Cancer is a leading cause of death and morbidity worldwide, and with the ageing of the population and lifestyle trends, its incidence is likely to continue to rise. Cancer is, therefore, an important core theme of medical research at the University of Plymouth. Our main research questions are (1) what are the differences between normal and aberrant signaling which promote metaplasia and cancer, and (2) how can biological information and genetics be used in translational and clinical research strategies to improve patient therapy globally?
The primary areas of our cancer research are:
- brain tumours
- oral cancer.
For a broader overview of work in this area across the Institute of Health and Care Research (PIHR) view our cancer page.
Human epithelial cells in culture. Image copyright (C) 2014 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.
Lymphoma and leukaemia drug targets
My research focuses on lymphoproliferative disorders especially mantle cell lymphoma and chronic lymphocytic leukaemia.
n particular understanding the biology and interactions of neoplastic lymphocytes within nodal and bone marrow niches with assessment of key signalling pathways and response to targeted novel agents such as BTK inhibitors.
My current studies are investigating mechanisms of drug resistance and establishing biomarkers to help predict or define response to treatment.
Treating low-grade brain tumours
My research is on neuromuscular disease, especially motor neuron disease and neurooncology.
Current work on motor neuron disease is mainly clinical and includes genotype-phenotype analysis and clinical trials.
In neurooncology we focus on cell biology studies to find and validate new therapeutic targets as there is a great medical need to find new treatments.
I lead our brain tumour research team, who make up one of four UK Brain Tumour Research Centres of Excellence supported by the charity Brain Tumour Research.
New drugs to treat lymphoma
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.
Cell control in the peripheral nervous system
My research interest is in 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. Most recently I have begun to investigate 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.
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, my group’s research focuses on the following.
(1) Molecular mechanism of cancer initiation, and early intervention and prevention, in skin non-melanoma cancer and oral cancer.
(2) Signalling interference in stem-cell fate determination.
(3) Epithelial-mesenchymal interactions in controlling organgensis and regeneration.
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. My 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.