Dr. Chunliang Xu is a Professor at the Zhongshan School of Medicine, Sun Yat-sen University, where his group focus on long-lived plasma cells. He earned his Ph.D. in Cell Biology from the Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, under the mentorship of Professor Yufang Shi. He completed postdoctoral training at Columbia University and the Albert Einstein College of Medicine, working with Professors Remi Creusot and Paul Frenette. Prior to joining Sun Yat-sen University in 2022, he served as an Assistant Professor at The Chinese University of Hong Kong (2021-2022). Dr. Xu is a recipient of the National High-Level Young Talents Program and has published in leading journals including Nature, Nature Medicine, Immunity, and Cell Stem Cell. His works has been cited over 6500 times. His laboratory aims to develop highly effective and durable vaccine strategies by targeting long-lived plasma cells, with the ultimate goal of empowering all vaccines to achieve efficient and sustained protection.

The durability of vaccine-induced protection varies dramatically—from lifelong immunity following smallpox vaccination to waning protection within months for influenza. This variation is likely caused by both intrinsic factors (vaccine platform, antigen properties) and extrinsic factors (metabolic state, environmental influences). Focusing on extrinsic influences, we recently find that metabolic states profoundly shape long-term humoral immunity. Using mouse models and human trials, we demonstrate that intermittent fasting elevates β-hydroxybutyrate (BHB), which activates HCAR2 signaling on long-lived plasma cells (LLPCs). This activation, via the HCAR2-Gαi-cAMP axis, downregulates CXCR4, disrupting LLPC retention in the bone marrow niche and triggering their egress and apoptosis, thereby depleting the LLPC pool and impairing immune memory. Our findings reveal that extrinsic metabolic states can override niche-mediated retention through the BHB-HCAR2-CXCR4 axis, providing a new framework for understanding vaccine durability. By integrating immunometabolism with niche biology within this framework, we aim to develop strategies to extend vaccine protection.


 

Publications:

  1. Fasting impairs humoral immunological memory by β-hydroxybutyrate-mediated depletion of plasma cells. Immunity. 2026 Feb 23:S1074-7613(26)00003-8.Zhu Y, Ding B, Lv H, Xu H, Chen J, Xu J, Wu Q, Hao X, Hu Y, Guo J, Chen J, Liang C, Li Y, We J, Cao N, Zhao J, Ren G, Jin H, Zhang Y, Li Y, Zhang H, Xu C. (Corresponding author)

    Highlighted by Nat Rev Immunol: Intermittent fasting evicts long-lived plasma cells from survival niche.

  2. The gut microbiome regulates psychological stress-induced inflammation. Immunity, 2020 Aug 18;53(2):417-428.e4. Xu C, Lee SK, Zhang D, Frenette PS. 

    Highlighted by Nature:Gut microbes and stress team up to make a painful disease worse.

    Preview in Immunity: Gut Feelings Block the Flow: Microbiota Links Stress to Vascular Disease.

    Highlighted by Science Translational Medicine:A gut feeling to stress enhances neutrophil-mediated vascular occlusion.

  3. Seasonal manifestations of sickle cell disease. Nature Medicine. 2019 Apr;25(4):536-537. Xu C, Frenette PS. 

  4. Nociceptive nerves regulate haematopoietic stem cell mobilization. Nature. 2021 Jan;589(7843):591-596. Gao X, Zhang D*, Xu C*, Li H, Caron KM, Frenette PS.(*Equal contribution). 

  5. Brain motor and fear circuits regulate leukocytes during acute stress. Nature. 2022 May. Poller WC, Downey J, Mooslechner AA, Khan N, Li L, Chan CT, McAlpine CS, Xu C, Kahles F, He S, Janssen H, Mindur JE, Singh S, Kiss MG, Alonso-Herranz L, Iwamoto Y, Kohler RH, Wong LP, Chetal K, Russo SJ, Sadreyev RI, Weissleder R, Nahrendorf M, Frenette PS, Divangahi M, Swirski FK. 
  6. Neutrophil ageing is regulated by the microbiome. Nature. 2015 Sep;525(7570):528-32. Zhang D, Chen G, Manwani D, Mortha A, Xu C, Faith J, Burk R, Kunisaki Y, Jang J, Scheiermann C, Merad M, Frenette PS. 
  7. Neutrophils, platelets, and inflammatory pathways at the nexus of sickle cell disease pathophysiology. Blood. 2016 Feb;127(7):801-9. Zhang D*, Xu C*, Manwani D*, Frenette PS. (* equal contribution).
  8. The microbiota regulates hematopoietic stem cell fate decisions by controlling iron availability in bone marrow.Cell Stem Cell. 2022 Feb 3;29(2):232-247. Zhang D, Gao X, Li H, Borger DK, Wei Q, Yang E, Xu C, Pinho S, Frenette PS.
  9. CCR2-dependent recruitment of macrophages by tumor-educated mesenchymal stromal cells promotes tumor development and is mimicked by TNFα. Cell Stem Cell. 2012 Dec;11(6):812-24. Ren G, Zhao X, Wang Y, Zhang X, Chen X, Xu C, Yuan ZR, Roberts AI, Zhang L, Zheng B, Wen T, Han Y, Rabson AB, Tischfield JA, Shao C, Shi Y. 
  10. Engineering a haematopoietic stem cell niche by revitalizing mesenchymal stromal cells. Nature Cell Biology. 2019 May;21(5):560-567. Nakahara F, Borger DK, Wei Q, Pinho S, Maryanovich M, Zahalka A, Suzuki M, Cruz CD, Wang Z, Xu C, Boulais PE, Ma'ayan A, Greally J, Frenette PS. 
  11. CD11b Regulates obesity-induced insulin resistance via limiting alternative Activation and proliferation of adipose tissue macrophages. Proceedings of the National Academy of Sciences of the United States of America. 2015 Dec;112(52):E7239-48. Zheng C, Yang Q, Xu C, Shou P, Cao J, Jiang M, Chen Q, Cao Q, Han Y, Li F, Cao W, Zhang L, Zhang L, Shi Y, Wang Y. 
  12. Transforming growth factor β promotes immune responses in the presence of mesenchymal stem cells. The Journal of Immunology. 2014 Jan;192(1):103-9. Xu C, Yu P, Han X, Du L, Gan J, Wang Y, Shi Y. (Highlighted in the “In This Issue” section). 
  13. miR-155 regulates immune modulatory properties of mesenchymal stem cells by targeting TAK1-binding protein 2. The Journal of Biological Chemistry. 2013 Apr;288(16):11074-9. Xu C, Ren G, Cao G, Chen Q, Shou P, Zheng C, Du L, Han X, Jiang M, Yang Q, Lin L, Wang G, Yu P, Zhang X, Cao W, Brewer G, Wang Y, Shi Y. 
  14. Mesenchymal stromal cells equipped by IFNα empower T cells with potent anti-tumor immunity.Oncogene. 2022 Mar;41(13):1866-1881. Zhang T, Wang Y, Li Q, Lin L, Xu C, Xue Y, Hu M, Shi Y, Wang Y. 
  15. Snai2 Maintains Bone Marrow Niche Cells by Repressing Osteopontin Expression. Developmental Cell. 2020 Jun 8;53(5):503-513.e5. Wei Q, Nakahara F, Asada N, Zhang D, Gao X, Xu C, Alfieri A, Brodin NP, Zimmerman SE, Mar JC, Guha C, Guo W, and Frenette PS. 
  16. MAEA is an E3 ubiquitin ligase promoting autophagy and maintenance of haematopoietic stem cells. Nature Communications volume 12, Article number: 2522 (2021). Wei Q, Pinho S, Dong S, Pierce H, Li H, Nakahara F, Xu J, Xu C, Boulais PE, Zhang D, Maryanovich M, Cuervo AM and Frenette PS.
  17. The good side of inflammation: Staphylococcus aureus proteins SpA and Sbi contribute to proper abscess formation and wound healing during skin and soft tissue infections. BBA-Molecular Basis of Disease. 2019 Oct;1865(10):2657-2670. Gonzalez CD, Ledo C, Cela E, Stella I, Xu C, Ojeda DS, Frenette PS, Gomez M. 
  18. The hematopoietic stem cell niche: from embryo to adult. Development. 2018 Jan;145(2). Gao X, Xu C, Asada N, Frenette PS. 
  19. Efficient presentation of multiple endogenous epitopes to both CD4+ and CD8+ diabetogenic T cells for tolerance. Molecular Therapy-Methods & Clinical Development. 2016 Dec;4:27-38. Dastagir SD*, Postigo-Fernandez J*, Xu C, Stoeckle J, Firdessa-Fite R, Creusot RJ. (* equal contribution).
  20. Downregulation of CXCL12 in mesenchymal stromal cells by TGFβ promotes breast cancer metastasis. Oncogene. 2017 Feb;36(6):840-849. Yu P, Huang Y, Xu C, Lin L, Han Y, Sun W, Hu G, Rabson AB, Wang Y, Shi Y. 
  21. Type I interferons exert anti-tumor effect via reversing immunosuppression mediated by mesenchymal stromal cells. Oncogene. 2016 Nov;35(46):5953-5962. Shou P, Chen Q, Jiang J, Xu C, Zhang J, Zheng C, Jiang M, Velletri T, Cao W, Huang Y, Yang Q, Han X, Zhang L, Wei L, Rabson AB, Chin YE, Wang Y, Shi Y. 
  22. SHP1 regulates bone mass by directing mesenchymal stem cell differentiation. Cell Report. 2016 Jul;16(3):769-80. Jiang M, Zheng C, Shou P, Li N, Cao G, Chen Q, Xu C, Du L, Yang Q, Cao J, Han Y, Li F, Cao W, Liu F, Rabson AB, Roberts AI, Xie W, Wang Y, Shi Y. 
  23. Fate decision of mesenchymal stem cells: adipocytes or osteoblasts? Cell Death Differentiation. 2016 Jul;23(7):1128-39. Chen Q, Shou P, Zheng C, Jiang M, Cao G, Yang Q, Cao J, Xie N, Velletri T, Zhang X, Xu C, Zhang L, Yang H, Hou J, Wang Y, Shi Y. 
  24. Interleukin-17A enhances immunosuppression by mesenchymal stem cells. Cell Death and Differentiation. 2014 Nov;21(11):1758-68. Han X, Yang Q, Lin L, Xu C, Zheng C, Chen X, Han Y, Li M, Cao W, Chen Q, Xu G, Zhang Y, Schneider R, Qian Y, Wang Y, Brewer G, Shi Y. 
  25. SSChighCD11bhighLy-6ChighLy-6Glow myeloid cells curtail CD4 T cell response by inducing nitric oxide synthase in murine hepatitis. The International Journal of Biochemistry & Cell Biology. 2014 Sep;54:89-97. Zhu K, Zhang N, Guo N, Yang J, Wang J, Yang C, Yang C, Zhu L, Xu C, Deng Q, Zhu R, Wang H, Chen X, Shi Y, Li Y, Leng Q. 
  26. Huang Y, Yu P, Li W, Ren G, Roberts A, Cao C, Zhang X, Su J, Chen X, Chen Q, Shou P, Xu C, Du L, Lin L, Xie N, Zhang L, Wang Y, Shi Y. p53 regulates mesenchymal stem cell-mediated tumor suppression in a tumor microenvironment through immune modulation. Oncogene. 2014 Jul;33(29):3830-8. 
  27. Mesenchymal stem cells prevent restraint stress-induced lymphocyte reduction via Interleukin-4. Brain, Behavior, and Immunity. 2014 May;38:125-32. Cao G, Yang Q, Zhang S, Xu C, Wang Y, Shi Y. 
  28. An osteopontin-Integrin interaction plays a critical role in directing adipogenesis and osteogenesis by mesenchymal stem cells. Stem Cells. 2014 Feb;32(2):327-37. Chen Q, Shou P, Zhang L, Xu C, Zheng C, Han Y, Li W, Huang Y, Zhang X, Shao C, Roberts, A, Robson A, Ren G, Zhang Y, Wang Y, Denhardt D, Shi Y. 
  29. Mesenchymal stem cells: a new strategy for immunosuppression and tissue repair. Cell Research. 2010 May;20(5):510-8. Shi Y, Hu G, Su J, Li W, Chen Q, Shou P, Xu C, Chen X, Huang Y, Zhu Z, Huang X, Han X, Xie N, Ren G. 
  30. A single point mutation in E2 enhances hepatitis C virus infectivity and alters lipoprotein association of viral particles. Virology. 2009 Dec;395(1):67-76. Tao W, Xu C, Ding Q, Li R, Xiang Y, Chung J, Zhong J. 
  31. The research of the relationship between cyclooxygenase-2 and monocyte endothelial cells adhesion. Chinese Journal of Laboratory Diagnosis. 2013 Nov; 17(10). Wang H, Xu C, Cai F, Cao J, Chen X, Wu F. 
  32. Randomized Phase 2 trial of Intravenous Gamma Globulin (IVIG) for the Treatment of Acute Vaso-Occlusive Crisis in Patients with Sickle Cell disease: Lessons Learned from the Midpoint Analysis. Complementary Therapies in Medicine, 2020 Aug; Volume 52, 102481. Manwani D, Xu C, Lee SK, Amatuni G, Cohen H, Carullo V, Morrone K, Davila J, Shi PA, Ireland K, Keenan J, Frenette PS.

  33. Haematopoietic stem cell numbers are not solely determined by niche availability. Nature. In press. Takeishi S, Marchand T, Koba WR, Borger DK, Xu C, Guha C, Bergman A, Frenette PS, Gritsman K, Steidl U. 

  34. Stem cell factor is selectively secreted by arterial endothelial cells in bone marrow. Nature Communications. 2018 Jun;9(1):2449. Xu C, Gao X, Wei Q, Nakahara F, Zimmerman SE, Mar J, Frenette PS.

  35. Nociceptors protect sickle cell disease mice from vaso-occlusive episodes and chronic organ damage. Journal of Experimental Medicine, 2021. 218 (1): e20200065.Xu C, Gulinello M, Frenette PS. Highlighted by Science Translational Medicine:A spicy solution for sickle cell disease. 

  36. IFNα-secreting MSCs exerts potent anti-tumor effect in vivo. Oncogene. 2014 Oct;33(42):5047-52. Xu C, Lin L, Cao G, Chen Q, Shou P, Huang Y, Han Y, Wang Y, Shi Y.