Vascular biology and stromal targeting


Student project opportunities

  • Analysing the “Blood-Tumour” Barrier

Analysing the “Blood-Tumour”-Barrier

Research area: Tumour Biology
Chief supervisor: Professor Ruth Ganss
Other supervisors:  Dr Anna Johansson
Project suitable for: Honours,  Masters, PhD  
Essential qualifications BSc/BSc (Hons)

Project outline
To reach tumour cells within malignant tissue, immune cells and drugs must enter the tumour blood vessels, cross the vessel wall, and penetrate through tumour stroma. We have previously shown that chaotic blood vessels and lack of tumour perfusion are critical barriers that limit anti-cancer therapy at the tumour site. These intratumoral parameters are in large part a manifestation of the tumour stroma which includes the newly formed, angiogenic vasculature. Our laboratory seeks to understand molecular mechanisms of stromal remodelling in tumours with the goal to develop improved therapies by modifying the tumour microenvironment. 

Tumour blood vesselsSpecifically, we are studying mouse models of pancreatic cancer to develop new approaches which exploit the dynamic nature of tumor stroma to reprogram rather than destroy vessels which provides longer lasting antitumor effects, in particular when combined with strategies to eliminate cancer cells such as cytotoxic and immune therapies. In the course of this project fundamental changes in the tumour vascular bed and stroma of pancreatic tumours before and after therapy will be analysed by histology, quantitative PCR and Western Blots. Vascular cells with overexpression or deletion of specific genes will be employed to assess cytoskeletal rearrangements, migration and signalling events. This project aims to identify molecular mechanisms and signalling pathways which define tumour stroma which is permissive for destruction.

Selected reading to this topic

  1. Hamzah, J., Jugold, M., Kiessling, F., Rigby, P., Manzur, M., Marti, H., Rabie, S., Kaden, H.-J.,Groene, G.J., Hämmerling, G., Arnold, B. and Ganss, R. (2008) Vessel Normalization in Regulator of G protein 5-deficient Tumors Promotes Immune Destruction, Nature, 453: 410-4.
  2. Johansson, A., J. Hamzah, C.J. Payne and R. Ganss. 2012. Tumor-targeted TNFα Stabilizes Tumor Vessels and Enhances Active Immunotherapy. PNAS, 109: 7841-7846.
  3. Johansson, A, J. Hamzah and R. Ganss. 2014. License for destruction: Tumor-specific cytokine targeting. Trends Mol. Med., 20, 16-24.
  4. Johansson-Percival A, ZJ Li, DD Lakhiani, B He, X Wang, J Hamzah, and R Ganss. 2015. Intratumoral LIGHT Restores Pericyte Contractile Properties and Vessel Integrity. Cell Reports 13: 2687-98.

Contact
Professor Ruth Ganss - ganss@perkins.uwa.edu.au

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