A5008262521- Immune Cell Function and Interaction
- IL-33, ST2, and ILC Pathways
- Eosinophilic Esophagitis
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Axon Guidance and Neuronal Signaling
- Immunodeficiency and Autoimmune Disorders
- Asthma and respiratory diseases
- Immune Response and Inflammation
- Fungal Infections and Studies
- Angiogenesis and VEGF in Cancer
- Extracellular vesicles in disease
- Antifungal resistance and susceptibility
- interferon and immune responses
- Nail Diseases and Treatments
- Eosinophilic Disorders and Syndromes
- RNA modifications and cancer
- Allergic Rhinitis and Sensitization
- Gut microbiota and health
- Ubiquitin and proteasome pathways
- Respiratory viral infections research
- Cancer-related molecular mechanisms research
- Gastroesophageal reflux and treatments
- Single-cell and spatial transcriptomics
- Pediatric health and respiratory diseases
McGill University
2014-2023
AstraZeneca (United States)
2022-2023
McGill University Health Centre
2018-2019
Inborn errors of human IFN-γ-dependent macrophagic immunity underlie mycobacterial diseases, whereas inborn IFN-α/β-dependent intrinsic viral diseases. Both types IFNs induce the transcription factor IRF1. We describe unrelated children with inherited complete IRF1 deficiency and early-onset, multiple, life-threatening diseases caused by weakly virulent mycobacteria related intramacrophagic pathogens. These have no history severe disease, despite exposure to many viruses, including...
Abstract Breast cancer diagnosed within 10 years following childbirth is defined as postpartum breast (PPBC) and highly metastatic. Interactions between immune cells other stromal the involuting mammary gland are fundamental in facilitating an aggressive tumor phenotype. The MNK1/2–eIF4E axis promotes translation of prometastatic mRNAs cells, but its role modulating function nontumor PPBC microenvironment has not been explored. Here, we used a combination vivo models vitro assays to study...
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...
Elicitation of type I interferon (IFN-I) has been shown to both enhance and impair cell-mediated immune responses in acute persistent viral infections, respectively. Here, we show that addition its effect on T cells, IFN-I drives impairment specific antibody through interaction with B cells the phase lymphocytic choriomeningitis virus (LCMV) infection. This was limited cell-dependent cell response associated disruption follicles, development hypergammaglobulinemia (HGG) expansion follicular...
Abstract Innate immune responses provoke the accumulation of leukocytes at sites inflammation. In addition to monocytes and granulocytes, B cells also participate in antimicrobial innate responses; however, mechanisms for inflammation are not well understood. To study cell following systemic inflammation, we used a model synthetic ligand that stimulates specific pattern recognition molecule, nucleotide-binding oligomerization domain–containing protein 1 (Nod1). Upon exposure Nod1 agonists,...
The regulatory properties of B cells have been studied in autoimmune diseases; however, their role allergic diseases is poorly understood. We demonstrate that Semaphorin 4C (Sema4C), an axonal guidance molecule, plays a crucial cell function. Mice deficient Sema4C exhibited increased airway inflammation after allergen exposure, with massive eosinophilic lung infiltrates and Th2 cytokines. This phenotype was reproduced by mixed bone marrow chimeric mice only cells, indicating lymphocytes were...
Group 2 innate lymphoid cells (ILC2s) play a key role in the initiation and orchestration of early type immune responses. Upon tissue damage, ILC2s are activated by alarmins such as IL-33 rapidly secrete large amounts signature cytokines. ILC2 activation is governed network transcriptional regulators including nuclear factor (NF)-κB family transcription factors. While it known that activating receptor signaling results downstream NF-κB activation, underlying molecular mechanisms remain...
Abstract MYSM1 is a chromatin-binding histone deubiquitinase. mutations in humans result lymphopenia whereas loss of Mysm1 mice causes severe hematopoietic abnormalities, including an early arrest B cell development. However, it remains unknown whether required at later checkpoints development or for cell–mediated immune responses. We analyzed conditional mouse models Mysm1fl/flTg.mb1-cre, Mysm1fl/flTg.CD19-cre, and Mysm1fl/flTg.CD21-cre with inactivation prepro-B, pre-B, follicular stages...
The genetic basis of natural susceptibility to progressive Cryptococcus neoformans infection is not well understood. Using C57BL/6 and CBA/J inbred mice, we previously identified three chromosomal regions associated with C. (Cnes1, Cnes2, Cnes3). To validate characterize the role Cnes2 during host response, constructed a congenic strain on background (B6.CBA-Cnes2). Phenotypic analysis B6.CBA-Cnes2 mice 35 days after showed significant reduction fungal burden in lungs spleen higher pulmonary...
Single-cell RNA sequencing (scRNA-seq) is the state-of-the-art approach to study transcriptomic signatures in individual cells respiratory health and disease. However, classical scRNA-seq approaches provide no spatial information are performed using either bronchoalveolar lavage fluid (BAL) or lung single cell suspensions assess transcript levels airway tissue immune cells, respectively. Herein we describe a simple method simultaneously characterize features of airway, parenchymal...
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 We have previously found that mice with Semaphorin 4C (Sema4C) deficient B cells exhibited exaggerated airway damage and pulmonary inflammation during allergic airways disease (AAD). aimed to determine the mechanisms by which Sema4C on B-cells regulates AAD. Following allergen exposure, Sema4C-/- AAD had significantly fewer CD138high IL-10+ (CD138high Breg) increased IL4+ in spleen. In vitro, consistently failed differentiate into Breg under Th2 culture conditions. Adoptive transfer...
Abstract Group 2 innate lymphoid cells (ILC2) are recently discovered lymphocyte subpopulations that have ability to produce large quantities of a specific set cytokines regulating and adaptive immune responses. Importantly, deregulated ILC2 responses implicated in detrimental type immunopathologies such as allergies, asthma atopic dermatitis, well fibrotic disease, both rodents humans. However, the progress our understanding biology has been hampered by their scarcity at steady state...
Abstract Purpose Breast cancer diagnosed within 10 years following childbirth is defined as postpartum breast (PPBC) and highly metastatic. Interactions between immune cells other stromal the involuting mammary gland are fundamental in facilitating an aggressive tumor phenotype. The MNK1/2-eIF4E axis promotes translation of pro-metastatic mRNAs cells, but its role modulating function non-tumor PPBC microenvironment, particular activity human PPBC, has not been explored. Experimental design...
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...