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Blizard Institute - Barts and The London

Dr Ana O'Loghlen, PhD

Ana

Lecturer

Centre: Genomics and Child Health

Email: a.ologhlen@qmul.ac.uk
Telephone: +44 (0)20 7882 6685
Twitter: @TheOLoghlenLAB

Profile

  • 2013 Group Leader - Blizard Institute
  • 2013 Senior Postdoc – London Research Institute - UK
  • 2007 - 2012 Postdoc Fellow – Imperial College London - UK
  • 2006 Postdoc Fellow - Spanish National Cancer Centre (CNIO) - Spain
  • 2005 PhD Biochemistry and Molecular Biology – Complutense University Madrid- Spain
  • 2001 BSc Biochemistry and Molecular Biology – Complutense University Madrid - Spain 

Summary

Cancer is a disease caused by the aberrant proliferation of normal cells induced by a variety of different elements such as environmental and genetic factors. However, the cells in our body have an initial way to prevent cancer by activating either the death of the “sick” cells – apoptosis – or by inducing a permanent proliferation arrest called senescence. In our lab we are interested in studying how you can keep the cells locked in this senescence state, how you can activate senescence and the mechanisms by which some cells manage to overcome this arrest and progress to cancer.

 

Another major interest in our group is to study the role of the Polycomb Group Proteins (PcG) epigenetic regulators in different contexts such as pluripotency, cancer and senescence. PcG are essential epigenetic regulators that are recruited to chromatin to repress the genes they target. However, the role they play in different contexts such as cancer is controversial and not well characterised. In our lab we are interested in addressing why the role of PcG proteins is controversial in cancer. We are particularly interested in one PcG protein, the chromobox polycomb protein, CBX7.

Centre:  Genomics and Child Health

Website: https://sites.google.com/view/theologhlenlab
Twitter: @TheOLoghlenLAB

Teaching

Teaching for several Problem Based Learning (PBL) medical courses.

Supervision of PhD students. If you are interested in our group please contact me to discuss potential funding bodies. Self-funded PhD are also welcome.

Research

Research Interests:

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).

Our lab is funded by a variety of sources including the MRC, BBSRC, The Royal Society and Barts and The London.

 

We are happy to support applications from exceptional candidates (1 first author paper recommended) for external and personal fellowships, such as EMBO, Marie Curie or other national and international funding bodies. Please contact Ana O'Loghlen for informal discussions.

Publications

Key Publications

Fafián-Labora J, Rodríguez-Navarro JA and O'Loghlen A. (2020) Small Extracellular Vesicles Have GST Activity and Ameliorate Senescence-Related Tissue Damage. Cell Metabolism 32(1):71-86.e5. * corresponding author. Research highlight in Nat Rev Mol Cell Biol. Selected in “Focus in Aging” issue (Cell Metabolism)

Fafián-Labora J and O’Loghlen, A.* (2020) Classical and Nonclassical Intercellular Communication in Senescence and Ageing. Trends in Cell Biology 30(8):628-39; *corresponding author

Borghesan M, Fafián-Labora J, …… O’Loghlen, A*. (2019) Small extracellular vesicles are key regulators of non-cell autonomous intercellular communication in senescence. Cell Reports 27, 3956–3971; * corresponding author

V Rapisarda, M Borghesan, …… O’Loghlen, A*. (2017) Role for integrin beta 3 in cellular senescence and aging by activating the TGFβ pathway. Cell Reports 18, 2480–2493; * corresponding author

O'Loghlen A, Muñoz-Cabello A, …… Gil J. (2012) MicroRNA regulation of Cbx7 mediates a switch of Polycomb orthologs during ESC differentiation. Cell Stem Cell 10:1-14 (Journal Cover)

All Publications