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免疫學(xué)系

張建民

何維&張建民課題組

1.  招生導(dǎo)師


        


何維教授,德國海德堡大學(xué)醫(yī)學(xué)博士。中國醫(yī)學(xué)科學(xué)院基礎(chǔ)醫(yī)學(xué)研究所,北京協(xié)和醫(yī)學(xué)院免疫學(xué)系主任,教授,博士生導(dǎo)師。中國農(nóng)工民主黨黨員,中國農(nóng)工民主黨十五屆中央專職副主席,中國人民政治協(xié)商會議第十二屆全國委員會副秘書長、常務(wù)委員。

張建民教授北京協(xié)和醫(yī)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(xiàn)任中國醫(yī)學(xué)科學(xué)院基礎(chǔ)醫(yī)學(xué)研究所/北京協(xié)和醫(yī)學(xué)院基礎(chǔ)學(xué)院免疫學(xué)系教授、協(xié)和學(xué)者特聘教授、博士生導(dǎo)師。

陳慧副教授,本科就讀于北京師范大學(xué),北京協(xié)和醫(yī)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(yàn)醫(yī)學(xué)系訪問學(xué)者。曾獲免疫學(xué)青年學(xué)者獎,北京醫(yī)學(xué)會微生物與免疫學(xué)分會青年委員,中國醫(yī)藥生物技術(shù)協(xié)會醫(yī)藥生物技術(shù)臨床應(yīng)用專業(yè)委員會第四屆委員會委員。現(xiàn)為中國醫(yī)學(xué)科學(xué)院基礎(chǔ)醫(yī)學(xué)研究所/北京協(xié)和醫(yī)學(xué)院基礎(chǔ)學(xué)院免疫學(xué)系副研究員,碩士生導(dǎo)師。

2.  課題組簡介

課題組主要研究方向包括:gdT細(xì)胞在腫瘤的免疫監(jiān)視中的作用及在抗腫瘤免疫治療中的應(yīng)用;神經(jīng)退行性疾病的病理機(jī)制及神經(jīng)系統(tǒng)與免疫系統(tǒng)之間相互調(diào)節(jié)的作用機(jī)制;誘導(dǎo)多能干細(xì)胞的定向分化、干細(xì)胞外泌體的改造及在疾病中的應(yīng)用。主持和參加國家重大、重點(diǎn)科技項(xiàng)目和中美、中日、中德國際合作項(xiàng)目50余項(xiàng),在國內(nèi)外期刊發(fā)表論文和綜述200余篇,主要研究成果發(fā)表在CellNat ImmunolPNASNeuro OncolBloodCell Mol Immunol等知名雜志上。主編學(xué)術(shù)專著6部,授權(quán)發(fā)明專利10項(xiàng),獲得國家科技進(jìn)步二等獎2項(xiàng),省部級科技進(jìn)步獎1項(xiàng)。

近年來課題組研究重心逐漸集中于臨床轉(zhuǎn)化應(yīng)用研究上,與多家三甲醫(yī)院合作,積極推進(jìn)同種異體γδT細(xì)胞腫瘤過繼免疫治療的臨床試驗(yàn);另一方面,實(shí)現(xiàn)多項(xiàng)技術(shù)專利的轉(zhuǎn)讓,積極推動與企業(yè)的全面合作與融合,參與細(xì)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(zhuǎn)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(xù)深造、進(jìn)入生物公司進(jìn)行科研轉(zhuǎn)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(xiàng)目

項(xiàng)目來源

項(xiàng)目名稱

起止年月

國家自然科學(xué)基金面上項(xiàng)目

Toll樣受體激動劑對人γδT細(xì)胞抗腫瘤功能的促進(jìn)作用及機(jī)制研究

202001——202312

國家自然科學(xué)基金面上項(xiàng)目

γδT細(xì)胞過繼免疫治療晚期原發(fā)性肝細(xì)胞肝癌和復(fù)發(fā)或難治性非霍奇金淋巴瘤的最佳適應(yīng)癥的組合分子標(biāo)志研究

202001——202312

細(xì)胞生態(tài)海河實(shí)驗(yàn)室創(chuàng)新基金項(xiàng)目

γδT細(xì)胞精準(zhǔn)腫瘤免疫治療的新策略

202204——202404

國家自然科學(xué)基金面上項(xiàng)目

線粒體轉(zhuǎn)運(yùn)蛋白TSPO在急性呼吸窘迫癥發(fā)生發(fā)展中的作用

202101——202412

國家自然基金委聯(lián)合基金重點(diǎn)項(xiàng)目

實(shí)體腫瘤γδT細(xì)胞新型免疫療法的基礎(chǔ)理論和關(guān)鍵技術(shù)研究

202101——202412

醫(yī)科院創(chuàng)新工程項(xiàng)目

風(fēng)濕免疫性疾病的精準(zhǔn)防治策略研究

202110——202512

醫(yī)科院創(chuàng)新工程項(xiàng)目

傳染病動物模型資源庫

202110——202512

醫(yī)科院創(chuàng)新工程項(xiàng)目

特色實(shí)驗(yàn)細(xì)胞資源建設(shè)

202110——202512

國家自然科學(xué)基金面上項(xiàng)目

γδT細(xì)胞識別的腫瘤相關(guān)膜異位抗原的篩選驗(yàn)證,機(jī)制探究及以其為靶點(diǎn)的新型基因工程γδT細(xì)胞的療效評價(jià)

202301——202612

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.