团队负责人
余国营教授，博士生导师，中科院百人计划，俄罗斯自然科学院院士、betway官方app 生命科学学院院长、卓越人才特聘教授，国家肺纤维化生物学过程及防控学科创新引智基地（111计划）主任，河南省-科技部共建细胞分化调控国家重点实验室培育基地主任，中国细胞生物学学会理事，河南省呼吸学科学术带头人。从事呼吸疾病（特发性肺纤维化、急性肺损伤和新冠肺炎等）的分子机制和药物研发研究，重点关注肺泡上皮细胞损伤及其所营造微环境的改变，靶向上皮细胞损伤修复过程，提出了“甲状腺激素缓解肺部损伤应激”理论，发现甲状腺激素的第四大功能。在国际上首次报道了甲状腺素能够显著抑制肺纤维化进展，研发的靶向药物GC-1已完成II期临床试验。小分子药物(MRG201)开发取得明显成效，正在进行临床前试验。在Nature Medicine、PNAS、AJRCCM、EMBO 等国际顶刊发表论文120 余篇，主持国家重点研发计划、科技部新冠防控专项，获得美国专利授权11项，中国专利受权1项。曾获得中国科协青年科学家奖、国际肺及肺泡纤维化组织青年科学家，肺纤维化基金会Albert科学家成就奖。
一、团队成员
团队现有骨干成员8名，其中，教授1人，副教授2人，博士5人（博士后2人）。近年来团队发展迅速，以团队带头人为核心，已汇聚形成了一支学历层次高、年龄结构、知识结构合理、密切协作的科研创新团队。
二、研究平台
团队依托betway官方app （一）国家肺纤维化生物学过程及防控学科创新引智基地(111计划)、 （二）平原实验室、 （三） 河南省-科技部共建细胞分化调控国家重点实验室培育基地、 （四）河南省生物工程研究应用中心、（五）河南省生物工程重点实验室、（六）河南省生物工程制药工程实验室、（七）河南省肺纤维化国际联合实验室、 （八）河南省纤维化生物学杰出外籍科学家工作室、（九）betway官方app 生物医学研究院，在肺纤维化细胞分化调控的分子生物学过程与机理研究、肺纤维化生物标志物的筛选与应用、靶向药物研发等领域开展研究，取得了一系列创新性成果。
三、研究方向及成果
（一）亚裔肺纤维化遗传与环境易感性研究
（二）肺纤维化细胞分化调控的分子生物学过程与机理研究
（三）肺纤维化生物标志物的筛选与应用
（四）靶向药物研发
四、科研成果
（一）发表国际学术论文 (2018-2023)：
1. Lan Wang; Zhongzheng Li; Ruyan Wan; Xin Pan; Bin Li; Huabin Zhao; Juntang Yang; Weiming Zhao; Shenghui Wang; Qiwen Wang; Peishuo Yan; Chi Ma; Hongmei Yuan; Ivan Rosas; Chen Ding; Baofa Sun; Guoying Yu*; Single-Cell RNA-seq Provides New Insights into Therapeutic Roles of Thyroid Hormone in the Idiopathic Pulmonary Fibrosis, Am J Respir Cell Mol Biol, 2023
2. Lan Wang; Minghui Zhu; Yan Li; Peishuo Yan; Zhongzheng Li; Xiuping Chen; Juntang Yang; Xin Pan; Huabin Zhao; Shenghui Wang; Hongmei Yuan; Mengxia Zhao; Xiaogang Sun; Ruyan Wan; Fei Li; Xiaobo Wang; Hongtao Yu; Ivan Rosas; Chen Ding; Guoying Yu*; Serum proteomics identify biomarkers associated with the pathogenesis of idiopathic pulmonary fibrosis, Molecular & Cellular Proteomics, 2023, 22(4):100524
3. Weiming Zhao; Lan Wang; Juntang Yang; Xinyu Chen; Xiaoshu Guo; Kai Xu; Ningdan Wang; Wenyu Zhao; Cong Xia; Hui Lian; Ivan Rosas; Guoying Yu*; Endothelial cell-derived MMP19 promotes pulmonary fibrosis by inducing E(nd)MT and monocyte infiltration, Cell Communication and Signaling, 2023, 21(56): 1-17
4. Weiming Zhao; Lan Wang; Yaxuan Wang; Hongmei Yuan; Mengxia Zhao; Hui Lian; Shuaichen Ma; Kai Xu; Zhongzheng Li; Guoying Yu*; Injured Endothelial Cell: A Risk Factor for Pulmonary Fibrosis, International Journal of Molecular Sciences, 2023, 24(10):8749
5. Juntang Yang; Chenxi Liang; Lulu Liu; Lan Wang; Guoying Yu*; High-Fat Diet Related Lung Fibrosis-Epigenetic Regulation Matters, Biomolecules, 2023, 13(3):558
6. Zhongzheng Li; Shenghui Wang; Huabin Zhao; Peishuo Yan; Hongmei Yuan; Mengxia Zhao; Ruyan Wan; Guoying Yu，Lan Wang; Artificial neural network identified the significant genes to distinguish Idiopathic pulmonary fibrosis, Scientific Reports, 2023, 13(1): 1-15
7. Wang, G; Tong, J; Li, Y; Qiu, X; Chen, A; Chang, C; Yu, G. Overview of CircRNAs Roles and Mechanisms in Liver Fibrosis. Biomolecules 2023, 13, 940.
8. Gaiping Wang, Anqi Chen , Yu Wu , Danlin Wang , Cuifang Chang , Guoying Yu *. Fat storage-inducing transmembrane proteins: beyond mediating lipid droplet formation. Cellular & Molecular Biology Letters. 2022，27(1)：98.
9. Lan Wang; Wenyu Zhao; Cong Xia; Zhongzheng Li; Weiming Zhao; Kai Xu; Ningdan Wang; Hui Lian; Ivan O. Rosas; Guoying Yu ; TRIB3 Mediates Fibroblast Activation and Fibrosis though Interaction with ATF4 in IPF, International Journal of Molecular Sciences, 2022, 23(24):15705
10. Lan Wang, Kai Xu, Ningdan Wang, Linke Ding, Wenyu Zhao, Ruyan Wan, Weiming Zhao, Xiaoshu Guo, Xin Pan, Juntang Yang, Ivan Rosas and Guoying Yu*. Fenbendazole attenuates bleomycin-Induced pulmonary fibrosis in mice via suppression of fibroblast-to-myofibroblast differentiation. Int. J. Mol. Sci. 2022,23, 14088.
11. Lan Wang, Ruyan Wan, Xinyu Chen, Xiaoshu Guo, Zhongzheng Li, Weiming Zhao, Peishuo Yan, Guoying Yu*. Inhibition of MAD2L1 mediates pulmonary fibrosis through impairment of mitochondrial function and induction of cell senescence. 2022, Article ID 9663354, 13
12. Maurizio Chioccioli, Subhadeep Roy, Rachel Newell, Linda Pestano, Brent Dickinson, Kevin Rigby, Jose Herazo-Maya, Gisli Jenkins, Steward Ian, Gauri Saini, Simon R. Johnson, Rebecca Braybrooke, Guoying Yu, Maor Sauler, Farida Ahangari, Shuizi Ding, Joseph DeIuliis, Nachelle Aurelien, Rusty L. Montgomery, and Naftali Kaminski. A lung targeted miR-29 mimic as a therapy for pulmonary fibrosis. eBioMedicine 2022;85: 104304. https://doi.org/10.1016/j.ebiom.2022.104304
13. Chunyan Zhang, Caifang Sun, Yabin Zhao, Qiwen Wang, Jianlin Quo, Bingyu Ye*, GuoYing Yu*. Overview of microRNAs as diagnostic and prognostic biomarkers for high-incidence cancers in 2021. International Journal of Molecular Sciences, 2022, 23(19): 11389.
14. Chunyan Zhang, Yabin Zhao, Qiwen Wang, Jianru Qin, Bingyu Ye, Cunshuan Xu*, GuoYing Yu*. Overexpression of miR-125a-5p inhibits hepatocyte proliferation through the STAT3 regulation in vivo and in vitro. International Journal of Molecular Sciences, 2022, 23: 8661
15. Bingyu Ye, Wenlong Shen, Chunyan Zhang, Mengli Yu, Xinru Ding, Man Yin, Yahao Wang, Xinjie Guo, Ge Bai, Kailin Lin, Shu Shi, Ping Li, Yan Zhang, Guoying Yu*, Zhihu Zhao*. The role of ZNF143 overexpression in rat liver cell proliferation. BMC Genomics, 2022, 23: 483.
16. Deming Li, Xiaoshu Guo, Wenyu Zhao , Jingyu Chen , Cong Xia , Guoying Yu*. Genome-wide DNA methylation dynamics in carbon tetrachloride-induced mice liver fibrosis Iran J Basic Med Sci 2023; 26: 85-92.
17. Chang C, Wang D, Xi L, Guo X, Wang G, Yu G*. The orphan GPR50 receptor interacting with TβRI induces G1/S-phase cell cycle arrest via Smad3-p27/p21 in BRL-3A cells. Biochem Pharmacol. 2022 Aug;202:115117. doi: 10.1016/j.bcp.2022.115117. Epub 2022 Jun 6. PMID: 35671788
18. Wang Y, Gong W, Zhou H, Hu Y, Wang L, Shen Y, Yu Guoying, Cao J. A novel miRNA from egg-derived exosomes of Schistosoma japonicum promotes liver fibrosis in murine schistosomiasis. Front. Immunol., 27 April 2022| https://doi.org/10.3389/fimmu.2022.860807.
19. Dong Yajuan, Zhao Yongjuan, Li Shenwei, Wan Zhenzhou, Lu Renfei, Yang Xianguang, Yu Guoying, Reboud Julien, Cooper Jonathan M, Tian Zhengan, Zhang Chiyu*. Multiplex, variant-tolerant, real-time RT-LAMP for SARS-CoV-2 detection using HFman probe. ACS Sensors, 2022. 25;7(3):730-739. DOI: 10.1021/acssensors.1c02079
20. Dong Y, Wan Zhengzhou, Li Shenwei, Wang Jian-Hua, Jin Xia, Yu Guoying*, Zhang Chiyu*. Genomic phylogenetic analyses of four major Hand, Foot and Mouth Disease-related Enteroviruses. Acta virologica. 2022. 66(1):27-38. DOI: 10.4149/av_2022_104
21. Zhang Y, Yu Guoying, Kaminski N, Lee PJ.PINK1 mediates the protective effects of thyroid hormone T3 in hyperoxia-induced lung injury. AJP Lung Cellular and Molecular Physiology, 320(2), 2021 DOI: 10.1152/ajplung.00598.2020
22. Wu MengLi, Liu FengLiang, Sun Jing, Li Xin, He Xiaoyan, Zheng Hongyi ,Zhou Yanheng, Qin Qihong, Chen Ling, Yu Guoying, Chang Junbiao, Jin Xia, Zhao Jincun, Chen Xinwen, Yong Tangzheng and Wang Jian-Hua*. SARS-CoV-2-triggered mast cell rapid degranulation induces alveolar epithelial inflammation and lung injury. Signal transduction and targeted therapy, 2021.Dec.17;6(1), 1-15. https://doi.org/10.1038/s41392-021-00849-0.
23. Dong Y, Wu X, Li S, Lu R, Li Y, Wan Z, Qin J, Yu Guoying, Jin X, Zhang C.Comparative evaluation of 19 reverse transcription loop-mediated isothermal amplification assays for detection of SARS-CoV-2. Scientific Reports 11: 2936, 2021. DOI:10.1038/s41598-020-80314
24. Yang J, Pan X, Wang L, Yu Guoying*.Alveolar cells under mechanical stressed niche: critical contributors to pulmonary fibrosis. Molecular medicine 2020, 26(1).
25. Zhang F, Yang B, Wang Y, Zhu J, Liu J, Yu Guoying, Qin J, Song W, Ding C.Time- and dose-resolved proteome of PM (2.5)-exposure-induced lung injury and repair in rats. J Proteome Res 2020 Aug 7;19(8):3162-3175.
26. Yang X, Chen X, Ding C, Bai Z, Zhu J, Sun G, Yu Guoying*.Epidemiological investigation and prevention control analysis of the longitudinal distribution of COVID-19 in Henan Province, China. mSphere 2020, 5(5).
27. Ye B, Yang G, Li Y, Zhang C, Wang Q, Yu Guoying*. ZNF143 in chromatin looping and gene regulation. Front Genet 2020, 11.
28. Nikos Xylourgidis, Kisuk Min, Farida Ahangari, Guoying Yu, Jose D. Herazo-Maya,Theodoros Karampitsakos, Vassilis Aidinis, Leonhard Binzenhöfer, Anton M. Bennett ,Naftali Kaminski, Argyrios Tzouvelekis. Role of mitogen activated-kinase (MAPK)-phosphatase (MKP)-5 in pulmonary fibrosis, Am J Physiol Lung Cell Mol Physiol. 2019 Sep 4. doi: 10.1152/ajplung.00264.2018
29. Yin L, Wang Y, Lin Y, Yu Guoying, Xia Q. Explorative analysis of the gene expression profile during liver regeneration of mouse: a microarray-based study. Artificial cells, nanomedicine, and biotechnology 2019, 47(1):1113-1121
30. Zhang C, Ye B, Wei J, Wang Q, Xu C, Yu Guoying*. MiR-199a-5p regulates rat liver regeneration and hepatocyte proliferation by targeting TNF-α TNFR1/TRADD/ CASPASE8/CASPASE3 signaling pathway. Atif Cells Nanomed Biotechnol. 2019;47(1):4110-4118
31. Lan Wang，Ming Lu Xu，Ling Xin，Chi Ma，Guoying Yu. Oxidative stress induced apoptosis mediated anticancer activity of Rhus typhina fruits extract in human colon cancer. Medicinal Chemistry Research, 2019, (28), 6, 917–925
32. Wang Q, Ye B, Wang P, Yao F, Zhang C, Yu Guoying*. Overview of microRNA-199a regulation in Cancer. Cancer Management 2019; 11: 10327–10335
33. Yin L, Wang Y, Guo X, Xu C, Yu Guoying*. Comparison of gene expression in liver regeneration and hepatocellular carcinoma formation, Cancer Management and Research 2018:10 5691–5708
34. Wandi Zhu , Song Li , Chao Wang , Guoying Yu , Mark R Prausnitz , Bao-Zhong Wang. Enhanced immune responses conferring cross-protection by skin vaccination with a tri-component influenza vaccine using a microneedle patch. Front. Immunol. 9:1705. doi: 10.3389/fimmu.2018.01705
35. Zhu W, Li S, Wang C, Yu Guoying, Prausnitz MR, Wang BZ. Enhanced Immune Responses Conferring Cross-Protection by Skin Vaccination with a Tri-Component Influenza Vaccine Using a Microneedle Patch. Front Immunol. 2018 Jul 30;9:1705. doi: 10.3389/fimmu.2018.01705. PMID: 30105019; PMCID: PMC6077188.
36. Deng L, Chang TZ, Wang Y, Li S, Wang S, Matsuyama S, Yu Guoying, Compans RW, Li JD, Prausnitz MR, Champion JA, Wang BZ. Heterosubtypic influenza protection elicited by double-layered polypeptide nanoparticles in mice. Proc Natl Acad Sci U S A. 2018 Aug 14;115(33):E7758-E7767. doi: 10.1073/pnas.1805713115. Epub 2018 Jul 31. PMID: 30065113; PMCID: PMC6099848.
37. Zhang X, Jin Z, Shen M, Chang Z, Yu Guoying, Wang L, Xia X. Accumulation of polyethylene microplastics induces oxidative stress, microbiome dysbiosis and immunoregulation in crayfish, Fish and Shellfish Immunology (2022), doi: https://doi.org/10.1016/j.fsi.2022.05.005
38. Yuyuan Zhang , Mengguo Han , Xiaoxue Sun , Guojun Gao , Guoying Yu, Liong Huang, Ying Chen. EGCG Promotes Neurite Outgrowth through the Integrinβ1/FAK/p38 Signaling Pathway after Subarachnoid Hemorrhage. Evid Based Complement Alternat Med. 25;2021:8810414. doi: 10.1155/2021/8810414.
39. Guoying Yu, Gabriel Iberra, Naftali Kaminksi. Fibrosis: Lessons from OMICS analyses of the human lung [J]. Matrix Biology 2018.68-69: 422-434
40. Guoying Yu; Tzouvelekis Argyris; Graham Morven; Liu Xinran; Homer Robert J.; Scanlan Thomas S.; Mannam Praveen; Lee Patty J.; Herzog Erica L.; Bianco Antonio C.; Kaminski Naftali ; Thyroid hormone inhibits lung fibrosis in mice by improving epithelial mitochondrial function, Nature Medicine, 2018, 24(1): 39-49.
（二）中国专利：
1、甲状腺激素及其药学上可接受的盐或前药在制备治疗和/或预防皮肤疾病的药物中的应用。授权公告号：CN 106983738 B
2、特发性肺纤维化疾病诊断标志物及其制备诊断或预后工具中的应用。201911277110.1
3、特发性肺纤维化疾病诊断标志物CBR1及其制备诊断或预后工具中的应用。 202011218094.1
4、特发性肺纤维化疾病诊断标志物CCT6A及其制备诊断或预后工具中的应用。202011218095.6
5、特发性肺纤维化血浆蛋白标志物及其在制备检测试剂或诊断工具中的应用。202210506078.5
（三）美国专利：
1、Methods of Treating or Preventing Acute Respiratory Distress Syndrome. Pub.No: 20210008020
2、Compositions and Methods of Treating or Preventing Fibrotic Lung Diseases. Pub.No: 20200113863
（四）科研项目（2018-2023）：
序号 |
课题名称 |
负责人 |
起止时间 |
类别 |
1 |
甲状腺激素对肺 纤维化的治疗作用与机理研究 |
余国营 |
2020-2023 |
科技部, 国家重点研发计划 |
2 |
基于S蛋白受体结合结构域（RBD）的 新冠肺炎病毒疫苗研发及肺纤维化控制 |
余国营 |
2020-2021 |
科技部, 外国专家引进计划新冠肺炎防控专项 |
3 |
肺纤维化新药GC-1研发 |
余国营 |
2021-2024 |
河南省新乡市重大科技创新专项 |
4 |
训练免疫通过PDK1调控肺泡巨噬细胞糖酵解参与急性肺损伤的作用及其机制研究 |
孙志恒 |
2023-2025 |
国家自然科学基金 |
5 |
器官纤维化生物学过程及防控研究 |
王兰 |
2023-2027 |
河南省科技厅 |
6 |
多组学解析甲状腺激素调控肺纤维化的机制 |
王兰 |
2023-2024 |
河南省科技厅 |
7 |
HMGCS2介导的脂代谢重编程在肺纤维化中的作用及机制研究 |
杨钧棠 |
2020-2022 |
河南省自然科学基金 |
8 |
靶向HMGCS2介导的肺泡2型上皮细胞线粒体稳态异常在肺纤维化治疗中的作用及机制 |
杨钧棠 |
2019-2021 |
河南省高等学校重点科研项目基础研究计划 |
9 |
LRRC15通过自噬调节特发性肺纤维化的作用研究 |
王棋文 |
2021-2022 |
河南省高等学校重点科研项目基础研究计划 |
10 |
FBXO16作为肺纤维化生物标志物和治疗靶点的应用研究 |
李亚军 |
2022-2023 |
河南省科技攻关 |
11 |
特发性肺纤维化诊断血清标志物的确立 |
王兰 |
2021-2022 |
河南省科技攻关 |
12 |
LRRC15用于特发性肺纤维化的诊疗靶点研究betway官方app |
王棋文 |
2023-2025 |
河南省科技厅 |
13 |
单细胞测序解析T3治疗肺纤维化的新机制 |
王兰 |
2023-2024 |
国家教育部 |
14 |
肺纤维化标志物的研发 |
王兰 |
2023-2025 |
横向项目 |
