Dr Helen Reeves
Senior Lecturer & Honorary Consultant Gastroenterologist at Newcastle Hospitals NHS Foundation Trust
- Email: firstname.lastname@example.org
- Telephone: +44 (0) 191 208 4423
- Fax: +44 (0) 191 208 4301
- Address: Northern Institute for Cancer Research
Paul O'Gorman Building
Newcastle upon Tyne
I am an academic hepatologist, looking after patients with primary liver cancer. My long term goal is to improve outcomes for these patients, in part by developing tools to detect their cancers earlier, but also by identifying novel therapeutic candidates to take forward into clinical use, alongside the biomarkers needed to implement them.
ROLES AND RESPONSIBILITIES
My clinical role is that of lead physician within the Hepatopancreatobiliary (HPB) Newcastle Hospitals NHS Foundation Trust, co-ordinating the care of patients with hepatocellular cancer in Northern England.
My research role and responsibility is that of a senior lecturer and lead PI in the Hepatopancreatobiliary group in the Northern Institute for cancer research. I work closely with Dr Ruchi Shukla, who has recently joined the group, as well as with Professor John Lunec and Professor Steven Wedge form the NICR, as well as with Dr Fiona Oakley and Dina Tiniakos from ICM. We presently supervise 4 PhD students, with two more joining the group in September.
I have just completed 3 years serving as the UK representative on the European Association for Study of the Liver (EASL) governing board.
- 1998 BMedSci (Hons) 2:1 (Nottingham University Medical School, UK)
- 1990 BM.BS. (Nottingham University Medical School, UK)
- 1993 Member of Royal College of Physicians (London, UK)
- 1995-1997 Wellcome Trust Clinical Training Fellowship
- 2000 PhD (University of Newcastle upon Tyne, UK)
- 2000 Peel Medical research Trust Travel Fellowship
- 2000-2002 American Association for Study of Liver Diseases Fellowship
- 2003-2008 GlaxoSmithKline Senior Fellowship
- 2005 Member of Association of Physicians
- 2007 Fellow Royal College Physicians (London, UK)
- 2007 Founding Member ILCA (International Liver Cancer Association)
- 2011-2014 British Association Cancer Research – Committee Member
- 2012 Founding member HCC-UK
- 2013-2016 European Association for Study of the Liver Governing Board – UK representative
AWARDS AND PRIZES
- 1994 British Liver Trust laboratory support grant
- 1995-1997 Wellcome Trust Clinical Training Fellowship
- 1997 Dewar Research Prize, Northern Association of Physicians
- 2000 Peel Medical Research Trust Travel Award
- 2001-2002 American Association for Study of Liver Diseases Fellowship
- 2002-2008 GlaxoSmithKline Senior Fellowship
- 2003-2005 European Brewers Association Project Grant - (Gene profiling in ALD) (PI)
- 2004-2006 Newcastle Special Trustees Set up Grant (KLF6 in Colorectal cancer) (PI)
- 2004 LiverNorth Laboratory Support grant (PI)
- 2005 Newcastle Special Trustees Award (DNA damage in Pancreatic cancer) (PI)
- 2009 Newcastle Special Trustees Award (Gene profiling in NAFLD) (PI)
- 2009-2013 LiverNorth & patient donations PhD studentship (DNA-PK in HCC) (PI)
- 2011-2012 The Dowager Countess Eleanor Peel Trust pilot – chemotherapy induced liver injury (PI)
FUNDING 2010 onwards
- FP7 European framework programme - Project Grant: FLIP – Fatty Liver Inhibition of Progression. Sub-project: HCC in NAFLD and HCC. 2010 - 2014. 1.3 million Euro (Subproject PI value €273,000).
- Newcastle Medical Faculty & Newcastle Cancer Centre studentship - Detection of circulating tumour cells in Liver cancer patients using the Imagestream system. 2011- 2014. £76,737 – Principal Investigator
- Newcastle Cancer Centre Pump-priming Consumable Award - Detection of circulating tumour cells in NAFLD patients with HCC, using the Imagestream system. 2011- 2013. £22,500 – Principal Investigator.
- EU H2020 Programme, EPOS – Elucidating Pathways of Steatohepatitis. €6,000,000, 2015-2019. Co-investigator, Sub-project PI – SULF2 in HCC development and progression.
- EASL Registry Grant, ‘The European NAFLD Registry’, €50,000 2015-2017. Co-investigator
- CRUK and ASTEX Alliance – Newcastle Cancer Centre Drug Discovery Programme. £3,500,000; 2012-2018, Collaborator.
- Cancer Research UK PhD Studentship. Translating novel therapeutic approaches into treatments for patients with hepatocellular cancer. Co-supervisor. 2013-2017.
- MRC Confidence in Concept. RNASeq to identify candidate drivers of non-alcoholic fatty liver disease progression to fibrosis and hepatocellular carcinoma. £41,500, 2015-2016. Principal Investigator
- Cancer Research UK PhD studentship. Neutrophils as drivers of hepatocellular carcinoma progression – predictive biomarker and target for therapeutic intervention? 2016 - 2020; Principal Investigator.
- MRC MICA- Exploring a new perspective on the mechanism of action of glucokinase activators in liver: a preclinical study. 3 years. £746,548. 2016-2019. Co-investigator
- CMAL (CR UK/Medimmune Alliance) collaboration - Exploring SULF2 as a therapeutic target in HCC.
Target discovery and validation
Our group is interested in the molecular pathogenesis of hepatocellular carcinoma (HCC) arising on a background of obesity, diabetes and non-alcoholic fatty liver disease (NAFLD). We are particularly interested in the role played by the diseased tumour microenvironment / extracellular matrix in cancer development and progression. We have developed a dietary model where mice fed a high fat and high sugar diet develop NAFLD and HCC and we have been exploring this for novel targets to exploit as preventive or antitumour therapies. These include a sulfatase (SULF2) which is overexpressed in tumour activated stromal cells, that alters the sulfation status of matrix molecules, receptors and ligands for signalling pathways, up-regulating growth and migration. We are also studying the contribution of inflammatory cells such as neutrophils in HCC development and progression. An associated interest is in the response to damage that occurs in cancer cells – either as a result of inflammation related damage or chemo-radiotherapies. We have shown that the cancers survive damage and resist treatment partially as a result of increased DNA damage repair – DNA-PK in particular. We are exploring DNA-PK inhibition in models of HCC.
Prognostic and predictive biomarker development
HCC is the 6th most common cancer worldwide, but actually the 2nd commonest cause of cancer death. This is because the majority of those affected present at an advanced stage, with poor liver function consequent to underlying chronic liver disease, and we have no effective treatments. We do know that early detection of HCC in patients with cirrhosis can result in cure. It is tragic therefore, that even though we know the patient group at risk, we do not have effective screening or surveillance tools. With our liver group colleagues in the institute of cellular medicine, we have an interest in identifying genetic markers associated with HCC risk. With national and international collaborators, we are also exploring serum surveillance biomarkers. For patients in who we diagnose an HCC, it is often hard to know which treatment is best for them. This is partly because we rarely have tissue from their cancer – the diagnosis is usually made on imaging and biopsy is risky. So we have no robust biomarkers to know if one or other treatment is best. Guidelines advise treatment based largely on the risk of making liver function worse, rather than shrinking a tumour. We have a major interest therefore, in emerging ‘liquid biopsy’ tools – circulating tumour cells, circulating tumour DNA. We are exploring these methods in hope that we will be able to stratify treatment for our patients, as well as monitor responses, more effectively. We do this alongside characterising tissue samples changes in those patients where we have them – looking at SULF2 and DNA-PK amongst other things. To support these translational studies, we have created a liver cancer tissue bank, which presently has donated samples from over 500 of our patients with HCC.
- Informal clinical ward based teaching on a monthly basis
- Lecturer on medical students on the yearly liver course
- Undergraduate tutor
- Undergraduate students
- Lecturer to Gastroenterology SpRs
- Lecturer to Oncology SpRs
- Lecturer to Transplant co-ordinators
- Informal ward based clinical teaching
- Non- clinical - 4 PhD students
- Reuillon T, Alhasan SF, Beale GS, Bertoli A, Brennan A, Cano C, Reeves HL, Newell DR, Golding BT, Miller DC, Griffin RJ. Design and synthesis of biphenyl and biphenyl ether inhibitors of sulfatases. Chemical Science 2016, 7(4), 2821-2826.
- Reeves HL, Zaki MYW, Day CP. Hepatocellular Carcinoma in Obesity, Type 2 Diabetes, and NAFLD. Digestive Diseases and Sciences 2016, 61(5), 1234-1245.
- Dent BM, Ogle LF, O'Donnell RL, Hayes N, Mallick U, Curtin NJ, Boddy AV, Plummer ER, Edmondson RJ, Reeves HL, May FEB, Jamieson D. High-resolution imaging for the detection and characterisation of circulating tumour cells from patients with oesophageal, hepatocellular, thyroid and ovarian cancers. International Journal of Cancer 2016, 138(1), 206-216.
- Ogle LF, Orr JG, Willoughby CE, Hutton C, McPherson S, Plummer R, Boddy AV, Curtin NC, Jamieson D, Reeves HL. Imagestream detection and characterisation of circulating tumour cells - a liquid biopsy for Hepatocellular Carcinoma?. Journal of Hepatology 2016, (ePub ahead of Print).
- Zaki MYW, Reeves HL. The genetic heterogeneity of hepatocellular carcinoma and the implications for personalised medicine. TRANSLATIONAL CANCER RESEARCH 2016, 5, S1-S4.
- Johnson PJ, Berhane S, Kagebayashi C, Satomura S, Teng M, Reeves HL, O'Beirne J, Fox R, Skowronska A, Palmer D, Yeo W, Mo F, Lai P, Inarrairaegui M, Chan SL, Sangro B, Miksad R, Tada T, Kumada T, Toyoda H. Assessment of Liver Function in Patients With Hepatocellular Carcinoma: A New Evidence-Based Approach - The ALBI Grade. Journal of Clinical Oncology 2015, 33(6), 550-558.
- Kolly P, Reeves HL, Sangro B, Knopfli M, Candinas D, Dufour JF. Assessment of the Hong Kong Liver Cancer Staging System in Europe. In: International Liver Congress 2015 - 50th Annual meeting of the European Association for the Study of the Liver. 2015, Vienna, Austria: Elsevier.
- Cornell L, Munck JM, Alsinet C, Villanueva A, Ogle L, Willoughby CE, Televantou D, Thomas HD, Jackson J, Burt AD, Newell D, Rose J, Manas DM, Shapiro GI, Curtin NJ, Reeves HL. DNA-PK-A Candidate Driver of Hepatocarcinogenesis and Tissue Biomarker That Predicts Response to Treatment and Survival. Clinical Cancer Research 2015, 21(4), 925-933.
- Whitehead A, Patman GL, Deuschle U, Day CP, Kremoser C, Tiniakos DG, Anstee QM, Reeves HL, FLIP Investigators FP7 2007-2013 H. Effects of FXR agonist PX20606 on tumour formation in animal models of non-alcoholic fatty liver disease. In: The International Liver Congress 2015 - 50th Annual meeting of the European Association for the Study of the Liver. 2015, Vienna, Austria: Elsevier.
- Reeves HL, Aisen AM. Hepatocellular Carcinoma: Optimal Staging Impacts Survival. Gastroenterology 2015, 148(7), 1274-1276.
- Whitehead A, Ogle L, Patman GL, Anwar G, Tiniakos DG, Anstee QM, Reeves HL, FLIP Investigators FP7 2007-2013 H. Ras and p-ERK in metabolic syndrome associated Hepatocellular Carcinoma (HCC). In: 50th Annual Meeting of the European Association for the Study of the Liver. 2015, Vienna, Austria: Elsevier.
- Miller DC, Carbain B, Beale GS, Alhasan SF, Reeves HL, Baisch U, Newell DR, Golding BT, Griffin RJ. Regioselective sulfamoylation at low temperature enables concise syntheses of putative small molecule inhibitors of sulfatases. Organic & Biomolecular Chemistry 2015, 13(18), 5279-5284.
- Piguet AC, Saran U, Simillion C, Keller I, Terracciano L, Reeves HL, Dufour JF. Regular exercise decreases liver tumors development in hepatocyte-specific PTEN-deficient mice independently of steatosis. Journal of Hepatology 2015, 62(6), 1296-1303.
- Berhane S, Toyoda H, Tada T, Kumada T, Kagebayashi C, Satomura S, Schweitzer N, Vogel A, Manns M, Benckert J, Berg T, Best J, Dechene A, Gerken G, Schlaak J, Reeves HL, Johnson P. The 'Galad Score' for serological Detection of Hepatocellular Cercinoma: International Validation and Assesment of the Influence of Tumor size and Aetiology on Model Utility. In: 50th Annual meeting of the European Association for the Study of the Liver. 2015, Vienna, Austria: Elsevier.
- Gautheron J, Vucur M, Reisinger F, Cardenas DV, Roderburg C, Koppe C, Kreggenwinkel K, Schneider AT, Bartneck M, Neumann UP, Canbay A, Reeves HL, Luedde M, Tacke F, Trautwein C, Heikenwalder M, Luedde T. A positive feedback loop between RIP3 and JNK controls non-alcoholic steatohepatitis. EMBO Molecular Medicine 2014, 6(8), 1062-1074.
- Liu Y-L, Patman GL, Leathart J, Piguet A-C, Burt AD, Dufour J-F, Day CP, Daly AK, Reeves HL, Anstee QM. Carriage of the PNPLA3 rs738409 C>G Polymorphism Confers an Increased Risk of Non-Alcoholic Fatty Liver Disease Associated Hepatocellular Carcinoma. Journal of Hepatology 2014, 61(1), 75-81.
- Johnson PJ, Pirrie SJ, Cox TF, Berhane S, Teng M, Palmer D, Morse J, Hull D, Patman G, Kagebayashi C, Hussain S, Graham J, Reeves H, Satomura S. The Detection of Hepatocellular Carcinoma Using a Prospectively Developed and Validated Model Based on Serological Biomarkers. Cancer Epidemiology, Biomarkers & Prevention 2014, 23(1), 144-153.
- Liu Y-L, Reeves HL, Burt AD, Tiniakos D, McPherson S, Leathart JBS, Allison MED, Alexander GJ, Piguet A-C, Anty R, Donaldson P, Aithal GP, Francque S, VanGaal L, Clement K, Ratziu V, Dufour J-F, Day CP, Daly AK, Anstee QM. TM6SF2 rs58542926 Influences Hepatic Fibrosis Progression in Patients with Non-Alcoholic Fatty Liver Disease. Nature Communications 2014, 5, 1-6.
- Whitehead A, Patman GL, Cornell L, Televantou D, Curtin N, Day CP, Burt AD, Piguet AC, Dufour JF, Anstee QM, Reeves HL, FLIP Investigators FP7-2007-2013. A Role for DNA Repair Protein Kinase (DNA-PK) in the Progression of Simple Steatosis to Steatohepatitis (NASH)?. In: 48th Annual meeting of the European Association for the Study of the Liver. 2013, Amsterdam, The Netherlands: Elsevier Science BV.
- Dyson J, Jaques B, Chattopadyhay D, Lochan R, Graham J, Das D, Aslam T, Patanwala I, Gaggar S, Cole M, Sumpter K, Stewart S, Rose J, Hudson M, Manas D, Reeves HL. Hepatocellular cancer: The impact of obesity, type 2 diabetes and a multidisciplinary team. Journal of Hepatology 2013, 60(1), 110-117.
- Patman GL, Televantou D, Whitehead A, Day CP, Oakley F, Mann DA, Burt AD, Anstee QM, Reeves HL, FLIP Investigators FP7-2007-2013. Mild Steatosis and Impaired Glucose Tolerance are Associated with Liver Cancer Development, While Progression to Nash Increases Number/Size in an Animal Model of NAFLD. In: 48th Annual meeting of the European Association for the Study of the Liver. 2013, Amsterdam, Netherlands: Elsevier BV.
- Patman GL, Televantou D, Whitehead A, Oakley F, Mann DA, Burt AD, Anstee QA, Reeves HL. NAFLD progression to NASH, fibrosis and hepatocellular cancer - development of a robust animal model. Journal of Hepatology 2013. In Preparation.
- Bechmann LP, Vetter D, Ishida J, Hannivoort RA, Lang UE, Kocabayoglu P, Fiel MI, Muñoz U, Patman GL, Ge F, Yakar S, Li X, Agius L, Lee YM, Zhang W, Hui KY, Televantou D, Schwartz GJ, Leroith D, Berk PD, Nagai R, Suzuki T, Reeves HL, Friedman SL. Post-transcriptional activation of PPAR alpha by KLF6 in hepatic steatosis. Journal of Hepatology 2013, 58(5), 1000-1006.
- Patman GL, Televantou D, Whitehead A, Piguet AC, Dufour JF, Day CP, Burt AD, Mann DA, Reeves HL. Sulfatase-2 (SULF2) Expressed in Hepatocytes and Stromal Cells Contributes to the Development of Steatosis, the Progression of NAFLD to Fibrosis and the Advancement of Cancer. In: 48th Annual meeting of the European Association for the Study of the Liver. 2013, Amsterdam, The Netherlands: Elsevier.
- Petrie JL, Patman GL, Sinha I, Alexander TD, Reeves HL, Agius L. The rate of production of uric acid by hepatocytes is a sensitive index of compromised cell ATP homeostasis. American Journal of Physiology 2013, 305(10), E1255-E1265.
- Bechmann LP, Gastaldelli A, Vetter D, Patman GL, Pascoe L, Hannivoort RA, Lee UE, Fiel I, Muñoz U, Ciociaro D, Buzzigoli E, Miele L, Hui KY, Bugianesi E, Burt AD, Day CP, Mari A, Agius L, Walker M, Friedman SL, Reeves HL. Glucokinase links Krüppel-like factor 6 to the regulation of hepatic insulin sensitivity in nonalcoholic fatty liver disease. Hepatology 2012, 55(4), 1083-1093.
- Alhasan SF, Beale GS, Newell DR, Reeves HL. Suppression of SULF2, an extracellular endosulfatase up-regulated in hepatocellular cancers, modulates WNT signalling and inhibits cell growth. In: Digestive Disorders Federation Meeting. 2012, Liverpool, UK: BMJ Group.
- Patman GL, Anstee Q, Reeves HL. Hepatocellular Carcinoma in NASH: Is there a biological Rationale?. In: 9th Meeting of Therapy in Liver Diseases. 2011, Barcelona, Spain.
- Gray J, Chattopadhyay D, Beale GS, Patman GL, Miele L, King BP, Stewart S, Hudson M, Day CP, Manas DM, Reeves HL. A proteomic strategy to identify novel serum biomarkers for liver cirrhosis and hepatocellular cancer in individuals with fatty liver disease. BMC Cancer 2009, 9.
- Beale GS, Chattopadhyay D, Gray J, Stewart SF, Hudson M, Day CP, Trerotoli P, Giannelli G, Manas DM, Reeves HL. AFP, PIVKAII, GP3, SCCA-1 and follisatin as surveillance biomarkers for hepatocellular cancer in non-alcoholic and alcoholic fatty liver disease. BMC Cancer 2008, 8, 200.
- Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Häussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J. Sorafenib in advanced hepatocellular cancer. N Engl J Med 2008, 359, 378-90.
- Miele L, Beale G, Patman G, Nobili V, Leathart J, Grieco A, Abate M, Friedman S, Narla G, Bugianesi E, Day C, Reeves H. The Kruppel-like factor 6 genotype is associated with fibrosis in nonalcoholic fatty liver disease. Gastroenterology 2008, 135(1), 282-291.