Our research focuses in two main areas: 1.) The study of the biology of selenium and the targeting of the metabolism of selenium in pathogens. 2.) The study of the anti-inflammatory properties of cerium oxide-based materials
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) is dependent on the presence of the selenium-dependent oxidoreductases glycine reductase and/or D-proline reductase for optimal growth. We are currently elucidating phenotypes from C. difficile mutants that lack one or more of these selenoenzymes.
Elucidating the anti-inflammatory properties of cerium oxide nanomaterials. Cerium oxide nanoparticles (nanoceria) have 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.
- Zhongxin Ma, Kyle T. Strickland, Michelle D. Cherne, Esha Sehanobish, Kyle H. Rohde, William T. Self and Victor L. Davidson (2018) The Rv2633c protein of Mycobacterium tuberculosis is a non-heme di-iron catalase with a possible role in defenses against oxidative stress. Biol. Chem. 293: 1590-1595.
- Kathleen McAllister, Laurent Bouillaut, Jennifer Kahn, William Self, and Joseph Sorg (2017) Using CRISPR-Cas9-mediated genome editing to generate difficile mutants defective in selenoproteins synthesis Scientific Reports 7, Article number: 14672
- Austin Burns and William T. Self (2017) Antioxidant Inorganic Nanoparticles and their potential Applications in Biomedicine. Book Chapter in Smart Nanoparticles for Biomedicine, Gianni Ciofanni (editor), Elsevier (book chapter).
- Atul Dhall, Austin Burns, Janet Dowding, Soumen Das, Sudipta Seal and William T. Self (2017) Characterizing the phosphatase mimetic activity of cerium oxide nanoparticles and distinguishing its active site from that for catalase mimetic activity using anionic inhibitors Environ Sci Nano 4, 1742 – 1749.
- Ragini Singh, Ajay Karakoti, William Self, Sudipta Seal and Sanjay Singh (2016)Redox-sensitive cerium oxide nanoparticles protect human keratinocytes from oxidative stress induced by glutathione depletion. Langmuir 32 (46), pp 12202–12211.
- Pulido-Reyes, S. Das, F. Leganés, S. O. Silva, S. Wu, W. T. Self, F Fernández-Piñas, R. Rosal, † and S. Seal (2016) Hypochlorite scavenging activity of cerium oxide nanoparticles. RSC Adv. 6, 62911-62915
- Carl Walkey, Soumen Das, Sudipta Seal, Joseph Erlichman , Karin Heckman, Lina Ghibelli , Enrico Traversa, James F. McGinnis, and William T. Self (2015) Catalytic Properties and Biomedical Applications of Cerium Oxide Nanoparticles. Environ Sci: Nano, 2, 33-53 (invited review)
- Janet M. Dowding, Wenjun Song, Kimberly Bossy, Ajay Karakoti, Amit Kumar, Andrew Kim, Blaise Bossy, Sudipta Seal, Mark Ellisman, Guy Perkins, William T. Self, and Ella Bossy-Wetzel (2014) Cerium oxide nanoparticles protect against A-Beta induced mitochondrial fragmentation and neuronal cell death. Cell Death and Differentiation 21, 1622–1632.