A5015102577- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- SARS-CoV-2 detection and testing
- Biotin and Related Studies
- Immunotherapy and Immune Responses
- Virus-based gene therapy research
- RNA and protein synthesis mechanisms
- COVID-19 Impact on Reproduction
- RNA Research and Splicing
- Animal Virus Infections Studies
- Zoonotic diseases and public health
- Identification and Quantification in Food
- Click Chemistry and Applications
- Viral Infections and Immunology Research
- vaccines and immunoinformatics approaches
- Neuroscience and Neural Engineering
- Leptospirosis research and findings
- Hippo pathway signaling and YAP/TAZ
- Inflammasome and immune disorders
- Molecular Biology Techniques and Applications
- Long-Term Effects of COVID-19
- ATP Synthase and ATPases Research
- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- Vitamin D Research Studies
Lunenfeld-Tanenbaum Research Institute
2018-2025
Mount Sinai Hospital
2020-2025
University of Toronto
2018-2025
Sinai Health System
2020-2025
Sinai Hospital
2021-2024
Canada Research Chairs
2022-2023
University of New Brunswick
2022-2023
Laboratory of Molecular Genetics
2022
Most of the patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mount a humoral immune response to virus within few weeks infection, but duration this and how it correlates clinical outcomes has not been completely characterized. Of particular importance is identification infection that would support public health decision-making on treatment approaches, vaccination strategies, convalescent plasma therapy. While ELISA-based assays detect quantitate antibodies...
The SARS-CoV-2 virus Omicron variant has now supplanted wild-type as the dominant circulating strain globally. Three doses of mRNA COVID-19 vaccine are recommended for transplant recipients their primary series. However, immunogenicity vaccines they specifically relate to not well studied. We analyzed Omicron-specific neutralization in after three-doses mRNA-1273 vaccine. Neutralization was determined using a spike pseudotyped lentivirus assay with constructs and Delta variants. A total 60...
Abstract Viral replication is dependent on interactions between viral polypeptides and host proteins. Identifying virus-host protein can thus uncover unique opportunities for interfering with the virus life cycle via novel drug compounds or repurposing. Importantly, many viral-host take place at intracellular membranes poorly soluble organelles, which are difficult to profile using classical biochemical purification approaches. Applying proximity-dependent biotinylation (BioID) fast-acting...
BACKGROUNDLimited information is available on the impact of immunosuppressants COVID-19 vaccination in patients with immune-mediated inflammatory diseases (IMID).METHODSThis observational cohort study examined immunogenicity SARS-CoV-2 mRNA vaccines adult bowel disease, rheumatoid arthritis, ankylosing spondylitis, or psoriatic without maintenance immunosuppressive therapies. Ab and T cell responses to SARS-CoV-2, including neutralization against variants, were determined before after 1 2...
Safe and effective vaccines are needed to end the COVID-19 pandemic. Here, we report preclinical development of a lipid nanoparticle–formulated SARS-CoV-2 mRNA vaccine, PTX-COVID19-B. PTX-COVID19-B was chosen among three candidates after initial mouse vaccination results showed that it elicited strongest neutralizing antibody response against SARS-CoV-2. Further tests in mice hamsters indicated induced robust humoral cellular immune responses completely protected vaccinated animals from...
Abstract Thousands of RNA-binding proteins (RBPs) crosslink to cellular mRNA. Among these are numerous unconventional RBPs (ucRBPs)—proteins that associate with RNA but lack known domains (RBDs). The vast majority ucRBPs have uncharacterized specificities. We analyzed 492 human for intrinsic in vitro and identified 23 bind specific sequences. Most (17/23), including 8 ribosomal proteins, were previously associated RNA-related function. the RBDs responsible sequence-specific several surveyed...
COVID-19 is more severe in transplant recipients. Variants of concern have supplanted wild-type virus. In recipients, data are limited on 2-dose or 3-dose vaccine immunogenicity against variant viruses.To assess neutralizing antibody responses SARS-CoV-2 variants recipients after 2 and 3 doses.Secondary analysis a randomized, double-blind, controlled trial third dose mRNA-1273 versus placebo. (ClinicalTrials.gov: NCT04885907).Single-center program.Organ recipients.Third placebo.Sera were...
The ability to sense and respond osmotic fluctuations is critical for the maintenance of cellular integrity. We used gene co-essentiality analysis identify an unappreciated relationship between TSC22D2, WNK1, NRBP1 in regulating cell volume homeostasis. All these genes have paralogs are functionally buffered osmo-sensing control. Within seconds hyperosmotic stress, TSC22D, WNK, NRBP family members physically associate into biomolecular condensates, a process that dependent on intrinsically...
Abstract Prioritizing Ontario’s long-term care home (LTCH) residents for vaccination against severe acute respiratory syndrome coronavirus 2 has drastically reduced their disease burden; however, recent LTCH outbreaks of variants concern (VOCs) have raised questions regarding immune responses. In 198 residents, mRNA vaccine dose 1 elicited partial spike and receptor binding domain antibody responses, while the second a response at least equivalent to convalescent individuals in most...
Abstract Continuously emerging SARS-CoV-2 Omicron subvariants pose a threat thwarting the effectiveness of approved COVID-19 vaccines. Especially, protection breadth and degree these vaccines against antigenically distant is unclear. Here, we report immunogenicity efficacy bivalent mRNA vaccine, PTX-COVID19-M1.2 (M1.2), which encodes native spike proteins from Wuhan-Hu-1 (D614G) BA.2.12.1, in mouse hamster models. Both primary series booster vaccination using M1.2 elicited potent broad nAbs...
Abstract Immunocompromised patients are predisposed to severe COVID-19. Here we compare homotypic and heterotypic humoral cellular immune responses Omicron BA.1 in organ transplant across a diverse clinical spectrum. We perform variant-specific pseudovirus neutralization assays for D614G, Omicron-BA.1, -BA.2, Delta variants. also measure poly-and monofunctional T-cell ancestral SARS-CoV-2 peptide pools. identify that partially or fully-vaccinated recipients after infection with have the...
Proximity-dependent biotinylation strategies have emerged as powerful tools to characterize the subcellular context of proteins in living cells. The popular BioID approach employs an abortive E. coli biotin ligase mutant (R118G; denoted BirA*), which when fused a bait protein eNAbles covalent endogenous proximal polypeptides. This has been mainly applied study proximity immortalized mammalian cell lines. To expand application space BioID, here we describe set lentiviral vectors that eNAble...
The ongoing COVID-19 pandemic has highlighted the immediate need for development of antiviral therapeutics targeting different stages SARS-CoV-2 life cycle. We developed a bioluminescence-based bioreporter to interrogate interaction between viral spike (S) protein and its host entry receptor, angiotensin-converting enzyme 2 (ACE2). assay is based on nanoluciferase complementation reporter, composed two subunits, large BiT small BiT, fused S receptor-binding domain (RBD) ACE2 ectodomain,...
Abstract Most of the patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mount a humoral immune response to virus within few weeks infection, but duration this and how it correlates clinical outcomes has not been completely characterized. Of particular importance is identification infection that would support public health decision-making on treatment approaches, vaccination strategies, convalescent plasma therapy. While ELISA-based assays detect quantitate...
Abstract Access to vaccines against SARS-CoV-2 virus was limited in poor countries during the COVID-19 pandemic. Therefore, a low-cost mRNA vaccine, PTX-COVID19-B, produced and evaluated Phase 1 trial. PTX-COVID19-B encodes Spike protein D614G variant without proline-proline (986–987) mutation present other vaccines. The aim of study evaluate safety, tolerability, immunogenicity vaccine healthy seronegative adults 18–64 years old. trial design observer-blinded, randomized,...
Abstract Although high titers of neutralizing Abs in human serum are associated with protection from reinfection by SARS-CoV-2, there is considerable heterogeneity serum-neutralizing against SARS-CoV-2 during convalescence between individuals. Standard live virus neutralization assays require inactivation serum/plasma prior to testing. In this study, we report that the convalescent sera were relatively consistent across all disease states except for severe COVID-19, which yielded...
Abstract Safe and effective vaccines are needed to end the COVID-19 pandemic caused by SARS-CoV-2. Here we report preclinical development of a lipid nanoparticle (LNP) formulated SARS-CoV-2 mRNA vaccine, PTX-COVID19-B. PTX-COVID19-B was chosen among three candidates after initial mouse vaccination results showed that it elicited strongest neutralizing antibody response against Further tests in mice hamsters indicated induced robust humoral cellular immune responses completely protected...
ABSTRACT Background Limited information is available on the impact of immunosuppressants COVID-19 vaccination in patients with immune-mediated inflammatory diseases (IMID). Methods This observational cohort study examined immunogenicity SARS-CoV-2 mRNA vaccines adult bowel disease, rheumatoid arthritis, ankylosing spondylitis, or psoriatic without maintenance immunosuppressive therapies. Antibody and T cell responses to SARS-COV-2, including neutralization against variants were determined...
The United States Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the use of COVID-19 convalescent plasma (CCP) to treat hospitalized patients with in August 2020. However, by 4 February 2021, FDA had revised EUA.
Abstract Background This pilot study assesses the ability of plasma collected from Canadian blood donors in first wave SARS‐CoV‐2 pandemic to neutralize later variants concern (VOCs). Study design and methods A repeated cross‐sectional was used, a random sample all available Blood Services retention samples (n = 1500/month) drawn monthly for April May 2020. Qualitative IgG analysis performed on aliquots specimens using anti‐spike, anti‐receptor binding domain, anti‐nucleocapsid protein...
This study attempted to understand the levels of neutralizing titers and breadth antibody protection against wild-type variant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Canadian blood donors during first 3 months 2021. During this period, it is unlikely that many had received a second dose, since vaccine rollout not yet ramped up, less than 2% population dose vaccine. A repeated cross-sectional design was used. random sampling all available Blood Services retention samples (
Abstract The ongoing COVID-19 pandemic has highlighted the` immediate need for the development of antiviral therapeutics targeting different stages SARS-CoV-2 lifecycle. We developed a bioluminescence-based biosensor to interrogate interaction between viral spike protein and its host entry receptor, angiotensin-converting enzyme 2 (ACE2). assay is based on Nanoluciferase complementation reporter, composed two subunits, Large BiT Small BiT, fused receptor-binding domain (RBD) S ACE2...
Abstract The continuous emergence of SARS-CoV-2 Omicron subvariants poses a serious threat thwarting the effectiveness currently approved COVID-19 vaccines, demanding vaccine that can provide broad protection against these subvariants. Although bivalent vaccines containing subvariant spikes have been shown to elicit high neutralizing antibodies (nAbs) and afford homologous or antigenically close subvariants, breadth degree provided by distant is unclear. Here, we report immunogenicity...
SUMMARY The ability to sense and respond osmotic fluctuations is critical for the maintenance of cellular integrity. Myriad redundancies have evolved across all facets osmosensing in metazoans, including among water ion transporters, regulators morphology, macromolecular crowding sensors, hampering efforts gain a clear understanding how cells rapid loss. In this study, we harness power gene co-essentiality analysis genome-scale CRISPR-Cas9 screening identify an unappreciated relationship...