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ZF-MEL-CHEMBIO SIGNED

Chemical Biology in Zebrafish: Drug-Leads and New Targets in the Melanocyte Lineage and Melanoma

Total Cost €

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EC-Contrib. €

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Project "ZF-MEL-CHEMBIO" data sheet

The following table provides information about the project.

Coordinator
THE UNIVERSITY OF EDINBURGH 

Organization address
address: OLD COLLEGE, SOUTH BRIDGE
city: EDINBURGH
postcode: EH8 9YL
website: www.ed.ac.uk

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country United Kingdom [UK]
 Total cost 1˙865˙345 €
 EC max contribution 1˙865˙345 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-CoG
 Funding Scheme ERC-COG
 Starting year 2015
 Duration (year-month-day) from 2015-09-01   to  2021-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE UNIVERSITY OF EDINBURGH UK (EDINBURGH) coordinator 1˙865˙345.00

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 Project objective

Melanoma (cancer of the melanocyte) kills over 20,000 Europeans each year and incidence continues to rise rapidly. BRAF(V600E) inhibitors have led to clinically significant improvements in outcomes for melanoma patients, yet many patients with metastatic melanoma rapidly succumb to the disease due to eventual chemoresistance, or insensitivity to the drug. Thus, it is critical to identify new therapies that can act alone, or be combined with available treatments for enhanced efficacy and/or to overcome drug resistance.

An important and new therapeutic concept for melanoma is to target the melanocyte lineage. Recent evidence reveals that a melanocyte lineage specific programme maintains melanoma survival, and we have engineered the first animal model in zebrafish to demonstrate that targeting the master melanocyte lineage transcription factor MITF leads to rapid melanoma regression. Thus, understanding and targeting the melanocyte lineage is directly relevant to melanoma, and reveals therapeutically targetable processes.

Our vision is to use live-imaging of the melanocyte lineage as the basis for phenotypic chemical screens in zebrafish to find drugs/leads and identify targetable processes that might elucidate pathways for cancer therapy. Screening for targets of the melanocyte lineage is highly relevant to melanoma because melanocytes are the melanoma cell of origin, and genes that specify the melanocyte stem cells and the lineage during embryogenesis are the same genes that play fundamental roles in cancer. We will use innovative chemical-biology to capture and validate targets in vivo, and perform chemo-preventative and -therapeutic trials in zebrafish melanoma models using known and novel drug-delivery methods.

Ultimately, we aim to translate our most promising drug/leads and targets into the mammalian system, to establish the basis for patent applications and clinical trials.

 Publications

year authors and title journal last update
List of publications.
2019 Jana Travnickova, Sonia Wojciechowska, Ava Khamseh, Philippe Gautier, Daniel V. Brown, Thomas Lefevre, Alessandro Brombin, Ailith Ewing, Amy Capper, Michaela Spitzer, Ramile Dilshat, Colin A. Semple, Marie E. Mathers, James A. Lister, Eiríkur Steingrimsson, Thierry Voet, Chris P. Ponting, E. Elizabeth Patton
Zebrafish MITF-Low Melanoma Subtype Models Reveal Transcriptional Subclusters and MITF-Independent Residual Disease
published pages: 5769-5784, ISSN: 0008-5472, DOI: 10.1158/0008-5472.can-19-0037
Cancer Research 79/22 2020-03-31
2019 E. Elizabeth Patton, David M. Tobin
Spotlight on zebrafish: the next wave of translational research
published pages: dmm039370, ISSN: 1754-8403, DOI: 10.1242/dmm.039370
Disease Models & Mechanisms 12/3 2020-03-31
2018 Zhiqiang Zeng, Juan Lopez-Baez, Laura Lleras-Forero, Hannah Brunsdon, Cameron Wyatt, Witold Rybski, Nicholas Hastie, Stefan Schulte-Merker, E Patton
Notochord Injury Assays that Stimulate Transcriptional Responses in Zebrafish Larvae
published pages: , ISSN: 2331-8325, DOI: 10.21769/bioprotoc.3100
BIO-PROTOCOL 8/23 2020-03-31
2018 Kao Chin Ngeow, Hans J. Friedrichsen, Linxin Li, Zhiqiang Zeng, Sarah Andrews, Laurent Volpon, Hannah Brunsdon, Georgina Berridge, Sarah Picaud, Roman Fischer, Richard Lisle, Stefan Knapp, Panagis Filippakopoulos, Helen Knowles, Eiríkur Steingrímsson, Katherine L. B. Borden, E. Elizabeth Patton, Colin R. Goding
BRAF/MAPK and GSK3 signaling converges to control MITF nuclear export
published pages: E8668-E8677, ISSN: 0027-8424, DOI: 10.1073/pnas.1810498115
Proceedings of the National Academy of Sciences 115/37 2020-03-31
2018 Thomas L. Bray, Mark Salji, Alessandro Brombin, Ana M. Pérez-López, Belén Rubio-Ruiz, Laura C. A. Galbraith, E. Elizabeth Patton, Hing Y. Leung, Asier Unciti-Broceta
Bright insights into palladium-triggered local chemotherapy
published pages: 7354-7361, ISSN: 2041-6520, DOI: 10.1039/c8sc02291g
Chemical Science 9/37 2020-03-31
2019 Karen Camargo-Sosa, Sarah Colanesi, Jeanette Müller, Stefan Schulte-Merker, Derek Stemple, E. Elizabeth Patton, Robert N. Kelsh
Endothelin receptor Aa regulates proliferation and differentiation of Erb-dependent pigment progenitors in zebrafish
published pages: e1007941, ISSN: 1553-7404, DOI: 10.1371/journal.pgen.1007941
PLOS Genetics 15/2 2020-03-31
2019 Ashani T. Weeraratna, E. Elizabeth Patton
Supporting women in science at PCMR
published pages: 484-485, ISSN: 1755-1471, DOI: 10.1111/pcmr.12798
Pigment Cell & Melanoma Research 32/4 2020-03-31
2018 Hannah Brunsdon, E Elizabeth Patton
Fishing for ancestry
published pages: , ISSN: 2050-084X, DOI: 10.7554/elife.39524
eLife 7 2020-03-31
2016 N. P. Macdonald, F. Zhu, C. J. Hall, J. Reboud, P. S. Crosier, E. E. Patton, D. Wlodkowic, J. M. Cooper
Assessment of biocompatibility of 3D printed photopolymers using zebrafish embryo toxicity assays
published pages: 291-297, ISSN: 1473-0197, DOI: 10.1039/C5LC01374G
Lab Chip 16/2 2020-01-24
2017 Ian J. Jackson, E. Elizabeth Patton
Cell signalling: Red alert about lipid\'s role in skin cancer
published pages: 337-339, ISSN: 0028-0836, DOI: 10.1038/nature23550
Nature 549/7672 2020-01-24
2015 Lidia Kos, E. Elizabeth Patton, Maria S. Soengas
Let\'s make it happen: for gender equality in science!
published pages: 641-642, ISSN: 1755-1471, DOI: 10.1111/pcmr.12421
Pigment Cell & Melanoma Research 28/6 2020-01-24
2017 Maria S. Soengas, E. Elizabeth Patton
Location, Location, Location: Spatio-Temporal Cues That Define the Cell of Origin in Melanoma
published pages: 559-561, ISSN: 1934-5909, DOI: 10.1016/j.stem.2017.10.009
Cell Stem Cell 21/5 2020-01-24
2016 S. Wojciechowska, E. van Rooijen, C. Ceol, E.E. Patton, R.M. White
Generation and analysis of zebrafish melanoma models
published pages: 531-549, ISSN: 0091-679X, DOI: 10.1016/bs.mcb.2016.03.008
Methods Cell Biol. 2020-01-24
2018 Lara Al-Olabi, Satyamaanasa Polubothu, Katherine Dowsett, Katrina A. Andrews, Paulina Stadnik, Agnel P. Joseph, Rachel Knox, Alan Pittman, Graeme Clark, William Baird, Neil Bulstrode, Mary Glover, Kristiana Gordon, Darren Hargrave, Susan M. Huson, Thomas S. Jacques, Gregory James, Hannah Kondolf, Loshan Kangesu, Kim M. Keppler-Noreuil, Amjad Khan, Marjorie J. Lindhurst, Mark Lipson, Sahar Mansour, Justine O’Hara, Caroline Mahon, Anda Mosica, Celia Moss, Aditi Murthy, Juling Ong, Victoria E. Parker, Jean-Baptiste Rivière, Julie C. Sapp, Neil J. Sebire, Rahul Shah, Branavan Sivakumar, Anna Thomas, Alex Virasami, Regula Waelchli, Zhiqiang Zeng, Leslie G. Biesecker, Alex Barnacle, Maya Topf, Robert K. Semple, E. Elizabeth Patton, Veronica A. Kinsler
Mosaic RAS/MAPK variants cause sporadic vascular malformations which respond to targeted therapy
published pages: 1496-1508, ISSN: 0021-9738, DOI: 10.1172/JCI98589
Journal of Clinical Investigation 128/4 2020-01-24
2016 Sonia Wojciechowska, Zhiqiang Zeng, James A. Lister, Craig J. Ceol, E. Elizabeth Patton
Melanoma Regression and Recurrence in Zebrafish
published pages: 143-153, ISSN: 1940-6029, DOI: 10.1007/978-1-4939-3771-4_10
Methods Mol Biol. 2020-01-24
2016 Louise van der Weyden, E Elizabeth Patton, Geoffrey A Wood, Alastair K Foote, Thomas Brenn, Mark J Arends, David J Adams
Cross-species models of human melanoma
published pages: 152-165, ISSN: 0022-3417, DOI: 10.1002/path.4632
The Journal of Pathology 238/2 2020-01-24
2016 Craig Fraser, John C. Dawson, Reece Dowling, Douglas R. Houston, Jason T. Weiss, Alison F. Munro, Morwenna Muir, Lea Harrington, Scott P. Webster, Margaret C. Frame, Valerie G. Brunton, E. Elizabeth Patton, Neil O. Carragher, Asier Unciti-Broceta
Rapid Discovery and Structure–Activity Relationships of Pyrazolopyrimidines That Potently Suppress Breast Cancer Cell Growth via SRC Kinase Inhibition with Exceptional Selectivity over ABL Kinase
published pages: 4697-4710, ISSN: 0022-2623, DOI: 10.1021/acs.jmedchem.6b00065
Journal of Medicinal Chemistry 59/10 2020-01-24
2016 Gareth Griffiths, Ferenc Müller, Johan Ledin, E. Elizabeth Patton, Tor Gjøen, Viola Hélène Lobert, Hanne Cecilie Winther-Larsen, Mary Mullins, Jean-Stephane Joly, Finn-Arne Weltzien, Charles McLean Press, Peter Aleström
Fish from Head to Tail: The 9th European Zebrafish Meeting in Oslo
published pages: 132-137, ISSN: 1545-8547, DOI: 10.1089/zeb.2015.1212
Zebrafish 13/2 2020-01-24
2017 Catherine M. Scahill, Zsofia Digby, Ian M. Sealy, Sonia Wojciechowska, Richard J. White, John E. Collins, Derek L. Stemple, Till Bartke, Marie E. Mathers, E. Elizabeth Patton, Elisabeth M. Busch-Nentwich
Loss of the chromatin modifier Kdm2aa causes BrafV600E-independent spontaneous melanoma in zebrafish
published pages: e1006959, ISSN: 1553-7404, DOI: 10.1371/journal.pgen.1006959
PLOS Genetics 13/8 2020-01-24
2018 Juan Carlos Lopez-Baez, Daniel J Simpson, Laura LLeras Forero, Zhiqiang Zeng, Hannah Brunsdon, Angela Salzano, Alessandro Brombin, Cameron Wyatt, Witold Rybski, Leonie F A Huitema, Rodney M Dale, Koichi Kawakami, Christoph Englert, Tamir Chandra, Stefan Schulte-Merker, Nicholas D Hastie, E Elizabeth Patton
Wilms Tumor 1b defines a wound-specific sheath cell subpopulation associated with notochord repair
published pages: , ISSN: 2050-084X, DOI: 10.7554/eLife.30657
eLife 7 2020-01-24
2018 Sana Sarvi, Richard Crispin, Yuting Lu, Lifan Zeng, Thomas D. Hurley, Douglas R. Houston, Alex von Kriegsheim, Che-Hong Chen, Daria Mochly-Rosen, Marco Ranzani, Marie E. Mathers, Xiaowei Xu, Wei Xu, David J. Adams, Neil O. Carragher, Mayumi Fujita, Lynn Schuchter, Asier Unciti-Broceta, Valerie G. Brunton, E. Elizabeth Patton
ALDH1 Bio-activates Nifuroxazide to Eradicate ALDHHigh Melanoma-Initiating Cells
published pages: , ISSN: 2451-9456, DOI: 10.1016/j.chembiol.2018.09.005
Cell Chemical Biology 2020-01-24

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