A5026865202- Liver Disease Diagnosis and Treatment
- Alcohol Consumption and Health Effects
- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- Mitochondrial Function and Pathology
- Metabolism and Genetic Disorders
- Bacteriophages and microbial interactions
- Adipose Tissue and Metabolism
- Liver Disease and Transplantation
- Diet, Metabolism, and Disease
- RNA Interference and Gene Delivery
- Substance Abuse Treatment and Outcomes
- Cancer, Hypoxia, and Metabolism
- Metabolism, Diabetes, and Cancer
- Reproductive tract infections research
- RNA and protein synthesis mechanisms
- ATP Synthase and ATPases Research
- Endoplasmic Reticulum Stress and Disease
- Hepatitis B Virus Studies
- Herpesvirus Infections and Treatments
- HIV/AIDS drug development and treatment
- Peroxisome Proliferator-Activated Receptors
- Lipid metabolism and disorders
- Pancreatic function and diabetes
- Hepatitis C virus research
Massachusetts General Hospital
2009-2024
Harvard University
2010-2024
Broad Institute
2020-2023
University of New Haven
2019-2023
Center for Systems Biology
2020
Howard Hughes Medical Institute
2016-2020
Brigham and Women's Hospital
2011
Boston University
2010
University of Oxford
2004-2009
Decatur Memorial Hospital
2009
Abstract The mammalian mitochondrial proteome is under dual genomic control, with 99% of proteins encoded by the nuclear genome and 13 originating from DNA (mtDNA). We previously developed MitoCarta, a catalogue over 1000 genes encoding proteome. This was compiled using Bayesian integration multiple sequence features experimental datasets, notably protein mass spectrometry mitochondria isolated fourteen murine tissues. Here, we introduce MitoCarta3.0. Beginning MitoCarta2.0 inventory,...
Practical components for three-dimensional molecular nanofabrication must be simple to produce, stereopure, rigid, and adaptable. We report a family of DNA tetrahedra, less than 10 nanometers on side, that can self-assemble in seconds with near-quantitative yield one diastereomer. They connected by programmable linkers. Their triangulated architecture confers structural stability; compressing tetrahedron an atomic force microscope, we have measured the axial compressibility observed buckling...
A tetrahedral nanostructure whose edges are DNA double helices self-assembles spontaneously when four appropriately designed oligonucleotides annealed together in solution; the ease of synthesis, rigidity, and adaptability this construct make it a promising candidate as cage for other large molecules building block more complicated nanostructures.
A decline in electron transport chain (ETC) activity is associated with many human diseases. Although diminished mitochondrial adenosine triphosphate production recognized as a source of pathology, the contribution reduction ratio amount oxidized nicotinamide adenine dinucleotide (NAD(+)) to that its reduced form (NADH) less clear. We used water-forming NADH oxidase from Lactobacillus brevis (LbNOX) genetic tool for inducing compartment-specific increase NAD(+)/NADH cells. LbNOX demonstrate...
Alcohol-associated liver disease (ALD) is one of the most devastating complications alcohol use disorder (AUD), an increasingly prevalent condition. Medical addiction therapy for AUD may play a role in protecting against development and progression ALD.To ascertain whether medical was associated with altered risk developing ALD patients AUD.This retrospective cohort study used Mass General Brigham Biobank, ongoing research initiative that had recruited 127 480 between its start 2010 August...
Abstract Glucose is vital for life, serving as both a source of energy and carbon building block growth. When glucose limiting, alternative nutrients must be harnessed. To identify mechanisms by which cells can tolerate complete loss glucose, we performed nutrient-sensitized genome-wide genetic screens PRISM growth assay across 482 cancer cell lines. We report that catabolism uridine from the medium enables in absence glucose. While previous studies have shown salvaged to support pyrimidine...
Behind bars: A single molecule of the protein cytochrome c has been incarcerated within a rigid tetrahedral DNA cage (see picture). The central cavity is estimated to be large enough accommodate sphere approximately 2.6 nm in radius, such as 60-kDa globular (Mr c: 12.4 kDa). finding demonstrates potential containers new kind drug-delivery system. Supporting information for this article available on WWW under http://www.wiley-vch.de/contents/jc_2002/2006/z603392_s.pdf or from author. Please...
Nanometer-scale DNA polyhedra, consisting of 3- or 4-arm branch junctions connected by rigid double-helical edges, can be created self-assembly protocols that exploit the specificity base-pairing interactions. The tetrahedron was first such structure to made rapidly and in high yield from multiple strands a single assembly step. Facile efficient synthesis is necessary enabling step toward application these controllable three-dimensional scaffolds as building blocks for nanofabrication...
Wide-spread protozoan parasites carry endosymbiotic dsRNA viruses with uncharted implications to the human host. Among them, Trichomonas vaginalis, a parasite adapted genitourinary tract, infects globally ∼250 million each year rendering them more susceptible devastating pregnancy complications (especially preterm birth), HIV infection and HPV-related cancer. While first-line antibiotic treatment (metronidazole) commonly kills pathogen, it fails improve reproductive outcome. We show that...
Significance Alcohol-related liver disease is a leading cause of mortality worldwide. Improved patient outcomes will be driven by advances in our understanding pathogenesis, allowing for the development novel, targeted therapeutics. By combining data with animal models alcohol-related disease, we demonstrate critical importance cyclic guanosine monophosphate–adenosine monophosphate synthase-interferon regulatory factor 3 (cGAS-IRF3) pathway and its amplification through hepatocyte...
Many DNA nanostructures have been produced and a wide range of potential applications proposed. However, confirmation accurate 3D construction is particularly challenging. Here, we demonstrate that cryoEM may be exploited to obtain structural information at sufficient resolution visualize the helix reveal absolute stereochemistry 7 nm self-assembled tetrahedron. Structural analysis such high by image unprecedented for any biological molecule this size.
ABSTRACT Trichomonas vaginalis , which causes the most common nonviral sexually transmitted disease worldwide, is itself commonly infected by nonsegmented double-stranded RNA (dsRNA) viruses from genus Trichomonasvirus family Totiviridae . To date, cDNA sequences of one or more strains each three trichomonasvirus species have been reported, and gel electrophoresis showing several different dsRNA molecules obtained a few T. isolates has suggested that than virus strain might concurrently...
We present a facile method for linking recombinant proteins to DNA. It is based on the nickel-mediated interaction between hexahistidine tag (His(6)-tag) and DNA functionalized with three nitrilotriacetic acid (NTA) groups. The resulting DNA-protein linkage site-specific. can be broken quickly controllably by addition of chelating agent that binds nickel. have used this new linker bind variety motifs commonly in fabrication nanostructures self-assembly.
Diagnostic challenges continue to impede development of effective therapies for successful management alcohol-associated hepatitis (AH), creating an unmet need identify noninvasive biomarkers AH. In murine models, complement contributes ethanol-induced liver injury. Therefore, we hypothesized that proteins could be rational diagnostic/prognostic in Here, performed a comparative analysis data derived from human hepatic and serum proteome characterize protein signatures severe AH (sAH). The...