Harvard Catalyst Profiles

Carnegie Mellon University, Pittsburgh, PA	B.S.	05/1992	Biology
University of Washington, Seattle, WA	Ph.D.	05/2001	Neurobiology & Behavior
Harvard Medical School, Belmont, MA		09/2004	Neuroscience

My research focuses on understanding the molecular mechanisms underlying depressive-like states that accompany withdrawal from drugs of abuse. Alleviation of aversive withdrawal symptoms is thought to be a primary motivation for continued drug taking. The mesolimbic dopamine system, which includes the nucleus accumbens (NAc), plays an important role in both the rewarding and aversive effects of drugs such as morphine and cocaine. Several independent but complimentery lines of research are being conducted in my lab. First, we are researching the molecular and circuit mechanisms that mediate opioid withdrawal-associated negative affective states, as these have been shown to contribute to maintenance of drug taking and relapse. We focus primarily on the prescription opioid, oxycodone, and we use intravenous drug self-administration to model different aspects of the addictive process. Second, we are interested in the effects of perinatal opioid exposure on molecular, cellular, and behavioral regulation of reward systems in the offspring. Neonatal abstinence syndrome (NAS) is a tragic and ever-increasing crisis in health care, and yet little is known about the immediate or long-tern neurobiological effects. We hypothesize that dysregulated microglia and microglia function contribute to abnormalities associated with perinatal opioid exposure. A third area of research is probing the effects of chronic opioid exposure and withdrawal on sleep stages and dynamics in rats. In people with opioid use disorder (OUD) or in opioid withdrawal, insomnia is described as one of the most debilitating symptoms. And yet little is understood about how this manifests or is regulated. Finally, my group has a long-standing interest in the neuropeptide dynorphin and its receptor, the kappa opioid receptor (KOR). Dyn/KOR systems produce negative affective states including anhedonia, dysphoria, and anxiety. We have demonstrated robust sex differences in the effects of KOR activation within reward-related behaviors and circuits. We are investigating the use of KOR antagonists as potential therapeutics for OUD and stress-related disorders.