糖心原创

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Kevin Gaston

Professor of Cancer Sciences, Faculty of Medicine & Health Sciences

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Biography

I graduated from Leicester University with a B.Sc. in Biological Sciences. I then completed a Ph.D. in gene regulation at the University of Birmingham. After post-doctoral work at the Pasteur Institute in Paris and the CRUK London Institute I was appointed as a lecturer at Bristol University. There I was promoted to senior lecturer and then Reader. I moved to the 糖心原创 in 2018 and I am currently Professor of Cancer Sciences, Director of the Cancer Sciences degree progamme, and co-Director of the Centre for Cancer Sciences.

Expertise Summary

Transcriptional control mechanisms in cancer and other disease states. Specific areas of expertise include: bile duct cancer, prostate cancer, blood platelet biology and the effects of platelets on cancer cells, endothelial cell biology, protein-DNA interactions, cell migration and cell invasion, and the analysis of signal transduction pathways

Teaching Summary

I am the course director for our BSc programme in Cancer Sciences. I have acted as an external examiner for undergraduate programmes at Edinburgh, Glasgow, and Newcastle Universities. I am currently… read more

Research Summary

The focus of my research is on transcription factors and the roles that these proteins play in tumourigenesis and other disease states. Understanding the molecular mechanisms that control gene… read more

Selected Publications

  • WADEY KS, BROWN BA, SALA-NEWBY GB, JAYARAMAN PS, GASTON K and GEORGE SJ, 2017. Vascular pharmacology. 99, 34-44
  • PUUSTUSMAA M, KIRSIP H, GASTON K and ABROI A, 2017. Viruses. 9(9),
  • SIDDIQUI YH, KERSHAW RM, HUMPHREYS EH, ASSIS JUNIOR EM, CHAUDHRI S, JAYARAMAN PS and GASTON K, 2017. Oncogenesis. 6(1), e293
  • KERSHAW RM, ROBERTS D, WRAGG J, SHAABAN AM, HUMPHREYS E, HALSALL J, PRICE L, BICKNELL R, GASTON K and JAYARAMAN PS, 2017. Oncogenesis. 6(6), e346

I am the course director for our BSc programme in Cancer Sciences. I have acted as an external examiner for undergraduate programmes at Edinburgh, Glasgow, and Newcastle Universities. I am currently an external examiner at UCL.

Current Research

The focus of my research is on transcription factors and the roles that these proteins play in tumourigenesis and other disease states. 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 current 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 as well as in vascular diseases.

Past Research

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. 糖心原创 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.

Future Research

(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.

(4) In collaboration with Professor Gonzalo de Prat-Gay (Fundaci贸n Instituto Leloir) we are studying the formation and function of membrane-less organelles formed by biomolecular condensation of macromolecules in a process known as liquid-liquid phase separation (LLPS). We are interested in the formation of ordered aggregates of the tumour-suppressor protein p53 and the human papillomavirus (HPV) E2 protein.

  • KITCHEN, P., LEE, K. Y., CLARK, D., LAU, N., LERTSUWAN, J., SAWASDICHAI, A., SATAYAVIVAD, J., OLTEAN, S., AFFORD, S., GASTON, K. and JAYARAMAN, P. S., 2020. Cancer Res. 80(4), 757-770
  • MARCOLINO, E., SIDDIQUI, Y. H., VAN DEN BOSCH, M., POOLE, A. W., JAYARAMAN, P. S. and GASTON, K., 2020. Oncogenesis. 9(2), 10
  • LERTSUWAN, J., LERTSUWAN, K., SAWASDICHAI, A., TASNAWIJITWONG, N., LEE, K. Y., KITCHEN, P., AFFORD, S., GASTON, K., JAYARAMAN, P. S. and SATAYAVIVAD, J., 2018. Cancers (Basel). 10(9),
  • WADEY KS, BROWN BA, SALA-NEWBY GB, JAYARAMAN PS, GASTON K and GEORGE SJ, 2017. Vascular pharmacology. 99, 34-44
  • PUUSTUSMAA M, KIRSIP H, GASTON K and ABROI A, 2017. 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. Oncogenesis. 6(6), e346
  • SIDDIQUI YH, KERSHAW RM, HUMPHREYS EH, ASSIS JUNIOR EM, CHAUDHRI S, JAYARAMAN PS and GASTON K, 2017. Oncogenesis. 6(1), e293
  • GASTON K, TSITSILIANOS MA, WADEY K and JAYARAMAN PS, 2016. Cell & bioscience. 6, 12
  • BEAZLEY-LONG N, GASTON K, HARPER SJ, ORLANDO A and BATES DO, 2015. Novel mechanisms of resistance to vemurafenib in melanoma - V600E B-Raf reversion and switching VEGF-A splice isoform expression. American journal of cancer research. 5(1), 433-41
  • KERSHAW RM, SIDDIQUI YH, ROBERTS D, JAYARAMAN PS and GASTON K, 2014. Oncogene. 33(49), 5592-600
  • NOY P, GASTON K and JAYARAMAN PS, 2012. Leukemia research. 36(11), 1434-7
  • NOY P, SAWASDICHAI A, JAYARAMAN PS and GASTON K, 2012. Nucleic acids research. 40(18), 9008-20
  • SHUKLA A, BURTON NM, JAYARAMAN PS and GASTON K, 2012. PloS one. 7(4), e35984
  • BROWN C, CAMPOS-LE脫N K, STRICKLAND M, WILLIAMS C, FAIRWEATHER V, BRADY RL, CRUMP MP and GASTON K, 2010. Nucleic acids research. 39(7), 2969-80
  • SAWASDICHAI A, CHEN HT, ABDUL HAMID N, JAYARAMAN PS and GASTON K, 2010. Journal of visualized experiments : JoVE.
  • SOUFI A, SAWASDICHAI A, SHUKLA A, NOY P, DAFFORN T, SMITH C, JAYARAMAN PS and GASTON K, 2010. Nucleic acids research. 38(21), 7513-25
  • NOY P, WILLIAMS H, SAWASDICHAI A, GASTON K and JAYARAMAN PS, 2010. Molecular and cellular biology. 30(9), 2120-34
  • SMAL C, WETZLER DE, DANTUR KI, CHEMES LB, GARCIA-ALAI MM, DELLAROLE M, ALONSO LG, GASTON K and DE PRAT-GAY G, 2009. Biochemistry. 48(50), 11939-49
  • WILLIAMS, HANNAH, JAYARAMAN, PADMA-SHEELA and GASTON, KEVIN, 2008. JOURNAL OF MOLECULAR BIOLOGY. 383(1), 10-23
  • BROWN, CRAIG, KOWALCZYK, ANNA M., TAYLOR, EWAN R., MORGAN, IAIN M. and GASTON, KEVIN, 2008. VIROLOGY JOURNAL. 5,
  • DE PRAT-GAY, GONZALO, GASTON, KEVIN and CICERO, DANIEL O., 2008. FRONTIERS IN BIOSCIENCE. 13, 6006-6021
  • SANCHEZ, IGNACIO E., DELLAROLE, MARIANO, GASTON, KEVIN and DE PRAT GAY, GONZALO, 2008. NUCLEIC ACIDS RESEARCH. 36(3), 756-769
  • GREEN, KATIE L., BROWN, CRAIG, ROEDER, GERALDINE E., SOUTHGATE, THOMAS D. and GASTON, KEVIN, 2007. HUMAN GENE THERAPY. 18(6), 547-561
  • BACON, ANDREA, KERR, NIALL C. H., HOLMES, FIONA E., GASTON, KEVIN and WYNICK, DAVID, 2007. JOURNAL OF NEUROSCIENCE. 27(24), 6573-6580
  • SOUFI, ABDENOUR, GASTON, KEVIN and JAYARAMAN, PADMA-SHEELA, 2006. INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES. 39(1-3), 45-50
  • KOWALCZYK AM, ROEDER GE, GREEN K, STEPHENS DJ and GASTON K, 2005. Methods in molecular medicine. 119, 419-32
  • ROEDER GE, PARISH JL, STERN PL and GASTON K, 2004. Biotechnology and applied biochemistry. 40(Pt 2), 157-65
  • DELL G, WILKINSON KW, TRANTER R, PARISH J, LEO BRADY R and GASTON K, 2003. Journal of molecular biology. 334(5), 979-91
  • DAVIDSON EJ, SEHR P, FAULKNER RL, PARISH JL, GASTON K, MOORE RA, PAWLITA M, KITCHENER HC and STERN PL, 2003. The Journal of general virology. 84(Pt 8), 2089-97
  • BESS KL, SWINGLER TE, RIVETT AJ, GASTON K and JAYARAMAN PS, 2003. The Biochemical journal. 374(Pt 3), 667-75
  • GASTON K and JAYARAMAN PS, 2003. Cellular and molecular life sciences : CMLS. 60(4), 721-41
  • BUTCHER AJ, GASTON K and JAYARAMAN PS, 2003. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences. 786(1-2), 3-6
  • REES LE, WOOD NA, GILLESPIE KM, LAI KN, GASTON K and MATHIESON PW, 2002. Cellular and molecular life sciences : CMLS. 59(3), 560-9
  • DELL G and GASTON K, 2002. Human papillomaviruses and their role in cervical cancer. Cellular and molecular life sciences : CMLS. 58(12-13), 1923-42
  • DAVIDSON EJ, BROWN MD, BURT DJ, PARISH JL, GASTON K, KITCHENER HC, STACEY SN and STERN PL, 2001. International journal of cancer. 94(6), 807-12
  • WEBSTER K, TAYLOR A and GASTON K, 2000. The Journal of general virology. 82(Pt 1), 201-13
  • LEWIS H and GASTON K, 1999. Journal of molecular biology. 294(4), 885-96
  • LEWIS H, WEBSTER K, SANCHEZ-PEREZ AM and GASTON K, 1999. The Journal of general virology. 80 ( Pt 8), 2087-96
  • SANCHEZ-PEREZ AM, SORIANO S, CLARKE AR and GASTON K, 1997. The Journal of general virology. 78 ( Pt 11), 3009-18
  • COLE EG and GASTON K, 1997. Nucleic acids research. 25(18), 3705-11
  • THAIN A, WEBSTER K, EMERY D, CLARKE AR and GASTON K, 1997. DNA binding and bending by the human papillomavirus type 16 E2 protein. Recognition of an extended binding site. The Journal of biological chemistry. 272(13), 8236-42
  • THAIN A, JENKINS O, CLARKE AR and GASTON K, 1996. Journal of virology. 70(10), 7233-5
  • THAIN A, GASTON K, JENKINS O and CLARKE AR, 1996. A method for the separation of GST fusion proteins from co-purifying GroEL. Trends in genetics : TIG. 12(6), 209-10
  • GASTON K and FRIED M, 1995. Gene. 157(1-2), 257-9
  • GASTON K and FRIED M, 1995. Nucleic acids research. 23(6), 901-9
  • LENNARD A, GASTON K and FRIED M, 1994. DNA and cell biology. 13(11), 1117-26
  • GASTON K and FRIED M, 1994. FEBS letters. 347(2-3), 289-94
  • GASTON K and FRIED M, 1992. Nucleic acids research. 20(23), 6297-301
  • GASTON K, BELL A, BUSBY S and FRIED M, 1992. Nucleic acids research. 20(13), 3391-6
  • BELL A, GASTON K, WILLIAMS R, CHAPMAN K, KOLB A, BUC H, MINCHIN S, WILLIAMS J and BUSBY S, 1990. Nucleic acids research. 18(24), 7243-50
  • SPIRO S, GASTON KL, BELL AI, ROBERTS RE, BUSBY SJ and GUEST JR, 1990. Molecular microbiology. 4(11), 1831-8
  • GASTON K, BELL A, KOLB A, BUC H and BUSBY S, 1990. Cell. 62(4), 733-43
  • GASTON K, KOLB A and BUSBY S, 1989. Binding of the Escherichia coli cyclic AMP receptor protein to DNA fragments containing consensus nucleotide sequences. The Biochemical journal. 261(2), 649-53
  • BELL AI, GASTON KL, COLE JA and BUSBY SJ, 1989. Nucleic acids research. 17(10), 3865-74
  • WEBSTER C, GASTON K and BUSBY S, 1988. Gene. 68(2), 297-305
  • GASTON K, CHAN B, KOLB A, FOX J and BUSBY S, 1988. Alterations in the binding site of the cyclic AMP receptor protein at the Escherichia coli galactose operon regulatory region. The Biochemical journal. 253(3), 809-18
  • JAYARAMAN PS, GASTON KL, COLE JA and BUSBY SJ, 1988. Molecular microbiology. 2(4), 527-30

School of Medicine

糖心原创
Medical School
Nottingham, NG7 2UH

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