Dr Jay Dudhia
Department: Clinical Science and Services
Research Groups: Musculoskeletal Biology, CPCS (Research Programme)
Research Centres: Clinical Investigation Centre
Jay is senior lecturer in the Department of Clinical Sciences and Services. His research interests are focussed on the ageing and pathogenic mechanisms of equine tendinopathies and human osteoarthritis. A major area is in regenerative medicine to investigate the therapeutic potential of mesenchymal stem cells for tendon repair and cardiac stem cells for heart diseases. The studies on tendon repair has led to the clinical use of mesenchymal stem cells for tendon injuries in the horse. He has established a Veterinary Medicines Directorate approved stem cell laboratory for the commercial expansion of MSCs (equine and canine) for the translation of regenerative strategies into the small and large veterinary clinic.
Jay graduated from Queen Elizabeth College University of London with a BSc Joint Honours degree in Biochemistry and Physiology and then gained a PhD in 1984 in Molecular Biology at Queen Elizabeth College (Kings College London). He took up a postdoctoral position with Professor Tim Hardingham in the Department of Biochemistry at the Kennedy Institute of Rheumatology (London) to pursue interests in the molecular changes in articular cartilage with ageing and in osteoarthritis, and the cloning and sequencing of a number of extracellular matrix proteins.
In 1997 he joined The Royal Veterinary College as a Senior Research Fellow to continue studies on articular and intervertebral disc cartilages with Professor Mike Bayliss in the Department of Veterinary Basic Sciences. In further collaborative work with Professor Roger Smith in the Department of Clinical Sciences and Services (CSS) he has investigated biomarkers of early tendon disease and in 2003 he moved to CSS to take up the opportunity to work closely with the equine clinic and run the tendon biology research group.
Following the pioneering studies at the RVC that led to the clinical use of MSCs for tendon injuries in the horse, he has established a Veterinary Medicine Directorate approved stem cell laboratory for the expansion and preparation of clinical grade MSCs for the equine and dog clinics to treat tendon and articular joint injuries.
Jay holds an Honorary Senior Lectureship at University College London at the Institute of Orthopaedics and Musculoskeletal Science and in the Department of Chemistry. He is a member of a number of national societies including the British Society for Matrix Biology where he has previously served as a Committee and Board Member and honorary treasurer, the Tissue and Cell Engineering Society and the British Society for Cell Biology. He recently worked as an Associate Editor for Cytometry Part A to edit a special issue of the Journal on Stem Cells across Species. He serves on the research review panel of Versus Arthritis (previously known as Arthritis Research UK). He has served on a number of scientific journal editorial panels and currently is an editorial board member of Nature Scientific Reports. He also acts as a consultant to industry and academic Institutions in the area of genetic modified organisms (GMOs).
He acts as an examiner, both internal (University of London) and external for PhD or MSc/MRes oral exams. He is currently external examiner for the MRes programme at the University of Liverpool.
Jay's research interests are on the extracellular matrices of articular cartilage and tendons. His grant funded research in tendinopathies has been closely linked with the equine clinic and clinicians to enable the translation of the basic research to the clinic. This has involved investigating age- and exercise-induced mechanisms of tendinopathies in the horse and has established ex vivo models of tendon injuries. Recent work using such models has given insight into the mechanisms of failed healing seen in clinic for tendon injuries that are located within the tendon synovial sheath (intrasynovial injuries). Current work is centered on the senescence associated secretory phenotype in equine tendon cells as a potential mechanism of age- and exercise-related tenon injuries. His work in regenerative medicine has been to develop the therapeutic potential of mesenchymal stem cells for the repair of tendon injuries in large animal models of spontaneous and experimental tendon injuries. Alongside this, he has been developing serological markers of the disease with equine clinical colleagues.
He has developed research with companion animal clinicians to investigate cardiac derived stem cells and induced pluripotent stem cells (iPSCs) with aim of translating their potential for heart repair or as in vitro (“disease in a dish”) models for developing and testing drugs.
His current research on cartilage is developing spectroscopic approaches for minimally invasive method of assessing early cartilage degeneration that is seen with osteoarthritis. This patented approach to assess molecular alterations of the cartilage in very early disease prior to signs of erosion has led to Jay leading a proof-of-concept test of the successfully first-in-man use of the technology via minimally invasive surgery in the knees of osteoarthritis patients. Together with collaborators at University College London this technology is being taken forward for further technological and commercial development.
Intra-operative Raman spectroscopy and ex vivo Raman mapping for assessment of cartilage degradation. Gaifulina R, Nunn ADG, Draper ERC, Strachan RK, Firth S, Blake N, Thomas G, McMillan PF, Dudhia J. Clinical Spectroscopy 3 (2021) 100012. https://doi.org/10.1016/j.clispe.2021.100012
Ribitsch IM, Baptista PM, Lange-Consiglio A, Melotti L, Patruno M, Jenner F, Schnabl-Feichter E, Dutton L, Connolly DJ, Van, Steenbeek F, Dudhia J and Penning LC. Large animal models in regenerative medicine and tissue engineering: To do or not to do. Front. Bioeng. Biotechnol. Aug 13;8:972. doi: 10.3389/fbioe.2020.00972
Rashid M, Dudhia J, Dakin SG, Snelling S, Lach A, De Godoy R, Mouthuy PA, Smith R, Morrey M, Carr AJ. Histological evaluation of cellular response to a multifilament electrospun suture for tendon repair. PLoS One. 2020 Jun 26;15(6):e0234982. doi: 10.1371/journal.pone.
Choi H, Simpson D, Wang D, Prescott M, Pitsillides AA, Dudhia J, Clegg PD, Ping P, Thorpe CT. Heterogeneity of proteome dynamics between connective tissue phases of adult tendon. eLife 2020;9:e55262. DOI: https://doi.org/10.7554/eLife.55262
Kelly E, Smith R, Dudhia J, Faragher RGA. Science-in-brief: The importance of senescence in tendinopathy: New opportunities. Equine Vet J. 2020 May;52(3):349-351. doi: 10.1111/evj.13228.
Smith R, Önnerfjord P, Holmgren K, di Grado S, Dudhia J. Development of a Cartilage Oligomeric Matrix Protein Neo-Epitope Assay for the Detection of Intra-Thecal Tendon Disease. Int J Mol Sci. 2020 Mar 20;21(6). pii: E2155. doi: 10.3390/ijms21062155.
Rashid M, Dudhia J, Dakin SG, Snelling SJB, De Godoy R, Mouthuy PA, Smith RKW, Morrey M, Carr AJ. Histopathological and immunohistochemical evaluation of cellular response to a woven and electrospun polydioxanone (PDO) and polycaprolactone (PCL) patch for tendon repair. Sci Rep. 2020 Mar 16;10(1):4754. doi: 10.1038/s41598-020-61725-5.
Dutton LC, Dudhia J, Guest DJ, Connolly DJ. Inducing Pluripotency in the Domestic Cat (Felis catus). Stem Cells Dev. 2019 Oct 1;28(19):1299-1309. doi: 10.1089/scd.2019.0142.
Khan MR, Smith RKW, David FH, Lam R, Hughes G, De Godoy R, Carr AJ, Goodship AE, Dudhia J. Evaluation of synovium multipotent cells on deep digital flexor tendon repair in a large animal model of intra-synovial tendinopathy J Orthop Res. 2019 Jul 22. doi: 10.1002/jor.24423.
Dutton LC DJ, Catchpole B, Hodgkiss-Geere H, Werling D, Connolly DJ: Cardiosphere-derived cells suppress allogeneic lymphocytes by production of PGE2 acting via the EP4 receptor. Sci Rep, 2018 Sep 6;8(1):13351. doi: 10.1038/s41598-018-31569-1.
Khan MR, Dudhia J, David FH, De Godoy R, Mehra V, Hughes G, Dakin SG, Carr AJ, Goodship AE, Smith RKW. Bone marrow mesenchymal stem cells do not enhance intra-synovial tendon healing despite engraftment and homing to niches within the synovium. Stem Cell Res Ther. 2018 Jun 19;9(1):169. doi: 10.1186/s13287-018-0900-7.
Dutton LC, Church SAV, Hodgkiss-Geere H, Catchpole B, Huggins A, Dudhia J, Connolly DJ: Cryopreservation of canine cardiosphere-derived cells: Implications for clinical application. Cytometry A 2018, 93(1):115-124.
Burk J, Brehm W, Smith RK, Dudhia J: Editorial to the Special Issue "Stem Cell Characterization Across Species". Cytometry A 2018, 93(1):16-18.
Yamamoto K, Santamaria S, Botkjaer KA, Dudhia J, Troeberg L, Itoh Y, Murphy G, Nagase H: Inhibition of Shedding of Low-Density Lipoprotein Receptor-Related Protein 1 Reverses Cartilage Matrix Degradation in Osteoarthritis. Arthritis Rheumatol 2017, 69(6):1246-1256.
Garvican ER, Salavati M, Smith RKW, Dudhia J: Exposure of a tendon extracellular matrix to synovial fluid triggers endogenous and engrafted cell death: A mechanism for failed healing of intrathecal tendon injuries. Connect Tissue Res 2017, 58(5):438-446.
Fields M, Spencer N, Dudhia J, McMillan PF: Structural changes in cartilage and collagen studied by high temperature Raman spectroscopy. Biopolymers 2017, 107(6).
Edmonds RE, Garvican ER, Smith RK, Dudhia J: Influence of commonly used pharmaceutical agents on equine bone marrow-derived mesenchymal stem cell viability. Equine Vet J 2017, 49(3):352-357.
Zaman G, Staines KA, Farquharson C, Newton PT, Dudhia J, Chenu C, Pitsillides AA, Dhoot GK: Expression of Sulf1 and Sulf2 in cartilage, bone and endochondral fracture healing. Histochem Cell Biol 2016, 145(1):67-79.
Yamamoto K, Okano H, Miyagawa W, Visse R, Shitomi Y, Santamaria S, Dudhia J, Troeberg L, Strickland DK, Hirohata Set al: MMP-13 is constitutively produced in human chondrocytes and co-endocytosed with ADAMTS-5 and TIMP-3 by the endocytic receptor LRP1. Matrix Biol 2016, 56:57-73.
Santamaria S, Fedorov O, McCafferty J, Murphy G, Dudhia J, Nagase H, Yamamoto K: Development of a monoclonal anti-ADAMTS-5 antibody that specifically blocks the interaction with LRP1. MAbs 2017, 9(4):595-602.
Khan MR, Chandrashekran A, Smith RK, Dudhia J: Immunophenotypic characterization of ovine mesenchymal stem cells. Cytometry A2016, 89(5):443-450.
Garvican ER, Cree S, Bull L, Smith RK, Dudhia J: Erratum to: Viability of equine mesenchymal stem cells during transport and implantation. Stem Cell Res Ther 2016, 7(1):161.
Clements LE, Garvican ER, Dudhia J, Smith RK: Modulation of mesenchymal stem cell genotype and phenotype by extracellular matrix proteins. Connect Tissue Res 2016, 57(6):443-453.
Dudhia J, Becerra P, Valdes MA, Neves F, Hartman NG, Smith RK: In Vivo Imaging and Tracking of Technetium-99m Labeled Bone Marrow Mesenchymal Stem Cells in Equine Tendinopathy. J Vis Exp 2015(106):e52748.
Borgeat K, Dudhia J, Luis Fuentes V, Connolly DJ: Circulating concentrations of a marker of type I collagen metabolism are associated with hypertrophic cardiomyopathy mutation status in ragdoll cats. J Small Anim Pract 2015, 56(6):360-365.
Bolton SN, Whitehead MP, Dudhia J, Baldwin TC, Sutton R: Investigating the Postmortem Molecular Biology of Cartilage and its Potential Forensic Applications. J Forensic Sci 2015, 60(4):1061-1067.
Yamamoto K, Owen K, Parker AE, Scilabra SD, Dudhia J, Strickland DK, Troeberg L, Nagase H: Low density lipoprotein receptor-related protein 1 (LRP1)-mediated endocytic clearance of a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4): functional differences of non-catalytic domains of ADAMTS-4 and ADAMTS-5 in LRP1 binding. J Biol Chem 2014, 289(10):6462-6474.
Muller C, Khabut A, Dudhia J, Reinholt FP, Aspberg A, Heinegard D, Onnerfjord P: Quantitative proteomics at different depths in human articular cartilage reveals unique patterns of protein distribution. Matrix Biol 2014, 40:34-45.
Garvican ER, Dudhia J, Alves AL, Clements LE, Plessis FD, Smith RK: Mesenchymal stem cells modulate release of matrix proteins from tendon surfaces in vitro: a potential beneficial therapeutic effect. Regen Med 2014, 9(3):295-308.
Garvican ER, Cree S, Bull L, Smith RK, Dudhia J: Viability of equine mesenchymal stem cells during transport and implantation. Stem Cell Res Ther 2014, 5(4):94.
Dakin SG, Smith RK, Heinegard D, Onnerfjord P, Khabut A, Dudhia J: Proteomic analysis of tendon extracellular matrix reveals disease stage-specific fragmentation and differential cleavage of COMP (cartilage oligomeric matrix protein). J Biol Chem 2014, 289(8):4919-4927.
Dakin SG, Dudhia J, Smith RK: Resolving an inflammatory concept: the importance of inflammation and resolution in tendinopathy. Vet Immunol Immunopathol 2014, 158(3-4):121-127.
Chandrashekran A, Isa I, Dudhia J, Thrasher AJ, Dibb N, Casimir C, Readhead C, Winston R: Lentiviral vector transduction of spermatozoa as a tool for the study of early development. FEBS Open Bio 2014, 4:266-275.
Smith RK, Werling NJ, Dakin SG, Alam R, Goodship AE, Dudhia J: Beneficial effects of autologous bone marrow-derived mesenchymal stem cells in naturally occurring tendinopathy. PLoS One 2013, 8(9):e75697.
Manning HB, Nickdel MB, Yamamoto K, Lagarto JL, Kelly DJ, Talbot CB, Kennedy G, Dudhia J, Lever J, Dunsby Cet al: Detection of cartilage matrix degradation by autofluorescence lifetime. Matrix Biol 2013, 32(1):32-38.
Dakin SG, Dudhia J, Smith RK: Science in brief: resolving tendon inflammation. A new perspective. Equine Vet J 2013, 45(4):398-400.
Becerra P, Valdes Vazquez MA, Dudhia J, Fiske-Jackson AR, Neves F, Hartman NG, Smith RK: Distribution of injected technetium(99m)-labeled mesenchymal stem cells in horses with naturally occurring tendinopathy. J Orthop Res 2013, 31(7):1096-1102.
Godwin EE, Young NJ, Dudhia J, Beamish IC, Smith RK: Implantation of bone marrow-derived mesenchymal stem cells demonstrates improved outcome in horses with overstrain injury of the superficial digital flexor tendon. Equine Vet J 2012, 44(1):25-32.
Dakin SG, Werling D, Hibbert A, Abayasekara DR, Young NJ, Smith RK, Dudhia J: Macrophage sub-populations and the lipoxin A4 receptor implicate active inflammation during equine tendon repair. PLoS One 2012, 7(2):e32333.
Dakin SG, Dudhia J, Werling NJ, Werling D, Abayasekara DR, Smith RK: Inflamm-aging and arachadonic acid metabolite differences with stage of tendon disease. PLoS One 2012, 7(11):e48978.
Smith MR, Wright IM, Minshall GJ, Dudhia J, Verheyen K, Heinegard D, Smith RK: Increased cartilage oligomeric matrix protein concentrations in equine digital flexor tendon sheath synovial fluid predicts intrathecal tendon damage. Vet Surg 2011, 40(1):54-58.
Dart AJ, Dart CM, Dudhia J, Perkins N, Canfield P, Smith RK: A preliminary study on the effect of wounding on transforming growth factor-beta1 and cartilage oligomeric matrix protein concentrations in the skin of horses. Vet Surg 2011, 40(1):59-65.
Dakin SG, Jespers K, Warner S, O'Hara LK, Dudhia J, Goodship AE, Wilson AM, Smith RK: The relationship between in vivo limb and in vitro tendon mechanics after injury: a potential novel clinical tool for monitoring tendon repair. Equine Vet J 2011, 43(4):418-423.
Alves AG, Stewart AA, Dudhia J, Kasashima Y, Goodship AE, Smith RK: Cell-based therapies for tendon and ligament injuries. Vet Clin North Am Equine Pract 2011, 27(2):315-333.
Williams R, Khan IM, Richardson K, Nelson L, McCarthy HE, Analbelsi T, Singhrao SK, Dowthwaite GP, Jones RE, Baird DMet al: Identification and clonal characterisation of a progenitor cell sub-population in normal human articular cartilage. PLoS One 2010, 5(10):e13246.
Briston L, Dudhia J, Lees P: Age-related differences in prostaglandin E2 synthesis by equine cartilage explants and synoviocytes. J Vet Pharmacol Ther 2010, 33(3):268-276.
Miller MC, Manning HB, Jain A, Troeberg L, Dudhia J, Essex D, Sandison A, Seiki M, Nanchahal J, Nagase Het al: Membrane type 1 matrix metalloproteinase is a crucial promoter of synovial invasion in human rheumatoid arthritis. Arthritis Rheum 2009, 60(3):686-697.
Vaughan-Thomas A, Dudhia J, Bayliss MT, Kadler KE, Duance VC: Modification of the composition of articular cartilage collagen fibrils with increasing age. Connect Tissue Res 2008, 49(5):374-382.
Richardson LE, Dudhia J, Clegg PD, Smith R: Stem cells in veterinary medicine--attempts at regenerating equine tendon after injury. Trends Biotechnol 2007, 25(9):409-416.
Dudhia J, Scott CM, Draper ER, Heinegard D, Pitsillides AA, Smith RK: Aging enhances a mechanically-induced reduction in tendon strength by an active process involving matrix metalloproteinase activity. Aging Cell 2007, 6(4):547-556.
Cappello R, Bird JL, Pfeiffer D, Bayliss MT, Dudhia J: Notochordal cell produce and assemble extracellular matrix in a distinct manner, which may be responsible for the maintenance of healthy nucleus pulposus. Spine (Phila Pa 1976) 2006, 31(8):873-882; discussion 883.
Sodersten F, Ekman S, Eloranta ML, Heinegard D, Dudhia J, Hultenby K: Ultrastructural immunolocalization of cartilage oligomeric matrix protein (COMP) in relation to collagen fibrils in the equine tendon. Matrix Biol 2005, 24(5):376-385.
Skioldebrand E, Heinegard D, Eloranta ML, Nilsson G, Dudhia J, Sandgren B, Ekman S: Enhanced concentration of COMP (cartilage oligomeric matrix protein) in osteochondral fractures from racing Thoroughbreds. J Orthop Res 2005, 23(1):156-163.
Seyfried NT, McVey GF, Almond A, Mahoney DJ, Dudhia J, Day AJ: Expression and purification of functionally active hyaluronan-binding domains from human cartilage link protein, aggrecan and versican: formation of ternary complexes with defined hyaluronan oligosaccharides. J Biol Chem 2005, 280(7):5435-5448.
Ilic MZ, Carter P, Tyndall A, Dudhia J, Handley CJ: Proteoglycans and catabolic products of proteoglycans present in ligament. Biochem J 2005, 385(Pt 2):381-388.
Dudhia J: Aggrecan, aging and assembly in articular cartilage. Cell Mol Life Sci 2005, 62(19-20):2241-2256.
Wells T, Davidson C, Morgelin M, Bird JL, Bayliss MT, Dudhia J: Age-related changes in the composition, the molecular stoichiometry and the stability of proteoglycan aggregates extracted from human articular cartilage. Biochem J 2003, 370(Pt 1):69-79.
Recent conference papers
"Mesenchymal stem cell derived extracellular vesicles to modulate the tendon microenvironment in repair strategies" 26/10/2018, Plenary lecture, European Orthopeadic Society 26thAnnual meeting, Galway, Ireland;
"Upsizing the lab: experiences with large animal translational models of tendinopathies". 06/09/2018, Plenary lecture, TERMIS Annual Meeting, Kyoto, Japan;
“Role of hyperthermia in the development of tendinopaties” 18/10/2018, Third Havemeyer Symposium on Tendons, Colorado, USA;
“Investigating the tendon microenvironment to develop engineered bioscaffolds for cell-based therapies” 13/09/2017, European Orthopeadic Society 25thAnnual meeting, Munich, Germany;
“Tendon Therapy – How relevant are small and large animal models” 13/09/2017, 28thAnnual Conference of the European Society for Biomaterials, Athens, Greece;
“Matrix-synovial fluid interactions in tendon injuries”. 17/11/2016, Plenary lecture, Matrix Biology Ireland Annual Meeting, Galway, Ireland
“Stem cell augmentation of tendon repair in a sheep model of intra-thecal tendon injury” 8/11/2018, Havemeyer Symposium on Stem Cells, Bonita, USA;
“Spontaneous and induced tendon disease models in the horse and sheep” 30/07/2016, TERMIS Annual Meeting, Uppsala, Sweden;
Jay holds a Postgraduate Certificate in Veterinary Education and is a Member of the Higher Education Academy. He teaches on the BSc BioVeterinary Sciences, BVetMed and Gateway to BVetMed programmes on extracellular matrix biology, development, structure and function of cartilage and tendons and associated pathologies in man and equids. He also supervises laboratory based projects for BSc (years 2 and 3) and BVetMed undergraduates (RP2 rotation). Jay acts as a departmental or non-departmental assessor for the annual appraisal system at the RVC for PhD students.
He has previously taught at UCL, Institute of Orthopaedics on the Intercalated BSc, MSc and distance learning programmes.
Although Jay does not have clinical duties, he is particulalry interested in clinical appliations of his research and has successful collaborations with both veterinary clinicians within the RVC hospitals as well as medical colleagues outside. More recently he has been developing a programme of research with small animal clinicians on applications of stem cells in feline and canine myocardial diseases.
CornealCellVision: Derivation of corneal keratocytes from canine induced pluripotent stem cells to develop disease models and novel treatments for corneal disease
This project will generate corneal stromal tissue in the laboratory to pave the way to the development of an artificial cornea for future disease modelling and clinical transplantation into injured and diseased dog eyes to restore vision. . Corneal diseases are one of the most common debilitating source of visual loss that may lead to permanent blindness in humans as well as in animals.
Understanding the genetic basis of catastrophic bone fracture in Thoroughbred horses using stem cells.
Bone fractures are a significant welfare problem in the Thoroughbred racing industry. Previous work has demonstrated that fracture is a complex condition with both environmental and genetic factors risk factors. However, the specific genetic factors that underpin fracture risk have not been identified. This has proved problematic to work out using patients due to the difficulty in accessing bone tissue and the large variability in exposure to environmental risk factors.
Using pluripotent stem cells to improve tendon regeneration in horses
Tendon injuries are common in horses taking part in a wide range of disciplines. After an injury, adult tendons undergo poor natural regeneration, instead repairing with functionally inferior scar tissue which leads to high re-injury rates.
Improving tendon regeneration is therefore key to reducing re-injury rates and enabling more horses to return to work following an injury.