Close

Dr Matt Silver

Honorary Associate Professor

United Kingdom

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 exposures including nutrition and some health conditions in later life.

One element of our epigenetics research involves the study of an ‘experiment of nature’ in rural Gambia whereby fluctuations in energy balance and maternal nutrition 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 suppressor ncRNA gene VTRNA2-1 which is linked to immune function. 

Our investigations probe multi-omic data using bioinformatics methods to gain insights into genetic and other factors that may be driving distinctive DNA methylation dynamics at MEs and other variably methylated regions in the early human embryo. 

 

Affiliations

MRC Unit The Gambia at LSHTM

Selected Publications

Missing genetic diversity impacts variant prioritisation for rare disorders
Tallman, S; Moutsianas, L; Nguyen, T; Cho, Y; Mackintosh, M; Kasperaviciute, D; Brown, MA; Ellingford, J; Kuchenbaecker, K; SILVER, MJ;
2024
Cold Spring Harbor Laboratory
Maternal age is related to offspring DNA methylation: A meta-analysis of results from the PACE consortium.
Yeung, E; Biedrzycki, RJ; Gómez Herrera, LC; ISSARAPU, P; Dou, J; Marques, IF; Mansuri, SR; Page, CM; Harbs, J; Khodasevich, D; Poisel, E; Niu, Z; Allard, C; Casey, E; Berstein, FM; Mancano, G; Elliott, HR; Richmond, R; He, Y; Ronkainen, J; Sebert, S; Bell, EM; Sharp, G; Mumford, SL; Schisterman, EF; ... Guan, W.
2024
Aging cell
A Pregnancy and Childhood Epigenetics Consortium (PACE) meta-analysis highlights potential relationships between birth order and neonatal blood DNA methylation.
Li, S; Spitz, N; Ghantous, A; Abrishamcar, S; Reimann, B; Marques, I; SILVER, MJ; Aguilar-Lacasaña, S; Kitaba, N; Rezwan, FI; Röder, S; Sirignano, L; Tuhkanen, J; Mancano, G; Sharp, GC; Metayer, C; Morimoto, L; Stein, DJ; Zar, HJ; Alfano, R; Nawrot, T; Wang, C; Kajantie, E; Keikkala, E; Mustaniemi, S; ... Wiemels, JL.
2024
Communications biology
Metastable epialleles in humans.
Derakhshan, M; Kessler, NJ; Hellenthal, G; SILVER, MJ;
2023
Trends in genetics : TIG
DNA methylation at the suppressor of cytokine signaling 3 (SOCS3) gene influences height in childhood.
ISSARAPU, P; Arumalla, M; Elliott, HR; Nongmaithem, SS; Sankareswaran, A; Betts, M; Sajjadi, S; Kessler, NJ; Bayyana, S; Mansuri, SR; Derakhshan, M; Krishnaveni, GV; Shrestha, S; Kumaran, K; Di Gravio, C; Sahariah, SA; Sanderson, E; RELTON, CL; Ward, KA; Moore, SE; PRENTICE, AM; Lillycrop, KA; Fall, CH D; SILVER, MJ; Chandak, GR; ... EMPHASIS study group,
2023
Nature communications
Early-set POMC methylation variability is accompanied by increased risk for obesity and is addressable by MC4R agonist treatment.
Lechner, L; Opitz, R; SILVER, MJ; Krabusch, PM; PRENTICE, AM; Field, MS; Stachelscheid, H; Leitão, E; Schröder, C; Fernandez Vallone, V; Horsthemke, B; Jöckel, K-H; Schmidt, B; Nöthen, MM; Hoffmann, P; Herms, S; Kleyn, PW; Megges, M; Blume-Peytavi, U; Weiss, K; Mai, K; Blankenstein, O; Obermayer, B; Wiegand, S; Kühnen, P;
2023
Science translational medicine
The influence of early environment and micronutrient availability on developmental epigenetic programming: lessons from the placenta
Sainty, R; SILVER, MJ; PRENTICE, AM; Monk, D;
2023
Frontiers in Cell and Developmental Biology
Tissue- and ethnicity-independent hypervariable DNA methylation states show evidence of establishment in the early human embryo.
Derakhshan, M; Kessler, NJ; Ishida, M; Demetriou, C; Brucato, N; Moore, GE; Fall, CH D; Chandak, GR; Ricaut, F-X; PRENTICE, AM; Hellenthal, G; SILVER, MJ;
2022
Nucleic Acids Research
Environmentally sensitive hotspots in the methylome of the early human embryo.
SILVER, MJ; Saffari, A; Kessler, NJ; Chandak, GR; Fall, CH D; ISSARAPU, P; Dedaniya, A; Betts, M; Moore, SE; Routledge, MN; Herceg, Z; Cuenin, C; Derakhshan, M; James, PT; Monk, D; PRENTICE, AM;
2022
eLife
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; Fall, CH D; SILVER, MJ; Chandak, GR; Lillycrop, KA; EMPHASIS study group,;
2022
Clinical epigenetics
See more information