Aneuploidy, an imbalanced number of chromosomes or chromosome arms, is a distinct feature of cancer. Recent years have seen conceptual, methodological and technical advances in the field of cancer aneuploidy research, but we are just beginning to scratch the surface of the underlying biology, and the potential vulnerabilities of aneuploid cancer cells remain under-explored. Cancer aneuploidy is therefore a biological enigma and a missed opportunity for cancer therapy.
Identifying the “Achilles heels” of aneuploidy remains a holy grail of cancer research. However, current models of aneuploidy fail to fully recapitulate the cellular consequences of aneuploidy in cancer, thus compromising the identification of aneuploidy-induced cellular vulnerabilities. The time is ripe to tackle cancer aneuploidy with state-of-the-art genomic and functional approaches.
In this project, we apply innovative genomic and functional approaches to overcome current barriers, and develop much-needed novel methodologies to study aneuploidy in relevant cellular contexts throughout tumorigenesis. We explore the evolution of aneuploidy in tumorigenesis, and uncover the functional consequences of cancer aneuploidy, with an emphasis on aneuploidy-associated cellular vulnerabilities. We envision that the results of this project will significantly improve our understanding of how aneuploidy evolves and how it can be targeted. Our vision is to ultimately bring aneuploidy into the focus of precision cancer medicine.
Our specific objectives are:
(1) To dissect the forces that shape the evoultion of aneuploidy in cancer.
(2) To identify synthetic lethalities of aneuploid cancer cells.
