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心血管病相关抗体

马远方

2020年05月05日         作者:         访问:[]

  说明: http://hdcms.henu.edu.cn/_vsl/401D7AFEFA8BAE607DFD776AC366A6BA/74C9D3D5/1376

马远方,博士、博导、二级教授; 中国免疫学会理事、中国免疫学会基础免疫学专业委员会委员、河南省抗癌协会副理事长;抗体药物开发技术国家地方联合工程实验室创始人及首任主任;原基础医学院院长、医学院常务副院长;国家自然科学奖、863计划、国家重大新药创制会评专家;国家政府特殊津贴、河南省优秀专家及河南省优秀教师。主要从事原创抗体药物研发;主持在研和完成国家自然科学基金5项、重点项目1项、863计划及国家重大新药创制子项目3项、河南省杰出人才创新基金2项等;以第一完成人获河南省科技进步二等奖2项等;申报国家级国际发明专利20余项,获批国家发明专利12项。主编专著6部;发表学术论文200余篇,其中SCI 收录90余篇。

代表性成果Blocking the death checkpoint protein TRAIL improves cardiac function after myocardial infarction in monkeys, pigs, and rats. Sci Transl Med. 2020 Apr 22;12(540).

     在国际上首先提出TRAIL心梗治疗新靶点,并进行新药研发。

一、科研项目

1. sDR5-Fc融合蛋白对心梗后心脏免疫微环境的调控作用及机制,U22A20382, 国家自然基金联合重点项目255万元,2023.01-2026.12

2. 心肌细胞-成纤维细胞对话机制在糖尿病心肌纤维化中的作用及绞股蓝皂苷的干预研究 81970322, 国家自然科学基金,55万元,2020.01-2023.12,主持人。

3. 心肌梗死治疗性抗体药物迪尔辛的临床前研究。开封市重大科技专项,19ZD0072019.01-2021.12100万,主持人。

4. sDR5-Fc抗体融合蛋白对猪缺血-再灌注心肌的保护作用及机制。81670271,国家自然科学基金,2017.01.01-2020.12.31,57万,主持人。

5. 河南省肿瘤免疫工程创新型科技团队,30万,2015.01-2017.12,负责人。

6. 热休克转录因子4b(Hsf4b)对晶状体上皮细胞增生和分化的调控机制,81270985,国家自然科学基金,2013.01-2016.12, 70万,主持人。

7. 抗体研发关键技术及产品研发,2012AA02A302,国家863计划分课题,2012.01-2015.1222 万,主持人。

8. 人源抗体亲和力成熟、噬菌体抗体库、抗体效应功能提高, 2011ZX09506-004,国家重大新药创制科技重大专项子课题,2011.01-2013.12,40万,主持人。

9. 免疫工程创新团队,2012-2015260万。负责人。

10. OCILRP2T细胞活化中的协同刺激作用及其机制,30972687,国家自然基金,2010.01-2012.1233万,主持人。

11. 抗死亡受体5基因工程抗体研制及其抗肿瘤作用,WKJ2007-021,卫生部科研项目,2007.1-2009.1215万,主持人。

12. 人源化及全人抗体构建及优化技术,2006AA02A254,国家863重大专项子课题,2006.12-2010.1250万,主持人。

13. 抗肿瘤DR5单抗的人源化改造,074200510014,河南省杰出人才创新基金,2007.1-2009.1250万,主持人。

14. 诱导细胞凋亡的抗DR5单抗与DR5相互作用位点分析,30571697,国家自然基金,2006.1-2008.1226万,主持人。

15. 死亡受体5单抗在恶性肿瘤诊断治疗中的应用研究,0321001800,河南省杰出人才创新基金,2004.1-2006.1220万,主持人。

二、主要成果

1. TRAIL-R2的表达与肿瘤诊断、治疗及预后相关性研究,2008-J-152-R01/01,河南省科技进步奖,二等奖,200811月,第一名。

2. 抗死亡受体5单抗在恶性肿瘤诊断治疗中的应用,2007-J-147- R01/01,河南省科技进步奖,二等奖,200711月,第一名。

三、专利

  1. SDR5-FC FUSION PROTEIN MUTANT AND USE THEREOF,申请号:PCT/CN2016/081552Ma yuanfang ,Wang yaohuiZhang hailong, Wang mingli, Zhang jun, Liu guangchao, Li shulian, Dun guoqing, Hu yanzhong, Zhu weina

  2. sDR5-Fc融合蛋白突变体及其应用。专利号:ZL 201510510981.9,发明人:马远方 王耀辉 张海龙 王明丽 张军 刘广超 李淑莲 顿国庆 胡延忠 祝伟娜。授权时间2018.03.16,申请美国PCT

  3. sDR5蛋白或sDR5-Fc抗体融合蛋白作为心肌梗死治疗药物的应用。ZL 201210442685.6,授权时间:2014.5.7,发明人:马远方,王耀辉,王明丽, 张军, 刘广超,李淑莲,刘峰涛,胡延忠。

  4. 死亡受体5激动性多价抗体及其制备抗肿瘤药物中的应用,专利号:ZL201210457342.7. 授权时间:2013.10.30;发明人:马远方,刘峰涛,张军,李淑莲,刘广超。

  5. 新型死亡受体激动性多价抗体及其在制备抗肿瘤药物中的应用。ZL201310725221.0,授权时间:2019.5.17发明人:马远方 刘峰涛 柴立辉 张军 刘广超 李淑莲。

  6. sDR5-Fc抗体融合蛋白作为肾损伤治疗药物的应用。申请号:201610041751.7。发明人:马远方,王志增,张军,王耀辉,李小全。

  7. GDF11-Fc融合蛋白在治疗溃疡性结肠炎中的应用,申请号:201810008965.3发明人:马远方、王耀辉、王兰菊、张海龙、魏寅祥、王珍凤。

五、近年代表论文(corresponding author)

1. Chunxia Chen , Hao Zhang , Ran Xie , Yaohui Wang *, Yuanfang Ma*. Gut microbiota aggravate cardiac ischemia-reperfusion injury via regulating the formation of neutrophils extracellular traps.  2022 Aug 15;303:120670.doi: 10.1016/j.lfs.2022.120670.

2. Chen C, Hu H, Li X, Zheng Z, Wang Z*, Wang X, Zheng P, Cui F, Li G, Wang Y, Liu Z*, Ma Y*. Rapid Detection of Anti-SARS-CoV-2 antibody Using a Selenium Nanoparticle-based Lateral Flow Immunoassay. IEEE Trans Nanobioscience. 2021 Aug 18;PP. doi: 10.1109/TNB. 2022 Jan;21(1):37-43.

3. Hao Liu, Chunxia QiaoNaijing Hu , Zhihong Wang, Jing Wang , Jiannan Feng , Beifen Shen, Yuanfang Ma*,Longlong Luo*. High-Affinity Decoy PD-1 Mutant Screened from an Epitope-Specific Cell Library. Engineering2021.IF7.5

4. Wang Z, Zhou Q, Guo Y, Hu H, Zheng Z, Li S, Wang Y, Ma Y*. Rapid Detection of Ractopamine and Salbutamol in Swine Urine by Immunochromatography Based on Selenium Nanoparticles. Int J Nanomedicine. 2021 Mar 9;16:2059-2070. doi: 10.2147/IJN.S292648. eCollection 2021.

5. Zhizeng Wang , Zhi Zheng , Hangzhan Hu , Qianwen Zhou , Wei Liu , Xiaoquan Li , Zhigang Liu , Yaohui Wang , Yuanfang Ma*. A point-of-care selenium nanoparticle-based test for the combined detection of anti-SARS-CoV-2 IgM and IgG in human serum and blood. Lab Chip, 2020 Nov 10;20(22):4255-4261.

6. Zhang H, Ma Y, Cao R, Wang G, Li S, Cao Y, Zhang H, Liu M, Liu G, Zhang J, Li S, Wang Y, Ma Y*.Soluble uric acid induces myocardial damage through activating the NLRP3 inflammasome. J Cell Mol Med. 2020 Jun 18. J Cell Mol Med. 2020;24:8849–8861.

7. Wang Y, Zhang H, Wang Z, Wei Y, Wang M, Liu M, Wang X, Jiang Y, Shi G, Zhao D, Yang Z, Ren Z, Li J, Zhang Z, Wang Z, Zhang B, Zong B, Lou X, Liu C, Wang Z, Zhang H, Tao N, Li X, Zhang X, Guo Y, Ye Y, Qi Y, Li H, Wang M, Guo R, Cheng G, Li S, Zhang J, Liu G, Chai L, Lou Q, Li X, Cui X, Gao E, Dong Z, Hu Y, Chen YH, Ma Y. Blocking the death checkpoint protein TRAIL improves cardiac function after myocardial infarction in monkeys, pigs, and rats. Sci Transl Med. 2020 Apr 22;12(540). pii: eaaw3172. doi: 10.1126/scitranslmed.aaw3172.

8. Cao R, Ma Y, Li S, Shen D, Yang S, Wang X, Cao Y, Wang Z, Wei Y, Li S, Liu G, Zhang H, Wang Y, Ma Y.1,25(OH)2 D3 alleviates DSS-induced ulcerative colitis via inhibiting NLRP3 inflammasome activation. J Leukoc Biol. 2020 Apr 1. doi: 10.1002/JLB.3MA0320-406RR. [Epub ahead of print]

9. Zhang J, Cui WW, Du C, Huang Y, Pi X, Guo W, Wang J, Huang W, Chen D, Li J, Li H, Zhang J, Ma Y, Mu H, Zhang S, Liu M, Cui X, Hu Y. Knockout of DNase1l1l abrogates lens denucleation process and causes cataract in zebrafish.Biochim Biophys Acta Mol Basis Dis. 2020 May 1;1866(5):165724. doi: 10.1016/j.bbadis. 2020.165724. Epub 2020 Feb 12.

10. Lou Q, Li Y, Hou B, Liu Y, Zhang Y, Hao J, Ma Y. Heat shock transcription factor 1 affects kidney tubular cell migration by regulating the TGF‑β1‑Smad2/3 signaling pathway. Mol Med Rep. 2019 Nov;20(5):4323-4330. doi: 10.3892/mmr.2019.10689. Epub 2019 Sep 16.

11. Wu S, Li W, Wu Z, Cheng T, Wang P, Li N,4, Liang X1, Chi M, Zhang S, Ma Y, Li Y, Chai L.TNFAIP8 promotes cisplatin resistance in cervical carcinoma cells by inhibiting cellular apoptosis. Oncol Lett. 2019 May;17(5):4667-4674. doi: 10.3892/ol.2019.10076. Epub 2019 Feb 26.

12. Zhang J, Gao F, Du C, Wang J, Pi X, Guo W, Li J, Li H, Ma Y, Zhang W, Mu H, Hu Y, Cui X.A novel RP2 missense mutation Q158P identified in an X-linked retinitis pigmentosa family impaired RP2 protein stability.Gene. 2019 Jul 30;707:86-92. doi: 10.1016/j.gene.2019.05.006. Epub 2019 May 6.

13. Guo L, Cheng X, Chen H, Chen C, Xie S, Zhao M, Liu D, Deng Q, Liu Y, Wang X, Chen X, Wang J, Yin Z, Qi S, Gao J, Ma Y, Guo N, Shi M. Induction of breast cancer stem cells by M1 macrophages through Lin-28B-let-7-HMGA2 axis.Cancer Lett. 2019 Jun 28;452:213-225. doi: 10.1016/j.canlet.2019.03.032. Epub 2019 Mar 24.

14. Wang L,Wang Y,Wang Z, Qi Y, Zong B, Liu M, Li X, Zhang X, Liu C, Cao R, Ma Y. Growth differentiation factor 11 ameliorates experimental colitis by inhibiting NLRP3 inflammasome activation.Am J Physiol Gastrointest Liver Physiol. 2018 Sep 6. doi: 10.1152/ajpgi.00159.2018. [Epub ahead of print]

15. Lou Q, Hu Y, Ma Y, Dong Z. RNA interference may suppresses stress granule formation by preventing Argonaute 2 recruitment.Am J Physiol Cell Physiol. 2018 Nov 7. doi: 10.1152/ajpcell.00251.2018. [Epub ahead of print]

16. Cui X, Han J, Li J, Cui WW, Wu DD, Liu S, Xue W, Wang XX, Ma Y, Zhang J, Zhang J, Mu H Zhang F, Hu Y. Downregulation of heat shock factor 4 transcription activity via MAPKinase phosphorylation at Serine 299.Int J Biochem Cell Biol. 2018 Oct 11;105:61-69. doi: 10.1016/j.biocel.2018.10.003. [Epub ahead of print]

17. Zhang H, Chen X, Zong B, Yuan H, Wang Z, Wei Y, Wang X, Liu G, Zhang J, Li S, Cheng G, Wang Y, Ma Y.Gypenosides improve diabetic cardiomyopathy by inhibiting ROS-mediated NLRP3 inflammasome activation. J Cell Mol Med. 2018 Jul 11. doi: 10.1111/jcmm.13743. [Epub ahead of print]

18. Wang W, Shi Q, Dou S, Li G, Shi X, Jiang X, Wang Z, Yu D, Chen G, Wang R, Xiao H, Hou C, Feng J, Shen B, Ma Y, Han G. Negative regulation of Nod-like receptor protein 3 inflammasome activation by T cell Ig mucin-3 protects against peritonitis.Immunology. 2018 ;153(1):71-83.

19. Liu RM, Sun DN, Jiao YL, Wang P, Zhang J, Wang M, Ma J, Sun M, Gu BL, Chen P, Liu K, Ma H, Gao SG, Ma YF, Qi YJ. Macrophage migration inhibitory factor promotes tumor aggressiveness of esophageal squamous cell carcinoma via activation of Akt and inactivation of GSK3β. Cancer Lett. 2018 Jan 1;412:289-296.

20. Ma N, Zhang Y, Liu Q, Wang Z, Liu X, Zhu G, Yu D, Han G, Chen G, Hou C, Wang T, Ma Y, Shen B, Li Y, Xiao H, Wang R. B cell activating factor (BAFF) selects IL-10-B cells over IL-10+B cells during inflammatory responses. Mol Immunol. 2017 May;85:18-26.

21. Li X, Zhang Q, Shi Q, Liu Y, Zhao K, Shen Q, Shi Y, Liu X, Wang C, Li N, Ma Y, Cao X. Demethylase Kdm6a epigenetically promotes IL-6 and IFN-β production in macrophages. J Autoimmun. 2017 Jun;80:85-94.

22. Chen H, Zhang W, Cheng X, Guo L, Xie S, Ma Y, Guo N, Shi M.β2-AR activation induces chemoresistance by modulating p53 acetylation through upregulating Sirt1 in cervical cancer cells.Cancer Sci. 2017 May 12. doi: 10.1111/cas.13275. [Epub ahead of print]

23. Y Li, T Zhou, Y Wang, C Ning, Z Lv, G Han, JC Morris, EN Taylor, R Wang, H Xiao, C Hou, Y Ma, B Shen, J Feng, R Guo, Y Li and G Chen.The protumorigenic potential of FTY720 by promoting extramedullary hematopoiesis and MDSC accumulation. Oncogene (2017), 1–12

24. Yinan Jiang, Xiaoyan Chen, Mengya Fan, Hui Li, Weina Zhu, Xi Chen,Chenghua Cao, Rui Xu, Yaohui Wang, Yuanfang Ma.TRAIL facilitates cytokine expression and macrophage migrationduring hypoxia/reoxygenation via ER stress-dependent NF- Bpathway. Molecular Immunology.2017;82:123-136.

25. SILEI ZHOU, HUANLING CAO, YAWEI ZHAO, XINYING LI, JIYAN ZHANG, CHUNMEI HOU, YUANFANG MA and QINGYANG WANG. RACK1 promotes hepatocellular carcinoma cell survival via CBR1 by suppressing TNF-α-induced ROS generation. ONCOLOGY LETTERS 2016;12: 5303-5308.

26. Wang Y, Jiang Y, Zhou J, Song W, Li J, Wang M, Chen J, Xu R, Zhang J, Ma F, Chen YH, Ma Y.Hepatitis C virus promotes hepatocellular carcinogenesis by targeting TIPE2, a new regulator of DNA damage response. Tumour Biol. 2016 Sep 30.


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