Virginia L Shepherd, Ph.D.

Official Affiliation: Pathology, Microbiology & Immunology

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The focus of research in our laboratory is the study of the function of macrophage receptors that are involved in control of inflammation and host defense. Two mannose-specific lectins that are localized to the lung are the membrane-associated mannose receptor (MR) and the soluble protein surfactant-associated protein A (SP-A). The MR binds directly to pathogens and extracellular glycoproteins and mediates internalization and delivery of ligand to the phagolysosomal compartment. SP-A binds to extracellular pathogens and glycoproteins, then these complexes interact with a specific macrophage surface receptor (SP-AR) that then mediates internalization. Expression of each of these receptors, the MR and the SP-AR, is dependent on the functional state of the macrophage. Activated macrophages and undifferentiated monocytes express predominantly the SP-AR, while deactivated macrophages express the MR. We have been studying the MR for the past several years, and have determined that its expression is regulated transcriptionally, translationally, and posttranslationally. Work is now underway to delineate the mechanisms involved at each of these levels. The work of SP-AR regulation is just beginning with the cloning of the SP-AR cDNA. A second major research area involves the role that the MR and SP-A/SP-AR play in pathogen clearance by macrophages. We are using both Mycobacterium and Candida albicans as model systems to investigate the direct binding of lectin and pathogen, to study the role of each receptor in internalization, and to determine if binding of pathogen to these receptors results in signaling for subsequent cytokine production. A component of this study is to examine the effect of HIV-derived proteins and mycobacteria-derived products on MR and SP-AR expression, and to determine if these products alter receptor expression and cytokine production by human macrophages.

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    615-322-7140 (p)
    615-321-6305 (f)
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    Keywords

    Biochemistry Host defense Immunology Infectious disease Lectins Macrophage biology Microbiology Pathology Pulmonary Receptor Tyrosine phosphorylation