Administration Component The Administrative Core is responsible for setting the overall direction of the NeuroLINCS center and for ensuring that the resources and components of the Center are optimally utilized. The successful development and evolution of the NeuroLINCS center requires strong interactions between the leaders and co-leaders of each Component and of the center as a whole. Hence, the NeuroLINCS Administrative Component plays a vital role in facilitating these interactions. Moreover, the Administrative Component and its personnel provide the necessary administrative and fiscal oversight to ensure that the NeuroLINCS center is run efficiently. The NeuroLINCS center involves 5 principal sites with defined responsibilities of growing, differentiating and generating new induced pluripotent stem cell lines (iPSCs), performing data generation assays on human brain cells made from iPSCs in response to perturbagens, performing basic analyses and developing cell signatures through integrated data analysis .methods, and establish community interactions. An integrated and highly collaborative group of investigators with expertise in stem cell biology, IPS cells, quantitative molecular phenotyping (""""""""omics"""""""" and single cell imaging) and bioinformatics will work closely together to generate significant and highly predictive cell signatures. The PIs of the NeuroLINCS center are Steven Finkbeiner (Gladstone), Ernest Frankel (MIT), Jeffrey Rothstein (JHU), Clive Svendsen (Cedars) and Leslie Thompson (UCI), who will serve as leaders and co-leaders of components. Each Component has identified co-investigators/collaborators/consultants appropriate for the planned scientific investigations. Component leaders and co-leaders will also be active participants in NeuroLINCS consortium working groups as they are developed to address specific issues. Results of the genetic, proteomic and other characterization conducted by consortium labs will provide important feedback for further enhancement of induction and differentiation protocols and related methodologies and it is anticipated that this collaborative and iterative approach will lead to the broadest success for the study. An Evaluation Program within the NeuroLINCS is in place to determine if the programs supported are meeting the needs of the research community, are efficiently managed, and demonstrably effective and annual objectives and milestones.

Public Health Relevance

The NeuroLINCS center will address key roadblocks in biomedical research, with an emphasis on the CNS and neurodegenerative disease. It brings together a unique group of investigators with the expertise to generate highly significant and predictive cell signatures using human iPS cells and their neural cell derivatives. These studies will address disease-specific features versus commonalities across human diseases including ALS, SMA, HD, and PD and define their responses to cellular perturbations.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZRG1)
Program Officer
Sutherland, Margaret L
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University of California Irvine
United States
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Shaby, Benjamin A; Skibinski, Gaia; Ando, Michael et al. (2016) A three-groups model for high-throughput survival screens. Biometrics 72:936-44
Pirhaji, Leila; Milani, Pamela; Leidl, Mathias et al. (2016) Revealing disease-associated pathways by network integration of untargeted metabolomics. Nat Methods 13:770-6
Holewinski, Ronald J; Parker, Sarah J; Matlock, Andrea D et al. (2016) Methods for SWATHâ„¢: Data Independent Acquisition on TripleTOF Mass Spectrometers. Methods Mol Biol 1410:265-79
Zhang, Yong-Jie; Gendron, Tania F; Grima, Jonathan C et al. (2016) C9ORF72 poly(GA) aggregates sequester and impair HR23 and nucleocytoplasmic transport proteins. Nat Neurosci 19:668-77
Haston, Kelly M; Finkbeiner, Steven (2016) Clinical Trials in a Dish: The Potential of Pluripotent Stem Cells to Develop Therapies for Neurodegenerative Diseases. Annu Rev Pharmacol Toxicol 56:489-510
Ho, Ritchie; Sances, Samuel; Gowing, Genevieve et al. (2016) ALS disrupts spinal motor neuron maturation and aging pathways within gene co-expression networks. Nat Neurosci 19:1256-67
Tuncbag, Nurcan; Gosline, Sara J C; Kedaigle, Amanda et al. (2016) Network-Based Interpretation of Diverse High-Throughput Datasets through the Omics Integrator Software Package. PLoS Comput Biol 12:e1004879
Milani, Pamela; Escalante-Chong, Renan; Shelley, Brandon C et al. (2016) Cell freezing protocol suitable for ATAC-Seq on motor neurons derived from human induced pluripotent stem cells. Sci Rep 6:25474
Fuller, Heidi R; Mandefro, Berhan; Shirran, Sally L et al. (2015) Spinal Muscular Atrophy Patient iPSC-Derived Motor Neurons Have Reduced Expression of Proteins Important in Neuronal Development. Front Cell Neurosci 9:506
Zhang, Ke; Donnelly, Christopher J; Haeusler, Aaron R et al. (2015) The C9orf72 repeat expansion disrupts nucleocytoplasmic transport. Nature 525:56-61