Mental Health Nursing

Cancer – Molecules to Man

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.

Professor John Greenman and Professor Michael Lind
Faculty of Health Sciences
Professor John Greenman and Professor Michael Lind

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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OUR 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

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

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Endothelial cell biology in health and disease

Lead: Leonid Nikitenko PhD DSc FHEA FRSB

The focus is on characterising novel molecular mechanisms which regulate human endothelial cell function in health and pathology, including cancer, lymphoedema and cardiovascular disease. The group was successful in obtaining a PhD cluster in the 2017/18 round.

Radiology

Tumour microenvironment and hypoxia

Lead: Isabel Pires PhD FHEA

This group is looking at aspects of radiation biology including novel radio sensitising agents and novel imaging methodologies. The group has been successful in obtaining a PhD cluster in the 2018/19 round.

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Biomedical microfluidics

Co-leads: John Greenman PhD, Mike Lind MD, FRCP

Developmental and optimisation of microfluidic devices for maintaining tissue biopsies that can be used to determine prognosis and understand sensitivity of tumours to anti-cancer agents (radiation and chemotherapy).

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Biomarkers

Lead: Barbara Guinn PhD

The biomarker group are using novel technologies (comparative proteomics, Serex). The main thrust of this research is to look for novel markers for therapy/ resistance including immunotherapies. The group was successful in obtaining a PhD cluster in the 2017/18 round.

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Lab on a chip

Molecular imaging

Lead: Steve Archibald

The group are investigating, the use of novel PET tracers in defining the molecular makeup of tumours to guide therapy. The preclinical facility at the University will be joined by a CT-PET/cyclotron facility at Castle Hill Hospital allowing these developments to be taken into the clinic.

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DNA

Cancer epigenetics

Lead: Mark Wade PhD

The purpose of this group is to understand the role of dysregulated histone modification in cancer and to identify and validate epigenetic regulatory proteins as novel cancer therapeutic targets.

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Endothelial cell biology in health and disease

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.

Microfluidic technology

Biochemistry workshop 

More details to follow

September 2019
University of Hull
Lab on a Chip
Members
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

Tumour microenvironment and hypoxia (Dr Isabel Pires, Dr Barbara Guinn)

Sarah Argyle

Radiosensitisers in organ on a chip.

Tumour microenvironment and hypoxia (Dr Isabel Pires)

Andy Riley

Understanding the behaviour of thyroid tumours on chip – radioiodine treatment

Biomedical microfluidics (Dr Vicky Green, Professor John Greenman)

Jon O’Connell

How do Extracellular vesicles affect the tumour microenvironment on chip?

Biomedical microfluidics (Professor John Greenman, Dr Vicky Green)

Lydia Baldwin

Development of models for studying the blood brain barrier and gut:brain axis (PhD)

Biomedical microfluidics (Dr Charlotte Dyer, Professor Nicole Pamme, Professor John Greenman)

Chris Sennett

Understanding the differences between 2D and 3D brain tumour models on chip (MSc)

Biomedical microfluidics (Professor John Greenman, Dr Victoria Green)

Srihari Deepak

Predicting Glioblastoma (GBM) response to treatment on chip

Biomedical microfluidics (Professor John Greenman, Dr Pedro Beltran-Alvarez)

Nkeiruka Ogidi

Determination of EGFR mutations in circulating tumours cells from lung cancer patients (PhD)

Biomedical microfluidics (Prof Greenman, Prof Lind)

Martin Christensen

Human on a chip – Development of liver on a chip

Biomedical microfluidics (Professor Nicole Pamme, Professor John Greenman)

Rebecca Humphries

Identification of genomic biomarkers in therapy-induced cancer

Cancer epigenetics (Dr Mark Wade, Dr Neil Kemp)

Inspired?

Our research impacts the world. Come and join us.

Be part of a vibrant research community at the University of Hull.

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