Jonathan King, Ph.D.
- Professor , Biology
My research program is interested in understanding the physiology of epithelial cell junctions. The projects I have undertaken revolve around understanding how the tight junction proteins are affected when epithelial cells are exposed to stressful stimuli (i.e. inflammation, stretch and oxidative stress). Tight junctions are important protein complexes that hold epithelial cells together.
These complexes help regulate movement of biological molecules within an organism (i.e. nutrients from intestine to blood) and play a critical role in preventing the metastases of tumors. I am primarily interested in cellular signals and molecular mechanisms that lead to the disruption of cellular junctions with the ultimate goal of being.
I am currently using two approaches to investigate the regulation of epithelial junctional proteins. The first approach employs cellular stressors such as inflammatory mediators or oxidative stress to dissect the cellular signaling events that disrupt junctions. By stressing the cell junctions I have learned about specific response and repair mechanisms. By employing specific inhibitors of various intracellular signal transduction molecules in the studies, the relative importance of individual signaling pathways contributing to junctional disruption is determined. The second approach involves using proteomics to learn about changes in cellular proteins that might contribute to the cells losing their junctions (this allows examination of what is going on inside the cells from a more global perspective).
Currently, a mammalian kidney and lung model are used to study aspects of junctional physiology. Cell barrier function and viability are measured while examining changes in tight junction gene expression and protein localization within the cell following exposure to stress.