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Nourshargh Lab

 

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.  

RESEARCH OVERVIEW

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Group Leader & Head of the CMR

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

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Dr Natalia Reglero-Real

Postdoctoral Researcher

GROUP MEMBERS

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.

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Dr Loïc Rolas

Postdoctoral Researcher

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.

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Dr Régis Joulia

Postdoctoral Researcher

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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.

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Laura Vazquez Martinez

Research Assistant

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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.

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Since joining the group in 2018, my main aim is to understand how aged endothelial cells specifically impact neutrophil vessel-wall interactions in vivo.

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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.

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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.

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Joshua Martin

PhD Student

Lorena Perez 

PhD Student

Dr Matthew Golding

Lab Manager

Joana Mateu

Centre Administrator

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.

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Dr Matthew Golding

Lab Manager

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.

Joana Mateu

Centre Administrator

GROUP ALUMNI

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I was born in Buckinghamshire in the UK. i completed a BSc in Biomedical Science at the University of Surrey and joined teh group in 2016 as 4 years PhD funded by BBSRC and GSK. My research focusses on the interplay between microvascular leakage and neutrophil migration. My hobbies include cooking, playing squash and visiting my two dogs.

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Charlotte Owen-Woods

PhD Student

Charlotte Owen-Woods

PhD Student

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I moved to the William Harvey Research Institute in 2014 where I conducted my masters studies, before joining CMR in 2015 to undertake a PhD which I have recently completed.  Now, within a postdoctoral role, my research focusses on investigating the impact of ageing on neutrophil-vessel wall interactions. Outside of the lab, I enjoy travelling, spending time with family and friends, and enjoying time outdoors in the countryside.

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I joined the group in 2016 as a 4 year PhD student and my research focusses on investigating the role of junctional adhesion molecule C (JAM-C) in endothelial cells in vivo.

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GROUP ALUMNI

Dr Anna Barkaway

Postdoctoral Researcher

Lorena Perez 

PhD Student

I moved to the William Harvey Research Institute in 2014 where I conducted my masters studies, before joining CMR in 2015 to undertake a PhD which I have recently completed.  Now, within a postdoctoral role, my research focusses on investigating the impact of ageing on neutrophil-vessel wall interactions. Outside of the lab, I enjoy travelling, spending time with family and friends, and enjoying time outdoors in the countryside.

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Dr Anna Barkaway

Postdoctoral Researcher

RECENT PUBLICATIONS

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

Leukocyte migration into inflamed tissues

Immunity, 2014 (694-707)

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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.

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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.

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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.

LATEST NEWS

CURRENT PROJECTS

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.

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