A5037001168- Protein Kinase Regulation and GTPase Signaling
- Melanoma and MAPK Pathways
- Alzheimer's disease research and treatments
- Streptococcal Infections and Treatments
- Antimicrobial Resistance in Staphylococcus
- Autophagy in Disease and Therapy
- Cytokine Signaling Pathways and Interactions
- Computational Drug Discovery Methods
- Cancer Mechanisms and Therapy
- Bacterial Identification and Susceptibility Testing
- Sphingolipid Metabolism and Signaling
- Cholinesterase and Neurodegenerative Diseases
- Parkinson's Disease Mechanisms and Treatments
- Amyotrophic Lateral Sclerosis Research
- PI3K/AKT/mTOR signaling in cancer
- Advanced biosensing and bioanalysis techniques
- Biochemical and Structural Characterization
- Infective Endocarditis Diagnosis and Management
- Genetic Neurodegenerative Diseases
- Advanced Biosensing Techniques and Applications
- Rabies epidemiology and control
- Gastroesophageal reflux and treatments
- Endoplasmic Reticulum Stress and Disease
- Pediatric Pain Management Techniques
- Synthesis of Tetrazole Derivatives
The Kids Research Institute Australia
2022-2025
Edith Cowan University
2010-2015
South Australia Pathology
2010
Dementia Australia
2010
Hanson Institute
2008
The University of Western Australia
2001-2005
University of Ottawa
1977
The c-Jun N-terminal kinases (JNKs) are a subfamily of the mitogen-activated protein (MAPKs). Although progress in evaluating functions other MAPKs has been facilitated by characterization specific inhibitors, no JNK-directed inhibitor is commercially available. We have identified 21-amino acid peptide activated JNKs, based on amino acids 143-163 JNK-binding domain (JBD) JNK scaffolding protein, JNK-interacting protein-1 (JIP-1). This peptide, I-JIP (Inhibitor JNK-based JIP-1), inhibited...
Latrepirdine (Dimebon™), an anti-histamine, has shown some benefits in trials of neurodegenerative diseases characterized by accumulation aggregated or misfolded protein such as Alzheimer's disease (AD) and been to promote the removal
The in-vivo plasma concentration of penicillin needed to prevent Streptococcus pyogenes pharyngitis, recurrent acute rheumatic fever, and progressive heart disease is not known. We used a human challenge model assess the minimum required streptococcal pharyngitis. In CHIPS, randomised, double-blind, placebo-controlled, trial, healthy adult volunteers were randomly assigned by computer-generated random sequence target steady-state concentrations (placebo, 3, 6, 9, 12, or 20 ng/mL). study was...
Sphingosine kinase 1 (SK1) is an important regulator of cellular signaling that has been implicated in a broad range processes. Cell exposure to wide array growth factors, cytokines, and other cell agonists can result rapid transient increase SK activity via activating phosphorylation. We have previously identified extracellular signal-regulated kinases 2 (ERK1/2) as the responsible for phosphorylation human SK1 at Ser225, but corresponding phosphatase targeting this remained undefined....
Background Four-weekly intramuscular (IM) benzathine penicillin G (BPG) injections to prevent acute rheumatic fever (ARF) progression have remained unchanged since 1955. A Phase-I trial in healthy volunteers demonstrated the safety and tolerability of high-dose subcutaneous infusions BPG which resulted a much longer effective exposure, fewer injections. Here we describe experiences young people living with ARF participating Phase-II S ub C utaneous I njections B P (SCIP). Methodology...
We previously reported that a small peptide based on amino acids 143-153 of the c-Jun N-terminal kinase (JNK)-binding domain JIP-1 functioned as an in vitro inhibitor JNK activity. This (TI-JIP: RP-KRPTTLNLF) resembles kinase-interaction motif (KIM = (K/R)(2-3)X(1-6)(L/I)X(L/I)), which is common to upstream activators, downstream substrates, phosphatases, and scaffold proteins present MAPK cascades. In this study, we characterized mechanism inhibition by further investigated biochemical...
Although the formation of β-amyloid (Aβ) deposits in brain is a hallmark Alzheimer disease (AD), soluble oligomers rather than mature amyloid fibrils most likely contribute to Aβ toxicity and neurodegeneration. Thus, discovery agents targeting highly desirable for early diagnosis prior manifestation clinical AD phenotype also more effective therapies. We have previously reported that novel 15-amino acid peptide (15-mer), isolated via phage display screening, targeted attenuated its...
The development of specific inhibitors for the c-Jun N-terminal kinase (JNK) family mitogen-activated protein kinases (MAPKs) has been a recent research focus because association JNK with cell death in conditions such as stroke and neurodegeneration. We have demonstrated previously presence critical inhibitory residues within an 11-mer peptide (TI-JIP) based on sequence JNK-interacting protein-1 (JIP-1). However, corresponding region bound by this JIP-1-based was unknown. To identify region,...
Regular intramuscular (i.m.) benzathine penicillin G (BPG) injections have been the cornerstone of rheumatic heart disease (RHD) secondary prophylaxis since 1950s. Patient adherence to IM BPG is poor, largely due pain, need for regular every 3-4 weeks and health sector delivery challenges in resource-limited settings. There an urgent new approaches prophylaxis, such as implant which could provide sustained concentrations more than 6 months.In this study we developed evaluated a slow release...
Regular intramuscular benzathine penicillin G injections have been the cornerstone of rheumatic heart disease (RHD) secondary prophylaxis since 1950s. As pharmacological correlate protection remains unknown, it is difficult to recommend changes this established regimen. Determining minimum effective exposure required prevent
Abstract Background Four-weekly intramuscular (IM) benzathine penicillin G (BPG) injections to prevent acute rheumatic fever (ARF) progression have remained unchanged since 1955. A Phase-I trial in healthy volunteers demonstrated the safety and tolerability of high-dose S ub C utaneous Infusions B P (SCIP) which resulted a much longer effective exposure, fewer injections. Here we describe experiences young people living with ARF participating Phase-II SCIP trial. Methodology Participants...
Latrepirdine (DimebonTM,) is the first drug to have produced improvements in cognition Alzheimer's disease (AD) while also showing signs of stabilising progress, however, its mechanism(s) action not fully understood. Recent evidence shows that acute doses latrepirdine can cause elevations extracellular levels Aβ vivo, chronic dosing reduces synuclein deposition a mouse model synucleinopathy, together suggesting may enhance clearance protein aggregates. Autophagy one pathway, considered be...
Latrepirdine (DimebonTM) is a promising drug for reducing the cognitive dysfunction of AD and currently in phase III clinical trials. Although its mechanism action not completely understood, latrepirdine has recently been reported to modulate Aβ metabolism do so an unexpected way: increases extracellular concentrations interstitial fluid living mouse brain releasate from isolated intact nerve terminals. Further investigations into how modulates metabolism, may otherwise be producing observed...