Grant: Regional Partnership Program New Investigator Award

Genome instability is a major initiating factor that predisposes individuals to cancer. It arises through two different mechanisms; A) CIN - chromosomes instability which defines an increase in the rate at which chromosomes are gained or lost, and, B) MIN - microsatellite instability which describes an increase in the rates at which genes are mutated. Concentrated investigations of CIN are highly needed as it is associated with a diverse array of tumor types, its basis is poorly understood, and it represents a novel targeting approach for cancer therapy. Our research interests go beyond a basic science platform by introducing key applied research elements. For instance, one of our basic research themes is to identify and characterize genes that regulate chromosome stability. This knowledge will provide valuable insights into how normal cells maintain chromosome stability and how these processes are altered in the initial stages of tumor development. One of our applied themes is to identify novel therapeutic targets by characterizing genetic interactions in a human cancer context. Gene mutations found in tumors but not normal cells, represent significant genetic differences distinguishing cancer cells from normal cells that we believe can be exploited for therapeutic benefit. Accordingly, CIN mutations represent a genetic "Achilles' heel" that could permit the selective targeting and destruction of cancer cells through an induced loss-of-function of a genetic interacting partner. Utilizing innovative genetic, biochemical and state-of-the-art imaging approaches in combination with data obtained from model organisms like yeast, we will uncover novel therapeutic targets. Information collected from our studies will contribute to the understanding of the how tumors develop and will uncover novel drug targets for cancer treatment.