Biography

Dr Oksana Kehoe is a Lecturer in Bioscience at the School of Medicine and Head 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 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.

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. Uncovering the role of heparan sulphate proteoglycans in extracellular vesicle biogenesis: potential tools for improved therapies
In collaboration with Dr Cathy Merry, Nottingham University we propose that EVs may be optimised for regenerative medicine therapies by controlling the cargo incorporated and efficiency of EV production, through manipulating EV biogenesis mechanisms. One such mechanism involves a family of proteoglycans called syndecans. Here we aim to develop a method of exosome optimisation through specific alterations to the syndecan structures on MSC surfaces.

3. 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.

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 delivers undergraduate teaching in the School of Medicine and postgraduate teaching in the School of Pharmacy and Bioengineering (MSc in Cell & Tissue Engineering). She delivers musculoskeletal and immunology teaching across Years 1 and 2 of MBChB curriculum. Her teaching roles in the School of Medicine include Year 1 Unit Lead and Year 2 Student Selected Component (SSC) Lead. Dr Kehoe is also a Problem-Based Learning tutor.

Leadership roles

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

Oksana Lab

Rheumatology Research laboratory at the RJAH Orthopaedic Hospital, Oswestry


Present PhD 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).  

Mairead Hyland funded by Keele ACORN, Rheumatology Trust Fund and Institute of Orthopaedics, Oswestry;  2017-2020.  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).

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


Past students:

Ms 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)

Kane Treadwell – British Society for Immunology Summer 2017 Placement
Bhagat Manku- INSPIRE 2016
 George Tyler- INSPIRE 2015
Ms 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?”

Oksana outside the Potteries

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/).

Selected Publications

  • Eustace AD, McNaughton EF, King S, Kehoe O, Kungl A, Mattey D, Nobbs AH, Williams N, Middleton J. 2019. Soluble syndecan-3 binds chemokines, reduces leukocyte migration in vitro and ameliorates disease severity in models of rheumatoid arthritis. Arthritis Research and Therapy, vol. 21(172), 1-13. link> doi> link> full text>
  • Stefan A, Kay AG, Forsyth N, Jones FK, Pisconti A, Kehoe O. 2018. The in vitro effect of syndecan-3 gene knockout on bone marrow-derived mesenchymal stem cells' properties. INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY (vol. 99, p. A8). link>
  • McNaughton EF, Eustace AD, King S, Sessions RB, Kay A, Farris M, Broadbridge R, Kehoe O, Kungl AJ, Middleton J. 2018. Novel Anti-Inflammatory Peptides Based on Chemokine-Glycosaminoglycan Interactions Reduce Leukocyte Migration and Disease Severity in a Model of Rheumatoid Arthritis. J Immunol, vol. 200(9), 3201-3217. link> doi> full text>
  • Chapman V, Markides H, Sagar DR, Xu L, Burston JJ, Mapp P, Kay A, Morris RH, Kehoe O, El Haj AJ. 2017. Therapeutic Benefit for Late, but Not Early, Passage Mesenchymal Stem Cells on Pain Behaviour in an Animal Model of Osteoarthritis. Stem Cells Int, vol. 2017, 2905104. link> doi> full text>
  • Kay AG, Long G, Tyler G, Stefan A, Broadfoot SJ, Piccinini AM, Middleton J, Kehoe O. 2017. Mesenchymal Stem Cell-Conditioned Medium Reduces Disease Severity and Immune Responses in Inflammatory Arthritis. Sci Rep, vol. 7(1), 18019. link> doi> full text>

Full Publications List show

Journal Articles

  • Eustace AD, McNaughton EF, King S, Kehoe O, Kungl A, Mattey D, Nobbs AH, Williams N, Middleton J. 2019. Soluble syndecan-3 binds chemokines, reduces leukocyte migration in vitro and ameliorates disease severity in models of rheumatoid arthritis. Arthritis Research and Therapy, vol. 21(172), 1-13. link> doi> link> full text>
  • McNaughton EF, Eustace AD, King S, Sessions RB, Kay A, Farris M, Broadbridge R, Kehoe O, Kungl AJ, Middleton J. 2018. Novel Anti-Inflammatory Peptides Based on Chemokine-Glycosaminoglycan Interactions Reduce Leukocyte Migration and Disease Severity in a Model of Rheumatoid Arthritis. J Immunol, vol. 200(9), 3201-3217. link> doi> full text>
  • Chapman V, Markides H, Sagar DR, Xu L, Burston JJ, Mapp P, Kay A, Morris RH, Kehoe O, El Haj AJ. 2017. Therapeutic Benefit for Late, but Not Early, Passage Mesenchymal Stem Cells on Pain Behaviour in an Animal Model of Osteoarthritis. Stem Cells Int, vol. 2017, 2905104. link> doi> full text>
  • Kay AG, Long G, Tyler G, Stefan A, Broadfoot SJ, Piccinini AM, Middleton J, Kehoe O. 2017. Mesenchymal Stem Cell-Conditioned Medium Reduces Disease Severity and Immune Responses in Inflammatory Arthritis. Sci Rep, vol. 7(1), 18019. link> doi> full text>
  • Rump L, Mattey DL, Kehoe O, Middleton J. 2017. An initial investigation into endothelial CC chemokine expression in the human rheumatoid synovium. Cytokine, vol. 97, 133-140. link> doi> full text>
  • Kehoe O. 2017. An initial investigation into endothelial CC chemokine expression in the human rheumatoid synovium. Cytokine. doi>
  • Kehoe O, Fox J, Middleton J. 2017. Anniversary Collection: 35 Years of STEM CELLS Homing of Mesenchymal Stem Cells An Update to: Concise Review: Mesenchymal Stem Cells: Their Phenotype, Differentiation Capacity, Immunological Features, and Potential for Homing. STEM CELLS.
  • Rump LJ, Mattey DL, Middleton J, Kehoe O. 2016. Novel Identification of LYVE-1 Positive Macrophages in Rheumatoid Synovial Tissue. Open Journal of Rheumatology and Autoimmune Diseases, vol. 2016(6), 74-78. doi> link> full text>
  • Rump LJ, Mattey DL, Middleton J, Kehoe O. 2016. Novel Identification of LYVE-1 Positive Macrophages in Rheumatoid Synovial Tissue. Open Journal of Rheumatology and Autoimmune Diseases, vol. 2016(6), 74-78. doi> link> full text>
  • Kehoe O, Kalia N, King S, Eustace A, Boyes C, Reizes O, Williams A, Patterson A, Middleton J. 2014. Syndecan-3 is selectively pro-inflammatory in the joint and contributes to antigen-induced arthritis in mice. Arthritis Res Ther, vol. 16(4), R148. link> doi> full text>
  • Markides H, Sagar DR, Kehoe O, Morris RH, Chapmann V, El Haj AJ. 2014. Correlating mesenchymal stem cell delivery with pain in an OA rat model. JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, vol. 8, 146. link>
  • Kehoe O, Carthwright A, Askari A, Haj AE, Middleton J. 2014. Intra-articular injection of mesenchymal stem cells leads to reduced inflammation and cartilage damage in murine antigen-induced arthritis. JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, vol. 8, 145-146. link>
  • Kehoe O, Cartwright A, Askari A, El Haj AJ, Middleton J. 2014. Intra-articular injection of mesenchymal stem cells leads to reduced inflammation and cartilage damage in murine antigen-induced arthritis. J Transl Med, vol. 12, 157. link> doi> full text>
  • Markides H, Kehoe O, Morris RH, El Haj AJ. 2013. Whole body tracking of superparamagnetic iron oxide nanoparticle-labelled cells--a rheumatoid arthritis mouse model. Stem Cell Res Ther, vol. 4(5), 126. link> doi> full text>
  • Whittall C, Kehoe O, King S, Rot A, Patterson A, Middleton J. 2013. A chemokine self-presentation mechanism involving formation of endothelial surface microstructures. J Immunol, vol. 190(4), 1725-1736. link> doi>
  • Cartwright A, King S, Middleton J, Kehoe O. 2012. Is Chemokine Receptor CCR9 Required for Synovitis in Rheumatoid Arthritis? Deficiency in CCR9 in a Murine Model of Antigen-Induced Arthritis. Open Journal of Rheumatology and Autoimmune Diseases, 77-84. doi>
  • Cai J, Kehoe O, Smith GM, Hykin P, Boulton ME. 2008. The angiopoietin/tie-2 system regulates pericyte survival and recruitment in diabetic retinopathy. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, vol. 49(5), 2163-2171. link> doi>
  • Kostyuk O, Nalovina O, Mubard TM, Regini JW, Meek KM, Quantock AJ, Elliott GF, Hodson SA. 2002. Transparency of the bovine corneal stroma at physiological hydration and its dependence on concentration of the ambient anion. JOURNAL OF PHYSIOLOGY-LONDON, vol. 543(2), 633-642. link> doi>
  • Kostyuk O, Nalovina O, Mubard TM, Regini JW, Meek KM, Quantock AJ, Elliott GF, Hodson SA. 2002. Transparency of the bovine corneal stroma at physiological hydration and its dependence on concentration of the ambient anion. J Physiol, vol. 543(Pt 2), 633-642. link> doi>
  • Ostapchenko LI, Nalevina OE, Kucherenko NE. 1999. [The use of nontraditional approaches to the analysis of the effects of radiation on the system of protein phosphorylation in spleen lymphocytes]. Radiats Biol Radioecol, vol. 39(2-3), 334-340. link>
  • Ostapchenko LI, Nalevina OE, Tomachinskaia LI, Kucherenko NE. 1998. [Effect of x-irradiation on the properties of cyclic AMP-dependent protein kinases from rat spleen lymphocytes]. Radiats Biol Radioecol, vol. 38(5), 650-656. link>
  • Ostapchenko LI, Parkhomets TI, Kehoe O, Kucherenko NE. 1995. Post-radiation disturbances in the cyclic nucleotide system in rat spleen and thymus lymphocytes. Ukr Biokhim Zh, vol. 67(1), 70-75.
  • Ruchko MV, Ostapchenko LI, Kehoe O, Kucherenko NE. 1994. [The effect of different doses of ionizing radiation on the functional activity and mechanisms of the activation of the lymphoid cells from the spleen and thymus of rats exposed to a stimulating signal]. Radiats Biol Radioecol, vol. 34(2), 247-250.

Chapters

  • Kay AG, Middleton J, Kehoe O. Mesenchymal Stem Cell Therapy in Rheumatoid Arthritis. In STEM CELLS IN CLINICAL APPLICATIONS Volume 1: Bone and Cartilage Regeneration, 149-176;. Springer Int..

Other

  • Stefan A, Kay AG, Forsyth N, Jones FK, Pisconti A, Kehoe O. 2018. The in vitro effect of syndecan-3 gene knockout on bone marrow-derived mesenchymal stem cells' properties. INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY (vol. 99, p. A8). link>
  • Kay AG, Long G, Manku B, Broadfoot S, Middleton J, Kehoe O. 2017. MESENCHYMAL STEM CELLS AND MESENCHYMAL STEM CELL CONDITIONED MEDIUM INDUCE REGULATORY T CELLS AND PROMOTE T HELPER 2 (TH2) DIFFERENTIATION IN MURINE ANTIGEN-INDUCED ARTHRITIS. RHEUMATOLOGY (vol. 56, p. 147). link>
  • Kay AG, Stefan A, Rump-Goodrich L, Tyler G, Kehoe O. 2016. Intra-articular injection of mesenchymal stem cell conditioned medium reduces inflammation and aggrecanase- and MMP-driven cartilage degradation in antigen-induced arthritis in mice. INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY (vol. 97, pp. A7-A8). link>
  • Stefan A, Kay AG, Forsyth NR, Kehoe O. 2016. Knockout of sdc-3 gene does not alter characterisation of bone marrow derived MSCs in vitro. INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY (vol. 97, p. A15). link>
  • Kay AG, Long G, Middleton J, Kehoe O. Mesenchymal Stem Cell and MSC Conditioned Medium influence T cell differentiation to moderate immune responses in Antigen Induced Arthritis. European Cells and Materials (ECM) (vol. 32). European Cells & Materials Ltd.
  • Kay AG, Rump-Goodrich L, Middleton J, Kehoe O. 2015. Treatment of Experimental Arthritis with Mesenchymal Stem Cell Conditioned Medium. TISSUE ENGINEERING PART A (vol. 21, pp. S74-S75). link> full text>
  • Kay AG, Parida S, Stefan A, Rump A, Middleton J, Kehoe O. 2015. Assessment of aggrecanase- and MMP-driven cartilage degradation following MSC treatment for Rheumatoid Arthritis. Cells and Materials (vol. 29). Scanning Microscopy International, Inc.. link>
  • Parida SS and Kehoe O. 2015. INVESTIGATING THE CHONDROPROTECTIVE POTENTIAL OF MESENCHYMAL STEM CELLS IN ARTHRITIS. RHEUMATOLOGY (vol. 54, p. 125). Oxford Journals. link> doi> full text>
  • Sagar DR, Markides H, Burston JJ, Kehoe O, El Haj AJ, Chapman V. 2014. INTRA-ARTICULAR INJECTION OF MESENCHYMAL STEM CELLS IMPROVES PAIN BEHAVIOUR IN A MODEL OF OA PAIN. ANNALS OF THE RHEUMATIC DISEASES (vol. 73, p. 791). link> doi>
  • Rump-Goodrich L, Mattey D, Kehoe O, Middleton J. 2013. DIFFERENTIAL GENERATION OF CC CHEMOKINES AT MICROVASCULAR ENDOTHELIAL CELLS OF BLOOD AND LYMPHATIC VESSELS UNDER INFLAMMATORY CONDITIONS. RHEUMATOLOGY (vol. 52, pp. 136-137). link>
  • Kehoe O, Cartwright A, Askari A, El Haj A, Middleton J. 2013. INTRA-ARTICULAR INJECTION OF MESENCHYMAL STEM CELLS LEADS TO REDUCED INFLAMMATION IN ANTIGEN-INDUCED ARTHRITIS. RHEUMATOLOGY (vol. 52, p. 78). link>
  • Hykin PG, Smith GM, Nalovina O, Cai J, Boyd S, Boulton M. 2004. Angiopoietin-1 promotes pericyte survival and activation. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE (vol. 45, p. U736). link>
  • Nalovina O, Cai J, Hykin P, Boulton M. 2002. The role of the angiopoietin/Tie-2 system in retinal neovascularisation. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE (vol. 43, p. U298). link>

Collaborators

Projects and funding

Funded project (current)

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)

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)

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