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Matt Silver

PhD

Associate Professor

Room
Room 139

LSHTM
Keppel Street
London
WC1E 7HT
United Kingdom

Tel.
020 7927 2557

Matt leads the nutritional epigenetics group within the Nutrition Theme of MRC Unit The Gambia at LSHTM. Before joining the group he took a MSc in Bioinformatics and Theoretical Systems Biology, followed by a PhD in bioinformatics / statistical genetics, both at Imperial College, London.

Affiliations

Department of Population Health
Faculty of Epidemiology and Population Health

Teaching

Statistics for Epidemiology and Public Health

MSc Nutrition for Global Health

MSc Epidemiology

Research

The MRC International Nutrition Group has a long-standing interest in exploring links between early life exposures and long-term health outcomes.  Much of our research is focussed on a rural community in The Gambia in Sub-Saharan West Africa. 

Matt's prime focus is on epigenetics - the study of modifications to the genome that can affect gene expression without altering the underlying DNA sequence.  Mounting evidence from animal and human studies suggests such modifications may mediate observed associations between early-life nutrition and later health and disease.

For our epigenetic studies we are able to exploit an ‘experiment of nature’ in rural Gambia whereby fluctuations in energy balance and maternal nutritional exposures show a distinct bimodal seasonal pattern. We have shown for example that season of conception and blood levels of key maternal nutritional biomarkers relating to one-carbon metabolism (B2, B6, cysteine and homocysteine) predict DNA methylation in infants at a number of metastable epialleles - genomic regions where methylation is established stochastically in the early embryo, leading to systemic (cross-tissue) inter-individual variation. 

Our work has highlighted interesting candidate MEs for follow up in our population including a region at the POMC gene with links to obesity in children and adults, and at the tumour supressor ncRNA gene VTRNA2-1 which is linked to immune function. We are also using bioinformatic techniques to explore genetic and other factors that may be driving the distinctive DNA methylation dynamics at MEs and other regions of interest in the early human embryo. 

Research Area
Human genetics
Discipline
Genetic epidemiology
Genomics
Genetics
Bioinformatics
Region
Sub-Saharan Africa (developing only)
Sub-Saharan Africa (all income levels)

Selected Publications

Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight
Kupers LK; Monnereau C; Sharp GC; Yousefi P; Salas LA; Ghantous A; Page CM; Reese SE; Wilcox AJ; Czamara D
2019
NATURE COMMUNICATIONS
A genomic atlas of systemic interindividual epigenetic variation in humans.
Gunasekara CJ; Scott CA; Laritsky E; Baker MS; MacKay H; Duryea JD; Kessler NJ; Hellenthal G; Wood AC; Hodges KR
2019
Genome biology
Establishment of environmentally sensitive DNA methylation states in the very early human embryo.
Kessler NJ; Waterland RA; Prentice AM; Silver MJ
2018
Science advances
Maternal one-carbon metabolism and infant DNA methylation between contrasting seasonal environments: A case study from The Gambia
James PT; Dominguez-Salas P; Hennig BJ; Moore SE; Prentice AM; Silver MJ
2018
Current Developments in Nutrition
Epigenetic supersimilarity of monozygotic twin pairs.
Van Baak TE; Coarfa C; Dugué PA; Fiorito G; Laritsky E; Baker MS; Kessler NJ; Dong J; Duryea JD; Silver MJ
2018
Genome Biol
Candidate genes linking maternal nutrient exposure to offspring health via DNA methylation: a review of existing evidence in humans with specific focus on one-carbon metabolism.
James P; Sajjadi S; Tomar AS; Saffari A; Fall CHD; Prentice AM; Shrestha S; Issarapu P; Yadav DK; Kaur L
2018
International journal of epidemiology
Protocol for the EMPHASIS study; epigenetic mechanisms linking maternal pre-conceptional nutrition and children’s health in India and Sub-Saharan Africa
Chandak GR; Silver MJ; Saffari A; Lillycrop KA; Shrestha S; Sahariah SA; di Gravio C; Goldberg G; Tomar AS; Betts M
2017
BMC nutrition
Influence of intergenerational in utero parental energy and nutrient restriction on offspring growth in rural Gambia.
Eriksen KG; Radford EJ; Silver MJ; Fulford AJC; Wegmüller R; Prentice AM
2017
FASEB journal
Estimation of a significance threshold for epigenome-wide association studies.
Saffari A; Silver MJ; Zavattari P; Moi L; Columbano A; Meaburn EL; Dudbridge F
2017
Genetic epidemiology
Interindividual Variation in DNA Methylation at a Putative POMC Metastable Epiallele Is Associated with Obesity.
Kühnen P; Handke D; Waterland RA; Hennig BJ; Silver M; Fulford AJ; Dominguez-Salas P; Moore SE; Prentice AM; Spranger J
2016
Cell metabolism
Evidence for negative selection of gene variants that increase dependence on dietary choline in a Gambian cohort.
Silver MJ; Corbin KD; Hellenthal G; da Costa KA; Dominguez-Salas P; Moore SE; Owen J; Prentice AM; Hennig BJ; Zeisel SH
2015
FASEB journal
Exposure to aflatoxin B1 in utero is associated with DNA methylation in white blood cells of infants in The Gambia.
Hernandez-Vargas H; Castelino J; Silver MJ; Dominguez-Salas P; Cros MP; Durand G; Le Calvez-Kelm F; Prentice AM; Wild CP; Moore SE
2015
International journal of epidemiology
Maternal nutrition at conception modulates DNA methylation of human metastable epialleles.
Dominguez-Salas P; Moore SE; Baker MS; Bergen AW; Cox SE; Dyer RA; Fulford AJ; Guan Y; Laritsky E; Silver MJ
2014
Nature communications
Identification of gene pathways implicated in Alzheimer's disease using longitudinal imaging phenotypes with sparse regression.
Silver M; Janousova E; Hua X; Thompson PM; Montana G; The Alzheimer's Disease Neuroimaging Initiative
2012
NeuroImage
False positives in neuroimaging genetics using voxel-based morphometry data.
Silver M; Montana G; Nichols TE; Alzheimer's Disease Neuroimaging Initiative
2011
NeuroImage
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