Research Summary

My laboratory studies receptor signaling in immune cells with a focus on the B cell antigen receptor (BCR) and Toll-like receptors (TLRs). In a longstanding collaboration with Clifford Lowell (UCSF), we have also studied the role of the Src-family kinase Lyn in inhibitory receptor signaling in B cells and the autoimmune disease that develops in Lyn-deficient mice. To study the in vivo function of TLRs in mice, we made a conditional (Cre/loxP) allele of the TLR signaling component MyD88 and have used this tool to characterize the role of MyD88 in dendritic cells and B cells for innate and adaptive immune responses. In recent years, we have discovered that BCR and TLR signaling reactions synergize to promote the germinal center response.

Research Funding

  • March 1, 2018 - February 28, 2023 - Organ-specific autoimmunity resulting from two genetic defects in tolerance, Principal Investigator. Sponsor: NIH/NIAID, Sponsor Award ID: R01AI138479
  • July 1, 2015 - June 30, 2017 - B cell TLRs and germinal centers, Principal Investigator. Sponsor: NIH/NIAID, Sponsor Award ID: R21AI117378
  • August 1, 2014 - July 31, 2015 - BCR regulation of antibody responses, Principal Investigator. Sponsor: NIH/NIAID, Sponsor Award ID: R56AI108684
  • July 1, 2013 - June 30, 2015 - The role of Apobec3 enzymes in regulation of marginal zone B cells, Co-Principal Investigator. Sponsor: NIH/NIAID, Sponsor Award ID: R21AI107101

Education

Harvard College, Cambridge MA, A.B., 1975, Biochemical & Molecular Biology
University of California, Berkeley, CA, Ph.D., 1979, Biochemistry
National Institutes of Health, Bethesda MD, Postdoctoral, 1979-83, Immunology

Honors & Awards

  • 1974
    Dreyfuss Foundation Fellow
  • 1975
    Phi Beta Kappa, Harvard University
  • 1975-78
    NSF Predoctoral Fellow
  • 1979-82
    Helen Hay Whitney Postdoctoral Fellow; 2nd Rose Lieberman Lecturer, NIH 10/93
  • 1994
    NIAID Merit Award
  • 1997-98
    NIH Fogarty Senior International Award

Selected Publications

  1. Anthony L DeFranco, Alexander J Finn, Julie Hambleton, Mary T Crowley, Mary Lee MacKichan, Steven L Weinstein The Role of MAP Kinases, Phosphatidylinositol 3-Kinase, and Ceramide in LPS-induced Signaling in Macrophages.  View on PubMed
  2. Wigton EJ, DeFranco AL, Ansel KM Antigen Complexed with a TLR9 Agonist Bolsters c-Myc and mTORC1 Activity in Germinal Center B Lymphocytes.  View on PubMed
  3. Faggioni M, Baber U, Chandrasekhar J, Sartori S, Claessen BE, Rao SV, Vogel B, Effron MB, Poddar K, Farhan S, Kini A, Weintraub W, Toma C, Sorrentino S, Weiss S, Snyder C, Muhlestein JB, Kapadia S, Keller S, Strauss C, Aquino M, Baker B, Defranco A, Pocock S, Henry T, Mehran R Use of prasugrel vs clopidogrel and outcomes in patients with and without diabetes mellitus presenting with acute coronary syndrome undergoing percutaneous coronary intervention.  View on PubMed
  4. DeFranco AL Multilayer Control of B Cell Activation by the B Cell Antigen Receptor: Following Themes Initiated With Bill Paul.  View on PubMed
  5. Tian M, Hua Z, Hong S, Zhang Z, Liu C, Lin L, Chen J, Zhang W, Zhou X, Zhang F, DeFranco AL, Hou B B Cell-Intrinsic MyD88 Signaling Promotes Initial Cell Proliferation and Differentiation To Enhance the Germinal Center Response to a Virus-like Particle.  View on PubMed
  6. Costa S, Marini O, Bevilacqua D, DeFranco AL, Hou B, Lonardi S, Vermi W, Rodegher P, Panato A, Tagliaro F, Lowell CA, Cassatella MA, Girolomoni G, Scapini P Role of MyD88 signaling in the imiquimod-induced mouse model of psoriasis: focus on innate myeloid cells.  View on PubMed
  7. DeFranco AL Innate B cells cleave to the marginal zone.  View on PubMed
  8. Lee LM, Ji M, Sinha M, Dong MB, Ren X, Wang Y, Lowell CA, Ghosh S, Locksley RM, DeFranco AL Determinants of Divergent Adaptive Immune Responses after Airway Sensitization with Ligands of Toll-Like Receptor 5 or Toll-Like Receptor 9.  View on PubMed
  9. Proekt I, Miller CN, Jeanne M, Fasano KJ, Moon JJ, Lowell CA, Gould DB, Anderson MS, DeFranco AL LYN- and AIRE-mediated tolerance checkpoint defects synergize to trigger organ-specific autoimmunity.  View on PubMed
  10. DeFranco AL Germinal centers and autoimmune disease in humans and mice.  View on PubMed
  11. Wang H, Li M, Hung CY, Sinha M, Lee LM, Wiesner DL, LeBert V, Lerksuthirat T, Galles K, Suresh M, DeFranco AL, Lowell CA, Klein BS, Wüthrich M MyD88 Shapes Vaccine Immunity by Extrinsically Regulating Survival of CD4+ T Cells during the Contraction Phase.  View on PubMed
  12. DeFranco AL The germinal center antibody response in health and disease.  View on PubMed
  13. Anthony L. DeFranco Signaling Pathways Downstream of TLRs and IL-1 Family Receptors.  View on PubMed
  14. Anthony L DeFranco B Lymphocytes: Receptors.  View on PubMed
  15. Beck-Engeser GB, Winkelmann R, Wheeler ML, Shansab M, Yu P, Wünsche S, Walchhütter A, Metzner M, Vettermann C, Eilat D, DeFranco A, Jäck HM, Wabl M APOBEC3 enzymes restrict marginal zone B cells.  View on PubMed
  16. Rookhuizen DC, DeFranco AL Toll-like receptor 9 signaling acts on multiple elements of the germinal center to enhance antibody responses.  View on PubMed
  17. Minjia Yu, Hao Zhou, Junjie Zhao, Nengming Xiao, Sanjoy Roychowdhury, David Schmitt, Bingqing Hu, Richard M. Ransohoff, Clifford V. Harding, Amy G. Hise, Stanley L. Hazen, Anthony L. DeFranco, Paul L. Fox, Richard E. Morton, Paul E. Dicorleto, Maria Febbraio, Laura E. Nagy, Jonathan D. Smith, Jian-an Wang, Xiaoxia Li MyD88-dependent interplay between myeloid and endothelial cells in the initiation and progression of obesity-associated inflammatory diseases.  View on PubMed
  18. Yu M, Zhou H, Zhao J, Xiao N, Roychowdhury S, Schmitt D, Hu B, Ransohoff RM, Harding CV, Hise AG, Hazen SL, DeFranco AL, Fox PL, Morton RE, Dicorleto PE, Febbraio M, Nagy LE, Smith JD, Wang JA, Li X MyD88-dependent interplay between myeloid and endothelial cells in the initiation and progression of obesity-associated inflammatory diseases.  View on PubMed
  19. Hua Z, Gross AJ, Lamagna C, Ramos-Hernández N, Scapini P, Ji M, Shao H, Lowell CA, Hou B, DeFranco AL Requirement for MyD88 signaling in B cells and dendritic cells for germinal center anti-nuclear antibody production in Lyn-deficient mice.  View on PubMed
  20. Lamagna C, Hu Y, DeFranco AL, Lowell CA B cell-specific loss of Lyn kinase leads to autoimmunity.  View on PubMed

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