Program Director/Principal Investigator (Last, First, Middle):
Clark, Edward A.
BIOGRAPHICAL SKETCH
Provide the following information for the Senior/key personnel and other significant contributors in the order listed on Form Page 2.
Follow this format for each person. DO NOT EXCEED FOUR PAGES.
NAME
POSITION TITLE
Edward A. Clark
Professor
eRA COMMONS USER NAME (credential, e.g., agency login)
eclark
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and
residency training if applicable.)
DEGREE
INSTITUTION AND LOCATION
MM/YY
FIELD OF STUDY
(if applicable)
University of California, Los Angeles
University of California, Los Angeles
University College London
BA
PhD
Postdoc
06/1969
06/1977
1977-79
Psychology/Zoology
Microbiol/Immunology
Immunology
A. Personal Statement.
For over 30 years my lab has carried out research in human immunology, most notably in the areas of B cell and
dendritic cell (DC) biology. My lab contributed to the discovery/characterization of a number of human B cellassociated surface molecules such as CD20, CD22, CD37, CD39, CD40, CD54, CD80 (B7.1), CD150 (SLAM)
and CD180 (RP105) as well as some of their mouse counterparts. Our discovery of CD40 and that CD40
ligation stimulates B cell activation led to a better understanding of the molecular basis of T cell helper activity.
More recently, my lab has focused on innate signaling pathways and investigating: 1) new C-type lectin
receptors (CLRs) on DC subsets (DCAL1, DCAL2 and DCIR2); 2) the programming of DC subsets by
pathogens or pathogenic products; and 3) novel methods for targeting antigens into the immune system to
program humoral immune responses. A major current goal is to develop new approaches that can be used for
treatments of autoimmune diseases such as systemic lupus erythematosus and Sjogren’s syndrome and in
vaccines. Our studies on B cell signaling and surface markers led me to help found in 2001 a biotechnology
company, Trubion Pharmaceuticals, which has developed scFv based drugs to human CD20 (now in clinical
trials run by Wyeth) and human CD37 (now in trials for CLL, now via Emerging Biosolutions, which purchased
Trubion). My lab investigates the programming of humoral immunity by measuring B cell activation and
differentiation, T cell-dependent and independent responses, affinity maturation and germinal center formation.
Positions and Honors
Positions
Current: 1979-present: Core Staff Scientist, Washington National Primate Research Center (WANPRC),
University of Washington (UW), Seattle, WA, (with absence, 1982-84); 1990-present: Professor, Microbiology,
UW; 2001-present: Professor, Immunology, UW; 2012-present: Adjunct Professor, Medicine (Rheumatology),
UW; 2005-present: ad hoc then Member, CMIA Study Section (term ending 2016)
Other: 1970-1974: Staff Research Associate and Renal Transplant Coordinator, Department of Surgery,
UCLA (with Paul I. Terasaki); 1974-1977: Postgraduate Research Assistant, Department of Microbiology and
Immunology, UCLA (with William H. Hildemann); 1977-1979: Honorary Staff Research Assistant, Department
of Zoology, University College, London (with N. Avrion Mitchison); 1979-1984: Assistant Professor, Genetics,
UW; 1981-1984: Founder and Senior Scientist, Genetic Systems Corporation, Seattle, WA; 1984-1990:
Associate Professor, Microbiology and Immunology, UW; 1988-2002: Member, Center for AIDS Research,
UW; 1987: Foreign Research Scholar, Division of Immunology, Institute of Molecular and Cellular Biology,
Osaka University, Osaka, Japan (with Tadamitsu Kishimoto); 1991-2001: Adjunct Professor, Immunology, UW;
2001-2008: Founder and Chair, Scientific Advisory Board, Trubion Pharmaceuticals, Inc., Seattle, WA (TRBN);
1990-1994: Member, Experimental Immunology Study Section.
Honors: 1965-1969: University of California Regents Scholar; 1977: Inter-Science Research Foundation
Graduate Student Research Prize; 1977-1979: Edna A. Old Memorial Fellow of the Cancer Research Institute
of New York; 1987: Japanese Ministry of Education (Mombusho), Foreign Research Scholar, Osaka
PHS 398/2590 (Rev. 06/09)
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Biographical Sketch Format Page
Program Director/Principal Investigator (Last, First, Middle):
Clark, Edward A.
University; 1995: Science Watch Most Highly Cited Authors in Immunology 1990-94, No. 15; 2001: Science
Watch Most Highly Cited Authors in Immunology 1981-2001; 2004-present: NIH, NIAID MERIT Award.
B. Relevant Publications (of >325)
1. 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. 2012. 209: 1797-1812 PMID: 22966002
2. Kasahara S, Clark EA. Dendritic cell-associated lectin 2 (DCAL2) defines a distinct CD8- dendritic cell
subset, J Leukocyte Biol, 91: 437-48, 2012. PMID: 22147811
3. 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. 2011 187:4199-4209.
PMID: 21918197
4. Hughes GC, Martin D, Zhang K, Hudkins KL, Alpers CE, Clark EA, Elkon KB. Decrease in
glomerulonephritis and Th1-associated autoantibody production after progesterone treatment in NZB/NZW
mice. Arthritis Rheum. 2009. 60:1775-84.PMID: 19479860
5. Chino T, Draves KE, Clark EA. Regulation of dendritic cell survival and cytokine production by
osteoprotegerin. J Leukocyte Biol, 86:933-940, 2009. PMID: 19641036
6. Hughes GC, Thomas S, Li C, Kaja MK, Clark EA. Progesterone regulates IFN- production by
plasmacytoid dendritic cells, J Immunol Cutting Edge, 180:2029-2033, 2008. PMID: 18250406
7. Chen CK, Floyd HE, Olson NE, Magaletti D, Li C, Draves KE, Clark EA. The human C-type lectin, DCAL-2
regulates dendritic cell-dependent T cell maturation, Blood, 107:1459-1467, 2006. PMID: 16239426
8. Craxton A, Draves KE, Gruppi A, Clark EA, BAFF regulates B cell survival by downregulating the BH3-only
homolog Bim via the ERK pathway, J Exp Med, 202:1363-1374, 2005. PMID: 16301744 [
9. Craxton A, Magaletti D, Ryan EJ, Clark EA. Macrophage- and dendritic cell-dependent regulation of human
B cell proliferation requires the TNF-family ligand, BAFF, Blood, 101:4464-4471, 2003. PMID: 12531790
10. Sidorenko SP, Clark EA. The dual-function CD150 receptor subfamily: the viral attraction. Nat Immunol
2003. 4:19-24. PMID: 12496974
11. Niiro H, Clark EA. Regulation of B cell fate by antigen receptor signals. Nat Rev Immunol 2:945-956, 2002.
PMID: 12461567
12. Aicher A, Hayden-Ledbetter M, Brady WA, Pezzutto A, Richter G, Magaletti D, Buckwalter S, Ledbetter JA,
Clark EA. Characterization of human inducible costimulator ligand expression and function, J Immunol 164:
4689-4696, 2000. PMID: 10779774
13. Clark EA, Ledbetter JA. How B and T cells talk to each other. Nature, 367: 425-428, 1994. PMID: 8107800
14. Linsley PS, Clark EA, Ledbetter JA. The T cell antigen CD28 mediates adhesion with B cells by interacting
with the activation antigen B7/BB1 Proc Nat Acad Sci USA 87: 5031-5035, 1990. PMID: 2164219
15. Stamenkovic I, Clark EA, Seed B. A B cell activation molecule related to the nerve growth factor receptor
and induced by cytokines in carcinomas. EMBO J. 8: 1403-1410, 1989. PMID: 2475341
C. Research Support
Principal Investigator: "FDCR1 and follicular dendritic cell signaling pathways, " NIAID Merit Award
R37AI44257-13, Merit Award began in year 06, July 2004-June 2014.
Principal Investigator: “Dendritic Cell-Associated C-Type Lectins,” NIAID R01 AI52203-10, 2003-June 2015.
Project Leader: “Regulation of B cell responses to West Nile virus” NIAID U19 Center ‘Immune Mechanisms of
Flavivirus Control’ (P.I.: Michael Gale, Jr) AI83019-04 May 2009-April 2014.
Co-investigator, ‘Program for Autoimmune Disease Intervention’ (P.I.: G. Nepom), State of Washington, Life
Sciences Discover Fund, June 2008-May 2013.
-Principal Investigator: “Establishing and characterizing BAFF RFP reporter and BAFF knockin mice,” NIAID
R03AI101467-01, May 2012-May 2014.
Dr. Clark has active member of an Immunology Training Grant for >20 years from NCI. He is also a member of
a Rheumatology Training Grant and a Molecular Medicine Training Grant.
Completed grant: Principal Investigator "Structure/function human B cell differentiation antigens," NIGMS
R01 GM37905, January 1986-March 2009.
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