I graduated from Leicester University with a B.Sc. in Biological Sciences in 1986. I then completed a Ph.D. in gene regulation at the University of Birmingham in 1989. After post-doctoral work at the Pasteur Institute in Paris and the CRUK London Institute I was appointed as a lecturer at Bristol University in 1994. There I was promoted to senior lecturer and then Reader. I moved to the University of Nottingham in March 2018 and I am currently Professor of Cancer Sciences.
Transcriptional control mechanisms in cervical cancer and HPV biology, prostate cancer, breast cancer, and bile duct cancer.
I am the course director for a new BSc/MSci programme in Cancer Sciences. I have acted as an external examiner for undergraduate programmes at Edinburgh, Glasgow and Newcastle Universities.
The focus of my research is on transcription factors and the roles that these proteins play in tumourigenesis. Understanding the molecular mechanisms that control gene expression is central to… read more
WADEY KS, BROWN BA, SALA-NEWBY GB, JAYARAMAN PS, GASTON K and GEORGE SJ, 2017. Protein kinase CK2 inhibition suppresses neointima formation via a proline-rich homeodomain-dependent mechanism. Vascular pharmacology. 99, 34-44 PUUSTUSMAA M, KIRSIP H, GASTON K and ABROI A, 2017. The Enigmatic Origin of Papillomavirus Protein Domains. Viruses. 9(9),
KERSHAW RM, ROBERTS D, WRAGG J, SHAABAN AM, HUMPHREYS E, HALSALL J, PRICE L, BICKNELL R, GASTON K and JAYARAMAN PS, 2017. Proline-Rich Homeodomain protein (PRH/HHEX) is a suppressor of breast tumour growth. Oncogenesis. 6(6), e346
The focus of my research is on transcription factors and the roles that these proteins play in tumourigenesis. Understanding the molecular mechanisms that control gene expression is central to understanding cell proliferation, cell migration, and tumourigenesis and work in this area has laid the foundations for targeted cancer therapies. My group is interested in the regulatory pathways that control the proliferation and migration of normal cells and the events that disrupt this control in tumourigenesis and metastasis. Our focus is the Proline Rich Homeodomain protein (PRH/Hhex), an oligomeric transcription factor that regulates cell proliferation and cell migration in multiple contexts. Changes in PRH localisation and PRH activity are associated with several diseases including prostate cancer, breast cancer, thyroid cancer, liver cancer and some types of leukaemia.
Our previous work looked at the human papillomavirus E2 proteins. The E2 proteins are an excellent model system in which to study DNA-protein interactions. Members of the E2 class of DNA binding proteins regulate human papillomavirus (HPV) gene expression and are required for HPV replication. Study of these proteins has provided several insights into how transcription factors find their binding sites and regulate gene expression. Our work investigated the DNA binding specificity of the HPV E2 proteins and their effects on gene regulation and cell survival.
(1) During Epithelial-Mesenchymal transition (EMT) epithelial cells begin to express different cell adhesion proteins and they start to become more migratory. Transforming Growth Factor-beta (TGFbeta) is up-regulated in many tumours and this protein can induce EMT and increase cell migration. Our previous work showed that PRH directly regulates transcription of a TGFbeta co-receptor and that this is important for the regulation of prostate cell migration by PRH. In our current work we will determine whether PRH counteracts the effects of TGFbeta on EMT and cell migration.
(2) Our recent work has shown that the PRH protein is important in bile duct cells and in bile duct cancer. Our current work is looking at the genes and pathways that are regulated by PRH in bile duct cells and bile duct cancer cells. We are are using RNA sequencing to examine these genes and pathways and chomatin-immunoprecipitation sequencing to map the binding sites of PRH across the genome.
(3) In collaboration with Professor Sarah George (University of Bristol) and Dr Sheela Jayaraman (University of Birmingham) we are investigating the importance of PRH and PRH phosphorylation in the regulation of vascular smooth muscle cell proliferation and migration. We have shown that PRH is important in intimal thickening during vein graft failure and our current work looks ways to inhibit intimal thickening by blocking PRH phosphorylation.