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INVESTIGATOR PROFILES |
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SENIOR SCIENTIST ASSOCIATE PROFESSOR OF BIOMEDICAL SCIENCES ADJUNCT PROFESSOR CONTACT |
Michael Fasullo, Ph.D.Research FocusThe goal of Dr. Fasullo’s laboratory is to understand how cellular responses induced by DNA damage suppress genomic instability, and how such DNA damage responses can be manipulated for cancer therapy. DNA damage-induced checkpoints are surveillance mechanisms that ensure that genomic integrity is maintained before sister chromatids are segregated to daughter cells. Failure to arrest the cell cycle or induce gene expression in response to DNA damage has been postulated to increase genetic instability and lead to carcinogenesis. The DNA Repair Laboratory team is interested in understanding the genetic control of genomic stability after exposure to carcinogens and radiation. They use Saccharomyces cerevisiae (budding yeast) as a model system, as well as breast cancer cells. The team has constructed specific yeast strains to measure gene conversion between heteroalleles, translocations, inversions, and sister-chromatid exchanges (SCEs) using prototrophic selections. The team also utilizes well established yeast strains that measure mutations, retrotransposition, and gross chromosomal rearrangements. The DNA damage response has been measured by checkpoint protein phosphorylation and by microarrays. To metabolically activate carcinogens, the DNA repair team expresses human cytochrome P450 genes in yeast. Recent studies have focused on the powerful liver carcinogen, aflatoxin B1, and carcinogens found in food, including heterocyclic arylamines and polyaromatic hydrocarbons. Because both cytochrome P450 genes and detoxification genes are highly variable in humans, it is difficult to ascribe a specific polymorphism as a risk factor for environmentally associated cancer. However, individual cytochrome P450 genes can be expressed in yeast, and the DNA repair team has been evaluating which cytochrome P450 polymorphism confers the highest levels of genotoxicity. These studies thus provide a new method for evaluating risk factors associated with individual polymorphisms in humans.Selected Publications (View)
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