Sussan Nourshargh graduated in Pharmacology from University College London in 1982 and obtained her PhD in Pharmacology from King’s College London in 1986. She initiated her academic career as a Lecturer at the National Heart & Lung Institute (NHLI) in London in 1988 and became Professor of Immunopharmacology at Imperial College London in 2006.

In 2007 she was appointed as Professor of Microvascular Pharmacology by the William Harvey Research Institute to establish and head a new Centre focussing on Microvascular Research.

Position

Head, Centre for Microvascular Research (s.nourshargh@qmul.ac.uk).

Fellowships

• Wellcome Trust Career Development Fellowship (1990),
• Wellcome Trust University Award (1996),
• Fellow of the British Pharmacological Society (2005) and
• Fellow of the Society of Biology (2010).

External activities

• British Heart Foundation Fellowship Committee (2011-2014),
• Treasurer of the UK Adhesion Society (2007 to date),
• Editor of British Journal of Pharmacology (2010 to date) and
• Microcirculation (2010 to date)
• Currently member of numerous European Scientific Advisory Boards.

Funding

Largely funded by a Wellcome Trust Programme Grant (2007-2012) and several grants from the British Heart Foundation.

 

 

Current research interests

Our work focuses on unraveling the mechanisms of leukocyte trafficking into sites of inflammation and the consequence of this response on regulating the phenotype of tissue infiltrated cells (Nourshargh et al., Nature Rev Cell Biol., 2010; Ley et al., Nature Rev Immunol., 2007). The overall objective of our work is to fully elucidate the cellular and molecular events that regulate polarized migration of leukocytes through venular walls (composed of endothelial cells, pericytes and a basement membrane) under physiological inflammatory conditions and the impact of pathological inflammation on this response. We believe that through rigorous and detailed analysis of the mechanisms of leukocyte trafficking in vivo our findings will contribute to the identification of potential novel targets that could be exploited for the development of strategies designed to enhance or suppress leukocyte migration in the clinic. Our experimental approach is multi-disciplinary, with a strong emphasis on the use of in vivo inflammatory disease models and the application of advanced imaging techniques such as confocal intravital microscopy.

Key recent findings:

• Identification of sequential and stimulus-specific roles for key endothelial cell (EC) junctional adhesion molecules (PECAM-1, ICAM-2 and JAM-A) in leukocyte transmigration into sites of inflammation in vivo.
  
  
• Characterization of expression and function of the adhesion molecule JAM-C in blood vessels and nerves in vivo and association of disrupted expression of this molecule with specific inflammatory disease models. 
  
  
• Identification of the endothelial cell JAM-C as a key regulator of polarized neutrophil transendothelial cell migration in vivo. This study also showed that disrupted expression of JAM-C can lead to neutrophil reverse transmigration, a response associated with dissemination of systemic inflammation following ischemia-reperfusion injury.

• Identification of the existence of permissive regions within the venular basement membrane expressing lower levels of matrix proteins and preferentially utilized by emigrating leukocytes to breach the venular wall. These previously un-described vascular sites have been termed low expression regions (LERs) by our group and we have conducted a comprehensive investigation into their characterization, localization and remodeling under different inflammatory conditions.
    
• Identification of distinct cellular and molecular mechanisms for breaching of venular walls by different sub-sets of leukocytes (neutrophils and monocytes).

Videos:

Video 1 - 3D image of a venule stained for laminin 10 (red). Leukocytes (PMN in blue and monocytes in green) are also labelled.

 

Video 2 - 3D image of a venule showing expression of PECAM-1 (green) at EC junctions.

 

Key publications

 

• Woodfin A, Voisin M-B, Beyrau M, Colom B, Caille D, Diapouli, F-M., Nash G. B, Chavakis T, Albelda S. M, Rainger G. E, Meda P, Imhof B. A, and Nourshargh S (2011). Junctional adhesion molecule-C (JAM-C) regulates polarized neutrophil transendothelial cell migration in vivo. Nature Immunol. Available online. 12:761-769.
  
  
• Nourshargh S., Hordijk PL., and Sixt M. (2010). Breaching multiple barriers: leukocyte motility through venular walls and the interstitium. Nat Rev Mol Cell Biol. 11:366-78.
  
  
• Woodfin A., Voisin MB., and Nourshargh S. (2010). Recent developments and complexities in neutrophil transmigration. Curr Opin Hematol. 17:9-17.
  
  
• Voisin M.B., Pröbstl D., and Nourshargh S. (2010). Venular basement membranes ubiquitously express matrix protein low expression regions: Characterisation in multiple tissues and remodelling during inflammation. Am J  Path. 176:482-95.
  
  
• Scheiermann,C., Colom,B., Meda,P., Patel,N.S., Voisin,M.B., Marrelli,A., Woodfin,A., Pitzalis,C., Thiemermann,C., urrand-Lions,M., Imhof,B.A., and Nourshargh S. (2009). Junctional Adhesion Molecule-C Mediates Leukocyte Infiltration in Response to Ischemia Reperfusion Injury. Arterioscler Thromb Vasc Biol. 29:1509-15.
  
  
• Voisin M.B., Woodfin A., and Nourshargh S. (2009). Monocytes and Neutrophils Exhibit Both Distinct and Common Mechanisms in Penetrating the Vascular Basement Membrane In Vivo. Arterioscler Thromb Vasc Biol. 29:1193-9
  
  
• Little M.A., Smyth L., Salama A.D., Mukherjee S., Smith J., Haskard D.,  Nourshargh S., Cook H.T., and Pusey D. (2009). Experimental autoimmune vasculitis: an animal model of anti-neutrophil cytoplasmic autoantibody-associated systemic vasculitis. Am J Pathol. 174:1212-1220.
  
  
• Woodfin A., Voisin M.B., Imhof B.A., Dejana E., Engelhardt B., and Nourshargh S. (2009). Endothelial cell activation leads to neutrophil transmigration as supported by the sequential roles of ICAM-2, JAM-A, and PECAM-1. Blood. 113:6246-6257.
  
  
• 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. (2007). Expression and function of junctional adhesion molecule-C in myelinated peripheral nerves. Science. 318:1472-5.
  
  
• Woodfin A, Voisin MB and Nourshargh S. (2007). PECAM-1: a multi-functional molecule in inflammation and vascular biology . Arterioscler Thromb Vasc Biol. 27:2514-23.
  
  
• Ley K, Laudanna C, Cybulsky MI and Nourshargh S. (2007). Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol.7:678-89.
  
  
• Wang S, Voisin MB, Larbi KY, Dangerfield J, Scheiermann C, Tran M, Maxwell PH, Sorokin L and Nourshargh S. (2006). Venular basement membranes contain specific matrix protein low expression regions that act as exit points for emigrating neutrophils. J Exp Med. 203:1519-32.

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