A5056162089- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- RNA modifications and cancer
- Cancer-related gene regulation
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Cancer-related molecular mechanisms research
- Renal and related cancers
- Hearing, Cochlea, Tinnitus, Genetics
- Virus-based gene therapy research
- Genetic Syndromes and Imprinting
- T-cell and B-cell Immunology
- Chromosomal and Genetic Variations
- Genetics and Neurodevelopmental Disorders
- IL-33, ST2, and ILC Pathways
- Prenatal Screening and Diagnostics
- Asymmetric Hydrogenation and Catalysis
- Muscle Physiology and Disorders
- Single-cell and spatial transcriptomics
- Reproductive Biology and Fertility
- Ubiquitin and proteasome pathways
- Molecular Biology Techniques and Applications
- Immune Cell Function and Interaction
University of Washington
2013-2023
University of Toronto
2023
Ted Rogers Centre for Heart Research
2023
University of Washington Medical Center
2014-2022
Virginia Mason Medical Center
2022
Benaroya Research Institute
2022
Medical Genetics Center
2015-2018
University of Turku
2011-2017
Turku Centre for Biotechnology
2011-2017
California Institute for Regenerative Medicine
2017
The reference human genome sequence set the stage for studies of genetic variation and its association with disease, but epigenomic lack a similar reference. To address this need, NIH Roadmap Epigenomics Consortium generated largest collection so far epigenomes primary cells tissues. Here we describe integrative analysis 111 as part programme, profiled histone modification patterns, DNA accessibility, methylation RNA expression. We establish global maps regulatory elements, define modules...
While genetic mutation is a hallmark of cancer, many cancers also acquire epigenetic alterations during tumorigenesis including aberrant DNA hypermethylation tumor suppressors, as well changes in chromatin modifications caused by mutations the chromatin-modifying machinery. However, extent cancer cells has not been fully characterized. Here, we describe complete methylome maps at single nucleotide resolution low-passage breast cell line and primary human mammary epithelial cells. We find...
Significance We report on generation of nontransgenic, naïve human pluripotent cells that represent the developmentally earliest state described for established cells. Existing ES cell lines in later primed can be toggled reverse to by exposure histone deacetylase inhibitors prior culture. A new line was directly from an eight-cell embryo under culture conditions. describe humans and show have expanded endoderm developmental capacity.
Abstract Gene replacement therapies utilizing adeno-associated viral (AAV) vectors hold great promise for treating Duchenne muscular dystrophy (DMD). A related approach uses AAV to edit specific regions of the DMD gene using CRISPR/Cas9. Here we develop multiple approaches editing mutation in dystrophic mdx 4cv mice single and dual vector delivery a muscle-specific Cas9 cassette together with single-guide RNA cassettes and, one approach, dystrophin homology region fully correct mutation....
Reports on the retention of somatic cell memory in induced pluripotent stem cells (iPSCs) have complicated selection optimal type for generation iPSC biobanks. To address this issue we compared transcriptomic, epigenetic, and differentiation propensities genetically matched human iPSCs derived from fibroblasts blood, two tissues most practical relevance biobanking. Our results show that lines same donor are highly similar to each other. However, genetic variation imparts a donor-specific...
It has long been hypothesized that changes in gene regulation have played an important role human evolution, but regulatory DNA much more difficult to study compared with protein-coding regions. Recent large-scale studies created genome-scale catalogs of DNase I hypersensitive sites (DHSs), which demark potentially functional DNA. To better define subject human-specific adaptive we performed comprehensive evolutionary and population genetics analyses on over 18 million DHSs discovered 130...
Activating germline mutations in STAT3 were recently identified as a cause of neonatal diabetes mellitus associated with beta-cell autoimmunity. We have investigated the effect an activating mutation, STAT3K392R, on pancreatic development using induced pluripotent stem cells (iPSCs) derived from patient and hypoplasia. Early endoderm differentiated similarly STAT3K392R healthy-control cells, but later stages, NEUROG3 expression was upregulated prematurely together insulin (INS) glucagon...
Base editors are capable of installing precise genomic alterations without creating double-strand DNA breaks. In this study, we targeted critical motifs regulating γ-globin reactivation with base delivered via HDAd5/35++ vectors. Through optimized design, successfully produced a panel cytidine and adenine editor (ABE) vectors targeting the erythroid BCL11A enhancer or recreating naturally occurring hereditary persistence fetal hemoglobin (HPFH) mutations in HBG1/2 promoter. All 5 tested...
Highlights•Broad-scale CpG methylation is largely stable during oocyte maturation•Non-CpG accumulates as oocytes mature•Non-CpG changes are genome wideSummaryThe establishment of DNA patterns in a highly dynamic process marking gene-regulatory events fertilization, embryonic development, and adulthood. However, after epigenetic reprogramming primordial germ cells, how when re-established developing human remains to be characterized. Here, using single-cell whole-genome bisulfite sequencing,...