張建民

何維&張建民課題組

1.  招生導師

        

何維教授，德國海德堡大學(xué)醫學(xué)博士。中國醫學(xué)科學(xué)院基礎醫學(xué)研究所，北京協(xié)和醫學(xué)院免疫學(xué)系主任，教授，博士生導師。中國農工民主黨黨員，中國農工民主黨十五屆中央專(zhuān)職副主席，中國人民政治協(xié)商會(huì )議第十二屆全國委員會(huì )副秘書(shū)長(cháng)、常務(wù)委員。

張建民教授，北京協(xié)和醫學(xué)院免疫學(xué)博士，先后在耶魯大學(xué)和約翰霍普金斯大學(xué)任博士后、講師、助理教授，現任中國醫學(xué)科學(xué)院基礎醫學(xué)研究所/北京協(xié)和醫學(xué)院基礎學(xué)院免疫學(xué)系教授、“協(xié)和學(xué)者”特聘教授、博士生導師。

陳慧副教授，本科就讀于北京師范大學(xué)，北京協(xié)和醫學(xué)院免疫學(xué)博士，美國賓夕法尼亞大學(xué)病原與實(shí)驗醫學(xué)系訪(fǎng)問(wèn)學(xué)者。曾獲免疫學(xué)青年學(xué)者獎，北京醫學(xué)會(huì )微生物與免疫學(xué)分會(huì )青年委員，中國醫藥生物技術(shù)協(xié)會(huì )醫藥生物技術(shù)臨床應用專(zhuān)業(yè)委員會(huì )第四屆委員會(huì )委員。現為中國醫學(xué)科學(xué)院基礎醫學(xué)研究所/北京協(xié)和醫學(xué)院基礎學(xué)院免疫學(xué)系副研究員，碩士生導師。

2.  課題組簡(jiǎn)介

課題組主要研究方向包括：gdT細胞在腫瘤的免疫監視中的作用及在抗腫瘤免疫治療中的應用；神經(jīng)退行性疾病的病理機制及神經(jīng)系統與免疫系統之間相互調節的作用機制；誘導多能干細胞的定向分化、干細胞外泌體的改造及在疾病中的應用。主持和參加國家重大、重點(diǎn)科技項目和中美、中日、中德國際合作項目50余項，在國內外期刊發(fā)表論文和綜述200余篇，主要研究成果發(fā)表在Cell，Nat Immunol，PNAS，Neuro Oncol，Blood，Cell Mol Immunol等知名雜志上。主編學(xué)術(shù)專(zhuān)著(zhù)6部，授權發(fā)明專(zhuān)利10項，獲得國家科技進(jìn)步二等獎2項，省部級科技進(jìn)步獎1項。

近年來(lái)課題組研究重心逐漸集中于臨床轉化應用研究上，與多家三甲醫院合作，積極推進(jìn)同種異體γδT細胞腫瘤過(guò)繼免疫治療的臨床試驗；另一方面，實(shí)現多項技術(shù)專(zhuān)利的轉讓?zhuān)e極推動(dòng)與企業(yè)的全面合作與融合，參與細胞治療領(lǐng)域共性技術(shù)和先進(jìn)關(guān)鍵技術(shù)的合作研發(fā)和臨床轉化。

3.  課題組成員介紹

許依，助理研究員，博士

胡愉，副主任技師，碩士

蔡孟華，博士后，博士

劉唱，博士后，博士

目前在讀博士生7名，碩士生6名。課題組為學(xué)生畢業(yè)后赴外繼續深造、進(jìn)入生物公司進(jìn)行科研轉化或者進(jìn)入科研院所和國家事業(yè)單位工作提供支持。

4.  課題組主要在研科研項目

5.  課題組代表性論文

1)    Wang W, Xu Y, Wang L, Zhu Z, Aodeng S, Chen H, Cai M, Huang Z, Han J, Wang L, Lin Y, Hu Y, Zhou L, Wang X, Zha Y, Jiang W, Gao Z, He W, Lv W, Zhang J. Single-cell profiling identifies mechanisms of inflammatory heterogeneity in chronic rhinosinusitis. Nat Immunol. 2022 Sep 22. doi: 10.1038/s41590-022-01312-0. Epub ahead of print. PMID: 36138182.

2)    Wang H, Chen H, Liu S, Zhang J, Lu H, Somasundaram R, Choi R, Zhang G, Ou L, Scholler J, Tian S, Dong L, Yeye G, Huang L, Connelly T, Li L, Huang A, Mitchell TC, Fan Y, June CH, Mills GB, Guo W, Herlyn M, Xu X. Costimulation of γδTCR and TLR7/8 promotes Vδ2 T-cell antitumor activity by modulating mTOR pathway and APC function. J Immunother Cancer. 2021 Dec;9(12):e003339. doi: 10.1136/jitc-2021-003339. PMID: 34937742; PMCID: PMC8705233.

3)    Chen H, Zhang J, He W. The role of microRNAs in γδ T cells: a long way to go. Cell Mol Immunol. 2021 Aug;18(8):2071-2072. doi: 10.1038/s41423-021-00711-x. Epub 2021 Jun 11. PMID: 34117372; PMCID: PMC8322083.

4)    You H, Dang G, Lu B, Zhang S, Li C, Wang L, Hu Y, Chen H, Zhang J, He W. Serum Sp17 Autoantibody Serves as a Potential Specific Biomarker in Patients with SAPHO Syndrome. J Clin Immunol. 2021 Apr;41(3):565-575. doi: 10.1007/s10875-020-00937-w. Epub 2021 Jan 3. PMID: 33392854; PMCID: PMC7921076.

5)    Fu Y, Wang D, Wang H, Cai M, Li C, Zhang X, Chen H, Hu Y, Zhang X, Ying M, He W, Zhang J. TSPO deficiency induces mitochondrial dysfunction, leading to hypoxia, angiogenesis, and a growth-promoting metabolic shift toward glycolysis in glioblastoma. Neuro Oncol. 2020 Feb 20;22(2):240-252. doi: 10.1093/neuonc/noz183. PMID: 31563962; PMCID: PMC7442372.

6)    Zhu Y, Zhang S, Li Z, Wang H, Li Z, Hu Y, Chen H, Zhang X, Cui L, Zhang J, He W. miR-125b-5p and miR-99a-5p downregulate human γδ T-cell activation and cytotoxicity. Cell Mol Immunol. 2019 Feb;16(2):112-125. doi: 10.1038/cmi.2017.164. Epub 2018 Feb 12. PMID: 29429995; PMCID: PMC6355834.

7)    Chen H, Zou M, Teng D, Hu Y, Zhang J, He W. Profiling the pattern of the human T-cell receptor γδ complementary determinant region 3 repertoire in patients with lung carcinoma via high-throughput sequencing analysis. Cell Mol Immunol. 2019 Mar;16(3):250-259. doi: 10.1038/cmi.2017.157. Epub 2018 Feb 5. PMID: 30886423; PMCID: PMC6460488.

8)    Chen H, He W. Human regulatory γδT cells and their functional plasticity in the tumor microenvironment. Cell Mol Immunol. 2018 Apr;15(4):411-413. doi: 10.1038/cmi.2017.73. Epub 2017 Aug 28. PMID: 28845043; PMCID: PMC6052840.

9)    Mo WX, Yin SS, Chen H, Zhou C, Zhou JX, Zhao LD, Fei YY, Yang HX, Guo JB, Mao YJ, Huang LF, Zheng WJ, Zhang W, Zhang JM, He W, Zhang X. Chemotaxis of Vδ2 T cells to the joints contributes to the pathogenesis of rheumatoid arthritis. Ann Rheum Dis. 2017 Dec;76(12):2075-2084. doi: 10.1136/annrheumdis-2016-211069. Epub 2017 Sep 2. PMID: 28866647; PMCID: PMC5705844.

10)    Mao Y, Yin S, Zhang J, Hu Y, Huang B, Cui L, Kang N, He W. A new effect of IL-4 on human γδ T cells: promoting regulatory Vδ1 T cells via IL-10 production and inhibiting function of Vδ2 T cells. Cell Mol Immunol. 2016 Mar;13(2):217-28. doi: 10.1038/cmi.2015.07. Epub 2015 Mar 16. PMID: 25942601; PMCID: PMC4786628.

11)    Li Z, Jiao Y, Hu Y, Cui L, Chen D, Wu H, Zhang J, He W. Distortion of memory Vδ2 γδ T cells contributes to immune dysfunction in chronic HIV infection. Cell Mol Immunol. 2015 Sep;12(5):604-14. doi: 10.1038/cmi.2014.77. Epub 2014 Sep 15. PMID: 25220734; PMCID: PMC4579648.

12)    Zheng J, Guo Y, Ji X, Cui L, He W. A novel antibody-like TCRγδ-Ig fusion protein exhibits antitumor activity against human ovarian carcinoma. Cancer Lett. 2013 Dec 1;341(2):150-8. doi: 10.1016/j.canlet.2013.07.036. Epub 2013 Aug 3. PMID: 23920126.

13)    Dai Y, Chen H, Mo C, Cui L, He W. Ectopically expressed human tumor biomarker MutS homologue 2 is a novel endogenous ligand that is recognized by human γδ T cells to induce innate anti-tumor/virus immunity. J Biol Chem. 2012 May 11;287(20):16812-9. doi: 10.1074/jbc.M111.327650. Epub 2012 Mar 20. PMID: 22433851; PMCID: PMC3351303.

14)    Mo C, Dai Y, Kang N, Cui L, He W. Ectopic expression of human MutS homologue 2 on renal carcinoma cells is induced by oxidative stress with interleukin-18 promotion via p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) signaling pathways. J Biol Chem. 2012 Jun 1;287(23):19242-54. doi: 10.1074/jbc.M112.349936. Epub 2012 Apr 9. PMID: 22493490; PMCID: PMC3365956.

15)     Zhang J, Wang Y, Chi Z, Keuss MJ, Pai YM, Kang HC, Shin JH, Bugayenko A, Wang H, Xiong Y, Pletnikov MV, Mattson MP, Dawson TM, Dawson VL. The AAA+ ATPase Thorase regulates AMPA receptor-dependent synaptic plasticity and behavior. Cell. 2011 Apr 15;145(2):284-99. doi: 10.1016/j.cell.2011.03.016. PMID: 21496646; PMCID: PMC3085003.

16)    Li X, Kang N, Zhang X, Dong X, Wei W, Cui L, Ba D, He W. Generation of human regulatory gammadelta T cells by TCRgammadelta stimulation in the presence of TGF-beta and their involvement in the pathogenesis of systemic lupus erythematosus. J Immunol. 2011 Jun 15;186(12):6693-700. doi: 10.4049/jimmunol.1002776. Epub 2011 May 11. PMID: 21562160.

17)    He X, Chen H, Wu D, Cui L, He W. Tandem-epitope peptide: a novel stimulator for gammadeltaT cells in tumor immunotherapy. Cancer Lett. 2010 Feb 1;288(1):86-93. doi: 10.1016/j.canlet.2009.06.024. Epub 2009 Aug 7. PMID: 19665289.

18)    Kong Y, Cao W, Xi X, Ma C, Cui L, He W. The NKG2D ligand ULBP4 binds to TCRgamma9/delta2 and induces cytotoxicity to tumor cells through both TCRgammadelta and NKG2D. Blood. 2009 Jul 9;114(2):310-7. doi: 10.1182/blood-2008-12-196287. Epub 2009 May 12. PMID: 19436053.

19)    Yu M, Wan M, Zhang J, Wu J, Khatri R, Chi T. Nucleoprotein structure of the CD4 locus: implications for the mechanisms underlying CD4 regulation during T cell development. Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3873-8. doi: 10.1073/pnas.0800810105. Epub 2008 Mar 5. Erratum in: Proc Natl Acad Sci U S A. 2008 Apr 29;105(17):6502. PMID: 18322012; PMCID: PMC2268827.