The overarching theme of this new program project proposal entitled "Pathobiology of Neurodegeneration in C9ORF72 Repeat Expansion" is to evaluate the mechanisms of C9ORF72 expanded repeats, the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), to improve the diagnosis of and prognosis for patients suffering from c9FTD/ALS. Core A will facilitate these goals by providing scientific and fiscal oversight. Core A will be responsible for managing fiscal responsibilities for the program project, ensuring ethical and responsible conduct of research, providing scientific direction and accountability, and reporting progress to the NIH and to the public. In order to assure the success of this research proposal, Core A will also leverage Mayo Clinic resources to foster a multidisciplinary program that advances research, generates valuable biological resources, and promotes education. Among institutional resources that Core A will avail itself on behalf of the P01 are administrative assistance with grants administration and all aspects of human subject research;access to biostatistics and bioinformatics;access to the latest in technology for biobanking (e.g., Nexus Universal BioStore);and institutional commitment to regenerative medicine (Center for Regenerative Medicine) for transformation of skin biopsies to fibroblast cell lines to be used by Projects 2 and 3. To accomplish these goals, the Core A will pursue the following specific aims.
Specific Aim 1 : Provide administrative structure and fiscal oversight for the program project grant.
Specific Aim 2 : Organize regular Executive Committee meetings composed of PLs of projects and cores, as well as other key personnel to assist in scientific administration and to facilitate integration and progress on research.
Specific Aim 3 : Establish an External Advisory Committee, conduct annual meetings, and report progress to the NIH.
Specific Aim 4 : Assume responsibility for quality control of program project activities and ensure the safety of human subjects and confidentiality of their data.
Specific Aim 5 : Ensure that research conforms to the standards of the ethical conduct of research and is compliant with HIPAA guidelines.
Specific Aim 6 : Promote compliance with the NIH Public Access publication policy to make the results of research funded by this proposal widely accessible to the general public.
Specific Aim 7 : Promote education of ALS and related disorders by leveraging Mayo Clinic resources for the invited speaker seminar series, scientific symposia, contribution to Mayo Clinic related social media, and encouragement of P01 scientists and clinicians to participate in patient and caregiver support groups.

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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Mayo Clinic Jacksonville
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Zhang, Yong-Jie; Jansen-West, Karen; Xu, Ya-Fei et al. (2014) Aggregation-prone c9FTD/ALS poly(GA) RAN-translated proteins cause neurotoxicity by inducing ER stress. Acta Neuropathol 128:505-24
Su, Zhaoming; Zhang, Yongjie; Gendron, Tania F et al. (2014) Discovery of a biomarker and lead small molecules to target r(GGGGCC)-associated defects in c9FTD/ALS. Neuron 83:1043-50