Abstract

The Cell Function and Pathophysiology Core will be led by Dr. Ted Dawson and will function to determine disease-associated phenotypes from the differentiated PDiPS cell lines. In addition, the members of the Cell Function and Pathophysiology Core will be responsible for developing the existing phenotypic assays into a format amenable for large-scale drug screening. In conclusion, we think that the talented clinical investigators and translational scientists that comprise our current PDiPS Consortium are well placed to transition our groundbreaking work into a U24 format that meets the criteria outlined in the new RFA (RFA-NS-11-011, see Fig. 3 for Milestones).

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Resource-Related Research Projects--Cooperative Agreements (U24)
Project #
1U24NS078338-01
Application #
8294095
Study Section
Special Emphasis Panel (ZNS1-SRB-S (53))
Project Start
2012-07-01
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
1
Fiscal Year
2012
Total Cost
$184,136
Indirect Cost
$35,140

  Institution

Name
Mclean Hospital
Department
Type
DUNS #
046514535
City
Belmont
State
MA
Country
United States
Zip Code
02478

  Publications

Kim, Sangjune; Yun, Seung Pil; Lee, Saebom et al. (2018) GBA1 deficiency negatively affects physiological ?-synuclein tetramers and related multimers. Proc Natl Acad Sci U S A 115:798-803
Mazzulli, Joseph R; Zunke, Friederike; Tsunemi, Taiji et al. (2016) Activation of ?-Glucocerebrosidase Reduces Pathological ?-Synuclein and Restores Lysosomal Function in Parkinson's Patient Midbrain Neurons. J Neurosci 36:7693-706
Chung, Sun Young; Kishinevsky, Sarah; Mazzulli, Joseph R et al. (2016) Parkin and PINK1 Patient iPSC-Derived Midbrain Dopamine Neurons Exhibit Mitochondrial Dysfunction and ?-Synuclein Accumulation. Stem Cell Reports 7:664-677
Mazzulli, Joseph R; Zunke, Friederike; Isacson, Ole et al. (2016) ?-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
Sanders, Laurie H; Laganière, Josée; Cooper, Oliver et al. (2014) LRRK2 mutations cause mitochondrial DNA damage in iPSC-derived neural cells from Parkinson's disease patients: reversal by gene correction. Neurobiol Dis 62:381-6
Sundberg, Maria; Bogetofte, Helle; Lawson, Tristan et al. (2013) Improved cell therapy protocols for Parkinson's disease based on differentiation efficiency and safety of hESC-, hiPSC-, and non-human primate iPSC-derived dopaminergic neurons. Stem Cells 31:1548-62
Miller, Justine D; Ganat, Yosif M; Kishinevsky, Sarah et al. (2013) Human iPSC-based modeling of late-onset disease via progerin-induced aging. Cell Stem Cell 13:691-705
Sundal, Christina; Fujioka, Shinsuke; Van Gerpen, Jay A et al. (2013) Parkinsonian features in hereditary diffuse leukoencephalopathy with spheroids (HDLS) and CSF1R mutations. Parkinsonism Relat Disord 19:869-77
Cooper, Oliver; Seo, Hyemyung; Andrabi, Shaida et al. (2012) Pharmacological rescue of mitochondrial deficits in iPSC-derived neural cells from patients with familial Parkinson's disease. Sci Transl Med 4:141ra90