Cancer Research foci

Cancer Research

Cancer Research in York encompasses most activities found in larger cancer centres, but like other York research, is carried out across various Departments and Units, which effectively collaborate and combine their expertise to further our understanding of this complex disorder.

 

To understand cancer at a cell/molecular level requires knowledge spanning many biological scales and disciplines: from the organisation of cells in tissues, the checkpoints and controls of cell division and the genetic and epigenetic control of gene expression, through to the detail of molecular assemblies or factories present within cells. 

Most tumours are in fact composed of several cell types all of which exert an influence on the cancer’s behaviour; this includes connective tissues (stromal cells) and the cells from a patient’s immune system.  Although the presence of these different cell types has been observed in tumours for many years, only recently has it begun to be exploited in a new generation of therapeutic approaches.

Impact

Impacting on health and disease

Nucleotide incorporation into sites of DNA replication in S phase.

Diagnosis:  Which patients will get (fatal) cancer

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Patient tissue showing an enlarged prostate gland

Histotech human Ureter labelling

Cancer Treatment

Examples of Cancer Research projects

‌‌‌Colonies of GFP-labelled human primary microvascular 
endothelial cells in co-culture with non-labelled 
VHL-negative kidney cancer cells

Mammalian microRNA silencing machinery

The Lagos group investigates the regulation and function of the mammalian microRNA silencing machinery in immune and vascular responses.

JAK2V617F expression causes bone marrow megakaryocyte hyperplasia in a myeloproliferative neoplasm model Myeloproliferative Neoplasia

This laboratory works on a group of haematological malignancies called myeloproliferative neoplasms (MPNs), which are characterized by increases in red blood cells, platelets and/or neutrophils. Haematopoiesis, the process by which all blood cells are made, requires stringent regulation to ensure the number of circulating blood cells are maintained within a normal range. When this balance is disturbed, as in the case of haematological malignancies, the effects on patient well-being can be severe. They are currently investigating the roles of haematopoietic cytokines and cytokine receptors in the regulation of MPNs, how these conditions lead to clotting abnormalities and identifying novel rare mutations leading the MPNs in children and young people.


Nuclear β-catenin activation consequential to autocrine stimulation of the epidermal growth factor receptor in normal human urothelial cells. (from Georgopoulos NT, Kirkwood LA, Southgate J. A novel bidirectional positive-feedback loop between Wnt-β-catenin and EGFR-ERK plays a role in context-specific modulation of epithelial tissue regeneration. J Cell Sci. 2014;127:2967-82. PMID: 24816560).
Human Urothelial cancer

The research of the JBU focuses on human urothelium – the epithelial tissue that lines the bladder and associated urinary tract and gives rise to the major forms of bladder cancer.  Their central hypothesis is that a deep understanding of the normal tissue-specific processes that orchestrate cell proliferation, differentiation and death during urothelial tissue homeostasis will provide a unique insight into the mechanisms deregulated in cancer.  Their distinctive approach has been to establish cell culture systems for investigating the biology and pathogenesis of normal human urothelium.  Important findings include the identification in 2004 that PPARγ is a nuclear receptor critical to the differentiation of urothelium as a specialised urinary barrier epitheliumand the finding that amphiregulin is an autocrine growth factor for urothelium. These findings have led to two recent publications demonstrating that these pathways are hijacked in urothelial tumorigenesis.  

Academic staff associated with Cancer Research

Dr Dimitris Lagos, Senior lecturer, Immunology: Mammalian microRNA silencing machinery

Dr Ian Hitchcock, Lecturer, Biomedical Sciences: Myeloproliferative neoplasia

Prof Jenny Southgate, Director, Jack Birch Unit: Human Urothelial cancer

Dr Will Brackenbury, Lecturer in Biomedical Sciences: Voltage-gated sodium channels

Prof Bob White, Chair, Biochemistry: The Biology of RNA polymerase III

Dr James Chong, Senior Lecturer: Minichromosome Maintenance proteins

Dr Gareth Evans, Senior Lecturer: Kinase signalling in neuroblastoma

Dr Nathalie Signoret, Lecturer, Immunology: Chemokine receptor biology

Dr Dawn Coverley, Reader: Organisation of the nucleus during DNA replication

Prof Norman J Maitland, Chair, Molecular Biology & Director of The Cancer Research Unit: Biology of the normal and malignant human prostate

Recent news

 Norman M (x70)

Why prostate cancer cells develop resistance to treatment

Breast cancer now

Protein research uncovers potential new diagnosis and therapy for breast cancer

 ‌ Prostate (x70)

New treatment for prostate condition

Research Centres linked to Cancer Research

The Cancer Research Unit

Jack Birch Unit for Molecular Carcinogenesis

Centre for Immunology and Infection

 

Examples of high profile publications

A redox state-dictated signalling pathway deciphers the malignant cell specificity of CD40-mediated apoptosis.  Southgate et al.  2016 Oncogene

Heterarchy of transcription factors driving basal and luminal cell phenotypes in human urothelium.  Southgate et al.  2017 Cell Death Differ

Epithelial-to-mesenchymal transition drives a pro-metastatic Golgi compaction process through scaffolding protein PAQR11.  Ungar et al 2016 Journal of Clinical Investigation

A redox state-dictated signalling pathway deciphers the malignant cell specificity of CD40-mediated apoptosis.  Southgate et al.  2016 Oncogene

The molecular and cellular origin of human prostate cancer.  Maitland et al.  2016 Biochim Biophys Acta.