Marcelo Pablo Coba, PhD

TitleAssistant Professor of Psychiatry
InstitutionUniversity of Southern California
DepartmentZilkha Neurogenetic Institute
AddressZNI 427, 1501 San Pablo Street
Health Sciences Campus
Los Angeles CA 90033
Phone+1 323 442 4345
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    Psychiatric diseases are complex developmental brain disorders, and human genomic studies have discovered many genes associated with disease susceptibility. For each of these disorders, synaptic proteins have been implicated, in particular those involved in synaptic plasticity and protein complexes associated to the post-synaptic density (PSD). Despite these discoveries, there has been a gap in understanding the underlying mechanisms that contribute to dysfunction in these disorders. Our long-term goal is to determine how psychiatric disorder candidate risk factors are functionally integrated at the synapse and how mutations affect their function, not individually, but in developmental signaling network.
    A common regulatory mechanism to ensure that signaling components encounter their intracellular partners in the right place and time is the association of components in protein complexes. These protein interactions commonly use protein scaffolds with specialized protein-interaction modules (protein domains) as a key mechanism to achieve specificity. We consider that common and rare risk factors might affect overlapping signaling networks, integrating protein interactions through different cellular compartments and developmental stages.
    We use a systems biology approach, combining state of the art proteomic assays to define protein complexes and post-translational modifications, together with mouse genetics, CRISPR technology, hiPSC derived neurons, computational biology, and synaptic physiology. These methods are used to integrate pyschiatric candidate risk factors into spatio-temporal signaling networks and determine how mutations associated to psychiatric disease regulate common signaling mechanisms. This will help us to define network maps that will allow us to stratify patients by their correspondent pathway signatures.

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    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
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    1. Wilkinson B, Evgrafov OV, Zheng D, Hartel N, Knowles JA, Graham NA, Ichida JK, Coba MP. Endogenous Cell Type-Specific Disrupted in Schizophrenia 1 Interactomes Reveal Protein Networks Associated With Neurodevelopmental Disorders. Biol Psychiatry. 2018 May 23. PMID: 29961565.
      View in: PubMed
    2. Shi Y, Lin S, Staats KA, Li Y, Chang WH, Hung ST, Hendricks E, Linares GR, Wang Y, Son EY, Wen X, Kisler K, Wilkinson B, Menendez L, Sugawara T, Woolwine P, Huang M, Cowan MJ, Ge B, Koutsodendris N, Sandor KP, Komberg J, Vangoor VR, Senthilkumar K, Hennes V, Seah C, Nelson AR, Cheng TY, Lee SJ, August PR, Chen JA, Wisniewski N, Hanson-Smith V, Belgard TG, Zhang A, Coba M, Grunseich C, Ward ME, van den Berg LH, Pasterkamp RJ, Trotti D, Zlokovic BV, Ichida JK. Haploinsufficiency leads to neurodegeneration in C9ORF72 ALS/FTD human induced motor neurons. Nat Med. 2018 Feb 05. PMID: 29400714.
      View in: PubMed
    3. Coba MP, Ramaker MJ, Ho EV, Thompson SL, Komiyama NH, Grant SGN, Knowles JA, Dulawa SC. Dlgap1 knockout mice exhibit alterations of the postsynaptic density and selective reductions in sociability. Sci Rep. 2018 Feb 02; 8(1):2281. PMID: 29396406.
      View in: PubMed
    4. Wilkinson B, Li J, Coba MP. Synaptic GAP and GEF Complexes Cluster Proteins Essential for GTP Signaling. Sci Rep. 2017 Jul 13; 7(1):5272. PMID: 28706196.
      View in: PubMed
    5. Li J, Zhang W, Yang H, Howrigan DP, Wilkinson B, Souaiaia T, Evgrafov OV, Genovese G, Clementel VA, Tudor JC, Abel T, Knowles JA, Neale BM, Wang K, Sun F, Coba MP. Spatiotemporal profile of postsynaptic interactomes integrates components of complex brain disorders. Nat Neurosci. 2017 Aug; 20(8):1150-1161. PMID: 28671696.
      View in: PubMed
    6. Li J, Wilkinson B, Clementel VA, Hou J, O'Dell TJ, Coba MP. Long-term potentiation modulates synaptic phosphorylation networks and reshapes the structure of the postsynaptic interactome. Sci Signal. 2016 08 09; 9(440):rs8. PMID: 27507650.
      View in: PubMed
    7. Xie Z, Li J, Baker J, Eagleson KL, Coba MP, Levitt P. Receptor Tyrosine Kinase MET Interactome and Neurodevelopmental Disorder Partners at the Developing Synapse. Biol Psychiatry. 2016 12 15; 80(12):933-942. PMID: 27086544.
      View in: PubMed
    8. 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. 2012 Oct 03; 32(40):13987-99. PMID: 23035106.
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    9. 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. 2009 Apr 28; 2(68):ra19. PMID: 19401593.
      View in: PubMed
    10. 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. 2008 Dec 05; 283(49):34101-7. PMID: 18815127; PMCID: PMC2662229.
    11. 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. 2007 Mar 07; 27(10):2673-82. PMID: 17344405.
      View in: PubMed
    12. Collins MO, Yu L, Coba MP, Husi H, Campuzano I, Blackstock WP, Choudhary JS, Grant SG. Proteomic analysis of in vivo phosphorylated synaptic proteins. J Biol Chem. 2005 Feb 18; 280(7):5972-82. PMID: 15572359.
      View in: PubMed
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