基本信息 >>>
张大川
肠道菌群与造血免疫组
电话：021-63846590-771056
邮箱：dachuanzhang@shsmu.edu.cn
研究方向与进展 >>>
髓系细胞，包括中性粒细胞、单核细胞以及巨噬细胞，是固有免疫系统的重要组成部分，在对病原体的免疫防御以及炎症性疾病的发生发展过程中起着重要作用。这些细胞来源于骨髓中的造血系统，而造血干细胞（HSC）则是分化产生所有血液和免疫细胞谱系的始祖细胞。研究髓系免疫细胞在机体内的运输、招募与激活，以及造血干细胞在骨髓中自我更新与分化命运的调控机制，对于理解免疫与造血系统的功能，炎症性疾病以及恶性血液病的发生发展过程有着十分重要的意义。
课题组致力于在分子、细胞和系统性层面探索造血干细胞和固有免疫细胞的调控机制，解析肠道菌群和外周神经系统在生理病理过程中的关键作用。课题组的前期研究发现肠道菌群可以通过调节中性粒细胞在循环系统中的炎症活性，诱导衰老表型，影响炎症性疾病的发生发展。近期的研究表明肠道菌群可以通过调节骨髓巨噬细胞对红细胞的吞噬控制骨髓微环境中的铁元素供给，从而影响造血干细胞在应激状态下自我更新与分化的命运决定。另一方面，课题组的前期研究揭示了交感神经、感觉神经以及神经内分泌系统对造血干细胞的动员、归巢以及骨髓微环境的重要调控作用。
实验室的研究方向主要包括：（1）微环境、肠道菌群对造血干细胞以及白血病发生发展的影响；（2）肠道菌群的筛选、编辑以及在血液和免疫系统疾病中的应用；（3）外周神经系统对造血干细胞与免疫细胞稳态、迁移、激活的调控。
研究组长介绍 >>>
张大川，本科毕业于南京大学生物科学系，2016年在美国阿尔伯特爱因斯坦欧洲杯竞猜平台 (Albert Einstein College of Medicine) 获得细胞生物学博士学位，师从血液以及干细胞领域专家Paul Frenette教授，并在其实验室从事博士后研究。 张大川在2021年获得国家自然科学基金优秀青年科学基金项目（海外），于2022年1月加入欧洲杯竞猜平台基础欧洲杯竞猜平台病理生理系，任课题组长。研究工作主要聚焦于肠道菌群对造血、免疫系统的调控作用，相关成果发表在Nature, Cell Stem Cell, Blood等国际知名期刊上。
科研项目 >>>
1. 国家自然科学基金优秀青年科学基金（海外），肠道菌群在免疫与造血系统中的调控作用 ，2022，在研，课题负责人
论文与专著 >>>
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.
根据Google Scholar，截至2022年4月11日，共发表期刊论文22篇（影响因子578.2），被引用3937次（h-index = 16，i10-index = 18）。
团队介绍 >>>
本团队依托欧洲杯竞猜平台细胞分化与凋亡教育部重点实验室，拥有一流的科学研究平台和研究环境。课题组初建，正在招聘助研、技术员与博士后，欢迎热爱科研、有志于探索相同方向的人士加入，具体招聘信息详见人事处网站。
