1. Aging and Prostate Cancer: Dr. Zhang has a long-standing interest in prostate cancer, particularly in aging's contribution to prostate carcinogenesis and the efficacies of candidate aging-associated prostate cancer interventions. The incidence of prostate cancer rises rapidly with increasing age beginning around50, with the highest rates seen in those aged 70 to 80. Optimal management of prostate cancer in old patients (>75 years) remains a significant clinical challenge. Low-grade inflammation (i.e., inflammaging) plays an essential role in the aging process, and chronic inflammation contributes to the onset and progression of prostate cancer. Inflammaging is often attributed to the progressive activation of immune cells. In that regard, a disruption in the balance of pro-inflammatory CD4+ T helper (Th) 17 cells and homeostatic regulatory T (Treg) cell responses in favor of Th17 cells has been reported in non-cancer-related aging humans and mice. More recent evidence has suggested a similar imbalance between Th17 and Treg as a prominent factor in cancer development; however, the mechanisms by which aging influences the balance of Th17 and Treg and the extent to which an imbalance contributes to the initiation and progression of prostate cancer are unclear. We are working on (1) identifying associations between Th17/Treg ratio alteration and human prostate cancer progression associated with advanced aging; (2) defining how aging-associated imbalances in the Th17/Treg axis drive prostate cancer; and(3) determining the efficacy of therapeutic targeting of Th17/Treg axis in preventing age-associated prostate cancer. An R01 award supported this project.
2. Obesity and Prostate Cancer: Obese men with prostate cancer are at increased risk for aggressive disease progression, treatment-related adverse effects, obesity-associated comorbidities, and all-cause mortality. Additionally, non-obese men undergoing long-term ADT to suppress tumor growth at the time of prostate cancer diagnosis are susceptible to becoming obese. Excess fat mass is characterized by chronic inflammation that leads to disrupted immune responses and metabolic irregularities. Innate immunity plays a vital role in promoting obesity-related inflammation; however, adaptive immunity, especially mechanisms involving CD4+ T cells, also regulates chronic inflammation and contributes to abnormal energy metabolism. Abnormal energy metabolism shapes T cell differentiation and manipulating metabolic pathways in T cells can shape their fate and function. Information about how an imbalance of Th17/Treg cells and metabolites contributes to obesity-related prostate cancer is limited. We have generated obesity-related prostate cancer mouse models and aim to identify mechanisms and preclinical target efficacy ofTh17/Treg axis disruption contributing to obesity-related prostate cancer progression.
3. Deuniquitinase (DUB) and Castration-Resistant Prostate Cancer (CRPC): Androgen deprivation therapy (ADT) remains the first-line therapy for advanced prostate cancer. Still, treatment resistance inevitably develops and leads to an abysmal prognosis of stage CRPC. Therefore, there is an urgent need to develop strategies for treating CRPC by targeting specific factors essential for tumor survival instead of targeting AR signaling. Ubiquitin-specific protease 26 (USP26) is a member of DUB involved in various cellular functions and plays a vital role in cancer progression. Our long-term goal is to contribute toward developing clinically effective, science-based strategies to prevent or treat CRPC. We have generated a prostate-specificUsp26 knockout mouse model using CRISP/Cas9 techniques and crossbreed these mice with prostate-specific Pten (tumor suppressor gene) knockout mice to generate Usp26 and Pten double knockout mice to elucidate the role of USP26 in Prostate cancer.
Education: B.S.1987, Biology
M.S. 2001, Reproductive Biology
Ph.D. 2004, Reproductive Biomedicine
ORCID identifier: 0000-0001-7346-5296
MyNCBI Link: https://www.ncbi.nlm.nih.gov/myncbi/qiuyang.zhang.1/bibliography/public/
Selected Publications:
1. ZhangQ, Jazwinski SM. A Novel Strategy to Model Age-RelatedCancer for Elucidation of the Role of Th17 Inflammaging in Cancer Progression. cancers. 2022 October; 14(21):5185.
2. LiuS, Zhang B, Rowan BG, Jazwinski SM, Abdel-Mageed AB, Steele C, Wang AR, SartorO, Niu T, Zhang Q. A Novel Controlled PTEN-Knockout Mouse Model for Prostate Cancer Study. Front Mol Biosci. 2021;8:696537. doi: 10.3389/fmolb.2021.696537. eCollection2021. PubMed PMID: 34150854; PubMed Central PMCID: PMC8211560.
3. LiuS, Liu F, Zhang B, Yan P, Rowan BG, Abdel-Mageed AB, Steele C, Jazwinski SM, Moroz K, Norton EB, Wang A, Myers L, Sartor O, Zhang Q. CD4+ T helper17 cell response of aged mice promotes prostate cancer cell migration and invasion. Prostate. 2020 Jul;80(10):764-776. doi:10.1002/pros.23990. Epub 2020 May 1. PubMed PMID: 32356608; PubMed Central PMCID: PMC7310589.
4. TianH, Huo Y, Zhang J, Ding S, Wang Z, Li H, Wang L, Lu M, Liu S, Qiu S, Zhang Q. Disruption of ubiquitin specific protease 26 gene causes male subfertility associated with spermatogenesis defects in mice†. Biol Reprod. 2019 Apr 1;100(4):1118-1128. doi:10.1093/biolre/ioy258. PubMed PMID: 30561524; PubMed CentralPMCID: PMC6698735.
5. ZhangQ, Liu S, Ge D, Cunningham DM, Huang F,Ma L, Burris TP, You Z. TargetingTh17-IL-17 Pathway in Prevention of Micro-Invasive Prostate Cancer in a MouseModel. Prostate. 2017 Jun;77(8):888-899. doi:10.1002/pros.23343. Epub 2017 Feb 27. PubMed PMID: 28240383; PubMed Central PMCID: PMC5400716.
6. ZhangQ, Liu S, Parajuli KR, Zhang W, Zhang K,Mo Z, Liu J, Chen Z, Yang S, Wang AR, Myers L, You Z. Interleukin-17promotes prostate cancer via MMP7-induced epithelial-to-mesenchymal transition. Oncogene. 2017 Feb 2;36(5):687-699. doi: 10.1038/onc.2016.240. Epub 2016 Jul 4. PubMed PMID: 27375020; PubMed Central PMCID: PMC5213194.
7. QuY, Zhang Q, Ma S, Liu S, Chen Z, Mo Z, You Z. Interleukin-17ADifferentially Induces Inflammatory and Metabolic Gene Expression in the Adipose Tissues of Lean and Obese Mice. Int J Mol Sci. 2016 Apr 7;17(4):522. doi:10.3390/ijms17040522. PubMed PMID: 27070576; PubMed Central PMCID: PMC4848978.
8. LiuS, Zhang Q, Chen C, Ge D, Qu Y, Chen R, Fan YM, Li N, Tang WW, Zhang W,Zhang K, Wang AR, Rowan BG, Hill SM, Sartor O, Abdel-Mageed AB, Myers L, Lin Q,You Z. Hyperinsulinemia enhances interleukin-17-induced inflammation to promote prostate cancer development in obese mice through inhibiting glycogen synthase kinase3-mediated phosphorylation and degradation of interleukin-17 receptor. Oncotarget. 2016 Mar 22;7(12):13651-66. doi:10.18632/oncotarget.7296. PubMed PMID: 26871944; PubMed Central PMCID: PMC4924668.
9. ZhangQ, Liu S, Zhang Q, Xiong Z, Wang AR,Myers L, Melamed J, Tang WW, You Z. Interleukin-17promotes development of castration-resistant prostate cancer potentially through creating an immunotolerant and pro-angiogenic tumor microenvironment. Prostate. 2014 Jun;74(8):869-79. doi:10.1002/pros.22805. Epub 2014 Apr 1. PubMed PMID: 24691769; PubMed Central PMCID: PMC4063299.
10. ZhangQ, Liu S, Ge D, Zhang Q, Xue Y, Xiong Z,Abdel-Mageed AB, Myers L, Hill SM, Rowan BG, Sartor O, Melamed J, Chen Z, You Z. Interleukin-17promotes formation and growth of prostate adenocarcinoma in mouse models. Cancer Res. 2012 May 15;72(10):2589-99. doi:10.1158/0008-5472.CAN-11-3795. E pub 2012 Mar 28. PubMed PMID: 22461511; PubMed Central PMCID: PMC3665158.
· “Topics” (Keywords/Tags):aging, prostate cancer, mouse models, IL-17, BATF, Th17, Treg, USP26
