Oksana Kehoe

Biography

Dr Oksana Kehoe is a Senior Lecturer in Inflammation Biology at the School of Medicine and Lead of Rheumatology Research laboratory in the Robert Jones & Agnes Hunt Orthopaedic Hospital at Oswestry.

Dr Kehoe completed her PhD in the RE Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of National Academy of Sciences of Ukraine, Kyiv where she was awarded a Fellowship of Ukrainian Government for young scientist.

Her academic career started in Ukraine, where she worked as a Research Scientist in the Department of Biochemistry, Taras Shevchenko National University of Kyiv, Ukraine. After moving to the UK in 2000, Dr Kehoe worked as a Postdoctoral Research Associate at Cardiff University (2000-2002) and the University of Manchester (2002-2005). She joined Keele University and Institute for Science & Technology in Medicine at the RJAH Orthopaedic Hospital as a Research Fellow in 2006. In 2014, Dr Kehoe was appointed as a Lecturer in Bioscience at the School of Medicine and promoted to a Senior Lecturer in 2021.

Research and scholarship

Research theme: Regenerative Medicine

The research within our laboratory is focused on understanding mechanisms of rheumatoid arthritis progression and possible treatments including mesenchymal stem cells (MSCs), mesenchymal stem cell conditioned medium and mesenchymal stem cell-derived extracellular vesicles. We also try to find out how stem cells can be “encouraged” to perform better in aging and in disease such as arthritis. In our research we use many approaches, from cell biology, to biochemistry, molecular biology and animal models.

Current active projects

1. Mesenchymal stem cell-derived extracellular vesicles as therapeutic agents in arthritis
   MSCs function predominantly through paracrine mechanisms, via growth factors, cytokines, chemokines and bioactive, membrane-bound extracellular vesicles (EVs) found in mesenchymal stem cell conditioned medium. We are pursuing simultaneous characterisation of EVs derived from human MSCs cultured in different conditions to determine the impact of culture conditions upon the molecular composition of EVs. We are using pre-clinical and clinical samples to test the anti-inflammatory and immunomodulatory properties of EVs.
2. The in vitro effect of syndecan-3 gene knockout on bone marrow derived mesenchymal stem cells’ properties
   Inflammation is a central feature of rheumatoid arthritis that affects around 1% of the population and can result in disability and morbidity. The immunomodulatory effects of bone marrow derived mesenchymal stem cells has been widely studied and the recent observations that syndecan-3 (SDC3) is selectively pro-inflammatory in the joint led us to hypothesise that SDC3 might play an important role in MSCs biology. Syndecans are heparan sulphate proteoglycans expressed by endothelial cells of blood vessels and play a role in trafficking of inflammatory cells in an arthritis model.
3. Achieving the large-scale expansion of allogeneic umbilical cord mesenchymal stromal cell
4. PARIS: Psoriatic Arthritis – Resistance to TNF Inhibitors Study
   Psoriatic arthritis (PsA) is a chronic inflammatory immune-mediated disease. It affects up to 40% of people with psoriasis and it is associated with several comorbidities such as obesity, diabetes, metabolic syndrome and hypertension. It is difficult to diagnose because of its diverse symptoms manifesting of axial and peripheral arthritis, enthesitis, dactylitis, skin changes and nail dystrophy. Currently, different treatments exist to treat inflammation and pain. When patients do not respond to standard first line treatment, they are treated with biologic drugs such as Tumor Necrosis Factor inhibitors (TNFi) in first instance. But these treatments are expensive and lack efficacy in 50% of the cases. It is important to find biomarkers that will predict the response of patients to TNFi, in order to treat them with the most appropriate biologic drug. In collaboration with Dr Jan Herman Kuiper, School of Pharmacy and Bioengineering, Keele and clinical Rheumatologists from the RJAH Orthopaedic Hospital, this project aims to analyze the concentration of potential biomarkers in blood of PsA patients to predict resistance to TNFi and help clinicians to prescribe the most appropriate treatment in the first instance.

Society membership

• UK Society for Extracellular Vesicles, member of the committee
• International Society for Extracellular Vesicles, member
• British Society for Immunology, member
• British Society for Matrix Biology, member
• Tissue and Cell Engineering Society, UK, member

Teaching

Dr Kehoe is delivering undergraduate teaching in the School of Medicine and postgraduate teaching in the School of Pharmacy and Bioengineering (MSc in Cell & Tissue Engineering). Dr Kehoe delivers musculoskeletal and immunology teaching across years 1 and 2 of MBChB and the Paramedic Science with Integrated Master's courses. She is a Year 1 Unit Lead and a Problem-Based Learning Tutor.

Leadership roles

Dr Kehoe is Director of Postgraduate Research, Faculty of Medicine and Health Sciences.

Dr Kehoe designed, implemented and delivered a new unit ‘Life Course’ within the revised MBChB curriculum in the 2018-2019 academic year.

Advance Higher Education

Dr Kehoe is a Fellow of the UK’s Advance HE.

Further information

The Rheumatology Research lab is based at the RJAH Orthopaedic Hospital, Oswestry as part of the FMHS Regenerative Medicine theme. The combined clinical and research excellence in Oswestry has contributed extensively to the current knowledge of mechanisms and therapy treatments for arthritis.

Rheumatology Research laboratory at the RJAH Orthopaedic Hospital, Oswestry

Present PhD students:

• Mairead Hyland funded by Keele ACORN, Rheumatology Trust Fund and Institute of Orthopaedics, Oswestry;  2017-2021.  Project  ‘Mesenchymal stem cell-derived extracellular vesicles as therapeutic agents in arthritis’.
• Rebecca Davies EPSRC/MRC Centre for Doctoral Training in Regenerative Medicine; 2019-2022. Project ‘Determining the role of microRNAs in extracellular vesicles produced by hypoxia-preconditioned mesenchymal stem cells in inflammation’ (collaboration with Dr Mark Platt, Loughborough University).
• Anais Makos ‘Psoriatic Arthritis: a Pilot study to Stratify biologic therapies (PSAPS)’ (2020-2024) funded by the RJAH Orthopaedic Hospital Charity (£96,000).

I welcome applications from students who wish to undertake PhD, MPhil, MSc or intercalated (MMedSci) postgraduate studies in my group.

Past students:

• Rebecca Morgan EPSRC/MRC Centre for Doctoral Training in Regenerative Medicine; 2016-2020. Project ‘Uncovering the role of proteoglycans in extracellular vesicles produced by mesenchymal stem cells’ (collaboration with Dr Cathy Merry, University of Nottingham).
• Grace Long – intercalated (MMedSci) student; 2015-2016. Project ‘The immunomodulatory effects of mesenchymal stem cells and mesenchymal stem cell derived conditioned medium in experimental arthritis’.
• Dr Hareklea Markides ‘The use of MRI and MNP to image and track cells in vivo for arthritic cell-based therapies’ (completed 2014) – co-supervisor.
• Dr Lisa Rump-Goodrich ‘Expression and functionality of beta-chemokines in endothelial cells of the rheumatoid synovium’ (completed 2016) – co-supervisor.

Undergraduate (Medicine)

• Shannen Allen - ASPIRE 2021
• Kane Treadwell - British Society for Immunology Summer 2017 Placement
• Bhagat Manku - INSPIRE 2016
• George Tyler - INSPIRE 2015
• Sweta Parida – INSPIRE 2014

Editorial roles

Dr Kehoe is an invited member of the Editorial Board of Scientific Reports (since 2018).

Outreach activities

Dr Kehoe promoted a career in STEM by participating at Stoke-on-Trent Soapbox Science event, in July 2019 with discussion topic “Could stem cells cure arthritis?”.

Dr Kehoe’s group is also implicated in several public outreach and engagement events organised by the RJAH Orthopaedic Hospital (https://www.rjah.nhs.uk/Research/Non-clinical-Studies.aspx) and Orthopaedic Institute (https://www.orthopaedic-institute.org/).

Collaborators

• Professor Victoria Chapman, School of Medicine, University of Nottingham, UK
• Professor Anwen Williams, Cardiff University, School of Medicine, UK
• Professor Aled Clayton, Cardiff University, School of Medicine, UK
• Dr Cathy Merry, Wolfson Centre for Stem Cells, University of Nottingham, UK
• Dr Mark Platt, Department of Chemistry, Loughborough University, UK
• Dr Daniel Tonge,School of Life Sciences, Keele University, UK
• Dr Dada Pisconti, Stony Brook University, NY, US
• Dr Roshan Amarasena, Consultant Rheumatologist, RJAH Orthopaedic Hospital NHS Foundation Trust, Oswestry, UK
• Dr Karen Davies, Consultant Rheumatologist, Royal Wolverhampton NHS Trust, UK

Projects and funding

Funded project (current)

2021- The British Society for Immunology - 6th European Congress of Immunology (ECI) registration grant

2021- Institute of Orthopaedics, Oswestry
PhD studentship “Regulatory T cell-derived extracellular vesicles in patients with rheumatoid arthritis: a cell-free modality for suppression of inflammation”

2020- RJAH Hospital Charitable Fund
PhD studentship ‘‘Psoriatic Arthritis: a Pilot study to Stratify biologic therapies (PSAPS)”

2019 EPSRC/MRC Centre for Doctoral Training in Regenerative Medicine
“Determining the role of microRNAs in extracellular vesicles produced by hypoxia-preconditioned mesenchymal stem cells in inflammation”

2019 TERMIS EU 2019 travel award, STEMCELL Technologies

2018 Institute of Orthopaedics, Oswestry
“Next generation sequencing-driven analysis of microRNA cargo of extracellular vesicles from mesenchymal stem cells” Principal Investigator (with Dr Daniel Tonge, Keele University)

2017 Keele University ACORN funding for 3-year PhD studentship
“Mesenchymal stem cell-derived extracellular vesicles as therapeutic agents in arthritis” Primary supervisor

2017 Institute of Orthopaedics, Oswestry
Matching funding for PhD project “Mesenchymal stem cell-derived extracellular vesicles as therapeutic agents in arthritis” Principal Investigator

2017 The British Society for Immunology summer placement award for medical student “Immunoregulatory effects of mesenchymal stem cell-derived extracellular vesicles on T lymphocytes” Primary supervisor

2016 EPSRC/MRC Centre for Doctoral Training in Regenerative Medicine
“Uncovering the role of proteoglycans in extracellular vesicles produced by mesenchymal stem cells” Primary supervisor (Co-supervisor Dr Cathy Merry, University of Nottingham)

2016 MRC Experimental Medicine Challenge Grant
“Pathfinder: How do cartilage injuries heal naturally? An experimental study in humans” Co-investigator (PI Dr Jan Herman Kuiper, ISTM, Keele University)

2016 RJAH Orthopaedic Hospital Charity
“Extracellular vesicles derived from mesenchymal stem cells and chondrocytes: characterisation and potential applications” Principal Investigator (with Dr N.Kuiper, Professor N. Forsyth and Dr P.Roach, Keele University)

Funded projects (completed)

2015 Institute of Orthopaedics, Oswestry
Equipment grant “InvivO2 Hypoxia workstation” Principal Investigator

2014 Oswestry Rheumatology Association
“Pre-clinical testing of hypoxic MSC as a novel cell therapy for Rheumatoid Arthritis” Principal Investigator
Funded projects (completed)

2013 Dowager Countess Eleanor Peel Trust Medical Research Grant
“Stem Cells as Therapeutic Agents in Arthritis” Principal Investigator (with Prof Jim Middleton, Bristol University)

2013 The Anne Duchess of Westminster Charity
Funding to purchase the EVOM2 (Epithelial volt-ohmeter) to measure the transendothelial resistance across a microvascular endothelial monolayer, Principal investigator

2013 Institute of Orthopaedics, Oswestry
“Defining the mechanisms of anti-inflammatory and chondroprotective effects of MSCs in arthritis” Principal Investigator

2012 Oswestry Rheumatology Association
“Chondrogenic effect of mMSC in antigen-induced arthritis model” Principal Investigator

2012 Arthritis Research UK Equipment grant
“BD FACSVerse Flow Cytometer (3 Laser 4-2-2)” Co-investigator (with Drs Karina Wright, Claire Mennan and Professors James Richardson and Sally Roberts)

2012 Institute of Orthopaedics, Oswestry
Equipment grant “Quantitative analysis of living cells: Cell IQ machine” Co-investigator (with Drs Karina Wright, Claire Mennan, Sharon Owen and professors James Richardson and Sally Roberts)

2011 Insitute of Orthopaedics Ltd, Oswestry
“The Therapeutic Potential of Mesenchymal Stem Cells in Mouse Model of Rheumatoid Arthritis” Principal Investigator

2011 EPSRC Centre for Innovative Manufacturing in Regenerative Medicine
“From the science bench to the clinical application. Establishing stem cell population with consistent and reproducible therapeutic behaviours” Principal Investigator (with Professors Alicia El Haj and James Richardson)