Vascular Biology and Cell Trafficking Laboratory
Blood vessels make up the vascular system that transports cells, oxygen and nutrients throughout all tissues and organs. Blood vessels are critical in the fight against disease and improved understanding of endothelial cells (ECs, specialised cells which form the inner lining of blood vessels), will provide new treatment options for many diseases, including cancer, heart disease and diabetes.
Our laboratory has three main areas of interest.
Firstly, vasculogenic mimicry (VM), a process wherein cancer cells themselves form vascular-like structures to increase access to the blood supply to assist in tumour growth. In both breast cancer and melanoma, increased VM is associated with poor clinical outcome. We have begun to identify novel elements in VM and are now targeting these in an attempt to prevent the progression of breast cancer and melanoma.
Secondly, endothelial progenitor cells (EPCs) directly contribute to blood vessel formation (vasculogenesis) and can be used to support organ transplantation. Using nanotechnology we are developing smart surface biomaterials to co-transplant EPCs with insulin-producing beta islet cells to help cure patients with type 1 diabetes.
Third, vascular occlusions are a major contributor to cardiovascular disease (CVD) which is a leading cause of death worldwide. Overcoming these occlusions requires insertion of devices (such as stents) to maintain vessel diameter. Our innovative concept modifies stents (first coated with a patented low-fouling surface and then topped with our novel peptides to specifically capture endothelial cells) to provide rapid revascularisation of implanted devices for minimal intervention and medication. This work is led by Dr Eli Moore (Biocompatible Devices Group).
Current research projects
- Vasculogenic mimicry in cancer progression: For solid tumours to grow they require access to the blood supply for the provision of oxygen and nutrients. Highly vascularised tumours correlate with poor survival for patients with e.g. melanoma and breast cancer. Tumour vascularisation can occur via a number of processes including angiogenesis (the proliferation of existing blood vessel endothelial cells (ECs), which form the inner monolayer of blood vessels) as well as an EC-independent manner known as vasculogenic mimicry (VM, wherein vascular-like channels are formed by the cancer cells themselves). Our work in melanoma, pancreatic cancer and breast cancer has identified key growth factors and adhesion molecules which underpin VM and are now of interest in terms of developing new treatment opportunities for patients.
- Endothelial progenitor cells (EPCs) in disease: With a focus on how the vasculature contributes to health and disease, we have a strong programme on endothelial progenitor cells (the precursors of cells which form the inner lining of all blood vessels). Having recently identified a suite of novel surface expressed proteins by EPCs we are have begun to unravel how EPCs contribute to health and disease. For example, in Type 1 Diabetes, pancreatic islet transplantation is the only current cure, but success is limited by death of insulin producing beta cells post-transplantation. EPCs have the potential to improve islet engraftment and production of insulin. Our work understanding the critical cross-talk between the vasculature and beta islet cells together with smart surface materials will advance our ability to cure diabetes.
- Nanotechnology and biomaterials for cardiovascular disease: Exposure of foreign materials (e.g. metal stents) directly with blood can immediately trigger platelet activations (thrombosis) while restenosis can build up over time as vascular smooth muscle cells (SMCs) migrate to the site of the trauma and accumulate on exposed portions of the device. Despite incremental advances in stents and post operative care, there still exists a large gap between the current best performing stents and what would be considered the ideal performance for these implanted devices. Our novel technology could see a closing of this gap with a new generation of low-fouling implantable medical devices.
Publication list available via: