Our lab is interested in the molecular regulation of angiogenesis, the process by which new blood vessels are formed from pre-existing vessels. This is a critical process for animal development and organ growth as it allows tissues to be adequately supplied with blood.
However, angiogenesis is also an important step during the development of a tumour, and unregulated angiogenesis can lead to conditions such as retinopathies. Thus a greater understanding of this process could have important clinical implications.
We have a particular interest in the regulation of the survival of endothelial cells that form the lining of blood vessel walls during angiogenesis. Our previous work has shown that endothelial cell survival is controlled by proteins belonging to the BCL2 family.
BCL2 family proteins are involved the regulation of cell death and cell survival in many cell types. Our research aims to identify which members of the BCL2 family are essential for endothelial cell survival and death during angiogenesis, and what regulates the life-or-death decision in these cells.
BCL2 family proteins are often dysregulated in cancer cells, making cells long-lived and resistant to chemotherapy. A new class of potential anti-cancer agents, called BH3-mimetics, prevent BCL2 family proteins from promoting cell survival. Our research into how BCL2 family proteins influence endothelial cell survival has the potential to highlight a role of BH3-minetics in preventing angiogenesis in tumours.
1. Understanding the role and regulation of apoptosis in endothelial cells
2. Discovery of BCL2 proteins essential for endothelial survival during angiogenesis
Find out more about Leigh Coultas' experience
Leigh Coultas' highlights
Leigh Coultas' selected work
Genome-wide functional analysis reveals central signaling regulators of lymphatic endothel..
Apoptosis regulates endothelial cell number and capillary vessel diameter but not vessel r..
Endothelial cell survival during angiogenesis requires the pro-survival protein MCL1
Displaying the 28 most recent scholarly works by Leigh Coultas.
Caspase-8 modulates physiological and pathological angiogenesis during retina development
Nathalie Tisch, Aida Freire-Valls, Rosario Yerbes, Isidora Paredes, Silvia La Porta, Xiaohong Wang, Rosa Martin-Perez, Laura Castro, Wendy Wei-Lynn Wong, Leigh Coultas, Boris Strilic, Hermann-Josef Grone, Thomas Hielscher, Carolin Mogler, Ralf H Adams, Peter Heiduschka, Lena Claesson-Welsh, Massimiliano Mazzone, Abelardo Lopez-Rivas, Thomas Schmidt, et al.
Journal article | 2019 | Journal of Clinical Investigation
During developmental angiogenesis, blood vessels grow and remodel to ultimately build a hierarchical vascular network. Whether and..
Genome-wide functional analysis reveals central signaling regulators of lymphatic endothelial cell migration and remodeling
Steven P Williams, Adam F Odell, Tara Karnezis, Rae H Farnsworth, Cathryn M Gould, Jason Li, Sophie Paquet-Fifield, Nicole C Harris, Anne Walter, Julia L Gregory, Sara F Lamont, Ruofei Liu, Elena A Takano, Cameron J Nowell, Neil I Bower, Daniel Resnick, Gordon K Smyth, Leigh Coultas, Benjamin M Hogan, Stephen B Fox, et al.
Journal article | 2017 | Science Signaling
Neuropilin 1 expression correlates with differentiation status of epidermal cells and cutaneous squamous cell carcinomas.
Shokoufeh Shahrabi-Farahani, Lili Wang, Bernadette MM Zwaans, Jeans M Santana, Akio Shimizu, Seiji Takashima, Michael Kreuter, Leigh Coultas, Patricia A D'Amore, Jeffrey M Arbeit, Lars A Akslen, Diane R Bielenberg
Journal article | 2014 | Laboratory Investigation
Neuropilins (NRPs) are cell surface receptors for vascular endothelial growth factor (VEGF) and SEMA3 (class 3 semaphorin) family ..
Enhanced stability of Mcl1, a prosurvival Bcl2 relative, blunts stress-induced apoptosis, causes male sterility, and promotes tumorigenesis
Toru Okamoto, Leigh Coultas, Donald Metcalf, Mark F van Delft, Stefan P Glaser, Megumi Takiguchi, Andreas Strasser, Philippe Bouillet, Jerry M Adams, David CS Huang
Journal article | 2014 | Proceedings of the National Academy of Sciences of the United States of America
Rhou maintains the epithelial architecture and facilitates differentiation of the foregut endoderm
David AF Loebel, Joshua B Studdert, Melinda Power, Tania Radziewic, Vanessa Jones, Leigh Coultas, Yvette Jackson, Renuka S Rao, Kirsten Steiner, Nicolas Fossat, Lorraine Robb, Patrick PL Tam
Journal article | 2011 | Development
Destruction of tumor vasculature and abated tumor growth upon VEGF blockade is driven by proapoptotic protein Bim in endothelial cells
Edwina Naik, Lorraine A O'Reilly, Marie-Liesse Asselin-Labat, Delphine Merino, Ann Lin, Michele Cook, Leigh Coultas, Philippe Bouillet, Jerry M Adams, Andreas Strasser
Journal article | 2011 | Journal of Experimental Medicine
Lunatic Fringe-mediated Notch signaling is required for lung alveogenesis.
Keli Xu, Erica Nieuwenhuis, Brenda L Cohen, Wei Wang, Angelo J Canty, Jayne S Danska, Leigh Coultas, Janet Rossant, Megan YJ Wu, Tino D Piscione, Andras Nagy, Achim Gossler, Geoff G Hicks, Chi-Chung Hui, R Mark Henkelman, Lisa X Yu, John G Sled, Thomas Gridley, Sean E Egan
Journal article | 2010 | American Journal of Physiology-Lung Cellular and Molecular Physiology
Distal lung development occurs through coordinated induction of myofibroblasts, epithelial cells, and capillaries. Lunatic Fringe ..
Three-dimensional analysis of vascular development in the mouse embryo.
Johnathon R Walls, Leigh Coultas, Janet Rossant, R Mark Henkelman
Journal article | 2008 | PLoS ONE
Key vasculogenic (de-novo vessel forming) and angiogenic (vessel remodelling) events occur in the mouse embryo between embryonic d..
Hrk/DP5 contributes to the apoptosis of select neuronal populations but is dispensable for haematopoietic cell apoptosis
Leigh Coultas, Susanna Terzano, Tim Thomas, Anne Voss, Kate Reid, Edouard G Stanley, Clare L Scott, Philippe Bouillet, Perry Bartlett, Jonathan Ham, Jerry M Adams, Andreas Strasser
Journal article | 2007 | J. Cell Sci.
Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis.
Mats Hellström, Li-Kun Phng, Jennifer J Hofmann, Elisabet Wallgard, Leigh Coultas, Per Lindblom, Jackelyn Alva, Ann-Katrin Nilsson, Linda Karlsson, Nicholas Gaiano, Keejung Yoon, Janet Rossant, M Luisa Iruela-Arispe, Mattias Kalén, Holger Gerhardt, Christer Betsholtz
Journal article | 2007 | Nature
In sprouting angiogenesis, specialized endothelial tip cells lead the outgrowth of blood-vessel sprouts towards gradients of vascu..