- 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
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.
PBL - Human Development, Locomotor
MSc Stem Cells and Regenerative Medicine course
Cellular senescence as a tumour suppressive mechanism
Cellular senescence is a stable cell cycle arrest caused by the loss of replicative potential of our cells. Although it has been typically associated with ageing and, more recently development and cellular reprogramming, this phenomenon is also activated by oncogenes or stress (named oncogene-induced senescence, OIS). OIS keeps the cells that are damaged under control, preventing them from aberrant proliferation and tumour initiation. Therefore, OIS is a crucial cancer-prevention mechanism, as senescence can be induced in the early stages of cancer development, suppress tumour growth and avoid further malignant transformation. OIS is also a defence mechanism that recruits immune cells to the damaged area, via cytokine and chemokine secretion, promoting the clearance of senescent cells. Our group is interested in discovering and characterising novel regulatory pathways implicated in cellular senescence and translating our findings to different primary cancers. For this, we perform a variety of functional screens, which include genetic screens and the use of small-molecule inhibitors. In fact, using different functional unbiased genetics approaches we have identified a number of novel regulators of senescence cancer, i.e. interleukin-8 receptor B (CXCR2), homeobox proteins (HLX), nuclear receptors (NR2E1), microRNAs (miR-125 and miR-181) and integrins (ITGB3).
Polycomb protein regulation in cancer initiation and progression
The Polycomb Group Proteins (PcG) are a family of modulators of chromatin dynamics that act as transcriptional repressors. PcG play key roles in different biological and pathological processes including development, pluripotency, senescence and cancer. Two main PcG protein complexes exist: Polycomb Repressive Complex 1 and 2 (PRC1 and 2). PcG proteins are frequently found deregulated in cancer and are currently emerging as “hot spots” therapeutic targets in cancer. Our group is focused on understanding how deregulation of PcG proteins affects cancer initiation and progression and whether PcG recruitment to chromatin and regulation of gene repression varies in cancer compared to non-tumourigenic cells. We are also interested in investigating how these PcG proteins themselves are regulated and have found different regulators for the chromobox protein CBX7 in cancer and pluripotency maintenance, i.e. transcriptional activators (NR2E1), post-translational modifiers (miR-125, miR-181).
Rapisarda V, Borghesan M, Miguela V, Encheva V, Snijders AP, Lujambio A, O’LOGHLEN A. Integrin Beta 3 Regulates Cellular Senescence by Activating the TGF-β Pathway. 2017; Cell Reports 18(10):2480-2493
Gil, J and O’LOGHLEN, A. 2015; PRC1 complex diversity: Where is it taking us? 2014; Trends in Cell Biology 24(11):632-41
Martin N, Popov N, Aguilo F, O’LOGHLEN A, Raguz S, Snijders AP, Dharmalingam G, Li S, Thymiakou E, Carroll T, Zeisig BB, So CW, Peters G, Episkopou V, Walsh MJ, Gil J. Interplay between Homeobox proteins and Polycomb repressive complexes in p16INK4a regulation. 2013; The EMBO Journal 32(7):982-95
O’LOGHLEN A, Muñoz-Cabello A, Gaspar-Maia A, Wu HA, Banito A, Kunowska N, Racek T, Pemberton H, Beolchi P, Lavial F, Masui O, Vermeulen M, Carroll T, Graumann J, Heard E, Dillon N, Azuara V, Snijders AP, Peters G, Bernstein E, Gil J. MicroRNA regulation of Cbx7 mediates a switch of Polycomb orthologs during ESC differentiation. 2012; Cell Stem Cell 10(1):33-46 (Journal Cover)
*Acosta JC, * O’LOGHLEN A, Banito A, Guijarro MV, Augert A, Raguz S, Fumagalli M, Da Costa M, Brown C, Popov N, Takatsu Y, Melamed J, d'Adda di Fagagna F, Bernard D, Hernando E, Gil J. Chemokine signaling via the CXCR2 receptor reinforces senescence. 2008; Cell 133(6):1006-18 *Equal contribution
View all Ana O'Loghlen's Research Publications at: http://www.researchpublications.qmul.ac.uk
Paula Carpintero – Postdoc
Juan Fafian Labora - Postdoc
Michela Borghesan – PhD student
Midusa Mahenthiran – iBSc
Sana Abdullah - MSc