Defining the Causes and Consequences of Chromosome Instability
Chromosome instability (CIN), broadly defined as the persistent gain or loss of whole chromosomes, is a hallmark of solid tumors and is known to facilitate tumor initiation, progression, and relapse. Consequently, CIN confers poor clinical prognosis. The development of CIN in cancer cells requires two distinct steps. First, genetic or cell biological defects that induce abnormal chromosome segregation and aneuploidy must arise within cells. Second, cells must adapt to overcome the tumor suppression mechanisms that normally act to restrain the proliferation of such genetically abnormal cells.
We use a combination of high-resolution microscopy, cell biology, genome-wide screening, and bioinformatics to mechanistically understand both the causes and consequences of chromosome instability in human cancer cells. A long-term goal of our work is to identify new therapeutic avenues that selectively kill abnormal, chromosomally unstable cancer cells while sparing the normal cells from which they originated.