My lab is investigating the cellular and molecular mechanisms underlying the construction of the brain and functional neural circuitry, particularly genesis, positioning, and interconnections of neurons in the brain. These processes are essential for communication across the brain and for generating cognitive, social, and emotional behaviors. Disruption in brain and circuit formation is associated with neurodevelopmental disorders, including autism spectrum disorders, intellectual disability, mood disorders, and schizophrenia. Our goal is to make a significant impact in the development of treatment strategies for neurodevelopmental and psychiatric disorders. We take neurobiological and genetic approaches to define pathogenesis of these neurological conditions affecting cognition, emotion, and social interaction.
Inhibitory GABA neuron Development and neurological diseases
Generation and differentiation of GABAergic inhibitory neurons play critical roles in the establishment of brain circuits controlling cognitive and emotional behaviors. Autism behaviors and intellectual dysfunction are frequently caused by altered inhibitory signaling due to abnormal GABAergic inhibitory neurons in humans and animal models of autism and intellectual disability. Molecular mechanisms for inhibitory neuron generation and positioning in the brain remain largely elusive, which has hindered research into potential treatments for neurodevelopmental and psychiatric disorders. Using multiple genetic mouse models, we study inhibitory neuron development.
Brain circuit development
Formation of neural circuits depends on migration and differentiation of neurons. Migration and axon/dendrite differentiation are fundamental processes during pyramidal neuron development in the brain. Abnormalities in these processes cause several types of brain malformations and are associated with neurodevelopmental disorders. We study mechanisms of abnormal migration/positioning and differentiation of cortical and hippocampal pyramidal neurons in mouse models of neurodevelopmental disorders. We focus on molecules involved in neurotrophin, Wnt, mTOR, and MACF1 signaling pathways.
Neural stem cell regulation in the brain
Balanced control of neural stem cell proliferation, maintenance, and neurogenesis is crucial in generating functional brain. However, the mechanisms and key molecules in neural stem regulation remain poorly understood. We study cross-talks among neurotrophin, mTOR, and GSK-3 signaling in the brain.
Mouse behavior testing
In utero manipulation of rodent brains
Stereotaxic gene delivery using viruses
Neural circuit analysis using genetic tools
Neural cell and slice culture
Molecular and biochemical techniques
Time-lapse and high resolution imaging
Ph.D. in Neuroscience, State University of New York at Buffalo
Ka, M. and Kim, W.Y. (2018) ANKRD11 associated with intellectual disability and autism regulates dendrite differentiation via the BDNF/TrkB signaling pathway. Neurobiology of Disease. 111: 138-152. PMCID: PMC5803300.
Jung, E.M., Moffat, J.J., Liu, J., Dravid, S.M., Gurumurthy, C., Kim, W.Y. (2017) Arid1b haploinsufficiency disrupts cortical interneuron development and mouse behavior. Nature Neuroscience. 20: 1694-1707. PMCID: PMC5726525.
Ka, M., Smith, A.L., Kim, W.Y. (2017) MTOR controls genesis and autophagy of GABAergic interneurons during brain development. Autophagy. 13 (8): 1348-1363. PMCID: PMC5584862.
Moffat, J.J., Ka, M., Jung, E.M., Smith, A.L., Kim, W.Y. (2017) The role of MACF1 in nervous system development and maintenance. Seminars in Cell and Developmental Biology. 69: 9-17. PMCID: PMC5583038.
Ka, M., Moffat, J.J., Kim, W.Y. (2017) MACF1 controls migration and positioning of cortical GABAergic interneurons in mice. Cerebral Cortex. 27 (12): 5525-5538. PMCID: In process.
Chen, C, Kim, W.Y., Jiang, P. (2016) Humanized neuronal chimeric mouse brain generated by neonatally engrafted human iPSC2 derived primitive neural progenitor cells. Journal of Clinical Investigation Insight. 1 (19): e88632. PMCID: PMC5111502.
Ka, M. and Kim, W.Y. (2016) Microtubule-Actin Crosslinking Factor 1 is required for dendritic arborization and axon outgrowth in the developing brain. Molecular Neurobiology. 53 (9): 6018-6032. PMCID: PMC4853297.
Ka, M., Kook, Y., Liao, K., Buch, S., Kim, W.Y. (2016) Transactivation of TrkB by Sigma-1 receptor mediates cocaine-induced changes in dendritic spine density and morphology in hippocampal and cortical neurons. Cell Death & Disease. 7 (10): e2414. PMCID:
Jung, E.M., Ka, M., Kim, W.Y. (2016) Loss of GSK-3 causes abnormal astrogenesis and behavior in mice. Molecular Neurobiology. 53(6): 3954-3966. PMCID: PMC4716001.
Ka, M., Chopra, D., Dravid, S., Kim, W.Y. (2016) Essential roles for ARID1B in dendritic arborization and spine formation of developing pyramidal neurons. Journal of Neuroscience. 36 (9): 2723-2742. PMCID: PMC4879215.
Jung, E.M., Moffat, J.J., Kim, W.Y. (2015) Regeneration potential of targeting GSK-3 signaling in neural tissues. Neural Regeneration Research. 10 (12): 1912-1913. PMCID: PMC4730800.
Moffat, J.J., Ka, M., Jung, E.M., Kim, W.Y. (2015) Genes and brain malformation associated with abnormal neuron positioning. Molecular Brain. 8: 72. PMCID: PMC4635534.
Kim, W.Y. (2015) Brain size is controlled by the mammalian target of rapamycin (mTOR) in mice. Communicative & Integrative Biology. 8 (1): e994377. PMCID: PMC4594332.
Ka, M., Condorelli, G., Woodgett, J.R., Kim, W.Y. (2014) mTOR regulates brain morphogenesis by mediating GSK-3 signaling. Development. 141: 4076-4086. PMCID: PMC4302893.
Ka., M., Jung, E.M., Mueller, U., Kim, W.Y. (2014) MACF1 regulates the migration of pyramidal neurons via microtubule dynamics and GSK-3 signaling. Developmental Biology. 395: 4-18. PMCID: PMC4190130.
Kim, W.Y.* and Snider W.D. (2011) Functions of GSK-3 signaling in development of the nervous system. Frontiers in Molecular Neuroscience. 4:44. PMCID: PMC3221276. * Corresponding author
Chen Y., Tian X., Kim, W.Y., Snider W.D. (2011) Adenomatous Polyposis Coli Regulates Axon Arborization and Cytoskeleton Organization via Its N-Terminus. PLOS ONE. 6(9): e24335. PMCID: PMC3167844.
Yokota, Y., Eom, T., Stance, A., Kim, W.Y., Rao, S., Snider, W., Anton E.S. (2010). Cdc42 and Gsk3 modulate the dynamics of radial glial growth, inter-radial glial interactions and polarity in the developing cerebral cortex. Development. 137:4101-4110. PM
Soutar, M.P., Kim, W.Y., Williamson, R., Peggie, M., James Hastie, C., McLauchlan, H., Snider, W.D., Gordon-Weeks, P.R., Sutherland, C. (2010) Evidence that Glycogen Synthase Kinase-3 isoforms have distinct substrate preference in the brain. Journal of Ne
Kim, W.Y., Wang, X., Wu, Y., Doble, B., Patel, S., Woodgett, J., Snider, W. (2009). GSK-3 is a master regulator of neural progenitor homeostasis in mammals. Nature Neuroscience. 12:1390-1397 (Selected by Faculty of 1000 as ‘Must Read FFa 8’ paper). PMCID
Yokota, Y., Kim, W.Y., Chen, Y., Wang, X., Komuro, Y., Snider, W., Anton E.S. (2009). The Adenomatous Polyposis Coli (APC) Protein is an Essential Regulator of Radial Glial Polarity and Construction of the Cerebral Cortex. Neuron. 61:42-56. PMCID: PMC2804
Kim, W.Y., Gonsiorek, E., Barnhart, C., Davare, M., Engebose, A., Lauridsen, H., Bruun, D., Lesiak, A., Wayman, G., Bucelli, R., Higgins, D., Lein, P. (2009) Statins decrease dendritic arborization in rat sympathetic neurons by blocking RhoA activation. J
Kim, W.Y., Snider, W. (2008) Neuroscience. Overcoming inhibitions. Science 322:869-72.
Bucelli, R., Gonsiorek, E., Kim, W.Y., Bruun, D., Rabin, R., Higgins, D., Lein, P. (2008) Statins decrease expression of the proinflammatory neuropeptides calcitonin gene-related peptide and substance P in sensory neurons. J Pharmacol Exp Ther. 324:1172-8
Kim, W.Y., Zhou, F.Q., Zhou, J., Yokota, Y., Wang, Y., Yoshimura, T., Kaibuchi, K., Woodgett, J., Anton, E., Snider, W. (2006) Essential Roles for GSK-3s and GSK-3-Primed Substrates in Neurotrophin-Induced and Hippocampal Axon Growth. Neuron. 52:981-996.
Kim, W.Y., Fayazi, Z., Bao, X., Higgins, D., Kazemi-Esfarjani, P. (2005) Evidence for sequestration of polyglutamine inclusions by Drosophila myeloid leukemia factor. Molecular and Cellular Neuroscience. 29:536-44.
Edelman, A., Kim, W.Y., Higgins, D., Goldstein, E., Oberdoerster, M., Sigurdson, W. (2005) Doublecortin kinase-2, a novel doublecortin-related protein kinase associated with terminal segments of axons and dendrites. Journal of Biological Chemistry. 2
Kim, W.Y., Horbinski, C., Sigurdson, W., Higgins, D. (2004) Proteasome inhibitors suppress formation of polyglutamine-induced nuclear inclusions in cultured postmitotic neurons. Journal of Neurochemistry. 91:1044-1056.
Kim, I.J., Drahushuk, K., Kim, W.Y., Gonsiorek, E., Lein, P., Andres, D., Higgins, D. (2004) Extracellular Signal-Regulated Kinases Regulate Dendritic Growth in Rat Sympathetic Neurons. Journal of Neuroscience. 24:3304-3312.
Kim, W.Y., Eum, J.S., Sim. W.S. (2000) Identification and purification of Trans-acting factors binding to the rbcL R2 promoter region in Zea mays. Journal of Plant Biology. 43:99-106.
Hwang, S.H., Kim, W.Y., Chun, S., Min, W.K. (2000) Allele frequencies of apo pentanucleotide (TTTTA) repeat polymorphism. Korean J Clin Pathol. 20: 268-74.