Nourshargh, Sussan

Head, Centre for Microvascular Research

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 a new Centre focusing on 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 (2015-2018)
  • 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) 

Summary of 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 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. 

Teaching 

Co-lead: Research Techniques in Pharmacology (BMD175) BSc Pharmacology and Innovative Therapeutics

Members of the Group 

Research staff: Tamara Girbl, Natalia Reglero, Ross King, Loïc Rolas, Regis Joulia, Yueng Lenn

PhD students: Anna Barkaway, Charlotte Owen-Woods, Lorena Perez

Support staff: Matthew Golding (Lab Manager); Phedre James (Centre Administrator)

Key Publications

For a full list of publist publications click here

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).

 

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