Melissa St. Hilaire, PhD, gets a glint in her eye when she talks about data. A biostatistician by training, St. Hilaire is delighted to work with the treasure troves of metrics and readouts that she and her colleagues collect during sleep studies, sometimes finding new questions to ask that the investigators didn’t think about when they first designed the experiment.
“There are so many exciting projects to work on and I’m grateful for the freedom and support to pursue new questions,” said St. Hilaire, who joined the Brigham in 2002 just after completing her bachelor’s degree. With mentorship from faculty members and access to robust datasets, St. Hilaire’s career and research interests have continued to bloom as she’s moved up within the division.
“There’s no reason to leave the Brigham because there’s always more to do and more questions to ask,” said St. Hilaire.
A Place Where Time Doesn’t Exist
Much of St. Hilaire’s work is possible because of a special research space known as Tower 9B. Tower 9B, which houses five intensive physiologic monitoring bed units, allows researchers to control key variables such as temperature, light and outside stimuli to carry out intensive sleep studies with research volunteers.
St. Hilaire is conducting studies on neurobehavioral performance to understand how insufficient sleep affects the brain and cognition. She is also interested in how the environment affects the internal body clock, known as circadian rhythm. St. Hilaire currently has a grant to study the metabolites in urine that seem to reflect the body’s circadian rhythm.
In a recent experiment, a study team led by Steven Lockley, PhD, one of St. Hilaire’s mentors, ran six-day-long studies in which participants were in Tower 9B’s “time-free environment” — which means no windows, no clocks, no outside visitors and no way for subjects to know the time of day. Researchers controlled the timing of all daily, routine activities — such as meal times, shower times and sleep/wake times — that might give hints about time of day. Participants came in for several days and lived in this environment on their normal schedule. Then, researchers put participants on a constant routine procedure, in which they were awake but in bed in a semi-recumbent position for 40 to 60 hours.
By chipping away all external factors, the study team is able to gather information on underlying circadian rhythm. Using the Brigham’s state-of-the-art technology, the study team can carefully monitor subjects and collect data on known markers of circadian rhythm such as temperature and melatonin. They are also collecting urine samples to assay metabolites to see which ones might exhibit a 24-hour circadian rhythm. These metabolites could be developed into a urine test to measure circadian rhythm.
“The key to this kind of study is to eliminate all external factors so that the subjects have no awareness of outside time,” St. Hilaire explained. “This is a very difficult procedure for subjects, but it yields a gold standard for measuring the internal body clock, which controls a lot of our behaviors and can be disrupted by shift work and other conditions. We want to be able to measure the internal body clock in an easy, non-invasive way. Once we have such a test, we’ll be able to take steps toward improving health for those whose circadian rhythm has been disrupted.”
Drifting into Sleep
St. Hilaire’s bachelor’s degree from Worcester Polytechnic Institute is in math and she brings her computational expertise to bear on the study of sleep. During her first job at the Brigham as a biomathematical programmer analyst, St. Hilaire helped refine a mathematical model to make predictions about sleep/wake and light/dark patterns and performance.
She continued to work at the Brigham while pursuing a master’s degree from Northeastern University in bioinformatics and a PhD from Boston University in cognitive and neural systems. Part of her dissertation used data collected from the Tower 9B lab to build a model of the brain circuitry that underlies neural behavioral sleep deprivation to see what regions of the brain are affected.
St. Hilaire has had many mentors in the Division of Sleep and Circadian Disorders, including Elizabeth Klerman, MD, PhD, who began mentoring St. Hilaire soon after she started here. She has also worked closely with other faculty members of the division including Lockley and Division Chief Charles Czeisler, MD, PhD. St. Hilaire and her colleagues in the Division of Sleep and Circadian Disorders have published findings on the effects of sleep on bone health, metabolism and more. Now, as an early-stage investigator, St. Hilaire is beginning to build her own collaborations, with colleagues both at and beyond the Brigham.
“I’m looking forward to opportunities to collaborate with experts on a variety of different diseases,” said St. Hilaire. “Sleep and circadian rhythm can have far-reaching effects. For example, studies have shown that the timing of chemotherapy relative to circadian rhythm can influence how effective these drugs are. We don’t yet know the extent or the number of medications that may be affected by the circadian system. Once we understand the influence of these factors on health, we can begin to expand our collaborations with other departments to develop a better and more personalized experience for our patients.”