A5103226016- Virus-based gene therapy research
- RNA Interference and Gene Delivery
- CRISPR and Genetic Engineering
- Viral Infectious Diseases and Gene Expression in Insects
- Viral Infections and Immunology Research
- Advanced biosensing and bioanalysis techniques
- CAR-T cell therapy research
- Cytomegalovirus and herpesvirus research
- Animal Virus Infections Studies
- RNA regulation and disease
- Child and Adolescent Health
- interferon and immune responses
- DNA Repair Mechanisms
- Infant Development and Preterm Care
- Childhood Cancer Survivors' Quality of Life
- RNA and protein synthesis mechanisms
- Telomeres, Telomerase, and Senescence
- RNA modifications and cancer
- Adolescent and Pediatric Healthcare
- Hematological disorders and diagnostics
- Mesenchymal stem cell research
- Pluripotent Stem Cells Research
- Hematopoietic Stem Cell Transplantation
- Acute Myeloid Leukemia Research
- ICT in Developing Communities
National Cancer Institute
2020-2025
University of Toronto
2015-2022
Division of Cancer Epidemiology and Genetics
2021-2022
Hospital for Sick Children
2015-2022
SickKids Foundation
2022
Stem Cell Network
2021
Western University
2021
Rice University
2013-2021
Community Care
2020
Bloomberg (United States)
2020
Targeted genome editing technology can correct the sickle cell disease mutation of β-globin gene in hematopoietic stem cells. This correction supports production red blood cells that synthesize normal hemoglobin proteins. Here, we demonstrate Transcription Activator-Like Effector Nucleases (TALENs) and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 nuclease system target DNA sequences around sickle-cell for site-specific cleavage facilitate precise when a homologous...
Abstract The chr12q24.13 locus encoding OAS1–OAS3 antiviral proteins has been associated with coronavirus disease 2019 (COVID-19) susceptibility. Here, we report genetic, functional and clinical insights into this in relation to COVID-19 severity. In our analysis of patients European ( n = 2,249) African 835) ancestries hospitalized versus nonhospitalized COVID-19, the risk was a common OAS1 haplotype, which also reduced severe acute respiratory syndrome 2 (SARS-CoV-2) clearance trial...
The systemic evolution of ligands by exponential enrichment (SELEX) technique is a powerful and effective aptamer-selection procedure. However, modifications to the process can dramatically improve selection efficiency aptamer performance. For example, droplet digital PCR (ddPCR) has been recently incorporated into SELEX protocols putatively reduce propagation byproducts avoid bias that result from differences in sequences within random library. detailed, parallel comparison efficacy...
Aptamers, short RNA or DNA molecules that bind distinct targets with high affinity and specificity, can be identified using high-throughput systematic evolution of ligands by exponential enrichment (HT-SELEX), but scalable analytic tools for understanding sequence-function relationships from diverse HT-SELEX data are not available. Here we present AptaTRACE, a computational approach leverages the experimental design protocol, secondary structure, potential presence many motifs to identify...
We explored the unique signal integration properties of self-assembling 60-mer protein capsid adeno-associated virus (AAV), a clinically proven human gene therapy vector, by engineering proteolytic regulation virus–receptor interactions such that processing proteases is required for infection. find transfer function our engineered protease-activatable viruses (PAVs), relating degree proteolysis (input) to PAV activity (output), highly nonlinear, likely due increased polyvalency. By...
Adeno-associated virus (AAV) has emerged as a promising gene delivery vector because of its non-pathogenicity, simple structure and genome, low immunogenicity compared to other viruses. However, adoption safe effective for certain diseases relies on altering tropism deliver transgenes desired cell populations. To this end, we have developed protease-activatable AAV vector, named provector, that responds elevated extracellular protease activity commonly found in diseased tissue...
The performance of adult stem cells is crucial for tissue homeostasis but their regenerative capacity declines with age, leading to failure multiple organs. In skeletal muscle this manifested by the loss functional tissue, accumulation fibrosis, and reduced satellite cell-mediated myogenesis in response injury. While recent studies have shown that changes composition cell niche are at least part responsible impaired function observed aging, little known about effects aging on intrinsic...
Abstract The majority of patients with acute myeloid leukemia (AML) will require second‐line chemotherapy for either relapsed or refractory disease. Currently, only allogeneic hematopoietic cell transplantation (HCT) offers a curative option in this setting and no preferred regimen has been established. reported efficacy regimens is widely disparate, thus limiting informed clinical decision making. A retrospective review 77 receiving therapy between 2001 2008 relapsed, 42, refractory, 35,...
Adeno-associated virus (AAV) recombination can result in chimeric capsid protein subunits whose ability to assemble into an oligomeric capsid, package a genome, and transduce cells depends on the inheritance of sequence from different AAV parents. To develop quantitative design principles for guiding site-directed capsids, we have examined how structural perturbations predicted by SCHEMA algorithm correlate with experimental measurements disruption seventeen proteins. In our small chimera...
Abstract Engineering immunity against cancer by the adoptive transfer of hematopoietic stem cells (HSC) modified to express antigen-specific T-cell receptors (TCR) or chimeric antigen generates a continual supply effector T cells, potentially providing superior anticancer efficacy compared with infusion terminally differentiated cells. Here, we demonstrate in vivo generation functional from CD34-enriched human peripheral blood lentiviral vector designed for clinical use encoding TCR...
Caregivers of children in the child welfare system (CWS) often need more support their parenting efforts. Some these caregivers only related advices, whereas others may intensive training to prevent recurrence maltreatment. Few interventions can be delivered both groups with satisfying results. This study investigated treatment change associated Positive Parenting Programme (Triple P) on 83 who completed either Level 4 version or 5 (Pathways) programme (mean age = 40.6 years). Repeated...
Integrase-defective lentiviral vectors (IDLVs) have been of limited success in the delivery zinc finger nucleases (ZFNs) to human cells, due low expression. A reason for reduced gene expression has proposed involve epigenetic silencing vector genomes, carried out primarily by histone deacetylases (HDACs). In this study, we tested valproic acid (VPA), a known HDAC inhibitor (HDACi), its ability increase transgene from IDLVs, especially context ZFN delivery. Using ZFNs targeting adenosine...
Introduction: PICU hospitalization can have a profound impact on child survivors and their families. There is limited research children's long-term recovery within the context of family following critical illness. This study aimed to explore parents' perceptions psychological behavioral responses one year hospitalization. Materials Methods: Caring Intensively mixed methods multi-site prospective cohort that aims examine over 3-year period In this study, part qualitative arm Intensively, an...
Protease-activatable viruses (PAV) based on adeno-associated virus have previously been generated for gene delivery to pathological sites characterized by elevated extracellular proteases. "Peptide locks", composed of a tetra-aspartic acid motif flanked protease cleavage sequences, were inserted into the capsid inhibit virus-host cell receptor binding and transduction. In presence proteases, peptide locks are cleaved off capsid, restoring virus' ability bind cells deliver cargo. Although...
ABSTRACT Genomic regions have been associated with COVID-19 susceptibility and outcomes, including the chr12q24.13 locus encoding antiviral proteins OAS1-3. Here, we report genetic, functional, clinical insights into genetic associations within this locus. In Europeans, risk of hospitalized vs. non-hospitalized was a single 19Kb-haplotype comprised 76 OAS1 variants included in 95% credible set large genomic fragment introgressed from Neandertals. The haplotype also impaired spontaneous but...
OBJECTIVES: Health care providers (HCPs) require ongoing support to meet the evolving needs of children with medical complexity (CMC). Project Extension for Community Healthcare Outcomes (ECHO) is a model delivering technology-enabled education and cultivating community practice. In this study, we focused on developing, implementing, evaluating first ECHO program dedicated CMC. Specific objectives were evaluate feasibility (participation acceptability) impact perceived HCP knowledge,...