基本信息 >>>
張大川
腸道菌群與造血免疫組
電話：021-63846590-771056
郵箱：[email protected]
研究方向與進(jìn)展 >>>
髓系細(xì)胞,，包括中性粒細(xì)胞,、單核細(xì)胞以及巨噬細(xì)胞,，是固有免疫系統(tǒng)的重要組成部分,，在對(duì)病原體的免疫防御以及炎癥性疾病的發(fā)生發(fā)展過程中起著重要作用,。這些細(xì)胞來源于骨髓中的造血系統(tǒng),，而造血干細(xì)胞（HSC）則是分化產(chǎn)生所有血液和免疫細(xì)胞譜系的始祖細(xì)胞。研究髓系免疫細(xì)胞在機(jī)體內(nèi)的運(yùn)輸,、招募與激活,，以及造血干細(xì)胞在骨髓中自我更新與分化命運(yùn)的調(diào)控機(jī)制，對(duì)于理解免疫與造血系統(tǒng)的功能,，炎癥性疾病以及惡性血液病的發(fā)生發(fā)展過程有著十分重要的意義,。
課題組致力于在分子、細(xì)胞和系統(tǒng)性層面探索造血干細(xì)胞和固有免疫細(xì)胞的調(diào)控機(jī)制,，解析腸道菌群和外周神經(jīng)系統(tǒng)在生理病理過程中的關(guān)鍵作用,。課題組的前期研究發(fā)現(xiàn)腸道菌群可以通過調(diào)節(jié)中性粒細(xì)胞在循環(huán)系統(tǒng)中的炎癥活性，誘導(dǎo)衰老表型,，影響炎癥性疾病的發(fā)生發(fā)展,。近期的研究表明腸道菌群可以通過調(diào)節(jié)骨髓巨噬細(xì)胞對(duì)紅細(xì)胞的吞噬控制骨髓微環(huán)境中的鐵元素供給，從而影響造血干細(xì)胞在應(yīng)激狀態(tài)下自我更新與分化的命運(yùn)決定,。另一方面,，課題組的前期研究揭示了交感神經(jīng)、感覺神經(jīng)以及神經(jīng)內(nèi)分泌系統(tǒng)對(duì)造血干細(xì)胞的動(dòng)員,、歸巢以及骨髓微環(huán)境的重要調(diào)控作用,。
實(shí)驗(yàn)室的研究方向主要包括：（1）微環(huán)境、腸道菌群對(duì)造血干細(xì)胞以及白血病發(fā)生發(fā)展的影響,；（2）腸道菌群的篩選,、編輯以及在血液和免疫系統(tǒng)疾病中的應(yīng)用；（3）外周神經(jīng)系統(tǒng)對(duì)造血干細(xì)胞與免疫細(xì)胞穩(wěn)態(tài),、遷移,、激活的調(diào)控。
研究組長(zhǎng)介紹 >>>
張大川,，本科畢業(yè)于南京大學(xué)生物科學(xué)系,，2016年在美國(guó)阿爾伯特愛因斯坦醫(yī)學(xué)院 (Albert Einstein College of Medicine) 獲得細(xì)胞生物學(xué)博士學(xué)位,，師從血液以及干細(xì)胞領(lǐng)域?qū)＜?/span>Paul Frenette教授,，并在其實(shí)驗(yàn)室從事博士后研究。 張大川在2021年獲得國(guó)家自然科學(xué)基金優(yōu)秀青年科學(xué)基金項(xiàng)目（海外）,，于2022年1月加入上海交通大學(xué)基礎(chǔ)醫(yī)學(xué)院病理生理系,，任課題組長(zhǎng),。研究工作主要聚焦于腸道菌群對(duì)造血、免疫系統(tǒng)的調(diào)控作用,，相關(guān)成果發(fā)表在Nature, Cell Stem Cell, Blood等國(guó)際知名期刊上,。
科研項(xiàng)目 >>>
1. 國(guó)家自然科學(xué)基金優(yōu)秀青年科學(xué)基金（海外），腸道菌群在免疫與造血系統(tǒng)中的調(diào)控作用 ,，2022,，在研，課題負(fù)責(zé)人
論文與專著 >>>
1. Pinho S, Wei Q, Maryanovich M, Zhang D, Balandrán JC, Pierce H, Nakahara F, Di Staulo A, Bartholdy BA, Xu J, Borger DK, Verma A, Frenette PS. VCAM1 confers innate immune tolerance on haematopoietic and leukaemic stem cells. Nat Cell Biol (2022), 24(3):290-298.
2. Zhang D*, Gao X, Li H, Borger DK, Wei Q, Yang E, Xu C, Pinho S, Frenette PS. The microbiota regulates hematopoietic stem cell fate decisions by controlling iron availability in bone marrow. Cell Stem Cell (2022), 29(2):232-247.e7. (* Correspondence)
3. Wei Q, Pinho S, Dong S, Pierce H, Li H, Nakahara F, Xu J, Xu C, Boulais PE, Zhang D, Maryanovich M, Cuervo AM, Frenette PS. MAEA is an E3 ubiquitin ligase promoting autophagy and maintenance of haematopoietic stem cells. Nat Commun (2021), 12(1):2522.
4. Renders S, Svendsen AF, Panten J, Rama N, Maryanovich M, Sommerkamp P, Ladel L, Redavid AR, Gibert B, Lazare S, Ducarouge B, Schönberger K, Narr A, Tourbez M, Dethmers-Ausema B, Zwart E, Hotz-Wagenblatt A, Zhang D, Korn C, Zeisberger P, Przybylla A, Sohn M, Mendez-Ferrer S, Heikenwälder M, Brune M, Klimmeck D, Bystrykh L, Frenette PS, Mehlen P, de Haan G, Cabezas-Wallscheid N, Trumpp A. Niche derived netrin-1 regulates hematopoietic stem cell dormancy via its receptor neogenin-1. Nat Commun (2021), 12(1):608.
5. Gao X, Zhang D, Xu C, Li H, Caron KM, Frenette PS. Nociceptive nerves regulate haematopoietic stem cell mobilization. Nature (2021), 589(7843):591-596.
6. Xu C, Lee SK, Zhang D, Frenette PS. The Gut Microbiome Regulates Psychological-Stress-Induced Inflammation. Immunity (2020), 18;53(2):417-428.e4.
7. Wei Q, Nakahara F, Asada N, Zhang D, Gao X, Xu C, Alfieri A, Brodin NP, Zimmerman SE, Mar JC, Guha C, Guo W, Frenette PS. Snai2 Maintains Bone Marrow Niche Cells by Repressing Osteopontin Expression. Dev Cell (2020), 53(5):503-513.
8. Jordan S, Tung N, Casanova-Acebes M, Chang C, Cantoni C, Zhang D, Wirtz TH, Naik S, Rose SA, Brocker CN, Gainullina A, Hornburg D, Horng S, Maier BB, Cravedi P, LeRoith D, Gonzalez FJ, Meissner F, Ochando J, Rahman A, Chipuk JE, Artyomov MN, Frenette PS, Piccio L, Berres ML, Gallagher EJ, Merad M. Dietary Intake Regulates the Circulating Inflammatory Monocyte Pool. Cell (2019), 178(5):1102-1114.
9. de Juan A, Ince LM, Pick R, Chen CS, Molica F, Zuchtriegel G, Wang C, Zhang D, Druzd D, Hessenauer MET, Pelli G, Kolbe I, Oster H, Prophete C, Hergenhan SM, Albrecht U, Ripperger J, Montanez E, Reichel CA, Soehnlein O, Kwak BR, Frenette PS, Scheiermann C. Artery-Associated Sympathetic Innervation Drives Rhythmic Vascular Inflammation of Arteries and Veins. Circulation (2019), 140(13):1100-1114.
10. Zhang D, Frenette PS. Crosstalk between neutrophils and the microbiota. Blood (2019), 133(20):2168-2177.
11. Wei Q, Boulais PE, Zhang D, Pinho S, Tanaka M, Frenette PS. Maea expressed by macrophages, but not erythroblasts, maintains postnatal murine bone marrow erythroblastic islands. Blood (2019), 133(11):1222-1232.
12. Pierce H, Zhang D, Magnon C, Lucas D, Christin JR, Huggins M, Schwartz GJ, Frenette PS. Cholinergic Signals from the CNS Regulate G-CSF-Mediated HSC Mobilization from Bone Marrow via a Glucocorticoid Signaling Relay. Cell Stem Cell (2017), 20(5):648-658.
13. Chen G, Chang J, Zhang D, Pinho S, Jang JE, Frenette PS. Targeting Mac-1-mediated leukocyte-RBC interactions uncouples the benefits for acute vaso-occlusion and chronic organ damage. Exp Hematol (2016), 44(10):940-6.
14. Zhang D#, Xu C#, Manwani D# and Frenette PS. Neutrophils, platelets, and inflammatory pathways, at the nexus of sickle cell disease pathophysiology. Blood (2015), 127(7):801-9. (# Co-first author)
15. Zhang D, Chen G, Manwani D, Mortha A, Xu C, Faith JJ, Burk RD, Kunisaki Y, Jang JE, Scheiermann C, Merad M, Frenette PS. Neutrophil ageing is regulated by the microbiome. Nature (2015), 525 (7570): 528-32.
16. Hanoun M, Zhang D, Mizoguchi T, Pinho S, Pierce H, Kunisaki Y, Lacombe J, Armstrong SA, Dührsen U, Frenette PS. Acute Myelogenous Leukemia-Induced Sympathetic Neuropathy Promotes Malignancy in an Altered Hematopoietic Stem Cell Niche. Cell Stem Cell (2014), 15(3): 365-75.
17. Chen G, Zhang D, Fuchs TA, Wagner DD, Frenette PS. Heme-induced neutrophil extracellular traps contribute to the pathogenesis of sickle cell disease. Blood (2014), 123(24): 3818-27.
18. Kunisaki Y, Bruns I, Scheiermann C, Ahmed J, Pinho S, Zhang D, Mizoguchi T, Wei Q, Lucas D, Ito K, Mar JC, Bergman A, Frenette PS. Arteriolar niches maintain haematopoietic stem cell quiescence. Nature (2013), 502: 637-43.
19. Casanova-Acebes M, Pitaval C, Weiss LA, Nombela-Arrieta C, Chèvre R, A-González N, Kunisaki Y, Zhang D, van Rooijen N, Silberstein LE, Weber C, Nagasawa T, Frenette PS, Castrillo A, Hidalgo A. Rhythmic modulation of the hematopoietic niche through neutrophil clearance. Cell (2013), 153(5): 1025-35.
20. Scheiermann C, Kunisaki Y, Lucas D, Chow A, Jang JE, Zhang D, Hashimoto D, Merad M, Frenette PS. Adrenergic nerves govern circadian leukocyte recruitment to tissues. Immunity (2012), 37(2): 290-301.
21. Huang Z, Zhang Z, Jiang Y, Zhang D, Chen J, Dong L, Zhang J. Targeted delivery of oligonucleotides into tumor-associated macrophages for cancer immunotherapy. J Control Release (2012), 158(2): 286-92.
22. Dong L, Xia S, Gao F, Zhang D, Chen J, Zhang J. 3,3'-Diindolylmethane attenuates experimental arthritis and osteoclastogenesis. Biochem Pharmacol (2010), 79(5): 715-21.
根據(jù)Google Scholar,，截至2022年4月11日,，共發(fā)表期刊論文22篇（影響因子578.2），被引用3937次（h-index = 16,，i10-index = 18）,。
團(tuán)隊(duì)介紹 >>>
本團(tuán)隊(duì)依托上海交通大學(xué)醫(yī)學(xué)院細(xì)胞分化與凋亡教育部重點(diǎn)實(shí)驗(yàn)室，擁有一流的科學(xué)研究平臺(tái)和研究環(huán)境,。課題組初建,，正在招聘助研、技術(shù)員與博士后,，歡迎熱愛科研,、有志于探索相同方向的人士加入，具體招聘信息詳見人事處網(wǎng)站,。
