Dr. Kelly Berg's lab centers on answering questions concerning the molecular nature of drug efficacy and
the mechanisms by which the efficacy of drugs can be regulated.
selectivity is a term used to describe the ability of drugs to differentially
activate signaling cascades coupled to a single receptor subtype. We were among
the first to describe ligand functional selectivity for both agonists and
inverse agonists that target serotonin receptors.
Currently, we are determining
functional selectivity profiles for ligands that target kappa opioid receptors
in primary (peripheral) sensory neurons. In addition, we study the regulation of ligand
efficacy at mu, delta and kappa opioid receptor systems as well as delta-kappa receptor
peripheral sensory neurons.
In our studies, we utilize peripheral sensory neurons in culture and
rat behavioral models of peripheral nociception. Our ultimate goal is to understand
cellular factors that regulate opioid agonist efficacy and thereby develop new pharmacological targets
for improved pain therapy.
Sullivan LC, Berg KA, Clarke WP. (2015) Dual regulation of delta-opioid receptor function by arachidonic acid metabolites in rat peripheral sensory neurons. J Pharmacol Exp Ther. 353(1):44-51
Broselid S, Berg KA, Chavera TA, Kahn R, Clarke WP, Olde
B, Leeb-Lundberg LM. (2014) G protein-coupled receptor 30 (GPR30) forms a plasma membrane complex with membrane-associated guanylate kinases (MAGUKs) and protein kinase A-anchoring protein 5 (AKAP5) that constitutively inhibits cAMP production. J
Biol Chem. 289(32):22117-27.
Clarke WP, Chavera TA, Silva M, Sullivan LC, Berg KA. Signalling profile differences: paliperidone versus risperidone. Br J Pharmacol. 2013 Oct;170(3):532-45.
Berg KA, Patwardhan AM, Akopian AN. Receptor and channel heteromers as pain targets. Pharmaceuticals (Basel). 2012 Feb 23;5(3):249-78.+
Berg KA, Rowan MP, Gupta A, Sanchez TA, Silva M, Gomes I, McGuire BA, Portoghese PS, Hargreaves KM, Devi LA, Clarke WP. Allosteric interactions between δ and κ opioid receptors in peripheral sensory neurons. Mol Pharmacol. 2012 Feb;81(2):264-72.
Berg KA, Rowan MP, Sanchez TA, Silva M, Patwardhan AM, Milam SB, Hargreaves KM, Clarke WP. Regulation of κ-opioid receptor signaling in peripheral sensory neurons in vitro and in vivo. J Pharmacol Exp Ther. 2011 Jul;338(1):92-9.
Berg KA, Clarke WP. Use of functional assays to detect and quantify functional selectivity. Drug Discovery Today: Technologies 7(1):e31-e36.