Research with David Hall

The long-range goal of Dr. David Hall’s (Faculty Co-mentor from Lawrence University) research is to understand the mechanisms by which macrophage activation through exposure to viral or bacterial pathogens leads to an inflammatory environment within the body. Previous studies have implicated the macrophage as playing an important role in the elaboration of the inflammatory environment observed in asthma exacerbations. Accordingly, this research is focused on evaluating the involvement of key signaling events in rhinovirus-stimulated mediator production by the macrophage and will examine how these events contribute to the inflammatory response.

In accordance with their overall goals, Dr. Hall’s group performed preliminary high density oligonucleotide microarray experiments with monocytes stimulated with and without rhinovirus. Of significance was the up-regulation of the virus receptor ICAM-1 and six types of IFN-alpha (some over 100-fold) as well as 46 different genes that are reported to be IFN-regulated including cylcooxygenase-2, 5-lipoxygenase, the transcription factors p53 and ISGF-3 (3-fold each) as well as PKR. Many undergraduate projects utilizing the Proteomics and Functional Genomics capabilities at UW Oshkosh are vital to achieve the long range goal of Dr. Hall’s research. The first project involves confirmation of the preliminary microarray information. Of immediate interest is the upregulation of cyclooxygenase-2 and 5-lipoxygenase noted in the microarray data. These two gene products may be important for the resolution of viral infections. Indeed, there are little or no data published on these proteins being involved in rhinovirus infection. A kinetics analysis, using 2-D gel electrophoresis, of proteins up- and down-regulated during viral infection of macrophages, will be most illuminating. A second project involves the investigation of the inhibitory properties of nitric oxide on rhinoviral protease 3C. Nitric oxide clearly inhibits release of infectious viral particles during rhinovirus infection; however, the mechanism is unclear. Hall’s group speculates that nitric oxide chemically modifies the viral proteins in various ways. To test this hypothesis, the 3C protease will be isolated from infected cells exposed to nitric oxide. Subsequent immunoprecipitation and MADLI-TOF mass spectrometry will be performed to determine if the 3C protease has been chemically modified after nitric oxide treatment.