In Mark Dawson’s laboratory, researchers aim to develop a molecular understanding of the role that epigenetic regulators play in the initiation and maintenance of cancer and uncover the epigenetic mechanisms by which malignancies evade therapeutic pressure. Our priority is to translate these discoveries into personalised approaches that advance clinical care.
A unifying theme in our multidisciplinary research is our primary focus in the field of cancer epigenetics. The term epigenetics is often used to describe the study of the molecular events that facilitate transcription, DNA repair and DNA replication. Due to the critical role of epigenetic proteins in regulating access to our DNA template, it is unsurprising that the most common class of mutations found within most cancer genomes are those that perturb the function of epigenetic regulators. This fact underpins our motivation to understand how epigenetics proteins facilitate cancer. Our ambition is to use these insights to develop and trial small molecules that exploit the inherent plasticity of the epigenome and abrogate malignant transcription programs.
Central to the culture of our laboratory is curiosity-based research that aims to make important scientific discoveries that may ultimately be translated into the clinical arena. Underpinning our research are unbiased genetic screens using RNA interference (RNAi) or gene editing (CRISPR/Cas9) and single cell analytical platforms. These methods have been optimised to function as the engine room of our research strategy. Our research spans several tumour streams including acute myeloid leukaemia, lymphoma, melanoma, breast and lung cancer. We have specifically assembled a diverse research team of clinicians and scientists that have broad expertise spanning biochemistry, cell biology, molecular biology, genomics, chemical biology, immunology, animal models of disease and bioinformatics. This multidisciplinary approach is critical in helping us pursue our scientific vision.
O. Gilan, I. Rioja, K. Knezevic, M.J. Bell, M.M. Yeung, N.R. Harker, E.Y.N. Lam, C.W. Chung, P. Bamborough, M. Petretich, M. Urh, S.J. Atkinson, A.K. Bassil, E.J. Roberts, D. Vassiliadis, M.L. Burr, A.G.S. Preston, C. Wellaway, T. Werner, J.R. Gray, A.M. Michon, T. Gobbetti, V. Kumar, P.E Soden, A. Haynes, J. Vappiani, D.F. Tough, S. Taylor, S.J. Dawson, M. Bantscheff, M. Lindon, G. Drewes, E.H. Demont, D.L. Daniels, P. Grandi, R.K. Prinjha & M.A. Dawson – “Selective targeting of BD1 and BD2 of the BET proteins in cancer and immune-inflammation”. Science; 2020 Apr 24; 368(6489):387-394.
L. MacPherson, J. Anokye, M.M. Yeung, E.Y.N. Lam, Y-C. Chan, C-F. Weng, P. Yeh, K. Knezevic, M.S. Butler, A. Hoegl, K-L. Chan, M.L. Burr, L.J. Gearing, T. Willson, J. Liu, J. Choi, Y. Yang, R.A. Bilardi, H. Falk, N. Nguyen, P. Stupple, T.S. Peat, M. Zhang, M. de Silva, C. Carrasco-Pozo, V.M. Avery, P.S. Khoo, O. Dolezal, M.L. Dennis, S. Nuttall, R. Surjadi, J. Newman, B. Ren, D.J. Leaver, Y. Sun, J.B. Baell, O. Dovey, G.S. Vassiliou, F. Grebien, S.J. Dawson, I.P. Street, B.J. Monahan, C.J. Burns, C. Choudhary, M.E. Blewitt, A.K. Voss, T.Thomas & M.A. Dawson – “HBO1 is required for the maintenance of leukaemia stem cells”. Nature; 2020 Jan; 577(7789):266-270.
M.L. Burr, C. E. Sparbier, K. L. Chan, Y.C. Chan, A. Kersbergen, E.Y.N. Lam, E. Azidis-Yates, D. Vassiliadis, C.C. Bell, O. Gilan, S. Jackson, L. Tan, S.Q. Wong, S. Hollizeck, E.M. Michalak, H.V. Siddle, M.T. McCabe, R.K. Prinjha, G.R. Guerra, B.J. Solomon, S. Sandhu, S.J. Dawson, P.A. Beavis, R.W. Tothill, C. Cullinane, T.J. Lehner, K.D. Sutherland & M.A. Dawson – “An evolutionary conserved function of polycomb silences the MHC Class I antigen presentation pathway and enables immune evasion in cancer”. Cancer Cell. 2019 Oct 14;36(4):385-401.
C.C. Bell, K.A. Fennell, Y.C. Chan, F. Rambow, M.M. Yeung, D. Vassiliadis, L. Lara, P. Yeh, L.G. Martelotto, A. Rogiers, B.E. Kremer, O. Barbash, H.P. Mohammad, T.M. Johanson, M.L. Burr, A. Dhar, N. Karpinich, L. Tian, D.S. Tyler, L. MacPherson, J. Shi, N. Pinnawala, C.Y. Fong, A.T. Papenfuss, S.M. Grimmond, S.J. Dawson, R.S. Allan, R.G. Kruger, C.R. Vakoc, D.L. Goode, S.H. Naik, O. Gilan, E.Y.N. Lam, J.C. Marine, R.K. Prinjha & M.A. Dawson – “Targeting enhancer switching overcomes non-genetic drug resistance in acute myeloid leukaemia”. Nature Communications. 2019 Jun 20;10(1):2723.
M. Burr, CE. Sparbier, YC. Chan, JC. Williamson, K. Woods, PA. Beavis, EYN. Lam, MA. Henderson, CC. Bell, S. Stolzenburg, O. Gilan, S. Bloor, T. Noori, D. Morgens, MC. Bassik, PJ. Neeson, A. Behren, PK. Darcy, SJ. Dawson, I. Voskoboinik, J. Trapani, J. Cebon, PJ. Lehner & M.A. Dawson - "CMTM6 maintains the expression of PD-L1 and regulates anti-tumour immunity". Nature, 2017 Sep 7; 549(7670): 101-105.
DS. Tyler, J. Vappiani, T. Caneque, EYN. Lam, A. Ward, O. Gilan, YC. Chan, A. Hienzsch, A. Rutkowska, T. Werner, AJ. Wagener, D. Lugo, R. Gregory, C. Ramirez Molina, N. Garton, CR. Wellaway, S. Jackson, L. MacPherson, M. Figueiredo, S. Stolzenburg, CC. Bell, C. House, SJ. Dawson, ED. Hawkins, G. Drewes, RK. Prinjha, R. Rodriguez, P. Grandi & M.A. Dawson - "Click chemistry enables preclinical evaluation of targeted epigenetic therapies". Science, 2017 Jun 30; 356(6345): 1397-1401.
O. Gilan, E. Y. N. Lam, I. Becher, D. Lugo, E. Cannizzaro, G. Joberty, A. Ward, M. Wiese, C. Y. Fong, S. Ftouni, D. Tyler, K. Stanley, L. MacPherson, C. F. Weng, Y. C. Chan, Margherita Ghisi, David Smil, Christopher Carpenter, Peter Brown, Neil Garton, M. E. Blewitt, A. J. Bannister, T. Kouzarides, B. J. P. Huntly, R. W. Johnstone, G. Drewes, SJ. Dawson, C. H. Arrowsmith, P. Grandi, R. K. Prinjha & M. A. Dawson - “Functional interdependence of BRD4 and DOT1L in MLL leukaemia”. Nature Structural & Molecular Biology; 2016 July; 23(7):673-81.
C.Y. Fong, O. Gilan, E. Lam, A.F. Rubin, S. Ftouni, D. Tyler, K. Stanley, D. Sinha, P. Yeh, J. Morison, G. Giotopoulos, D. Lugo, P. Jeffrey, S. Chun-Wei Lee, C. Carpenter, R. Gregory, R.G. Ramsay, S.W. Lane, O. Abdel-Wahab, T. Kouzarides, R. Johnstone, SJ. Dawson, B.J.P. Huntly, R.K. Prinjha, A.T. Papenfuss & M.A. Dawson – “BET inhibitor resistance emerges from leukaemia stem cells”. Nature. 2015 Sep; 525(7570): 538-42.