Imperial College London

ProfessorJesusGil

Faculty of MedicineInstitute of Clinical Sciences

Professor of Cell Proliferation
 
 
 
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Contact

 

+44 (0)20 3313 8263jesus.gil

 
 
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Location

 

CRB room 5005CRB (Clinical Research Building)Hammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

93 results found

Apps JR, Carreno G, Gonzalez-Meljem JM, Haston S, Guiho R, Cooper JE, Manshaei S, Jani N, Hölsken A, Pettorini B, Beynon RJ, Simpson DM, Fraser HC, Hong Y, Hallang S, Stone TJ, Virasami A, Donson AM, Jones D, Aquilina K, Spoudeas H, Joshi AR, Grundy R, Storer LCD, Korbonits M, Hilton DA, Tossell K, Thavaraj S, Ungless MA, Gil J, Buslei R, Hankinson T, Hargrave D, Goding C, Andoniadou CL, Brogan P, Jacques TS, Williams HJ, Martinez-Barbera JPet al., 2018, Tumour compartment transcriptomics demonstrates the activation of inflammatory and odontogenic programmes in human adamantinomatous craniopharyngioma and identifies the MAPK/ERK pathway as a novel therapeutic target., Acta Neuropathol

Adamantinomatous craniopharyngiomas (ACPs) are clinically challenging tumours, the majority of which have activating mutations in CTNNB1. They are histologically complex, showing cystic and solid components, the latter comprised of different morphological cell types (e.g. β-catenin-accumulating cluster cells and palisading epithelium), surrounded by a florid glial reaction with immune cells. Here, we have carried out RNA sequencing on 18 ACP samples and integrated these data with an existing ACP transcriptomic dataset. No studies so far have examined the patterns of gene expression within the different cellular compartments of the tumour. To achieve this goal, we have combined laser capture microdissection with computational analyses to reveal groups of genes that are associated with either epithelial tumour cells (clusters and palisading epithelium), glial tissue or immune infiltrate. We use these human ACP molecular signatures and RNA-Seq data from two ACP mouse models to reveal that cell clusters are molecularly analogous to the enamel knot, a critical signalling centre controlling normal tooth morphogenesis. Supporting this finding, we show that human cluster cells express high levels of several members of the FGF, TGFB and BMP families of secreted factors, which signal to neighbouring cells as evidenced by immunostaining against the phosphorylated proteins pERK1/2, pSMAD3 and pSMAD1/5/9 in both human and mouse ACP. We reveal that inhibiting the MAPK/ERK pathway with trametinib, a clinically approved MEK inhibitor, results in reduced proliferation and increased apoptosis in explant cultures of human and mouse ACP. Finally, we analyse a prominent molecular signature in the glial reactive tissue to characterise the inflammatory microenvironment and uncover the activation of inflammasomes in human ACP. We validate these results by immunostaining against immune cell markers, cytokine ELISA and proteome analysis in both solid tumour and cystic fluid from ACP pat

JOURNAL ARTICLE

Herranz N, Gil J, 2018, Mechanisms and functions of cellular senescence., J Clin Invest, Vol: 128, Pages: 1238-1246

Cellular senescence is a highly stable cell cycle arrest that is elicited in response to different stresses. By imposing a growth arrest, senescence limits the replication of old or damaged cells. Besides exiting the cell cycle, senescent cells undergo many other phenotypic alterations such as metabolic reprogramming, chromatin rearrangement, or autophagy modulation. In addition, senescent cells produce and secrete a complex combination of factors, collectively referred as the senescence-associated secretory phenotype, that mediate most of their non-cell-autonomous effects. Because senescent cells influence the outcome of a variety of physiological and pathological processes, including cancer and age-related diseases, pro-senescent and anti-senescent therapies are actively being explored. In this Review, we discuss the mechanisms regulating different aspects of the senescence phenotype and their functional implications. This knowledge is essential to improve the identification and characterization of senescent cells in vivo and will help to develop rational strategies to modulate the senescence program for therapeutic benefit.

JOURNAL ARTICLE

McHugh D, Gil J, 2018, Senescence and aging: Causes, consequences, and therapeutic avenues, JOURNAL OF CELL BIOLOGY, Vol: 217, Pages: 65-77, ISSN: 0021-9525

JOURNAL ARTICLE

Wagner V, Gil J, 2018, An Epigenetic Switch: From Senescent Melanocytes to Malignant Melanoma (and Back)., Cancer Cell, Vol: 33, Pages: 162-163

Oncogene-induced senescence is an important barrier during melanomagenesis. In this issue of Cancer Cell, Yu et al. show how elevated expression of structurally unrelated H3K9 demethylases disables senescence and constitutes a liability that can be exploited to restore senescence in melanoma by pharmacological inhibition of these epigenetic regulators.

JOURNAL ARTICLE

Aarts M, Georgilis A, Beniazza M, Beolchi P, Banito A, Carroll T, Kulisic M, Kaemena DF, Dharmalingam G, Martin N, Reik W, Zuber J, Kaji K, Chandra T, Gil Jet al., 2017, Coupling shRNA screens with single-cell RNA-seq identifies a dual role for mTOR in reprogramming-induced senescence, GENES & DEVELOPMENT, Vol: 31, Pages: 2085-2098, ISSN: 0890-9369

JOURNAL ARTICLE

Mario Gonzalez-Meljem J, Haston S, Carreno G, Apps JR, Pozzi S, Stache C, Kaushal G, Virasami A, Panousopoulos L, Mousavy-Gharavy SN, Guerrero A, Rashid M, Jani N, Goding CR, Jacques TS, Adams DJ, Gil J, Andoniadou CL, Martinez-Barbera JPet al., 2017, Stem cell senescence drives age-attenuated induction of pituitary tumours in mouse models of paediatric craniopharyngioma, NATURE COMMUNICATIONS, Vol: 8, ISSN: 2041-1723

JOURNAL ARTICLE

Mellone M, Hanley CJ, Thirdborough S, Mellows T, Garcia E, Woo J, Tod J, Frampton S, Jenei V, Moutasim KA, Kabir TD, Brennan PA, Venturi G, Ford K, Herranz N, Lim KP, Clarke J, Lambert DW, Prime SS, Underwood TJ, Vijayanand P, Eliceiri KW, Woelk C, King EV, Gil J, Ottensmeier CH, Thomas GJet al., 2017, Induction of fibroblast senescence generates a non-fibrogenic myofibroblast phenotype that differentially impacts on cancer prognosis, AGING-US, Vol: 9, Pages: 128-146, ISSN: 1945-4589

JOURNAL ARTICLE

Young HL, Rowling EJ, Bugatti M, Giurisato E, Luheshi N, Arozarena I, Acosta J-C, Kamarashev J, Frederick DT, Cooper ZA, Reuben A, Gil J, Flaherty KT, Wargo JA, Vermi W, Smith MP, Wellbrock C, Hurlstone Aet al., 2017, An adaptive signaling network in melanoma inflammatory niches confers tolerance to MAPK signaling inhibition, JOURNAL OF EXPERIMENTAL MEDICINE, Vol: 214, Pages: 1691-1710, ISSN: 0022-1007

JOURNAL ARTICLE

Adrados I, Larrasa-Alonso J, Galarreta A, Lopez-Antona I, Menendez C, Abad M, Gil J, Moreno-Bueno G, Palmero Iet al., 2016, The homeoprotein SIX1 controls cellular senescence through the regulation of p16INK4A and differentiation-related genes, ONCOGENE, Vol: 35, Pages: 3485-3494, ISSN: 0950-9232

JOURNAL ARTICLE

Apps JR, Jani N, Gonzalez-Meljem JM, Tossell K, Carroll T, Ungless MA, Gil J, Williams H, Jacques TS, Martinez-Barbera JPet al., 2016, Clusters of Nuclear Beta-Catenin Accumulating Cells Form Secretory Hubs in Adamantinomatous Craniopharyngioma, 205th Meeting of the Pathological-Society-of-Great-Britain-and-Ireland, Publisher: WILEY-BLACKWELL, Pages: S5-S5, ISSN: 0022-3417

CONFERENCE PAPER

Gallage S, Gil J, 2016, Mitochondrial Dysfunction Meets Senescence, TRENDS IN BIOCHEMICAL SCIENCES, Vol: 41, Pages: 207-209, ISSN: 0968-0004

JOURNAL ARTICLE

Georgilis A, Gil J, 2016, Controlling secretion to limit chemoresistance, GENES & DEVELOPMENT, Vol: 30, Pages: 1791-1792, ISSN: 0890-9369

JOURNAL ARTICLE

Gil J, Rodriguez T, 2016, Cancer: The Transforming Power of Cell Competition, CURRENT BIOLOGY, Vol: 26, Pages: R164-R166, ISSN: 0960-9822

JOURNAL ARTICLE

Gil J, Withers DJ, 2016, AGEING Out with the old, NATURE, Vol: 530, Pages: 164-165, ISSN: 0028-0836

JOURNAL ARTICLE

Guerrero A, Gil J, 2016, HMGB2 holds the key to the senescence-associated secretory phenotype, JOURNAL OF CELL BIOLOGY, Vol: 215, Pages: 297-299, ISSN: 0021-9525

JOURNAL ARTICLE

Herranz N, Gil J, 2016, Mitochondria and senescence: new actors for an old play, EMBO JOURNAL, Vol: 35, Pages: 701-702, ISSN: 0261-4189

JOURNAL ARTICLE

Tordella L, Khan S, Hohmeyer A, Banito A, Klotz S, Raguz S, Martin N, Dhamarlingam G, Carroll T, Meljem JMG, Deswal S, Martinez-Barbera JP, Garcia-Escudero R, Zuber J, Zender L, Gil Jet al., 2016, SWI/SNF regulates a transcriptional program that induces senescence to prevent liver cancer, GENES & DEVELOPMENT, Vol: 30, Pages: 2187-2198, ISSN: 0890-9369

JOURNAL ARTICLE

Wong CL, Innes A, Ma B, Gerrard G, Norziha ZA, Cheong SK, Leong CF, Bee PC, Sathar J, Lye SF, Foroni L, Aitman T, Liang L, Gil J, Laffan Met al., 2016, Differential Expression of Genes Associated with Oncogene-Induced Senescence and Senescence Associated Secretory Phenotype in the Absence of Differential Expression of High Molecular Risk Genes and Genes Associated with JAK-STAT Pathway in Sorted Cells of Patients with Polycythemia Vera and Primary Myelofibrosis, 58th Annual Meeting and Exposition of the American-Society-of-Hematology, Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971

CONFERENCE PAPER

Esposito MT, Zhao L, Fung TK, Rane JK, Wilson A, Martin N, Gil J, Leung AY, Ashworth A, So CWEet al., 2015, 7Synthetic lethal targeting of oncogenic transcription factors in acute leukemia by PARP inhibitors, NATURE MEDICINE, Vol: 21, Pages: 1481-+, ISSN: 1078-8956

JOURNAL ARTICLE

Guerrero A, Iglesias C, Raguz S, Floridia E, Gil J, Pombo CM, Zalvide Jet al., 2015, The cerebral cavernous malformation 3 gene is necessary for senescence induction, AGING CELL, Vol: 14, Pages: 274-283, ISSN: 1474-9718

JOURNAL ARTICLE

Herranz N, Gallage S, Gil J, 2015, TORn about SASP regulation., Cell Cycle, Vol: 14, Pages: 3771-3772

JOURNAL ARTICLE

Herranz N, Gallage S, Mellone M, Wuestefeld T, Klotz S, Hanley CJ, Raguz S, Acosta JC, Innes AJ, Banito A, Georgilis A, Montoya A, Wolter K, Dharmalingam G, Faull P, Carroll T, Martinez-Barbera JP, Cutillas P, Reisinger F, Heikenwalder M, Miller RA, Withers D, Zender L, Thomas GJ, Gill Jet al., 2015, mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype, NATURE CELL BIOLOGY, Vol: 17, Pages: 1205-+, ISSN: 1465-7392

JOURNAL ARTICLE

Herranz N, Gallage S, Mellone M, Wuestefeld T, Klotz S, Hanley CJ, Raguz S, Acosta JC, Innes AJ, Banito A, Georgilis A, Montoya A, Wolter K, Dharmalingam G, Faull P, Carroll T, Martínez-Barbera JP, Cutillas P, Reisinger F, Heikenwalder M, Miller RA, Withers D, Zender L, Thomas GJ, Gil Jet al., 2015, Erratum: mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype., Nat Cell Biol, Vol: 17

JOURNAL ARTICLE

Lin M-L, Patel H, Remenyi J, Banerji CRS, Lai C-F, Periyasamy M, Lombardo Y, Busonero C, Ottaviani S, Passey A, Quinlan PR, Purdie CA, Jordan LB, Thompson AM, Finn RS, Rueda OM, Caldas C, Gil J, Coombes RC, Fuller-Pace FV, Teschendorff AE, Buluwela L, Ali Set al., 2015, Expression profiling of nuclear receptors in breast cancer identifies TLX as a mediator of growth and invasion in triple-negative breast cancer, ONCOTARGET, Vol: 6, Pages: 21685-21703, ISSN: 1949-2553

JOURNAL ARTICLE

O'Loghlen A, Brookes S, Martin N, Rapisarda V, Peters G, Gil Jet al., 2015, CBX7 and miR-9 are part of an autoregulatory loop controlling p16(INK4a), AGING CELL, Vol: 14, Pages: 1113-1121, ISSN: 1474-9718

JOURNAL ARTICLE

O'Loghlen A, Martin N, Krusche B, Pemberton H, Alonso MM, Chandler H, Brookes S, Parrinello S, Peters G, Gil Jet al., 2015, The nuclear receptor NR2E1/TLX controls senescence, ONCOGENE, Vol: 34, Pages: 4069-4077, ISSN: 0950-9232

JOURNAL ARTICLE

Ozmadenci D, Feraud O, Markossian S, Kress E, Ducarouge B, Gibert B, Ge J, Durand I, Gadot N, Plateroti M, Bennaceur-Griscelli A, Scoazec J-Y, Gil J, Deng H, Bernet A, Mehlen P, Lavial Fet al., 2015, Netrin-1 regulates somatic cell reprogramming and pluripotency maintenance, NATURE COMMUNICATIONS, Vol: 6, ISSN: 2041-1723

JOURNAL ARTICLE

Gallage S, Gil J, 2014, Primary cilia and senescence: A sensitive issue, CELL CYCLE, Vol: 13, Pages: 2653-2654, ISSN: 1538-4101

JOURNAL ARTICLE

Gil J, O'Loghlen A, 2014, PRC1 complex diversity: where is it taking us?, TRENDS IN CELL BIOLOGY, Vol: 24, Pages: 632-641, ISSN: 0962-8924

JOURNAL ARTICLE

Martin N, Beach D, Gill J, 2014, Ageing as developmental decay: insights from p16(INK4a), TRENDS IN MOLECULAR MEDICINE, Vol: 20, Pages: 667-674, ISSN: 1471-4914

JOURNAL ARTICLE

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