Personal Introduction

Dr. Zhang received his BS degree at Nanjing University in China in 2010, and PhD degree at Albert Einstein College of Medicine in the United States in 2016. He conducted his PhD and postdoctoral studies under the supervision of Dr. Paul Frenette, a leading scientist in the field of hematology. He received the National Natural Science Fund for Excellent Young Scientists (Overseas) in 2021, and joined Shanghai Jiao Tong University School of Medicine as a Principal Investigator in 2022.

The Zhang lab is interested in the regulatory networks for hematopoietic stem cells (HSCs) and innate immune cells, and the key roles of microbiota and peripheral nervous system (PNS) in homeostasis and pathophysiology. Our previous studies have found that the microbiota plays an important role in regulating neutrophil functional activity and inflammatory disease progression (Nature 2015); the microbiota regulates hematopoietic stem cell fate and functions by modulating local iron recycle and supply via macrophages (Cell Stem Cell 2022). In addition, we collaborated in multiple studies showing key roles of the PNS in regulating HSC mobilization, homing, and bone marrow microenvironment. These studies have been published in high-impact journals including Nature, Cell Stem Cell, Blood etc.

Our research directions include: (1) The roles of microbiota and microenvironment in regulating HSC functions and leukemia pathogenesis; (2) Isolation, manipulation, and application of gut commensals in hematopoietic and inflammatory diseases; (3) The roles of PNS in the homeostasis, migration and activation of hematopoietic stem cell and innate immune cells.

Scientific Research Projects

• National Natural Science Fund for Excellent Young Scientists (Overseas), “Regulatory role of the microbiota in immunity and hematopoiesis”, 2021

Publications

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 Mantains 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. 2Scheiermann 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.