Our work aims to unravel the cellular and molecular basis of several fundamental aspects of immunity, inflammation and vascular biology. Most notably we have made internationally rated contributions to the mechanisms through which white blood cells (in particular neutrophils) breach blood vessel walls to enter inflamed tissues.
Principal research objectives include:
Investigations into the molecular and cellular basis of white blood cell trafficking (in particular neutrophils) in response to inflammatory insults.
Exploring the interplay between vascular, tissue and immune cells that regulate vascular integrity and function.
Investigating the above fundamental concepts under physiological and pathological conditions and in response to ageing.
The team employs a multidisciplinary approach in addressing its objectives and in particular applies advanced microscopy techniques (e.g. confocal intravital microscopy) to analyse white blood cell behaviours in relation to blood vessel walls.
I obtained my PhD at Universidad Autónoma of Madrid, where I studied the role of apicobasal polarity in hepatocyte-leukocyte interactions during liver inflammation. I joined the group in 2015 as a postdoctoral researcher and currently investigate the molecular mechanisms through which endothelial cells regulate leukocyte-vessel walls interactions. In my spare time I love travelling, reading and I’m a huge fan of contemporary dance
My entire life was spent in Paris, from when I was born until obtaining my PhD in 2015. In 2016 I moved to London to join the group as a post-doctoral fellow. My current project investigates neutrophil migration through blood vessels in the context of ageing. Here I’ve learnt to properly use a confocal microscope and it's been fascinating to discover how similar this is to photography, one of my passions.
I studied a Biology degree at the University of Manchester, with a year abroad at the University of Kentucky, before completing a PhD at the University of Edinburgh. My PhD research focussed on understanding myeloid cell dynamics during acute brain inflammation. I joined the group in 2021 as a postdoctoral researcher to explore novel candidates involved in leukocyte extravasion into inflamed tissues. My personal interests include reading, exploring new places and spending time with friends
I am from Spain and studied for a Biology Degree at the Complutense University of Madrid before completing an MSc in Neuroscience at the Autonomous University of Madrid. After this, I worked at Imperial College London for two years within a group investigating atherosclerosis, before joining my current group in August 2019 as a research assistant. I really like travelling and getting to know other cultures, dancing (Latin music) and cooking.
Dr Natalia Reglero-Real
Dr Loïc Rolas
Dr Clare Latta
Laura Vazquez Martinez
I obtained a BSC in Reproductive Biology and an MSC in Biomedical Science at the University of Edinburgh, with a year abroad at the Queens University in Canada. In September 2020 I began a CRUK funded PhD focussing on how cancer cells hijack immune cell mechanisms to cross endothelial barriers.
Outside the lab I am keen cyclist and skier and enjoy watching rugby, playing golf and exploring London.
Since joining the group in 2018, my main aim is to understand how aged endothelial cells specifically impact neutrophil vessel-wall interactions in vivo.
Prior to joining the CMR in 2014 as a lab manager, I worked as a Scientific Officer over a 15-year period at three different Cancer Research UK-funded laboratories researching various topics including breast and liver cancer, endothelial biology and neuropathology. My current role has allowed me to add to this knowledge base through learning about immunological processes with a particular focus on neutrophil mediated inflammatory responses. My personal interests include understanding and exploring the natural world, and I keenly follow international rugby and athletics.
I was born in a small town near Barcelona and moved to Barcelona to study for my higher education degree. I worked there for several years and then came to England in 1999 where I completed my Masters degree. Before joining CMR, I worked for a number of years at the National Oceanography Centre in Southampton. I enjoy movies, visiting art galleries and spending time with my friends and family.
Dr Matthew Golding
I come from Nanjing, China, a beautiful ancient capital of six dynasties. I got my PhD at Nanjing Medical University. I join WHRI at Queen Mary University of London in early 2022 and start my post-doctoral research work. I love the research and exploration of tissue imaging and hope to have better harvest in beautiful London.
Dr Hai tao Wang
I have a BSC in Biochemistry and Biophysics from Rensselaer Polytechnic Institute in New York. I completed my PhD in Cell and Developmental Biology at Vanderbilt University in 2021. My PhD research was focused on understanding the role of cytokine-induced ECM alterations in diabetic retinopathy pathology. I joined the group in 2022 and will be working to characterize the transcriptome of rTEM neutrophils.
Dr Charlotte Owen-Woods
Dr Anna Barkaway
Dr Lorena Perez
My research aims to understand the impact of vascular permeability and the role of perivascular mast cells on neutrophil migration through the use of intra-vital microscopy.
Dr Régis Joulia
Age-related changes in the local milieu of inflamed tissues cause aberrant neutrophil trafficking and subsequent remote organ damage
Immunity, 2021 Jul 13;54(7):1494-1510.e7
Barkaway A, Rolas L, Joulia R , Bodkin J, Lenn T, Owen-Woods C, Reglero-Real N, Stein M, Vázquez-Martínez L, Girbl T, Poston RN, Golding M, Saleeb RS, Thiriot A, von Andrian UH, Duchene J, Voisin MB, Bishop CL, Voehringer D, Roers A, Rot A, Lämmermann T and Nourshargh S
Autophagy modulates endothelial junctions to restrain neutrophil diapedesis during inflammation
Immunity, 2021 Aug 5;S1074-7613(21)00298-3
Reglero-Real N, Pérez-Gutiérrez L,Yoshimura A, Rolas L, Garrido-Mesa J, Barkaway A, Pickworth C, Saleeb RS, Gonzalez-Nuñez M,Austin-Williams SN, Cooper D, Vázquez-Martínez L, Fu T, De Rossi G, Golding M, Benoit-Voisin M, Boulanger CM, Kubota Y, Muller WA, Tooze SA, Nightingale TD, Collinson L, Perretti M, Aksoy E and Nourshargh S
Local microvascular leakage promotes trafficking of activated neutrophils to remote organs
The Journal of Clinical Investigation, 2020 (130; 2301-2318)
Owen-Woods C, Joulia R, Barkaway A, Rolas L, Ma B, Nottebaum AF, Arkill KP, Stein M, Girbl T, Golding M, Bates DO, Vestweber D, Voisin MB, and Nourshargh S.
Development of a CRISPR/Cas9-based therapy for Hutchinson-Gilford progeria syndrome
Nature Medicine, 2019 (25; 423-426)
Santiago-Fernández O, Osorio FG, Quesada V, Rodríguez F, Basso S, Maeso D, Rolas L, Barkaway A, Nourshargh S, Folgueras AR, Freije JMP and López-Otín C
Distinct compartmentalization of the chemokines CXCL1 and CXCL2 and the atypical receptor ACKR1 determine discrete stages of neutrophil diapedesis
Immunity, 2018 (49; 1062-1076)
Girbl T, Lenn T, Perez L, Rolas L, Barkaway A, Thiriot A, Del Fresno C, Lynam E, Hub E, Thelen M, Graham G, Alon R, Sancho D, von Andrian UH, Voisin MB, Rot A and Nourshargh S
ICAM-1 expressing neutrophils exhibit enhanced effector functions in murine models of endotoxemia
Blood, 2016 (127; 898-907)
Woodfin A, Beyrau M, Voisin MB, Ma B, Whiteford JR, Hordijk PL, Hogg N and Nourshargh S
Leukotriene B4-neutrophil elastase axis drives neutrophil reverse transendothelial cell migration in vivo
Immunity, 2015 (42; 1075-1086)
Colom B, Bodkin JV, Beyrau M, Woodfin A, Ody C, Rourke C, Chavakis T, Brohi K, Imhof BA and Nourshargh S
Pericytes support neutrophil sub-endothelial cell crawling and breaching of venular walls in vivo
Journal of Experimental Medicine, 2012 (209; 1219-1234)
Proebstl D, Voisin MB, Woodfin A, Whiteford J, D'Acquisto F, Jones GE, Rowe D and Nourshargh S
The junctional adhesion molecule JAM-C regulates polarized transendothelial cell migration of neutrophils in vivo
Nature Immunology, 2011 (12; 761–769)
Woodfin A, Voisin MB, Beyrau M, Colom B, Caille D, Diapouli FM, Nash GB, Chavakis T, Albelda SM, Rainger GE, Meda P, Imhof BA and Nourshargh S
Expression and function of junctional adhesion molecule-C in myelinated peripheral nerves
Science, 2007 (318; 1472-1475)
Scheiermann C, Meda P, Aurrand-Lions M, Madani R, Yiangou Y, Coffey P, Salt TE, Ducrest-Gay D, Caille D, Howell O, Reynolds R, Lobrinus A, Adams RH, Yu AS, Anand P, Imhof BA, and Nourshargh S
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 research on reverse migration published
London, February 2020
The latest research from the Nourshargh lab has been published, which demonstrates that increased microvascular leakage reverses the localization of directional cues across venular walls, thus causing neutrophils engaged in diapedesis to reenter the systemic circulation. This offers a mechanism to explain how local tissue inflammation and vascular permeability can induce downstream pathological effects in remote organs.
Access the full article here.
Anna Barkaway’s PhD Graduation ceremony
London, December 2019
We are thrilled to celebrate Dr Anna Barkaway's graduation! Anna received her doctorate for her work in Prof. Sussan Nourshargh's team researching the mechanisms behind neutrophil migration.
The principal objective of our research is to investigate the mode, dynamics and mechanisms of leukocyte transmigration, the final stage in the leukocyte adhesion cascade that describes the movement of leukocytes from the vascular lumen into inflamed and/or injured tissues. To achieve this goal, we employ a multi-disciplinary approach to investigate the associated molecular and cellular pathways involved in neutrophil-vessel wall interactions. A key approach is the application of confocal intravital microscopy that enables rigorous and direct means of investigating the interactions of leukocytes with different components of microvessel walls (endothelial cells, pericytes and the vascular basement membrane) in real-time in vivo.
We employ both physiological and pathological inflammatory models to analyse neutrophil trafficking. Within this overall remit, a key component of our work is investigations into how pathological inflammatory insults impact the dynamics of neutrophil-vessel wall interactions and the implications of disrupted modes of neutrophil transmigration (e.g. neutrophil reverse transendothelial cell migration) on inflammatory disease development and dissemination.
Collectively through the application of molecular and cellular assays, and advanced imaging platforms, our work aims to unravel previously unexplored cellular and molecular physiological concepts and identify disease-specific phenomena in immunity, inflammation and vascular biology.
Our work is largely funded by the Wellcome Trust (Investigator Award), the British Heart Foundation, BBSRC and the European Commission.