A5057611393- Single-cell and spatial transcriptomics
- Nephrotoxicity and Medicinal Plants
- Molecular Biology Techniques and Applications
- Pharmacological Effects of Medicinal Plants
- Advanced Biosensing Techniques and Applications
- Cancer Immunotherapy and Biomarkers
- Cancer Genomics and Diagnostics
- DNA Repair Mechanisms
- Fungal and yeast genetics research
- Heavy Metals in Plants
- Genomics and Chromatin Dynamics
- Chromosomal and Genetic Variations
- Microtubule and mitosis dynamics
- Cancer Research and Treatments
- Drug-Induced Hepatotoxicity and Protection
- Immune cells in cancer
- Advanced Fluorescence Microscopy Techniques
- Arsenic contamination and mitigation
- Evolution and Genetic Dynamics
- Radiomics and Machine Learning in Medical Imaging
- Bladder and Urothelial Cancer Treatments
- T-cell and B-cell Immunology
- Genetic Mapping and Diversity in Plants and Animals
- RNA regulation and disease
- Cell Image Analysis Techniques
Nanostring Technologies (United States)
2019-2024
Bruker (Switzerland)
2024
North Seattle College
2019
Howard Hughes Medical Institute
2010-2017
Department of Embryology
2010-2017
Johns Hopkins University
2010-2017
Sidney Kimmel Cancer Center
2012-2016
Cancer Genetics (United States)
2013-2016
Sidney Kimmel Comprehensive Cancer Center
2016
National Taiwan University
2012
Immune responses to cancer are highly variable, with mismatch repair-deficient (MMRd) tumors exhibiting more anti-tumor immunity than repair-proficient (MMRp) tumors. To understand the rules governing these varied responses, we transcriptionally profiled 371,223 cells from colorectal and adjacent normal tissues of 28 MMRp 34 MMRd individuals. Analysis 88 cell subsets their 204 associated gene expression programs revealed extensive transcriptional spatial remodeling across discover hubs...
The mutational signature of aristolochic acid exemplifies how genome-wide sequencing can be used to identify environmental exposures leading cancer.
Abstract Metastatic prostate cancer (mPC) comprises a spectrum of diverse phenotypes. However, the extent inter- and intra-tumor heterogeneity is not established. Here we use digital spatial profiling (DSP) technology to quantitate transcript protein abundance in spatially-distinct regions mPCs. By assessing multiple discrete areas across metastases, find high level intra-patient homogeneity with respect tumor phenotype. there are notable exceptions including tumors comprised low androgen...
Significance While we age, our body accumulates random somatic mutations. These mutations spontaneously arise from endogenous and exogenous sources, such as DNA replication errors or environmental insults like smoking sunlight. Direct measurement of rare could help us understand the role in human aging, normal biology, disease processes. Here, develop bottleneck sequencing system (BotSeqS) a simple genome-wide sequencing-based method that accurately quantitates nuclear mitochondrial...
Hybridization is often considered maladaptive, but sometimes hybrids can invade new ecological niches and adapt to novel or stressful environments better than their parents. The genomic changes that occur following hybridization facilitate genome resolution and/or adaptation are not well understood. Here, we examine hybrid evolution using experimental of de novo interspecific yeast Saccharomyces cerevisiae × uvarum parentals. We evolved these strains in nutrient-limited conditions for...
Breast cancer is a heterogenous disease with variability in tumor cells and the surrounding microenvironment (TME). Understanding molecular diversity breast critical for improving prediction of therapeutic response prognostication. High-plex spatial profiling tumors enables characterization heterogeneity TME, which can holistically illuminate biology growth, dissemination and, ultimately, to therapy. The GeoMx Digital Spatial Profiler (DSP) researchers spatially resolve quantify proteins RNA...
Abstract The Spatial Molecular Imaging platform (CosMx TM SMI, NanoString Technologies, Seattle, WA) utilizes high-plex in-situ imaging chemistry for both RNA and protein detection. This automated instrument provides 1000’s of plex, at high sensitivity (1 to 2 copies/cell), very low error rate (0.0092 false calls/cell) background (∼0.04 counts/cell). system generates three-dimensional super-resolution localization analytes ∼2 million cells per sample, four samples run. Cell segmentation is...
Aristolochia species used in the practice of traditional herbal medicine contains aristolochic acid (AA), an established human carcinogen contributing to urothelial carcinomas upper urinary tract. AA binds covalently genomic DNA, forming aristolactam (AL)-DNA adducts. Here we investigated whether is also etiologic factor clear cell renal carcinoma (ccRCC).We conducted a population-based case-control study investigate linkage between prescription history, cumulative consumption, and ccRCC...
Emerging spatial profiling technology has enabled high-plex molecular in biological tissues, preserving the and morphological context of gene expression. Here, we describe expanding chemistry for Digital Spatial Profiling platform to quantify whole transcriptomes human mouse tissues using a wide range strategies sample types. We designed multiplexed situ hybridization probes targeting protein-coding genes transcriptomes, referred as or Whole Transcriptome Atlas (WTA). Human WTAs were...
Genome rearrangements often result from non-allelic homologous recombination (NAHR) between repetitive DNA elements dispersed throughout the genome. Here we systematically analyze NAHR Ty retrotransposons using a genome-wide approach that exploits unique features of Saccharomyces cerevisiae purebred and cerevisiae/Saccharomyces bayanus hybrid diploids. We find double-strand breaks (DSBs) induce NAHR–dependent located 12 to 48 kilobases distal break site. This break-distal (BDR) occurs...
ABSTRACT We have developed Digital Spatial Profiling (DSP), a non-destructive method for high-plex spatial profiling of proteins and RNA, using oligonucleotide detection technologies with unlimited multiplexing capability. The key breakthroughs underlying DSP are threefold: (1) multiplexed readout proteins/RNA oligo-tags; (2) oligo-tags attached to affinity reagents (antibodies/RNA probes) through photocleavable (PC) linker; (3) photocleaving light projected onto the tissue sample release...
Eukaryotic chromosomal replication is a complicated process with many origins firing at different efficiencies and times during S phase. Prereplication complexes are assembled on all in G(1) phase, yet only subset of activated phase by DDK (for Dbf4-dependent kinase) (Cdc7-Dbf4). The yeast mcm5-bob1 (P83L) mutation bypasses but results reduced intrinsic efficiency 11 endogenous located minichromosomes. Origin may result from Mcm5 protein assuming an altered conformation, as predicted the...
In the ribosomal DNA of Saccharomyces cerevisiae, sequences in nontranscribed spacer 3 35S RNA gene are important to polar arrest replication forks at a site called fork barrier (RFB) and also cis-acting, mitotic hyperrecombination HOT1.We have found that RFB HOT1 activity share some but not all their essential sequences.Many mutations reduce recombination decrease or eliminate one two closely spaced sites, RFB1 RFB2.A simple model for juxtaposition is breakage strands arrested stimulates...
Evolutionary outcomes depend not only on the selective forces acting upon a species, but also genetic background. However, large timescales and uncertain historical selection pressures can make it difficult to discern such important background differences between species. Experimental evolution is one tool compare evolutionary potential of known genotypes in controlled environment. Here we utilized highly reproducible adaptation Saccharomyces cerevisiae investigate whether experimental other...
Abstract Emerging spatial profiling technology has enabled high-plex molecular in biological tissues, preserving the and morphological context of gene expression. Here we describe expanding chemistry for Digital Spatial Profiling platform to quantify whole transcriptomes human mouse tissues using a wide range strategies sample types. We designed multiplexed situ hybridization probe pools targeting protein-coding genes transcriptomes, hereafter referred as or Whole Transcriptome Atlas (WTA)....
Interleukin-2 (IL-2)-dependent large granular lymphocytes (LGL) with a distinctive surface phenotype were generated from histologically normal duodenal biopsy tissues. Immunoperoxidase staining of the mucosa an anti-CD56 monoclonal antibody revealed LGL localized in lamina propria rather than epithelium. Light and electron microscopy demonstrated azurophilic electron-dense cytoplasmic granules. Flow cytometry analysis that these cells express CD45, CD56, CD2, CD7, CD11a, CD18, CD69...
Abstract Addition of HER2-targeted agents to neoadjuvant chemotherapy has dramatically improved pathological complete response (pCR) rates in early-stage HER2-positive breast cancer. Still, up 50% patients have residual disease following treatment, while others are likely overtreated. Here, we performed multiplex spatial proteomic characterization 122 samples from 57 tumors the TRIO-US B07 clinical trial sampled pre-treatment, after 14-21 days therapy, and at surgery. We demonstrate that...
DNA double-strand breaks impact genome stability by triggering many of the large-scale rearrangements associated with evolution and cancer. One first steps in repairing this damage is 5′→3′ resection beginning at break site. Recently, tools have become available to study consequences not extensively resecting breaks. Here we examine role Sgs1- Exo1-dependent on using a non-selective assay that previously developed diploid yeast. We find Saccharomyces cerevisiae lacking Sgs1 Exo1 retains very...
ABSTRACT Hybridization is often considered maladaptive, but sometimes hybrids can invade new ecological niches and adapt to novel or stressful environments better than their parents. However, the genomic changes that occur following hybridization facilitate genome resolution and/or adaptation are not well understood. Here, we address these questions using experimental evolution of de novo interspecific hybrid yeast Saccharomyces cerevisiae x uvarum parentals. We evolved strains in nutrient...