A5057206655- Chronic Lymphocytic Leukemia Research
- Immune Cell Function and Interaction
- Protein Tyrosine Phosphatases
- Virus-based gene therapy research
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Cancer Research and Treatments
- Immune cells in cancer
- CRISPR and Genetic Engineering
- CAR-T cell therapy research
- Pancreatic function and diabetes
- Neuroinflammation and Neurodegeneration Mechanisms
- Melanoma and MAPK Pathways
- Cytokine Signaling Pathways and Interactions
- Synthesis and biological activity
- Acute Lymphoblastic Leukemia research
- PI3K/AKT/mTOR signaling in cancer
- Monoclonal and Polyclonal Antibodies Research
- Apelin-related biomedical research
- Lung Cancer Treatments and Mutations
- Diabetes and associated disorders
- Inflammation biomarkers and pathways
- Reproductive System and Pregnancy
- Glycosylation and Glycoproteins Research
- Adenosine and Purinergic Signaling
Brock University
2025
Q Therapeutics (United States)
2021-2024
Brigham and Women's Hospital
2018-2022
Editas Medicine (United States)
2020-2021
Novartis (United States)
2016-2020
Dana-Farber Cancer Institute
2015-2018
Harvard University
2015-2018
Dana-Farber Brigham Cancer Center
2018
University of Toronto
2003-2016
Sunnybrook Health Science Centre
2011-2012
Abstract Purpose: SHP2 inhibitors offer an appealing and novel approach to inhibit receptor tyrosine kinase (RTK) signaling, which is the oncogenic driver in many tumors or frequently feedback activated response targeted therapies including RTK MAPK inhibitors. We seek evaluate efficacy synergistic mechanisms of combinations with a inhibitor, TNO155, inform their clinical development. Experimental Design: The TNO155 EGFR (EGFRi), BRAFi, KRASG12Ci, CDK4/6i, anti–programmed cell death-1 (PD-1)...
Abstract PD-1 immune checkpoint blockade occasionally results in durable clinical responses advanced metastatic cancers. However, mechanism-based predictors of response to this immunotherapy remain incompletely characterized. We performed comprehensive genomic profiling on a tumor and germline sample from patient with refractory lung adenocarcinoma who achieved marked long-term benefit anti–PD-L1 therapy. discovered activating somatic amino acid variants JAK3 that promoted PD-L1 induction...
Abstract CD200 is a transmembrane molecule with an important immunoregulatory role that overexpressed on most chronic lymphocytic leukemia (CLL) cells. In this study, we characterized previously unknown soluble form of in human plasma termed sCD200. Levels sCD200 were elevated the patients CLL as compared healthy controls, and there was significant correlation disease stage. Infusion sCD200hi into severely immunocompromised NOD.SCIDγcnull (NSG) mice enhanced engraftment splenocytes receiving...
CD200:CD200R interactions deliver immunoregulatory signals. A family of CD200Rs (CD200R1-5) has been described, and engagement CD200R1 by its ligand CD200 suppresses LPS-induced macrophage cytokine production, decreases alloimmune responses in vivo vitro, collagen-induced arthritis.We generated C57BL/6 mice lacking the genomic exons encoding extracellular domains molecule using transformation ES cells explored cell subtypes immune these mice.Myeloid cells/splenocytes from CD200R1(-/-) were...
Abstract CD200 expression on lymphoma/CLL cells, or in CLL serum, suppresses immunity yet is overcome by neutralizing antibody, siRNAs, absorption of from serum. a transmembrane protein broadly expressed variety cell types, which delivers immunoregulatory signals through binding to receptors (CD200Rs) monocytes/myeloid cells and T lymphocytes. Signals delivered the CD200:CD200R axis have been shown play an important role regulation anti-tumor immunity, overexpression has reported number...
Cell therapies such as tumor-infiltrating lymphocyte (TIL) therapy have shown promise in the treatment of patients with refractory solid tumors, improvement response rates and durability responses nevertheless sought. To identify targets capable enhancing antitumor activity T cell therapies, large-scale vitro vivo clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 screens were performed, SOCS1 gene identified a top cell-enhancing target. In murine CD8+ cell-therapy...
Peroxisome proliferator activated receptor-γ (PPARγ) is a lipid-activated nuclear receptor that promotes immune tolerance through effects on macrophages, dendritic cells (DCs), and regulatory T (Tregs). Granulocyte-macrophage colony stimulating factor (GM-CSF) induces PPARγ expression in multiple myeloid cell types. GM-CSF contributes to both protection, but the role of these pathways poorly understood. Here, we reveal an unexpected stimulatory for generation antitumor immunity with...
We have previously reported the existence of a soluble form CD200 (sCD200) in human plasma, and found sCD200 to be elevated plasma Chronic Lymphocytic Leukemia (CLL) patients. CLL cells release at constitutive level, which could attenuated partially by ADAM28 silencing. In this study, we further explored mechanisms shedding beyond that ADAM28, performed biochemical analysis using materials derived from purified Hek293 stably transfected with CD200, antibodies generated specifically against...
Natural scaffolds have been shown to induce T helper 2 (TH2)-specific immune responses in host tissues; however, the precise mechanisms that underlie this response are unknown. Using a porcine animal model, we evaluated role of Toll-like receptors (TLRs) and matrix remodelling implantation bladder acellular (ACM) grafts ACMs fortified with biomimetic materials.Bladders were decellularized detergent treated 3 different ways prior implantation: ACM alone, hyaluronic acid (HA)-ACM HA-vascular...
To examine the reported rates and predictive factors for sleep disturbance in patients with bone metastases.Patients symptomatic metastases treated palliative radiotherapy (RT) were eligible. At initial consultation, demographic information, baseline Brief Pain Inventory (BPI) questionnaire, analgesic consumption recorded. The BPI functional interference item was categorized into none (0), mild (1-3), moderate (4-6), severe (7-10). Follow-up collected person or via telephone post-RT at week...
The novel immunosuppressive molecule, CD200, has been reported to induce immunoregulation after interaction with its receptor(s), CD200R(s), in part at least through augmented induction of regulatory T-cell populations. Independent studies have also described increased expression indoleamine-2,3-dioxygenase CD200R triggering, whereas others provided evidence that TGF-beta is important for the or function many populations T cells. We asked whether a hybrid molecule which soluble fusion...
Abstract Cell therapies such as Tumor Infiltrating Lymphocyte (TIL) therapy have shown promise in the treatment of patients with refractory solid tumors, improvement response rates and durability responses nevertheless sought. To identify targets capable enhancing anti-tumor activity T cell therapies, large-scale vitro vivo CRISPR/Cas9 screens were performed, suppressor cytokine signaling 1 (SOCS1) gene identified a top cell-enhancing target. In murine CD8 models, SOCS1 served critical...
CD200:CD200R interactions regulate immune responses. Since CD200Rs show extensive homology in their extracellular region, generating anti-CD200R specific antibodies is a challenge. We report below on the generation of mAbs for murine (m)R1/R2 and evidence that mR2 expressed cell surface absence adaptor protein Dap12. Despite between mR1 mR4, unexpected reduction molecular mass (i.e. 90kDa vs 48kDa) two receptors suggested TM cytoplasmic region mR4 regulated glycosylation. Substitution with...