A5073629323- Neuropeptides and Animal Physiology
- Receptor Mechanisms and Signaling
- Pharmacological Receptor Mechanisms and Effects
- Pancreatic function and diabetes
- Renin-Angiotensin System Studies
- Neuroendocrine regulation and behavior
- Peptidase Inhibition and Analysis
- Pain Mechanisms and Treatments
- Cancer, Stress, Anesthesia, and Immune Response
- Blood Coagulation and Thrombosis Mechanisms
- Cellular transport and secretion
- Diabetes Treatment and Management
- Ion Transport and Channel Regulation
- Neuroscience and Neuropharmacology Research
- Alzheimer's disease research and treatments
- Adenosine and Purinergic Signaling
- Nicotinic Acetylcholine Receptors Study
- Gestational Diabetes Research and Management
- Neuroscience of respiration and sleep
- Ion channel regulation and function
- Breastfeeding Practices and Influences
Monash University
2014-2021
Australian Research Council
2018
Florey Institute of Neuroscience and Mental Health
2007-2016
The University of Melbourne
2007-2016
Neurosciences Institute
2008
Significance Activated G protein-coupled receptors (GPCRs) internalize and can continue to signal from endosomes. The contribution of endosomal signaling human disease is unknown. Proteases that are generated in the colon patients with irritable bowel syndrome (IBS) cleave protease-activated receptor-2 (PAR 2 ) on nociceptors cause pain. We evaluated whether PAR generates signals endosomes mediate persistent hyperexcitability Biopsies colonic mucosa IBS released proteases induced...
Approximately one-quarter of people over the age 65 are estimated to suffer some form cognitive impairment, underscoring need for effective cognitive-enhancing agents. Insulin-regulated aminopeptidase (IRAP) is potentially an innovative target development enhancers, as its peptide inhibitors exhibit memory-enhancing effects in both normal and memory-impaired rodents. Using a homology model catalytic domain IRAP virtual screening, we have identified class nonpeptide, small-molecule IRAP....
Differences in plasma membrane mobility or clustering of an opioid receptor may underlie the different effects its agonists.
Available crystal structures of opioid receptors provide a high-resolution picture ligand binding at the primary ("orthosteric") site, that is, site targeted by endogenous ligands. Recently, positive allosteric modulators have also been discovered, but their modes and action remain unknown. Here, we use metadynamics-based strategy to efficiently sample process recently discovered modulator δ-opioid receptor, BMS-986187, in presence orthosteric agonist SNC-80, with receptor embedded an...
Allosteric modulators are an attractive approach to achieve receptor subtype-selective targeting of G protein-coupled receptors. Benzyl quinolone carboxylic acid (BQCA) is unprecedented example a highly selective positive allosteric modulator the M1 muscarinic acetylcholine (mAChR). However, despite favorable pharmacological characteristics BQCA in vitro and vivo, there limited evidence impact modulation on regulatory mechanisms such as β-arrestin recruitment or internalization endocytic...
G-protein-coupled receptors (GPCRs) are traditionally known for signaling at the plasma membrane, but they can also signal from endosomes after internalization to control important pathophysiological processes. In spinal neurons, sustained endosomal of neurokinin 1 receptor (NK1R) mediates nociception, as demonstrated in models acute and neuropathic pain. An NK1R antagonist, Spantide I (Span), conjugated cholestanol (Span-Chol), accumulates endosomes, inhibits signaling, causes prolonged...
Neuroinflammation occurs in Alzheimer's disease (AD) brains response to pathological deposition of amyloid beta and subsequent neurodegeneration. Scrutiny conventional anti-inflammatory drug trials has revealed mixed outcomes patients, identification alternative targets is key for the development improved treatment strategies. We investigated role insulin-regulated aminopeptidase (IRAP), a neuronal metalloprotease, inflammation associated with IRAP was previously described human AD an...
Endogenous opioids released from CD4+T cells are increased in inflammatory bowel disease patients (IBD) and pre-clinical models of IBD, have an important analgesic effect. We shown that endogenous supernatant cDSS mice antinociceptive action on dorsal root ganglia (DRG) neurons is mediated by δ (DOR) μ (MOR) opioid receptors. also found acute application for minutes had unexpectedly sustained effect but the mechanism was unclear. hypothesized a nociceptors via endosomal signaling. Chronic...