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Seung-Hoi Koo, Ph.D, Assistant Professor

Laboratory for Transcriptional Regulation of Hepatic Energy Metabolism
Department of Molecular Cell Biology
School of Medicine, Sungkyunkwan University
300 Chunchun-dong, Jangan-gu
Suwon, 440-746, Gyeonggi-do, Korea

Tel: :+82-31-299-6136
Fax: +82-31-299-6159
e-mail: shkoo@med.skku.ac.kr
Lab homepage: http://home.skku.edu/~metabolism

Background:

1992: Chemistry, B.S., Department of Chemistry, Seoul National University, Seoul, Korea
1995: Biochemistry, M.S., Department of Chemistry, Seoul National University, Seoul, Korea
2000: Biochemistry, Ph.D., Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA
2000-2001: Postdoctoral Fellow, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA
2001-2002: Postdoctoral Fellow, Department of Molecular Pharmacology, Stanford University, Stanford, CA, USA
2002-2005: Research Associate, Peptide Biology Laboratories, Salk Institute for Biological Studies, La Jolla, CA, USA
2005 – Present: Assistant Professor, Department of Molecular Cell Biology, School of Medicine, Sungkyunkwan University, Suwon, Korea

Research:

Increased incidence of people with metabolic syndrome is closely related to the current pandemic occurrence of metabolic diseases such as type 2 diabetes in the developed countries. Perturbation of energy homeostasis that would lead to the development of such diseases stems from the malfunction of metabolic tissues such as liver, muscle or fat. In mammals, liver is especially important to control energy homeostasis for the whole body by modulating glucose and fat metabolism. We are interested in studying the mechanism for the signal transduction cascades that would regulate glucose and fat metabolism. Especially, we have focused on understanding the regulation of transcriptional machinery that would convey such signals to affect the aforementioned pathway in an adaptive manner. To this end, we utilize biochemical, molecular biological and physiological experimental techniques both in ex vivo (primary hepatocytes) and in vivo animal models. Our basic study will unravel the molecular mechanism by which transcriptional regulations of key genes in the metabolic pathway is regulated both in physiological and pathophysiological conditions and will lead to the identification of potential cures for the metabolic syndrome.

Major research projects:

1. Regulation of hepatic glucose production by modulating TORC2 activity
TORC2 is a critical component for cAMP-mediated transcriptional machinery that regulates fasting glucose metabolism in liver. We will attempt to identify physiological and pharmacological reagents to modulate TORC2 activity and glucose production from liver. We are currently developing optical in vivo imaging systems to monitor the dynamic changes of transcriptional response to external stimuli in live mouse models by a collaboration with Samsung biomedical research institute.
2. Differential role of LKB1 and its downstream kinases in regulating hepatic glucose and fat metabolism
Previous studies have indicated the functional importance of LKB1 in the transcriptional regulation of hepatic glucose and fat metabolism. We will attempt to investigate the divergent roles of AMPK and SIK kinase families, a family of kinases that are activated by LKB1, in modulating different transcription factors/coactivators to control differential metabolic pathways. This study will employ adenoviral RNAi system to knockdown the critical components of kinase signaling cascades in vivo.
3. Study of roles for mammalian SMEKs in hepatic energy metabolism
SMEKs are a novel family of proteins that are implicated in stress response in nematode Caenorhabditis Elegans, potentially linked to the forkhead transcription factors. We will attempt to elaborate the roles of mammalian SMEKs in liver to uncover the potential relations with forkhead transcription factors in the metabolic pathways using mouse models as well as primary hepatocytes.

Publications :

  1. Charles Y. Cho*, Seung-Hoi Koo*, Yan Wang, Scott Callaway, Susan Hedrick, Puiying A. Mak, Anthony P. Orth, Eric C. Peters, Enrique Saez, Marc Montminy, Peter G. Schultz, and Sumit K. Chanda. Identification of the tyrosine phosphatase PTP-MEG2 as an antagonist of hepatic insulin signaling. Cell Metabolism. 3(5):367-78. 2006 (*co-first authors)
  2. Wenwei Zhang, Sandip Patil, Balwant Chauhan, Shaodong Guo, David R. Powell, Jamie Le, Angelos Klotsas, Ryan Matika, Xiangshan Xiao, Roberta Franks, Kim A. Heidenreich, Mini P. Sajan, Robert V. Farese, Donna Beer Stolz, Patrick Tso, Seung-Hoi Koo, Marc Montminty, and Terry G. Unterman. FOXO1 regulates multiple metabolic pathways in the liver: Effects on gluoconeogenic, glycolytic and lipogenic gene expression. J Biol Chem.281(15):10105-17, 2006
  3. Seung-Hoi Koo, and Marc Montminy . Fatty acids and insulin resistance: a perfect storm. Mol Cell. 21(4):449-50, 2006.
  4. Reuben J. Shaw, Katja A. Lamia, Debbie Vasquez, Seung-Hoi Koo, Nabeel Bardeesy, Ronald A. DePinho, Marc Montminy, and Lewis C. Cantley. The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science. 310(5754):1642-6, 2005.
  5. Gianluca Canettieri*, Seung-Hoi Koo*, Rebecca Berdeaux, Jose Heredia, Susan Hedrick, Xinmin Zhang, and Marc Montminy. Dual role of the coactivator TORC2 in modulating hepatic glucose output and insulin signaling. Cell Metabolism. 2(5):331-8. 2005 (*co-first authors)
  6. Seung-Hoi Koo*, Lawrence Flechner*, Ling Qi, Xinmin Zhang, Robert Screaton, Shawn Jeffries, Susan Hedrick, Wu Xu , Faycal Boussouar , Paul Brindle, Hiroshi Takemori, and Marc Montminy. CREB coactivator TORC2 is a key regulator of fasting glucose metabolism. Nature. 437(7062): 1109-11, 2005 (*co-first authors)
  7. Xinmin Zhang, Duncan T. Odom, Seung-Hoi Koo, Michael D. Conkright, Gianluca Canettieri, Jennifer Best, Richard Jenner, Elizabeth Herbolsheimer, Elizabeth Jacobsen, Shilpa Kadam, Beverly Emerson, John B. Hogenesch, Terry Unterman, Richard A. Young, and Marc Montminy. Genome-wide analysis of cAMP-response element binding protein occupancy, phosphorylation, and target gene activation in human tissues. Proc Natl Acad Sci U S A. 102(12):4459-64, 2005
  8. Marc Montminy and Seung-Hoi Koo. Diabetes: outfoxing insulin resistance? Nature. 432(7020):958-9, 2004
  9. Seung-Hoi Koo, Hiroaki Satoh, Stephan Herzig, Chih-Hao Lee, Susan Hedrick, Rohit Kulkarni, Ronald M Evans, Jerrold Olefsky and Marc Montminy. PGC-1 promotes insulin resistance in liver through PPAR-alpha-dependent induction of TRB-3. Nature Medicine. 10(5): 530-4, 2004
  10. Marc Montminy, Seung-Hoi Kooand Xinmin Zhang. The CREB Family: key regulators of hepatic metabolism. Ann Endocrinol (Paris). 65(1):73-5. 2004
  11. Stephan Herzig, Susan Hedrick, Ianessa Morantte, Seung-Hoi Koo, Francesco Galimi and Marc Montminy. CREB controls hepatic lipid metabolism through nuclear hormone receptor PPAR-gamma??Nature. 426(6963):190-3, 2003
  12. Caterina Rufo, Margarita Teran-Garcia, Manabu T. Nakamura, Seung-Hoi Koo, Howard C. Towle and Steven D. Clarke. Involvement of a unique carbohydrate-responsive factor in the glucose regulation of rat liver fatty-acid synthase gene transcription. Journal of Biological Chemistry. 276(24): 21969-75, 2001
  13. Brennon L. O'Callaghan, Seung-Hoi Koo, Yue Wu, Hedley C. Freake and Howard C. Towle. Glucose regulation of the acetyl-CoA carboxylase promoter PI in rat hepatocytes. Journal of Biological Chemistry. 276(19): 16033-9, 2001
  14. Seung-Hoi Koo, Angela K Dutcher and Howard C, Towle. Glucose and insulin function through two distinct transcription factors to stimulate expression of lipogenic enzyme genes in liver. Journal of Biological Chemistry. 276(12): 9437-45, 2001
  15. Seung-Hoi Koo and Howard C. Towle. Glucose regulation of mouse S14 gene expression in hepatocytes: Involvement of a novel transcription factor complex. Journal of Biological Chemistry. 275(7): 5200-7, 2000
  16. Marisa M. Magana, Seung-Hoi Koo, Howard C. Towle and Timothy F. Osborne. Different sterol regulatory element-binding protein-1 isoforms utilize distinct co-regulatory factors to activate the promoter for fatty acid synthase. Journal of Biological Chemistry. 275(7): 4726-33, 2000