博士生导师
韩文玲 教授
一、个人简介:
韩文玲,女,1970年9月出生,山东龙口人。现任北京大学免疫学系教授,博士生导师,免疫学系副主任,北京大学人类疾病基因研究中心副主任。1998年,韩文玲利用SSH技术开始人类新细胞因子和免疫膜分子研究。在国际上,首次报道了新基因家族CMTM。在人类,该家族包括9个成员,即CKLF和CMTM1-8,在免疫系统、男性生殖系统发挥重要作用,并参与肿瘤的发生、发展。国内、外研究发现CMTM成员定位于网格蛋白包被的囊泡和内体中,调控EGFR、VE-Cadherin、PD-L1等膜分子的转运、降解,其中CMTM6/4稳定PD-L1,是潜在的肿瘤治疗新靶点。2008年,韩文玲与国家人类基因组北方研究中心合作,利用免疫组学技术鉴定新细胞因子和免疫膜分子,发现多个具有重要免疫调控功能的新分子。作为第一作者或责任作者发表SCI论文44篇,包括Cancer Res、Oncogene、J Immunol、Oncoimmunology等;申请发明专利12项。上述成果得到了国际同行验证和拓展,相关文章被Nature、Blood等引用。独立培养博士生20名,联合培养博士生4名,多名学生获北京大学优秀博士论文、北京大学及北京市优秀毕业生等荣誉。
二、研究方向:
新细胞因子和免疫膜分子的功能、机制与应用研究。细胞因子和膜分子介导免疫细胞间相互作用,具有重要的生理功能;此外,其是药物研发的关键靶点,2018年全球排名前10的最畅销药物中有7个是细胞因子或膜分子相关产品。因此,进行相关研究具有重要理论意义和潜在应用价值。我们在明确新细胞因子和膜分子的表达、功能基础上,深入研究其在肿瘤发生、发展、重塑肿瘤微环境及自身免疫病中的作用机制,推动临床转化:重组细胞因子、抗细胞因子或膜分子抗体、拮抗肽在肿瘤治疗中的研究;与PD-1、PD-L1抗体等免疫检查点阻断疗法、TKI靶向治疗的协同作用;重组细胞因子、抗体在银屑病、多发性硬化等自身免疫病中的应用。此外,我们与北京大学各附属医院开展了广泛深入合作,近5年合作单位以本室发现的新细胞因子和膜分子为基础,获得国自然重点项目等12项,总经费超过1000万。
三、教育、工作经历:
1989年9月-1994年7月,泰山医学院医疗系,获医学学士学位;
1994年9月-1999年7月,北京医科大学,导师马大龙教授,获医学博士学位;
1999年8月-2001年7月,北京大学医学部,讲师;
2001年8月-2006年7月,北京大学医学部,副教授;
2006年8月-至今,北京大学医学部,教授。
四、联系方式:
电话:010-82805479;电子信箱:hanwl@bjmu.edu.cn;通讯地址:北京市海淀区学院路38号,北京大学医学部基础医学院免疫学系,北京大学人类疾病基因研究中心,邮编:100191。
五、作为第一作者或通讯作者发表的SCI论文:
1. Han W#, Lou Y, Tang J, Zhang Y, Chen Y, Li Y, Gu W, Huang J, Gui L, Tang Y, Li F, Song Q, Di C, Wang L, Shi Q, Sun R, Xia D, Rui M, Tang J, Ma D*. Molecular cloning and characterization of chemokine-like factor 1 (CKLF1), a novel human cytokine with unique structure and potential chemotactic activity.Biochem J. 2001 Jul 1; 357(Pt 1):127-35.
2. Han W#, Ding P#, Xu M, Wang L, Rui M, Shi S, Liu Y, Zheng Y, Chen Y, Yang T, Ma D*. Identification of eight genes encoding chemokine-like factor superfamily members 1-8 (CKLFSF1-8) by in silico cloning and experimental validation.Genomics. 2003 Jun; 81(6):609-17.
3. Li T, Han W*, Yang T, Ding P, Rui M, Liu D, Wang Y, Ma D. Molecular cloning and identification of mouse Cklfsf2a and Cklfsf2b, two homologues of human CKLFSF2.Int J Biochem Cell Biol. 2006 Mar; 38(3):420-9.
4. Li T, Zhong J, Chen Y, Qiu X, Zhang T, Ma D, Han W*. Expression of chemokine-like factor 1 is upregulated during T lymphocyte activation.Life Sci. 2006 Jul 4; 9(6):519-24.
5. Zhong J, Wang Y, Qiu X, Mo X, Liu Y, Li T, Song Q, Ma D, Han W*. Characterization and expression profile of CMTM3/CKLFSF3.J Biochem Mol Biol. 2006 Sep 30; 39(5):537-45.
6. Wang Y, Li T, Qiu X, Mo X, Zhang Y, Song Q, Ma D, Han W*. CMTM3 can affect the transcription activity of androgen receptor and inhibit the expression level of PSA in LNCaP cells. Biochem Biophys Res Commun.2008, Jun 20; 371 (1): 54-8
7. Yu C#,Han W#,Shi T, Lv B, He Q, Zhang Y, Li T, Zhang Y, Song Q, Wang L, Ma D*. PTPIP51, a novel 14-3-3 binding protein, regulates cell morphology and motility via Raf-ERK pathway. Cell Signal. 2008 Dec; 20(12):2208-20.
8. Shao L, Guo X, Plate M, Li T, Wang Y, Ma D, Han W*. CMTM5-v1 induces apoptosis in cervical carcinoma cells.Biochem Biophys Res Commun. 2009 Feb 20; 379 (4):866-71.
9. Wang Y, Li J, Cui Y, Li T, Ng KM, Geng H, Li H, Shu XS, Li H, Liu W, Luo B, Zhang Q, Mok TS, Zheng W, Qiu X, Srivastava G, Yu J, Sung JJ, Chan AT, Ma D, Tao Q*, Han W*. CMTM3, Located at the Critical Tumor Suppressor Locus 16q22.1, is Silenced by CpG Methylation in Carcinomas and Inhibits Tumor Cell Growth through Inducing Apoptosis. Cancer Res 2009; 69: (12), 5194-5201
10. Guo X, Li T, Wang Y, Shao L, Zhang Y, Ma D, Han W*. CMTM5 induces apoptosis of pancreatic cancer cells and has synergistic effects with TNF-alpha. Biochem Biophys Res Commun. 2009; 387(1):139-42.
11. Shao L, Li T, Mo X, Majdic O, Zhang Y, Seyerl M, Schrauf C, Ma D, Stöckl J, Han W*. Expressional and functional studies of CKLF1 during dendritic cell maturation. Cell Immunol. 2010; 263(2):188-95.
12. Plate M, Li T, Wang Y, Mo X, Zhang Y, Ma D, Han W*. Identification and characterization of CMTM4, a novel gene with inhibitory effects on HeLa cell growth through inducing G2/M phase accumulation. Mol Cells. 2010 Apr; 29(4):355-61.
13. Li H, Guo X, Shao L, Plate M, Mo X, Wang Y, Han W*.CMTM5-v1, a four-transmembrane protein, presents a secreted form released via a vesicle-mediated secretory pathway. BMB Rep. 2010 Mar; 43(3):182-7.
14. Guo X, Zhang Y, Wang P, Li T, Fu W, Mo X, Shi T, Zhang Z, Chen Y, Ma D, Han W*. VSTM1-v2, a novel soluble glycoprotein, promotes the differentiation and activation of Th17 cells. Cell Immunol.2012 Jul; 278(1-2):136-42.
15. Li T, Wang W, Chen Y, Han W*. Preparation and characterization of monoclonal antibodies against VSTM1.Monoclon Antib Immunodiagn Immunother. 2013 Aug; 32(4):283-9.
16. Zhang Y, Wang JY, Han W*. A role for CMTM7 in BCR expression and survival in B-1a but not B-2 cells.Int Immunol. 2014 Jan;26(1):47-57.
17. Su Y, Lin Y, Zhang L, Liu B, Yuan W, Mo X, Wang X, Li H, Xing X, Cheng X, Dong B, Hu Y, Du H, Zhu Y, Ding N, Li J, Liu W, Ma Y, Qiu X, Ji J*, Han W*. CMTM3 inhibits cell migration and invasion and correlates with favorable prognosis in gastric cancer.Cancer Sci. 2014 Jan; 105(1):26-34.
18. Wang X, Wang W, Lin Z, Wang X, Li T, Yu J, Liu W, Tong Z, Xu Y, Zhang J, Guan L, Dai L, Yang Y, Han W*, Li R*.CARD9 mutations linked to subcutaneous phaeohyphomycosis and TH17 cell deficiencies.J Allergy Clin Immunol. 2014 Mar; 133(3):905-8.
19. Li H, Li J, Su Y, Fan Y, Guo X, Li L, Su X, Rong R, Ying J, Mo X, Liu K, Zhang Z, Yang F, Jiang G, Wang J, Zhang Y, Ma D, Tao Q*, Han W*. A novel 3p22.3 gene CMTM7 represses oncogenic EGFR signaling and inhibits cancer cell growth.Oncogene. 2014 Jun 12; 33(24):3109-18.
20. Pan W, Cheng Y, Zhang H, Liu B, Mo X, Li T, Li L, Cheng X, Zhang L, Ji J, Wang P, Han W*. CSBF/C10orf99, a novel potential cytokine, inhibits colon cancer cell growth through inducing G1 arrest. Sci Rep.2014 Oct 29; 4:6812.
21. Wang W, Li T, Wang X, Yuan W, Cheng Y, Zhang H, Xu E, Zhang Y, Shi S, Ma D, Han W*. FAM19A4 is a novel cytokine ligand of formyl peptide receptor 1 (FPR1) and is able to promote the migration and phagocytosis of macrophages.Cell Mol Immunol. 2015 Sep;12(5):615-24.
22. Li T, Guo X, Wang W, Mo X, Wang P, Han W*.V-set and transmembrane domain containing 1 is silenced in human hematopoietic malignancy cell lines with promoter methylation and has inhibitory effects on cell growth.Mol Med Rep. 2015 Feb; 11(2):1344-51.
23. Liang P, Wang X, Wang R, Wan Z, Han W*, Li R*. CARD9 deficiencies linked to impaired neutrophil functions against Phialophora verrucosa.Mycopathologia. 2015 Jun;179(5-6):347-57.
24. Fu W, Cheng Y, Zhang Y, Mo X, Li T, Liu Y, Wang P, Pan W, Chen Y, Xue Y, Ma D, Zhang Y, Han W*. The Secreted Form of Transmembrane Protein 98 Promotes the Differentiation of T Helper 1 Cells.J Interferon Cytokine Res. 2015 Sep;35(9):720-33.
25. Liu H, Wang X, Shi S, Chen Y, Han W*. Efficient production of FAM19A4, a novel potential cytokine, in a stable optimized CHO-S cell system.Protein Expr Purif. 2015 Sep;113:1-7.
26. Li T, Cheng Y, Wang P, Wang W, Hu F, Mo X, Lv H, Xu T*, Han W*. CMTM4 is frequently downregulated and functions as a tumour suppressor in clear cell renal cell carcinoma.J Exp Clin Cancer Res. 2015 Oct 16;34:122. doi: 10.1186/s13046-015-0236-4.
27. Liu B, Su Y, Li T, Yuan W, Mo X, Li H, He Q, Ma D, Han W*. CMTM7 knockdown increases tumorigenicity of human non-small cell lung cancer cells and EGFR-AKT signaling by reducing Rab5 activation.Oncotarget. 2015 Dec 1;6(38):41092-107.
28. Cheng Y, Wang X, Wang P, Li T, Hu F, Liu Q, Yang F, Wang J*, Xu T*, Han W*. SUSD2 is frequently downregulated and functions as a tumor suppressor in RCC and lung cancer.Tumour Biol. 2016 Jan 27.
29.Liu H, Zou X, Li T, Wang X, Yuan W, Chen Y, Han W*. Enhanced production of secretory glycoprotein VSTM1-v2 with mouse IgGκ signal peptide in optimized HEK293F transient transfection.J Biosci Bioeng. 2016 Feb;121(2):133-9.
30. Wang X, Liu H, Yuan W, Cheng Y, Han W*. Efficient production of CYTL1 protein using mouse IgGκ signal peptide in the CHO cell expression system.Acta Biochim Biophys Sin. 2016 Feb 27.
31. Wang X, Li T, Wang W, Yuan W, Liu H, Cheng Y, Wang P, Zhang Y, Han W*. Cytokine like-1 Chemoattracts Monocytes/Macrophages via CCR2. J Immunol. 2016 May 15;196 (10):4090-9.
32. Yuan W, Li T, Mo X, Wang X, Liu B, Wang W, Su Y, Xu L, Han W*. et al. Knockdown of CMTM3 promotes metastasis of gastric cancer via the STAT3/Twist1/EMT signaling pathway. Oncotarget. 2016 May 17;7(20):29507-19.
33. Yuan W, Liu B, Wang X, Li T, Xue H, Mo X, Yang S, Ding S*, Han W*.CMTM3 decreases EGFR expression and EGF-mediated tumorigenicity by promoting Rab5 activity in gastric cancer. Cancer Lett. 2017 Feb 1; 386:77-86.
34. Liu H, Zhang Y, Liu Z, Wang P, Mo X, Fu W, Liu W, Cheng Y, Han W*.LYG1 exerts antitumor function through promoting the activation, proliferation, and function of CD4+ T cells.Oncoimmunology. 2017 Mar 7;6(4):e1292195.
35. Li T, Wang W, Cheng Y, Han W*.Method for quantitative detection of FAM19A4 by flow cytometry using latex beads as solid carrier.J Biosci Bioeng. 2018 Mar;125(3):359-364.
36. Zhang K, Shi S, Han W*. Research progress in cytokines with chemokine-like function.
Cell Mol Immunol. 2018 Jul;15(7):660-662.Review.
37. Liu W, Li T, Wang P, Liu W, Liu F, Mo X, Liu Z, Song Q, Lv P, Ruan G, Han W*. LRRC25 plays a key role in all-trans retinoic acid-induced granulocytic differentiation as a novel potential leukocyte differentiation antigen.Protein Cell. 2018 Sep;9(9):785-798.
38. Wang X, Li T, Cheng Y, Wang P, Yuan W, Liu Q, Yang F, Liu Q, Ma D, Ding S*, Wang J*, Han W*. CYTL1 inhibits tumor metastasis with decreasing STAT3 phosphorylation. Oncoimmunology. 2019 Feb 18;8(5):e1577126.
39. Liu F, Liu X, Liu X, Li T, Zhu P, Liu Z, Xue H, Wang W, Yang X, Liu J, Han W*. Integrated Analyses of Phenotype and Quantitative Proteome of CMTM4 Deficient Mice Reveal Its Association with Male Fertility.Mol Cell Proteomics. 2019 Jun;18(6):1070-1
40. Xue H, Li T, Wang P, Mo X, Zhang H, Ding S, Ma D, Lv W*, Zhang J*, Han W*. CMTM4 inhibits cell proliferation and migration via AKT, ERK1/2, and STAT3 pathway in colorectal cancer.Acta Biochim Biophys Sin (Shanghai). 2019 Sep 6;51(9):915-924.
41. Liu Z, Liu Y, Li T, Wang P, Mo X, Lv P, Ge Q, Ma D, Han W*. Cmtm7 knockout inhibits B-1a cell development at the transitional (TrB-1a) stage.Int Immunol. 2019 Oct 16;31(11):715-728.
42. Liu Z, Liu Y, Li T, Wang P, Mo X, Lv P, Ma D, Han W*. CMTM7 plays key roles in TLR-induced plasma cell differentiation and p38 activation in murine B-1 B cells. Eur J Immunol. 2020 Jun;50(6):809-821.
43. Liu Z, Liu Y, Li T, Wang P, Mo X, Lv P, Ma D, Han W*. Essential role for Cmtm7 in cell-surface phenotype, BCR signaling, survival and Igμ repertoire of splenic B-1a cells. Cell Immunol. 2020 Jun;352:104100.
44. Deng W, Su Z, Liang P, Ma Y, Liu Y, Zhang K, Zhang Y, Liang T, Shao J, Liu X, Han W*, Li R*. Single-cell immune checkpoint landscape of PBMCs stimulated with Candida albicans. Emerg Microbes Infect. 2021 Dec;10(1):1272-1283.
六、代表性奖励:
1. 2002年,全国优秀博士论文奖及北京大学优秀博士论文一等奖;
2. 2002年,北京大学医学部优秀青年教师;
3. 2003年,第一届细胞因子与医学国际大会:最佳口头报告奖;
4. 2004年,第九届霍英东青年教师奖;
5. 2004年,作为第一完成人,获教育部自然科学二等奖;
6. 2005年,北京大学医学部及北京市青年岗位能手;
7. 2007年,教育部跨世纪优秀人才;
8. 2007年,第四届中国青年女科学家提名奖;
9. 2008年,北京市三八红旗手;
10. 2008年,北京大学医学部青年学者;
11. 2010年,北京大学医学部良师益友;
12. 2013年,北京大学基础医学院优秀SCI论文奖;
13. 2015年,北京大学优秀博士论文指导奖;
14. 2017年,北京大学优秀博士论文指导奖;
15. 2021年,北京大学医学部第十届女教职工之星;
16. 2021年,北京大学仲外医学奖。