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Staff Profile

Dr Louise Reynard

Senior Lecturer

  • Address: Skeletal Research Group
    Chromosome Biology and the Cell Cycle Theme
    Biosciences Institute
    International Centre for Life
    Central Parkway
    Newcastle upon Tyne
    NE1 3BZ
Background

Contact Details

Email

louise.reynard@newcastle.ac.uk


Address              

Skeletal Research Group

Chromosome Biology and the Cell Cycle Theme

Biosciences Institute

International Centre for Life

Central Parkway

Newcastle upon Tyne

NE1 3BZ


Background

Louise Reynard is a Senior Lecturer within the Biosciences Institute at Newcastle University, UK. She graduated from the University of Cambridge with a 1st Class MA Cantab in Natural Sciences, specialising in Genetics. She completed her PhD studies in Developmental Genetics at the MRC National Institute for Medical Research and University College London. Louise joined Newcastle University in 2009 as a post-doctoral researcher, was made a Research Fellow in 2010 and was promoted to Lecturer in 2017. Her research focuses on elucidating the molecular mechanisms through which genetic variation and epigenetic mechanisms impact on gene expression to predispose to musculoskeletal ageing and disease.


Research

Dr Reynard's research focuses on functional genetic and epigenetic analysis of musculoskeletal diseases, in particular osteoarthritis (OA) and rheumatoid arthritis (RA). She also has an interest in spermatogenesis and male infertility. One of Dr Reynard’s main research goals is to elucidate the molecular mechanisms through which genetic variation and epigenetic mechanisms impact on gene expression to predispose to disease. Current research includes examining the role of DNA methylation in modulating or mediating OA and RA genetic disease risk, investigating the impact of age-related and joint site methylation differences in cartilage function, functional analysis of OA-associated methylation changes in cartilage, and analysing alternative RNA splicing in cartilage differentiation, ageing and disease.


Laboratory Techniques

  • targeted chromosome confirmation capture (Capture-C) to identify promoter-transcriptional enhancer interactions
  • ATACseq open chromatin profiling
  • histone ChIPseq and chromatin state learning
  • CRISPR mediated genetic deletion (Cas9) and epigenetic editing (dCas9-DNMT3, dCas9-TET), CRISPRa (dCas9-VPR), CRISPRi (dCas9-KRAB) and CRISPR tagging (dCas9-FLAG)
  • human cell line and primary cell culture
  • transcriptional enhancer reporter assays (luciferase, B -gal)
  • targeted and genome wide DNA methylation profiling (bisulphite pyrosequencing, methylation arrays)
  • transcriptional analysis (RNAseq, qRT-PCR, RNA splicing quantification)
  • EMSAs and in vitro methylation to study effect of DNA methylation on regulatory activity and transcription factor binding
  • western blot, IHC and ICC protein analysis
  • Lentiviral mediated overexpression and siRNA knock downs
  • cloning and bacterial cell culture


Collaborations

Dr Reynard has a wide-ranging network of local, national and international collaborators. Within Newcastle University, Dr Reynard collaborates with Professor David Young to understand the contribution of epigenetics in cartilage development, ageing and disease, and with Professor David Elliott to examine alternative RNA splicing in male infertility and in cartilage development, differentiation, ageing and disease. She also investigates the role of DNA methylation as a mediator, modulator and biomarker of the autoimmune disease rheumatoid arthritis through collaborations with Dr Arthur Pratt, Dr Faye Cooles and Professor John Isaacs, and has recently established a collaboration with Professor Mark Pearce and Dr Andrew Kingston to explore if DNA methylation can act as a biomarker of biological age and predictor of disease risk in the Newcastle 1000 families and 85+ longitudinal cohorts. Dr Reynard is a member of the MRC-ARUK Centre for Integrated Research into Musculoskeletal Ageing and collaborates closely several researchers at the University of Liverpool and University of Manchester. She also works with researchers from Maastrict University and Leiden University in the Netherlands, Harvard University, University of Oklahoma and The Scripps Research Institute in the USA and the University of Sydney, Australia. 


Funding

Dr Reynard’s research is funded by the BBSRC, MRC, Versus Arthritis, the JGW Patterson Foundation, the Dunhill Medical Trust, the Community Foundation, the Newcastle upon Tyne Hospitals Joint Research Executive Scientific Committee and the Lincoln Centre, Sydney, Australia. 


Teaching

Dr Reynard lectures on the undergraduate modules Medical genomics: from DNA to disease, Research in Biochemistry & Genetics, Research in Pharmacological Sciences, and Research in Physiological Sciences, and Masters level modules Chromosome Biology and Cell Cycle Control in Health and Disease, Clinical Epidemiology, Developmental Genetics and Bioinformatics for Biomedical Scientists. Her lectures cover a range of topics from sex-linked genetic disorders and techniques for measuring gene expression to epigenetics and bioinformatic analysis.


Dr Reynard is a member of the MRes Programmes academic team, the largest Masters programme within Newcastle University Faculty of Medical Science, with between 180 and 260 students per year. As part of this role, Dr Reynard is a member of the MRes Curriculum Committee, MRes Board of Studies and MRes Examination Committee. She was the Examination Committee Deputy Chair from 2018 to 2022 and was a member of MRes Moderation and Scaling Committee, MRes Staff-Student Committee, MRes Disciplinary Committee and the MRes Personal Extenuating Circumstances committee during this time.


Dr Reynard supervises undergraduate and MRes laboratory project students, undergraduate vacation project students and PhD students. She was nominated for The Education Awards in 2022 and 2023 in the ‘Research Supervisor of the Year’ category. Louise sits on several PhD progression panels and has acted as an external PhD examiner for the University of Liverpool, University of Manchester and Leiden University, the Netherlands.


Publications

Research Articles

Interferon-α-mediated therapeutic resistance in early rheumatoid arthritis implicates epigenetic reprogramming. Cooles FAH, Tarn J, Lendrem DW, Naamane N, Lin CM, Millar B, Maney NJ, Anderson AE, Thalayasingam N, Diboll J, Bondet V, Duffy D, Barnes MR, Smith GR, Ng S, Watson D, Henkin R, Cope AP, Reynard LN, Pratt AG; RA-MAP Consortium, Isaacs JD. Ann Rheum Dis. 2022 Jun9. doi:10.1136/annrheumdis-2022-222370. PMID: 35680389.

Cryptic splicing: common pathological mechanisms involved in male infertility and neuronal diseases. Aldalaqan S, Dalgliesh C, Luzzi S, Siachisumo C, Reynard LN, Ehrmann I, Elliott DJ. Cell Cycle. 2022 Feb;21(3):219-227. doi:10.1080/15384101.2021.2015672. PMID: 34927545

A Bayesian network approach incorporating imputation of missing data enables exploratory analysis of complex causal biological relationships. Howey R, Clark AD, Naamane N, Reynard LN, Pratt AG, Cordell HJ. PLoS Genet. 2021 Sep 29;17(9):e1009811. doi: 10.1371/journal.pgen.1009811. PMID: 34587167;

microRNA-seq of cartilage reveals an overabundance of miR-140-3p which contains functional isomiRs. 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. RNA. 2020 Nov;26(11):1575-1588. doi: 10.1261/rna.075176.120. PMID: 32660984.

Histone ChIP-Seq identifies differential enhancer usage during chondrogenesis as critical for defining cell-type specificity. Cheung K, Barter MJ, Falk J, Proctor CJ, Reynard LN, Young DA. FASEB J. 2020 Apr;34(4):5317-5331. doi:10.1096/fj.201902061RR. PMID: 32058623.

DNA hypomethylation during MSC chondrogenesis occurs predominantly at enhancer regions. Barter MJ, Bui C, Cheung K, Falk J, Gómez R, Skelton AJ, Elliott HR, Reynard LN, Young DA. Sci Rep. 2020 Jan 24;10(1):1169. doi:10.1038/s41598-020-58093-5. PMID: 31980739.

Lymphocyte DNA methylation mediates genetic risk at shared immune-mediated disease loci. Clark AD, Nair N, Anderson AE, Thalayasingam N, Naamane N, Skelton AJ, Diboll J, Barton A, Eyre S, Isaacs JD, Pratt AG, Reynard LN. J Allergy Clin Immunol. 2020 May;145(5):1438-1451. doi: 10.1016/j.jaci.2019.12.910. Epub 2020 Jan 13. PMID: 31945409; PMCID: PMC7201180.

Correlation of Infinium HumanMethylation450K and MethylationEPIC BeadChip arrays in cartilage. Cheung K, Burgers MJ, Young DA, Cockell S, Reynard LN. Epigenetics. 2020 Jun-Jul;15(6-7):594-603. doi: 10.1080/15592294.2019.1700003. PMID: 31833794

Expression analysis of the osteoarthritis genetic susceptibility mapping to the matrix Gla protein gene MGP. Shepherd C, Reese AE, Reynard LN, Loughlin J. Arthritis Res Ther. 2019 Jun 18;21(1):149. doi: 10.1186/s13075-019-1934-7. PMID: 31215457.

Discovery and analysis of methylation quantitative trait loci (mQTLs) mapping to novel osteoarthritis genetic risk signals. Rice SJ, Cheung K, Reynard LN, Loughlin J. Osteoarthritis Cartilage. 2019 Oct;27(10):1545-1556. doi: 10.1016/j.joca.2019.05.017. PMID: 31173883.

Prioritization of PLEC and GRINA as Osteoarthritis Risk Genes Through the Identification and Characterization of Novel Methylation Quantitative Trait Loci. Rice SJ, Tselepi M, Sorial AK, Aubourg G, Shepherd C, Almarza D, Skelton AJ, Pangou I, Deehan D, Reynard LN, Loughlin J. Arthritis Rheumatol. 2019Aug;71(8):1285-1296. doi: 10.1002/art.40849. PMID: 30730609.

 Identification of a novel, methylation-dependent, RUNX2 regulatory region associated with osteoarthritis risk. Rice SJ, Aubourg G, Sorial AK, Almarza D, Tselepi M, Deehan DJ, Reynard LN, Loughlin J. Hum Mol Genet. 2018 Oct1;27(19):3464-3474. doi: 10.1093/hmg/ddy257. PMID: 30010910; PMCID: PMC6140783.

Cytokine-induced cysteine- serine-rich nuclear protein-1 (CSRNP1) selectively contributes to MMP1 expression in human chondrocytes. Macdonald CD, Falconer AMD, Chan CM, Wilkinson DJ, Skelton A, Reynard L, Litherland GJ, Europe-Finner GN, Rowan AD. PLoS One 2018 13(11):e0207240. DOI: 10.1371/journal.pone.0207240. PMID: 30440036 PMCID: PMC6237337.

Functional Characterization of the Osteoarthritis Genetic Risk Residing at ALDH1A2 Identifies rs12915901 as a Key Target Variant. Shepherd C, Zhu D, Skelton AJ, Combe J, Threadgold H, Zhu L, Vincent TL, Stuart P, Reynard LN, Loughlin J. Arthritis Rheumatol. 2018 Oct;70(10):1577-1587. doi:10.1002/art.40545. PMID: 29732726.

CD4+ and B Lymphocyte Expression Quantitative Traits at Rheumatoid Arthritis Risk Loci in Patients With Untreated Early Arthritis: Implications for Causal Gene Identification. Thalayasingam N, Nair N, Skelton AJ, Massey J, Anderson AE, Clark AD, Diboll J, Lendrem DW, Reynard LN, Cordell HJ, Eyre S, Isaacs JD, Barton A, Pratt AG. Arthritis Rheumatol. 2018 Mar;70(3):361-370. doi:10.1002/art.40393. Epub 2018 Jan 30. PMID: 29193869; PMCID: PMC5888199.

Whole-genome sequencing identifies rare genotypes in COMP and CHADL associated with high risk of hip osteoarthritis. Styrkarsdottir U, Helgason H, Sigurdsson A, Norddahl GL, Agustsdottir AB, Reynard LN, Villalvilla A, Halldorsson GH, Jonasdottir A, Magnusdottir A, Oddson A, Sulem G, Zink F, Sveinbjornsson G, Helgason A, Johannsdottir HS, Helgadottir A, Stefansson H, Gretarsdottir S, Rafnar T, Almdahl IS, Brækhus A, Fladby T, Selbæk G, Hosseinpanah F, Azizi F, Koh JM, Tang NLS, Danesphour M, Mayordomo JI, Welt C, Braund PS, Samani NJ, Kiemeney LA, Lohmander LS, Christiansen C, Andreassen OA, Consortium A, Magnusson O, Masson G, Kong A, Jonsdottir I, Gudbjartsson D, Sulem P, Jonsson H, Loughlin J, Ingvarsson T, Thorsteinsdottir U, Stefansson K.  Nat Genet. 2017 May;49(5):801-805. doi: 10.1038/ng.3816. Epub 2017 Mar 20.

 A consistent and potentially exploitable response during chondrogenesis of mesenchymal stem cells from osteoarthritis patients to the protein encoded by the susceptibility gene GDF5. Ratnayake M, Tselepi M, Bloxham R, Plöger F, Reynard LN, Loughlin J. PLoS One. 2017 May 8;12(5):e0176523. doi: 10.1371/journal.pone.0176523. PMID: 28481944; PMCID: PMC5421763.

Functional Characterization of the Osteoarthritis Susceptibility Mapping to CHST11-A Bioinformatics and Molecular Study. Reynard LN, Ratnayake M, Santibanez-Koref M, Loughlin J. PLoS One. 2016 Jul 8;11(7):e0159024. doi:10.1371/journal.pone.0159024. PMID: 27391021; PMCID: PMC4938163.

The first international workshop on the epigenetics of osteoarthritis. Meulenbelt IM, Bhutani N, den Hollander W, Gay S, Oppermann U, Reynard LN, Skelton AJ, Young DA, Beier F, Loughlin J. Connect Tissue Res. 2017 Jan;58(1):37-48.doi: 10.3109/03008207.2016.1168409. Epub 2016 Mar 30. PMID: 27028588.

Defective Leukocyte Adhesion and Chemotaxis Contributes to Combined Immunodeficiency in Humans with Autosomal Recessive MST1 Deficiency. Dang TS, Willet JD, Griffin HR, Morgan NV, O'Boyle G, Arkwright PD, Hughes SM, Abinun M, Tee LJ, Barge D, Engelhardt KR, Jackson M, Cant AJ, Maher ER, Koref MS, Reynard LN, Ali S, Hambleton S. J Clin Immunol. 2016 Feb;36(2):117-22. doi: 10.1007/s10875-016-0232-2. Epub 2016 Jan 22.

Expression analysis of the osteoarthritis genetic susceptibility locus mapping to an intron of the MCF2L gene and marked by the polymorphism rs11842874. Shepherd C, Skelton AJ, Rushton MD, Reynard LN, Loughlin J. BMC Med Genet. 2015 Nov 19;16:108. doi: 10.1186/s12881-015-0254-2. PMID: 26584642; PMCID:

PMC4653905.

Methylation quantitative trait locus analysis of osteoarthritis links epigenetics with genetic risk. Rushton MD, Reynard LN, Young DA, Shepherd C, Aubourg G, Gee F, Darlay R, Deehan D, Cordell HJ, Loughlin J.

Hum Mol Genet. 2015 Dec20;24(25):7432-44. doi: 10.1093/hmg/ddv433. Epub 2015 Oct 13. PMID: 26464490;PMCID: PMC4664171.

Functional characterisation of the osteoarthritis susceptibility locus at chromosome 6q14.1 marked by the

polymorphism rs9350591. Johnson K, Reynard LN, Loughlin J. BMC Med Genet. 2015 Sep 7;16:81. doi:

10.1186/s12881-015-0215-9. PMID: 26346884; PMCID: PMC4562116.

Correlation of the osteoarthritis susceptibility variants that map to chromosome 20q13 with an expression

quantitative trait locus operating on NCOA3 and with functional variation at the polymorphism rs116855380. Gee F, Rushton MD, Loughlin J, Reynard LN. Arthritis Rheumatol. 2015 Nov;67(11):2923-32. doi:10.1002/art.39278. PMID: 26211391; PMCID: PMC4832313.

Differential DNA methylation and expression of inflammatory and zinc transporter genes defines subgroups of osteoarthritic hip patients. Rushton MD, Young DA, Loughlin J, Reynard LN. Ann Rheum Dis. 2015 Sep;74(9):1778-82. doi:10.1136/annrheumdis-2014-206752. Epub 2015 Apr 8. PMID: 25854584; PMCID:

PMC4552898.

Dual proteolytic pathways govern glycolysis and immune competence. Lu W, Zhang Y, McDonald DO, Jing H, Carroll B, Robertson N, Zhang Q, Griffin H, Sanderson S, Lakey JH, Morgan NV, Reynard LN, Zheng L, Murdock HM, Turvey SE, Hackett SJ, Prestidge T, Hall JM, Cant AJ, Matthews HF, Koref MF, Simon AK,

Korolchuk VI, Lenardo MJ, Hambleton S, Su HC. Cell. 2014 Dec 18;159(7):1578-90. doi: 10.1016/j.cell.2014.12.001. PMID: 25525876; PMCID: PMC4297473.

Allelic expression analysis of the osteoarthritis susceptibility locus that maps to chromosome 3p21

reveals cis-acting eQTLs at GNL3 and SPCS1. Gee F, Clubbs CF, Raine EV, Reynard LN, Loughlin J.

BMC Med Genet. 2014 May 4;15:53. doi: 10.1186/1471-2350-15-53. PMID: 24886551; PMCID: PMC4101866.

CpG methylation regulates allelic expression of GDF5 by modulating binding of SP1 and SP3 repressor proteins to the osteoarthritis susceptibility SNP rs143383. Reynard LN, Bui C, Syddall CM, Loughlin J. Hum Genet. 2014Aug;133(8):1059-73. doi: 10.1007/s00439-014-1447-z. Epub 2014 May 27. PMID:24861163; PMCID: PMC4099533.

Characterization of the cartilage DNA methylome in knee and hip osteoarthritis. Rushton MD, Reynard LN, Barter MJ, Refaie R, Rankin KS, Young DA, Loughlin J. Arthritis Rheumatol. 2014 Sep;66(9):2450-60. doi:

10.1002/art.38713. PMID: 24838673; PMCID: PMC4314681.

Identification and analysis of a SMAD3 cis-acting eQTL operating in primary osteoarthritis and in the aneurysms and osteoarthritis syndrome. Raine EV, Reynard LN, van de Laar IM, Bertoli-Avella AM, Loughlin J. Osteoarthritis Cartilage. 2014 May;22(5):698-705. doi: 10.1016/j.joca.2014.02.931. Epub 2014Feb 28. PMID: 24583347; PMCID: PMC4032576.

The identification of trans-acting factors that regulate the expression of GDF5 via the osteoarthritis

susceptibility SNP rs143383. Syddall CM, Reynard LN, Young DA, Loughlin J. PLoS Genet. 2013 Jun;9(6):e1003557. doi:10.1371/journal.pgen.1003557. Epub 2013 Jun 27. PMID: 23825960; PMCID:

PMC3694828.

Allelic expression analysis of the osteoarthritis susceptibility gene COL11A1 in human joint tissues. Raine EV, Dodd AW, Reynard LN, Loughlin J. BMC Musculoskelet Disord. 2013 Mar 8;14:85. doi: 10.1186/1471-2474-14-85. PMID:23497244; PMCID: PMC3599795.

Gene expression analysis reveals HBP1 as a key target for the osteoarthritis susceptibility locus that maps to chromosome 7q22. Raine EV, Wreglesworth N, Dodd AW, Reynard LN, Loughlin J. Ann Rheum Dis. 2012 Dec;71(12):2020-7. doi:10.1136/annrheumdis-2012-201304. Epub 2012 May 14. PMID: 22586168.

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. Bui C, Barter MJ, Scott JL, Xu Y, Galler M, Reynard LN, Rowan AD, Young DA. FASEB J. 2012 Jul;26(7):3000-11. doi: 10.1096/fj.12-206367. Epub 2012 Apr 13. PMID: 22505473.

Allelic expression analysis of the osteoarthritis susceptibility locus that maps to MICAL3. Ratnayake M, Reynard LN, Raine EV, Santibanez-Koref M, Loughlin J. BMC Med Genet. 2012 Mar 2;13:12. doi: 10.1186/1471-2350-13-12. PMID:22385522; PMCID: PMC3366887.

Exome sequencing identifies GATA-2 mutation as the cause of dendritic cell, monocyte, B and NK lymphoid deficiency. Dickinson RE, Griffin H, Bigley V, Reynard LN, Hussain R, Haniffa M, Lakey JH, Rahman T, Wang XN, McGovern N, Pagan S, Cookson S, McDonald D, Chua I, Wallis J, Cant A, Wright M, Keavney B, Chinnery PF, Loughlin J, Hambleton S, Santibanez-Koref M, Collin M. Blood. 2011 Sep 8;118(10):2656-8. doi: 10.1182/blood-2011-06-360313. Epub 2011 Jul 15. PMID: 21765025; PMCID: PMC5137783.

Expression of the osteoarthritis-associated gene GDF5 is modulated epigenetically by DNA methylation. Reynard LN, Bui C, Canty-Laird EG, Young DA, Loughlin J. Hum Mol Genet. 2011 Sep 1;20(17):3450-60. doi: 10.1093/hmg/ddr253. Epub 2011 Jun 3. PMID: 21642387.

Deep sequencing of GDF5 reveals the absence of rare variants at this important osteoarthritis susceptibility locus. Dodd AW, Rodriguez-Fontenla C, Calaza M, Carr A, Gomez-Reino JJ, Tsezou A, Reynard LN, Gonzalez A, Loughlin J. Osteoarthritis Cartilage. 2011 Apr;19(4):430-4. doi: 10.1016/j.joca.2011.01.014. PMID: 21281725.

Increased sex chromosome expression and epigenetic abnormalities in spermatids from male mice with Y chromosome deletions. Reynard LN, Turner JM. J Cell Sci. 2009 Nov 15;122(Pt 22):4239-48. doi: 10.1242/jcs.049916. Epub 2009 Oct 27. PMID: 19861498; PMCID: PMC2776507.

The multi-copy mouse gene Sycp3-like Y-linked (Sly) encodes an abundant spermatid protein that interacts with a histone acetyltransferase and an acrosomal protein. Reynard LN, Cocquet J, Burgoyne PS. Biol Reprod. 2009 Aug;81(2):250-7. doi: 10.1095/biolreprod.108.075382. Epub 2009 Jan 28. PMID: 19176879; PMCID: PMC2849823.

Expression analysis of the mouse multi-copy X-linked gene Xlr-related, meiosis-regulated (Xmr), reveals that Xmr encodes a spermatid-expressed cytoplasmic protein, SLX/XMR. Reynard LN, Turner JM, Cocquet J, Mahadevaiah SK, Touré A, Höög C, Burgoyne PS. Biol Reprod. 2007 Aug;77(2):329-35. doi:

10.1095/biolreprod.107.061101. Epub 2007 May 2. PMID: 17475928.

Identification of novel Y chromosome encoded transcripts by testis transcriptome analysis of mice with deletions of the Y chromosome long arm. Touré A, Clemente EJ, Ellis P, Mahadevaiah SK, Ojarikre OA, Ball PA, Reynard L, Loveland KL, Burgoyne PS, Affara NA. Genome Biol 2005;6(12):R102. doi: 10.1186/gb-2005-6-12-r102. PMID: 16356265 PMCID: PMC1414076.

 

Review articles

Osteoarthritis year in review 2019: genetics, genomics and epigenetics. Reynard LN, Barter MJ. Osteoarthritis Cartilage. 2020 Mar;28(3):275-284. doi:10.1016/j.joca.2019.11.010. Epub 2019 Dec 23. PMID: 31874234.

Analysis of genetics and DNA methylation in osteoarthritis: What have we learnt about the disease? Reynard LN. Semin Cell Dev Biol. 2017 Feb;62:57-66. doi: 10.1016/j.semcdb.2016.04.017. Epub 2016 Apr 26. PMID: 27130636.

The role of inflammation-related genes in osteoarthritis. Rogers EL, Reynard LN, Loughlin J.

Osteoarthritis Cartilage. 2015 Nov;23(11):1933-8. doi:10.1016/j.joca.2015.01.003. PMID: 26521739.

Osteoarthritis: Epigenetics of articular cartilage in knee and hip OA. Loughlin J, Reynard LN.  Nat Rev Rheumatol. 2015 Jan;11(1):6-7. doi:10.1038/nrrheum.2014.189. Epub 2014 Nov 4. PMID: 25366188.

Insights from human genetic studies into the pathways involved in osteoarthritis. Reynard LN, Loughlin J. Nat Rev Rheumatol. 2013 Oct;9(10):573-83.doi: 10.1038/nrrheum.2013.121. Epub 2013 Aug 20. PMID: 23958796.

The genetics and functional analysis of primary osteoarthritis susceptibility. Reynard LN, Loughlin J. Expert Rev Mol Med. 2013 Feb 18;15:e2. doi:10.1017/erm.2013.4. PMID: 23414786; PMCID: PMC3575889.

Genetics and epigenetics of osteoarthritis. Reynard LN, Loughlin J. Maturitas. 2012 Mar;71(3):200-4. doi: 10.1016/j.maturitas.2011.12.001. Epub 2011 Dec 29. PMID: 22209350


 





Research

Research Interests

Dr Reynard's research focuses on functional genetic and epigenetic analysis of musculoskeletal diseases, in particular osteoarthritis (OA) and rheumatoid arthritis (RA). She also has an interest in spermatogenesis and male infertility. One of Dr Reynard’s main research goals is to elucidate the molecular mechanisms through which genetic variation and epigenetic mechanisms impact on gene expression to predispose to disease. Current research includes examining the role of DNA methylation in modulating or mediating OA and RA genetic disease risk, investigating the impact of age-related and joint site methylation differences in cartilage function, functional analysis of OA-associated methylation changes in cartilage, and analysing alternative RNA splicing in cartilage differentiation, ageing and disease.


Laboratory Techniques

  • targeted chromosome confirmation capture (Capture-C) to identify promoter-transcriptional enhancer interactions
  • ATACseq open chromatin profiling
  • histone ChIPseq and chromatin state learning
  • CRISPR mediated genetic deletion (Cas9) and epigenetic editing (dCas9-DNMT3, dCas9-TET), CRISPRa (dCas9-VPR), CRISPRi (dCas9-KRAB) and CRISPR tagging (dCas9-FLAG)
  • human cell line and primary cell culture
  • transcriptional enhancer reporter assays (luciferase, B -gal)
  • targeted and genome wide DNA methylation profiling (bisulphite pyrosequencing, methylation arrays)
  • transcriptional analysis (RNAseq, qRT-PCR, RNA splicing quantification)
  • EMSAs and in vitro methylation to study effect of DNA methylation on regulatory activity and transcription factor binding
  • western blot, IHC and ICC protein analysis
  • Lentiviral mediated overexpression and siRNA knock downs
  • cloning and bacterial cell culture


Publications

Research Articles

Interferon-α-mediated therapeutic resistance in early rheumatoid arthritis implicates epigenetic reprogramming. Cooles FAH, Tarn J, Lendrem DW, Naamane N, Lin CM, Millar B, Maney NJ, Anderson AE, Thalayasingam N, Diboll J, Bondet V, Duffy D, Barnes MR, Smith GR, Ng S, Watson D, Henkin R, Cope AP, Reynard LN, Pratt AG; RA-MAP Consortium, Isaacs JD. Ann Rheum Dis. 2022 Jun9. doi:10.1136/annrheumdis-2022-222370. PMID: 35680389.

Cryptic splicing: common pathological mechanisms involved in male infertility and neuronal diseases. Aldalaqan S, Dalgliesh C, Luzzi S, Siachisumo C, Reynard LN, Ehrmann I, Elliott DJ. Cell Cycle. 2022 Feb;21(3):219-227. doi:10.1080/15384101.2021.2015672. PMID: 34927545

A Bayesian network approach incorporating imputation of missing data enables exploratory analysis of complex causal biological relationships. Howey R, Clark AD, Naamane N, Reynard LN, Pratt AG, Cordell HJ. PLoS Genet. 2021 Sep 29;17(9):e1009811. doi: 10.1371/journal.pgen.1009811. PMID: 34587167;

microRNA-seq of cartilage reveals an overabundance of miR-140-3p which contains functional isomiRs. 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. RNA. 2020 Nov;26(11):1575-1588. doi: 10.1261/rna.075176.120. PMID: 32660984.

Histone ChIP-Seq identifies differential enhancer usage during chondrogenesis as critical for defining cell-type specificity. Cheung K, Barter MJ, Falk J, Proctor CJ, Reynard LN, Young DA. FASEB J. 2020 Apr;34(4):5317-5331. doi:10.1096/fj.201902061RR. PMID: 32058623.

DNA hypomethylation during MSC chondrogenesis occurs predominantly at enhancer regions. Barter MJ, Bui C, Cheung K, Falk J, Gómez R, Skelton AJ, Elliott HR, Reynard LN, Young DA. Sci Rep. 2020 Jan 24;10(1):1169. doi:10.1038/s41598-020-58093-5. PMID: 31980739.

Lymphocyte DNA methylation mediates genetic risk at shared immune-mediated disease loci. Clark AD, Nair N, Anderson AE, Thalayasingam N, Naamane N, Skelton AJ, Diboll J, Barton A, Eyre S, Isaacs JD, Pratt AG, Reynard LN. J Allergy Clin Immunol. 2020 May;145(5):1438-1451. doi: 10.1016/j.jaci.2019.12.910. Epub 2020 Jan 13. PMID: 31945409; PMCID: PMC7201180.

Correlation of Infinium HumanMethylation450K and MethylationEPIC BeadChip arrays in cartilage. Cheung K, Burgers MJ, Young DA, Cockell S, Reynard LN. Epigenetics. 2020 Jun-Jul;15(6-7):594-603. doi: 10.1080/15592294.2019.1700003. PMID: 31833794

Expression analysis of the osteoarthritis genetic susceptibility mapping to the matrix Gla protein gene MGP. Shepherd C, Reese AE, Reynard LN, Loughlin J. Arthritis Res Ther. 2019 Jun 18;21(1):149. doi: 10.1186/s13075-019-1934-7. PMID: 31215457.

Discovery and analysis of methylation quantitative trait loci (mQTLs) mapping to novel osteoarthritis genetic risk signals. Rice SJ, Cheung K, Reynard LN, Loughlin J. Osteoarthritis Cartilage. 2019 Oct;27(10):1545-1556. doi: 10.1016/j.joca.2019.05.017. PMID: 31173883.

Prioritization of PLEC and GRINA as Osteoarthritis Risk Genes Through the Identification and Characterization of Novel Methylation Quantitative Trait Loci. Rice SJ, Tselepi M, Sorial AK, Aubourg G, Shepherd C, Almarza D, Skelton AJ, Pangou I, Deehan D, Reynard LN, Loughlin J. Arthritis Rheumatol. 2019Aug;71(8):1285-1296. doi: 10.1002/art.40849. PMID: 30730609.

 Identification of a novel, methylation-dependent, RUNX2 regulatory region associated with osteoarthritis risk. Rice SJ, Aubourg G, Sorial AK, Almarza D, Tselepi M, Deehan DJ, Reynard LN, Loughlin J. Hum Mol Genet. 2018 Oct1;27(19):3464-3474. doi: 10.1093/hmg/ddy257. PMID: 30010910; PMCID: PMC6140783.

Cytokine-induced cysteine- serine-rich nuclear protein-1 (CSRNP1) selectively contributes to MMP1 expression in human chondrocytes. Macdonald CD, Falconer AMD, Chan CM, Wilkinson DJ, Skelton A, Reynard L, Litherland GJ, Europe-Finner GN, Rowan AD. PLoS One 2018 13(11):e0207240. DOI: 10.1371/journal.pone.0207240. PMID: 30440036 PMCID: PMC6237337.

Functional Characterization of the Osteoarthritis Genetic Risk Residing at ALDH1A2 Identifies rs12915901 as a Key Target Variant. Shepherd C, Zhu D, Skelton AJ, Combe J, Threadgold H, Zhu L, Vincent TL, Stuart P, Reynard LN, Loughlin J. Arthritis Rheumatol. 2018 Oct;70(10):1577-1587. doi:10.1002/art.40545. PMID: 29732726.

CD4+ and B Lymphocyte Expression Quantitative Traits at Rheumatoid Arthritis Risk Loci in Patients With Untreated Early Arthritis: Implications for Causal Gene Identification. Thalayasingam N, Nair N, Skelton AJ, Massey J, Anderson AE, Clark AD, Diboll J, Lendrem DW, Reynard LN, Cordell HJ, Eyre S, Isaacs JD, Barton A, Pratt AG. Arthritis Rheumatol. 2018 Mar;70(3):361-370. doi:10.1002/art.40393. Epub 2018 Jan 30. PMID: 29193869; PMCID: PMC5888199.

Whole-genome sequencing identifies rare genotypes in COMP and CHADL associated with high risk of hip osteoarthritis. Styrkarsdottir U, Helgason H, Sigurdsson A, Norddahl GL, Agustsdottir AB, Reynard LN, Villalvilla A, Halldorsson GH, Jonasdottir A, Magnusdottir A, Oddson A, Sulem G, Zink F, Sveinbjornsson G, Helgason A, Johannsdottir HS, Helgadottir A, Stefansson H, Gretarsdottir S, Rafnar T, Almdahl IS, Brækhus A, Fladby T, Selbæk G, Hosseinpanah F, Azizi F, Koh JM, Tang NLS, Danesphour M, Mayordomo JI, Welt C, Braund PS, Samani NJ, Kiemeney LA, Lohmander LS, Christiansen C, Andreassen OA, Consortium A, Magnusson O, Masson G, Kong A, Jonsdottir I, Gudbjartsson D, Sulem P, Jonsson H, Loughlin J, Ingvarsson T, Thorsteinsdottir U, Stefansson K.  Nat Genet. 2017 May;49(5):801-805. doi: 10.1038/ng.3816. Epub 2017 Mar 20.

 A consistent and potentially exploitable response during chondrogenesis of mesenchymal stem cells from osteoarthritis patients to the protein encoded by the susceptibility gene GDF5. Ratnayake M, Tselepi M, Bloxham R, Plöger F, Reynard LN, Loughlin J. PLoS One. 2017 May 8;12(5):e0176523. doi: 10.1371/journal.pone.0176523. PMID: 28481944; PMCID: PMC5421763.

Functional Characterization of the Osteoarthritis Susceptibility Mapping to CHST11-A Bioinformatics and Molecular Study. Reynard LN, Ratnayake M, Santibanez-Koref M, Loughlin J. PLoS One. 2016 Jul 8;11(7):e0159024. doi:10.1371/journal.pone.0159024. PMID: 27391021; PMCID: PMC4938163.

The first international workshop on the epigenetics of osteoarthritis. Meulenbelt IM, Bhutani N, den Hollander W, Gay S, Oppermann U, Reynard LN, Skelton AJ, Young DA, Beier F, Loughlin J. Connect Tissue Res. 2017 Jan;58(1):37-48.doi: 10.3109/03008207.2016.1168409. Epub 2016 Mar 30. PMID: 27028588.

Defective Leukocyte Adhesion and Chemotaxis Contributes to Combined Immunodeficiency in Humans with Autosomal Recessive MST1 Deficiency. Dang TS, Willet JD, Griffin HR, Morgan NV, O'Boyle G, Arkwright PD, Hughes SM, Abinun M, Tee LJ, Barge D, Engelhardt KR, Jackson M, Cant AJ, Maher ER, Koref MS, Reynard LN, Ali S, Hambleton S. J Clin Immunol. 2016 Feb;36(2):117-22. doi: 10.1007/s10875-016-0232-2. Epub 2016 Jan 22.

Expression analysis of the osteoarthritis genetic susceptibility locus mapping to an intron of the MCF2L gene and marked by the polymorphism rs11842874. Shepherd C, Skelton AJ, Rushton MD, Reynard LN, Loughlin J. BMC Med Genet. 2015 Nov 19;16:108. doi: 10.1186/s12881-015-0254-2. PMID: 26584642; PMCID:

PMC4653905.

Methylation quantitative trait locus analysis of osteoarthritis links epigenetics with genetic risk. Rushton MD, Reynard LN, Young DA, Shepherd C, Aubourg G, Gee F, Darlay R, Deehan D, Cordell HJ, Loughlin J.

Hum Mol Genet. 2015 Dec20;24(25):7432-44. doi: 10.1093/hmg/ddv433. Epub 2015 Oct 13. PMID: 26464490;PMCID: PMC4664171.

Functional characterisation of the osteoarthritis susceptibility locus at chromosome 6q14.1 marked by the

polymorphism rs9350591. Johnson K, Reynard LN, Loughlin J. BMC Med Genet. 2015 Sep 7;16:81. doi:

10.1186/s12881-015-0215-9. PMID: 26346884; PMCID: PMC4562116.

Correlation of the osteoarthritis susceptibility variants that map to chromosome 20q13 with an expression

quantitative trait locus operating on NCOA3 and with functional variation at the polymorphism rs116855380. Gee F, Rushton MD, Loughlin J, Reynard LN. Arthritis Rheumatol. 2015 Nov;67(11):2923-32. doi:10.1002/art.39278. PMID: 26211391; PMCID: PMC4832313.

Differential DNA methylation and expression of inflammatory and zinc transporter genes defines subgroups of osteoarthritic hip patients. Rushton MD, Young DA, Loughlin J, Reynard LN. Ann Rheum Dis. 2015 Sep;74(9):1778-82. doi:10.1136/annrheumdis-2014-206752. Epub 2015 Apr 8. PMID: 25854584; PMCID:

PMC4552898.

Dual proteolytic pathways govern glycolysis and immune competence. Lu W, Zhang Y, McDonald DO, Jing H, Carroll B, Robertson N, Zhang Q, Griffin H, Sanderson S, Lakey JH, Morgan NV, Reynard LN, Zheng L, Murdock HM, Turvey SE, Hackett SJ, Prestidge T, Hall JM, Cant AJ, Matthews HF, Koref MF, Simon AK,

Korolchuk VI, Lenardo MJ, Hambleton S, Su HC. Cell. 2014 Dec 18;159(7):1578-90. doi: 10.1016/j.cell.2014.12.001. PMID: 25525876; PMCID: PMC4297473.

Allelic expression analysis of the osteoarthritis susceptibility locus that maps to chromosome 3p21

reveals cis-acting eQTLs at GNL3 and SPCS1. Gee F, Clubbs CF, Raine EV, Reynard LN, Loughlin J.

BMC Med Genet. 2014 May 4;15:53. doi: 10.1186/1471-2350-15-53. PMID: 24886551; PMCID: PMC4101866.

CpG methylation regulates allelic expression of GDF5 by modulating binding of SP1 and SP3 repressor proteins to the osteoarthritis susceptibility SNP rs143383. Reynard LN, Bui C, Syddall CM, Loughlin J. Hum Genet. 2014Aug;133(8):1059-73. doi: 10.1007/s00439-014-1447-z. Epub 2014 May 27. PMID:24861163; PMCID: PMC4099533.

Characterization of the cartilage DNA methylome in knee and hip osteoarthritis. Rushton MD, Reynard LN, Barter MJ, Refaie R, Rankin KS, Young DA, Loughlin J. Arthritis Rheumatol. 2014 Sep;66(9):2450-60. doi:

10.1002/art.38713. PMID: 24838673; PMCID: PMC4314681.

Identification and analysis of a SMAD3 cis-acting eQTL operating in primary osteoarthritis and in the aneurysms and osteoarthritis syndrome. Raine EV, Reynard LN, van de Laar IM, Bertoli-Avella AM, Loughlin J. Osteoarthritis Cartilage. 2014 May;22(5):698-705. doi: 10.1016/j.joca.2014.02.931. Epub 2014Feb 28. PMID: 24583347; PMCID: PMC4032576.

The identification of trans-acting factors that regulate the expression of GDF5 via the osteoarthritis

susceptibility SNP rs143383. Syddall CM, Reynard LN, Young DA, Loughlin J. PLoS Genet. 2013 Jun;9(6):e1003557. doi:10.1371/journal.pgen.1003557. Epub 2013 Jun 27. PMID: 23825960; PMCID:

PMC3694828.

Allelic expression analysis of the osteoarthritis susceptibility gene COL11A1 in human joint tissues. Raine EV, Dodd AW, Reynard LN, Loughlin J. BMC Musculoskelet Disord. 2013 Mar 8;14:85. doi: 10.1186/1471-2474-14-85. PMID:23497244; PMCID: PMC3599795.

Gene expression analysis reveals HBP1 as a key target for the osteoarthritis susceptibility locus that maps to chromosome 7q22. Raine EV, Wreglesworth N, Dodd AW, Reynard LN, Loughlin J. Ann Rheum Dis. 2012 Dec;71(12):2020-7. doi:10.1136/annrheumdis-2012-201304. Epub 2012 May 14. PMID: 22586168.

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. Bui C, Barter MJ, Scott JL, Xu Y, Galler M, Reynard LN, Rowan AD, Young DA. FASEB J. 2012 Jul;26(7):3000-11. doi: 10.1096/fj.12-206367. Epub 2012 Apr 13. PMID: 22505473.

Allelic expression analysis of the osteoarthritis susceptibility locus that maps to MICAL3. Ratnayake M, Reynard LN, Raine EV, Santibanez-Koref M, Loughlin J. BMC Med Genet. 2012 Mar 2;13:12. doi: 10.1186/1471-2350-13-12. PMID:22385522; PMCID: PMC3366887.

Exome sequencing identifies GATA-2 mutation as the cause of dendritic cell, monocyte, B and NK lymphoid deficiency. Dickinson RE, Griffin H, Bigley V, Reynard LN, Hussain R, Haniffa M, Lakey JH, Rahman T, Wang XN, McGovern N, Pagan S, Cookson S, McDonald D, Chua I, Wallis J, Cant A, Wright M, Keavney B, Chinnery PF, Loughlin J, Hambleton S, Santibanez-Koref M, Collin M. Blood. 2011 Sep 8;118(10):2656-8. doi: 10.1182/blood-2011-06-360313. Epub 2011 Jul 15. PMID: 21765025; PMCID: PMC5137783.

Expression of the osteoarthritis-associated gene GDF5 is modulated epigenetically by DNA methylation. Reynard LN, Bui C, Canty-Laird EG, Young DA, Loughlin J. Hum Mol Genet. 2011 Sep 1;20(17):3450-60. doi: 10.1093/hmg/ddr253. Epub 2011 Jun 3. PMID: 21642387.

Deep sequencing of GDF5 reveals the absence of rare variants at this important osteoarthritis susceptibility locus. Dodd AW, Rodriguez-Fontenla C, Calaza M, Carr A, Gomez-Reino JJ, Tsezou A, Reynard LN, Gonzalez A, Loughlin J. Osteoarthritis Cartilage. 2011 Apr;19(4):430-4. doi: 10.1016/j.joca.2011.01.014. PMID: 21281725.

Increased sex chromosome expression and epigenetic abnormalities in spermatids from male mice with Y chromosome deletions. Reynard LN, Turner JM. J Cell Sci. 2009 Nov 15;122(Pt 22):4239-48. doi: 10.1242/jcs.049916. Epub 2009 Oct 27. PMID: 19861498; PMCID: PMC2776507.

The multi-copy mouse gene Sycp3-like Y-linked (Sly) encodes an abundant spermatid protein that interacts with a histone acetyltransferase and an acrosomal protein. Reynard LN, Cocquet J, Burgoyne PS. Biol Reprod. 2009 Aug;81(2):250-7. doi: 10.1095/biolreprod.108.075382. Epub 2009 Jan 28. PMID: 19176879; PMCID: PMC2849823.

Expression analysis of the mouse multi-copy X-linked gene Xlr-related, meiosis-regulated (Xmr), reveals that Xmr encodes a spermatid-expressed cytoplasmic protein, SLX/XMR. Reynard LN, Turner JM, Cocquet J, Mahadevaiah SK, Touré A, Höög C, Burgoyne PS. Biol Reprod. 2007 Aug;77(2):329-35. doi:

10.1095/biolreprod.107.061101. Epub 2007 May 2. PMID: 17475928.

Identification of novel Y chromosome encoded transcripts by testis transcriptome analysis of mice with deletions of the Y chromosome long arm. Touré A, Clemente EJ, Ellis P, Mahadevaiah SK, Ojarikre OA, Ball PA, Reynard L, Loveland KL, Burgoyne PS, Affara NA. Genome Biol 2005;6(12):R102. doi: 10.1186/gb-2005-6-12-r102. PMID: 16356265 PMCID: PMC1414076.

 

Review articles

Osteoarthritis year in review 2019: genetics, genomics and epigenetics. Reynard LN, Barter MJ. Osteoarthritis Cartilage. 2020 Mar;28(3):275-284. doi:10.1016/j.joca.2019.11.010. Epub 2019 Dec 23. PMID: 31874234.

Analysis of genetics and DNA methylation in osteoarthritis: What have we learnt about the disease? Reynard LN. Semin Cell Dev Biol. 2017 Feb;62:57-66. doi: 10.1016/j.semcdb.2016.04.017. Epub 2016 Apr 26. PMID: 27130636.

The role of inflammation-related genes in osteoarthritis. Rogers EL, Reynard LN, Loughlin J.

Osteoarthritis Cartilage. 2015 Nov;23(11):1933-8. doi:10.1016/j.joca.2015.01.003. PMID: 26521739.

Osteoarthritis: Epigenetics of articular cartilage in knee and hip OA. Loughlin J, Reynard LN.  Nat Rev Rheumatol. 2015 Jan;11(1):6-7. doi:10.1038/nrrheum.2014.189. Epub 2014 Nov 4. PMID: 25366188.

Insights from human genetic studies into the pathways involved in osteoarthritis. Reynard LN, Loughlin J. Nat Rev Rheumatol. 2013 Oct;9(10):573-83.doi: 10.1038/nrrheum.2013.121. Epub 2013 Aug 20. PMID: 23958796.

The genetics and functional analysis of primary osteoarthritis susceptibility. Reynard LN, Loughlin J. Expert Rev Mol Med. 2013 Feb 18;15:e2. doi:10.1017/erm.2013.4. PMID: 23414786; PMCID: PMC3575889.

Genetics and epigenetics of osteoarthritis. Reynard LN, Loughlin J. Maturitas. 2012 Mar;71(3):200-4. doi: 10.1016/j.maturitas.2011.12.001. Epub 2011 Dec 29. PMID: 22209350

Teaching

Teaching

Dr Reynard lectures on the undergraduate modules Medical genomics: from DNA to disease, Research in Biochemistry & Genetics, Research in Pharmacological Sciences, and Research in Physiological Sciences, and Masters level modules Chromosome Biology and Cell Cycle Control in Health and Disease, Clinical Epidemiology, Developmental Genetics and Bioinformatics for Biomedical Scientists. Her lectures cover a range of topics from sex-linked genetic disorders and techniques for measuring gene expression to epigenetics and bioinformatic analysis.


Dr Reynard is a member of the MRes Programmes academic team, the largest Masters programme within Newcastle University Faculty of Medical Science, with between 180 and 260 students per year. As part of this role, Dr Reynard is a member of the MRes Curriculum Committee, MRes Board of Studies and MRes Examination Committee. She was the Examination Committee Deputy Chair from 2018 to 2022 and was a member of MRes Moderation and Scaling Committee, MRes Staff-Student Committee, MRes Disciplinary Committee and the MRes Personal Extenuating Circumstances committee during this time.


Dr Reynard supervises undergraduate and MRes laboratory project students, undergraduate vacation project students and PhD students. She was nominated for The Education Awards in 2022 and 2023 in the ‘Research Supervisor of the Year’ category. Louise sits on several PhD progression panels and has acted as an external PhD examiner for the University of Liverpool, University of Manchester, University of Sheffield, Kings College, London and Leiden University, the Netherlands.

Publications