UMass Boston

Transcription regulation, Nuclear receptor biology, Prostate cancer research

PhD, Molecular Biology, University of Toledo

MS, Bioengineering, University of Toledo

BS, Biomedical Engineering, Tsinghua University, China

• Han W, Liu M, Han D, Toure AA, Li M, Besschetnova A, Wang Z, Patalano S, Macoska JA, Lam HM, Corey E, He HH, Gao S, Balk SP, and Cai C. (2022) Exploiting the tumor-suppressive activity of the androgen receptor by CDK4/6 inhibition in castration-resistant prostate cancer. Molecular Therapy. 30(4):1628-1644.
• Han W, Liu M, Han D, Li M, Toure AA, Wang Z, Besschetnova A, Patalano S, Macoska JA, Gao S, He HH, and Cai C. (2022) RB1 loss in castration-resistant prostate cancer confers vulnerability to LSD1 inhibition. Oncogene. 41(6):852-864.
• Liao Y, Chen CH, Yang M, Xiao T, Cai C, Gao S, Xue P, Liu Z, Xu H, Lee J, Li W, Mei S, McKeown M, Pierre R, Shu S, Fei T, Duarte MS, Zhao J, Bradner JE, Polyak K, Kantoff PW, Long H, Balk SP, Liu XS, Brown M, and Xu K. (2022) Pharmacological EZH2 inhibition enhances cancer cell sensitivity to genotoxic insults through suppressing DNA damage repair. PNAS. 119(3): e2105898119.
• Han D, Owiredu JN, Healy BM, Li M, Labaf M, Steinfeld JS, Patalano S, Gao S, Liu M, Macoska JA, Zarringhalam K, Siegfried KR, Yuan X, Rebbeck TR, and Cai C. (2021) Susceptibility-associated genetic variation in NEDD9 contributes to prostate cancer initiation and progression. Cancer Research. 81(14): 3766-3776.
• Teng M, Zhou S, Cai C, Lupien M, and He HH. (2021) Pioneer of prostate cancer – past, present, and the future of FOXA1. Protein & Cell. 12(1):29-38.
• Gao S, Chen S, Han D, Wang Z, Li M, Han W, Besschetnova A, Liu M, Zhou F, Barrett D, Luong MP, Owiredu J, Liang L, Ahmed M, Petricca J, Patalano S, Macoska JA, Corey E, Chen S, Balk SP, He HH, and Cai C. (2020) Chromatin binding of FOXA1 is promoted by LSD1-mediated demethylation in prostate cancer. Nature Genetics. 52:1011-1017.
• Han D, Owiredu JN, Healy BM, Li M, Labaf M, Steinfeld JS, Patalano S, Gao S, Liu M, Macoska JA, Zarringhalam K, Siegfried KR, Yuan X, Rebbeck TR, and *Cai C. (2021) Susceptibility-associated genetic variation in NEDD9 contributes to prostate cancer initiation and progression. Cancer Research. Epub.
• Gao S, Chen S, Han D, Wang Z, Li M, Han W, Besschetnova A, Liu M, Zhou F, Barrett D, Luong MP, Owiredu J, Liang L, Ahmed M, Petricca J, Patalano S, Macoska JA, Corey E, Chen S, Balk SP, He HH, and *Cai C. (2020) Chromatin binding of FOXA1 is promoted by LSD1-mediated demethylation in prostate cancer. Nature Genetics. 52:1011-1017.
• Han D, Chen S, Han W, Gao S, Owiredu NJ, Li M, Balk SP, He HH, and *Cai C. (2019) ZBTB7A mediate transcriptional repression activity of the androgen receptor in prostate cancer. Cancer Research. 79(20): 5260-5271.
• Wang Z, Gao S, Han D, Han W, Li M, and *Cai C. (2019) LSD1 activates PI3K/AKT signaling through regulating p85 expression in prostate cancer cells. Frontiers in Oncology. eCollection 2019.
• Gao S, Chen S, Han D, Barrett D, Han W, Ahmed M, Patalano S, Macoska JA, He HH, and *Cai C. (2019) Forkhead domain mutations in FOXA1 drive prostate cancer progression. Cell Research. 29(9):770-772.
• Zhou F, Gao S, Han D, Han W, Chen S, Patalano SC, Macoska JA, He HH, and *Cai C. (2019) TMPRSS2-ERG activates NO-cGMP signaling in prostate cancer cells. Oncogene. 38(22):4397-4411.
• Han W, Gao S, Barrett D, Ahmed M, Han D, Macoska JA, He HH, and *Cai C. (2018) Reactivation of androgen receptor-regulated lipid biosynthesis drives progression of castration-resistant prostate cancer. Oncogene. 37(6):710-21.
• Han D, Gao S, Valencia K, Owiredu J, Han W, de Waal E, Macoska JA, and *Cai C. (2017) A novel nonsense mutation in androgen receptor confers resistance to CYP17 inhibitor treatment in prostate cancer. Oncotarget. 8(4):6796-08
• Gao S, Gao Y, He HH, Han D, Han W, Avery A, Macoska JA, Liu X, Chen S, Ma F, Chen S, Balk SP, and *Cai C. (2016) Androgen receptor tumor suppressor function mediated by recruitment of Retinoblastoma Protein. Cell Reports.
• Gao S, Ye H, Gerrin S, Wang H, Sharma A, Chen S, Akash P, Sowalsky AG, Voznesensky O, Han W, Yu Z, Mostaghel EA, Nelson PS, Taplin ME, Balk SP, and *Cai C. (2016) ErbB2 signaling increases androgen receptor expression in abiraterone-resistant prostate cancer. Clinical Cancer Research. 22(14):3672-82.

Previous Experiences

• Postdoctoral fellow,  Dr. Steven P. Balk lab at Beth Israel Deaconess Medical Center/Harvard Medical School (2007-2011) 
• Instructor, Department of Medicine at Beth Israel Deaconess Medical Center/Harvard Medical School (2011-2014) 
• Assistant professor, Department of Medicine at Beth Israel Deaconess Medical Center/Harvard Medical School (2014-2015)

Professional Interests

My lab focuses on basic aspects of prostate cancer (PCa) biology and the central role of androgens and androgen receptor (AR) in driving PCa and more aggressive castration-resistant prostate cancer (CRPC). Currently, we are actively working on four projects:

1. Study AR transcriptional repression activity: We systematically studied this distinct activity of AR and identified the subset of biologically relevant directly AR repressed genes include AR and AKR1C3, revealing a negative feedback mechanism for regulation of AR signaling, and genes involved in DNA replication. Mechanistically, we found that this AR repression activity on DNA replication is mediated by the recruitment of hypophosphorylated Rb that reinforces Rb-E2F repressor complex and the recruitment of ZBTB7A that can directly act on suppressing E2F1.
2. Study epigenetic regulations of FOXA1/AR axis: FOXA1 and AR axis is a major transcriptional pathway that regulates the lineage of prostate epithelial cells and the development of prostate cancer. We show that Lysine Specific Demethylase 1 (LSD1/KDM1A) plays a major role in regulating AR activity in PCa cells as a major coactivator of AR through interaction with FOXA1. We have also found that the pioneer factor FOXA1 can be directly demethylated by LSD1 and blocking this demethylation activity resulted in a massive disruption of FOXA1 binding and a global impairment of subsequent AR recruitment. In addition to studying LSD1 regulation of FOXA1, we have also functionally characterized the Forkhead domain mutations in FOXA1 and show that these mutations allow PCa cells to reduce the dependency of AR and further drive PCa progression through an AR independent mechanism.
3. Study the function and activity of AR splice variants in PCa resistant to abiraterone or enzalutamide: We reported that AR-V7 expression can be rapidly increased after androgen deprivation such as abiraterone treatment. We further show that this elevated AR-V7 expression can restore the AR activation on lipid synthesis, which contributes to the resistance of androgen deprivation.  We also reported an AR variant-mimic mutation (AR-Q784*) in CYP17 inhibitor-resistant cancer that can drive the progression of PCa cells.
4. Study the regulation and function of ETS fusion genes in prostate cancer: ETS gene fusion is the most frequent genomic alteration (~50%) in prostate cancer. We demonstrated that the expression of TMPRSS2-ERG is restored and AR-dependent in CRPC. We then discovered two major downstream effector pathways of TMPRSS2-ERG: (1) oncogenic transcription factor SOX9 and (2) NO-cGMP signaling.

Current Funding

• Targeting androgen receptor signaling in prostate cancer in men with African ancestry (NIH-U54, 2021-2024)
• Study the mechanism of Retinoblastoma protein mediated androgen receptor transcriptional repression activity on DNA replication (NIH-R01, 2017-2022)
• Inhibiting lysine specific demethylase 1 activity as a potential therapeutic treatment for castration resistant prostate cancer (DoD-Idea Expansion Award, 2019-2022)
• Targeting FOXA1 methylation in castration-resistant prostate cancer  (DoD-Idea Expansion Award, 2021-2024)