A5065980382- Acute Lymphoblastic Leukemia research
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Advanced Proteomics Techniques and Applications
- Glycosylation and Glycoproteins Research
- Hematopoietic Stem Cell Transplantation
- Immune Response and Inflammation
- RNA Interference and Gene Delivery
- CAR-T cell therapy research
- Virus-based gene therapy research
- Gut microbiota and health
- Neonatal Respiratory Health Research
- Lung Cancer Research Studies
- Chronic Lymphocytic Leukemia Research
- Cancer Research and Treatments
- T-cell and B-cell Immunology
- Cancer Genomics and Diagnostics
- Chronic Myeloid Leukemia Treatments
- Immunodeficiency and Autoimmune Disorders
- Phagocytosis and Immune Regulation
- Endoplasmic Reticulum Stress and Disease
- Neuroblastoma Research and Treatments
- Antimicrobial Peptides and Activities
- Escherichia coli research studies
- Acute Myeloid Leukemia Research
British Columbia Children's Hospital
2016-2025
University of British Columbia
2016-2025
Western University
1999-2022
Lawson Health Research Institute
2001-2022
Okanagan University College
2021
Child and Family Research Institute
2004-2016
Philadelphia University
2006-2013
Children's Hospital of Philadelphia
2006-2011
Family Research Institute
2011
University of Pennsylvania
2006-2009
Abstract Dendritic cells (DC) are instrumental in orchestrating an appropriately polarized Th cell response to pathogens. DC exhibit considerable phenotypic and functional plasticity, influenced by lineage, Ag engagement, the environment which they develop mature. In this study, we identify human cationic peptide LL-37, found abundance at sites of inflammation, as a potent modifier differentiation, bridging innate adaptive immune responses. LL-37-derived displayed significantly up-regulated...
Significance Group 3 innate lymphoid cells enriched in the gut mediate host resistance against intestinal pathogens. Their function and development can be regulated by diverse factors, including neuropeptides secreted enteric nervous system. We show that neuropeptide vasoactive peptide (VIP) promotes recruitment of these other immune to through a receptor. Mice lacking VIP or its receptor were highly susceptible an pathogen infection. Replenishing their products into mice was able partially...
Efficient delivery of therapeutics to the central nervous system (CNS) remains a major challenge for treatment neurological diseases. Huntington disease (HD) is dominantly inherited neurodegenerative disorder caused by CAG trinucleotide expansion mutation in HTT gene which codes toxic mutant huntingtin (mHTT) protein. Pharmacological reduction mHTT CNS using antisense oligonucleotides (ASO) ameliorates HD-like phenotypes rodent models HD, with such therapies being investigated clinical...
Melanotransferrin, also called p97, is a cell surface glycoprotein which was first described as marker antigen for human melanoma cells. Although p97 has striking structural similarity to serum transferrin and lactoferrin, its function not yet been determined. One feature that distinguishes from the other members of family presence stretch 24 hydrophobic amino acids at C terminus, previously assumed form proteinacious transmembrane domain. In this study, sensitivity bacterial...
B cells appear to play a role in chronic graft-versus-host disease (cGVHD) as shown murine models and the success of anti-CD20 cell antibody treatment humans. Recent studies have that immunostimulatory microbial CpG-DNA splenic responses were enhanced GVHD. We hypothesized CpG-induced are increased human cGVHD. Newly diagnosed cGVHD patients enrolled on COG protocol ASCT0031 divided into early (3-8 months postblood marrow transplant [BMT]) late (≥9 post-BMT) onset groups compared...
Abstract CD47 is a cell-surface marker well recognized for its anti-phagocytic functions. As such, an emerging avenue targeted cancer therapies involves neutralizing the function using monoclonal antibodies (mAbs) to enhance tumour cell immunogenicity. A lesser known consequence of receptor ligation direct induction death. While several mAbs and their derivatives with this property have been studied, best characterized commercially available mAb B6H12, which requires immobilization Here, we...
Ulcerative colitis (UC) is a chronic inflammatory condition linked to intestinal microbial dysbiosis, including the expansion of E. coli strains related extra-intestinal pathogenic coli. These "pathobionts" exhibit properties, but their potential promote UC unclear due lack relevant animal models. Here, we established mouse model using representative pathobiont strain (p19A), and mice lacking single immunoglobulin toll-interleukin 1 receptor domain (SIGIRR), deficiency increasing...
Lipid nanoparticles (LNP) have been successfully used as a platform technology for delivering nucleic acids to the liver. To broaden application of LNPs in targeting non-hepatic tissues, we developed LNP-based RNA therapies (siRNA or mRNA) respiratory tract. Such optimized LNP systems could offer an early treatment strategy viral tract infections such COVID-19.We generated small library six formulations with varying helper lipid compositions and characterized their hydrodynamic diameter,...
Cytotoxic T lymphocytes (CTL) recognize antigenic peptides bound to major histocompatibility complex class I antigens on the cell surface of virus-infected cells. It is believed that majority originate from cytoplasmic degradation proteins assumed be mediated by "20S" proteasome. Cytosolic are then translocated, presumably transporters associated with antigen processing (TAP-1 and -2), into lumen endoplasmic reticulum (ER) where binding formation ternary between heavy chain,...
Abstract Intravenous Ig is used to treat autoimmune or autoinflammatory disorders, but the mechanism by which it exerts its immunosuppressive activity not understood completely. To examine impact of intravenous on macrophages, we compared cytokine production LPS-activated macrophages in presence and absence Ig. treatment induced robust IL-10 response LPS, relative LPS stimulation alone, reduced proinflammatory cytokines. This anti-inflammatory, Ig-induced activation was sustained for 24 h...
Abstract Genomics has transformed the diagnostic landscape of pediatric malignancies by identifying and integrating actionable features that refine diagnosis, classification, treatment. Yet, translating precision oncology data into effective therapies for hard-to-cure childhood, adolescent, young adult remains a significant challenge. We present case combining proteomics with patient-derived xenograft models to identify personalized treatment an adolescent primary metastatic spindle...
Cell-cycle progression and the acquisition of a migratory phenotype are hallmarks human carcinoma cells that perceived as independent processes but may be interconnected by molecular pathways control microtubule nucleation at centrosomes. Here, cell-cycle dramatically impacts engraftment kinetics 4T1-luciferase2 breast cancer in immunocompetent BALB/c or immunocompromised NOD-SCID gamma (NSG) mice. Multiparameter imaging wound closure assays was used to track progression, cell migration,...
Murine xenografts of pediatric leukemia accurately recapitulate genomic aberrations. How this translates to the functional capacity cells remains unclear. Here, we studied global protein abundance, phosphorylation, and maturation by proteolytic processing in 11 B- T- cell ALL patients 19 corresponding xenografts.Xenograft models were generated for each patient leukemia. Mass spectrometry-based methods used investigate limited proteolysis paired xenografted acute lymphocytic leukemia, as well...
Therapy-induced presentation of cell surface calreticulin (CRT) is a pro-phagocytic immunogen beneficial for invoking anti-tumor immunity. Here, we characterized the roles ERp57 and α-integrins as CRT-interacting proteins that coordinately regulate CRT translocation from ER to during immunogenic death. Using T-lymphoblasts genetic model, found drug-induced dependent on ERp57, while independent CRT. Differential subcellular immunostaining assays revealed ERp57-/- cells have minimal cytosolic...