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Output Catalog
ASAP is committed to accelerating the pace of discovery and informing a path to a cure for Parkinson’s disease through collaboration, research-enabling resources, and data sharing. We’ve created this catalog to showcase the research outputs and tools developed by ASAP-funded programs.
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Cholesterol-mediated Lysosomal Dysfunction in APOE4 Astrocytes Promotes α-Synuclein Pathology in Human Brain Tissue
Development of a 3D model mimicking human brain tissue to investigate neurodegenerative diseases. It found that APOE4 increases α-Synuclein aggregation, linking astrocytes, cholesterol, and protein inclusions, offering potential therapeutic…
TNF-NF-κB-p53 axis restricts in vivo survival of hPSC-derived dopamine neurons
The ASAP-related findings are the DA neuron purification strategy developed (CD49e-/CD184+) developed and validated in this manuscript, which is suitable for PD-iPSC based disease modeling and DA-neuron related CRISPR screens from our consortium.
Rapid iPSC inclusionopathy models shed light on formation, consequence, and molecular subtype of α-synuclein inclusions
The authors developed an iPSC toolbox utilizing piggyBac-based or targeted transgenes to rapidly induce CNS cells with concomitant expression of aggregation-prone proteins.
The Parkinson’s disease protein alpha-synuclein is a modulator of processing bodies and mRNA stability
The paper describes the ability of alpha-synuclein to bind to P-bodies, machinery that regulates the expression of our genes through mRNAs. When alpha-synuclein abnormally accumulates, the physiologic structure and functions of the P-body are lost.
The SATB1-MIR22-GBA axis mediates glucocerebroside accumulation inducing a cellular senescence-like phenotype in dopaminergic neurons
Study shows SATB1, MIR22HG, and GBA genes form a pathway in Parkinson's Disease. Dysregulation leads to GluCer accumulation, causing cellular senescence in dopaminergic neurons, potentially explaining neuroinflammation seen in PD and aging.
Deep sequencing of proteotoxicity modifier genes uncovers a Presenilin-2/beta-amyloid-actin genetic risk module shared among alpha-synucleinopathies
The authors study patients based on protein aggregation phenotype to detect variants in a targeted set of genes.
Integrating population genetics, stem cell biology and cellular genomics to study complex human diseases
This review describes current state-of-the art of pooled "village-style" hPSC-based assays. This is a major topic for disease modeling including PD and for linking disease with genetic and/or environmental risk and part of our experimental ASAP work.
Contextual AI models for single-cell protein biology
This study describes PINNACLE a deep learning approach establish context dependent networks. PINNACLE is a key algorithm used in our ASAP project to provide cell type , age-or disease context to our experimental datasets.
Genome-wide CRISPR screen identifies neddylation as a regulator of neuronal aging and AD neurodegeneration.
We found that neddylation-inhibition triggers age-related features in PSC-derived neurons for modeling AD or PD. This strategy can induce late-onset phenotypes including degeneration when applied to DA neurons from PD- versus isogenic control PSCs.
SARS-CoV-2 infection causes dopaminergic neuron senescence.
The ASAP-supported aspect of this study involves the DA neuron senescence work, and experiments using ASAP lines (isogenic a-SYN triplication) to assess interaction of genetic vulnerability with viral-induced senescence as PD penetrance factor.
Immune stimulation of human induced pluripotent stem cells (hiPSC)-derived glia with lipopolysaccharide (LPS)
hiPSCs are used to model human development and diseases. Lipopolysaccharide activates immune cells and triggers cytokine secretion. LPS activates toll-like receptor 4 and NFkB. Protocol how to use LPS to activate iPSC-derived microglia.
Available ASAP-related hPSC collection from Team Studer
Collection of human pluripotent stem cell lines consisting of isogenic GBA, LRRK2, SNCA series, KI-reporter lines for TOMM20, b-actin, LAMB1, LAMP1, a-synuclein overexpression lines, and other hPSC resources.
Poly-ornithine/laminin substrate for neural cell culture V.2
Protocol to generate a sticky substrate for neurons.
hPSC Passaging and Propagation on laminin521 V.1
Highly efficient passaging and propagation of human PSC.
Seeded amplification assay (SAA) from neuronal cell lysates
Seeded amplification assay (SAA) from neuronal cell lysates