University of Exeter Medical School

Dr Rebecca G. Smith

Dr Rebecca G. Smith

Lecturer in Neuroscience

 R.G.Smith@exeter.ac.uk

 8213

 +44 (0) 1392 728213

 RILD Building 

 

University of Exeter Medical School, RILD Building, RD&E Hospital Wonford, Barrack Road, Exeter, EX2 5DW, UK

Overview

Qualifications

  • Post-Graduate Certificate of Academic Practices (PGCAP) (2014, Kings College London)        
  • PhD in Psychiatric Genetics (2012, Kings College London)
  • BSc Honours in Genetics  (2005, University of Leeds)

Career

I earned a BSc (Hons) in Genetics from the University of Leeds which was completed in 2005. In 2007, I began working at the Social, Genetic and Developmental Psychiatry Centre (SGDP), King’s College London as a research assistant working under Prof Ian Craig, Dr Katherine Aitchison and Prof Peter McGuffin on the GENDEP project in which I performed genotyping of genetic polymorphisms such as SNPs and VNTRs in a large unipolar depression cohort. In 2009, I started my PhD at the SGDP in psychiatric genetics with Prof Jonathan Mill and Prof Ian Craig working on my thesis investigating behavioural and molecular changes associated with advanced paternal age in a mouse model, and also contributing to work on allele-specific methylation and the role of epigenetics in psychiatric disease.

I completed my first post-doctoral research position at the SGDP with Dr Katie Lunnon and Prof Jonathan Mill investigating epigenetic changes associated with Alzheimer’s disease in a post-mortem brain sample, as well as continuing my research in paternal age and psychiatric disease with Dr Cathy Fernandes and Dr Abraham Reichenberg. My second post-doctoral position was working on a genome-wide epigenetic project investigating DNA methylation changes and differences at birth and in childhood, for children with different trajectories of conduct problems. This work used blood samples from a subsample of the Avon Longitudinal Study of Parents and Children (ALSPAC) and was carried out under the supervision of Dr Edward Barker and Prof Mill.

After moving to Exeter as a research fellow, I worked on several projects relating to Alzheimer's disease and epigenetics and genomics, including a meta-analysis of cross-cortical methylation in six brain cohorts, identifying consistent methylation changes associated with Braak staging.

My current position is as a lecturer in neuroscience. In this role, I am module lead in the Methods in Neuroscience module, as well as contributing to other modules in the BSc. neuroscience programme, including advanced methods in neuroscience, brain and behaviour, neural circuits, and provide projects for final year students.

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Research

Research interests

Rebecca's main research interests are epigenetics and Alzheimer's Disease and dementia. She also has an interest in environmental exposure on the epigenome and how the epigenome may be an intermediary to disease causation.

Research grants

  • 2020 University of Exeter
    Investigate allele-specific methylation in APOE
  • 2019 ARUK
    Pyrosequencer to support dementia genomics research
  • 2019 ARUK
    Stratified Medicine Strategies with an Inflammatory Signature against Alzheimer’s Disease (SMashIng-AD)
  • 2018 BRACE
    A role for epigenetic changes in the HOXA gene cluster in driving Alzheimer’s disease
  • 2017 Alzheimers Society
    Molecular characterisation of the role of systemic infections in Alzheimer's disease brain
  • 2017 ARUK
    An integrated "omics" analysis to elucidate the role of miRNAs in Alzheimer's disease
  • 2017 ARUK
    Determining the potential utility of epigenetic modulators to treat Alzheimer’s disease: A collaboration between Exeter and Oxford ARUK Network Centres and the Oxford DDI
  • 2016 ARUK
    APOE methylation and APOE e4 alleles in the development of Alzheimer’s disease risk and other neurological diseases

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Publications

Journal articles

Pegoraro G, Smith RG, MacBean LF, Smith AR, Boche D, Pishva E, Lunnon K (2023). A transcriptome‐wide analysis of Alzheimer’s disease brain during systemic inflammation. Alzheimer's & Dementia, 19(S13).
Wheildon G, Smith AR, Soanes D, Smith RG, Moore K, O'Neill P, Morgan K, Thomas AJ, Love S, Francis PT, et al (2023). Targeted bisulfite sequencing analysis of Alzheimer’s disease candidate genes reveals differential methylation across neurofibrillary tangle burden in the prefrontal cortex. Alzheimer's & Dementia, 19(S12).
Harvey J, Smith AR, Weymouth LS, Smith RG, Hubbard L, Bresner K, Pishva E, Williams N, Lunnon K, Creese B, et al (2022). An epigenome wide association study of sub‐phenotypes in Parkinson’s disease. Alzheimer's & Dementia, 18(S4).
MacBean LF, Smith AR, Smith RG, Lunnon K (2022). An integrated systems‐level analysis of the molecular changes resulting from systemic infections in Alzheimer’s disease. Alzheimer's & Dementia, 18(S4).
MacBean LF, Smith AR, Smith RG, Boche D, Lunnon K (2022). An integrated systems‐level analysis of the molecular changes resulting from systemic inflammation and amyloid‐beta immunisation in Alzheimer’s disease. Alzheimer's & Dementia, 18(S3).
Wheildon G, Weymouth LS, Smith AR, Smith RG, Troakes C, Al‐Sarraj S, Lunnon K (2022). DNA methylation profiling across brain regions in Huntington’s disease. Alzheimer's & Dementia, 18(S4).
Shireby G, Dempster EL, Policicchio S, Smith RG, Pishva E, Chioza B, Davies JP, Burrage J, Lunnon K, Seiler Vellame D, et al (2022). DNA methylation signatures of Alzheimer’s disease neuropathology in the cortex are primarily driven by variation in non-neuronal cell-types. Nature Communications, 13(1). Abstract.
Ma Y, Yu L, Olah M, Smith R, Oatman SR, Allen M, Pishva E, Zhang B, Menon V, Ertekin-Taner N, et al (2022). Epigenomic features related to microglia are associated with attenuated effect of <i>APOE</i> ε4 on Alzheimer's disease risk in humans. ALZHEIMERS & DEMENTIA, 18(4), 688-699.  Author URL.
Devall M, Soanes DM, Smith AR, Dempster EL, Smith RG, Burrage J, Iatrou A, Hannon E, Troakes C, Moore K, et al (2022). Genome-wide characterization of mitochondrial DNA methylation in human brain. Front Endocrinol (Lausanne), 13 Abstract.  Author URL.
MacBean LF, Smith AR, Smith RG, Lunnon K (2022). Investigating the molecular consequences of co‐morbidites in Alzheimer’s disease. Alzheimer's & Dementia, 18(S4).
Wheildon G, Smith AR, Soanes D, Smith RG, Moore K, O'Neill P, Morgan K, Thomas AJ, Francis PT, Love S, et al (2022). Targeted bisulfite sequencing analysis of candidate genes associated with Alzheimer’s disease. Alzheimer's & Dementia, 18(S4).
Smith RG, Pishva E, Shireby G, Smith AR, Roubroeks JAY, Hannon E, Wheildon G, Mastroeni D, Gasparoni G, Riemenschneider M, et al (2021). A meta-analysis of epigenome-wide association studies in Alzheimer's disease highlights novel differentially methylated loci across cortex. Nat Commun, 12(1). Abstract.  Author URL.
MacBean LF, Smith RG, Smith AR, Nicoll JA, Boche D, Lunnon K (2021). An integrated systems-level analysis of the molecular changes resulting from systemic inflammation in Alzheimer's disease. Alzheimers Dement, 17 Suppl 3 Abstract.  Author URL.
Wheildon G, Smith AR, Smith RG, Lunnon K (2021). Targeted bisulfite sequencing analysis of candidate genes associated with Alzheimer's disease. Alzheimers Dement, 17 Suppl 3 Abstract.  Author URL.
Smith AR, Smith RG, Macdonald R, Marzi SJ, Burrage J, Troakes C, Al-Sarraj S, Mill J, Lunnon K (2021). The histone modification H3K4me3 is altered at the <i>ANK1</i> locus in Alzheimer's disease brain. Future Science OA, 7(4). Abstract.
Smith RG, Pishva E, Shireby G, Smith AR, Roubroeks JAY, Hannon E, Wheildon G, Mastroeni D, Gasparoni G, Riemenschneider M, et al (2020). A meta-analysis of epigenome-wide association studies in Alzheimer’s disease highlights novel differentially methylated loci across cortex. Abstract.
Dabin L, Guntoro F, Campbell T, Bélicard T, Smith AR, Smith RG, Raybould R, Schott JM, Lunnon K, Sarkies P, et al (2020). Altered DNA methylation profiles in blood from patients with sporadic Creutzfeldt-Jakob disease. Abstract.
Dabin LC, Guntoro F, Campbell T, Bélicard T, Smith AR, Smith RG, Raybould R, Schott JM, Lunnon K, Sarkies P, et al (2020). Altered DNA methylation profiles in blood from patients with sporadic Creutzfeldt–Jakob disease. Acta Neuropathologica, 140(6), 863-879. Abstract.
Roubroeks JAY, Smith AR, Smith RG, Pishva E, Ibrahim Z, Sattlecker M, Hannon EJ, Kłoszewska I, Mecocci P, Soininen H, et al (2020). An epigenome-wide association study of Alzheimer's disease blood highlights robust DNA hypermethylation in the HOXB6 gene. Neurobiol Aging, 95, 26-45. Abstract.  Author URL.
Ma Y, Yu L, Olah M, Smith R, Oatman SR, Allen M, Pishva E, Zhang B, Menon V, Ertekin-Taner N, et al (2020). EPIGENOMIC FEATURES RELATED TO MICROGLIA ARE ASSOCIATED WITH ATTENUATED EFFECT OF APOE ε4 ON ALZHEIMER'S DISEASE RISK IN HUMANS. Alzheimers Dement, 16(Suppl 2). Abstract.  Author URL.
Shireby GL, Davies JP, Francis PT, Burrage J, Walker EM, Neilson GWA, Dahir A, Thomas AJ, Love S, Smith RG, et al (2020). Recalibrating the Epigenetic Clock: Implications for Assessing Biological Age in the Human Cortex. Abstract.
Shireby GL, Davies JP, Francis PT, Burrage J, Walker EM, Neilson GWA, Dahir A, Thomas AJ, Love S, Smith RG, et al (2020). Recalibrating the epigenetic clock: implications for assessing biological age in the human cortex. Brain, 143(12), 3763-3775. Abstract.  Author URL.
Smith AR, Smith RG, Burrage J, Troakes C, Al-Sarraj S, Kalaria RN, Sloan C, Robinson AC, Mill J, Lunnon K, et al (2019). A cross-brain regions study of ANK1 DNA methylation in different neurodegenerative diseases. Neurobiology of Aging, 74, 70-76. Abstract.
Lardenoije R, Roubroeks JAY, Pishva E, Leber M, Wagner H, Iatrou A, Smith AR, Smith RG, Eijssen LMT, Kleineidam L, et al (2019). Alzheimer's disease-associated (hydroxy)methylomic changes in the brain and blood. Clin Epigenetics, 11(1). Abstract.  Author URL.
Wong CCY, Smith RG, Hannon E, Ramaswami G, Parikshak NN, Assary E, Troakes C, Poschmann J, Schalkwyk LC, Sun W, et al (2019). Genome-wide DNA methylation profiling identifies convergent molecular signatures associated with idiopathic and syndromic autism in post-mortem human brain tissue. Hum Mol Genet, 28(13), 2201-2211. Abstract.  Author URL.
Smith RG, Pishva E, Shireby G, Smith AR, Hannon E, Sharp AJ, Mastroeni DF, Schalkwyk LC, Haroutunian V, Coleman PD, et al (2019). O4‐10‐06: INTEGRATED GENETIC‐EPIGENETIC ANALYSES OF ALZHEIMER'S DISEASE. Alzheimer's & Dementia, 15(7S_Part_24), p1261-p1261.
Smith AR, Smith RG, Pishva E, Hannon E, Roubroeks JAY, Burrage J, Troakes C, Al-Sarraj S, Sloan C, Mill J, et al (2019). Parallel profiling of DNA methylation and hydroxymethylation highlights neuropathology-associated epigenetic variation in Alzheimer's disease. Clin Epigenetics, 11(1). Abstract.  Author URL.
Smith RG, Hannon E, De Jager PL, Chibnik L, Lott SJ, Condliffe D, Smith AR, Haroutunian V, Troakes C, Al-Sarraj S, et al (2018). Elevated DNA methylation across a 48-kb region spanning the HOXA gene cluster is associated with Alzheimer's disease neuropathology. Alzheimers Dement, 14(12), 1580-1588. Abstract.  Author URL.
Huezo-Diaz P, Uher R, Smith R, Rietschel M, Henigsberg N, Marušiˇ A, Mors O, Maier W, Hauser J, Souery D, et al (2018). Moderation of antidepressant response by the serotonin transporter gene. The British Journal of Psychiatry, 195(1), 30-38.
Cecil CAM, Walton E, Jaffee SR, O'Connor T, Maughan B, Relton CL, Smith RG, McArdle W, Gaunt TR, Ouellet-Morin I, et al (2018). Neonatal DNA methylation and early-onset conduct problems: a genome-wide, prospective study. Dev Psychopathol, 30(2), 383-397. Abstract.  Author URL.
Smith RG, Lunnon K (2017). DNA Modifications and Alzheimer's Disease. Adv Exp Med Biol, 978, 303-319. Abstract.  Author URL.
Roubroeks JAY, Smith RG, van den Hove DLA, Lunnon K (2017). Epigenetics and DNA methylomic profiling in Alzheimer's disease and other neurodegenerative diseases. J Neurochem, 143(2), 158-170. Abstract.  Author URL.
Janecka M, Marzi SJ, Parsons MJ, Liu L, Paya-Cano JL, Smith RG, Fernandes C, Schalkwyk LC (2017). Genetic polymorphisms and their association with brain and behavioural measures in heterogeneous stock mice. Scientific Reports, 7(1).
Devall M, Smith RG, Jeffries A, Hannon E, Davies MN, Schalkwyk L, Mill J, Weedon M, Lunnon K (2017). Regional differences in mitochondrial DNA methylation in human post-mortem brain tissue. Clin Epigenetics, 9 Abstract.  Author URL.
Cecil CAM, Walton E, Smith RG, Viding E, McCrory EJ, Relton CL, Suderman M, Pingault J-B, McArdle W, Gaunt TR, et al (2016). DNA methylation and substance-use risk: a prospective, genome-wide study spanning gestation to adolescence. Transl Psychiatry, 6(12). Abstract.  Author URL.
Smith AR, Mill J, Smith RG, Lunnon K (2016). Elucidating novel dysfunctional pathways in Alzheimer's disease by integrating loci identified in genetic and epigenetic studies. Neuroepigenetics, 6, 32-50. Abstract.
Cecil CAM, Smith RG, Walton E, Mill J, McCrory EJ, Viding E (2016). Epigenetic signatures of childhood abuse and neglect: Implications for psychiatric vulnerability. J Psychiatr Res, 83, 184-194. Abstract.  Author URL.
Lunnon K, Hannon E, G.Smith R, Dempster E, Wong C, Burrage J, Troakes C, Al-Sarraj S, Kepa A, Schalkwyk L, et al (2016). Erratum to: Variation in 5-hydroxymethylcytosine across human cortex and cerebellum [Genome Biol. 2016, 17, 27]. Genome Biology, 17(1).
Smith AR, Smith RG, Condliffe D, Hannon E, Schalkwyk L, Mill J, Lunnon K (2016). Increased DNA methylation near TREM2 is consistently seen in the superior temporal gyrus in Alzheimer's disease brain. Neurobiol Aging, 47, 35-40. Abstract.  Author URL.
Smith A, Smith R, Roubroeks J, Hannon E, Burrage J, Troakes C, van den Hove D, Mill J, Lunnon K (2016). O2‐06‐05: Hydroxymethylomic Profiling Implicates Cortical Deregulation of ANK1 and APP in the Alzheimer's Disease Brain. Alzheimer's & Dementia, 12(7S_Part_5), p240-p241.
Marzi SJ, Meaburn EL, Dempster EL, Lunnon K, Paya-Cano JL, Smith RG, Volta M, Troakes C, Schalkwyk LC, Mill J, et al (2016). Tissue-specific patterns of allelically-skewed DNA methylation. Epigenetics, 11(1), 24-35. Abstract.  Author URL.
Lunnon K, Hannon E, Smith RG, Dempster E, Wong C, Burrage J, Troakes C, Al-Sarraj S, Kepa A, Schalkwyk L, et al (2016). Variation in 5-hydroxymethylcytosine across human cortex and cerebellum. Genome Biol, 17 Abstract.  Author URL.
Lunnon K, Smith RG, Cooper I, Greenbaum L, Mill J, Beeri MS (2015). Blood methylomic signatures of presymptomatic dementia in elderly subjects with type 2 diabetes mellitus. Neurobiology of Aging, 36(3), 1600.e1-1600.e4. Abstract.
Lunnon K, Smith RG, Cooper I, Greenbaum L, Mill J, Beeri MS (2015). Blood methylomic signatures of presymptomatic dementia in elderly subjects with type 2 diabetes mellitus. Neurobiol Aging, 36(3), 1600.e1-1600.e4. Abstract.  Author URL.
Spiers H, Bray NJ, Hannon E, Schalkwyk LC, Wong CC, Pidsley R, Smith RG, Mill J (2015). Dynamic and sex-specific changes in DNA methylation during human fetal brain development. Int J Dev Neurosci, 47(Pt A), 50-51.  Author URL.
Janecka M, Manduca A, Servadio M, Trezza V, Smith R, Mill J, Schalkwyk LC, Reichenberg A, Fernandes C (2015). Effects of advanced paternal age on trajectories of social behavior in offspring. Genes Brain Behav, 14(6), 443-453. Abstract.  Author URL.
Spiers H, Hannon E, Schalkwyk LC, Smith R, Wong CCY, O'Donovan MC, Bray NJ, Mill J (2015). Methylomic trajectories across human fetal brain development. Genome Res, 25(3), 338-352. Abstract.  Author URL.
Cecil CAM, Lysenko LJ, Jaffee SR, Pingault J-B, Smith RG, Relton CL, Woodward G, McArdle W, Mill J, Barker ED, et al (2014). Environmental risk, Oxytocin Receptor Gene (OXTR) methylation and youth callous-unemotional traits: a 13-year longitudinal study. Mol Psychiatry, 19(10), 1071-1077. Abstract.  Author URL.
Lunnon K, Smith R, Hannon E, De Jager PL, Srivastava G, Volta M, Troakes C, Al-Sarraj S, Burrage J, Macdonald R, et al (2014). Methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer's disease. Nat Neurosci, 17(9), 1164-1170. Abstract.  Author URL.
Lunnon K, Smith RG, Cooper I, Greenbaum L, Mill J, Beeri MS (2014). TEMPORARY REMOVAL: Blood methylomic signatures of presymptomatic dementia in elderly subjects with type 2 diabetes mellitus. Neurobiol Aging  Author URL.
Smith RG, Fernandes C, Kember R, Schalkwyk LC, Buxbaum J, Reichenberg A, Mill J (2014). Transcriptomic changes in the frontal cortex associated with paternal age. Mol Autism, 5(1). Abstract.  Author URL.
Smith RG, Reichenberg A, Kember RL, Buxbaum JD, Schalkwyk LC, Fernandes C, Mill J (2013). Advanced paternal age is associated with altered DNA methylation at brain-expressed imprinted loci in inbred mice: implications for neuropsychiatric disease. Mol Psychiatry, 18(6), 635-636.  Author URL.
Powell TR, Smith RG, Hackinger S, Schalkwyk LC, Uher R, McGuffin P, Mill J, Tansey KE (2013). DNA methylation in interleukin-11 predicts clinical response to antidepressants in GENDEP. Transl Psychiatry, 3(9). Abstract.  Author URL.
Hodgson K, Tansey K, Dernovšek MZ, Hauser J, Henigsberg N, Maier W, Mors O, Placentino A, Rietschel M, Souery D, et al (2013). Genetic differences in cytochrome P450 enzymes and antidepressant treatment response. Journal of Psychopharmacology, 28(2), 133-141.
Pidsley R, Fernandes C, Viana J, Paya-Cano JL, Liu L, Smith RG, Schalkwyk LC, Mill J (2012). DNA methylation at the Igf2/H19 imprinting control region is associated with cerebellum mass in outbred mice. Mol Brain, 5 Abstract.  Author URL.
Huezo-Diaz P, Perroud N, Spencer EP, Smith R, Sim S, Virding S, Uher R, Gunasinghe C, Gray J, Campbell D, et al (2011). CYP2C19 genotype predicts steady state escitalopram concentration in GENDEP. Journal of Psychopharmacology, 26(3), 398-407.
Schalkwyk LC, Meaburn EL, Smith R, Dempster EL, Jeffries AR, Davies MN, Plomin R, Mill J (2010). Allelic skewing of DNA methylation is widespread across the genome. Am J Hum Genet, 86(2), 196-212. Abstract.  Author URL.
Keers R, Uher R, Huezo-Diaz P, Smith R, Jaffee S, Rietschel M, Henigsberg N, Kozel D, Mors O, Maier W, et al (2010). Interaction between serotonin transporter gene variants and life events predicts response to antidepressants in the GENDEP project. The Pharmacogenomics Journal, 11(2), 138-145.
Drago A, Serretti A, Smith R, Huezo-Diaz P, Malitas P, Albani D, De Ronchi D, Pae C-U, Aitchison KJ (2010). No association between genetic markers in BDNF gene and lithium prophylaxis in a Greek sample. International Journal of Psychiatry in Clinical Practice, 14(2), 154-157.
Smith RG, Kember RL, Mill J, Fernandes C, Schalkwyk LC, Buxbaum JD, Reichenberg A (2009). Advancing paternal age is associated with deficits in social and exploratory behaviors in the offspring: a mouse model. PLoS One, 4(12). Abstract.  Author URL.
Perroud N, Aitchison KJ, Uher R, Smith R, Huezo-Diaz P, Marusic A, Maier W, Mors O, Placentino A, Henigsberg N, et al (2009). Genetic Predictors of Increase in Suicidal Ideation During Antidepressant Treatment in the GENDEP Project. Neuropsychopharmacology, 34(12), 2517-2528.
Uher R, Huezo-Diaz P, Perroud N, Smith R, Rietschel M, Mors O, Hauser J, Maier W, Kozel D, Henigsberg N, et al (2009). Genetic predictors of response to antidepressants in the GENDEP project. The Pharmacogenomics Journal, 9(4), 225-233.

Chapters

Smith R, Lunnon K (2017). DNA Modifications and Alzheimer’s Disease. In  (Ed) Neuroepigenomics in Aging and Disease, Springer. Abstract.
Smith R, Mill J (2011). Epigenetics and Chronic Diseases: an Overview. In  (Ed) Epigenetic Aspects of Chronic Diseases, Springer London, 1-20.

Conferences

Lardenoije R, Roubroeks J, Pishva E, Leber M, Wagner H, Iatrou A, Smith A, Smith R, Eijssen L, Kleineidam L, et al (2019). Alzheimer's Disease DNA (Hydroxy)Methylome in the Brain and Blood: Evidence for OXT Methylation as a Preclinical Marker.  Author URL.
Wong CCY, Smith RG, Hannon E, Assary E, Parikshak N, Prabhakar S, Geschwind D, Mill J (2019). CONVERGENT METHYLOMIC SIGNATURES BETWEEN AUTISM ASSOCIATED WITH DUPLICATIONS OF CHROMOSOME 15Q AND IDIOPATHIC AUTISM.  Author URL.
Lunnon K, Smith R, Hannon E, Smith A, Schalkwyk LC, Haroutunian V, Mill J (2015). O3‐05‐01: Systems‐level evidence for epigenetic dysfunction in Alzheimer's disease.
Lunnon K, Smith R, Hannon E, Volta M, Troakes C, Haroutunian V, Katsel P, Al‐Sarraj S, Lovestone S, Schalkwyk L, et al (2014). O3‐04‐03: CROSS‐TISSUE METHYLOMIC PROFILING IN ALZHEIMER'S DISEASE.

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Teaching

Neuroscience, epigenetics, statistics

Modules

2023/24


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Supervision / Group

Postgraduate researchers

  • Josan Gandawijaya
  • Giulia Pegoraro
  • Luke Weymouth
  • Greg Wheildon

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