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Full NameProfessor Walter Kolch
Department:Systems Biology Ireland
Organisation:University College Dublin
- genetics, genomics and molecular biology
- cell and developmental biology/regenerative medicine
Postgrad Medical Specialties
- Vascular Medicine
Systems Biology Ireland (SBI) designs new therapeutic approaches to cancer. Our research enables development of technologies that can be used for early identification of responsive patient groups and accelerated discovery of new combination therapies.
The communication networks inside the human body are incredibly complex with millions of cells constantly 'talking' to each other. Occasionally, these communication networks can break down or messages can misfire leading to diseases such as cancer. Deciphering how cells 'talk' to each other is the task of systems biology. SBI researchers apply mathematics and computer science to enormous data sets arising from biological techniques.
SBI research is trying to find out what genes do, how they work together and what goes wrong in disease, working towards a personalised approach to medicine.
Kolch, W et al.. The dynamic control of signal transduction networks in cancer cells. Nature reviews. Cancer 15, 515-527 (2015)
Duffy DJ et al.. GSK3 Inhibitors Regulate MYCN mRNA Levels and Reduce Neuroblastoma Cell Viability through Multiple Mechanisms, Including p53 and Wnt Signaling. Molecular cancer therapeutics 13, 454-467 (2014)
Romano, D et al.. Protein interaction switches coordinate Raf-1 and MST2/Hippo signalling. Nat Cell Biol 16, 673-684 (2014)
Generating and characterising immortalised human syngenic normal and tumour endothelial cells for investigating molecular mechanisms of tumour angiogenesis
Solid tumours depend on a supply of nutrients to the expanding malignant tissue. Angiogenic signals from areas of tumour cell hypoxia and from the tumour microenvironment activate tumour infiltration by non-cancerous endothelial cells, forming new blood vessels. These vessels are functionally abnormal due to phenotypic changes between tumoural (TuECs) and normal endothelial cells (nECs). A wealth of data suggests that understanding the nEC-to-TuEC transition will provide new targets for cancer therapy. However, this research is severely hampered by a lack of suitable cell lines. This project aims to close this gap by isolating, immortalising, and characterising TuECs and nECs from human colorectal cancer specimens.
The cell lines will be immortalised via telomerase expression, and extensively characterised to assure their EC nature using both molecular methods (DNA sequencing, transcriptomic and proteomic profiling) and biological assays including 3D cultures. Salient differences will be verified in primary nECs and TuECs. Having well characterised immortal TuEC and nECs lines available will enable further projects aiming at (i) investigating the mechanisms underlying the nEC-to-TuEC transition; and (ii) identifying new markers or targets for interfering with or reversing tumour angiogenesis. The cell lines will be made available as resource to the scientific community.