Department: Clinical Sciences and Services

Campus: Hawkshead

Research Groups: Musculoskeletal Biology

Jay is a Senior Lecturer in Matrix Biology in the Department of Veterinary Clinical Sciences. His research interest in the ageing of soft tissue and involves investigations into equine tendon disease and in human osteoarthitis with a focus on the age-associated alterations of extracellular matrices and markers of early disease.

Jay graduated from Queen Elizabeth College, University of London with a BSc 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 Professor Tim Hardingham in the Department of Biochemistry at the Kennedy Institute of Rheumatology in 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 in Professor Mike Bayliss' group in the Department of Veterinary Basic Sciences. It was at this time that his research interest into tendon disease in the horse developed in collaborative work with Professor Roger Smith to investigate markers of early tendon disease. In 2003 he moved to the Department of Veterinary Clinical Sciences to continue work on age- and exercise-induced mechanisms of tendon disease and the opportunity to work closely with the Equine Clinic has led to developing an interest in stem cell research and the application of this technology in Clinic. Jay's research on osteoarthritis has continued and he is currently developing Raman spectroscopy as a minimally invasive method of assessing early cartilage disease.

He holds an Honorary Senior Lectureship at University College London. 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, the Tissue and Cell Engineering Society and the British Society for Cell Biology. He is an Editorial Board Member of the Open Geriatric Medicine Journal. He also acts as a Consultant to Industry and academic Institutions in the area of genetic modified organisms (GMOs) and related health and safety aspects.
 

The main area of Jay's research is on the extracellular matrices of articular cartilage and tendons and the mechanisms of ageing and exercise that lead to osteoarthritis and tendinopathy.

His research in osteoarthritis has concentrated on the disease in man and has recently been investigating the potential of Raman spectroscopy to assess molecular alterations of the cartilage in very early disease prior to signs of erosion. This work has led to Jay leading a pilot clinical trial in which the successfully technology was applied via minimally invasive surgery in the knees of osteoarthritis patients. Together with collaborators at University College London and Charing Cross Hospital, Imperial College, this technology is now being taken forward for further technological and commercial development.

His research on tendon has two aims: identifying disease mechanisms and developing clinical application of stem cell based therapies. A major part of this research is in tendinitis occurring in athletic horses and he also is developing serological markers of the disease with equine clinical colleagues.

He has recently established a stem cell centre that is authorised by the VMD for the preparation of clinical grade stem cells for use in the horse and in the dog.

 

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. Scientific Reports 2018, in press.

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.

Jay teaches on the BSc in 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 offers and supervises laboratory based projects for BSc and BVetMed undergraduates. He holds a Postgraduate Certificate in Veterinary Education from the RVC and is a Member of the Higher Education Academy. He lectures and examines at UCL, Institute of Orthopaedics for Intercalated BSc, MSc and distance learning programmes.

 

Jay is particulalry interested in clinical appliations of his research and has successful collaborations with both veterinary clinicians within the RVC equine hospital and 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.

 

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