主要研究方向 |
研究方向一: Mitreva M的研究表明旋毛虫的非凡之处就在于它是一种可引起宿主肌纤维分化的细胞内寄生的线虫,在通过蛋白组分析已鉴定的旋毛虫蛋白中,有些作为宿主与寄生虫互作蛋白可能对疾病感染和发病机制是极其重要的,许多寄生虫蛋白对于旋毛虫也是独一无二的,未来可能会发展成为好的靶向治疗药物。因此获得旋毛虫的具有去分化作用的“parakines”并应用于调控肿瘤细胞的分化、增殖对肿瘤治疗具有重大意义。 我们的研究表明旋毛虫虫体蛋白可通过调控线粒体及死亡受体信号传导途径诱导H7402细胞凋亡为了获得这种具有去分化作用的“parakines”并应用于调控肿瘤细胞的分化、增殖,我们在国家自然基金面上项目“旋毛虫抗肿瘤蛋白基因及其功能研究”(30972177/C120205)的资助下构建了旋毛虫T7噬菌体cDNA展示文库,利用该文库采用有机相多细胞亲和淘选法筛选出和人白血病细胞系K562、人肝癌细胞系H7402特异结合的蛋白A200711。该蛋白分子量为16736.3,分子式为C765H1163N205O205S7,疏水性指数是84.04。通过Hochest-PI双染法和流式细胞术检测,结果表明A200711可通过调控细胞凋亡相关酶天冬氨酸特异性半胱氨酸蛋白酶(cysteine-containing aspartate-specific proteases 9,caspase9)和caspase3表达诱导H7402肝癌细胞凋亡。我们的研究主要是通过对宿主与寄生虫互作蛋白的筛选获取可调控癌细胞增殖、侵袭及分化的功能蛋白并对其生物学功能及立体空间构造进行研究以期获得可提高癌细胞凋亡敏感性的生物药物。 研究方向二: TLR3是识别双链RNA ( dsRNA)的受体。TLR3的活化及其随后 IFN-α/β的分泌有助于建立局部的抗病毒状态, 限制病毒在感染部位的复制。Schulz等证实 TLR3能识别脑炎、心肌炎病毒和塞姆利基森林病毒感染期间产生的 dsRNA。这2种病毒均属单股正链 RNA病毒, 仅在病毒复制期间产生dsRNA。该发现扩大了TLR3对病毒识别的范围。SARS和H1N1流感病毒均属单股RNA病毒,研究表明SARS和H1N1流感病毒均属TLR3识别范围,因此TLR3受体激动剂筛选模型的构建及其应用的研究对新型抗病毒药物的研发具有重大意义。 本研究以建立TLR3受体激动剂高通量复式筛选模型筛选抗病毒药物,研发通过激活TLR3介导天然免疫应答抗病毒机制药物。利用TLR3受体配体PolyICLC和单克隆抗体结合受体竞争结合原理构建TLR3激动剂高通量筛选模型,利用该模型采用流式细胞术从筛选TLR3激动剂,采用实时荧光定量RT-PCR技术检测目的药物在促进人类抗IFN-β和IFN-α抗病毒免疫方面的药理作用。
|
主要学术成果 |
科研项目: 1.吉林省科技厅重点研发“基于旋毛虫期特异性新型诊断标识分子猪旋毛虫病诊断无盲区Tsp-UPT-LF-POCT试纸条研制”(20230202086)(课题主持单位) 2.国家科技部“十三五”重大专项“食品中生物性及放射性危害物高效识别与确证关键技术及产品研发”-食源性寄生虫特异、高灵敏检测与确证技术研发(2018YFC1602504)(课题主持单位) 3.国家科技部“十三五”重大专项“猪重要疫病混合感染鉴别诊断技术研究-猪重要疫病的诊断与检测新技术研究-猪旋毛虫病抗体快速检测技术研究(2016YFD0500707) 4.国家自然基金“ 旋毛虫抗肿瘤蛋白基因及其功能研究“(30972177/C120205) 5.教育部新教师基金“旋毛虫虫体蛋白A200711、A200712、A200713 抗肿瘤分子机制研究“(20070183160) 6国家自然基金“旋毛虫肠道感染性肌幼虫、成虫和新生幼虫T7噬菌体展示文库的构建“(30825033/C200103) 7国家自然基金“旋毛虫病的病原侵袭机制研究“(3130064/C180501) 学术论文: [1] Qiao W, Zhang P, Jiang N, Zhang S, Bai H, Xie L, Sun L, Wang X. Albuminnanostructure assisted ABZ anti-parasite immune therapy for T. spiralis muscle infection. Biomater Adv. 2023 Jul;150:213434. doi: 10.1016/j.bioadv.2023.213434. Epub 2023 Apr 18. PMID: 37087912. Impactor:8.457 [2] Bai H, Tang B, Qiao W, Wu X, Liu M, Wang X. The Prevalence of Trichinella spiralis in Domestic Pigs in China: A Systematic Review and Meta-Analysis. Animals (Basel). 2022 Dec 15;12(24):3553. [3] Chen X, Zhao L, Wang J, Wang H, Qiu Y, Dong Z, Zhang C, Liu M, Wang X, Bai X. Rapid visual detection of anisakid nematodes using recombinase polymerase amplification and SYBR Green I. Front Microbiol. 2022 Dec 2;13:1026129. doi:10.3389/fmicb.2022.1026129. PMID: 36532447; PMCID: PMC9756439. [4] Yang J, Sun L, Hui S, Zhang P, Li J, Wang D, Wang X, Jiang S. Ag functionalized SnS<sub>2</sub> with enhanced photothermal activity for safe and efficient wound disinfection.. 2021 May 25. doi:10.1039/d1bm00429h. Epub ahead of print. PMID: 34032227.Impactor:6.843 [5]Sun L, Bai H, Jiang H, Zhang P, Li J, Qiao W, Wang D, Liu G, Wang X. MoS<sub>2</sub>/LaF<sub>3</sub> for enhanced photothermal therapy performance of poorly-differentiated hepatoma. Colloids Surf B Biointerfaces. 2022 Mar 16;214:112462. doi: 10.1016/j.colsurfb.2022.112462. Epub ahead of print. PMID: 35349941. Impactor:5.268 [6] Li J, Ding J, Liu XL, Tang B, Bai X, Wang Y, Qiao WD, Liu MY, Wang XL.Upconverting phosphor technology-based lateral flow assay for the rapid and sensitive detection of anti-Trichinella spiralis IgG antibodies in pig serum. Parasit Vectors. 2021 Sep 22;14(1):487. doi: 10.1186/s13071-021-04949-2. PMID:34551787; PMCID: PMC8456594.(top) [7] Li J, Ding J, Liu X, Tang B, Bai X, Wang Y, Li S, Wang X. Label-free serum detection of Trichinella spiralis using surface-enhanced Raman spectroscopy combined with multivariate analysis. Acta Trop. 2020 Mar;203:105314. doi:10.1016/j.actatropica.2019.105314. Epub 2019 Dec 19. PMID: 31866336. [8] Ding J, Tang B, Liu X, Bai X, Wang Y, Li S, Li J, Liu M, Wang X. Excretory-secretory product of Trichinella spiralis inhibits tumor cell growth by regulating the immune response and inducing apoptosis. Acta Trop. 2021 Oct 7:106172. doi: 10.1016/j.actatropica.2021.106172. Epub ahead of print. PMID:34627760. [9] Li J, Liu X, Ding J, Tang B, Bai X, Wang Y, Li S, Liu M, Wang X. Effect of Trichinella spp. or derived antigens on chemically induced inflammatory bowel disease (IBD) in mouse models: A systematic review and meta-analysis. Int Immunopharmacol. 2020 Aug;85:106646. doi: 10.1016/j.intimp.2020.106646. Epub 2020 May 30. PMID: 32485355. [10] Qu Z, Jin X, Wang Y, Yang Y, Yang Li, Bai X, Yang Y, Xu N, Wang X, Liu M. Effect of recombinant serine protease from newborn larval stage of Trichinella spiralis on 2,4,6-trinitrobenzene sulfonic acid-induced experimental colitis in mice. Acta Trop. 2020 Jun 17;211:105553. doi: 10.1016/j.actatropica.2020.105553. Epub ahead of print. PMID: 32562622. [11] Ding J, Liu X, Bai X, Wang Y, Li J, Wang C, Li S, Liu M, Wang X.Trichinella spiralis: inflammation modulator. J Helminthol. 2020 Sep 21;94:e193. doi: 10.1017/S0022149X20000802. PMID: 32951619. [12] Ding J, Liu X, Tang B, Bai X, Wang Y, Li S, Li J, Liu M, Wang X. Murine hepatoma treatment with mature dendritic cells stimulated by Trichinella spiralis excretory/secretory products. Parasite. 2020;27:47. doi:10.1051/parasite/2020045. Epub 2020 Jul 21. PMID: 32692308; PMCID: PMC7373160. [13] Tang B, Liu X, Liu M, Bai X, Wang Y, Ding J, Wang X. Effects of TLR agonists on immune responses in Trichinella spiralis infected mice. Parasitol Res. 2020 Aug;119(8):2505-2510. doi: 10.1007/s00436-020-06747-8. Epub 2020 Jun 13. PMID: 32535733; PMCID: PMC7292931. [14] Liu XD, Wang XL, Bai X, Liu XL, Wu XP, Zhao Y, Sun SM, Yu L, Su XZ, Wang ZQ,Wang F, Liu MY. Oral administration with attenuated Salmonella encoding a Trichinella cystatin-like protein elicited host immunity. Exp Parasitol. 2014Jun;141:1-11.(1.85) [15] Feng S, Wu X, Wang X, Bai X, Shi H, Tang B, Liu X, Song Y, Boireau P, Wang F, Zhao Y, Liu M. Vaccination of mice with an antigenic serine protease-like proteinelicits a protective immune response against Trichinella spiralis infection. J Parasitol. 2013 Jun;99(3):426-32. (1.32) 中文论文:(2017-2020) [1] 李仕存,丁静,刘晓雷,唐斌,白雪,王学林.旋毛虫感染诱导的宿主免疫对H22荷瘤小鼠肿瘤生长的影响[J].黑龙江畜牧兽医,2020(07):8-11+15+157. [2]王春,张平平,赵勇,唐斌,刘晓雷,白雪,李仕存,刘明远,王学林.上转发光免疫层析技术快速检测猪抗旋毛虫IgG抗体方法的建立[J].中国兽医学报,2019,39(05):931-935. 专利授权: [1]刘明远 王学林 刘晓雷 唐 斌 丁静 王洋 白雪 杨勇 王楠.猪旋毛虫病上转发光检测试剂盒,2021.810,中国,专利授权号:ZL 2019 1 0742899.7. [2]王学林;刘明远;刘晓雷;唐斌;丁静;王洋;白雪;杨勇;王楠;一种人兽共患旋毛虫病免疫调控的预防、治疗及诊断制剂,2022-09-09,中国,ZL201910742897.8。 [3] 王学林;刘明远;刘晓雷;唐斌;丁静;王洋;白雪;杨勇;王楠;用于猪旋毛虫病预防、治疗及诊断的旋毛虫ES复合诱导剂诱导的DC疫苗,2023年04-14,中国,ZL 2019 1 0742898.2。 . GenBank注册旋毛虫新基因序列28条 [1] Liu, M.Y., Wang, X.L., Fu, B.Q., Li, C.Y., Wu, X.P., Le Rhun, D., Chen, Q.J. and Boireau, P. EF066649 [2] Liu, M.Y., Wang, X.L., Fu, B.Q., Li, C.Y., Wu, X.P., Le Rhun, D., Chen, Q.J. and Boireau, P.EF066645 [3] Liu, M.Y., Wang, X.L., Fu, B.Q., Li, C.Y., Wu, X.P., Le Rhun, D., Chen, Q.J. and Boireau, P.EF066644 [4] Liu, M.Y., Wang, X.L., Fu, B.Q., Li, C.Y., Wu, X.P., Le Rhun, D., Chen, Q.J. and Boireau, P.EF066639 [5] Liu, M.Y., Wang, X.L., Fu, B.Q., Li, C.Y., Wu, X.P., Le Rhun, D., Chen, Q.J. and Boireau, P.EF066637 [6] Liu, M.Y., Wang, X.L., Fu, B.Q., Li, C.Y., Wu, X.P., Le Rhun, D., Chen, Q.J. and Boireau, P.EF066636 [7] Liu, M.Y., Wang, X.L., Fu, B.Q., Li, C.Y., Wu, X.P., Le Rhun, D., Chen, Q.J. and Boireau, P. EF066635 [8] Liu, M.Y., Wang, X.L., Fu, B.Q., Li, C.Y., Wu, X.P., Le Rhun, D., Chen, Q.J. and Boireau, P.EF066634 [9] Liu, M.Y., Wang, X.L., Fu, B.Q., Li, C.Y., Wu, X.P., Le Rhun, D., Chen, Q.J. and Boireau, P.EF066633 [10] Liu, M.Y., Wang, X.L., Fu, B.Q., Li, C.Y., Wu, X.P., Le Rhun, D., Chen, Q.J. and Boireau, P.EF066632 [11] Liu, M.Y., Wang, X.L., Fu, B.Q., Li, C.Y., Wu, X.P., Le Rhun, D., Chen, Q.J. and Boireau, P.EF066631 [12] Liu, M.Y., Wang, X.L., Fu, B.Q., Li, C.Y., Wu, X.P., Le Rhun, D., Chen, Q.J. and Boireau, P.EF066630 [13] Liu, M.Y., Wang, X.L., Fu, B.Q., Li, C.Y., Wu, X.P., Le Rhun, D., Chen, Q.J. and Boireau, P.EF066629 [14] Liu, M.Y., Wang, X.L., Fu, B.Q., Li, C.Y., Wu, X.P., Le Rhun, D., Chen, Q.J. and Boireau, P.EF041144 [15] Liu, M.Y., Wang, X.L., Fu, B.Q., Li, C.Y., Wu, X.P., Le Rhun, D., Chen, Q.J. and Boireau, P.EF041143 [16] Liu, M.Y., Wang, X.L., Fu, B.Q., Li, C.Y., Wu, X.P., Le Rhun, D., Chen, Q.J. and Boireau, P.EF041142 [17] Liu, M.Y., Wang, X.L., Fu, B.Q., Li, C.Y., Wu, X.P., Le Rhun, D., Chen, Q.J. and Boireau, P.EF041141 [18] Liu, M.Y., Wang, X.L., Fu, B.Q., Li, C.Y., Wu, X.P., Le Rhun, D., Chen, Q.J. and Boireau, P.EF041139 [19] Liu, M.Y., Wang, X.L., Fu, B.Q., Li, C.Y., Wu, X.P., Le Rhun, D., Chen, Q.J. and Boireau, P. EF041138 [20] Liu, M.Y., Wang, X.L., Fu, B.Q., Li, C.Y., Wu, X.P., Le Rhun, D., Chen, Q.J. and Boireau, P. EF041137 [21] Liu, M.Y., Wang, X.L., Fu, B.Q., Li, C.Y., Wu, X.P., Le Rhun, D., Chen, Q.J. and Boireau, P.EF041136 [22] Liu, M.Y., Wang, X.L., Fu, B.Q., Li, C.Y., Wu, X.P., Le Rhun, D., Chen, Q.J. and Boireau, P.EF041135 [23] Liu, M.Y., Wang, X.L., Fu, B.Q., Li, C.Y., Wu, X.P., Le Rhun, D., Chen, Q.J. and Boireau, P.EF041134 [24] Liu, M.Y., Wang, X.L., Fu, B.Q., Li, C.Y., Wu, X.P., Le Rhun, D., Chen, Q.J. and Boireau, P.EF041133 [25] Liu, M.Y., Wang, X.L.,, Fu, B.Q., Li, C.Y., Wu, X.P., Le Rhun, D., Chen, Q.J. and Boireau, P.EF041132 [26] Liu, M.Y., Wang, X.L., Fu, B.Q., Li, C.Y., Wu, X.P., Le Rhun, D., Chen, Q.J. and Boireau, P.EF041131 [27] Liu, M.Y., Wang, X.L., Fu, B.Q., Li, C.Y., Wu, X.P., Le Rhun, D., Chen, Q.J. and Boireau, P.EF041130 [28] Guo, H., Wu, X.P., Wang, X.L., Li, L.R., Cui, G.Z., Xia, H.Q., Boireau, P., Sun, L., Deng, H.K., Yang, Z.D. and Liu, M.Y.EF041129
|