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Biomimetic collagen-based scaffolds for the study of pancreatic cancer and delivery anti-tumoural miRNA for enhanced cancer therapy.

Project description

3D model for targeted pancreatic cancer therapy

The tumour extracellular matrix (ECM) is a complex network of proteins and glycoproteins that offers structural support to and promotes tumour growth. Alterations in the ECM can influence tumour behaviour, including invasion and resistance to therapy. Therefore, accurately mimicking the tumour ECM is crucial for understanding malignant transformation. With the support of the Marie Skłodowska-Curie Actions programme, the PancmiR project aims to create a 3D pancreatic cancer model and replicate the tumour ECM through a collagen-based scaffold. The study will focus on the KRAS oncogene, which is frequently mutated in pancreatic cancer. Researchers will test the delivery of specific microRNAs to downregulate KRAS as a therapeutic strategy.

Objective

Pancreatic tumours are among the most aggressive, and are associated with the lowest survival rates. The main reason of this is their characteristic dense fibrotic stroma, which creates a perfect environment to promote cancer progression. To accurately mimic the Extracellular Matrix (ECM) is challenging, but is essential to understanding the interaction that occurs during malignant transformation. KRAS mutation is the most frequent alteration in pancreatic cancer. Micro(mi)RNA-143-3p and miRNA-216b have been shown to decrease KRAS gene expression and suppress tumour cell growth. My overarching Aim is to generate a 3D model of pancreatic cancer in which I can test the ability of a miRNA-activated scaffold to suppress tumour growth and facilitate local delivery of miRNA (miRNA-143-3p and miRNA-216b) that downregulate KRAS expression. Prof. Fergal O’Brien’s group in Royal College of Surgeon in Ireland has an extensive experience with development of biomimetic scaffolds to recreate the tumoural ECM and activating scaffolds to release therapeutic molecules (e.g. miRNAs). Using techniques established in his group, I will develop a 3D collagen-based scaffold that recreates the structure of pancreatic tumour ECM and then utilise this form as miRNA-activated scaffolds that will be used as local delivery systems in a radical new treatment for this disease. I will be supervised by Prof. O’Brien, and he will guide my Career Development Plan. I will develop complementary skills in project management, leadership, entrepreneurship, commercialisation, dissemination, and profile enhancement. Acquiring advanced research competences and complementary skills, I will maturate as an independent scientist, enhancing my professional visibility, capacity, and competitiveness in the field of biomaterials. This Fellowship will significantly contribute to the achievement of my long-term career goal, which is becoming an independent scientist leading my own biomaterials research group.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

(opens in new window) HORIZON-MSCA-2023-PF-01

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Coordinator

ROYAL COLLEGE OF SURGEONS IN IRELAND
Net EU contribution
€ 199 694,40
Address
ST STEPHEN GREER 123
D02 YN77 DUBLIN 2
Ireland
Region
Ireland Eastern and Midland Dublin
Activity type
Higher or Secondary Education Establishments
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Total cost
No data