Investigator: Nicanor Austraco, Providence College

Scientific Theme: Cancer

Abstract: One of the most striking characteristics of cancer genomes is whole chromosome aneuploidy, the presence of more or fewer than the typical species-typical diploid number. Another characteristic of cancer cells is their ability to evade programmed cell death. It is still not clear if there is a direct link between these two hallmarks of malignant cells.

A few years ago, the Amon Laboratory at M.I.T. used a chromosome transfer strategy to generate a yeast model for aneuploidy. They constructed a set of aneuploid strains that contain an extra copy of one of the budding yeast cell’s sixteen chromosomes. Their systematic characterization of these aneuploid strains illustrated that aneuploidy, per se, regardless of the identity of the specific chromosome that is either increased or decreased in number in the cell’s genome, could radically alter the physiology of the eukaryotic cell. However, at this time, it is not clear whether aneuploidy alters a yeast cell’s ability to undergo programmed cell death. Therefore there is a need to answer a pressing question in the field: Does aneuploidy make yeast cells more or less sensitive to environment insults that trigger cell death?

To fill this knowledge gap, my laboratory at Providence College has just initiated studies to investigate programmed cell death in the aneuploid yeast strains that we have obtained from the Amon Laboratory. In this RI-INBRE SURF proposal, we describe genetic and molecular experiments that build on our decade- long expertise in studying yeast cell death to characterize the link between aneuploidy and cell death in eukaryotic cells. Since a significant number of cancer cells are aneuploid and are able to evade programmed cell death, we expect our research program to have a positive impact by revealing the links between abnormal chromosomal number and the other hallmarks of malignancy.

Human Health Relevance: Cancer cells usually do not contain a normal number of chromosomes. They are also able to escape molecular triggers that usually initiate cell suicide. Using a yeast model system, we would like to uncover the cellular links between having an abnormal number of chromosomes and losing one’s ability to undergo cell suicide to better understand that transformation process that leads to malignant tumors.