一、个人简介
教授,医学博士,中国疾病预防控制中心博士后,山东大学肝病研究所所长,山东大学齐鲁医院内科副主任,肝病科主任,教授,主任医师,博士生导师,中华医学会感染病学分会委员,中国医师协会感染科医师分会常务委员,中国肿瘤微创治疗技术创新战略联盟常务委员,吴阶平医学基金会微创介入医学专家委员会副主任委员,山东省医学会传染病专业委员会主任委员,山东省医师协会感染科医师分会名誉主任委员,第十届吴阶平医学研究奖-保罗·杨森药学研究奖三等奖获得者。《Liver international》、《Digestive Diseases and Sciences》、《Chinese Medical Journal》、《Clinical Nutrition》、《Journal of Medicinal Plants Research A 》、《中华医学杂志》、《世界华人消化杂志》等多家国内外期刊审稿专家,《中华传染病杂志》编委,《中华实验和临床病毒学杂志》执行编委,《中华临床感染病杂志》编委,《国际流行病学传染病学杂志》编委,《世界华人消化杂志》编委,《临床肝胆病杂志》编委,《胃肠病学和肝病学杂志》编委。
王凯教授勤于学习和实践,在博士研究生学习期间获校长奖学金;博士毕业后在中国疾病预防控制中心病毒基因工程国家重点实验室从事博士后研究工作,期间获中国博士后科学基金。1999年在日本研修病毒性肝炎防治。目前开展各种肝病诊治相关的临床应用和基础研究,近5年内承担国家科技重大专项、国家科技支撑计划、国家自然科学基金、山东省科技发展基金等多项国家和省部级课题,总经费约700万元。近年来获国家发明专利10项,多项科研成果获奖,多项科研成果转让给生产企业投产。在国内外学术核心期刊发表学术论文50 余篇,其中SCI收录31篇,主编《中西医结合肝胆病治疗学》、《肝胆病学》、《临床肝病治疗学》、《简明临床肝病学》专著4部。
二、主要研究方向
(1)肝病表观遗传分子分型和个体化诊断:建立了DNA甲基化分子标志物为基础的疾病诊断标准和评估体系,提高了包括肝衰竭、肝癌等重大肝病的个体化诊疗水平。结合肝病的临床特点,系统开发了肝病临床诊断和预后密切相关的甲基化诊断试剂盒,用于疾病诊断具有较高的准确率,获国家发明专利,已有四项科研成果经转让给生产企业,社会效益显著。
(2)肝病免疫细胞调控的基础和临床研究:系统开展慢性乙型肝炎的免疫研究,以Th17细胞、Th22细胞以及CTL细胞为重点,着眼于建立乙型肝炎表面抗原转阴的临床预警分子标志物,优化乙型肝炎的抗病毒治疗方案,提高乙型肝炎表面抗原转阴率,研究成果达到国际领先水平。
(3)氧化损伤在肝病中的基础和临床研究:通过临床流行病学方法和生物化学方法相结合,发现慢性乙型肝炎患者存在氧化损伤平衡状态紊乱,提出抗氧化损伤可能有助于慢性乙型肝炎患者高胆红素血症的治疗,应用于临床治疗,取得较好的临床效果。
(4)内病外治研究和保健产品研发,已有六项科研成果经转让给生产企业投产。
三、联系方式
地址:山东大学齐鲁医院肝病科, (济南市文化西路107号,邮编250012)
Tel. 086-531-82169596
E-mail: wangdoc2010@163.com
四、近年来以课题负责人承担的课题及发表论文、专利
1. 用于早期诊断肝癌的IGFBP7和XPO4基因甲基化检测试剂盒关键技术研究,山东省科技发展计划,2014.01-2016.12(项目编号:2014GSF118068)
2. DNA甲基化在HBV感染患者CD4+T细胞分化中的作用及机制研究。国家自然科学基金面上项目,2014.01-2017.12(项目编码:81371832)
3. 干扰素与阿德福韦酯联合治疗HBeAg阳性慢乙肝HBsAg阴转率的研究,国家十二五重大专项,2013.1-2015.12(项目编号:2013ZX10002001)
4. 甲基化标志物在乙型重型肝炎预警预测评估体系中的研究,国家十二五科技重大专项,2012.01-2015.12(编号:2012ZX10002007-002-006)
5. Bart蛋白调节Th17细胞分化的机制及其在慢性HBV感染中的作用研究,国家自然科学基金面上项目,58万元,2012.01-2015.12(编号:81171579)
6. Th17细胞在慢性HBV感染中的作用及其调控机制研究。山东省自然科学基金(面上项目),2010.11-2013.11(编号:ZR2010HM070)
7. 甲基化参与乙型病毒性肝炎重症化转归的机制研究,国家十一五科技重大专项,2008.10-2010.12(编号:2008ZX10002-007)
近年以通讯作者或第一作者发表文章(*为通讯作者):
1. Xiang-Fen Ji, Xin-You Li, Yu-Chen Fan, Ze-Hua Zhao, Shuai Gao, Feng-Kai Sun, Jing Zhao, kai wang*. Serum wnt5a is a predictor for the prognosis of acute on chronic hepatitis B liver failure. Biomarkers. 2014 Nov 21:1-9.
2. Shuai Gao, Shu-Ling Huan, Li-Yan Han, Feng Li, Xiang-Fen Ji, Xin-You Li, Yu-Chen Fan, kai Wang*. Overexpression of serum sST2 associate with poor prognosis in acute-on-chronic hepatitis B liver failure. Clin Res Hepatol Gastroenterol. 2014 Nov 11. pii: S2210-7401(14)00281-2. doi: 10.1016/j.clinre.2014.10.012. [Epub ahead of print]
3. Gao S, Ji XF, Li F, Sun FK, Zhao J, Fan YC, Wang K*. Aberrant DNA methylation of G-protein-coupled bile acid receptor Gpbar1 predicts prognosis of acute-on-chronic hepatitis B liver failure. J Viral Hepat. 2014 Jul 4. doi: 10.1111/jvh.12277. [Epub ahead of print].
4. Jian-Jun Zhang, Yu-Chen Fan, Ze-Hua Zhao, Jie Han, Li-Yuan Wang, Tao Li, Feng Zhang, Yan-Ping Yin, Lei-Hua Hu, Yang Yang, Feng-Kai Sun, Kai Wang*. Methylation of Suppressor of Cytokine Signaling 1 Gene Promoter Is Associated with Acute-on-Chronic Hepatitis B Liver Failure. Journal of viral hepatitis. 2014 Jul 21. doi: 10.1111/jvh.12286. [Epub ahead of print].
5. Xiang-Fen Ji, Yu-Chen Fan, Shuai Gao, Yang Yang, Jian-Jun Zhang, Kai Wang*. MT1M and MT1G promoter methylation as a biomarker for hepatocellular carcinoma. World Journal of Gastroenterology. 2014 Apr 28;20(16):4723-9.
6. Yang Yang, Yu-Chen Fan, Shuai Gao, Cheng-Yun Dou, Jian-Jun Zhang, Feng-Kai Sun, Kai Wang*. Methylated Cysteine Dioxygenase-1 Gene Promoter in Serum is A Potential Biomarker for Hepatitis B Virus-Related Hepatocellular Carcinoma. The Tohoku Journal of Experimental Medicine. 2014;232(3):187-94.
7. Jian-Jun Zhang, Yu-Chen Fan, Ze-Hua Zhao, Yang Yang, Cheng-Yun Dou, Shuai Gao, Kai Wang*. Prognoses of patients with acute-on-chronic hepatitis B liver failure are closely associated with altered SOCS1 mRNA expression and cytokine production following glucocorticoid treatment .Cellular & Molecular Immunology. 2014 Jul;11(4):396-404.
8. Li-Yan Han, Yu-Chen Fan, Nan-Nan Mu, Shuai Gao, Feng Li, Xiang-Fen Ji, Cheng-Yun Dou, Kai Wang*. Aberrant DNA Methylation of G-protein-coupled Bile Acid Receptor Gpbar1 (TGR5) is a Potential Biomarker for Hepatitis B Virus Associated Hepatocellular Carcinoma. Int J Med Sci 2014; 11(2):164-171.
9. Feng Li, Yu-Chen Fan, Shuai Gao, Feng-Kai Sun, Yang Yang, Kai Wang* Methylation of Serum Insulin-Like Growth Factor-Binding Protein 7 (IGFBP7) Promoter in Hepatitis B Virus Associated Hepatocellular Carcinoma. Genes, Chromosomes and Cancer. 2014 Jan;53(1):90-7
10. Shuai Gao, Yu-Chen Fan, Jing Zhao, Feng-Kai Sun, Jie Han, Ze-Hua Zhao, Kai Wang*. A model to predict antiviral treatment in HBeAg negative chronic hepatitis B with alanine aminotransferase ≤2upper limit of normal. Liver International. 2014 Aug;34(7):e229-37.
11. Feng Zhang, Yu-Chen Fan, Jing Zhao , Feng-Kai Sun , Ze-Hua Zhao ,Shuai Gao, Kai Wang*. Exportin 4 gene expression and DNA promoter methylation status in chronic hepatitis B virus infection. Journal of viral hepatitis. 2014 Apr;21(4):241-50.
12. Li-Yuan Wang, Yu-Chen Fan, Jing Zhao, Shuai Gao, Feng-Kai Sun, Jie Han, Yang Yang, Kai Wang*. Elevated expression of TIPE2 mRNA in peripheral blood mononuclear cells is associated with disease progression of acute-on-chronic hepatitis B liver failure. Journal of viral hepatitis. 2014 Jan;21(1):64-73
13. Ze-Hua Zhao, Yu-Chen Fan, Yang Yang, Kai Wang*.Association between RASSF1A promoter methylation and hepatocellular carcinoma: A meta-analysis. World Journal of Gastroenterology. 2013 Nov 7;19(41):7189-96.
14. Hong Ye, Li-Yuan Wang, Jing Zhao, Kai Wang*. Increased CD163 expression is associated with acute-on-chronic hepatitis B liver failure. World Journal of Gastroenterology. 2013 May 14;19(18):2818-25.
15. Tao Li, Xin-Ping Zhao, Li-Yuan Wang, Shuai Gao, Jing Zhao, Yu-Chen Fan, Kai Wang*. Glutathione S-transferase P1 correlated with oxidative stress in hepatocellular carcinoma. International Journal of Medical Sciences. 2013;10(6):683-90
16. Jing Zhao, Yu-Chen Fan, Feng-Kai Sun, Ze-Hua Zhao, Li-Yuan Wang, Lei-Hua Hu, Yan-Ping Yin, Tao Li, Shuai Gao, Kai Wang*. Peripheral Type I Interferon Receptor Correlated with Oxidative Stress in Chronic Hepatitis B Virus Infection. Journal of Interferon & Cytokine Research. 2013 May 10. [Epub ahead of print]
17. Bing Wang, Xin-Ping Zhao, Yu-Chen Fan, Jian-Jun Zhang, Jing Zhao, Kai Wang*. IL-17A but not IL22 Suppresses the Replication of Hepatitis B Virus mediated by over-expression of MxA and OAS mRNA in the HepG2.2.15 cell line. Antiviral research. 2013 Mar;97(3):285-92.
18. Qi Zhao, Yu-Chen Fan, Jing Zhao, Shuai Gao, Ze-Hua Zhao, Kai Wang*. DNA methylation patterns of PPAR gamma gene associated with liver fibrosis and inflammation in chronic hepatitis B. Journal of Viral Hepatitis. 2013 Jun;20(6):430-7.
Epigenetic modifications in hepatic stellate cells contribute to liver fibrosis. Tohoko Journal of Experimental Medicine. 2013,229(1):35-43.
19. Qi Zhao, Cheng-Yong Qin, Ze-Hua Zhao, Yu-Chen Fan, Kai Wang*.
20. Sun FK, Fan YC, Zhao J, Zhang F, Gao S, Zhao ZH, Sun Q, Wang K*. Detection of TFPI2 Methylation in the Serum of Hepatocellular Carcinoma Patients. Dig Dis Sci. 2013 Apr;58(4):1010-5.
21. Li Qi, Zhiqiang Zou, Liyuan Wang, Shuai Gao, Yuchen Fan, Bo Long, Yanmei Guo, Ailing Xu,Jie Han,Tao Li, Kai Wang*. Methylation of Glutathione-S-transferase M3 Promoter is Associated with Oxidative Stress in Acute-on-chronic Hepatitis B Liver Failure. Tohoku J Exp Med. 2012;228(1):43-51
22. Meng F, Wang K, Aoyama T, Grivennikov SI, Paik Y, Scholten D, Cong M, Iwaisako K, Liu X, Zhang M, Osterreicher CH, Stickel F, Ley K, Brenner DA, Kisseleva T. Interleukin-17 Signaling in Inflammatory Cells, Kupffer, and Hepatic Stellate Cells Exacerbates Liver Fibrosis in Mice. Gastroenterology. 2012 Sep;143(3):765-76
23. Zhao-Xia Qi, Li-Yuan Wang, Yu-Chen Fan, Jian-Jun Zhang, Tao Li, Kai Wang*. Increased peripheral RORα and RORγt mRNA expression is associated with acute-on-chronic hepatitis B liver failure. J Viral Hepat.2012 Nov;19(11):811-22.
24. Li-Yuan Wang, Qing-Hua Meng, Zhi-Qiang Zou, Yu-Chen Fan, Jie Han, Zhao-Xia Qi, Jian Ge, Ai-ling Xu, Si-Kui Wang, Kai Wang*. Increased Frequency of Circulating Th17 Cells in Acute-on-chronic Hepatitis B Liver Failure. Dig Dis Sci. 2012 Mar;57(3):667-74. Epub 2011 Oct 8.
25. Xiao-Peng Fan, Zhi-Qiang Zou, Bo Long, Yan-Mei Guo, Si-Kui Wang, De-Xing Jia, Ai-Ling Xu, Feng-Cai Li, Yu-Chen Fan, Kai Wang*. Enhanced Demethylation of Interferon-gamma Gene Promoter in Peripheral Blood Mononuclear Cells Is Associated with Acute-on-Chronic Hepatitis B Liver Failure. Tohoku J Exp Med 2011, 224:13-9.
26. Fanli Meng, Jiefei Wang, Jian Ge,Xiaopeng Fan, Bing Wang, Liyan Han, Tatiana Kisseleva, YongHan Paik, David A Brenner, Kai Wang*. Alteration of interferon-α/β receptors in chronic hepatitis B patients. Journal of clinical immunology. 2011 Jun;31(3):521-32.
27. Ling Gao, Jie-Fei Wang, Xiang Ming, Yu-Chen Fan, Zheng-Guo Zhang, Kai Wang*. Expression of Human Glucocorticoid Receptor in T Lymphocytes in Acute-on-Chronic Hepatitis B Liver Failure. Dig Dis Sci. 2011 Sep;56(9):2605-12. Epub 2011 Mar 5.
28. Li T, Meng QH, Zou ZQ, Fan YC, Long B, Guo YM, Hou W, Zhao J, Li Juan, Yu HW, Zhu YK, Wang K*. Correlation between Promoter Methylation of Glutathione-S-tranferase 1 P1 and Oxidative Stress in Acute-on-chronic Hepatitis B Liver Failure. Journal of Viral Hepatitis, 2011 Jul;18(7):e226-31
29. Ge J, Wang K*, Meng QH, Qi ZX, Meng FL, Fan YC. Implication of Th17 and Th1 cells in patients with chronic active hepatitis B. Journal of clinical immunology, 2010, 30(1):60-67
30. Xiao-Peng Fan, Kai Wang*, Yi Liu,Jie-Fei Wang. Plasma α-Tocopherol is Negatively Correlated with Hepatocyte Apoptosis in Chronic Hepatitis B Patients. Intern Med. 2009, 48: 1585-1593
31. K. Wang*, X. Fan, Y. Fan, B. Wang, L. Han, Y. Hou. Study on the function of circulating plasmacytoid dendritic cells in the immunoactive phase of patients with chronic genotype B and C HBV infection. Journal of Viral Hepatitis,2007,14:276-282
专利:
1. 专利号:ZL 95 1 10321.0
2. 专利号:ZL 95 1 10302.4
3. 专利号:ZL 96 1 15886.7
4. 专利号:ZL 96 1 15887.5
5. 专利号:ZL 97 1 05700.1
6. 专利号:ZL 97 1 05701.X
7. 专利号:ZL 95 1 10322.9
8. 专利号:ZL 94 1 14177.2
9. 专利号 ZL 201010589826.8
10. 专利号 201110001339.x