Nightingale Lab
Research in my lab centres on the biology of the cells that line blood vessels (endothelial cells). These have important roles during injury and inflammation, helping to mediate the recruitment of white blood cells and to promote the process of blood clotting.
We are particularly interested in the way in which key proteins are regulated by being moved intracellularly, this is used as a means to control dynamic changes in endothelial function, secretion etc. We monitor this using live cell imaging, electron microscopy, molecular biology and proximity labelling proteomics.
By defining some of the molecular pathways required we aim to identify new ways to control inflammation and blood clotting.
My PhD is focusing on protein trafficking in the endothelium, and the consequences it can have on vascular function. Proteins of particular interest are JAM-C and NRP1.
Tom Mitchell
PhD Student
GROUP MEMBERS
All the way from Scotland, this cell biologist, fly-fishing guru is interested in how endothelial cells release a blood clotting factor in response to injury.
I am interested in the immunological consequences of a single nucleotide polymorphism within the ACKR1 gene which is prevalent in African populations.
My research aims to understand the role of atypical chemokine receptors in the alteration of the immune system and subsequent impacts on tumour growth and progression.
Dr Sammy El Mansi
Postdoctoral Researcher
Dr Caroline Anderson
Postdoctoral Researcher
Dr Maryna Samus
Postdoctoral Researcher
My PhD is focused on investigating the expression and function of ACKR4 in the heart. My work aims to characterise localisation and cell type expression of ACKR4, as well as its effect on heart function and health.
Stefan Russo
PhD Student
Background:
Physician Surgeon (UNAM, Mexico); MSc. Regenerative Medicine (QMUL, London)
Current research:
Exosomes and biomaterials for heart failure. Other interests: Immunology, 3D printing, patient specific implants & biofabrication.
Dr Esteban Ortega
PhD Student
I am a Cardiology SpR based at Barts Hospital and am currently undertaking a PhD investigating the efficacy of stem-cell therapy in patients with DCM.
Dr Mohsin Hussain
PhD Student
GROUP ALUMNI
Fields of research interest:
Tissue engineering, stem cell therapy
Research:
Biomaterials design for epicardial placement of mesenchymal stem cells for the treatment of myocardial infarction
Yaqi You
PhD Student
Graduate of The University of Aberdeen (BSc Sport & Exercise Science) and Queen Mary University of London (MRes Inflammation) with an interest in the role of M2-like macrophages in cardiac repair after myocardial infarction.
GROUP ALUMNI
Mihai Podaru
PhD Student
RECENT PUBLICATIONS
You can see our full publication list here. If you cannot access any of our papers, please do contact us, we would be happy to share a copy.
LATEST NEWS
An investigation into novel regulatory mechanisms for Von Willebrand factor secretion from endothelial cells
Funded by the British Heart Foundation
The response to vascular injury or infection is fast; this minimises loss of blood and spread of pathogens. As such, endothelial cells harbour specialised rod shaped storage organelles (WPB) that contain multiple pre-made pro-inflammatory and pro-haemostatic proteins. Within minutes of endothelial cell stimulation WPB are exocytosed and release their stored content into the vasculature thus starting the processes of both haemostasis and leukocyte recruitment.
The most important haemostatic component of WPB is the glycoprotein VWF that comprises 90% of stored protein. Upon exocytosis these tubules are unfurled by the shear force present in the blood vasculature to produce millimetre-long protein strings revealing multiple binding sites for platelets. Failure to secrete properly processed VWF either due to mutation of the protein itself or due to defects in cellular machinery associated with WPB formation result in bleeding (Von Willebrands disease). Conversely, a failure to appropriately remove VWF from the blood stream due to an inactivity or absence of the shear dependent metalloprotease ADAMSTS13, results in thrombotic thrombocytopenic purpura, a syndrome that is typified by multiple microvascular occlusions. These two syndromes additionally serve to highlight the importance of VWF in cardiovascular disease and stroke. Animal models and patients with VWF disease exhibit a decreased incidence of atherosclerosis. Conversely patients with elevated levels of VWF have an increased risk of major cardiac events and stroke.
We are investigating novel means to regulate VWF secretion that are controlled by an actomyosin ring. By understanding this mechanism we hope, in the long term, to develop novel strategies for limiting cardiovascular disease and stroke.
Trafficking of endothelial tight junction proteins during cell migration and angiogenesis
Blood vessels are essential for providing cells and tissues with oxygen and nutrients. New blood vessel formation (angiogenesis) occurs naturally during growth and development as well as during wound healing. In certain disease states angiogenesis can be subverted to support tumour formation and growth, whilst in other situations it becomes uncontrolled causing eye disease by blocking normal visual responses. Our research has shown that during cell migration intracellular trafficking is used as a means to remove junctional proteins, such as Jam-C, allowing cells to move, these junctions then reform.
We are characterising the mechanism for this remodelling to find new ways to control pathological angiogenesis.
Trafficking of endothelial tight junction proteins during inflammation
Funded by the Medical Research Council
Leukocyte recruitment from the blood vascular to infected tissues is a crucial part of the normal inflammatory response and allows clearance of pathogens from the affected area. However in some situations inappropriate and excessive recruitment of leukocytes can result in chronically inflamed tissues. The control of this process is therefore central to a normal resolution of an inflammatory situation. The blood vascular endothelium plays a key part in this process as a number of endothelial cell surface receptors such as P- and E-selectin, CD31 and the Junctional Adhesion Molecules (JAMs) have important roles in the recruitment and transmigration of leukocytes through blood-vessel walls.
Some of these adhesion receptors such as Jam-C are known to undergo intracellular trafficking and are found on intracellular vesicles and non-junctional plasma membrane following certain stimuli. Our research centres on the mechanisms and machinery required for this intracellular trafficking and the subsequent impact on transmigration of leukocytes through the endothelial cell layer.
