Psychiatry & the Behavioral Sciences
Zilkha Neurogenetic Institute
Keck School of Medicine of USC
Synaptic signaling complexes
Over recent years advances in genomic and proteomic technologies have made it possible to describe in detail the signaling mechanisms involved in cellular function. It is now clear that cells contain different signaling pathways arranged in a variety of macromolecular complexes, that diverge, converge, cross-talk and have feedback-control mechanisms. These networks integrate signals from multiple inputs thus modulating successive responses; therefore, cells future outputs are based on how they have been stimulated in the past. This complexity is formulated in the generation of large signaling networks, and novel approaches are needed for the global analysis of these networks and the complexity of cellular systems. Proteomic and bioinformatics based methods have emerged as fundamental tools in the identification of protein complexes and protein-phosphorylation events involved in protein function. The mammalian postsynaptic proteome (PSP) is a clear example of cell signaling complexity, it is comprised of ~1500 proteins in tightly linked macromolecular assemblies, including the postsynaptic density (PSD) and neurotransmitter receptor protein complexes. Although recent human genetic studies have identified numerous mutations associated with psychiatric and neurodevelopmental disorders within these complexes, translating these findings into a deeper understanding of the biological mechanisms underlying disease has been challenging. This is in part because the cellular processes regulated by many of these molecules are poorly understood. Moreover, little is known regarding how these sets of genes are integrated into common biochemical networks, such as postsynaptic signaling complexes. I am interested in the systems biology study of signaling networks and their role in developmental and psychiatric disorders. My research uses of a combination of multi-targeted, and large scale approaches, including proteomics, analysis of synaptic signaling complexes, post translational modification studies, computational biology and mouse genetics, directed to the analysis of cell signaling networks, their role controlling synaptic function and the mechanisms affecting disease.