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The William Harvey Research Institute - Barts and The London

Professor Sussan Nourshargh

Sussan

Head of the Centre for Microvascular Research

Centre: Microvascular Research

Email: s.nourshargh@qmul.ac.uk
Telephone: +44(0) 20 7882 8240 


Profile

Sussan Nourshargh is a pharmacologist who studied at University College London (BSc) and King’s College London (PhD) and became Professor of Immunopharmacology at Imperial College London in 2006. In 2007 she joined Queen Mary University of London where she established the Centre for Microvascular Research within the William Harvey Research Institute. 

Awards

  • The Gabor Kaley Prize in Microcirculation Research from the American Societies of Physiology and Microcirculation (2016)
  • The Astra Zeneca Prize for Women in Pharmacology from the British Pharmacology Society (2014)
  • Quintiles Prize for outstanding contribution to Immunopharmacology from the British Pharmacology Society (2001)

Fellowships

  • Wellcome Trust Senior Investigator Award (2012)
  • Fellow of the Academy of Medical Sciences (2012)
  • Fellow of the Society of Biology (2010)
  • Fellow of the British Pharmacological Society (2005)
  • Wellcome Trust University Award (1996)
  • Wellcome Trust Career Development Fellowship (1990) 

Memberships

  • British Heart Foundation Board of Trustees and Advisory Council (2015 - date)
  • Wellcome Trust’s Biomedical Resources & Multi-User Equipment Committee (2015-2018)
  • Academy of Medical Sciences Springboard Panel (2015-2017)
  • Chair and Member of the Academy of Medical Sciences Committee (SC3) for selection of new Fellows (2012-2017)
  • Royal Society’s Newton Advanced Fellowship Panel (2014-2016)
  • British Heart Foundation Fellowship Committee (2011-2014)
  • Wellcome Trust’s Peer Review College (2012-2016)
  • Treasurer of the UK Adhesion Society (2007-2016)
  • Editor, European Journal of Immunology (2013 to date)
  • Editor, British Journal of Pharmacology (2010-2013) 

Research

Group members

Research staff: Natalia Reglero, Loïc Rolas, Regis Joulia
PhD students: Anna Barkaway, Charlotte Owen-Woods, Lorena Perez, Monja Stein
Support staff: Matthew Golding (Lab Manager), Joana Mateu (Centre Administrator)

Summary 

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 models for analysis of both physiologically relevant as well as pathological inflammatory models and a key component of our work is a research programme that investigates 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 (Senior Investigator Award), the British Heart Foundation, BBSRC and the European Commission. 

Key Publications

For a full list of publications click here

  • Voisin M. B.,& Nourshargh S. Neutrophil trafficking to lymphoid tissues: physiological and pathological implications. J Pathol,. (2019). In press.
  • 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 U. H., Voisin M. B., Rot A. & Nourshargh S.Distinct compartmentalization of the chemokines CXCL1 and CXCL2 and the atypical receptor ACKR1 determine discrete stages of neutrophil diapedesis. Immunity, 49 (2018): 1062-1076.
  • Callender L. A., Carroll E. C., Beal R. W. J., Chambers E. S., Nourshargh S., Akbar A. N. & Henson S. M. “Human CD8+ EMRA T cells display a senescence-associated secretory phenotype regulated by p38 MAPK”. Ageing Cell, (2018).
  • Schulz-Fincke A-C., Tikhomirov A.S., Braune A., Girbl T., Gilberg E., Bajorath J., Blaut M., Nourshargh S. & Gütschow M. “Design of an activity-based probe for human neutrophil elastase: Implementation of the lossen rearrangement to induce Förster resonance energy transfers”. Biochemistry, 57 (2018): 742-752.
  • Arokiasamy S., Zakian C., Dilliway J., Wang W., Nourshargh S. & Voisin M. B. “Endogenous TNFα orchestrates the trafficking of neutrophils into and within lymphatic vessels during acute inflammation”. Scientific Reports, 7 (2017): 44189.
  • Gittens B. R., Bodkin J. V., Nourshargh S. Perretti M. & Cooper D. “Galectin-3: A positive regulator of leukocyte recruitment in the inflamed microcirculation.” J. Immunol. 198 (2017): 4458-4469.
  • Cabrera C. P., Manson J., Shepherd J. M., Torrance H. D., Watson D., Longhi M. P., Hoti M., Patel M., O’Dwyer M., Nourshargh S., Pennington D. J., Barnes M. R. & Brohi K. “Signatures of inflammation and impending multiple organ dysfunction in the hyperacute phase of trauma – A multimodal prospective cohort study”. PLOS Medicine 14 (7) (2017):  e1002352.
  • Barzilai S., Yadav S. K., Morrell S., Roncato F., Klein E., Stoler-Barak L., Golani O., Feigelson S. W., Zemel A., Nourshargh S. & Alon R. “Leukocytes breach endothelial barriers by insertion of nuclear lobes and disassembly of endothelial actin filaments”. Cell Reports, 18: 685-699 (2017).
  • Reglero-Real N, Colom B, Bodkin JV, Nourshargh S. Endothelial Cell Junctional Adhesion Molecules: Role and Regulation of Expression in Inflammation. Arterioscler Thromb Vasc Biol., 36: 2048-2057 (2016). [Cover image provided].
  • Nourshargh S, Renshaw SA, Imhof BA. Reverse Migration of Neutrophils: Where, When, How, and Why? Trends in Immunol., 37: 273-286 (2016).
  • Woodfin A, Beyrau M, Voisin MB, Ma B, Whiteford JR, Hordijk PL, Hogg N,  Nourshargh S. ICAM-1-expressing neutrophils exhibit enhanced effector functions in murine models of endotoxemia. Blood, 127: 898-907 (2016).
  • Colom B., Bodkin J., Beyrau M., Woodfin A., Voisin M-B., Brohi K., Chavakis T., Imhof B. A., and   Nourshargh S. Leukotriene B4-neutrophil elastase axis drives neutrophil reverse transendothelial cell migration in vivo. Immunity, 42: 1075-1086 (2015).
  • Nourshargh S and Alon R. Leukocyte migration into inflamed tissues: cross-talks between effector leukocytes and venular walls. Immunity, 41: 694-707 (2014). 
  • Finsterbusch M., Voisin M-B., Beyrau M., Williams T. J. and Nourshargh S. Neutrophils recruited by chemoattractants in vivo induce microvascular plasma protein leakage through secretion of TNF. J Exp Med., 21:1307-1314 (2014).
  • Leinster D.A., Colom B., Whiteford J. R., Ennis D. P., Lockley M., McNeish I. A., Aurrand-Lions M., Chavakis T., Imhof B. A., Balkwill F. R. and  Nourshargh S. Endothelial cell junctional adhesion molecule-C plays a key role in the development of tumours in a murine model of ovarian cancer. FASEB J., 27: 4244-4253 (2013).
  • Proebstl, D., M.B. Voisin, A. Woodfin, J. Whiteford, F. D'Acquisto, G.E. Jones, D. Rowe and  S. Nourshargh. Pericytes support neutrophil subendothelial cell crawling and breaching of venular walls in vivo. J Exp Med., 209:1219-34 (2012).
  • Colom, B., Y. Poitelon, W. Huang, A. Woodfin, S. Averill, U. Del Carro, D. Zambroni, S.D. Brain, M. Perretti, A. Ahluwalia, J.V. Priestley, T. Chavakis, B.A. Imhof, M.L. Feltri and  S. Nourshargh. Schwann cell-specific JAM-C-deficient mice reveal novel expression and functions for JAM-C in peripheral nerves. FASEB J., 26:1064-76 (2012).
  • Woodfin, A., M.B. Voisin, M. Beyrau, B. Colom, D. Caille, F.M. Diapouli, G.B. Nash, T. Chavakis, S.M. Albelda, G.E. Rainger, P. Meda, B.A. Imhof and  S. Nourshargh. The junctional adhesion molecule JAM-C regulates polarized transendothelial migration of neutrophils in vivo. Nat Immunol., 12:761-9 (2011).
  • Nourshargh, S., P.L. Hordijk and M. Sixt. Breaching multiple barriers: leukocyte motility through venular walls and the interstitium. Nat Rev Mol Cell Biol., 11:366-78 (2010) 
  • Voisin, M.B., D. Probstl and S. Nourshargh. Venular basement membranes ubiquitously express matrix protein low-expression regions: characterization in multiple tissues and remodeling during inflammation. Am J Pathol., 176:482-95 (2010).
  • Scheiermann, C., B. Colom, P. Meda, N.S. Patel, M.B. Voisin, A. Marrelli, A. Woodfin, C. Pitzalis, C. Thiemermann, M. Aurrand-Lions, B.A. Imhof and  S. Nourshargh. Junctional adhesion molecule-C mediates leukocyte infiltration in response to ischemia reperfusion injury. Arterioscler Thromb Vasc Biol., 29:1509-15 (2009). 
  • Voisin, M.B., A. Woodfin and S. Nourshargh. Monocytes and neutrophils exhibit both distinct and common mechanisms in penetrating the vascular basement membrane in vivo. Arterioscler Thromb Vasc Biol., 29:1193-9 (2009).
  • Woodfin, A., M.B. Voisin, B.A. Imhof, E. Dejana, B. Engelhardt and S. Nourshargh. Endothelial cell activation leads to neutrophil transmigration as supported by the sequential roles of ICAM-2, JAM-A, and PECAM-1. Blood, 113:6246-57 (2009).
  • Scheiermann, C., P. Meda, M. Aurrand-Lions, R. Madani, Y. Yiangou, P. Coffey, T.E. Salt, D. Ducrest-Gay, D. Caille, O. Howell, R. Reynolds, A. Lobrinus, R.H. Adams, A.S. Yu, P. Anand, B.A. Imhof and  S. Nourshargh. Expression and function of junctional adhesion molecule-C in myelinated peripheral nerves. Science, 318:1472-5 (2007). 
  • Ley, K., C. Laudanna, M.I. Cybulsky and S. Nourshargh. Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol., 7:678-89 (2007).
  • Woodfin, A., C.A. Reichel, A. Khandoga, M. Corada, M.B. Voisin, C. Scheiermann, D.O. Haskard, E. Dejana, F. Krombach and  S. Nourshargh. JAM-A mediates neutrophil transmigration in a stimulus-specific manner in vivo: evidence for sequential roles for JAM-A and PECAM-1 in neutrophil transmigration. Blood, 110: 1848-56 (2007).
  • Wang, S., M.B. Voisin, K.Y. Larbi, J. Dangerfield, C. Scheiermann, M. Tran, P.H. Maxwell, L. Sorokin and  S. Nourshargh. Venular basement membranes contain specific matrix protein low expression regions that act as exit points for emigrating neutrophils. J Exp Med., 203:1519-32 (2006).
  • Huang, M.T., K.Y. Larbi, C. Scheiermann, A. Woodfin, N. Gerwin, D.O. Haskard and  S. Nourshargh. ICAM-2 mediates neutrophil transmigration in vivo: evidence for stimulus specificity and a role in PECAM-1-independent transmigration. Blood, 107:4721-7 (2006).

Collaborators

  • Professor Beat Imhof, Department of Pathology & Immunology, University of Geneva.
  • Professor Karim Brohi, Trauma Centre, Queen Mary University of London.
  • Professor Antal Rot, Centre for Microvascular Research, William Harvey Research Institute, Queen Mary University of London.
  • Professor Carlos Lopez Otin, University of Oviedo, Spain.
  • Professor Trian Chavakis, Department of Internal Medicine, Technical University of Dresden.
  • Professor Axel Roers, Director Institute of Immunology, Technical University of Dresden.
  • Dr Sharon Tooze, Crick Institute, London.

News

  • The paper by Girbl et al., Immunity, 2018, receives the prestigious Servier Award in Microcirculation. This award is given every two years by the European Society for Microcirculation and European Vascular Biology Society to an outstanding publication on microcirculation/vascular biology in basic or clinical research (http://esm-evbo2019.org/registration/travel-awards/).
  • BHF Accelerator Award (Director Prof Federica Marelli-Berg & Deputy Director Prof Sussan Nourshargh), £1,000,000 for 5 years starting in April 2019.
  • Plenary Lecture at the 1st Meeting in Translational Pharmacology of the joint Spanish, Italian, Portuguese and Greek Pharmacological Societies, Santiago de Compostela, Spain, June 2018. 
  • Plenary Speaker at World Congress of Microcirculation, Vancouver, September 2018 (www.wcm2018.org).
  • Royal Society Newton Advanced Fellowship Grant (2018) in collaboration with Dr Michael Schnoor, Department of Molecular Biomedicine, CINESTAV, Mexico-City, Mexico.
  • Awarded a BHF Project Grant (2018).
  • Awarded a BHF Infrastructure Grant towards the purchase of a multiphoton confocal microscope (2017).
  • Professor Antal Rot, University of York, joins Centre for Microvascular Research (2017).
  • Dr Regis Joulia (University of Toulouse) joins the group and is awarded a Marie Curie EU Horizon CoFund Grant (2017).
  • Dr Loic Rolas (INSERM, Paris) joins the group and is awarded a Marie Curie EU Horizon CoFund Grant (2016).
  • Awarded the Gabor Kaley Prize in Microcirculation Research from the American Societies of Physiology and Microcirculation (2016).
  • Professor Ken Suzuki and team join Centre for Microvascular Research (2016).
  • Dr Natalia Reglero (UAM, Madrid) joins the group and is awarded a Marie Curie EU Horizon CoFund grant (2015).
  • Professor Sussan Nourshargh joins the British Heart Foundation Board of Trustees and Advisory Council (2015).
  • Awarded the Astra Zeneca Prize for Women in Pharmacology from the British Pharmacology Society (2014).