Advanced Patient-Derived Breast Organoids
Research type
Research Study
Full title
Advanced Patient-Derived Breast Organoids
IRAS ID
339850
Contact name
Salah Elias
Contact email
Sponsor organisation
University of southampton
Duration of Study in the UK
4 years, 11 months, 31 days
Research summary
A better understanding of how normal breast architecture is established and maintained is urgently needed to advance our knowledge of how breast cancer arises and provide a rationale for developing new and improved approaches for the prevention, early detection and treatment of breast cancer, a disease that kills over 11,500 women annually in the UK.
Here we propose a research project, bringing together a multidisciplinary team at the University of Southampton, to address outstanding significant questions of how regulation of epithelial architecture drives breast functional maturation and how this prevents carcinogenesis. To achieve this, we build on our long-standing collaboration Dr Salah Elias (University of Southampton) and Dr Colinda Scheele lab (VIB KU Leuven, Belgium) labs to developed advanced three-dimensional organotypic cultures (referred to as organoids) derived from healthy and predisposed patients, faithfully recapitulating human breast branched architecture and development. In this three-year project we plan to use our branched patient-derived organoids, combined with advanced quantitative whole-mount microscopy and a gene loss-of-function strategy to track the fate and dynamics of single mitotic stem/progenitor cells at the highest spatial and temporal resolution possible and uncover the mechanisms of their dynamic contribution to lumen formation and integrity and determine how this dictates breast tissue architecture and differentiation. Ultimately, we will build on our generated imaging clonal data to develop and implement artificial intelligence (AI)-guided mathematical/computational models, which will provide the means to validate with high confidence our hypotheses and draw a model explaining how loss of lumen integrity initiates breast carcinogenesis in a permissive mutant background.
Our work will represent a blueprint for the design of next generation, cost-effective patient-derived organoid methods, reducing the use of animals in research, while enhancing the quality of life, and decreasing the burden on the healthcare system.
REC name
Wales REC 5
REC reference
25/WA/0135
Date of REC Opinion
8 May 2025
REC opinion
Favourable Opinion