Xuesen Zhang, Ph.D., Prof.

Principal Investigator

Secretary General of Liaoning Society for Anatomical Sciences

Dean of the Department of Histology and Embryology, College of Basic Medical Science, China Medical University

Email: zhangxs@cmu.edu.cn

Tel: +86-18900919805

Address: 77 Puhe Road, Shenbei New District, Shenyang, 110122, China

Research Interests:

(1) Protein post-translational modifications and tumors;

(2) Maintaining the female primordial follicle pool.

Publications:

1. Christophorou MA, Sharma P, Zhang X. Citrullination: new tricks for an old mod. Philos Trans R Soc Lond B Biol Sci. 2023 Nov 20;378(1890):20220235.

2. Xue T, Fei S, Gu J, Li N, Zhang P, Liu X, Thompson PR, Zhang X. Inhibiting MEK1 R189 citrullination enhances the chemosensitivity of docetaxel to multiple tumour cells. Philos Trans R Soc Lond B Biol Sci. 2023 Nov 20;378(1890):20220246.

3. Chen W, E Q, Sun B, Zhang P, Li N, Fei S, Wang Y, Liu S, Liu X, Zhang X. PARP1-catalyzed PARylation of YY1 mediates endoplasmic reticulum stress in granulosa cells to determine primordial follicle activation. Cell Death Dis. 2023 Aug 15;14(8):524.

4. Fan Z, Zhang X, Shang Y, Zou M, Zhou M, E Q, Fei S, Chen W, Li J, Zhang X, Liu X. Intestinal Flora Changes Induced by a High-Fat Diet Promote Activation of Primordial Follicles through Macrophage Infiltration and Inflammatory Factor Secretion in Mouse Ovaries. Int J Mol Sci. 2022 Apr 27;23(9):4797.

5. Zhou M, Liu X, Qiukai E, Shang Y, Zhang X, Liu S, Zhang X. Long non-coding RNA Xist regulates oocyte loss via suppressing miR-23b-3p/miR-29a-3p maturation and upregulating STX17 in perinatal mouse ovaries. Cell Death Dis. 2021 May 25;12(6):540.

6. Xue T, Liu XQ, Zhang M,E QK, Liu ST, Zou MS, Li Y, Ma ZN, Han Y, Thompson P, Zhang X. PADI2-Catalyzed MEK1 Citrullination Activates ERK1/2 and Promotes IGF2BP1-Mediated SOX2 mRNA Stability in Endometrial Cancer. Advanced Science 2021 Jan 29;8(6):2002831.

7. Han Y, Song C, Zhang T, Zhou Q, Zhang X, Wang J, Xu B, Zhang X, Liu X, Ying X. Wilms’ tumor 1 (WT1) promotes ovarian cancer progression by regulating E-cadherin and ERK1/2 signaling. Cell Cycle. 2020 Oct;19(20):2662.

8. Zhang X, Xiao H, Zhang X, E Q, Gong X, Li T, Han Y, Ying X, Cherrington BD, Xu B, Liu X, Zhang X. Decreased microRNA-125b-5p disrupts follicle steroidogenesis through targeting PAK3/ERK1/2 signalling in mouse preantral follicles. METABOLISM-CLINICAL AND EXPERIMENTAL. 2020 Jun;107:154241.

9. Li F, Miao L, Xue T, Qin H, Mondal S, Thompson PR, Coonrod SA, Liu X, Zhang X. Inhibiting PAD2 enhances the anti-tumor effect of docetaxel in tamoxifen-resistant breast cancer cells. J Exp Clin Cancer Res. 2019 Oct 10;38(1):414.

10. Mondal S, Gong X, Zhang X, Salinger AJ, Zheng L, Sen S, Weerapana E, Zhang X, Thompson PR. Halogen Bonding Increases the Potency and Isozyme Selectivity of Protein Arginine Deiminase 1 Inhibitors. Angew Chem Int Ed Engl. 2019 Sep 2;58(36):12476-12480.

11. Li T, Liu X, Gong X, E Q, Zhang X, Zhang X. microRNA 92b-3p regulates primordial follicle assembly by targeting TSC1 in neonatal mouse ovaries. Cell Cycle. 2019 Apr;18(8):824-833.

12. Zhou Q, Song C, Liu X, Qin H, Miao L, Zhang X. Peptidylarginine deiminase 4 overexpression resensitizes MCF-7/ADR breast cancer cells to adriamycin via GSK3β /p53 activation. Cancer Manag Res. 2019 Jan 10;11:625-636.

13. Li X, Bao C, Ma Z, Xu B, Ying X, Liu X, Zhang X. Perfluorooctanoic acid stimulates ovarian cancer cell migration, invasion via ERK/NF-κ B/MMP-2/-9 pathway. Toxicol Lett. 2018 Sep 15;294:44-50.

14. Qin H, Liu X, Li F, Miao L, Li T, Xu B, An X, Muth A, Thompson PR, Coonrod SA, Zhang X. PAD1 promotes epithelial-mesenchymal transition and metastasis in triple negative breast cancer cells by regulating MEK1-ERK1/2-MMP2 signaling. Cancer Lett. 2017 Nov 28;409:30-41.

15. Liu X, Morency E, Li T, Qin H, Zhang X, Zhang X, Coonrod S. Role for PADI6 in securing the mRNA-MSY2 complex to the oocyte cytoplasmic lattices. Cell Cycle. 2017 Feb 16;16(4):360-366.

16. Zhang X, Liu X, Zhang M, Li T, Muth A, Thompson PR, Coonrod SA, Zhang X. Peptidylarginine deiminase 1-catalyzed histone citrullination is essential for early embryo development. Sci Rep. 2016 Dec 8;6:38727.

17. Ma Z, Liu X, Li F, Wang Y, Xu Y, Zhang M, Zhang X, Ying X, Zhang X. Perfluorooctanoic acid induces human Ishikawa endometrial cancer cell migration and invasion through activation of ERK/mTOR signaling. Oncotarget. 2016 Oct 11;7(41):66558-66568.

18. Hou X, Zhang L, Han L, Ge J, Ma R, Zhang X, Moley K, Schedl T, Wang Q. Differing roles of pyruvate dehydrogenase kinases during mouse oocyte maturation. J Cell Sci. 2015 Jul 1;128(13):2319-29.

19. Boram Kim; Xuesen Zhang; Rui Kan; Roy Cohen; Chinatsu Mukai; Alexander J Travis; Scott A Coonrod. The role of MATER in endoplasmic reticulum distribution and calcium homeostasis in mouse oocytes. Dev Biol. 2014 Feb 15;386(2):331-9.

20. Guertin MJ, Xuesen Zhang, Anguish L, Kim S, Varticovski L, Lis JT, Hager GL, Coonrod SA. Targeted H3R26 deimination specifically facilitates estrogen receptor binding by modifying nucleosome structure. PLoS Genet. 2014 Sep 11;10(9):e1004613.

21. Guertin MJ, Xuesen Zhang , Coonrod SA, Hager GL. Transient estrogen receptor binding and p300 redistribution support a squelching mechanism for estradiol-repressed genes. Mol Endocrinol. 2014 Sep;28(9):1522-33.

22. Zhang X, Bolt M, Guertin MJ, Chen W, Zhang S, Cherrington BD, et al. Peptidylarginine deiminase 2- catalyzed histone H3 arginine 26 citrullination facilitates estrogen receptor α target gene activation. Proc Natl Acad Sci U S A. 2012 Aug 14;109(33):13331-6.

23. Cherrington BD, Zhang X, McElwee JL, Morency E, Anguish LJ, et al. Potential Role for PAD2 in Gene Regulation in Breast Cancer Cells. Plos One. 2012 7(7): e41242.

24. Zhang X, Gamble MJ, Stadler S, Cherrington BD, Causey CP, Thompson PR, Roberson MS, Kraus WL, Coonrod SA. Genome-wide Analysis Reveals PADI4 Cooperates with Elk-1 to Activate c-fos Expression in Breast Cancer Cells. PLoS Genet. 2011 Jun;7(6):e1002112.

25. Stadler SC, Vincent CT, Fedorov VD, Patsialou A, Cherrington BD, Wakshlag JJ, Mohanan S, Zee BM, Zhang X, Garcia BA, Condeelis JS, Brown AM, Coonrod SA, Allis CD. Dysregulation of PAD4-mediated citrullination of nuclear GSK3β activates TGF-β signaling and induces epithelial-to-mesenchymal transition in breast cancer cells. Proc Natl Acad Sci U S A. 2013 Jul 16;110(29):11851-6.

26. Clark PA, Xie J, Li S, Zhang X, Coonrod S, Roberson MS. Matrix metalloproteinase 9 is a distal-less 3 target- gene in placental trophoblast cells. Am J Physiol Cell Physiol. 2013 Jul 15;305(2):C173-81.

27. Bicker KL, Anguish L, Chumanevich AA, Cameron MD, Cui X, Witalison E, Subramanian V, Zhang X, Chumanevich AP, Hofseth LJ, Coonrod SA, Thompson PR. D-amino acid based protein arginine deiminase inhibitors: Synthesis, pharmacokinetics, and in cellulo efficacy. ACS Med Chem Lett. 2012 Oct 26;3(12):1081-1085.

28. Jones JE, Slack JL, Fang P, Zhang X, Subramanian V, Causey CP, Coonrod SA, Guo M, Thompson PR. Synthesis and screening of a haloacetamidine containing library to identify PAD4 selective inhibitors. ACS Chem Biol. 2012 Jan 20;7(1):160-5.

29. Guan R, Feng X, Wu X, Zhang M, Zhang X, Hébert TE, Segaloff DL. Bioluminescence Resonance Energy Transfer Studies Reveal Constitutive Dimerization of the Human Lutropin Receptor and a Lack of Correlation between Receptor Activation and the Propensity for Dimerization. J Biol Chem. 2009, Mar 20;284(12):7483-94.

30. Zhang XS, Zhang ZH, Jin X, Wei P, Hu XQ, Chen M, Lu CL, Lue YH, Hu ZY, Sinha Hikim AP, Swerdloff RS, Wang C, Liu YX. Dedifferentiation of adult monkey Sertoli cells through activation of extracellularly regulated kinase 1/2 induced by heat treatment. Endocrinology. 2006 Mar;147(3):1237-45.

31. Zhang XS, Yuan JX, Liu T, Lue YH, Jin X, Tao SX, Hu ZY, Hikim AP, Swerdloff RS, Wang C, Liu YX. Expression of orphan receptors TR2, TR3, TR4 and p53 in heat- treated testis of cynomolgus monkeys (Macaca fascicularis). J Androl. 2006 May-Jun;27(3):405-13.

32. Zhang XS, Zhang ZH, Guo SH, Yang W, Zhang ZQ, Yuan JX, Jin X, Hu ZY, Liu YX. Activation of extracellular signal-related kinases 1 and 2 in Sertoli cells in experimentally cryptorchid rhesus monkeys. Asian J Androl. 2006, May;8(3):265-72.

33. Zhang XS, Lue YH, Guo SH, Yuan JX, Hu ZY, Han CS, Hikim AP, Swerdloff RS, Wang C, Liu YX. Expression of HSP105 and HSP60 during germ cell apoptosis in the heat-treated testes of adult cynomolgus monkeys (macaca fascicularis). Front Biosci. 2005, Sep 1;10:3110-21.

34. Jin X, Xiao LJ, Zhang XS, Liu YX. Apoptosis in ovary. Front Biosci. 2011 Jan 1;3:680-97.

35. Liu T, Huang JC, Zuo WL, Lu CL, Chen M, Zhang XS, Li YC, Cai H, Zhou WL, Hu ZY, Gao F, Liu YX. A novel testis-specific Na+/H+ exchanger is involved in sperm motility and fertility. Front Biosci. 2010 Jan 1;2:566-81.

36. Guo J, Jia Y, Tao SX, Li YC, Zhang XS, Hu ZY, Chiang N, Lue YH, Hikim AP, Swerdloff RS, Wang C, Liu YX. Expression of nitric oxide synthase during germ cell apoptosis in testis of cynomolgus monkey after testosterone and heat treatment. J Androl. 2009, MarApr;30(2):190-9.

37. Yuan JX, Xiao LJ, Lu CL, Zhang XS, Liu T, Chen M, Hu ZY, Gao F, Liu YX. Increased expression of heat shock protein 105 in rat uterus of early pregnancy and its significance in embryo implantation. Reprod Biol Endocrinol. 2009 Mar 13;7:23.

38. Li X, Liu Q, Liu S, Zhang X, Liu Y, Zhang Y. The spatiotemporal expression changes of 16 epididymis-specific genes induced by testosterone, heat, and combination treatment in cynomolgus monkey. Acta Biochim Biophys Sin (Shanghai). 2008 Aug;40(8):721-8.

39. Chen M, Yuan JX, Shi YQ, Zhang XS, Hu ZY, Gao F, Liu YX. Effect of 43 degrees treatment on expression of heat shock proteins 105, 70 and 60 in cultured monkey Sertoli cells. Asian J Androl. 2008,May;10(3):474- 85.

40. Johnson C, Jia Y, Wang C, Lue YH, Swerdloff RS, Zhang XS, Hu ZY, Li YC, Liu YX, Hikim AP. Role of caspase 2 in apoptotic signaling in primate and murine germ cells. Biol Reprod. 2008,Nov;79(5):806-14.

41. Guo J, Tao SX, Chen M, Shi YQ, Zhang ZQ, Li YC, Zhang XS, Hu ZY, Liu YX. Heat treatment induces liver receptor homolog-1 expression in monkey and rat Sertoli cells. Endocrinology. 2007, Mar;148(3):1255-65.

42. Jia Y, Hikim AP, Lue YH, Swerdloff RS, Vera Y, Zhang XS, Hu ZY, Li YC, Liu YX, Wang C. Signaling pathways for germ cell death in adult cynomolgus monkeys (Macaca fascicularis) induced by mild testicular hyperthermia and exogenous testosterone treatment. Biol Reprod. 2007 Jul;77(1):83-92.

43. Tao SX, Guo J, Zhang XS, Li YC, Hu ZY, Han CS and Liu YX. Germ cell apoptosis induced by experimental cryptorchidism is mediated by multiple molecular pathways in Cynomolgus Macaque. Front Biosci. 2006 Jan 1;11: 1077-89.

44. Lue Y, Wang C, Liu YX, Hikim AP, Zhang XS, Ng CM, Hu ZY, Li YC, Leung A, Swerdloff RS. Transient testicular warming enhances the suppressive effect of testosterone on spermatogenesis in adult cynomolgus monkeys (Macaca fascicularis). J Clin Endocrinol Metab. 2006 Feb;91(2):539-45.

45. Jin X, Han CS, Zhang XS, Yuan JX, Hu ZY, Liu YX. Signal transduction of stem cell factor in promoting early follicle development. Mol Cell Endocrinol. 2005, 229(1-2):3-10.

46. Wei P, Jin X, Zhang XS, Hu ZY, Han CS, Liu YX. Expression of Bcl-2 and p53 at the fetalmaternal interface of rhesus monkey. Reprod Biol Endocrinol. 2005, 14;3:4.

47. Jin X, Han CS, Zhang XS, Yu FQ, Guo SH, Hu ZY, Liu YX. Stem cell factor modulates the expression of steroidogenesis related proteins and FSHR during ovarian follicular development. Front Biosci. 2005, 10:1573-80.

48. Wei P, Tao SX, Zhang XS, Hu ZY, Liu YX. Effect of RU486 on apoptosis and p53 expression at the boundary of fetal-maternal interface of rhesus monkey (Macaca mulatta). Acta Physiologica Sinica. 2004, 56(1):60-5.

49. Zhang ZH, Jin X, Zhang XS, Hu ZY, Zou RJ, Han CS, Liu YX. Bcl-2 and Bax are involved in experimental cryptorchidism-induced testicular germ cell apoptosis in rhesus monkey. Contraception. 2003, 68(4):297- 301.