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OncoNichPath

Financiado

Unmasking the dynamic influence of the hematopoietic niche as an oncogenic path...

Unmasking the dynamic influence of the hematopoietic niche as an oncogenic path to myeloid neoplasms evolution Although oncogenic driver mutations are found in healthy tissues sometimes at a prenatal stage, they do not often result in overt cancer. This genotype – phenotype discrepancy warrens the search for extrinsic mechanisms of cancer... ver más

31/12/2028

UPCité

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

UNIVERSITE PARIS CITE No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-12-06

ERC-2023-STG: ERC STARTING GRANTS Scope:Objectives

I+D

Cerrada hace 2 años

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1 Participantes

UPCité

1.91M€ | Lider

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Duración del proyecto: 60 meses Fecha Inicio: 2023-12-06
Fecha Fin: 2028-12-31

Líder del proyecto

UNIVERSITE PARIS CITE No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 2M€

Descripción del proyecto Although oncogenic driver mutations are found in healthy tissues sometimes at a prenatal stage, they do not often result in overt cancer. This genotype – phenotype discrepancy warrens the search for extrinsic mechanisms of cancer development and maintenance, such as aging or exposition to specific environments. Using myeloid neoplasms as a cancer model, I aim here at dissecting the hematopoietic-niche partnership at the pre-leukemic, leukemic and post-leukemic stage to identify innovative therapeutic strategies to prevent acute myeloid leukemia (AML) development, maintenance and recurrence. To enable experimental modelling of the bone marrow niche at different disease stages, I collected longitudinal paired stromal and hematopoietic primary patient samples, and generated physiologically-relevant in vitro and in vivo humanized models. In this proposal, I will first apply large-scale pooled genetic screening approaches to gain insights into the role of the hematopoietic-niche cellular communication processes in leukemic transformation of pre-leukemic clonal myeloid conditions. In the second part of the proposal, I will combine cutting-edge spatial single-cell RNA sequencing technologies with functional genetic screening to dissect the leukemic-niche crosstalk and ultimately fuel the development of concomitant seeds and soil therapeutic strategies. Finally, I will design a functional single-cell screening approach allowing modulation of the post-leukemic niche, to open the road for novel maintenance treatment strategies re-establishing healthy hematopoietic stem cells fitness advantage to prevent relapse. Overall, the proposed research project provides a framework for defining and understanding the dynamic influence of the hematopoietic niche as an oncogenic path to myeloid neoplasms evolution, and represents a key step towards therapeutic niche reprogramming from a malignant to a healthy state, to improve cancer patients’ prognosis.

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