A5040335760- Immune Cell Function and Interaction
- Autoimmune and Inflammatory Disorders Research
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- RNA Interference and Gene Delivery
- Cell death mechanisms and regulation
- Parvovirus B19 Infection Studies
- Lysosomal Storage Disorders Research
- Urticaria and Related Conditions
- Genetics, Aging, and Longevity in Model Organisms
- Pancreatic and Hepatic Oncology Research
- Lymphoma Diagnosis and Treatment
- Cancer Mechanisms and Therapy
- Gut microbiota and health
- Dermatology and Skin Diseases
- Adenosine and Purinergic Signaling
- Chronic Lymphocytic Leukemia Research
- Cell Image Analysis Techniques
- Autophagy in Disease and Therapy
- Immunodeficiency and Autoimmune Disorders
- T-cell and B-cell Immunology
- Mitochondrial Function and Pathology
- Viral-associated cancers and disorders
- Diverse Education Studies and Reforms
- Peptidase Inhibition and Analysis
Peter MacCallum Cancer Centre
2014-2025
The University of Melbourne
2014-2024
MRC Unit for Lifelong Health and Ageing
2013
University College London
2013
The biguanide drug metformin is widely prescribed to treat type 2 diabetes and metabolic syndrome, but its mode of action remains uncertain. Metformin also increases lifespan in Caenorhabditis elegans cocultured with Escherichia coli. This bacterium exerts complex nutritional pathogenic effects on nematode predator/host that impact health aging. We report by altering microbial folate methionine metabolism. Alterations metformin-induced longevity mutation worm synthase (metr-1)...
Abstract Killer T cells (cytotoxic lymphocytes, CTLs) maintain immune homoeostasis by eliminating virus-infected and cancerous cells. CTLs achieve this forming an immunological synapse with their targets secreting a pore-forming protein (perforin) pro-apoptotic serine proteases (granzymes) into the synaptic cleft. Although CTL target cell are both exposed to perforin within synapse, only membrane is disrupted, while invariably spared. How escape unscathed remains mystery. Here, we report...
Abstract Cytotoxic lymphocytes are crucial to our immune system, primarily eliminating virus-infected or cancerous cells via perforin/granzyme killing. Perforin forms transmembrane pores in the plasma membrane, allowing granzymes enter target cell cytosol and trigger apoptosis. The prowess of cytotoxic efficiently eradicate has been widely harnessed immunotherapies against haematological cancers. Despite efforts achieve a similar outcome solid tumours, immunosuppressive acidic tumour...
Abstract The loss of p300/CBP-associated protein (PCAF) expression is associated with poor clinical outcome in gastric cancer, and a potential bio-marker for invasive aggressive tumors. However, the mechanism linking PCAF to onset cancer has not been identified. Given that its binding partner transcriptional adaptor 3 (ADA3) were recently shown regulate intrinsic (mitochondrial) pathway apoptosis via epigenetic regulation phosphofurin acidic cluster sorting proteins 1 2 (PACS1, PACS2), we...
The ability of cytotoxic lymphocytes (CL) to eliminate virus-infected or cancerous target cells through the granule exocytosis death pathway is critical immune homoeostasis. Congenital loss CL function due bi-allelic mutations in PRF1, UNC13D, STX11 STXBP2 leads a potentially fatal dysregulation, familial haemophagocytic lymphohistiocytosis (FHL). This occurs failure CLs release functional pore-forming protein perforin and, therefore, inability kill cell. Bi-allelic partner proteins impair...
Cytotoxic lymphocytes are essential for anti-tumor immunity, and effective responses to cancer immunotherapy. Natural killer cell granule protein 7 (NKG7) is expressed at high levels in cytotoxic infiltrating tumors from patients treated with immunotherapy, but until recently, the role of this lymphocyte function was largely unknown. Unexpectedly, we found that highly CD8+ T cell-immunogenic murine colon carcinoma (MC38-OVA) grew an equal rate Nkg7 +/+ -/- littermate mice, suggesting NKG7...
When killing through the granule exocytosis pathway, cytotoxic lymphocytes release key effector molecules into immune synapse, perforin and granzymes, to initiate target cell killing. The pore-forming is essential for function of lymphocytes, as its pores disrupt membrane allow diffusion pro-apoptotic serine proteases, granzyme, cell, where they various death cascades. Unlike human perforin, detection murine counterpart in a live system has been problematic due relatively low expression...
Recently developed small-molecule inhibitors of the lysosomal protease dipeptidyl peptidase 1 (DPP1), also known as cathepsin C (CatC), can suppress suppurative inflammation in vivo by blocking processing zymogenic (pro-) forms neutrophil serine proteases (NSPs), including elastase, proteinase 3, and G. DPP1 plays an important role activating granzyme that are expressed cytotoxic T lymphocytes (CTL) natural killer (NK) cells. Therefore, it is critical to determine whether inhibition cause...
Abstract Cytotoxic lymphocytes are pivotal effectors in our immune system. Their most potent way to delete virus infected or cancerous target cells is by perforin/granzyme dependent killing. Perforin secreted into the immunological synapse and forms transmembrane pores cell plasma membrane, allowing granzymes enter cytosol trigger apoptosis. The prowess of cytotoxic efficiently eradicate has been widely harnessed immunotherapies against haematological cancers. Despite efforts achieve a...