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职业迁徙
个人简介
After completing my Bachelor’s degree in Life Sciences (Pharmacology and Microbiology) at the University of Manchester, I moved to the Department of Life Sciences at Imperial College London to pursue my doctoral studies, working in Professor Martin Buck’s lab. My Graduate work focused on understanding the mechanisms of transcription regulation of the Phage Shock Protein operon in E.coli. PspA is a repressor which regulates the transcription factor PspF. My PhD research was centred on determining the mechanism of action of PspA which led to two first author publications in the Journal of Molecular Biology and Journal of Bacteriology as well as contributing to a Genes and Development paper. In addition to this I collaborated with Dr Hankamer and solved the structure of PspA at a resolution of 30Å using negative staining and single particle analysis. This work resulted in a co-first author paper in the Journal of Biological Chemistry.
After completing my PhD in 2003, I moved to the Marie Curie Research Institute. Here my worked with Dr. Patrick Patrick Varga-Weisz, where I worked on ACF1 dependent chromatin remodelling. I determined the role of histone fold proteins CHRAC-15/17 in nucleosome sliding and assembly by the chromatin remodelling complex ACF. For this study I used in vitro chromatin assembly assays showing a general role for the histone fold proteins of the H2A/H2B type in enhancing chromatin assembly mediated by ACF. This work resulted in a co-first author paper in Molecular Cell.
In 2004 I moved to Professor Neil Brockdorff’s lab at the MRC Clinical Sciences Centre in London My work focused on determining the role of the Polycomb Repressor Complex 1 (PRC1) in ubiquitylation of histone H2A. I characterised a novel PRC1 like complex containing the Bmi1 paralogue Mel-18 (melPRC1). I have found that melPRC1 can functionally compensate for loss of bmiPRC1 in the regulation of homeotic gene expression in embryonic stem cells. In addition I found that phosphorylation of Mel-18 is essential for target specificity of the E3 ligase in the context of a nucleosome substrate, providing a direct link between epigenetic modifications and cell signalling pathways. This work resulted in a first author publication recently published in Molecular Cell.
In 2009, I moved to the Babraham Institute funded by a Wellcome Trust Career Development Award. During my time at Babraham, I continued to be a pioneer in the Polycomb field. The historical model for Polycomb complex recruitment involves recruitment of PRC2 which tri-methylates histone H3 lysine 27 (H3K27me3). This histone modification is then recognised by PRC1, which then mono-ubiquitylates H2AK119 (H2AK119ub1). Our results, published in Cell, were instrumental in overturning this recruitment model. We showed PRC1 is recruited independently of PRC2 and H3K27me3 via a novel Polycomb complex RYBP-PRC1 and that RYBP is required in ES cells for the global maintenance of H2AK119ub1.
More recently my research has focused on the role of Polycomb in Genome organisation, gene regulation and stem cell fate decisions. Emerging evidence suggests that Polycomb complexes regulate gene expression by controlling spatial genome organisation. Our work shows the strongest spatial network in ES cells is composed of PRC1 bound promoters including the four Hox clusters, key early developmental transcription factor genes and their associated poised enhancers. Removal of PRC1 repression leads to complete disruption of promoter-promoter contacts. In contrast, promoter-enhancer contacts are maintained; enhancers acquire active chromatin signatures resulting in pronounced transcriptional up-regulation of network genes. We show PRC1 physically constrains promoters and regulatory elements of developmental transcription factor genes in a silenced but poised spatial network published in Nature Genetics in 2015.
研究兴趣
论文共 19 篇作者统计合作学者相似作者
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Hashem Koohy,Daniel J. Bolland,Louise S. Matheson,Stefan Schoenfelder,Claudia Stellato,Andrew Dimond,Csilla Várnai,Peter Chovanec,Tamara Chessa,Jeremy Denizot,Raquel Manzano Garcia,Steven W. Wingett,Paula Freire-Pritchett,Takashi Nagano,Phillip Hawkins,Len Stephens,Sarah Elderkin,Mikhail Spivakov,Peter Fraser,Anne E. Corcoran,Patrick D. Varga-Weisz
Nuclear Architecture and Dynamicspp.297-320, (2018)
Stefan Schoenfelder,Mayra Furlan-Magaril,Borbala Mifsud,Filipe Tavares-Cadete,Robert Sugar,Biola-Maria Javierre,Takashi Nagano,Yulia Katsman,Moorthy Sakthidevi,Steven W Wingett,Emilia Dimitrova,Andrew Dimond, Lucas B Edelman,Sarah Elderkin,Kristina Tabbada,Elodie Darbo,Simon Andrews,Bram Herman,Andy Higgs,Emily LeProust,Cameron S Osborne,Jennifer A Mitchell,Nicholas M Luscombe,Peter Fraser
Genome researchno. 4 (2015): 582-97
Stefan Schoenfelder,Robert Sugar,Andrew Dimond,Biola-Maria Javierre,Harry Armstrong,Borbala Mifsud,Emilia Dimitrova,Louise Matheson,Filipe Tavares-Cadete,Mayra Furlan-Magaril,Anne Segonds-Pichon,Wiktor Jurkowski,Steven W Wingett,Kristina Tabbada,Simon Andrews,Bram Herman,Emily LeProust,Cameron S Osborne,Haruhiko Koseki,Peter Fraser,Nicholas M Luscombe,Sarah Elderkin
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作者统计
#Papers: 20
#Citation: 2767
H-Index: 17
G-Index: 20
Sociability: 5
Diversity: 0
Activity: 0
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