Epigenetics & Cellular Senescence Group
The Epigenetics & Cellular Senescence lab is interested in understanding the basic mechanisms regulating cellular senescence and its influence on the microenvironment
Cellular senescence is a stable cell cycle arrest, whereby cells are still metabolically and transcriptionally active. Many reports have shown activation of cellular senescence not only in cancer, but also during ageing, development and tissue plasticity, revealing the importance of this phenotype in vivo. It was long believed that senescence activation was an end-point to a stress situation. However, this theory has been extensively challenged as our group and others found that senescent cells secrete a variety of proteins collectively named SASP (senescence-associated secretory phenotype) (*Acosta, *O’Loghlen et al. 2008, Cell; Acosta et al. 2008, Cell Cycle).
In order to unveil novel regulatory pathways implicated in senescence our group performs unbiased functional screens. For this purpose, we have different libraries in the lab including RNAi, genome editing CRISPR/Cas9 and small molecule inhibitors. By performing different unbiased functional screens, we have previously identified: (i) a role for the receptor CXCR2 as part of the SASP (*Acosta, *O’Loghlen et al. 2008, Cell), (ii) a role for different microRNAs regulating development, senescence and ageing (O’Loghlen et al. 2012, Cell Stem Cell; O’Loghlen et al. 2015, Ageing Cell) and (iii), a regulatory function for the transcription factors, HLX and TLX/NR2E1, during leukemia (Martin et al. 2013, The EMBO Journal, Gil and O’Loghlen 2014, Trends Cell Biol) and glioblastoma progression (O’Loghlen et al. 2015, Oncogene). Our latest work has identified the integrin beta 3 subunit, ITGB3, as a marker and regulator of senescence (Rapisarda et al. 2017, Cell Reports).