Dr Oksana Kehoe

Title: Lecturer in Bioscience
Head of Rheumatology Research Laboratory at RJAH Orthopaedic Hospital
Phone: +44 (0)1691 404149 (RJAH) or +44(0)1782 734738 (Keele)
Email: o.kehoe@keele.ac.uk
oksana.kehoe@nhs.net
Location: 1. Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Trust, Oswestry, Shropshire SY10 7AG United Kingdom
2. School of Medicine, Keele University, Keele, Staffordshire ST5 5BG United Kingdom
Role: ISTM Research theme: Regenerative Medicine
Contacting me: By phone or e-mail please.
Oksana_Kehoe_DSC_0603_150x225

Research Career

2014- present: Lecturer in Bioscience & Head of Rheumatology Research laboratory,   Keele University School of Medicine, and Institute for Science & Technology in Medicine at RJAH Orthopaedic Hospital, Oswestry, UK

2006 - 2013:  Research  Fellow and Acting Head of Rheumatology Research Laboratory, Institute for Science & Technology in Medicine at RJAH Orthopaedic Hospital, Oswestry, UK. 

2002 – 2005: Postdoctoral Research Associate, Faculty of Life Sciences, University of Manchester, UK. Investigation into role of an immunoglobulin-like cell adhesionmolecule nectin-1 in palatal shelf fusion and desmosome assembly.

2000, December- 2002:  Postdoctoral Research Associate, Cell and Molecular Biology Group, School of Optometry and Vision Sciences, Cardiff University, Wales. Investigation into role of Angiopoietin-1/Tie-2 system in pericyte survival and recruitment in diabetic retinopathy.

2000, February – 2000, November:  Postdoctoral Research Associate, Biophysics Group, School of Optometry and Vision Sciences, Cardiff University, Wales. Studying the biophysics of corneal transparency under varying ambient anion concentration.

1995-2000- Research Scientist, Department of Biochemistry, Taras Shevchenko National University of Kyiv, Ukraine.

1991-1995- PhD, RE Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, Kyiv. ”Influence of X-ray radiation on maintenance of cyclic nucleotides and activity of cAMP-dependent protein kinase in rat’s lymphoid cells”.

 

ISTM 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:  the British Society for Immunology (BSI), the British Society for Matrix Biology (BSMB); Tissue and Cell Engineering Society (TCES); the UK Society for Extracellular Vesicles (UKEV); International Society for Extracellular Vesicles (ISEV)

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 Res Ther, vol. 21(1), 172. link> doi>
  • 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 Res Ther, vol. 21(1), 172. link> doi>
  • 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>

In 2014 I was appointed as a Lecturer in the School of Medicine. Currently I am year 1 Unit ‘Life Course’ Lead and Y2 student-selected components (SSC) co-lead.  I deliver musculoskeletal and immunology teaching across years 1 and 2.  I have extensive experience as a PBL tutor in the pre-clinical years 1 and 2 of Medicine.

I gained valuable experience in curriculum development at Keele School of Medicine where I designed and developed a new Unit Life Course for the revised and refreshed MBChB curriculum 2018.

I am also delivering teaching for the M.Sc in Cell & Tissue Engineering (ISTM, Keele University). I hold the Certificate in Teaching and Learning in Higher Education from Keele University. 

Team Members

The Rheumatology Research lab is based at the RJAH Orthopaedic Hospital, Oswestry as part of the ISTM 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. 

  Photo of Oksana Kehoe's Rheumatology Laboratory at RJAH 2019

Rheumatology Research laboratory at the RJAH Orthopaedic Hospital, Oswestry

Present PhD Students

Ms Rebecca Morgan  EPSRC Centre for Doctoral Training in Regenerative Medicine PhD student; 2016-2020. Project “Uncovering the role of proteoglycans in extracellular vesicles produced by mesenchymal stem cells” (collaboration with Dr Cathy Merry, University of Nottingham). 

Ms Mairead Hyland  2017-2020. Project “Mesenchymal stem cell-derived extracellular vesicles as therapeutic agents in arthritis”

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’.

Lisa Rump-Goodrich, PhD  2010-2016 “Expression and functionality of beta-chemokines in endothelial cells of the rheumatoid synovium” (co-supervisor)  

Undergraduate (Medicine)

Mr Kane Treadwell – British Society for Immunology Summer 2017 Placement;

Ms Bhagat Manku- INSPIRE 2016;

Mr George Tyler- INSPIRE 2015;

Ms Sweta Parida – INSPIRE 2014.

Collaborators:

Funded projects (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 Institute 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)