Gregory David, PhD

The research conducted in our laboratory centers on the interplay between aging and cancer. In particular, we are interested in identifying the cellular hallmarks of aging and their impact on cancer initiation and progression. Among these hallmarks of aging, cellular senescence recently emerged as one of the most universally recognized feature of organismal and cellular aging. Cellular Senescence is defined as a stable cell cycle exit triggered by different stress, including oncogene activation and telomere attrition. Strikingly, markers of cellular senescence are commonly found in pre-malignant cells. As it limits the proliferation of damaged cells, senescence was first hypothesized to serve as a barrier against cancer progression. Paradoxically, recent studies by us and others have indicated that cellular senescence can promote cancer progression in specific contexts. These seemingly opposite effects of cellular senescence on tumor progression can be reconciled by the recent realization that cellular senescence encompasses additional phenotypes, including the secretion of a specific set of proteins collectively referred to as SASP (for Senescence-Associated Secretory Phenotype). The SASP reinforces senescence, induces neighboring cells to senesce, and modulates immune-mediated clearance of pre-cancerous senescent cells. Conversely, accumulating evidence indicate that the SASP may also have pro-tumorigenic effects, including the stimulation of cancer cell proliferation, motility, and the generation of an inflammatory environment that promotes tumor growth. Our research aims at understanding how the SASP is generated by senescent cells and its impact on inflammation, immune response and cancer heterogeneity and progression using cellular and mouse models. Our long-term goal is to harness our understanding of senescence for therapeutic purposes. In addition, we are also interested in the impact of ageing and age-associated alterations of the chromatin landscape on cellular function, with a focus on the hematopoietic system.