We study how neural circuits give rise to complex behaviors, and how dysfunction of neural processes can cause mental illness. Our particular focus is in understanding how sleep -- a highly conserved behavior whose core function remains a mystery -- contributes to sculpting brain circuits during development and in other times of life. To answer these questions, we primarily utilize the powerful genetic system Drosophila melanogaster (the fruit fly). The fly provides unparalleled neurogenetic approaches towards unraveling the neural logic of complex behaviors. In addition, genetic and molecular insights from Drosophila have repeatedly translated to higher organisms, even humans.
We are a "question-driven" lab. We use or develop any approaches necessary to further our understanding of biological processes that, when awry, contribute to neuropsychiatric disease.
1. Genetic and molecular regulation of sleep ontogeny
All animals also exhibit changes to sleep throughout development (sleep ontogeny), suggesting a crucial role for sleep in young animals. Indeed, disrupted sleep specifically within sensitive development periods can have severe neurobehavioral sequelae. Sleep disturbances are also a comm. However, knowledge of the genetic and molecular factors that drive sleep maturation is lacking. We have identified the first known gene to regulate sleep ontogeny, and ongoing work aims to map the cells, circuits, and downstream molecular cues coordinating sleep in early life.
2. Sleep function during early neurodevelopmental periods
Examination of a function for sleep in even earlier phases of brain development, when neurons are first being born, has been limited by the lack of tractable experimental systems. We have developed a novel sleep system using Drosophila larvae, facilitating the study of sleep during earlier neurodevelopmental periods than ever before. Ongoing work has begun to define small subpopulations of neurons that control sleep/wake during this time. We have also found that sleep loss in early development attenuates proliferation of neural stem cells, and are using the larval sleep system to understand how sleep and neurogenesis are mechanistically coupled.
3. A Drosophila model for sleep restriction therapy
Insomnia is the most common sleep disorder among adults. Cognitive behavioral therapy for insomnia (CBT-I) is the first-line treatment for insomnia; a key component of this intervention is restriction of sleep opportunity, which optimizes matching of sleep ability and opportunity, leading to enhanced sleep drive. Despite the well-documented efficacy of CBT-I, little is known regarding how CBT-I works at a cellular and molecular level to improve sleep, due in large part to an absence of experimentally-tractable animals models of this intervention. Guided by human behavioral sleep therapies, we developed a Drosophila model for sleep restriction therapy (SRT) of insomnia, and are applying this to study sleep as a modifiable risk factor in neurodegeneration.
In addition to work in the laboratory, we have ongoing clinical research interests that include biomarkers of treatment response to Cognitive Behavioral Therapy for Insomnia (CBT-I). Please contact us with any questions about clinical research interests.