Samuel Lessard
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View article: Genetic liability to psoriasis predicts severe disease outcomes
Genetic liability to psoriasis predicts severe disease outcomes Open
Background Psoriasis is a common inflammatory skin disease with heterogeneous presentation. Up to 30% of individuals have severe disease with a greater surface area of skin involvement, co-morbidity burden and impact on quality of life. Pr…
View article: Selective AMPKβ1 activation induces fetal hemoglobin in human erythroid cells and sickle cell mice via the noncanonical NRF2 pathway
Selective AMPKβ1 activation induces fetal hemoglobin in human erythroid cells and sickle cell mice via the noncanonical NRF2 pathway Open
Sickle cell disease (SCD), an inherited blood disorder caused by mutation of the β-globin gene, results in sickle-shaped erythrocytes, organ damage, and increased mortality. Current therapeutic options are limited, and innovative treatment…
View article: Multi-omic triangulation identifies molecular candidates of atopic dermatitis severity
Multi-omic triangulation identifies molecular candidates of atopic dermatitis severity Open
Atopic dermatitis (AD) is a common skin disease with most of the health, social and economic impact driven by those with more severe disease. Determining the molecular pathways that influence severity is therefore crucial, offering opportu…
View article: Building a human genetic data lake to scale up insights for drug discovery
Building a human genetic data lake to scale up insights for drug discovery Open
Genome-wide association studies (GWAS) have identified numerous disease-associated variants, yet efficient storage and analysis of genetic data remain a challenge. Here, we propose a scalable genetic data lake (GDL) integrating GWAS, molec…
View article: Genetic liability to psoriasis predicts severe disease outcomes
Genetic liability to psoriasis predicts severe disease outcomes Open
Background Psoriasis is a common inflammatory skin disease with heterogeneous presentation. Up to 30% of individuals have severe disease with a greater surface area of skin involvement, co-morbidity burden and impact on quality of life. Pr…
View article: Leveraging large-scale multi-omics evidences to identify therapeutic targets from genome-wide association studies
Leveraging large-scale multi-omics evidences to identify therapeutic targets from genome-wide association studies Open
Background Therapeutic targets supported by genetic evidence from genome-wide association studies (GWAS) show higher probability of success in clinical trials. GWAS is a powerful approach to identify links between genetic variants and phen…
View article: Common α-globin variants modify hematologic and other clinical phenotypes in sickle cell trait and disease
Common α-globin variants modify hematologic and other clinical phenotypes in sickle cell trait and disease Open
Co-inheritance of α-thalassemia has a significant protective effect on the severity of complications of sickle cell disease (SCD), including stroke. However, little information exists on the association and interactions for the common Afri…
View article: Genome-wide association study analysis of disease severity in Acne reveals novel biological insights
Genome-wide association study analysis of disease severity in Acne reveals novel biological insights Open
Acne vulgaris is a common skin disease that affects >85% of teenage young adults among which >8% develop severe lesions that leaves permanent scars. Genetic heritability studies of acne in twin cohorts have estimated that the heritability …
View article: Genetic analyses of inflammatory polyneuropathy and chronic inflammatory demyelinating polyradiculoneuropathy identified candidate genes
Genetic analyses of inflammatory polyneuropathy and chronic inflammatory demyelinating polyradiculoneuropathy identified candidate genes Open
Objective Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare, immune-mediated disorder in which an aberrant immune response causes demyelination and axonal damage of the peripheral nerves. Genetic contribution to CIDP is un…
View article: Leveraging large-scale multi-omics to identify therapeutic targets from genome-wide association studies
Leveraging large-scale multi-omics to identify therapeutic targets from genome-wide association studies Open
BACKGROUND : Therapeutic targets supported by genetic evidence from genome-wide association studies (GWAS) show higher probability of success in clinical trials. GWAS is a powerful approach to identify links between genetic variants and ph…
View article: Genomic discovery and functional validation of MRP1 as a novel fetal hemoglobin modulator and potential therapeutic target in sickle cell disease
Genomic discovery and functional validation of MRP1 as a novel fetal hemoglobin modulator and potential therapeutic target in sickle cell disease Open
Sickle cell disease (SCD) remains a major health burden with limited treatment options. Despite promising gene-editing clinical trials, there is an unmet need for cost-effective therapies. As induction of fetal hemoglobin (HbF) is an estab…
View article: SGK1 inhibition induces fetal hemoglobin expression and delays polymerization in sickle erythroid cells
SGK1 inhibition induces fetal hemoglobin expression and delays polymerization in sickle erythroid cells Open
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View article: Genome-Wide Association Study and Gene-Based Analysis of Participants With Hemophilia A and Inhibitors in the My Life, Our Future Research Repository
Genome-Wide Association Study and Gene-Based Analysis of Participants With Hemophilia A and Inhibitors in the My Life, Our Future Research Repository Open
Introduction Up to 30% of individuals with hemophilia A develop inhibitors to replacement factor VIII (FVIII), rendering the treatment ineffective. The underlying mechanism of inhibitor development remains poorly understood. The My Life, O…
View article: Atlas of epistasis
Atlas of epistasis Open
We performed a genome-wide epistasis search across 502 phenotypes in case control matched cohorts from the UK Biobank. We identified 152,519 genome wide significant interactions in 68 distinct phenotypes, and 3,398 interactions in 19 pheno…
View article: Exome Genotyping Identifies Pleiotropic Variants Associated with Red Blood Cell Traits
Exome Genotyping Identifies Pleiotropic Variants Associated with Red Blood Cell Traits Open
Red blood cell (RBC) traits are important heritable clinical biomarkers and modifiers of disease severity. To identify coding genetic variants associated with these traits, we conducted meta-analys ...
View article: Testing the role of predicted gene knockouts in human anthropometric trait variation
Testing the role of predicted gene knockouts in human anthropometric trait variation Open
Although the role of complete gene inactivation by two loss-of-function mutations inherited in trans is well-established in recessive Mendelian diseases, we have not yet explored how such gene knockouts (KOs) could influence complex human …
View article: A saturating mutagenesis CRISPR-Cas9 mediated functional genomic screen identifies<i>cis-</i>and<i>trans-</i>regulatory elements of<i>Oct4</i>in murine ESCs
A saturating mutagenesis CRISPR-Cas9 mediated functional genomic screen identifies<i>cis-</i>and<i>trans-</i>regulatory elements of<i>Oct4</i>in murine ESCs Open
Regulatory elements (REs) consist of enhancers and promoters that occupy a significant portion of the non-coding genome and control gene expression programs either in –cis or in – trans . Putative REs have been identified largely based on …
View article: PF736 ZINC FINGER NUCLEASE‐MEDIATED DISRUPTION OF THE BCL11A ERYTHROID ENHANCER IN PLERIXAFOR MOBILIZED CD34+ CELLS RESULTS IN ENRICHED BIALLELEIC EDITING AND ALLELE‐ADDITIVE INCREASES IN FETAL HEMOGLOBIN
PF736 ZINC FINGER NUCLEASE‐MEDIATED DISRUPTION OF THE BCL11A ERYTHROID ENHANCER IN PLERIXAFOR MOBILIZED CD34+ CELLS RESULTS IN ENRICHED BIALLELEIC EDITING AND ALLELE‐ADDITIVE INCREASES IN FETAL HEMOGLOBIN Open
Background: High fetal hemoglobin (HbF) levels are associated with decreased severity in sickle cell disease (SCD) and beta thalassemia (BT). We developed a novel gene‐edited cell therapy using autologous hematopoietic stem and progenitor …
View article: Common α-globin variants modify hematologic and other clinical phenotypes in sickle cell trait and disease
Common α-globin variants modify hematologic and other clinical phenotypes in sickle cell trait and disease Open
Co-inheritance of α-thalassemia has a significant protective effect on the severity of complications of sickle cell disease (SCD), including stroke. However, little information exists on the association and interactions for the common Afri…
View article: 14q32 and let-7 microRNAs regulate transcriptional networks in fetal and adult human erythroblasts
14q32 and let-7 microRNAs regulate transcriptional networks in fetal and adult human erythroblasts Open
In humans, fetal erythropoiesis takes place in the liver whereas adult erythropoiesis occurs in the bone marrow. Fetal and adult erythroid cells are not only produced at different sites, but are also distinguished by their respective trans…
View article: Human genetic variation alters CRISPR-Cas9 on- and off-targeting specificity at therapeutically implicated loci
Human genetic variation alters CRISPR-Cas9 on- and off-targeting specificity at therapeutically implicated loci Open
Significance CRISPR-Cas9 holds enormous potential for therapeutic genome editing. Effective therapy requires treatment to be efficient and safe with minimal toxicity. The sequence-based targeting for CRISPR systems necessitates considerati…
View article: An erythroid-specific ATP2B4 enhancer mediates red blood cell hydration and malaria susceptibility
An erythroid-specific ATP2B4 enhancer mediates red blood cell hydration and malaria susceptibility Open
The lack of mechanistic explanations for many genotype-phenotype associations identified by GWAS precludes thorough assessment of their impact on human health. Here, we conducted an expression quantitative trait locus (eQTL) mapping analys…
View article: Frameshift indels introduced by genome editing can lead to in-frame exon skipping
Frameshift indels introduced by genome editing can lead to in-frame exon skipping Open
The introduction of frameshift indels by genome editing has emerged as a powerful technique to study the functions of uncharacterized genes in cell lines and model organisms. Such mutations should lead to mRNA degradation owing to nonsense…
View article: Deciphering causal genetic determinants of red blood cell traits
Deciphering causal genetic determinants of red blood cell traits Open
Les études d’association pan-génomiques ont révélé plusieurs variants génétiques associés à des traits complexes. Les mesures érythrocytaires ont souvent fait l’objet de ce genre d’études, étant mesurées de façon routinière et précise. Com…
View article: Lower Methylation of the ANGPTL2 Gene in Leukocytes from Post-Acute Coronary Syndrome Patients
Lower Methylation of the ANGPTL2 Gene in Leukocytes from Post-Acute Coronary Syndrome Patients Open
DNA methylation is believed to regulate gene expression during adulthood in response to the constant changes in environment. The methylome is therefore proposed to be a biomarker of health through age. ANGPTL2 is a circulating pro-inflamma…