Chronic stress is thought to contribute to most aging related disorders including ocular disorders. Oxidative stress is thought to be the major source of chronic stress. This can be generated by metabolism, by light exposure, diabetes, infections, etc. Two approaches have been taken to study chronic stress. The focus of one study is to define the mechanisms cells use for protection against hydrogen peroxide and lipid peroxides and to elucidate differences in the mechanisms, if any, that cells use against different peroxides. In this case, cells were adapted to growth on high concentrations of peroxides and changes in the respective proteomes were determined. A proteomics approach was used to determine quantitative differences in protein expression in the presence and absence of each peroxide and to identify the proteins with altered expression. The results demonstrate that cells use several approaches to survive under chronic stress conditions. These include altering gene expression, protein expression, and the post-translational modifications of proteins. The results further show there are common mechanisms used with different peroxides but survival in the presence of lipid peroxides require additional cellular responses. The second approach has been to use RNA interference approaches to study the effects of knocking down genes that have a role in tumorigenesis, inflammation etc. The initial studies have been done in B16 melanoma tumor cells and syngeneic non-tumorigenic cells. A number of technical approaches have been used to understand the effects on cells of knocking down specific genes.
| Eriksson, Fredrik; Culp, W David; Massey, Robert et al. (2007) Tumor specific phage particles promote tumor regression in a mouse melanoma model. Cancer Immunol Immunother 56:677-87 |
| Culp, W David; Neal, Rachel; Massey, Robert et al. (2006) Proteomic analysis of tumor establishment and growth in the B16-F10 mouse melanoma model. J Proteome Res 5:1332-43 |
| Neal, R E; Bettelheim, F A; Lin, C et al. (2005) Alterations in human vitreous humour following cataract extraction. Exp Eye Res 80:337-47 |
