Dr Joanna Birch, Prof David Chang, Prof Vincenzo D'Angiolella, Dr Mathias Tesson
Project Description
Radiotherapy (RT) is an effective treatment used in a wide range of solid cancers for both curative intents, and in neo-adjuvant and palliative settings to gain local control and symptom relief. However, our own group and others have made the important observation that RT can also induce a pro-metastatic phenotype in cancer cells that remain after treatment. This induction of metastasis may oppose the clinical benefits of RT in some cancers, leading to suboptimal overall response to therapy. Understanding why this occurs will allow us to identify novel therapeutic targets that can be exploited in the future to use alongside radiotherapy.
This project will focus on pancreatic ductal adenocarcinoma (PDAC; median survival <5 years) where novel treatment combinations are urgently required. The project will investigate signaling changes within cancer and stromal cells induced by RT with the aim of identifying new, druggable targets that can be used in combination with radiotherapy, using the state-of-the-art in vitro, ex vivo and in vivo radiotherapy modalities and models of PDAC available in Glasgow. This includes the establishment of ex vivo culture of resected patient tissue, a model that bridges the gap between simplistic in vitro models and resource heavy in vivo approaches and maintains key aspects of the tumour micro-environment. In addition, the candidate will gain experience in advanced imaging and bioinformatic analysis of sequencing data as the project begins to dissect the role of the cancer cells and tumour microenvironment in creating a pro-metastatic niche following RT.
The candidate will be primarily supervised by Dr Joanna Birch, a researcher with extensive experience in radiation driven metastasis across a range of tumours. The project will also be co-supervised by Prof. David Chang (Professor of Surgical Oncology and clinical expert on PDAC), Dr Mathias Tesson (expert in preclinical models of PDAC and RT) and Prof Vincenzo D’Angiolella (expert in cellular response to radiation), and supported through collaboration with Prof. Jen Morton (pre-clinical models of PDAC). The candidate will have access to ‘state of the art’ facilities across the University of Glasgow, CRUK Scotland Institute and the University of Edinburgh as well as all necessary training opportunities.
Training offered
The candidate will be trained in pre-clinical mouse models of PDAC, in vitro and in vivo radiotherapy, tissue culture (including patient derived primary lines), bioinformatic analysis of genome/transcriptome/proteome data and advanced imaging techniques (in vitro and in vivo).
For further information on the project or informal enquiries, please contact Dr Joanna Birch, This email address is being protected from spambots. You need JavaScript enabled to view it..
To place an application, please visit this site at the University of Glasgow.
When submitting your application please upload the completed recruitment form.
Lab Websites
Dr Joanna Birch
Dr David Chang
References
1. Birch et al., A Novel Small-Molecule Inhibitor of MRCK Prevents Radiation-Driven Invasion in Glioblastoma. Cancer Res, 2018. 78: 6509-6522.
2. Lee et al., Induction of metastasis, cancer stem cell phenotype, and oncogenic metabolism in cancer cells by ionizing radiation Mol Cancer. 2017; 16: 10.
3. Doudou Li et al., Radiation promotes epithelial-to-mesenchymal transition and invasion of pancreatic cancer cell by activating carcinoma-associated fibroblasts. Am J Cancer Res, 2016
4. Mueller, A.C. et al., Induction of ADAM10 by Radiation Therapy Drives Fibrosis, Resistance, and Epithelial-to-Mesenchymal Transition in Pancreatic Cancer. Cancer Res, 2021. 81: 3255-3269.