Biography

Dr. Lai is a Professor of Psychological and Brain Sciences and a Linda and Jack Gill Scholar at the Gill Institute for Neuroscience. He earned his BS in Biology from California Institute of Technology and his PhD in Biology from the University of California.

His lab uses molecular biological approaches to study the nervous system. One major area of interest is the role of neuregulin-ErbB signaling in neuronal and glial function. The neuregulins are a collection of polypeptides that activate a family of transmembrane signaling molecules, the receptor tyrosine kinases known as the "ErbBs". There is considerable interest in this signaling pathway as the neuregulin-1 gene has been implicated as a risk factor for the neuropsychiatric disorder schizophrenia. The neuregulin receptor ErbB4 is expressed by multiple populations of migrating neuronal precursors in the developing brain and our studies have helped to show that alterations in ErbB4 function may influence the final placement of these cells. These changes may lead to alterations in brain circuitry, a finding that provides one potential mechanism by which neuregulin-ErbB signaling may contribute to an increased risk for schizophrenia. One of the current lab interests is to understand the precise molecular role that ErbB4 plays within the migrating neuronal precursors.

A second focus of the lab has been the development of transgenic mouse tools useful for studying the nervous system. Our goal has been to produce lines of mice that permit both temporal and spatial regulation of gene expression in specific subsets of cells in the brain. Using a BAC-based approach, the lab has successfully produced lines of transgenic mice that permit regulated expression in cholinergic neurons and are developing similar lines for use in dopaminergic neurons and in the medium spiny neurons in the striatum. The overall goal is to use these mice to study the neurodegenerative process, and we anticipate that these lines will facilitate efforts to gain an improved understanding of Alzheimer's, Parkinson's and Huntington's diseases.

Publications

  • Prieto AL, Lai C. (2024) The TAM Subfamily of Receptor Tyrosine Kinases: The Early Years. Int J Mol Sci. 25(6):3369. 
  • Barettino C, Ballesteros-Gonzalez Á, Aylón A, Soler-Sanchis X, Ortí L, Díaz S, Reillo I, García-García F, Iborra FJ, Lai C, Dehorter N, Leinekugel X, Flames N, Del Pino I. (2021) "Developmental Disruption of Erbb4 in Pet1+ Neurons Impairs Serotonergic Sub-System Connectivity and Memory Formation."Front Cell Dev Biol. 9:770458. 
  • Grieco SF, Qiao X, Johnston KG, Chen L, Nelson RR, Lai C, Holmes TC, Xu X. (2021) "Neuregulin signaling mediates the acute and sustained antidepressant effects of subanesthetic ketamine." Transl Psychiatry. 11(1):144.
  • Grieco SF, Qiao X, Zheng X, Liu Y, Chen L, Zhang H, Yu Z, Gavornik JP, Lai C, Gandhi SP, Holmes TC, Xu X. (2020) "Subanesthetic Ketamine Reactivates Adult Cortical Plasticity to Restore Vision from Amblyopia." Curr Biol. 30(18):3591-3603.e8. 
  • Rahman-Enyart A, Lai C, Prieto AL. (2020) "Neuregulins 1, 2, and 3 Promote Early Neurite Outgrowth in ErbB4-Expressing Cortical GABAergic Interneurons." Mol Neurobiol. 57(8):3568-3588. 
  • Grieco SF, Wang G, Mahapatra A, Lai C, Holmes TC, Xu X. (2020) "Neuregulin and ErbB expression is regulated by development and sensory experience in mouse visual cortex." J Comp Neurol. 528(3):419-432. 
  • Rahman A, Weber J, Labin E, Lai C, Prieto AL. (2019)  "Developmental expression of Neuregulin-3 in the rat central nervous system." J Comp Neurol. 527(4):797-817.
  • Sun Y, Ikrar T, Davis MF, Gong N, Zheng X, Luo ZD, Lai C, Mei L, Holmes TC, Gandhi SP, Xu X. (2016) "Neuregulin-1/ErbB4 Signaling Regulates Visual Cortical Plasticity." Neuron. 92(1):160-173. 
  • Seshadri S, Faust T, Ishizuka K, Delevich K, Chung Y, Kim SH, Cowles M, Niwa M, Jaaro-Peled H, Tomoda T, Lai C, Anton ES, Li B, Sawa A. (2015) "Interneuronal DISC1 regulates NRG1-ErbB4 signalling and excitatory-inhibitory synapse formation in the mature cortex." Nat Commun. 6:10118. 
  • Koyama S, Soini HA, Wager-Miller J, Alley WR, Pizzo MJ, Rodda C, Alberts J, Crystal JD, Lai C, Foley J, Novotny MV. (2015) "Cross-generational impact of a male murine pheromone 2-sec-butyl-4,5- dihydrothiazole in female mice." Proc Biol Sci. 282(1811):20151074. 
  • Lai C, Fischer T, Munroe E. (2015) "Homologous recombination using bacterial artificial chromosomes."Cold Spring Harb Protoc. 2015(2):180-90.
  • Ahrens S, Jaramillo S, Yu K, Ghosh S, Hwang GR, Paik R, Lai C, He M, Huang ZJ, Li B. (2014) "ErbB4 regulation of a thalamic reticular nucleus circuit for sensory selection." Nat Neurosci. 18(1):104-11.
  • Koyama S, Soini HA, Foley J, Novotny MV, Lai C. (2014) "Pheromone-induced cell proliferation in the murine subventricular zone." Biochem Soc Trans. 42(4):882-5.
  • Koyama S, Soini HA, Foley J, Novotny MV, Lai C. (2013) "Stimulation of cell proliferation in the subventricular zone by synthetic murine pheromones." Front Behav Neurosci. 7:101.
  • Higginbotham H, Eom TY, Mariani LE, Bachleda A, Hirt J, Gukassyan V, Cusack CL, Lai C, Caspary T, Anton ES. (2012) "Arl13b in primary cilia regulates the migration and placement of interneurons in the developing cerebral cortex." Dev Cell. 23(5):925-38. 
  • Brown JE, Krodel M, Pazos M, Lai C, Prieto AL. (2012) "Cross-phosphorylation, signaling and proliferative functions of the Tyro3 and Axl receptors in Rat2 cells."PLoS One. 7(5):e36800.
  • Chen, Y.-J., Zhang, M., Yin, D.-M., Wen, L., Ting, A., Wang, P., Lu, Y.-S., Zhu, X.-H., Li, S.-J., Wu, C.-Y., Wang, X.-M., Lai, C., Xiong, W.-C.-, Mei, L., and Gao, T.-M. (2010) "ErbB4 in parvalbumin-positive interneurons is critical for neuregulin 1 regulation of long-term potentiation."Proc Natl Acad Sci (USA) 107:21818-21823.
  • Brinkmann, B.G., Agarwal, A., Sereda, M.W., Garratt, A.N., Muller, T., Wende, H., Stassart, R.M., Nawaz, S., Humml, C., Velanac, V., Radyushkin, K., Goebbels, S., Fischer, T.M., Franklin, R. J., Lai, C., Ehrenreich, H., Birchmeier, C., Schwab, M.H., and Nave, K.-A. (2008) "Neuregulin-1/ErbB signaling serves distinct functions in myelination of the peripheral and central nervous system."Neuron, 59: 581-595.
  • Prieto, A.L., O’Dell, S., Varnum, B., and Lai, C. (2007) "Localization and signaling of the receptor protein tyrosine kinase Tyro-3 in cortical and hippocampal neurons."Neuroscience, 150:319-334.
  • Ghashghaei, H.T., Weber, J.L., Pevny, L., Schmid, R., Schwab, M.H., Lloyd, K.C., Eisenstat, D.D., Lai, C., and Anton E. S. (2006). "The role of neuregulin-erbB4 interactions on the proliferation and organization of cells in the adult subventricular zone."Proc Natl Acad Sci (USA), 103:1930-1935.
  • Michailov, G.V., Sereda, M.W., Brinkmann, B.G., Fischer, T.M., Haug, B., Birchmeier, C., Role, L., Lai, C., Schwab, M.H. and Nave, K.-A. (2004) "Axonal neuregulin-1 regulates myelin sheath thickness."Science 304, 700-3.
  • Anton, E.S., Ghashghaei, H.T., Weber, J.L., McCann, C., Fischer, T.M., Cheung, I.D., Gassmann, M., Messing, A., Klein, R., Schwab, M.H., Lloyd, K.C.K. and Lai, C. (2004) "Receptor tyrosine kinase ErbB4 modulates neuroblast migration and placement in the adult forebrain."Nat. Neurosci. 7, 1319-1328.

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