A5077508197- Genomics and Chromatin Dynamics
- Immune Cell Function and Interaction
- Epigenetics and DNA Methylation
- Immune cells in cancer
- CRISPR and Genetic Engineering
- Autophagy in Disease and Therapy
- Plant Virus Research Studies
- Cancer-related molecular mechanisms research
- Hippo pathway signaling and YAP/TAZ
- CAR-T cell therapy research
- Geological Modeling and Analysis
- Virus-based gene therapy research
- interferon and immune responses
- Genetics, Aging, and Longevity in Model Organisms
- Barrier Structure and Function Studies
- RNA Research and Splicing
- IL-33, ST2, and ILC Pathways
- Insect symbiosis and bacterial influences
- RNA modifications and cancer
- Psychology Research and Bibliometrics
- Polyamine Metabolism and Applications
- Plant and Fungal Interactions Research
- Plant Disease Management Techniques
- Plant Molecular Biology Research
- Quinazolinone synthesis and applications
Institute for Research in Biomedicine
2022
Massachusetts General Hospital
2016-2021
Harvard University
2016-2021
Broad Institute
2015-2020
Center for Systems Biology
2019
University of Cambridge
2009-2015
The Gurdon Institute
2009-2014
University of Magdalena
2012
Wellcome Trust
2010
Baylor College of Medicine
2003-2006
From Genome to Regulatory Networks For biologists, having a genome in hand is only the beginning—much more investigation still needed characterize how used help produce functional organism (see Perspective by Blaxter ). In this vein, Gerstein et al. (p. 1775 ) summarize for Caenorhabditis elegans genome, and The modENCODE Consortium 1787 Drosophila melanogaster full transcriptome analyses over developmental stages, genome-wide identification of transcription factor binding sites,...
A large collection of new modENCODE and ENCODE genome-wide chromatin data sets from cell lines developmental stages in worm, fly human are analysed; this reveals many conserved features organization among the three organisms, as well notable differences composition locations repressive chromatin. This study describes numerous Homo sapiens, Drosophila melanogaster Caenorhabditis elegans generated by consortia. The results point to while identifying Genome function is dynamically regulated...
Chromatin immunoprecipitation identifies specific interactions between genomic DNA and proteins, advancing our understanding of gene-level chromosome-level regulation. Based on chromatin experiments using validated antibodies, we define the genome-wide distributions 19 histone modifications, one variant, eight chromatin-associated proteins in Caenorhabditis elegans embryos L3 larvae. Cluster analysis identified five groups marks with shared features: Two correlate gene repression, two...
Genomic sequences obtained through high-throughput sequencing are not uniformly distributed across the genome. For example, data of total genomic DNA show significant, yet unexpected enrichments on promoters and exons. This systematic bias is a particular problem for techniques such as chromatin immunoprecipitation, where signal target factor plotted features. We have focused from Illumina's Genome Analyser platform, at least three factors contribute to sequence bias: GC content, mappability...
The development of human cancers is frequently associated with a failure epithelial cells to form tight junctions and establish proper apicobasal polarity. Interestingly, the oncogenic potential adenovirus E4-ORF1 protein correlates its binding cellular PDZ proteins MUPP1, MAGI-1, ZO-2 SAP97, first three which assemble complexes at junctions. Given that sequesters these in cytoplasm fibroblasts, we postulated would inhibit junction formation cells. Providing further support for this idea,...
Salt-inducible kinases (SIKs) are promising therapeutic targets for modulating cytokine responses during innate immune activation. The study of SIK inhibition in animal models disease has been limited by the lack selective small-molecule probes suitable function vivo. We used pan-SIK inhibitor HG-9-91-01 as a starting point to develop improved analogs, yielding novel probe 5 (YKL-05-099) that displays increased selectivity SIKs versus other and enhanced pharmacokinetic properties....
The DREAM (DP, Retinoblastoma [Rb]-like, E2F, and MuvB) complex controls cellular quiescence by repressing cell cycle genes, but its mechanism of action is poorly understood. Here we show that Caenorhabditis elegans targets have an unusual pattern high gene body HTZ-1/H2A.Z. In mutants lin-35 , the sole p130/Rb-like in C. reduced HTZ-1/H2A.Z increased expression. Consistent with a repressive role for H2A.Z, many are up-regulated htz-1 /H2A.Z mutants. Our results indicate facilitates...
Significance Given the importance of autophagy in a number human diseases, we have identified small-molecule modulators that affect disease-associated phenotypes relevant cell types. BRD5631 and related compounds can serve as tools for studying how regulates immune pathways, evaluating therapeutic potential modulating variety disease contexts. Deeper investigation into their mechanisms action may reveal proteins pathways could targets future discovery.
Abstract The immortalized human ReNcell VM cell line represents a reproducible and easy-to-propagate culture system for studying the differentiation of neural progenitors. To better characterize starting its subsequent differentiation, we assessed protein phospho-protein levels morphology over 15-day period during which progenitors differentiated into neurons, astrocytes oligodendrocytes. Five resulting datasets measured or states phosphorylation based on tandem-mass-tag (TMT) mass...
Bacillus Calmette-Guérin (BCG) vaccine is one of the most widely used vaccines worldwide. In addition to protection against tuberculosis, BCG confers a degree non-specific other infections by enhancing secondary immune responses heterologous pathogens, termed "trained immunity." To better understand BCG-induced reprogramming, we perform single-cell transcriptomic measurements before and after vaccination using stimulation with bacterial lipopolysaccharide (LPS). We find that reduces systemic...
Lysosomes perform a critical cellular function as site of degradation for diverse cargoes including proteins, organelles, and pathogens delivered through distinct pathways, defects in lysosomal have been implicated number diseases. Recent studies elucidated roles the lysosome regulation protein synthesis, metabolism, membrane integrity, other processes involved homeostasis. Complex small-molecule natural products greatly contributed to investigation physiology. Here we report discovery...
Abstract Th17 cells play a role as an inflammation mediator in variety of autoimmune disorders, including inflammatory bowel disease, and thus are widely considered to be pathogenic. However, present the normal intestine show homeostatic phenotype; that is, they participate maintenance intestinal homeostasis rather than inducing inflammation. We observed enlarged population small C57BL/6.IgA−/− mice compared with wild-type mice, which was further amplified cholera toxin (CT) immunization...
Abstract Genome-wide association studies have identified common genetic variants impacting human diseases; however, there are indications that the functional consequences of polymorphisms can be distinct depending on cell type–specific contexts, which produce divergent phenotypic outcomes. Thus, impact variation and underlying mechanisms disease risk modified by effects genotype pathological phenotypes. In this study, we extend these concepts to interrogate interdependence type–...