Programmed cell death and angiogenesis
Project type
Honours and/or PhD
| Supervisor(s) | Division | |
Dr Leigh Coultas (Primary) |
Cancer and Haematology | .(JavaScript must be enabled to view this email address) |
| (Co-supervisor) | Molecular Genetics of Cancer | .(JavaScript must be enabled to view this email address) |
Details of project
As a tumour grows, its associated blood vascular network must expand with it to meet its increased oxygen and nutritional demands. Knowing how to prevent the expansion of the tumour-associated vascular network or to remove existing vessels from a tumour may help block further tumour growth and even cause its regression. Blood vessel networks (including those in tumours) expand through a process termed ‘angiogenesis’: the branching, splitting, pruning and proliferation of pre-existing vessels.
Angiogenesis poses distinct survival challenges to blood vessels, yet how they survive this critical period of vessel growth remains poorly understood. Inhibiting angiogenic blood vessel survival may be an effective means for preventing tumour blood vessel growth. The Bcl-2 family of proteins are critical regulators of cell survival through their prevention of apoptosis (‘programmed cell death’). This project will determine the role of select Bcl-2 family members in regulating the survival of angiogenic blood vessels.
Skills and Techniques: This project is expected to involve the following skills and techniques: micro-dissection techniques, whole organ immunohistochemistry, imaging techniques, Q-PCR, FACS.
Research interests
My research seeks to define mechanisms that govern development of the blood vascular system, particularly blood vessel regression. Blood vessel regression is essential both for the removal of redundant and harmful vessels during development and is also active during angiogenesis (the process by which blood vessels grow), where it helps the maturation of the newly emerging vessel network.
Blood vessel regression is known to occur by one of two mechanisms: involution or pruning. Involution is driven by apoptosis (programmed cell death), whereas pruning is believed to occur by cell migration. The molecular regulation of both these regression events remains poorly defined. By understanding the mechanisms that drive normal blood vessel regression, we hope to learn more about how the vascular system develops and potentially identify new ways of combating pathologic blood vessel growth, such as occurs in tumour angiogenesis.
Selected publications
- Naik E, O'Reilly LA, Asselin-Labat ML, Merino D, Lin A, Cook M, Coultas L, Bouillet P, Adams JM, Strasser A. Destruction of tumor vasculature and abated tumor growth upon VEGF blockade is driven by proapoptotic protein Bim in endothelial cells. J Exp Med. 2011 Jul 4;208(7):1351-8.
- Walls JR, Coultas L, Rossant J, Henkelman RM. Three-dimensional analysis of vascular development in the mouse embryo. PLoS One. 2008 Aug 6;3(8):e2853
- Coultas L, Chawengsaksophak K, Rossant J. Endothelial cells and VEGF in vascular development. Nature. 2005 Dec 15;438(7070):937-45
Research theme
Cancer
Scientific discipline
- Developmental Biology
Keywords
angiogenesis, endothelial cells