![Professor Eamonn Kelly](https://research-information.bris.ac.uk/ws/files/380563981/Photo_EK_PURE.png)
Professor Eamonn Kelly
B.Sc.(Sheff.), Ph.D.(Lond.)
Current positions
Professor of Molecular Pharmacology
School of Physiology, Pharmacology & Neuroscience
Contact
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Research interests
The family of G protein-coupled receptors (GPCRs) contains more than 800 members, and are responsive to many different ligands in the body including amino acids and other small molecules, peptides, ions, hormones and even light. We are particularly interested in the opioid receptors, GPCRs that are activated by endogenous peptides such as the enkephalins and endorphins, and which are also the target of important drugs such as morphine.
Opioid drugs are of great therapeutic and societal importance, as they are used for the treatment of pain but are also abused by addicts. We study the pharmacology of µ and δ opioid receptors, from in silico Molecular Dynamics simulations which enable us to model opioid drug interactions with the receptor, through in vitro signalling assays in cells to experiments on opioid-induced respiratory depression. Our cell signalling assays involve measurements of ligand binding to opioid receptors, as well as opioid receptor coupling to G proteins and arrestins, and the phosphorylation and trafficking of the receptors. In all our studies we strongly emphasise the ideas of basic pharmacology such as efficacy and ligand kinetics to explore and explain the effects of opioid drugs.
One area of particular interest is that of ligand bias, where different agonists acting at a receptor are thought to induce distinct conformations of the receptor, leading to different downstream signalling effects and hence different effects in the organism. We are interested in exploring the nature of biased agonism at opioid receptors, and also in developing novel biased agonists for the µ and δ opioid receptors, to provide better, safer analgesic drugs with fewer adverse effects.
Another area of interest is that of opioid receptor desensitization, leading to tolerance to the effects of opioid agonist drugs, and loss of their effectiveness. The molecular mechanisms involved include receptor phosphorylation by GPCR kinases (GRKs) and arrestin binding to the receptor, but importantly other kinases are involved in opioid receptor regulation, such as protein kinase C. We are currently exploring these mechanisms in order to understand them fully.
Projects and supervisions
Research projects
MICA:Defining G protein- and arrestin-dependent signalling pathways of biased DOPr agonists and the relevance to their in vivo effects
Principal Investigator
Managing organisational unit
School of Physiology, Pharmacology & NeuroscienceDates
01/08/2016 to 31/10/2019
Do biased agonists at the mu-opioid receptor induce different patterns of receptor phosphorylation?
Principal Investigator
Managing organisational unit
School of Physiology, Pharmacology & NeuroscienceDates
01/03/2012 to 01/03/2015
MECHANISM OF PKC-MEDIATED DESENSITIZATION OF THE MORPHINE-ACTIVATED MU-OPIOID RECEPTOR IN NEURONES
Principal Investigator
Managing organisational unit
School of Physiology, Pharmacology & NeuroscienceDates
01/04/2007 to 01/04/2010
AGONIST - INDUCED REGULATION OF METABOTROPIC GLUTAMATE RECEPTORS
Principal Investigator
Dates
01/04/2000 to 01/04/2003
A DOMINANT NEGATIVE MUTANT APPROACH TO STUDY 6-PROTEIN COUPLED RECEPTER KINASE FUNCTION
Principal Investigator
Dates
01/01/1996 to 01/01/1999
Thesis supervisions
Molecular dynamics simulations and mutagenesis to identify the mechanisms of ligand efficacy and bias at the μ opioid receptor
Supervisors
Effect of Psychotomimetic and Schizophrenia-associated Drugs on Rat Visual Perceptual Grouping
Supervisors
Characterisation of Compounds as Potential Inhibitors of G Protein-Coupled Receptor Kinases
Supervisors
Studies in opioid induced respiratory depression
Supervisors
The affinities and efficacies of synthetic opioid agonists at the MOPr
Supervisors
Publications
Recent publications
02/04/2023Carfentanil is a β-arrestin-biased agonist at the μ opioid receptor
British Journal of Pharmacology
Comparison of the effects of fentanyls and other μ opioid receptor agonists on the electrical activity of respiratory muscles in the rat
Frontiers in Pharmacology
The Concise Guide to PHARMACOLOGY 2023/24
British Journal of Pharmacology
Biased Agonism: Lessons from Studies of Opioid Receptor Agonists
Annual review of pharmacology and toxicology
Interaction With the Lipid Membrane Influences Fentanyl Pharmacology
Advances in drug and alcohol research