Professor Microbiology and of Immunology
Phone: (206) 543-8706
Office Location: Health Sciences I-321
Campus Box: 357735
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 departmental appointment, he is Professor of Immunology and a Core Scientist in the Regional Primate Center. Dr. Clark serves on several editorial boards of immunology journals.
One major research area in Dr. Clark's laboratory focuses on factors which regulate the survival and death of B lymphocytes. The expansion and contraction of lymphoid tissues during infections is due in part to rapid proliferation and death of B cells, as they are selected to produce protective antibodies against pathogens. Dr. Clark's laboratory is interested in how antibody-forming B lymphocytes are maintained or activated to divide, differentiate or die . B lymphocytes 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 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 receptors or the CD40 receptor. The roles adaptor proteins such as Bam32 play in regulating B cell fate are being investigated with knockout mice.
Dr. Clark's laboratory also investigates receptors regulating dendritic cells (DCs). Dendritic cells (DCs) not only are key 'sentinels' of the immune system, but also coordinate and bridge innate and adaptive immune responses. They respond to infectious agents through different families of ligands and receptors such as the Toll-like receptor (TLR) and C-type lectin receptor (CLR) families. Dr. Clark's lab studies the important growing family of type II DC-Associated C-type Lectins (DCALs), which includes, e.g., DC-SIGN, dectin-1, DCAL-1 and DCAL-2 discovered by the Clark lab. Dr. Clark's group is currently testing how C-type lectins on DCs function to capture and present intact antigens to the immune system and how they transmit pathogen-specific information about how best to respond to a pathogen. His work will help in the development of new vaccine strategies. In related projects, Dr. Clark's lab is investigating factors regulating DC survival and how DCs respond differently to commensal vs. pathogenic bacteria found in the oral cavity.
Niiro, H., Maeda, A., Kurosaki, T., and Clark, E.A. The Bam32 adaptor protein regulates B cell antigen receptor signaling and cell fate, J. Exp. Med., 195: 143-149, 2002.
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.
Olson, N.E., Graves, J. D., Shu, G. L., Ryan, E.J., and Clark, E.A. Caspase activity is required for stimulated B lymphocytes to enter the cell cycle, J. Immunol., 170: 6065-6072, 2003.
Bengtsson, A.K., Ryan, E.J., Magaletti, D.M., and Clark, E.A. 17-fl-estradiol (E2) modulates cytokine and chemokine expression in human monocyte-derived dendritic cells, Blood, 104: 1404-1410, 2004.
Yankee, T.M., Yun, T.J., Draves, K.E., Ganesh, K., Bevan, M.J., Muali-Krishna, K. and Clark, E.A. The Gads (GrpL) adaptor protein regulated T cell homeostasis, J. Immunol., 173: 1711-1720, 2004.