8 results match your criteria: "USA. Electronic address: lander@broadinstitute.org.[Affiliation]"
2018 William Allan Award: Discovering the Genes for Common Disease: From Families to Populations.
Am J Hum Genet
March 2019
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address:
Optimal-Transport Analysis of Single-Cell Gene Expression Identifies Developmental Trajectories in Reprogramming.
Cell
February 2019
Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Systems Biology Harvard Medical School, Boston, MA 02125, USA. Electronic address:
Understanding the molecular programs that guide differentiation during development is a major challenge. Here, we introduce Waddington-OT, an approach for studying developmental time courses to infer ancestor-descendant fates and model the regulatory programs that underlie them. We apply the method to reconstruct the landscape of reprogramming from 315,000 single-cell RNA sequencing (scRNA-seq) profiles, collected at half-day intervals across 18 days.
View Article and Find Full Text PDFType 2 Diabetes Variants Disrupt Function of SLC16A11 through Two Distinct Mechanisms.
Cell
June 2017
Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Biology, MIT, Cambridge, MA 02139, USA; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address:
Type 2 diabetes (T2D) affects Latinos at twice the rate seen in populations of European descent. We recently identified a risk haplotype spanning SLC16A11 that explains ∼20% of the increased T2D prevalence in Mexico. Here, through genetic fine-mapping, we define a set of tightly linked variants likely to contain the causal allele(s).
View Article and Find Full Text PDFGene Essentiality Profiling Reveals Gene Networks and Synthetic Lethal Interactions with Oncogenic Ras.
Cell
February 2017
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; David H. Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address:
The genetic dependencies of human cancers widely vary. Here, we catalog this heterogeneity and use it to identify functional gene interactions and genotype-dependent liabilities in cancer. By using genome-wide CRISPR-based screens, we generate a gene essentiality dataset across 14 human acute myeloid leukemia (AML) cell lines.
View Article and Find Full Text PDFThe Heroes of CRISPR.
Cell
January 2016
Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address:
Three years ago, scientists reported that CRISPR technology can enable precise and efficient genome editing in living eukaryotic cells. Since then, the method has taken the scientific community by storm, with thousands of labs using it for applications from biomedicine to agriculture. Yet, the preceding 20-year journey--the discovery of a strange microbial repeat sequence; its recognition as an adaptive immune system; its biological characterization; and its repurposing for genome engineering--remains little known.
View Article and Find Full Text PDFA 3D map of the human genome at kilobase resolution reveals principles of chromatin looping.
Cell
December 2014
The Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Computer Science, Department of Computational and Applied Mathematics, Rice University, Houston, TX 77005, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Center for Theoretical Biological Physics, Rice University, Houston, TX 77030, USA. Electronic address:
We use in situ Hi-C to probe the 3D architecture of genomes, constructing haploid and diploid maps of nine cell types. The densest, in human lymphoblastoid cells, contains 4.9 billion contacts, achieving 1 kb resolution.
View Article and Find Full Text PDFRNA-RNA interactions enable specific targeting of noncoding RNAs to nascent Pre-mRNAs and chromatin sites.
Cell
September 2014
Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Biology, MIT, Cambridge, MA 02139, USA; Department of Systems Biology, Harvard Medical School, Boston, MA 02114, USA. Electronic address:
Article Synopsis
- Intermolecular RNA-RNA interactions play a crucial role in the functions of noncoding RNAs (ncRNAs), prompting researchers to create a new method (RAP-RNA) to map these interactions systematically.* -
- The study focuses on U1 small nuclear RNA and Malat1, showing U1 directly binds to specific RNA sequences, while Malat1 engages indirectly via proteins.* -
- Both ncRNAs localize to active gene sites, indicating their role in RNA processing, and the RAP-RNA method is versatile enough to explore various ncRNAs, even those present in lower amounts.*
Perturbation of m6A writers reveals two distinct classes of mRNA methylation at internal and 5' sites.
Cell Rep
July 2014
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, MD 20815, USA. Electronic address:
N6-methyladenosine (m6A) is a common modification of mRNA with potential roles in fine-tuning the RNA life cycle. Here, we identify a dense network of proteins interacting with METTL3, a component of the methyltransferase complex, and show that three of them (WTAP, METTL14, and KIAA1429) are required for methylation. Monitoring m6A levels upon WTAP depletion allowed the definition of accurate and near single-nucleotide resolution methylation maps and their classification into WTAP-dependent and -independent sites.
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