University of Nebraska Medical Center
Autism spectrum disorders represent a heterogeneous group of neurodevelopmental disorders characterized by deficits in social interaction, communication skills and repetitive behavior. These disorders are often co-morbid with other disorders including intellectual disability. A major challenge in autism and related disorders has been to define cellular and molecular aberrations specifically within different cell types implicated in the pathology and elucidate convergent pathways. Defining the pathological molecular network in autism will likely yield pharmacological targets that will make therapy tractable. Identifying commons themes across various forms of autism has been extremely challenging. The one common theme that has emerged indicates that autism is a “synaptopathy”, a disorder associated with aberrations in synaptic structure and function. Synaptic density and function in neurons can be influenced by signaling pathways in specific types of neurons, astrocytes and microglia. We propose that identifying cell type specific and neuron-type specific molecular aberrations in autism are key to defining the molecular pathology of autism and providing routes for therapy. The central goal of my lab is to take advantage of in vitro and in vivo approaches and genetic mouse models of autism and related disorders and dissect out aberrant cell type specific signaling pathways in neurons, astrocytes and microglia that contribute to synaptic signaling in neurons with the ultimate goal of correcting these aberrations for therapy. Our current focus is on two known genetic causes of autism and related disorders, mutations in the CTNND2 and CDKL5 genes. By dissecting out aberrant signaling pathways in these genetic forms of autism and related disorders, we expect to identify convergent pathways relevant to other forms of autism and related disorders.