Scientific sessions, CRG Group Leader Seminars
Mechanisms of Cancer and Aging Group, Gene Regulation, Stem Cells and Cancer Programme, CRG
Bill Keyes got his Ph.D in Developmental Biology in 1997 from the University of Alberta, Canada. Next, he moved to Cold Spring Harbor Laboratory, NY, for his postdoc work, where he studied the role of the p63 gene in senescence, cancer and aging. Following this, he started his lab at the CRG in May 2009, investigating common mechanisms in cancer and aging, with a particular focus on investigating the biological function of cellular senescence.
Senescence is a form of cell cycle arrest that prevents the proliferation of damaged cells. This state can be reached at the end of the replicative lifespan of a cell, or induced prematurely in response to oncogenes and chemotherapeutic drugs. Yet, even while arrested, senescent cells can interact extensively with their microenvironment through the secretion of a variety of proteins termed the senescence-associated secretory phenotype (SASP). This can act to reinforce the arrest, or recruit immune cells to clear the senescent population. However, in other cases, the SASP can favor tissue growth and repair, such as during wound healing, or can even promote tumor growth. Recently, we identified the existence of senescence in a non-pathological setting for the first time, identifying the widespread distribution of senescent cells in the developing embryo. Interestingly, we identified senescent cells in major signaling centers in the embryo that play critical roles in tissue morphogenesis and cell fate specification. In this setting, we identified an overlap with developmental senescence and the adult SASP, suggesting a broader more complex physiological role for senescence and the SASP than currently understood. Here, I will discuss our ongoing studies investigating the role of cellular senescence and the SASP in tissue development, regeneration and cancer, with a particular emphasis on the role of senescence in epithelial tissues.