Research Project

We are looking for highly motivated scientists with great communication skills, collaborative spirit and that love for science. The projects will mainly focus on genome stability but are open to novel and unexpected directions. The maintenance of a normal complement of the genome is a requirement for the success of multicellular organisms. Aneuploidy refers to the presence of an abnormal (lower or higher than euploid) number of chromosomes or chromosome arms (segmental aneuploidy). Although detrimental at the organismal level, aneuploidy is extremely frequent (~90%) in human tumors (Beroukhim et al., Nature 2010).

We recently conducted a combined analysis of point mutation and copy number data in primary human tumor samples and demonstrated that the distribution and potency of cancer driver genes on each chromosome or chromosome arm can predict the frequency of whole chromosome or chromosome arm aneuploidy across cancers (Davoli et al. Cell, 2013; Sack, Davoli et al., Cell 2018). This suggests that the recurrent patterns of aneuploidy in cancer act as driver events during tumorigenesis. Furthermore, through an analysis of genomics and transcriptomic data from primary human tumors, we recently identified a negative association between the level of cancer aneuploidy and the extent of tumor immune infiltrate, especially of cytotoxic T cells (Davoli et al. Science, 2017; William et al., PNAS 2021). For example, in oral cancer, chromosome 9p loss predicts immune-cold phenotypes and resistance to immunotherapy. Our ongoing research interest is to determine how cancer aneuploidy regulates the immune microenvironment, utilizing a combination of experimental and computational approaches.