A5063019382- COVID-19 Clinical Research Studies
- Wound Healing and Treatments
- Sepsis Diagnosis and Treatment
- Cardiac Fibrosis and Remodeling
- Mesenchymal stem cell research
- Immune responses and vaccinations
- Inflammasome and immune disorders
- Single-cell and spatial transcriptomics
- Dermatologic Treatments and Research
- Nerve injury and regeneration
- Peptidase Inhibition and Analysis
- Tendon Structure and Treatment
- Hair Growth and Disorders
- Connective Tissue Growth Factor Research
- Immune cells in cancer
- Skin Protection and Aging
- Pulmonary Hypertension Research and Treatments
- Muscle Physiology and Disorders
- Neurogenesis and neuroplasticity mechanisms
- Tissue Engineering and Regenerative Medicine
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Electrospun Nanofibers in Biomedical Applications
- Cancer Cells and Metastasis
- Cellular Mechanics and Interactions
- Microbial metabolism and enzyme function
University of Calgary
2016-2024
Alberta Children's Hospital
2023-2024
Allen Institute for Brain Science
2023
University of British Columbia
2010-2017
Dalhousie University
2010-2015
Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases
2015
Abstract Although critical for host defense, innate immune cells are also pathologic drivers of acute respiratory distress syndrome (ARDS). Innate dynamics during Coronavirus Disease 2019 (COVID-19) ARDS, compared to ARDS from other pathogens, is unclear. Moreover, mechanisms underlying the beneficial effects dexamethasone severe COVID-19 remain elusive. Using single-cell RNA sequencing and plasma proteomics, we discovered that, bacterial was associated with expansion distinct neutrophil...
Highlights•Macrophages persist in the injured nerve rodents and humans•Macrophages regulate Schwann cells conduction velocity post-injury•Macrophages have a complex transcriptional profile•Macrophage-derived Gas6 regulates cell maturationSummaryPro-regenerative macrophages are well known for their role promoting tissue repair; however, specific roles regeneration of not defined. Specifically, how interact with following injury during remyelination has been largely unexplored. We demonstrate...
Adult mammalian skin wounds heal by forming fibrotic scars. We report that full-thickness injuries of reindeer antler (velvet) regenerate, whereas back forms scar. Single-cell multi-omics reveal uninjured velvet fibroblasts resemble human fetal fibroblasts, express inflammatory mediators mimicking pro-fibrotic adult and rodent fibroblasts. Consequently, injury elicits site-specific immune responses: amplify myeloid infiltration maturation during repair, adopt an immunosuppressive phenotype...
Lipid nanoparticles (LNPs) are currently the most effective in vivo delivery systems for silencing target genes hepatocytes employing small interfering RNA. Antigen-presenting cells (APCs) also potential targets LNP siRNA. We examined uptake, intracellular trafficking, and gene potency primary bone marrow macrophages (bmMΦ) dendritic of siRNA formulated LNPs containing four different ionizable cationic lipids namely DLinDAP, DLinDMA, DLinK-DMA, DLinKC2-DMA. DLinKC2-DMA were potent...
Highlights•In vivo ablation of anagen DP cells initiates activation and repopulation by hfDSCs•Single-cell RNA-seq reveals dysfunction aged HF mesenchyme progressive loss•hfDSCs are seconded to replenish the in HFs•Aging causes hfDSC depletion progenitor poolSummarySkin aging is accompanied hair loss due impairments follicle (HF) epithelial their mesenchymal niche. This inductive mesenchyme, called dermal papilla (DP), undergoes cell eventual miniaturization that contributes pathogenesis....
ABSTRACT Major impediments to developing a Chlamydia vaccine lie in identifying immunologically relevant T-cell antigens and delivery manner stimulate protective immunity. Using an immunoproteomic approach, we previously identified three immunodominant (PmpG-1, PmpE/F-2, RplF). Because RplF has high homology human ortholog, it may not be suitable for development. Therefore, this study, evaluated protection against infection the genital tract C57BL/6 mice immunized with -specific membrane...
Cell-based therapies have recently been the focus of much research to enhance skin wound healing. An important challenge will be develop vehicles for cell delivery that promote survival and uniform distribution cells across bed. These systems should stiff enough facilitate handling, whilst soft limit damage newly synthesized tissue minimize patient discomfort. Herein, we developed several novel modifiable nanofibre scaffolds comprised Poly (ε-caprolactone) (PCL) gelatin (GE). We asked...
The lung naturally resists Aspergillus fumigatus ( Af ) in healthy individuals, but multiple conditions can disrupt this resistance, leading to lethal invasive infections. Core processes of natural resistance and its breakdown are undefined. We investigated three distinct predisposing aspergillosis—severe SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection, influenza A viral pneumonia, systemic corticosteroid use—in human patients murine models. found a conserved essential...
Conventional dendritic cells (cDCs) generate protective cytotoxic T lymphocyte (CTL) responses against extracellular pathogens and tumors. This is achieved through a process known as cross-presentation (XP), and, despite its biological importance, the mechanism(s) driving XP remains unclear. Here, we show that cDC-specific pore-forming protein called apolipoprotein L 7C (APOL7C) up-regulated in response to innate immune stimuli recruited phagosomes. Association of APOL7C with phagosomes led...
Gene therapies and associated technologies are transforming biomedical research enabling novel therapeutic options for patients living with debilitating incurable genetic disorders. The vector system based on recombinant adeno-associated viral vectors (AAVs) has shown great promise in recent clinical trials diseases of multiple organs, such as the liver nervous system. Despite successes toward development bioengineered AAV variants improved transduction primary human tissues cells, that can...
DNA double-strand breaks (DSBs) are highly toxic lesions, which, if not properly repaired, can give rise to genomic instability. Non-homologous end-joining (NHEJ), a well-orchestrated, multistep process involving numerous proteins essential for cell viability, represents one major pathway repair DSBs in mammalian cells, and mutations different NHEJ components have been described microcephalic syndromes associated, e.g. with short stature, facial dysmorphism immune dysfunction. By using...
Cystatin C (CyC), a secreted cysteine protease inhibitor, has unclear biological functions. Many patients exhibit elevated plasma CyC levels, particularly during glucocorticoid (GC) treatment. This study links GCs with CyC's systemic regulation by utilizing genome-wide association and structural equation modeling to determine production genetics in the UK Biobank. Both polygenic score (PGS) capturing predisposition were associated increased all-cause cancer-specific mortality. We found that...
Brain pericytes are one of the critical cell types that regulate endothelial barrier function and activity, thus ensuring adequate blood flow to brain. The genetic pathways guiding undifferentiated cells into mature not well understood. We show here pericyte precursor populations from both neural crest head mesoderm zebrafish express transcription factor nkx3 . 1 develop brain pericytes. identify gene signature these precursors an -, foxf2a cxcl12b -expressing population is present around...
Understanding the cellular interactions and molecular signals underlying hair follicle (HF) regeneration may have significant implications for restorative therapies skin disease that diminish growth, whilst also serving to provide fundamental insight into mechanisms adult tissue regeneration. One of major, yet underappreciated, players in this process is HF mesenchyme. Here, we an overview a mesenchymal progenitor pool referred as dermal stem cells (hfDSCs), discuss their potential functions...
Pulmonary innate immunity is required for host defense; however, excessive neutrophil inflammation can cause life-threatening acute lung injury. B lymphocytes be regulatory, yet little known about peripheral transitional IgM+ cells in terms of regulatory properties. Using single-cell RNA sequencing, we discovered eight cell subsets with unique gene networks the circulation dominated by type 1 and 2 (T2B) cells. Lung intravital confocal microscopy revealed that T2B marginate pulmonary...
Abstract Poor quality (eg. excessive scarring) or delayed closure of skin wounds can have profound physical and pyschosocial effects on patients as well pose an enormous economic burden the healthcare system. An effective means improving both rate wound healing is needed for all suffering from injury. Despite care being a multi-billion-dollar industry, treatments aimed at rapidly restoring barrier function mitigating severity fibrotic scar remain elusive. Previously, hydrogel conjugated...