1. Aging and Prostate Cancer: Dr. Zhang has a long-standing interest in prostatecancer, particularly in aging's contribution to prostate carcinogenesis and theefficacies of candidate aging-associated prostate cancer interventions. Theincidence of prostate cancer rises rapidly with increasing age beginning around50, with the highest rates seen in those aged 70 to 80. Optimal management ofprostate cancer in old patients (>75 years) remains a significant clinicalchallenge. Low-grade inflammation (i.e., inflammaging) plays an essential rolein the aging process, and chronic inflammation contributes to the onset andprogression of prostate cancer. Inflammaging is often attributed to theprogressive activation of immune cells. In that regard, a disruption in thebalance of pro-inflammatory CD4+ T helper (Th) 17 cells andhomeostatic regulatory T (Treg) cell responses in favor of Th17 cells has beenreported in non-cancer-related aging humans and mice. More recent evidence hassuggested a similar imbalance between Th17 and Treg as a prominent factor incancer development; however, the mechanisms by which aging influences thebalance of Th17 and Treg and the extent to which an imbalance contributes tothe initiation and progression of prostate cancer are unclear. We are workingon (1) identifying associations between Th17/Treg ratio alteration and human prostatecancer progression associated with advanced aging; (2) defining howaging-associated imbalances in the Th17/Treg axis drive prostate cancer; and(3) determining the efficacy of therapeutic targeting of Th17/Treg axis inpreventing age-associated prostate cancer. An R01 award supported thisproject.
2. Obesity and Prostate Cancer: Obese men with prostatecancer are at increased risk for aggressive disease progression,treatment-related adverse effects, obesity-associated comorbidities, andall-cause mortality. Additionally, non-obese men undergoing long-term ADT tosuppress tumor growth at the time of prostate cancer diagnosis are susceptibleto becoming obese. Excess fat mass is characterized by chronic inflammationthat leads to disrupted immune responses and metabolic irregularities. Innateimmunity plays a vital role in promoting obesity-related inflammation; however,adaptive immunity, especially mechanisms involving CD4+ T cells, also regulateschronic inflammation and contributes to abnormal energy metabolism. Abnormalenergy metabolism shapes T cell differentiation and manipulating metabolicpathways in T cells can shape their fate and function. Information about how animbalance of Th17/Treg cells and metabolites contributes to obesity-relatedprostate cancer is limited. We have generated obesity-related prostate cancermouse models and aim to identify mechanisms and preclinical target efficacy ofTh17/Treg axis disruption contributing to obesity-related prostate cancerprogression.
3. Deuniquitinase (DUB) and Castration-Resistant ProstateCancer (CRPC): Androgen deprivation therapy (ADT) remains the first-linetherapy for advanced prostate cancer. Still, treatment resistance inevitablydevelops and leads to an abysmal prognosis of stage CRPC. Therefore, there isan urgent need to develop strategies for treating CRPC by targeting specificfactors essential for tumor survival instead of targeting AR signaling.Ubiquitin-specific protease 26 (USP26) is a member of DUB involved in variouscellular functions and plays a vital role in cancer progression. Our long-termgoal is to contribute toward developing clinically effective, science-basedstrategies to prevent or treat CRPC. We have generated a prostate-specificUsp26 knockout mouse model using CRISP/Cas9 techniques and crossbreed thesemice with prostate-specific Pten (tumor suppressor gene) knockout mice togenerate Usp26 and Pten double knockout mice to elucidate the role of USP26 inProstate cancer.
Education: B.S.1987, Biology
M.S. 2001, ReproductiveBiology
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
