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Personal profile

Area of academic expertise - outline

I am an immunologist interested in the cellular and molecular pathways which drive inflammation within the arthritic joint. Much of my expertise lies in synovial biology and understanding the immune cell mechanisms (both innate and adaptive) which drive synovitis in rheumatoid arthritis (RA) and more recently in osteoarthritis (OA). I am also interested in the synovial fibroblast and its role in the development and perpetuation of both inflammation and tissue remodelling during arthritic joint disease.

Through my research activity I have developed expertise in a range of techniques, including induction and monitoring of in vivo models of arthritis. In addition to this I have expertise in a variety of in vitro techniques, including  cell culture (primary and cell lines), isolation and characterisation of immune cell populations (from buffy coats, spleen and bone marrow) and polarisation assays (macrophage subsets, Th17 and T regulatory (Treg) cells), explant culture (including synovial tissue and cartilage), isolation of synovial fibroblasts, generation of primary osteoclast cultures (murine and human), immunohistochemistry, multi-colour flow cytometry and western blot. I also have experience in ELISA and multiplex technology. 

Current research activities

The primary aim of my work is identification of novel molecular targets which hold therapeutic promise for future drug discovery programmes.  My research activity is aligned with the Centre for Musculoskeletal Science (CMS) within the Institute of Biomedical and Environmental Health Research (IBEHR), University of the West of Scotland (UWS). My current work is focused around proteinase activated receptor 2 (PAR2) which has been shown to be a critical molecular checkpoint in inflammatory joint disease and cartilage homeostasis. I am specifically interested in the mechanisms by which PAR2 drives the pathological changes associated with arthritis. This includes projects looking at the role of PAR2 in innate and adaptive immune responses. PAR2 is known to have a fundamental role in innate immunity where it can acts as a protease sensor, allowing cells such as macrophages, to respond quickly to changes in their microenvironment. I am interested in the role of PAR2 in macrophage subset development and effector function, including response to toll like receptor (TLR) challenge and how this fits within the context of joint pathology.

In a project funded by a Carnegie Research Incentive Grant,  I am looking at PAR2 regulation of T regulatory (Treg) cell development and function in an effort to underpin the mechanism by which this receptor regulates interleukin 17 (IL-17) in inflammatory arthritis. I am also interested in understanding how PAR2 regulated pathways in osteoarthritis synovial tissue impact on cartilage integrity within the diseased joint.

Desired research direction

My future research will be centred on understanding the mechanisms by which PAR2 regulates pathology within the arthritic joint. Elucidation of molecular pathways up and down stream of PAR2 will be critical in the development of novel therapies focused around this target. This work will be taken forward as part of a recently funded University of the West of Scotland PhD studentship (to commence in October 2016), looking at the secretome of OA synovial membrane, using an ‘omics’ approach to interrogate PAR2 relevant pathways. In addition to the work focused around PAR2, I am interested in identifying other cellular pathways which may hold therapeutic promise for the treatment of OA.  This includes taking forward a project recently funded by a Carnegie Collaborative Research Grant (due to commence in October 2016). The project will investigate the impact of novel IKKa inhibitors (developed at the University of Strathclyde) on osteoclast biology. This is an exciting new collaborative project with Dr Andrew Paul at the University of Strathclyde and Dr Carl Good Year, University of Glasgow and is an opportunity to add breadth to on-going research activity. 

Target collaborative organisations

With future research activity and elucidation of the cellular mechanisms which underpin OA joint pathology, it is hoped that there will be opportunities to foster industrial partnerships. I am keen to build on current external collaborations and to develop new partnerships with multidisciplinary teams to address the challenging research questions within the field of arthritis.     

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Research Output 1992 2018

pollution policy
health policy
atmospheric pollution
particulate matter
air

Assessment of the effects of exercise on a murine model of OA

Huesa, C., Dunning, L., Macdougall, K., Ortiz, A., Villaluz, M. M., Fegen, M., Crilly, A., Litherland, G., MacKenzie, A., van't Hof, R., Goodyear, C. & Lockhart, J. 8 Jan 2018 (Accepted/In press)

Research output: Contribution to conferencePoster

Tibial Meniscus
Osteoarthritis
Exercise
Joints
Osteosclerosis

Rheumatic disease: protease-activated receptor-2 in synovial joint pathobiology

McCulloch, K., McGrath, S., Huesa, C., Dunning, L., Litherland, G., Crilly, A., Hultin, L., Ferrell, W. R., Lockhart, J. & Goodyear, C. 23 May 2018 In : Frontiers in Endocrinology. 9, 257

Research output: Contribution to journalReview article

Open Access
PAR-2 Receptor
Rheumatic Diseases
Joints
Osteoarthritis
Cartilage

The synovial secretome contributes to cartilage pathology in osteoarthritis: a role for exosomes

Asghar, S., Litherland, G., Meek, D., Goodyear, C., Lockhart, J. & Crilly, A. 8 Jan 2018 (Accepted/In press)

Research output: Contribution to conferencePoster

Exosomes
Osteoarthritis
Cartilage
Pathology
Chondrocytes

The synovial secretome contributes to cartilage pathology in osteoarthritis (OA): an Exosome Study

Asghar, S., Litherland, G., Meek, D., Goodyear, C., Lockhart, J. & Crilly, A. 5 Dec 2017 (Accepted/In press)

Research output: Contribution to conferencePoster

Exosomes
Osteoarthritis
Cartilage
Pathology
Chondrocytes

Prizes

Asthma/COPD Project of the Year, 19th Northern Ireland Healthcare Awards 2018

Lorraine Martin (Recipient), Lorcan McGarvey (Recipient), Fionnuala Lundy (Recipient), Gary Litherland (Recipient), John Lockhart (Recipient), Anne Crilly (Recipient), Carl Goodyear (Recipient), Keith Thornbury (Recipient), Mark Hollywood (Recipient), Gerard Sergeant (Recipient) & Noel McHale (Recipient), 22 Feb 2018

Prize: National/international honour

Activities 2000 2018

UWS Showcase Event

Lockhart, J. (Invited speaker), Crilly, A. (Invited speaker)
31 May 2018

Activity: Participation in workshop, seminar, course

BREATH Schools Public Engagement Drive - Stranraer Cluster (week)

Lockhart, J. (Speaker), Crilly, A. (Organiser), Litherland, G. (Contributor), McCallum, K. (Contributor), Black, K. (Contributor), Thomas, M. (Contributor), Bailo, M. (Contributor)
24 Sep 201828 Sep 2018

Activity: Other

BREATH Annual Conference

Lockhart, J. (Invited speaker), Litherland, G. (Invited speaker), Crilly, A. (Invited speaker), MacKenzie, A. (Invited speaker), McLellan, I. (Invited speaker), Bakhshi, A. (Invited speaker), Thomas, M. (Invited speaker), Bailo, M. (Invited speaker), Black, K. (Invited speaker), McCallum, K. (Invited speaker)
19 Jun 201820 Jun 2018

Activity: Participation in conference

Meeting with Finlay Carson (MSP) in Scottish Parliament

Lockhart, J. (Visitor), Litherland, G. (Visitor), Crilly, A. (Visitor), McLellan, I. (Visitor), Finlay Carson (Host)
10 Jan 2018

Activity: Other

Press / Media

Scientists honoured for their bid to ease lung disease misery

John Lockhart, Gary Litherland, Anne Crilly, Carl Goodyear, Lorraine Martin, Keith Thornbury, Mark Hollywood, Gerard Sergeant, Fionnuala Lundy & Lorcan McGarvey

9/03/18

1 item of media coverage

Press/Media: Research

Health Gong for Uni Link

John Lockhart, Gary Litherland, Anne Crilly, Iain McLellan, Andrew Hursthouse & Carl Goodyear

22/01/18

1 media contribution

Press/Media: Research

CHSS-BREATH Meeting

John Lockhart, Gary Litherland & Anne Crilly

10/01/18

1 media contribution

Press/Media: Research

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Sabha Asghar

Exosomes
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Cartilage
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nuclei
neutrons
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