Imperial College London

Professor Vasso Episkopou

Faculty of MedicineDepartment of Brain Sciences

Professor in Developmental Biology
 
 
 
//

Contact

 

+44 (0)20 7594 6587vasso.episkopou

 
 
//

Location

 

Burlington DanesHammersmith Campus

//

Summary

 

Publications

Publication Type
Year
to

61 results found

Xu H, Wu L, Nguyen HH, Mesa KR, Raghavan V, Episkopou V, Littman DRet al., 2021, Arkadia-SKI/SnoN signaling differentially regulates TGF-β-induced iTreg and Th17 cell differentiation, Journal of Experimental Medicine, Vol: 218, ISSN: 0022-1007

TGF-β signaling is fundamental for both Th17 and regulatory T (Treg) cell differentiation. However, these cells differ in requirements for downstream signaling components, such as SMAD effectors. To further characterize mechanisms that distinguish TGF-β signaling requirements for Th17 and Treg cell differentiation, we investigated the role of Arkadia (RNF111), an E3 ubiquitin ligase that mediates TGF-β signaling during development. Inactivation of Arkadia in CD4+ T cells resulted in impaired Treg cell differentiation in vitro and loss of RORγt+FOXP3+ iTreg cells in the intestinal lamina propria, which increased susceptibility to microbiota-induced mucosal inflammation. In contrast, Arkadia was dispensable for Th17 cell responses. Furthermore, genetic ablation of two Arkadia substrates, the transcriptional corepressors SKI and SnoN, rescued Arkadia-deficient iTreg cell differentiation both in vitro and in vivo. These results reveal distinct TGF-β signaling modules governing Th17 and iTreg cell differentiation programs that could be targeted to selectively modulate T cell functions.

Journal article

Birkou M, Chasapis CT, Marousis KD, Loutsidou AK, Bentrop D, Lelli M, Herrmann T, Carthy JM, Episkopou V, Spyroulias GAet al., 2017, A Residue Specific Insight into the Arkadia E3 Ubiquitin Ligase Activity and Conformational Plasticity, JOURNAL OF MOLECULAR BIOLOGY, Vol: 429, Pages: 2373-2386, ISSN: 0022-2836

Arkadia (Rnf111) is an E3 ubiquitin ligase that plays a central role in the amplification of transforming growth factor beta (TGF-β) signaling responses by targeting for degradation the negative regulators of the pathway, Smad6 and Smad7, and the nuclear co-repressors Ski and Skil (SnoN). Arkadia's function in vivo depends on the really interesting new gene (RING)–H2 interaction with the E2 enzyme UbcH5b in order to ligate ubiquitin chains on its substrates. A conserved tryptophan (W972) in the C-terminal α-helix is widely accepted as essential for E2 recruitment and interaction and thus also for E3 enzymatic activity.The present NMR-driven study provides an atomic-level investigation of the structural and dynamical properties of two W972 Arkadia RING mutants, attempting to illuminate for the first time the differences between a functional and a nonfunctional mutant W972A and W972R, respectively. A TGF-β-responsive promoter driving luciferase was used to assay for Arkadia function in vivo. These experiments showed that the Arkadia W972A mutant has the same activity as wild-type (WT) Arkadia in enhancing TGF-β signaling responses, while W972R does not. Only minor structural differences exist between the W972A RING domain and WT-RING. In contrast, the W972R mutant hardly interacts with E2. The loss of function correlates with structural changes in the C-terminal α-helix and an increase in the distance between the Zn(II) ions. Our data show that the position occupied by W972 within WT Arkadia is critical for the function of RING and that it depends on the nature of the residue at this position.

Journal article

Kicheva A, Bollenbach T, Ribeiro A, Valle HP, Lovell-Badge R, Episkopou V, Briscoe Jet al., 2014, Coordination of progenitor specification and growth in mouse and chick spinal cord, Science, Vol: 345, Pages: 1-11, ISSN: 0036-8075

Development requires tissue growth as well as cell diversification. To address how these processes are coordinated, we analyzed the development of molecularly distinct domains of neural progenitors in the mouse and chick neural tube. We show that during development, these domains undergo changes in size that do not scale with changes in overall tissue size. Our data show that domain proportions are first established by opposing morphogen gradients and subsequently controlled by domain-specific regulation of differentiation rate but not differences in proliferation rate. Regulation of differentiation rate is key to maintaining domain proportions while accommodating both intra- and interspecies variations in size. Thus, the sequential control of progenitor specification and differentiation elaborates pattern without requiring that signaling gradients grow as tissues expand.

Journal article

Birkou M, Tsapardoni M, Marousis K, Chasapis CT, Bentrop D, Episkopou V, Spyroulias GAet al., 2013, CONFORMATIONAL DYNAMICS AND DRUG DESIGN APPROACHES THROUGH NMR, EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, Vol: 50, Pages: E37-E37, ISSN: 0928-0987

Journal article

Martin N, Popov N, Aguilo F, O'Loghlen A, Raguz S, Snijders AP, Dharmalingam G, Li S, Thymiakou E, Carroll T, Zeisig BB, So CWE, Peters G, Episkopou V, Walsh MJ, Gil Jet al., 2013, Interplay between Homeobox proteins and Polycomb repressive complexes in p16(INK4a) regulation, EMBO JOURNAL, Vol: 32, Pages: 982-995, ISSN: 0261-4189

Journal article

Kelly CE, Thymiakou E, Dixon JE, Tanaka S, Godwin J, Episkopou Vet al., 2013, Rnf165/Ark2C Enhances BMP-Smad Signaling to Mediate Motor Axon Extension, PLOS BIOLOGY, Vol: 11, ISSN: 1544-9173

Journal article

Redshaw N, Camps C, Sharma V, Motallebipour M, Guzman-Ayala M, Oikonomopoulos S, Thymiakou E, Ragoussis J, Episkopou Vet al., 2013, TGF-beta/Smad2/3 Signaling Directly Regulates Several miRNAs in Mouse ES Cells and Early Embryos, PLOS ONE, Vol: 8, ISSN: 1932-6203

Journal article

Chasapis CT, Kandias NG, Episkopou V, Bentrop D, Spyroulias GAet al., 2012, NMR-based insights into the conformational and interaction properties of Arkadia RING-H2 E3 Ub ligase, PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS, Vol: 80, Pages: 1484-1489, ISSN: 0887-3585

Journal article

Sharma V, Antonacopoulou AG, Tanaka S, Panoutsopoulos AA, Bravou V, Kalofonos HP, Episkopou Vet al., 2011, Enhancement of TGF-beta Signaling Responses by the E3 Ubiquitin Ligase Arkadia Provides Tumor Suppression in Colorectal Cancer, CANCER RESEARCH, Vol: 71, Pages: 6438-6449, ISSN: 0008-5472

Journal article

Thymiakou E, Kelly CE, Episkopou V, 2011, BMP SIGNALING ENHANCEMENT BY ARKADIA2C IS REQUIRED FOR MOTOR NEURON AXON ELONGATION, Publisher: WILEY, Pages: 195-195, ISSN: 0022-3042

Conference paper

Bami M, Episkopou V, Gavalas A, Gouti Met al., 2011, Directed Neural Differentiation of Mouse Embryonic Stem Cells Is a Sensitive System for the Identification of Novel Hox Gene Effectors, PLOS ONE, Vol: 6, ISSN: 1932-6203

Journal article

Thymiakou E, Episkopou V, 2011, Detection of Signaling Effector-Complexes Downstream of BMP4 Using in situ PLA, a Proximity Ligation Assay, JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, ISSN: 1940-087X

Journal article

Messller S, Kropp S, Episkopou V, Felici A, Wuerthner J, Lemke R, Jerabek-Willemsen M, Willecke R, Scheu S, Pfeffer K, Wurthner JUet al., 2011, The TGF-beta signaling modulators TRAP1/TGFBRAP1 and VPS39/Vam6/TLP are essential for early embryonic development, IMMUNOBIOLOGY, Vol: 216, Pages: 343-350, ISSN: 0171-2985

Journal article

Guzman-Ayala M, Lee KL, Mavrakis KJ, Goggolidou P, Norris DP, Episkopou Vet al., 2009, Graded Smad2/3 Activation Is Converted Directly into Levels of Target Gene Expression in Embryonic Stem Cells, PLOS ONE, Vol: 4, ISSN: 1932-6203

Journal article

Kandias NG, Chasapis CT, Bentrop D, Episkopou V, Spyroulias GAet al., 2009, High yield expression and NMR characterization of Arkadia E3 ubiquitin ligase RING-H2 finger domain, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol: 378, Pages: 498-502, ISSN: 0006-291X

Journal article

Bravou V, Antonacopoulou A, Papadaki H, Floratou K, Stavropoulos M, Episkopou V, Petropoulou C, Kalofonos Het al., 2009, TGF-beta repressors SnoN and Ski are implicated in human colorectal carcinogenesis, CELLULAR ONCOLOGY, Vol: 31, Pages: 41-51, ISSN: 2211-3428

Journal article

Serafimidis I, Rakatzi I, Episkopou V, Gouti M, Gavalas Aet al., 2008, Novel effectors of directed and Ngn3-mediated differentiation of mouse embryonic stem cells into endocrine pancreas progenitors, STEM CELLS, Vol: 26, Pages: 3-16, ISSN: 1066-5099

Journal article

Kan L, Jalali A, Zhao L-R, Zhou X, McGuire T, Kazanis I, Episkopou V, Bassuk AG, Kessler JAet al., 2007, Dual function of Sox1 in telencephalic progenitor cells, DEVELOPMENTAL BIOLOGY, Vol: 310, Pages: 85-98, ISSN: 0012-1606

Journal article

Levy L, Howell M, Das D, Harkin S, Episkopou V, Hill CSet al., 2007, Arkadia activates Smad3/Smad4-Dependent transcription by triggering signal-induced SnoN degradation, MOLECULAR AND CELLULAR BIOLOGY, Vol: 27, Pages: 6068-6083, ISSN: 0270-7306

Journal article

Nagano Y, Mavrakis KJ, Lee KL, Fujii T, Koinuma D, Sase H, Yuki K, Isogaya K, Saitoh M, Imamura T, Episkopou V, Miyazono K, Miyazawa Ket al., 2007, Arkadia induces degradation of SnoN and c-Ski to enhance transforming growth factor-beta signaling, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 282, Pages: 20492-20501

Journal article

Donner AL, Ko F, Episkopou V, Maas RLet al., 2007, Pax6 is misexpressed in Sox1 null lens fiber cells, GENE EXPRESSION PATTERNS, Vol: 7, Pages: 606-613, ISSN: 1567-133X

Journal article

Donner AL, Episkopou V, Maas RL, 2007, Sox2 and Pou2f1 interact to control lens and olfactory placode development, DEVELOPMENTAL BIOLOGY, Vol: 303, Pages: 784-799, ISSN: 0012-1606

Journal article

Mavrakis KJ, Andrew RL, Lee KL, Petropoulou C, Dixon JE, Navaratnam N, Norris DP, Episkopou Vet al., 2007, Arkadia enhances nodal/TGF-beta signaling by coupling phospho-Smad2/3 activity and turnover, PLOS BIOLOGY, Vol: 5, Pages: 586-603, ISSN: 1545-7885

Journal article

Wilson ME, Yang KY, Kalousova A, Lau J, Kosaka Y, Lynn FC, Wang JH, Mrejen C, Episkopou V, Clevers HC, German MSet al., 2005, The MHG box transcription factor Sox4 contributes to the development of the endocrine pancreas, DIABETES, Vol: 54, Pages: 3402-3409, ISSN: 0012-1797

Journal article

Ekonomou A, Kazanis I, Malas S, Wood H, Alifragis P, Denaxa M, Karagogeos D, Constanti A, Lovell-Badge R, Episkopou Vet al., 2005, Neuronal migration and ventral subtype identity in the telencephalon depend on SOX1, PLOS BIOLOGY, Vol: 3, Pages: 1111-1122, ISSN: 1545-7885

Journal article

Ekonomou A, Kazanis I, Malas S, Wood H, Alifragis P, Denaxa M, Karagogeos D, Constanti A, Lovell-Badge R, Episkopou Vet al., 2005, Neuronal migration and ventral subtype identity in the telencephalon depend on SOX1., PLoS biology., Vol: 3

Little is known about the molecular mechanisms and intrinsic factors that are responsible for the emergence of neuronal subtype identity. Several transcription factors that are expressed mainly in precursors of the ventral telencephalon have been shown to control neuronal specification, but it has been unclear whether subtype identity is also specified in these precursors, or if this happens in postmitotic neurons, and whether it involves the same or different factors. SOX1, an HMG box transcription factor, is expressed widely in neural precursors along with the two other SOXB1 subfamily members, SOX2 and SOX3, and all three have been implicated in neurogenesis. SOX1 is also uniquely expressed at a high level in the majority of telencephalic neurons that constitute the ventral striatum (VS). These neurons are missing in Sox1-null mutant mice. In the present study, we have addressed the requirement for SOX1 at a cellular level, revealing both the nature and timing of the defect. By generating a novel Sox1-null allele expressing beta-galactosidase, we found that the VS precursors and their early neuronal differentiation are unaffected in the absence of SOX1, but the prospective neurons fail to migrate to their appropriate position. Furthermore, the migration of non-Sox1-expressing VS neurons (such as those expressing Pax6) was also affected in the absence of SOX1, suggesting that Sox1-expressing neurons play a role in structuring the area of the VS. To test whether SOX1 is required in postmitotic cells for the emergence of VS neuronal identity, we generated mice in which Sox1 expression was directed to all ventral telencephalic precursors, but to only a very few VS neurons. These mice again lacked most of the VS, indicating that SOX1 expression in precursors is not sufficient for VS development. Conversely, the few neurons in which Sox1 expression was maintained were able to migrate to the VS. In conclusion, Sox1 expression in precursors is not sufficient for VS neuro

Journal article

Episkopou V, 2005, SOX2 functions in adult neural stem cells, TRENDS IN NEUROSCIENCES, Vol: 28, Pages: 219-221, ISSN: 0166-2236

Journal article

Malas S, Postlethwaite M, Ekonomou A, Whalley B, Nishiguchi S, Wood H, Meldrum B, Constanti A, Episkopou Vet al., 2003, SOX1-deficient mice suffer from epilepsy associated with abnormal ventral forebrain development and olfactory cortex hyperexcitability, NEUROSCIENCE, Vol: 119, Pages: 421-432, ISSN: 0306-4522

Journal article

Graf D, Timmons PM, Hitchins M, Episkopou V, Moore G, Ito T, Fujiyama A, Fisher AG, Merkenschlager Met al., 2001, Evolutionary conservation, developmental expression, and genomic mapping of mammalian Twisted gastrulation, MAMMALIAN GENOME, Vol: 12, Pages: 554-560, ISSN: 0938-8990

Journal article

Episkopou V, Arkell R, Timmons PM, Walsh JJ, Andrew RL, Swan Det al., 2001, Induction of the mammalian node requires Arkadia function in the extraembryonic lineages, NATURE, Vol: 410, Pages: 825-830, ISSN: 0028-0836

Journal article

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

Request URL: http://wlsprd.imperial.ac.uk:80/respub/WEB-INF/jsp/search-html.jsp Request URI: /respub/WEB-INF/jsp/search-html.jsp Query String: respub-action=search.html&id=00328401&limit=30&person=true