Professional Education
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BA, Rice University, Biochemistry and Cell Biology (2013)
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Ph.D., University of California, Berkeley, Molecular and Cell Biology (2019)
All Publications
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Double stranded DNA breaks and genome editing trigger loss of ribosomal protein RPS27A
FEBS JOURNAL
2022; 289 (11): 3101-3114
Abstract
DNA damage activates a robust transcriptional stress response, but much less is known about how DNA damage impacts translation. The advent of genome editing with Cas9 has intensified interest in understanding cellular responses to DNA damage. Here, we find that DNA double-strand breaks (DSBs), including those induced by Cas9, trigger the loss of ribosomal protein RPS27A from ribosomes via p53-independent proteasomal degradation. Comparisons of Cas9 and dCas9 ribosome profiling and mRNA-seq experiments reveal a global translational response to DSBs that precedes changes in transcript abundance. Our results demonstrate that even a single DSB can lead to altered translational output and ribosome remodeling, suggesting caution in interpreting cellular phenotypes measured immediately after genome editing.
View details for DOI 10.1111/febs.16321
View details for Web of Science ID 000740693000001
View details for PubMedID 34914197
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Ribosomal protein RPL26 is the principal target of UFMylation
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2019; 116 (4): 1299–1308
View details for DOI 10.1073/pnas.1816202116
View details for Web of Science ID 000456336100035
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Multi-endpoint, High-Throughput Study of Nanomaterial Toxicity in Caenorhabditis elegans
ENVIRONMENTAL SCIENCE & TECHNOLOGY
2015; 49 (4): 2477–85
Abstract
The booming nanotechnology industry has raised public concerns about the environmental health and safety impact of engineered nanomaterials (ENMs). High-throughput assays are needed to obtain toxicity data for the rapidly increasing number of ENMs. Here we present a suite of high-throughput methods to study nanotoxicity in intact animals using Caenorhabditis elegans as a model. At the population level, our system measures food consumption of thousands of animals to evaluate population fitness. At the organism level, our automated system analyzes hundreds of individual animals for body length, locomotion speed, and lifespan. To demonstrate the utility of our system, we applied this technology to test the toxicity of 20 nanomaterials at four concentrations. Only fullerene nanoparticles (nC60), fullerol, TiO2, and CeO2 showed little or no toxicity. Various degrees of toxicity were detected from different forms of carbon nanotubes, graphene, carbon black, Ag, and fumed SiO2 nanoparticles. Aminofullerene and ultraviolet-irradiated nC60 also showed small but significant toxicity. We further investigated the effects of nanomaterial size, shape, surface chemistry, and exposure conditions on toxicity. Our data are publicly available at the open-access nanotoxicity database www.QuantWorm.org/nano.
View details for DOI 10.1021/es5056462
View details for Web of Science ID 000349806400061
View details for PubMedID 25611253
View details for PubMedCentralID PMC4336152
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QuantWorm: A Comprehensive Software Package for Caenorhabditis elegans Phenotypic Assays
PLOS ONE
2014; 9 (1): e84830
Abstract
Phenotypic assays are crucial in genetics; however, traditional methods that rely on human observation are unsuitable for quantitative, large-scale experiments. Furthermore, there is an increasing need for comprehensive analyses of multiple phenotypes to provide multidimensional information. Here we developed an automated, high-throughput computer imaging system for quantifying multiple Caenorhabditis elegans phenotypes. Our imaging system is composed of a microscope equipped with a digital camera and a motorized stage connected to a computer running the QuantWorm software package. Currently, the software package contains one data acquisition module and four image analysis programs: WormLifespan, WormLocomotion, WormLength, and WormEgg. The data acquisition module collects images and videos. The WormLifespan software counts the number of moving worms by using two time-lapse images; the WormLocomotion software computes the velocity of moving worms; the WormLength software measures worm body size; and the WormEgg software counts the number of eggs. To evaluate the performance of our software, we compared the results of our software with manual measurements. We then demonstrated the application of the QuantWorm software in a drug assay and a genetic assay. Overall, the QuantWorm software provided accurate measurements at a high speed. Software source code, executable programs, and sample images are available at www.quantworm.org. Our software package has several advantages over current imaging systems for C. elegans. It is an all-in-one package for quantifying multiple phenotypes. The QuantWorm software is written in Java and its source code is freely available, so it does not require use of commercial software or libraries. It can be run on multiple platforms and easily customized to cope with new methods and requirements.
View details for DOI 10.1371/journal.pone.0084830
View details for Web of Science ID 000329862500176
View details for PubMedID 24416295
View details for PubMedCentralID PMC3885606