University Lecturer in Integrative Human Genomics
Departments and Institutes
Functional genomics of cardiovascular diseases
The goal of the Integrative Human Genomics Team at the Department of Public Health and Primary Care is to identify and validate causal pathways in cardiovascular disease. Large-scale genome-wide association studies (GWAS) have been very fruitful in pinpointing genomic regions that associate with the disease. However, the precise mechanism underlying most of these genetic associations remains elusive. To this end, we use both computational and experimental approaches to expose new mechanisms leading to atherosclerosis, the major cause of cardiovascular disease. We apply cutting-edge technology, including human induced pluripotent stem cells and CRISPR/Cas9 (epi-)genome editing, to elucidate the biological underpinnings of candidate causal genes and pathways. In parallel, we conduct recall-by-genotype studies, in which individuals with a potential functional genetic variant are called back for additional hypothesis-driven phenotyping. Our efforts, which integrate genetic epidemiology, functional genomics and epigenomics, as well as clinical medicine, facilitate a better understanding of the aetiology of cardiovascular disease to inform the development of new therapeutics.
functional genomics ; cardiovascular genomics ; epigenomics ; iPSC ; cardiovascular biology ; bioinformatics
*joint first author, #joint last author
Ecker E, Chen L, Pancaldi V, Bagger FO, Fernández JM, Carrillo de Santa Pau E, Juan D, Mann AL, [...], Rico D#, Valencia A#, Beck S#, Soranzo N# & Paul DS# (2017). Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types. Genome Biol. 18(1), 18.
Chen L*, Ge B*, Casale FP*, Vasquez L*, Kwan T, Garrido-Martín D, Watt S, Yang Y, [...], Paul DS, Stunnenberg HG, Stegle O, Downes K, Pastinen T# & Soranzo N# (2016). Genetic drivers of epigenetic and transcriptional variation in human immune cells. Cell 167(5), 1398–1414.
Paul DS*, Teschendorff AE*, Dang MA*, Lowe R*, Hawa MI, Ecker S, Beyan H, Cunningham S, [...], Rakyan VK#, Beck S# & Leslie RD# (2016). Increased DNA methylation variability in type 1 diabetes across three immune effector cell types. Nature Commun. 7, 13555.
Paul DS, Jones A, Sellar RS, Mayor NP, Feber A, Webster AP, Afonso N, Sergeant R, [...], Rakyan VK#, Peggs KS# & Beck S# (2015). A donor-specific epigenetic classifier for acute graft-versus-host disease severity in hematopoietic stem cell transplantation. Genome Med. 7(1), 128.
Paul DS*, Albers CA*, Rendon A*, Voss K, Stephens J, HaemGen Consortium, van der Harst P, Chambers JC, Soranzo N, Ouwehand WH# & Deloukas P# (2013). Maps of open chromatin highlight cell type-restricted patterns of regulatory sequence variation at hematological trait loci. Genome Res. 23(7), 1130-41.
van der Harst P*, Zhang W*, Mateo Leach I*, Rendon A*, Verweij N*, Sehmi J*, Paul DS*, Elling U*, [...], Hicks AA#, Penninger JM#, Gieger C#, Kooner JS#, Ouwehand WH#, Soranzo N# & Chambers JC# (2012). Seventy-five genetic loci influencing the human red blood cell. Nature 492(7429), 369-75.
Albers CA*, Paul DS*, Schulze H*, Freson K, Stephens JC, Smethurst PA, Jolley JD, Cvejic A, [...], Newbury-Ecob R#, Ouwehand WH# & Ghevaert C# (2012). Compound inheritance of a low-frequency regulatory SNP and a rare null mutation in exon-junction complex subunit RBM8A causes TAR syndrome. Nature Genet. 44(4), 435-9.
Paul DS, Nisbet JP, Yang TP, Meacham S, Rendon A, Hautaviita K, Tallila J, White J, [...], Soranzo N, Ouwehand WH & Deloukas P (2011). Maps of open chromatin guide the functional follow-up of genome-wide association signals: application to hematological traits. PLOS Genet. 7(6), e1002139.