Translational Research > Liverpool Lung Project > Dr Lakis Liloglou

Dr Liloglou joined John Field’s group at Liverpool University as a postdoc and worked in the field of identifying molecular abnormalities in lung and head and neck cancer, with particular focus on p53 mutations and genomic instability. He was very soon attracted by the idea of utilising molecular abnormalities in sputum and bronchial lavage for assisting in early diagnosis of lung cancer. In 1999 he joined the Liverpool Lung Project, leading initially the Genomic Instability and later the Biomarkers research group. Dr Liloglou has focused on cancer epigenetics and DNA methylation in the last eight years and established his group nationally and internationally for its quality of work on DNA methylation and early lung and head and neck cancer biomarkers. He was recently been awarded a CR-UK grant for

validating epigenetic biomarkers in sputum. His group works on a number of collaborative projects with international academic and industrial partners bringing science closer to the bedside. He pioneered the use of Pyrosequencing for DNA methylation detection in the UK and has recently developed a new DNA methylation detection technique that has now received a US patent, in collaboration with Applied Biosystems. Contact Details Tel: 0151 794 8920 Email: T.Liloglou@liverpool.ac.uk

Education and qualifications

1994: PhD Molecular Oncology, University of Crete Medical School.

1988: BSc (Hons), Biology, Aristotelian University of Thessaloniki, Greece.

Appointments

2010: Lecturer in Molecular Oncology, School of Dentistry, University of Liverpool.

2007: Biomarkers Group Lead, Liverpool Cancer Research UK Centre, University of Liverpool.

1999: Genomic Instability Group Lead, Liverpool Lung Project, University of Liverpool.
                        
1994: PostDoc , Molecular abnormalities in lung and head and neck cancer, University of Liverpool.

Molecular Biomarkers Group
The Molecular Biomarkers group (led by Dr Lakis Liloglou) focus in cancer epigenetics. Dr Liloglou has pioneered the use of Pyrosequencing in DNA methylation detection in the UK and has recently developed a novel DNA methylation analysis technique utilising dideoxy-terminator analogues, in collaboration with Applied Biosystems (Liloglou T & Finkelnburg B, Provisional patent on Nucleic Acid Methylation Analysis, US Patent office 61/264,626 / 25/11/2009). Our research interests focus on the mechanisms of epigenetic deregulation in cancers of the respiratory tract and their association to genomic instability and retrotransposition. In parallel, particular effort is given to develop epigenetic biomarkers for cancer diagnostics (lung and oral tumours)

Our core objectives include: The in-depth understanding of the genetic and epigenetic instability in lung cancer The identification of the most frequent abnormalities in primary lung tumours The development of robust molecular assays able to detect these abnormalities in very high dilution in clinical specimens such as sputum, bronchial washings, buccal scrapes, plasma etc.

Genetic Predisposition to Lung Cancer
LLP took part in a large international lung cancer consortium which undertook a genome-wide association study, eventually screening 17,000 individuals, in order to identify SNPs that may increase the risk for lung cancer development. This study has revealed a number of polymorphisms in certain loci that are significantly associated to tobacco addiction and lung cancer development.

Epidemiology Group
The LLP Epidemiology group undertakes epidemiological and statistical research investigating causative factors and determinants of lung cancer. This activity provides support towards advancing the body of knowledge on early detection and prevention of lung cancer, thereby improving patient survival from the disease. The group has conducted and/or participated in a variety of epidemiological research projects focusing on a wide range of themes including those of risk modelling, screening and prevention and genetic susceptibility.

Our research utilises the LLP recruited participants from the case-control arm, the population cohort and the selected high risk follow-up participants, and those from independent external studies. The research area of the epidemiology group includes:

The development, validation and refinement of the LLP risk prediction model for estimating an individual’s absolute risk of developing lung cancer within a 5-year period

The incorporation into the risk assessment model of SNPs from genome-wide association studies (GWAS) as well as epigenetic biomarkers in clinical specimens such as sputum and plasma.

Follow up of high risk individuals within the LLP prospective cohort.

Expression & methylation profiling and next generation sequencing in lung cancer.

1. Prediction of progressive disease in lung cancer

The risk of recurrence, metastasis or second primary lung cancers is a major issue in individuals who have had a lung cancer. The identification of these patients with a poor outcome has been the basis of a number of large research programmes. We are now in a position to take this forward and contribute to the early detection of lung cancer reappearing in individuals who have had a successful surgical resection. The research group have already made a significant contribution to this field through the EUELC collaboration.

The EU Early Lung cancer (EUELC) collaboration was funded by an EU Framework V grant 2002-06 involving 12 centres across Europe. Professor JK Field is the PI of this Consortium.

The aims of this study are:
•           Utilise the current lung cancer expression datasets within the RCF Lung cancer Programme, as well as collaborators datasets.
•           Integrate the new next generation sequencing datasets from the LLP tumours into the progressive disease (PD) v disease free (DF) analysis.
•           Validate the major genes in LLP tumour datasets utilising Real time PCT and Pyrosequencing platforms.
•           Access to the major dataset from the second generation, expression and methylation information from the major EU FP7 collaborative studies EU (CURELUNG and LACOS) Programme.

2. Molecular profiling of COPD and lung cancer for early diagnosis.

Chronic obstructive pulmonary disease (COPD) and lung cancer are leading causes of morbidity and mortality in the UK and worldwide. Treatment of lung cancer and COPD has lagged behind that of other diseases, despite the fact that inflammation is recognised to play a major role in the development and progression of both diseases.   They share common environmental risk factors and COPD increases the risk of lung cancer up to 4.5 fold.

Hypothesis: Utilisation of focused exon sequencing in lung cancer, with and without a history of COPD, will identify the different pathways involved in their pathogenesis.

1.         Utilising a focused approach, identify the mutational profile, SNP’s and allelic imbalance of lung cancer specimens utilising Exon sequencing on the SOLiD platform in order to identify critical genes and pathways.
2.         Ascertain whether patients with a history of COPD who (i) have no history of lung cancer, (ii) develop lung cancer; i.e. composition of the genomic sequence with information on SNP data, mutations and allelic imbalance profiles.
3.         Investigate if specific Pathways are involved in the development of lung cancer from individuals with and without COPD.

This work is being undertaken with Professor Neil Hall, Dr Keith Ashelford and Dr Olga Vasieva, University of Liverpool and Professor Andy Brass, University of Manchester.

Schache AG, Hall G, Woolgar JA, Nikolaidis G, Triantafyllou A, Lowe D, Risk JM, Shaw RJ, Liloglou T. Quantitative promoter methylation differentiates carcinoma ex pleomorphic adenoma from pleomorphic salivary adenoma. Br J Cancer. 2010 Dec 7;103(12):1846-51.

Schmidt B, Liebenberg V, Dietrich D, Schlegel T, Kneip C, Seegebarth A, Flemming N, Seemann S, Distler J, Lewin J, Tetzner R, Weickmann S, Wille U, Liloglou T, Raji O, Walshaw M, Fleischhacker M, Witt C, Field JK. SHOX2 DNA methylation is a biomarker for the diagnosis of lung cancer based on bronchial aspirates. BMC Cancer. 2010 Nov 3;10:600.

Liloglou T, Field JK. Detection of DNA methylation changes in body fluids. Adv Genet. 2010; 71:177-207

Daskalos A, Logotheti S, Markopoulou S, Xinarianos G, Gosney JR, Kastania AN, Zoumpourlis V, Field JK, Liloglou T. Global DNA hypomethylation-induced ΔNp73 transcriptional activation in non-small cell lung cancer. Cancer Lett. 2011 Jan 1;300(1):79-86.PMID: 20926182

Bediaga NG, Acha-Sagredo A, Guerra I, Viguri A, Albaina C, Ruiz Diaz I, Rezola R, Alberdi MJ, Dopazo J, Montaner D, de Renobales M, Fernández AF, Field JK, Fraga MF, Liloglou T, de Pancorbo MM. DNA methylation epigenotypes in breast cancer molecular subtypes. Breast Cancer Res. 2010 Sep 29;12(5):R77.

Daskalos A, Oleksiewicz U, Filia A, Nikolaidis G, Xinarianos G, JR Gosney, A Malliri, Field JK, Liloglou T. UHRF1-mediated tumor suppressor gene inactivation in non-small cell lung cancer. Cancer, Nov 2010, [Epub ahead of print]

Logotheti, S, Michalopoulos, I, Sideridou, M, Daskalos, A, Kossida,S, Spandidos, D, Field, JK, Vojtesek, B, Liloglou, T, Gorgoulis, V, Zoumpourlis, V. Sp1 binds to the external promoter of the p73 gene and induces the expression of TAp73 ? isoform in lung cancer FEBS J. 277: 3014–3027, 2010.

Daskalos A, Nikolaidis G, Xinarianos G, Savvari P, Cassidy A, Zakopoulou R, Kotsinas A, Gorgoulis V, Field JK, Liloglou. Hypomethylation of retrotransposable elements correlates with genomic instability in non-small cell lung cancer. Int J Cancer, 24: 81-7, 2009

Barh D, Kumar A, Chatterjee S, and Liloglou T. Molecular Features, Markers, Drug Targets, and Prospective Targeted Therapeutics in Cardiac Myxoma. Current Cancer Drug Targets 9:705-716, 2009

Dunn J, Baborie A, Alam F, Joyce K, Moxham M, Sibson R, Crooks D, Husband D, Shenoy A, Brodbelt A, Wong H, Liloglou T, Haylock B, Walker C. Extent of MGMT promoter methylation correlates with outcome in glioblastomas given temozolomide and radiotherapy. Br J Cancer. 101: 124-131, 2009.

Knight LJ, Burrage J.Bujac SR, Haggerty C, GrahamA, Gibson NJ, Ellison J, Growcott JW, Brooks AN, Hughes AM,, Xinarianos G, Nikolaidis G, Field JK, Liloglou T. Epigenetic silencing of the endothelin-B receptor gene in non-small cell lung cancer. Int J Oncol.;34(2):465-71. 2009

Cassidy A, Balsan J, Vesin A, Wu X, Liloglou T, Brambilla C, Timsit J-F, Field JK, European Early Lung Cancer (EUELC) Study Group. Cancer diagnosis in a first-degree relative and lung cancer risk: results from a multicenter case-control study of early lung cancer in Europe (EUELC). Eur J Cancer May 29. [Epub ahead of print], 2009.

Johnson GG, Sherrington PD, Carter A, Lin K, Liloglou T, Field JK, Pettitt AR. A Novel Type of p53 Pathway Dysfunction in Chronic Lymphocytic Leukemia Resulting from Two Interacting Single Nucleotide Polymorphisms within the p21 Gene.Cancer Res. Jun 2. [Epub ahead of print], 2009.

Shaw RJ, Omar MM, Rokadiya S, Kogera FA, Lowe D, Hall GL, Woolgar JA, Homer J, Liloglou T, Field JK and Risk JM. Cytoglobin is up-regulated by tumour hypoxia and silenced by promoter hypermethylation in head and neck cancer British Journal of Cancer. 101(1):139-44, 2009

Lips EH, Gaborieau V, McKay JD, Chabrier A, Hung RJ, Boffetta P, Hashibe M, Zaridze D, Szeszenia-Dabrowska N, Lissowska J, Rudnai P, Fabianova E, Mates D, Bencko V, Foretova L, Janout V, Field JK, Liloglou T, Xinarianos G, McLaughlin J, Liu G, Skorpen F, Elvestad MB, Hveem K, Vatten L, Study E, Benhamou S, Lagiou P, Holcátová I, Merletti F, Kjaerheim K, Agudo A, Castellsagué X, Macfarlane TV, Association between a 15q25 gene variant, smoking quantity and tobacco-related cancers among 17 000 individuals.Barzan L, Canova C, Lowry R, Conway DI, Znaor A, Healy C, Curado MP, Koifman S, Eluf-Neto J, Matos E, Menezes A, Fernandez L, Metspalu A, Heath S, Lathrop M, Brennan P. Association between a 15q25 gene variant, smoking quantity and tobacco-related cancers among 17 000 individuals. Int J Epidemiol. 2009 Sep 23. [Epub ahead of print]

Field JK, Liloglou T, Niaz A, Bryan J, Gosney JR, Giles T, Brambilla C, Brambilla E, Vesin A, Timsit JF, Hainaut P, Martinet Y, Vignaud JM, Thunnissen FB, Prinsen C, Snijders PJ, Smit EF, Sozzi G, Roz L, Risch A, Becker HD, Elborn JS, Magee ND, Montuenga LM, Pajares MJ, Lozano MD, O'Byrne KJ, Harrison DJ, Niklinski J, Cassidy A; EUELC Collaborators. EUELC project: a multi-centre, multipurpose study to investigate early stage NSCLC, and to establish a biobank for ongoing collaboration. Eur Respir J. 2009 Dec;34(6):1477-86.

Cassidy A, Myles JP, van Tongeren M, Page RD, Liloglou T, Duffy SW, Field JK. The LLP Risk Model: an individual risk prediction model for lung cancer. British J Cancer ;98(2):270-6, 2008

Hung RJ, McKay JD, Gaborieau V, Boffetta P, Hashibe M, Zaridze D, Mukeria A, Szeszenia-Dabrowska N, Lissowska J, Rudnai P, Fabianova E, Mates D, Bencko V, Foretova L, Janout V, Chen C, Goodman G, Field JK, Liloglou T, Xinarianos G, Cassidy A, McLaughlin J, Liu G, Narod S, Krokan HE, Skorpen F, Elvestad MB, Hveem K, Vatten L, Linseisen J, Clavel-Chapelon F, Vineis P, Bueno-de-Mesquita HB, Lund E, Martinez C, Bingham S, Rasmuson T, Hainaut P, Riboli E, Ahrens W, Benhamou S, Lagiou P, Trichopoulos D, Holcátová I, Merletti F, Kjaerheim K, Agudo A, Macfarlane G, Talamini R, Simonato L, Lowry R, Conway DI, Znaor A, Healy C, Zelenika D, Boland A, Delepine M, Foglio M, Lechner D, Matsuda F, Blanche H, Gut I, Heath S, Lathrop M, Brennan P A genome-wide association study identifies a susceptibility locus for lung cancer encompassing nicotinic acetylcholine receptor subunit genes on 15q25. Nature 452(7187):633-7, 2008

Shaw RJ, Hall GL , Lowe D, Liloglou T, Field JK, Sloan P, Risk JM. The Role of Pyrosequencing in Head and Neck Cancer Epigenetics Correlation of Quantitative Methylation Data With Gene Expression. Arch Otolaryngol Head Neck Surg. 134(3):251-256, 2008.

Hall GL, Shaw RJ, Field EA, Rogers SN, Sutton DN, Woolgar JA, Lowe D, Liloglou T, Field JK , Risk JM. p16 promoter methylation is a potential predictor of malignant transformation in oral epithelial dysplasia. Cancer Epidemiol Biomarkers Prev. (8):2174-9, 2008

Shivapurkar N, Stastny V, Okumura N, Girard L, Xie Y, Prinsen C, Thunnissen FB, Wistuba II, Czerniak B, Frenkel E, Roth JA, Liloglou T, Xinarianos G, Field JK, Minna JD, Gazdar AF. Cytoglobin, the newest member of the globin family, functions as a tumor suppressor gene. Cancer Res 68(18):7448–56. 2008.

McKay JD, Hung RJ, Gaborieau V, Boffetta P, Chabrier A, Byrnes G, Zaridze D, Mukeria A, Szeszenia-Dabrowska N, Lissowska J, Rudnai P, Fabianova E, Mates D, Bencko V, Foretova L, Janout V, McLaughlin J, Shepherd F, Montpetit A, Narod S, Krokan HE, Skorpen F, Elvestad MB, Vatten L, Njølstad I, Axelsson T, Chen C, Goodman G, Barnett M, Loomis MM, Lubiñski J, Matyjasik J, Lener M Oszutowska D, Field JK, Liloglou T, Xinarianos G, Cassidy A; EPIC Study, Vineis P, Clavel-Chapelon F, Palli D, Tumino R, Krogh V, Panico S, González CA, Ramón Quirós J, Martínez C, Navarro C, Ardanaz E, Larrañaga N, Kham KT, Key T, Bueno-de-Mesquita HB, Peeters PH, Trichopoulou A, Linseisen J, Boeing H, Hallmans G, Overvad K, Tjønneland A, Kumle M, Riboli E, Zelenika D, Boland A, Delepine M, Foglio M, Lechner D, Matsuda F, Blanche H, Gut I, Heath S, Lathrop M, Brennan P. Lung cancer susceptibility locus at 5p15.33. Nat Genet. 2008 Nov 2. [Epub ahead of print]

V Verri C., Roz L, Conte D, Liloglou T, Livio A, Vesin A, Fabbri A, Andriani F, Brambilla C, Tavecchio L, Calarco G, Calabrò E, Mancini A, Tosi D, Bossi P, Field JK, Brambilla E, Sozzi G, EUELC consortium. FHIT gene inactivation in lung cancer patients: results of a prospective European study (EUELC). Am J Respir Crit Care Med. 2008 Dec 18. [Epub ahead of print].

Shaw R.J, Hall G.L, Lowe D, Bowers N, Liloglou T, Field J.K, Woolgar J.A. &. Risk J.M. CpG island methylation phenotype (CIMP) in oral cancer: Associated with a marked inflammatory response and less aggressive tumour biology. Oral Oncol. 43(9); 878-86, 2007.

Shaw RJ , Hall G, Woolgar JA, Lowe D, Rogers SN, Field JK, Liloglou T, Risk JM. Quantitative methylation analysis of resection margins and lymph nodes in oral squamous cell carcinoma. Br J Oral Max Surgery 45(8); 617-22,2007

Gorlov IP, Meyer P, Liloglou T, Myles JP, Boettger MB, Cassidy A, Girard L, Minna MD, Fischer R, Duffy SW, Spitz MR, Haeussinger K, Kammerer S, Hoyal CR, Cantor C, Dierkesmann R+, Field JK+, Amos CI+. SEZ6L Gene and Risk for Lung Cancer. Cancer Research. 7: 8406-11, 2007.

Shaw R J, Hall G L, Lowe D, Liloglou T, Field J K, Sloan P and Risk J M The role of pyrosequencing in head and neck cancer epigenetics: Correlation of quantitative methylation data with gene expression. Arch Otolaryngology ,133, 9: 2007.

Cassidy A, Myles J, Liloglou T, Duffy S, Field JK. Defining high-risk individuals in a population-based molecular-epidemiological study of lung cancer. Int J Oncol. May;28(5):1295-301. 2006

McRonald FE, Rowbottom L, Langan JE, Ellis A, Shaw JM, Liloglou T, Xinarianos G, Field JK, Risk JM. Downregulation of the Cytoglobin gene on 17q25 in Tylosis with Oesophageal Cancer (TOC): evidence for trans-allele repression. Hum Mol Genet. Apr 15;15(8):1271-7, 2006.

Xinarianos G, McRonald FE, Risk JM, Bowers N, Nikolaidis G, Field JK, Liloglou T. Frequent genetic and epigenetic abnormalities contribute to the deregulation of Cytoglobin in non-small cell lung cancer. Hum Mol Genet.1;15(13):2038-44. 2006

Cassidy A, Duffy SW, Myles JP, Liloglou T, Field JK. Lung cancer risk prediction: a tool for early detection. International Journal of Cancer 120(1):1-6.2006.

Shaw RJ, Akufo-Tetteh EK, Risk JM, Field JK, Liloglou T. Methylation Enrichment Pyrosequencing: combining the specificity of MSP with validation by Pyrosequencing. Nuc Acid Res 2006 34: (11): e76. 2006

Pateras IS, Kotsinas A, Liloglou T, Nikolaidis G, Foukas P, Koutsami M, Apostolopoulou K, Field JK, Kittas C, Gorgoulis VG. Down-regulation of the KIP family members p27 KIP1 and p57 KIP2 by SKP2 and the role of methylation in p57KIP2 Int J. Cancer, 119: 2546-56, 2006

Ehrich M, Field JK, Liloglou T, Xinarianos G, Oeth P, Nelson MR, Cantor CR, van den Boom D. Cytosine Methylation Profiles as a Molecular Marker in Non–Small Cell Lung Cancer. Cancer Res 66: 10911-10918. 2006

Cassidy A, Myles JP, Duffy SW, Liloglou T, Field JK. Family history and risk of lung cancer: age-at-onset in both cases and first-degree relatives. British Journal of Cancer 95(9):1288-90. 2006.

Vageli D, Daniil Z, Dahabreh J, Karagianni E, Liloglou T, Koukoulis G, Gourgoulianis K. Microsatellite instability and loss of heterozygosity at the MEN1 locus in lung carcinoid tumors: A novel approach using real-time PCR with melting curve analysis in histopathologic material. Oncol Rep. 15: 557-64, 2006.

Liverpool Lung Project - programme award 2008-2010. Roy Castle Lung Cancer Foundation. Programme Grant - £1,913,370

Liverpool Experimental Cancer Medicine Centre (LECMC) (with Professor B K Park, Professor J Neoptolemos, Dr P Clark, Dr E Costello, Dr N Kitteringham) CR-UK & UK Department of Health. Grant awarded (2006-2010), £124,023 in first year.

A Pilot Study of Lung Cancer Early Detection and Clinical Intervention in Primary Care. Knowsley PCT. Grant awarded: £75,500 (2006-09).

UK Lung Cancer Screening feasibility & Protocol development. HTA £155,000 (2008-2009).

Chinese LLP. Merseyside and Cheshire Cancer Research Network (M&CCRN) for Flexibility and Sustainability Funding (FSF) 36,550 (2009-10).

Risk Stratification: Modelling and accessibility. Royal Liverpool and Broadgreen University NHS Hospitals Trust, NIHR F&S Funding. (with W Greenhalf, A Taktak, S Coupland, E Costello, B Damato) (2010) £45,000.

Validation of DNA Methylation biomarkers for early lung cancer diagnosis in case-control populations and in primary care high risk population. CR-UK . £59,671 (year 1).

A Nanoscale Artificial Nose to easily detect Volatile Biomarkers at Early stages of Lung Cancer and Related Genetic Mutations FP7-HEALTH-2010- Awarded to Liverpool €980,898 (2010 – 2014).

Determining (epi)genetic therapeutic signatures for improving lung cancer prognosis. FP7-HEALTH-2010-Proposal No: 258677-2 Acroym CURELUNG Grant award to Liverpool €298,000 (2010-2013)

A genome-wide study of lung cancer in never smokers. NIH Proposal to form a Consortium. Grant awarded To Liverpool $88,453.91 (2010–2015)

The development and validation of an ethnic specific lung cancer risk prediction model for the Liverpool Chinese community. Liverpool PCT PhD post Grant awarded £39,870. (2010-2013).