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:
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Investigations into the molecular and cellular basis of white blood cell trafficking (in particular neutrophils) in response to inflammatory insults.
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Exploring the interplay between vascular, tissue and immune cells that regulate vascular integrity and function.
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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
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.
Projects
Members
Prof. Sussan Nourshargh
Group Leader & Head of the CMR
Dr Loïc Rolas
Fellow
Dr Hai tao Wang
Postdoctoral Researcher
Dr Matthew Golding
Lab Manager
Laura Vazquez Martinez
Research Assistant
Dr Yue Yang
Postdoctoral Researcher
Joana Mateu
Centre Administrator
Dr Clare Latta
Postdoctoral Researcher
Publications
Neutrophil breaching of the blood vessel pericyte layer during diapedesis requires mast cell-derived IL-17A
Nat Commun. 2022 Nov 17;13(1):7029.
Joulia R, Guerrero-Fonseca IM, Girbl T, Coates JA, Stein M, Vázquez-Martínez L, Lynam E, Whiteford J, Schnoor M, Voehringer D, Roers A, Nourshargh S, Voisin MB.
Circulating BMP9 Protects the Pulmonary Endothelium during Inflammation-induced Lung Injury in Mice
Am J Respir Crit Care Med. 2021 Jun1 ;203(11):1419-1430.
Wei Li , Lu Long, Xudong Yang , Zhen Tong , Mark Southwood , Ross King , Paola Caruso , Paul D Upton , Peiran Yang , Geoffrey A Bocob , Ivana Nikolic , Angelica Higuera , Richard M Salmon , He Jiang , Katharine M Lodge , Kim Hoenderdos , Rebecca M Baron , Paul B Yu , Alison M Condliffe , Charlotte Summers , Sussan Nourshargh , Edwin R Chilvers , Nicholas W Morrell
Isoprenylcysteine Carboxylmethyltransferase-Based Therapy for Hutchinson-Gilford Progeria Syndrome
ACS Cent Sci. 2021 Aug 25;7(8):1300-1310.
Marcos-Ramiro B, Gil-Ordóñez A, Marín-Ramos NI, Ortega-Nogales FJ, Balabasquer M, Gonzalo P, Khiar-Fernández N, Rolas L, Barkaway A, Nourshargh S, Andrés V, Martín-Fontecha M, López-Rodríguez ML, Ortega-Gutiérrez 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
Cardiovascular Progerin Suppression and Lamin A Restoration Rescue Hutchinson-Gilford Progeria Syndrome
Circulation. 2021 Nov 30;144(22):1777-1794.
Sánchez-López A, Espinós-Estévez C, González-Gómez C, Gonzalo P, Andrés-Manzano MJ, Fanjul V, Riquelme-Borja R, Hamczyk MR, Macías Á, Del Campo L, Camafeita E, Vázquez J, Barkaway A, Rolas L, Nourshargh S, Dorado B, Benedicto I, Andrés V.
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
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.
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