Identifying biomarkers and therapeutic targets in primary breast angiosarcoma using iPSC-derived endothelial models

Primary breast angiosarcoma (PBA) is a rare, aggressive soft tissue tumour arising from endothelial cells, with poor prognosis and limited treatment options. This project addresses the unmet clinical need by using induced pluripotent stem cell (iPSC)-derived endothelial models carrying PIK3CA and KDR mutations, key oncogenic drivers in PBA. The work integrates stem cell biology, genetic engineering, and molecular profiling to advance understanding of PBA pathogenesis and therapy response. The student will establish arterial and venous endothelial models carrying PIK3CA and KDR mutations via inducible gene expression systems and advanced lineage barcoding. Experimental approaches include 2D and 3D culture, microfluidics, high-content imaging, mass cytometry, proteomics, spatial transcriptomics, and drug screening with clinically relevant compounds. This interdisciplinary training prepares the student for diverse career path. Expected Outcomes The project will elucidate early transformation events, signalling dependencies, and therapeutic vulnerabilities unique to PBA. Identification of robust diagnostic markers and actionable targets aims to improve clinical management and develop rational combination therapies for this lethal disease. Why It Matters PBA lacks established management protocols and presents diagnostic challenges due to its rarity and molecular distinctiveness. Understanding how PIK3CA and KDR mutations drive tumour biology is critical to inform precision oncology strategies, addressing a vital gap in rare cancer research with significant potential to impact patient survival and quality of life.

Strong background relevant to cancer biology, cell biology, genetics, stem cell biology, or related fields
Interest in disease modelling, molecular profiling, and therapeutic discovery

Preferred:

interest in stem cell biology
interest in cancer research
interest in multi-omics and quantitative analysis

Application process details are not fully stated in the text provided
For questions about the application process or studentships, contact:
phdstudentships@crukscotlandinstitute.ac.uk