I have been focused on determining the function of sleep and more recently the function of the peptide hypocretin (Hcrt or orexin).

We were the first to report the loss of hypothalamic hypocretin neurons in human narcolepsy, in 2000 (see below-left) and in 2005 were the first to record hypocretin neurons in behaving animals, finding that they fired in relation to approach/pleasureable behavior (click here to see video). In 2025 we discovered that all humans with narcolepsy also have a loss of locus coeruleus noradrenergic neurons. Our studies in 2025 show that the loss of locus coeruleus neurons is not caused by the loss of hypocretin neurons. The two neuronal losses, of hypocretin in the forebrain and of norepinephrine in the brainstem locus coeruleus, underlie human narcolepsy and may both be caused by an autoimmune process. About 150,000 Americans have narcolepsy, a lifelong disorder. 

In 2018, 2024 and 2025 we discovered that hypocretin neurons have a major role in opioid addiction and that opioid dependence can be prevented in animals by deleting hypocretin neurons. In 2024 we found that opioid dependence can also be prevented, without reducing opioid analgesia, by blocking hypocretin receptors with suvorexant, a hypocretin receptor antagonist, when administering opioids. About 8 million Americans have opioid dependence. Opioid dependence caused more than 80,000 opioid overdose deaths last year in the United States.

Director: Jerome Siegel  My Bibliography: https://www.ncbi.nlm.nih.gov/myncbi/jerome.siegel.1/bibliography/public/