Current Research Projects

Basal ganglia dysfunction in autism spectrum disorders

The basal ganglia are a group of sub-cortical structures responsible for integrating sensory and motivational information to select and learn appropriate actions. We are investigating how dysfunction of the basal ganglia contributes to the behavioral manifestations of autism spectrum disorder (ASD); in particular the repetitive, inflexible patterns of behavior that are a hallmark of ASD. To investigate this, we analyze neuronal physiology and behavior in genetic mouse models of ASD to determine the relevant circuits, cells, and synapses that may be compromised in autism.

Modeling neurodevelopmental disorders with human brain organoids

Recent advances in cellular reprograming and genome editing have enabled the generation of genetically engineered human cells for in vitro disease modeling. We are leveraging these approaches to generate human neuronal models of the neurodevelopmental disorder Tuberous Sclerosis Complex (TSC), caused by mutations in the mTOR regulators TSC1 and TSC2. Our goal is to determine how mutations in the TSC genes impact human brain development and function.

Unraveling the complexity of neuronal mTOR signaling

The mTOR pathway is a central signaling hub that integrates intra- and extracellular signals to control cellular processes related to growth and metabolism. Mutations in components of the mTOR pathway lead to syndromic neurodevelopmental disorders including TSC, which are often associated with ASD, epilepsy, and intellectual disability. To understand how deregulated mTOR activity leads to neurological and psychiatric dysfunction, we are using molecular profiling and biochemical assays in cultures of mouse and human neurons. Our goals are to elucidate the mechanisms of mTOR signaling in neurons and identify new approaches to restore balanced mTOR activity in the context of disease. In parallel, we are using imaging and electrophysiology to determine how mTOR signaling affects the functional properties of neurons and neural circuits.

Elucidating cell type diversity

The brain is composed of myriad cell types, each with unique physiology, morphology, connectivity, and function. These specific properties are likely conferred by unique patterns of gene expression that define each cell type. We are using single cell profiling approahces to probe and catalog the genetic diversity of cells in the brain, with a focus on the basal ganglia. Our goals are to define the cell type architecture of the basal ganglia as well as identify novel marker genes that can be used to access specific neuronal populations.

Thank you to our research and fellowship sponsors!