EPIGENETIC THERAPIES AS MOLECULAR PROBES TO INVESTIGATE THE MOLECULAR PATHOGENESIS OF LEUKAEMIA
Grant number: 1106444 | Funding period: 2016 - 2020
A major limitation to the success of targeted therapies in cancer is the fact that we have few if any tools to study in detail their mechanism of action within cancerous and normal cells. If we were able to visualise these drugs within cells and precisely characterise the proteins, DNA and RNA within a cell that interact with these therapies we will be able to identify strategies that can optimise their efficacy and reduce the side-effects of these treatments.
Related publications (8)
Selective targeting of BD1 and BD2 of the BET proteins in cancer and immunoinflammation
Omer Gilan, Inmaculada Rioja, Kathy Knezevic, Matthew J Bell, Miriam M Yeung, Nicola R Harker, Enid YN Lam, Chun-wa Chung, Paul Bamborough, Massimo Petretich, Marjeta Urh, Stephen J Atkinson, Anna K Bassil, Emma J Roberts, Dane Vassiliadis, Marian L Burr, Alex GS Preston, Christopher Wellaway, Thilo Werner, James R Gray
The two tandem bromodomains of the BET (bromodomain and extraterminal domain) proteins enable chromatin binding to facilitate tran..
An Evolutionarily Conserved Function of Polycomb Silences the MHC Class I Antigen Presentation Pathway and Enables Immune Evasion in Cancer
Marian L Burr, Christina E Sparbier, Kah Lok Chan, Yih-Chih Chan, Ariena Kersbergen, Enid YN Lam, Elizabeth Azidis-Yates, Dane Vassiliadis, Charles C Bell, Omer Gilan, Susan Jackson, Lavinia Tan, Stephen Q Wong, Sebastian Hollizeck, Ewa M Michalak, Hannah Siddle, Michael T McCabe, Rab K Prinjha, Glen R Guerra, Benjamin J Solomon
Loss of MHC class I (MHC-I) antigen presentation in cancer cells can elicit immunotherapy resistance. A genome-wide CRISPR/Cas9 sc..
Targeting enhancer switching overcomes non-genetic drug resistance in acute myeloid leukaemia
Charles C Bell, Katie A Fenne, Yih-Chih Chan, Florian Rambow, Miriam M Yeung, Dane Vassiliadis, Luis Lara, Paul Yeh, Luciano G Martelotto, Aljosja Rogiers, Brandon E Kremer, Olena Barbash, Helai P Mohammad, Timothy M Johanson, Marian L Burr, Arindam Dhar, Natalie Karpinich, Luyi Tian, Dean S Tyler, Laura MacPherson
Non-genetic drug resistance is increasingly recognised in various cancers. Molecular insights into this process are lacking and it..
CMTM6 maintains the expression of PD-L1 and regulates anti-tumour immunity
Marian L Burr, Christina E Sparbier, Yih-Chih Chan, James C Williamson, Katherine Woods, Paul A Beavis, Enid YN Lam, Melissa A Henderson, Charles C Bell, Sabine Stolzenburg, Omer Gilan, Stuart Bloor, Tahereh Noori, David W Morgens, Michael C Bassik, Paul J Neeson, Andreas Behren, Phillip K Darcy, Sarah-Jane Dawson, Ilia Voskoboinik
Cancer cells exploit the expression of the programmed death-1 (PD-1) ligand 1 (PD-L1) to subvert T-cell-mediated immunosurveillanc..
Click chemistry enables preclinical evaluation of targeted epigenetic therapies
Dean S Tyler, Johanna Vappiani, Tatiana Caneque, Enid YN Lam, Aoife Ward, Omer Gilan, Yih-Chih Chan, Antje Hienzsch, Anna Rutkowska, Thilo Werner, Anne J Wagner, Dave Lugo, Richard Gregory, Cesar Ramirez Molina, Neil Garton, Christopher R Wellaway, Susan Jackson, Laura MacPherson, Margarida Figueiredo, Sabine Stolzenburg
The success of new therapies hinges on our ability to understand their molecular and cellular mechanisms of action. We modified BE..
Molecular disease monitoring using circulating tumor DNA in myelodysplastic syndromes
Paul Yeh, Michael Dickinson, Sarah Ftouni, Tane Hunter, Devbarna Sinha, Stephen Q Wong, Rishu Agarwal, Ravikiran Vedururu, Kenneth Doig, Chun Yew Fong, Piers Blombery, David Westerman, Mark A Dawson, Sarah-Jane Dawson
The diagnosis and monitoring of myelodysplastic syndromes (MDSs) are highly reliant on bone marrow morphology, which is associated..
Functional interdependence of BRD4 and DOT1L in MLL leukemia
Omer Gilan, Enid YN Lam, Isabelle Becher, Dave Lugo, Ester Cannizzaro, Gerard Joberty, Aoife Ward, Meike Wiese, Chun Yew Fong, Sarah Ftouni, Dean Tyler, Kym Stanley, Laura MacPherson, Chen-Fang Weng, Yih-Chih Chan, Margherita Ghisi, David Smil, Christopher Carpenter, Peter Brown, Neil Garton
Targeted therapies against disruptor of telomeric silencing 1-like (DOT1L) and bromodomain-containing protein 4 (BRD4) are current..