Dr Helen McGettrick PhD, MSc, BSc

Image of Helen McGettrick

Institute of Inflammation and Ageing
Senior Research Fellow

Contact details

Address
Institute of Inflammation and Ageing
College of Medical and Dental Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

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, British Heart Foundation, Enterprise Birmingham Fund, and Pfizer.

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 Institute of Inflammation and Ageing. She subsequently joined Gerard Nash’s Cardiovascular Rheology Group in the Institute of Cardiovascular Sciences, 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 a five year Arthritis Research Career Development Fellowship to explore the role of synovial fibroblasts in regulating leukocyte accumulation during the development of persistent arthritis. Moreover, she was awarded the prestigious “Garrod Prize” by the British Society for Rheumatology in 2016.

Helen co-organised the 1st British Microcirculation Society and UK Cell Adhesion Society Joint Meeting held in 2017 at the University of Birmingham.

Teaching

Postgraduate

Undergraduate

Widening Participation

  • Academic Lead                       Access to Birmingham – Biomedical Sciences         
  • Academic Lead                       Realising Opportunities – Biomedical Sciences       
  • Assignment Tutor                   Access to Birmingham – Biomedical Sciences         
  • Assignment Tutor                   Realising Opportunities – Biomedical Sciences       
  • Assignment Tutor                   Realising Opportunities – Medicine                           

Previous undergraduate research projects

  • Investigating the therapeutic window and effect of PEPITEM treatment in rheumatoid arthritis progression (2017)
  • Fibroblasts regulate inflammation: What changes in early rheumatoid arthritis to make it persist? (2015)
  • Characterising the ability of mesenchymal stem cell-derived adipocytes and osteoblasts to influence leukocyte recruitment to vascular endothelial cells (2015)
  • Investigating how platelets influence the recruitment of mesenchymal stem cells from the blood (2015)
  • 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)

Previous summer research projects

  • Improving engineered tissue constructs for compatibility with human leukocytes (2014)
  • 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:

  • Regulation of leukocyte recruitment by fibroblast-endothelial interactions: Understanding the stromal switch from resolution to persistent inflammation; J. Griffiths (2017-2021)
  • Accelerated ageing as cause of disease pathogenesis, progression and multi-morbidity in Chronic Obstructive Pulmonary Disease; M Hughes (2017-2020) 
  • Investigating the impact of pathogenic stroma on lymphocyte behaviour in chronic inflammation. ARUK RACE PhD studentship based at University of Glasgow; M Bedaji (Oct 2015-present)

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

Previous PhD projects

  • Manipulating the immunomodulatory effects of mesenchymal stem cells; H Munir (2012-2016)
  • MSC as endogenous regulators of inflammation: Changes in chronic inflammation; L Clarke (2014-2017)

Previous Masters projects

  • Investigating the therapeutic window and effect of PEPITEM treatment in rheumatoid arthritis progression (April 2017-Aug 2017)
  • Examining the effects of CXCL4L1 released by fibroblasts on endothelial cell function (April 2016-Aug 2016)
  • Examining the differential bioactivity of soluble mediators released by MSC or MSC-derived adipocytes when co-cultured with endothelial cells (April 2016-Aug 2016)
  • Examining the immunomodulatory capacity of mesenchymal stem cells: Is there a role for metabolites? (Oct 2014-Mar 2015)
  • 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 are investigating 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 

Chronic Inflammation – Rheumatoid Arthritis

  • Fibroblast-endothelial cell crosstalk regulating lymphocyte recruitment in resolving and persistent arthritis
  • Adiponectin-PEPITEM axis  and regulation of T-cell migration in Rheumatoid Arthritis

Mesenchymal Stem Cells

  • Immunomodulatory effects of mesenchymal stem cells on leukocyte recruitment and vascular inflammation
  • Modulation of mesenchymal stem cell responses by their local microenvironment

Regulation of Migration

  • Vascular-lymphatic endothelial cell crosstalk and leukocyte exit from tissue
  • Multi-cellular 3-D in vitro models examining the migration, fate and function of leukocytes entering inflamed tissue

RESEARCH GRANTS

Principle Investigator:

2017-2021 - MRC CASE Studentship (Industrial Collaborator – Novartis, Basel)

Regulation of leukocyte recruitment by fibroblast-endothelial interactions: Understanding the stromal switch from resolution to persistent inflammation

2015-2017 - Pfizer
Defining the therapeutic potential of a novel peptide regulator of T-cell recruitment in rheumatoid arthritis.

2014-2016 - Enterprise Birmingham Fund
Demonstrating the utility of a biomarker to detect Rheumatoid Arthritis at a very early pre-symptomatic stage.

2012-2017 – Arthritis Research UK Career Development Fellowship
Exploring the role of synovial fibroblasts in regulating leukocyte accumulation during the development of persistent arthritis.

2009 – Wellcome Trust VIP Fellowship
Regulation of lymphocyte migration and retention by the stromal microenvironment.

Co-investigator:

2017-2021 Wellcome Trust PhD Studentship in Basic Sciences

Accelerated ageing as cause of disease pathogenesis, progression and multi-morbidity in Chronic Obstructive Pulmonary Disease

2017-2018 Arthritis Research UK – Innovation Seed Fund

In vivo efficacy of human S2-selected mesenchymal stromal cells in preclinical models of rheumatoid arthritis

2016-2017 - Wellcome Trust Pathfinder Award
New therapeutic avenues in Sjogren’s syndrome: exploring the role of PEPITEM in an orphan disease.

2015-2018 – British Heart Foundation
Mechanisms, optimisation, and in vivo application of the vascular protective effects of mesenchymal stem cells.

2010-2012 – Wellcome Trust
Role of fibroblasts in induction of tissue-specific recruitment of memory T-cell subsets.

Other activities

Editoral Board

  • Scientific Reports (2015 - present) 
  • Annals of Autoimmunity and Research

Committee Membership

Conference Organisation

  • Ist British Microcirculation Society and  UK Cell Adhesion Society Meeting - Birmingham, 2017
  • 27th UK Cell Adhesion Society Meeting - Birmingham, 2015
  • 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

Prizes and Awards

  • Garrod Prize - British Society of Rheumatology, 2016
  • European League of Rheumatism - Basic Science Oral Highlights Session, 2015
  • Enterprise Birmingham Innovation Competition - 2nd Place, 2015

Publications

Recent Peer Reviewed Publications

A. Filer, L.S.C. Ward, S. Kemble, C.S. Davies, H. Munir, R. Rogers, K. Raza, C.D. Buckley, G.B. Nash and H.M. McGettrick. Identification of a transitional fibroblast functional phenotype in very early rheumatoid arthritis. Annals of Rheumatic Diseases – Epub ahead of print https://www.ncbi.nlm.nih.gov/pubmed/28847766

H. Munir, L.S.C. Ward, L. Sheriff, S. Kemble, S. Nayar, F. Barone, G.B. Nash, and H.M. McGettrick. (2017) Adipogenic differentiation of MSC alters their immunomodulatory properties in a tissue-specific manner. Stem Cell 35(6):1636-1646. doi: 10.1002/stem.2622 https://www.ncbi.nlm.nih.gov/pubmed/28376564

M. Chimen, C.M. Yates, H.M. McGettrick, L.S. Ward, M.J. Harrison, B. Apta, L.H. Dib, B. Imhof, P. Harrison, G.B. Nash and G.E. Rainger. (2017) Monocyte subsets coregulate inflammatory responses by integrated signalling through TNF-alpha and IL-6 at the endothelial cell interface. Journal of Immunology198(7):2834-2843. doi: 10.4049/jimmunol.1601281 https://www.ncbi.nlm.nih.gov/pubmed/28193827

S. Nayar, M-M. Chung, L. Navarro-Nunez, M. Chachlani, P. Rankin, T. Cloake, J. Campos, N. Steinthal, H.M. McGettrick, S.P. Watson, C.D. Buckley and F. Barone (2016). Bimodal expansion of the lymphatic vessels is regulated by the sequential expression of IL-7 and Ltα1β2 in newly formed tertiary lymphoid structures.  Journal of Immunology: 197(5):1957-67. doi: 10.4049/jimmunol.1500686. 

Munir H, Luu NT, Clarke LS, Nash GB and McGettrick HM (2016) Comparative ability of mesenchymal stem cells from different tissues to limit neutrophil recruitment to inflamed endothelium. PLoS One 11(5):e0155161

Juarez M*, McGettrick HM*, Scheel-Toellner D, Yeo L, Spengler J, de Paz B, Hardy R, Cooper M, Raza K, Buckley CD and Filer A (2016) DKK1 expression by synovial fibroblasts in very early rheumatoid arthritis associates with lymphocyte adhesion in an in vitro flow co-culture system. Arthritis Res Ther 18:14 (* joint authorship)

Chimen M, McGettrick HM, Apta B, Kuravi SJ, Yates CM, Kennedy A, Odedra A, Alassiri M, Harrison M, Martin A, Barone F, Nayar S, Hitchcock JR, Cunningham AF, Raza K, Filer A, Copland DA, Dick AD, Robinson J, Kalia N, Walker LS, Buckley CD, Nash GB, Narendran P and Rainger GE (2015) Homeostatic regulation of T cell trafficking by a B cell derived peptide is impaired in autoimmune and chronic inflammatory disease. Nature Medicine 21(5):467-75

Recent Reviews:

Munir H and McGettrick HM (2015) Mesenchymal stem cell therapy for autoimmune disease: risks and rewardsStem Cells Dev24(18):2091-100

McGettrick HM, Butler LM, Buckley CD, Rainger GE and Nash GB (2012) Tissue stroma as a regulator of leukocyte recruitment in inflammation. J Leukoc Biol 91(3):385-400

Full listing of publications