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
Publications
Leukocytes use endothelial membrane tunnels to extravasate the vasculature
Cell Rep
. 2025 Sep 23;44(9):116242.
Werner J van der Meer , Abraham C I van Steen , Eike Mahlandt, Loïc Rolas , Haitao Wang , Janine J G Arts , Lanette Kempers , Max L B Grönloh , Rianne M Schoon , Amber Driessen, Jos van Rijssel , Ingeborg Klaassen, Reinier O Schlingemann , Yosif Manavski , Mark Hoogenboezem , Reinier A Boon , Satya Khuon , Eric Wait , John Heddleston , Teng-Leong Chew , Martijn A Nolte , Sussan Nourshargh , Joachim Goedhart , Jaap D van Buul
Exacerbated atherosclerosis in progeria is prevented by progerin elimination in vascular smooth muscle cells but not endothelial cells
Proc Natl Acad Sci U S A
. 2024 Apr 30;121(18):e2400752121
Ignacio Benedicto, Rosa M Carmona, Ana Barettino , Carla Espinós-Estévez , Pilar Gonzalo, Rosa M Nevado, Miguel de la Fuente-Pérez , María J Andrés-Manzano, Cristina González-Gómez , Loïc Rolas , Beatriz Dorado, Sussan Nourshargh, Magda R Hamczyk , Vicente Andrés
ICAM-1 nanoclusters regulate hepatic epithelial cell polarity by leukocyte adhesion-independent control of apical actomyosin
Elife
. 2024 Apr 10:12:RP89261.
Cristina Cacho-Navas, Carmen López-Pujante, Natalia Reglero-Real , Natalia Colás-Algora , Ana Cuervo , Jose Javier Conesa , Susana Barroso , Gema de Rivas , Sergio Ciordia , Alberto Paradela , Gianluca D'Agostino , Carlo Manzo , Jorge Feito , Germán Andrés , Francisca Molina-Jiménez , Pedro Majano , Isabel Correas , José-Maria Carazo , Sussan Nourshargh , Meritxell Huch, Jaime Millán
Senescent endothelial cells promote pathogenic neutrophil trafficking in inflamed tissues
EMBO Rep
. 2024 Sep;25(9):3842-3869.
Loïc Rolas , Monja Stein, Anna Barkaway , Natalia Reglero-Real, Elisabetta Sciacca, Mohammed Yaseen, Haitao Wang, Laura Vazquez-Martinez, Matthew Golding, Isobel A Blacksell , Meredith J Giblin , Edyta Jaworska, Cleo L Bishop , Mathieu-Benoit Voisin, Carles Gaston-Massuet , Liliane Fossati-Jimack, Costantino Pitzalis, Dianne Cooper, Thomas D Nightingale, Carlos Lopez-Otin, Myles J Lewis, Sussan Nourshargh
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







