Marcelo P. Coba
Psychiatry & the Behavioral Sciences
Zilkha Neurogenetic Institute
Keck School of Medicine of USC
- Synaptic signaling complexes
- Psychiatric disorders
- Protein phosphorylation
- Cellular Neurobiology
- Systems Biology
Research OverviewOver 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.
Coba MP, Komiyama NH, Nithianantharajah J, Kopanitsa MV, Indersmitten T, Skene NG, Tuck EJ, Fricker DG, Elsegood KA, Stanford LE, Afinowi NO, Saksida LM, Bussey TJ, O'Dell TJ, Grant SG. TNiK Is Required for Postsynaptic and Nuclear Signaling Pathways and Cognitive Function. J Neurosci.  Oct 3;32(40):13987-13999.
Arbuckle MI,Komiyama NH,Delaney A,Coba M,Garry EM,Rosie R,Allchorne AJ,Forsyth LH,Bence M,Carlisle HJ,O'Dell TJ,Mitchell R,Fleetwood-Walker SM,Grant SG - The SH3 domain of postsynaptic density 95 mediates inflammatory pain through phosphatidylinositol-3-kinase recruitment. - EMBO Rep  Jun;11(6):473-8 -PubMed -Link
Coba MP,Pocklington AJ,Collins MO,Kopanitsa MV,Uren RT,Swamy S,Croning MD,Choudhary JS,Grant SG - Neurotransmitters drive combinatorial multistate postsynaptic density networks. - Sci Signal  Apr 28;2(68):ra19 -PubMed -Link
Coba MP,Valor LM,Kopanitsa MV,Afinowi NO,Grant SG - Kinase networks integrate profiles of N-methyl-D-aspartate receptor-mediated gene expression in hippocampus. - J Biol Chem  Dec 5;283(49):34101-7 -PubMed -Link
Delgado JY,Coba M,Anderson CN,Thompson KR,Gray EE,Heusner CL,Martin KC,Grant SG,O'Dell TJ - NMDA receptor activation dephosphorylates AMPA receptor glutamate receptor 1 subunits at threonine 840. - J Neurosci  Nov 28;27(48):13210-21 -PubMed -Link
Cuthbert PC,Stanford LE,Coba MP,Ainge JA,Fink AE,Opazo P,Delgado JY,Komiyama NH,O'Dell TJ,Grant SG - Synapse-associated protein 102/dlgh3 couples the NMDA receptor to specific plasticity pathways and learning strategies. - J Neurosci  Mar 7;27(10):2673-82 -PubMed -Link