Prof. Lior Appelbaum

Telephone
Email
lior.appelbaum@biu.ac.il
Office
Institute of Nanotechnology and Advanced Materials, Building 206, 9th floor, Rooms B-938 (office); 937 (lab)
Fields of Interest

Neuron, Glia, Sleep, Epilepsy, Live imaging, Two photon microscope, Behavior, Autism, Hyperbaric therapy, Zebrafish, Reef fish, Cnidarians

Research Categories
    Research

    Molecular and cellular neuroscience of sleep and neurodevelopmental disorders

    The Appelbaum Lab at Bar-Ilan University investigates the biological mechanisms of sleep, neuronal function, and neurodevelopmental disorders. Using zebrafish and advanced live-imaging techniques, including two-photon microscopy, we study the activity of neurons and glial cells, neural circuits, and the relationship between brain activity, sleep, and behavior. Our research has demonstrated that sleep increases chromosome dynamics, facilitating the repair of DNA damage accumulated in neurons during wakefulness.

    A central focus of our research is understanding why sleep is essential and how its biological functions evolved. By studying zebrafish, coral reef fish, and cnidarians such as jellyfish and sea anemones, we investigate the evolutionary origins of sleep, its role in maintaining neuronal genomic stability, and the effects of environmental factors, including artificial light pollution, on sleep and brain function.

    We also investigate the cellular and molecular mechanisms underlying neurological and neurodevelopmental disorders, including Fragile X syndrome, epilepsy, and sleep disturbances. By combining behavioral analysis, genetic approaches, and advanced imaging technologies, we seek to understand how disruptions in neuronal activity and sleep regulation contribute to these conditions. In parallel, we explore potential therapeutic approaches, including pharmacological and genetic interventions and hyperbaric oxygen therapy.

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    Top view of the head of a five-day-old zebrafish. Fluorescent protein labeling reveals neurons in the brain in red and green.

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    Top view of the head of a transparent zebrafish, with neurons labeled using fluorescent proteins of different colors. Photo by Tali Levitas.

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    Sensory neuron. Red - Nueron Green(yellow) - Synapses (David Zada)

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    Hypocretin cell in Zebrafish head

     

    Courses
    • 80349-01 - Endocrinology
    • 806952-01 - Reef Fish Neurobiology
    • 80925-01 - Seminar
    • 80334-01 - Non-Mammalian Organisms As Model for Bio-Medical Research
    • 80489-01 - Biotechnology Seminar
    Publications

    Selected Publications

    1. Ben-Ezra, S., Harpaz, R., Krayden, G., Ohavia, M., Engert, F., Appelbaum, L., & Levy, O. (2026). Artificial light pollution disrupts sleep and neuronal genomic stability in wild reef fish. Current Biology, 36, 3435–3445.e5. https://doi.org/10.1016/j.cub.2026.05.058

      Demonstrates that artificial light pollution at night disrupts sleep and alters behavior in coral reef fish. Reduced sleep duration and consolidation were associated with increased DNA damage in brain neurons, revealing a connection between environmental light pollution, sleep disruption, and neuronal genomic stability.

    2. Aguillon, R., Harduf, A., Sagi, D., Simon-Blecher, N., Levy, O., & Appelbaum, L. (2026). DNA damage modulates sleep drive in basal cnidarians with divergent chronotypes. Nature Communications, 17, Article 3. https://doi.org/10.1038/s41467-025-67400-5

      Investigates the relationship between DNA damage and sleep in jellyfish and sea anemones, two evolutionarily ancient groups with different daily activity patterns. The findings suggest that DNA damage contributes to the regulation of sleep even in animals without centralized brains, supporting an ancient evolutionary role for sleep in maintaining genomic integrity.

    3. Sagi, D., Tibi, T., Admati, I., Lerer-Goldshtein, T., Hochgerner, H., Zeisel, A., & Appelbaum, L. (2024). Single-cell profiling uncovers evolutionary divergence of Hypocretin/Orexin neuronal subpopulations. Journal of Neuroscience, 44, e0095242024.

      Uses single-cell profiling to characterize Hypocretin/Orexin neurons, which play an important role in regulating sleep and wakefulness. The study identifies distinct neuronal subpopulations and examines their evolutionary divergence, contributing to our understanding of how sleep-regulating neural circuits have evolved across vertebrates.

    4. Uribe-Arias, A., Rozenblat, R., Vinepinsky, E., Marachlian, E., Kulkarni, A., Zada, D., Privat, M., Topsakalian, D., Charpy, S., Candat, V., Nourin, S., Appelbaum, L., & Sumbre, G. (2023). Radial astrocyte synchronization modulates the visual system during behavioral-state transitions. Neuron, 111, 4040–4057.e6. https://doi.org/10.1016/j.neuron.2023.09.022

      Reveals how synchronized activity in radial astrocytes influences visual processing during transitions between behavioral states. Using zebrafish, the researchers demonstrate that interactions between glial cells and neurons alter functional connectivity and visual responses, contributing to freezing behavior following heightened alertness.

    5. Zada, D., Sela, Y., Matosevich, N., Monsonego, A., Lerer-Goldshtein, T., Nir, Y., & Appelbaum, L. (2021). Parp1 promotes sleep, which enhances DNA repair in neurons. Molecular Cell, 81, 4979–4993.e7. https://doi.org/10.1016/j.molcel.2021.10.026

      Identifies the DNA damage response protein PARP1 as a regulator of sleep. Experiments in zebrafish and mice demonstrate that accumulated neuronal DNA damage promotes sleep through PARP1-related mechanisms, while sleep enhances chromosome dynamics and DNA repair.

    6. Zada, D., Bronshtein, I., Lerer-Goldshtein, T., Garini, Y., & Appelbaum, L. (2019). Sleep increases chromosome dynamics to enable reduction of accumulating DNA damage in single neurons. Nature Communications, 10, Article 895. https://doi.org/10.1038/s41467-019-08806-w

      Provides direct evidence that sleep facilitates the repair of DNA damage in neurons. Using live imaging of individual neurons in transparent zebrafish, the researchers demonstrate that chromosome movement increases during sleep, enabling the reduction of DNA damage accumulated during wakefulness.

    7. Shamay-Ramot, A., Khermesh, K., Porath, H. T., Pinto, Y., Wachtel, C., Barak, M., Lerer-Goldshtein, T., Levanon, E. Y., & Appelbaum, L. (2015). Impaired neural circuit formation and augmented RNA editing enzyme activity in fragile X syndrome. PLoS Genetics, 11, e1005702. https://doi.org/10.1371/journal.pgen.1005702

      Investigates abnormalities in neural circuit development associated with fragile X syndrome. The study links impaired neural connectivity with increased activity of RNA-editing enzymes, providing insights into molecular and developmental mechanisms associated with this neurodevelopmental disorder.

    Media

    Media Coverage 

    Sleep Helps to Repair Damaged DNA in Neurons, Scientists Find | The Guardian | March 5, 2019

    Explores the laboratory's landmark discovery that chromosome movement increases during sleep, facilitating the repair of DNA damage accumulated in neurons during waking hours.

    Sleep Is Critical for the Zebrafish Brain to Repair DNA Damage | The Scientist | March 6, 2019

    Examines the laboratory's use of three-dimensional live imaging to observe chromosome dynamics in individual neurons, revealing how sleep supports the repair of DNA damage in the brain.

    To Sleep, Perchance to Let DNA Be Repaired: Study Finds New Reason for Slumber | The Times of Israel | March 5, 2019

    Reports on research using zebrafish models to identify a cellular maintenance mechanism through which sleep facilitates DNA repair, offering a physiological explanation for the need to sleep.

    BIU Study Reveals That Origin of Sleeping in Humans Is Deduced from Jellyfish, Sea Anemones | The Jerusalem Post | January 10, 2026

    Covers collaborative research demonstrating that the relationship between DNA damage and sleep extends to jellyfish and sea anemones, suggesting that this fundamental biological function emerged hundreds of millions of years ago.

    Cracking the Evolutionary Code of Sleep | EurekAlert! / Bar-Ilan University | January 6, 2026

    Presents findings on the evolutionary origins of sleep, showing how the relationship between sleep and DNA maintenance may have emerged long before the development of complex brains.

    Woke Up at 4 a.m. Today? You're Not Alone | Ynet | 2023

    An article exploring the functions of sleep and its underlying biological mechanisms. Prof. Lior Appelbaum explains how experiments using transparent zebrafish enabled researchers to observe the accumulation of DNA damage in neurons and discover how sleep facilitates DNA repair.

    Video and Audio

    Sleep and DNA Repair – Podcast with Professor Lior Appelbaum (Episode 063) | humanOS Radio | August 27, 2019

    An in-depth interview with Prof. Lior Appelbaum exploring the biological purpose of sleep, chromosome dynamics in neurons, and the mechanisms through which sleep facilitates DNA repair.

    Sleep and Zebrafish | ARTE

    A European television segment featuring the laboratory's zebrafish research and live microscopy techniques used to investigate chromosome movement and DNA repair during sleep.

    Last Updated Date : 01/11/2026