SubsidieMeestersExposing hidden targets of drug resistance in cancer by mapping the epitranscriptome at single-cell resolution
This project aims to develop a method for single-cell m6A mapping in breast cancer to uncover novel drug resistance targets and improve therapeutic strategies against chemoresistance.
Projectdetails
Introduction
Drug resistance is one of the biggest challenges in the clinical management of breast cancer (BC), but the underlying mechanisms are still not fully understood. What we do know is that epigenetic mechanisms play a key role in the adaptation of cancer cells to therapy, which is why they have become a prime field of investigation.
Current Understanding
Single-cell profiling of epigenetic DNA and histone modifications have already revealed intriguing and actionable insights into tumor heterogeneity. For the most recently discovered epigenetic layer, however, which consists of RNA modifications, we have not yet reached single-cell resolution.
Epitranscriptomics
The exciting potential of RNA modifications to fine-tune the processing and expression of mRNAs is currently an area of intense research termed ‘Epitranscriptomics’. The most prevalent and best-studied of these mRNA modifications, N6-methyladenosine (m6A), has recently been linked to drug resistance in cancer.
Research Findings
Our lab has uncovered a new m6A-based layer of dysregulation of a major cancer pathway driving therapy resistance in BC. The ability to study m6A in single cells holds great promise as it would enable us to further delineate tumor heterogeneity and to find novel drug resistance targets that have eluded us so far.
Proposed Aims
I propose to:
- Develop a method for streamlined m6A mapping at single-cell resolution (Aim 1).
- Apply it to triple-negative BC (TNBC) cells driven to chemoresistance in cell culture, mice, and human samples to determine uncharted targets of drug resistance (Aim 2).
- Disrupt m6A-regulated chemoresistance targets in order to prevent therapy failure (Aim 3).
Alignment with Skills
These aims are aligned with my knowledge and skills related to both m6A and drug resistance. This unique and comprehensive analysis of the single-cell m6A methylome will provide invaluable new insights into the unknown epigenetic characteristics of chemoresistance and will pave the way for new therapeutic interventions.
Financiële details & Tijdlijn
Financiële details
| Subsidiebedrag | € 1.496.578 |
| Totale projectbegroting | € 1.496.578 |
Tijdlijn
| Startdatum | 1-1-2024 |
| Einddatum | 31-12-2028 |
| Subsidiejaar | 2024 |
Partners & Locaties
Projectpartners
- UNIVERSITE LIBRE DE BRUXELLESpenvoerder
Land(en)
Vergelijkbare projecten binnen European Research Council
| Project | Regeling | Bedrag | Jaar | Actie |
|---|---|---|---|---|
Dynamics of Adaptation and Resistance in Cancer: MApping and conTrolling Transcriptional and Epigenetic RecurrenceThis project aims to uncover the mechanisms of drug resistance in colorectal cancer through innovative models and computational methods, ultimately improving treatment strategies and patient outcomes. | ERC Consolid... | € 1.995.582 | 2024 | Details |
Deciphering Cancer Heterogeneity and Drug resistance using Single-Clone Genomic and Epigenomic LandscapesThis project aims to develop innovative single-cell technologies to analyze tumor subclones, enhancing understanding of drug resistance and identifying new therapeutic targets in brain cancers. | ERC Consolid... | € 2.000.000 | 2023 | Details |
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Comprehensive Platform for the Functional Characterization of Cancer Epigenetics and DiagnosisEpiCancer aims to develop single-cell epigenetic analysis tools to understand cancer heterogeneity and improve diagnostics through blood tests, enhancing early detection and monitoring of tumors. | ERC Starting... | € 1.500.000 | 2024 | Details |
Dynamics of Adaptation and Resistance in Cancer: MApping and conTrolling Transcriptional and Epigenetic Recurrence
This project aims to uncover the mechanisms of drug resistance in colorectal cancer through innovative models and computational methods, ultimately improving treatment strategies and patient outcomes.
Deciphering Cancer Heterogeneity and Drug resistance using Single-Clone Genomic and Epigenomic Landscapes
This project aims to develop innovative single-cell technologies to analyze tumor subclones, enhancing understanding of drug resistance and identifying new therapeutic targets in brain cancers.
Cancer cell plasticity on targeted therapy
This project aims to develop innovative cancer therapies by analyzing tumor heterogeneity and targeting drug-tolerant persister cells to prevent resistance and improve patient outcomes.
Applying novel single-cell multiomics to elucidate leukaemia cell plasticity in resistance to targeted therapy
This project aims to develop a single-cell multiomics method to understand epigenetic resistance mechanisms in AML, enhancing treatment strategies against drug resistance.
Comprehensive Platform for the Functional Characterization of Cancer Epigenetics and Diagnosis
EpiCancer aims to develop single-cell epigenetic analysis tools to understand cancer heterogeneity and improve diagnostics through blood tests, enhancing early detection and monitoring of tumors.