A5083436266- Virus-based gene therapy research
- SARS-CoV-2 and COVID-19 Research
- CAR-T cell therapy research
- interferon and immune responses
- Herpesvirus Infections and Treatments
- Immunotherapy and Immune Responses
- Animal Virus Infections Studies
- COVID-19 Clinical Research Studies
- vaccines and immunoinformatics approaches
- Viral gastroenteritis research and epidemiology
- Cytokine Signaling Pathways and Interactions
- bioluminescence and chemiluminescence research
- Immune cells in cancer
- SARS-CoV-2 detection and testing
- Viral Infectious Diseases and Gene Expression in Insects
- Advanced biosensing and bioanalysis techniques
- Hippo pathway signaling and YAP/TAZ
- Immune Cell Function and Interaction
- Extracellular vesicles in disease
- PI3K/AKT/mTOR signaling in cancer
- Influenza Virus Research Studies
- Caveolin-1 and cellular processes
- Cell death mechanisms and regulation
- Medicinal Plant Pharmacodynamics Research
- Helicobacter pylori-related gastroenterology studies
Ottawa Hospital Research Institute
2019-2024
Ottawa Hospital
2019-2024
University of Ottawa
2020-2023
Queen's University
2016-2019
University of Baghdad
2017
Abstract Recent advances in cancer therapeutics clearly demonstrate the need for innovative multiplex therapies that attack tumour on multiple fronts. Oncolytic or “cancer-killing” viruses (OVs) represent up-and-coming multi-mechanistic immunotherapeutic drugs treatment of cancer. In this study, we perform an in-vitro screen based virus-encoded artificial microRNAs (amiRNAs) and find a unique amiRNA, herein termed amiR-4, confers replicative advantage to VSVΔ51 OV platform. Target validation...
Despite sequence similarity to SARS-CoV-1, SARS-CoV-2 has demonstrated greater widespread virulence and unique challenges researchers aiming study its pathogenicity in humans. The interaction of the viral receptor binding domain (RBD) with main host cell receptor, angiotensin-converting enzyme 2 (ACE2), emerged as a critical focal point for development anti-viral therapeutics vaccines. In this study, we selectively identify characterize impact mutating certain amino acid residues RBD ACE2,...
Colorectal cancer is the third most diagnosed and second leading cause of mortality worldwide, highlighting an urgent need for new therapeutic options combination strategies patients. The orchestration potent T cell responses against human cancers necessary effective antitumour immunity. However, regression a limited number has been induced by immune checkpoint inhibitors, engagers (TCEs) and/or oncolytic viruses. Although one TCE FDA-approved treatment hematological malignancies, many...
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,...
The clinical efficacy of VSVΔ51 oncolytic virotherapy has been limited by tumor resistance to viral infection, so strategies transiently repress antiviral defenses are warranted. Pevonedistat is a first-in-class NEDD8-activating enzyme (NAE) inhibitor currently being tested in trials for its antitumor potential. In this study, we demonstrate that pevonedistat sensitizes human and murine cancer cells increase cell death, improve therapeutic outcomes resistant syngeneic models. Increased...
Poxvirus vectors represent versatile modalities for engineering novel vaccines and cancer immunotherapies. In addition to their oncolytic capacity immunogenic influence, they can be readily engineered express multiple large transgenes. However, the integration of payloads into poxvirus genomes by traditional recombination-based approaches highly inefficient, time-consuming cumbersome. Herein, we describe a simple, cost-effective approach rapidly generate purify vector with By utilizing...
The coronavirus disease 2019 (COVID-19) pandemic requires the continued development of safe, long-lasting, and efficacious vaccines for preventive responses to major outbreaks around world, especially in isolated developing countries. To combat severe acute respiratory syndrome 2 (SARS-CoV-2), we characterize a temperature-stable vaccine candidate (TOH-Vac1) that uses replication-competent, attenuated vaccinia virus as vector express membrane-tethered spike receptor binding domain (RBD)...
The antimicrobial medication malarone (atovaquone/proguanil) is used as a fixed-dose combination for treating children and adults with uncomplicated malaria or chemoprophylaxis preventing in travelers. It an inexpensive, efficacious, safe drug frequently prescribed around the world. Following anecdotal evidence from 17 patients provinces of Quebec Ontario, Canada, suggesting that malarone/atovaquone may present some benefits protecting against COVID-19, we sought to examine its antiviral...
The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic presents an urgent need for effective vaccine. Molecular characterization of SARS-CoV-2 is critical to the development vaccine and therapeutic strategies. In present study, we show that fusion spike protein receptor-binding domain its transmembrane sufficient mediate trimerization. Our findings may have implications drug design strategies targeting As global efforts developing vaccines are rapidly underway,...
SARS-CoV-2, the etiological agent behind coronavirus disease 2019 (COVID-19) pandemic, has continued to mutate and create new variants with increased resistance against WHO-approved spike-based vaccines. With a significant portion of worldwide population still unvaccinated waning immunity newly emerging variants, there is pressing need develop novel vaccines that provide broader longer-lasting protection. To generate protective COVID-19, we developed our second-generation vaccinia...
Targeted antineoplastic immunotherapies have achieved remarkable clinical outcomes. However, resistance to these therapies due target absence or antigen shedding limits their efficacy and excludes tumours from candidacy. To address this limitation, here we engineer an oncolytic rhabdovirus, vesicular stomatitis virus (VSVΔ51), express a truncated targeted antigen, which allows for HER2-targeting with trastuzumab. The HER2 (HER2T) lacks signaling capabilities is efficiently expressed on...
The approval of different cytokines as anti-neoplastic agents has been challenged by dose-limiting toxicities. Although reducing dose levels affords improved tolerability, efficacy is precluded at these suboptimal doses. Strategies combining with oncolytic viruses have proven to elicit potent survival benefits in vivo, despite promoting rapid clearance the virus itself. Herein, we developed an inducible expression system based on a Split-T7 RNA polymerase for poxviruses regulate spatial and...
Abstract We have demonstrated that microtubule destabilizing agents (MDAs) can sensitize tumors to oncolytic vesicular stomatitis virus (VSVΔ51) in various preclinical models of cancer. The clinically approved T-DM1 (Kadcyla®) is an antibody-drug conjugate consisting HER2-targeting trastuzumab linked the potent MDA and maytansine derivative DM1. reveal combining with VSVΔ51 leads increased viral spread tumor killing trastuzumab-binding, VSVΔ51-resistant cancer cells. In vivo, co-treatment...
Background Established mouse models of HER2+ cancer are based on the over-expression rodent Neu/Erbb2 homologues, which incompatible with human HER2 (huHER2) targeted therapeutics. Additionally, use immune-deficient xenograft or transgenic precludes assessment native anti-tumour immune responses. These hurdles have been a challenge for our understanding mechanisms behind huHER2-targeting immunotherapies. Methods To assess impacts huHER2-targeted combination strategy, we generated syngeneic...
Oncolytic viruses (OVs) are promising anticancer treatments that specifically replicate in and kill cancer cells have profound immunostimulatory effects. We previously reported the potential of vanadium-based compounds such as vanadyl sulfate (VS) enhancers OV immunotherapy. These compounds, conjunction with RNA-based OVs oncolytic vesicular stomatitis virus (VSVΔ51), improve viral spread oncolysis, leading to long-term antitumor immunity prolonged survival resistant tumor models. This...
We established a split nanoluciferase complementation assay to rapidly screen for inhibitors that interfere with binding of the receptor domain (RBD) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein its target receptor, angiotensin-converting enzyme (ACE2). After 1,200 US Food and Drug Administration (FDA)-approved compounds, we identified bifonazole, an imidazole-based antifungal agent, as competitive inhibitor RBD-ACE2 binding. Mechanistically, bifonazole...
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...
Immunotherapy and specifically oncolytic virotherapy has emerged as a promising option for cancer patients, with herpes simplex virus-1 (oHSV-1) expressing granulocyte macrophage colony stimulating factor being the first OV to be approved by FDA treatment of melanoma. However, not all cancers are sensitive responsive viruses (OVs). Our group demonstrated that fumaric maleic acid esters (FMAEs) very effective in sensitizing cells infection. Of note, these FMAEs include dimethyl fumarate (DMF,...
Due to their crucial role in tumor immunity, NK cells have quickly became a prime target for immunotherapies, with the adoptive transfer of and use cell engagers moving clinical stage. On other hand, only few studies focused on small molecule drugs capable unleashing against cancer. In this context, repurposing molecules is an attractive strategy identify new immunotherapies from already approved drugs. Here, we developed platform screen compounds based high-throughput luciferase-release...
We recently demonstrated that Cav1 (caveolin-1) is a negative regulator of Stat3 (signal transducer and activator transcription-3) activity in mouse fibroblasts human lung carcinoma SHP77 cells. now examined whether the cellular context may affect their levels as well relationship between them, by assessing Stat3-ptyr705 amounts different cell lines. In MDA-MB-231, A549, HaCat cells, were high low, consistent with notion effect endogenous on these addition, manipulation revealed MCF7...
Abstract The purpose of this study was to examine the role Stat3α and Stat3β in survival apoptosis normal tumor cells. Stat3 transcription factor is activated by cytokine receptors IL6 family, receptor non-receptor tyrosine kinases, plays an etiological neoplasia. activation entails phosphorylation at tyr-705, dimerization through a reciprocal, SH2 domain-phosphotyrosine interaction, nuclear translocation. This triggers genes involved primarily cellular such as survivin, MCl1 Bcl-xL, well...