A5015604524- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Genetic Associations and Epidemiology
- Pancreatic function and diabetes
- SARS-CoV-2 and COVID-19 Research
- RNA modifications and cancer
- Autoimmune and Inflammatory Disorders Research
- SARS-CoV-2 detection and testing
- Endoplasmic Reticulum Stress and Disease
- Genomics and Rare Diseases
- Lymphoma Diagnosis and Treatment
- RNA and protein synthesis mechanisms
- Genetics and Neurodevelopmental Disorders
- Acute Lymphoblastic Leukemia research
- COVID-19 Impact on Reproduction
- Cancer-related Molecular Pathways
- Immune responses and vaccinations
- Cancer therapeutics and mechanisms
- Advanced biosensing and bioanalysis techniques
- Single-cell and spatial transcriptomics
- Evolution and Genetic Dynamics
- Epigenetics and DNA Methylation
- Agriculture, Soil, Plant Science
- Viral Infections and Outbreaks Research
- Modular Robots and Swarm Intelligence
Jackson Laboratory
2020-2024
Baylor College of Medicine
2018
Merck & Co., Inc., Rahway, NJ, USA (United States)
2013
The SARS-CoV-2 Delta variant rose to dominance in mid-2021, likely propelled by an estimated 40%–80% increased transmissibility over Alpha. To investigate if this ostensible difference is uniform across populations, we partner with public health programs from all six states New England the United States. We compare logistic growth rates during each variant's respective emergence period, finding that emerged 1.37–2.63 times faster than Alpha (range states). compute variant-specific effective...
Cis-regulatory elements (CREs) control gene expression, orchestrating tissue identity, developmental timing and stimulus responses, which collectively define the thousands of unique cell types in body
Identifying the causal variants and mechanisms that drive complex traits diseases remains a core problem in human genetics. The majority of these have individually weak effects lie non-coding gene-regulatory elements where we lack complete understanding how single nucleotide alterations modulate transcriptional processes to affect phenotypes. To address this, measured activity 221,412 trait-associated had been statistically fine-mapped using Massively Parallel Reporter Assay (MPRA) 5 diverse...
Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant quickly rose to dominance in mid-2021, displacing other variants, including Alpha. Studies using data from the United Kingdom and India estimated that was 40-80% more transmissible than Alpha, allowing become globally dominant variant. However, it unclear if ostensible difference relative transmissibility due mostly innate properties of Delta’s infectiousness or differences study populations. To...
Cis-regulatory elements (CREs) control gene expression, orchestrating tissue identity, developmental timing, and stimulus responses, which collectively define the thousands of unique cell types in body. While there is great potential for strategically incorporating CREs therapeutic or biotechnology applications that require specificity, no guarantee an optimal CRE intended purpose has arisen naturally through evolution. Here, we present a platform to engineer validate synthetic capable...
Abstract Despite advances in next generation sequencing technologies, determining the genetic basis of ocular disease remains a major challenge due to limited access and prohibitive cost human forward genetics. Thus, less than 4,000 genes currently have available phenotype information for any organ system. Here we report ophthalmic findings from International Mouse Phenotyping Consortium, large-scale functional screen with goal generating phenotyping null mutant every mouse gene. Of 4364...
Genome-wide association studies (GWAS) have linked single nucleotide polymorphisms (SNPs) at >250 loci in the human genome to type 2 diabetes (T2D) risk. For each locus, identifying functional variant(s) among multiple SNPs high linkage disequilibrium is critical understand molecular mechanisms underlying T2D genetic Using massively parallel reporter assays (MPRA), we test cis-regulatory effects of associated with and altered vivo islet chromatin accessibility MIN6 β cells under steady state...
Abstract Infection with Lassa virus (LASV) can cause fever, a haemorrhagic illness an estimated fatality rate of 29.7%, but causes no or mild symptoms in many individuals. Here, to investigate whether human genetic variation underlies the heterogeneity LASV infection, we carried out genome-wide association studies (GWAS) as well seroprevalence surveys, leukocyte antigen typing and high-throughput variant functional characterization assays. We analysed fever susceptibility fatal outcomes 533...
Abstract Background Although genome-wide association studies (GWAS) have identified multiple regions conferring genetic risk for juvenile idiopathic arthritis (JIA), we are still faced with the task of identifying single nucleotide polymorphisms (SNPs) on disease haplotypes that exert biological effects confer risk. Until identify risk-driving variants, genes influenced by these and therefore translating information to improved clinical care, will remain an insurmountable task. We used a...
Both upregulation and downregulation by
Abstract CRISPR screens for cis-regulatory elements (CREs) have shown unprecedented power to endogenously characterize the non-coding genome. To CREs we developed HCR-FlowFISH (Hybridization Chain Reaction Fluorescent In-Situ Hybridization coupled with Flow Cytometry), which directly quantifies native transcripts within their endogenous loci following perturbations of regulatory elements, eliminating need restrictive phenotypic assays such as growth or transcript-tagging. accurately gene...
Abstract While genome-wide association studies (GWAS) and positive selection scans identify genomic loci driving human phenotypic diversity, functional validation is required to discover the variant(s) responsible. We dissected IVD gene locus—which encodes isovaleryl-CoA dehydrogenase enzyme—implicated by statistics, multiple GWAS, clinical genetics as important function fitness. combined luciferase assays, CRISPR/Cas9 genome-editing, massively parallel reporter assays (MPRA), a deletion...
Genome-wide association studies have identified >500 loci associated with type 2 diabetes (T2D). Most of these variants are in non-coding regions and may play regulatory roles, but they not been comprehensively tested for this role. Here, we assessed transcriptional activity 6,109 fine-mapped 204 T2D-associated from DIAGRAM, UKBB, BBJ cohorts using massively parallel reporter assays (MPRA) HepG2 hepatocytes, SGBS (pre)adipocytes, EndoC-βH3 beta-cells, three cell types implicated T2D...
Abstract Introduction Although genome-wide association studies (GWAS) multiple regions conferring genetic risk for juvenile idiopathic arthritis (JIA), we are still faced with the task of identifying single nucleotide polymorphisms (SNPs) on disease haplotypes that exert biological effects confer risk. Until identify risk-driving variants, genes influenced by these and therefore translating information to improved clinical care, will remain an insurmountable task. We used a function-based...
Abstract Both upregulation and downregulation by cis -regulatory elements help establish precise gene expression. Our understanding of how repress transcriptional activity is far more limited than activating elements. To address this gap, we characterized RE1, a group silencers bound REST, on genome-wide scale using an modified massively parallel reporter assay (MPRAduo). MPRAduo empirically defined minimal binding strength REST required for silencing (REST m-value), above which multiple...
Abstract A major goal in functional genomics and complex disease genetics is to identify cis- regulatory elements (CREs) single nucleotide polymorphisms (SNPs) altering CRE activity disease-relevant cell types environmental conditions. We tested >13,000 sequences containing each allele of 6,628 SNPs associated with altered vivo chromatin accessibility human islets and/or type 2 diabetes risk (T2D GWAS SNPs) for transcriptional ß under steady state endoplasmic reticulum (ER) stress...
ABSTRACT While genome-wide association studies (GWAS) and selection scans identify genomic loci driving human phenotypic diversity, functional validation is required to discover the variant(s) responsible. We dissected IVD locus, implicated by statistics, multiple GWAS, clinical genetics as important function fitness. combined luciferase assays, CRISPR/Cas9 genome-editing, massively parallel reporter assays (MPRA), bashing of regulatory loci. identified three variants, including an indel,...