A5044146927- Immune Cell Function and Interaction
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Immune cells in cancer
- IL-33, ST2, and ILC Pathways
- Eosinophilic Esophagitis
- Histone Deacetylase Inhibitors Research
- Cancer Immunotherapy and Biomarkers
- Liver physiology and pathology
- Alzheimer's disease research and treatments
- DNA Repair Mechanisms
- Vascular Tumors and Angiosarcomas
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer therapeutics and mechanisms
- Lung Cancer Treatments and Mutations
- Cancer-related gene regulation
- Medical Imaging and Pathology Studies
- Liver Disease Diagnosis and Treatment
- Protein Degradation and Inhibitors
- Hepatitis C virus research
- Tryptophan and brain disorders
- Heme Oxygenase-1 and Carbon Monoxide
- Genomics and Chromatin Dynamics
- PI3K/AKT/mTOR signaling in cancer
- Epigenetics and DNA Methylation
University of Ottawa
2014-2023
Ottawa Hospital
2016-2023
Ottawa Hospital Research Institute
2016-2023
Institute of Infection and Immunity
2020-2021
Trogocytosis modulates immune responses, with still unclear underlying molecular mechanisms. Using leukemia mouse models, we found that lymphocytes perform trogocytosis at high rates tumor cells. While performing trogocytosis, both Natural Killer (NK) and CD8 + T cells acquire the checkpoint receptor PD-1 from In vitro in vivo investigation revealed on surface of NK cells, rather than being endogenously expressed, was derived entirely a SLAM receptor–dependent fashion. acquired via actively...
Cell behavior is highly dependent upon microenvironment. Thus, to identify drugs targeting metastatic cancer, screens need be performed in tissue mimetic substrates that allow cell invasion and matrix remodeling. A novel biomimetic 3D hydrogel platform enables quantitative analysis of viability at the individual level developed using automated data acquisition methods with an invasive lung disease (lymphangioleiomyomatosis, LAM) characterized by hyperactive mammalian target rapamycin complex...
Type 1 innate lymphoid cells (ILC1) are tissue-resident lymphocytes that provide early protection against bacterial and viral infections. Discrete transcriptional states of ILC1 have been identified in homeostatic pathological contexts. However, whether these delineate with different functional properties is not completely understood. Here, we show liver heterogeneous for the expression distinct effector molecules surface receptors, including granzyme A (GzmA) CD160, mice. expressing high...
Blockade of epidermal growth factor receptor (EGFR) activity has been a primary therapeutic target for non-small cell lung cancers (NSCLC). As patients with wild-type EGFR have demonstrated only modest benefit from tyrosine kinase inhibitors (TKIs), there is need additional approaches in EGFR. key component downstream integrin signalling and known cross-talk EGFR, we hypothesized that targeting focal adhesion (FAK) activity, which also shown to correlate aggressive stage NSCLC, would lead...
Non–small cell lung carcinoma (NSCLC) is the most common cause of cancer deaths, with platin-based combination chemotherapy efficacious therapies. Gains in overall survival are modest, highlighting need for novel therapeutic approaches including development next-generation platin regimens. The goal this study was to identify regulators platin-induced cytotoxicity as potential targets further enhance cytotoxicity. Employing RNA-seq transcriptome analysis comparing two parental NSCLC lines...
One of the hallmarks Alzheimer's disease (AD) is accumulation and deposition amyloid-β (Aβ) peptides in brain cerebral vasculature. Aβ evokes neuroinflammation has been implicated insulin signaling disruption JNK-AP1 acti
Anthracyclines, such as doxorubicin, are used first-line chemotherapeutics, usually in combination therapies, for the treatment of advanced breast cancer. While these drugs have been successful therapeutic options, their use is limited due to serious drug related toxicities and acquired tumor resistance. Uncovering molecular mechanisms that mediate doxorubicin's cytotoxic effect will lead identification novel more efficacious therapies allow reduced doses doxorubicin be administered while...
Abstract Leucocytes often perform trogocytosis, the process by which cells acquire parts of plasma membrane from interacting cells. Accumulating evidence indicates that trogocytosis modulates immune responses, but underlying molecular mechanisms are unclear. Here, using two mouse models leukemia, we found cytotoxic lymphocytes at high rates with tumor While performing both Natural Killer and CD8 + T checkpoint receptor PD-1 leukemia In vitro in vivo investigation revealed protein on surface...
Due to their crucial role in tumor immunity, NK cells have quickly became a prime target for immunotherapies, with the adoptive transfer of and use cell engagers moving clinical stage. On other hand, only few studies focused on small molecule drugs capable unleashing against cancer. In this context, repurposing molecules is an attractive strategy identify new immunotherapies from already approved drugs. Here, we developed platform screen compounds based high-throughput luciferase-release...
Abstract Natural Killer (NK) cells are critical for immunosurveillance yet become dysfunctional in contexts such as chronic stimulation by viral infections or cancer. This phenomenon is similar to T cell exhaustion but less well characterized, which limits therapeutic interventions. As shown cells, NK often display an increased expression of immune checkpoint proteins (ICP) following stimulation, and ICP blockade therapies currently being explored several cancer types, have remarkable...
Abstract Immune dysfunction, both depression and hyperactivation, in liver disease contributes to significant morbidities mortalities, depending on damage severity etiology. The underlying causes of immune dysfunction advanced disease, whether pathogen or host-mediated, remain unclear. We reported lasting generalized CD8 + T cell hyperfunction individuals with fibrosis chronic HCV infection. separation viral fibrosis-driven effects the association this phenomenon clinical outcomes remains be...
Abstract Because of their crucial role in tumor immunity, NK cells have quickly become a prime target for immunotherapies, with adoptive transfer and the use cell engagers moving to clinical stage. On other hand, only few studies focused on small molecule drugs capable unleashing against cancer. In this context, repurposing is an attractive strategy identify new immunotherapies from already approved drugs. Here, we screened 1,200 FDA-approved Prestwick Chemical Library, compounds that...