Dr. Kenneth Bradley's lab is interested in identifying host factors that are usurped by bacterial pathogens in order to promote virulence. Specifically, they are studying two protein exotoxins secreted by Bacillus anthracis. These anthrax toxins are major virulence factors and one, lethal toxin, can itself cause death when injected into animals. Death at the cellular level induced by lethal toxin is not well understood, but macrophages and endothelial cells are sensitive to toxin in vitro. Within 90 minutes of toxin translocation into murine macrophages, cell lysis occurs. Furthermore, destruction of lymph nodes is commonly seen in anthrax patients. The interaction of toxin with host immune cells seems to play an important role in disease progression. To better understand this interaction, Bradley's lab is performing somatic cell and chemical genetic screens to elucidate the cellular events that occur after toxin enters the cytosol of macrophages. Additionally, they are using genetic, biochemical, biophysical and nanotechnology based techniques to characterize the interaction of anthrax toxins with their host cellular receptors.
Selected Cancer-Related Publications:
Banks, DJ, Bradley KA. Silence: a new forward somatic cell genetic selection platform technology. Nature Methods. 2007; 4(1):51-53.
Christman KL, Requa MV, Enriquez-Rios VD, Ward SC, Bradley KA, Turner KL, Maynard HD. Submicron streptavidin patterns for protein assembly. Langmuir. 2006; 22(17): 7444-50.
Bradley KA, Mogridge J, Jonah G, Rainey A, Batty S, Young JA. Binding of anthrax toxin to its receptor is similar to alpha integrin-ligand interactions. J Biol Chem. 2003; 278(49): 49342-7.
Scobie HM, Rainey GJ, Bradley KA, Young JA. Human capillary morphogenesis protein 2 functions as an anthrax toxin receptor. Proc Natl Acad Sci U S A. 2003; 100(9): 5170-4.
Bradley KA, Mogridge J, Mourez M, Collier RJ, Young JAT. Identification of the cellular receptor for anthrax toxin. Nature. 2001; 414:225-229.