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Biological Sciences Profiles


Xianzhong Yu

Associate Professor
Biological Sciences Department

Office: LSF 051B
Phone: 864-656-0718
Email: xyu@clemson.edu

 

 Educational Background

Ph.D. Molecular & Cellular Biology
Ohio university 1998

MS Reproductive Biology
Changchun University of Agriculture and Animal Sciences 1988

 Research Interests

Tumor associated macrophages (TAMs)
As the most abundant immune cells recruited to the tumor milieu, tumor associated macrophages (TAMs) present at every stage of tumor development. Clinical data and animal models suggest that TAMs are skewed by tumor microenvironment to adopt a M2 phenotype and play a pro-tumoral role via stimulating angiogenesis, enhancing tumor cell invasion, motility and intravasation. TAMs are also involved in maintaining the immune suppressive state of the tumor microenvironment by mechanisms such as production of reactive oxygen species (ROS), production of IL-10 which in turn can induce the expression of costimulatory molecule PD-L1 in monocytes to inhibit CTL responses, production of prostaglandin E2(PGE2), IL-10, and indoleamine 2,3-dioxygenase to induce Tregs. Thus, TAMs are considered as a very attractive prognostic biomarker and a therapeutic target.
My lab is interested in re-educating TAMs to fight tumor by the manipulation of the TLR-IRF signal transduction pathway. TLR receptors on macrophages can recognize pathogens by binding to pathogen associated molecular pattern (PAMPs), leading to the secretion of a wide array of pro-inflammatory cytokines. By conjugation to Zymosan particles which are yeast derived glucan particles and a natural ligand of TLR4, we can target recombinant adenoviral particles encoding constant active IRF3 and IRF7 to macrophages by phagocytosis. Expression of active IRF3 and IRF7 by TAMs can polarize TAMs to M1 phenotype which in turn can push the tumor microenvironment into an immune active state.

 Publications

1: Liu X, Yang Y, Jiang P, Li X, Ge Y, Cao Y, Zhao Z, Fang X, Yu X. Effect of QSOX1 on cattle carcass traits as well as apoptosis and triglyceride production in bovine fetal fibroblasts and mammary epithelial cells. J Vet Med Sci. 2018 Aug 30;80(8):1329-1336. doi: 10.1292/jvms.17-0705. Epub 2018 May 30. PubMed PMID: 29848850; PubMed Central PMCID: PMC6115246.
2: Yang X, Yu X, Wei Y. Lentiviral delivery of novel fusion protein IL12/FasTI for cancer immune/gene therapy. PLoS One. 2018 Jul 25;13(7):e0201100. doi: 10.1371/journal.pone.0201100. eCollection 2018. PubMed PMID: 30044833; PubMed Central PMCID: PMC6059467.
3: Herbert GS, Vreeland TJ, Clifton GT, Greene JM, Jackson DO, Hardin MO, Hale DF, Berry JS, Nichol P, Yin S, Yu X, Wagner TE, Peoples GE. Initial phase I/IIa trial results of an autologous tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine in patients with solid tumors. Vaccine. 2018 May 31;36(23):3247-3253. doi: 10.1016/j.vaccine.2018.04.078. Epub 2018 May 1. PubMed PMID: 29724512.
4: Hardin MO, Vreeland TJ, Clifton GT, Hale DF, Herbert GS, Greene JM, Jackson DO, Berry JE, Nichols P, Yin S, Yu X, Wagner TE, Peoples GE. Tumor lysate particle loaded dendritic cell vaccine: preclinical testing of a novel personalized cancer vaccine. Immunotherapy. 2018 Apr;10(5):373-382. doi: 10.2217/imt-2017-0114. PubMed PMID: 29473470.
5: Jiang P, Fang X, Zhao Z, yu x, Sun B, et al. The effect of short/branched chain acyl-coenzyme A dehydrogenase gene on triglyceride synthesis of bovine mammary epithelial cells. Arch. Anim. Breed.. 2018; 61:115-122.
6: Fang X, Zhao Z, Yu H, Li G, Jiang P, Yang Y, Yang R, Yu X. Comparative genome-wide methylation analysis of longissimus dorsi muscles between Japanese black (Wagyu) and Chinese Red Steppes cattle. PLoS One. 2017 Aug 3;12(8):e0182492. doi: 10.1371/journal.pone.0182492. eCollection 2017. PubMed PMID: 28771560; PubMed Central PMCID: PMC5542662.
7: Yu H, Zhao Z, Yu X, Li J, Lu C, Yang R. Bovine lipid metabolism related gene GPAM: Molecular characterization, function identification, and association analysis with fat deposition traits. Gene. 2017 Apr 20;609:9-18. doi: 10.1016/j.gene.2017.01.031. Epub 2017 Jan 26. PubMed PMID: 28131819.
8: Tietje A, Yang X, Yu X, Wei Y. MICA/IL-12: A novel bifunctional protein for killer cell activation. Oncol Rep. 2017 Mar;37(3):1889-1895. doi: 10.3892/or.2017.5375. Epub 2017 Jan 16. PubMed PMID: 28098874.
9: Yang Y, Pan Q, Sun B, Yang R, Fang X, Liu X, Yu X, Zhao Z. miR-29b Targets LPL and TDG Genes and Regulates Apoptosis and Triglyceride Production in MECs. DNA Cell Biol. 2016 Dec;35(12):758-765. Epub 2016 Nov 17. PubMed PMID: 27854545.
10: Zhang YH, Meng JL, Gao Y, Zhang JY, Niu SL, Yu XZ, Li YB, Guan YT, Sun BX, Zhao ZH. Changes in methylation of genomic DNA from chicken immune organs in response to H5N1 influenza virus infection. Genet Mol Res. 2016 Sep 16;15(3). doi: 10.4238/gmr.15037382. PubMed PMID: 27706718.
11: Yang X, Tietje AH, Yu X, Wei Y. Mouse interleukin-12/FasTI: A novel bi-functional fusion protein for cancer immuno/gene therapy. Int J Oncol. 2016 Jun;48(6):2381-6. doi: 10.3892/ijo.2016.3475. Epub 2016 Apr 7. PubMed PMID: 27081758.
12: Greene JM, Schneble EJ, Jackson DO, Hale DF, Vreeland TJ, Flores M, Martin J, Herbert GS, Hardin MO, Yu X, Wagner TE, Peoples GE. A phase I/IIa clinical trial in stage IV melanoma of an autologous tumor-dendritic cell fusion (dendritoma) vaccine with low dose interleukin-2. Cancer Immunol Immunother. 2016 Apr;65(4):383-92. doi: 10.1007/s00262-016-1809-6. Epub 2016 Feb 19. PubMed PMID: 26894495.
13: Jackson D, Greene J, Hale D, Schneble E, Wagner T, et al. Preclinical testing of a novel personalized cancer vaccine for all solid tumors and all patients. J Immunother Cancer. 2015; 3 (suppl):208.
14: Li J, Yu X, Wagner TE, Wei Y. A biotin-streptavidin-biotin bridge dramatically enhances cell fusion. Oncol Lett. 2014 Jul;8(1):198-202. Epub 2014 Apr 15. PubMed PMID: 24959245; PubMed Central PMCID: PMC4063645.
15: Zhang Y, Guo J, Gao Y, Niu S, Yang C, Bai C, Yu X, Zhao Z. Genome-wide methylation changes are associated with muscle fiber density and drip loss in male three-yellow chickens. Mol Biol Rep. 2014 May;41(5):3509-16. doi: 10.1007/s11033-014-3214-6. Epub 2014 Feb 25. PubMed PMID: 24566679.
16: Tietje A, Li J, Yu X, Wei Y. MULT1E/mIL-12: a novel bifunctional protein for natural killer cell activation. Gene Ther. 2014 May;21(5):468-75. doi: 10.1038/gt.2014.15. Epub 2014 Feb 27. PubMed PMID: 24572784.
17: Gao F, Sun B, Xing S, Yu X, Lu C, Li A, Zhao Z, Yang R. The effect of leader peptide mutations on the biological function of bovine myostatin gene. Gene. 2014 May 1;540(2):171-7. doi: 10.1016/j.gene.2014.02.052. Epub 2014 Feb 26. PubMed PMID: 24583167.
18: Schneble EJ, Yu X, Wagner TE, Peoples GE. Novel dendritic cell-based vaccination in late stage melanoma. Hum Vaccin Immunother. 2014;10(11):3132-8. doi: 10.4161/hv.29110. Review. PubMed PMID: 25483650; PubMed Central PMCID: PMC4514042.
19: Li J, Chang LC, Wall M, Wong DK, Yu X, Wei Y. Antitumor activity of fermented noni exudates and its fractions. Mol Clin Oncol. 2013 Jan;1(1):161-164. Epub 2012 Sep 19. PubMed PMID: 24649140; PubMed Central PMCID: PMC3956231.
20: Zhu L, Zhao Z, Wei Y, Marcotte W Jr, Wagner TE, Yu X. An IL-12/Shh-C domain fusion protein-based IL-12 autocrine loop for sustained natural killer cell activation. Int J Oncol. 2012 Aug;41(2):661-9. doi: 10.3892/ijo.2012.1466. Epub 2012 May 8. PubMed PMID: 22581115.
21: Zhao Z, Holle L, Song W, Wei Y, Wagner TE, Yu X. Antitumor and anti-angiogenic activities of Scutellaria barbata extracts in vitro are partially mediated by inhibition of Akt/protein kinase B. Mol Med Rep. 2012 Mar;5(3):788-92. doi: 10.3892/mmr.2011.694. Epub 2011 Dec 6. PubMed PMID: 22160152.
22: Damiri B, Holle E, Yu X, Baldwin WS. Lentiviral-mediated RNAi knockdown yields a novel mouse model for studying Cyp2b function. Toxicol Sci. 2012 Feb;125(2):368-81. doi: 10.1093/toxsci/kfr309. Epub 2011 Nov 14. PubMed PMID: 22083726; PubMed Central PMCID: PMC3262856.
23: Kotturi HS, Li J, Branham-O'Connor M, Yu X, Wagner TE, Wei Y. In vitro and in vivo delivery of novel anticancer fusion protein MULT1E/FasTI via adenoviral vectors. Cancer Gene Ther. 2010 Mar;17(3):164-70. doi: 10.1038/cgt.2009.69. Epub 2009 Oct 9. PubMed PMID: 19816522.
24: Branham-O'Connor M, Li J, Kotturi HS, Yu X, Wagner TE, Wei Y. Fusion induced reversal of dendritic cell maturation: an altered expression of inflammatory chemokine and chemokine receptors in dendritomas. Oncol Rep. 2010 Feb;23(2):545-50. PubMed PMID: 20043120.
25: Holle L, Song W, Holle E, Wei Y, Li J, Wagner TE, Yu X. In vitro- and in vivo-targeted tumor lysis by an MMP2 cleavable melittin-LAP fusion protein. Int J Oncol. 2009 Oct;35(4):829-35. PubMed PMID: 19724919.
26: Holle L, Song W, Holle E, Nilsson J, Wei Y, Li J, Wagner TE, Yu X. In vivo targeted killing of prostate tumor cells by a synthetic amoebapore helix 3 peptide modified with two γ-linked glutamate residues at the COOH terminus. Mol Med Rep. 2009 May-Jun;2(3):399-403. doi: 10.3892/mmr_00000112. PubMed PMID: 21475841.
27: Collins NH, Lessey EC, DuSell CD, McDonnell DP, Fowler L, Palomino WA, Illera MJ, Yu X, Mo B, Houwing AM, Lessey BA. Characterization of antiestrogenic activity of the Chinese herb, prunella vulgaris, using in vitro and in vivo (Mouse Xenograft) models. Biol Reprod. 2009 Feb;80(2):375-83. doi: 10.1095/biolreprod.107.065375. Epub 2008 Oct 15. Erratum in: Biol Reprod. 2009 Jun;80(6):1306. PubMed PMID: 18923163; PubMed Central PMCID: PMC2746405.
28: Wagner AY, Holle E, Holle L, Yu X, Schwamberger G. Immunological tolerance and tumor rejection in embryo-aggregated chimeric mice - lessons for tumor immunity. BMC Cancer. 2008 Dec 16;8:370. doi: 10.1186/1471-2407-8-370. PubMed PMID: 19087311; PubMed Central PMCID: PMC2628932.
29: Li J, Stickel SL, Bouton-Verville H, Burgin KE, Yu X, Wong DK, Wagner TE, Wei Y. Fermented Noni exudate (fNE): a mediator between immune system and anti-tumor activity. Oncol Rep. 2008 Dec;20(6):1505-9. PubMed PMID: 19020734.
30: Matsui Y, Nakano N, Shao D, Gao S, Luo W, Hong C, Zhai P, Holle E, Yu X, Yabuta N, Tao W, Wagner T, Nojima H, Sadoshima J. Lats2 is a negative regulator of myocyte size in the heart. Circ Res. 2008 Nov 21;103(11):1309-18. doi: 10.1161/CIRCRESAHA.108.180042. Epub 2008 Oct 16. Erratum in: Circ Res. 2009 Feb 13;104(3):e27-9. PubMed PMID: 18927464; PubMed Central PMCID: PMC2775813.
31: Kotturi HS, Li J, Branham-O'Connor M, Stickel SL, Yu X, Wagner TE, Wei Y. Tumor cells expressing a fusion protein of MULT1 and Fas are rejected in vivo by apoptosis and NK cell activation. Gene Ther. 2008 Oct;15(19):1302-10. doi: 10.1038/gt.2008.77. Epub 2008 May 8. PubMed PMID: 18463688.