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'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.

Giordano, D., Magaletti, D., and Clark, E. A. Nitric oxide and cGMP protein kinase (cGK) regulate dendritic cell migration toward the lymph node-directing chemokine CCL19, Blood, 107:1537-1545, 2006.

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Updated July 2006