EpiTALL
Financiado
Dynamic interplay between DNA methylation histone modifications and super enhan...
Dynamic interplay between DNA methylation histone modifications and super enhancer activity in normal T cells and during malignant T cell transformation
Dynamic interplay between histone modifications and DNA methylation defines the chromatin structure of the humane genome and serves as a conceptual framework to understand transcriptional regulation in normal development and human...
Dynamic interplay between histone modifications and DNA methylation defines the chromatin structure of the humane genome and serves as a conceptual framework to understand transcriptional regulation in normal development and human disease. The ultimate goal of this research proposal is to study the chromatin architecture during normal and malignant T cell differentiation in order to define how DNA methylation drives oncogenic gene expression as a novel concept in cancer research.
T-cell acute lymphoblastic leukemia (T-ALL) accounts for 15% of pediatric and 25% of adult ALL cases and was originally identified as a highly aggressive tumor entity. T-ALL therapy has been intensified leading to gradual improvements in survival. However, 20% of pediatric and 50% of adult T-ALL cases still relapse and ultimately die because of refractory disease. Research efforts have unravelled the complex genetic basis of T-ALL but failed to identify new promising targets for precision therapy.
Recent studies have identified a subset of T-ALLs whose transcriptional programs resemble those of early T-cell progenitors (ETPs), myeloid precursors and hematopoietic stem cells. Importantly, these so-called ETP-ALLs are characterized by early treatment failure and an extremely poor prognosis. The unique ETP-ALL gene expression signature suggests that the epigenomic landscape in ETP-ALL is markedly different as compared to other genetic subtypes of human T-ALL.
My project aims to identify genome-wide patterns of DNA methylation and histone modifications in genetic subtypes of human T-ALL as a basis for elucidating how DNA methylation drives the expression of critical oncogenes in the context of poor prognostic ETP-ALL. Given that these ETP-ALL patients completely fail current chemotherapy treatment, tackling this completely novel aspect of ETP-ALL genetics will yield new targets for therapeutic intervention in this aggressive haematological malignancy.
ver más
Duración del proyecto: 60 meses
Fecha Inicio: 2015-06-11
Fecha Fin: 2020-06-30
Fecha Fin: 2020-06-30
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2020-06-30
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-StG-2014:
ERC Starting Grant
Cerrada
hace 10 años
Presupuesto
El presupuesto total del proyecto asciende a
959K€
Líder del proyecto
UNIVERSITEIT GENT
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5
250.46K€ |
Participante