Research Biographies

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PROFESSOR MALCOLM DUNLOP, MD FRCS FMedSci FRSE

Colon Cancer Genetics Group and Academic Coloproctology

Head of Colon Cancer Genetics


Malcolm Dunlop

Contact Details

E-mail address: malcolm.dunlop@hgu.mrc.ac.uk
Telephone: +44 (0)131 332 2471
Fax: +44 (0)131 467 8456
Address: Medical Research Council
Human Genetics Unit
Western General Hospital
Crewe Road
Edinburgh EH4 2XU
Research Programme: Colon Cancer Genetics and Chemoprevention

 


Research Areas

My primary research focus is on the genetic basis of colorectal cancer in order to shed new light on disease causation and to combat the disease through preventative approaches and early detection.  Genetic studies include investigation of the effect and contribution of known susceptibility alleles as well as to identify novel cancer predisposition genes. Genetics of colorectal cancer is a major theme of the group. We are engaged in population-based studies amounting to several thousand patients and controls from Scotland, cancer families and highly enriched patient groups with extreme phenotype colorectal cancer. We have undertaken a genome-wide scan for low penetrance alleles in colorectal cancer and this has led to identification of novel genes, and we are pursuing the basis of cancer susceptibility through functional studies for a number of these associations.


Cancer chemoprevention is another central theme of the group, focussed primarily on the effect of aspirin and other nonsteroidal anti-inflammatory drugs on NF-kappa-B signalling as a key mechanism of the anti-tumour effect of these agents. The work involves basic molecular and cell biology, animal studies and clinical translational studies in patients with rectal cancer, premalignant and also in patients at high risk of colorectal cancer due genetic predisposition.


Cancer screening in the general population and also in high risk groups is another focus of research activity. I was involved in the initiation of the UK Colorectal Cancer Screening Pilot Schemes as well as contributing to the assessment of outcome measures. I lead the UK initiative for developing surveillance guidelines for high risk genetic groups and published under the auspices of the British Society of Gastroenterology and the Association of Coloproctology of GB and Ireland.

 

Recent/Selected Publications

  • Turnbull CL, Bacon AL, Dunlop MG, Farrington SM: In vitro stability of APC gene sequences and the influence of DNA repair status
    Mutagenesis 27:233-238, 2012
    PubMed Abstract
  • Tomlinson IP, Houlston RS, Montgomery GW, Sieber OM, Dunlop MG: Investigation of the effects of DNA repair gene polymorphisms on the risk of colorectal cancer. Mutagenesis 27:219-223, 2012.
    PubMed Abstract
  • Spain SL, Carvajal-Carmona LG, Howarth KM, Jones AM, Su Z, Cazier JB, Williams J, Aaltonen LA, Pharoah P, Kerr DJ, Cheadle J, Li L, Casey G, Vodicka P, Sieber O, Lipton L, Gibbs P, Martin NG, Montgomery GW, Young J, Baird PN, Morreau H, van WT, Ruiz-Ponte C, Fernandez-Rozadilla C, Carracedo A, Castells A, Castellvi-Bel S, Dunlop M, Houlston RS, Tomlinson IP: Refinement of the associations between risk of colorectal cancer and polymorphisms on chromosomes 1q41 and 12q13.13 Hum Mol Genet 21:934-946, 2012. PubMed Abstract
  • Zgaga L, Theodoratou E, Farrington SM, Agakov F, Tenesa A, Walker M, Knox S, Wallace AM, Cetnarskyj R, McNeill G, Kyle J, Porteous ME, Dunlop MG, Campbell H: Diet, environmental factors, and lifestyle underlie the high prevalence of vitamin D deficiency in healthy adults in Scotland, and supplementation reduces the proportion that are severely deficient. J Nutr 141:1535-1542, 2011.
    PubMed Abstract
  • Aldhous MC, Soo K, Stark LA, Ulanicka AA, Easterbrook JE, Dunlop MG, Satsangi J: Cigarette smoke extract (CSE) delays NOD2 expression and affects NOD2/RIPK2 interactions in intestinal epithelial cells PLoS One 6:e24715, 2011PubMed Abstract
  • Burn, S.F.; Webb, A.; Berry, R.L.; Davies, J.A.; Ferrer-Vaquer, A.; Hadjantonakis, A.K.; Hastie, N.D. and Hohenstein, P. Calcium/NFAT signalling promotes early nephrogenesis. Dev.Biol. 352(2):288-98, 2011 PubMed Abstract
  • Tomlinson IP, Carvajal-Carmona LG, Dobbins SE, Tenesa A, Jones AM, Howarth K, Palles C, Broderick P, Jaeger EE, Farrington S, Lewis A, Prendergast JG, Pittman AM, Theodoratou E, Olver B, Walker M, Penegar S, Barclay E, Whiffin N, Martin L, Ballereau S, Lloyd A, Gorman M, Lubbe S, Howie B, Marchini J, Ruiz-Ponte C, Fernandez-Rozadilla C, Castells A, Carracedo A, Castellvi-Bel S, Duggan D, Conti D, Cazier JB, Campbell H, Sieber O, Lipton L, Gibbs P, Martin NG, Montgomery GW, Young J, Baird PN, Gallinger S, Newcomb P, Hopper J, Jenkins MA, Aaltonen LA, Kerr DJ, Cheadle J, Pharoah P, Casey G, Houlston RS, Dunlop MG: Multiple common susceptibility variants near BMP pathway loci GREM1, BMP4, and BMP2 explain part of the missing heritability of colorectal cancer
    9. PLoS Genet 7:e1002105, 2011. PubMed Abstract
  • Albagha, O.M.; Visconti, M.R.; Alonso, N.; Langston, A.L.; Cundy, T.; Dargie, R.; Dunlop, M.G.; Fraser, W.D.; Hooper, M.J.; Isaia, G.; Nicholson, G.C.; Del Pino, M.J.; Gonzalez-Sarmiento, R.; di Stefano, M.; Tenesa, A.; Walsh, J.P. and Ralston, S.H. Genome-wide association study identifies variants at CSF1, OPTN and TNFRSF11A as genetic risk factors for Paget's disease of bone. Nat.Genet. e-pub May 2, 2010 PubMed Abstract
  • Baglietto, L.; Lindor, N.M.; Dowty, J.G.; White, D.M.; Wagner, A.; Gomez Garcia, E.B.; Vriends, A.H.; Cartwright, N.R.; Barnetson, R.A.; Farrington, S.M.; Tenesa, A.; Hampel, H.; Buchanan, D.; Arnold, S.; Young, J.; Walsh, M.D.; Jass, J.; Macrae, F.; Antill, Y.; Winship, I.M.; Giles, G.G.; Goldblatt, J.; Parry, S.; Suthers, G.; Leggett, B.; Butz, M.; Aronson, M.; Poynter, J.N.; Baron, J.A.; Le Marchand, L.; Haile, R.; Gallinger, S.; Hopper, J.L.; Potter, J.; de la, C.A.; Vasen, H.F.; Dunlop, M.G.; Thibodeau, S.N. and Jenkins, M.A. Risks of Lynch syndrome cancers for MSH6 mutation carriers. J Natl.Cancer Inst. 102(3):193-201, 2010 PubMed Abstract
  • Theodoratou, E.; Din, F.V.; Farrington, S.M.; Cetnarskyj, R.; Barnetson, R.A.; Porteous, M.E.; Dunlop, M.G.; Campbell, H. and Tenesa, A. Association between common mtDNA variants and all-cause or colorectal cancer mortality. Carcinogenesis 31(2):296-301, 2010 PubMed Abstract
  • Thoms, H.C.; Loveridge, C.J.; Simpson, J.; Clipson, A.; Reinhardt, K.; Dunlop, M.G. and Stark, L.A. Nucleolar targeting of RelA(p65) is regulated by COMMD1-dependent ubiquitination
    Cancer Res 70(1):139-149, 2010 PubMed Abstract
  • Brady, R. R. W.; McDermott, C.; Graham, C.; Harrison, E. H.; Eunson, G. J.; Fraise, A. P.; Dunlop, M. G., and Gibb, A. P. A prevalence screen of MRSA Nasal Colonisation amongst UK Doctors in a Non-Clinical Environment. Eur J Clin Microbiol Infect Dis 28(8):991-5, 2009 PubMed Abstract
  • Dunlop, M.G. and Farrington, S.M. MUTYH-associated polyposis and colorectal cancer. Surg.Oncol.Clin N.Am 18(4):599-610, 2009 PubMed Abstract
  • Elstner, M.; Morris, C.M.; Heim, K.; Lichtner, P.; Bender, A.; Mehta, D.; Schulte, C.; Sharma, M.; Hudson, G.; Goldwurm, S.; Giovanetti, A.; Zeviani, M.; Burn, D.J.; McKeith, I.G.; Perry, R.H.; Jaros, E.; Kruger, R.; Wichmann, H.E.; Schreiber, S.; Campbell, H.; Wilson, J.F.; Wright, A.F.; Dunlop, M.; Pistis, G.; Toniolo, D.; Chinnery, P.F.; Gasser, T.; Klopstock, T.; Meitinger, T.; Prokisch, H. and Turnbull, D.M. Single-cell expression profiling of dopaminergic neurons combined with association analysis identifies pyridoxal kinase as Parkinson's disease gene. Ann.Neurol. 66(6):792-798, 2009 PubMed Abstract
  • Johansson, A.; Marroni, F.; Hayward, C.; Franklin, C.S.; Kirichenko, A.V.; Jonasson, I.; Hicks, A.A.; Vitart, V.; Isaacs, A.; Axenovich, T.; Campbell, S.; Dunlop, M.G.; Floyd, J.; Hastie, N.; Hofman, A.; Knott, S.; Kolcic, I.; Pichler, I.; Polasek, O.; Rivadeneira, F.; Tenesa, A.; Uitterlinden, A.G.; Wild, S.H.; Zorkoltseva, I.V.; Meitinger, T.; Wilson, J.F.; Rudan, I.; Campbell, H.; Pattaro, C.; Pramstaller, P.; Oostra, B.A.; Wright, A.F.; van Duijn, C.M.; Aulchenko, Y.S. and Gyllensten, U. Common variants in the JAZF1 gene associated with height identified by linkage and genome-wide association analysis. Hum Mol Genet 18(2):373-380, 2009 PubMed Abstract
  • Tenesa, A.; Campbell, H.; Theodoratou, E.; Dunlop, L.; Cetnarskyj, R.; Farrington, S.M. and Dunlop, M.G. Common genetic variants at the MC4R locus are associated with obesity, but not with dietary energy intake or colorectal cancer in the Scottish population. Int J Obes 33(2):284-288, 2009 PubMed Abstract
  • Tenesa, A. and Dunlop, M. New insights into the aetiology of colorectal cancer from genome-wide association studies. Nature Reviews Genetics 10(6):353-358, 2009 PubMed Abstract

Selected Recent Chemoprevention Papers

  1. Burn, J.; Bishop, D.T.; Mecklin, J.P.; Macrae, F.; Moslein, G.; Olschwang, S.; Bisgaard, M.L.; Ramesar, R.; Eccles, D.; Maher, E.R.; Bertario, L.; Jarvinen, H.J.; Lindblom, A.; Evans, D.G.; Lubinski, J.; Morrison, P.J.; Ho, J.W.; Vasen, H.F.; Side, L.; Thomas, H.J.; Scott, R.J.; Dunlop, M.; Barker, G.; Elliott, F.; Jass, J.R.; Fodde, R.; Lynch, H.T. and Mathers, J.C. Effect of aspirin or resistant starch on colorectal neoplasia in the Lynch syndrome. N Engl J Med 359(24):2567-2578, 2008 PubMed Abstract
  2. Loveridge, C.J.; MacDonald, A.D.; Thoms, H.C.; Dunlop, M.G. and Stark, L.A. The proapoptotic effects of sulindac, sulindac sulfone and indomethacin are mediated by nucleolar translocation of the RelA(p65) subunit of NF-kappaB. Oncogene 27(18):2648-2655, 2008 PubMed Abstract
  3. Thoms, H.C.; Dunlop, M.G. and Stark, L.A. CDK4 inhibitors and apoptosis: a novel mechanism requiring nucleolar targeting of RelA. Cell Cycle 6(11):1293-1297, 2007 PubMed Abstract
  4. Thoms, H.C.; Dunlop, M.G. and Stark, L.A. p38-mediated inactivation of cyclin D1/cyclin-dependent kinase 4 stimulates nucleolar translocation of RelA and apoptosis in colorectal cancer cells. Cancer Res 67(4):1660-1669, 2007 PubMed Abstract
  5. Stark, L.A.; Reid, K.; Sansom, O.J.; Din, F.V.; Guichard, S.; Mayer, I.; Jodrell, D.I.; Clarke, A.R. and Dunlop, M.G. Aspirin activates the NF-{kappa}B signalling pathway and induces apoptosis in intestinal neoplasia in two in vivo models of human colorectal cancer. Carcinogenesis 28(5):968-976, 2007 PubMed Abstract
  6. Stark, L.A. and Dunlop, M.G. Nucleolar sequestration of RelA (p65) regulates NF-kappaB-driven transcription and apoptosis. Mol Cell Biol 25(14):5985-6004, 2005 PubMed Abstract