A5103156535- Adenosine and Purinergic Signaling
- Diabetes Treatment and Management
- Monoclonal and Polyclonal Antibodies Research
- Receptor Mechanisms and Signaling
- Pancreatic function and diabetes
- Glycosylation and Glycoproteins Research
- Plant Reproductive Biology
- Nanoparticle-Based Drug Delivery
- Ultrasound and Hyperthermia Applications
- Nanoplatforms for cancer theranostics
- melanin and skin pigmentation
- Hormonal and reproductive studies
- Advanced biosensing and bioanalysis techniques
- Metal complexes synthesis and properties
- Inflammasome and immune disorders
- Magnetism in coordination complexes
- Heat shock proteins research
- Peptidase Inhibition and Analysis
- T-cell and B-cell Immunology
- Calcium signaling and nucleotide metabolism
- Photoacoustic and Ultrasonic Imaging
- RNA modifications and cancer
- Inorganic and Organometallic Chemistry
- Cancer-related molecular mechanisms research
- Neurological Complications and Syndromes
Novartis (Switzerland)
2021-2025
Curtin University
2024
Dartmouth–Hitchcock Medical Center
2023
UCB Pharma (United Kingdom)
2014-2023
King's College London
2011-2023
University of Liverpool
2022
Teledyne e2v (United Kingdom)
2022
New South Wales Department of Health
2020
Prince of Wales Hospital
2015-2020
University of Colorado Anschutz Medical Campus
2016-2020
GPR40 (FFAR1), a clinically proven anti-diabetes target, is Gq-coupled receptor for long chain fatty acids (LCFA) stimulating insulin secretion directly and mediating major part of the dietary triglyceride-induced incretins GLP-1 GIP. In phase-II studies agonist TAK-875 decreased blood glucose but surprisingly without incretins.Here we find that can signal through not only Gq IP3 also Gs cAMP when stimulated with certain agonists such as AM-1638 AM-5262 in contrast to endogenous LCFA ligands...
A potent, selective glucagon receptor antagonist 9m, N-[(4-{(1S)-1-[3-(3,5-dichlorophenyl)-5-(6-methoxynaphthalen-2-yl)-1H-pyrazol-1-yl]ethyl}phenyl)carbonyl]-β-alanine, was discovered by optimization of a previously identified lead. Compound 9m is reversible and competitive with high binding affinity (IC(50) 6.6 nM) functional cAMP activity 15.7 nM). It for relative to other family B GPCRs, showing IC(50) values 1020 nM GIPR, 9200 PAC1, >10000 GLP-1R, VPAC1, VPAC2. blunted glucagon-induced...
Glucagon and insulin have opposing action in governing glucose homeostasis. In type 2 diabetes mellitus (T2DM), plasma glucagon is characteristically elevated, contributing to increased gluconeogenesis hyperglycemia. Therefore, receptor (GCGR) antagonism has been proposed as a pharmacologic approach treat T2DM. support of this concept, potent small-molecule GCGR antagonist (GRA), MK-0893, demonstrated dose-dependent efficacy reduce hyperglycemia, with an HbA1c reduction 1.5% at the 80 mg...
Activation of the NLRP3 inflammasome in response to danger signals is a key innate immune mechanism and results production pro-inflammatory cytokines interleukin-1β (IL-1β) interleukin-18 (IL-18) as well pyroptotic cell death. Aberrant activation has been linked many acute chronic conditions ranging from atherosclerosis Alzheimer's disease cancer, based on clinical success IL-1-targeting therapies, emerged an attractive therapeutic target. Herein we describe our discovery, characterization,...
An efficient and high-yielding synthesis of 4-guanidino Neu5Ac2en, the potent anti-influenza A B compound, is described. The route exploits a stereospecific introduction key nitrogen functionality at C-4 via an oxazoline intermediate. Three different methods for final-step conversion 4-amino into derivatives are To explore structure–activity relationship in this region molecule, series substituted guanidino were synthesized their activity
Protein pharmacokinetic modulation is becoming an important tool in the development of biotherapeutics. Proteins can be chemically or recombinantly modified to alter their half-lives and bioavailability suit particular applications as well improve side effect profiles. The most successful clinically used approach date chemical conjugation with poly(ethylene glycol) polymers (PEGylation). Here, therapeutic protein half-life increased significantly while retaining biological function, reducing...
Single B cell technologies, which avoid traditional hybridoma fusion and combinatorial display, provide a means to interrogate the naturally-selected antibody repertoire of immunized animals. Many methods enable sampling memory subsets, but few allow for direct interrogation plasma repertoire, i.e., subset cells responsible producing immunoglobulin in serum. Here, we describe use robust simple fluorescence-based technique, called fluorescent foci method, identification isolation...
Every human possesses millions of distinct antibodies. It is now possible to analyze this diversity via Next Generation Sequencing Immunoglobulins Genes (Ig-seq). This technique produces large volume sequence snapshots B-cell receptors that are indicative the antibody repertoire. In paper we enrich these scale datasets with structural information. Enriching a its data allows better approximation many vital features, such as binding site and specificity. Here, describe Structural Annotation...
Abstract Protein:protein interactions are fundamental in living organism homeostasis. Here we introduce VHH6, a junctional epitope antibody capable of specifically recognizing neo-epitope when two proteins interact, albeit transiently, to form complex. Orthogonal biophysical techniques have been used prove the “junctional epitope” nature camelid single domain IL-6–gp80 complex but not individual components alone. X-ray crystallography, HDX-MS and SPR analysis confirmed that CDR regions VHH6...
Rationale: Image-guided, triggerable, drug delivery systems allow for precisely placed and highly localised anti-cancer treatment. They contain labels spatial mapping tissue uptake tracking, providing key location timing information the application of an external stimulus to trigger release. High Intensity Focused Ultrasound (HIFU or FUS) is a non-invasive approach treating small volumes particularly effective at inducing release from thermosensitive nanocarriers. Here, we present novel...