A5100625283- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immune Response and Inflammation
- interferon and immune responses
- Heme Oxygenase-1 and Carbon Monoxide
- Antimicrobial Peptides and Activities
- High Altitude and Hypoxia
- Cytomegalovirus and herpesvirus research
- RNA Research and Splicing
- Malaria Research and Control
- Systemic Lupus Erythematosus Research
- Immune cells in cancer
- Adenosine and Purinergic Signaling
- Lipid Membrane Structure and Behavior
- Neurogenetic and Muscular Disorders Research
- Algal biology and biofuel production
- Microbial Metabolic Engineering and Bioproduction
- Enzyme Catalysis and Immobilization
- Neonatal Health and Biochemistry
- RNA and protein synthesis mechanisms
- Immunodeficiency and Autoimmune Disorders
- Calcium signaling and nucleotide metabolism
- Biomarkers in Disease Mechanisms
Western University
2023
The Francis Crick Institute
2023
Johns Hopkins Medicine
2019-2022
Johns Hopkins University
2019-2022
Australian Regenerative Medicine Institute
2020-2021
The University of Melbourne
2014-2021
Peter Doherty Institute
2014-2021
Monash University
2016-2021
Simon Fraser University
2020
Peter MacCallum Cancer Centre
2020
Cationic antimicrobial peptides (CAPs) occur as important innate immunity agents in many organisms, including humans, and offer a viable alternative to conventional antibiotics, they physically disrupt the bacterial membranes, leading membrane lysis eventually cell death. In this work, we studied biophysical microbiological characteristics of designed CAPs varying hydrophobicity levels charge distributions by variety biochemical approaches, in-tandem atomic force microscopy, attenuated total...
Heparin/heparan sulfate (HS) proteoglycans are found in the extracellular matrix (ECM) and on cell surface. A considerable body of evidence has established that heparin heparan (HSPGs) interact with numerous protein ligands including fibroblast growth factors, vascular endothelial factor (VEGF), cytokines, chemokines. These interactions highly dependent upon pattern sulfation modifications within glycosaminoglycan chains. We previously cloned a cDNA encoding novel human endosulfatase,...
Background: High altitude is a challenging condition caused by insufficient oxygen supply. Inability to adjust hypoxia may lead pulmonary edema, stroke, cardiovascular dysfunction, and even death. Thus, understanding the molecular basis of adaptation high reveal novel therapeutics counteract detrimental consequences hypoxia. Methods: Using high-throughput, unbiased metabolomic profiling, we report that metabolic pathway responsible for production erythrocyte 2,3-bisphosphoglycerate...
Background: Nucleic acid binding proteins are frequently targeted as autoantigens in systemic lupus erythematosus (SLE) and other interferon (IFN)-linked rheumatic diseases. The AIM-like receptors (ALRs) IFN-inducible innate sensors that form supramolecular assemblies along double-stranded (ds)DNA of various origins. Here, we investigate the ALR absent melanoma 2 (AIM2) a novel autoantigen SLE, with similar properties to established interferon-inducible protein 16 (IFI16). We examined...
Abstract Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative diseases that exist on a clinico-pathogenetic spectrum, designated ALS/FTD. The most common genetic cause of ALS/FTD is expansion the intronic hexanucleotide repeat (GGGGCC) n in C9orf72 . Here, we investigate formation nucleic acid secondary structures these repeats, their role generating condensates characteristic We observe significant aggregation sequence , which associate to...
Abstract Faster acclimatization to high altitude upon re-ascent is seen in humans; however, the molecular basis for this enhanced adaptive response unknown. We report that healthy lowlanders, plasma adenosine levels are rapidly induced by initial ascent and achieved even higher re-ascent, a feature positively associated with quicker acclimatization. Erythrocyte equilibrative nucleoside transporter 1 (eENT1) reduced humans at mice under hypoxia. eENT1 deletion allows rapid accumulation of...
Targeting antigens to dendritic cell (DC) surface receptors using antibodies has been successfully used generate strong immune responses and is currently in clinical trials for cancer immunotherapy. Whilst immunotherapy focuses on the induction of CD8(+) T-cell responses, many successful vaccines pathogens or their toxins utilize humoral immunity as primary effector mechanism. Universally, these approaches have adjuvants pathogen material that augment responses. However, are associated with...
Abstract Ab-targeted vaccination involves targeting a receptor of choice expressed by dendritic cells (DCs) with Ag-coupled Abs. Currently, there is little consensus as to which criteria determine selection ensure superior Ag presentation and immunity. In this study, we investigated parameters DC internalization determined how they impact outcomes. First, using mixed bone marrow chimeras, established that Ag-targeted, but not nontargeted, DCs are responsible for in settings vivo. Next,...
Phaeodactylum tricornutum has been highly studied for its potential as a platform metabolic engineering. While the possible applications of extrachromosomal expression via an episome have investigated, there is still lack information concerning efficacy and limitations. Therefore, we system in P. tricornutum, aiming to elucidate limitations regarding heterologous protein production rearrangement events. Our objectives were screen positive transconjugants by fluorescent signal indicating...
This study explored the novel immune checkpoint poliovirus receptor-related immunoglobulin domain-containing (PVRIG) in acute myeloid leukemia (AML). We showed that AML patient blasts consistently expressed PVRIG ligand (poliovirus 2, PVRL2). Furthermore, blockade significantly enhanced NK cell killing of PVRL2+, receptor (PVR)lo lines, and increased activation degranulation context primary blasts. However, bone marrow, expression levels were not increased. To understand how might...
Abstract Inter-individual differences in T helper (Th) cell responses affect susceptibility to infectious, allergic and autoimmune diseases. To identify factors contributing these response differences, here we analyze vitro differentiated Th1 cells from 16 inbred mouse strains. Haplotype-based computational genetic analysis indicates that the p53 family protein, p73, affects differentiation. In under conditions vitro, p73 negatively regulates IFNγ production. binds within, or upstream of,...
The increasing demand for novel natural compounds has prompted the exploration of innovative approaches in bioengineering. This study investigates bioengineering potential marine diatom Phaeodactylum tricornutum through introduction cannabis genes, specifically, tetraketide synthase (TKS), and olivetolic acid cyclase (OAC), production cannabinoid precursor, (OA). P. is a promising biotechnological platform due to its fast growth rate, amenability genetic manipulation, ability produce...
Significance Our identification and characterization of the ubiquitin (Ub) Y59-E51 loop have uncovered a pivotal determinant for lysine 48 (K48) linkage-specific Ub chain synthesis catalyzed by Cdc34 E2 Ub-conjugating enzyme. The appears to anchor E2-engaging zone, allowing landing enabling it gain access receptor K48. These findings will provide strong starting point future biochemical structural studies aiming elucidate detailed interactions between E2/E3 enzymes that produce K48 linkage....
DEC-205 (CD205), a member of the macrophage mannose receptor protein family, is prototypic endocytic dendritic cells, whose ligands include phosphorothioated cytosine-guanosine oligonucleotides, motif often seen in bacterial or viral DNA. However, despite growing biological and clinical significance, little known about structural arrangement this any its family members. Here, we describe 3.2 Å cryo-EM structure human DEC-205, thereby illuminating family. The monomer forms compact comprising...
Abstract DEC-205 is a cell-surface receptor that transports bound ligands into the endocytic pathway for degradation or release within lysosomal endosomes. This has been reported to bind number of ligands, including keratin, and some classes CpG oligodeoxynucleotides (ODN). In this study, we explore in detail requirements binding ODNs, revealing efficiently binds single-stranded, phosphorothioated ODN ≥14 bases, with preference DNA base thymidine, but no requirement motif. fails...
In single-cell RNA sequencing (scRNA-seq), doublets form when two cells are encapsulated into one reaction volume by chance. The existence of doublets, which appear as but not real cells, is a key confounder in scRNA-seq data analysis. Computational methods have been developed to detect data; however, the field lacks comprehensive benchmarking these methods, making it difficult for researchers choose an appropriate method their specific analysis needs. Here, we conducted first, systematic...
Commercial kits can provide a convenient solution for measuring circulating biomarkers to support drug development. However, their suitability should be assessed in the disease matrix of interest.Twelve were evaluated samples from patients with rheumatoid arthritis. We used immunoassay five vendors on three multiplexed platforms. Kit was basis detectability and prespecified performance acceptance criteria.Assays had varying levels sensitivity susceptibility interference by components. Only...
Abstract Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative diseases that exist on a clinico-pathogenetic spectrum, designated ALS/FTD. The most common genetic cause of ALS/FTD is the expansion intronic hexanucleotide repeat (GGGGCC) n in C9orf72 . Here, we investigated formation nucleic-acid secondary structures these repeats, their role generating condensates characteristic diseases. We observed significant aggregation sequence , which associated to...