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Yi-Fen Lee

TitleAssociate Professor
InstitutionSchool of Medicine and Dentistry
DepartmentUrology
AddressUniversity of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 656
Rochester NY 14642
Other Positions
TitleAssociate Professor
InstitutionSchool of Medicine and Dentistry
DepartmentPathology and Laboratory Medicine

 
 Awards And Honors
      New York Academy of Medicine Edwin Beer Fellowship Award 2003-2005
      Third Prize, Cap CURE Award 2002 AUA
 
 Overview
My research focuses on elucidating two nuclear receptors (NRs), vitamin D receptor (VDR) and Testicular receptor 4 (TR4) and their ligand-induced signals for their impacts on the prostate, bladder cancer, and other hormone-related diseases by utilizing biochemical/molecular approaches and genetically engineered animal models.
In the vitamin D projects, we focus on two areas. (1) The first is the chemotherapy and chemopreventive effects of vitamin D on urologically-related cancers, including prostate cancer and bladder cancer. We applied molecular approaches and cell and mice carcinogenesis models to study the underlying molecular mechanisms by which vitamin D/VDR inhibits prostate and bladder carcinogenesis. (2) The second is investigating the impacts of the vitamin D/VDR signal to the response of non-muscle invading bladder cancer to intravesical Bacillus Calmette-Guerin (BCG) immunotherapy in experimental models. In order to dissect VDR in different cellular compartments to mediate anti-tumor activity as well as immune response, tissue-specific VDR knockout mice are being established in my laboratory.
TR4 belongs to the NR superfamily that controls a broad range of biologic programs. Via knockout mice studies, we discover TR4 roles in anti-aging and anti-prostate cancer which reinforce the strong correlation between aging and prostate cancer for which peak incidence and mortality rates occur in the older population. Dysfunction of TR4, including gene mutations and abnormal nucleocytoplasmic translocation found in human prostate cancer compromises TR4 protective effects, thereby promoting cancer. Many directions, such as identifying the upstream modulators, dissecting the TR4-mediated signaling pathways, and analyzing TR4 gene/protein profile from cancer patients are ongoing. Our ultimate goal is to design preventive and/or therapeutic approaches that exploit the responsible factors or pathways to stop or slow down prostate cancer progression, as well as to retard other aging-related diseases.

 
 Selected Publications
List All   |   Timeline
  1. Ting HJ, Messing J, Yasmin-Karim S, Lee YF. Identification of microRNA-98 as a therapeutic target inhibiting prostate cancer growth and a biomarker induced by vitamin D. J Biol Chem. 2013 Jan 4; 288(1):1-9.
    View in: PubMed
  2. Lin SJ, Ho HC, Lee YF, Liu NC, Liu S, Li G, Shyr CR, Chang C. Reduced osteoblast activity in the mice lacking TR4 nuclear receptor leads to osteoporosis. Reprod Biol Endocrinol. 2012; 10:43.
    View in: PubMed
  3. Yan SJ, Lee YF, Ting HJ, Liu NC, Liu S, Lin SJ, Yeh SD, Li G, Chang C. Deficiency in TR4 nuclear receptor abrogates Gadd45a expression and increases cytotoxicity induced by ionizing radiation. Cell Mol Biol Lett. 2012 Jun; 17(2):309-22.
    View in: PubMed
  4. Ting HJ, Yasmin-Karim S, Yan SJ, Hsu JW, Lin TH, Zeng W, Messing J, Sheu TJ, Bao BY, Li WX, Messing E, Lee YF. A positive feedback signaling loop between ATM and the vitamin D receptor is critical for cancer chemoprevention by vitamin D. Cancer Res. 2012 Feb 15; 72(4):958-68.
    View in: PubMed
  5. Collins LL, Lee YF, Ting HJ, Lin WJ, Liu NC, Meshul CK, Uno H, Bao BY, Chen YT, Chang C. The roles of testicular nuclear receptor 4 (TR4) in male fertility-priapism and sexual behavior defects in TR4 knockout mice. Reprod Biol Endocrinol. 2011; 9:138.
    View in: PubMed
  6. Liu S, Yan SJ, Lee YF, Liu NC, Ting HJ, Li G, Wu Q, Chen LM, Chang C. Testicular nuclear receptor 4 (TR4) regulates UV light-induced responses via Cockayne syndrome B protein-mediated transcription-coupled DNA repair. J Biol Chem. 2011 Nov 4; 286(44):38103-8.
    View in: PubMed
  7. Liu S, Lee YF, Chou S, Uno H, Li G, Brookes P, Massett MP, Wu Q, Chen LM, Chang C. Mice lacking TR4 nuclear receptor develop mitochondrial myopathy with deficiency in complex I. Mol Endocrinol. 2011 Aug; 25(8):1301-10.
    View in: PubMed
  8. Lee YF, Liu S, Liu NC, Wang RS, Chen LM, Lin WJ, Ting HJ, Ho HC, Li G, Puzas EJ, Wu Q, Chang C. Premature aging with impaired oxidative stress defense in mice lacking TR4. Am J Physiol Endocrinol Metab. 2011 Jul; 301(1):E91-8.
    View in: PubMed
  9. Xie S, Ni J, Lee YF, Liu S, Li G, Shyr CR, Chang C. Increased acetylation in the DNA-binding domain of TR4 nuclear receptor by the coregulator ARA55 leads to suppression of TR4 transactivation. J Biol Chem. 2011 Jun 17; 286(24):21129-36.
    View in: PubMed
  10. Kim E, Liu NC, Yu IC, Lin HY, Lee YF, Sparks JD, Chen LM, Chang C. Metformin inhibits nuclear receptor TR4-mediated hepatic stearoyl-CoA desaturase 1 gene expression with altered insulin sensitivity. Diabetes. 2011 May; 60(5):1493-503.
    View in: PubMed
  11. Hsu JW, Yasmin-Karim S, King MR, Wojciechowski JC, Mickelsen D, Blair ML, Ting HJ, Ma WL, Lee YF. Suppression of prostate cancer cell rolling and adhesion to endothelium by 1a,25-dihydroxyvitamin D3. Am J Pathol. 2011 Feb; 178(2):872-80.
    View in: PubMed
  12. Bao BY, Ting HJ, Hsu JW, Yasmin-Karim S, Messing E, Lee YF. Down-regulation of NF-kappaB signals is involved in loss of 1alpha,25-dihydroxyvitamin D3 responsiveness. J Steroid Biochem Mol Biol. 2010 May; 120(1):11-21.
    View in: PubMed
  13. Xie S, Lee YF, Kim E, Chen LM, Ni J, Fang LY, Liu S, Lin SJ, Abe J, Berk B, Ho FM, Chang C. TR4 nuclear receptor functions as a fatty acid sensor to modulate CD36 expression and foam cell formation. Proc Natl Acad Sci U S A. 2009 Aug 11; 106(32):13353-8.
    View in: PubMed
  14. Liu NC, Lin WJ, Yu IC, Lin HY, Liu S, Lee YF, Chang C. Activation of TR4 orphan nuclear receptor gene promoter by cAMP/PKA and C/EBP signaling. Endocrine. 2009 Oct; 36(2):211-7.
    View in: PubMed
  15. Cai Y, Lee YF, Li G, Liu S, Bao BY, Huang J, Hsu CL, Chang C. A new prostate cancer therapeutic approach: combination of androgen ablation with COX-2 inhibitor. Int J Cancer. 2008 Jul 1; 123(1):195-201.
    View in: PubMed
  16. Bao BY, Ting HJ, Hsu JW, Lee YF. Protective role of 1 alpha, 25-dihydroxyvitamin D3 against oxidative stress in nonmalignant human prostate epithelial cells. Int J Cancer. 2008 Jun 15; 122(12):2699-706.
    View in: PubMed
  17. Li G, Lee YF, Liu S, Cai Y, Xie S, Liu NC, Bao BY, Chen Z, Chang C. Oxidative stress stimulates testicular orphan receptor 4 through forkhead transcription factor forkhead box O3a. Endocrinology. 2008 Jul; 149(7):3490-9.
    View in: PubMed
  18. Chen LM, Wang RS, Lee YF, Liu NC, Chang YJ, Wu CC, Xie S, Hung YC, Chang C. Subfertility with defective folliculogenesis in female mice lacking testicular orphan nuclear receptor 4. Mol Endocrinol. 2008 Apr; 22(4):858-67.
    View in: PubMed
  19. Liu NC, Lin WJ, Kim E, Collins LL, Lin HY, Yu IC, Sparks JD, Chen LM, Lee YF, Chang C. Loss of TR4 orphan nuclear receptor reduces phosphoenolpyruvate carboxykinase-mediated gluconeogenesis. Diabetes. 2007 Dec; 56(12):2901-9.
    View in: PubMed
  20. Ting HJ, Bao BY, Reeder JE, Messing EM, Lee YF. Increased expression of corepressors in aggressive androgen-independent prostate cancer cells results in loss of 1alpha,25-dihydroxyvitamin D3 responsiveness. Mol Cancer Res. 2007 Sep; 5(9):967-80.
    View in: PubMed
  21. Zhang Y, Chen YT, Xie S, Wang L, Lee YF, Chang SS, Chang C. Loss of testicular orphan receptor 4 impairs normal myelination in mouse forebrain. Mol Endocrinol. 2007 Apr; 21(4):908-20.
    View in: PubMed
  22. Chen TC, Persons KS, Zheng S, Mathieu J, Holick MF, Lee YF, Bao B, Arai MA, Kittaka A. Evaluation of C-2-substituted 19-nor-1alpha,25-dihydroxyvitamin D3 analogs as therapeutic agents for prostate cancer. J Steroid Biochem Mol Biol. 2007 Mar; 103(3-5):717-20.
    View in: PubMed
  23. Wang CP, Lee YF, Chang C, Lee HJ. Transactivation of the proximal promoter of human oxytocin gene by TR4 orphan receptor. Biochem Biophys Res Commun. 2006 Dec 8; 351(1):204-8.
    View in: PubMed
  24. Ting HJ, Hsu J, Bao BY, Lee YF. Docetaxel-induced growth inhibition and apoptosis in androgen independent prostate cancer cells are enhanced by 1alpha,25-dihydroxyvitamin D3. Cancer Lett. 2007 Mar 8; 247(1):122-9.
    View in: PubMed
  25. Bao BY, Yao J, Lee YF. 1alpha, 25-dihydroxyvitamin D3 suppresses interleukin-8-mediated prostate cancer cell angiogenesis. Carcinogenesis. 2006 Sep; 27(9):1883-93.
    View in: PubMed
  26. Bao BY, Yeh SD, Lee YF. 1alpha,25-dihydroxyvitamin D3 inhibits prostate cancer cell invasion via modulation of selective proteases. Carcinogenesis. 2006 Jan; 27(1):32-42.
    View in: PubMed
  27. Ting HJ, Bao BY, Hsu CL, Lee YF. Androgen-receptor coregulators mediate the suppressive effect of androgen signals on vitamin D receptor activity. Endocrine. 2005 Feb; 26(1):1-9.
    View in: PubMed
  28. Chuang KH, Lee YF, Lin WJ, Chu CY, Altuwaijri S, Wan YJ, Chang C. 9-cis-retinoic acid inhibits androgen receptor activity through activation of retinoid X receptor. Mol Endocrinol. 2005 May; 19(5):1200-12.
    View in: PubMed
  29. 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.
    View in: PubMed
  30. Lee YF, John M, Falconer A, Edwards S, Clark J, Flohr P, Roe T, Wang R, Shipley J, Grimer RJ, Mangham DC, Thomas JM, Fisher C, Judson I, Cooper CS. A gene expression signature associated with metastatic outcome in human leiomyosarcomas. Cancer Res. 2004 Oct 15; 64(20):7201-4.
    View in: PubMed
  31. 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.
    View in: PubMed
  32. Chen HH, Lee YF, Chan MH, Lo PS. The role of N-methyl-D-aspartate receptors in neurobehavioral changes induced by toluene exposure during synaptogenesis. Ann N Y Acad Sci. 2004 Oct; 1025:552-5.
    View in: PubMed
  33. 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.
    View in: PubMed
  34. 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.
    View in: PubMed
  35. 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.
    View in: PubMed
  36. 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.
    View in: PubMed
  37. 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.
    View in: PubMed
  38. 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.
    View in: PubMed
  39. 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.
    View in: PubMed
  40. 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.
    View in: PubMed
  41. 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.
    View in: PubMed
  42. Lee YF, Young WJ, Lin WJ, Shyr CR, Chang C. Differential regulation of direct repeat 3 vitamin D3 and direct repeat 4 thyroid hormone signaling pathways by the human TR4 orphan receptor. J Biol Chem. 1999 Jun 4; 274(23):16198-205.
    View in: PubMed
  43. Lee HJ, Lee YF, Chang C. Identification of the histamine H1 receptor gene as a differentially repressed target of the human TR2 orphan receptor. Mol Cell Biochem. 1999 Apr; 194(1-2):199-207.
    View in: PubMed
  44. Inui S, Lee YF, Haake AR, Goldsmith LA, Chang C. Induction of TR4 orphan receptor by retinoic acid in human HaCaT keratinocytes. J Invest Dermatol. 1999 Apr; 112(4):426-31.
    View in: PubMed
  45. Young WJ, Lee YF, Smith SM, Chang C. A bidirectional regulation between the TR2/TR4 orphan receptors (TR2/TR4) and the ciliary neurotrophic factor (CNTF) signaling pathway. J Biol Chem. 1998 Aug 14; 273(33):20877-85.
    View in: PubMed
  46. Lee YF, Young WJ, Burbach JP, Chang C. Negative feedback control of the retinoid-retinoic acid/retinoid X receptor pathway by the human TR4 orphan receptor, a member of the steroid receptor superfamily. J Biol Chem. 1998 May 29; 273(22):13437-43.
    View in: PubMed
  47. Chang C, Lee HJ, Lee YF. Identification of the human aldolase A gene as the first induced target for the TR2 orphan receptor, a member of the steroid hormone receptor superfamily. Biochem Biophys Res Commun. 1997 Jun 9; 235(1):205-11.
    View in: PubMed
  48. Lee YF, Pan HJ, Burbach JP, Morkin E, Chang C. Identification of direct repeat 4 as a positive regulatory element for the human TR4 orphan receptor. A modulator for the thyroid hormone target genes. J Biol Chem. 1997 May 2; 272(18):12215-20.
    View in: PubMed

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