Research Summary
Dr. Meyers' research focuses on drug delivery, the study of non-mammalian isoprenoid biosynthesis and the development of potential therapeutic agents for cancer and infectious disease.
Targeting non-mammalian isoprenoid biosynthesis: The fight against rapid progression of clinical resistance to anti-infective agents demands the sustained discovery and development of new agents and exploration of novel anti-infective targets. Dr. Meyer's long-term goal is to develop novel approaches to kill human pathogens, including bacterial pathogens and malaria parasites, with the ultimate objective of developing potential therapeutic agents. Toward this goal, she and her team are pursuing studies of bacterial isoprenoid biosynthetic enzymes comprising the methylerythritol phosphate (MEP) pathway essential in many human pathogens. Studies focus on understanding mechanism throughout the pathway toward the development of selective inhibitors of isoprenoid biosynthesis.
Drug delivery: Current efforts in Dr. Meyer's lab focus on intracellular delivery of polyphosphorylated molecules, including clinically used bisphosphonates, for the treatment of cancer and/or infectious diseases. They are also pursuing the development of antibiotic prodrug approaches for the delivery of drugs that exhibit potent antibiotic activity but exhibit problems of low solubility, poor pharmacokinetics and toxicity.
Selected Publications
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Freel Meyers C.L.; Hong L.; Joswig C. and Borch R.F. Synthesis and biological activity of novel 5-fluoro-2'-deoxyuridine phosphoramidate prodrugs. J. Med. Chem. 2000, 43, 4313-4318. PMID: 11063625
Webster, M.; Zhao, M.; Rudek, M.A., Hann, C.; Freel Meyers, C.L. Bisphosphonamidate clodronate prodrug exhibits potent anticancer activity in non-small-cell lung cancer cells. J. Med. Chem. 2011, 54, 6647-6656 PMCID: PMC3188694
Webster, M. R,; Kamat, C.; Connis, N.; Zhao, M.; Weeraratna, A. T.; Rudek, M. A.; Hann, C. L.; Freel Meyers, C. L. Bisphosphonamidate Clodronate Prodrug Exhibits Selective Cytototxic Activity Against Melanoma Cell Lines Mol. Cancer. Ther. 2014, 13, 297-306. PMCID: PMC3945958
Surcel, A.; Ng, W.P.; West-Foyle, H.; Zhu, Q.; Ren, Y.; Avery, L. B.; Krenc, A. K.; Meyers, D. J.; Rock, R. S.; Anders, R. A.; Freel Meyers, C. L.; Robinson, D. N. Pharmacological activation of myosin II paralogs to correct cell mechanics defects. Proc. Natl. Acad. Sci. U.S.A. 2015, 112, 1428-1433. PMCID: PMC4321244