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Matt Silver

PhD

Associate Professor

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.

Affiliations

Department of Population Health
Faculty of Epidemiology and Population Health

Teaching

MSc Nutrition for Global Health

MSc Epidemiology

MSc Health Data Science

Research

Our 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. 

Our primary focus is on epigenetics - the study of modifications to the genome that can affect gene expression without altering the underlying DNA sequence.  Evidence from animal and human studies suggests such modifications could mediate observed associations between early-life nutrition and later health and disease.

One element of our epigenetics research involves the study of 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 that Gambian season of conception (SoC) and blood levels of certain maternal nutritional biomarkers relating to one-carbon metabolism are associated with DNA methylation in infants at a number of metastable epialleles (MEs) - 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 loci linking early exposures to later health outcomes including a differentially methylated region of the PAX8 gene implicated in thyroid gland differentiation and function which is associated with thryoid volume and free thyroxine (T4) in Gambian children. Other SoC-associated candidate MEs include a region at the POMC gene with links to obesity in children and adults, and the tumour supressor ncRNA gene VTRNA2-1 which is linked to immune function. 

We also use multi-omic data and bioinformatic techniques to explore genetic and other factors that may be driving the distinctive DNA methylation dynamics at MEs and other variably methylated regions in the early human embryo. 

Research Area
Child health
Human genetics
Micronutrients
Global Health
Discipline
Genetic epidemiology
Genomics
Genetics
Bioinformatics
Country
The Gambia
India
Region
South Asia
Sub-Saharan Africa (developing only)
Sub-Saharan Africa (all income levels)

Selected Publications

DNA methylation signatures associated with cardiometabolic risk factors in children from India and The Gambia: results from the EMPHASIS study.
Antoun E; Issarapu P; di Gravio C; Shrestha S; Betts M; Saffari A; Sahariah SA; Sankareswaran A; Arumalla M; Prentice AM
2022
Clinical epigenetics
Environmentally sensitive hotspots in the methylome of the early human embryo.
Silver MJ; Saffari A; Kessler NJ; Chandak GR; Fall CHD; Issarapu P; Dedaniya A; Betts M; Moore SE; Routledge MN
2022
eLife
DNA methylation at a nutritionally sensitive region of the PAX8 gene is associated with thyroid volume and function in Gambian children.
Candler T; Kessler NJ; Gunasekara CJ; Ward KA; James P; Laritsky E; Baker MS; Dyer R; Elango R; Jeffries D
2021
Science Advances
The Role of Nutrition in COVID-19 Susceptibility and Severity of Disease: A Systematic Review.
James PT; Ali Z; Armitage AE; Bonell A; Cerami C; Drakesmith H; Jobe M; Jones KS; Liew Z; Moore SE
2021
The Journal of Nutrition
Periconceptional environment predicts leukocyte telomere length in a cross-sectional study of 7-9 year old rural Gambian children.
Maasen K; James PT; Prentice AM; Moore SE; Fall CH; Chandak GR; Betts M; Silver MJ; Buxton JL
2020
Sci Rep
Effect of maternal preconceptional and pregnancy micronutrient interventions on children's DNA methylation: Findings from the EMPHASIS study.
Saffari A; Shrestha S; Issarapu P; Sajjadi S; Betts M; Sahariah SA; Tomar AS; James P; Dedaniya A; Yadav DK
2020
The American journal of clinical nutrition
Intergenerational Influences on Child Development: An Epigenetic Perspective.
Silver MJ
2020
Nestle Nutrition Institute workshop series
Fetal programming and epigenetics
Stevenson K; Lillycrop KA; Silver MJ
2020
Current Opinion in Endocrine and Metabolic Research
Epigenetic regulation of POMC; implications for nutritional programming, obesity and metabolic disease.
Candler T; Kühnen P; Prentice AM; Silver M
2019
Frontiers in Neuroendocrinology
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
A novel nutritional supplement to reduce plasma homocysteine in nonpregnant women: A randomised controlled trial in The Gambia.
James PT; Jawla O; Mohammed NI; Ceesay K; Akemokwe FM; Sonko B; Sise EA; Prentice AM; Silver MJ
2019
PLoS medicine
Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight.
Küpers LK; Monnereau C; Sharp GC; Yousefi P; Salas LA; Ghantous A; Page CM; Reese SE; Wilcox AJ; Czamara D
2019
NATURE COMMUNICATIONS
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
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
Establishment of environmentally sensitive DNA methylation states in the very early human embryo.
Kessler NJ; Waterland RA; Prentice AM; Silver MJ
2018
Science advances
Epigenetic supersimilarity of monozygotic twin pairs.
Van Baak TE; Coarfa C; Dugué P-A; Fiorito G; Laritsky E; Baker MS; Kessler NJ; Dong J; Duryea JD; Silver MJ
2018
Genome Biol
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
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 M-P; Durand G; Le Calvez-Kelm F; Prentice AM; Wild CP; Moore SE
2015
International journal of epidemiology
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 K-A; Dominguez-Salas P; Moore SE; Owen J; Prentice AM; Hennig BJ; Zeisel SH
2015
FASEB journal
Independent genomewide screens identify the tumor suppressor VTRNA2-1 as a human epiallele responsive to periconceptional environment.
Silver MJ; Kessler NJ; Hennig BJ; Dominguez-Salas P; Laritsky E; Baker MS; Coarfa C; Hernandez-Vargas H; Castelino JM; Routledge MN
2015
Genome biology
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; 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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