A5110849675- Neuroinflammation and Neurodegeneration Mechanisms
- GDF15 and Related Biomarkers
- Neurogenesis and neuroplasticity mechanisms
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- DNA Repair Mechanisms
- Genomics and Chromatin Dynamics
- SARS-CoV-2 and COVID-19 Research
- Prion Diseases and Protein Misfolding
- Nanoplatforms for cancer theranostics
- Redox biology and oxidative stress
- Cancer Research and Treatments
- Cancer Genomics and Diagnostics
- Glioma Diagnosis and Treatment
- RNA modifications and cancer
- Animal Virus Infections Studies
- Hedgehog Signaling Pathway Studies
- Infectious Encephalopathies and Encephalitis
- Polyamine Metabolism and Applications
- Tryptophan and brain disorders
- Barrier Structure and Function Studies
- Single-cell and spatial transcriptomics
- vaccines and immunoinformatics approaches
- Long-Term Effects of COVID-19
- Bioinformatics and Genomic Networks
Public Health Agency of Canada
2021-2024
University of Manitoba
2013-2023
CancerCare Manitoba
2017-2022
Research Institute in Oncology and Hematology
2015-2019
Research Manitoba
2014
Centre for Drug Research and Development
2013
Harnessing genetic differences between cancerous and noncancerous cells offers a strategy for the development of new therapies. Extrapolating from yeast interaction data, we used cultured human siRNA to construct evaluate synthetic lethal network comprised chromosome instability (CIN) genes that are frequently mutated in colorectal cancer. A small number this were found have interactions with large cancer CIN genes; these thus attractive targets anticancer therapeutic development. The...
The Zika virus (ZIKV) epidemic is an ongoing public health concern. ZIKV a flavivirus reported to be associated with microcephaly, and recent work in animal models demonstrates the ability of cross placenta affect fetal brain development. Recent findings suggest that preferentially infects neural stem cells thereby deregulates gene expression, cell cycle progression, increases death. However, neuronal are not only susceptible infection other may contribute disease progression. Herein, we...
Synthetic lethality is a rational approach to identify candidate drug targets for selective killing of cancer cells harboring somatic mutations that cause chromosome instability (CIN). To set the most highly connected synthetic lethal partner genes in yeast subsequent testing mammalian cells, we used entire 692 CIN query genome-wide datasets. Hierarchical clustering revealed partners whose human orthologs are somatically mutated colorectal cancer. Testing small matrix gene pairs suggested...
// Babu V. Sajesh 1, 2 , Kirk J. McManus 1 Department of Biochemistry and Medical Genetics, University Manitoba, Winnipeg, Canada Research Institute Oncology Hematology, Correspondence to: McManus, e-mail: Kirk.McManus@umanitoba.ca Keywords: BLM, CHEK2, SOD1, synthetic lethality, drug targeting Received: June 01, 2015 Accepted: July 21, Published: 31, ABSTRACT Cancer is a major cause death throughout the world, there large need for better more personalized approaches to combat disease. Over...
Cancer is a leading cause of death throughout the World. A limitation many current chemotherapeutic approaches that their cytotoxic effects are not restricted to cancer cells, and adverse side can occur within normal tissues. Consequently, novel strategies urgently needed better target cells. As we approach era personalized medicine, targeting specific molecular defect(s) given patient's tumor will become more effective treatment strategy than traditional often type or sub-type. Synthetic...
Spermidine/spermine N1-acetyltransferase 1 (SAT1) responsible for cell polyamine catabolism is overexpressed in glioblastoma multiforme (GB). Its role tumor survival and promoting resistance towards radiation therapy has made it an interesting target therapy. In this study, we prepared a lipid nanoparticle-based siRNA delivery system (LNP-siSAT1) to selectively knockdown (KD) SAT1 enzyme human line. The LNP-siSAT1 containing ionizable DODAP was following microfluidics mixing method the...
Abstract Background Chromosome instability manifests as an abnormal chromosome complement and is a pathogenic event in cancer. Although correlation between numbers cancer exist, the underlying mechanisms that cause are poorly understood. Recent data suggests aberrant sister chromatid cohesion causes thus contributes to development of Cohesion normally functions by tethering nascently synthesized chromatids together prevent premature segregation instability. prevalence has been reported for...
Abstract Prion diseases are neurodegenerative disorders with long asymptomatic incubation periods, followed by a rapid progression of cognitive and functional decline culminating in death. The complexity intercellular interactions the brain is challenging to unravel basis disease pathobiology remains poorly understood. In this study, we employed single cell RNA sequencing (scRNAseq) produce an atlas 147,536 transcriptomes from cortex hippocampus mice infected prions showing clinical signs....
The blood-brain barrier (BBB) poses a major obstacle by preventing potential therapeutic agents from reaching their intended brain targets at sufficient concentrations. While transient disruption of the BBB has been used to enhance chemotherapeutic efficacy in treating tumors, limitations terms magnitude and duration exist. In present study, preliminary safety profile HAV6, peptide that binds external domains cadherin, transiently open improve delivery agent, was evaluated murine tumor...
Increasing cases of SARS-CoV-2 breakthrough infections from immunization with current spike protein-based COVID-19 vaccines highlight the need to develop alternative using different platforms and/or antigens. In this study, we expressed and nucleocapsid proteins based on a novel vaccinia virus (VACV) ACAM2000 platform (rACAM2000). platform, host range immunoregulatory gene E3L was deleted make attenuated enhance innate immune responses, another gene, K3L, replaced poxvirus ortholog taterapox...
Harnessing genetic differences between cancerous and noncancerous cells offers a strategy for the development of new therapies.Extrapolating from yeast interaction data, we used cultured human siRNA to construct evaluate synthetic lethal network comprised chromosome instability (CIN) genes that are frequently mutated in colorectal cancer.A small number this were found have interactions with large cancer CIN genes; these thus attractive targets anticancer therapeutic development.The protein...
The numerous neurological syndromes associated with COVID-19 implicate an effect of viral pathogenesis on neuronal function, yet reports direct SARS-CoV-2 infection in the brain are conflicting. We used a well-established organotypic slice culture to determine permissivity hamster tissues infection. found levels live virus waned after inoculation and observed no evidence cell-to-cell spread, indicating that was non-productive. Nonetheless, we identified small number infected cells glial...
DIPG is the most common brainstem tumor in children and uniformly fatal. The BBB intact plays an active role restricting delivery of systemically administered therapies into tumor. Recent studies have shown that SHH signalling a major maintenance integrity this pathway highly DIPG. We hypothesized critical maintaining integrity. Primary PDX (patient derived xenografts) secretes significantly higher quantities (~2-fold) compared to astrocytes human brain microvascular endothelial cells...
Group-3 medulloblastoma (MBL) is highly resistant to radiation (IR) and chemotherapy has the worst prognosis. Hence, there an urgent need elucidate targets that sensitize these tumors IR. Employing standard assays for viability sensitization IR, we identified PRDX1 as a therapeutic target in MBL. Specifically, targeting by RNAi or inhibition Adenanthin led specific killing IR of MBL cells. We rescued Daoy UW228 cells hypermorphic expression PRDX1. knockdown caused oxidative DNA damage...
SUMMARY Increasing cases of SARS-CoV-2 breakthrough infections from immunization with predominantly spike protein based COVID-19 vaccines highlight the need for alternative using different platforms and/or antigens. In this study, we expressed and nucleocapsid proteins in a novel vaccinia virus ACAM2000 platform (rACAM2000). Following single intramuscular immunization, rACAM2000 co-expressing induced significantly improved protection against challenge comparison to expressing individual...
Abstract Synthetic lethality is a rare genetic interaction that results when two independently viable mutations occur within the same organism/cell and in cell death. thus rational approach to identify drug targets can specifically kill cancer cells harboring somatic specific genes. RAD54B encodes protein involved homologous recombination repair whose expression normally required maintain genome integrity. somatically altered ∼4% of colorectal cancers numerous other tumor types including...
Abstract Diffuse Midline Glioma of the Pons (DMG-P) is most common brainstem tumor in children and universally lethal this age group. The intact Blood-Brain Barrier (BBB) these tumors are believed to play a major role preventing systemically administered therapeutic agents from reaching concentrations tumor. factors that contribute integrity BBB DMG-P not well understood. Sonic Hedgehog (SHH) signaling promotes developing adult brain plays an important formation maintenance tumors. In...
Group-3 Medulloblastomas (MBL) has the worst prognosis due to its resistance radiation and chemotherapy with a 5-year survival of 30%. Thus, there is an urgent need elucidate targets that can sensitize tumors conventional treatments. We identified PRDX1 as candidate therapeutic target for therapy sensitization in group-3 tumors. catalyzes conversion hydrogen peroxide water oxygen. hypothesized inhibiting would lead oxidative stress increase susceptibility ionizing via extensive DNA damage....