A5057259259- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- Fungal and yeast genetics research
- Evolution and Genetic Dynamics
- Cancer-related gene regulation
- Microbial Metabolic Engineering and Bioproduction
- Gene Regulatory Network Analysis
- CAR-T cell therapy research
- Cancer-related Molecular Pathways
- Evolutionary Game Theory and Cooperation
- Caveolin-1 and cellular processes
- Virus-based gene therapy research
- Cancer Research and Treatments
- Gene expression and cancer classification
- Biofuel production and bioconversion
- Bioinformatics and Genomic Networks
- RNA Research and Splicing
- Cancer Genomics and Diagnostics
- Mathematical and Theoretical Epidemiology and Ecology Models
Stanford University
2024-2025
University of Michigan–Ann Arbor
2019-2023
University of Illinois Urbana-Champaign
2021
ABSTRACT Somatic genome editing in mouse models has increased our understanding of the vivo effects genetic alterations areas ranging from neuroscience to cancer biology and beyond. However, existing are limited their ability create multiple targeted edits. Thus, complex interactions that underlie development, homeostasis, disease remains incomplete. Cas12a is an RNA-guided endonuclease with unique attributes enable simple targeting genes crRNA arrays containing tandem guides. To accelerate...
Abstract The impact of cancer driving mutations in regulating immunosurveillance throughout tumor development remains poorly understood. To better understand the contribution genotype to immunosurveillance, we generated and validated lentiviral vectors that create an epi-allelic series increasingly immunogenic neoantigens. This vector system is compatible with autochthonous Cre-regulated models, CRISPR/Cas9-mediated somatic genome editing, barcoding. Here, show context KRAS-driven lung...
In the yeast Saccharomyces cerevisiae, microbial fuels and chemicals production on lignocellulosic hydrolysates is constrained by poor sugar transport. For biotechnological applications, it desirable to source transporters with novel or enhanced function from nonconventional organisms in complement engineering known transporters. Here, we identified functionally screened genes three strains of early-branching anaerobic fungi (Neocallimastigomycota) that encode recently discovered Sugars Will...
It is debated whether the pervasive intergenic transcription from eukaryotic genomes has functional significance or simply reflects promiscuity of RNA polymerases. We approach this question by comparing chance promoter activities with expression levels regions in model eukaryote Saccharomyces cerevisiae. build a library over 105 strains, each carrying 120-nucleotide, chromosomally integrated, completely random sequence driving potential barcode. Quantifying concentration barcode two...
Functionally related genes tend to be chromosomally clustered in eukaryotic genomes even after the exclusion of tandem duplicates, but biological significance this widespread phenomenon is unclear. We propose that stochastic expression fluctuations neighboring resulting from chromatin dynamics are more or less synchronized such their ratio stable than for unlinked genes. Consequently, chromosomal clustering could advantageous when needs stay constant, example, because accumulation toxic...
Abstract Epigenetic dysregulation is widespread in cancer. However, the specific epigenetic regulators and processes they control to drive cancer phenotypes are poorly understood. Here, we employed a novel, scalable high-throughput vivo method perform iterative functional screens of over 250 regulatory genes within autochthonous oncogenic KRAS-driven lung tumors. We identified multiple novel tumor suppressor dependency genes. show that HBO1 complex MLL1 among most impactful suppressive lung....
The cohesin complex is a critical regulator of gene expression. STAG2 the most frequently mutated subunit across several cancer types and key tumor suppressor in lung cancer. Here, we coupled somatic CRISPR-Cas9 genome editing barcoding with an autochthonous oncogenic KRAS-driven model show that uniquely suppressive among all core auxiliary components. heterodimeric components PAXIP1 PAGR1 have highly correlated effects human cell lines, are suppressors vivo, epistatic to tumorigenesis vivo....
Abstract TP53 , the most frequently mutated gene in human cancer, encodes a transcriptional activator that induces myriad downstream target genes. Despite importance of p53 tumor suppression, specific genes important for suppression remain unclear. Recent studies have identified p53-inducible Zmat3 as critical effector but many questions regarding its p53-dependence, activity across contexts, and mechanism alone cooperation with other To address these questions, we used Tuba-seq Ultra...
ABSTRACT Even genetically identical cells in a homogeneous environment can exhibit heterogeneous mRNA abundance because of widely unavoidable random fluctuations, typically referred to as ‘gene expression noise’. Recent studies showed that noise, not just nuisance, is indeed involved cellular activities (e.g., immune response), evolutionary processes, and diseases mechanisms. However, determinants the gene noise its functional role variations human complex traits remain largely unexplored....
The cohesin complex is a critical regulator of gene expression. STAG2 the most frequently mutated subunit across several cancer types and key tumor suppressor in lung cancer. Here, we coupled somatic CRISPR-Cas9 genome editing barcoding with an autochthonous oncogenic KRAS-driven model showed that uniquely tumor-suppressive among all core auxiliary components. heterodimeric components PAXIP1 PAGR1 have highly correlated effects human cell lines, are suppressors vivo, epistatic to...
Abstract Shenhav and Zeevi conclude in a recent article ( Science 370:683-687) that the universal genetic code (UGC) is optimized for resource conservation because mutations are less likely to increase proteomic nitrogen carbon uses under UGC than random codes (RGCs). Their finding results from miscalculating mutational effects benchmarking against biased RGCs. Our reanalysis refutes their conclusion.