- CRISPR and Genetic Engineering
- Hemoglobinopathies and Related Disorders
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Prenatal Screening and Diagnostics
- Epigenetics and DNA Methylation
- Insect symbiosis and bacterial influences
- Chromosomal and Genetic Variations
- Cytomegalovirus and herpesvirus research
- Genomics and Chromatin Dynamics
- Plant Virus Research Studies
- RNA Interference and Gene Delivery
- COVID-19 epidemiological studies
- RNA modifications and cancer
- Iron Metabolism and Disorders
- RNA regulation and disease
- COVID-19 Clinical Research Studies
- HIV/AIDS drug development and treatment
- Adenosine and Purinergic Signaling
- Cancer-related molecular mechanisms research
- Neurogenetic and Muscular Disorders Research
- Advanced biosensing and bioanalysis techniques
- Viral Infections and Outbreaks Research
- Biochemical and Molecular Research
- Erythrocyte Function and Pathophysiology
Broad Center
2021-2024
University of California, San Francisco
2020-2022
Neurological Surgery
2022
Boston Children's Hospital
2017-2021
Harvard Stem Cell Institute
2017-2021
Harvard University
2017-2021
Dana-Farber Cancer Institute
2017-2021
Broad Institute
2018-2021
CRISPR/Cas9 pooled screening permits parallel evaluation of comprehensive guide RNA libraries to systematically perturb protein coding sequences in situ and correlate with functional readouts. For the analysis visualization resulting datasets, we develop CRISPRO, a computational pipeline that maps scores associated RNAs genomes, transcripts, coordinates structures. No currently available tool has similar functionality. The ensuing genotype-phenotype linear three-dimensional raise hypotheses...
Human chromosomes are pervasively transcribed, but systematic understanding of coding and lncRNA genome function in cell differentiation is lacking. Using CRISPR interference (CRISPRi) human induced pluripotent stem cells, we performed dual genome-wide screens - assessing 18,905 protein-coding 10,678 loci identified 419 201 genes that regulate neural induction. Integrative analyses revealed distinct properties function, including a 10-fold enrichment for roles compared to proliferation....
Abstract The nuclear genome is spatially organized into a three-dimensional (3D) architecture by physical association of large chromosomal domains with subnuclear compartments including the lamina at radial periphery and speckles within nucleoplasm 1–5 . However, how spatial regulates human brain development has been overlooked owing to technical limitations. Here, we generate high-resolution maps genomic interactions in cells neurogenic lineage isolated from midgestational cortex,...
Author(s): Crawford, Emily D; Acosta, Irene; Ahyong, Vida; Anderson, Erika C; Arevalo, Shaun; Asarnow, Daniel; Axelrod, Shannon; Ayscue, Patrick; Azimi, Camillia S; Azumaya, Caleigh M; Bachl, Stefanie; Bachmutsky, Iris; Bhaduri, Aparna; Brown, Jeremy Bancroft; Batson, Joshua; Behnert, Astrid; Boileau, Ryan Bollam, Saumya R; Bonny, Alain Booth, David; Borja, Michael Jerico B; Buie, Bryan; Burnett, Cassandra E; Byrnes, Lauren Cabral, Katelyn A; Cabrera, Joana P; Caldera, Saharai; Canales,...
Abstract Genome editing technologies are rapidly evolving, and analysis of deep sequencing data from target or off-target regions is necessary for measuring efficiency evaluating safety. However, no software exists to analyze base editors, perform allele-specific quantification that incorporates biologically-informed scalable alignment approaches. Here, we present CRISPResso2 fill this gap illustrate its functionality by experimentally analyzing the properties six genome agents.
Abstract Tiling screens using CRISPR-Cas technologies provide a powerful approach to map regulatory elements phenotypes of interest, but computational methods that effectively model these experimental approaches for different CRISPR are not readily available. Here we present CRISPR-SURF, deconvolution framework identify functional regions in the genome from data generated by nuclease, interference (CRISPRi), or activation (CRISPRa) tiling screens. We validated CRISPR-SURF on previously...
Abstract Major effectors of adult-stage fetal globin silencing include the transcription factors (TFs) BCL11A and ZBTB7A/LRF NuRD chromatin complex, although each has potential on-target liabilities for rational β -hemoglobinopathy therapeutic inhibition. Here through CRISPR screening we discover ZNF410 to be a novel hemoglobin (HbF) repressing TF. does not bind directly γ -globin genes but rather its occupancy is solely concentrated at CHD4 , encoding nucleosome remodeler, itself required...
Abstract CRISPR/Cas9 pooled screening permits parallel evaluation of comprehensive guide RNA libraries to systematically perturb protein coding sequences in situ and correlate with functional readouts. For the analysis visualization resulting datasets we have developed CRISPRO, a computational pipeline that maps scores associated RNAs genome, transcript, coordinates structure. No available tool has similar functionality. The ensuing genotype-phenotype linear 3D raise hypotheses about...