PROMINENT

Progression factors in melanoma leading to novel therapeutic targets

Coordinatore	THE UNIVERSITY OF MANCHESTER    more Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.
Nazionalità Coordinatore	United Kingdom [UK]
Totale costo	1˙498˙500 €
EC contributo	1˙498˙500 €
Programma	FP7-IDEAS-ERC Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	ERC-2011-StG_20101109
Funding Scheme	ERC-SG
Anno di inizio	2012
Periodo (anno-mese-giorno)	2012-02-01   -   2017-01-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	THE UNIVERSITY OF MANCHESTER  Organization address address: OXFORD ROAD city: MANCHESTER postcode: M13 9PL contact info Titolo: Dr. Nome: Adam Felix Lloyd Cognome: Hurlstone Email: send email Telefono: +44 161 2751574 Fax: +44 161 275	UK (MANCHESTER)	hostInstitution	1˙498˙500.00
2	THE UNIVERSITY OF MANCHESTER  Organization address address: OXFORD ROAD city: MANCHESTER postcode: M13 9PL contact info Titolo: Ms. Nome: Claire Cognome: Faichnie Email: send email Telefono: 441613000000	UK (MANCHESTER)	hostInstitution	1˙498˙500.00

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 Obiettivo del progetto (Objective)

'Presently, there is little hope of cure for patients with metastatic melanoma. Greater insight into the molecular and cellular biology of melanoma and the immune response mounted against it is required to indicate new therapeutic approaches. We have created zebrafish models for analyzing melanoma initiation and progression. Using whole genome transcriptome profiling, we have identified a number of genes that are induced during malignant progression. Moreover, we have established an efficient method for assessing the ability of a given gene to promote melanoma progression in its natural setting. Having analysed the ontologies of our malignancy-associated gene set, we propose screening multiple exemplars from various functional categories, including classes of gene function not previously validated as therapeutic targets. We also propose using recombinant zinc-finger nucleases to delete candidate progression-inducing genes and determine their impact on melanoma progression. Experiments performed in cultured human melanoma cells will demonstrate conserved action. Recent collaborative work shows that melanoma cells, even when present as small clones, interact with neutrophils and macrophages, which appear to play both immunosurveillance and tumour-promoting roles. Likewise, CD4 T cells play dual roles in shaping the immune response to melanoma. We have access to a macrophage-specific driver line and are in the process of developing a CD4 T-cell specific driver line. Using these tools and other reagents, we propose to perform detailed analyses of neoplastic-melanocye–immune-cell interactions during malignant progression. Moreover, by driving expression of immunomodulatory factors, we shall follow the impact on progression of melanocyte neoplasms of manipulating the differentiation of these two leukocyte lineages. Pursuing these objectives will move us beyond the current boundaries of knowledge and lead to the discovery of novel therapeutic targets.'