Abstract

Description) The major specific aims for this grant are: 1) Define mechanisms involved in signal transduction and the regulation of gene expression in cells of the immune system. Identify genes whose expression changes in response to differentiation or activation signals. Characterize genetic defects in signal transduction mutants that fail to respond to inflammatory cytokines or other immunostimulatory agents. Develop a second FACS-detectable reporter gene system and establish methods for independently measuring the expression of this gene and the expression of the Lac-Z (B-galactosidase) reporter gene in the same cell. Define the pathways through which oxidants and antioxidants regulate the expression of genes stimulated by tumor necrosis factor-alpha (TNF-a) and other inflammatory cytokines; 2) Further define immunoglobulin structure/function relationships. Select and characterize additional hybridoma variants whose binding affinities differ from a parental antidigoxin monoclonal antibody whose structure has now been solved by X-ray crystallography. Explore the functional and developmental characteristics of the CD5 and other B cell subsets in relation to the model of the evolutionary layered immune system proposed by the applicant; and 3) Create innovative software and hardware that will bring new and improved capabilities to the FACS and make the instrument easier to use for complex sorting and analysis experiments.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Unknown (R35)
Project #
2R35CA042509-08
Application #
3479339
Study Section
Special Emphasis Panel (SRC (88))
Project Start
1986-07-01
Project End
2000-06-30
Budget Start
1993-09-30
Budget End
1994-06-30
Support Year
8
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
Stanford University
Department
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305

  Publications

Fong, Lawrence; Mengozzi, Manuela; Abbey, Nancy W et al. (2002) Productive infection of plasmacytoid dendritic cells with human immunodeficiency virus type 1 is triggered by CD40 ligation. J Virol 76:11033-41
De Rosa, S C; Mitra, D K; Watanabe, N et al. (2001) Vdelta1 and Vdelta2 gammadelta T cells express distinct surface markers and might be developmentally distinct lineages. J Leukoc Biol 70:518-26
De Rosa, S C; Herzenberg, L A; Herzenberg, L A et al. (2001) 11-color, 13-parameter flow cytometry: identification of human naive T cells by phenotype, function, and T-cell receptor diversity. Nat Med 7:245-8
Tjioe, I; Legerton, T; Wegstein, J et al. (2001) Phycoerythrin-allophycocyanin: a resonance energy transfer fluorochrome for immunofluorescence. Cytometry 44:24-9
Nakamura, H; Herzenberg, L A; Bai, J et al. (2001) Circulating thioredoxin suppresses lipopolysaccharide-induced neutrophil chemotaxis. Proc Natl Acad Sci U S A 98:15143-8
Mengozzi, M; Malipatlolla, M; De Rosa, S C et al. (2001) Naive CD4 T cells inhibit CD28-costimulated R5 HIV replication in memory CD4 T cells. Proc Natl Acad Sci U S A 98:11644-9
Salomon, A R; Voehringer, D W; Herzenberg, L A et al. (2001) Apoptolidin, a selective cytotoxic agent, is an inhibitor of F0F1-ATPase. Chem Biol 8:71-80
Torres-Roca, J F; Tung, J W; Greenwald, D R et al. (2000) An early oxygen-dependent step is required for dexamethasone-induced apoptosis of immature mouse thymocytes. J Immunol 165:4822-30
De Rosa, S C; Zaretsky, M D; Dubs, J G et al. (2000) N-acetylcysteine replenishes glutathione in HIV infection. Eur J Clin Invest 30:915-29
Salomon, A R; Voehringer, D W; Herzenberg, L A et al. (2000) Understanding and exploiting the mechanistic basis for selectivity of polyketide inhibitors of F(0)F(1)-ATPase. Proc Natl Acad Sci U S A 97:14766-71

Showing the most recent 10 out of 83 publications