Dr Helen McGettrick PhD, MSc, BSc

Arthritis Research UK Career Development Fellow

School of Immunity and Infection

HelenMcGettrick-Cropped-110x146

Contact details

School of Immunity and Infection
College of Medical and Dental Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

About

Helen McGettrick is an experimental biologist who specialises in developing multi-cellular in vitro models to examine the processes by which tissue resident cells influence leukocyte adhesion and migration during inflammation.

Helen’s research focuses on leukocyte recruitment and stromal cell biology in health and disease, in which she has several publications. She is currently using this expertise in the fields of rheumatology, diabetes, stem cell biology and cancer biology. She has received grants from Arthritis Research UK, in the form of a Career Development Fellowship, Wellcome Trust and Enterprise Birmingham.

Video clipFrustrated migration of human peripheral blood lymphocytes on cytokine-stimulated endothelium:
During inflammation, lymphocytes migrate over the surface (white, bright cells), through and underneath (dark cells) activated endothelial cells to enter the tissue. If the lymphocytes do not receive an appropriate signal, their migration becomes frustrated, as they transit into and out of the endothelial monolayer searching for it.

Qualifications

  • PhD in Medical Science - University of Birmingham, 2006
  • MSc in Immunology – Distinction, University of Birmingham, 2002
  • BSc (Hons) in Biochemistry - First Class, University of Lancaster, 2001

Biography

Helen graduated from the University of Lancaster in 2001 with a BSc (Hons) in Biochemistry, during this course she spent a year studying aboard at Oregon State University, USA. She obtained a MSc. in Immunology from the University of Birmingham in 2002, undertaking a research project looking at neutrophil apoptosis (cell death) with Janet Lord and Dagmar Scheel-Toellner in the School of Immunity and Infection. She subsequently joined Gerard Nash’s Cardiovascular Rheology Group in the School of Clinical and Experimental Medicine, where she completed her PhD in Medical Sciences in 2006.

Helen has continued to work in Birmingham investigating the processes controlling leukocyte recruitment and fate both in health and disease, focusing on the role of the tissue microenvironment. She was appointed as a University Fellow in Inflammation Biology within the System Science for Health multidisciplinary translational research consortium at Birmingham in 2011.

In 2012, Helen was awarded an Arthritis Research Career Development Fellowship to explore the role of synovial fibroblasts in regulating leukocyte accumulation during the development of persistent arthritis.

Helen is co-organising the 2nd British Society for Immunology, Leukocyte Migration Meeting in conjuction with colleagues at the University of Glasgow to be held in February 2015 at the University of Birmingham. She also co-organises a monthly seminar series for the Vascular, Thrombosis, Inflammation and Angiogenesis (VITA) arm of the Centre for Cardiovascular Sciences.

Teaching

Previously

Previous undergraduate research projects

  • Examining the immunomodulatory properties of MSC (2014)
  • Characterising the ability of mesenchymal stem cells to influence the migration of leukocytes through vascular endothelial cells (2013)
  • How do lymphatic endothelial cells influence lymphocyte migration during inflammation? (2013)
  • Establishing the role of CD248 in influencing PDGF signalling during angiogenesis (2012-2013)
  • Characterising the process of leukocyte migration through lymphatic endothelium:  which leukocytes can exit tissue? (2012)
  • Characterising new steps in T-cell migration into tissue during inflammation (2011)
  • Characterisation of a new regulatory step in T-cell penetration of tissue during inflammation (2010)

Previous summer research projects

  • Characterising how MSC influence leukocyte migration through endothelium  using novel in vitro constructs (2013).
  • Developing an in vitro construct to model the entry and exit of lymphocytes in inflamed tissue (2013).

Postgraduate supervision

Helen currently supervises PhD students on the following projects:

  • MSC as endogenous regulators of inflammation: Changes in chronic inflammation. Lewis Clarke (Oct 2014).
  • Manipulating the immunomodulatory effects of mesenchymal stem cells. Hafsa Munir (Oct 2012-present).

Find a PhD - http://www.findaphd.com/search/ProjectDetails.aspx?PJID=53722&LID=139

Helen currently supervises Masters level students on the following projects:

  • Examining the immunomodulatory capacity of mesenchymal stem cells: Is there a role for metabolites? (Oct 2014)

Previous Masters projects

  • Examining the impact of migration on T cell function (May-Aug 2014).
  • Characterising the effects of chronic inflammation on the phenotype of MSC (May-Aug 2014).
  • Mesenchymal stem cells as modulators of neutrophil recruitment (Jan-Apr 2014).
  • A new regulatory step in T-cell migration into tissue during inflammation; separating the wanted from the unwanted (May-Aug 2011).

Research

Helen’s research concentrates on the concept that the state of the local tissue (stromal) microenvironment defines the responsiveness of endothelial cells, and also the subsequent fate of recruited leukocytes. This has involved the development and validation of novel in vitro, multi-cellular, multi-layered static and flow-based culture systems. Her goal is to develop a more complete understanding of the molecular circuitry regulating tissue migration and egress during acute and chronic inflammation reactions, with a view to developing anti-inflammatory, pro-resolution therapeutic strategies. A novel approach that we areinvestigating is to manipulate the local stroma to instruct recruited cells to leave chronically inflamed tissue, in effect to “switch on” resolution, or alternatively to stop leukocytes entering the inflamed site by “turning off” recruitment.

RESEARCH THEMES 

  • Endothelial-fibroblast interactions and leukocyte recruitment to the synovium
  • Immunomodulatory effects of mesenchymal stem cells on leukocyte recruitment
  • Vascular-lymphatic endothelial cell crosstalk and leukocyte exit from tissue

RESEARCH ACTIVITY 
 
Endothelial-fibroblast interactions and leukocyte recruitment to the synovium
Access to unique clinical samples from healthy and diseased synovium has allowed the simultaneous comparison of physiological and pathological responses. Rheumatoid synovial fibroblasts continuously activated adjacent endothelial cells inducing unwanted leukocyte infiltration. Conversely, healthy dermal fibroblasts demonstrated a regulatory capacity, reducing lymphocyte recruitment in vascular constructs exposed to inflammatory cytokines. Fibroblasts (dermal, synovial and bone marrow) also have the ability to retain/trap endothelially recruited cells. Extending this work further, Arthritis Research are funding a Career Development Fellowship to examine the hypothesis that as non-resolving disease develops, a fibroblast phenotype is acquired that perpetuates leukocyte infiltration, and that in resolving arthritis this phenotype is never established. Results of this work will be important in the development of novel therapies for Rheumatoid Arthritis.

Immunomodulatory effects mesenchymal stem cells on leukocyte recruitment

Mesenchymal stem cells (MSC) are multipotent stromal precursor cells. As well as having the potential to differentiate and repair tissue, MSC are increasingly recognised as being able to modulate immune responses. Evidence suggests that they can dampen the innate immune response, but interestingly they may also modulate development of adaptive immune responses relevant to chronic inflammatory disorders by modifying recruitment and fate of T-cells. For example, MSC reduce the levels of leukocyte recruitment when they are cultured with vascular endothelial cells. Alternatively, differentiation in situ may modulate their ability to influence the progress of a local chronic inflammatory response.  

Vascular-lymphatic endothelial cell crosstalk and leukocyte exit from tissue
The key step in leaving tissue is for leukocytes (namely T-cells) to migrate through endothelial cells lining the lymphatic vessels. Leukocytes obtain messages as they migrate into tissue though vascular endothelium, which change their subsequent behaviour and ability to migrate through lymphatic endothelium. In addition, vascular endothelial cells communicate with neighbouring cells, including lymphatic cells, to regulate migration. This project investigates how lymphatic endothelial cells 'talk' to vascular endothelial cells and leukocytes, to modulate (i) entry, (ii) transit through and (iii) exit of T-cells from inflamed tissue.

Other activities

Editoral Board

  • Annals of Autoimmunity and Research

Committee Membership

Conference Organisation

  • 2nd BSI Leukocyte Migration Affinity Group - Birmingham, 2015
  • 26th UK Adhesion Society - Birmingham, 2013
  • 24th UK Adhesion Society - Birmingham, 2011
  • British Microvascular Society - Workshop - Birmingham, 2009

Membership and Affiliation

  • Fellow of the Higher Education Academy
  • British Society of Immunology
  • Society of Leukocyte Biology

Publications

Recent Peer Reviewed Publications

A. Naylor*, H.M. McGettrick*, W. Maynard, P. May, F. Barone, A. Croft, S. Egginton and C.D. Buckley (2014).A differential role for CD248 (Endosialin) in different forms of physiological angiogenesis in skeletal muscle. PLoS One In press (* joint authorship)

J.S. Kuravi*, H.M. McGettrick*, S.C. Satchell, M.A. Saleem, L. Harper, J.M. Williams, G.E. Rainger and C.O. Savage (2014). Podocytes regulate neutrophil recruitment by glomerular endothelial cells via IL-6 mediated cross-talk. Journal of Immunology193:234-243(* joint authorship)

R. Bayley, K.A. Kite, H.M McGettrick, J.P. Smith, G.D. Kitas, C.D. Buckley and S.P Young. (2014). The genetic variant PTPN22 R620W enhances neutrophil activation and function. Annuals in Rheumatic Diseasesdoi: 10.1136/annrheumdis-2013-204796 Epub

N.T. Luu, H.M. McGettrick, C.D. Buckley, P. Newsome, G.E. Rainger, J. Frampton and G.B. Nash. (2013). Cross-talk between mesenchymal stem cells and endothelial cells leads to down-regulation of cytokine-induced leukocyte recruitment. Stem Cells, 31:2690-702

Recent Reviews

J. Wragg, S. Durant, H.M. McGettrick, K. Sample, S. Egginton and R. Bicknell (2014). Shear stress regulated gene expression and angiogenesis – origins and development. Microcirculation 21:290-300

H.M. McGettrick, L.M. Butler, C.D. Buckley and G.E. Rainger and G.B. Nash. (2012). Stromal tissue as a regulator of leukocyte recruitment in inflammation. Journal of Leukocyte Biology, 91:385-400


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