My lab is investigating the cellular and molecular mechanisms underlying the construction of the brain and functional neural circuitry, particularly genesis, positioning, and connectivity 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, and emotional disturbance. 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 behavior.
Inhibitory GABA neuron development and neurological diseases
Generation and differentiation of GABAergic inhibitory neurons play critical roles in the establishment of brain functions controlling cognition and emotion. Autistic behavior and intellectual dysfunction are frequently caused by altered inhibitory signaling in humans and animal models of neurodevelopmental disorders. However, molecular mechanisms for inhibitory neurogenesis and positioning in the brain remain largely elusive, which has hindered research progress into potential treatments for neurodevelopmental and psychiatric disorders. Using multiple genetic mouse models, we study inhibitory neuron development.
Brain circuits assoiciated with autism, intellectual disability, and emotional disturbance
Emotional and social impariments in neurodevelopmental and psychiatric disorders are most closly linked to neural circuit organization and function. While gene mutations recently emerge as a causal player for those neurological conditions, it is poorly understood how the gene alteration disrupts neuronal connectivity in the pathological brain. Using mouse chemo- and optogenetics, we map social and emotion brain citcuits in normal and neurodevelopmental conditions. Core brain domains and specific cell types comprising the neural circuits are also examined in the lab. We focus on dopaminergic, seortonergic and oxytocinergic pathways.
Epigenetics in brain formation
Studeis have shown that epigenetic genes and epigenetic patterns are altered in neurodevelopmental disorders. Still, the impact of these changes on brain construction is elusive. Thus, we study the functions and mechanisms of epigenetic factors in the formation of the developing brain. Neurogenesis, migration and axon/dendrite differentiation are examined in the lab because these are the fundamental steps during brain development. Abnormalities in these processes cause various types of brain malformations.
Mouse behavior testing
In utero manipulation of rodent brains
Stereotaxic gene delivery using viruses
Neural circuit analysis using chemo and optogenetics
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
Xu, R, Brawner A, Li, S, Liu, J, Kim, H, Xue, H, Pang, Z, Kim, W.Y., Hart, R, Liu, Y, Jiang, P. (2019) OLIG2 drives abnormal neurodevelopmental phenotypes in human iPSC-based organoid and chimeric mouse models of Down Syndrome. Cell Stem Cell. 24:908-926.
Moffat, J.J., Jung, E.M., Ka, M., Smith, A.L., Jeon, B.T., Santen, G.W.E., Kim, W.Y. (2019) The role of ARID1B, a BAF chromatin remodeling complex subunit, in neural development and behavior. Prog Neuropsychopharmacol Biol Psychiatry. 89:30-38. PMCID: PMC6249083.
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: PMC6075562.
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. PMCID: PMC2976289.
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 Neurochemistry. 137: 4101-4110.
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: PMC5328673.
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. Journal of Neurochemistry. 108: 1057-1071. PMCID: PMC4277848.
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. PMCID: PMC4167845.
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. 280: 8531-8543.
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. Annals of Laboratory Medicine. 20: 268-74.