A5032515183- Neuropeptides and Animal Physiology
- Complement system in diseases
- S100 Proteins and Annexins
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cancer, Stress, Anesthesia, and Immune Response
- Cytomegalovirus and herpesvirus research
- Virus-based gene therapy research
- Neuroinflammation and Neurodegeneration Mechanisms
- Renin-Angiotensin System Studies
- Mosquito-borne diseases and control
- Metabolism and Genetic Disorders
- Protease and Inhibitor Mechanisms
- CRISPR and Genetic Engineering
- Renal Diseases and Glomerulopathies
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Apelin-related biomedical research
- Parkinson's Disease Mechanisms and Treatments
- Systemic Lupus Erythematosus Research
- Viral Infections and Immunology Research
- CAR-T cell therapy research
- Neurogenesis and neuroplasticity mechanisms
- Regulation of Appetite and Obesity
- Neurogenetic and Muscular Disorders Research
- Genetics and Neurodevelopmental Disorders
- interferon and immune responses
Children's Medical Research Institute
2021-2024
Sydney Children’s Hospitals Network
2021-2024
The University of Sydney
2021-2023
University of Technology Sydney
2020-2023
Success in the treatment of infants with spinal muscular atrophy (SMA) underscores potential vectors based on adeno-associated virus (AAV). However, a major obstacle to full realization this is pre-existing natural and therapy-induced anti-capsid humoral immunity. Structure-guided capsid engineering one possible approach surmounting challenge but necessitates an understanding capsid-antibody interactions at high molecular resolution. Currently, only mouse-derived monoclonal antibodies (mAbs)...
Evidence suggests that rapid changes to supporting glia may predispose individuals with spinal cord injury (SCI) such comorbidities. Here, we interrogated the expression of astrocyte- and microglial-specific markers glial fibrillary acidic protein (GFAP) ionized calcium binding adaptor molecule 1 (Iba1) in rat brain first 24 hours following SCI. Female Sprague-Dawley rats underwent thoracic laminectomy; half received a mild contusion at level T10 vertebral body (SCI group), other did not...
Significance The complement system is integral to innate immunity and host defense. However, inappropriate activation causes tissue damage disease. In health, this prevented by a complex protein network that includes the factor H proteins. Understanding control of critical treat complement-mediated We demonstrate gain-of-function mutant H–related 5 (FHR5) results in glomerular damage. interfered with regulation within kidney, resulting accumulation glomeruli kidney Administration regulator...
High-fat diet (HFD)-induced comorbid cognitive and behavioural impairments are thought to be the result of persistent low-grade neuroinflammation. Metformin, a first-line medication for treatment type-2 diabetes, seems ameliorate these comorbidities, but underlying mechanism(s) not clear. Pituitary adenylate cyclase-activating peptide (PACAP) vasoactive intestinal (VIP) neuroprotective peptides endowed with anti-inflammatory properties. Alterations PACAP/VIP system could pivotal during...
Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are two structurally related immunosuppressive peptides. However, the underlying mechanisms through which these peptides regulate microglial activity not fully understood. Using lipopolysaccharide (LPS) to induce an inflammatory challenge, we tested whether PACAP or VIP differentially affected activation, morphology cell migration. We found that both attenuated LPS-induced expression of...
Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are two structurally-related immunosuppressive peptides. However, the underlying mechanisms through which these peptides regulate microglial activity not fully understood. Using lipopolysaccharide (LPS) to induce an inflammatory challenge, we tested whether PACAP or VIP differentially affected activation, morphology cell migration. We found that both attenuated LPS-induced expression of...
The complement system is a key component of innate immunity, but impaired regulation influences disease susceptibility, including age-related macular degeneration and some kidney diseases. While complete inhibition has been used successfully to treat acute disease, unresolved challenges include strategies modulate rather than completely inhibit the deliver therapy potentially over decades. Elevating concentrations factor I (CFI) restricts activation in vitro this approach was extended...
ABSTRACT Extracellular DNA (ecDNA) released from injured and dying cells powerfully induces injurious inflammation. In this study we show ecDNA renal presence in patients experimental mice with myeloperoxidase anti-neutrophil cytoplasmic antibody-associated glomerulonephritis (MPO-ANCA GN). Twice daily administration of intravenous DNase I (ivDNase I) two models anti-MPO GN was effective at reducing glomerular deposition ecDNA, histological injury, leukocyte infiltration NETosis....
Realization of the immense therapeutic potential epigenetic editing requires development clinically predictive model systems that faithfully recapitulate relevant aspects target disease pathophysiology. In female patients with ornithine transcarbamylase (OTC) deficiency, an X-linked condition, skewed inactivation X chromosome carrying wild-type OTC allele is associated increased severity. The majority affected can be managed medically, but a proportion require liver transplantation. With...
Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the most common and severe manifestations lupus; however, its pathogenesis still poorly understood. While there sparse evidence suggesting that ongoing autoimmunity may trigger pathogenic changes to central nervous system (CNS) microvasculature, culminating in inflammatory/ischemic damage, further needed. In this study, we used spontaneous mouse model SLE (NZBWF1 mice) investigate expression genes proteins associated with...
Adeno-associated virus (AAV) vectors are proving to be clinically transformative tools in the treatment of monogenic genetic disease. Rapid ongoing development this technology promises not only increase number disorders amenable approach but also bring diseases with complex multigenic and nongenetic etiologies within therapeutic reach. In study, we explore broader paradigm converting liver into a biofactory for systemic output molecules using AAV-mediated delivery endonuclease DNaseI as an...
Previous evidence shows that rapid changes occur in the brain following spinal cord injury (SCI). Here, we interrogated expression of neuropeptides pituitary adenylyl cyclase-activating peptide (PACAP), vasoactive intestinal peptides (VIP), and their binding receptors rat 24 h SCI. Female Sprague-Dawley rats underwent thoracic laminectomy; half received a mild contusion at level T10 vertebrate (SCI group); other sham surgery (sham group). Twenty-four hours post-surgery, hypothalamus,...