Worm Institute for Research and Medicine (WIRM)
Faculty, Graduate Program
Strategies to Combat Evolving Human Disease
Our research is broadly focused at the interface of chemical biology, immunology, and medicine with particular interest in the development of technologies that allow questions of biological and clinical relevance to be addressed. A large focus of our work is the generation of methods that recreate in vitro the co-evolution of infectious diseases and the immune system. The technology we have developed, termed phage escape, also can be implemented as a novel high throughput screening method for small molecule protein-ligand antagonists, as well as a single molecule diagnostic platform. Application of these tools to diseases including avian influenza, cancer and neglected tropical diseases (NTDs) are currently underway. We also study the immunological basis of NTDs, including onchocerciasis and lymphatic filariasis, to both treat these diseases as well as apply the mechanisms used by these parasites to modern medicine. An additional focus of our laboratory is aimed at understanding the biochemical mechanism of botulinum neurotoxin, the most lethal protein known and a rapidly expanding clinical tool, with the goal of developing molecules that modulate toxin function.
Ph.D., Chemistry, The Scripps Research Institute, 2004
M.A., Bioorganic Chemistry, University of Virginia, 2000
B.S., Chemistry, University of Virginia, 1999
Editorial Advisory Board, Current Organic Chemistry, 2009-present
Editorial Advisory Board, Current Topics in Medicinal Chemistry, 2009-present
Editorial Board, Journal of Bioterrorism and Biodefense, 2011-present
Miller, M. L.; Creehan. K. M.; Angrish, D.; Barlow, D. J.; Houseknecht, K. L.; Dickerson, T. J.; Taffe, M. A. Changes in ambient temperature differentially alter the thermoregulatory, cardiac and locomotor stimulant effects of 4-methylmethcathinone (mephedrone). Drug Alcohol Depend. 2013, 127, 248-253.
Wright, M. J.; Vandewater, S. A.; Angrish, D.; Dickerson, T. J.; Taffe, M. A. Mephedrone (4-methylmethcathinone) and d-methamphetamine improve visuo-spatial associative memory, but not spatial working memory, in rhesus macaques. Brit. J. Pharmacol., 2012, 167, 1342-1352.
Huang, P.-K.; Aarde, S. A.; Angrish, D.; Houseknecht, K. L.; Dickerson, T. J.; Taffe, M. A. Contrasting effects of d-methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4- methylenedioxypyrovalerone, and 4-methylmethcathinone on wheel activity in rats. Drug Alcohol Depend. 2012, 126, 168-175.
Wright, M. J.; Angrish, D.; Aarde, S. A.; Creehan, K. M.; Vandewater, S. A.; Dickerson, T. J.; Taffe, M. A. Effect of ambient temperature on the thermoregulatory and locomotor stimulant effects of 4-methylmethcathinone (mephedrone) in Wistar and Sprague-Dawley rats. PLOS ONE 2012, 7, e44652.
Smith, G. R.; Cagli?, D.; ?apek, P.; Zhang, Y.; Godbole, S.; Reitz, A. B.; Dickerson, T. J. Reexamining hydroxamate inhibitors of botulinum neurotoxin serotype A: Extending towards the β-exosite. Bioorg. Med. Chem. Lett. 2012, 11, 3754-3757.
?apek, P.; Zhang, Y.; Barlow, D. J.; Houseknecht, K. L.; Smith, G. R.; Dickerson, T. J. Enhancing the pharmacokinetic properties of botulinum neurotoxin serotype A protease inhibitors through rational design. ACS Chem. Neurosci. 2011, 2, 288-293.
Denery, J. R.; Nunes, A. A. K.; Dickerson , T. J. Characterization of differences between blood sample matrices in untargeted metabolomics. Anal. Chem. 2011, 132, 13126-13128.
Denery, J. R.; Nunes, A. A. K.; Hixon, M.; Dickerson, T. J.; Janda, K. D. Mass spectrometry based metabolomics: Discovery of diagnostic biomarkers for onchocerciasis. PLOS Negl. Trop. Dis. 2010, 4, e834.
Dickerson, T. J.; McKenzie, K. M.; Hoyt, A. S.; Wood, M. R.; Janda, K. D.; Brenner, S.; Lerner, R. A. Phage escape libraries for checkmate analysis. Proc. Natl. Acad. Sci. USA 2007, 104, 12703-12708.
?apek, P.; Kirkconnell, K. S.; Dickerson, T. J. A bacteriophage-based platform for rapid trace detection of proteases. J. Am. Chem. Soc. 2010, 132, 13126-13128.
Willis, B.; Eubanks, L. M.; Dickerson, T. J.; Janda, K. D. The strange case of botulinum neurotoxin: Using chemistry and biology to modulate the most deadly poison. Angew. Chem. Intl. Ed. 2008, 47, 8360-8379.
Eubanks, L. M.; Hixon, M. S.; Jin, W.; Hong, S.; Clancy, C. M.; Tepp, W. H.; Baldwin, M. R.; Malizio, C. J.; Goodnough, M. C.; Barbieri, J. T.; Johnson, E. A.; Boger, D. L.; Dickerson, T. J.; Janda, K. D. An in vitro and in vivo disconnect uncovered through high throughput identification of botulinum neurotoxin A antagonists. Proc. Natl. Acad. Sci. USA 2007, 104, 2602-2607.
McAllister, L. A.; Hixon, M. S.; Kennedy, J. P.; Dickerson, T. J.; Janda, K. D. Superactivation of the botulinum neurotoxin serotype A light chain metalloprotease: A new wrinkle in Botox. J. Am. Chem. Soc. 2006, 128, 4176-4177.
Willis, B.; Eubanks, L. M.; Wood, M. R.; Janda, K. D.; Dickerson, T. J., Lerner, R. A. Biologically templated organic polymers with nanoscale order. Proc. Natl. Acad. Sci. USA 2008, 105, 1416-1419.
Park, J.; Dickerson, T. J.; Janda, K. D. Major sperm protein as a diagnostic antigen for onchocerciasis. Bioorg. Med. Chem. 2008, 16, 7206-7209