Jerome Siegel, Ph.D.

Faculty Member

Professor in Residence
Chief, Neurobiology Research, Sepulveda VA Medical Center
Department of Psychiatry & Biobehavioral Sciences
David Geffen School of Medicine
University of California, Los Angeles

Research:

Our primary interest is in understanding the evolution, function and disorders of sleep. We are analyzing the brainstem-forebrain interactions responsible for the control of muscle tone in waking and across the sleep cycle. This is of importance in understanding REM sleep behavior disorder, cataplexy and sleep apnea. We are studying the phylogeny of sleep by investigating the physiology and neurochemistry of sleep in reptiles, marine mammals and human hunter gatherers.

A major focus of the laboratory is on narcolepsy, its anatomy, pathophysiology and treatment. We found that human narcolepsy is linked to a loss of locus coeruleus and hypocretin neurons as well as changes in other neuronal groups. The loss of locus coeruleus neurons, which project both rostrally as part of the ascending reticular activating system, and caudally to spinal motor systems, can explain the unique symptoms of narcolepsy, sleepiness and cataplexy. The loss of hypocretin (orexin) neurons, which we find are linked to opioid addiction, can explain the elevated incidence of depression in narcolepsy. We are investigating ways of controlling and reversing the symptoms of narcolepsy in narcoleptic animals and in humans.

See two recent publications below:

Thannickal, T.C., Wu, Ming-Fung, Cornford, M.C. and Siegel, Jerome M., Human narcolepsy is linked to degeneration of both locus coeruleus and hypocretin neurons.  Nature Communications [PMID 41904178] 2026. https://doi.org/10.1038/s41467-026-70899-x

McGregor, R., Wu, Ming-Fung, Thannickal, T.C., Siegel, Jerome M. Opioid-induced neuroanatomical, microglial and behavioral changes are blocked by suvorexant without diminishing opioid analgesia. Nature Mental Health. PMCID: PMC11845277  NIHMSID: NIHMS2053716  PMID: 39989723, 2024