Kenneth A. Christensen
BS Chemistry, Brigham Young University (1992)
PhD Chemistry, University of Michigan (1997)
Postdoctoral Fellow studying Host-Pathogen Interactions with Stanley Joel Swanson, University of Michigan Medical School, Ann Arbor (1998-2002)
Postdoctoral Fellow studying Protein-Protein Interactions with John Collier, Harvard Medical School, Boston, MA (2002-2004)
Dr. Christensen’s lab works in the fields of biochemistry and bioanalytical chemistry. His lab develops methods that apply optical spectroscopy, time-lapse microscopy, and other current analytical and biophysical techniques to questions in biochemistry, biophysics, cell and microbiology.
A current area of research in my lab grew out of our discovery several years ago that the anthrax toxin receptors capillary morphogenesis gene protein 2 (ANTRX2/CMG2) and tumor endothelial marker 8 (ANTRX1/TEM8) were involved in angiogenesis in pathological conditions in the eye and in tumor models. We developed and used fluorescence resonance energy transfer (FRET)-based high throughput screening assays aimed at identifying molecules that block protein-protein interactions with anthrax toxin receptors. Small molecules that were identified in this screen continue to be developed as potential therapeutics for corneal neovascularization and other pathologies of angiogenesis. We have recently begun using phage display technology to identify short peptide sequences with similar antiangiogenic effects. In parallel with these discovery efforts, we are working to identify the native role of CMG2 and TEM8 and how these receptors interact with extracellular matrix proteins. We believe that this may be important to understand the receptor’s roles in important signaling pathways of angiogenesis.
A second project focuses on measuring and monitoring glucose metabolism in eukaryotic parasites. For example, in Trypanosoma brucei (the causative agent of Human African Trypanosomiasis), the sole source for generating ATP during the infectious lifecycle stage of the African trypanosome occurs exclusively in a unique peroxisome-like compartment called the glycosome. We are developing and using both recombinant protein-based FRET sensors and peptide-targeted small molecule sensors to quantitatively measure intraglycosomal pH, glucose, and ATP levels in live parasites. We are interested in the mechanisms the organism uses for regulation of pH, glucose, ATP production, and other important metabolites. Since glycolysis is key to parasite survival, inhibiting glycolysis in the glycosome could be an excellent targeted therapeutic approach for treatment of African Trypanosomiasis. Other parasites of interest are Leishmania donovoni and Trypanosoma cruzi.
1. Rogers, M.S., Christensen, K.A., Wigelsworth, D.J., Collier, R.J., and D’Amato, R.J., “Mutant Anthrax Toxin B-moiety (Protective Antigen) Inhibits Angiogenesis and Tumor Growth”, Cancer Research, 67, 9980-9985 (2007)
2. Dodson, H.C., Lyda, T.L., Chambers, J.W., Morris, M.T., Christensen, K.A., Morris, J., “Quercetin, a fluorescent bioflavanoid, inhibits Trypanosoma brucei hexokinase 1” Experimental Parasitology, 127, 423-428 (2011)
3. Rogers, M.S., Cryan, L.M., Habeshian, K.A., Bazinet, L., Caldwell, T.P., Ackroyd, P.C., and Christensen, K.A., “A FRET-based High Throughput Screening Assay to Identify Inhibitors of Anthrax Protective Antigen Binding to Capillary Morphogenesis Gene 2 Protein” PLOS One, 7(6): e39911 (2012).
4. Cryan, L.M., Habeshian, K.A., Caldwell, T.P., Morris, M.T., Ackroyd, P.C., and Christensen, K.A., D’Amato, R., Rogers, M.S. "Identification of Small Molecules that Inhibit the Interaction of TEM8 with Anthrax Protective Antigen using a FRET Assay" Journal of Biomolecular Screening, 18, 714-725 (2013), DOI: 10.1177/1087057113478655
5. Cryan, L.; Bazinet, L.; Habeshian, K.; Cao, S.; Clardy, J.; Christensen, K.; Rogers, M., "1,2,3,4,6-Penta-O-galloyl-β-D-glucopyranose inhibits angiogenesis via inhibition of capillary morphogenesis gene 2", Journal of Medicinal Chemistry, 56, 1940-1945 (2013), DOI: 10.1021/jm301558t
6. Lin, S., Morris, M.T., Ackroyd, P.C., Morris, J.C., Christensen, K.A., "Peptide targeted delivery of pH sensor for quantitative measurements of intraglycosomal pH in live Trypanosoma brucei" Biochemistry, 52, 3629-3637 (2013), DOI: 10.1021/bi400029m
See CV above for full list.