transduction pathway mediating cellular responses to guidance cues. Slit protein binds to the transmembrane receptor Roundabout (Robo). One component downstream of Robo is a GTPase Activation Protein (GAP) that regulates the activity of small GTPases of the Rho subfamily. Functional studies indicate that the Rho GTPases are important for Slit-Robo signaling, providing a basis to further understand the signal transduction pathways for neuronal guidance cues.

发表文章Publications:
1. Rao Y, Jan LY, and Jan YN (1990). Similarity of the product of the Drosophila neurogenic gene big brain to transmembrane channel proteins. Nature 345:163-167.
2. Rao Y, Vaessin H, Jan LY and Jan YN (1991). Neuroectoderm in Drosophila embryos is dependent on the mesoderm for the positioning but not for formation. Genes Dev 5:1577-1588.
3. Rao Y, Bodmer R, Jan LY and Jan YN (1992). The big brain gene of Drosophila functions to control the number of neuronal precursors in the peripheral nervous system. Development 116:31-40.
4. Rao Y (1994). Conversion of a mesodermalizing molecule, the Xenopus Brachyury gene, into a neuralizing factor. Genes Dev 8:939-947.
5. Wu JY, Wen L, Zhang, WJ and Rao Y (1996). The secreted product of Xenopus gene lunatic fringe, a vertebrate signaling molecule. Science 273:355-358.
6. Li HS, Tierney C, Wen L, Wu JY and Rao Y (1997). A single morphogenetic field gives rise to two retina primordia under the influence of the prechordal mesoderm. Development 124:603-615.
7. Li HS, Chen JH, Wu W, Fagaly T, Yuan WL, Zhou L, Dupuis S, Jiang Z, Nash W, Gick C, Ornitz D, Wu JY, and Rao Y (1999). Vertebrate Slit, a Secreted Ligand for the Transmembrane Protein Roundabout, is a Repellent for Olfactory Bulb Axons. Cell 96:807-818.
8. Wu W, Wong K, Chen JH, Jiang ZH, Dupuis S, Wu JY, and Rao Y (1999). Directional Guidance of Neuronal Migration in the Olfactory System by the Protein Slit. Nature 400:331-336.
9. Zhu Y, Li HS, Zhou L, Wu JY, and Rao Y (1999). Cellular and Molecular Guidance of GABAergic Neuronal Migration from the Striatum to the Neocortex. Neuron 23:473-485.
10. Yuan W, Zhou L, Chen JH, Wu JY, Rao Y, and Ornitz DM (1999). The mouse Slit family: secreted ligands for Robo expressed in patterns that suggest a role in morphogenesis and axon guidance. Dev Biol 212:290-306.
11. He M, Wen L, Campbell C, Wu JY, and Rao Y (1999). Transcription Repression by ET, an Ortholog of Human Tbx3, a Gene Involved in Ulnar-Mammary Syndrome. Proc. Natl. Acad. Sci. USA 96:10212-10217.
12. Wu JY and Rao Y (1999). Fringe: defining borders by regulating the Notch pathway. Current Opinion in Neurobiology 9:537-543.
13. Chen J, Wu W, Li HS, Fagaly T, Zhou L, Wu JY and Rao Y (2000). Embryonic expression and extracellular secretion of Xenopus Slit. Neuroscience 96:231-236.
14. Chen J, Wen L, Dupuis S, Wu JY, and Rao Y (2001). The N-terminal leucine rich regions in Slit are sufficient to repel olfactory bulb axons and subventricular zone neurons. J. Neurosci. 21:1548-1556.
15. Hirata T, Fujisawa H, Wu JY, and Rao Y (2001). Independence of short-range guidance for olfactory bulb axons from repulsive factor Slit. J. Neurosci. 21:2373-2379.
16. Wu JY, Feng L, Park H-T, Havlioglu N, Wen L, Tang H, Bacon KB, Jiang Z, Zhang X-C, and Rao Y (2001). Slit, a molecule known to guide axon projection and neuronal migration, inhibits leukocyte chemotaxis induced by chemotactic factors. Nature 410:948-952.
17. Rao Y and Wu JY (2001). Neuronal migration and the evolution of the human brain. Nature Neurosci 4:860-862.
18. Wong K, Ren X-R, Huang Y-Z, Xie Y, Liu G, Saito H, Tang H, Wen L, Brady-Kalnay SM, Mei L, Wu JY, Xiong W-C, and Rao Y (2001). Signal transduction in neuronal migration: roles of GTPase activating proteins and the small GTPase Cdc42 in the Slit-Robo pathway. Cell 107:209-221.
19. Zhu Y, Yu T, Zhang X-C, Nagasawa T, Wu JY, and Rao Y (2002). Role of the chemokine SDF-1 as the meningeal attractant for embryonic cerebellar neurons. Nature Neurosci. 5:719-720.
20. Sang Q, Wu JY, Rao Y, Hsueh, Y-P, and Tan S-S (2002). Slit promotes branching and elongation of neurites of interneurons but not projection neurons from the developing telencephalon. Mol Cell Neurosci 21:250-65.
21. Wong K, Wu JY and Rao Y (2002). Neuronal migration. Encyclopedia of Life Sciences, Nature Publishing Group
22. Park HT, Wu JY and Rao Y (2002). Molecular control of neuronal migration. BioEssays 24:821-827.
23. Wong K, Park HT, Wu JY and Rao Y (2002). Slit proteins: guidance cues for cells ranging from neurons to leukocytes. Curr Op Genet Dev 12:583-591.
24. Rao Y, Wong K, Ward M, Jurgensen C, and Wu JY (2002). Neuronal migration and molecular conservation with leukocyte chemotaxis. Genes Dev 16:2973-2984.
25. Jin Z, Zhang J, Klar A, Chédotal A, Rao Y, Cepko CL, Bao Z-Z (2003). Irx4-mediated regulation of Slit1 expression contributes to the definition of early axonal paths inside the retina. Development 130: 1037-1048.
26. Yuan W, Rao Y, Babiuk RP, Greer J, Wu JY, and Ornitz DM (2003). A genetic model for a central (septum transversum) congenital diaphragmatic hernia in mice lacking Slit3. Proc Natl Acad Sci USA 100: 5217-5222.
27. Ward M, McCann C, DeWulf M, Wu JY and Rao Y (2003). Distinguishing between directional guidance and motility regulation in neuronal migration. J Neurosci 23:5170-5177.
28. Liu G and Rao Y (2003). Neuronal migration from the forebrain to the olfactory bulb requires a new attractant persistent in the olfactory bulb. J Neurosci 23:6651– 6659.
29. Wang B, Xiao Y, Ding B-B, Zhang N, Yuan X-B, Gui L, Qian, K-X, Duan S, Chen Z, Rao Y, and Geng J-G (2003). Induction of tumor angiogenesis by Slit-Robo signaling and inhibition of cancer growth by blocking Robo activity. Cancer Cell 4:19-29.
30. DeBellard ME, Rao Y, and Bronner-Fraser M (2003). Dual function of Slit2 in repulsion and enhanced migration of trunk, but not vagal, neural crest cells. J Cell Biol 162:269-279.
31. Park KW, Morrison CM, Sorensen LK, Jones CA, Rao Y, Chien C-B, Wu JW, Urness LD and Li DY (2003). Robo4 is a vascular-specific receptor that inhibits endothelial migration. Dev Biol 261: 251-267.
32. Guan KL and Rao Y (2003). Signal transduction mechanisms mediating neuronal responses to guidance cues. Nature Rev Neurosci, in press, December.
33. Ward ME and Rao Y (2004). Investigations of neuronal migration in the central nervous system. In Guan, J.-L. (ed), Cell Migration: Developmental Methods and Protocols. Humana Press, Totowa, NJ.
34. Liu G and Rao Y (2004). Neuronal migration in the central nervous system. The New Cognitive Neurosciences, 3rd edition, Gazzaniga MS, editor in chief, MIT press, Cambridge, MA. 

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