Biochemist (B.S., M.S., Ph.D.) who came to ISU in 1985 and teachs in the Chemistry Department.
299Independent Honor Study In Chemistry
499Independent Research For The Master'S Thesis
290Research In Biological Sciences
290Research in Chemistry
490Research In Chemistry
Research Directions for the Jones' Lab: Choline is a molecule used to make the membrane component phosphatidylcholine. Although most organisms make their own choline, one class of parasitic protozoans, called Leishmania, is not able to do so and therefore must get the choline from their hosts. These parasitic protozoans infect more than 20-25 million people world-wide and some 350 million people are at risk since they live in areas where Leishmania diseases are endemic. At least 12 species of the genus Leishmania are human pathogens and other species infect animals such as horses, cows, dogs, as well as reptiles. Such diseases can be expressed as skin infections, infections in the mucus membranes of mouth and throat, as well as infections in the internal organs. There are very few good therapies currently being used to treat human Leishmania diseases. This is, in part, because the treatments are expensive, have severe side effects, and drug resistance is also developing. Thus a major area of research in the Jones' Lab is the use of unique inorganic and organic molecules such as choline derivatives as potential cytotoxic agents for Leishmania diseases. We test various compounds for their ability to affect the growth of these protozoans in culture. We specifically use the Leishmania tarentolae species which is not pathogenic for humans but is for reptiles. We can thus safely use this species which is easily cultured as our model system. Microscopic changes in cell shape, size, and motility as well as analysis for cell viability are done following addition of derivatives at various concentrations. We are working to determine the mechanism of cytotoxicity of the effective compounds. We are also testing some metal complexes (especially vanadium) to assess their potential toxicity for Leishmania. The long term goal is to develop these various classes of materials as selective pharmaceutical drugs to treat human or domestic animal Leishmania diseases.
J. D. Hooker, V. H. Nguyen, V. M. Taylor, D. L. Cedeño, T. D. Lash, S. M. Robledo, I. D. Vélez and M. A. Jones, “New Application for Expanded Porphyrins: Sapphyrin and Heterosapphyrins as Inhibitors of Leishmania Parasities”, Photochemistry and Photobiology 2012, 88, 194-200.
T. D. Lash, T. R. Lamm, J. A. Schaber, W.-h. Chung, E. K. Johnson and M. A. Jones, “Normal and abnormal heme biosynthesis. Part 7. Synthesis and metabolism of coproporphyrinogen-III analogues with acetate or butyrate side chains on rings C and D. Development of a modified model for the active site of coproporphyrinogen oxidase”, Bioorganic & Medicinal Chemistry 2011, 19, 1492-1504.
V. M. Taylor, D. L. Cedeño, D. L. Muñoz, M. A. Jones, T. D. Lash, A. M. Young, M. H. Constantino, N. Esposito, I. D. Vélez and S. M. Robledo, “In Vivo and In Vitro Studies of the Utility of Dimethyl and Diethyl Carbaporphyrin ketals in the Treatment of Cutaneous Leishmaniasis”, Antimicrobial Agents and Chemotherapy 2011, 55, 4755-4764.
D. M. Gardner, V. M. Taylor, D. L. Cedeño, S. Padhee, S. M. Robledo, M. A. Jones, T. D. Lash and I. D. Vélez, “Association of acenaphthoporphyrins with liposomes for the photodynamic treatment of leishmaniasis”, Photochemistry and Photobiology 2010, 86, 645-652.
T. D. Lash, U. N. Mani, A.-S. I. M. Keck and M. A. Jones, “Normal and abnormal heme biosynthesis. Part 6. Synthesis and metabolism of a series of monovinylporphyrinogens related to harderoporphyrinogen. Further insights into the oxidative decarboxylation of porphyrinogen substrates by coproporphyrinogen oxidase”, Journal of Organic Chemistry 2010, 75, 3183-3192.
J. B. Morganthaler, R. L. Barto, T. D. Lash and M. A. Jones, “Use of di- and tripropionate substrate analogs to probe the active site of human recombinant coproporphyrinogen oxidase”, Medical Science Monitor 2008, 14, BR1-7.
J. B. Morgenthaler, S. J. Peters, D. L. Cedeño, M. H. Constantino, K. A. Edwards, E. M. Kamowski, J. C. Passini, B. E. Butkus, A. M. Young, T. D. Lash and M. A. Jones, “Carbaporphyrin ketals as potential agents for a new photodynamic therapy treatment of leishmaniasis”, Bioorganic & Medicinal Chemistry 2008, 16, 7033-7038.
J. R. Stephenson, J. A. Stacey, J. B. Morgenthaler, J. A. Friesen, T. D. Lash and M. A. Jones, “Role of aspartate 300, arginine 162 and arginine 301 in the catalytic mechanism of coproporphyrinogen oxidase”, Protein Science 2007, 16, 401-410
C. L. Cooper, C. M. Stob, M. A. Jones and T. D. Lash, “Metabolism of Pentacarboxylate Porphyrinogens by Highly Purified Human Coproporphyrinogen Oxidase. Further Evidence for the Existence of an Abnormal Pathway for Heme Biosynthesis”, Bioorganic & Medicinal Chemistry 2005, 13, 6244-6251.
C. L. Cooper, T. D. Lash and M. A. Jones, “Kinetic Evaluation of Human Cloned Coproporphyrinogen Oxidase Using an A Ring Isomer of the Natural Substrate and Implications for Porphyrias”, Medical Science Monitor 2005, 11, BR420-425.
M. A. Jones, M. Taneja, Y. Xu, W. Chung, C. M. Stob and T. D. Lash, “An effective chromatographic separation of chicken red blood cell coproporphyrinogen oxidase and uroporphyrinogen decarboxylase, two enzymes in heme biosynthesis”, Bioorganic & Medicinal Chemistry Letters 2004, 14, 5559-5564.