Seth Shipman will apply newly developed technology, called ‘molecular recordings,’ to determine the precise timing of transcriptional events that occurs within individual cell types in the developing brain, in order to provide a more robust framework to guide investigations into how ASD-linked mutations alter brain development.

Tingting Wang will examine the role of the autism risk gene CHD2 in glia and identify downstream targets regulating homeostatic synaptic plasticity by using both in vitro and in vivo systems, including Drosophila and mice. This work will provide a better understanding of the role of CHD2 and glia-signaling pathways in autism.

Michael Gandal’s project combines basic science and translational investigations to provide a comprehensive characterization of the spatiotemporal trajectory, functional significance and translational potential of glial cell activation in autism.

Sung Eun “Samuel” Kwon plans to use a recently developed optical reporter of ERK activity, combined with a neuronal activity reporter, to monitor the dynamics of ERK signaling and neuronal activity in awake-behaving SynGAP mutant mice.

While glia-neuron interactions are critical to neural functions, glial functions are molecularly ill defined in health or diseases like autism spectrum disorder (ASD). Aakanksha Singhvi aims to understand how dysregulation of KCC co-transporter functions and glial engulfment, both of which have been implicated in ASD, underlie glial control of sensory neuron shape and behavior in the model organism C. elegans.

Tomasz Nowakowski will determine whether autism-relevant signaling pathways regulate the specification of radial glia cells during development and whether radial glia effects on resident microglia maturation are affected by environmental risk factors, such as immunological challenges.

Sleep plays an important role in cognitive functions such as learning and memory, and sleep disruptions are associated with neurodevelopmental disorders, including Rett syndrome. The current project aims to understand the molecular mechanisms by which sleep supports cognitive function and to test the role of sleep disruption in the progression of Rett syndrome using an MeCP2 knockout mouse model. With detailed knowledge of the mechanisms underlying the restorative functions of sleep, new therapies could be developed to restore sleep in individuals with neurodevelopmental disorders.

Stessman aims to use human cell lines engineered to express patient mutations to determine how these genes contribute to disease etiology, particularly during early development of the human brain. These cell lines will also be a useful tool for therapeutic development in the future.

The cellular and developmental basis of autism spectrum disorder (ASD) still represents a significant gap in our knowledge of this developmental disorder. To understand how ASD affects brain development, comprehensive disease models are needed. Such models will yield insight into the developmental programs that are affected in ASD and how these perturbations ultimately affect behavioral output.

Most individuals with autism experience at least one form of hypersensitivity from the five senses. These alterations in sensory-related behaviors can lead to profound limitations on an individual’s ability to work, interact with family and participate in leisure activities. Furthermore, these atypical responses to otherwise normal sensory stimuli may be closely associated with the core symptoms of autism, such as social deficits and repetitive behaviors. Despite the importance of sensory abnormalities in the pathogenesis of autism, how the brains of individuals with autism receive information from the five senses at the subcortical level and how such information becomes transformed into aversive responses has not been investigated.