A5072771208- Receptor Mechanisms and Signaling
- Diabetes Treatment and Management
- Pancreatic function and diabetes
- Neuropeptides and Animal Physiology
- Metabolism, Diabetes, and Cancer
- Diet and metabolism studies
- Monoclonal and Polyclonal Antibodies Research
- Neurotransmitter Receptor Influence on Behavior
- Cellular transport and secretion
- Advanced Biosensing Techniques and Applications
- Schizophrenia research and treatment
- Dietary Effects on Health
- Advanced biosensing and bioanalysis techniques
- Neuroscience and Neuropharmacology Research
- Endoplasmic Reticulum Stress and Disease
- Electrochemical sensors and biosensors
- Diabetes Management and Research
- Protein Kinase Regulation and GTPase Signaling
- Adenosine and Purinergic Signaling
- Advanced Fluorescence Microscopy Techniques
- Circadian rhythm and melatonin
- Retinal Development and Disorders
- Neurobiology and Insect Physiology Research
- Lipid Membrane Structure and Behavior
- Biochemical Analysis and Sensing Techniques
University of Pittsburgh
2017-2024
Queen Mary University of London
2023
University of Glasgow
2015
Abstract Dopamine (DA) and norepinephrine (NE) are catecholamines primarily studied in the central nervous system that also act pancreas as peripheral regulators of metabolism. Pancreatic catecholamine signaling has been increasingly implicated a mechanism responsible for metabolic disturbances produced by antipsychotic drugs (APDs). Critically, however, mechanisms which modulate pancreatic hormone release not completely understood. We show human mouse α- β-cells express biosynthetic...
For decades, there have been observations demonstrating significant metabolic disturbances in people with schizophrenia including clinically relevant weight gain, hypertension, and glucose lipid homeostasis. Many of these findings pre-date the use antipsychotic drugs (APDs) which on their own are also strongly associated side effects. The combination APD-induced changes common adverse environmental factors made it difficult to determine specific contributions each overall picture. Data from...
Ribosome-associated vesicles are a novel, dynamic ER-derived organelle.
cAMP production upon activation of G s by protein-coupled receptors has classically been considered to be plasma membrane-delimited, but a shift in this paradigm occurred recent years with the identification several that continue signal from early endosomes after internalization. The molecular mechanisms regulating aspect signaling remain incompletely understood. Here, we investigated role q/11 parathyroid hormone (PTH) type 1 receptor (PTHR) mediating endosomal responses. Inhibition...
Abstract Age is the greatest risk factor for Parkinson's disease (PD) which causes progressive loss of dopamine (DA) neurons, with males at greater than females. Intriguingly, some DA neurons are more resilient to degeneration others. Increasing evidence suggests that vesicular glutamate transporter (VGLUT) expression in plays a role this selective vulnerability. We investigated neuron VGLUT sex‐ and age‐related differences vulnerability using genetically tractable Drosophila model. found...
Bromocriptine is approved as a diabetes therapy, yet its therapeutic mechanisms remain unclear. Though bromocriptine's actions have been mainly attributed to the stimulation of brain dopamine D2 receptors (D2R), bromocriptine also targets pancreas. Here, we employ tool elucidate roles catecholamine signaling in regulating pancreatic hormone secretion. In β-cells, acts on D2R and α2A-adrenergic receptor (α2A-AR) reduce glucose-stimulated insulin secretion (GSIS). Moreover, α-cells, via...
G protein-coupled receptors are among the most widely studied classes of drug targets. A major challenge in this field is to develop ligands that will selectively modulate a single receptor subtype overcome disadvantages undesired "off target" effects caused by lack target and thus signaling specificity. In current study, we explored ligand design for melanocortin 4 (MC4R) since it an attractive developing antiobesity drugs. Endogenously, activated peptide ligands, i.e., three...
Dopamine (DA) D2-like receptors in both the central nervous system (CNS) and periphery are key modulators of metabolism. Moreover, disruption receptor signaling is implicated dysglycemia. Yet, respective metabolic contributions CNS versus peripheral receptors, including D2 (D2R) D3 (D3R) remain poorly understood. To address this, we developed new pharmacological tools, agonists with diminished delayed blood-brain barrier capability, to selectively manipulate D2R/D3R periphery. We designated...
Each subtype of the muscarinic receptor family G protein-coupled receptors is activated by similar concentrations neurotransmitter acetylcholine or closely related synthetic analogs such as carbachol. However, pharmacological selectivity can be generated introduction a pair mutations to produce Receptor Activated Solely Synthetic Ligand (RASSL) forms receptors. These display loss potency for acetylcholine/carbachol alongside concurrent gain in ligand clozapine N-oxide. Co-expression form...
The detection of insulin secretion is critical for elucidating mechanisms regulated as well in studies metabolism. Though numerous assays have existed decades, the recent advent homogeneous time-resolved Förster Resonance Energy Transfer (HTRF) technology has significantly simplified these measurements. This a rapid, cost-effective, reproducible, and robust optical assay reliant upon antibodies conjugated to bright fluorophores with long lasting emission which facilitates Transfer. Moreover,...
Dopamine (DA) D
<p dir="ltr">Dopamine (DA) D<sub>2</sub>-like receptors in both the central nervous system (CNS) and periphery are key modulators of metabolism. Moreover, disruption receptor signaling is implicated dysglycemia. Yet, respective metabolic contributions CNS versus peripheral including D<sub>2</sub> (D2R) D<sub>3</sub> (D3R) remain poorly understood. To address this, we developed new pharmacological tools, agonists with diminished delayed blood-brain...
<p dir="ltr">Dopamine (DA) D<sub>2</sub>-like receptors in both the central nervous system (CNS) and periphery are key modulators of metabolism. Moreover, disruption receptor signaling is implicated dysglycemia. Yet, respective metabolic contributions CNS versus peripheral including D<sub>2</sub> (D2R) D<sub>3</sub> (D3R) remain poorly understood. To address this, we developed new pharmacological tools, agonists with diminished delayed blood-brain...
Age is the greatest risk factor for Parkinson’s disease (PD) which causes progressive loss of dopamine (DA) neurons, with males at greater than females. We found that vesicular glutamate transporter (VGLUT) expression mediates vulnerability to age-related DA neurodegeneration in a sex-dependent manner, providing new mechanism sex differences selective neuron vulnerability. These findings lay groundwork novel therapeutic strategies boost neuronal resilience throughout aging.