Funding Summary
Dr. Reiter’s lab looks at stem cell lines from the teeth of PWS subjects to look at the sleep/wake cycle, called the circadian rhythm. People with PWS have a hard time with regulating this cycle. This project will use these stem cell lines to look at the PWS circadian rhythm patterns, as well as changes in DNA that are known to happen at different times during the day and night.
Dr. Theresa Strong, Director of Research Programs, shares details on this project in this short video clip.
Watch the full webinar describing all 9 research projects funded in this grant cycle here.
Lay Abstract
In this study, we will use our unique stem cell lines from the teeth of PWS subjects (dental pulp stem cells) to investigate a phenomenon called circadian rhythm. Normal circadian rhythm occurs even at the single cell level, to control the normal sleep/wake cycle in humans. Individuals with PWS have serious sleep problems like daytime sleepiness and disrupted REM sleep that can seriously impact the lives of families with PWS members. We will use our stem cell lines to look for the normal and PWS circadian rhythm patterns in these cells and also to look at changes in DNA that are known to occur at different times during the day/night cycle. If we succeed, we will have a PWS derived cell culture system that will be useful for doing drug screening. In the future, we may identify drugs that correct the circadian rhythm defects in PWS which lead to sleep problems.
Research Outcomes: Public Summary
Our laboratory has been constructing a repository of PWS dental pulp stem cells (DPSC) to better
understand the molecular and cellular changes occurring in neurons from individuals with PWS. We can do this by stimulating the DPSC to develop into neurons in culture dishes. In this study we used cellular reporters of circadian rhythm designed by our collaborator Dr. Andrew Liu at the University of Florida to measure circadian rhythm in neurons from PWS individuals. The goal is to better understand “daytime sleepiness” and other sleep related problems in PWS by looking for defects in normal circadian rhythm in neurons. We were able to detect normal circadian cycling for the Per2 reporter and Bmal1 reporters in our cell lines. We also detected a significant defect in period length in some neuronal cells lines from PWS subjects. This decreased period length means that these individuals may not sleep during “normal” bedtime hours and may result in daytime sleepiness. We were also able to rescue this defect using a drug currently on the market for shifting circadian rhythm called Longdaysin. Treatment of short period length neuronal cultures with Longdaysin shifted the rhythm back to the average period length for the neurotypical control neurons. This work is now published in the journal Human Genetics and Genomics Advances (link below).
Research Outcomes: Publications
Circadian rhythm defects in Prader-Willi syndrome neurons. Victor AK, Hedgecock T, Ramanathan C, Shen Y, Liu AC, Reiter LT. HGG Adv. 2025 Apr 10;6(2):100423. doi: 10.1016/j.xhgg.2025.100423. Epub 2025 Mar 1. PMID: 40023766; PMCID: PMC11957785.
Funded Year:
2020
Awarded to:
Larry Reiter, PhD
Amount:
$108,000
Institution:
University of Tennessee Health Sciences Center
Researcher:
Larry Reiter, PhD
