Imperial College London

Professor Dame Amanda Fisher

Faculty of MedicineInstitute of Clinical Sciences

Head of the Institute of Clinical Sciences
 
 
 
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Contact

 

amanda.fisher

 
 
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Assistant

 

Ms Alessandra Lisini +44 (0)20 3313 8236

 
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Location

 

CRB (Clinical Research Building)Hammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

124 results found

Tsubouchi T, Fisher AG, 2013, Reprogramming and the Pluripotent Stem Cell Cycle, EPIGENETICS AND DEVELOPMENT, Editors: Heard, Publisher: ELSEVIER ACADEMIC PRESS INC, Pages: 223-241, ISBN: 978-0-12-416027-9

Book chapter

Fisher AG, Brockdorff N, 2012, Epigenetic memory and parliamentary privilege combine to evoke discussions on inheritance, DEVELOPMENT, Vol: 139, Pages: 3891-3896, ISSN: 0950-1991

Journal article

Soza-Ried J, Fisher AG, 2012, Reprogramming somatic cells towards pluripotency by cellular fusion, CURRENT OPINION IN GENETICS & DEVELOPMENT, Vol: 22, Pages: 459-465, ISSN: 0959-437X

Journal article

Merkenschlager M, Seitan V, Tachibana K, Hao B, Fisher AG, Nasmyth K, Krangel M, Merkenschlager Met al., 2012, Cohesin regulates T cell receptor rearrangement and thymocyte differentiation, 1st Biennial Symposium on Regulatory T Cells and T Helper Cells, Publisher: WILEY-BLACKWELL, Pages: 3-3, ISSN: 0019-2805

Conference paper

Seitan V, Tachibana K, Hao B, Fisher AG, Nasmyth K, Krangel M, Merkenschlager Met al., 2011, How cohesin regulates gene expression and differentiation in non-dividing mammalian cells, Annual Congress of the British-Society-for-Immunology, Publisher: WILEY-BLACKWELL, Pages: 21-21, ISSN: 0019-2805

Conference paper

Seitan VC, Hao B, Tachibana-Konwalski K, Lavagnolli T, Mira-Bontenbal H, Brown KE, Teng G, Carroll T, Terry A, Horan K, Marks H, Adams DJ, Schatz DG, Aragon L, Fisher AG, Krangel MS, Nasmyth K, Merkenschlager Met al., 2011, A role for cohesin in T-cell-receptor rearrangement and thymocyte differentiation, Nature, Vol: 476, Pages: 467-U126, ISSN: 0028-0836

Cohesin enables post-replicative DNA repair and chromosome segregation by holding sister chromatids together from the time of DNA replication in S phase until mitosis1. There is growing evidence that cohesin also forms long-range chromosomal cis-interactions2,3,4 and may regulate gene expression2,3,4,5,6,7,8,9,10 in association with CTCF8,9, mediator4 or tissue-specific transcription factors10. Human cohesinopathies such as Cornelia de Lange syndrome are thought to result from impaired non-canonical cohesin functions7, but a clear distinction between the cell-division-related and cell-division-independent functions of cohesion—as exemplified in Drosophila11,12,13—has not been demonstrated in vertebrate systems. To address this, here we deleted the cohesin locus Rad21 in mouse thymocytes at a time in development when these cells stop cycling and rearrange their T-cell receptor (TCR) α locus (Tcra). Rad21-deficient thymocytes had a normal lifespan and retained the ability to differentiate, albeit with reduced efficiency. Loss of Rad21 led to defective chromatin architecture at the Tcra locus, where cohesion-binding sites flank the TEA promoter and the Eα enhancer, and demarcate Tcra from interspersed Tcrd elements and neighbouring housekeeping genes. Cohesin was required for long-range promoter–enhancer interactions, Tcra transcription, H3K4me3 histone modifications that recruit the recombination machinery14,15 and Tcra rearrangement. Provision of pre-rearranged TCR transgenes largely rescued thymocyte differentiation, demonstrating that among thousands of potential target genes across the genome4,8,9,10, defective Tcra rearrangement was limiting for the differentiation of cohesin-deficient thymocytes. These findings firmly establish a cell-division-independent role for cohesin in Tcra locus rearrangement and provide a comprehensive account of the mechanisms by which cohesin enables cellular differentiation in a well-characterized mammali

Journal article

Piccolo FM, Pereira CF, Cantone I, Brown K, Tsubouchi T, Soza-Ried J, Merkenschlager M, Fisher AGet al., 2011, Using heterokaryons to understand pluripotency and reprogramming, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 366, Pages: 2260-2265, ISSN: 0962-8436

Journal article

Fisher CL, Fisher AG, 2011, Chromatin states in pluripotent, differentiated, and reprogrammed cells, CURRENT OPINION IN GENETICS & DEVELOPMENT, Vol: 21, Pages: 140-146, ISSN: 0959-437X

Journal article

Cantone I, Fisher AG, 2011, Unraveling Epigenetic Landscapes: The Enigma of Enhancers, CELL STEM CELL, Vol: 8, Pages: 128-129, ISSN: 1934-5909

Journal article

Landeira D, Fisher AG, 2011, Inactive yet indispensable: the tale of Jarid2, TRENDS IN CELL BIOLOGY, Vol: 21, Pages: 74-80, ISSN: 0962-8924

Journal article

Mazzarella L, Jorgensen HF, Soza-Ried J, Terry AV, Pearson S, Lacaud G, Kouskoff V, Merkenschlager M, Fisher AGet al., 2011, Embryonic stem cell-derived hemangioblasts remain epigenetically plastic and require PRC1 to prevent neural gene expression, BLOOD, Vol: 117, Pages: 83-87, ISSN: 0006-4971

Journal article

Jorgensen HF, Fisher AG, 2010, Can controversies be put to REST?, NATURE, Vol: 467, Pages: E3-E4, ISSN: 0028-0836

Journal article

Liber D, Domaschenz R, Holmqvist P-H, Mazzarella L, Georgiou A, Leleu M, Fisher AG, Labosky PA, Dillon Net al., 2010, Epigenetic Priming of a Pre-B Cell-Specific Enhancer through Binding of Sox2 and Foxd3 at the ESC Stage, CELL STEM CELL, Vol: 7, Pages: 114-126, ISSN: 1934-5909

Journal article

Schnetz MP, Handoko L, Akhtar-Zaidi B, Bartels CF, Pereira CF, Fisher AG, Adams DJ, Flicek P, Crawford GE, LaFramboise T, Tesar P, Wei C-L, Scacheri PCet al., 2010, CHD7 Targets Active Gene Enhancer Elements to Modulate ES Cell- Specific Gene Expression, PLOS GENETICS, Vol: 6, ISSN: 1553-7390

Journal article

Hadjur S, Williams L, Mira H, Fisher AG, Merkenschlager Met al., 2010, Cohesins Contribute to Long-Range Chromosomal cis-Interactions, 11th International Congress on Cleft Lip and Palate and Related Craniofacial Anomalies, Publisher: WILEY-LISS, Pages: 1634-1634, ISSN: 1552-4825

Conference paper

Fisher AG, Merkenschlager M, 2010, Fresh powder on Waddington's slopes, EMBO REPORTS, Vol: 11, Pages: 490-492, ISSN: 1469-221X

Journal article

Kanhere A, Viiri K, Araujo CC, Rasaiyaah J, Bouwman RD, Whyte WA, Pereira CF, Brookes E, Walker K, Bell GW, Pombo A, Fisher AG, Young RA, Jenner RGet al., 2010, Short RNAs Are Transcribed from Repressed Polycomb Target Genes and Interact with Polycomb Repressive Complex-2, MOLECULAR CELL, Vol: 38, Pages: 675-688, ISSN: 1097-2765

Journal article

Landeira D, Sauer S, Poot R, Dvorkina M, Mazzarella L, Jorgensen HF, Pereira CF, Leleu M, Piccolo FM, Spivakov M, Brookes E, Pombo A, Fisher C, Skarnes WC, Snoek T, Bezstarosti K, Demmers J, Klose RJ, Casanova M, Tavares L, Brockdorff N, Merkenschlager M, Fisher AGet al., 2010, Jarid2 is a PRC2 component in embryonic stem cells required for multi-lineage differentiation and recruitment of PRC1 and RNA Polymerase II to developmental regulators, NATURE CELL BIOLOGY, Vol: 12, Pages: 618-U214, ISSN: 1465-7392

Journal article

Pereira CF, Piccolo FM, Tsubouchi T, Sauer S, Ryan NK, Bruno L, Landeira D, Santos J, Banito A, Gil J, Koseki H, Merkenschlager M, Fisher AGet al., 2010, ESCs Require PRC2 to Direct the Successful Reprogramming of Differentiated Cells toward Pluripotency, Cell stem cell, Vol: 6, Pages: 547-556

Stem Cell, 6 (2010) 547-556. doi:10.1016/j.stem.2010.04.013

Journal article

Santos J, Pereira CF, Di-Gregorio A, Spruce T, Alder O, Rodriguez T, Azuara V, Merkenschlager M, Fisher AGet al., 2010, Differences in the epigenetic and reprogramming properties of pluripotent and extra-embryonic stem cells implicate chromatin remodelling as an important early event in the developing mouse embryo, Epigenetics & Chromatin, Vol: 3, ISSN: 1756-8935

BackgroundDuring early mouse development, two extra-embryonic lineages form alongside the future embryo: the trophectoderm (TE) and the primitive endoderm (PrE). Epigenetic changes known to take place during these early stages include changes in DNA methylation and modified histones, as well as dynamic changes in gene expression.ResultsIn order to understand the role and extent of chromatin-based changes for lineage commitment within the embryo, we examined the epigenetic profiles of mouse embryonic stem (ES), trophectoderm stem (TS) and extra-embryonic endoderm (XEN) stem cell lines that were derived from the inner cell mass (ICM), TE and PrE, respectively. As an initial indicator of the chromatin state, we assessed the replication timing of a cohort of genes in each cell type, based on data that expressed genes and acetylated chromatin domains, generally, replicate early in S-phase, whereas some silent genes, hypoacetylated or condensed chromatin tend to replicate later. We found that many lineage-specific genes replicate early in ES, TS and XEN cells, which was consistent with a broadly 'accessible' chromatin that was reported previously for multiple ES cell lines. Close inspection of these profiles revealed differences between ES, TS and XEN cells that were consistent with their differing lineage affiliations and developmental potential. A comparative analysis of modified histones at the promoters of individual genes showed that in TS and ES cells many lineage-specific regulator genes are co-marked with modifications associated with active (H4ac, H3K4me2, H3K9ac) and repressive (H3K27me3) chromatin. However, in XEN cells several of these genes were marked solely by repressive modifications (such as H3K27me3, H4K20me3). Consistent with TS and XEN having a restricted developmental potential, we show that these cells selectively reprogramme somatic cells to induce the de novo expression of genes associated with extraembryonic differentiation.ConclusionsThese data p

Journal article

Savarese F, Davila A, Nechanitzky R, De La Rosa-Velazquez I, Pereira CF, Engelke R, Takahashi K, Jenuwein T, Kohwi-Shigematsu T, Fisher AG, Grosschedl Ret al., 2009, Satb1 and Satb2 regulate embryonic stem cell differentiation and Nanog expression, GENES & DEVELOPMENT, Vol: 23, Pages: 2625-2638, ISSN: 0890-9369

Journal article

Bruno L, Mazzarella L, Hoogenkamp M, Hertweck A, Cobb BS, Sauer S, Hadjur S, Leleu M, Naoe Y, Telfer JC, Bonifer C, Taniuchi I, Fisher AG, Merkenschlager Met al., 2009, Runx proteins regulate Foxp3 expression, Journal of Experimental Medicine, Vol: 206, Pages: 2329-2337, ISSN: 0022-1007

Runx proteins are essential for hematopoiesis and play an important role in T cell development by regulating key target genes, such as CD4 and CD8 as well as lymphokine genes, during the specialization of naive CD4 T cells into distinct T helper subsets. In regulatory T (T reg) cells, the signature transcription factor Foxp3 interacts with and modulates the function of several other DNA binding proteins, including Runx family members, at the protein level. We show that Runx proteins also regulate the initiation and the maintenance of Foxp3 gene expression in CD4 T cells. Full-length Runx promoted the de novo expression of Foxp3 during inducible T reg cell differentiation, whereas the isolated dominant-negative Runt DNA binding domain antagonized de novo Foxp3 expression. Foxp3 expression in natural T reg cells remained dependent on Runx proteins and correlated with the binding of Runx/core-binding factor β to regulatory elements within the Foxp3 locus. Our data show that Runx and Foxp3 are components of a feed-forward loop in which Runx proteins contribute to the expression of Foxp3 and cooperate with Foxp3 proteins to regulate the expression of downstream target genes.

Journal article

Hadjur S, Williams LM, Ryan NK, Cobb BS, Sexton T, Fraser P, Fisher AG, Merkenschlager Met al., 2009, Cohesins form chromosomal cis-interactions at the developmentally regulated IFNG locus, Nature, Vol: 460, Pages: 410-U130, ISSN: 0028-0836

Cohesin-mediated sister chromatid cohesion is essential for chromosome segregation and post-replicative DNA repair1,2. In addition, evidence from model organisms3,4,5,6 and from human genetics7 suggests that cohesin is involved in the control of gene expression8,9. This non-canonical role has recently been rationalized by the findings that mammalian cohesin complexes are recruited to a subset of DNase I hypersensitive sites and to conserved noncoding sequences by the DNA-binding protein CTCF10,11,12,13. CTCF functions at insulators (which control interactions between enhancers and promoters) and at boundary elements (which demarcate regions of distinct chromatin structure)14, and cohesin contributes to its enhancer-blocking activity10,11. The underlying mechanisms remain unknown, and the full spectrum of cohesin functions remains to be determined. Here we show that cohesin forms the topological and mechanistic basis for cell-type-specific long-range chromosomal interactions in cis at the developmentally regulated cytokine locus IFNG. Hence, the ability of cohesin to constrain chromosome topology is used not only for the purpose of sister chromatid cohesion1,2, but also to dynamically define the spatial conformation of specific loci. This new aspect of cohesin function is probably important for normal development3,4,5,6 and disease7.

Journal article

Caparros M-L, Fisher AG, Merkenschlager M, 2009, Chromosomes and expression mechanisms: life on the edge, CURRENT OPINION IN GENETICS & DEVELOPMENT, Vol: 19, Pages: 97-98, ISSN: 0959-437X

Journal article

Pereira CF, Fisher AG, 2009, Heterokaryon-based reprogramming for pluripotency., Curr Protoc Stem Cell Biol, Vol: Chapter 4, Pages: Unit-4B.1

Embryonic stem (ES) cells have the ability to self-renew, execute multiple lineage paths, and dominantly reprogram differentiated cells upon cell fusion. Here, we describe an approach that reprograms human B lymphocytes toward pluripotency by generating inter-species heterokaryons with mouse ES cells. This induces a human ES-specific gene expression profile, in which the extent and the rapidity of conversion allows us to compare the capacity of different mouse ES cell lines to dominantly induce pluripotency. This approach, coupled with pharmacological inhibition, gene knock-out, or knock-down permits factors that are required to directly induce reprogramming to be defined individually, as well as in combination. Experimental heterokaryons provide a simple and tractable approach to address the mechanisms underlying direct reprogramming to pluripotency. The procedure requires 5 days to complete.

Journal article

Jorgensen HF, Fisher AG, 2009, LOCKing in Cellular Potential, CELL STEM CELL, Vol: 4, Pages: 192-194, ISSN: 1934-5909

Journal article

Jorgensen HF, Terry A, Beretta C, Pereira CF, Leleu M, Chen Z-F, Kelly C, Merkenschlager M, Fisher AGet al., 2009, REST selectively represses a subset of RE1-containing neuronal genes in mouse embryonic stem cells, DEVELOPMENT, Vol: 136, Pages: 715-721, ISSN: 0950-1991

Journal article

Jorgensen HF, Chen Z-F, Merkenschlager M, Fisher AGet al., 2009, Is REST required for ESC pluripotency?, NATURE, Vol: 457, Pages: E4-E5, ISSN: 0028-0836

Journal article

Hadjur S, Bruno L, Hertweck A, Cobb BS, Taylor B, Fisher AG, Merkenschlager Met al., 2009, IL4 blockade of inducible regulatory T cell differentiation: The role of Th2 cells, Gata3 and PU.1, IMMUNOLOGY LETTERS, Vol: 122, Pages: 37-43, ISSN: 0165-2478

Journal article

Taylor B, Cobb BS, Bruno L, Webste Z, Fisher AG, Merkenschlager Met al., 2009, A reappraisal of evidence for probabilistic models of allelic exclusion, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 106, Pages: 516-521, ISSN: 0027-8424

Journal article

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