| 1. Anti-tumor effects of Vitamin D. Using prostate cancer
as a experimental model to study the mechanisms how vitamin
D exerts its chemopreventive, anti-proliferative, anti-invasive,
and anti-angiogenesis effects.
2. Investigation of the combination of vitamin D
and COX-2 inhibitor therapy in treatment. Development of vitamin D-based
therapy to reduced the vitamin D treatment-mediated adverse
effect, and enhanced the vitamin D efficiency in treatment
of cancer.
3. Aging: Use TR4 knockout mice as a model to study the
aging process, in which accumulation of un-repaired
DNA damages
results in acceleration of aging process. Our study focuses
on how cells response to oxidative stress, stress-induced
DNA damage, and DNA repair to maintain genomic stability
and longevity.
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Collins LL, Lee YF, Heinlein CA, Liu NC, Chen YT, Shyr CR,
Meshul CK, Uno H, Platt KA, Chang C. Growth
retardation and abnormal maternal behavior in mice lacking
testicular orphan
nuclear receptor 4. Proc Natl Acad Sci U S A. 2004 Oct 19;101(42):15058-63.
Epub 2004 Oct 11.
Lee YF, Bao BY, Chang C. Modulation
of the retinoic acid-induced cell apoptosis and differentiation
by the human TR4 orphan
nuclear receptor. Biochem Biophys Res Commun. 2004 Oct 22;323(3):876-83.
Mu X, Lee YF, Liu NC, Chen YT, Kim E, Shyr CR, Chang C.
Targeted
inactivation of testicular nuclear orphan receptor 4 delays
and disrupts late meiotic prophase and subsequent
meiotic divisions of spermatogenesis. Mol Cell Biol. 2004 Jul;24(13):5887-99.
Bao BY, Hu YC, Ting HJ, Lee YF. Androgen
signaling is required for the vitamin D-mediated growth
inhibition in human prostate
cancer cells. Oncogene. 2004 Apr 22;23(19):3350-60.
Kim E, Xie S, Yeh SD, Lee YF, Collins LL, Hu YC, Shyr CR,
Mu XM, Liu NC, Chen YT, Wang PH, Chang C. Disruption
of TR4 orphan nuclear receptor reduces the expression of liver
apolipoprotein
E/C-I/C-II gene cluster. J Biol Chem. 2003 Nov 21;278(47):46919-26.
Epub 2003 Sep 03.
Inui S, Lee YF, Chang E, Shyr CR, Chang C. Differential
and bi-directional regulation between TR2/TR4 orphan nuclear
receptors and a specific ligand mediated-peroxisome proliferator-activated
receptor alpha in human HaCaT keratinocytes. J Dermatol Sci.
2003 Feb;31(1):65-71.
Lin WJ, Li J, Lee YF, Yeh SD, Altuwaijri S, Ou JH, Chang
C. Suppression
of hepatitis B virus core promoter by the nuclear orphan receptor
TR4. J Biol Chem. 2003 Mar 14;278(11):9353-60.
Epub 2003 Jan 08.
Lee YF, Lin WJ, Huang J, Messing EM, Chan FL, Wilding G,
Chang C. Activation
of mitogen-activated protein kinase pathway by the antiandrogen
hydroxyflutamide in androgen receptor-negative
prostate cancer cells. Cancer Res. 2002 Nov 1;62(21):6039-44.
Lee YF, Lee HJ, Chang C. Recent
advances in the TR2 and TR4 orphan receptors of the nuclear
receptor superfamily. J
Steroid Biochem Mol Biol. 2002 Aug;81(4-5):291-308.
Lee HJ, Lee YF, Chang C. TR4
orphan receptor represses the human steroid 21-hydroxylase
gene expression through the
monomeric AGGTCA motif. Biochem Biophys Res Commun. 2001 Aug
3;285(5):1361-8.
Lee YF, Shyr CR, Thin TH, Lin WJ, Chang C. Convergence
of two repressors through heterodimer formation of androgen
receptor and testicular orphan receptor-4: a unique signaling
pathway in the steroid receptor superfamily. Proc Natl Acad
Sci U S A. 1999 Dec 21;96(26):14724-9.
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