Research

Our lab is interested in finding strategies and drug targets to better treat substance use disorders and to find non-opioid alternatives to treat chronic pain. We study molecular and circuit adaptations to drugs of abuse that contribute to substance use disorders, and animal models of conditions that confer addiction risk, such as excessive anxiety and chronic pain. Our studies use a variety of molecular (gene targeting, transgenic expression, RNA interference) and circuit mapping (electrophysiology, chemogenetics, immunohistochemistry, in situ hybridization) techniques in rodents to study the role of specific signaling proteins and circuits that regulate behavior. We also use systems-based computational strategies that compare gene expression signatures of disease and pharmaceuticals with the goal of repurposing approved drugs for treating substance use disorders. Our major contributions include determining that protein kinase C epsilon, protein kinase C delta, protein kinase M zeta, N-type voltage-dependent calcium channels, the type 1 equilibrative nucleoside transporter, and phosphodiesterase 4 (PDE4) regulate alcohol intoxication and self-administration in mice. Our work with PDE4 has lead to a human trial with the PDE4 inhibitor apremilast in people with alcohol use disorder. Research on protein kinase C epsilon has led to ongoing efforts to develop a PKC epsilon inhibitor as a treatment for chronic pain and alcohol use disorder.