About

David M. Raizen, MD, PhD, is a Professor of Neurology at the University of Pennsylvania and a member of the Mahoney Institute of Neurological Sciences, the Institute for Translational Medicine and Therapeutics, and the Chronobiology and Sleep Institute. His research focuses on the regulation and function of sleep and fatigue, exploring these phenomena through the model organism Caenorhabditis elegans. Raizen's work investigates the universal behavioral states of quiescence, including sleep, and aims to understand their core functions and molecular regulation. He studies sleep-like states in C. elegans, such as lethargus, which shares similarities with sleep in other animals, and examines how genetic regulation influences these states. His research also extends to stress-induced sleep and sickness behavior, involving neuropeptides and specific neurons that promote sleep, which has implications for understanding fatigue during illness. Raizen's contributions include identifying novel sleep regulators and elucidating mechanisms underlying sleep and behavioral quiescence, addressing fundamental questions about why sleep evolved and its biological significance.

Research topics

• Biology
• Neuroscience
• Medicine
• Cell biology
• Psychology

Selected publications

• Tricyclic antidepressants suppress sleep in <i>Caenorhabditis elegans</i>

  SLEEP · 2026-02-05

  articleOpen accessSenior author

  STUDY OBJECTIVES: Sleepiness and fatigue are common symptoms during illness and may persist after the resolution of illness. To gain insight into the neurochemistry of sickness-induced sleep and to discover therapeutic candidates, we performed a high throughput chemical screen using the animal model Caenorhabditis elegans. METHODS: Worms were irradiated with ultraviolet light to induce sickness and then transferred to wells of a 96-well plate each containing a different bioactive chemical dissolved in an aqueous solution. The fraction of quiescent animals was assessed via stereomicroscopic observation. We performed 12 vehicle-only controls for each 96-well plate and considered sleep-inhibiting chemicals as those with a fraction quiescent at least 3 standard deviations less than controls. We followed up the screen with dedicated mechanistic studies of the drug amitriptyline. RESULTS: Among 3683 bioactive chemicals screened, 42 strongly reduced sleep behavior. We retested 26 and replicated 23 chemicals as sleep-disrupting. Among replicated compounds were amitriptyline (AMI) and other tricyclic anti-depressants (TCAs). AMI acted downstream of or in parallel to activation of sleep-promoting neurons. In addition to suppressing sleep in sickness (SIS), AMI also suppressed sleep in health and reduced survival. We tested and rejected the hypothesis that AMI acts by increasing monoaminergic tone, providing evidence that TCAs act via a novel mechanism to block sleep. CONCLUSIONS: This is the first high-throughput screen for chemicals modulating SIS. Elucidating the mechanism by which AMI and other chemicals regulate sleep will lead to new biological insights regarding the mechanisms of sleep.

  PublisherDOI

• An automated genetic screen identifies modulators of stress-induced sleep in <i>Caenorhabditis elegans</i>

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-05-19

  articleOpen access

  Abstract Animals sleep more when they are sick. In C. elegans , stress-induced sleep (SIS) follows cellular injury such as exposure to ultraviolet (UV) light. The genetic regulators of SIS remain incompletely defined. Using a worm-picking robot, multi-well WorMotel imaging, and association analysis we performed a semi-automated screen of 941 whole-genome–sequenced Million Mutation Project (MMP) strains. We quantified behavioral activity and quiescence before and after ultraviolet (UV) radiation. We applied the Sequence Kernel Association Test (SKAT) to this behavioral data to prioritize 6,663 genes and observed significant enrichment of known SIS genetic regulators. Based on these results, we conducted a candidate validation screen for additional genes regulating SIS. We identified three genes ( strd-1, egl-8, cla-1), mutations in which reproducibly influence SIS. Further exploration of these genes holds potential for enhancing our understanding of the molecular basis of SIS. These findings establish a pipeline for automated behavioral phenotyping coupled with gene-based association to accelerate studies of C. elegans neurogenetics.

  PublisherOA PDFDOI

• GravSorter: a forward-genetics tool for studying gravity response in <i>Caenorhabditis elegans</i>

  The Analyst · 2026-01-01

  articleOpen access

  animals. GravSorter provides an efficient and generalizable platform for identifying genes and neural circuits that govern directed locomotion in response to environmental stimuli and for assessing drug efficacy. The underlying principle, opposing active taxis-driven thrust with a passive taxis-independent force, provides a generalizable framework for high-throughput forward genetic screens to investigate diverse taxis modalities and their underlying neural circuits.

  PublisherDOI

• Author response for "GravSorter: A Forward-Genetics Tool for Studying Gravity Response in Caenorhabditis elegans"

  2026-04-01

  peer-review
  PublisherDOI

• Can sleep be “banked”? A PRO-CON debate

  SLEEP · 2025-08-23

  articleOpen access1st authorCorresponding
  PublisherOA PDFDOI

• The Effect of Sickness-Induced Sleep and SIK Homolog KIN-29 on Glycolysis in C.elegans

  ScholarlyCommons (University of Pennsylvania) · 2025-09-15

  otherOpen accessSenior author

  The microscopic nematode, Caenorhabiditis elegans, is an ideal model in studying post-illness fatigue and sleep that aids in the processes of repair following injury illness, referred to as sickness-induced sleep (SIS). SIS can be induced by several environmental factors, such as infection, heat, or UV radiation exposure, resulting in decreased movement and feeding (quiescence). By using the biosensor Hylight that detects Fructose 1,6-biphosphate (FBP) in KIN-29 C.elegans mutants, we are able to observe the effects of SIS on metabolic processes like glycolysis, especially in C.elegans lacking the Salt-Inducible Kinase homolog. Using WorMotel imaging after exposure to UV radiation, we show that wild-type C.elegans exhibit quiescence in response to UV stress, and find that mutations in certain strains of C.elegans inhibit quiescence in response to stress. By using compound microscope fluorescent imaging after exposure to UV radiation, we determine that wild-type worms exhibit increases in FBP ratios following exposure to UV stress, indicating that the rate of glycolysis increases in SIS. KIN-29 mutant worms exhibit similar increases in FBP ratios to wild-type worms following exposure to UV stress, and show no significant differences in baseline FBP ratios compared to wild-type worms. Our findings indicate that while KIN-29 affects ATP levels in C.elegans, KIN-29 does not regulate the increased rate of glycolysis in SIS. These results clarify that glycolysis in relation to FBP, involving exposure to UV stress, is unaffected by the KIN-29 homolog in worms, providing insight on metabolic processes in sleep.

  Publisher

• Structural neuroplasticity after sleep loss modifies behavior and requires neurexin and neuroligin

  iScience · 2024-03-11 · 7 citations

  articleOpen access

  mediate the morphologic and behavioral consequences of sleep loss, providing insight into the relationship between sleep, neuroplasticity, behavior, and neurologic disease.

  PublisherDOI

• Genetic variants associated with chronic fatigue syndrome predict population-level fatigue severity and actigraphic measurements

  SLEEP · 2024-10-15 · 3 citations

  articleOpen access

  STUDY OBJECTIVES: The diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (CFS) is based on a constellation of symptoms which center around fatigue. However, fatigue is commonly reported in the general population by people without CFS. Does the biology underlying fatigue in patients with CFS also drive fatigue experienced by individuals without CFS? METHODS: We used UK Biobank actigraphy data to characterize differences in physical activity patterns and daily temperature rhythms between participants diagnosed with CFS compared to controls. We then tested if single nucleotide variants (SNVs) previously associated with CFS are also associated with the variation of these actigraphic CFS correlates and/or subjective fatigue symptoms in the general population. RESULTS: Participants diagnosed with CFS (n = 295) had significantly decreased overall movement (Cohen's d = 0.220, 95% CI of -0.335 to -0.106, p-value = 2.42 × 10-15), lower activity amplitudes (Cohen's d = -0.377, 95% CI of -0.492 to -0.262, p-value = 1.74 × 10-6), and lower wrist temperature amplitudes (Cohen's d = -0.173, 95% CI of -0.288 to -0.059, p-value = .002) compared to controls (n = 63,133). Of 30 tested SNVs associated in the literature with CFS, one was associated in the control population with subjective fatigue and one with actigraphic measurements (FDR < 0.05). CONCLUSIONS: The genetic overlap of CFS risk with actigraphy and subjective fatigue phenotypes suggests that some biological mechanisms underlying pathologic fatigue in patients with CFS also underlie fatigue symptoms at a broader population level. Therefore, understanding the biology of fatigue in general may inform our understanding of CFS pathophysiology.

  PublisherOA PDFDOI

• A perfect storm: sleep loss causes systemic inflammation and death

  Cell Research · 2024-01-11 · 9 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• 1150 Isolated Nightmares: An Unusual Presentation of Narcolepsy?

  SLEEP · 2024-04-20

  articleSenior author

  Abstract Introduction A nightmare involves an internally generated conscious experience of negative emotional valence. Nightmares typically occur during REM sleep, which is most prevalent during the second half of the night. A young female presented with isolated nightmares, occurring near sleep onset and raising suspicion for narcolepsy. Report of case(s) A 21-year-old female presented to the sleep center due to experiencing daily nightmares for five years. Nightmares were described as “super realistic”, “distressing”, and occurred minutes after sleep onset. Nightmare content varied. Some of her nightmare themes included an apocalypse, family members dying, and animals chasing her. She had a remote history of anxiety and was previously prescribed sertraline, which had been discontinued two years ago. She reported no hallucinations, cataplexy, sleep paralysis, dream enactment or excessive sleepiness. She had been using a hormonal transdermal patch for about 2 years. On physical exam, she was noted to have mild bilateral proptosis with white sclera visible above the iris on primary gaze. Polysomnography (PSG) revealed a sleep onset latency of 30.5 minutes, N1 1.5%, N2 47.5%, N3 20.9%, and REM 30.1%. REM sleep latency was short at 63.5 minutes. There were 21.6 arousals per hour. The apnea-hypopnea index was of 0.3 events per hour. The PSG was followed by a multiple sleep latency test (MSLT), which measured a mean sleep latency of 5 minutes 42 seconds during five nap opportunities. The patient experienced REM sleep in both the first and third nap, with a REM sleep latency of 4.5 minutes. The patient’s MSLT revealed pathological sleepiness, which supported a diagnosis of narcolepsy without cataplexy, although the patient reported nightmares and not sleepiness. Conclusion This is an atypical presentation for narcolepsy, which is characterized by REM sleep abnormalities. Further research, classifications, and diagnostic criteria for clinical REM phenomena associated with narcolepsy should be investigated. Clinicians who treat patients with narcolepsy should monitor not only the characteristic symptoms of narcolepsy, such as cataplexy or sleepiness, but also inquire about oneiric activity. Support (if any)

  PublisherDOI

Recent grants

• NIH Grant R01NS064030

  NIH · $1.7M · 2015

• NIH Grant R21NS091500

  NIH · $429k · 2018

• NIH Grant R03AG042690

  NIH · $74k · 2015

• Mechanism of Sleep Regulation by SIK3

  NIH · $2.9M · 2019–2029

• NIH Grant K08NS048914

  NIH · $878k · 2010

Frequent coauthors

• Haim H. Bau

  University of Pennsylvania

  40 shared

• Jinzhou Yuan

  Research Institute of Dallas

  34 shared

• Christopher Fang‐Yen

  The Ohio State University

  26 shared

• Nicholas F. Trojanowski

  University of Pennsylvania

  15 shared

• Matthew D. Nelson

  14 shared

• Young‐Jai You

  The University of Texas Southwestern Medical Center

  12 shared

• Matthew S. Kayser

  University of Pennsylvania

  10 shared

• Gihan Tennekoon

  Children's Hospital of Philadelphia

  9 shared

Education

• BA

  University of Texas at Austin

  1989