A5049531033- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunodeficiency and Autoimmune Disorders
- Immunotherapy and Immune Responses
- Hippo pathway signaling and YAP/TAZ
- Cell Adhesion Molecules Research
- Cellular Mechanics and Interactions
- Cellular transport and secretion
- Microtubule and mitosis dynamics
- CAR-T cell therapy research
- Gut microbiota and health
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Lymphoma Diagnosis and Treatment
- Cancer Immunotherapy and Biomarkers
- IL-33, ST2, and ILC Pathways
- Asthma and respiratory diseases
- HER2/EGFR in Cancer Research
- Ubiquitin and proteasome pathways
- Inflammatory Biomarkers in Disease Prognosis
- Protein Tyrosine Phosphatases
- 14-3-3 protein interactions
Université de Montréal
2015-2024
Parker Institute for Cancer Immunotherapy
2024
Montreal Clinical Research Institute
2015-2024
Cornell University
2024
Weill Cornell Medicine
2024
Swim Across America
2024
ICOS is a T-cell costimulatory receptor critical for Tfh cell generation and function. However, the role of in Tfr differentiation remains unclear. Using Foxp3-Cre–mediated knockout (ICOS FC) mice, we show that deficiency Treg-lineage cells drastically reduces number during GC reactions but has minimal impact on conventional Treg cells. Single-cell transcriptome analysis Foxp3 + at an early stage reaction suggests normally inhibits Klf2 expression to promote follicular features including...
Abstract ICOS is a key costimulatory receptor facilitating differentiation and function of follicular helper T cells inflammatory cells. Rheumatoid arthritis patients were shown to have elevated levels ICOS+ in the synovial fluid, suggesting potential role ICOS-mediated cell costimulation autoimmune joint inflammation. In this study, using knockout knockin mouse models, we found that signaling required for induction maintenance collagen-induced (CIA), murine model rheumatoid arthritis. For...
Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive peripheral driven by a pool of neoplastic cells originating from T follicular helper (Tfh) and concomitant expansion B cells. Conventional chemotherapies for AITL have shown limited efficacy, as such, there need improved therapeutic options. Because originates Tfh cells, we hypothesized that tumors continue to rely on essential components intimate T-cell-B-cell (T-B) interactions. Using spontaneous mouse model (Roquinsan/+ mice),...
Protein kinases carry out important functions in cells both by phosphorylating substrates and means of regulated non-catalytic activities. Such have been ascribed to many kinases, including some members the Ste20 family. The Drosophila kinase Slik phosphorylates activates Moesin developing epithelial tissues promote tissue integrity. It also non-catalytically cell proliferation growth. We carried a structure-function analysis determine how these two distinct activities are controlled. find...
The role of ICOS in antitumor T cell responses and overall tumor progression has been controversial. In this study, we compared mice lacking selectively regulatory (Treg) cells or all cells. Using an experimental melanoma lung metastasis model, found that Treg cell-specific knockout reduces the burden with Cre control mice, increased CD4+-to-Treg CD8+-to-Treg ratios tumor. contrast, there was no difference compartments. This suggests a dual costimulation promoting protumor responses....
Abstract The protein kinase Mst1 is a key component of the evolutionarily conserved Hippo pathway that regulates cell survival, proliferation, differentiation, and migration. In humans, deficiency causes primary immunodeficiency. Patients with MST1-null mutations show progressive loss naive T cells but, paradoxically, mildly elevated serum Ab titers. Nonetheless, role in humoral immunity remains poorly understood. this study, we found early cell–dependent IgG1 responses young adult...
Talin is the major scaffold protein linking integrin receptors with actin cytoskeleton. In Drosophila, extended generates a stable link between sarcomeric cytoskeleton and tendon matrix at muscle attachment sites. Here, we identify phosphorylation sites on Drosophila by mass spectrometry. phosphorylated in late embryogenesis when muscles differentiate, especially T152 exposed loop of F1 domain head. Localization mutated version (Talin-T150/T152A) reduced can only partially rescue compared...
ICOS is induced in activated T cells and its main role to boost differentiation function of effector cells. also constitutively expressed a subpopulation Foxp3+ regulatory under steady-state condition. Studies using germline knockout mice or ICOS-blocking reagents suggested that has supportive roles (Treg) cell homeostasis, migration, function. To avoid any compounding effects may arise from ICOS-deficient non-Treg cells, we generated conditional system which expression selectively abrogated...
Abstract The crosstalk between gut microbiome and anti-tumor immunity has recently gained attention in clinical settings. administration of antibiotics during immune checkpoint blockade (ICB) therapies been correlated with poorer outcomes cancer patients, suggesting that alterations affect overall responses to ICB. establishment microbiota-specific T cell clones tumor cross-reactivity potential was proposed as one the mechanisms linking responses. Vaccine-based strategies aimed at...
Abstract Cysteine-binding targeted drugs AMG-510 and MRTX-849 provide a new therapeutic approach for advanced KRASG12C mutant cancers. However, clinical response has been limited. Responders eventually develop adaptive resistance by gaining additional MAPK pathway mutations, resulting in limited benefit. High-dose pulsatile treatment with inhibitors proposed as an alternative strategy to alleviate while maintaining tumor control. The sensitivity of cells pan-inhibitors the pathway, crucial...
Abstract The Inducible Costimulator (ICOS) is a T cell costimulatory receptor critical for humoral immunity. ICOS-deficient patients suffer from recurrent infections due to lack of protective antibodies. However, some also display signs antibody-mediated autoimmunity. These findings may reflect dual role ICOS: facilitating the differentiation and function follicular helper (Tfh) regulatory (Tfr) cells. While Tfh cells are known provide help B produce high affinity antibodies, main Tfr seems...
Abstract The inducible T-cell costimulator (ICOS) is a key costimulatory receptor facilitating differentiation and function of follicular helper T cells inflammatory cells. Rheumatoid arthritis patients were shown to have elevated levels ICOS+ in the synovial fluid suggesting potential role ICOS-mediated cell costimulation autoimmune joint inflammation. In this study, using ICOS knockout knockin mouse models, we found that phosphoinositide 3-kinase (PI3K) signaling required for induction...
ABSTRACT ICOS is a T cell costimulatory receptor critical for Tfh generation and function. However, the role of in Tfr differentiation remains unclear. Using Foxp3-Cre-mediated knockout (ICOS FC) mice, we show that deficiency Treg-lineage cells drastically reduces number during GC reactions but has minimal impact on conventional Treg cells. Single-cell transcriptome analysis Foxp3 + at an early stage reaction suggests normally inhibits Klf2 expression to promote follicular features including...