Research in Dr. William Clarke's lab is focused on understanding the molecular mechanisms that
underlie drug efficacy (the ability of a drug to produce a response) and its
We study the behavioral effects and cellular signaling profiles of
opioid agonists (e.g. morphine) that act on peripheral pain-sensing neurons
that reside outside the CNS. Peripheral pain-sensing neurons sense actual or
potential tissue damage and send signals into the CNS that are interpreted as
Drugs that target opioid receptors expressed by these sensory neurons have
the potential to inhibit neuronal signaling and reduce pain neurotransmission.
Thus, peripherally-restricted opioid drugs would be effective analgesics, but
would be devoid of debilitating and life-threatening CNS-mediated adverse
effects (e.g. respiratory depression, addiction, etc.) that plague current
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, 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.
Clarke WP, Berg KA. Use of functional assays to detect and quantify functional selectivity. Drug Discovery Today: Technologies. 7:
Berg KA, Maayani S, Goldfarb J, Scaramellini C, Leff P, Clarke WP. Effector
pathway-dependent relative efficacy at serotonin type 2A and 2C
receptors: evidence for agonist-directed trafficking of receptor
stimulus. Mol Pharmacol. 1998 Jul;54(1):94-104.