Clinical and Biomedical Sciences

RNA-Research Projects

Using RNA splicing factors to predict future health outcomes

This research follows on from some of our earlier work on alternative RNA splicing, and builds on our findings that the regulators of the splicing machinery (splicing factors) associate with ageing and lifespan.

For this study, we used a human "healthy ageing" cohort study from Italy, called the InCHIANTI study. This excellent resource has RNA taken from blood samples as well as detailed clinical data from several follow-up visits since the beginning of the study in 1998. This allows us to look for variation in gene expression at an earlier time-point and how this is linked to health outcomes in later life.

DNA strand

In this particular piece of research, we measured the gene expression levels of splicing factors in the RNA from the third follow-up visit (2007-2010) and looked for associations with measures of cognitive decline and frailty at the fourth follow-up (2012-2014).

We found that expression levels of three of the splicing factors at the third follow-up were predictive of a decline in performance between the third and fourth follow-up on three different measures of cognitive ability – the Mini Mental State Exam (MMSE), the Trail-Making Test (TMT) and the Purdue Pegboard Test (PPT).

Levels of one of these three splicing factors was also found to be predictive of a decline in physical performance over the same time period, as measured by hand-grip strength, a Short Physical Performance Battery (ESE-SPPB) and fast walking speed over 400m.

These results strengthen the case that RNA regulation by alternative splicing is important in the ageing process and opens up the possibility that measurement of splicing factors may be useful as biomarkers of cognitive decline or declining physical ability in the aging population.

RNA-mediated mechanisms of disease - Who we are

Current team members

Professor Lorna Harries  Professor 
Emad Manni PhD Student 
Ryan Frankum PhD Student 
Laura Bramwell PhD Student 
Zhuofan Mou PhD Student
Merlin Davies-Abraham PhD Student 
Dr Samantha Gould Post Doc. Research Associate 

Alumni

Dr Faer Morrison (PhD)

Dr Alice Holly (PhD)

Dr Rachel Bradley Smith (MbyRes)

Dr Ben Lee

Dr Shahnaz Haque

Dr Nicola Jeffery

Collaborations

The RNA-mediated mechanisms of disease group has close links with the Monogenic diseases group, the Polygenetic Molecular Genetics Group, the Obesity and Adipose Tissue Biology group, and the Epidemiology and Public Health Group.

Publications

  1. Kuo CL, Joaquim M, Kuchel GA, Ferrucci L, Harries LW, Pilling LC, Melzer D. The Longevity-Associated SH2B3 (LNK) Genetic Variant: Selected Aging Phenotypes in 379,758 Subjects. J Gerontol A Biol Sci Med Sci. 2020 Sep 16;75(9):1656-1662.

 

  1. Stuart RG Calimport, Barry L Bentley, Claire E Stewart, Graham Pawelec, Angelo Scuteri, Manlio Vinciguerra, Cathy Slack, Danica Chen, Lorna W Harries, Gary Marchant, G Alexander Fleming, Michael Conboy, Adam Antebi, Gary W Small, Jesus Gil, Edward G Lakatta, Arlan Richardson, Clifford Rosen, Karoly Nikolich, Tony Wyss-Coray, Lawrence Steinman, Thomas Montine, João Pedro de Magalhães, Judith Campisi, George Church. The inherent challenges of classifying senescence —Response. Science Vol. 368 issue 6491, pp595-596. 2020.

 

This is a response to a letter submitted in response to our policy paper (see below).

 

  1. Shahnaz Haque, Ryan M. Ames, Karen Moore, Benjamin P. Lee, Nicola Jeffery, and Lorna W Harries. Islet-expressed circular RNAs are associated with type 2 diabetes status in human primary islets and in peripheral blood. BMC Medical Genomics 13 (1), 1-15. 2020

 

  1. B.P Lee, M. Smith, R. Buffenstein, L.W.Harries. Negligible senescence in naked mole rats may be a consequence of well-maintained splicing regulation. 2020 GeroScience in press doi:10.1007/s11357-019-00150-7

 

  1. Stuart R. G. Calimport, Barry L. Bentley, Claire E. Stewart, Graham Pawelec, Angelo Scuteri, Manlio Vinciguerra, Cathy Slack, Danica Chen, Lorna W. Harries, Gary Marchant, G. Alexander Fleming, Michael Conboy, Adam Antebi, Gary W. Small, Jesus Gil, Edward G. Lakatta, Arlan Richardson, Clifford Rosen, Karoly Nikolich, Tony Wyss-Coray, Lawrence Steinman, Thomas Montine, João Pedro de Magalhães, Judith Campisi, George Church. To help aging populations, classify organismal senescence. Science 2019. Vol. 366, Issue 6465, pp. 576-578

 

This is a policy paper aiming to classify cellular senescence. Such a classification is necessary before clinical trials for intervention can conducted, a disease can be diagnosed, intervention can be prescribed or treatment can be administered. This is an important first step towards the realising the potential of senotherapeutic approaches to age-related disease.

 

  1. Shahnaz Haque, Ryan M. Ames, Karen Moore, Luke C. Pilling, Luanne L. Peters, Stefania Bandinelli, Benjamin P. Lee, Luigi Ferrucci, and Lorna W Harries. CircRNAs expressed in human peripheral blood are associated with human aging phenotypes, cellular senescence and mouse lifespan. Geroscience 42 (1), 183-199. 2020.

This paper reports the first circRNAome for perphepral human blood in an ageing population, and relates the expression of the most age-dysregulated circRNAs to ageing phenotype, median strain lifespan in mouse and cellular senescence in primary human cells.

 

  1. Danny Galvis, Darren Walsh, Lorna W. Harries, Eva Latorre, James Rankin. A dynamical systems model for the measurement of cellular senescence J R Soc Interface. 2019 Oct 31;16(159):20190311.

 

  1. Benjamin P. Lee, Lorna Mulvey, Gregory Barr, Jemma Garratt, Emily Goodman, Colin Selman, Lorna W. Harries. Dietary restriction in ILSXISS mice is associated with widespread changes in splicing regulatory factor expression levels. Exp Gerontol. 2019 Sep 12:110736.

 

  1. Jed J. Lye*, Eva Latorre*, Ben P. Lee, Stefania Bandinelli, Janet E. Holley, Nicholas J Gutowski, Luigi Ferrucci and Lorna W. Harries. Astrocyte senescence may drive alterations in GFAPa, CDKN2A p14ARF and TAU3 transcript expression and contribute to cognitive decline. Geroscience. 2019 Oct 25.

 

  1. Kuo CL, Joaquim M, Kuchel GA, Ferrucci L, Harries L, Pilling LC, Melzer D. The Longevity Associated Sh2b3 (LNK) Genetic Variant: Selected Aging Phenotypes in 379,758 Subjects. J Gerontol A Biol Sci Med Sci. 2019 Aug 20

 

  1. Lee BP, Pilling LC, Bandinelli S, Ferrucci L, Melzer D, Harries LW. The transcript expression levels of HNRNPM, HNRNPA0 and AKAP17A splicing factors may be predictively associated with ageing phenotypes in human peripheral blood. Biogerontology. 2019 Oct;20(5):649-663. 

 

  1. Jennifer Munkley, Li Ling, S R Gokul Krishnan,Gerald Hysenaj, Emma Scott,Caroline Dalgliesh, Htoo Zarni Oo, Teresa Mendes Maia, Kathleen Cheung, Ingrid Ehrmann, Karen E Livermore, Hanna Zielinska, Oliver Thompson, Bridget Knight, Paul McCullagh,  John McGrath, Malcolm Crundwell, Lorna W Harries, Mads Daugaard, Simon Cockell, Nuno L Barbosa-Morais, Sebastian Oltean, David J Elliott.  Androgen-regulated transcription of ESRP2 drives alternative splicing patterns in prostate cancer. Elife. 2019 Sep 3;8. pii: e47678.

 

  1. Nicola Jeffery and Lorna W. Harries. miRNAs responsive to the diabetic microenvironment in the human beta cell line EndoC-βH1 may target genes in the FOXO, HIPPO and Lysine degradation pathways. Exp Cell Res. 2019 Nov 1;384(1):111559.

 

  1. Nicola Jeffery, Sarah Richardson, David Chambers, Noel G. Morgan, Lorna W. Harries. Cellular stressors may alter islet hormone cell proportions by moderation of alternative splicing patterns. Human Molecular Genetics 2019 Aug 15;28(16):2763-2774. First Quartile journal.

 

This paper is the first to document reversible beta cell to delta cell transdifferentiation in isolated human beta cells In vitro, and in pancreatic sections from individuals with either type 1 diabetes or type 2 diabetes.

 

  1. Ari Meerson, Yaniv Eliraz, Hila Yehuda, Bridget Knight, Malcolm Crundwell, Douglas Ferguson, Benjamin P Lee and Lorna W Harries. Obesity impacts the regulation of miR-10b and its targets in primary breast tumors. BMC Cancer. 2019 Jan 18;19(1):86 First Quartile journal.

 

  1. Daniel C. J. Ferguson, Gary R. Smerdon, Lorna W. Harries, Nicholas J. F. Dodd, Michael P. Murphy, Alison Curnow and Paul G. Winyard. Altered cellular redox homeostasis and redox responses under standard oxygen cell culture conditions versus physioxia. Free Radic Biol Med. 2018 Aug 21. S0891-5849(18)31225-5. First Quartile journal.

 

  1. Eva Latorre, Elizabeth L. Ostler, Richard G.A. Faragher and Lorna W. Harries. FOXO1 and ETV6 genes may represent novel regulators of splicing factor expression in cellular senescence. FASEB J. 2019 Jan;33(1):1086-1097. First Quartile journal.

This paper is the first report documenting the role of specific cellular signalling pathways and target genes in attenuation of splicing factor expression in cellular senescence. Furthermore, it showcases the potential for reversal of this phenomenon by moderation of these genes and pathways. Despite the fact that it is not yet fully out in print, it has accrued an Altmetric score of 105 which places it in the top 5% of all published outputs scored by this system and has received global media coverage in 26 media outlets. It also elicited an invitation to deliver a BBC World Service Podcast on ageing and senescence.

 

  1. Eva Latorre, Roberta Torregrossa, Mark E. Wood, Matthew Whiteman and Lorna W. Harries. Mitochondria-targeted hydrogen sulfide attenuates endothelial senescence by selective induction of splicing factors HNRNPD and SRSF2. Aging (Albany NY). 2018 Jul 19;10(7):1666-1681. First Quartile journal.

 

This paper is the first report that hydrogen sulfide is a regulator of splicing factor expression, and that targeted delivery to the mitochondria is associated with rescue of cellular senescence. The paper has an Altmetric score of 372 which places it in the top 5% of all published outputs scored by this system. It has received global media coverage in the Mail, the Express and a full page in The Independent. A Conversation article commissioned based on this work has accrued 170000 reads, of which 80000 were from the USA. It has also appeared on Reddit, where it has received 93% ‘upvotes’, over 24000 reads and almost 2000 comments. It also resulted in an opportunity to record a BBC World Service Podcast on cellular ageing which was featured in the Sunday Times Culture section in October 2018.

 

  1. Locke, Jonathan; Saint-Martin, Cécile; Laver, Thomas; Patel, Kashyap; Wood, Andrew; Sharp, Seth; Ellard, Sian; Bellanné-Chantelot, Christine; Hattersley, Andrew; Harries, Lorna (joint senior author); Weedon, Michael. The common HNF1A variant I27L is a modifier of age at diabetes diagnosis in HNF1A-MODY individuals. Diabetes. 2018 Sep;67(9):1903-1907. First Quartile journal.

 

  1. Tamara S Galloway, Nigel Baglin, Benjamin P Lee, Anna L Kocur, Maggie H Shepherd, Anna M Steele, BPA Schools Study Consortium, Lorna W Harries. An engaged research study to assess the effect of a ‘real-world’ dietary intervention on urinary bisphenol A (BPA) levels in teenagers. BMJ Open 2018; 8:e018742. First Quartile journal. 2 citations

 

This work reports the first large scale dietary intervention study in a population demographic with amongst the highest exposure to BPA to date. It is an Engaged Research project and all 124 researcher participants were authors on the paper. The paper has an Altmetric score of 121 which places it in the top 5% of all published outputs scored by this system. It has received widespread media coverage in over 142 media outlets globally, including the BBC Today program and Newsweek. The paper has resulted in a Change petition, and was cited in a motion to Taunton Deane Borough Council for abolition of single use plastics.

 

  1. Eva Latorre, Luke C. Pilling, Benjamin P. Lee, Stefania Bandinelli David Melzer, Luigi Ferrucci and Lorna W. Harries. The VEGFA156b isoform is dysregulated in senescent endothelial cells and may be associated with prevalent and incident coronary heart disease. Clin Sci (Lond). 2018 Feb 2;132(3):313-325. First Quartile journal. 3 citations

 

  1. Clissold RL, Harries LW, Ellard S, Bingham C, Hattersley AT. Comment on Dubois-Laforgue et al. Diabetes, Associated Clinical Spectrum, Long-term Prognosis, and Genotype/Phenotype Correlations in 201 Adult Patients With Hepatocyte Nuclear Factor 1B (HNF1B) Molecular Defects. Diabetes Care 2017;40:1436-1443.Diabetes Care. 2018 Jan;41(1):e7. First Quartile journal. 2 citations
  1. Luke C. Pilling, Chia-Ling Kuo, Kamil Sicinski, Jone Tamosauskaite, George A. Kucheld, Lorna W. Harries, Pamela Herd, Robert Wallace, Luigi Ferrucci, David Melzer. Human longevity: 25 genetic loci associated in 389,166 UK biobank participants. Aging 2017 Dec 6;9(12):2504-2520. First Quartile journal. 15 citations

 

This paper documents one of the largest genetic association studies for human longevity published to date. It has accrued an Altmetric score of 157, which places it in the top 5% of all published outputs scored by this system. It has accrued 15 citations in the year since publication.

 

  1. Jeynes JCG, Geraki K, Jeynes C, Zhaohong M, Bettiol AA, Latorre E, Harries LW, Soeller C. Nanoscale Properties of Human Telomeres Measured with a Dual Purpose X-ray Fluorescence and Super Resolution Microscopy Gold Nanoparticle Probe. ACS Nano. 2017 Dec 26;11(12):12632-12640. First Quartile journal. 3 citations

 

  1. Jeffery, N, Richardson, S, Beall, C, and Harries L.W. The species origin of the cellular microenvironment influences markers of beta cell fate and function in EndoC-bH1 cells. Exp Cell Res 2017 Dec 15;361(2):284-291. Second Quartile journal 1 citation.

 

  1. Latorre E, Birar VC, Sheerin AN, Jeynes JCC, Hooper A, Dawe HR, Melzer D, Cox LS, Faragher RGA, Ostler EL, Harries LW. Small molecule modulation of splicing factor expression is associated with rescue from cellular senescence. BMC Cell Biol. 2017 Oct 17;18(1):31. Second Quartile journal. 14 citations.

 

This paper is the first report that cellular senescence is reversible by moderation of splicing patterns in primary human cells. It has accrued an Altmetric score of 690, which places it in the top 5% of all published outputs scored by this system. It has received widespread coverage in 165 media outlets, including the BBC, The Mail, The Guardian, Newsweek and the Independent and was the subject of a Conversation article in November 2017. It has accrued 14 citations in the year since publication.

 

  1. Pilling LC, Atkins JL, Duff MO, Beaumont RN, Jones SE, Tyrrell J, Kuo CL, Ruth KS, Tuke MA, Yaghootkar H, Wood AR, Murray A, Weedon MN, Harries LW, Kuchel GA, Ferrucci L, Frayling TM, Melzer D. Red blood cell distribution width: Genetic evidence for aging pathways in 116,666 volunteers. PLoS One. 2017 Sep 28;12(9):e0185083. First Quartile journal. 7 citations

 

  1. Munkley J, McClurg UL, Livermore KE, Ehrmann I, Knight B, Mccullagh P, Mcgrath J, Crundwell M, Harries LW, Leung HY, Mills IG, Robson CN, Rajan P, Elliott DJ. The cancer-associated cell migration protein TSPAN1 is under control of androgens and its upregulation increases prostate cancer cell migration. Sci Rep. 2017 Jul 12;7(1):5249. First Quartile journal. 4 citations. 

 

  1. Flanagan S, Dũng VC, Houghton J, De Franco E, Ngoc CTB, Damhuis A, Ashcroft F, Harries L, Ellard S. An ABCC8 nonsense mutation causing neonatal diabetes through altered transcript expression. J Clin Res Pediatr Endocrinol. 2017 Sep 1;9(3):260-264. Third Quartile journal. 1 citation.

 

  1. Benjamin P. Lee, Ivana Burić, Anupriya George-Pandeth, Kevin Flurkey, David E. Harrison, Rong Yuan, Luanne L. Peters, George A. Kuchel, David Melzer and Lorna W. Harries. MicroRNAs miR-203-3p, miR-664-3p and miR-708-5p are associated with median strain lifespan in mice. Sci Rep. 2017 Mar 17;7:44620. First Quartile journal. 4 citations.
  1. Chen, Brian; Hivert, Marie-France; Peters, Marjolein; Pilling, Luke; Hogan, John; Pham, Lisa; Harries, Lorna; Fox, Caroline; Bandinelli, Stefania ; Dehghan, Abbas ; Hernandez, Dena; Hofman, Albert ; Hong, Jaeyoung ; Joehanes, Roby; Johnson, Andrew; Munson, Peter; Rybin, Denis; Singleton, Andrew; Uitterlinden, Andre; Ying, Saixia ; Melzer, David; Levy, Daniel; van Meurs, Joyce; Ferrucci, Luigi; Florez, Jose; Dupuis, Josee; Meigs, James and Kolaczyk, Eric. Peripheral blood transcriptomic signatures of fasting glucose and insulin concentrations. Diabetes. 2016 Dec;65(12):3794-3804. First Quartile journal. 3 citations.

 

  1. Munkley J, Vodak D, Livermore KE, James K, Wilson BT, Knight B, Mccullagh P, Mcgrath J, Crundwell M, Harries LW, Leung HY, Robson CN, Mills IG, Rajan P, Elliott DJ. Glycosylation is an Androgen-Regulated Process Essential for Prostate Cancer Cell Viability. EBioMedicine. 2016 Jun;8:103-16. First Quartile journal. 15 citations.

 

  1. Lee BP, Pilling LC, Emond F, Flurkey K, Harrison DE, Yuan R, Peters LL, Kuchel GA, Ferrucci L, Melzer D, Harries LW. Changes in the expression of splicing factor transcripts and variations in alternative splicing are associated with lifespan in mice and humans. Aging Cell 2016 Oct;15(5):903-13. First Quartile journal. 24 citations

 

This paper was recommended for the Faculty of 1000 and documents the first evidence that changes in splicing regulatory proteins are associated with lifespan in laboratory mice and with parental longevity score in human peripheral blood. It has accrued 24 citations in the 2 years since publication.

 

  1. Kamenska A, Simpson C, Vindry C, Broomhead H, Bénard M, Ernoult-Lange M, Lee BP, Harries LW, Weil D, Standart N. The DDX6-4E-T interaction mediates translational repression and P-body assembly. Nucleic Acids Res. 2016 Jul 27;44(13):6318-34. First Quartile journal. 28 citations.

 

  1. Janice Atkins, Luke Pilling, Alessandro Ble, Ambarish Dutta, Lorna Harries, Anna Murray, Carol Brayne, Jean-Marie Robine, George Kuchel, Luigi Ferrucci, David Melzer. Longer-lived parents and cardiovascular outcomes: 8 year follow-up in 186,000 UK biobank participants. J Am Coll Cardiol. 2016 Aug 23;68(8):874-5. First Quartile journal. 5 citations.

 

This paper documents amongst the largest epidemiological assessment of the association between parental lifespan and cardiovascular outcomes. It has accrued an Altmetric score of 492, which places it in the top 5% of all published outputs scored by this system.

 

  1. Pilling LC, Atkins JL, Bowman K, Jones SE, Tyrrell J, Beaumont RN, Ruth KS, Tuke MA, Yaghootkar H, Wood AR, Freathy RM, Murray A, Weedon MN, Xue L, Lunetta K, Murabito JM, Harries LW, Robine JM, Brayne C, Kuchel GA, Ferrucci L, Frayling TM, Melzer D. Human longevity is influenced by many genetic variants: evidence from 75,000 UK Biobank participants. Aging (Albany NY). 2016 Mar;8(3):547-63. First Quartile journal. 56 citations.

 

  1. Lee BP, Lloyd Laney HO, Locke JM, McCulloch LJ, Knight B, Yaghootkar H, Cory G, Kos K, Frayling TM, Harries LW. Functional characterisation of ADIPOQ variants using individuals recruited by genotype. Mol Cell Endocrinol. 2016 Mar 17. S0303-7207(16)30068-5. First Quartile journal. 6 citations.

 

  1. Pilling LC, Joehanes R, Kacprowski T, Peters MJ, Jansen R, Karasik D, Kiel DP, Harries LW, Teumer A, Powell JE, Levy D, Lin H, Lunetta K, Munson PJ, Bandinelli S, Henley WE, Hernandez DG, Singleton AB, Tanaka T, van Grootheest G, Hofman A, Uitterlinden AG, Biffar R, Gläser S, Homuth G, Malsch C, Völker U, Penninx BW, van Meurs JB, Ferrucci L, Kocher T, Murabito JM, Melzer D. Gene transcripts associated with muscle strength: a CHARGE meta-analysis of 7,781 persons. Physiol Genomics. 2016 Jan;48(1):1-11. Second Quartile journal. 4 citations

 

  1. Ksenia Tugay, Claudiane Guay, Ana Claudia Marques, Florent Allagnat, Jonathan Locke, Lorna W. Harries, Guy A. Rutter and Romano Regazzi. Role of miRNAs in age-associated decline of pancreatic beta cell function. Diabetologia. 2016 Jan;59(1):161-9. First Quartile journal. 18 citations
  1. Jennifer Munkley*, Karen E Livermore, Gabriela Kalna, Hing Y Leung, Craig N Robson, Lorna W Harries, Prabhakar Rajan and David J Elliott. The PI3K regulatory subunit gene PIK3R1 is under direct control of androgens and repressed in prostate cancer cells. Oncoscience. 2015 Sep 14;2(9):755-64. Second Quartile journal. 12 citations

 

  1. Jennifer Munkley*, Karen E Livermore, Gabriela Kalna, Hing Y Leung, Craig N Robson, Lorna W Harries, Prabhakar Rajan and David J Elliott. The androgen receptor controls expression of the cancer-associated sTn antigen and cell adhesion through induction of ST6GalNAc1 in prostate cancer.  Oncotarget. 2015 Oct 27;6(33):34358-74. First Quartile journal. 29 citations.

 

  1. Luke C. Pilling, Roby Joehanes, David Melzer, Lorna W. Harries, William Henley, Josée Dupuis,  Honghuang Lin, Marcus Mitchell, Dena Hernandez, Sai-Xia Ying, Kathryn L. Lunetta6, Emelia J Benjamin, Andrew Singleton, Daniel Levy, Peter Munson, Joanne M. Murabito, Luigi Ferrucci. Leading Mediators of Inflammation in Aging: Results from Transcriptome-Wide Analysis in Two Human Cohorts. Exp Gerontol. 2015 Oct;70:37-45. Second Quartile journal. 9 citations.

 

  1. Holly AC, Grellscheid S, van de Walle P, Dolan D, Pilling LC, Daniels DJ, von Zglinicki T, Ferrucci L, Melzer D, Harries LW. Comparison of senescence-associated miRNAs in primary skin and lung fibroblasts. Biogerontology. 2015 Aug;16(4):423-34. First Quartile journal. 6 citations

 

  1. Locke JM, Wei FY, Tomizawa K, Weedon MN, Harries LW. A cautionary tale: the non-causal association between type 2 diabetes risk SNP, rs7756992, and levels of non-coding RNA, CDKAL1-v1. Diabetologia. 2015 Apr;58(4):745-8. First Quartile journal. 6 citations

 

  1. Tamara S. Galloway, Tony Fletcher, David Melzer, Oliver J. Thomas, Ben P. Lee, Luke Pilling and Lorna W. Harries. Associations between exposure to PFOA, PFOS, Osteoarthritis and the parathyroid hormone signalling pathway. Chemosphere. Chemosphere. 2015 Feb;120:555-62. First Quartile journal. 7 citations

 

This paper was the first to document that the endocrine disrupter chemicals PFOA and PFOS can influence the expression of genes involved in parathyroid hormone signalling.

 

  1. Jamie Blackwell, Lorna W. Harries (Joint first author), Luke C. Pilling, Luigi Ferrucci, Andrew Jones, David Melzer. Changes in CEBPB expression in circulating leukocytes following eccentric elbow-flexion exercise. J Physiol Sci. 2015 Jan;65(1):145-50. Third Quartile journal. 5 citations

 

  1. Locke JM, Hysenaj G, Wood AR, Weedon MN, Harries LW. Targeted allelic expression profiling in human islets identifies cis-regulatory effects for multiple variants identified by type 2 diabetes genome-wide association studies. Diabetes. 2015 Apr;64(4):1484-91. First Quartile journal. 20 citations

Holly AC, Pilling LC, Hernandez D, Lee BP, Singleton A, Ferrucci L, Melzer D, Harries LW. Splicing Factor 3B1 hypomethylation is associated with altered SF3B1 transcript expression in older humans. Mech Ageing Dev. 2014 Jan 23.

Cipelli R, Harries L* (joint first author), Okuda K, Yoshihara S, Melzer D, Galloway T. Bisphenol A modulates the metabolic regulator oestrogen-related receptor-α in T-cells. Reproduction. 2014 Mar 2;147(4):419-26.

Locke JM, da Silva Xavier G, Dawe HR, Rutter GA, Harries LW. Increased expression of miR-187 in human islets from individuals with type 2 diabetes is associated with reduced glucose-stimulated insulin secretion. Diabetologia. 2014 Jan;57(1):122-8.

Morrison FS, Locke JM, Wood AR, Tuke M, Pasko D, Murray A, Frayling T, Harries LW. The splice site variant rs11078928 may be associated with a genotype-dependent alteration in expression of GSDMB transcripts. BMC Genomics. 2013 Sep 17;14(1):627.

Harries LW, McCulloch LJ, Holley JE, Rawling TJ, Welters HJ, Kos K. A role for SPARC in the moderation of human insulin secretion. PloS One. 2013 Jun 28;8(6):e68253.

Morrison F, Locke J, Arif M, Murray A, Brown JE, Harries LW. Expression profiling of type 2 diabetes susceptibility genes in the pancreatic islets, adipose tissue and liver of obese mice. Exp Clin Endocrinol Diabetes. 2013 Jul;121(7):413-9.

Locke JM, Lango Allen H, Harries LW. A rare SNP in pre-miR-34a is associated with increased levels of miR-34a in pancreatic beta cells. Acta Diabetol. 2013 Jul 5.

Holly AC, Melzer D, Pilling LC, Fellows AC, Tanaka T, Ferrucci L, Harries LW. Changes in splicing factor expression are associated with advancing age in man. Mech Ageing Dev. 2013 Jun 6. Doi:pii: S0047-6374(13)00065-1.

Fletcher T, Galloway TS, Melzer D, Holcroft P, Cipelli R, Pilling LC, Mondal D, Luster M, Harries LW. Associations between PFOA, PFOS and changes in the expression of genes involved in cholesterol metabolism in humans. Environ Int. 2013 Jul;57-58:2-10. Recommended for the Faculty of 1000.

Kendall AC, Whatmore JL, Harries LW, Winyard PG, Eggleton P, Smerdon GR. Different oxygen treatment pressures alter inflammatory gene expression in human endothelial cells. Undersea Hyperb Med. 2013 Mar-Apr;40(2):115-23

Holly AC, Melzer D, Pilling LC, Henley W, Hernandez DG, Singleton AB, Bandinelli S, Guralnik JM, Ferrucci L, Harries LW. Towards a gene expression biomarker set for human biological age. Aging Cell. 2013 Apr;12(2):324-6.

Faer Morrison, Jonathan Locke, Anna Murray, Lorna W. Harries. Expression profiling of putative Type 2 diabetes susceptibility genes in human islets and in rat beta cell lines. J Diabetes Mellitus, Vol.3, No.1, 27-32 (2013).

Alexander D. Fellows, Alice C. Holly, Luke C. Pilling, David Melzer, Lorna W. Harries. Age related changes in mTOR-related gene expression in two primary human cell lines. Healthy Aging Research 2012, 1:3

Harries LW, Fellows AD, Pilling LC, Hernandez D, Singleton A, Bandinelli S, Guralnik J, Powell J, Ferrucci L, Melzer D. Advancing age is associated with gene expression changes resembling mTOR inhibition: Evidence from two human populations. Mech Ageing Dev. 2012 Aug;133(8):556-62.

Harries LW, Bradley-Smith RM, Llewellyn DJ, Pilling LC, Fellows A, Henley W, Hernandez D, Guralnik JM, Bandinelli S, Singleton A, Ferrucci L, Melzer D. Leukocyte CCR2 Expression Is Associated with Mini-Mental State Examination Score in Older Adults. Rejuvenation Res. 2012 2012 Aug;15(4):395-404.

Melzer D, Harries L* (Joint first author), Cipelli R, Henley W, Money C, McCormack P, Young A, Guralnik J, Ferrucci L, Bandinelli S, Corsi AM, Galloway T. Bisphenol A exposure is associated with in vivo estrogenic gene expression in adults. Environ Health Perspect. 2011 Dec;119(12):1788-93. Recommended for the faculty of 1000.

Morrison F, Johnstone K, Murray A, Locke J, Harries LW. Oxidative metabolism genes are not responsive to oxidative stress in rodent Beta cell lines. Exp Diabetes Res. 2012;2012:793783.

Intza Garin, Guiomar Perez de Nanclares, Elena Gastaldo, Lorna W Harries, Luis Castaño. Permanent neonatal diabetes caused by ectopic splice site at the INS gene. PloS One. 2012;7(1):e29205.

Harries LW, Pilling LC, Hernandez LD, Bradley-Smith R, Henley W, Singleton AB, Guralnik JM, Bandinelli S, Ferrucci L, Melzer D. CCAAT-enhancer-binding protein-beta expression in vivo is associated with muscle strength. Aging Cell. 2012 Apr;11(2):262-268.

Kendall AC, Whatmore JL, Harries LW, Winyard PG, Smerdon GR, Eggleton P. Changes in inflammatory gene expression induced by hyperbaric oxygen treatment in human endothelial cells under chronic wound conditions. Exp. Cell Res 2012 Feb 1;318(3):207-16.

Locke JM, Harries LW. MicroRNA expression profiling of human islets from individuals with and without type 2 diabetes: promises and pitfalls. INVITED REVIEW Biochem Soc Trans. 2012 Aug;40(4):800-3.

Harries LW. Long non-coding RNAs and human disease. INVITED REVIEW Biochem Soc Trans. 2012 Aug;40(4):902-6.

Pilling LC, Harries LW (joint first author), Powell J, Llewellyn DJ, Ferrucci L, Melzer D. Genomics and Successful Aging: Grounds for Renewed Optimism? INVITED REVIEW J Gerontol A Biol Sci Med Sci. 2012 Mar 27.

Andrew R Wood, Dena G Hernandez, Michael A Nalls, Hanieh Yaghootkar, J Raphael Gibbs, Lorna W Harries, Sean Chong, Matthew Moore, Michael N Weedon, Jack M Guralnik, Stefania Bandinelli, Anna Murray, Luigi Ferrucci, Andrew B Singleton, David Melzer, Timothy M Frayling. Allelic heterogeneity and more detailed analyses of known loci explain additional phenotypic variation and reveal complex patterns of association. Hum Mol Genet 2011 Oct 15;20(20):4082-92.

Locke JM, Da Silva Xavier G, Rutter GA, Harries LW. An alternative polyadenylation signal in TCF7L2 generates isoforms that inhibit T cell factor/lymphoid-enhancer factor (TCF/LEF)-dependent target genes. Diabetologia. 2011 Dec;54(12):3078-82.

Lorna W. Harries, Dena Hernandez, William Henley, Andrew Wood, Alice C. Holly, Rachel M. Bradley-Smith, Hanieh Yaghootkar, Ambarish Dutta, Anna Murray, Timothy M. Frayling, Jack M. Guralnik, Stefania Bandinelli, Andrew Singleton, Luigi Ferrucci and David Melzer. Human aging is characterized by focused changes in gene expression and deregulation of alternative splicing. Aging Cell. 2011 Oct; 10(5):868-78.

Dr. Kaixin Zhou , Celine Bellenguez , Dr. Chris Spencer , Amanda Bennett , Miss Ruth Coleman, Roger Tavendale , Dr. Simon Hawley , Dr. Louise Donnelly , Dr. Chris Schofield , Christopher Groves , Dr. Lindsay Burch , Mrs. Fiona Carr , Amy Strange , Dr. Colin Freeman , Prof. Jenefer Blackwell , Elvira Bramon , Prof. Matthew Brown , Juan Casas , Aiden Corvin , Dr. Nick Craddock , Panos Deloukas , Serge Dronov , Dr. Audrey Duncanson , Dr. Sarah Edkins , Emma Gray , Dr. Sarah Hunt , Janusz Jankowski , Dr. Cordelia Langford , Hugh Markus , Prof. Christopher Mathew , Robert Plomin , Anna Rautanen , Dr. Stephen Sawcer , Dr. Nilesh Samani , Prof. Richard Trembath , Ananth Viswanathan , Prof. Nicholas Wood , Dr. Lorna Harries , Andrew Hattersley , Alex Doney , Prof. Helen Colhoun , Dr. Andrew Morris , Dr. Calum Sutherland , Prof. D Hardie , Prof. Leena Peltonen , Prof. Mark McCarthy , Prof. Rury Holman , Prof. Colin Palmer , Prof. Peter Donnelly and Dr Ewan Pearson. Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes. Nature Genetics 2011 Feb;43(2):117-20.

Karen A. Johnstone, Eleftheria Diakogiannaki, Shalinee Dhayal, Noel G. Morgan and Lorna W. Harries. Dysregulation of Hnf1b gene expression in cultured beta-cells in response to cytotoxic fatty acid. Journal of the Pancreas, 2011 Jan 5;12(1):6-10.

Lorna W. Harries. RD Lawrence Lecture 2011. Messenger RNA processing and its role in diabetes. INVITED REVIEW Diabetic Medicine 2011 Sep;28(9):1010-7.