BOWEL DISEASE RESEARCH FOUNDATION of The Association of Coloproctology of Great Britain and Ireland APPLICATION FORM FOR THE BDRF OBSERVATIONAL RESEARCH GRANTS

Applications should be a maximum of 4 pages, including any images, and also accompanied by a CV (1 side of A4) for each applicant. Please send the form with CVs electronically as one single Word document using 12pt typeface . 1. Name of the investigator Mr Graham Branagan2. Job title Consultant colorectal surgeon

3. Email address graham.branagan@salisbury.nhs.uk4. Tel. No. Work: 01722 336262 ext. 4483 mobile: 07757402805. Institution Sponsor: Salisbury NHS Foundation Trust

Collaborator: The Christie NHS Foundation Trust & University of Manchester (UoM)

6. Name of supervisor Not applicable7. Name of Co-investigators Salisbury:

Mr Graham Branagan, Consultant Colorectal SurgeonDr Clare Fuller, Consultant PathologistManchester:Professor Andrew Renehan, Consultant Colorectal SurgeonDr Ian Hampson, Lead Scientist, Viral Oncology Group, UoMDr Ivona Baricevic-Jones, Post-doctoral scientist, Viral Oncology Group, UoMDr Matthew Sperrin, Lecturer in Biostatistics, UoM

8. Ordinary member of ACPGBI Mr Graham Branagan9. Title of Project HomeR: Development of HPV genotyping as a predictive

biomarker of chemo-radiotherapy response in patients with Rectal Cancer

10. Length of project 12 monthsFunding requested11.a Total amount £30,00011.b Breakdown of costs Salisbury

Tissue retrieval: £2,600Tissue transfer: £800

ManchesterPost-doc scientist salary: £15,000Laboratory consumables: £4,000Tissue retrieval: £1,600DNA extraction: £3,000ABI Veriti PCR thermo-cycler: £3,000

11.c How many instalments Not applicable11.d In which months instalments need to be paid

Project start date: 1st February 2014

11.e Justification of support requested

The requested funding is for the following:1. Retrieval of targeted tissue samples under existing biobank

retrospective ethics arrangements; TISUE transfer to Manchester

2. 6 month salary for a post-doctoral scientist (IB-J), already in post in Hampson laboratory, Manchester

3. Laboratory consumables (e.g. primers) and updating PCR thermo-cycler equipment

4. DNA extraction from the paraffin blocks using established SOPs12. Has the institution administering funding agreed exemption from overheads ? Yes No

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Project Details

13. Background to projectHuman papilloma virus (HPV) is an established aetiological factor for the development of ano-genital and oro-pharyngeal cancers, but less appreciated, HPV is also associated with the development of rectal cancer . Moreover, in ano-genital and oro-pharyngeal cancers, the presence of HPV16, the commonest oncogenic genotype, is associated with better prognosis and improved response to treatment, mainly chemo-radiotherapy (CRT) . A parallel hypothesis has not been tested in rectal cancer.

In the UK, there are approximately 15,000 new cases of rectal cancer per year. Surgery is the mainstay of treatment. Locally advanced disease is treated initially with ‘downstaging’ pre-operative CRT, followed by surgery 8 to 15 weeks later, but this combination is associated with considerable peri-operative mortality and long-term morbidity. In 15% to 20% of cases, CRT may result in complete disappearance of tumour. In patients without residual tumour on imaging and endoscopy (clinical complete response), a wait-and-see policy (omission of surgery with follow-up) might be considered an alternative to major resection - and represents a new paradigm for treating rectal cancer - but to-date, there are no predictors for this response, and no recognised adjuvants to enhance this response.

The aim of this study is to extend an established HPV genotyping research programme, using high-sensitivity assays in anal cancer (Renehan & Hampson, Manchester), to rectal cancer, with the two-fold objectives to:i) Describe the proportions of HPV 16, 18 and 33 in pre-treatment rectal cancer specimens, and relations

with age, gender and stage (CRUK biomarker classification: BM Discovery Stage 1), and;ii) Test the hypothesis that HPV16 positivity is greater in patients who subsequently develop a complete

response compared with those without a complete response to CRT (CRUK biomarker classification: BM Discovery Stage 2).

We consider these objectives as ‘proof of concept’, forming a platform for future biomarker validation (see below).Knowns and unknowns: (i) There is evidence of a causal association between HPV infection and rectal cancer based on Bradford-Hill criteria of analogy, biological plausibility, strength of association, and to a lesser extent the criteria of consistency, specificity and coherence ; (ii) a recent meta-analyses estimated that HPV is present in 42% of colorectal tumours versus 6% of non-diseased normal mucosa ; (iii) many of the earlier studies (reviewed in ) used crude methodologies (e.g. Southern blots and immunohistochemistry of the oncoproteins) and probably underestimated prevalence; (iv) most series are small - only four studies had greater than 100 patients ; (v) HPV16 appears to the dominant genotype; but HPV18 and 33 also appear dominant in some series ; (vi) there is yet no consistent 'correlation' between HPV positivity and tumour location or stage ; and (vii) there is no substantive study of HPV positivity and treatment outcome.

14. Methodology Setting: Salisbury NHS Foundation Trust and the University of Manchester (2006-2013)Patients: Pre-treatment biopsy tissue in patients with rectal adenocarcinoma undergoing CRT.Study design: The design is shown in the flow diagram (Figure 1) – consists of two levels corresponding to the two objectives. Level I is a baseline characterisation (descriptive) study; level II is a case-control study.Controls: From both centre databases, patients with rectal cancer who underwent CRT and subsequently proceeded to respective surgery with visible tumour

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Figure 1 Project study design OnCoRe: BDRF funded North West registry of complete respondersMCRC: Manchester Cancer Research Centre

Salisbury

Rectal cancerDatabase

(2006-2013)

Manchester

Rectal cancerDatabase

(2006-2013)

CasesN ≈ 10

ControlsN ≈ 70 + Cases

N ≈30ControlsN ≈ 50 +

OnCoRe d/bN > 130

Pathology-assisted tissue retrieval MCRC Biobank-facilitated tissue retrieval

Hampson laboratory (N = 160)

DNA extraction

HPV genotyping

Baseline characterisation

CasesN = 40

ControlsN = 120 vs.

Level I - objective (i)

Level II - objective (ii)

Tissue blocks transfer

present (non- or partial responders) – considered the ‘normal’ clinical pathway – will be identified and tissue blocks retrieved.Cases: Patients with rectal cancer who had either a complete clinical or pathological response to CRT will be identified from both centre databases. For Manchester, we will additionally use the OnCoRe database (a BDRF funded project of clinical complete responders across the North West of England) to identify cases. We will use ‘real-world’ definitions of complete responses i.e. as determined by the MDT.Tissue transfer: Whole paraffin-embedded tissue blocks will be transferred to Manchester. DNA extraction: DNA will be extracted from all the blocks in the NHS BRC Biobank laboratory following GCLP QC standards. QIAamp DNA FFPE tissue kit will be used for purification of genomic DNA from formalin-fixed, paraffin-embedded tissues. H&E staining will be performed on the slides of the first and last cuts for each sample for pathological examination (to confirm presence of adenocarcinoma). The quality of the DNA will be checked using polymerase chain reaction (PCR) to detect the presence of a house-keeping gene (beta-2-microglobulin). If the quality of samples is adequate, all the DNA samples will undergo whole genome amplification (WGA). The quality of the DNA will be checked again using PCR (determination of the presence of beta-2-microglobulin).Laboratory measurements: Multiplex PCR will be performed for all HPVs that will be done in this study. Using two sets of primers for each HPV genotype, higher sensitivity/accuracy for HPV genotyping will be performed. This approach is novel and increases sensitivity of each HPV genotype. Each PCR will be performed with an appropriate positive control as well as with negative control that will be run at the beginning of each PCR and at the end of each PCR to avoid any contamination (Figure 2). Planned statistical analysis: Analyses for objective (i) will be standard chi-squared tests (e.g. proportions by gender); Mann-Whitney tests (e.g. median age by HPV positivity); and trends across ordinal categories (e.g. proportions by stage).For objective (ii), we will use logistic regression to test differences between complete responders versus others, allowing for adjustment for potential confounders identified in the baseline analysis.Power calculations: We stipulate from the outset that to demonstrate ‘proof of concept’ the minimal odds ratio is 3.0. Based on deliverable tissue retrieval in the timeframe and clinical practices of the two centres, the control sample size = 120. The estimated cases sample size = 40 i.e. a 1:3 case-control design. We estimate the HPV16 positivity among responders will be 69%; and among non-responders will be 36% (chosen to achieve an odds ratio of 4, and population prevalence of HPV16 positivity of 42%). The power at these sample sizes to show this difference is 95%  (sampsi command in STATA).In a worst-case scenario analyses, if we only retrieve and extract high-quality DNA in 30 cases (complete responders), the power to show difference is 88%. If the HPV positivity in the responders arm were only 63% (odds ratio = 3) the power to show difference is 80%.Existing Infrastructure: Manchester – the Manchester Cancer Research Centre (MCRC) Biobank will retrieve the targeted archival tissues. An already funded biobank technician (through the Christie Surgical Oncology Research Group – lead: Renehan) will facilitate this. DNA will be extracted through the Manchester Central Biobank (site of Hampson laboratory) using existing protocols. The HPV detection work will be performed by a project-dedicated post-doctoral scientist experienced in these techniques, the Hampson laboratory, a leading Viral Oncology laboratory.

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Figure 2 Double band PCR readouts Upper panel: high-quality DNA extract confirmed.Lower panel: example of HPV16 in anal cancer samples. This approach increases sensitivity –for example, in our laboratory, the detection rate for HPV16 in anal cancer is 89%

M 98 99 101 102 103 ….100

100 bp

1000 bp

W1112111 114113 115 NCW2Beta-microglobulin

M 98 99 101 102 103 …100NC

100 bp

1000 bp

neg

112111 114113 115 PC NC

209 bp148 bpprimers

HPV16

Salisbury – targeted archival tissue will be retrieved through the Pathology Department (Fuller). Clinical data will be taken from existing NBOCAP-compliant databases at both centres. Data/tissue transfer agreements have been commonly used between Manchester and other UK centres.Ethics: A strength of this study is the MCRC Biobank existing ethics – this allows tissue retrieval from clinical archives without need for individual patient retrospective consent (see supporting letter). The ‘Salisbury arm’ of the proposal will be suitable for proportionate ethics review, reducing delays.Platform for future research: If our hypothesis is upheld, two research directions will emerge:1. Biomarker validation i.e. retrospective 2x2 interactive (predictive) analysis of HPV positivity versus

HPV negativity in patients within a prospective trial of CRT versus no CRT;2. Development of adjuvants to enhance radiosensitivity – ultimately reducing treatment-related toxicity.

Examples include: (i) engineering HPV oncoproteins into HPV-negative HNC cells; and (ii) AKT inhibition (e.g. nelfinavir) specifically enhances radiosensitvity in HPV positive tumours (based on oropharyngeal cancer studies) .

5. References (if any): Maximum of 41. Burnett-Hartman AN, Newcomb PA, Potter JD (2008) Infectious agents and colorectal cancer: a review

of Helicobacter pylori, Streptococcus bovis, JC virus, and human papillomavirus. Cancer Epidemiol Biomarkers Prev 17: 2970-2979.

2. O'Rorke MA, Ellison MV, Murray LJ, Moran M, James J, et al. (2012) Human papillomavirus related head and neck cancer survival: a systematic review and meta-analysis. Oral Oncol 48: 1191-1201.

3. Lorenzon L, Ferri M, Pilozzi E, Torrisi MR, Ziparo V, et al. (2011) Human papillomavirus and colorectal cancer: evidences and pitfalls of published literature. Int J Colorectal Dis 26: 135-142.

4. Lui VW, Grandis JR (2012) Primary chemotherapy and radiation as a treatment strategy for HPV-positive oropharyngeal cancer. Head Neck Pathol 6 Suppl 1: S91-97.

16. Sample size and source of statistical advice (if appropriate)

Controls = 120; cases = 40. Total = 160 Power calculations in main text.

17. Have you applied for or acquired funding from any other sources(s)?

Yes No If Yes, where?

Lay summary (200-300 word summary)Problem addressed, back ground and strategic significance: Large bowel cancer is a major cause of death worldwide. The cause of non-genetic cancer is poorly understood with a number of potential causative agents. Recent evidence suggests that high-risk human papillomavirus (HPV) can be identified in >40% of large bowel cancer tissue compared with 6% of tissues from normal patients. Further evidence suggests i) HPV is more likely to be found in tumours of the rectum rather than the colon ii) HPV is associated with less advanced disease. HPV is also associated with other cancers especially of the throat and in these patients is associated with improved responses to radiotherapy and improved survival. Methods: HPV genotyping will be performed on rectal cancer specimens from 2 centres (Manchester and Salisbury). Funding will support tissue collection, DNA extraction and HPV genotyping to identify 3 HPV genotypesResults of this research: We hope to confirm that high risk HPV can be identified in a proportion of patients with rectal cancer and compare whether patients with HPV positive rectal cancers respond better to radiotherapy and whetehr this impacts on recurrence and survival..Changes to the current position: This study may add to the body of evidence that HPV is associated with rectal cancer and identify whether HPV positive tumours respond better to radiotherapy.

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NAME Graham William Branagan

TELEPHONE 01725 518478(H) 07775 740280 (M)

E-MAIL gbr1911@yahoo.co.uk, graham.branagan@salisbury.nhs.uk

D.O.B. 19.11.68

GMC No. 4105260

HOSPITAL Salisbury Foundation Trust (SFT)

POST Consultant Colorectal Surgeon

RESEARCH

Master of Surgery, University of Portsmouth July 2002. PI for the Mercury II low rectal cancer studyPI for DREAMSPI for LARSPI for ISAAC Past member of the Research and Audit Committee of the ACPGBI.Past member of the NCRI anal cancer subgroup.Reviewer for Digestive Diseases, BJS, Surgical Oncology, Colorectal Disease and the Annals of the Royal College of Surgeons, Annals of Surgery, Diseases of the Colon and Rectum and the international Journal of Urology .Publications: One book chapter, two invited articles, twenty-three peer-reviewed articles.Presentations: Five invited lectures, 13 oral presentations (international / national).

MOST RECENT PUBLICATIONS

Barker T, Branagan G, Wright E, Crick A, McGuiness C, Chave H. Vertical rectus abdominis myocutaneous flap reconstruction of the perineal defect after abdominoperineal excision is associated with low morbidity. Colorectal Dis. 2013 May 15. doi: 10.1111/codi.12286. [Epub ahead of print]

Byrne BE, Branagan G, Chave HS. Unselected rectal cancer patients undergoing low anterior resection with defunctioning ileostomy can be safely managed within an Enhanced Recovery Programme. Tech Coloproctol. 2013 Feb;17(1):73-8.

Foster JD, Pathak S, Smart NJ, Branagan G, Longman RJ, Thomas MG, Francis N. Reconstruction of the perineum following extralevator abdominoperineal excision for carcinoma of the lower rectum: a systematic review. Colorectal Dis. 2012 Sep;14(9):1052-9

Dabbas N, Adams K, Chave H, Branagan G. Current practice in abdominoperineal resection: an email survey of the membership of the Association of Coloproctology. Ann R Coll Surg Engl. 2012 Apr;94(3):173-6

How P, Stelzner S, Branagan G, Bundy K, Chandrakumaran K, Heald RJ, Moran B. Comparative quality of life in patients following abdominoperineal excision and low anterior resection for low rectal cancer. Dis Colon Rectum. 2012 Apr;55(4):400-6

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CURRICULUM VITAE

Surname Forename(s)

Fuller Clare Elizabeth

Work address:

Salisbury District Hospital

Salisbury

Wiltshire

SP2 8BJ UK

Telephone No: 01722 429001

Fax No: 01722 341499

E-mail address: clare.fuller@salisbury.nhs.uk

GMC registration no: 3091894

Qualifications:

BM BCh MA FRCPath

Present Post

Consultant Histopathologist 1994-present

Previous appointments:

Lecturer Pathology Sheffield Medical School 1990-1994

Clinical research experience:

Recently Mecury II and BACCHUS, supplying blocks, slides and reports for multicentre national studies

Clinical research training (eg, ICH GCP/EU Directive etc) including date of course attended:

None

Signed:Clare Fuller Dated:30.07.2013

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Andrew Renehan PhD FRCS FRCS(Gen Surg)

Current post: Professor in Cancer Studies and Surgery and Honorary Consultant Colorectal Surgeon, Peritoneal Tumour Service at the Department of Surgery, the Christie NHS Foundation Trust, Manchester. Academic affiliation: Faculty Institute of Cancer Sciences, University of ManchesterI work a split 50: 50 clinical: academic biweekly job plan. Tel (W): 0161 446 3157 e-mail: arenehan@picr.man.ac.uk Prestigious award: Hunterian Professor 2011/2012Research / Editorial roles: STROBE reporting revision group/COSMOS writing groupDiabetes & Research Cancer ConsortiumNICE Colorectal Cancer Guidelines Development group ACPGBI Research & Audit CommitteeNCRN ano-rectal trials subgroupCOLOFOL steering committee– European trial in colorectal cancer follow-upDutch CEA follow-up in colorectal cancer trial advisory groupMember of editorial board: Cochrane Collaboration Colorectal Cancer GroupMember of editorial board: British Journal of SurgeryLead cancer & obesity research group, Manchester CRC & MRC Health eResearch CentreGrants awarded: last 2 years2011: Novo Nordisk Independent research award £50,0002011-2013: NAEDI Cancer screening in type 2 diabetes £122,0002012-2014: NORD/Christie charitable funds £103,0002012-2013: Sanofi-Pasteur MPS Independent research award £30,0002013-2014: WCRF global attributable risk of BMI to cancer incidence - £500,000 (Co-investigator)2013-2015: Pancreatic Cancer UK £74,0002013-2015: Bowel Disease Research Foundation £94,0002013-2018: MRC Health eResearch Centre - £5.5M (Co-investigator)LIST OF KEY PUBLICATIONS (SELECTED SINCE 2012)1. McDonald JR, O'Dwyer ST, Rout S, Chakrabarty B, Sikand K, Fulford PE, et al. Classification of and

cytoreductive surgery for low-grade appendiceal mucinous neoplasms. Br J Surg 2012;99(7):987-92.2. Renehan AG. Insulin analogues and cancer risk: the emergence of second-generation studies.

Diabetologia 2012;55(1):7-9.3. Renehan AG, Flood A, Adams KF, Olden M, Hollenbeck AR, Cross AJ, et al. Body Mass Index at

Different Adult Ages, Weight Change, and Colorectal Cancer Risk in the National Institutes of Health-AARP Cohort. Am J Epidemiol 2012.

4. Renehan AG, M Z, Egger M. Obesity and cancer risk: seeking new mechanistic insights from epidemiology [commissioned]. Nature Reviews Cancer 2012.

5. Renehan AG, Solomon M, Zwahlen M, Morjaria R, Whatmore A, Audi L, et al. Growth hormone receptor polymorphism and growth hormone therapy response in children: a Bayesian meta-analysis. Am J Epidemiol 2012;175(9):867-77.

6. Renehan AG, Yeh HC, Johnson JA, Wild SH, Gale EA, Moller H. Diabetes and cancer (2): evaluating the impact of diabetes on mortality in patients with cancer. Diabetologia 2012.

7. Parkin E, O’Reilly DA, Adam R, Kaiser GM, Laurent C, Elias E, et al. The effect of hepatic steatosis on survival following resection of colorectal liver metastases in patients without pre-operative chemotherapy [in press] DOI:10.1111/hpb.12007. HPB 2013.

8.. Sperrin M, Marshall AD, Higgins V, Buchan IE, Renehan AG. Levelling off of adult body mass index trends in England: a latent class analysis of cross-sectional surveys (1992-2009). PLoS Medicine 2013.

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Curriculum VitaeDr Ian N. HampsonDate of birth: 26th February, 1954Degrees: 1974-1977 BSc. Hon, Bio Sci, University of Lancaster1978-1982 PhD. Faculty of Medicine, PICR, Christie Hospital, Manchester, UK.

Posts Held:Past 1982-1985 Post Doctoral Research Fellow, Clinical Research,Christie Hospital, Manchester, UK. 1985-1997 Grade I Post Doctoral Scientist, Department of Experimental Haematology, Paterson Institute for Cancer Research, Christie Hospital, Manchester, UK.Present; July1997 Reader in Viral Oncology, Inst of Cancer Sciences, University of Manchester, St. Mary’s Hospital, Oxford Road, Manchester M13 9WL.

Contact Details; Telephone 016 1 701 6938, Mobile 07500900871e-mail ian.hampson@manchester.ac.uk

Recent Peer-Reviewed PublicationsMaranga IO, Hampson L, Oliver AW, He X, Gichangi P, Rana F, Opiyo A, Hampson IN. HIV Infection Alters the Spectrum of HPV Subtypes Found in Cervical Smears and Carcinomas from Kenyan Women. Open Virol J. 2013;7:19-27..

Stern PL, van der Burg SH, Hampson IN, Broker TR, Fiander A, Lacey CJ, Kitchener HC, Einstein MH. Therapy of human papillomavirus-related disease. Vaccine. 2012 Nov 20;30 Suppl 5:F71-82.

He X, Walker TD, Maranga IO, Oliver AW, Hampson L, Hampson IN. No biological evidence of XMRV infection in cervical smears from HIV/ HPV positive and negative Kenyan women. PLoS One. 2012;7(10):e47208.

Shalaby MA, Hampson L, Oliver A, Hampson I. Plexin D1: new potential biomarker for cervical cancer. J Immunoassay Immunochem. 2012;33(3):223

Hampson IN, Oliver AW, Hampson L. Targeting activated Rho proteins: a new approach for treatment of HPV and other virus-related cancers? Expert Rev Anticancer Ther. 2011; Jul;11(7):975-8. (Invited Editorial)

Batman G, Oliver AW, Zehbe I, Richard C, Hampson L, Hampson IN. Lopinavir up-regulates expression of the antiviral protein ribonuclease L in human papillomavirus-positive cervical carcinoma cells. Antivir Ther. 2011;16(4):515-25

Zehbe I, Richard C, Lee KF, Campbell M, Hampson L, Hampson IN. Lopinavir shows greater specificity than zinc finger ejecting compounds as a potential treatment for human papillomavirus-related lesions. Antiviral Res. 2011 Aug;91(2):161-6

Oliver AW, He X, Borthwick K, Donne AJ, Hampson L, Hampson IN. The HPV16 E6 binding protein Tip-1 interacts with ARHGEF16, which activates Cdc42. Br J Cancer. 2011; Jan 18;104(2):324-31

Kim DH, Jarvis RM, Allwood JW, Batman G, Moore RE, Marsden-Edwards E, Hampson L, Hampson IN, Goodacre R. Raman chemical mapping reveals site of action of HIV protease inhibitors in HPV16 E6 expressing cervical carcinoma cells. Anal Bioanal Chem. 2010 Dec;398(7-8):3051-61.

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Dr Ivona Baricevic-Jones

Date of birth: 23/10/1971 (Belgrade, Serbia)

Telephone: 0161 4855603, mobile 07999515895

Electronic mail: ivona.baricevic-jones@manchester.ac.uk and ibaricevicjones@yahoo.com

Degrees:

1990-1995 Biochemistry BSc First Class (honours). Department of Biochemistry, Faculty of Chemistry, University of Belgrade, Belgrade, Serbia.

1995-1999 Biochemistry MSc (by research). INEP and Department of Biochemistry, Faculty of Chemistry, University of Belgrade, Belgrade, Serbia

2001-2004 Biochemistry PhD. INEP and Department of Biochemistry, Faculty of Chemistry, University of Belgrade, Belgrade, Serbia.

Posts Held:

2004-2009 Postdoctoral researcher at the Institute for the Application of Nuclear Energy (INEP) belonging to the University of Belgrade, Belgrade, Serbia.

2009-2012 Postdoctoral researcher at the Paterson Institute for Cancer Reasearch, (Department of Clinical and Experimental Pharmacology), University of Manchester, Manchester, UK. Supervisor: Dr. Andrew Renehan.

2012-present Postdoctoral researcher at Viral Oncology laboratory at St Mary’s Hospital, University of Manchester, Manchester, UK. Supervisor: Dr. Andrew Renehan and Dr. Ian Hampson.

Recent Peer-Reviewed Publications:

Baričević I, Roberts D & Renehan A (2013). Chronic insulin exposure does not cause insulin-resistance but is associated with chemo-resistance in colon cancer cells. Manuscript submitted to Hormone Metabolic Research.

Baričević I, Masnikosa R, Lagundžin D, Golubović V & Nedić O (2010) Alterations of insulin-like growth factor binding protein 3 (IGFBP-3) glycosylation in patients with breast tumours. Clin Biochem 43, 725-731.

Masnikosa R, Baričević I, Lagundžin D & Nedić O (2010) Characterisation of N-glycans bound to IGFBP-3 in sera from healthy adults. Biochimie 92(1), 97-101.

Ćujić D, Golubović S, Bojić-Trbojević Ž, Ilić N, Baričević I & Nedić O (2010). Differential diagnosis of liver diseases using serum biomarkers. Journal of BUON 15, 141-146.

Masnikosa R, Baričević I, Lagundžin D & Nedić O (2010) Detection of insulin-like growth factor binding proteins (IGFBPs) in porcine serum. Acta Veterinaria (Beograd) 60 (4), 327-337.

Nedić O, Malenković V, Dukanović & Baričević I (2008) Association of elevated IGFBP-1 with increased IGF-II concentration in patients with carcinoma of the liver. Int J Biol Markers 23 (4), 225-230.

Kirovski D, Lazarević M, Baričević-Jones I, Nedić O, Masnikosa R & Nikolić JA (2008) Effects of peroral insulin and glucose on circulating insulin-like growth factor-I (IGF-I), its binding proteins and thyroid hormones in neonatal calves. Can. J. Vet. Res. 72 (3), 253-258.

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Curriculum Vitae: Dr Matthew Sperrin

General Information

Employment History Lecturer in Health Data Science, Centre for Health Informatics, Institute of Population Health, May

2013 - Present Lecturer in Statistics, Lancaster University, Jan 2011 – Apr 2013 Statistician, Northwest Institute for Biohealth Informatics, University of Manchester, Jan 2010 – Dec

2010

Academic/Professional Qualifications Ph.D. in Statistics, Lancaster University, 2010

o Title: Statistical Methodology Motivated by Problems in Genetics; Supervisor : Dr Thomas Jaki MMORSE, Master of Maths, Operational Research, Statistics and Economics, University of Warwick,

2006, First Class Honours GradStat (Graduate Statistician Status), Royal Statistical Society, 2010 – Present Higher Education Academy, Fellow since 2012

ResearchThe focus of my research is maximising the potential of available data to improve healthcare. I am interested in developing principled statistical methodology that can be applied to provide improved decision support in health and medicine. This can be decisions on a micro-level, such as what treatments are best for an individual patient, or on a strategic level, such as understanding the potential health impact of population-level interventions.

Recent Funded Projects Co-Investigator (PI: Thomas Jaki), Towards full use of available data to improve clinical outcome

prediction, National Institute for Health Research (NIHR), Oct 2013 - Sept 2014, £30,000. Co-Investigator (PI: Andrew Renehan), PanORAMA project: Pancreatic Cancer Predisposition,

Obesity-Related Deposition Assessment using Magnetic Resonance ImAging: a development and discovery study to evaluate the assessment of pancreatic fat deposition using MR imaging as a predisposition biomarker for pancreatic cancer, Cancer Research UK, Aug 2013 – Jul 2014, £75,000.

Co-Investigator (PI: Iain Buchan), Health e-Research Centre (HeRC), Medical Research Council (MRC), Mar 2013 - Feb 2018, £4,500,000.

Management of food allergens: from threshold doses to analysis in food, Food Standards Agency (PI: Clare Mills), Feb 2012 – Jan 2013.

Optimal and pragmatic designs for pre-clinical studies to detect interaction between two compounds: a simulation study, Funded by AstraZeneca through the Medical and Pharmaceutical Research Unit (PI: Prof Anne Whitehead), Jan 2011-Dec 2011.

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