The Center for Sleep has a rich, multi-disciplinary research program in both basic science and patient-oriented research.
The goals of basic science research in the Center include the understanding of the molecular mechanisms regulating sleep and wakefulness, the functions of sleep at a most basic molecular level, and how aging and disease disrupt these processes.
New molecular mechanisms that regulate sleep are being identified. By examining the relevance of these molecules across different species, investigators at the CSCN have the ability to identify evolutionary conserved molecules regulating sleep. While investigators come from diverse fields, there is a focused emphasis of the research: understanding the molecular mechanisms regulating sleep and wakefulness, the functions of sleep at a most basic molecular level, and how aging and disease disrupt these processes. Studies are being conducted in multiple model systems, each with particular strengths for exploring sleep - C. elegans, Drosophila, and mice.
The labs of Drs. Allan Pack (Medicine) and Amita Sehgal (Neuroscience) are studying sleep in Drosophila, the fruit fly. Within the past year, the group has identified several key proteins whose transcriptional regulation is different between sleep and wake based on microarray studies. Dr. Nirinjini Naidoo (Medicine) is pursuing proteomic approaches in mice. At the same time, there are strong ongoing collaborations with the mouse genetics group at the Jackson Laboratory in Maine, to develop high-throughput screens for abnormal mouse sleep/wake patterns and models of specific sleep disorders. In addition, Dr. Sigrid Veasey (Medicine) has developed a major program of research on oxidative injury neurons in murine models of obstructive sleep apnea (OSA), work that is ready for clinical translation. Dr. Marcos Frank (Neuroscience) is also doing seminal studies on the role of sleep in synaptic plasticity during development. Dr. Leszek Kubin (Veterinary Medicine and Medicine) has an active program of research studying the neurochemistry, neuroanatomy and neurophysiology of the effects of rapid eye movement (REM) sleep on the neural control of upper airway muscles using a rodent-based, pharmacological model of REM sleep. And Dr. David Raizen (Neurology) has identified a sleep-like state in the roundworm, Caenorhabditis elegans. His laboratory has identified several key proteins whose transcriptional regulation is different between sleep and wake.
Penn Sleep has a comprehensive program of patient-oriented research and
a major commitment to this area. We have developed important cores to
support this. First, we have a Research Sleep Core, with both adult and
pediatric components. These are part of the recently awarded Center for Translational Science Award (CTSA). The University of Pennsylvania was a recipient of a CTSA in the first round of applications. On the adult side, there are four bedrooms dedicated for sleep research and on the pediatric sleep center, two such bedrooms. These facilities are managed by experienced
staff and we provide a broad range of studies: overnight sleep studies; multiple sleep latency and maintenance of wakefulness tests;
actigraphy; neurobehavioral tests of function. These facilities are
available to all faculty at Penn and Children's Hospital of
Philadelphia (CHOP) who have an interest in sleep research. This
approach has greatly facilitated our development of a vibrant program
of research in this area.
Another facility that we have developed, under Dr. Sam Kuna's leadership, is for centralized scoring of sleep studies from multiple locations. This facility is being used for two NIH-funded multicenter studies: CPAP (continuous positive airway pressure) Apnea Trial - North American Program (CATNAP, PI: T. Weaver), assessing outcomes of therapy with CPAP in patients with mild-to-moderate sleep apnea who are excessively sleepy; and Sleep Action for Health in Diabetes (Sleep AHEAD, PI: G . Foster) evaluating prevalence of OSA in obese Type 2 diabetics, progression of disease and effects of behaviorally induced weight loss.
Dr. Richard Schwab has developed an upper airway imaging core to facilitate analysis of three-dimensional images of the upper airway, surrounding soft tissues and craniofacial structure. This core is being used for studies in adults (Dr. Schwab) and in children (Dr. C. Marcus). It is also being used to analyze MR images collected in Iceland as part of our ongoing study of genetics of sleep apnea (Dr. T. Gislason, Dr. A. Pack).
Currently, we have funded programs of research in several distinct
areas. Tools developed at the University of Pennsylvania such as the
Multivariable Apnea Prediction (Maislin et al, Sleep 18:158-166, 1995)
and Functional Outcomes of Sleepiness Questionnaire (Weaver et al, Sleep 20:835-843, 1997) are now used in patient-oriented research
around the world and have been translated into many languages.
The current programs of research include:
- OSA in obese Type 2 diabetics (G. Foster/S. Kuna)
- Insomnia and other disorders in older adults (N. Gooneratne)
- Screening strategies for OSA (I. Gurubhagavatula)
- Metabolic syndrome and OSA in children
(A. Kelly, L.
- New strategies for diagnosis of sleep apnea (S. Kuna)
- Pathophysiology of childhood OSA (C. Marcus)
- Pediatric parasomnias (A. Mason)
- Genetics of sleep and OSA (A. Pack)
Patient-Centered Outcomes Research
Patient-Centered Outcomes Research (PCOR) also known as comparative effectiveness research, is defined as the conduct and synthesis of research comparing the benefits and harms of different interventions and strategies to prevent, diagnose, treat and monitor health conditions in “real world” settings. The purpose of this research is to improve health outcomes by developing and disseminating evidence-based information to patients, clinicians, and other decision-makers, responding to their expressed needs, about which interventions are most effective for which patients under specific circumstances.
The growing support for PCOR rests on an underlying premise that better information comparing the benefits and harms of alternative therapeutic or diagnostic strategies will enable patients, providers, and policymakers to make better choices.
The Center for Sleep and Circadian Neurobiology has developed a series of seminars and resources to facilitate development of PCOR protocols in sleep and sleep disorders. Below please find a link to a list of articles and guidelines, including from the Institute of Medicine (IOM).
Announcement: AHRQ RFA - "Mentored Career Enhancement Award in Patient Centered Outcomes Research (PCOR) for Mid-Career and Senior Investigators" can be found at:
For more information on the research programs in the Center for Sleep, contact Dr. Allan Pack.