Home| Non-clinical Lecturer in Epigenetics |
Contact details:
| Tel: | +44 20 7882 8140 |
| Fax: | +44 20 7882 2186 |
| Email: | v.rakyan@qmul.ac.uk |
| Address: | Centre for Diabetes, |
Biography
For my PhD (1999-2002), I investigated epigenetic inheritance under the supervision of Prof. Emma Whitelaw, University of Sydney, Australia. From 2003-2007, I was a CJ Martin Postdoctoral Fellow at the Sanger Institute, Cambridge, UK where, under the guidance of Dr Stephan Beck, I developed functional genomics tools for genome-wide DNA methylation analyses.
Research Interests
The overall goals of my lab are to understand how epigenetic mechanisms influence complex phenotypes and diseases in multi-cellular organisms. We are particularly interested in exploring the notion of the ‘epiallele' – loci at which the epigenetic state varies as a result of genetic and/or environmental influences. We are pursuing several complementary lines of investigation that integrate molecular genetics, functional genomics, bioinformatics, model organisms, and human cohorts:
(1) The epigenetic basis of human complex diseases: Elucidating the mechanisms that cause complex human diseases remains one of biology's principal challenges. We are testing the hypothesis that complex human phenotypes (e.g. aging) and diseases (e.g. diabetes and celiac disease) are associated with aberrant epigenetic profiles. These projects currently involve microarray-based profiling of disease-discordant monozygotic twins and individuals from recent landmark genome-wide association studies.
(2) Environment and the epigenome: There is increasing evidence that environmental influences on genome function can be mediated by epigenetic mechanisms. We are studying key environmental factors that potentially alter the epigenome e.g. exposure to an adverse in utero environment. These projects employ ultra high-throughput sequencing-based epigenetic analyses of model organisms and human cohorts.
(3) Non-canonical roles of DNA methylation: The overwhelming majority of studies aimed at understanding the role of DNA methylation focus on a limited set of genomic features (usually CpG islands and promoters) in mammals. However, DNA methylation is found genome-wide in a variety of mammalian and non-mammalian eukaryotes. Using ultra high-throughput sequencing-based approaches, we are exploring the role of DNA methylation in the Honey Bee ( Apis Mellifera), and gene-body methylation in mammals.
Lab Members
Lisa Nanty (PhD student)
Dr. Sarah Finer (Clinical Research Fellow/PhD student, jointly supervised with Prof. Graham Hitman, ICMS)
Collaborators
Thomas Down (Gurdon Institute, Cambridge, UK)
Stephan Beck (UCL Cancer Institute, London, UK)
David Leslie (ICMS, London, UK)
Graham Hitman (ICMS, London, UK)
David van Heel (ICMS, London, UK)
Timothy Spector (KCL, London, UK)
Mark McCarthy (University of Oxford, UK)
Paul Flicek (EBI, Cambridge, UK)
Francis Ratnieks (University of Sussex, UK)
Funding
BBSRC, JDRF, Barts and The London Charity.
Key Publications
• Rakyan VK*, Down TA*, Thorne NP*, Flicek P*, (*equal first authors), Kulesha E, Gräf S, Tomazou EM, Bäckdahl L, Johnson N, Herberth M, Howe KL, Jackson DK, Miretti MM, Fiegler H, Marioni JC, Birney E, Hubbard TJ, Carter NP, Tavaré S, Beck S. (2008) An integrated resource for genome-wide identification and analysis of human tissue-specific differentially methylated regions (tDMRs ). Genome Res . 18: 1518.
• Down TA*, Rakyan VK* (*equal first authors), Turner DJ, Flicek P, Li H, Kulesha E, Gräf S, Johnson N, Herrero J, Tomazou EM, Thorne NP, Bäckdahl L, Herberth M, Howe KL, Jackson DK, Miretti MM, Marioni JC, Birney E, Hubbard TJ, Durbin R, Tavaré S, Beck S. (2008) A Bayesian deconvolution strategy for immunoprecipitation-based DNA methylome analysis. Nat Biotechnol. 26: 779.
• Eckhardt F, Lewin J, Cortese R, Rakyan VK, Attwood J, Burger M, Burton J, Cox TV, Davies R, Down TA, Haefliger C, Horton R, Howe K, Jackson DK, Kunde J, Koenig C, Liddle J, Niblett D, Otto T, Pettett R, Seemann S, Thompson C, West T, Rogers J, Olek A, Berlin K, Beck S. (2006) DNA methylation profiling of human chromosomes 6, 20 and 22. Nat Genet. 38: 1378.
• Rakyan VK, Hildmann T, Novik KL, Lewin J, Tost J, Cox AV, Andrews TD, Howe KL, Otto T, Olek A, Fischer J, Gut IG, Berlin K, Beck S. (2004) DNA methylation profiling of the human major histocompatibility complex: a pilot study for the human epigenome project. PLoS Biol. 2: e405.
• Rakyan VK, Chong S, Champ ME, Cuthbert PC, Morgan HD, Luu KV, Whitelaw E. (2003) Transgenerational inheritance of epigenetic states at the murine AxinFu allele occurs after maternal and paternal transmission. Proc Natl Acad Sci U S A. 100: 2538-43.
