科学研究

Principal Investigators

Yi Rao Ph.D

E-mail: yrao@pku.edu.cn

Phone:

Lab Homepage: http://raolab.org

Education

1978-1983 Jiangxi Medical College (medical student)

1983-1985 Shanghai Medical College (graduate student in neuropharmacology)

1985-1991 University of California San Francisco (Ph.D. in Neurobiology)

1991-1994 Harvard University (postdoc in Biochemistry and Molecular Biology)

Professional Experience

1994-2004 Washington University School of Medicine Assistant to Full Professor of Neurobiology

2004-2007 Northwestern University School of Medicine, Elsa Swanson Professor of Neurology

2007-2013 Dean of the School of Life Sciences, Peking University

2011-present Director, Peking-Tsinghua Center for Life Sciences (CLS), Peking University

2012-present Director, PKU-IDG/McGovern Institute for Brain Research, Peking University

2016-present Dean of Sciences, Peking University

2002-2005 (part time): Co-director, Shanghai Institute for Advanced Study of the CAS

2004-2009 (part time) Deputy Director, National Institute for Biological Sciences, Beijing


Research Description

       My lab investigates molecular and cellular mechanisms underlying behavior and cognition.

In animals, we use genetics, molecular biology and biophysics to study transmissome, including chemical transmitters and receptors. We generate mutant flies and rodents that lack a transmitter or its receptor to determine their roles. Neural circuits of defined neurochemistry are revealed anatomically by modern imaging and manipulated functionally by logic gates created by specific transcriptional promoters. Our transmissome approach has led to discoveries of molecules and cells regulating sleep and social behaviors. We demonstrate that it is possible to identify neurotransmitters and receptors for different behaviors.

In humans, we use genetics, genomics and functional magnetic resonance imaging (fMRI) to investigate genes and brain regions important for behavior and cognition.

Our goal is to identify neurotransmitters and receptors in the brain for behavior and cognition. Mechanisms conserved from animals to humans allow fundamental understanding of behaviors of evolutionary significance. Mechanisms unique to humans help to further the understanding of ourselves.

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 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 secreted 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 an extra-cortical origin 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) 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.

13) 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.

14) 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.

15) Wu JY, Feng L, Park H-T, Havlioglu N, Wen L, Tang H, Bacon KB, Jiang Z, Zhang X-C, and Rao Y (2001). The neuronal repellent Slit inhibits leukocyte chemotaxis induced by chemotactic factors.

      Nature 410:948-952.

16) 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.

17) 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.

18) 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.

19) 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.

20) 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.

21) 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.

22) 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.

23) 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.

24) 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.

25) 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.

26) Guan H, Zu G, Xie Y, Tang H, Johnson M, Xu X, Kevil C, Xiong W-C, Elmets C, Rao Y, Wu JY, and Hui Xu H (2003). Neuronal repellent Slit2 inhibits dendritic cell migration and the development of immune responses.  J Immunol 171:6519-6526.

27) Zhu Y, Yu T and Rao Y (2004). Developmental regulation of EGL migration through a switch in cellular responsiveness to cerebellar meninges. Dev Biol 267:153-64.

28) Ward ME, Wu JY and Rao Y (2004). Visualization of spatially and temporally regulated N-WASP activity during cytoskeletal reorganization in living cells. Proc Natl Acad Sci USA 101:970-974.

29) Prasad A, Fernandis AZ, Rao Y, and Ganju RK (2004). Slit-3 protein-mediated inhibition of CXCR4-induced chemotactic and chemoinvasive signaling pathways in breast cancer cells. J Biol Chem 279:9115-24.

30) Molle, K. D., Chédotal, A., Rao, Y., Lumsden, A., and Wizenmann, A. (2004). Local inhibition guides the trajectory of early longitudinal tracts in the developing chick brain. Mech. Dev. 121:143-156.

31) Kanellis J, Garcia GE, Li P, Parra G, Wilson CB, Rao Y, Han S, Smith CW, Johnson RJ, Wu JY, Feng L (2004). Modulation of inflammation by Slit protein in vivo in experimental crescentic glomerulonephritis. Am J Pathol 165:341-52.

32) Liu G, Beggs H, Jürgensen C, Park HT, Tang H, Gorski J, Jones KR, Reichardt LF, Wu JY, and Rao Y (2004). Netrin requires the focal adhesion kinase and the Src family kinases to induce axon outgrowth and to attract axons. Nat Neurosci 7:1222-1232.

33) Li W, Lee J, Vikis HG, Lee S-H, Liu G., Aurandt J, Shen T-L, Fearon ER, Guan J-L, Han M, Rao Y, Hong K, and Guan KL (2004). Activation of FAK and Src are receptor proximal events required for netrin signaling. Nat Neurosci 7:1213-1221.

34) Jiang H, Guo W, Liang XH, Y Rao (2005). Both the establishment and the maintenance of neuronal polarity require active mechanisms: critical roles of GSK-3b and its upstream
regulators. Cell 120:123-135.

35) Ding YQ, Kim JY, Xu YS, Rao Y, and Chen ZF (2005). Ventral migration of early-born neurons requires Dcc and is essential for the projections of primary afferents in the spinal cord. Development 132: 2047-2056.

36) Lin L, Rao Y, Isacson O. (2005). Netrin-1 and slit-2 regulate and direct neurite growth of ventral midbrain dopaminergic neurons. Mol Cell Neurosci 28:547-55.

37) Ward ME, Jiang H, and Rao Y (2005). Regulated formation and selection of neuronal processes underlie directional guidance of neuronal migration. Mol Cell Neurosci 30:378-387.

38) Kim TH, Lee HK, Seo IA, Bae HR, Suh DJ, Wu J, Rao Y, Hwang KG, and Park HT. (2005). Netrin induces down-regulation of its receptor, Deleted in Colorectal Cancer, through the ubiquitin-proteasome pathway in the embryonic cortical neuron. J Neurochem 95:1-8.

39) Li W, Aurandt J, Jürgensen C, Rao Y, and Guan KL (2006). FAK and Src kinases are required for netrin-induced tyrosine phosphorylation of UNC5. J Cell Sci 119:47-55.

40) Werbowetski-Ogilvie TE, Sadr MS, Jabado N, Angers-Loustau A, Agar NYR, Wu J, Bjerkvig R, Antel JP, Faury D, Rao Y, and Del Maestro RF (2006). Inhibition of medulloblastoma cell invasion by Slit. Oncogene 25: 5103-5112.

41) Liu G, Li W, Gao X, Li X, Jurgensen C, Park HT, Shin NY, Yu J, He ML, Hanks SK, Wu JY, Guan KL, and Rao Y. (2007). p130(CAS) is required for netrin signaling and commissural axon guidance.

      J Neurosci 27:957-68.

42) Guo W, Jiang H, Gray V, Dedhar S, and Rao Y (2007). Role of the integrin-linked kinase (ILK) in determining neuronal polarity. Dev Biol 306:457-468.

43) Lu W, van Eerde AM, Fan X, Quintero-Rivera F, Kulkarni S, Ferguson H, Kim H-G, Fan Y, Xi Q, Li Q-G, Sanlaville D, Andrews W, Sundaresan V, Bi W, Yank J, Giltay JC, Wijmeng C, V.M. de Jong TVM, Feather SA, Woolf AS, Rao Y, Lupsk JR, Eccles MR, Quad BJ, Gusell JF, Morton C, Maas RL (2007). Disruption of ROBO2 is associated with urinary tract anomalies and confers risk of vesicoureteral reflux. Am J Hum Genet 80:616–632.

44). Li X, Gao X, Liu G, Xiong W, Wu J, Rao Y (2008). Netrin signal transduction and the guanine nucleotide exchange factor DOCK180 in attractive signaling Nature Neurosci 11:28-35.

45) Zhou C, Rao Y, and Rao Y (2008). A subset of octopaminergic neurons are important for Drosophila aggression. Nature Neurosci 11:1059-1061.

46) Liu G, Li W, Wang L, Kar A, Guan KL, Rao Y, and Wu JY (2009). DSCAM functions as a netrin receptor in commissural axon pathfinding. Proc Natl Acad Sci USA 106:2951-6.

47) Yuasa-Kawada J, Kinoshita-Kawada M, Rao Y, and Wu JY (2009). Deubiquitinating enzyme USP33/VDU1 is required for Slit signaling in inhibiting breast cancer cell migration Proc Natl Acad Sci USA 106:14530-14535.

48) Yuasa-Kawada J, Kinoshita-Kawada M, Wu G, Rao Y, and Wu JY (2009). Midline crossing and Slit responsiveness of commissural axons require USP33. Nature Neurosci 12:1087-1089.

49) Liu Y, Jiang Y, Si Y, Kim J-Y, Chen Z-F, and Rao Y (2011). Molecular regulation of sexual preference revealed by genetic studies of 5-HT in the brain of male mice. Nature 472:95-99.

50) Liu WW, Liang XH, Li YN, Gong JX, Yang Z, Zhang YH, Zhang JX and Rao Y (2011). Social regulation of aggression mediated by pheromonal activation of Or65a olfactory receptor neurons in Drosophila.

     Nature Neurosci 7:896-902.

51) Masuyama K, Zhang Y, Rao Y, Wang JW (2012). Mapping neural circuits with activity-dependent nuclear import of a transcription factor. J Neurogenet 26:89-102.

52) Zhou C, Huang H, Kim SM, Lin H, Meng X, Chiang A-S, Wang JW, Jiao R, Rao Y (2012) Molecular genetic analysis of sexual rejection: roles of octopamine and its receptor OAMB in Drosophila courtship conditioning. J Neurosci 32:14281-14287.

53) Zhang SS, Liu Y, Rao Y (2013). Serotonin signaling in the brain of adult female mice is required for sexual preference. Proc Natl Acad Sci USA 110:9968-9973.

54) Gasque G, Conway S, Huang J, Rao Y and Vosshall (2013) Small molecule drug screening in Drosophila identifies the 5HT2A receptor as a feeding modulation target. Scientific Reports 3:2120/doi:10.1038/srep02120.

55) Ishimoto H, Wang Z, Rao Y, Wu C-F, Kitamoto T (2013) A Novel Role for Ecdysone in Drosophila Conditioned Behavior: Linking GPCR-Mediated Non-canonical Steroid Action to cAMP Signaling in the Adult Brain. PLoS Genet 9:e1003843. doi:10.1371/journal.pgen.1003843.

56) Zhu ZJ, Wang YY, Cao ZJ, Chen BQ, Cai HQ, Wu YH, Rao Y (2016). Cue-independent memory impairment by reactivation-coupled interference in human declarative memory. Cognition 155:125-134

57) Qian YJ, Cao Y, Deng BW, Yang G, Li JY, Xu R, Zhang DD, Huang J and Rao Y (2017). Sleep homeostasis regulated by 5HT2b receptor in a single pair of neurons in the dorsal fan-shaped body of Drosophila. Submitted.

58) Zhou EX, Dai XHM, Yang W and Rao Y (2017). D-Serine promotes sleep through the NMDA receptor in Drosophila melanogaster. Submitted.

59) Yu TH, Zhang EE, Luo TP, Rao Y (2017). Discovery of a small molecule modifier of the circadian clock by coupling chemical and biological screens. Submitted.

60) Chen BQ, Zhu, ZJ, Wang YY, Ding XH, Guo XB, He MG, Fang W, Zhou SB, Zhou Q, Huang AL, Chen TM, Ni DS, Gu YP, Liu JN, Rao Y (2017). Nature vs. nurture in human sociality: multi-level genomic analyses of social conformity. Submitted

61) Chen BQ, Zhu ZJ, Na R, Fang W, Zhou SB, Zhou Q, Fang F and Rao Y (2017). Genomic analysis of visual cognition identified genes underlying spontaneous perceptual reversal and voluntary modulation in bistable perception. Submitteed