Edward A. Clark, Ph.D.
Professor, Department of Microbiology
Professor, Department of Immunology
Adjunct Professor of Medicine
750 Republican Street
Box 358059, Room E343
Seattle, WA 98109
EDUCATION AND TRAINING
- B.A., Psychology and Zoology, University of California, Los Angeles
- Ph.D., Microbiology/Immunology, University of California, Los Angeles
CURRENT RESEARCH INTERESTS
- Adaptive Immune Responses
- Infectious Diseases
- Innate Immunity
- Tolerance & Autoimmunity
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 including DCAL2, which is a useful marker to identify and isolate DC subsets. In order to assess the function of CLRs and their possible use for vaccine development, Dr. Clark’s lab has coupled antigens (Ags) to monoclonal antibodies (mAbs) specific for CLRs expressed on DC subsets. The Ag-mAb conjugates are inoculated into mice as a kind of ‘antigen-delivery system’, which enables Ags to be selectively targeted to a particular DC subset, which then responses and programs an appropriate, protective immune response. Targeting antigens to DCIR2 or CD180, in particular, induces strong and rapid antibody responses and has great potential in platforms for vaccines.
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 CD22 and other B cell/DC-associated receptors play in protective immune responses to West Nile virus; 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.
- Porakishvili N, Vispute K, Steele AJ, Rajakaruna N, Kulikova N, Tsertsvadze T, Nathwani A, Damle RN, Clark EA, Rai KR, Chiorazzi N, Lydyard PM.Rewiring of sIgM-mediated intracellular signaling through the CD180 Toll-like receptor. Mol Med. 2015 Jan 14. doi: 10.2119/molmed.2014.00265. [Epub ahead of print] PMID: 25611435
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Kasahara S, Clark EA. Dendritic cell-associated lectin 2 (DCAL2) defines a distinct CD8α- dendritic cell subset, J Leukocyte Biol, 91:437-448, 2012.
- Watanabe C, Shu GL, Clark EA. Caspase 6 regulates early B cell differentiation, Europ J Immunol, submitted 2011.
- Richards SM, Li C, Draves KE, Niiro H, Dinauer MC, Clark EA. The adaptor protein Bam32 regulates G1 cycle progression downstream of B cell receptor signaling, Europ J Immunol, submitted, 2011.
- Chaplin JW, Kasahara S, Clark EA, Ledbetter JA. Anti-CD180 (RP105) activates B cells to rapidly produce polyclonal Ig via a T cell and MyD88-independent pathway, J Immunol 187:4199-4209, 2011.
- Porakishvili N, Memon A, Vispute K, Kulikova N, Clark EA, Rai K, Nathwani A, Damle RN, Chiorazzi N, Lydyard PM. CD180 functions in activation, survival and cycling of B chronic lymphocytic leukaemia cells, Bri J Hematol 153:486-498, 2011.
- Giordano D, Li C, Suthar MS, Draves KE, Ma DY, Gale MG Jr, Clark EA. Role of nitric oxide in dendritic cell survival, cytokine production and induction of Th17 and Th1 T cell responses, J Leukocyte Biol, 89: 443-455, 2011.
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