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Yi-Fen Lee, Ph.D.

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Office: (585) 275-9702

Research Labs

Faculty Appointments


My laboratory has been focused on two nuclear receptors, vitamin D receptor (VDR) and testicular orphan receptor 4 (TR4) because their functions seem to be connected to aging and prostate cancer. When a mouse is born without these genes, it ages prematurely and its lifespan is greatly reduced. The proper function of these genes is important to keep the prostate from damages that would eventually lead to cancer, therefore, the behavior of these genes could be used as biomarkers for prostate cancer diagnosis and prognosis. We aim to elucidate the mechanisms by which the genes regulate the cell's response to stress that causes damage to DNA, as well as how the gene promotes the DNA repair that protect cells from more harm. Our goal is to reveal the roles of VDR and TR4 in aging and the etiology of prostate cancer and provide therapeutic approaches that would have significant effects on retarding aging and preventing prostate cancer.
In addition, my laboratory also develops pre-clinical trials to investigate the vitamin D based combination therapies that aim to improve the current therapy for prostate cancer as well as bladder cancer. The outcomes from these studies not only provide a mechanistic-based chemoprevention strategy that utilizes vitamin D for improving therapy and/or protecting people from long-term effects of cancer formation, but also adds the appreciation of the multifaceted protective actions of vitamin D that have recently entered a new era.


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.



BS | Tung-Hai University

MS | Tung-Hai University

PhD | Univ Wisconsin-Madison
Endocrinology/Molecular Oncology

Post-doctoral Training & Residency

1997 - 2001
Post-Doctoral Fellow, Department of Pathology

1997 - 2002
Lab Manager, Department of Pathology


2006 - Present
Research Scholar
Sponsor: American Cancer Society

2003 - 2005
Edwin Beer Fellowship Award
Sponsor: New York Academy of Medicine

Cap CURE Award, Third Prize
Sponsor: AUA

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Journal Articles

Vanood A, Lee YA, Leleszi E, Krishnan A. "Symptomatic neurocutaneous melanosis: mild clinical onset in a teenager." BMJ case reports.. 2020 Nov 30; 13(11)Epub 2020 Nov 30.

Lai GR, Lee YF, Yan SJ, Ting HJ. "Active vitamin D induced gene-specific hypomethylation in prostate cancer cells developing vitamin D resistance." American journal of physiology. Cell physiology.. 2020 Mar 11; Epub 2020 Mar 11.

Liu YR, Yin PN, Silvers CR, Lee YF. "Enhanced metastatic potential in the MB49 urothelial carcinoma model." Scientific reports.. 2019 May 15; 9(1):7425. Epub 2019 May 15.