The goal of the Administrative Core is to coordinate regular communication among all the Project Investigators, plan the periodic meetings of the investigators and the External Advisory Committee, prepare progress reports and grant renewals, and maintain financial accounting between the home institution (Wisconsin), all of the participating institutions (Alabama, Columbia/Rochester, and Brigham and Women's Hospital), and the NIH. Much of this core has already been described in the context of the budget justification and General Introduction for the entire Program Project. Selected sections are repeated here for convenience. The administrative home of this Program Project is at the Waisman Center of the University of Wisconsin-Madison, with Dr. Albee Messing as the Program Director. An administrative assistant manages day-to-day Program business. This person is responsible for grant accounting, coordination with the consortium sites, assurance of compliance with NIH regulations involving human subjects (currently none) and animal care, and collection of updated materials for grant renewals. The administrative assistant also acts as liaison between the Program Director, Project Investigators and NINDS grant management personnel. The annual meetings with our External Advisory Committee are essential to the Program Project. For this group we have recruited an outstanding group of individuals who evaluate progress annually during the grant period and report their findings to the Program Director. Each member of the External Advisory Committee is an experienced researcher who has made substantial contributions in areas of research related to the Program: Dr. Virginia Lee (Dept. of Pathology and Laboratory Medicine, University of Pennsylvania -authority on the molecular pathology of tauopathies, a-synucleinopathies, and Alzheimer's disease, including mouse models), Dr. Richard Ransohoff (Department of Neurology, Cleveland Clinic - authority on the role of astrocytes in neuroinflammatory diseases, multiple sclerosis, including mouse models, and a practicing neurologist), and Dr. Pierre Coulombe (Department of Biological Chemistry, Johns Hopkins - authority on the keratins and their role in biology and diseases of epithelium, including mouse models - one of the first to discover intermediate filament mutations in disease). All members of the External Advisory Committee have agreed to continue serving in this capacity (see attached letters at the end of the General Introduction). To supplement the regular contact and sharing of results that will occur electronically, all five Project Investigators participate in monthly teleconferences. Travel costs to support the period face-to-face meetings of the Project Investigators with each other and the External Advisory Committee are included within the budget of the Administrative Core (see budget justification). More frequent meetings between two or more of the PIs will also occur in the context of attending various conferences, such as the Gordon Conference on Intermediate Filaments, the American Society for Neurochemistry, or the Society for Neuroscience.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Program Projects (P01)
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National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
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University of Wisconsin Madison
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Wang, Liqun; Hagemann, Tracy L; Messing, Albee et al. (2016) An In Vivo Pharmacological Screen Identifies Cholinergic Signaling as a Therapeutic Target in Glial-Based Nervous System Disease. J Neurosci 36:1445-55
Heaven, Michael R; Flint, Daniel; Randall, Shan M et al. (2016) Composition of Rosenthal Fibers, the Protein Aggregate Hallmark of Alexander Disease. J Proteome Res 15:2265-82
Wang, Liqun; Hagemann, Tracy L; Kalwa, Hermann et al. (2015) Nitric oxide mediates glial-induced neurodegeneration in Alexander disease. Nat Commun 6:8966
Olabarria, Markel; Putilina, Maria; Riemer, Ellen C et al. (2015) Astrocyte pathology in Alexander disease causes a marked inflammatory environment. Acta Neuropathol 130:469-86
LaPash Daniels, Christine M; Paffenroth, Elizabeth; Austin, Elizabeth V et al. (2015) Lithium Decreases Glial Fibrillary Acidic Protein in a Mouse Model of Alexander Disease. PLoS One 10:e0138132
Sosunov, Alexander A; McGovern, Robert A; Mikell, Charles B et al. (2015) Epileptogenic but MRI-normal perituberal tissue in Tuberous Sclerosis Complex contains tuber-specific abnormalities. Acta Neuropathol Commun 3:17
Jany, Paige L; Agosta, Guillermo E; Benko, William S et al. (2015) CSF and Blood Levels of GFAP in Alexander Disease(1,2,3). eNeuro 2:
Minkel, Heather R; Anwer, Tooba Z; Arps, Kara M et al. (2015) Elevated GFAP induces astrocyte dysfunction in caudal brain regions: A potential mechanism for hindbrain involved symptoms in type II Alexander disease. Glia 63:2285-97
Brenner, Michael; Messing, Albee (2015) A new mutation in GFAP widens the spectrum of Alexander disease. Eur J Hum Genet 23:1-2
Cotrina, Maria Luisa; Chen, Michael; Han, Xiaoning et al. (2014) Effects of traumatic brain injury on reactive astrogliosis and seizures in mouse models of Alexander disease. Brain Res 1582:211-9

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