Dr Chryso Kanthou BSc, MPhil, PhD

Reader

Department of Oncology & Metabolism
Cancer Research UK Tumour Microcirculation Group
The Medical School
Beech Hill Road
Sheffield
S10 2RX

Office: FU31

Tel: +44 (0)114 215 9052
Fax: +44 (0)114 271 3314

email: c.kanthou@sheffield.ac.uk

Biography

I joined the University of Sheffield in 2005 as Senior Lecturer in the Department of Oncology. Before joining Sheffield, I worked at the Gray Cancer Institute in Northwood, Middlesex, as senior scientist (1999-2005) and as post-doctoral scientist at the Thrombosis Research Institute in London (1994-1999). In 1994, I and was awarded my PhD in Cell and Molecular Biology by the University of London. Before embarking on my PhD studies I worked as a research assistant at the Ludwig Institute for Cancer Research London and King´s College Hospital Medical School. In addition to my PhD, I also hold a BSc degree in Cell Biology and an MPhil degree also in Cell Biology, both from King´s College, London.

Research Interests

My interests are in the field of endothelial vascular biology and angiogenesis. A main aim of my research is to understand the role played by factors within the tumour microenvironment in vessel network development and to decipher how this impacts on tumour response to vascular-targeted therapies. I am particularly interested in studying molecular signalling pathways associated with the remodelling of the endothelial cytoskeleton, a target of vascular disrupting agents (VDAs) and ionizing radiation. My research is part of a multidisciplinary approach aimed at investigating mechanisms at the molecular and cellular level that can then be tested at the level of the whole organism.

Teaching Interests

I supervise and co-supervise several PhD, MSc and BMed Sciences students and Clinical Research Fellows. I lecture on the MSc Molecular Medicine course at the School of Medicine in Sheffield, an MSc Radiation Biology course at University College London, and MSc Oncology course at the University of Nottingham. I also tutor MSc students and mentor PhD and Medical students.

Professional Activities

I am a member of a sub-group of the Advisory Group on Ionising Radiation set up by the Health Protection Agency to consider circulatory disease risks of radiation and perform critical appraisal (since April 2008). I am also currently a member of the executive committee of the British Association for Cancer Research.

Current Projects

I am co-investigator on Professor Gillian Tozer´s `Tumour Microcirculation´ programme grant funded by Cancer Research UK. This programme focuses on the maturation phase of angiogenesis and interactions with vascular disrupting therapies. The main aim is to investigate molecular mechanisms through which alternatively spliced variants of VEGF influence pericyte recruitment, differentiation and vessel stabilization and their relationship with endothelial responsiveness to VDAs. Part of this work involves modeling the tumour microenvironment using co-culture systems of endothelial cells, pericytes and tumour cells under conditions of hypoxia and analysing signalling interactions.
I am principal investigator and work package leader on a collaborative European FP7-funded study investigating mechanisms of microvascular damage by ionizing radiation in the context of normal tissue damage, which is a crucial dose-limiting factor in radiotherapy. Our main aim is to establish cellular and molecular mechanisms that mediate damaging effects of radiation on repair and angiogenesis within the microvasculature of the heart myocardium.

Key Publications

1. Al-Jamal KT, Al-Jamal WT, Akerman S, Podesta JE, Yilmazer A, Turton JA, Bianco A, Vargesson N, Kanthou C, Florence AT, Tozer GM, Kostarelos K. (2010). Systemic antiangiogenic activity of catinic poly-L-lysine dendrimer delays tumor growth. PNAS 107: 3966-3971.

2. Tozer GM, Akerman S, Cross NA, Barber PR, Bjorndahl MA, Greco O, Harris S, Hill SA, Honess DA, Ireson CR, Pettyjohn KL, Prise VE, Reyes-Alsdasoro CC, Ruhrberg C, Shima DT, Kanthou C. (2008). Blood vessel maturation and response to vascular-disrupting therapy in single vascular endothelial growth factor-A isoform-producing tumors. Cancer Res. 68:2301-11.

3. Kanthou C, Tozer GM (2009). Microtubule depolymerizing vascular disrupting agents: novel therapeutic agents for oncology and other pathologies. Int J Exp Pathol 90:284-94.

4. Kanthou C, Tozer GM (2008). Selective destruction of the tumour vasculature by targeting the endothelial cytoskeleton. Drug Discovery Today: Therapeutic Strategies 4: 237-243.

5. Gabrys D, Greco O, Patel G, Prise KM, Tozer GM, Kanthou C. (2007). Radiation effects on the cytoskeleton of human endothelial cells and on endothelial monolayer permeability. Int J Rad Biol Phys 69:1553-62.

6. Kanthou C, Kranjc S, Sersa G, Tozer G, Zupanic A, Cemazar M. (2006). The endothelial cytoskeleton as a target of electroporation-based therapies. Mol Cancer Therap 5:3145-52.

7. Tozer GM, Kanthou C, Baguley BC. (2005). Disrupting tumour blood vessels. Nat Rev Cancer 5:423-435.

8. Kanthou C, Greco O, Stratford A, Cook I, Knight R, Benzakour O, Tozer G. (2004). The tubulin-binding agent combretastatin A-4-phosphate arrests endothelial cells in mitosis and induces mitotic cell death. Am J Pathol. 165:1401-1411.

9. Kanthou C, Tozer M. (2002). The tumour vascular targeting agent combretastatin A-4-phosphate induces reorganisation of the actin cytoskeleton and early membrane blebbing in human endothelial cells. Blood 99:2060-2069.