Description of Research Program
Research in the Beeson group is a fusion of chemistry and cell biology. Assays for cell metabolism are being combined with proteomic, NMR and mass spectrometric techniques to develop quantitative descriptions of biochemical networks. Analyses of these networks identify key molecular species that are potential targets for therapeutic agents. Our primary focus is the biochemical network responsible for the regulation of energy metabolism and cellular proliferation. Specific projects include studies of T-cell activation and myocardial glucose utilization. The results of the T-cell studies are being used to develop possible treatments for autoimmune diseases such as Multiple Sclerosis. A byproduct of these studies has been the development novel peptide mimetics and library based synthesis and screening techniques, which are also being used to develop inhibitors of the M. tuberculosis iron dependent repressor and Topoisomerase I. Our studies of myocardial glucose utilization have defined critical roles for lipoproteins in the regulation of mitochondrial respiration and glycolysis. These results are being used to evaluate the mechanisms of tissue injury due to ischemia-reperfusion.
ridharan, V., R.M. Bailey, H. Kasiganesan, C. Beeson & G.L. Wright, The prolyl hydroxylase oxygen-sensor confers cytoprotection through multiple mechanisms that include the maintenance of mitochondrial membrane potential during metabolic inhibition. Am. J. Phys., 2006, in revision, MS# 2005-09611.
McFarland, B.J., J. Katzt, A.J. Sant & C. Beeson, J. Mol. Biol. 2006, 350, 170-183. Energetics and cooperativity of the hydrogen bonding and anchor interactions that bind peptides to MHC class II protein.
Babic, N., N.J. Dovichi & C. Beeson, J. Proteome Res., 2005, 4, 344-348. “The Effect of High Density Lipoproteins on Protein Expression in Myoblast Cell Lines”.
Chou, J.C., Wisedchaisri, G., Monfeli, R. R., Oram, D. M. Holmes, R.K., Hol, W.J., & Beeson, C., J. Biol. Chem. 2004, 279, 53554-53561. Functional studies of the Mycobacterium tuberculosis iron dependent regulator protein.
Beeson, C., J.E. Butrynski, M.J. Hart, C.L Nourigat, D.C. Matthews, O.W. Press, P.D. Senter & I.D. Bernstein. Bioconj. Chem. 2003, 14, 727-933. Conditional Cleavable Radioimmunoconjugates- A Novel Approach for the Release of Radioisotopes from Radioimmunoconjugates.
Seamons, A., J. Sutton, D. Bai, E. Baird, N. Bonn, B.F.C. Kafsack, J. Shabanowitz, D.F. Hunt, C. Beeson & J. Goverman. J. Exp. Med. 2003, 197, 1391-1397. Competition Between Two MHC Binding Registers In A Single Peptide Processed From Myelin Basic Protein Influences Tolerance And Susceptibility To Autoimmunity.
Wiley, C. & C. Beeson, Anal. Biochem. 2002, 304, 139-146. Continuous measurement of glucose utilization in heart myoblasts.