A5101762218- Cytokine Signaling Pathways and Interactions
- CAR-T cell therapy research
- Multiple Sclerosis Research Studies
- interferon and immune responses
- Immunotherapy and Immune Responses
- Urticaria and Related Conditions
- Systemic Lupus Erythematosus Research
- Immune Response and Inflammation
- Chronic Lymphocytic Leukemia Research
- Dermatology and Skin Diseases
- Acute Lymphoblastic Leukemia research
- Hematopoietic Stem Cell Transplantation
- T-cell and B-cell Immunology
- Autoimmune and Inflammatory Disorders Research
- Immune Cell Function and Interaction
- Sphingolipid Metabolism and Signaling
- Cancer Immunotherapy and Biomarkers
- Chronic Myeloid Leukemia Treatments
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Psoriasis: Treatment and Pathogenesis
- Virus-based gene therapy research
- Inflammasome and immune disorders
- NF-κB Signaling Pathways
- IL-33, ST2, and ILC Pathways
- Cell death mechanisms and regulation
Incyte (United States)
2019-2023
Recludix Pharma (United States)
2023
Imperial College London
2002-2022
Geological Society of London
2022
Novartis Institutes for BioMedical Research
2015-2019
Novartis (Switzerland)
2015-2019
University College London
2014-2017
Cancer Research UK
2014-2017
Merck Serono (Switzerland)
2013-2014
Coe College
1967
Abstract The paracaspase MALT1 plays an important role in immune receptor-driven signaling pathways leading to NF-κB activation. promotes by acting as a scaffold, recruiting downstream proteins, well proteolytic cleavage of multiple substrates. However, the relative contributions these two different activities T and B cell function are not understood. To investigate how activity contributes overall regulation, we generated protease-deficient mice (Malt1PD/PD) compared their phenotype with...
Multiple sclerosis (MS) is a chronic inflammatory disease affecting the central nervous system (CNS). While multiple effective immunomodulatory therapies for MS exist today, they lack scope of promoting CNS repair, in particular remyelination. Microglia play pivotal role regulating myelination processes, and colony-stimulating factor 1 (CSF-1) pathway key regulator microglia differentiation survival. Here, we investigated effects CSF-1 receptor kinase inhibitor, BLZ945, on processes 5-week...
Abstract Purpose: T cells engineered to express a chimeric antigen receptor (CAR) are promising cancer immunotherapy. Such targeted therapies have shown long-term relapse-free survival in patients with B-cell leukemia and lymphoma. However, cytokine release syndrome (CRS) represents serious, potentially life-threatening side effect often associated CAR T-cell therapy. CRS manifests as rapid (hyper)immune reaction driven by excessive inflammatory release, including IFNγ IL6. Experimental...
Background: Cutaneous lupus erythematosus (CLE) is an interferon (IFN) -driven autoimmune skin disease characterized by extensive cytotoxic lesional inflammation with activation of different innate immune pathways. Aim our study was to investigate the specific role Janus kinase 1 (JAK1) in this and potential benefit selective JAK1 inhibitors as targeted therapy a preclinical CLE model. Methods: Lesional patients subtypes healthy controls (N=31) were investigated on expression IFN-associated...
Hyperinflammatory syndromes comprise a heterogeneous group of disorders characterized by severe inflammation, multiple organ dysfunction, and potentially death. In response to antigenic stimulus (e.g., SARS-CoV-2 infection), overactivated CD8+ T-cells macrophages produce high levels proinflammatory cytokines, such as IFN-γ, TNF-α, IL-6, IL-12. Multiple inflammatory mediators implicated in hyperinflammatory utilize the Janus kinase–signal transducers activators transcription (JAK-STAT)...
We have generated transgenic mice that harbor humanized type I interferon receptors (IFNARs) enabling the study of human interferons (Hu-IFN-Is) in mice. These "HyBNAR" (Hybrid IFNAR) encode variants IFNAR1 and IFNAR2 with extracellular domains being fused to transmembrane cytoplasmic segments mouse sequence. B16F1 melanoma cells harboring HyBNAR construct specifically bound Hu-IFN-Is were rendered sensitive Hu-IFN-I stimulated anti-proliferation, STAT1 activation a prototypical IFN-I...
Ofatumumab is the first, fully human, anti-CD20 monoclonal antibody in Phase 3 development for multiple sclerosis (MS). The study focused on changes lymphocyte subsets blood and lymphoid tissues potential novel biomarkers as a result of action Cynomolgus monkeys treated with human equivalent doses subcutaneous (s.c.) ofatumumab Days 0, 7, 14. Axillary lymph nodes (LNs) samples were collected at various time points until Day 90. Lymphocyte quantified by flow cytometry, while morphological...
Abstract Glucocorticoid (GC) hormones play a central role in the bidirectional communication between neuroendocrine and immune systems exert, via GC receptors (GR), potent immunosuppressive anti-inflammatory effects. In this study, we report that GR deficiency of transgenic mice expressing antisense RNA from early embryonic life has dramatic impact programming susceptibility to experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. renders resistant myelin...
Abstract Background Bruton’s tyrosine kinase (BTK) is a key signaling node in B cell receptor (BCR) and Fc (FcR) signaling. BTK inhibitors (BTKi) are an emerging oral treatment option for patients suffering from multiple sclerosis (MS). Remibrutinib (LOU064) potent, highly selective covalent BTKi with promising preclinical clinical profile MS other autoimmune or autoallergic indications. Methods The efficacy mechanism of action remibrutinib was assessed two different experimental...
Aim: Graft-versus-host disease (GvHD) is a major complication arising in patients undergoing allogenic hematopoietic stem cell transplantation. Material & methods: We tested ruxolitinib (a selective JAK1/2 inhibitor) efficacy three different preclinical models of GvHD. Results: Ruxolitinib, at doses that mimic clinically achievable human JAK/signal transducers and activators transcription target inhibition, significantly reduced alloreactive T-cell activation infiltration the lung skin,...
Objective: First head-to-head comparison of ofatumumab- and rituximab-mediated B-cell depletion in non-human primates following clinically relevant treatment protocols. Background: Anti-CD20 therapies (rituximab, ocrelizumab, ofatumumab) have shown clinical efficacy multiple sclerosis (MS) studies. Rituximab ocrelizumab are administered as high-dose intravenous (i.v.) infusion, whereas ofatumumab is a relatively low-dose subcutaneous (s.c.) formulation. Currently, two Phase 3 trials...
<h3>Background:</h3> Cutaneous lupus erythematosus (CLE) is an autoimmune disease with heterogenous subtypes presenting inflammatory skin lesions, a histological pattern called “Interface-dermatitis” and enhanced type-1-interferon (IFN)-regulated JAK/STAT (Janus kinase/signal transducers activators of transcription) pathway signaling. Despite deeper understanding the pathogenesis still no specifically approved drugs for CLE exist. <h3>Objectives:</h3> The aim our study was to investigate...
OBJECTIVE: Investigate the ability of fingolimod to modulate brain-derived neurotrophic factor (BDNF) expression and decrease established CNS pathology in late-stage chronic neuroinflammation. BACKGROUND: Fingolimod (FTY720, Gilenya®) was first FDA-approved oral treatment for relapsing forms MS. It readily crosses blood-brain barrier (BBB) can interact with sphingosine 1-phosphate (S1P) receptors expressed on cells within immune system CNS. This study represents very analysis BDNF tissue...