A5032891902- Viral Infections and Immunology Research
- CAR-T cell therapy research
- Monoclonal and Polyclonal Antibodies Research
- Cytomegalovirus and herpesvirus research
- Immune Cell Function and Interaction
- Cancer, Hypoxia, and Metabolism
- Nanofabrication and Lithography Techniques
- Cytokine Signaling Pathways and Interactions
- Metabolism, Diabetes, and Cancer
- T-cell and B-cell Immunology
- Pancreatic function and diabetes
- Vitamin C and Antioxidants Research
- Epigenetics and DNA Methylation
- Helicobacter pylori-related gastroenterology studies
- Cancer Research and Treatments
- Autophagy in Disease and Therapy
- MicroRNA in disease regulation
- Diabetes and associated disorders
- Heme Oxygenase-1 and Carbon Monoxide
- Asthma and respiratory diseases
- RNA modifications and cancer
- Tracheal and airway disorders
- Cystic Fibrosis Research Advances
- Genetic factors in colorectal cancer
- RNA regulation and disease
Zymeworks (Canada)
2021-2025
McGill University
2013-2018
McGill University Health Centre
2013-2017
Occupational Cancer Research Centre
2014
Goodman (Japan)
2014
Czech Academy of Sciences, Institute of Physiology
2014
Case Western Reserve University
2010
University of British Columbia
2007-2010
University School
2010
Microbial infection triggers assembly of inflammasome complexes that promote caspase-1–dependent antimicrobial responses. Inflammasome is mediated by members the nucleotide binding domain leucine-rich repeat (NLR) protein family respond to cytosolic bacterial products or disruption cellular processes. Flagellin injected into host cells invading Salmonella induces activation through NLRC4, whereas NLRP3 required for in response multiple stimuli, including microbial infection, tissue damage,...
Germline mutations in STK11, which encodes the tumor suppressor liver kinase B1 (LKB1), promote Peutz-Jeghers syndrome (PJS), a cancer predisposition characterized by development of gastrointestinal (GI) polyps. Here, we report that heterozygous deletion Stk11 T cells (LThet mice) is sufficient to GI polyposis. Polyps from LThet mice, Stk11+/- and human PJS patients display hallmarks chronic inflammation, marked inflammatory immune-cell infiltration, signal transducer activator transcription...
Abstract Mesothelin (MSLN) is a tumor associated antigen overexpressed in many cancer indications and an attractive target for immunotherapies including bispecific T cell engagers (TCE) chimeric receptor (CART) cells. While MSLN-targeting have shown signs of clinical activity, their success has been hindered by dose-limiting toxicities with on-target off-tumor effects cytokine release syndrome (CRS). To overcome these issues, we engineered ZW171, TCE, enhanced safety antitumor activity....
Background Chronic myocarditis is often initiated by viral infection, the most common of which coxsackievirus infection. The precise mechanism infection leads to chronic autoimmune pathology poorly understood, however it clear that early immune response plays a critical role. Previous results have shown inflammatory cytokine interleukin (IL)-6 integral development experimental-induced myocarditis. However, function IL-6 during viral-mediated autoimmunity has yet be elucidated. Methods and...
Cystic fibrosis (CF) transmembrane conductance regulator ( Cftr) knockout mice present the clinical features of low body weight and intestinal disease permitting an assessment interrelatedness these phenotypes in a controlled environment. To identify alterations that are affected by CF mice, histological crypt-villus axis height, goblet cell hyperplasia, mast infiltrate, crypt proliferation, apoptosis were measured population 12-wk-old (C57BL/6 × BALB/cJ) F2 Cftr tm1UNC non-CF presenting...
Development of viral-induced chronic myocarditis is thought to involve both environmental and genetic factors. However, date, no susceptibility genes have been identified.We sought identify loci that confer with the use chromosome substitution strain mice are composed 1 from disease susceptible A/J on an otherwise resistant C57BL/6 background. By this method, we identified 17 susceptibility. To further isolate region susceptibility, 8 strains congenic for different portions were generated....
Interleukin (IL)‐6 is a pleiotropic cytokine that plays key role in wide variety of diseases. Based on number adjuvant‐induced experimental models, IL‐6 critical to the development autoimmune diseases including encephalomyelitis, arthritis, and myocarditis. However, whether it pathogenic viral‐induced myocarditis has been less well defined. While models have clearly linked generation autoreactive T cells, exhibited protective disease models. As pathogen infection majority patients,...
Coxsackievirus infections are a major cause of chronic autoimmune myocarditis, known precursor to dilated cardiomyopathy. Dilated cardiomyopathy leads heart failure and is responsible for nearly half all transplant cases. The induction autoimmunity following coxsackievirus infection governed by the interplay several genetic immunological factors. In this review, we will focus on how innate immune response viral directs cascade events that ultimately results in disease.
Abstract IL-12 is a cytokine produced by antigen-presenting cells that increases T cell proliferation, IFN gamma mediated Th1 effector functions and NK cytotoxicity. While these effects generate potent anti-tumor immunity in mouse models, the high toxicity of cancer patients has limited its clinical utility. Potency attenuation intratumoral localization may improve tolerability, but approaches can reduce efficacy or be delivery tumor antigen expression. To both tolerability IL-12, we...
Abstract Bispecific T cell engagers (TCEs) have exhibited clinical successes in the treatment of hematological cancers, while solid tumors remains a challenge. Treatment with conventional CD3-engaging TCEs can result limited proliferation and recruitment to tumor site, related anergy, thus restricting ability bispecific inhibit growth these poorly infiltrated rapidly growing tumors. Next generation tumor-targeting, trispecific integrated costimulation (TriTCE Co-Stim) potential provide more...
Abstract CD3-bispecific T cell engager (TCE) therapies have exhibited clinical utility against hematological malignancies, but successes in solid tumor indications been limited. Compared to heme treatment of tumors is hindered by immunosuppressed microenvironments that can be refractory traditional TCEs. Immunosuppression the microenvironment limits responses part due expression inhibitory immune checkpoints, such as PD-1 on exhausted cells and PD-L1 cells. To improve anti-tumor activity...
Abstract IL-12 is a pleiotropic cytokine that potently stimulates anti-tumor cytotoxic T and NK cell mediated immunity. Recombinant reduces tumor growth in multiple mouse models, but its therapeutic application has been limited by severe toxicities. Protease dependent activation of therapeutics with high on-target, off-tumor toxicities may be used to localize activity the achieving sufficient exposure activated microenvironment remains challenge. We have previously shown our design strategy...
<h3>Background</h3> Bispecific T cell engagers (TCEs) have shown clinical benefit in treating hematological cancers, but limited success solid tumors. Overcoming the immunosuppressive environment and low infiltration remain some of key challenges limiting activity traditional CD3-engaging bispecific TCEs. Conventional activation requires signaling via CD3 (signal 1) costimulatory molecules 2), such as CD28. Superagonist anti-CD28 antibodies activate cells resulted toxicities with severe...
<h3>Background</h3> Immunosuppression in the solid tumor microenvironment (TME) is a critical obstacle that has limited efficacy of T cell engager (TCE) immunotherapies. Though TCEs can direct cytotoxicity towards tumors, activation and inflammation induce expression immune checkpoint proteins, such as PD-L1. This treatment-related increase suppression TME further limits clinical responses. We have previously presented screening data on panel trispecific engagers (TriTCEs). Preliminary...