A5048060049- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- Inflammatory Bowel Disease
- Inflammasome and immune disorders
- T-cell and B-cell Immunology
- Invertebrate Immune Response Mechanisms
- Neurobiology and Insect Physiology Research
- Immunotherapy and Immune Responses
- Antifungal resistance and susceptibility
- Immune cells in cancer
- Viral Infectious Diseases and Gene Expression in Insects
- Immune Response and Inflammation
- Complement system in diseases
- Eosinophilic Esophagitis
- Thyroid and Parathyroid Surgery
- Gut microbiota and health
- Biosimilars and Bioanalytical Methods
- Plant Pathogens and Fungal Diseases
- Immune responses and vaccinations
- Gastrointestinal motility and disorders
- Cystic Fibrosis Research Advances
- Psoriasis: Treatment and Pathogenesis
- Microscopic Colitis
- Mosquito-borne diseases and control
- Ultrasound and Hyperthermia Applications
Age UK
2019-2023
The Francis Crick Institute
2016-2021
Annamalai University
2021
GlaxoSmithKline (United Kingdom)
2019-2020
University of Oxford
2010-2015
Cancer Research UK
2014
University of Cape Town
2009-2012
Cross-presentation of antigens from dead tumor cells by type 1 conventional dendritic (cDC1s) is thought to underlie priming anti-cancer CD8
ABSTRACT The innate recognition of fungal pathogens is a crucial first step in the induction protective antifungal immunity. Complement thought to be one key component this process, facilitating and inducing early inflammation. However, roles individual complement components have not been examined extensively. Here we used mice lacking C3 examine its role immunity opportunistic show that essential for resistance infections with Candida albicans glabrata . We demonstrate absence impairs...
Damage-associated molecular patterns (DAMPs) are molecules released by dead cells that trigger sterile inflammation and, in vertebrates, adaptive immunity. Actin is a DAMP detected mammals the receptor, DNGR-1, expressed dendritic (DCs). DNGR-1 phosphorylated Src-family kinases and recruits tyrosine kinase Syk to promote DC cross-presentation of cell-associated antigens. Here we report actin also invertebrates lack DCs Administration Drosophila melanogaster triggers response characterised...
The innate recognition of fungi by leukocytes is mediated pattern receptors (PRR), such as Dectin-1, and thought to occur at the cell surface triggering intracellular signalling cascades which lead induction protective host responses. In lung, this aided surfactant also serves maintain balance between inflammation pulmonary function, although underlying mechanisms are unknown. Here we have explored a variety fungal particles, including zymosan, Candida albicans Aspergillus fumigatus,...
Lymphocyte activation gene [LAG]-3 is an immune checkpoint and its expression identifies recently activated lymphocytes that may contribute to inflammation. We investigated the role of LAG-3 by analysing function in cells from blood tissue patients with ulcerative colitis [UC].The phenotypic properties LAG-3+ T were determined flow cytometry, qRT-PCR single-cell RNA-sequencing. quantified correlated disease activity. The functional effects tested using a depleting anti-LAG-3 monoclonal...
Activated T cells drive a range of immune‐mediated inflammatory diseases. LAG‐3 is transiently expressed on recently activated CD4 + and CD8 cells. We describe the engineering first‐in‐human clinical study (NCT02195349) GSK2831781 (an afucosylated humanized IgG1 monoclonal antibody enhanced with high affinity for Fc receptors antibody‐dependent cellular cytotoxicity capabilities), which depletes expressing was tested in phase I/Ib, double‐blind, placebo‐controlled study, randomized 40...
Damage-associated molecular patterns (DAMPs) are molecules exposed or released by dead cells that trigger modulate immunity and tissue repair. In vertebrates, the cytoskeletal component F-actin is a DAMP specifically recognised DNGR-1, an innate immune receptor. Previously we suggested actin also in
Summary Background Selective depletion of T cells expressing LAG‐3, an immune checkpoint receptor that is upregulated on activated cells, has been investigated in pre‐clinical models as a potential therapeutic approach inflammatory and autoimmune diseases where are implicated. Aims GSK2831781, depleting monoclonal antibody specifically binds LAG‐3 proteins, may deplete + ulcerative colitis (UC). Methods Patients with moderate to severe UC were randomised GSK2831781 or placebo. Safety,...
BACKGROUND Chronic conditions of Ulcerative Colitis and Crohn’s Disease with unknown aetiology relapse were collectively known as inflammatory bowel disease (IBD). The occurrence the in recent years has increased developing countries like India higher rate prevalence. objective study was to evaluate sociodemographic, clinical characteristics knowledge at a tertiary care hospital also associate variables that provided pictorial education. Significantly, about condition informational demands...
The temporal cell surface expression of lymphocyte activated gene 3 (LAG3) on recently T cells presents an opportunity for targeted therapy in certain inflammatory diseases. LAG3+ are enriched inflamed lesions ulcerative colitis,1 Crohn’s disease and psoriasis. GSK2831781 is a highly potent, humanised IgG1, antibody-dependent cellular cytotoxicity-enhanced monoclonal antibody that depletes cells. A single escalating intravenous dose or placebo was administered to 40 healthy volunteers (up...
Abstract This study investigated ethnic differences in the safety, tolerability, pharmacokinetics, and pharmacodynamics of GSK2831781, an anti–lymphocyte activation gene 3 (LAG3) monoclonal antibody, healthy participants, determined local tolerability bioavailability following subcutaneous (SC) administration. A double‐blind, randomized (A) single intravenous (IV) doses GSK2831781 450 mg or placebo Japanese White participants; (B) SC 150 mg, was conducted. Blood samples for analyses were...
Lymphocyte activation gene (LAG)-3 is upregulated early after T-cell stimulation, and therefore a marker of recently activated T cells. Targeting these cells for therapeutic depletion might provide mechanism selectively eliminating lymphocytes contributing to the pathogenesis chronic inflammatory disease, while sparing non-activated population that are then available combat infection. We explored potential role viability as novel drug target LAG-3 expressing in ulcerative colitis (UC). The...
LAG-3 is a transmembrane protein expressed on T cells following antigen-driven activation. Although it functions as negative co-stimulatory receptor, similar to PD-1 and CTLA-4, its expression identifies lymphocytes that may contribute initiation persistence of inflammation in patients with inflammatory disease. We quantified ulcerative colitis before after treatment, characterised the sub-populations activated mucosa express LAG-3, examining particular effector cells, memory regulatory...