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KWANG-SOO KIM, PH.D.

• Harvard title(s): Professor of Psychiatry and Neuroscience
• McLean title(s): Directory, Molecular Neurobiology Laboratory
• Email: kskim@mclean.harvard.edu
• Telephone: (617) 855-2024
• Fax: (617) 855-3479
• Office Address: Molecular Neurobiology Laboratory, Mail Stop 149
• Degree(s): 1977 B.Sc. (SNU), 1979 M.S. (KAIST), 1983 Ph.D. (KAIST), 2011 M.S. (hon.)(Harvard Univ).
• Clinical Interests: Neurological and psychiatric diseases in which dopamine neurons are dysregulated/degenerated.
• Bio: Dr. Kim obtained a B.Sc. in Microbiology from Seoul National University, Korea. He then moved to Korea Advanced Institute of Science and Technology (Seoul, Korea) where he obtained a Master degree and Ph.D. in Microbial Genetics. In 1983 he joined the laboratory of Dr. L. Guarente at the Massachusetts Institute of Technology where he focused his attention on transcriptional control mechanisms. In 1989 he took the position of Assistant Professor in the Department of Neurology and Neuroscience at Cornell University Medical School. In 1994 he moved to the University of Tennessee College of Medicine where he acted as Associate Professor in the Department of Neurology and the Department of Anatomy and Neurobiology. Since 1988, he has been the Director of the Molecular Neurobiology Laboratory, at McLean Hospital, Harvard Medical School, and is now Professor of Psychiatry and Neuroscience of Harvard Medical School. Dr. Kim has received several awards including two times Independent Investigator awards from the National Alliance for Research on Schizophrenia and Depression (NARSAD) and a prestigious NIH Director's RO1 Award. He is serving as a reviewer at NIH study sections and is currently an editorial board member of the Journal, Stem Cells.
• Publications: (Selected)
  Pubmed search for Kim KS [au]
  • Kim, K.S. and Guarente, L. (1989) Mutations that Alter transcriptional Activation but not DNA Binding in the Zinc Finger of Yeast Activator HAPI. Nature 342, 200-203.
  • Pfeifer, K., Kim, K.S., Kogan, S. and Guarente, L. (1989) Functional Dissection and Sequence of Yeast HAPI Activator, Cell 56, 291-301.
  • Kim, K.S., Pfeifer, K., Powell, L. and Guarente, L. (1990) Internal Deletions in the Yeast Transcriptional Activator HAPI Have Opposite Effects at Two Sequence Elements. P.N.A.S. (USA) 87, 4524-4528.
  • Kim, K.S., Park, D.H., Wessel, T.C., Song, B., Wagner, J.A., Joh, T.H. (1993) A dual role of the cAMP-dependent protein kinase on tyrosine hydroxylase gene expression. P.N.A.S. (USA) 90, 3471-3475.
  • Kim, K.S., Ishiguro, H., Tinti, C., Wagner, J.A. and Joh, T.H. (1994) The cAMP-dependent protein kinase regulates transcription of the dopamine ?-hydroxylase gene. J. Neurosci. 14, 7200-7207.
  • Seo, H., Yang, C., Kim, H.-S., and Kim, K.S. (1996) Multiple protein factors interact with the cis-regulatory elements of the proximal promoter in a cell-specific manner and regulate transcription of the dopamine ?-hydroxylase gene. J. Neurosci. 16, 4102-4112.
  • Tinti, C., Yang, C.Y., Seo, H., Conti, B., Kim, C., Joh, T.H., and Kim, K.S. (1997) Structure/function relationship of the cAMP response element in TH gene transcription. J. Biol. Chem. 272, 19158-19164.
  • Kim, H.S., Seo, H., Brunet, J.F., and Kim, K.S. (1998) Noradrenergic-specific transcription of the dopamine ?-hydroxylase gene requires synergy of multiple cis-regulatory elements including at least two Phox2a-binding sites J. Neurosci. 18:8247-8260.
  • Kim, C.H., Ardayfio, P., and Kim, K.S. (2001) An E-box motif residing in the exon/intron 1 junction regulates both transcriptional activation and splicing of the hNET gene. J. Biol. Chem. 276:24797-805.
  • Hwang, D., Carlezon, W., Isacson, O., and Kim, K.S. (2001) A high-efficiency synthetic promoter that drives transgene expression selectively in noradrenergic neurons. Human Gene Ther. 12:1731-1740.
  • Bjoklund, L., Chung, S., Andersson, T., Costantini, L.C., Kim, K.S., and Isacson, O. (2002) Transplanted embryonic stem cells differentiate into dopaminergic neurons in vivo and restore behavioral function in a Parkinson's disease model. P.N.A.S. (USA) 99:2344-9.
  • Kim, C.H., Hwang, D.Y., Park, J.J., and Kim, K.S. (2002) A proximal promoter domain containing a homeodomain-binding core motif interacts with multiple transcription factors including HoxA5 and Phox2 proteins and critically regulate cell type-specific transcription of the hNET gene. J. Neurosci. 22(7):2579-89.
  • Chung, S., Sonntag, K.-C., Andersson, T., Bjorklund, L.M., Park, J.J., Isacson, O., Kim, K.S. (2002) Genetic engineering of mouse embryonic stem cells by Nurr1 enhances differentiation and maturation into dopaminergic neurons. Eur. J. Neurosci. 16:1829-1838.
  • Kim, K.S., Kim, C.H., Hwang, D.Y., Seo H., Chung, S., Hong, S.J., Anderson, T., and Isacson, O. (2003) The orphan nuclear receptor Nurr1 directly transactivates the promoter of the tyrosine hydroxylase gene in a cell-specific manner. J. Neurochem. 85(3):622-34.
  • Hwang, D.-Y., Hwang, M.M., Kim, H.S., and Kim, K.S. (2005) Genetically engineered human dopamine ?-hydroxylase gene promoters with better Phox2a-binding sites drive significantly enhanced transgene expression in a noradrenergic cell type-specific manner. Mol. Therapy 11:131-142.
  • Chung, S., Hwang, M., Kim, D.W., Hedlund, E., Hwang, D.-Y., Kang, U.J., Isacson, O., Kim, K.S. (2005) The homeodomain transcription factor Pitx3 facilitates differentiation of mouse embryonic stem cells into A9-like DA neurons. Mol. Cell. Neurosci. 28:241-252.
  • Hwang, D.Y., Fleming, S.M., Ardayfio, P., Moran-Gates, T, Kim, H, Tarazi, F.I., Chesselet, M.-F., and Kim, K.S. (2005) 3,4-dihydroxyphenylalanine reverses the motor deficits in Pitx3-deficient aphakia mice: behavioral characterization of a novel genetic model of Parkinson's disease. J. Neurosci. 25:2132-2137.
    Kim, D.W., Hwang, M., Chung, S., Ferree, A., Tsai, S, Kang, U.J., Isacson, O., Kim, K.S. (2006) Stromal cell-derived inducing activity, Nurr1, and signaling molecules synergistically induce dopaminergic neurons from mouse embryonic stem cells. Stem Cells 24(3):557-67.
  • Ardayfio, PA, Tsai, HC, Kim, CH, Berger-Sweeney, J, and Kim, K.S. (2006) Effects of chronic hypercortisolemia on aversive and appetitive learning in mice: Implications for depression. Behavioral Neuroscience 120(2):249-56.
  • Chung, S., Shin, B.-S., Hedlund, Hwang, M., Ferree, A., Kang, U.J., Iacson, O., and Kim, K.S. (2006) Genetic selection of sox1GFP-expressing neural precursors removes residual tumorigenic pluripotent stem cells and attenuates tumor formation after transplantation. J. Neurochem. 97(5):1467-80.
  • Hong, S.J., Chae, H, Huh, Y, and Kim, K.S. (2006) GATA-3 regulates the transcriptional activity of tyrosine hydroxylase by interacting with CREB. J. Neurochem. 98(3):773-81.
  • Kim, C.H., Hahn, M., Joung, Y., Anderson, S., Steele, A.H., Mazei-Robinson, M.S., Gizer, I., Teicher, M.H., Cohen, B.M., Robertson, D., Waldman, I.D., Blakely, R.D., and Kim, K.S.
    (2006) A polymorphism in the human norepinephrine transporter gene alters promoter activity and is associated with attention deficit hyperactivity disorder. P.N.A.S. 103, 19164-19169 (this paper was featured in ScienceNow (Nov 28, 2006) and Nature Rev. Neuroscie 8:4, 2007).
  • Hedlund, E., Pruszak, J., Ferree, A., Viñuela, A., Hong, S., Isacson, O., and Kim, K.S. (2007) Selection of embryonic stem cell derived eGFP+ dopamine neurons using the tyrosine hydroxylase promoter is confounded by reporter gene expression in immature cell populations. Stem Cells. 25(5):1126-35.
  • Warburton, D., Koh, C., Chung, H.M., Cha, K.W., and Kim, K.S. (2007) Meeting report: The 1st International Collaborative Symposium on Stem Cell Research, Seoul, Korea. Stem Cells 25(5):1337-8.
  • Hong, S., Hwang, D.-Y., Hwang, M., Yoon, S., Isacson, O., Ramezani, A., Hawley, R.G. and Kim, K.S. (2007) Functional analysis of different promoters in lentiviral vectors for transgene expression at different stages of in vitro differentiated mouse embryonic stem cells. Mol. Therapy 15(9):1630-9.
  • Hong, S., Kang, U.J., Isacson, O., and Kim, K.S. (2008) Neural precursors derived from human embryonic stem cells maintain long-term proliferation and the potential to differentiate into three cell types of neural lineage, including dopaminergic neurons. J. Neurochem. 104(2):316-24.
  • Ardayfio, P., Moon, J.S., Hwang, D.Y., Leung, A., and Kim, K.S. (2008) Cognitive impairments in a genetic model of Parkinson's disease. Neurobiol. Disease 31(3):406-12.
  • Hong, S.J., Lardaro, T., Oh, M.S., Huh, Y., Ding, Y., Kang, U.J., Kirfel, J., Buettner, R., and Kim, K.S. (2008) Regulation of the noradrenergic neurotransmitter identity by the transcription factor AP-2b. J. Biol. Chem. 283(24):16860-7.
  • Hedlund, E.M., Pruszak, J., Lardaro, T., Ludwig, W., Viñuela, A., Kim, K.S., Isacson, O. (2008) Embryonic Stem (ES) Cell-derived Pitx3-eGFP Midbrain Dopamine Neurons Survive Enrichment by FACS and Function in an Animal Model of Parkinson's Disease. Stem Cells. 26(6):1526-36.
  • Oh, M.S., Hong, S.J., Huh, Y., and Kim, K.S. (2009). Expression of transgenes in midbrain dopamine neurons using the tyrosine hydroxylase promoter. Gene Therapy 16(3):437-40.
  • Riccio, A., Li, Y., Moon, J., Kim, K.S., Gapon, S., Yao, G.L., Tsvetkov, E., Rodig, S.J., Meloni, E.G., Carlezon, W.A., Clapham, D.E., and Bolshakov, V.Y., (2009) Essential role for TRPC5 in amygdale function and fear-related behavior. Cell 137(4):761-72.
  • Kim, D., Kim, C.-H., Moon, J., Chung, Y.-G., Chang, M.-Y., Han, B.-S., Ko, S., Yang, E., Cha, K.Y., Lanza, R., Kim, K.S. (2009). Generation of Human Induced Pluripotent Stem Cells by Direct Delivery of Reprogramming Proteins. Cell Stem Cell 4(6):472-6. (this paper was featured in >150 web media including sites shown below; also selected as one of 2009 Research Highlights by Nature 2009, 462:960).
  • Chung, S., Leung, A., Hong, S.H., Chang, M.Y., Pruszak, J., Han, B.-S., Isacson, O. and Kim, K.S. (2009) Wnt1 and Lmx1a form a novel autoregulatory loop and critically regulate midbrain dopaminergic development at multiple steps. Cell Stem Cell 5:646-58.
  • Hwang, D.Y., Hong, S., Jeong, J.W., Choi, S. Kim, H., Kim, J.W., and Kim, K.S. (2009) Vesicular monoamine transporter 2 and dopamine transporter are molecular targets of Pitx3 in midbrain dopaminergic neurons. J. Neurochem. 111:1202-12.
  • Ardayfio, P.A., Leung, A., Park, J., Hwang, D.-Y., Moran-Gates, T., Carlezon Jr, W.A., Tarazi, F.I., and Kim, K.S. (2010) Pitx3-deficient aphakia mice display unique behavioral responses to psychostimulant and antipsychotic drugs. Neuroscience 166: 391-396.
  • Joung, Y., Kim, C.-H., Moon, J., Jang, W.-S., Yang, J., Shin, D., Lee, S., and Kim, K.S. (2010) Association studies of -3081(A/T) polymorphism of norepinephrine transporter gene with attention deficit/hyperactivity disorder in Korean population. Amer. J. Med. Genet. Part B 153B:691-694.
  • Feng, Q., Lu, S.-J., Klimanskaya, I., Gomes, I., Kim, D., Chung, Y., Honig, G.R., Kim, K.S., Lanza, R. (2010) Hemangioblastic derivatives from human induced pluripotent stem cells exhibit limited expansion and early senescence. Stem Cells, 28: 704-712. (featured in Science, 2010, 327: 1191)
  • Lee, H.-S., Kim, E.-Y., Kim, K.-H., Moon, J., Park, K.-S., Kim, K.S., Lee, K.-A., (2010) Obox4 critically regulates cAMP-dependent meiotic arrest and MI-MII transition in oocytes. Faseb J., 24:2314-24.
  • Chang, M.-Y., Kim, D., Kim, C.-H., Kang, H.-C., Yang, E., Moon, J-I., Ko, S., Park, J., Park, K.-S., Lee, K.A., Hwang, D.-Y., Chung, Y., Lanza, R., Kim, K.S. (2010) Direct Reprogramming of Rat Neural Precursor Cells and Fibroblasts into Pluripotent Stem Cells. PlosONE, 5(3): e9838.
    Kim, H.M., Ahn, H.J., Lee, H.S., Lee, K.A., Lee, S.M., Kim, H.H., Kim, K.S., Park, K.S. (2010) Obox4 regulates the expression of histone family genes and promotes differentiation of mouse embryonic stem cells. FEBS Lett. 584(3):605-11.
  • Neveu, P., Kye, M.J., Qi, S., Buchholz, D.E., Clegg, D.O., Sahin, M., Park, I.-H., Kim, K.S., Daley, G.Q., Kornblum, H.I., Shraiman, B.I., and Kosik, K.S. (2010) MicroRNA profiling reveals two distinct p53-related human pluripotent stem cell states. Cell Stem Cell, 7:671-81 (Comment in Cell Stem Cell. 2010, 7(6):649-50).
  • Hong, S.J., Huh, Y.H., Leung, A, Choi, H.J., Ding, Y, Kang, U.J., Yoo, S.H., Buettner, R., and Kim, K.S. (2011) Transcription factor AP-2b regulates the neurotransmitter phenotype and maturation of chromaffin cells. Mol. Cell. Neurosci., 46:245-51.
  • Kim, C.H., Leung, A., Huh, Y.H., Yang, E., Kim, D.J., Leblanc, P., Ryu, H., Kim, K., Kim, D.W., Garland, E.M., Raj, S.R., Biaggioni, I., Robertson, D., and Kim, K.S. (2011)
    Norepinephrine deficiency is caused by combined abnormal mRNA processing and defective protein trafficking of dopamine b-hydroxylase. J Biol Chem. 286(11):9196-204.
  • Rhee, Y.-H., Ko, J.-Y., Chang, M.-Y., Yi, S.-H., Kim, D., Kim, C.-H., Shim, J.-W., Jo, A.-Y., Kim, B.-W., Lee, H., Lee, S.-H., Suh, W., Park, C.-H., Koh, H.-C., Lee, Lee, Y.-S., Lanza, R., Kim, K.S.* and Lee, S.-H.* (*co-corresponding authors) (2011) Protein-based human iPS cells efficiently generate functional dopamine neurons without abnormal phenotypes associated with genome integration. J. Clin. Invest. 121(6):2326-35. Epub 2011 May 16. (featured in Nature Review Neurology 14 June 2011, 7:357 and in Sciencedaily; http://www.sciencedaily.com/releases/2011/05/110516121419.htm).
  • Chung, S., Moon, J.-I., Leung, A., Aldrich, D., Lukianov, S., Kitayama, Y., Park, S., Li, Y., Bolshakov, V.Y., Lamonerie, R., and Kim, K.S. (2011) ES cell-derived renewable and functional midbrain dopaminergic progenitors. P.N.A.S. 108(23):9703-8.

Updated: 01.2012

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