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Yi-Fen Lee, Ph.D.

Yi-Fen Lee, Ph.D.

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About Me

My lab is studying extracellular vesicles (EVs), often called exosomes, for their roles in cancer development, progression and response to treatment, with a focus on Urology cancers such as bladder and prostate cancers.

This is a relatively new and exciting area of research: small vesicles, i...
My lab is studying extracellular vesicles (EVs), often called exosomes, for their roles in cancer development, progression and response to treatment, with a focus on Urology cancers such as bladder and prostate cancers.

This is a relatively new and exciting area of research: small vesicles, in size ranging from 30-250 nm, are secreted by almost all types of cells and contain bio-information (such as DNA, RNA and proteins) resembling the cells of origins. They travel distances via circulation, and can be taken up by recipient cells, consequently affecting their behavior. The genetic and molecular contents of EVs can become an attractive resource of biomarkers for prediction of disease and response to therapy.

In my lab, we have isolated EVs from cancer cell lines and urine and blood of patients with bladder cancer at different stages. Via miRNA array, gene array, and proteomics, we are aiming to identify the signature protein profiles that can be used for disease prognosis. Through the CRISPR/Cas9 gene editing system, we have attempted to inhibit cancer growth by targeting EV biogenesis pathways in cancer cells.

We are also studying potential involvement of EV secretion in response to two treatments that often apply in bladder cancer: BCG immunotherapy for superficial bladder cancer, and cisplatin chemotherapy for muscle invasive bladder cancer. Since the EVs are quite small - the size of a virus - we utilize the Nanosight nanoparticle tracking system, which allow us to trace and monitor EVs based on the Brownian motion of each single particle in a real time manner. In collaborations with URMC investigators, in addition to our participation in the SWOG S1602 clinical trial, we’ve started to collect and analyze patients’ urine- and blood-borne EV profiles before, during, and after therapy. Our goal is to establish rapid body fluid biopsy assays that can be used as indicators of patients’ responsiveness to therapy. The molecular/genetic contents within EVs from each individual patient could provide an opportunity to develop precision, personalized medicine in the future.

Yi-Fen Lee, Ph.D.
Yi-Fen Lee, Ph.D.
Principal Investigator

Faculty Appointments

Professor - Department of Urology (SMD)

Credentials

Post-doctoral Training & Residency

Post-Doctoral Fellow, Department of Pathology 1997 - 2001

Lab Manager, Department of Pathology 1997 - 2002

Education

PhD | Univ Wisconsin-Madison. Endocrinology/Molecular Oncology. 1997

MS | Tung-Hai University. Biology. 1988

BS | Tung-Hai University. Biology. 1986

Awards

Research Scholar. 2006

Edwin Beer Fellowship Award. 2003 - 2005

Cap CURE Award, Third Prize. 2002

Research

My lab is studying extracellular vesicles (EVs), often called exosomes, for their roles in cancer development, progression and response to treatment, with a focus on Urology cancers such as bladder and prostate cancers.

This is a relatively new and exciting area of research: small vesicles, i...
My lab is studying extracellular vesicles (EVs), often called exosomes, for their roles in cancer development, progression and response to treatment, with a focus on Urology cancers such as bladder and prostate cancers.

This is a relatively new and exciting area of research: small vesicles, in size ranging from 30-250 nm, are secreted by almost all types of cells and contain bio-information (such as DNA, RNA and proteins) resembling the cells of origins. They travel distances via circulation, and can be taken up by recipient cells, consequently affecting their behavior. The genetic and molecular contents of EVs can become an attractive resource of biomarkers for prediction of disease and response to therapy.

In my lab, we have isolated EVs from cancer cell lines and urine and blood of patients with bladder cancer at different stages. Via miRNA array, gene array, and proteomics, we are aiming to identify the signature protein profiles that can be used for disease prognosis. Through the CRISPR/Cas9 gene editing system, we have attempted to inhibit cancer growth by targeting EV biogenesis pathways in cancer cells.

We are also studying potential involvement of EV secretion in response to two treatments that often apply in bladder cancer: BCG immunotherapy for superficial bladder cancer, and cisplatin chemotherapy for muscle invasive bladder cancer. Since the EVs are quite small - the size of a virus - we utilize the Nanosight nanoparticle tracking system, which allow us to trace and monitor EVs based on the Brownian motion of each single particle in a real time manner. In collaborations with URMC investigators, in addition to our participation in the SWOG S1602 clinical trial, we’ve started to collect and analyze patients’ urine- and blood-borne EV profiles before, during, and after therapy. Our goal is to establish rapid body fluid biopsy assays that can be used as indicators of patients’ responsiveness to therapy. The molecular/genetic contents within EVs from each individual patient could provide an opportunity to develop precision, personalized medicine in the future.

Yi-Fen Lee, Ph.D.
Yi-Fen Lee, Ph.D.
Principal Investigator

Publications

Journal Articles

Prevention of Radiation-Induced Bladder Injury: A Murine Study Using Captopril.

Groves AM, Paris N, Hernady E, Johnston CJ, Aljitawi O, Lee YF, Kerns SL, Marples B

International journal of radiation oncology, biology, physics.. 2023 March 15115 (4):972-982. Epub 11/16/2022.

Bladder Cancer Extracellular Vesicles Elicit a CD8 T Cell-Mediated Antitumor Immunity.

Ortiz-Bonilla CJ, Uccello TP, Gerber SA, Lord EM, Messing EM, Lee YF

International journal of molecular sciences.. 2022 March 823 (6)Epub 03/08/2022.

Tenascin-C expression in the lymph node pre-metastatic niche in muscle-invasive bladder cancer.

Silvers CR, Messing EM, Miyamoto H, Lee YF

British journal of cancer.. 2021 November 125 (10):1399-1407. Epub 09/25/2021.

Non-stem bladder cancer cell-derived extracellular vesicles promote cancer stem cell survival in response to chemotherapy.

Chung WM, Molony RD, Lee YF

Stem cell research & therapy.. 2021 October 912 (1):533. Epub 10/09/2021.

Active vitamin D induces gene-specific hypomethylation in prostate cancer cells developing vitamin D resistance.

Lai GR, Lee YF, Yan SJ, Ting HJ

American journal of physiology. Cell physiology.. 2020 May 1318 (5):C836-C847. Epub 03/11/2020.

Bladder cancer extracellular vesicles drive tumorigenesis by inducing the unfolded protein response in endoplasmic reticulum of nonmalignant cells.

Wu CH, Silvers CR, Messing EM, Lee YF

The Journal of biological chemistry.. 2019 March 1294 (9):3207-3218. Epub 12/28/2018.

A Festschrift in Honor of Edward M. Messing, MD, FACS.

Joseph JV, Brasacchio R, Fung C, Reeder J, Bylund K, Sahasrabudhe D, Yeh SY, Ghazi A, Fultz P, Rubens D, Wu G, Singer E, Schwarz E, Mohile S, Mohler J, Theodorescu D, Lee YF, Okunieff P, McConkey D, Rashid H, Chang C, Fradet Y, Guru K, Kukreja J, Sufrin G, Lotan Y, Bailey H, Noyes K, Schwartz S, Rideout K, Bratslavsky G, Campbell SC, Derweesh I, Abrahamsson PA, Soloway M, Gomella L, Golijanin D, Svatek R, Frye T, Lerner S, Palapattu G, Wilding G, Droller M, Trump D

Bladder cancer.. 2018 October 34 (Suppl 1):S1-S43. Epub 10/03/2018.

Extracellular Vesicles in Bladder Cancer: Biomarkers and Beyond.

Liu YR, Ortiz-Bonilla CJ, Lee YF

International journal of molecular sciences.. 2018 September 1819 (9)Epub 09/18/2018.

Characterization of urinary extracellular vesicle proteins in muscle-invasive bladder cancer.

Silvers CR, Miyamoto H, Messing EM, Netto GJ, Lee YF

Oncotarget.. 2017 October 318 (53):91199-91208. Epub 08/08/2017.

Identification of extracellular vesicle-borne periostin as a feature of muscle-invasive bladder cancer.

Silvers CR, Liu YR, Wu CH, Miyamoto H, Messing EM, Lee YF

Oncotarget.. 2016 April 267 (17):23335-45. Epub 1900 01 01.

E-selectin ligand-1 controls circulating prostate cancer cell rolling/adhesion and metastasis.

Yasmin-Karim S, King MR, Messing EM, Lee YF

Oncotarget.. 2014 December 155 (23):12097-110. Epub 1900 01 01.

Bladder cancer exosomes contain EDIL-3/Del1 and facilitate cancer progression.

Beckham CJ, Olsen J, Yin PN, Wu CH, Ting HJ, Hagen FK, Scosyrev E, Messing EM, Lee YF

The Journal of urology.. 2014 August 192 (2):583-92. Epub 02/14/2014.

TR4 nuclear receptor functions as a tumor suppressor for prostate tumorigenesis via modulation of DNA damage/repair system.

Lin SJ, Lee SO, Lee YF, Miyamoto H, Yang DR, Li G, Chang C

Carcinogenesis.. 2014 June 35 (6):1399-406. Epub 02/28/2014.

1 alpha, 25-dihydroxylvitamin D3 promotes Bacillus Calmette-Guérin immunotherapy of bladder cancer.

Hsu JW, Yin PN, Wood R, Messing J, Messing E, Lee YF

Oncotarget.. 2013 December 4 (12):2397-406. Epub 1900 01 01.

Identification of microRNA-98 as a therapeutic target inhibiting prostate cancer growth and a biomarker induced by vitamin D.

Ting HJ, Messing J, Yasmin-Karin S, Lee YF

The Journal of biological chemistry.. 2013 January 4288 (1):1-9. Epub 11/27/2012.

Reduced osteoblast activity in the mice lacking TR4 nuclear receptor leads to osteoporosis.

Lin SJ, Ho HC, Lee YF, Liu NC, Liu S, Li G, Shyr CR, Chang C

Reproductive biology and endocrinology : RB&E.. 2012 June 710 :43. Epub 06/07/2012.

Deficiency in TR4 nuclear receptor abrogates Gadd45a expression and increases cytotoxicity induced by ionizing radiation.

Yan SJ, Lee YF, Ting HJ, Liu NC, Liu S, Lin SJ, Yeh SD, Li G, Chang C

Cellular & molecular biology letters.. 2012 June 17 (2):309-22. Epub 03/07/2012.

A positive feedback signaling loop between ATM and the vitamin D receptor is critical for cancer chemoprevention by vitamin D.

Ting HJ, Yasmin-Karim S, Yan SJ, Hsu JW, Lin TH, Zeng W, Messing J, Sheu TJ, Bao BY, Li W, Messing E, Lee YF

Cancer research.. 2012 February 1572 (4):958-68. Epub 12/29/2011.

Testicular nuclear receptor 4 (TR4) regulates UV light-induced responses via Cockayne syndrome B protein-mediated transcription-coupled DNA repair.

Liu S, Yan SJ, Lee YF, Liu NC, Ting HJ, Li G, Wu Q, Chen LM, Chang C

The Journal of biological chemistry.. 2011 November 4286 (44):38103-38108. Epub 09/14/2011.

The roles of testicular nuclear receptor 4 (TR4) in male fertility-priapism and sexual behavior defects in TR4 knockout mice.

Collins LL, Lee YF, Ting HJ, Lin WJ, Liu NC, Meshul CK, Uno H, Bao BY, Chen YT, Chang C

Reproductive biology and endocrinology : RB&E.. 2011 October 139 :138. Epub 10/13/2011.

Mice lacking TR4 nuclear receptor develop mitochondrial myopathy with deficiency in complex I.

Liu S, Lee YF, Chou S, Uno H, Li G, Brookes P, Massett MP, Wu Q, Chen LM, Chang C

Molecular endocrinology.. 2011 August 25 (8):1301-10. Epub 05/26/2011.

Premature aging with impaired oxidative stress defense in mice lacking TR4.

Lee YF, Liu S, Liu NC, Wang RS, Chen LM, Lin WJ, Ting HJ, Ho HC, Li G, Puzas EJ, Wu Q, Chang C

American journal of physiology. Endocrinology and metabolism.. 2011 July 301 (1):E91-8. Epub 04/26/2011.

Increased acetylation in the DNA-binding domain of TR4 nuclear receptor by the coregulator ARA55 leads to suppression of TR4 transactivation.

Xie S, Ni J, Lee YF, Liu S, Li G, Shyr CR, Chang C

The Journal of biological chemistry.. 2011 June 17286 (24):21129-36. Epub 04/22/2011.

Metformin inhibits nuclear receptor TR4-mediated hepatic stearoyl-CoA desaturase 1 gene expression with altered insulin sensitivity.

Kim E, Liu NC, Yu IC, Lin HY, Lee YF, Sparks JD, Chen LM, Chang C

Diabetes.. 2011 May 60 (5):1493-503. Epub 04/08/2011.

Suppression of prostate cancer cell rolling and adhesion to endothelium by 1?,25-dihydroxyvitamin D3.

Hsu JW, Yasmin-Karim S, King MR, Wojciechowski JC, Mickelsen D, Blair ML, Ting HJ, Ma WL, Lee YF

The American journal of pathology.. 2011 February 178 (2):872-80. Epub 1900 01 01.

Down-regulation of NF-kappaB signals is involved in loss of 1alpha,25-dihydroxyvitamin D3 responsiveness.

Bao BY, Ting HJ, Hsu JW, Yasmin-Karim S, Messing E, Lee YF

The Journal of steroid biochemistry and molecular biology.. 2010 May 120 (1):11-21. Epub 03/04/2010.

Activation of TR4 orphan nuclear receptor gene promoter by cAMP/PKA and C/EBP signaling.

Liu NC, Lin WJ, Yu IC, Lin HY, Liu S, Lee YF, Chang C

Endocrine.. 2009 October 36 (2):211-7. Epub 07/18/2009.

TR4 nuclear receptor functions as a fatty acid sensor to modulate CD36 expression and foam cell formation.

Xie S, Lee YF, Kim E, Chen LM, Ni J, Fang LY, Liu S, Lin SJ, Abe JI, Berk B, Ho FM, Chang C

Proceedings of the National Academy of Sciences of the United States of America.. 2009 August 11106 (32):13353-8. Epub 07/28/2009.

A new prostate cancer therapeutic approach: combination of androgen ablation with COX-2 inhibitor.

Cai Y, Lee YF, Li G, Liu S, Bao BY, Huang J, Hsu CL, Chang C

International journal of cancer.. 2008 July 1123 (1):195-201. Epub 1900 01 01.

Oxidative stress stimulates testicular orphan receptor 4 through forkhead transcription factor forkhead box O3a.

Li G, Lee YF, Liu S, Cai Y, Xie S, Liu NC, Bao BY, Chen Z, Chang C

Endocrinology.. 2008 July 149 (7):3490-9. Epub 04/03/2008.

Protective role of 1 alpha, 25-dihydroxyvitamin D3 against oxidative stress in nonmalignant human prostate epithelial cells.

Bao BY, Ting HJ, Hsu JW, Lee YF

International journal of cancer.. 2008 June 15122 (12):2699-706. Epub 1900 01 01.

Subfertility with defective folliculogenesis in female mice lacking testicular orphan nuclear receptor 4.

Chen LM, Wang RS, Lee YF, Liu NC, Chang YJ, Wu CC, Xie S, Hung YC, Chang C

Molecular endocrinology.. 2008 April 22 (4):858-67. Epub 01/03/2008.

Loss of TR4 orphan nuclear receptor reduces phosphoenolpyruvate carboxykinase-mediated gluconeogenesis.

Liu NC, Lin WJ, Kim E, Collins LL, Lin HY, Yu IC, Sparks JD, Chen LM, Lee YF, Chang C

Diabetes.. 2007 December 56 (12):2901-9. Epub 09/07/2007.

Increased expression of corepressors in aggressive androgen-independent prostate cancer cells results in loss of 1alpha,25-dihydroxyvitamin D3 responsiveness.

Ting HJ, Bao BY, Reeder JE, Messing EM, Lee YF

Molecular cancer research : MCR.. 2007 September 5 (9):967-80. Epub 1900 01 01.

Loss of testicular orphan receptor 4 impairs normal myelination in mouse forebrain.

Zhang Y, Chen YT, Xie S, Wang L, Lee YF, Chang SS, Chang C

Molecular endocrinology.. 2007 April 21 (4):908-20. Epub 01/16/2007.

Evaluation of C-2-substituted 19-nor-1alpha,25-dihydroxyvitamin D3 analogs as therapeutic agents for prostate cancer.

Chen TC, Persons KS, Zheng S, Mathieu J, Holick MF, Lee YF, Bao B, Arai MA, Kittaka A

The Journal of steroid biochemistry and molecular biology.. 2007 March 103 (3-5):717-20. Epub 01/04/2007.

Evaluation of C-2-substituted 19-nor-1alpha,25-dihydroxyvitamin D(3) analogs as therapeutic agents for prostate cancer

Chen,T. C.; Persons,K. S.; Zheng,S.; Mathieu,J.; Holick,M. F.; Lee,Y. F.; Bao,B.; Arai,M. A.; Kittaka,A.;.

J.Steroid Biochem.Mol.Biol. 2007; .

Loss of Testicular Orphan Receptor 4 Impairs Normal Myelination in Mouse Forebrain

Zhang,Y.; Chen,Y. T.; Xie,S.; Wang,L.; Lee,Y. F.; Chang,S. S.; Chang,C.;.

Mol.Endocrinol. 2007; .

Transactivation of the proximal promoter of human oxytocin gene by TR4 orphan receptor.

Wang CP, Lee YF, Chang C, Lee HJ

Biochemical and biophysical research communications.. 2006 December 8351 (1):204-8. Epub 10/12/2006.

1alpha, 25-dihydroxyvitamin D3 suppresses interleukin-8-mediated prostate cancer cell angiogenesis.

Bao BY, Yao J, Lee YF

Carcinogenesis.. 2006 September 27 (9):1883-93. Epub 04/19/2006.

1alpha,25-dihydroxyvitamin D3 inhibits prostate cancer cell invasion via modulation of selective proteases.

Bao BY, Yeh SD, Lee YF

Carcinogenesis.. 2006 January 27 (1):32-42. Epub 06/29/2005.

9-cis-retinoic acid inhibits androgen receptor activity through activation of retinoid X receptor.

Chuang KH, Lee YF, Lin WJ, Chu CY, Altuwaijri S, Wan YJ, Chang C

Molecular endocrinology.. 2005 May 19 (5):1200-12. Epub 01/13/2005.

Androgen-receptor coregulators mediate the suppressive effect of androgen signals on vitamin D receptor activity.

Ting HJ, Bao BY, Hsu CL, Lee YF

Endocrine.. 2005 February 26 (1):1-9. Epub 1900 01 01.

Modulation of the retinoic acid-induced cell apoptosis and differentiation by the human TR4 orphan nuclear receptor.

Lee YF, Bao BY, Chang C

Biochemical and biophysical research communications.. 2004 October 22323 (3):876-83. Epub 1900 01 01.

Growth retardation and abnormal maternal behavior in mice lacking testicular orphan nuclear receptor 4.

Collins LL, Lee YF, Heinlein CA, Liu NC, Chen YT, Shyr CR, Meshul CK, Uno H, Platt KA, Chang C

Proceedings of the National Academy of Sciences of the United States of America.. 2004 October 19101 (42):15058-63. Epub 10/11/2004.

A gene expression signature associated with metastatic outcome in human leiomyosarcomas.

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

Cancer research.. 2004 October 1564 (20):7201-4. Epub 1900 01 01.

The role of N-methyl-D-aspartate receptors in neurobehavioral changes induced by toluene exposure during synaptogenesis.

Chen HH, Lee YF, Chan MH, Lo PS

Annals of the New York Academy of Sciences.. 2004 October 1025 :552-5. Epub 1900 01 01.

Targeted inactivation of testicular nuclear orphan receptor 4 delays and disrupts late meiotic prophase and subsequent meiotic divisions of spermatogenesis.

Mu X, Lee YF, Liu NC, Chen YT, Kim E, Shyr CR, Chang C

Molecular and cellular biology.. 2004 July 24 (13):5887-99. Epub 1900 01 01.

Androgen signaling is required for the vitamin D-mediated growth inhibition in human prostate cancer cells.

Bao BY, Hu YC, Ting HJ, Lee YF

Oncogene.. 2004 April 2223 (19):3350-60. Epub 1900 01 01.

Disruption of TR4 orphan nuclear receptor reduces the expression of liver apolipoprotein E/C-I/C-II gene cluster.

Kim E, Xie S, Yeh SD, Lee YF, Collins LL, Hu YC, Shyr CR, Mu XM, Liu NC, Chen YT, Wang PH, Chang C

The Journal of biological chemistry.. 2003 November 21278 (47):46919-26. Epub 09/03/2003.

Suppression of hepatitis B virus core promoter by the nuclear orphan receptor TR4.

Lin WJ, Li J, Lee YF, Yeh SD, Altuwaijri S, Ou JH, Chang C

The Journal of biological chemistry.. 2003 March 14278 (11):9353-60. Epub 01/08/2003.

Activation of mitogen-activated protein kinase pathway by the antiandrogen hydroxyflutamide in androgen receptor-negative prostate cancer cells.

Lee YF, Lin WJ, Huang J, Messing EM, Chan FL, Wilding G, Chang C

Cancer research.. 2002 November 162 (21):6039-44. Epub 1900 01 01.

Recent advances in the TR2 and TR4 orphan receptors of the nuclear receptor superfamily.

Lee YF, Lee HJ, Chang C

The Journal of steroid biochemistry and molecular biology.. 2002 August 81 (4-5):291-308. Epub 1900 01 01.

TR4 orphan receptor represses the human steroid 21-hydroxylase gene expression through the monomeric AGGTCA motif.

Lee HJ, Lee YF, Chang C

Biochemical and biophysical research communications.. 2001 August 3285 (5):1361-8. Epub 1900 01 01.

Convergence of two repressors through heterodimer formation of androgen receptor and testicular orphan receptor-4: a unique signaling pathway in the steroid receptor superfamily.

Lee YF, Shyr CR, Thin TH, Lin WJ, Chang C

Proceedings of the National Academy of Sciences of the United States of America.. 1999 December 2196 (26):14724-9. Epub 1900 01 01.

Differential regulation of direct repeat 3 vitamin D3 and direct repeat 4 thyroid hormone signaling pathways by the human TR4 orphan receptor.

Lee YF, Young WJ, Lin WJ, Shyr CR, Chang C

The Journal of biological chemistry.. 1999 June 4274 (23):16198-205. Epub 1900 01 01.

Induction of TR4 orphan receptor by retinoic acid in human HaCaT keratinocytes.

Inui S, Lee YF, Haake AR, Goldsmith LA, Chang C

The Journal of investigative dermatology.. 1999 April 112 (4):426-31. Epub 1900 01 01.

Identification of the histamine H1 receptor gene as a differentially repressed target of the human TR2 orphan receptor.

Lee HJ, Lee YF, Chang C

Molecular and cellular biochemistry.. 1999 April 194 (1-2):199-207. Epub 1900 01 01.

A bidirectional regulation between the TR2/TR4 orphan receptors (TR2/TR4) and the ciliary neurotrophic factor (CNTF) signaling pathway.

Young WJ, Lee YF, Smith SM, Chang C

The Journal of biological chemistry.. 1998 August 14273 (33):20877-85. Epub 1900 01 01.

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.

Lee YF, Young WJ, Burbach JP, Chang C

The Journal of biological chemistry.. 1998 May 29273 (22):13437-43. Epub 1900 01 01.

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.

Chang C, Lee HJ, Lee YF

Biochemical and biophysical research communications.. 1997 June 9235 (1):205-11. Epub 1900 01 01.

Identification of direct repeat 4 as a positive regulatory element for the human TR4 orphan receptor. A modulator for the thyroid hormone target genes.

Lee YF, Pan HJ, Burbach JP, Morkin E, Chang C

The Journal of biological chemistry.. 1997 May 2272 (18):12215-20. Epub 1900 01 01.