Julie A Williams, Ph.D.

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Research Assistant Professor of Neuroscience
Department: Neuroscience

Contact information
Perelman School of Medicine, University of Pennsylvania
Smilow Research Center, 10-142
3400 Civic Center Boulevard
Philadelphia, PA 19104
Office: 215-573-1900
B.A. (Psychology)
Bard College, 1989.
Ph.D. (Neuroscience)
University of British Columbia, 1997.
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Description of Research Expertise

Excess sleep and fatigue are commonly experienced during infectious illness in humans. Increased sleep associated with infection has also been documented in a wide range of animals, including Drosophila. It has therefore been proposed that sleep is an adaptive response to infection and has a role in fighting infection. Sleep disturbance and inflammation are also associated with a number of human diseases, including cancer, cardiovascular, metabolic, and depressive disorders. These findings underscore the importance of the relationship between sleep and the innate immune system in sustaining human health. However, the molecular mechanisms of excess sleep and fatigue during illness and its relationship to clinical outcome remain poorly understood.

The research that I direct is focused on identifying mechanisms of restorative sleep, as well as how sleep disintegrates during illness. We have found that acute stress produced by bacterial infection, aseptic injury, and heat shock all induced a transient increase in sleep in fruit flies. Although sleep increases with acute stress, during chronic stress, such as a later stage of infection, the quality of sleep declines. It becomes progressively more fragmented as indicated by shorter and more frequent sleep bouts, similar to that in aged flies. We have shown that enhancing sleep both before and after infection promoted survival. The restorative properties of sleep are not well understood, and the mechanisms by which sleep disintegrates during infection are unknown. Thus specific questions addressed are 1) what are the mechanisms of stress/infection-induced sleep; 2) why does the acute restorative sleep response that occurs with infection not persist but turns into poor quality fragmented sleep over the course of the infection; and 3) how can this poor quality sleep be ameliorated to promote recovery? My approach to addressing these questions is to exploit the Drosophila genetic model to evaluate mechanisms by which a cellular stress response promotes sleep and how chronic stress, such as infection, suppresses sleep. We also plan to investigate the neuronal circuitry that is involved in mediating these responses.

Selected Publications

Toda H, Williams JA, Gulledge M, Sehgal A: A sleep-inducing gene, nemuri, links sleep and immune function in Drosophila. Science 363(6426): 509, February 2019.

Bai Lei, Lee Yool, Hsu Cynthia T, Williams Julie A, Cavanaugh Daniel, Zheng Xiangzhong, Stein Carly, Haynes Paula, Wang Han, Gutmann David H, Sehgal Amita: A Conserved Circadian Function for the Neurofibromatosis 1 Gene. Cell reports 22(13): 3416-3426, Mar 2018.

Bi Jie, Sehgal Amita, Williams Julie A, Wang Yu-Feng: Wolbachia affects sleep behavior in Drosophila melanogaster. Journal of insect physiology 107: 81-88, Feb 2018.

Gardner B, Strus E, Meng QC, Coradetti T, Naidoo NN, Kelz MB, Williams JA: Sleep Homeostasis and General Anesthesia: Are Fruit Flies Well Rested after Emergence from Propofol? Anesthesiology 124(2): 404, February 2016.

Lenz O, Xiong J, Nelson M, Raizen D, Williams JA: FMRFamide signaling promotes stress-induced sleep in Drosophila. Brain Behav Immun 47: 141, July 2015.

Kuo T-H, Williams JA: Increased sleep promotes survival during a bacterial infection in Drosophila. Sleep 37(6): 1077-86, June 2014.

Kuo, T-H and Williams JA: Acute sleep deprivation enhances post-infection sleep and promotes survival during bacterial infection in Drosophila. Sleep 37(5): 859-69, May 2014.

Kuo, T-H, Handa, A, and Williams JA: Quantitative measurement of the immune response and sleep in Drosophila. Journal of Visualized Experiments 70: e4355, December 2012.

Kuo, T. H., Pike, D. H., Beizaeipour, Z., Williams, J. A.: Sleep triggered by an immune response in Drosophila is regulated by the circadian clock and requires the NFkappaB Relish. BMC Neurosci 11: 17, 2010.

Williams, J. A., Sathyanarayanan, S., Hendricks, J. C., Sehgal, A.: Interaction between sleep and the immune response in Drosophila: a role for the NFkappaB relish. Sleep 30(4): 389-400, 2007.

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Last updated: 12/05/2023
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