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Research

Cancer – Molecules to Man

We focus on molecular mechanisms which regulate human cell function in health and pathology, including cancer, lymphoedema and cardiovascular disease.

Professor John Greenman and Professor Michael Lind

We are a multidisciplinary collection of biomedical scientists, clinicians, chemists and physicists involved in translational cancer research.

Our work is a three-way collaboration between the University's Faculty of Health Sciences, Hull York Medical School and the Hull University Hospitals Trust.

Group leads

Professor John Greenman

Email J.Greenman@hull.ac.uk
Telephone +44 (0)1482 465502

Professor Michael Lind

Email M.J.Lind@hull.ac.uk

The Challenge

The main focus of our research group is on characterising novel molecular mechanisms which regulate human endothelial cell function in health and pathology, including cancer, lymphoedema and cardiovascular disease.

Recent decades have seen many advances in making 3D structures that mimic the in vivo situation. As an alternative, we have been characterising and optimising devices that can maintain fresh tissue biopsies, mainly from solid tumours, in a functional state.

The group aims to further understand the role of dysregulated histone modification in cancer, and to identify and validate epigenetic regulatory proteins as novel cancer therapeutic targets.

The Approach

We apply a range of cell and molecular biology methods and techniques to model human diseases. This includes the use of primary human cells, two- and three-dimensional in-vitro models, gene editing, clinically relevant materials, next-generation sequencing technology and bioinformatics.

We also make extensive use of the Fabrication Unit, based in Chemistry, to design and make robust microfluidic devices from polymers or glass. These are used to maintain tissue in a viable state with optimised processing, fluid flow and analysis.

The group also uses genetic and molecular biology techniques to determine the mechanistic role of specific epigenetic regulatory proteins on cancer cell development, progression and regulation of gene expression.

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Aims

  • To contribute to the development of more efficient therapies for chronic diseases associated with vascular and lymphatic dysfunction, including cancer, lymphoedema and cardiovascular disease
  • To demonstrate the clinical utility of tissue-on-a-chip models in planning patient treatment
  • To reduce and replace animal models in biomedical research with human and/or tissue-on-a-chip devices as appropriate
  • To understand the role and extent of dysregulated histone modification in hard-to-treat and therapy-resistant cancers, particularly breast cancer
  • To identify epigenetic regulatory proteins which play a role in cancer development and progression, and to validate their potential as novel therapeutic targets
  • To develop target validation technologies and assays

The Impact

We are developing a human tissue-based microfluidic system that will allow clinicians to test a variety of different treatment options on a person’s malignancy, before selecting the most efficacious regimen for administration to the patient.

The rational basis of treatment selection, using available drugs and treatments, does not require costly new drug development. The adoption of such technology by the pharmaceutical industry would also significantly reduce and hopefully replace the use of some animal models.

Our work identifies and validates novel cancer therapeutic targets to be introduced into drug development pipelines to generate new options for hard-to-treat cancers. This work directly links to future patient benefit.

Projects

Healthcare_Science
Radiology
Biomedical microfluidics

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Lab on a chip
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  • Projects

    HEALTH*GDP

    Health Global Data Pipeline for biomedical research and clinical applications. This PhD cluster is the core of our group and consists of three PhD scholarships which utilise high-throughput approaches to decipher the role of human endothelial cells in chronic diseases.

    • PhD Project 1, Discovery and characterisation of novel (lymph)angiogenic regulators of human endothelial cell function in drug-resistant cancers
    • PhD Project 2, Novel molecular regulators of human endothelial cell barrier function in cardiovascular disease
    • PhD Project 3, Genomics of human endothelial cell function in chronic disease

    Further research projects include

    • Understanding the behaviour of thyroid tumours on chip – radioiodine treatment (PhD)
    • Evaluating Extracellular vesicles as a therapeutic target in Graves’ disease (MSc)
    • How do Extracellular vesicles affect the tumour microenvironment on chip? (PhD)
    • Development of models for studying the blood brain barrier and gut:brain axis (PhD)
    • Understanding the differences between 2D and 3D brain tumour models on chip (MSc)
    • Predicting Glioblastoma (GBM) response to treatment on chip (MD)
    • Determination of EGFR mutations in circulating tumours cells from lung cancer patients (PhD)
    • Human on a chip – Development of liver on a chip (PhD)

    We are also involved in a collaboration with Dr Luke Gaughan (Newcastle University), on the validation of the histone demethylase enzymes KDM3A and KDM4B as novel therapeutic targets in oestrogen positive breast cancer.

  • Group members

    Dr Leonid Nikitenko

    Lecturer in Biomedical Sciences | l.nikitenko@hull.ac.uk

    Dr Camille Ettelaie

    Professor John Greenman

    Professor of Tumour Immunology | j.greenman@hull.ac.uk

    Dr Katharina C Wollenberg Valero

    Senior Lecturer | k.wollenberg-valero@hull.ac.uk

    Dr Francisco Rivero-Crespo

    Reader in Biomedical Sciences (HYMS) | francisco.rivero@hyms.ac.uk

    Professor Anthony Maraveyas

    Professor and Honorary Consultant in Oncology (HYMS) | 

    anthony.maraveyas@hey.nhs.uk

    Professor John Greenman

    Professor of Tumour Immunology | j.greenman@hull.ac.uk

    Professor Mike Lind

    Foundation Professor of Oncology | m.j.lind@hull.ac.uk

    Dr Victoria Green

    Biomedical Microfluidics

    Dr Charlotte Dyer

    Lecturer in Biomedical Sciences | c.e.dyer@hull.ac.uk

    Dr Pedro Beltran-Alvarez

    Lecturer in Biomedical Sciences | p.beltran-alvarez@hull.ac.uk

    Professor Nicole Pamme

    Professor in Analytical Chemistry | n.pamme@hull.ac.uk

    Dr Alex Iles

    Experimental Officer | a.iles@hull.ac.uk

    James England

    ENT Surgeon

    Shailendra Achawal

    Neurosurgeon

  • Outputs and publications

    Bates A*, Hasan S*, Stephenson E, Wharton L, Drydale E, Moverley A, Blancher C, Collins C, Pillay N, Watson S P, Wollenberg V K, Nikitenko L L (* joint first authors), 'Adrenomedullin and CGRP induce different transcriptional and CLR internalisation profiles in primary human dermal lymphatic endothelial cells', oral presentation to the 1st UK Lymphatic Science Meeting, Birmingham, 8 February (2019)

    Poujade F-A, Mannion A, Brittain A, Theodosi A, Beeby E R, Leszczynska K B, Hammond E M, Greenman J, Cawthorne C, Pires I M, 'WSB-1 regulates the metastatic potential of hormone receptor negative breast cancer', British Journal of Cancer, 118, pp 1229-1237 (2018)

    Pridgeon C S, Schlott C, Wong M W, Heringa M B, Heckel T, Leedale J, Launay L, Gryshkova V, Przyborski S, Bearon R N, Wilkinson E L, Ansari T, Greenman J, Hendriks D F G, Gibbs S, Sidaway J, Sison-Young R L, Walker P, Cross M J, Park B K, Goldring C E P, 'Innovative Organotypic In Vitro Models for Safety Assessment: Aligning with regulatory requirements and understanding models of the heart, skin and liver as paradigms', Archives in Toxicology, 92(2), pp 557-569 (2018)

    Cheah R, Srivastava R, Stafford N D, Beavis A W, Green V L, Greenman J, 'A microfluidic approach to determine the radio-sensitivity of head and neck squamous cell carcinoma biopsies', International Journal of Oncology, 51(4), pp 1227-1238 (2017)

    Wade M A*, Jones D*, Nakjang S, Chayto L, Grey J, Robson C N, Gaughan L (*both authors contributed equally), 'FOXA1 regulates androgen receptor variant activity in models of castrate-resistant prostate cancer', Oncotarget, 6(30), pp 29782-29794 (2015)

    Wade M A, Jones D, Wilson L, Stockley J, Coffey K, Robson C N, Gaughan L, 'The histone demethylase enzyme KDM3A is a key estrogen receptor regulator in breast cancer', Nucleic Acids Research, 43(1), pp 196-207 (2015)

  • Research students

    Adam Bates

    Endothelial cell biology in health and disease (Dr Katharina Wollenberg Valero and Dr Leonid Nikitenko)

    Ines Hosni 

    Endothelial cell biology in health and disease (Dr Leonid Nikitenko and Professor Anthony Maraveyas)

    Matthew Morfitt

    Endothelial cell biology in health and disease (Dr Leonid Nikitenko and Professor John Greenman)

    Paulo Saldanha

    Endothelial cell biology in health and disease (Dr Francisco Rivero-Crespo and Dr Leonid Nikitenko)

    Thomas Collins

    Tumour microenvironment and hypoxia (Dr Isabel Pires and Professor Nicole Pamme)

    Emily Pyne

    Developing a spheroid in chip model to evaluate biomarkers or early- and pre-metastatic disease (Dr Isabel Pires, Dr Barbara Guinn)

    Sarah Argyle

    Radiosensitisers in organ on a chip (Dr Isabel Pires)

    Andy Riley

    Understanding the behaviour of thyroid tumours on chip – radioiodine treatment (Dr Vicky Green, Professor John Greenman)

    Jon O’Connell

    How do Extracellular vesicles affect the tumour microenvironment on chip? (Professor John Greenman, Dr Vicky Green)

    Lydia Baldwin

    Development of models for studying the blood brain barrier and gut:brain axis (Dr Charlotte Dyer, Professor Nicole Pamme, Professor John Greenman)

    Chris Sennett

    Understanding the differences between 2D and 3D brain tumour models on chip (Professor John Greenman, Dr Victoria Green)

    Srihari Deepak

    Predicting Glioblastoma (GBM) response to treatment on chip (Professor John Greenman, Dr Pedro Beltran-Alvarez)

    Nkeiruka Ogidi

    Determination of EGFR mutations in circulating tumours cells from lung cancer patients (Prof Greenman, Prof Lind)

    Martin Christensen

    Human on a chip – Development of liver on a chip (Professor Nicole Pamme, Professor John Greenman)

    Rebecca Humphries

    Identification of genomic biomarkers in therapy-induced cancer (Dr Mark Wade, Dr Neil Kemp)

  • Completed PhDs
    • Erica McCarthy, 2017. ‘Ships’ Figureheads in Britain: An evaluation of their changing purpose and interpretation’ (AHRC CDA Studentship, on time, with National Maritime Museum)
    • Helen Bergin, 2017. ‘Captain William Colbeck’s Antarctic experience: Being Human in the Heroic Age’ (University Studentship, on time, David Atkinson, main supervisor)
    • Alex Ombler, 2016. ‘The Port of Hull, 1945-2000: Change, Adaptation and Memory’ [University Studentship, on time; David Atkinson, main supervisor]
    • Joanne Byrne, 2015. ‘“After the Tide”:Memory and Afterlife in the Wake of Hull’s Distant-Water trawl fishery after 1976’ [AHRC CDA Studentship, on time; with Hull Maritime Museum]
    • Brian Lavery, 2015. ‘“Headscarf Revolutionaries”: Lil Bilocca and the Triple Trawler Tragedy’ [University Studentship, on time; Martin Goodman, main supervisor]
    • Emma Taaffe, 2014. ‘“We suffered in silence”: An analysis of the Cause and Management of Occupational Hazards at Chatham Dockyard, 1945 to 1984’ [self funded]
    • Robert Gear, 2012. ‘The development of Shetland’s pelagic Fishing Industry, since 1945’ [Shetland Harbour Trust; on time]
    • Matthew McCarthy, 2011. ‘A Sure Defence against the Foe?’ Maritime Predation & British Commercial Policy during the Spanish American Wars of Independence, 1810-1830 [AHRC Studentship, on time. Boydell & Brewer Prize, 2011]
    • Tegwyn Roberts, 2011. ‘Topographies of memory and everyday space in Hull’ [AHRC Studentship, on time; David Atkinson, main supervisor]
    • Stephen Friend, 2010. ‘A Sense of Belonging: Religion and Identity in Yorkshire and Humber Fishing Communities, c.1815-1914’ [self funded]
    • John Dacam, 2009. ‘Wanton and Torturing Punishments: Patterns of Discipline and Punishment in the Royal Navy, 1783-1815’ [AHRC Studentship, on time; R Gorski, main supervisor]
    • John Golding, 2009. ‘The English Coastal Motor Barge Trade since 1918’ [self funded]
    • Martin Wilcox, 2006. ‘Apprenticed Labour in the English Fishing Industry, 1850-1914’ [ESRC Studentship, on time]
    • Adrian Osler, 2006. ‘Responding to Change: Shipping Deployments in the Baltic Trade of the Tyne, 1860-1880’ [self funded]
    • Michael Smale, 2006.’Patterns and Processes of Migration to the Port of Hull, 1850-1900’ [self funded]
    • Nicholas Evans, 2006. ‘Aliens en route: Transmigration through Britain, 1836-1914’ [self funded]
    • Mohammed Salman, 2005. ‘Aspects of Portuguese Rule in the Arabian Gulf, 1521-1622’ in the 17th Century’ [self funded; R Gorski, main supervisor]
    • Hanna Hagmark, 2003. ‘Women in the Åland Maritime Community’ [funded by Åland Shipowners Association, Finland, on time]
    • Mark Hunter, 2003 ‘Nineteenth-Century Anglo-American Naval Relations’[funded by Social Science Research Council, Canada, on time]
    • Michael Haines, 1998. ‘Technological in the Fisheries, 1850-1914’ [funded by National Fishing Heritage Centre, Grimsby, on time]
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