Dr. Kim graduated from the Korea University in South Korea with a bachelor degree in Biology. During graduate study at University of Medicine & Dentistry of New Jersey (UMDNJ, formerly Rutgers University Medical School at Piscataway, NJ), he studied the molecular mechanisms and regulation of eukaryotic gene expression under the supervision of Dr. Danny Reinberg (HHMI, currently at NYU). After obtaining a Ph.D. degree in Biochemistry, he continued his research career in the laboratory of Dr. Michael Greenberg (Harvard Medical School) as a postdoctoral fellow, studying how neuronal activity controls gene expression in neurons to mediate synapse remodeling and plasticity. He joined the faculty in the Department of Neuroscience at University of Texas Southwestern Medical School in 2010.
Major research interests in Kim’s laboratory are to define the program of gene expression that is tightly regulated by neuronal activity and to understand how the activity-regulated nuclear gene expression contributes to brain development and cognitive behaviors. Many key players in the activity-regulated calcium signaling pathways and nuclear gene expression are implicated in several human cognitive disorders such as Autism Spectrum Disorder (ASD) and epilepsy.
Global analysis of activity-regulated gene expression in the brain
In an effort to define activity-regulated program of gene expression in neurons, Kim has been utilizing recently developed RNA-Seq and ChIP-Seq methods to 1) profile RNA expression, 2) identify specific targets for individual activity-regulated or inducible transcription factors (TFs), and 3) monitor epigenetic changes, from mouse cortical neurons. These combined genome-wide approaches provide an important framework for Kim’s ongoing studies to understand how nuclear gene expression mediates sensory experience-dependent changes in neural circuit formation, synaptic plasticity, and cognitive behaviors.
Characterization of neuronal enhancers that control temporal and spatial-specific gene expression in the brain
Enhancers are known to control temporal and spatial expression of genes. However how neuronal activity utilizes neuronal enhancers to control stimulus and region-specific gene expression in brain has never been explored. Kim’s lab is in the process of identifying and characterizing neuron-specific enhancers whose function is tightly regulated by neuronal activity to understand biological function of the enhancer-dependent transcription in neurons. The study will be expanded further to define the cellular and molecular mechanisms that underlie the establishment of neuron-specific enhancers during early brain development. Specific role of enhancers in the sensory experience-dependent signaling and gene expression, and its implication in cognitive behavior will also be investigated in vivo by using a mouse model system.
Mechanism and function of activity-dependent poly-adenylation (poly-A) site switching
Kim’s recent study demonstrated that many activity-regulated gene products are truncated at the level of either mRNA or protein as a result of alternative poly-A site usage. This finding has revealed a novel aspect of activity-dependent transcriptional regulation. Kim’s lab is currently investigating the molecular mechanism of activity-regulated poly-A site switching as well as biological function of altered gene products during the development and refinement of neural circuitry.
Tae-Kyung Kim, Hemberg M, Gray JM, Costa AM, Bear DM, Wu J, Harmin DA, Laptewicz M, Barbara-Haley K, Kuersten S, Markenscoff-Papadimitriou E, Kuhl D, Bito H, Worley PF, Kreiman G, Greenberg ME: Widespread transcription at neuronal activity-regulated enhancers. Nature (Article), 2010 Apr 14. [Epub ahead of print].
Greer PL, Hanayama R, Bloodgood BL, Mardinly AR, Lipton DM, Flavell SW, Tae-Kyung Kim, Griffith EC, Waldon Z, Maehr R, Ploegh HL, Chowdhury S, Worley PF, Steen J, Greenberg ME (2010) The Angelman Syndrome Protein Ube3A Regulates Synapse Development by Ubiquitinating Arc. Cell 140(5):704-716.
Fiore R, Khudayberdiev S, Christensen M, Siegel G, Flavell SW, Tae-Kyung Kim, Greenberg ME, Schratt G. (2009) Mef2-mediated transcription of the miR379-410 cluster regulates activity-dependent dendritogenesis by fine-tuning Pumilio2 protein levels. EMBO J. 28(6): 697-710.
Pazyra-Murphy MF, Hans A, Karch C, Courchesne S, Heerssen HM, Watson FL, Tae-Kyung Kim, Greenberg ME, Segal RA (2009) A retrograde neuronal survival response: target-derived neurotrophins regulate MEF2D and bcl-w J. Neurosci. 29(20): 6700-6709.
Flavell SW*, Tae-Kyung Kim*, Gray JD, Harmin D, Bear D, Markenscoff-Papadimitriou E, Hu LS, Greenberg ME (2008) Genome-wide analysis of the target genes of MEF2, a transcription factor that coordinates synapse development. Neuron, 60(6):1022-38. (* equal contribution).
Lin Y, Hauser JL, Bloodgood BL, Lapan AD, Koon AC, Tae-Kyung Kim, Hu LS, Malik AN, Greenberg ME (2008) Activity-dependent regulation of GABAergic synapse development by Npas4. Nature (Article), 455(7217):1198-204.
Morrow EM, Yoo SY, Flavell SW, Tae-Kyung Kim, Lin Y, Hill RS, Mukaddes NM, Balkhy S, Gascon G, Hashmi A, Al-Saad S, Ware J, Joseph RM, Greenblatt R, Gleason D, Ertelt JA, Apse KA, Bodell A, Partlow JN, Barry B, Yao H, Markianos K, Ferland RJ, Greenberg ME, Walsh CA (2008) Identifying autism loci and genes by tracing recent shared ancestry. Science (Article), 321(5886):218-23.
Mikkelsen TS, Ku M, Jaffe DB, Issac B, Lieberman E, Giannoukos G, Alvarez P, Brockman W, Tae-Kyung Kim, Koche RP, Lee W, Mendenhall E, O'Donovan A, Presser A, Russ C, Xie X, Meissner A, Wernig M, Jaenisch R, Nusbaum C, Lander ES, Bernstein BE (2007)Genome-wide maps of chromatin state in pluripotent and lineage-committed cells . Nature (Article), 448(7153):553-60.
Marinescu VD, Kohane IS, Tae-Kyung Kim, Harmin DA, Greenberg ME, Riva A (2006) START: an automated tool for serial analysis of chromatin occupancy data . Bioinformatics, 22(8):999-1001.
Flavell SW, Cowan CW, Tae-Kyung Kim, Paradis S, Griffith EC, Hu, LS, Chen, C, Greenberg ME (2006) Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number. Science, 311:1008-12.
Pavri R, Lewis B, Tae-Kyung Kim, Dilworth FJ, Erdjument-Bromage H, Tempst P, de Murcia G, Evans R, Chambon P, Reinberg D (2005) PARP-1 determines specificity in a retinoid signaling pathway via direct modulation of mediator. Mol Cell., 18:83-96.
Lewis BA, Tae-Kyung Kim, Orkin SH (2000) A Novel Downstream Element in the Human beta-globin Promoter: Evidence of Extended Sequence-Specific Transcription Factor IID Contacts. Proc. Natl. Acad. Sci. USA, 97, 7172-7177.
Tae-Kyung Kim, Richard H. Ebright, and Danny Reinberg (2000) Mechanism of ATP-Dependent Promoter Melting by Transcription Factor IIH. Science, 288, 1418-1421.
Cho, H., Tae-Kyung Kim, Mancebo, H., Lane, W., Flores, O., Reinberg, D (1999) A Protein Phosphatase Functions To Recycle RNA Polymerase II. Genes Dev., 13, 1540-1552.
Tae-Kyung Kim, Thierry Lagrange, Yuh-Hwa Wang, Jack D. Griffith, Danny Reinberg, and Richard Ebright (1997) Trajectory of DNA in the RNA Polymerase II Transcription Preinitiation Complex . Proc. Natl. Acad. Sci. USA, 94, 12268-12273.
Thierry Lagrange, Tae-Kyung Kim, George Orphanides, Yon W. Ebright, Richard Ebright, and Danny Reinberg (1996) High-Resolution Mapping of Nucleoprotein Complexes by Site-Specific Protein-DNA Photocrosslinking: Organization of the Human TBP-TFIIA-TFIIB-DNA Quaternary Complex. Proc. Natl. Acad. Sci. USA, 93, 10620-10625.