Edward A. Clark, Ph.D.
Professorof Microbiology and Immunology

Department of Microbiology
University of Washington
Office I 319 A HSC, Box 357242
1959 NE Pacific Street
Seattle, WA 98195-7650
Tel: 206.543-8706
Fax: 206.685-0305
Email: eclark@bart.rprc.washington.edu

Clark Lab Members

Dr. Clark received a Ph.D. in microbiology and immunology from the University of California, Los Angeles. He did postdoctoral research at University College London with Dr. N. A. Mitchison.  In addition to his faculty appointments, Dr. Clark is a Core Scientist in the Regional Primate Center.

Dr. Clark's laboratory is interested in how B lymphocytes are activated to survive, proliferate or undergo programmed cell death. B cells are very social cells, and their behavior is influenced not only by various forms of specific antigen, but also by receptor-ligand interactions with T lymphocytes (e.g., CD40 ligand), dendritic cells (DCs) and macrophages (e.g., BAFF). A major goal of the laboratory is to define key signaling pathways regulating the fate of B cells after they are activated through antigen, CD40 or BAFF receptors. Recent studies have focused on how DCs regulate B cell activation. Molecules currently under study include BH3-only Bcl-2 family members suchas Bim, the adaptor protein Bam32 and caspase-6.

Dr. Clark's laboratory also investigates receptors regulating DC activation and functions. DCs are sentinels within the immune system, which respond to pathogens through pattern recognition receptors such as Toll-like receptors (TLR) or C-type lectin receptors (CLRs). These receptors program DCs to migrate to lymph nodes and instruct T cells and B cells to make appropriate responses to infections. Dr. Clark's lab is elucidating the functions of novel CLRs on DCs, including DCAL-1, which may regulate IL-4 responses in T cells, and DCAL-2, which may regulate IL-12 production by DCs. In another project, the lab is investigating how DCs are regulated by female sex hormones, estrogen and progesterone and the estrogen-regulated decoy receptor, OPG. Many autoimmune diseases are much more prevalent in women than men; it is possible that this is due in part to dysregulation of DCs.

Students currently training in the Clark Lab: Sabrina Richards, Shinji Kasahara, Daphne Ma (Immunology) and Taka Chino (Oral Biology)

Representative publications:

Niiro, H. and Clark, E.A. Regulation of B cell fate by antigen receptor signals. Nat. Rev. Immunol., 2:945-956, 2002.

Craxton, A., Magaletti, D., Ryan, E.J., and Clark, E.A. Macrophage- and dendritic cell-dependent regulation of human B cell proliferation requires the TNF-family ligand, BAFF, Blood, 101:4464-4471, 2003.

Graves, J.D., Craxton, A., and Clark, E.A. Modulation and function of caspase pathways in B lymphocytes, Immunol. Rev., 197:129-146, 2004.

Craxton, A., Draves, K.E., Gruppi, A., and Clark, E. A., BAFF regulates B cell survival by downregulating the BH3-only homolog Bim via the ERK pathway, J. Exp. Med., 202:1363-1374, 2005.

Chen, C.K., Floyd, H.E., Olson, N.E., Magaletti, D., Li, C., Draves, K.E., and Clark, E. A. The human C-type lectin, DCAL-2 regulates dendritic cell-dependent T cell maturation, Blood, 107:1459-1467, 2006.

Hughes GC, Thomas S, Li C, Kaja MK, Clark EA. Progesterone regulates IFN-a production by plasmacytoid dendritic cells, J Immunol Cutting Edge, 180:2029-2033, 2008.

Santos L, Draves KE, Boton M, Grewal PK, Marth JD, Clark EA. Dendritic cell-dependent inhibition of B cell proliferation requires CD22, J Immunol 180:4561-4569, 2008.

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Updated June 25, 2008