A5073551074- RNA Research and Splicing
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- Single-cell and spatial transcriptomics
- RNA modifications and cancer
- Advanced biosensing and bioanalysis techniques
- MicroRNA in disease regulation
- RNA Interference and Gene Delivery
- Immune Response and Inflammation
- Gene Regulatory Network Analysis
- Cell Image Analysis Techniques
- Cancer-related molecular mechanisms research
- Pancreatic function and diabetes
- Genomics and Chromatin Dynamics
- Advanced Proteomics Techniques and Applications
- Cell Adhesion Molecules Research
- RNA regulation and disease
- Advanced Fluorescence Microscopy Techniques
- Metabolomics and Mass Spectrometry Studies
- Gene expression and cancer classification
- HVDC Systems and Fault Protection
- FOXO transcription factor regulation
- Plant Virus Research Studies
- Machine Learning and Data Classification
- Gaussian Processes and Bayesian Inference
New York Genome Center
2019-2025
New York University
2019-2025
Humboldt-Universität zu Berlin
2018-2021
Max Delbrück Center
2013-2021
Regnase-1 and Roquin are RNA binding proteins essential for degradation of inflammation-related mRNAs maintenance immune homeostasis. However, their mechanistic relationship has yet to be clarified. Here, we show that, although regulate an overlapping set via a common stem-loop structure, they function in distinct subcellular locations: ribosome/endoplasmic reticulum processing-body/stress granules, respectively. Moreover, specifically cleaves degrades translationally active requires the...
Highlights•Silencing of miR-184 during insulin resistance promotes its target Ago2•Loss Ago2 blocks pancreatic β cell proliferation•Ago2 mediates the suppression Cadm1 by miR-375 in cell•Administration ketogenic diet to ob/ob mice rescues isletsSummaryPancreatic cells adapt compensate for increased metabolic demand resistance. Although microRNA pathway has an essential role proliferation, extent contribution is unclear. Here, we report that silenced islets insulin-resistant mouse models and...
Abstract N6‐methyladenosine (m 6 A) regulates a variety of physiological processes through modulation RNA metabolism. This modification is particularly enriched in the nervous system several species, and its dysregulation has been associated with neurodevelopmental defects neural dysfunctions. In Drosophila , loss m A alters fly behavior, albeit underlying molecular mechanism role during development have remained elusive. Here we find that impairment pathway leads to axonal overgrowth...
ABSTRACT Recent advancements in functional genomics have provided an unprecedented ability to measure diverse molecular modalities, but learning causal regulatory relationships from observational data remains challenging. Here, we leverage pooled genetic screens and single cell sequencing (i.e. Perturb-seq) systematically identify the targets of signaling regulators biological contexts. We demonstrate how Perturb-seq is compatible with recent commercially available advances combinatorial...
Early embryogenesis is characterized by the maternal to zygotic transition (MZT), in which maternally deposited messenger RNAs are degraded while transcription begins. Before MZT, post-transcriptional gene regulation RNA-binding proteins (RBPs) dominant force embryo patterning. We used two mRNA interactome capture methods identify RBPs bound polyadenylated transcripts within first 2 h of Drosophila melanogaster embryogenesis. identified a high-confidence set 476 putative and confirmed...
RNA-binding proteins (RBPs) control and coordinate each stage in the life cycle of RNAs. Although vivo binding sites RBPs can now be determined genome-wide, most studies typically focused on individual RBPs. Here, we examined a large compendium 114 high-quality transcriptome-wide RBP–RNA cross-linking interaction datasets generated by same protocol cell line representing 64 distinct Comparative analysis categories target RNA preference, sequence transcript region specificity was performed,...
A key limitation of the widely used CRISPR enzyme S. pyogenes Cas9 is strict requirement an NGG protospacer-adjacent motif (PAM) at target site. This constraint can be limiting for genome editing applications that require precise positioning. Recently, two variants with a relaxed PAM (NG) have been developed (xCas9 and Cas9-NG), but their activity has measured only small number endogenous sites. Here, we devise high-throughput pooled competition screen to compare performance thousands...
The recent characterization of RNA-targeting CRISPR nucleases has enabled diverse transcriptome engineering and screening applications that depend crucially on prediction selection optimized guide RNAs (gRNAs). Previously, we developed a computational model to predict RfxCas13d gRNA activity for all human protein-coding genes. Here, extend this framework six organisms (human, mouse, zebrafish, fly, nematode, flowering plants) genes noncoding (ncRNAs) also four RNA virus families (severe...
MicroRNAs (miRNAs) are key mediators of post-transcriptional gene expression silencing. So far, no comprehensive experimental annotation functional miRNA target sites exists in Drosophila. Here, we generated a transcriptome-wide vivo map miRNA-mRNA interactions Drosophila melanogaster, making use single nucleotide resolution Argonaute1 (AGO1) crosslinking and immunoprecipitation (CLIP) data. Absolute quantification cellular levels presents the pool cell lines to be more diverse than...
While CRISPR-Cas13 systems excel in accurately targeting RNA, the potential for collateral RNA degradation poses a concern therapeutic applications and limits broader adoption transcriptome perturbations. We evaluate extent to which cleavage occurs when
Argonaute2 (Ago2) is an established component of the microRNA-induced silencing complex. Similar to miR-375 loss-of-function studies, inhibition Ago2 in pancreatic β-cell resulted enhanced insulin release underlining relationship between these two genes. Moreover, as most abundant microRNA endocrine cells, was also observed be enriched Ago2-associated complexes. Both and regulate secretome, by using quantitative mass spectrometry, we identified a set proteins or secretion "signatures "...
CLIP-seq methods allow the generation of genome-wide maps RNA binding protein – interaction sites. However, due to differences between different assays, existing computational approaches analyze data can only be applied a subset assays. Here, we present probabilistic model called omniCLIP that detect regulatory elements in RNAs from all jointly models across replicates and integrate background information. Therefore, greatly simplifies analysis, increases reliability results paves way for...
ABSTRACT The expression of inhibitory immune checkpoint molecules such as PD-L1 is frequently observed in human cancers and can lead to the suppression T cell-mediated responses. Here we apply ECCITE-seq, a technology which combines pooled CRISPR screens with single-cell mRNA surface protein measurements, explore molecular networks that regulate expression. We also develop computational framework, mixscape , substantially improves signal-to-noise ratio perturbation by identifying removing...