I hold an Imperial College Research Fellowship in the Department of Life Sciences at Imperial College London. My research focuses on the molecular mechanisms of genetic disease and combines experimental and theoretical biology. This encompasses large scale data analysis, modelling approaches and experimental stem cell systems.
Despite the surge in genomics research over the past few decades, we are still often unable to define the molecular mechanisms linking genotype to phenotype. By starting with simple models of genetic disease, we can address this challenge and subsequently apply the knowledge gained to understand more complex disease such as cancer. My current research focuses on a class of Mendelian genetic diseases termed haploinsufficient diseases and extends to haploinsufficient genetic mutations in cancer. Combining theoretical modelling with wet-lab experimental techniques offers new approaches to understand the missing molecular link between genotype and phenotype and propose novel therapies for disease.
I completed my PhD at the University of Cambridge with Anne Ferguson-Smith on stem cell epigenetics, focused on genomic imprinting. Here I analysed the first genome-wide epigenetic maps and have since incorporated computational analysis with experimental biology to uncover new findings (e.g. E&C 2010 publication). During my post-doctoral work with Petra Hajkova I generated and analysed whole-genome transcription and epigenetic data from pluripotent stem cells. One particularly interesting discovery was that DNA methylation is much more dynamic in pluripotent stem cells than previously thought (see NSMB publication). I am further investigating mechanisms of transcription variability in stem cells, combining modelling techniques to address emerging questions in the new field of single-cell biology.
- Imperial College Research Fellowship
- University of Cambridge Lundgren Award
- Cambridge Philosophical Society Studentship
- AAAS/Science Program for Excellence in Science
- New Zealand Top Achiever Doctoral Scholarship
McEwen KR*, Leitch HG*, Turp A, Encheva V, Carroll T, Grabole N, Mansfield W, Nashun B, Knezovich JG, Smith A, Surani MA, Hajkova P, 2013, Naive pluripotency is associated with global DNA hypomethylation,Nature Structural & Molecular Biology, Vol: 20, Pages: 311-316, ISSN: 1545-9993 *Joint first authorship
McEwen KR, Leitch HG, Amouroux R, Hajkova P, 2013, The impact of culture on epigenetic properties of pluripotent stem cells and pre-implantation embryos, Biochemical Society Transactions, Vol: 41, Pages: 711-719, ISSN: 0300-5127
Amouroux R, McEwen KR, Hajkova P, Current technological advances in mapping new DNA modifications, Drug Discovery Today: Disease Models, Vol: 12, Pages: 15-26, ISSN: 1740-6757
Ferron SR, Charalambous M, Radford E, McEwen K, Wildner H, Hind E, Manuel Morante-Redolat J, Laborda J, Guillemot F, Bauer SR, Farinas I, Ferguson-Smith AC, 2011, Postnatal loss of Dlk1 imprinting in stem cells and niche astrocytes regulates neurogenesis, Nature, Vol: 475, Pages: 381-U136
McEwen KR, Ferguson-Smith AC, 2010, Distinguishing epigenetic marks of developmental and imprinting regulation., Epigenetics & Chromatin, Vol: 3, ISSN: 1756-8935
Strogantsev R, Krueger F, Yamazawa K, Shi H, Gould P, Goldman-Roberts M, McEwen K, Sun B, Pedersen R, Ferguson-Smith AC, 2015, Allele-specific binding of ZFP57 in the epigenetic regulation of imprinted and non-imprinted monoallelic expression., Genome Biology, Vol: 16
Aziz A, Baxter EJ, Edwards C, Cheong CY, Ito M, Bench A, Kelley R, Silber Y, Beer PA, Chng K, Renfree MB, McEwen K, Gray D, Nangalia J, Mufti GJ, Hellstrom-Lindberg E, Kiladjian JJ, McMullin MF, Campbell PJ, Ferguson-Smith AC, Green AR, 2013, Cooperativity of imprinted genes inactivated by acquired chromosome 20q deletions., Journal of Clinical Investigation, Vol: 123, Pages: 2169-2182
Radford EJ, Isganaitis E, Jimenez-Chillaron J, Schroeder J, Molla M, Andrews S, Didier N, Charalambous M, McEwen K, Marazzi G, Sassoon D, Patti ME, Ferguson-Smith AC, 2012, An unbiased assessment of the role of imprinted genes in an intergenerational model of developmental programming., PLoS Genetics, Vol: 8
McEwen KR, Ferguson-Smith AC, 2009, Genomic Imprinting – A Model for Roles of Histone Modifications in Epigenetic Control, Epigenomics, Editors: Ferguson-Smith, Greally, Martienssen, Netherlands, Publisher: Springer Publishing Company, Pages: 235-258