Research Summary

We study the intercellular communications and cell migration dynamics underlying anti-pathogen and anti-tumor immune responses. We are recognized for defining how lymphoid microenvironments are organized to support adaptive immunity. We played a key role in the discovery of lymphoid tissue chemokines and established the concept that chemokines continuously guide cells to supportive niches. Our group led the way in defining how cells exit from lymphoid organs, a process essential for immune function. We showed the egress-promoting role of sphingosine-1-phosphate and identified the mechanism of action of key egress regulators, including the immunosuppressive molecule FTY720 (Fingolimod). We use immunological, genetic, cell biological, biochemical, and intravital imaging techniques to study these processes. As well as performing mechanistic studies in mouse models, we have translated key findings to humans, such as our identification of a gene pathway that is disrupted in germinal center B cell-type diffuse large B cell lymphoma.

Research Funding

  • April 1, 1999 - August 31, 2024 - Chemokines and Lymphoid Tissue Organization and Function , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01AI045073
  • September 1, 1988 - July 31, 2024 - Molecular and Cellular Immunology , Principal Investigator . Sponsor: NIH, Sponsor Award ID: T32AI007334
  • June 1, 2021 - May 31, 2023 - GPR35 function in the immune system , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21AI163036
  • April 1, 1997 - March 31, 2022 - B lymphocyte Migration and Homeostasis , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01AI040098

Education

University of Western Australia, B.S., 1988, Biochemistry and Microbiology
University of Oxford, England, D.Phil., 1992, Immunology
Stanford Univ. Med Center, Stanford, CA, PD Fellow, 1992-1995, Immunology

Honors & Awards

  • 1984
    The Beazely Award for secondary education in Western Australia
  • 1988
    J.A. Wood Memorial prize from the University of Western Australia
  • 1989-1992
    Commonwealth Overseas Studentship
  • 1992-1995
    Cancer Research Institute Postdoctoral Fellowship
  • 1996-2000
    Pew Scholar in the Biomedical Sciences
  • 1997
    Cheryl Whitlock Memorial Prize for Postdoctoral Studies
  • 1998-2003
    David and Lucile Packard Foundation Fellowship
  • 2005
    AAI BD Biosciences Investigator Award
  • 2005
    External Speaker, Harvard Medical School Annual Immunology Retreat
  • 2009
    Alexandre Goidl Memorial Lectureship, University of Maryland Baltimore
  • 2009
    Keynote Speaker, Microanatomy of Immune Responses in Health and Disease, Birmingham, UK
  • 2010
    Organizing Committee Member, International Congress of Immunology, Kobe, Japan
  • 2010
    Keynote Presentation, Antibody Biology & Engineering Gordon Research Conference, Ventura, CA
  • 2010
    14th Köhler Lecture in Immunology, University of Freiburg, Germany
  • 2010
    CRI Fredrick W. Alt Award for New Discoveries in Immunology
  • 2011
    Distinguished Lecture, AAI Annual Meeting, San Francisco
  • 2011
    Elected as an AAAS Fellow
  • 2013
    Keynote Speaker, 14th International TNF conference
  • 2013
    Keynote Speaker, FASEB Meeting on Lysophospholipids
  • 2013
    Keynote Speaker, Gordon Conference on Follicular helper T cells.
  • 2018
    Elected, American Academy of Arts and Sciences

Selected Publications

  1. Nie Y, Qiu Z, Chen S, Chen Z, Song X, Ma Y, Huang N, Cyster JG, Zheng S. Specific binding of GPR174 by endogenous lysophosphatidylserine leads to high constitutive Gs signaling. Nat Commun. 2023 Sep 22; 14(1):5901.  View on PubMed
  2. Winer BY, Settle AH, Yakimov AM, Jeronimo C, Lazarov T, Tipping M, Saoi M, Sawh A, Sepp AL, Galiano M, Wong YY, Perry JSA, Geissmann F, Cross J, Zhou T, Kam LC, Pasoli HA, Hohl T, Cyster JG, Weiner OD, Huse M. Plasma membrane abundance dictates phagocytic capacity and functional crosstalk in myeloid cells. bioRxiv. 2023 Sep 13.  View on PubMed
  3. Theusch E, Ting FY, Qin Y, Stevens K, Naidoo D, King SM, Yang N, Orr J, Han BY, Cyster JG, Chen YI, Rotter JI, Krauss RM, Medina MW. Participant-derived cell line transcriptomic analyses and mouse studies reveal a role for ZNF335 in plasma cholesterol statin response. bioRxiv. 2023 Jun 15.  View on PubMed
  4. De Giovanni M, Dang EV, Chen KY, An J, Madhani HD, Cyster JG. Platelets and mast cells promote pathogenic eosinophil recruitment during invasive fungal infection via the 5-HIAA-GPR35 ligand-receptor system. Immunity. 2023 07 11; 56(7):1548-1560.e5.  View on PubMed
  5. Torres RM, Cyster J. Lipid mediators in the regulation of innate and adaptive immunity. Immunol Rev. 2023 08; 317(1):4-7.  View on PubMed
  6. Chou MY, Liu D, An J, Xu Y, Cyster JG. B cell peripheral tolerance is promoted by cathepsin B protease. Proc Natl Acad Sci U S A. 2023 04 18; 120(16):e2300099120.  View on PubMed
  7. Chen H, Qin Y, Chou M, Cyster JG, Li X. Transmembrane protein CD69 acts as an S1PR1 agonist. Elife. 2023 04 11; 12.  View on PubMed
  8. De Giovanni M, Chen H, Li X, Cyster JG. GPR35 and mediators from platelets and mast cells in neutrophil migration and inflammation. Immunol Rev. 2023 Mar 16.  View on PubMed
  9. Frascoli M, Ferraj E, Miu B, Malin J, Spidale NA, Cowan J, Shissler SC, Brink R, Xu Y, Cyster JG, Bhandoola A, Kang J, Reboldi A. Skin γδ T cell inflammatory responses are hardwired in the thymus by oxysterol sensing via GPR183 and calibrated by dietary cholesterol. Immunity. 2023 03 14; 56(3):562-575.e6.  View on PubMed
  10. Chen H, Qin Y, Chou M, Cyster JG, Li X. Transmembrane protein CD69 acts as an S1PR1 agonist. bioRxiv. 2023 Feb 15.  View on PubMed
  11. Ceglia S, Berthelette A, Howley K, Li Y, Mortzfeld B, Bhattarai SK, Yiew NKH, Xu Y, Brink R, Cyster JG, Hooper LV, Randolph GJ, Bucci V, Reboldi A. An epithelial cell-derived metabolite tunes immunoglobulin A secretion by gut-resident plasma cells. Nat Immunol. 2023 03; 24(3):531-544.  View on PubMed
  12. Kotov JA, Xu Y, Carey ND, Cyster JG. LTβR overexpression promotes plasma cell accumulation. PLoS One. 2022; 17(8):e0270907.  View on PubMed
  13. Wolf EW, Howard ZP, Duan L, Tam H, Xu Y, Cyster JG. GPR174 signals via Gαs to control a CD86-containing gene expression program in B cells. Proc Natl Acad Sci U S A. 2022 06 07; 119(23):e2201794119.  View on PubMed
  14. Simona Ceglia, Alyssa Berthelette, Kelsey Howley, Yun Li, Nicole K. H. Yiew, Ying Xu, Robert Adrian Brink, Jason G. Cyster, Lora V. Hooper, Gwendalyn J. Randolph, Andrea Reboldi. Epithelial-derived oxysterol production tunes intestinal IgA secretion against commensals and enteric pathogen in tissue. The Journal of Immunology. 2022 May 1; 208(1_Supplement):115.07-115.07.  View on PubMed
  15. Chen H, Chen K, Huang W, Staudt LM, Cyster JG, Li X. Structure of S1PR2-heterotrimeric G13 signaling complex. Sci Adv. 2022 Apr; 8(13):eabn0067.  View on PubMed
  16. De Giovanni M, Tam H, Valet C, Xu Y, Looney MR, Cyster JG. GPR35 promotes neutrophil recruitment in response to serotonin metabolite 5-HIAA. Cell. 2022 Mar 17; 185(6):1103-1104.  View on PubMed
  17. Liu D, Duan L, Cyster JG. Chemo- and mechanosensing by dendritic cells facilitate antigen surveillance in the spleen. Immunol Rev. 2022 03; 306(1):25-42.  View on PubMed
  18. Liu D, Duan L, Rodda LB, Lu E, Xu Y, An J, Qiu L, Liu F, Looney MR, Yang Z, Allen CDC, Li Z, Marson A, Cyster JG. CD97 promotes spleen dendritic cell homeostasis through the mechanosensing of red blood cells. Science. 2022 02 11; 375(6581):eabi5965.  View on PubMed
  19. De Giovanni M, Tam H, Valet C, Xu Y, Looney MR, Cyster JG. GPR35 promotes neutrophil recruitment in response to serotonin metabolite 5-HIAA. Cell. 2022 03 03; 185(5):815-830.e19.  View on PubMed
  20. He Y, Gallman AE, Xie C, Shen Q, Ma J, Wolfreys FD, Sandy M, Arsov T, Wu X, Qin Y, Zhang P, Jiang S, Stanley M, Wu P, Tan J, Ding H, Xue H, Chen W, Xu J, Criswell LA, Nititham J, Adamski M, Kitching AR, Cook MC, Cao L, Shen N, Cyster JG, Vinuesa CG. P2RY8 variants in lupus patients uncover a role for the receptor in immunological tolerance. J Exp Med. 2022 01 03; 219(1).  View on PubMed

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