A5055017065- Complement system in diseases
- Neuroinflammation and Neurodegeneration Mechanisms
- Adenosine and Purinergic Signaling
- Receptor Mechanisms and Signaling
- Immune cells in cancer
- Amyotrophic Lateral Sclerosis Research
- Immunotherapy and Immune Responses
- Cancer Research and Treatments
- Immune Cell Function and Interaction
- Blood Coagulation and Thrombosis Mechanisms
- Cancer Immunotherapy and Biomarkers
- Monoclonal and Polyclonal Antibodies Research
- Bladder and Urothelial Cancer Treatments
- Nanoplatforms for cancer theranostics
- Neurogenetic and Muscular Disorders Research
- Alzheimer's disease research and treatments
- S100 Proteins and Annexins
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Immune Response and Inflammation
- Pregnancy and preeclampsia studies
- Inflammasome and immune disorders
- SARS-CoV-2 and COVID-19 Research
- Reproductive System and Pregnancy
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Advanced Drug Delivery Systems
The University of Queensland
2016-2025
Wesley Hospital
2018-2021
Wesley Research Institute
2018-2021
Queensland Eye Institute
2020
Institute of Biomedical Science
2017
Queensland Children’s Hospital
2016
Royal Brisbane and Women's Hospital
2016
QIMR Berghofer Medical Research Institute
2016
Bioengineering Center
2013
National Center for Genetic Engineering and Biotechnology
2013
Parkinson's disease (PD) is characterized by a profound loss of dopaminergic neurons in the substantia nigra, accompanied chronic neuroinflammation, mitochondrial dysfunction, and widespread accumulation α-synuclein-rich protein aggregates form Lewy bodies. However, mechanisms linking α-synuclein pathology neuronal death to microglial neuroinflammation have not been completely elucidated. We show that activation NLR family pyrin domain containing 3 (NLRP3) inflammasome common pathway...
Traumatic injury to the central nervous system results in disruption of blood brain/spinal barrier, followed by invasion cells and other components immune that can aggravate affect subsequent repair regeneration. Although studies chronic neuroinflammation injured spinal cord animals are clinically relevant most patients living with traumatic brain or cord, very little is known about neuroinflammation, though several have tested role acute period after injury. The present study characterizes...
Stroke is the world's second leading cause of mortality, with a high incidence severe morbidity in surviving victims. There are currently relatively few treatment options available to minimize tissue death following stroke. As such, there pressing need explore, at molecular, cellular, tissue, and whole body level, mechanisms damage CNS an ischemic brain event. This review explores etiology pathogenesis stroke, provides general model such. The pathophysiology cerebral injury explained,...
The NLRP3 inflammasome controls interleukin-1β maturation in antigen-presenting cells, but a direct role for human adaptive immune cells has not been described. We found that the assembles CD4(+) T and initiates caspase-1-dependent secretion, thereby promoting interferon-γ production helper 1 (T(H)1) differentiation an autocrine fashion. assembly requires intracellular C5 activation stimulation of C5a receptor (C5aR1), which is negatively regulated by surface-expressed C5aR2. Aberrant...
Microglial NLRP3 inflammasome activation is emerging as a key contributor to neuroinflammation during neurodegeneration. Pathogenic protein aggregates such β-amyloid and α-synuclein trigger microglial activation, leading caspase-1 IL-1β secretion. Both contribute disease progression in the mouse SOD1G93A model of amyotrophic lateral sclerosis (ALS), suggesting role for NLRP3. Prior studies, however, suggested mice microglia do not express NLRP3, generated independent Here, we demonstrate...
Coronavirus disease-2019 (COVID-19) is primarily a respiratory disease, however, an increasing number of reports indicate that SARS-CoV-2 infection can also cause severe neurological manifestations, including precipitating cases probable Parkinson's disease. As microglial NLRP3 inflammasome activation major driver neurodegeneration, here we interrogated whether promote activation. Using transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) as COVID-19 pre-clinical model,...
This study shows how highly processed foods can cause innate immune inflammation that promotes chronic microvascular disease.
Abstract Alzheimer’s disease (AD) is an age-related dementia, characterized by amyloid plaques, neurofibrillary tangles, neuroinflammation, and neuronal loss in the brain. Components of complement system, known to produce a local inflammatory reaction, are associated with plaques tangles AD brain, thus role for complement-mediated inflammation acceleration or progression has been proposed. A activation product, C5a, recruit activate microglia astrocytes vitro G protein-coupled cell-surface...
Abstract Complement activation products are elevated in the cerebrospinal fluid and spinal cord of patients with amyotrophic lateral sclerosis (ALS). In this study, we demonstrate complement system involvement a rodent model ALS (human SOD1G93A transgenic rats). With end-stage disease, rats displayed marked deposition C3/C3b, significant up-regulation C5aR lumbar cord. This was associated increased numbers C5aR-positive astrocytes. However, expression C5L2, alternative receptor for C5a,...
C3a is a key complement activation fragment, yet its neutrophil-expressed receptor (C3aR) still has no clearly defined role. In this study, we used neutrophil-dependent mouse model of intestinal ischemia-reperfusion (IR) injury to explore the role C3aR in acute tissue injuries. deficiency worsened injury, which corresponded with increased numbers tissue-infiltrating neutrophils. Circulating neutrophils were significantly −/− mice after ischemia, and also mobilized more circulating...
Abstract The complement peptide C3a is a key component of the innate immune system and major fragment produced following activation. We used murine model melanoma (B16-F0) to identify hitherto unknown role for C3a–C3aR signaling in promoting tumor growth. results show that development growth B16-F0 melanomas retarded mice lacking C3aR, whereas established can be arrested by C3aR antagonism. Flow cytometric analysis showed alterations tumor-infiltrating leukocytes absence C3aR. Specifically,...
This study investigated the role of complement activation fragment C5a in secondary pathology following contusive spinal cord injury (SCI). C5ar(-/-) mice, which lack signaling receptor for C5a, displayed signs improved locomotor recovery and reduced inflammation during first week SCI compared with wild-type mice. Intriguingly, early mice deteriorated from day 14 onward, absence C5aR ultimately leading to poorer functional outcomes, larger lesion volumes, myelin content, more widespread at...