Frederik Lindberg, M.D., Ph.D.
Assistant Professor of Medicine and Molecular Microbiology

Office/Lab: (314)  747-0119
FAX:  (314)  362-9230
E-mail: lindberg@id.wustl.edu

Office/Lab: 8844/8843 Wohl Clinic, Box 8051

We have cloned the cDNA for Integrin-Associated Protein (IAP/CD47), and made knockout mice deficient in this receptor.  IAP is a unique immunoglobulin superfamily member with an extracellular Ig variable domain, a five times membrane-spanning domain and a short cytoplasmic tail that is alternatively spliced in a tissue-specific manner.  IAP is important in neutrophil activation by extracellular matrix proteins and in migration of leukocytes through endothelium into inflamed tissue.  This has been shown both by using primary IAP-deficient murine cells and by antibody inhibition of human cells.  IAP also functions as a costimulator of T cells in vitro.  Showing that these effects are relevant, IAP-deficient mice have decreased resistance against bacterial infection, fewer T cells, and reduced T cell proliferation in response to inflammatory stimuli.

We are interested in elucidating structure-function relationships in IAP and the signal transduction that leads from IAP to activation and transmigration.  We investigate structure function relationships by transfecting IAP mutant constructs into IAP-deficient cells, assaying transmigration and integrin activation.  For many of these assays, we use IAP-deficient and normal primary murine cells.  Soluble IAP variants are used to characterize IAP ligands.  T cell receptor transgenic systems are used for in vitro proliferation and cytokine release experiments.  In vivo, we test the consequences of the various in vitro defects to inflammation, immune response, and to the severity of inflammatory diseases.