- Scientific Computing and Data Management
- Enzyme Structure and Function
- RNA Research and Splicing
- Distributed and Parallel Computing Systems
- Genomics and Rare Diseases
- Research Data Management Practices
- RNA modifications and cancer
- Genetics, Bioinformatics, and Biomedical Research
- Glycosylation and Glycoproteins Research
- MicroRNA in disease regulation
- RNA and protein synthesis mechanisms
- Genomics and Phylogenetic Studies
- Carbohydrate Chemistry and Synthesis
- Protein Structure and Dynamics
- Immunodeficiency and Autoimmune Disorders
- COVID-19 Clinical Research Studies
- SARS-CoV-2 and COVID-19 Research
- Lipid Membrane Structure and Behavior
- Long-Term Effects of COVID-19
- Bacteriophages and microbial interactions
- Developmental Biology and Gene Regulation
- Biochemical and Molecular Research
- Machine Learning in Healthcare
- BRCA gene mutations in cancer
- RNA Interference and Gene Delivery
Harvard University
2016-2025
Boston Children's Hospital
2016-2025
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
2021-2024
Boston University
2012-2022
Institut Pasteur
2022
Software (Spain)
2022
English Heritage
2022
Boston VA Research Institute
2019-2021
Boston Children's Museum
2018-2020
Harvard Stem Cell Institute
2008
By centralizing many of the tasks associated with upkeep scientific software, SBGrid allows researchers to spend more their time on research.
Substitution for aspartic acid (D) by glycine (G) at position 614 in the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appears to facilitate rapid viral spread. The G614 strain and its recent variants are now dominant circulating forms. Here, we report cryo-electron microscopy structures a full-length S trimer, which adopts three distinct prefusion conformations that differ primarily one receptor-binding domain. A loop disordered D614 trimer wedges between...
Integral beta-barrel proteins are found in the outer membranes of mitochondria, chloroplasts, and Gram-negative bacteria. The machine that assembles these contains an integral membrane protein, called YaeT Escherichia coli, which has one or more polypeptide transport-associated (POTRA) domains. crystal structure a periplasmic fragment reveals POTRA domain fold suggests model for how domains can bind different peptide sequences, as required handles numerous protein precursors. Analysis...
The developmentally regulated RNA-binding protein Lin28 blocks processing of let-7 family microRNAs (miRNAs) in embryonic cells. molecular basis for this selective miRNA block is unknown. Here we find that selectively binds the terminal loop region precursors vitro and mediates inhibition vivo. Additionally, identify domains required inhibition. These findings establish a regulatory role maturation provide insight into mechanism by which negatively regulates processing.
We leveraged the largely untapped resource of electronic health record data to address critical clinical and epidemiological questions about Coronavirus Disease 2019 (COVID-19). To do this, we formed an international consortium (4CE) 96 hospitals across five countries (www.covidclinical.net). Contributors utilized Informatics for Integrating Biology Bedside (i2b2) or Observational Medical Outcomes Partnership (OMOP) platforms map a common model. The group focused on temporal changes in key...
Multisystem inflammatory syndrome in children (MIS-C) is a pediatric complication of severe acute respiratory coronavirus 2 infection that characterized by multiorgan inflammation and frequently cardiovascular dysfunction. It occurs predominantly otherwise healthy children. We previously reported haploinsufficiency suppressor cytokine signaling 1 (SOCS1), negative regulator type I II interferons, as genetic risk factor for MIS-C.
Funders, publishers, and research institutions must act to ensure that computer code is made widely available.
Notch receptors control differentiation and contribute to pathologic states such as cancer by interacting directly with a transcription factor called CSL (for CBF-1/Suppressor of Hairless/Lag-1) induce expression target genes. A number Notch-regulated targets, including genes the hairy/enhancer-of-split family in organisms ranging from Drosophila humans, are characterized paired CSL-binding sites characteristic head-to-head arrangement. Using combination structural molecular approaches, we...
Peptidoglycan is an essential polymer that forms a protective shell around bacterial cell membranes. biosynthesis the target of many clinically used antibiotics, including β-lactams, imipenems, cephalosporins, and glycopeptides. Resistance to these other antibiotics has prompted interest in atomic-level understanding enzymes make peptidoglycan. Representative structures have been reported for most pathway. Until now, however, there no any peptidoglycan glycosyltransferases (also known as...
Abstract Access to experimental X-ray diffraction image data is fundamental for validation and reproduction of macromolecular models indispensable development structural biology processing methods. Here, we established a publication dissemination system, Structural Biology Data Grid (SBDG; data.sbgrid.org), preserve primary sets that support scientific publications. are accessible researchers through community driven grid, which facilitates global access. Our analysis pilot collection...
LIN28 is an RNA-binding protein that regulates the maturation of let-7 family microRNAs by bipartite interactions with precursors through its two distinct cold shock and zinc-knuckle domains. Through inhibition biogenesis, functions as a pluripotency factor, well driver tumorigenesis. Here, we report fluorescence polarization assay to identify small-molecule inhibitors for both domains involved in interactions. Of 101,017 compounds screened, six inhibit LIN28:let-7 binding impair...
Recent small RNA sequencing data has uncovered 3′ end modification of mature microRNAs (miRNAs). This non-templated nucleotide addition can impact miRNA gene regulatory networks through the control stability or by interfering with repression target mRNAs. The modifying enzymes responsible for this regulation remain largely uncharacterized. Here we describe ability two related terminal uridyl transferases (TUTases), Zcchc6 (TUT7) and Zcchc11 (TUT4), to mono-uridylate a specific subset miRNAs...
Coincident with the tsunami of COVID-19-related publications, there has been a surge studies using real-world data, including those obtained from electronic health record (EHR). Unfortunately, several these high-profile publications were retracted because concerns regarding soundness and quality EHR data they purported to analyze. These retractions highlight that although small community informatics experts can readily identify strengths flaws in EHR-derived studies, many medical editorial...
Abstract Ribosome profiling (Ribo-seq) is a powerful technology for globally monitoring RNA translation; ranging from codon occupancy profiling, identification of actively translated open reading frames (ORFs), to the quantification translational efficiency under various physiological or experimental conditions. However, analyzing and decoding translation information Ribo-seq data not trivial. Although there are many existing tools analyze data, most these designed specific limited...
Abstract Objectives Cerebral palsy (CP) is the most common childhood motor disability, yet its link to single‐gene disorders under‐characterized. To explore genetic landscape of CP, we conducted whole exome sequencing (WES) in a cohort patients with CP. Methods We performed comprehensive phenotyping and WES on prospective individuals cryptogenic CP (who meet criteria for CP; have no risk factors), non‐cryptogenic at least one factor), masqueraders could be diagnosed but...