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National Yang-Ming University, Department & Institute of Physiology
National Yang-Ming University, Department & Institute of Physiology
Jiuan-Jiuan Hwang

Research Field    Publications    Research grant    Lab intro    (2016.03.10  update)

Name Jiuan-Jiuan Hwang  

Position Professor
Tel. 886-2-2826-7087
Fax No. 886-2-2826-4049




Department of Physiology & Biophysics, University of Illinois, Urbana-Champaign, Illinois, USA



Department of Physiology & Biophysics, University of Illinois



Department of Zoology, National Taiwan University, Taipei, Taiwan


Research Associate, Department of Environmental Health Sciences, Case Western Reserve University, Cleveland, Ohio, USA (1990-1992)

Chairman, Institute of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan (2005/8-2006/7) 

Research Interests:

Q1. How ovarian follicle-granulosa cells develop to cope with the mission to promote oocyte maturation and ovulation?

1st fundamental issue: Steroidogenesis

  •  Regulation of steroidogenesis per se
  •  Regulation of cholesterol availability
  •  Regulation of mitochondrial function
  •  Regulation of cellular metabolism

2nd fundamental issue: Antral follicle growth - survival & ovulation

  •  Regulation of gap junction formation & function
  •  Regulation of angiogenesis
  •  Regulation of ovulation – matrix remodeling


Q2.  How tumor/cancer cells manage to evade the original niche, and migrate-invade to other niches?

  •  Metastasis – matrix remodeling
  •  Epithelial-mesenchymal transition (EMT) process
  •  Flavonoid effects


Publications(*,corresponding author):

Reproductive Endocrinology - Ovarian cell physiological functions & Metabolism

  1. Fang W-L, Lai S-Y, Lai W-A, Lee M-T, Liao C-F, Ke F-C, Hwang J-J*. (2015) CRTC2 and Nedd4 ligase involvement in FSH and TGFb1 upregulation of connexin43 gap junction. J Mol Endocrinol 55:263–275. [Corresponding author]
  2. Lai W-A, Yeh Y-T,Fang W-L,Wu L-S,Harada N,Wang P-H,ke F-C,Lee W-L,Hwang J-J* . (2014) Calcineurin and CRTC2 mediate FSH and TGFβ1 upregulation of Cyp19a1 and Nr5a in ovary granulosa cell. J Mol Endocrinol 53:259-270. [Corresponding author]
  3. Lai W-A, Yeh Y-T, Lee M-T, Wu L-S, Ke F-C, Hwang J-J*. (2013) Ovarian granulosa cells utilize scavenger receptor SR-BI to evade cholesterol homeostatic control for steroid synthesis. J Lipid Res 54:365-378. [Corresponding author]
  4. Fang W-L, Lee M-T, Wu L-S, Chen Y-J, Mason JI, Ke F-C, Hwang J-J*. (2012) CREB coactivator CRTC2/TORC2 and its regulator calcineurin crucially mediate follicle-stimulating hormone and transforming growth factor b1 upregulation of steroidogenesis. J Cell Physiol 227: 2430–2440. [Corresponding author]
  5. Kuo S-W, Ke F-C, Chang G-D, Lee M-T, Hwang J-J*. (2011) Potential role of follicle-stimulating hormone (FSH) and transforming growth factor (TGFb1) in the regulation of ovarian angiogenesis. J Cell Physiol 226:1608-1619. [Corresponding author]
  6. Chen Y-J, Lee M-T, Yao H-C, Hsiao P-W, Ke F-C, Hwang J-J*. (2008) Crucial role of estrogen receptor-a interaction with transcription coregulators in FSH and TGFb1 upregulation of steroidogenesis in rat ovarian granulosa cells. Endocrinology 149:4658-4668. [Corresponding author]
  7. Chen Y-J, Hsiao P-W, Lee M-T, Mason JI, Ke F-C, Hwang J-J*. (2007) Interplay of PI3K and cAMP/PKA signaling, and rapamycin-hypersensitivity in TGFb1 enhancement of FSH-stimulated steroidogenesis in rat ovarian granulosa cells. J Endocrinol 192:405-419. [Corresponding author]
  8. Ke F-C, fang S-H, Lee M-T, Sheu S-Y, Lai S-Y, Chen YJ, Huang F-L, Wang PS, Stocco DM, Hwang J-J*. (2005) Lindane, a gap junction blocker, suppresses FSH and transforming growth factor b1-induced connexin43 gap junction formation and steroidogenesis in rat granulosa cells. J Endocrinol 184:555-566. [Corresponding author]
  9. Ke F-C, Chuang L-C, Lee M-T, Chen Y-J, Lin S-W, Wang PS, Stocco DM, Hwang J-J*. (2004) The modulatory role of transforming growth factor b1 and androstenedione on follicle-stimulating hormone-induced gelatinase secretion and steroidogenesis in rat granulosa cells. Biol Reprod 70:1292-1298. [Corresponding author]


Cellular senescence & Metabolism

  1. Liao G-Y, Lee M-T, Fan J-J, Hsiao P-W, Lee C-S, Su S-Y, Hwang J-J*, Ke F-C*. (2019) Blockage of glutamine-dependent anaplerosis affects mTORC1/2 activity and ultimately leads to cellular senescence-like response. Biol Open 8: bio038257. [Corresponding author]

Cancer Biology

  1. Tsai C-H, Tzeng S-F, Chao T-K, Tsai C-Y, Yang Y-C, Lee M-T, Hwang J-J, Chou Y-C, Tsai M-H, Cha T-L, Hsiao P-W*. (2016) Metastatic progression of prostate cancer is mediated by autonomous binding of galectin-4-O-glycan to cancer cells. Cancer Res 76:5756-5767.

  2. Tsai P-H, Cheng C-H, Lin C-Y, Huang Y-T, Lee L-T, Kandaswami CC, Lin Y-C, Lee K-P, Hung C-C, Hwang J-J, Ke F-C, Chang G-D, Lee M-T*. (2016) Properties and metastatic potential of isolated prostate cancer cells. Anticancer Res 36:6367-6380.

  3. Lin Y-C, Tsai P-H, Lin C-Y, Cheng C-H, Lin T-H, Lee K-P, Huang K-Y, Chen S-H, Hwang J-J, Kandaswami CC, Lee M-T*. (2013) Impact of flavonoids on matrix metalloproteinase secretion and invadopodia formation in highly invasive A431-III cancer cells. PLoS ONE 8:e71903.

  4. Lin C-Y, Tsai P-H, Kandaswami CC, Chang G-D, Cheng C-H, Huang C-J, Lee P-P, Hwang J-J*, Lee M-T*. (2011) Role of tissue transglutaminase 2 in the acquisition of a mesenchymal-like phenotype in highly invasive A431 tumor cells. Mol Cancer 10:87. [Co-corresponding author]
  5. Lin Y-S, Tsai P-H, Kandaswami CC, Cheng C-H, Ke F-C, Lee P-P, Hwang J-J*, Lee M-T*. (2011) Effects of dietary flavonoids, luteolin, and quercetin on the reversal of epithelial-mesenchymal transition in A431 epidermal cancer cells. Cancer Sci 102: 1829–1839. [Co-corresponding author]
  6. Lin C-Y, Tsai P-H, Kandaswami CC, Lee P-P, Huang C-J, Hwang J-J*, Lee M-T*. (2011) Matrix metalloproteinase-9 cooperates with transcription factor Snail to induce epithelial-mesenchymal transition. Cancer Sci 102:815-827. [Co-corresponding author]
  7. Chen S-H, Lin C-Y, Lee L-T, Chang G-D, Lee P-P, Hung C-C, Kao W-T, Tsai P-H, Schally AV, Hwang J-J*, Lee M-T*. (2010) Upregulation of fibronectin and tissue transglutaminase promotes cell invasion involving increased association with integrin and MMP expression in A431 cells. Anticancer Res 30: 4177-4186. [Co-corresponding author]
  8. Kao W-T, Lin C-Y, Lee L-T, Lee P-P, Hung C-C, Lin Y-S, Chen S-H, Ke F-C, Hwang J-J, Lee M-T*. (2008) Investigation of MMP-2 and MMP-9 in a highly invasive A431 tumor cell sub-line selected from a boyden chamber assay. Anticancer Res 28:2109-2120.
  9. Lin S-W, Ke F-C, Hsiao P-W, Lee P-P, Lee M-T, Hwang J-J*. (2007) Critical involvement of ILK in TGFβ1-stimulated invasion/migration of human ovarian cancer cells is associated with urokinase plasminogen activator system. Exp Cell Res 313:602-613. [Corresponding author]
  10. Kanadaswami C, Lee L-T, Lee P-PH, Hwang J-J, Ke F-C, Huang Y-T, Lee M-T*. (2005) The antitumor activities of flavonoids. In Vivo 19:895-910. (review)
  11. Lee L-T, Huang Y-T, Hwang J-J, Lee AYL, Ke F-C, Huang CJ, Kanadaswami C, Lee HP-P, Lee M-T*. (2004) Transactivation of EGFR tyrosine kinase by the dietary flavonoids decreases focal adhesion kinase phosphorylation and inhibits invasive potential of human carcinoma cells. Biochem Pharmacol 67:2103-2114.
  12. Huang Y-T, Hwang J-J, Lee L-T, Liebow C, Lee P-PH, Ke F-C, Lo T-B, Schally AV, Lee M-T*. (2002) Inhibitory effects of a luteinizing hormone-releasing hormone agonist on basal and epidermal growth factor-induced cell proliferation and metastasis-associated properties in human epidermoid carcinoma A431 cells. Int J Cancer 99:505-513.
  13. Lee L-T, Huang Y-T, Hwang J-J, Lee P-P, Ke F-C, Nair MP, Kanadaswami C, Lee M-T*. (2002) Blockade of the epidermal growth factor receptor tyrosine kinase activity by quercetin and luteolin leads to growth inhibition and apoptosis of pancreatic tumor cells. Anticancer Res 22:1615-1628.
  14. Lin S-W, Lee M-T, Ke F-C, Lee H P-P, Huang C-J, Ip MM, Chen L, Hwang J-J*. (2001) TGFb1 stimulates the secretion of matrix metalloproteinase 2 (MMP2) and the invasive behavior in human ovarian cancer cells, which is suppressed by MMP inhibitor BB3103. Clin Exp Metastat 18:493-499. [Corresponding author]
  15. Huang Y-T, Hwang J-J, Lee P-P, Ke F-C, Huang J-H, Huang C-J, Kandaswami C, Middleton Jr E, Lee M-T*. (1999) Effects of luteolin and quercetin, inhibitors of tyrosine kinase, on cell growth and metastasis-associated properties in A431 cells overexpressing epidermal growth factor receptor. Br J Pharmacol 128:999-1010.

Reproductive Endocrinology - Relaxin hormone in reproductive system

  1. Teng C-H, Ke F-C, Lee M-T, Lin S-W, Chen L, Hwang J-J*. (2000) Pituitary adenylate cyclase activating polypeptide acts synergistically with relaxin in modulating ovarian cell function in rats. J Endocrinol 167:63-71. [Corresponding author]
  2. Hwang J-J*, Lin S-W, Teng C-H, Ke F-C, Lee M-T. (1996) Relaxin modulates the ovulatory process and increases secretion of different gelatinases from granulosa and theca-interstitial cells in rats. Biol Reprod 55:1276-1283. [First & Corresponding author]
  3. Hwang J-J, Macinga D, Rorke EA*. (1996) Relaxin modulates human cervical stromal cell activity. J Clin Endocrinol Metab 81:3379-3384.
  4. Lee AB, Hwang J-J, Haab LM, Fields PA, Sherwood OD*. (1992) Monoclonal antibodies specific for rat relaxin VI. Passive immunization with monoclonal antibodies throughout the second half of pregnancy disrupts histological changes associated with cervical softening at parturition in rats. Endocrinology 130:2386-2391.
  5. Fields PA, Lee AB, Haab LM, Hwang J-J, Sherwood OD*. (1992) Evidence for a dual source of relaxin in the pregnant rat: Immunolocalization in the corpora lutea and endometrium. Endocrinology 130:2985-2990, 1992.
  6. Hwang J-J, Lee AB, Fields PA, Mojonnier LE and Sherwood OD*. (1991) Monoclonal Antibodies Specific for Rat Relaxin. V. Passive immunization with monoclonal antibodies throughout the second half of pregnancy disrupts development of the mammary apparatus and, hence, lactational performance in rats. Endocrinology 129:3034-3042.
  7. Hwang J-J, Shanks RD, Sherwood OD*. (1989) Monoclonal antibodies specific for rat relaxin. IV. Passive immunization with monoclonal antibodies during the antepartum period reduces cervical growth and extensibility, disrupts birth, and reduces pup survival in intact rats. Endocrinology 125:260-266.
  8. Hwang J-J, Sherwood OD*. (1988) Monoclonal antibodies specific for rat relaxin. III. Passive immunization with monoclonal antibodies throughout the second half of pregnancy reduces cervical growth and extensibility in intact rats. Endocrinology 123:2486-2490.
  9. Sherwood OD*, Downing SJ, Lao Guico-Lamm M, Hwang J-J, O'Day-Bowman MB, Fields PA. (1993) The physiological effects of relaxin during pregnancy: studies in rats and pigs. In: Milligan SR (ed) Oxford Reviews of Reproductive Biology. Oxford University Press, Oxford, vol 15, pp 143-189.
  10. Sherwood OD*, Downing SJ, Lao Guico-Lamm M, Hwang J-J. (1990) Relaxin promotes diverse physiological processes in the pregnant rat. In: Garfield RE (ed) Uterine Contractility, Mechanisms of Control. Serono Symposia, USA, pp 237-252.

Reproductive Endocrinology - International collaborative work

  1. Lee P-P, Hwang J-J, Murphy G, Ip MM*. (2001) The functional role of matrix metalloproteinases (MMPs) in mammary epithelial cell development. J Cell Physiol 188:75-88.
  2. Lee P-P, Hwang J-J, Ip MM*. (2000) Functional significance of MMP-9 in tumor necrosis factor-induced proliferation and branching morphogenesis of mammary epithelial cells. Endocrinology 141:3764-3773.

Reproductive Endocrinology - Domestic collaborative work

  1. Tsai S-C, Lu C-C, Chen J-J, Chiao Y-C, Wang S-W, Hwang J-J, Wang PS*. (1999) Inhibition of salmon calcitonin on secretion of progesterone and GnRH-stimulated pituitary luteinizing hormone. Am J Physiol 277:E49-E55.
  2. Wang S-W, Lin H, Hwang J-J, Wang PS*. (1999) Inhibition of testosterone secretion by digitoxin in rat testicular interstitial cells. J Cell Biochem 74:74-80.
  3. Chiao Y-C, Lee H-Y, Wang S-W, Hwang J-J, Chien C-H, Huang S-W, Lu C-C, Chen J-J, Tsai S-C, Wang PS*. (1999) Regulation of thyroid hormones on the production of testosterone in rats. J Cell Biochem 73:554-562.

Methodology - Biochemical analysis of steroid hormones

Huang F-L*, Ke F-C, Hwang J-J, Lo T-B. (1983) High-pressure liquid chromatographic separation of a mixture of corticosteroids, androgens, and progestins. Arch Biochem Biophys 225:512-517.

Research grant: 


Lab membership:

Master Student: Tsung-Ta Tsai, Ting-Chieh I, Liang-Yu Chen

Post-doctor: Geng-You Liao

Graduate Associate: Wei-Ling Fang, Wei-Yu Chen


2016 Lab gathering party 2015 Lab gathering party
2014 Lab gathering party 2013 Lab gathering party 
2013 Lab gathering party 2008 Lab membership
2006 year-end dinner party 2005 year-end dinner party


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