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Personal History
- Born and raised through college education in Seoul, South Korea.
- Ph.D. (1987) in Physiology from the SUNY Buffalo on the Fulbright Scholarship.
- After post-doctoral training at the NIH, was Assistant and Associate Professor at the Johns Hopkins School of Medicine.
- Moved to the current position in November 2002.
Research Interests
My research interests are centered around the transcription factor TonEBP. Like other Rel proteins such as NFkB and NFAT, TonEBP is involved in many diseases including tumor metastasis, immunity, and replication of HIV virus.
TonEBP in diesease
Our work showed that TonEBP is involved in a couple of kidney diseases. We are currently focusing on three areas: diabetic nephropathy, blood pressure regulation, and neonatal death. Genetically modified mice and cultured cells are used.
Tonicity Sensor
Tonicity is defined as the effective osmolality relevant to net water movement across the plasma membrane and cell volume. Tonicity is the key signal to TonEBP for its role in lymphatic angiogenesis, T cell development, and renal water homeostasis. We are trying to understand how changes in tonicity regulate TonEBP focusing on three areas: 1. Tonicity sensor within the TonEBP molecule that controls the nuclear trafficking. 2. Tonicity-dependent SUMO modification that inhibits transactivation. 3. Tonicity-dependent acetylation that controls the nuclear export.
Lab Techniques and Equipment
Breeding genetically modified mice, surgical techniques to investigate acute renal injury, tail-cuff procedure for blood pressure, and histological methods are used for animal studies. Contemporary techniques are used for cell culture, cell biological and molecular biological analysis of gene products and post-translational modifications. In my lab, there are 16 sets of metabolic cages, a complete set of equipment for histology, Nikon microscope for fluorescence and differential-interference contrast light microscopy, and Bio-Rad real-time PCR machine.
Current Personnel:
Post-doctoral Fellows:
- Sun Woo Lim
- Soo Youn Choi
- Satoru Sanada
Selected Former Trainees:
- Hiroshi Miyakawa, M.D., 9/94 to 5/98. Assistant Professor of Medicine, Tokyo University and Director of Nephrology, Showa General Hospital, Japan.
- Mohamed Atta, M.D., 7/95 to 6/97. Assistant Professor of Medicine, Johns Hopkins University.
- Ki-Young Na, M.D., Assistant Professor of Medicine, Seoul National University, South Korea.
- Sang Do Lee, Ph.D. Assistant Professor of Physiology, Chungnam National University, South Korea.
Publications
Selected Publications
Miyakawa H, Woo SK, Dahl SC, Handler JS, Kwon HM: Tonicity-responsive enhancer binding protein, a Rel-like protein that stimulates transcription in response to hypertonicity. Proc. Natl. Acad. Sci. USA 96: 2538-2542, 1999.
Woo SK, Dahl SC, Handler JS, Kwon HM: Bi-directional regulation of tonicity-responsive enhancer binding protein in response to changes in tonicity. Am. J. Physiol. Renal Physiol. 278: F1006-F1012, 2000.
Cha JH, Woo SK, Han KH, Kim YH, Handler JS, Kim J, Kwon HM: Hydration status affects nuclear distribution of transcription factor TonEBP in rat kidney. J. Am. Soc. Nephrol. 12: 2221-2230, 2001.
Woo SK, Na KY, Park WK, Kwon HM: TonEBP/NFAT5 stimulates transcription of HSP70 in response to hypertonicity. Mol. Cell. Biol. 22: 5753-5760, 2002.
Na KY, Woo SK, Kwon HM: Silencing of TonEBP/NFAT5 transcriptional activator by RNA interference. J. Am. Soc. Nephrol. 14: 283-288, 2003.
Lee SD, Colla E, Sheen MR, Na KY, Kwon HM: >Multiple domains of TonEBP cooperate to stimulate transcription in response to hypertonicity. J. Biol. Chem. 278: 47571-47577. 2003.
Loyher ML, Mutin M, Woo SK, Kwon HM, Tapaz ML: Transcription factor TonEBP which transactivates osmoprotective genes is expressed and upregulated following acute systemic hypertonicity in neurons in brain. Neuroscience 124: 89-104, 2004.
Colla E, Lee SD, Sheen MR, Woo SK, Kwon HM: TonEBP is inhibited by RNA helicase A via interaction involving the E’F loop. Biochem J 393: 411-419, 2006.
Hasler U, Jeon US, Kim JA, Mordasini D, Kwon HM, Feraille E, Martin P-Y: TonEBP is an essential regulator of aquaporin-2 expression in renal collecting duct principal cells. J. Am. Soc. Nephrol. 17: 1521-1531, 2006.
Yang B, Hodgkinson AD, Oates P, Kwon HM, Millward BA, Demaine AG: Implications of transcription factor tonicity response element binding protein (TonEBP/NFAT5) in the pathogenesis of diabetic nephropathy. Diabetes 55:1450-1455, 2006.
Lim SW, Ahn KO, Sheen MR, Jeon US, Kim J, Yang CW, Kwon HM. Downregulation of renal sodium transporters and tonicity-responsive enhancer binding protein by long-term treatment with cyclosporin A. J. Am. Soc. Nephrol. 18: 421-429, 2007.
Jeon US, Han K-H, Park SH, Lee SD, Sheen MR, Jung J-Y, Kim WY, Sands JM, Kwon HM. Downregulation of renal TonEBP in hypokalemic rats. Am. J. Physiol. Renal Physiol. 293: F408-F415, 2007.
Dagan A, Kwon HM, Dwarakanath V, Baum M. Effect of renal denervation on prenatal programming of hypertension and renal tubular transporter abundance. Am J Physiol Renal Physiol 295: F29-F34, 2008.
Navarro P, Chiong M, Volkwein K, Moraga F, Ocaranza MP, Jalil JE, Lim SW, Kim JA, Kwon HM*, Lavandero S*. Osmotically-induced genes are controlled by the transcription factor TonEBP in cultured cardiomyocytes. Biochem Biophys Res Comm 372: 326-330, 2008. (*shared corresponding authorship) PMCID: PMC2522383
Kwon MS, Lee SD, Kim JA, Colla E, Choi YJ, Suh PG, Kwon HM. Novel nuclear localization signal regulated by ambient tonicity in vertebrates. J Biol Chem 283: 22400-22409, 2008. PMCID: PMC2504888
Kim JA, Sheen MR, Lee SD, JY Jung, Kwon HM. Hypertonicity stimulate PGE2 signaling in the renal medulla by promoting expression of its receptors EP3 and EP4. Kidney International 75(3): 278-284, 2009.
Sheen MR, Kim JA, Lim SW, Jung J-Y, Han K-H, Jeon US, Park S-H, Kim J, Kwon HM. Interstitial tonicity controls TonEBP expression in the renal medulla. Kidney International 75: 518-525, 2009. (selected for Faculty of 1000 Biology)
Kwon MS, Lim SW, Kwon HM. Hypertonic stress in the kidney: A necessary evil. Physiology 24: 186-191, 2009.