A5103228390- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- Hemoglobinopathies and Related Disorders
- DNA Repair Mechanisms
- Congenital heart defects research
- Epigenetics and DNA Methylation
- Mosquito-borne diseases and control
- Telomeres, Telomerase, and Senescence
- Mycotoxins in Agriculture and Food
- Iron Metabolism and Disorders
- Single-cell and spatial transcriptomics
- Microtubule and mitosis dynamics
- Evolution and Genetic Dynamics
- Cancer-related gene regulation
- Carcinogens and Genotoxicity Assessment
- RNA Research and Splicing
- Insect and Pesticide Research
- Polyomavirus and related diseases
- Cell Image Analysis Techniques
- Advanced Fluorescence Microscopy Techniques
- Genetics, Aging, and Longevity in Model Organisms
- Fluid Dynamics and Heat Transfer
- Listeria monocytogenes in Food Safety
- Plant Genetic and Mutation Studies
- Systemic Lupus Erythematosus Research
Genomics (United Kingdom)
2025
UCSF Benioff Children's Hospital
2016-2022
University of California, San Francisco
2016-2022
Institute of Electrical and Electronics Engineers
2020
Lawrence Berkeley National Laboratory
2004-2011
The University of Tokyo
1998-2002
GeneCare Research Institute (Japan)
1999-2001
Tokyo University of Science
1999
Hematopoietic stem cells from patients with sickle cell disease can be edited by CRISPR/Cas9 and maintain the edits in vivo.
Telomeres are protective structures at chromosome ends and crucial for genomic stability. Mammalian TRF1 TRF2 bind the double-stranded telomeric repeat sequence in turn bound by TIN2, TANK1, TANK2, hRAP1. is a negative regulator of telomere length telomerase-positive cells, whereas important capping. TIN2 was identified as TRF1-interacting protein that mediates function. We show here also interacts with vitro yeast mammalian cells. mutants defective binding or induce DNA damage response...
Cytosine methylation in the genome of Drosophila melanogaster has been elusive and controversial: Its location function have not established. We used a novel highly sensitive genomewide cytosine assay to detect map stage 5 embryos. The we observe with this method is localized strand asymmetrical, limited regions covering ∼1% genome, dynamic early embryogenesis, concentrated specific 5-base sequence motifs that are CA- CT-rich but depleted guanine. Gene body associated lower expression, many...
Background Werner syndrome (WS) is an autosomal recessive disorder with many features of premature ageing. Cells derived from WS patients show genomic instability, aberrations in the S‐phase and sensitivity to genotoxic agents. The gene responsible for ( WRN ) encodes a DNA helicase belonging RecQ family. Although biochemical studies showed that product (WRNp) interacts proteins participate metabolism, its precise biological function remains unclear . Results Using immunocytochemistry, we...
Significance The epithelial to mesenchymal transition (EMT) is a driving force behind normal morphogenesis and tumor metastasis. We have found evidence that the EMT in both malignant nonmalignant mammary cells requires enzyme activation-induced cytidine deaminase (AID). AID induced cell lines by inflammatory stimuli also induce EMT. Deficiency of these blocks morphological transcriptional changes typical increases promoter cytosine methylation genes encoding key factors. These findings...
A point mutation in sickle cell disease (SCD) alters one amino acid the β-globin subunit of hemoglobin, with resultant anemia and multiorgan damage that typically shortens lifespan by decades. Because SCD is caused a single mutation, hematopoietic stem cells (HSCs) can be harvested, manipulated, returned to an individual, it attractive target for gene correction.An optimized Cas9 ribonucleoprotein (RNP) ssDNA oligonucleotide donor together generated correction at least allele more than 30%...
Abstract CRISPR genome editing approaches theoretically enable researchers to define the function of each human gene in specific cell types, but challenges remain efficiently perform genetic perturbations relevant models. In this work, we develop a library cloning protocol that increases sgRNA uniformity and greatly reduces bias existing genome-wide libraries. We demonstrate our libraries can achieve equivalent or better statistical power compared previously reported screens using an order...
Background Bloom's syndrome (BS) is an autosomal recessive disorder causing short stature, immunodeficiency, and increased risk of cancer. Increased rates sister chromatid exchange chromosomal aberration have been observed in cells having defects the BLM gene. Among five kinds human RecQ helicases cloned, mutations WRN RecQL4 known as causes premature ageing. Little is, however, about function helicase Results We show that , but not can prevent ageing homologous recombination at rDNA loci...
Telomeres are maintained by three DNA-binding proteins (telomeric repeat binding factor 1 [TRF1], TRF2, and protector of telomeres [POT1]) several associated factors. One factor, TRF1-interacting protein 2 (TIN2), binds TRF1 TRF2 directly POT1 indirectly. Along with two other proteins, TPP1 hRap1, these form a soluble complex that may be the core telomere maintenance complex. It is not clear whether subcomplexes also exist in vivo. We provide evidence for TIN2 distinct functions human cells....
Werner's syndrome (WS) is a rare autosomal recessive disorder characterized by premature aging. The gene responsible for WS encodes protein homologous to Escherichia coli RecQ. Here we describe novel Wernerhelicase interacting (WHIP), which interacts with the N-terminal portion of Werner (WRN), containing exonuclease domain. WHIP, shows homology replication factor C family proteins, conserved from E. human. Ectopically expressed WHIP and WRN co-localized in granular structures nucleus....
Abstract High-throughput phenotypic screening has historically relied on manually selected features, limiting our ability to capture complex cellular processes, particularly neuronal activity dynamics. While recent advances in self-supervised learning have revolutionized the study morphology and transcriptomics, dynamic processes remained challenging phenotypically profile. To address this limitation, we developed Plexus, a novel model specifically designed quantify network-level Unlike...
Sickle Cell Disease and ß-thalassemia, which are caused by defective or deficient adult ß-globin (HBB) respectively, the most common serious genetic blood diseases in world. Persistent expression of fetal ß-like globin, also known as 𝛾-globin, can ameliorate both disorders serving place a part hemoglobin tetramer (HbF). Here we use CRISPR-Cas9 gene editing to explore potential 𝛾-globin silencer region upstream δ-globin identified comparison naturally-occurring deletion mutations associated...
To examine the contributions of sequence and function conservation in evolution enhancers, we systematically identified enhancers whose sequences are not conserved among distant groups vertebrate species, but have homologous likely to be derived from a common ancestral sequence. Our approach combined comparative genomics epigenomics identify potential enhancer genomes three distantly related species. We searched for that were within closely species between more associated with an epigenetic...
Human lymphoblastoid cell lines (LCLs), generated through Epstein–Barr Virus (EBV) transformation of B-lymphocytes (B-cells), are a commonly used model system for identifying genetic influences on human diseases and drug responses. We have previously LCLs to examine the cellular effects variants that modulate efficacy statins, most prescribed class cholesterol-lowering drugs prevention treatment cardiovascular disease. However, statin-induced gene expression differences observed in may be...
ABSTRACT Sickle Cell Disease (SCD), one of the world’s most common genetic disorders, causes anemia and progressive multiorgan damage that typically shortens lifespan by decades; currently there is no broadly applicable curative therapy. Here we show Cas9 RNP-mediated gene editing with an ssDNA oligonucleotide donor yields markerless correction sickle mutation in more than 30% long-term engrafting human hematopoietic stem cells (HSCs), using a selection-free protocol directly to clinical...
Piwi-interacting RNAs (piRNAs) are a class of small RNAs; distinct types piRNAs expressed in the mammalian testis at different stages development. The function adult is not well established. We conducted detailed characterization aligning or near 3' UTRs protein-coding genes deep dataset from mouse testis.We identified 2710 piRNA clusters associated with UTRs, including 1600 that overlapped previously piRNAs. 35% extend beyond annotated transcript; we find these correspond to, and likely...
ABSTRACT The development of CRISPR genetic screening tools has improved functional genomics, as these enable precise genomic editing, provide broad access to regions beyond protein-coding genes, and have fewer off-target effects than other genomics modalities, allowing for novel applications with smaller library sizes compared prior technologies. Pooled screens require high cellular coverage per perturbation accurately quantify phenotypes average out phenotype-independent variability across...
Abstract Sickle Cell Disease and ß-thalassemia, which are caused by defective or deficient adult ß-globin (HBB) respectively, the most common serious genetic blood diseases in world. Expression of fetal ß-like globin, also known as γ-globin, can ameliorate both disorders serving place ß-globin. Here we use CRISPR-Cas9 gene editing to explore a putative γ-globin silencer region identified comparison naturally-occurring deletion mutations associated with up-regulated γ-globin. We find that 1.7...