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Tracking and Targeting Tumor States at single-cell resolution in real time in vivo

Project description

Defining tumour state identities and functions at single-cell resolution in real time in vivo

Not all cancer cells in a tumour are alike. Some cancer cells proliferate, others differentiate, migrate and metastasise. Yet others enter a dormant state and resist chemotherapy. Scientists therefore need to identify distinct tumour states (TSs) and the mechanisms regulating their identities and functions. The EU-funded TrackingTumorStates project aims to comprehensively define the identities and functions of distinct TSs at single-cell resolution in squamous cell carcinoma. It will develop new genetically engineered tumour models to visualise the dynamics of TSs in real time in vivo. It will also evaluate the roles of the identified TSs by lineage ablation and determine their regulating mechanisms. This work will help to identify new tumour vulnerabilities and pave the way for new therapies.

Objective

It is now widely recognized that within a tumor, not all cancer cells are alike and different tumor states (TS) exist. This process is known as tumor heterogeneity. Some cancer cells actively proliferate, while others differentiate, migrate and give rise to metastasis, or enter in a dormant state and resist to chemotherapy. The identification of distinct TS and the mechanisms that regulate their identities and functions is critical for our understanding of tumor heterogeneity. The different TS can acquire distinct phenotypes responsible for tumor progression, metastasis, and therapy resistance. In this project, using multidisciplinary approaches that combine single-cell lineage tracing, single-cell genomics, epigenomics and transcriptomics together with pharmacological treatment and genetic perturbations, we will define in a comprehensive and integrated manner the identities and functions of distinct TS at single-cell resolution in squamous cell carcinoma (SCC). Then, we will develop new genetically engineered tumor models expressing different fluorescent proteins to visualize the dynamics of TS in real time in vivo using intravital microscopy. Moreover, we will assess the roles of the identified TS by lineage ablation and identify the intrinsic and extrinsic mechanisms that regulate their transitions and functions, which will help to define new tumor vulnerabilities and provide new therapeutic opportunities.

Coordinator

UNIVERSITE LIBRE DE BRUXELLES
Net EU contribution
€ 2 500 000,00
Address
Avenue franklin roosevelt 50
1050 Bruxelles / brussel
Belgium

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Region
Région de Bruxelles-Capitale/Brussels Hoofdstedelijk Gewest Région de Bruxelles-Capitale/ Brussels Hoofdstedelijk Gewest Arr. de Bruxelles-Capitale/Arr. Brussel-Hoofdstad
Activity type
Higher or Secondary Education Establishments
Links
Other funding
€ 0,00

Beneficiaries (1)