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. 

Projects

1. Genetic and molecular regulation of sleep ontogeny

All animals 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 common co-morbidity in many neurodevelopmental disorders, including autism. However, knowledge of the genetic and molecular factors that drive sleep maturation is lacking. We have identified signals that regulate sleep ontogeny and the development of sleep circuits. 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. Developmental emergence of rhythmic sleep

In addition to increased sleep amount/depth, another prominent feature of early life sleep is that it lacks a clear circadian pattern. Little is known regarding mechanisms that control emergence of circadian sleep, or how circadian sleep benefits an animal. In flies, we have discovered precisely when and how sleep rhythms are initiated. Moreover, our findings suggest sleep rhythms facilitate the ability to make enduring memories. Current work aims to understand 1) what triggers the connection between clock and sleep-wake cells at a specific developmental time; and 2) how rhythmic sleep modulates memory stability in early life.

4. 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.

5. Social behavioral deficits in a fly model of Neurofibromatosis Type 1 (NF1)

That’s right, we don’t only work on sleep. Accumulating evidence indicates that sensory processing errors drive core symptoms in autism spectrum disorders (ASDs). Autism is a major feature of NF1 in humans, with social communication deficits as one of the most prominent symptoms. We have shown that NF1 mutant flies exhibit dysregulated social behaviors. These behavioral deficits arise from an unexpected role for Nf1 in a small group of peripheral sensory neurons. Current projects are examining what function Nf1 has in these sensory cells, and how peripheral sensory disturbances are transformed in the brain to shape behavior.

 

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.