Our research investigates the mechanisms underlying regulation of blood vessel formation and function of the mature cardiovascular system by Vascular Endothelial Growth Factor (VEGF) and other growth factors. A major focus of this work is to identify the signalling pathways and receptors involved in these biological functions of VEGF, communication between them and how they integrate into physiologically relevant networks. We are pursuing these aims through in vivo analysis in disease and genetic models, combined with imaging and biochemical studies in cell culture. Another important aspect of our work is the development of new therapeutic approaches designed either to promote or to inhibit VEGF functions dependent on the disease context. Research in our centre is supported by major programme grant funding from the British Heart Foundation, and additional funding from the European Commission (EC), and Biotechnology and Biological Sciences Research Council (BBSRC).
Key research activities
- Role of Neuropilins in Angiogenesis and VEGF Signalling
Neuropilins (NRP) are co-receptors for VEGF with an essential role in angiogenesis in development. Our recent work has highlighted selective roles for NRP1 both in VEGF signalling and in cell migration and our aim is to investigate the mechanisms involved in these key processes and the important molecular partners for NRP1 in angiogenesis using novel in vivo models and diverse experimental analysis of cell cultures.
- Developing Neuropilin-Targeted Therapies
NRPs have emerged as novel targets for the development of new therapeutic approaches to inhibiting angiogenesis involved in diverse human diseases, including cancer and eye disease. Together with a small biotechnology company called Ark Therapeutics, we are developing novel small molecules designed to inhibit the function of NRP1 in the vasculature, which have therapeutic potential as novel anti-angiogenic drugs. To generate new opportunities for developing therapies targeted at the VEGF/NRP1 signalling axis, we are also investigating the structure of Neuropilins complexed with VEGF in collaboration with investigators in the UCL Department of Structural and Molecular Biology.
- Neuropilin in Regenerative Cardiovascular Medicine
Dr Mullen is the Chief Investigator for the AIMS study (Aortic Irbesartan Marfan Syndrome Study).
This randomised controlled multi centre UK study is evaluating the effect of Irbesartan on aortic dilatation in patients with Marfan syndrome. The study is supported by a British Heart Foundation grant of £1.5M.