Overview of the Center and the Administrative Core Regenerative medicine is one of the great biomedical challenges of the 21st century. The potential for meeting this challenge was greatly augmented by the discovery that it is possible to reprogram somatic cells into pluripotent cells (induced pluripotent stem cells - iPSCs) that share many of the properties of embryonic stem cells (1-5). The ability to create and differentiate human iPSC lines has transformed both investigations of basic human cellular neurobiology and the examination of the cellular basis of human diseases of the nervous system. This technology makes it possible to study the development and cell biology of human neural stem cells as well as their neuronal and glial progeny. Further, somatic cells from patients with a variety of neurological diseases can reprogrammed to allow study of neurons and glia with the genotypes of the afflicted individuals. At NU there are two overiapping and rapidly growing groups of NINDS funded neuroscientists whose research programs will be dramatically advanced by access to and use of iPCs and their progeny. One group is focused on understanding the causes of neurodegenerative disease, describing the anatomic and physiologic properties of diseased cells, and finding ways of ameliorating cell death iri the brain. Specifically this includes NU investigators in the Udall Center and several departments studying the pathophysiology of Parkinson's disease, several labs focused on motor neuron disease (ALS) and Huntington's disease, several focused on the spinocerebellar atrophies, and a large number of investigators examining disorders leading to dementia. The second group is focused on neural stem cell biology and development ofthe nervous system. Neuroscience research has been targeted by NU as an area of special focus, and the neuroscience community at NU is a large and productive one with about $50 million of NlH-sponsored research grants. This creates a rich environment with a wide diversity of technological and intellectual assets. However the inclusion of iPSC technology into these research programs has been hampered by the difficulties involved in creating and maintaining the cells with the highest standards of quality control. This proposed center will provide access to such cells to NINDS-funded investigators.
|Huang, Tianzhi; Alvarez, Angel A; Pangeni, Rajendra P et al. (2016) A regulatory circuit of miR-125b/miR-20b and Wnt signalling controls glioblastoma phenotypes through FZD6-modulated pathways. Nat Commun 7:12885|
|Mazzulli, Joseph R; Zunke, Friederike; Tsunemi, Taiji et al. (2016) Activation of Î²-Glucocerebrosidase Reduces Pathological Î±-Synuclein and Restores Lysosomal Function in Parkinson's Patient Midbrain Neurons. J Neurosci 36:7693-706|
|Mazzulli, Joseph R; Zunke, Friederike; Isacson, Ole et al. (2016) Î±-Synuclein-induced lysosomal dysfunction occurs through disruptions in protein trafficking in human midbrain synucleinopathy models. Proc Natl Acad Sci U S A 113:1931-6|
|Duan, Lishu; Peng, Chian-Yu; Pan, Liuliu et al. (2015) Human pluripotent stem cell-derived radial glia recapitulate developmental events and provide real-time access to cortical neurons and astrocytes. Stem Cells Transl Med 4:437-47|
|Nathamgari, S Shiva P; Dong, Biqin; Zhou, Fan et al. (2015) Isolating single cells in a neurosphere assay using inertial microfluidics. Lab Chip 15:4591-7|
|Duan, Lishu; Bhattacharyya, Bula J; Belmadani, Abdelhak et al. (2014) Stem cell derived basal forebrain cholinergic neurons from Alzheimer's disease patients are more susceptible to cell death. Mol Neurodegener 9:3|
|Kang, Wonmo; Giraldo-Vela, Juan P; Nathamgari, S Shiva P et al. (2014) Microfluidic device for stem cell differentiation and localized electroporation of postmitotic neurons. Lab Chip 14:4486-95|