A5077537092- Cancer-related molecular mechanisms research
- Plant and Fungal Interactions Research
- RNA Research and Splicing
- RNA modifications and cancer
- Prenatal Screening and Diagnostics
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- interferon and immune responses
- Genomics and Chromatin Dynamics
- Reproductive Biology and Fertility
- Genetics and Neurodevelopmental Disorders
- NF-κB Signaling Pathways
- RNA regulation and disease
- Birth, Development, and Health
- Pluripotent Stem Cells Research
- Reproductive Health and Technologies
- Intestinal and Peritoneal Adhesions
- Congenital Anomalies and Fetal Surgery
- Vitamin D Research Studies
- Reproductive System and Pregnancy
- Pancreatic and Hepatic Oncology Research
- Toxoplasma gondii Research Studies
- Genetic Associations and Epidemiology
- Immune Response and Inflammation
- Cancer Cells and Metastasis
- Vitamin C and Antioxidants Research
Whitehead Institute for Biomedical Research
2021-2023
Harvard University
2013-2020
Harvard Stem Cell Institute
2018-2020
Center for Systems Biology
2015-2019
Broad Institute
2013-2018
Stanford University
2012
University of Wisconsin–Madison
2009
Many studies are uncovering functional roles for long noncoding RNAs (lncRNAs), yet few have been tested in vivo relevance through genetic ablation animal models. To investigate the of lncRNAs various physiological conditions, we developed a collection 18 lncRNA knockout strains which locus is maintained transcriptionally active. Initial characterization revealed peri- and postnatal lethal phenotypes three mutant (Fendrr, Peril, Mdgt), latter two exhibiting incomplete penetrance growth...
The "inactive" X chromosome (Xi) has been assumed to have little impact, in trans, on the "active" (Xa). To test this, we quantified Xi and Xa gene expression individuals with one zero three Xis. Our linear modeling revealed modular transcriptomes significant Xi-driven changes for 38% (162/423) of expressed genes. By integrating allele-specific analyses, found that modulation transcript levels by contributes many these (≥121 genes). incorporating metrics evolutionary constraint, identified...
Long noncoding RNAs (lncRNAs) have been implicated in numerous cellular processes including brain development. However, the vivo expression dynamics and molecular pathways regulated by these loci are not well understood. Here, we leveraged a cohort of 13 lncRNA-null mutant mouse models to investigate spatiotemporal lncRNAs developing adult transcriptome alterations resulting from loss lncRNA loci. We show that several differentially expressed both time space, with some presenting highly...
The Linc-p21 locus, encoding a long non-coding RNA, plays an important role in p53 signaling, cell-cycle regulation, and tumor suppression. However, despite extensive study, confusion exists regarding its mechanism of action: is activity driven by the transcript acting trans, cis, or underlying functional enhancer? Here, using knockout mouse model massively parallel enhancer assay, we delineate elements at this locus. We observe that, even tissues with no detectable transcript, deletion...
An inducible gene expression program is a hallmark of the host inflammatory response. Recently, long intergenic non-coding RNAs (lincRNAs) have been shown to regulate magnitude, duration, and resolution these responses. Among lincRNA-Cox2, dynamically regulated that broadly controls immune expression. To evaluate in vivo functions this lincRNA, we characterized multiple models lincRNA-Cox2-deficient mice. LincRNA-Cox2-deficient macrophages murine tissues had altered genes. Transcriptomic...
Abstract Background Several long noncoding RNAs (lncRNAs) have been shown to function as components of molecular machines that play fundamental roles in biology. While the number annotated lncRNAs mammalian genomes has greatly expanded, studying lncRNA a challenge due their diverse biological and because loci can contain multiple modes may exert function. Results We previously generated characterized cohort 20 knockout mice. Here, we extend this initial study provide more detailed analysis...
RNA has been classically known to play central roles in biology, including maintaining telomeres, protein synthesis, and sex chromosome compensation. While thousands of long noncoding RNAs (lncRNAs) have identified, attributing RNA-based lncRNA loci requires assessing whether phenotype(s) could be due DNA regulatory elements, transcription, or the lncRNA. Here, we use conserved X locus Firre, as a model discriminate between DNA- RNA-mediated effects vivo. We demonstrate that (i) Firre mutant...
The majority of embryos created through in vitro fertilization (IVF) do not implant. It seems plausible that rates implantation would improve if we had a better understanding molecular factors affecting embryo competence. Currently, the process selecting an for uterine transfer uses ad hoc combination morphological criteria, kinetics development, and genetic testing aneuploidy. However, no single criterion can ensure selection viable embryo. In contrast, RNA-sequencing (RNA-seq) could yield...
Article1 April 2020Open Access Transparent process Resolving mechanisms of immune-mediated disease in primary CD4 T cells Christophe Bourges Cambridge Institute Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Campus, University Cambridge, UK Department Medicine, School Clinical Addenbrooke's Hospital, Search for more papers by this author Abigail F Groff Stem Cell Regenerative Biology, Harvard University, MA, USA Oliver S Burren Chiara Gerhardinger Kaia...
Recently, it has become clear that some promoters function as long-range regulators of gene expression. However, direct and quantitative assessment enhancer activity at long intergenic noncoding RNA (lincRNA) or mRNA bodies not been performed. To unbiasedly assess the capacity across lincRNA loci, we performed a massively parallel reporter assay (MPRA) on six loci their closest protein-coding neighbors.For both classes, find significantly more MPRA in promoter regions than bodies. three...
This manuscript follows a single patient with pancreatic adenocarcinoma for five year period, detailing the clinical record, pathology, dynamic evolution of molecular and cellular alterations as well responses to treatments chemotherapies, targeted therapies immunotherapies. DNA RNA samples from biopsies blood identified set changes in allelic imbalances copy number variations response therapies. Organoid cultures established over time were employed extensive drug testing determine if this...
ABSTRACT RNA has been classically known to play central roles in biology, including maintaining telomeres 1 , protein synthesis 2 and sex chromosome compensation certain species 3,4 . At the center of these important biological systems are noncoding RNAs. While thousands long RNAs (lncRNAs) have identified mammalian genomes 5–8 attributing RNA-based lncRNA loci requires an assessment whether observed effect could be due DNA regulatory elements, act transcription, or transcript. Here, we use...
ABSTRACT Background Several long noncoding RNAs (lncRNAs) have been shown to function as central components of molecular machines that play fundamental roles in biology. While the number annotated lncRNAs mammalian genomes has greatly expanded, their functions remain largely uncharacterized. This is compounded by fact identifying lncRNA loci robust and reproducible phenotypes when mutated a challenge. Results We previously generated cohort 20 knockout mice. Here, we extend our initial study...
Summary Researchers have presumed that the “inactive” X chromosome (Xi) has little impact, in trans, on “active” (Xa). To test this, we quantified Xi and Xa gene expression individuals with one zero to three Xi’s. Our linear modeling revealed modular transcriptomes significant Xi-driven changes for 38% (162/423) of expressed X-chromosome genes. By integrating allele-specific analyses, found modulation transcript levels by contributes many these (≥ 121 genes). incorporating metrics...