Faculty

Marcelo Pablo Coba

Marcelo Pablo Coba

Associate Professor of Psychiatry & the Behavioral Sciences
Medicine
ZNI 427, 1501 San Pablo Street Health Sciences Campus Los Angeles

A "multi-omics" analysis of blood-brain barrier and synaptic dysfunction in APOE4 mice J Exp Med. 2022 Nov 07; 219(11). . View in PubMed

Mapping genomic loci implicates genes and synaptic biology in schizophrenia Nature. 2022 04; 604(7906):502-508. . View in PubMed

Endogenous Syngap1 alpha splice forms promote cognitive function and seizure protection Elife. 2022 04 08; 11. . View in PubMed

Genome Sequencing Variations in the Octodon degus, an Unconventional Natural Model of Aging and Alzheimer's Disease Front Aging Neurosci. 2022; 14:894994. . View in PubMed

Endogenous Cell Type-Specific Disrupted in Schizophrenia 1 Interactomes Reveal Protein Networks Associated With Neurodevelopmental Disorders Biol Psychiatry. 2019 02 15; 85(4):305-316. . View in PubMed

SynGO: An Evidence-Based, Expert-Curated Knowledge Base for the Synapse Neuron. 2019; (103):1-18. . View in PubMed

Haploinsufficiency leads to neurodegeneration in C9ORF72 ALS/FTD human induced motor neurons Nat Med. 2018 03; 24(3):313-325. . View in PubMed

Dlgap1 knockout mice exhibit alterations of the postsynaptic density and selective reductions in sociability Sci Rep. 2018 02 02; 8(1):2281. . View in PubMed

Spatiotemporal profile of postsynaptic interactomes integrates components of complex brain disorders Nat Neurosci. 2017 Aug; 20(8):1150-1161. . View in PubMed

Synaptic GAP and GEF Complexes Cluster Proteins Essential for GTP Signaling Sci Rep. 2017 07 13; 7(1):5272. . View in PubMed

Long-term potentiation modulates synaptic phosphorylation networks and reshapes the structure of the postsynaptic interactome Sci Signal. 2016 08 09; 9(440):rs8. . View in PubMed

Receptor Tyrosine Kinase MET Interactome and Neurodevelopmental Disorder Partners at the Developing Synapse Biol Psychiatry. 2016 12 15; 80(12):933-942. . View in PubMed

TNiK is required for postsynaptic and nuclear signaling pathways and cognitive function J Neurosci. 2012 Oct 03; 32(40):13987-99. . View in PubMed

Neurotransmitters drive combinatorial multistate postsynaptic density networks Sci Signal. 2009 Apr 28; 2(68):ra19. . View in PubMed

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. . View in PubMed

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. . View in PubMed

Proteomic analysis of in vivo phosphorylated synaptic proteins J Biol Chem. 2005 Feb 18; 280(7):5972-82. . View in PubMed

Rough surface interferometry at 106 microm. Appl Opt. 1980 Jun 01; 19(11):1862-9. . View in PubMed

The purification and characterization of the low molecular weight human folate binding protein using affinity chromatography Biochemistry. 1975 Dec 16; 14(25):5422-8. . View in PubMed

Digitoxin metabolism by rat liver microsomes Biochem Pharmacol. 1975 Sep 01; 24(17):1639-41. . View in PubMed

Neurodevelopmental neurodegenerative and psychiatric disease are complex brain disorders, and a multitude of genes have been described to contribute to their pathology with different penetrance. Human genetic studies have discovered many genes associated with disease susceptibility that are usually described as risk factors. 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 cellular dysfunction in these disorders. Our long-term goal is to determine how candidate risk factors are functionally integrated and how mutations affect their function, not individually, but in developmental signaling networks.

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 cell types, 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, computational biology, synaptic physiology, CRISPR technology, and hiPSC derived cell types from patients with mutations associated to complex brain disorders. This will help us to define network maps that will allow us to stratify patients by their correspondent pathway signatures, their genotype-phenotype relationship, and their genetic background.
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Affiliated Faculty at UPC