Sabo, Shasta

• Research Associate, Stanford University, 2005-2007
• Postdoctoral Fellow, University of California, Davis, 2001-2005
• Postdoctoral Fellow, University of California, San Diego, 2000-2001
• Ph.D., Rockefeller University, 2000
• B.A., Integrated Science & B.A., Biological Sciences, 1994

• Neuroscience
• Molecular and Cellular Mechanisms of Synapse Formation and Neuronal Development
• Pathogenesis of Neurodevelopmental Disorders, such as Autism Spectrum Disorders
• Live Fluorescence Imaging

Research projects

The neural circuits that govern perception and behavior are composed of networks of neurons that communicate with one another via synapses. As our brains develop, the roughly 10-20 billion neurons that comprise the human cerebral cortex are presented with the enormous and complex task of forming trillions of synapses with appropriate partners. Defects in neural circuit development have been linked to diseases as diverse as anxiety disorders, depression, epilepsy, amblyopia, schizophrenia, intellectual disability and autism. Therefore, the long-term goal of our research is to understand how cortical circuits develop and how these processes are compromised in neurodevelopmental disorders.

Currently, we are working to understand the mechanisms underlying GRIN2B-related neurodevelopmental disorder. Symptoms of the disease include developmental delay and intellectual disability, often accompanied by motor problems, epilepsy, sensory dysfunction, and autism.

This debilitating disease is caused by de novo mutations in the GRIN2B gene, so individuals with the disease have one functional allele and one mutant allele of GRIN2B. GRIN2B encodes the GluN2B subunit of NMDA receptors, best known for their prominent

role in synaptic plasticity. A variety of disease-causing mutations reduce functional GluN2B-containing NMDA receptors in developing neurons. Therefore, we hope to understand how loss of GluN2B disrupts the trajectory of neural circuit development.

One exciting approach that we are taking utilizes a rat model that is heterozygous for Grin2b. These rats were generated through the Simons Foundation Autism Research Initiative (SFARI). We are using a multi-pronged strategy to discover which aspects of neural circuit development are abnormal in these animals. Our hope is to ultimately correlate neurodevelopmental changes with functional and behavioral deficits to better understand disease pathophysiology and to help identify new targets for therapeutics to treat symptoms of the disease.