A5083753737- Virus-based gene therapy research
- Herpesvirus Infections and Treatments
- RNA regulation and disease
- interferon and immune responses
- Animal Virus Infections Studies
- Viral gastroenteritis research and epidemiology
- CRISPR and Genetic Engineering
- Genetics, Aging, and Longevity in Model Organisms
- Animal Disease Management and Epidemiology
- Viral Infections and Outbreaks Research
- Viral Infectious Diseases and Gene Expression in Insects
- Viral Infections and Immunology Research
- Immunodeficiency and Autoimmune Disorders
- NF-κB Signaling Pathways
- Cytomegalovirus and herpesvirus research
- RNA modifications and cancer
- Immune responses and vaccinations
- HIV Research and Treatment
Harvard University
2018-2021
Boston VA Research Institute
2018-2021
University of Colorado Boulder
2016-2019
Howard Hughes Medical Institute
2016
Beth Israel Deaconess Medical Center
2016
Although it is clear that trisomy 21 causes Down syndrome, the molecular events acting downstream of remain ill defined. Using complementary genomics analyses, we identified interferon pathway as major signaling cascade consistently activated by in human cells. Transcriptome analysis revealed activates transcriptional response fibroblast and lymphoblastoid cell lines, well circulating monocytes T Trisomy cells show increased induction interferon-stimulated genes decreased expression...
The mechanisms by which mammalian cells recognize and epigenetically restrict viral DNA are not well defined. We used herpes simplex virus with bioorthogonally labeled genomes to detect host factors recruited shortly after its nuclear entry found that the cellular IFI16, PML, ATRX proteins colocalized 15 min post infection. HSV-1 infection of ATRX-depleted fibroblasts resulted in elevated mRNA accelerated accumulation. Despite early association vDNA, we initial heterochromatin formation is...
Anelloviridae is a family of non-enveloped viruses with negative-sense, circular, single-stranded deoxyribonucleic acid (ssDNA) genomes that infect vertebrates and are ubiquitous component the human virome. Human anelloviruses evade induction humoral immune responses appear to be non-pathogenic. These properties, in conjunction their enormous genomic diversity wide tissue distribution, make compelling candidates as vectors for next-generation genetic medicines. Here we report first gene...
Anelloviridae is a family of single-stranded DNA viruses that are thought to be nonpathogenic and commensal. Despite their ubiquitous presence in human populations, little known about the anellovirus mechanism replication host cells. We identified protein coded by ORF2/3 as necessary sufficient initiate from minimal origin for both Beta- Alphatorquevirus genera. Supporting this observation, we components polymerase alpha BTR complexes interacting with viral initiation (Rip) during...
An important focus in vaccine research is the design of vectors with low seroprevalence and high immunogenicity. Replication-incompetent lymphocytic choriomeningitis virus (rLCMV) do not elicit vector-neutralizing antibody responses, homologous prime-boost regimens rLCMV induce boostable protective T cell responses to model antigens mice. However, cellular humoral immune following have been rigorously evaluated non-human primates (NHPs). To test whether constitute an effective platform NHPs,...
Histones are rapidly loaded on the HSV genome upon entry into nucleus of human fibroblasts, but effects histone loading viral replication have not been fully defined. We showed recently that ATRX is dispensable for de novo deposition H3 to genomes after nuclear restricted infection through maintenance heterochromatin. To further investigate roles and other chaperones play in restriction HSV, we infected fibroblasts were systematically depleted chaperones. found ATRX/DAXX complex unique among...
We observed that heat shock of Caenorhabditis elegans leads to the formation nuclear double-stranded RNA (dsRNA) foci, detectable with a dsRNA-specific monoclonal antibody. These foci significantly overlap HSF-1 granules. To investigate molecular mechanism(s) underlying dsRNA formation, we used RNA-seq globally characterize total and immunoprecipitated from control shocked worms. find subset both sense antisense transcripts enriched in pool by deletion tdp-1, which encodes C. ortholog...
ABSTRACT Human anelloviruses are acquired universally in infancy, highly prevalent, abundant blood, and extremely diverse. Their apparent lack of pathogenicity indicates that they a major component the commensal human virome. Despite their being extensively intertwined with biology, these viruses poorly understood. A impediment studying is an vitro system for production and/ or propagation. Here we show T cell-derived cell line MOLT-4 can be transfected plasmids comprising tandem anellovirus...
Abstract We observed that heat shock of Caenorhabditis elegans leads to the formation nuclear double-stranded RNA (dsRNA) foci, detectable with a dsRNA-specific monoclonal antibody. These foci significantly overlap HSF-1 granules. To investigate molecular mechanism(s) underlying dsRNA formation, we used RNA-seq globally characterize total and immunoprecipitated from control shocked worms. find antisense transcripts are generally increased after shock, subset both sense enriched in pool by...