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Glenn L. Wilson,
Ph.D.
Professor and Chair Postdoctoral Studies: Harvard Medical School and University of Vermont Ph.D. – University of
Illinois |
A major focus of the studies conducted in this laboratory is on the role of environmental factors in the etiologies of the various forms of diabetes mellitus. Present work is centered on the mechanisms by which xenobiotics can interact with insulin producing pancreatic beta cells to either kill these cells directly, to elicit an inflammatory response against these cells which results in their destruction, or to cause their functional impairment. Currently, new molecular biological technology is being employed to study the damage and repair in specific sequences of both nuclear and mitochondrial DNA. Of particular interest is how specific lesions are repaired and what are some of the factors that may prevent this repair and cause alterations in DNA which ultimately may produce diabetes mellitus.
A second area of interest is in the normal process of aging. This work is designed to test the hypothesis that it is the accumulation of damage within DNA that causes some of the phenotypes associated with aging. Specifically, the objective of this work is to determine how DNA repair mechanisms change with aging. Repair in both the nucleus and the mitochondria is being evaluated in cells from individuals of differing age, in cells aged in tissue culture and in cells from individuals with genetic syndromes of premature aging. When successfully completed this work should provide new insights into how the natural process of aging can be slowed or how the consequences of its various manifestations can be lessened.
Representative Publications:
Druzhyna, NM, Hollensworth, SB, Kelley, MR, Wilson, GL, and Ledoux, SP. Targeting human 8-oxoguanine glysosylase to mitochondria of oligodendrocytes protects against menadione-induced oxidative stress. Glia 42:370-378 (2003).
- Bozner, P, Druzhyna, NM, Bryant-Thomas, TK, LeDoux, SP, Wilson, GL, and Pappolla, MA. Deficiency of chaperonin 60 in Down's syndrome. J Alzheimer's Dis. 4:479-486 (2002).
Shokolenko, IN, Alexeyev, MF, Robertson, FM, LeDoux, SP, and Wilson, GL. The expression of Exonuclease III from E. coli in mitochondria of breast cancer cells diminishes mitochondrial repair capacity and cell survival after oxidative stress. DNA Repair (Amst.) 2:471-482 (2003).
- Dobson, AW, Grishko, V, LeDoux, SP, Kelley, MR, Wilson, GL, and Gillespie, MN. Enhanced mtDNA repair capacity protects pulmonary artery endothelial cells from oxidant-mediated death. Am J Physiol Lung Cell Mol Physiol. 283:L205-210 (2002).
Dobson, AW, Kelley MR, Wilson, GL, and LeDoux, SP. Targeting DNA repair proteins to mitochondria. Methods Mol Biol. 197:351-362 (2002).
Rachek, LI, Oberyszn, TM, D'Ambrosio, SM, Saavedra, JE, Keefer, LK, LeDoux, and Wilson, GL. Conditional targeting of the DNA repair enzyme hOGG1 into mitchondria. J Biol Chem. 277:44932-44937 (2002).
Shokolenko, I, Oberyszyn, T.M., D’Ambrosio, S.M., Saavedra, J.E., Keefer, L.K., LeDoux, S.P., Wilson, G.L., and Robertson, F.M. Protection of human keratinocyte mtDNA by low-level nitric oxide. Nitric Oxide 5:555-60 (2001).
Grishko, V., Solomon, M., Breit, J.F., Killilea, D.W., LeDoux, S.P., Wilson, G.L., and Gillespie, M.N. Hypoxia promotes oxidative base modifications in the pulmonary artery endothelial cell VEGF gene. FASEB Journal 15:1267-1269 (2001).
Grishko, V., Solomon, M., Wilson, G.L., LeDoux, S.P., and Gillespie, M.N. Oxygen radical-induced mitochondrial DNA damage and repair in pulmonary vascular endothelial cell phenotypes. Am J Physiol. Lung Cell Mol Physiol. 280:L1300-L1308 (2001).
Wang, G., Chen, Z., Zhang, S., Wilson, G.L., and Jing, K. Detection and determination of oligonucleotide triplex formation-mediated transcription-coupled DNA repair in HeLa nuclear extracts. Nucleic Acids Res. 29:1801-1807 (2001).
Dobson, A.W., Xu, Y., LeDoux, S.P., and Wilson, G.L. Enhanced mtDNA repair and cellular survival following oxidative stress by targeting the hOGG repair enzyme to mitochondria. J Biol Chem. 275:37518-37523 (2000).
Druzhyna, N., Smulson, M.E., LeDoux, S.P., and Wilson G.L. Poly (ADP-ribose) polymerase facilitates the repair of N-methylpurines in mtDNA. Diabetes 49:1849-1855 (2000).
Hollensworth B.S., Shen C., Sim, J.E., Spitz, D.R., Wilson, G.L., and LeDoux, S.P. Glial cell type specific responses to menadione-induced oxidative stress. Free Radical Biology and Medicine 28:161-174 (2000).
Pappolla, M.A., Chyan Y.J., Poeggler, B., Frangione B., Wilson, G.L. Ghiso, J., and Reiter R.J. An assessment of the antioxidant and the antiamyloidogenic properties of melatonin: implications for Alzheimer’s disease. J of Neural Transmisson 107:203-231 (2000).
Grishko, V.I., Druzhyna, N., LeDoux, S.P., and Wilson, G.L. Nitric oxide-induced damage to mtDNA and its subsequent repair. Nucleic Acids Res. 27:4510-4516 (1999).
Pappolla, M.A., Chyan, Y.J., Poeggeler, B. Bozner, P., Ghiso, J.,
LeDoux, S.P., and Wilson, G.L. Alzheimer 
protein mediated oxidative damage
of mitochondrial DNA: Prevention by melatonin. J Pineal Res.
27:226-229 (1999).
LeDoux, S.P., Driggers W.J., Hollensworth, B.S., and Wilson, G.L. Repair of alkylation and oxidative damage in mitochondrial DNA. Mutat Res. 434:149-159 (1999).
Druzhyna, N., Nair, R.G., LeDoux, S.P., and Wilson, G.L. Defective repair of oxidative damage in mitochondrial DNA in Down’s syndrome. Mutat Res. 409:81-89 (1998).
LeDoux, S.P., Shen, C., Grishko, V.I., Fields, P.A., Gard, A.L., and Wilson, G.L. Glial cell-specific differences in response to alkylation damage. Glia 24:304-312 (1998).
Gillespie, M.N., Killilea, D.W., Solomon, M., Babal, P., LeDoux, S.P., and Wilson, G.L. Hypoxia causes oxidant lesions in the rat pulmonary artery smooth muscle cell VEGF gene; Potential link to VEGF mRNA expression. Chest 114:45 (1998).
Bozner, P., Grishko, V., LeDoux, S.P., Wilson, G.L., and Pappolla,
M.A. The amyloid 
-protein induces oxidative damage of mitochondrial DNA. J
Neuropathol Exp Neurol. 56:1356-1362 (1997).
Driggers, W.J., Holmquist, G.P., LeDoux, S.P., and Wilson, G.L. Repair of oxidative damage within mitochondrial DNA at the strand- and nucleotide-specific levels. Nucleic Acids Res. 25:4362-4369 (1997).
Grishko, V.I., LeDoux, S.P., and Wilson, G.L. The repair of oxidative damage in nuclear DNA sequences with different transcriptional activities is homogeneous. Mut Res. 334:73-80 (1997).