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The William Harvey Research Institute - Faculty of Medicine and Dentistry

Dr Christopher Bell

Christopher

Senior Lecturer in Functional Genomics

Centre: Clinical Pharmacology

Email: c.bell@qmul.ac.uk
Website: http://qmulepigenetics.com/bell
Twitter: @EpigenomicMed

Profile

ORCID iD: 0000-0003-4601-1242


Christopher Bell gained his PhD in human genomics from Imperial College London, investigating genetic susceptibility to type 2 diabetes and obesity under the supervision of Prof. Philippe Froguel. His post-doctoral training was with Prof. Stephan Beck at the UCL Cancer Institute, University College London, where they pioneered the epigenomic analysis of common human disease. This included publishing some of the very first Epigenome-wide Association Studies (EWAS) as well as ground-breaking integrative analyses of the DNA methylome within common disease-associated loci. He subsequently furthered his epigenomics expertise interrogating the deeply-phenotyped TwinsUK cohort, with Prof. Tim Spector, at King’s College London, and then as an independent group leader at the MRC Lifecourse Epidemiology Unit. He is a medical graduate of the University of Otago, New Zealand and, through training with the Royal College of Pathologists of Australasia, in Sydney, gained his fellowship of genetic pathology. 

He is an expert in human epigenomics and its role in the pathology of common disease, with a specific focus on type 2 diabetes, cardiometabolic disorders, and chronic ageing-related diseases. His research involves large-scale computational, statistical, and functional integration of multi-omic human datasets.

Research

Group members

  • Mr Richard Acton (PhD Student – Primary Supervisor)
  • Dr Nicholas Fuggle (PhD Student – Secondary Supervisor)

Summary

Our research is focused on understanding the pathophysiology of common and chronic human diseases, by investigating and integrating large-scale epigenomic, genomic, and transcriptomic data. This knowledge will enable a more precise insight into the perturbed molecular mechanisms involved in these diseases, with the ultimate aim of identifying novel avenues for treatment and prevention.

Due to the power now available from population-based multi-omic datasets, human diseases can be directly studied at scale with the human as model. Our work centres on:

  • How disease-related genetic variation impacts on the epigenome and, thereby, leads to pathological functional changes in disease-relevant cell-types. This, for example, has included defining obligatory or facilitative allelic DNA methylome variation within disease-associated loci in the human genome.
  • Interrogating the ageing-related deterioration of the epigenome. Recent fascinating discoveries have revealed these changes capture aspects of ‘biological’ ageing that impact on population variability in age-related phenotypes and may bring novel mechanistic insights to chronic ageing-related diseases.
  • The robust biomarker ability of DNA methylation to capture and quantitate both internal and external chronic disease-related exposures. We are investigating their predictive power in combination with ageing- and phenotype-related DNA methylation ‘clocks’ (constructed with ML methodology) as well as genetic risk scores. The aim is to determine the potential clinical utility of these biomarkers, with the analysis of longitudinal datasets taking advantage of the long-term stability of DNA modifications.

This research into metabolic disorders, type 2 diabetes and cardiovascular diseases encompasses the broad themes of epigenomics; functional genomics; computational medicine; statistical genomics, bioinformatics, and genomic medicine. We are also a core member of the cross-cutting QMUL Epigenetics Hub.

 

Key Publications

For a full list of publications click here

  • Acton R, Yuan W, Gao F, …, Hysi P, Cooper C & Bell C.G. “The Genomic Loci of Specific Human tRNA Genes Exhibit Ageing-Related DNA Hypermethylation” BioRxiv 2020 doi.org/10.1101/870352v2
  • Bell C.G., Lowe R, Adams PD, Baccarelli AA, Beck S, Bell JT, Christensen BC, Gladyshev VN, Heijmans BT, Horvath S, Ideker T, Issa J-PJ, Kelsey KT, Marioni RE, Reik W, Relton CL, Schalkwyk LC, Teschendorff AE, Wagner W, Zhang K, & Rakyan VK. “DNA methylation aging clocks: challenges and recommendations” Genome Biology 2019 20 (1), 249
  • Bell C.G., Gao F, Yuan W, …, Hysi P, Wang J, & Spector T. “Obligatory and Facilitative Allelic Variation in the DNA Methylome Within Common Disease-Associated Loci” Nature Communications 2018 - 9(1):8.
  • Thurner M, van de Bunt M, Gaulton K, …, Bell C.G., Beck S, Rakyan V, Gloyn A, & McCarthy M. “Integration of human pancreatic islet epigenomic data refines regulatory mechanisms at Type 2 Diabetes susceptibility loci.” eLife 2018; e31977eLife
  • Bell C.G. “Epigenomic Analysis in Human Obesity” Obesity 2017 - 10.1002/oby.21909
  • Bell C.G., Xia Y, Yuan W, Gao F, Ward K, Roos L, Mangino M, Hysi P, Bell J, Wang J, & Spector T. “Novel Age-Associated DNA Methylation Changes within Human Common Disease-Associated Loci.” Genome Biology 2016; 17:193
  • Maiarù M, Tochiki K, Cox M, …, Bell C.G., Feng X, Hausch F, & Géranton S. “The stress regulator FKBP51 drives chronic pain by modulating spinal glucocorticoid signaling.” Science Translational Medicine 2016; 325ra19.
  • Yuan W, Xia Y, Bell C.G., …, Wang J, & Spector T. “An Integrated Epigenomic Analysis for Type 2 Diabetes Susceptibility Loci in Monozygotic Twins.” Nature Communications 2014; 5:5719
  • Wilson G, Butcher L, Foster H, …, Woszczek G, Beck S, & Bell C.G. “Human-specific epigenetic variation in the immunological Leukotriene B4 Receptor (LTB4R/BLT1) implicated in common inflammatory diseases” Genome Medicine 2014; 6:19
  • Teschendorff A, Menon U, Gentry-Maharaj A, …, Bell C.G., Maxwell P, Savage D, Gayther S, Jones A, Beck S, Wagner W, Laird P, Jacobs I, & Widschwendter M. “Age-dependent DNA methylation of genes that are suppressed in stem cells is a hallmark of Cancer.” Genome Research 2010; 20:440-446
  • Bell C.G., Finer S, Lindgren C, …, McCarthy M, Beck S, & Hitman G. “Integrated Epigenetic and Genetic Analysis Identifies Haplotype-Specific Methylation in the FTO Type 2 Diabetes and Obesity Susceptibility Locus.” PLoS One 2010; 5(11): e14040
  • Bell CG, Walley A, & Froguel P. “The genetics of human obesity” Nature Reviews Genetics 2005; 6(3), 221-234

Collaborators

Internal: Patricia Munroe (WHRI)

External: Dr Sandrine Géranton (Cell & Developmental Biology; University College London); Dr Pirro G. Hysi (Dept. of Twin Research; King’s College London); Stephan Beck (UCL Cancer Institute, University College London); Dr Peter McErlean (National Heart & Lung Institute; Imperial College London); Dr Michelle Holland (Genetics & Molecular Medicine; King’s College London); Dr Luca Urbani (Institute of Hepatology; King’s College London)

 

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