Staff Profile

Current

My group are members of the Regenerative Medicine, Stem Cells and Transplantation Theme, Biosciences Institute, Newcastle University. Twitter:@IGM_YoungLab 

Qualifications

BSc, University of Sheffield, 1989-1992
PhD, Cambridge laboratory, John Innes Centre, Norwich (UEA affiliated), 1992-1996

Previous Positions

1997-1998. ARC Post-doctoral Research Assistant, Wellcome Trust Centre for Matrix Research, University of Manchester.
1998-2003. ARC Senior Post-doctoral Research Assistant, School of Biological Sciences, University of East Anglia.
2003-2004. Dunhill Medical Trust Post-doctoral Research Assistant, School of Biological Sciences, University of East Anglia.

Memberships

Member of the Biochemical Society
Previously honorary treasurer and committee member of the British Society for Matrix Biology (BSMB)

Areas of expertise

• Cartilage biology
• Osteoarthritis
• Epigenetics
• MicroRNA

Google scholar: Click here.
ORCID: Click here.

Research Interests

We are members of the Regenerative Medicine, Stem Cells and Transplantation Theme.

My research interests include gene expression and regulation in the context of cartilage development and the main cartilage disease, osteoarthritis (OA). My laboratory focus is how these genes are epigenetically regulated; by microRNAs, DNA methylation and chromatin modifications.

Other Expertise

Main techniques: Gene expression analysis/profiling (Real-time PCR, microarray, RNA-seq). Cell signalling analysis. RNAi (siRNA, shRNA). miRNA analysis. Cas9/CRISPR. ChIP-seq, ATAC-seq. Transcription factor analysis (EMSA, mutagenesis, reporter assays). Epigenetic analysis. Models of osteoarthritis.

Current Work

Age is the major risk factor for Osteoarthritis. We are investigating the molecular mechanisms of how ageing impacts on cartilage.

Manipulating gene expression in cartilage is currently not possible therefore we have developed an interest in tissue engineering, to generate cartilage from the differentiation of stem cells. Using this model we have generated a series of -omics scale data to help understand what controls a chondrocyte phenotype.

We are developing CRISPR technology in the group both in terms of their ability to edit genes and also to regulate transcription. With collaborators we are using CRISPR to generate novel transgenics.

Postgraduate (current) Supervision

• Yao Hao, PhD main supervisor
• Dan Hayman, PhD main supervisor

Research Assistant

• Hua Lin

Post-doctoral Scientists

• Matt Barter

• Jamie Soul (Versus Arthritis Foundation Fellow)

Clinical trainee fellow

• Adam Farrier
  

Past Lab members

• David Wilkinson
• Adrian Falconer
• Marta Radwan
• Siliva Lecci
• Bola Ajekigbe
• Dimitra Tsompani
• Heather Bromby
• Steven Woods
• Rodolfo Gomez
• Katie Crossland
• Wang Hui
• Yaobo Xu
• Catherine Bui
• Christos Gavriilidis
• Jenny Scott
• Hannah Elliott
• Martin Galler

Esteem Indicators

Previously British Society for Matrix Biology (BSMB) Honorary Treasurer
http://www.bsmb.ac.uk

Funding

Current funding is mainly from the Dunhill Medical Trust, the JGW Patterson Foundation, Versus Arthritis, Newcastle NHS Hospital Charity, and CIMA (MRC/Arthritis Research UK).

Industrial Relevance

More than 7 million adults in the UK (15% of the population) have long-term health problems due to arthritis and related conditions. In 2001 incapacity benefit alone cost the nation £2.4 billion.
Metalloproteinases are the enzymes ultimately responsible for the collagen loss to cartilage seen in arthritic diseases. The design of small molecule inhibitors of the metalloproteinases remains a major focus of the pharmaceutical industry, yet has been largely unsuccessful, probably due to a lack of specificity of the compounds and side effects. Since arthritis is a debilitating, but not fatal disease, such side effects need to be minimised. We suggest that HDACi will be chondroprotective in all destructive arthritides, including both rheumatoid arthritis and osteoarthritis (other examples include: reactive arthritis, gout/pseudogout, psoriatic arthritis). They may also show utility in cartilage engineering/transplantation to protect cartilage explants or engineered/cultured cartilage from degradation. Many pharmaceutical companies are currently testing HDACi in cancer therapy trials, therefore these molecules potentially represent the next wave of drugs to fight the arthiitis.

Postgraduate Teaching

I regularly supervise MRes/BMS students for laboratory projects and lecture on the MRes Biology or Ageing  and Current trends in musculoskeletal disease modules..

I was DPD for MRes projects .

• Barter MJ, Butcher A, Wang H, Tsompani D, Galler M, Rumsby EL, Culley KL, Clark IM, Young DA. HDAC6 regulates NF-κB signalling to control chondrocyte IL-1-induced MMP and inflammatory gene expression. Scientific Reports 2022, 12(1), 6640.
• Chaudhry N, Muhammad H, Seidl C, Downes D, Young DA, Hao Y, Zhu L, Vincent TL. Highly efficient CRISPR-Cas9-mediated editing identifies novel mechanosensitive microRNA-140 targets in primary human articular chondrocytes. Osteoarthritis and Cartilage 2022, 30(4), 596-604.
• Patel K, Chandrasegaran S, Clark IM, Proctor CJ, Young DA, Shanley DP. TimiRGeN: R/Bioconductor package for time series microRNA–mRNA integration and analysis. Bioinformatics 2021, 37(20), 3604–3609.
• Barter MJ, Cheung K, Falk J, Panagiotopoulos AC, Cosimini C, OBrien S, TejaPutri K, Neill G, Deehan DJ, Young DA. Dynamic chromatin accessibility landscape changes following interleukin-1 stimulation. Epigenetics 2021, 16(1), 106-119.
• Hayman DJ, Modebadze T, Charlton S, Cheung K, Soul J, Lin H, Hao Y, Miles CG, Tsompani D, Jackson RM, Briggs MD, Piróg KA, Clark IM, Barter MJ, Clowry GJ, LeBeau FEN, Young DA. Increased hippocampal excitability in miR-324-null mice. Scientific Reports 2021, 11(1), 10452.
• Wilkinson DJ, Falconer AMD, Wright HL, Lin H, Yamamoto K, Cheung K, Charlton SH, Arques MDC, Janciauskiene S, Refaie R, Rankin KS, Young DA, Rowan AD. Matrix metalloproteinase-13 is fully activated by neutrophil elastase and inactivates its serpin inhibitor, alpha-1 antitrypsin: Implications for osteoarthritis. The FEBS Journal 2021, 289(1), 121-139.
• Soul J, Barter MJ, Little CB, Young DA. OATargets: A knowledge base of genes associated with osteoarthritis joint damage in animals. Annals of the Rheumatic Diseases 2021, 80(3), 376-383.
• Jones TL, Esa MS, Li KHC, Krishnan SRG, Elgallab GM, Pearce MS, Young DA, Birrell FN. Osteoporosis, fracture, osteoarthritis & sarcopenia: A systematic review of circulating microRNA association. Bone 2021, 152, 116068.
• Stadnik PS, Gilbert SJ, Tarn J, Charlton S, Skelton AJ, Barter MJ, Duance VC, Young DA, Blain EJ. Regulation of microRNA-221, -222, -21 and -27 in articular cartilage subjected to abnormal compressive forces. Journal of Physiology 2021, 599(1), 143-155.
• Dennis EP, Edwards SM, Jackson RM, Hartley CL, Tsompani D, Capulli M, Teti A, Boot-Handford RP, Young DA, Piróg KA, Briggs MD. CRELD2 is a novel LRP1 chaperone that regulates non-canonical WNT signalling in skeletal development. Journal of Bone and Mineral Research 2020, 35(8), 1452-1469.
• Barter MJ, Bui C, Cheung K, Falk J, Gomez R, Skelton AJ, Elliott HR, Reynard LN, Young DA. DNA hypomethylation during MSC chondrogenesis occurs predominantly at enhancer regions. Scientific Reports 2020, 10(10), 1169.
• Cheung K, Barter MJ, Falk J, Proctor CJ, Reynard LN, Young DA. Histone ChIP-Seq identifies differential enhancer usage during chondrogenesis as critical for defining cell-type specificity. FASEB Journal 2020, 34(4), 5317-5531.
• Rice SJ, Beier F, Young DA, Loughlin J. Interplay between genetics and epigenetics in osteoarthritis. Nature Reviews Rheumatology 2020, 16, 268-281.
• Coelho-Lima J, Mohammed A, Cormack S, Jones S, Ali A, Panahi P, Barter M, Bagnall A, Ali S, Young D, Spyridopoulos I. Kinetics Analysis of Circulating MicroRNAs Unveils Markers of Failed Myocardial Reperfusion. Clinical Chemistry 2020, 66(1), 247-256.
• Woods S, Charlton S, Cheung K, Hao Y, Soul J, Reynard LN, Crowe N, Swingler TE, Skelton AJ, Piróg KA, Miles CG, Tsompani D, Jackson RM, Dalmay T, Clark IM, Barter MJ, Young DA. microRNA-seq of cartilage reveals an over-abundance of miR-140-3p which contains functional isomiRs. RNA 2020, 26, 1575-1588.
• Le L, Niu L, Barter MJ, Young DA, Dalmay T, Clark IM, Swingler TE. The role of microRNA-3085 in chondrocyte function. Scientific Reports 2020, 10(1), 21923.
• Cheung K, Burgers MJ, Young DA, Cockell S, Reynard LN. Correlation of Infinium HumanMethylation450K and MethylationEPIC BeadChip arrays in cartilage. Epigenetics 2019, 15(6-7), 594-603.
• Ajekigbe B, Cheung K, Xu Y, Skelton AJ, Panagiotopoulos A, Soul J, Hardingham TE, Deehan DJ, Barter MJ, Young DA. Identification of long non-coding RNAs expressed in knee and hip osteoarthritic cartilage. Osteoarthritis and Cartilage 2019, 27(4), 694-702.
• Woods S, Barter MJ, Elliott HR, McGillivray CM, Birch MA, Clark IM, Young DA. miR-324-5p is up regulated in end-stage osteoarthritis and regulates Indian Hedgehog signalling by differing mechanisms in human and mouse. Matrix Biology 2019, 77, 87-100.
• Young DA, Barter MJ, Wilkinson DJ. Recent advances in understanding the regulation of metalloproteinases. F1000Research 2019, 8, 195.
• Swingler TE, Niu L, Smith P, Paddy P, Le L, Barter MJ, Young DA, Clark IM. The function of microRNAs in cartilage and osteoarthritis. Clinical and Experimental Rheumatology 2019, 37(5), 40-47.
• Steinbusch MMF, Fang Y, Milner PI, Clegg PD, Young DA, Welting TJM, Peffers MJ. Serum snoRNAs as biomarkers for joint ageing and post traumatic osteoarthritis. Scientific Reports 2017, 7, 43558.
• Barter MJ, Gomez R, Hyatt S, Cheung K, Skelton AJ, Xu Y, Clark IM, Young DA. The long non-coding RNA ROCR contributes to SOX9 expression and chondrogenic differentiation of human mesenchymal stem cells. Development 2017, 144, 4510-4521.
• Crowe N, Swingler TE, Le LTT, Barter MJ, Wheeler G, Pais H, Donell ST, Young DA, Dalmay T, Clark IM. Detecting new microRNAs in human osteoarthritic chondrocytes identifies miR-3085 as a human, chondrocyte-selective, microRNA. Osteoarthritis and Cartilage 2016, 24(3), 534-543.
• Le LTT, Swingler TE, Crowe N, Vincent TL, Barter MJ, Donell ST, Delany AM, Dalmay T, Young DA, Clark IM. The microRNA-29 family in cartilage homeostasis and osteoarthritis. Journal of Molecular Medicine 2016, 94(5), 583-596.
• Rushton MD, Young DA, Loughlin J, Reynard LN. Differential DNA methylation and expression of inflammatory and zinc transporter genes defines subgroups of osteoarthritic hip patients. Annals of the Rheumatic Diseases 2015, 74(9), 1778-1782.
• Rushton MD, Young DA, Loughlin J, Reynard LN. Differential DNA methylation and expression of inflammatory and zinc transporter genes defines sub-groups of osteoarthritic hip patients. In: 2015 OARSI World Congress on Osteoarthritis: Celebrating 25 Years of Osteoarthritis Research. 2015, Seattle, WA, USA: Elsevier.
• Barter MJ, Tselepi M, Gomez R, Woods S, Hui W, Smith GR, Shanley DP, Clark IM, Young DA. Genome-wide microRNA and gene analysis of mesenchymal stem cell chondrogenesis identifies an essential role and multiple targets for miR-140-5p. Stem Cells 2015, 33(11), 3266-3280.
• Rushton MD, Reynard LN, Young DA, Shepherd C, Aubourg G, Gee F, Darlay R, Deehan D, Cordell HJ, Loughlin J. Methylation quantitative trait locus (meQTL) analysis of osteoarthritis links epigenetics with genetic risk. Human Molecular Genetics 2015, 24(25), 7432-7444.
• Purvis HA, Anderson AE, Young DA, Isaacs JD, Hilkens CMU. A Negative Feedback Loop Mediated by STAT3 Limits Human Th17 Responses. Journal of Immunology 2014, 193(3), 1142-1150.
• Rushton MD, Reynard LN, Barter MJ, Refaie R, Rankin KS, Young DA, Loughlin J. Characterization of the cartilage DNA methylome in knee and hip osteoarthritis. Arthritis & Rheumatology 2014, 66(9), 2450-2460.
• Litherland GJ, Hui W, Elias MS, Wilkinson DJ, Watson S, Huesa C, Young DA, Rowan AD. Glycogen Synthase Kinase 3 Inhibition Stimulates Human Cartilage Destruction and Exacerbates Murine Osteoarthritis. Arthritis & Rheumatology 2014, 66(8), 2175-2187.
• James K, Tarn JR, Al-Ali S, Hallinan J, Young DA, Ng WF. Integration of Gene Expression Data with Interaction and Annotation Data Reveals Patterns of Connection Between Primary Sjögren’s Syndrome Associated Genes and Immune Processes. In: Rheumatology 2014. 2014, Liverpool, UK: Oxford University Press.
• Hui W, Young DA, Rowan AD, Xu X, Cawston TE, Proctor CJ. Oxidative changes and signalling pathways are pivotal in initiating age-related changes in articular cartilage. Annals of the Rheumatic Diseases 2014, 1-10.
• Radwan M, Wilkinson DJ, Hui W, Destrument AP, Charlton SH, Barter MJ, Gibson B, Coulombe J, Gray DA, Rowan AD, Young DA. Protection against murine osteoarthritis by inhibition of the 26S proteasome and lysine-48 linked ubiquitination. Annals of the Rheumatic Diseases 2014.
• Cawston TE, Young DA, Rowan DD. Tissue destruction and repair. In: Hochberg MC; Silman AJ; Smolen JS; Weinblatt ME; Weisman MH, ed. Rheumatology: Sixth Edition. Philadelphia, PA: Elsevier Inc, 2014, pp.152-159.
• Barter MJ, Young DA. Epigenetic Mechanisms and Non-coding RNAs in Osteoarthritis. Current Rheumatology Reports 2013, 15(9), 353.
• Radwan M, Gavriilidis C, Robinson JH, Davidson R, Clark IM, Rowan AD, Young DA. Matrix metalloproteinase-13 expression in response to double-stranded RNA in human chondrocytes. Arthritis & Rheumatism 2013, 65(5), 1290-1301.
• Gavriilidis C, Miwa S, von Zglinicki T, Taylor RW, Young DA. Mitochondrial dysfunction in osteoarthritis is associated with down-regulation of superoxide dismutase 2. Arthritis & Rheumatism 2013, 65(2), 378-387.
• Young DA. More evidence for a role of CpG methylation in the pathogenesis of osteoarthritis. Arthritis and Rheumatism 2013, 65(3), 555-558.
• Syddall CM, Reynard LN, Young DA, Loughlin J. The Identification of Trans-acting Factors That Regulate the Expression of GDF5 via the Osteoarthritis Susceptibility SNP rs143383. PLoS Genetics 2013, 9(6), e1003557.
• Pratt AG, Swan DC, Richardson S, Wilson G, Hilkens C, Young DA, Isaacs JD. A CD4 T cell gene signature for early rheumatoid arthritis implicates interleukin 6-mediated STAT3 signalling, particularly anti-citrullinated peptide antibody-negative disease. Annals of the Rheumatic Diseases 2012, 71(8), 1374-1381.
• Bui C, Barter MJ, Scott JL, Xu Y, Galler M, Reynard LN, Rowan AD, Young DA. cAMP response element-binding (CREB) recruitment following a specific CpG demethylation leads to the elevated expression of the matrix metalloproteinase 13 in human articular chondrocytes and osteoarthritis. FASEB Journal 2012, 26(7), 3000-3011.
• Barter MJ, Bui C, Young DA. Epigenetic mechanisms in cartilage and osteoarthritis: DNA methylation, histone modifications and microRNAs. Osteoarthritis and Cartilage 2012, 20(5), 339-349.
• Xu Y, Barter MJ, Swan DC, Rankin KS, Rowan AD, Santibanez-Koref M, Loughlin J, Young DA. Identification of the pathogenic pathways in osteoarthritic hip cartilage: commonality and discord between hip and knee OA. Osteoarthritis and Cartilage 2012, 20(9), 1029-1038.
• Hui W, Litherland GJ, Elias MS, Kitson GI, Cawston TE, Rowan AD, Young DA. Leptin produced by joint white adipose tissue induces cartilage degradation via upregulation and activation of matrix metalloproteinases. Annals of the Rheumatic Diseases 2012, 71(3), 455-462.
• Swingler TE, Wheeler G, Carmont V, Elliott HR, Barter MJ, Abu-Elmagd M, Donell ST, Boot-Handford RP, Hajihosseini MK, Münsterberg A, Dalmay T, Young DA, Clark IM. The expression and function of microRNAs in chondrogenesis and osteoarthritis. Arthritis and Rheumatism 2012, 64(6), 1909-1919.
• Young DA, Bui C, Barter MJ. Understanding CpG methylation in the context of osteoarthritis. Epigenomics 2012, 4(6), 593-595.
• Reynard LN, Bui C, Canty-Laird EG, Young DA, Loughlin J. Expression of the osteoarthritis-associated gene GDF5 is modulated epigenetically by DNA methylation. Human Molecular Genetics 2011, 20(17), 3450-3460.
• Cui Y, Yu J, Urban JPG, Young DA. Differential Gene Expression Profiling of Metalloproteinases and Their Inhibitors A Comparison Between Bovine Intervertebral Disc Nucleus Pulposus Cells and Articular Chondrocytes. Spine 2010, 35(11), 1101-1108.
• Barter MJ, Pybus L, Litherland GJ, Rowan AD, Clark IM, Edwards DR, Cawston TE, Young DA. HDAC-mediated control of ERK- and PI3K-dependent TGF-beta-induced extracellular matrix-regulating genes. Matrix Biology 2010, 29(7), 602-612.
• Barter MJ, Hui W, Lakey RL, Catterall JB, Cawston TE, Young DA. Lipophilic statins prevent matrix metalloproteinase-mediated cartilage collagen breakdown by inhibiting protein geranylgeranylation. Annals of the Rheumatic Diseases 2010, 69(12), 2189-2198.
• Hui W, Litherland GJ, Jefferson M, Barter MJ, Elias MS, Cawston TE, Rowan AD, Young DA. Lithium protects cartilage from cytokine-mediated degradation by reducing collagen-degrading MMP production via inhibition of the P38 mitogen-activated protein kinase pathway. Rheumatology 2010, 49(11), 2043-2053.
• Milner JM, Patel A, Davidson RK, Swingler TE, Desilets A, Young DA, Kelso EB, Donell ST, Cawston TE, Clark IM, Ferrell WR, Plevin R, Lockhart JC, Leduc R, Rowan AD. Matriptase is a novel initiator of cartilage matrix degradation in osteoarthritis. Arthritis & Rheumatism 2010, 62(7), 1955-1966.
• Swingler TE, Kevorkian L, Culley KL, Illman SA, Young DA, Parker AE, Lohi J, Clark IM. MMP28 gene expression is regulated by Sp1 transcription factor acetylation. Biochemical Journal 2010, 427, 391-400.
• Cawston TE, Young DA. Proteinases involved in matrix turnover during cartilage and bone breakdown. Cell and Tissue Research 2010, 339(1), 221-235.
• Scott JL, Gabrielides C, Davidson RK, Swingler TE, Clark IM, Wallis GA, Boot-Handford RP, Kirkwood TBL, Talyor RW, Young DA. Superoxide dismutase downregulation in osteoarthritis progression and end-stage disease. Annals of the Rheumatic Diseases 2010, 69(8), 1502-1510.