Wayne Cawthorne
A5030608093- Cell death mechanisms and regulation
- Phagocytosis and Immune Regulation
- Cell Image Analysis Techniques
- Bacillus and Francisella bacterial research
- Alzheimer's disease research and treatments
- Amyotrophic Lateral Sclerosis Research
- Nuclear Structure and Function
- interferon and immune responses
- Cell Adhesion Molecules Research
- Inflammatory Bowel Disease
- PARP inhibition in cancer therapy
- Biomarkers in Disease Mechanisms
- Trace Elements in Health
Walter and Eliza Hall Institute of Medical Research
2019-2025
The University of Melbourne
2023-2024
Parks Victoria
2024
Abstract Mixed lineage kinase domain-like (MLKL) is the terminal protein in pro-inflammatory necroptotic cell death program. RIPK3-mediated phosphorylation thought to initiate MLKL oligomerization, membrane translocation and disruption, although precise choreography of events incompletely understood. Here, we use single-cell imaging approaches map chronology endogenous human activation during necroptosis. During effector phase necroptosis, observe that phosphorylated assembles into higher...
Abstract Background Dysregulated programmed cell death plays a key role in IBD pathogenesis, with clinical trials exploring anti-necroptotic therapies (1,2). While apoptosis and necroptosis are well-studied murine colitis models, their prevalence, mechanisms, therapeutic relevance human remains unclear. We examined pathways patients on advanced therapies, uncovering unique signalling mechanisms that could inform future treatments. Methods Over 900 paired intestinal biopsies were analysed...
ABSTRACT Inflammatory bowel disease (IBD) is a chronic condition caused by altered cytokine signaling, maladaptive immunity, dysbiosis, and intestinal barrier dysfunction. Patients with IBD receive therapy to correct these imbalances achieve remission. However, most patients relapse, suggesting that pathological mechanisms persist during Here, we show excess epithelial cell death an underlying feature of arises in remission on advanced therapy. Mechanistically, nascent inflammation...
Abstract Mixed lineage kinase domain-like (MLKL) is a pseudokinase, best known for its role as the terminal effector of necroptotic cell death pathway. MLKL-mediated necroptosis has long been linked to various age-related pathologies including neurodegeneration, atherosclerosis and male reproductive decline, however many these attributions remain controversial. Here, we investigated MLKL in adult mouse testis: an organ divided into sperm-producing seminiferous tubules surrounding...
Abstract Necroptosis is a lytic form of regulated cell death reported to contribute inflammatory diseases the gut, skin and lung, as well ischemic-reperfusion injuries kidney, heart brain. However, precise identification cells tissues that undergo necroptotic in vivo has proven challenging absence robust protocols for immunohistochemical detection. Here, we provide automated immunohistochemistry detect core necroptosis regulators – Caspase-8, RIPK1, RIPK3 MLKL formalin-fixed mouse human...