Hyekyung Cho Plumley, Ph.D.
Drug Discovery Scientist II
B.S. Sungshin University, Seoul, Korea, 1993
Ph.D. University of Texas at Austin, 2000
Phone: (615) 322-6730
Fax: (615) 343-3088
Email: hyekyung.c.plumley@vanderbilt.edu
Location: 1215 Light Hall
Biosketch and Research Interests
Hyekyung earned her doctoral degree from the University of Texas at Austin under Dr.Steven D. Clarke in the area of glucose and lipid metabolism. Her research focused on the molecular characterization of polyunsaturated fatty acid biosynthesis that plays an important role in inhibiting lipogenesis and stimulating lipolysis. She cloned the first mammalian cDNAs for delta-6 and delta-5 desaturases, the rate-limiting enzymes for de novo synthesis of n-6 and n-3 series of polyunsaturated fatty acids, respectively. Utilizing the cDNA and genomic sequences, she first demonstrated the transcriptional regulation of delta-6 and delta-5 desaturase gene expression by PPAR-alpha activators and by their downstream products, arachidonic and docosahexaenoic acids, as a feedback control. Her work further led to identification and characterization of the regulatory elements in the promoter regions of delta-6 and delta-5 desaturase genes.
In 2000, She began her postdoctoral training in the Biochemistry department at Vanderbilt University where she studied the regulation of retinoic acid synthesis in breast cancer cells and investigated the effect of retinoic acid on gene expression using microarray technique. In 2002, she moved to east Tennessee and obtained cell cycle regulation and cell biology training under Dr.Yisong Wang at Functional Genomics group at Oak Ridge National laboratory. Her research focused on identification of a novel function of mammalian Cdc14B dual-specificity phosphatase in cell cycle regulation. She demonstrated that Cdc14B is a microtubule-stabilizing and bundling protein and it may regulate cell cycle by monitoring proper bipolar spindle formation and progression from anaphse through early G1 phase. Using the siRNA and inducible-shRNA expression systems, she also showed Cdc14B plays an essential role in controlling centrosome duplication cycle. Depletion of Cdc14B leads to centrosome over duplication and its overexpression prevents unscheduled centrosome hyperamplification. Since centrosome overduplication is observed in almost all types of cancer cells and it leads to aneuploidy, a hallmark of cancer, her work discovered Cdc14B as a novel tumor suppressor protein. In 2006, she came back to Vanderbilt University as a staff scientist and worked under Dr. H. Alex Brown. She investigated the GPCR- and EGFR-mediated activation of phospholipase D signaling pathway and generated a series of stable HEK293 cell lines including muscarinic 1 and EGF receptors and tetracycline-inducible systems for cDNA and shRNA expression. She was also involved in characterization of novel phospholipase D inhibitors in breast cancer cell invasion and in EGFR/mTOR signaling pathway.
She joined the Drug Discovery Program in 2009 to investigate the molecular mechanism of how modulation of muscarinic acetylcholine receptor can affect amyloid precursor protein (APP) processing in Alzheimer disease. In part of screening the subtype-selective allosteric modulators developed and synthesized by the medicinal chemists here, currently she generates stable cell lines expressing each muscarinic receptor isoform and APP protein in neuronal cells.
Selected Publications
Zeng, X-X; Zheng, X; Xiang, Y; Cho, HP; Jessen, JR; Zhong, TP; Solnica-Krezel, L; Brown, HA. Phospholipase D1 is required for angiogenesis of intersegmental blood vessels in zebrafish. Developmental Biology. in press
Scott, SA; Selvy, PE; Buck, JR; Cho, HP; Criswell, TL; Thomas, AL; Armstrong, MD; Arteaga, CL; Lindsley, CW and Brown, HA. Design of isoform-selective phospholipase D inhibitors that modulate cancer cell invasiveness. Nat Chem Biol, 2009, 5: 108-17.
Wu, J; Cho, HP (co-first author); Rhee, DB; Johnson, DK; Dunlap, J; Liu, Y; and Wang, Y. Cdc14B depletion leads to centriole amplification, and its overexpression prevents unscheduled centriole duplication. J. Cell Biol. 2008; 181: 475 - 483.
Dreesen, TD; Adamson, AW; Tekle, M; Tang, C; Cho, HP; Clarke, SD, and Gettys, TW. A newly discovered member of the fatty acid desaturase gene family: a non-coding, antisense RNA gene to delta5-desaturase. Prostaglandins Leukot Essent Fatty Acids, 2006; 75: 97-106.
Cho, HP; Liu, Y; Gomez, M; Dunlap, J; Tyers, M, and Wang, Y. The Dual-Specificity Phosphatase CDC14B Bundles and Stabilizes Microtubules. Mol. Cell. Biol., 2005; 25: 4541 - 4551.
Tang, C; Cho, HP (co-first author); Nakamura, MT, and Clarke, SD. Regulation of human delta-6 desaturase gene transcription: identification of a functional direct repeat-1 element. J. Lipid Res., 2003; 44: 686-695.
Cho, HP; Nakamura, MT, and Clarke, SD. Cloning, Expression, and Fatty Acid Regulation of the Human delta-5 Desaturase. J. Biol. Chem., 1999; 274: 37335-37339.
Cho, HP; Nakamura, MT, and Clarke, SD. Cloning, Expression, and Nutritional Regulation of the Mammalian delta-6 Desaturase. J. Biol. Chem., 1999; 274: 471-477.
