A5065590722- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Single-cell and spatial transcriptomics
- Hippo pathway signaling and YAP/TAZ
- Pluripotent Stem Cells Research
- Nuclear Structure and Function
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Cancer-related gene regulation
- Chromosomal and Genetic Variations
- Paleontology and Stratigraphy of Fossils
- Cancer Genomics and Diagnostics
- Microbial infections and disease research
- Space Exploration and Technology
- SARS-CoV-2 detection and testing
- Plant Taxonomy and Phylogenetics
- Hydrocarbon exploration and reservoir analysis
- Geological Studies and Exploration
- Plant Molecular Biology Research
- Firm Innovation and Growth
- Glioma Diagnosis and Treatment
- Quantum Dots Synthesis And Properties
- Cellular Mechanics and Interactions
- Geological Modeling and Analysis
Northwestern University
2023-2025
The Ohio State University
2025
Fred Hutch Cancer Center
2017-2022
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2018
Cancer Research Center
2018
The Evergreen State College
2016
Institut des Sciences des Plantes de Paris Saclay
1995
Université Paris-Saclay
1995
Understanding chromatin organization requires integrating measurements of genome connectivity and physical structure. It is well established that cohesin essential for TAD loop features in Hi-C, but the corresponding change structure has not been studied using electron microscopy. Pairing scanning transmission tomography with multiomic analysis single-molecule localization microscopy, we study role regulating conformationally defined nanoscopic packing domains. Our results indicate domains...
B-type lamins are critical nuclear envelope proteins that interact with the three-dimensional genomic architecture. However, identifying direct roles of B-lamins on dynamic genome organization has been challenging as their joint depletion severely impacts cell viability. To overcome this, we engineered mammalian cells to rapidly and completely degrade endogenous using Auxin-inducible degron technology.
Abstract Understanding chromatin organization requires integrating measurements of genome connectivity and physical structure. Prior work demonstrates that RAD21 depletion results in the complete loss topologically associated loop domains on Hi-C, but corresponding change structure has not been studied using electron microscopy. Pairing scanning transmission tomography with we study role cohesin regulating spatially resolved, conformationally defined packing domains. We find only 20% are...
Abstract Many of the regulatory features governing erythrocyte specification, maturation, and associated disorders remain enigmatic. To identify new regulators erythropoiesis, we utilize a functional genomic screen for genes affecting expression erythroid marker CD235a/GYPA. Among validating hits are coding N 6 -methyladenosine (m A) mRNA methyltransferase (MTase) complex, including, METTL14 , METTL3 WTAP . We demonstrate that m A MTase activity promotes gene programs through selective...
In single cells, variably sized nanoscale chromatin structures are observed, but it is unknown whether these form a cohesive framework that regulates RNA transcription. Here, we demonstrate the human genome an emergent, self-assembling, reinforcement learning system. Conformationally defined heterogeneous, nanoscopic packing domains by interplay of transcription, nucleosome remodeling, and loop extrusion. We show not topologically associated domains. Instead, exist across structure-function...
While spICP-MS has been used mainly to measure nanoparticles, it can also be microparticles. The transport efficiency of nanoparticles is typically independent their size. However, the microparticles particle size (mass) dependent as well being on sample uptake rate and introduction system used. To both a very large linear dynamic range (where signal intensity linearly proportional measured analyte(s) mass within short measurement time (∼300 500 µs, width signals produced by an individual...
Due to its small particle size, nanoparticle (NPs) and microparticles (μPs) could reside in the air for a long time affecting human health environment. Understanding of sources dynamics atmosphere remains complex challenge since direct observations are limited. Ice cores drilled from glaciers around world contain records atmospheric composition over time. Single Inductively Coupled Plasma Time-of-Flight Mass Spectrometry (spICP-TOFMS) is uniquely capable quickly (in ~10 minutes)...
SARS-CoV-2 has infected over 128 million people worldwide, and until a vaccine is developed widely disseminated, vigilant testing contact tracing are the most effective ways to slow spread of COVID-19. Typical clinical only confirms presence or absence virus, but rather, simple rapid procedure that sequences entire genome would be impactful allow for virus variants, as well appearance new variants. However, traditional short read sequencing methods time consuming expensive. Herein, we...
ABSTRACT BACKGROUND B-type lamins are critical nuclear envelope proteins that interact with the 3D genomic architecture. However, identifying direct roles of B-lamins on dynamic genome organization has been challenging as their joint depletion severely impacts cell viability. To overcome this, we engineered mammalian cells to rapidly and completely degrade endogenous using Auxin-inducible degron (AID) technology. RESULTS Paired a suite novel technologies, live-cell Dual Partial Wave...
Abstract Single cell RNA-seq has emerged as a powerful tool for resolving cellular states associated with normal and maligned developmental processes. Here, we used scRNA-seq to examine the cycle of expanding human neural stem cells (hNSCs). From this data, created classifier, which, in addition traditional phases, also identifies putative quiescent-like state neuroepithelial-derived types during mammalian neurogenesis gliomas. This state, Neural G0, is enriched expression quiescent NSC...
The identity of human protein-coding genes is well known, yet our in-depth knowledge their molecular functions and domain architecture remains limited by shortcomings in homology-based predictions experimental approaches focused on whole-gene depletion. To bridge this gap, we developed a method that leverages CRISPR-Cas9-induced mutations across for the priori identification functional regions at sequence level. As test case, applied to 48 mitotic genes, revealing hundreds required cell...
The relationship between gene transcription and chromatin organization is an area of active study. Due to its role in mRNA synthesis, many studies have focused on the regulaton RNA polymerase II (Pol-II) function by supranucleosomal structure vice-versa. In contrast, there little work I (Pol-I) non-nucleolar chromatin. Prior has shown that Pol-I engages with components Pol-II rDNA, but it's global beyond nucleolus largely been ignored. By pairing auxin-inducible degron technology nanoscopic...
The coordination of developmental potential and proliferation in stem progenitor cells is essential for mammalian development tissue homeostasis. To better understand this human neural (hNPCs), we performed CRISPR-Cas9 screens identified genes that limit their expansion. These revealed knockout growth-limiting genes, including CREBBP, NF2, PTPN14, TAOK1, or TP53, caused increased hNPC expansion via skipping a transient G0-like state, accompanied by transcriptional reprogramming G1...
Abstract Many of the regulatory features governing erythrocyte specification, maturation, and associated disorders remain enigmatic. To identify new regulators erythropoiesis, we performed a functional genomic screen for genes affecting expression erythroid marker CD235a/GYPA. Among validating hits were coding N 6 -methyladenosine (m A) mRNA methyltransferase (MTase) complex, including, METTL14 , METTL3 WTAP . We found that m A MTase activity promotes gene programs lineage specification...
Summary In solid tumors, G0-like states are likely critical for maintaining developmental hierarchies and cellular heterogeneity promoting tumor growth/recurrence, yet little is known about G0 or regulation of their ingress/egress. To discover regulators glioblastoma (GBM), we analyzed populations in an orthotopic model GBM using single cell RNA-seq performed a genome-wide CRISPR-Cas9 screen patient-derived stem-like cells (GSCs) genes that trap when inhibited. We identify the protein...
SUMMARY Kinetochores are large protein complexes that assemble at the centromere and bind to mitotic spindle microtubules ensure accurate chromosome segregation. Like most protein-coding genes, full multifunctional nature of kinetochore factors remains uncharacterized due limited experimental tools for unbiased dissection human sequences. We developed a method leverages CRISPR-Cas9 induced mutations identify key functional regions within sequences required cellular outgrowth. Our analysis 48...