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Research Interests

The research in my laboratory investigates both the detrimental health effects and the potential novel therapeutic effects of opiate drugs, such as heroin and morphine. There is a high incidence of bacterial, viral, and fungal infections among long-term heroin users suggesting that the use of opioids increases susceptibility to infectious disease. While usually attributed to the poor health behavior, studies in my laboratory have shown that opiates themselves induce pronounced alterations of immune responses that are mediated through neural immune pathways. Interestingly, the results of our investigations have demonstrated that stimuli associated with the administration of heroin can induce alterations of immune functioning, indicating that the detrimental health consequences of opiate use may also be conditioned to environmental stimuli and not solely due to the pharmacological properties of the drug. How is it that drug-associated stimuli engage both the peripheral immune system and the associative learning circuitry such that the immune consequences of drug use persist despite the absence of drug use? The overall aim of our research is to unravel the complex neural circuitry and cellular mechanisms mediating drug-conditioned immune alterations and cue-evoked drug craving. To date, this work has shown that a circuit from the ventral tegmental area to the basolateral amygdala and the nucleus accumbens is critical for the expression of opiate-conditioned immunomodulation. Most recently, we have shown that the dorsal hippocampus is a critical link in this reward circuitry.

Cell-specific expression of hippocampal interleukin-1β in microglia and astrocytes. Our laboratory uses fluorescence immunohistochemistry, confocal microscopy, and Bitplane Imaris image analysis technology to isolate specific cell types expressing key cytokines in brain regions that are critical to opioid-induced changes in neural immune signaling. This 3-dimensional reconstruction shows interleukin-1β (green, Alexa488), one proinflammatory cytokine that we have shown to be critical to heroin-conditioned immunosuppression, expressed by both astrocytes (anti-GFAP, blue, Alexa405) and microglia (anti-Iba-1, red, Alexa568) in the dorsal hippocampus.

While our efforts to map the neural circuitry mediating heroin-conditioned immunosuppression have been informative, the cellular mechanisms that contribute to this effect have yet to be explored. Alterations in neuroimmune signaling within the brain may be integral to both impaired immune responses and addictive behavior in drug abusers. Recently, there has been a conceptual shift regarding the functional significance of cytokines in the brain. Once viewed primarily as immune molecules that mediate inflammatory events during pathology, cytokines are now recognized to be key participants in neuronal communication – more akin to neurotransmitters and neuropeptides. Importantly, cytokines play a critical role as signaling molecules in the acquisition and expression of associative learning. These effects are mediated by neural and glial cell activity. We have initiated interdisciplinary research using pharmacological and chemogenetic methods to identify the contributions that brain cytokines make in the both the health consequences and addictive properties of conditioned stimuli associated with drug use.

Opiates also have well established therapeutic applications such as pain relief. Our work is focused on more unique uses of opiates in the treatment of anxiety disorders. We have initiated studies of opiates as pharmacotherapeutic agents in the prevention of stress related disorders such as post-traumatic stress disorder (PTSD). This research provides the first key steps towards the development of a preventative therapy for PTSD. Clinical studies have shown a correlation between morphine administration and a decrease in post traumatic symptoms following trauma. Our research has provided strong basic research support for this relationship. Our goal is to understand the neural mechanisms by which opiates impact the development of PTSD. Currently, there is little known about PTSD formation and how it can be prevented in the aftermath of a major stress or trauma, but our newly evolving research focusing on opioid pharmacotherapy and neuroinflammatory processes will provide new insights and potential treatments for this devastating disorder.

Morphological analysis of individual hippocampal astrocytes. In collaboration with Dr. Kathryn Reissner’s laboratory at UNC, we have also recently begun employing a membrane-tagged GFP expressed under a GFAP promotor to isolate and analyze the morphometric properties of hippocampal astrocytes. Above, a 3-dimensional reconstruction of an individual hippocampal astrocyte is shown.