A5006442726- Antimicrobial Peptides and Activities
- Ubiquitin and proteasome pathways
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- T-cell and B-cell Immunology
- Immune cells in cancer
- Immune responses and vaccinations
- interferon and immune responses
- Epigenetics and DNA Methylation
- Hematopoietic Stem Cell Transplantation
- Aquaculture disease management and microbiota
- Acute Myeloid Leukemia Research
- Biochemical and Structural Characterization
- Pediatric health and respiratory diseases
- Biomedical Text Mining and Ontologies
- RNA modifications and cancer
- DNA Repair Mechanisms
- Bioinformatics and Genomic Networks
- Histone Deacetylase Inhibitors Research
- Immunodeficiency and Autoimmune Disorders
- NF-κB Signaling Pathways
- Invertebrate Immune Response Mechanisms
- CAR-T cell therapy research
- Sphingolipid Metabolism and Signaling
McGill University
2016-2025
Czech Academy of Sciences, Institute of Physiology
2015-2020
Wellcome Sanger Institute
2011-2014
University of British Columbia
2008-2012
Institute of Infection and Immunity
2009-2010
University of Oxford
2006-2009
Advisory Board Company (United States)
2009
University of San Francisco
2009
Centre for Human Genetics
2003-2006
A greater understanding of hematopoietic stem cell (HSC) regulation is required for dissecting protective versus detrimental immunity to pathogens that cause chronic infections such as Mycobacterium tuberculosis (Mtb). We have shown systemic administration Bacille Calmette-Guérin (BCG) or β-glucan reprograms HSCs in the bone marrow (BM) via a type II interferon (IFN-II) interleukin-1 (IL1) response, respectively, which confers trained against Mtb. Here, we demonstrate that, unlike BCG...
Abstract With the rapid rise in incidence of multidrug resistant infections, there is substantial interest host defense peptides as templates for production new antimicrobial therapeutics. Natural are multifunctional mediators innate immune response, with some direct activity and diverse immunomodulatory properties. We have previously developed an regulator (IDR) 1, protective against bacterial infection mediated entirely through its effects on immunity host, a novel approach to...
Abstract The human cationic host defense peptide LL-37 has a broad range of immunomodulatory, anti-infective functions. A synthetic innate regulator peptide, 1 (IDR-1), based conceptually on LL-37, was recently shown to selectively modulate immunity protect against wide bacterial infections. Using advanced proteomic techniques, ELISA, and Western blotting procedures, GAPDH identified as direct binding partner for in monocytes. Enzyme kinetics mobility shift studies also indicated IDR-1...
Innate immunity is triggered by a variety of bacterial molecules, resulting in both protective and potentially harmful pro-inflammatory responses. Further, innate also provides mechanism for the maintenance homeostasis between host immune system symbiotic or non-pathogenic microorganisms. However, factors that mediate these effects have been incompletely defined. Here, it was demonstrated lantiobiotic nisin Z able to modulate responses immunity. Nisin induced secretion chemokines MCP-1, IL-8...
The rapidly increasing incidence of multidrug-resistant infections and the alarmingly low rate discovery conventional antibiotics create an urgent need for alternative strategies to treat bacterial infections. Host defence peptides are short cationic molecules produced by immune systems most multicellular organisms; they a class compounds being actively researched. In this review, we provide overview antimicrobial immunomodulatory activities natural host peptides, discuss creating artificial...
Abstract The human cathelicidin peptide LL-37 is a multifunctional immunomodulatory and antimicrobial host defense of the immune system. modulates cell responses to microbial stimuli also affects action other endogenous mediators such as IL-1β GM-CSF. This activity known be complex, with functional outcomes being dependent on type activation status, timing exposure, present. It was demonstrated in this study that inhibited cellular IFN-γ, key cytokine Th1-polarized immunity. inhibitory IFN-γ...
Abstract Sphingosine-1-phosphate (S1P) is lipid messenger involved in the regulation of embryonic development, immune system functions, and many other physiological processes. However, mechanisms S1P transport across cellular membranes remain poorly understood, with several ATP-binding cassette family members spinster 2 (Spns2) member major facilitator superfamily known to mediate cell culture. Spns2 was also shown control activities zebrafish vivo play a critical role cardiovascular...
Spinster homolog 2 (Spns2) acts as a Sphingosine-1-phosphate (S1P) transporter in zebrafish and mice, regulating heart development lymphocyte trafficking respectively. S1P is biologically active lysophospholipid with multiple roles signalling. The mechanism of action Spns2 still elusive mammals. Here, we report that Spns2-deficient mice rapidly lost auditory sensitivity endocochlear potential (EP) from to 3 weeks old. We found progressive degeneration sensory hair cells the organ Corti, but...
p53 is a central mediator of cellular stress responses, and its precise regulation essential for the normal progression hematopoiesis. MYSM1 an epigenetic regulator maintenance hematopoietic stem cell (HSC) function, progenitor survival, lymphocyte development. We recently demonstrated that all developmental phenotypes Mysm1 deficiency are p53-mediated rescued in Mysm1−/−p53−/− mouse model. However, mechanisms triggering activation Mysm1−/− HSPCs, pathways downstream driving different...
The rapidly increasing incidence of multidrug-resistant infections and the alarmingly low rate discovery conventional antibiotics create an urgent need for alternative strategies to treat bacterial infections. Host defence peptides are short cationic molecules produced by immune systems most multicellular organisms; they a class compounds being actively researched. In this review, we provide overview antimicrobial immunomodulatory activities natural host peptides, discuss creating artificial...
Cathelicidin LL-37 is a multifunctional immunomodulatory and antimicrobial host defense peptide that has an important role in the immune defenses of skin other epithelial barriers. We have previously demonstrated at physiological concentrations synergistically augments production mediators response to microbial compounds human primary keratinocytes. Here we define signaling mechanisms responsible for this activity. demonstrate inhibition Src family kinases (SFKs) strongly inhibited...
Abstract The pathophysiology of fibromyalgia syndrome (FMS) remains elusive, leading to a lack objective diagnostic criteria and targeted treatment. We globally evaluated immune system changes in FMS by conducting multiparametric flow cytometry analyses peripheral blood mononuclear cells identified natural killer (NK) cell decrease patients with FMS. Circulating NK were exhausted yet activated, evidenced lower surface expression CD16, CD96, CD226 more CD107a TIGIT. These hyperresponsive,...
Hematopoietic stem cells (HSCs) serve as a life-long reservoir for all blood cell types and are clinically useful variety of HSC transplantation-based therapies. Understanding the role chromatin organization regulation in homeostasis may provide important insights into development. Bromodomain- PHD finger-containing protein 1 (BRPF1) is multivalent regulator that possesses 4 nucleosome-binding domains activates 3 lysine acetyltransferases (KAT6A, KAT6B, KAT7), suggesting this has potential...
Abstract Low dose methotrexate (LD-MTX) remains the gold standard in rheumatoid arthritis (RA) therapy. Multiple mechanisms on a variety of immune cells contribute to anti-inflammatory effects LD-MTX. Inflammatory signaling is deeply implicated hematopoiesis by regulating hematopoietic stem and progenitor cell (HSPC) fate decisions; raising question whether HSPC are also modulated This first study characterize LD-MTX HSPC. CD34+ were isolated from healthy donors’ non-mobilized peripheral...