A5065538398- RNA Research and Splicing
- Virology and Viral Diseases
- Viral Infections and Immunology Research
- MicroRNA in disease regulation
- Respiratory viral infections research
- Hepatitis C virus research
- Virus-based gene therapy research
- Animal Virus Infections Studies
- interferon and immune responses
- Viral Infections and Vectors
- RNA Interference and Gene Delivery
- CRISPR and Genetic Engineering
- Viral gastroenteritis research and epidemiology
- RNA regulation and disease
- Neurogenetic and Muscular Disorders Research
- RNA and protein synthesis mechanisms
- Hepatitis B Virus Studies
- Extracellular vesicles in disease
- Mosquito-borne diseases and control
- HIV Research and Treatment
- RNA modifications and cancer
- Hepatitis Viruses Studies and Epidemiology
- Telomeres, Telomerase, and Senescence
- vaccines and immunoinformatics approaches
- Histone Deacetylase Inhibitors Research
University of Saskatchewan
2012-2025
Cameco (Canada)
2021-2025
Icahn School of Medicine at Mount Sinai
2015-2024
Global Virus Network
2021
Saskatchewan Health Authority
2012
Abstract Neurodegeneration is the primary driver of disease progression in multiple sclerosis (MS) resulting permanent disability, creating an urgent need to discover its underlying mechanisms. Herein, we establish that dysfunction RNA binding protein heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) results differential targets causing alternative splicing, which contributes neurodegeneration MS and models. Using RNAseq brains, discovered expression aberrant splicing hnRNP target RNAs...
miR-122 is a liver-specific microRNA (miRNA) that binds to two sites (S1 and S2) on the 5' untranslated region (UTR) of hepatitis C virus (HCV) genome promotes viral life cycle. It positively affects RNA stability, translation, replication, but mechanism not well understood. To unravel roles binding at each site alone or in combination, we employed mutant RNAs, Hep3B cells (which lack detectable miR-122), complementation with wild-type miR-122, an matching mutation, both. We found either...
The advent of RNA-guided endonuclease (RGEN)-mediated gene editing, specifically via CRISPR/Cas9, has spurred intensive efforts to improve the efficiency both RGEN delivery and targeted mutagenesis. major viral vectors in use for Cas9 its associated guide RNA, lentiviral adeno-associated systems, have potential undesired random integration into host genome. Here, we repurpose Sendai virus, an RNA virus with no DNA phase that replicates solely cytoplasm, as a system efficient Cas9-mediated...
Negative-sense RNA viruses (NSVs) rely on prepackaged viral RNA-dependent polymerases (RdRp) to replicate and transcribe their genomes. Their replication machinery consists of an RdRp bound which is wound around a nucleoprotein (NP) scaffold, forming ribonucleoprotein complex. NSV NP known regulate transcription genomic RNA; however, its role in maintaining protecting the genetic material unknown. Here, we exploited host microRNA expression target influenza A virus Sendai ascertain how this...
The mechanism by which miR-122 promotes the HCV life cycle is not well understood, and a role in directly promoting genome amplification still debated. In this study, we have shown that increases rate of viral RNA accumulation establishment an infection greater number cells than absence miR-122.
Telomerase reverse transcriptase (hTERT) overexpression, a hallmark of most cancers, drives tumorigenesis by enabling limitless replicative potential. Direct targeting hTERT is challenging, necessitating alternative strategies. Through genome-wide synthetic dosage lethality (SDL) screening in cancer models, including patient-derived organoids, we identify FTSJ3, an RNA 2'-O-methyltransferase, as critical vulnerability hTERT-overexpressing cells. FTSJ3 methylates telomeric repeat-containing...
DDX6 and other P-body proteins are required for efficient replication of Hepatitis C Virus (HCV) by unknown mechanisms. has been implicated in miRNA induced gene silencing, since HCV translation relies on the cellular microRNA, miR-122, we hypothesized that had a role mechanism action miR-122. However, using multiple assays have found this is not case. silencing decreased translation, but did affect ability miR-122 to stimulate or promote RNA accumulation. In addition, negative effect was...
Evidence indicates that dysfunctional heterogeneous ribonucleoprotein A1 (hnRNPA1; A1) contributes to the pathogenesis of neurodegeneration in multiple sclerosis. Understanding molecular mechanisms sclerosis may result novel therapies attenuate neurodegeneration, thereby improving lives MS patients with Using an vitro, blue light induced, optogenetic protein expression system containing optogene Cryptochrome 2 and a fluorescent mCherry reporter, we examined effects sclerosis-associated...
Paramyxoviruses are negative-sense single-stranded RNA viruses that comprise many important human and animal pathogens, including parainfluenza viruses. These bud from the plasma membrane of infected cells after viral ribonucleoprotein complex (vRNP) is transported cytoplasm to cell via Rab11a-marked recycling endosomes. The proteins critical for mediating this initial step in assembly unknown. Here, we used model paramyxovirus, murine virus 1, or Sendai (SeV), investigate roles...
Abstract Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is an RNA binding protein (RBP) that localized within neurons and plays crucial roles in metabolism. Its importance neuronal functioning underscored from the study of its pathogenic features many neurodegenerative diseases where hnRNP mislocalized nucleus to cytoplasm resulting loss function. Here, we model loss-of-function by siRNA-mediated knock-down differentiated Neuro-2a cells. Through sequencing (RNA-seq) followed gene...
Neurodegeneration, the progressive loss or damage to neurons and axons, underlies permanent disability in multiple sclerosis (MS); yet its mechanisms are incompletely understood. Recent data indicates autoimmunity several intraneuronal antigens, including RNA binding protein (RBP) heterogenous nuclear ribonucleoprotein A1 (hnRNP A1), as contributors neurodegeneration. We previously showed that addition of anti-hnRNP antibodies, which target same immunodominant domain MS IgG, mice with...
Oligodendrocyte (OL) damage and death are prominent features of multiple sclerosis (MS) pathology, yet mechanisms contributing to OL loss incompletely understood. Dysfunctional RNA binding proteins (RBPs), hallmarked by nucleocytoplasmic mislocalization altered expression, have been shown result in cell neurologic diseases, including MS. Since we previously observed that the RBP heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) was dysfunctional neurons MS, hypothesized it might also...
In humans, lymph nodes are the primary site of measles virus (MeV) replication. To understand immunological events that occur at this site, we infected human lymphoid tissue explants using a pathogenic strain MeV expresses GFP. We found 5%-15% cells across donors. Using single-cell RNA-Seq and flow cytometry, while most 29 cell populations identified in culture were susceptible to MeV, there was broad preferential infection B reduced T cells. Further subsetting revealed reduction may be...
ABSTRACT The transformative potential of gene editing technologies hinges on the development safe and effective delivery methods. In this study, we developed a temperature-sensitive interferon-silent Sendai virus (ts SeV) as novel vector for CRISPR-Cas9 efficient in sensitive human cell types without inducing IFN responses. ts SeV demonstrates unprecedented transduction efficiency CD34+ hematopoietic stem progenitor cells (HSPCs) including CD34+/CD38-/CD45RA-/CD90+(Thy1+)/CD49f high enriched...
ABSTRACT The therapeutic potential of gene editing technologies hinges on the development safe and effective delivery methods. In this study, we developed a temperature-sensitive less immunogenic Sendai virus (ts SeV) as novel vector for CRISPR-Cas9 efficient in sensitive human cell types with limited induction an innate immune response. ts SeV demonstrates high transduction efficiency CD34 + hematopoietic stem progenitor cells (HSPCs) including /CD38 − /CD45RA /CD90 (Thy1 )/CD49f enriched...
The RNA binding protein heterogeneous nuclear ribonucleoprotein A1 (A1) regulates metabolism, which is crucial to maintaining cellular homeostasis. dysfunction mechanistically contributes reduced cell viability and loss, but molecular mechanisms of how affects methodologies attenuate its dysfunction, are lacking. Utilizing in silico modeling an vitro optogenetic system, this study examined the consequences oligonucleotide (RNAO) treatment on attenuating downstream effects. In thermal shift...