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AML-SynergyX

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Systematic identification of genetic modifiers in the response to targeted thera...

Systematic identification of genetic modifiers in the response to targeted therapies in acute myeloid leukemia. In the last decade, we have witnessed tremendous progress in understanding the genetic landscape of acute myeloid leukemia (AML), which has been translated into several approved targeted therapies. Although these therapies are eff... ver más

31/08/2024

FORSCHUNGSINSTITUT...

186K€

Presupuesto del proyecto: 186K€

Líder del proyecto

FORSCHUNGSINSTITUT FUR MOLEKULARE PATHOLOGIE... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2024-08-31

MSCA-IF-2020: Individual Fellowships

I+D

Cerrada hace 4 años

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Información adicional privada

No hay información privada compartida para este proyecto. Habla con el coordinador.

1 Participantes

FORSCHUNGSINSTITUT FUR MOLEK...

186.17K€ | Lider

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Duración del proyecto: 41 meses Fecha Inicio: 2021-03-22
Fecha Fin: 2024-08-31

Líder del proyecto

FORSCHUNGSINSTITUT FUR MOLEKULARE PATHOLOGIE... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 186K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto In the last decade, we have witnessed tremendous progress in understanding the genetic landscape of acute myeloid leukemia (AML), which has been translated into several approved targeted therapies. Although these therapies are effective initially, most patients eventually develop resistance through a variety of genetic and/or epigenetic mechanisms that remain incompletely understood. While it is widely accepted that transient responses to oncogene-targeted therapeutics into cure will require drug combinations, the pre-clinical and clinical development of rational combination therapies remains challenging. The advent of high-throughput genetic screens and transcriptome profiling methods fundamentally changes the way we can address this problem. The overall goal of this proposal is to apply and integrate these innovative technologies to deeply investigate genetic and gene-regulatory mechanisms in the response to small-molecule inhibitors of FLT3 and the MLL-Menin interaction, which hold promise as targeted therapeutics for more than 50% of AML patients. Using advanced CRISPR/Cas9- and shRNA-based screening platforms, I will systematically identify genes that modify the response to FLT3 and MLL-Menin inhibition. Complementary to functional-genetic screens, I will apply SLAMseq, a scalable time-resolved mRNA profiling method co-developed by the host lab, to dynamically investigate transcriptional programs underlying the primary response and adaptation to FLT3 and MLL-Menin inhibition. Functional-genetic and time-resolved transcriptome profiles will be integrated to select promising candidates for validation and mechanistic follow-up studies in patient AML samples and genetically engineered mouse models. In summary, by providing deep insight into the response to FLT3- and MLL-Menin inhibition, I thrive to identify candidate targets and new concepts for rational combination therapies that would address an unmet clinical need with a clear path towards clinical translation.

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