I received the degree in Pharmacy at the University of Palermo (Italy) in 1993, and trained in in vivo electrophysiology at the Department of Neuroscience “Bernard B. Brodie” (University of Cagliari, Italy) under the mentorship of GianLuigi Gessa in the lab led by Marco Diana. The team focused on the understanding of cellular basis of acute and chronic effects of drugs of abuse on reward dopamine neurons.
We discovered that the psychoactive ingredient of marijuana (THC) acts on these neurons similarly to alcohol and morphine. In fact, we provided for the first time in vivo electrophysiological evidence for the mechanisms of both THC acute recreational effects (Gessa et al., 1998; Diana et al., 1998a), and the state of dysphoria during withdrawal from its chronic use (Diana et al., 1998b). These studies laid the foundations for postulating the state of hypodopaminergia following chronic drug use (Melis et al., 2005), which was subsequently discovered in addicted humans.
In 2000, I moved to San Francisco to the “Ernest Gallo Clinic and Research Center” at University of California San Francisco (UCSF) in the laboratory of Antonello Bonci, where I investigated on the effects of a single in vivo exposure to alcohol in the modulation of neuronal excitability and plasticity at synapses impinging upon dopamine neurons ex vivo (Melis et al., 2002; Wanat et al., 2009).
Upon my return to “Bernard B. Brodie” Department of Neuroscience in 2002, I discovered that dopamine neurons can also synthesize and release endocannabinoids (Melis et al., 2004a* and b*). For this discovery, which showed for the first time that endocannabinoids can fine tune dopamine neuronal activity both ex vivo and in vivo, I was recipient of both the “Farmindustria-SIF Award” for Pharmacological Research and the NIDA Travel award for Society for Neuroscience held in San Diego, where I was an invited speaker.
I earned my PhD in Neuroscience in 2011 with Marco Pistis. During my PhD studies, I investigated with him the functional modulation of endocannabinoid-related molecules (i.e., fatty acid ethanolamines) on dopamine neuronal activity via a non-genomic mechanism downstream activation of a nuclear receptor transcription factor that is PPARα, by using a combination of electrophysiological, behavioral and biochemical approaches (Melis et al., 2008; 2010*; 2013a*). This work revealed a specific role of the interaction between the cholinergic system and PPARα on dopamine neurons (Melis et al., 2013b*), which relates to diverse disorders associated with unbalanced dopamine-acetylcholine systems (e.g. depression, nicotine addiction, ADHD, stress). In 2010, I was a recipient of the “Award for Best innovative business idea” at the contest “Talento delle idee” (sponsored by Unicredit Group Bank and Confindustria) for technological transfer of a nutraceutical product to quit tobacco smoking.
In 2011, I visited the Department of Neuroscience at the Biomedical Center (University of Lund, Sweden) in the Experimental Epilepsy Group led by Merab Kokaia, in order to master optogenetics (Berglind et al., 2014; Toft Sorensen et al., 2018). Upon my return, I remained in the same group led by Marco Pistis at Department of Biomedical Sciences. During those years, the findings on the interaction between cholinergic system and PPARα were extended to other brain regions and pathological conditions, such as epilepsy and depression (Puligheddu et al., 2013; Scheggi, Melis et al., 2016). In particular, PPARα activation proves useful in both a pharmacological and a genetic mouse model of nocturnal frontal lobe epilepsy, which we subsequently and successfully implemented in a clinical setting (Puligheddu, Melis et al., 2017).
In september 2023, I was appointed full professor of Pharmacology at the same Department of Biomedical Sciences in Cagliari, where I served as an associate professor since the fall of 2016.
My long term goal is to understand the neurobiological mechanisms underlying resilience and vulnerability to neuropsychiatric disorders (e.g., substance use disorder, antisocial behavior, anxiety, depression) with a focus on the adaptations of both mesocorticolimbic dopamine pathway and endocannabinoid system. I began to address my research question before I could lead my own team (Melis et al. 2013c*, 2014*) and I continued once I could establish my own lab (Frau et al 2019a*; Frau et al. 2019b*; Sagheddu et al. 2021*; Traccis et al. 2021*; Serra et al. 2023*).
A complete list of my publication can be found on PubMed