Edward A. Clark, Ph.D.

Edward A. Clark, Ph.D.

Professor, Microbiology and Immunology

Dr. Clark received a Ph.D. in Microbiology and Immunology from the University of California, Los Angeles. After completing his postdoctoral research at University College London, he joined the faculty of the University of Washington in 1979.

Contact Info

Department of Microbiology
University of Washington  
Office E343, Box 358059
750 Republican Street
Seattle WA 98109-8059
Phone: 206-543-8706
Fax: 206-685-7120

Research Areas

  • Tolerance & Autoimmunity
    Innate Immunity
    Adaptive Immune Responses

LAB

Pubmed

Edward A. Clark

A major goal of Dr. Clark’s lab has been to define receptors and ligands regulating B cells and dendritic cells (DCs) and to help translate findings for use in clinical immunology. His lab helped discover and characterize human B cell/DC-associated surface molecules like CD20, CD22, CD40, CD80 (B7.1), CD150 (SLAM) and CD180 (RP105). Recently, the lab has focused on defining C-type lectin receptors (CLRs) on DCs and assessing immune responses after antigens (Ags) are targeted in vivo to receptors. Dr. Clark’s lab has coupled Ags to monoclonal antibodies (mAbs) specific for receptors including DCIR2 and BDCA2 that are selectively expressed on DC subsets. The Ag-mAb conjugates are inoculated into mice as a kind of ‘antigen-delivery system’, and depending on where the Ag is targeted, a different kind of immune response is programmed. When Ag is delivered to DCIR2+ DCs in splenic bridging channels, a rapid extrafollicular Ab response is induced but not germinal center formation unless a second signal is provided. When Ag is targeted to BDCA2 on plasmacytoid DCs, Ag-specific immunologic tolerance is induced. When Ag is targeted to CD180 expressed on both B cells and DCs, a strong protective immune response is induced that includes high affinity Abs and Ag-specific CD8 T cells. The lab is currently testing recombinant protein anti-CD180 based vaccines for treatment of patients with hepatitis B virus (HBV) and for protection against viruses like West Nile virus (WNV) and Zika virus. Dr. Clark has helped to found two successful biotech companies in Seattle, and from 2014-2016 was a UW Entrepreneurial Faculty Fellow. A current goal is to launch another company using the CD180-based platform technology.

B cells are very social cells; their behavior is influenced not only by T cells, but also by Ag presented in different forms including in association with DCs or macrophages. DCs and macrophages also produce cytokines like BAFF, which are essential for B cell survival and maturation. The Clark lab investigates how DCs regulate B cell responses. Current projects in this area include: 1) defining the role innate immune pathways involving MAVS and IFNAR play in protective humoral immune responses to WNV; 2) characterizing how TLR7 regulates and dysregulates B cell development and antibody production; 3) defining how DCs program B cells to develop extrafollicular Ab responses or germinal centers and long-lived humoral immunity; 4) investigating how BAFF from different cell sources regulates B cell responses to Ag.

  1. Chappell CP, Giltiay NV, Draves KE, Chen CK, Hayden-Ledbetter MS, Shlomchik MJ, Kaplan DH, Clark EA. Targeting antigens through blood dendritic cell 2 (BCDA2) on plasmacytoid dendritic cells promotes immunologic tolerance, J Immunol 192:5789-5801, 2014.
  2. Giordano D, Li C, Draves KE, Hohl T, Clark EA. Nitric oxide regulates B cell activating factor (BAFF) expression and T cell-independent antibody responses, J Immunol 193:1110-1120, 2014.
  3. Clark EA. Perspective: A short history of the B cell-associated surface molecule CD40. Frontiers Immunol 5:472, doi:10.3389/fimmu.2014.00472, 2014.
  4. Giltiay NV, Chappell CP, Sun X, Kolhatkar N, Teal TH, Kim J, Tanka L, Buechler MB, Hamerman JA, Imanishi-Kari T, Clark EA, Elkon KB. Overexpression of toll-like receptor 7 promotes cell-intrinsic expansion and autoantibody production by transitional T1 B cells, J Exp Med 210:2773-89, 2013.
  5. Chaplin JW, Chappell CP, Clark EA. Targeting antigens to CD180 rapidly induces antigen-specific IgG, affinity maturation and immunologic memory, J Exp Med 210:2135-2146, 2013.
  6. Ma DY, Suthar MS, Kasahara S, Gale M Jr, Clark EA. CD22 is required for protection against West Nile virus infection, J Virol 87: 3361-3375, 2013.
  7. Suthar MS, Ramos HJ, Brassil M, Netland J, Chappell CP, Blahnik G, McMillian, Diamond MS, Clark EA, Bevan MJ, Gale M Jr. The RIG-I-like receptor, LGP2 controls CD8 T cell survival and fitness, Immunity 37:1-14, 2012.
  8. Chappell CP, Draves KE, Giltiay NV, Clark EA. Extrafollicular B cell activation by marginal zone dendritic cells drives T cell-dependent antibody responses, J Exp Med 209:1825-1849, 2012.
B.A., Psychology and Zoology, University of California, Los Angeles 
Ph.D., Microbiology/Immunology, University of California, Los Angeles

Graduate Students
Justin Theophilus Ulrich-Lewis, julrlew@uw.edu

Postdoctoral Fellows and Instructors
Natalia Giltiay, Research Assistant Professor, Division of Rheumatology (Clark Lab Affiliate), giltiayn@uw.edu
Runa Kuley, kuleyr@uw.edu
Kelsey Roe, roek2@uw.edu
Lucy Young, lbyoung@uw.edu

Laboratory Staff
Kevin Draves, kedraves@uw.edu
Daniela Giordano, giordano@uw.edu
Ursula Holder, ursulah@uw.edu
Geraldine Shu, glshu@uw.edu