About Dr. William T. Self

Studies the role of metalloenzymes in Clostridium difficile that play a primary role in energy metabolism, and in the role of selenoenzymes in a variety of bacterial model systems.

Our research focuses in two main areas: 1.) The study of the anti-inflammatory properties of cerium oxide-based materials and 2.) The study of the biology of selenium and the targeting of the metabolism of selenium in pathogens.

Elucidating the anti-inflammatory properties of cerium oxide nanomaterials. Cerium oxide nanoparticles (nanoceria) have recently been shown to reduce oxidative and nitrosative stress in large number of studies using both cell culture and animal models. We have discovered that these nanoparticles can effectively act as superoxide dismutase and catalase mimetics. We have also observed nitric oxide radical scavenging and recently shown that these nanoparticles can accelerate the decay of the harmful oxidant peroxynitrite. In collaboration with Dr. Sudipta Seal, we are continuing to study the anti-inflammatory properties of this material and beginning to development various biomaterials using these interesting rare earth oxides.

The uptake and metabolism of selenium. To date no specific transport proteins have been identified in any biological organism for the high-affinity transport of selenium. However it is known that selenium can be taken up with high affinity by mammalian cells and also by some bacteria, including E. coli. We continue to search for the molecular mechanism behind high affinity transport of selenium for the synthesis of selenoproteins in a variety of model systems.

The role of selenoenzymes in pathogenic microbes. We are elucidating the role of Stickland reactions in the energy metabolism and toxin regulation of the nosocomial pathogen Clostridium difficile. Our underlying hypothesis: Growth of this and related anaerobes (C. botulinum, C. sporogenes, C. sticklandii, Treponema denticola) requires the presence of the selenium-dependent oxidoreductases glycine reductase and/or D-proline reductase for optimal growth.

Recent Publications

  1. Janet M. Dowding, Wenjun Song, Kimberly Bossy, Ajay Karakoti, Amit Kumar, Andrew Kim, Blaise Bossy, Sudipta Seal, Mark Ellisman, Guy Perkins, William T. Self, Ella Bossy-Wetzel (2014) Cerium oxide nanoparticles protect against A-Beta induced mitochondrial fragmentation and neuronal cell death. Cell Death and Differentiation advance online publication 6 June 2014; doi: 10.1038/cdd.2014.72
  2. Dowding, J. M., Das, S., Kumar, A., Dosani, T., McCormack, R., Gupta, A., Sayle, T. X. T., Sayle, D. C., von Kalm, L., Seal, S. and W. T. Self (2013) Cellular Interaction and Toxicity Depends on Physiochemical Properties and Surface Modification of Redox Active Nanomaterial,  ACS Nano, 7 (6): 4855 -4868.
  3. Schanen, B. C., Das, S., Reilly, C., Warren, W. L., Self, W. T., Seal, S., and D. R. Drake III (2013) Immunomodulation and T helper TH1/TH2 response polarization by CeO2 and TiO2 nanoparticles. PLoS ONE 8(5): e62816.
  4. Dowding, J., Seal, S. and W. T. Self (2013) Cerium oxide nanoparticles accelerate the decay of peroxynitrite (ONOO-). Drug Deliv Transl Res. Volume 3, Issue 4, pp 375-379.
  5. Boullait, L., Self, W. T. and A. L. Sonenshein (2013) Proline-Dependent Regulation of Clostridium difficile Stickland Metabolism. J. Bacteriol. 195(4):844.
  6. Das, S., Singh, S., Singh, V., Joung, D., Dowding, J.M., Zhai, L., Khondaker, S.I., Self, W. T. and Sudipta Seal (2013) Oxygenated functional group density on graphene oxide: Its effect on cell toxicity. Part. Part. Syst. Charact. 30: 148 -157.
  7. Das, S, Dowding, J. M., Klump, K. E., McGinnis, J. F., Self, W. T. and S. Seal (2013) Cerium oxide nanoparticles: Applications and prospects in nanomedicine. Nanomedicine. 8(9):1483-508.
  8. W. T. Self and S. Rosario (2013) “Selenoenzymes and selenium trafficking: an emerging target for therapeutics”, in Metals in Cells, edited by Valeria Culotta and Robert S. Scott. Chichester, UK: John Wiley & Sons, Ltd, pp.421-428.
  9. Das, S., Singh, S., Dowding, J. M., Oommen, S., Kumar, A., Sayle, T.X.T., Saraf, S., Patra, C. R., Vlahakis, N. E., Sayle, D. C., Self, W. T. and S. Seal (2013) The induction of angiogenesis by cerium oxide nanoparticles through the modulation of oxygen in intracellular environments. Biomaterials 33(31): 7746-7755.
  10. Self, W. T. (2013) Selenium proteins containing selenocysteine. (book chapter) in Encyclopedia of Inorganic and Bioinorganic Chemistry. Robert A. Scott, Editor. John Wiley & Sons, Ltd, Chichester, United Kingdom.
  11. Dowding, J. M., Dosani, T., Kumar, A., Seal, S. and W. T. Self (2012) Cerium oxide nanoparticles scavenge nitric oxide radical (·NO). Chem. Comm. 48: 4896-4898.
  12. Singh, V., Das, S., Kumar, A., Singh, S., Self, W. T. and S. Seal (2012) A facile synthesis of PLGA encapsulated cerium oxide nano particles: Release kinetics and biological activity. Nanoscale. 4: 2597-2605.
  13. Srivastava, M., Singh, S. and W. T. Self (2011) Exposure to Silver Nanoparticles Inhibits Selenoprotein Synthesis and the Activity of Thioredoxin Reductase. Environ. Health Persp. 120:56-61.
  14. Singh, S., Dosani, T., Karakoti, A., Kumar, A., Seal, S. and W. T. Self (2011) A phosphate-dependent shift in redox state of cerium oxide nanoparticles and its effects on catalytic properties. Biomaterials 32:6745-6753.
  15. Srivastava, M., Mallard, C., Burke, T., Hancock, L. E. and W. T. Self (2011) A selenium-dependent xanthine dehydrogenase triggers biofilm proliferation in Enterococcus faecalis through oxidant production. J. Bacteriol. 193(7):1643-52.
  16. Cho J-H, Bass, M., Babu, S., Dowding, J. M., Self, W. T. and S. Seal (2011) Up conversion luminescence of Yb3+ -Er3+ codoped CeO2 nanocrystals with imaging applications. J. Luminescence 132(3):743-749.
  17. Hirst, S. M., Karakoti, A., Singh, S., Self, W. T, Seal, S., and C. M. Reilly (2011) Bio-distribution and In Vivo Antioxidant Effects of Cerium Oxide Nanoparticles in Mice. Environ. Toxicol. DOI: 10.1002/tox.20704
  18. Karakoti, A., Singh, S., Dowding, J. M., Seal, S. and William T. Self* (2010) Redox-active Radical Scavenging Nanomaterials. Chem. Soc. Rev. 39, 4422 -4432.
  19. Singh, S., Kumar, A., Karakoti, A., Seal, S. and W. T. Self (2010) Unveiling the mechanism of uptake and sub-cellular distribution of cerium oxide nanoparticles. Mol. Biosyst., 6, 1813-1820.
  20. Babu, S., Cho, J-H., Dowding, J., Heckert, E., Komanski, C., Soumen, D., Colon, J., Baker, C. H., Bass, M., Self, W. T. and S. Seal (2010) Multicolored redox active upconverter cerium oxide nanoparticle for bio-imaging and therapeutics. Chem. Comm., 46(37):6915-7.
  21. Pirmohamed, T., Dowding, J. M., Singh S., Wasserman, B., Heckert, E., Karakoti, A. S., King, J. E. S., Seal, S. and W. T. Self (2010) Nanoceria exhibit redox state-dependent catalase mimetic activity.  Chem. Comm., 46, 2736-2738.
  22. Vincent, A., Inerbaev, T., Babu, S., Karakoti, A., Self, W. T., Masunov, A., and Sudipta Seal (2010) Tuning Hydrated Nanoceria Surfaces: Experimental/Theoretical Investigations of Ion Exchange and Implications in Organic and Inorganic Interactions. Langmuir 26(10):7188-98.
  23. Wolfram M. Brück, W. M., Brück, T. B., Self, W. T., Reed, J. K., Nitecki, S. S. and Peter J. McCarthy (2010) Comparison of the anaerobic microbiota of deep water Geodia sp. and sandy sediments in the Florida straits The ISME Journal 4(5):686-99.
  24. Jackson-Rosario, S. and W. T. Self (2010) Targeting Selenium metabolism and selenoproteins: Novel avenues for drug discovery. Metallomics. 2:112-116.
  25. Self, W. T. (2010). “Selenium containing amino acids and selenoproteins”, In “Comprehensive Natural products Chemistry II Chemistry and Biology (CONAP II), Mander, L., Lui, H.-W., Eds.; Elsevier: Oxford, 2010, Volume 5, pp. 121-148.
  26. Karakoti, A., Singh, S., Kumar, A., Malinska, M., Kuchibhatla, S., Wozniak, K., Self, W., and S. Seal (2009) PEGylated Nanoceria as Radical Scavenger with Tunable Redox Chemistry. J. Amer. Chem. Soc. 131 (40): 14144 -14145.
  27. Schanen, B. C., Karakoti, A. S., Seal, S., Drake, D. R., Warren, W. L. and W. T. Self (2009) Exposure to Titanium Dioxide Nanomaterials Provokes Inflammation of an in Vitro Human Immune Construct. ACS Nano. 3 (9): 2523-2532.
  28. Jackson-Rosario, S. and W. T. Self (2009) Stannous salts inhibit selenium metabolism in the oral pathogen Treponema denticola. J. Bacteriol. 191(12): 4035-4040.
  29. Vincent, A., Babu, S, Heckert, E., Dowding, J., Hirst, S. M., Inerbaev, T. M., Self, W. T., Reilly, C. M., Masunov, A. M., and Sudipta Seal (2009) Protonated nanoparticle surface governing ligand tethering and cellular targeting. ACS Nano. 3 (5): 1203-1211.
  30. Jackson-Rosario, S., Cowart, D., Myers, A., Tarrien, R., Levine, R. L., Scott, R. and W. T. Self (2009). Auranofin disrupts selenium metabolism in Clostridium difficile by forming a stable Au-Se adduct: Identification and validation of a novel target for antimicrobial development. J. Biol. Inorg. Chem. May;14(4):507-19.
  31. Meno, S., Nelson, R., Hintze, K. J. and W. T. Self (2009). Exposure to monomethylarsonous acid (MMAIII) leads to altered selenoprotein synthesis in a primary human lung cell model.  Toxicol. Appl. Pharm. 239(2):130-136.

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