Changmeng Cai
Biography
I have been deeply involved in prostate cancer (PCa) research for over 20 years, with a primary focus on the biology of the androgen receptor (AR) and epigenetic regulation. Our ultimate goal is to develop novel therapeutic strategies to target the most aggressive forms of PCa. Throughout my career, I have authored approximately 60 research papers in high-impact journals, including both basic and translational studies. My research has been continuously supported by external funding from the NIH/NCI and the Department of Defense. We have also had great success in training graduate students, with many going on to pursue postdoctoral training at top universities.
Area of Expertise
Prostate cancer research, androgen receptor signaling, transcriptional and epigenetic regulation, lineage plasticity, translational medicine
Degrees
Ph.D., Molecular Biology, University of Toledo, USA
M.S., Bioengineering, University of Toledo, USA
B.S., Biomedical Engineering, Tsinghua University, China
Professional Publications & Contributions
(Selected publications since 2019)
- Wang Z, Townley SL, Zhang S, Liu M, Li M, Labaf M, Patalano S, Michaela MJ, Venkatarmani K, Siegfried KR, Macoska JA, Han D, Gao S, Risbridger GP, Taylor RA, Lawrence MG, He HH, Selth LA, and Cai C. (2024) FOXA2 rewires AP-1 for transcriptional reprogramming and lineage plasticity in prostate cancer. Nature Communications. 159(1):4914
- Han D, Labaf M, Zhao Y, Owiredu J, Zhang S, Patel K, Venkataramani K, Steinfeld JS, Han W, Li M, Liu M, Wang Z, Besschetnova A, Patalano S, Mulhearn MJ, Macoska JA, Yuan X, Balk SP, Nelson PS, Plymate SR, Gao S, Siegfried KR, Liu R, Stangis MM, Foxa G, Czernik PJ, Williams BO, Zarringhalam K, Li X & Cai C. (2024) Androgen receptor splice variants drive castration-resistant prostate cancer metastasis by activating distinct transcriptional programs. The Journal of Clinical Investigation. 134(11):e168649.
- Wang Z, Petricca J, Liu M, Chen S, Zhang S, Li M, Besschetnova A, Patalano S, Venkaaramani K, Siegfried KR, Macoska JA, Han D, Gao S, Vedadi M, Arrowsmith C, He HH & Cai C. (2023) SETD7 functions as a transcription repressor in prostate cancer via methylating FOXA1. Proceedings of the National Academy of Sciences. 120(33): e2220472120.
- Li M, Liu M, Han W, Wang Z, Han D, Patalano S, Macoska JA, Balk SP, He HH, Corey E, Gao S & Cai C. (2023) LSD1 inhibition disrupts super-enhancer driven oncogenic transcription programs in castration-resistant prostate cancer. Cancer Research. 83(10):1684-1698.
- 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.
- 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.
- 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.
- 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.
Additional Information
Professional Interests:
Currently, my team is focused on two main research areas:
Androgen Receptor Signaling Reprogramming: We have identified the transcriptional suppressive activity of AR and conducted systematic studies to explore this distinct function. This has led to the discovery of key corepressors, including Rb, RBL2, and ZBTB7A. Our research has uncovered the molecular basis for high-dose testosterone therapies in prostate cancer. Additionally, we are investigating the unique regulation and functions of AR splice variants in castration-resistant prostate cancer (CRPC). Our work has demonstrated that AR variants can reprogram AR signaling to promote tumor metastasis.
Epigenetic Reprogramming in Prostate Cancer Progression and Therapy Resistance: Our research focuses on the role of histone modifiers and their noncanonical activities in driving prostate cancer progression and therapy resistance through lineage plasticity. Notably, we have uncovered an epigenetic circuit involving LSD1 and SETD7, which dynamically regulates the chromatin binding of prostate cancer-specific pioneer factors FOXA1 and FOXA2 via non-histone lysine methylations. Dysregulation of the LSD1/SETD7 balance may lead to transcriptional reprogramming and lineage plasticity in prostate cancer cells. We are actively evaluating epigenetic therapies, particularly LSD1 inhibitors, in aggressive prostate cancer variants.
(My lab offers graduate assistantships to highly qualified students who are passionate about cancer research. We are particularly interested in candidates with a background in cancer biology or bioinformatics.)