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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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  • 4 Similar Profiles
PAR-2 Receptor Medicine & Life Sciences
Rheumatoid Arthritis Medicine & Life Sciences
Osteoarthritis Medicine & Life Sciences
Interleukin-6 Medicine & Life Sciences
Exosomes Medicine & Life Sciences
Interleukin-2 Receptors Medicine & Life Sciences
Cartilage Medicine & Life Sciences
Joints Medicine & Life Sciences

Network Recent external collaboration on country level. Dive into details by clicking on the dots.

Research Output 1992 2020

Exosomes in intercellular communication and implications for osteoarthritis

Asghar, S., Litherland, G. J., Lockhart, J. C., Goodyear, C. S. & Crilly, A., 1 Jan 2020, In : Rheumatology. 59, 1, p. 57-68 12 p.

Research output: Contribution to journalReview article

Exosomes
Osteoarthritis
Joints
Synovial Membrane
Articular Cartilage

Differential effects of exosomes derived from separate osteoarthritis synovial compartments: implications for erosive cartilage disease

Asghar, S., Litherland, G., Meek, D., Cole, J., Lockhart, J., Goodyear, C. S. & Crilly, A., 30 Apr 2019, In : Osteoarthritis and Cartilage. 27, S1, p. S192 1 p., 260.

Research output: Contribution to journalMeeting Abstract

Cartilage Diseases
Exosomes
Cartilage
Osteoarthritis
RNA

Enhanced airway smooth muscle relaxation via proteinase activated receptor 2

Black, K., MacKenzie, A., Dunning, L., Crilly, A., Brzeszczynska, J., McGarvey, L., Thornbury, K., Goodyear, C. S., Lockhart, J. C. & Litherland, G. J., 22 Nov 2019, In : Irish Journal of Medical Science. 188, SUPPL 10, p. 286-286 1 p.

Research output: Contribution to journalMeeting Abstract

Proteinase activated receptor 2 (PAR2) modulation of murine airway function

Black, K., MacKenzie, A., Dunning, L., Crilly, A., Brzeszczyńska, J., McGarvey, L., Thornbury, K., Goodyear, C. S., Lockhart, J. & Litherland, G., 10 Sep 2019.

Research output: Contribution to conferencePoster

Open Access
File
PAR-2 Receptor
Smooth Muscle
Trypsin
Chronic Obstructive Pulmonary Disease
Oxidative Stress

Proteinase activated receptor 2 modulates expression of autophagy markers in murine lungs

McCallum, K., Dunning, L., McGarvey, L., Hollywood, M., Goodyear, C. S., Brzeszczynska, J., Crilly, A., Lockhart, J. C. & Litherland, G. J., 22 Nov 2019, In : Irish Journal of Medical Science. 188, SUPPL 10, p. S270-S270 1 p., 2.6.

Research output: Contribution to journalMeeting Abstract

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 2019

David Anderson

John Lockhart (Host), Gary Litherland (Host), Anne Crilly (Host)
23 Oct 2019

Activity: Hosting a visitorHosting an academic visitor

GSK Site Visit

John Lockhart (Organiser), Mark Thomas (Participant), Kimberly Black (Participant), Kirsty McCallum (Participant), Sabha Asghar (Participant), Fawziye Tarhini (Participant), Mari Bailo (Participant), Gary Litherland (Organiser), Anne Crilly (Organiser), Carly Woods (Participant), Bryn Short (Participant)
14 Mar 201915 Mar 2019

Activity: Participating in or organising an eventParticipation in workshop, seminar, course

BREATH PI Meeting, Belfast (QUB)

John Lockhart (Speaker), Anne Crilly (Speaker), Gary Litherland (Speaker)
15 Jan 2019

Activity: Participating in or organising an eventParticipation in workshop, seminar, course

Chris Carlin

John Lockhart (Host), Gary Litherland (Host), Anne Crilly (Host)
13 Nov 2019

Activity: Hosting a visitorHosting an academic visitor

European Respiratory Society International Congress

John Lockhart (Participant), Gary Litherland (Participant), Anne Crilly (Participant), Joanna Brzeszczynska (Participant), Lynette Dunning (Participant)
28 Sep 20192 Oct 2019

Activity: Participating in or organising an eventParticipation in conference

Press / Media

Profiles

Exosomes
Osteoarthritis
Cartilage
Cartilage Diseases
Chondrocytes
PAR-2 Receptor
Premature Aging
Autophagy
Lung
Chronic Obstructive Pulmonary Disease
Interferons
Antiviral Agents
Viruses
Cytomegalovirus
Human respiratory syncytial virus