@article{11160,
  abstract     = {Mutations in the chromodomain helicase DNA-binding 8 (CHD8) gene are a frequent cause of autism spectrum disorder (ASD). While its phenotypic spectrum often encompasses macrocephaly, implicating cortical abnormalities, how CHD8 haploinsufficiency affects neurodevelopmental is unclear. Here, employing human cerebral organoids, we find that CHD8 haploinsufficiency disrupted neurodevelopmental trajectories with an accelerated and delayed generation of, respectively, inhibitory and excitatory neurons that yields, at days 60 and 120, symmetrically opposite expansions in their proportions. This imbalance is consistent with an enlargement of cerebral organoids as an in vitro correlate of patients’ macrocephaly. Through an isogenic design of patient-specific mutations and mosaic organoids, we define genotype-phenotype relationships and uncover their cell-autonomous nature. Our results define cell-type-specific CHD8-dependent molecular defects related to an abnormal program of proliferation and alternative splicing. By identifying cell-type-specific effects of CHD8 mutations, our study uncovers reproducible developmental alterations that may be employed for neurodevelopmental disease modeling.},
  author       = {Villa, Carlo Emanuele and Cheroni, Cristina and Dotter, Christoph and López-Tóbon, Alejandro and Oliveira, Bárbara and Sacco, Roberto and Yahya, Aysan Çerağ and Morandell, Jasmin and Gabriele, Michele and Tavakoli, Mojtaba and Lyudchik, Julia and Sommer, Christoph M and Gabitto, Mariano and Danzl, Johann G and Testa, Giuseppe and Novarino, Gaia},
  issn         = {2211-1247},
  journal      = {Cell Reports},
  keywords     = {General Biochemistry, Genetics and Molecular Biology},
  number       = {1},
  publisher    = {Elsevier},
  title        = {{CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories}},
  doi          = {10.1016/j.celrep.2022.110615},
  volume       = {39},
  year         = {2022},
}

@article{546,
  abstract     = {The precise control of neural stem cell (NSC) proliferation and differentiation is crucial for the development and function of the human brain. Here, we review the emerging links between the alteration of embryonic and adult neurogenesis and the etiology of neuropsychiatric disorders (NPDs) such as autism spectrum disorders (ASDs) and schizophrenia (SCZ), as well as the advances in stem cell-based modeling and the novel therapeutic targets derived from these studies.},
  author       = {Sacco, Roberto and Cacci, Emanuele and Novarino, Gaia},
  journal      = {Current Opinion in Neurobiology},
  number       = {2},
  pages        = {131 -- 138},
  publisher    = {Elsevier},
  title        = {{Neural stem cells in neuropsychiatric disorders}},
  doi          = {10.1016/j.conb.2017.12.005},
  volume       = {48},
  year         = {2018},
}

@article{1228,
  abstract     = {Since 2006, reprogrammed cells have increasingly been used as a biomedical research technique in addition to neuro-psychiatric methods. These rapidly evolving techniques allow for the generation of neuronal sub-populations, and have sparked interest not only in monogenetic neuro-psychiatric diseases, but also in poly-genetic and poly-aetiological disorders such as schizophrenia (SCZ) and bipolar disorder (BPD). This review provides a summary of 19 publications on reprogrammed adult somatic cells derived from patients with SCZ, and five publications using this technique in patients with BPD. As both disorders are complex and heterogeneous, there is a plurality of hypotheses to be tested in vitro. In SCZ, data on alterations of dopaminergic transmission in vitro are sparse, despite the great explanatory power of the so-called DA hypothesis of SCZ. Some findings correspond to perturbations of cell energy metabolism, and observations in reprogrammed cells suggest neuro-developmental alterations. Some studies also report on the efficacy of medicinal compounds to revert alterations observed in cellular models. However, due to the paucity of replication studies, no comprehensive conclusions can be drawn from studies using reprogrammed cells at the present time. In the future, findings from cell culture methods need to be integrated with clinical, epidemiological, pharmacological and imaging data in order to generate a more comprehensive picture of SCZ and BPD.},
  author       = {Sauerzopf, Ulrich and Sacco, Roberto and Novarino, Gaia and Niello, Marco and Weidenauer, Ana and Praschak Rieder, Nicole and Sitte, Harald and Willeit, Matthaeus},
  journal      = {European Journal of Neuroscience},
  number       = {1},
  pages        = {45 -- 57},
  publisher    = {Wiley-Blackwell},
  title        = {{Are reprogrammed cells a useful tool for studying dopamine dysfunction in psychotic disorders? A review of the current evidence}},
  doi          = {10.1111/ejn.13418},
  volume       = {45},
  year         = {2017},
}

@article{540,
  abstract     = {RNA-dependent RNA polymerases (RdRps) play a key role in the life cycle of RNA viruses and impact their immunobiology. The arenavirus lymphocytic choriomeningitis virus (LCMV) strain Clone 13 provides a benchmark model for studying chronic infection. A major genetic determinant for its ability to persist maps to a single amino acid exchange in the viral L protein, which exhibits RdRp activity, yet its functional consequences remain elusive. To unravel the L protein interactions with the host proteome, we engineered infectious L protein-tagged LCMV virions by reverse genetics. A subsequent mass-spectrometric analysis of L protein pulldowns from infected human cells revealed a comprehensive network of interacting host proteins. The obtained LCMV L protein interactome was bioinformatically integrated with known host protein interactors of RdRps from other RNA viruses, emphasizing interconnected modules of human proteins. Functional characterization of selected interactors highlighted proviral (DDX3X) as well as antiviral (NKRF, TRIM21) host factors. To corroborate these findings, we infected Trim21-/-mice with LCMV and found impaired virus control in chronic infection. These results provide insights into the complex interactions of the arenavirus LCMV and other viral RdRps with the host proteome and contribute to a better molecular understanding of how chronic viruses interact with their host.},
  author       = {Khamina, Kseniya and Lercher, Alexander and Caldera, Michael and Schliehe, Christopher and Vilagos, Bojan and Sahin, Mehmet and Kosack, Lindsay and Bhattacharya, Anannya and Májek, Peter and Stukalov, Alexey and Sacco, Roberto and James, Leo and Pinschewer, Daniel and Bennett, Keiryn and Menche, Jörg and Bergthaler, Andreas},
  issn         = {1553-7366},
  journal      = {PLoS Pathogens},
  number       = {12},
  publisher    = {Public Library of Science},
  title        = {{Characterization of host proteins interacting with the lymphocytic choriomeningitis virus L protein}},
  doi          = {10.1371/journal.ppat.1006758},
  volume       = {13},
  year         = {2017},
}

@article{460,
  abstract     = {NF-κB signaling is a central pathway of immunity and integrates signal transduction upon a wide array of inflammatory stimuli. Noncanonical NF-κB signaling is activated by a small subset of TNF family receptors and characterized by NF-κB2/p52 transcriptional activity. The medical relevance of this pathway has recently re-emerged from the discovery of primary immunodeficiency patients that have loss-of-function mutations in the MAP3K14 gene encoding NIK. Nevertheless, knowledge of protein interactions that regulate noncanonical NF-κB signaling is sparse. Here we report a detailed state-of-the-art mass spectrometry-based protein–protein interaction network including the noncanonical NF-κB signaling nodes TRAF2, TRAF3, IKKα, NIK, and NF-κB2/p100. The value of the data set was confirmed by the identification of interactions already known to regulate this pathway. In addition, a remarkable number of novel interactors were identified. We provide validation of the novel NIK and IKKα interactor FKBP8, which may regulate processes downstream of noncanonical NF-κB signaling. To understand perturbed noncanonical NF-κB signaling in the context of misregulated NIK in disease, we also provide a differential interactome of NIK mutants that cause immunodeficiency. Altogether, this data set not only provides critical insight into how protein–protein interactions can regulate immune signaling but also offers a novel resource on noncanonical NF-κB signaling.},
  author       = {Willmann, Katharina and Sacco, Roberto and Martins, Rui and Garncarz, Wojciech and Krolo, Ana and Knapp, Sylvia and Bennett, Keiryn and Boztug, Kaan},
  issn         = {1535-3907},
  journal      = {Journal of Proteome Research},
  keywords     = {noncanonical NF-κB signaling, tandem affinity purification, protein−protein interaction network, NF-κB inducing kinase},
  number       = {9},
  pages        = {2900 -- 2909},
  publisher    = {American Chemical Society},
  title        = {{Expanding the interactome of the noncanonical NF-κB signaling pathway}},
  doi          = {10.1021/acs.jproteome.5b01004},
  volume       = {15},
  year         = {2016},
}