ESC
Functional Genomics

CRISPR Screening Outcomes

Interactive visualizations of CRISPR-based functional screening campaigns spanning mitophagy pathway discovery in iPSC-derived neurons, α-synuclein fibril uptake mechanism dissection, and SARS-CoV-2 viral entry characterization — from genome-wide pooled screens to arrayed target validation.

0
Genes Screened
0
Validated Hits
0
Cell Models
0
Screen Campaigns
0
Total Citations
01

Mitophagy Pathway CRISPR Screen

Nature · Under Review

Genome-wide CRISPR knockout screen in iPSC-derived dopaminergic neurons identifying regulators of PARK2-dependent mitophagy and neuroprotective targets. Integrated multiomics, quantitative imaging, and LC-MS/MS PK to demonstrate small-molecule neuroprotection in iPSC-derived and in vivo Parkinson’s disease models.

Volcano Plot — Mitophagy Screen Hits

Each dot represents a gene. X-axis: log₂ fold-change of mitophagy flux; Y-axis: −log₁₀(p-value). Hover over significant hits for gene details. Dashed line = FDR < 0.05 threshold.

Top 15 Mitophagy Regulators

Ranked by phenotype Z-score from the primary pooled screen in iPSC-derived dopaminergic neurons.

Parkin Agonist Dose-Response

Neuroprotection of iPSC-derived dopaminergic neurons treated with small-molecule Parkin agonist (compound ABY-101). IC₅₀ determined by mitochondrial membrane potential rescue.

02

α-Synuclein Uptake CRISPR Screen

Cell Reports · 2022 · 50+ Citations

Arrayed CRISPR screen in RPE1 cells identifying RAC1-dependent macropinocytosis as the major α-synuclein preformed fibril internalization pathway. RAC1 knockout reduced internalization, characterized by quantitative confocal and electron microscopy.

Waterfall Plot — PFF Uptake Modulators

Ranked effect sizes for top endocytic regulators. Negative values indicate reduced α-synuclein PFF uptake upon gene knockout.

Endocytic Pathway Contributions

Relative contribution of each endocytic mechanism to α-synuclein fibril internalization, quantified by CRISPR KO effect sizes.

03

SARS-CoV-2 Viral Entry Screen

J. Biol. Chem. · 2021 · 500+ Citations

siRNA screen across endocytic machinery genes defining clathrin-mediated endocytosis as the primary SARS-CoV-2 cellular entry route. Established using pseudotyped lentivirus infectivity assays, siRNA knockdown of clathrin heavy chain, and quantitative confocal imaging across four cell lines.

Pseudovirus Infection — siRNA Knockdown Panel

GFP⁺ cell quantification (Opera Phenix) across four cell lines after siRNA knockdown of endocytic regulators.

Entry Kinetics — Clathrin vs. Caveolin Inhibition

Time-course of pseudovirus internalization with Pitstop-2 (clathrin inhibitor) vs. filipin (caveolin inhibitor) vs. DMSO control.

04

Cross-Screen Validation & Transcriptomic Integration

eLife · 2025

Multi-screen validation heatmap and single-cell transcriptomic embedding of CRISPR-perturbed iPSC-derived neurons. Integrates AutoMorphoTrack quantitative imaging with Seahorse XF metabolic flux analysis across all three screening campaigns.

Cross-Screen Validation Heatmap

Z-score normalized phenotypic effects of top hits across three independent CRISPR campaigns (mitophagy, α-syn uptake, viral entry). Rows = genes, columns = assay readouts.

scRNA-seq UMAP — CRISPR Perturbations

Single-cell transcriptome embedding of iPSC-derived neurons after CRISPR KO of top mitophagy regulators. Colors indicate perturbation identity.

Seahorse XF Metabolic Profiling

Oxygen consumption rate (OCR) in iPSC-derived neurons following CRISPR KO of PINK1, PARK2, BNIP3L, and FUNDC1 vs. non-targeting control.