A5056764614- Adenosine and Purinergic Signaling
- Immune Cell Function and Interaction
- HIV Research and Treatment
- T-cell and B-cell Immunology
- Cancer Immunotherapy and Biomarkers
- Cancer Mechanisms and Therapy
- Peptidase Inhibition and Analysis
- interferon and immune responses
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Connective Tissue Growth Factor Research
- RNA Interference and Gene Delivery
- Inflammation biomarkers and pathways
- HER2/EGFR in Cancer Research
- Vagus Nerve Stimulation Research
- Lung Cancer Treatments and Mutations
- Prostate Cancer Treatment and Research
- HIV/AIDS drug development and treatment
- Developmental Biology and Gene Regulation
- Polyomavirus and related diseases
- Synthesis of Tetrazole Derivatives
- Synthesis and Biological Evaluation
- Kruppel-like factors research
- Adolescent and Pediatric Healthcare
- Wireless Power Transfer Systems
Clinical Research Institute
2011-2025
Montreal Clinical Research Institute
2001-2023
Centre Hospitalier de l’Université de Montréal
2015-2023
Université de Montréal
2015-2023
MRC Laboratory of Molecular Biology
2013
Abstract The ectonucleotidases CD39 and CD73 catalyze extracellular ATP to immunosuppressive adenosine, as such, represent potential cancer targets. We investigated biological impacts of in pancreatic ductal adenocarcinoma (PDAC) by studying clinical samples experimental mouse tumors. Stromal tumoral expression significantly associated with worse survival human PDAC abolished the favorable prognostic impact presence tumor-infiltrating CD8+ T cells. In transplanted KPC tumors, both on myeloid...
Inhibition of adenosine A2A receptor (A2AR) is a promising approach for cancer immunotherapy currently evaluated in several clinical trials. We here report that anti-obesogenic and anti-inflammatory functions A2AR, however, significantly restrain hepatocellular carcinoma (HCC) development. Adora2a deletion mice triggers obesity, non-alcoholic steatohepatitis (NASH), systemic inflammation, leading to spontaneous HCC promoting dimethylbenzyl-anthracene (DMBA)- or diethylnitrosamine...
Abstract Rheumatoid arthritis (RA) is a chronic autoimmune disease with significant morbidity and mortality. Recent studies suggest that modulation of adenosine signaling, potent immunosuppressive pathway, promising approach for treatment RA. Extracellular can come from two sources: transport intracellular hydrolysis extracellular adenine nucleotides by CD73. In this study, we investigated the susceptibility CD73-deficient C57BL/6 mice to collagen-induced (CIA), well-established mouse model...
The formation of new lymphatic vessels, or lymphangiogenesis, is a critical step the tissue repair program. In pathological conditions involving chronic inflammation tumorigenesis, this process often dysregulated and can contribute to disease progression. Yet, lymphangiogenesis still incompletely understood. study, we identified A2a adenosinergic signaling as an important regulator inflammatory tumor-associated lymphangiogenesis. Using Adora2a (A2a)-deficient mice, demonstrated that was...
Abstract Human in vitro studies of HIV Nef on TcR proximal signaling have been controversial and not provided an integrated picture its impact. Tyrosine (Y) phosphorylation (pY) Lck substrates (CD3ζ, Zap-70) was investigated vivo, Nef-expressing transgenic (Tg) thymocytes. In Tg cells, mis-localized activated, but the pY-CD3ζ levels were unexpectedly lower, both constitutively after anti-CD3ε Ab stimulation. also favors hyperphosphorylation Y505 site accumulation doubly phosphorylated (Y394,...
Innate and adaptive immune cells play an important role in the therapeutic activity of anti-ErbB2 mAbs, such as trastuzumab. In clinic, breast tumors poorly infiltrated with are more resistant to trastuzumab, patients have a worse prognosis. Because type I II IFNs critical immune-mediated mAb, we investigated effect combining polyI:C CpG trastuzumab-like therapy immunocompetent mouse models ErbB2+ cancer. We demonstrated that situ delivery combined systemic mAb triggered potent inflammatory...
Background: WNT1-Inducible Signaling Pathway Protein 1 (WISP1) is implicated in prostate cancer growth and metastasis the regulation of inflammation diverse benign diseases. The objectives this study were to assess prognostic value WISP1, its association relevance as a biomarker for immune checkpoint blockade (ICB) response.Methods: Publicly available RNA-seq datasets used evaluate WISP1 gene expression with tumor-infiltrating lymphocytes, inflamed tumor microenvironment, anti-PD-1 ICB...
ABSTRACT In order to study the functions of simian immunodeficiency virus (SIV) Nef in vivo a small-animal model, we constructed transgenic (Tg) mice expressing SIV mac 239 nef gene natural target cells under control human CD4 promoter (CD4C). These CD4C/SHIV- Tg develop severe AIDS-like disease, with manifestations including premature death, failure thrive or weight loss, wasting, thymic atrophy, an especially low number peripheral CD8 + T as well cells, diarrhea, splenomegaly, and kidney...
The cellular and molecular mechanisms of dysfunction depletion CD4+ T lymphocytes over the course human immunodeficiency virus type 1 (HIV-1) infection are still incompletely understood, but chronic immune activation is thought to play an important role in disease progression. We studied T-cell biology CD4C/HIV transgenic (Tg) mice, which Nef expression sufficient induce a severe AIDS-like including preferential decrease cells. show here that Nef-expressing Tg cells exhibit...
CD4(+)- and CD8(+)-T-cell death is a frequent immunological dysfunction associated with the development of human AIDS. We studied murine model AIDS, CD4C/HIV transgenic (Tg) mouse model, to assess importance apoptotic pathway in immunodeficiency virus type 1 (HIV-1) pathogenesis. In these Tg mice, Nef major determinant disease expressed immature mature CD4(+) T cells macrophage/myeloid lineage. report here novel AIDS-like phenotype: enhanced death, most likely by apoptosis (as assessed...
ABSTRACT CD4C/HIV nef transgenic (Tg) mice express Nef in CD4 + T cells and the of macrophage/monocyte/dendritic lineage, they develop an AIDS-like disease similar to human AIDS. In these mice, is constitutively expressed throughout life. To rule out contribution any developmental defects caused by early expression Nef, we generated inducible immunodeficiency virus type 1 (HIV-1) Tg using tetracycline-inducible system. Faithful transgene was induced (CD4C/rtTA × TRE/HIV ) or (CD4C/rtTA2 S...
ABSTRACT We previously reported that CD4C/human immunodeficiency virus (HIV) Nef transgenic (Tg) mice, expressing in CD4 + T cells and of the macrophage/dendritic cell (DC) lineage, develop a severe AIDS-like disease, characterized by depletion cells, as well lung, heart, kidney diseases. In order to determine contribution distinct populations hematopoietic development this five additional Tg strains through restricted cell-specific regulatory elements were generated. These express DCs,...
The HIV-1 Nef protein is a major determinant of pathogenicity. It has been found to induce thymocyte depletion, but the mechanisms involved are not completely understood. Also, nothing known about its effects on selection. We used CD4C/HIV(Nef) transgenic (Tg) mice, which develop profound CD4(+) T cell lymphopenia, study their thymic development. report that causes depletion double-positive thymocytes and impairs selection lineage commitment single-positive thymocytes. This latter defect...
We have previously characterized a human blood CD19+CD1c+IgM+CD27+CD21loCD10+ innate-like B-cell population, which presents features shared by both transitional immature and marginal zone (MZ) B-cells, named herein "precursor-like" MZ B-cells. B-cells with similar attributes been associated regulatory potential (Breg). In order to clarify this issue better characterize we proceeded RNA-Seq transcriptome profiling of mature precursor-like taken from the healthy donors. report that ex vivo...
HIV-1 infection causes depletion and/or dysfunction of distinct CD4(+) T cell subsets and may affect these differently. Using the CD4C/HIV-1(Nef) transgenic (Tg) mice as a model, we report that Nef total cells, but preserves relatively enriches regulatory cells (Treg). We found Nef-mediated Treg enrichment is direct result expression in occurs independently Nef-induced lymphopenia, most likely results from multiple mechanisms: lower apoptosis, enhanced division, increased generation...
Abstract We previously found that provirus insertion in T cell tumors of mouse mammary tumor virus/c-myc transgenic (Tg) mice induced two forms Notch1 mutations. Type I mutations generated truncated molecules, one intracellular (IC) (Notch1IC) and extracellular (Notch1EC), while type II was deleted its C terminus (Notch1ΔCT). expressed these mutants Tg using the CD4 promoter. Both Notch1IC Notch1ΔCT, but not Notch1EC, developed double-positive (DP) thymomas. These disseminated more...
The ecto-nucleotidase CD73 is an important immune checkpoint in tumor immunity that cooperates with CD39 to hydrolyze pro-inflammatory extracellular ATP into immunosuppressive adenosine. While the role of evasion solid cancers well established, its leukemia remains unclear. To investigate pathogenesis chronic lymphocytic (CLL), Eµ-TCL1 transgenic mice spontaneously develop CLL were crossed CD73−/− mice. Disease progression peripheral blood and spleen, markers evaluated by flow cytometry...
Many individuals at risk of streptococcal infection respond poorly to the pneumococcal polysaccharide vaccine Pneumovax 23. Identification actionable pathways able enhance responsiveness is highly relevant. We investigated contribution extracellular adenosine pathway regulated by ecto-nucleotidase CD73 in Pneumovax-induced antibody responses. Using gene-targeted mice, we demonstrated that CD73-or A2a receptor deficiency significantly delayed isotype switching. Nevertheless, CD73- or A2aR-...