A major focus in our research laboratory is directed toward the goal of understanding the genetic, cellular and biochemical controls of cellular responses to ionizing radiation and radiomimetic anticancer antibiotics, particularly the bleomycins. These studies help us understand basic cellular mechanisms, including DNA repair and oxidant injury, and have significant implications for human diseases as well as clinical cancer management. Mechanisms of action of oxidative DNA-damaging agents and cellular responses to these agents are problems of considerable medical importance.
Oxidative damage suffered by cells contributes heavily to aging and cancer in humans.
Our approach is to acquire knowledge from interrelated studies at the molecular, biochemical and cellular levels, using genetic characterizations, molecular biology, biochemistry, DNA sequence analyses, and methodologies for studying DNA damage and repair. Saccharomyces cerevisiae is used as a eucaryotic model. Additional research projects include collaborative studies to understand the mechanism of the specific antifungal action of the bleomycins that we discovered, properties of a cytotoxic diffusable factor from yeast, and mechanisms of action of bleomycin and phleomycin. The genetic sophistication, molecular flexibility and availability of mutant yeast strains permit these studies and technical approaches. Human cells have also been employed for our projects involving mechanisms of action at the cellular level of ionizing radiation and bleomycins, and a long-term goal is to determine the role of the BLM genes in human cells.