• Seldin, Michael F (PI)
  • Singer, Kay (PI)
  • St Clair, E. William (PI)
  • Kaufman, Russel E. (PI)
  • McCachren, S. Spence (PI)
  • Denning, Stephen (PI)
  • Krangel, Michael (PI)
  • Palker, Thomas (PI)
  • Keefe, Francis (PI)
  • Haynes, Barton (PI)
  • Patel, Dhavalkumar D. (PI)
  • Weinberg, Joe Brice (PI)
  • Pisetsky, David S. (PI)

Project: Research project

Project Details


The theme of this grant is modulation of pathogenic and
therapeutic mechanisms in rheumatoid arthritis (RA). Projects 1,
2, and 3 will focus on T cell-macrophage and T cell-synovial cell
interactions and cytokine-synovial cell interactions in the
generation of synovial lesions of RA. Using new monoclonal
antibodies, new assay systems for the study of molecules involved
in T cell interaction with RA synovial microenvironment cells,
and measurements of cytokine (e.g. IL-1 and TNF) effect on
synovial microenvironment cells and cytokine messenger RNA
production using Northern blot and in situ hybridization analysis,
the specific mechanisms and molecules in T cell-synovial
microenvironment cell interactions and their sequelae will be
studied. In addition cellular and molecular events associated with
synovial lining cell activation to proliferation on inflammatory
cytokine release with be studied. Project 4 will investigate B cell
auto-antibody production in Sjogren's Syndrome and RA using
cloned Ro and La recombinant autoantigens. Project 5 explores
the pathogenesis of the MRL mouse model of arthritis using many
of the same techniques and concepts discussed in projects 1, 2,
and 3. Project 6 uses proven and innovative modalities of pain
modification to alter RA patients' response to chronic pain --
thereby modifying a pathogenic mechanism (chronic pain) that is a
major cause of morbidity in RA. Taken together, the work
proposed in this SCOR grant represents a multidisciplinary effort
to use innovative and novel approaches to modify joint
inflammation, bone loss, and chronic pain in RA. By
understanding basic mechanisms of pathogenesis of RA at the
molecular, cellular, metabolic, and neuropsychiatric levels,
hopefully novel therapies capable of modifying, and ultimately
abrogating, the pathogenic mechanisms that lead to morbidity and
mortality in RA can be developed.
Effective start/end date9/30/878/31/01


  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health


  • Medicine(all)


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