Our goal is to understand molecular and neurobiological mechanisms of opioid action integrating chemical synthesis with biochemical, genetic and pharmacological approaches. Our eventual goal is to discover novel chemical probes/drugs, which can be useful in the treatment of pain and substance abuse, and which separate the opioid agonist mediated liabilities from its utility in medications development. Opiates such as morphine have been the preferred treatment of moderate to severe chronic pain. Clinically used mu opiate agonists/ analgesics (MOR) like morphine are associated with severe adverse-effects such as respiratory depression, constipation, physical dependence, reward, addiction and abuse liability. To overcome these problems, drugs in the kappa category were developed; however, kappa opioid agonists/ analgesics (KOR) had additional problems such as aversion, dysphoria and hallucinations. Delta opioid agonists (DOR) have been investigated as well, but the role of small molecule delta agonists has been limited due to the implication of these drugs in causing seizures. Thus, there remains a need for opioid drug targets/molecules, which will provide pain relief without side-effects. 
Work from the laboratory has led to probes which display G-protein biased signaling, truncated transmembrane splice variants of mu opioid receptor agonists and aided the crystallization of kappa opioid receptor in its active form and cryo-EM structures of natural product bound mu opioid modulators. Presently we use two distinct strategies to achieve opioid functional selectivity using natural products pharmacology, targeting allosteric sub pockets in receptors and identifying the molecular blueprint of arrestin recruitment using structure based approaches. 

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