Williams, Marshall V. PhD
Department of Molecular Virology, Immunology and Medical Genetics
Department of Microbiology
353 Institute for Behavioral Medicine Research
460 Medical Center Drive
Columbus, Oh. 43210
Ph. (614) 293-6175
2167L Graves Hall
333 W. 10th Avenue
Columbus, Oh. 43210
Ph. (614) 292-0986
Pyrimidine deoxyribonucleotide metabolism in human and herpesviruses infected cells. Mechanism(s) of mutagenesis by environmental pollutants.
Project 1: DNA Replication and Repair: Elucidating the role(s) of deoxyuridine triphosphate nucleotidohydrolase (dUTPase) and uracil-DNA glycosylase (UNG) in normal cellular (human) metabolism and virus replication. For the past 20 years research in my laboratory has focused on determining the role(s) of these deoxyuridine triphosphate nucleotidohydrolase (dUTPase) and uracil-DNA glycosylase (UNG) in normal cellular metabolism and in virus replication (herpes simplex virus type 2, Epstein-Barr virus and human immunodeficiency type-1). The goal of this research is to use these enzymes as targets for the development of novel agents for use in cancer and viral chemotherapy.
Project 2: Epidemiological studies have demonstrated that there is a positive correlation between the inhalation of airborne particulate matter and increased morbidity and mortality due to respiratory and cardiovascular disease, especially in individuals with previous history of pulmonary dysfunction and/or cardiovascular disease and in the elderly. However the molecular mechanism(s) by which these airborne particles, particularly ultrafine particles, exacerbate disease is unknown. This is due in part to the heterogeneity of the particles. This project being performed in collaboration with faculty in the Departments of Chemistry, Pathology and Veterinary Biosciences that is focused on determining the mechanism(s) by which small airborne particulates influence cardiopulmonary disease. My role in the project, in addition to the genotoxicity studies, is in determining the relationship between oxidative stress (metal-based Fenton- chemistry and metal activation of xanthine oxidase), nitric oxide and vascular tone following exposure of cells (human endothelial) to synthetic particles
For current publications please visit The National Center for Biotechnology Information's PubMed website at http://www.ncbi.nlm.nih.gov/pubmed?term=williams%2C%20marshall%20v
Lohner T.W., Reash R.J. and Williams M.V. 2001. Assessment of tolerant sunfish populations (Lepomis sp.) inhabiting selenium-laden coal ash effluents. 2. Tissue biochemistry and histochemical evaluation. Ecotoxicology and Environmental Safety. 50:217-224.
Studebaker AW., Balendiran GK. and Williams, MV. 2001. The herpesviruses encoded dUTPase as a potential chemotherapeutic target. Invited. Current Protein and Peptide Science. 2:371-379.
Fach E., Waldman J., Williams M., Long J., Meister R. and Dutta P.K. 2002. Analysis of the biological and chemical reactivity of aluminosilicates fibers and particulates. Environmental Health Perspectives. 110:1087-1096.
Cornwell, DG., Williams, MV., Wani AA., Wani G., Shen E. and Jones KH. 2002. Mutagenicity of tocopheryl quinones: evolutionary advantage of selective accumulation of dietary a-tocopherol. Nutrition and Cancer 43:111-118.
Kim, H.W., Murakami, A., Williams, M.V. and Ohigashi, H. 2003. Mutagenicity of reactive oxygen and nitrogen species as detected by co-culture of activated inflammatory leukocytes and AS52 cells. Carcinogenesis 24:235-241.
Fach E., Kristovich R, Long JF, Waldman WJ, Dutta PK and Williams MV. 2003. The effect of iron on the biological activities of erionite and mordenite. Environment International 29:451-458.
Kim H.W., Murakami A., Williams M.V. and Ohigashi, H. 2004. Suppressive effects of selective antioxidants on the activated leukocytes-induced mutagenesis in co-culture assays systems. Biosci. Biotechnol. Biochem. 68:238-242.
Studebaker AW, Ariza, ME, Balendiran GK and Williams, MV. 2004. Novel Approaches for modulating dUTPase and Uracil-DNA glycosylase: Potential uses for Antiviral and Cancer Therapy. Drug Design Reviews.1: 1-13.
Williams, M.V and Studebaker A.D. 2004. Down-regulation of human deoxyuridine triphosphate nucleotidohydrolase (dUTPase) using small interfering RNA (siRNA). Nucleosides, Nucleotides and Nucleic Acids. 23(8/9):1467-1470.
Padgett, DA, Hotchkiss AK, Pyter LM, Nelson RJ, Yang E, Yeh PE, Litsky M, Williams M, and Glaser R. 2004. Epstein-Barr Virus-Encoded dUTPase Modulates Immune Function and Induces Sickness Behavior in Mice. J. Med. Virol. 74:442-448.
Kristovich, R, Knight, D, Onchoke, K, Long, JF Williams, MV, Dutta, PK and Waldman, WJ. 2004. Macrophage-mediated endothelial inflammatory responses to airborne particulates: Impact of particulate physiochemical properties. Chem. Res. Toxicol. 17:1303-1312.
Glaser R, Padgett DA, Litsky ML., Baiocchi RA, Yang EV, Chen M, Yeh PE, Klimas NG, Marshall GD, Whiteside T, Herberman R, Kiecolt-Glaser J and Williams MV. 2005. Stress-associated changes in the steady state expression of latent Epstein-Barr virus: implications for chronic fatigue syndrome and cancer. Brain Behavior and Immunity 19: 91-103
Studebaker AW, Lafuse WP, Kloesel W and Williams MV. 2005. Modulation of human dUTPase using small interfering RNA. Biochem. Biophys. Res. Comm. 327: 306-310.
Ariza, ME, Pederson I, and Williams, MV. 2005. Inhibition of human melanoma cell replication using protein transduction technology. Letters in Drug Design 2:92-96.
Kim HW, Murakami A, Abe M, Ozawa Y, Morimitsu Y, Williams MV and Ohigashi, H. 2005. Suppressive effects of mioga ginger and ginger constituents on reactive oxygen and nitrogen species generation, and the expression of inducible proinflammatory genes in macrophages. In Press. Anti-oxidant and Redox Signaling.
Long, JF, Waldman, WJ, Kristovich, R. Williams, M. and Dutta, PK. 2005. Cytotoxicity studies of carbon particles: ultrastructural studies of macrophages. Environmental Health Perspectives 113: 170-174.
Studebaker AW, Ariza ME and Williams, MV. 2005. Depletion of uracil-DNA glycosylase activity using a novel protein transduction approach results in decreased cell proliferation. Biochem Biophys Res Comm 334:509-515.
Glaser R., Litsky ML, Padgett DA, Litsky M., Baiocchi RA, Yang EV, Chen M, Yeh PE, Green-Church, KB, Caligiuri MA and Williams M. 2004. EBV-encoded dUTPase induces immune dysregulation: Implications for the pathophysiology of EBV-associated malignant disease. Submitted Virology.