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The Rusyn lab applies molecular, biochemical
and genomics approaches toward understanding the mechanisms of chemical-induced
carcinogenesis. Specifically, they are interested in nuclear receptor-mediated
pathways in chemical carcinogenesis, oxidative DNA damage and repair, and
the role that alcohol and diet play in cancer. Through a combination of
in vivo animal studies and experiments using cellular and molecular models,
the lab aims to understand why certain chemicals cause cancer in rodents
and whether humans are at risk from similar exposures. Carcinogens may
act via several mechanisms such as DNA damage, altered gene expression,
induction of cell proliferation, reduction of apoptosis, and aberrant cell
differentiation. Indirect oxidative stress on DNA has also been suggested
to play a role in the carcinogenicity of many environmental agents and
is considered to be the most common insult affecting the genome. Current
and future topics of research in the lab include:
1. DNA Repair and Susceptibility to Environmental Agents
This project focuses on characterizing the cellular and molecular changes
induced by xenobiotics in human and mouse cells from different tissues.
2. Molecular Mechanisms of Phthalate-Induced Carcinogenesis
This study aims to understand the peroxisome proliferator-induced molecular
pathways that lead to carcinogenesis via production of oxidants, activation
of Kupffer cells, and increased proliferation of rodent liver parenchymal
cells.
3. Modulation of DNA Damage and Repair by Nutrients
This project focuses on defining the molecular mechanisms underlying the
dietary modulation of DNA damage and repair. This work will also aid the
discovery of ultra-sensitive and specific biomarkers for assessment of
DNA damage and repair.
4. Genomic Profiling of Nuclear Receptor-Mediated Toxicity
Through their membership in the Toxicogenomics Research Consortium
established by the National Institute of Environmental Health Sciences,
the Rusyn lab
is characterizing environmental stress responses at the genomic level
by correlating toxicological endpoints with changes in gene-expression
profiles.
Selected Publications:
Woods CG, Burns AM, Maki A, Bradford BU, Cunningham ML, Connor HD, Kadiiska MB, Mason RP, Peters JM, Rusyn I. (2007) Sustained formation of alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone radical adducts in mouse liver by peroxisome proliferators is dependent upon peroxisome proliferator-activated receptor-alpha, but not NADPH oxidase. Free Radic Biol Med. 42:335-42.
Maki A, Kono H, Gupta M, Asakawa M, Suzuki T, Matsuda M, Fujii H, Rusyn I. (2007) Predictive power of biomarkers of oxidative stress and inflammation in patients with hepatitis C virus-associated hepatocellular carcinoma. Ann Surg Oncol.14:1182-90.
Powell CL, Kosyk O, Ross PK, Schoonhoven R, Boysen G, Swenberg JA, Heinloth AN, Boorman GA, Cunningham ML, Paules RS, Rusyn I. (2006) Phenotypic anchoring of acetaminophen-induced oxidative stress with gene expression profiles in rat liver. Toxicol Sci. 93:213-22.
Powell CL, Swenberg JA, Rusyn I. (2005) Expression of base
excision DNA repair genes as a biomarker of oxidative DNA
damage. Cancer Lett 229:1-11.
Rusyn
I, Asakura S, Li Y, Kosyk O, Koc H, Nakamura J, Upton PB, Swenberg
JA. (2005)
Effects of ethylene oxide and ethylene
inhalation on DNA adducts, apurinic/apyrimidinic sites and
expression
of base excision DNA repair genes in rat brain, spleen, and
liver. DNA Repair (Amst). 4:1099-110.
Bradford BU, Kono H, Isayama F, Kosyk O, Wheeler MD, Akiyama
TE, Bleye L, Krausz KW, Gonzalez FJ, Koop DR, Rusyn I. (2005)
Cytochrome P450 CYP2E1, but not nicotinamide adenine dinucleotide
phosphate oxidase, is required for ethanol-induced oxidative
DNA damage in rodent liver. Hepatology 41:336-344.
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