Responsable/s del laboratorio

 

intro

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 communicate with their microenvironment through the release of a variety of proteins and extracellular vesicles collectively named SASP (senescence-associated secretory phenotype) (*Acosta, *O’Loghlen et al. 2008, Cell; Fafian-Labora et al. 2020, Cell Metabolism; Fafian-Labora and O’Loghlen 2020, Trends Cell Biol; *Borghesan, *Fafian-Labora et al. , Cell Reports ).

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). In addition, we found a role for the interferon (IFITM3) and glutathione (GSTM2) pathways in senescence and ageing through extracellular vesicles (*Borghesan, *Fafian-Labora et al. , Cell Reports; Fafian-Labora et al. 2020, Cell Metabolism; Fafian-Labora and O’Loghlen 2020, Trends Cell Biol).

 

Fondos

Agencia Estatal Investigación (AEI) - Proyecto PID2021-125656OB financiado por MCIN/AEI/10.13039/501100011033/FEDER,UE

Comunidad Autonoma de Madrid (CAM) - BIOMEDICINA 2022 SenesceX-CM P2022/BMD-7393

Consolidación. - CNS2022-135134, financiado por MCIN/AEI/10.13039/ 501100011033 y por la Unión Europea “NextGenerationEU”/PRTR”.

 

 

Más información

Página web del grupo: https://sites.google.com/view/theologhlenlab

Para puestos de trabajo y becas visitar la página web externa del grupo: https://sites.google.com/view/theologhlenlab

Cuenta Twitter: @TheOLoghlenLAB