Cancer

Cancer is an important core theme of medical research at the  Plymouth Institute of Health and Care Research with a particular focus on lymphoma, brain tumours and oral cancer. 

We are seeking to understand the differences between normal and aberrant signalling which promote metaplasia and cancer; and how biological information and genetics can be used in translational and clinical research strategies to improve patient therapy globally

Brain Tumour Research

Our team of researchers, led by Professor Oliver Hanemann, works closely with the charity Brain Tumour Research as one of three UK universities with a Brain Tumour Research Centre of Excellence. 

We are leaders in the investigation of low-grade brain tumours, which are usually slow-growing and frequently affect children and young adults. Areas of specific research activity include mechanisms of tumour initiation, setting international standards for biomarker development in Neurofibromatosis, defining new drug targets in merlin-deficient brain tumours and investigating use of combination therapy through research into brain tumour micro-environment and tumour immunology.

Cell control in the peripheral nervous system

Our research focuses on the control of myelination and repair in the peripheral nervous system (PNS). 

The PNS is myelinated by Schwann cells which ensheath and myelinate the large caliber axons and allow rapid (saltatory) conduction of nerve impulses. A key interest is the investigation of what underlies the remarkable ability of Schwann cells to regenerate and repair injury in the peripheral nervous system and how proteins such as c-Jun and Sox-2, both transcription factors, facilitate this repair and cell plasticity. Loss of the tumour suppressor Merlin causes tumours of Schwann cells, schwannomas, and we are also interested in the initiation events and changes in cell signalling that occur in these tumours.

Professor David Parkinson

Hematopoiesis and immune cell cancer

Hematopoiesis is a complex but precisely regulated process, with hematopoietic stem cells (HSC) differentiating to give rise to the progenitor cells of lymphoid, myeloid and erythroid lineages. An array of transcription factors (TF) and other signalling molecules control this lineage differentiation process in order to keep us healthy and immune competent. Anomaly in these TFs' activity or loss of any component of the signalling pathways very often results in pathological conditions such as immunodeficiency or leukemia and lymphoma. 

Our lab is working to elucidate the role of the Nuclear Factor of Activated T cell (NFAT) family of TFs in HSC maintenance, differentiation of various lineages, and in the disorders that are associated with this process.

Liver cancer

This work has focused on universal tumour associated antigens (U-TAA) and their possible role in primary liver tumours. Through telomerase and survivin sequencing (from both tumour and non-tumour tissue) in formalin fixed, paraffin embedded, archived tissue samples, we have highlighted clear differences both between tumour and non-tumour tissues and between primary liver tumour types. We plan to complete further work looking for serum biomarkers of liver tumour development in the exosomal fraction of sera stored in the biobank.

(Cramp, Rupar).

Lymphoma and leukaemia drug targets

This research focuses on understanding behaviour of neoplastic lymphocytes of mantle cell lymphoma and chronic lymphocytic leukaemia within tissue microenvironments and applying that understanding to look at how novel treatments targeted at signal molecules (such as BTK) achieve their effects.

Doctor Claire Hutchinson

Molecular basis of stem cell activation and maintenance in development and cancer

Using various in vivo and in vitro models, and through broad international collaborations, this group’s research focuses on the following:

  • Molecular mechanism of cancer initiation, and early intervention and prevention, in skin non-melanoma cancer and oral cancer. 
  • Signalling interference in stem-cell fate determination. 
  • Epithelial-mesenchymal interactions in controlling organgensis and regeneration.

Professor Bing Hu

Neural Stem Cell (De)regulation and Brain Tumour Initiation

The controlled generation of new neurons and glia cells in the brain from Neural Stem Cell (NSC) progenitors is crucial not only during embryonic development but throughout adult life. Deregulation of adult NSCs or their lineage can lead to a variety of brain disorders, including tumour formation. 

Our team uses one of the best in vivo genetic models available, the Drosophila central nervous system, to reveal signals controlling Neural Stem Cell mitotic activation, cell fate and lineage maturation in both normal and pathological conditions such as upon brain tumour initiation and growth. Our studies involve functional genetics, gene expression analysis, biochemical and imaging assays. We translate our findings to the human brain using human brain cell cultures, tissues and tumour samples.

Dr Claudia Barros

New targets for cancer treatment

CCN genes modulate core stem cell signalling pathways including TGF beta, BMP, Wnt – Beta-catenin and Notch. Deregulated stem cell signalling forms the basis of tumourigenesis and also resistance to therapy. Abberations in CCN expression have been associated with haematological malignancy and also many solid tumours. 

Current projects investigate the roles of CCN1 in driving disease aggression and resistance in prostate cancer, leukaemia and lymphoma. Identification of novel strategies will enable development of specific targeted agents for patient benefit in modern medicine.

Dr Lynne McCallum