Leukocyte Trafficking

Leukocyte Trafficking Group banner June 2013

Group leaders: Prof Gerard Nash, Prof Ed Rainger and Dr Helen McGettrick

Overview

Our research aims to understand the mechanisms that regulate recruitment of leukocytes into inflamed tissues during protective resolving responses, and how these processes go wrong in chronic inflammatory and auto-immune diseases.  We have described new pathways which regulate migration of leukocytes into tissue through the endothelial cells which line blood vessels, and the roles of local flow and of the surrounding tissue in defining normal or pathological inflammatory responses.

Leukocyte Trafficking Group - local environment 4

 

Our research group

The Group Leads work in a highly collaborative manner with over-lapping projects, using in vitro and in vivo models for studying a variety of factors that influence leukocyte trafficking. In vitro models of the vasculature allow us to visualise the effects of blood flow on the behaviour of endothelial cells, and on the recruitment of leukocytes, platelets and stem cells. We have also developed sophisticated co-culture models to examine how platelets, monocytes or stromal cells (e.g. fibroblasts, mesenchymal stem cells) regulate the delivery of leukocytes to foci of disease. More recently, we have extended this concept using integrated 3-D multi-cellular models which allow us to track leukocytes through layers of primary human cells and determine their behaviour and ultimately their fate. To complement this work we use transgenic and preclinical models of disease, along with intravital microscopy, to further dissect these processes in vivo and elucidate mechanisms and potential therapeutic targets.

Leukocyte Trafficking Group - Lipid mediators

Leukocyte Trafficking Group - platelet monocyte interactions

Current Projects

  • Immunomodulatory properties of mesenchymal stem cells and endothelial progenitors, specifically in terms of vascular inflammatory responses and leukocyte recruitment (British Heart Foundation Project Grant and BBSRC PhD studentship)
  • Role of synovial fibroblasts in shaping endothelial responses and lymphocyte recruitment during resolving and persistent arthritis (Arthritis Research UK Career Development Fellowship)
  • Characterising the endothelial cell receptor for PEPITEM, a novel peptide that regulates T cell trafficking during inflammation (Medical Research Council Confidence in Concept Grant)
  • Development of 3-D models to examine the migration, fate and function of leukocytes entering inflamed tissue (Wellcome Trust)
  • Ability of lymphatic endothelial cells to communicate with vascular endothelial cells and influence the migration of leukocytes
  • Modulation of migratory behaviour of lymphatic endothelial cells by platelets and the interaction between CLEC-2 and podoplanin (British Heart Foundation project Grant)
  • The role of Src-family kinases in regulating transforming growth factor-β1 driven platelet and monocyte recruitment to endothelial cells (British Heart Foundation Project Grant)
  • Do platelets exacerbate the atherogenic process by regulating the recruitment, differentiation and inflammatory function of monocytes (British Heart Foundation Programme Grant)
  • Characterisation of blood-borne microvesicles in patients suffering trauma and investigation of their influence on inflammatory and thrombotic responses (NIHR Surgical Reconstruction and Microbiology Research Centre)

Recent Publications

For full publication lists see:

Staff

Principal Investigators
Professor Gerard Nash - School of Clinical and Experimental Medicine
Professor Ed Rainger - School of Clinical and Experimental Medicine
Dr Helen McGettrick - School of Immunity and Infection

Postdoctoral Researchers
Dr Matt Harrison - School of Clinical and Experimental Medicine
Dr Myriam Chimen
Dr Sahithi Kuravi

Technicians
Paul Newby

PhD Students
Stacey Langan
Asma Alanazi
Mohammed Alassiri
Bonita Apta
Hafsa Munir
Jasmeet Reyat
Lewis Clarke

Internal Collaborators
Prof David Adams - School of Immunity and Infection
Dr Francesca Barone - School of Immunity and Infection
Prof Roy Bicknell - School of Immunity and Infection and Cancer Studies
Prof Andrew Bradbury - School of Clinical and Experimental Medicine
Prof Chris Buckley - School of Immunity and Infection
Dr Jorge Caamano - School of Immunity and Infection
Prof Adam Cunningham - School of Immunity and Infection
Dr Andrew Filer - School of Immunity and Infection
Prof Jon Frampton - School of Immunity and Infection
Dr Paul Harrison - School of Immunity and Infection
Dr Victoria Heath - School of Immunity and Infection
Dr Peter Hewett - School of Clinical and Experimental Medicine
Dr Nick Jones - School of Immunity and Infection
Dr Neena Kalia - School of Clinical and Experimental Medicine
Dr Trish Lalor - School of Immunity and Infection
Prof Janet Lord - School of Immunity and Infection
Dr Melanie Madhani - School of Clinical and Experimental Medicine
Dr Ashley Martin - School of Cancer Sciences
Prof Paul Murray - School of Cancer Sciences
Dr Parth Narendran - School of Clinical and Experimental Medicine
Dr Phil Newsome - School of Immunity and Infection
Prof Karim Raza - School of Immunity and Infection
Prof Antal Rot - School of Immunity and Infection
Dr Yotis Senis - School of Clinical and Experimental Medicine
Prof David Thickett - School of Clinical and Experimental Medicine
Dr Mike Tomlinson - School of Biosciences
Prof Steve Watson - School of Clinical and Experimental Medicine
Prof Mark Wheatley - School of Biosciences
Dr Steve Young - School of Immunity and Infection
Prof Paul Moss - School of Cancer Sciences
Dr Warwick Dunn - School of Biosciences
Dr Shan He - School of Computer Sciences

NHS Collaborators
Surgeon Captain Mark Midwinter - Centre for Defence Medicine, University Hospitals Birmingham NHS Trust, UK
Mr Naiem Moiemen - Midlands Burn Network, University Hospitals Birmingham NHS Trust, UK
Mr Alok Tiwari - Birmingham Vascular Clinics, University Hospitals Birmingham NHS Trust, UK

External Collaborators
Prof Philip Calder - University of Southampton
Prof Andrew Dick - University of Bristol
Prof Stuart Egginton - University of Leeds
Prof Lucy Walker - University College London
Dr Jim Middleton - University of Bristol
Prof Nick Morrell - University of Cambridge
Prof Sussan Nourshargh - Barts and The London School of Medicine and Dentistry
Prof Valerie O’Donnell - Cardiff University
Prof Susan Wong - Cardiff University