Robert Wood Johnson Medical School
Dept. of Neuroscience & Cell Biology
The Child Health Institute of NJ
89 French Street, Room 4274
New Brunswick, NJ 08903
Visit the Comoletti Lab
Structural and molecular basis of synapse formation and connectivity in relation to autism spectrum disorders
Autism is a general term used to describe a group of complex developmental brain disorders known as Pervasive Developmental Disorders (PDD). Today, it is estimated that one in every 110 children is diagnosed with autism, making it more common than childhood cancer, juvenile diabetes, and pediatric AIDS combined. The vast majority of cases of autism are idiopathic, however, a wealth of genetic studies point to the role of synaptic adhesion proteins such as the neuroligins, neurexins, and others, in the pathogenesis of some form of the disease. Most of these proteins are important in controlling synaptic function, neuronal connectivity, and recognition patterns in the developing brain. Interestingly, some of these genes have also been implicated in the pathogenesis of epilepsy, schizophrenia, ADHD, and Tourette syndrome, suggesting that some of these disorders may share common molecular pathways.
In our lab we study the structural and molecular basis of synapse formation and connectivity in relation to autism spectrum disorders. Our focus is on the three-dimensional structure and cellular functions of several trans-synaptic adhesion molecules such as the neuroligins, neurexins, LRRTMs (see selected publication below). Besides these well-known proteins, other novel associating proteins also have been recently discovered by us and by others and are currently under investigation in the lab. We use structural biology and cellular neuroscience to gain insights into how mutations of these proteins associate with autism and other common neurodevelopmental disorders.