Staff Profile

I received my BSc (Hons) in Applied Science from Cumbria University where I did a desk top dissertation on DNA methylation and its role in cancer development, differential diagnosis and possible treatment regimes. I then went on to do an MRes in Cancer Studies at Newcastle University and did a six month project at The Northern Institute for Cancer Research (NICR) in Prof Helen Reeves's Liver Group, developing liquid biopsy techniques and using patients' circulating tumour cells to stratify treatment.

I am currently continuing my work for Prof Reeves as her research technician. My research revolves around identifying biomarkers in hepatocellular carcinoma (HCC) and managing the HCC Biobank at the NICR. This job involves supervising undergraduate and postgraduate students, providing HCC research samples to international collaborators, tracking donor clinical data, and continuing with my own research.

I am currently undertaking a PhD funded by the NIHR Biomedical Research Council "Impact of lifestyle on liver cancer development and progression", started 2023.

Lifestyle and the Progression of Hepatocellular Carcinoma

Introduction

Genetics and lifestyle are responsible for most of the chronic diseases associated with aging with environmental factors also contributing. While the vast majority of us are stuck aging according to our genetic make-up, lifestyle can be altered to mitigate genetic susceptibilities and/or improve quality of life by slowing or reversing health deterioration brought on by less beneficial lifestyle choices. The reverse, therefore, is also true. Unhealthy lifestyle choices can accumulate and exacerbate the aging process and lead to chronic health conditions, including metabolic diseases and cancer.

Cancer Prevention

It is estimated that only 5-10% of cancer diagnoses are down to genetic defects alone. The other 90-95% can be attributed to environment and lifestyle. While environmental pollutants are difficult, costly or impossible to avoid, there are specific choices that can greatly impact the risk of developing cancer. Global figures indicate that 25-30% of cancer-related deaths are due to tobacco use, 30-35% can be attributed to poor diet choices and 25-30% are related to infections. Important contributing factors also include inactivity, and stress(1).

Dangerous UK Lifestyle Trends Related to Cancer

Prolonged tobacco exposure can be almost entirely avoided with the introduction of prohibitive public smoking laws, alcohol use can be limited to levels advised by government health officials, there is a plethora of diet and exercise literature to inform public knowledge and stress management is the new healthy hot topic. However, it is not hyperbole to state that most of the UK population do not adhere to all health advice. 

PhD Aims Relating Lifestyle Specifically to Liver Cancer Development and Progression

·        Identify measurable elements associated with lifestyle choices and health implications.

·        Use a retrospective HCC cohort to quantify risks and determine clinical impact associated with HCC progression and patient survival.

·        Research mechanism and discover biomarkers for prognosis and surveillance.

·        Determine most appropriate measuring tools for clinical setting.

• Articles

  • Zadran B, Sudhindar PD, Wainwright D, Bury Y, Luli S, Howarth R, McCain MV, Watson R, Huet H, Palinkas F, Palmini RB, Casement J, Mann DA, Oakley F, Lunec J, Reeves H, Faulkner GJ, Shukla R. Impact of retrotransposon protein L1 ORF1p expression on oncogenic pathways in hepatocellular carcinoma: the role of cytoplasmic PIN1 upregulation. British Journal of Cancer 2023, 128, 1236-1248.
  • Lu H, George J, Eslam M, Villanueva A, Bolondi L, Reeves HL, McCain M, Chambers E, Ward C, Sartika D, Sands C, Maslen L, Lewis MR, Ramaswami R, Sharma R. Discriminatory Changes in Circulating Metabolites as a Predictor of Hepatocellular Cancer in Patients with Metabolic (Dysfunction) Associated Fatty Liver Disease. Liver Cancer 2023, 12(1), 19-31.
  • Zaki MYW, Alhasan SF, Shukla R, McCain M, Laszczewska M, Geh D, Patman GL, Televantou D, Whitehead A, Mauricio JP, Barksby B, Gee LM, Paish HL, Leslie J, Younes R, Burt AD, Borthwick LA, Thomas H, Beale GS, Govaere O, Sia D, Anstee QM, Tiniakos D, Oakley F, Reeves HL. Sulfatase-2 from Cancer Associated Fibroblasts: An Environmental Target for Hepatocellular Carcinoma?. Liver Cancer 2022, 11(6), 540-557.
  • Gonzalez-Recio I, Simon J, Goikoetxea-Usandizaga N, Serrano-Macia M, Mercado-Gomez M, Rodriguez-Agudo R, Lachiondo-Ortega S, Gil-Pitarch C, Fernandez-Rodriguez C, Castellana D, Latasa MU, Abecia L, Anguita J, Delgado TC, Iruzubieta P, Crespo J, Hardy S, Petrov PD, Jover R, Avila MA, Martin C, Schaeper U, Tremblay ML, Dear JW, Masson S, McCain MV, Reeves HL, Andrade RJ, Lucena MI, Buccella D, Martinez-Cruz LA, Martinez-Chantar ML. Restoring cellular magnesium balance through Cyclin M4 protects against acetaminophen-induced liver damage. Nature Communications 2022, 13(1), 6816.
  • Leslie J, Mackey JBG, Jamieson T, Ramon-Gil E, Drake TM, Fercoq F, Clark W, Gilroy K, Hedley A, Nixon C, Luli S, Laszczewska M, Pinyol R, Esteban-Fabro R, Willoughby CE, Haber PK, Andreu-Oller C, Rahbari M, Fan C, Pfister D, Raman S, Wilson N, Muller M, Collins A, Geh D, Fuller A, Mcdonald D, Hulme G, Filby A, Cortes-Lavaud X, Mohamed N-E, Ford CA, Raffo Iraolagoitia XL, Mcfarlane AJ, Mccain MV, Ridgway RA, Roberts EW, Barry ST, Graham GJ, Heikenwalder M, Reeves HL, Llovet JM, Carlin LM, Bird TG, Sansom OJ, Mann DA. CXCR2 inhibition enables NASH-HCC immunotherapy. Gut 2022, 71(10), 2093-2106.
  • Leslie J, Hunter JE, Collins A, Rushton A, Russell LG, Ramon-Gil E, Laszczewska M, McCain M, Zaki MYW, Knox A, Seow Y, Sabater L, Geh D, Perkins ND, Reeves HL, Tiniakos D, Mann DA, Oakley F. c-Rel–dependent Chk2 signaling regulates the DNA damage response limiting hepatocarcinogenesis. Hepatology 2023, 78(4), 1050-1063.
  • Geh D, Watson R, Sen G, French JJ, Hammond J, Turner P, Hoare T, Anderson K, Mcneil M, Mcpherson S, Masson S, Dyson J, Donnelly M, Macdougal L, Patel P, Hudson M, Anstee QM, White S, Robinson S, Pandanaboyana S, Walker L, Mccain M, Bury Y, Raman S, Burt A, Parkinson D, Haugk B, Darne A, Wadd N, Asghar S, Mariappan L, Margetts J, Stenberg B, Scott J, Littler P, Manas DM, Reeves HL. COVID-19 and liver cancer: Lost patients and larger tumours. BMJ Open Gastroenterology 2022, 9(1), e000794.
  • Zaki MYW, Mahdi AK, Patman GL, Whitehead A, Mauricio JP, McCain MV, Televantou D, Abou-Beih S, Ramon-Gil E, Watson R, Cox C, Leslie J, Wilson C, Govaere O, Lunec J, Mann DA, Nakjang S, Oakley F, Shukla R, Anstee QM, Tiniakos D, Reeves HL. Key features of the environment promoting liver cancer in the absence of cirrhosis. Scientific Reports 2021, 11(1), 16727.
  • Sudhindar PD, Wainwright D, Saha S, Howarth R, McCain M, Bury Y, Saha SS, McPherson S, Reeves H, Patel AH, Faulkner GJ, Lunec J, Shukla R. HCV Activates Somatic L1 Retrotransposition—A Potential Hepatocarcinogenesis Pathway. Cancers 2021, 13(20), 5079.
  • SiejkaZielinska P, Cheng J, Jackson F, Liu Y, Soonawalla Z, Reddy S, Silva M, Puta L, McCain MV, Culver E, Bekkali N, SchusterBockler B, Palamara PF, Mann D, Reeves H, Barnes E, Sivakumar S, Song C. Cell-free DNA TAPS provides multimodal information for early cancer detection. Science Advances 2021, 7(36).
  • Fernandez-Tussy P, Rodriguez-Agudo R, Fernandez-Ramos D, Barbier-Torres L, Zubiete-Franco I, Davalillo SL, Herraez E, Goikoetxea-Usandizaga N, Lachiondo-Ortega S, Simon J, Lopitz-Otsoa F, Juan VG-D, McCain MV, Perugorria MJ, Mabe J, Navasa N, Rodrigues CMP, Fabregat I, Boix L, Sapena V, Anguita J, Lu SC, Mato JM, Banales JM, Villa E, Reeves HL, Bruix J, Reig M, Marin JJG, Delgado TC, Martinez-Chantar ML. Anti-miR-518d-5p overcomes liver tumor cell death resistance through mitochondrial activity. Cell Death and Disease 2021, 12(6), 555.
  • Eldafashi N, Darlay R, Shukla R, McCain MV, Watson R, Liu YL, McStraw N, Fathy M, Fawzy MA, Zaki MYW, Daly AK, Mauricio JP, Burt AD, Haugk B, Cordell HJ, Bianco C, Dufour J-F, Valenti L, Anstee QM, Reeves HL. A pdcd1 role in the genetic predisposition to nafld-hcc?. Cancers 2021, 13(6), 1412.
  • Shukla R, Reeves HL, McPherson S, McCain M, Sudhindar P, Bury Y, Faulkner G, Lunec G. Hepatitis C virus infection, endogenous retrotransposons activation and cancer risk. Journal of Hepatology 2020, 73, S401–S652.
  • Bartneck M, Schrammen P, Mockel D, Govaere O, Liepelt A, Krenkel O, Ergen C, McCain M, Eulberg D, Luedde T, Trautwein C, Kiessling F, Lammers T, Tacke F. The CCR2+ Macrophage Subset Promotes Pathogenic Angiogenesis for Tumor Vascularization in Fibrotic Livers. Cellular and Molecular Gastroenterology and Hepatology 2019, 7(2), 371-390.
  • Pelusi S, Baselli G, Pietrelli A, Dongiovanni P, Donati B, McCain MV, Meroni M, Fracanzani AL, Romagnoli R, Petta S, Grieco A, Miele L, Soardo G, Bugianesi E, Fargion S, Aghemo A, D'Ambrosio R, Xing C, Romeo S, De Francesco R, Reeves HL, Valenti LVC. Rare Pathogenic Variants Predispose to Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease. Scientific Reports 2019, 9(1), 3682.
  • Barbier-Torres L, Iruzubieta P, Fernández-Ramos D, Delgado TC, Taibo D, Guitiérrez-de-Juan V, Varela-Rey M, Azkargorta M, Navasa N, Fernández-Tussy P, Zubiete-Franco I, Simon J, Lopitz-Otsoa F, Lachiondo-Ortega S, Crespo J, Masson S, McCain MV, Villa E, Reeves H, Elortza F, Lucena MI, Hernández-Alvarez MI, Zorzano A, Andrade RJ, Lu SC, Mato JM, Anguita J, Rincon M, Martínez-Chantar ML. The mitochondrial negative regulator MCJ is a therapeutic target for acetaminophen-induced liver injury. Nature Communications 2017, 8, 2068.
  • Donati B, Dongiovanni P, Romeo S, Meroni M, McCain M, Miele L, Petta S, Maier S, Rosso C, De Luca L, Vanni E, Grimaudo S, Romagnoli R, Colli F, Ferri F, Mancina R, Iruzubieta P, Craxi A, Fracanzani A, Grieco A, Corradini S, Aghemo A, Colombo M, Soardo G, Bugianesi E, Reeves H, Anstee Q, Fargion S, Valenti L. MBOAT7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals. Scientific Reports 2017, 7, 4492.

• Conference Proceedings (inc. Abstracts)

  • Hallsworth K, Orange ST, McCain M, Fallen-bailey R, Reeves HL. Feasibility of a home-based, virtually-delivered, group exercise intervention in older patients with liver cancer (TELEX-Liver Cancer). In: EASL Congress 2023. 2023, Vienna, Austria: Elsevier BV.
  • Peluis S, Baselli A, Cespiati A, Dongiovanni P, McCain M, Meroni M, Fracanzani A, Romagnoli R, Petta S, Grieco A, Miele L, Soardo G, Bugianesi E, Fargion S, De Francesco R, Romeo S, Reeves H, Valenti L. FRI-333-ATG7 genetic variant and defective autophagy: A novel risk factor for non-alcoholic fatty liver disease progression in patients with type 2 diabetes mellitus. In: Journal of Hepatology. 2019, Elsevier. In Preparation.
  • Albertella M, Rizoska B, McCain M, Kirk C, Öberg F, Bethell R, Reeves H. The biomarker potential of Ki67 and pH2AX immunohistochemistry in guiding use of the liver-targeting nucleotide MIV-818 in patients with hepatocellular carcinoma. In: EASL HCC Summit 2018. 2018, Geneva, Switzerland.
  • Macheka S, Jamieson D, Reeves H, McCain M. The isolation and characterisation of circulating tumour cells from patients with hepatocellular carcinoma. In: 6th Christie International Student Cancer Conference. 2016, Manchester: International Institute of Anticancer Research.