A5068034920- Cancer Genomics and Diagnostics
- Immunotherapy and Immune Responses
- Histone Deacetylase Inhibitors Research
- CAR-T cell therapy research
- Immune cells in cancer
- Single-cell and spatial transcriptomics
- Epigenetics and DNA Methylation
- Immune Cell Function and Interaction
- Genomics and Chromatin Dynamics
- Ferroptosis and cancer prognosis
- RNA modifications and cancer
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Genomics and Phylogenetic Studies
- Cancer-related molecular mechanisms research
- Atherosclerosis and Cardiovascular Diseases
- Ovarian cancer diagnosis and treatment
- Cancer Immunotherapy and Biomarkers
- T-cell and B-cell Immunology
- Skin and Cellular Biology Research
- Chromosomal and Genetic Variations
- Evolution and Genetic Dynamics
- Plant Molecular Biology Research
- Cancer Cells and Metastasis
- Bioinformatics and Genomic Networks
- RNA Research and Splicing
University of Wisconsin–Madison
2020-2024
University of Wisconsin Carbone Cancer Center
2022-2024
Cedars-Sinai Medical Center
2016-2023
La Jolla Institute for Immunology
2018-2023
Wisconsin Division of Public Health
2023
University of California, Los Angeles
2018-2022
Ronald Reagan UCLA Medical Center
2022
Samueli Institute
2021
Vietnam National University, Hanoi
2021
Anna Needs Neuroblastoma Answers
2020
Atherosclerosis is a chronic inflammatory disease that driven by the interplay of pro- and anti-inflammatory leukocytes in aorta. Yet, phenotypic transcriptional diversity aortic poorly understood.We characterized from healthy atherosclerotic mouse aortas in-depth single-cell RNA-sequencing mass cytometry (cytometry time flight) to define an atlas immune cell landscape atherosclerosis.Using chow diet- Western diet-fed Apoe-/- Ldlr-/- mice, we detected 11 principal leukocyte clusters with...
Alternative splicing (AS) coupled to nonsense-mediated decay (NMD) is a post-transcriptional mechanism for regulating gene expression. We have used high-resolution AS RT–PCR panel identify endogenous isoforms which increase in abundance when NMD impaired the Arabidopsis factor mutants, upf1-5 and upf3-1 . Of 270 genes (950 transcripts) on panel, 102 transcripts from 97 (32%) were identified as targets. Extrapolating these data around 13% of intron-containing genome are potentially regulated...
Abstract Epigenetic factors determine responses to internal and external stimuli in eukaryotic organisms. Whether how environmental conditions feed back the epigenetic landscape is more a matter of suggestion than substantiation. Plants are suitable organisms with which address this question due their sessile lifestyle diversification regulators. We show that several repetitive elements Arabidopsis thaliana under regulation by transcriptional gene silencing at ambient temperatures upon short...
Abstract Understanding the intratumoral heterogeneity of hepatocellular carcinoma is instructive for developing personalized therapy and identifying molecular biomarkers. Here we applied whole-exome sequencing to 69 samples from 11 patients resolve genetic architecture subclonal diversification. Spatial genomic diversity was found in all cases, with 29% driver mutations being heterogeneous, including TERT, ARID1A, NOTCH2, STAG2. Similar other cancer types, TP53 were always shared between...
Neutrophils are short-lived cells that play important roles in both health and disease. monocytes originate from the granulocyte monocyte progenitor (GMP) bone marrow; however, unipotent neutrophil progenitors not well defined. Here, we use cytometry by time of flight (CyTOF) single-cell RNA sequencing (scRNA-seq) methodologies to identify a committed early-stage (NeP) adult mouse marrow. Importantly, found similar NeP (hNeP) human Both hNeP generate only neutrophils. significantly increase...
Abstract The tumor microenvironment is a highly complex ecosystem of diverse cell types, which shape cancer biology and impact the responsiveness to therapy. Here, we analyze esophageal squamous carcinoma (ESCC) using single-cell transcriptome sequencing in 62,161 cells from blood, adjacent nonmalignant matched samples 11 ESCC patients. We uncover heterogeneity most types stroma, particularly fibroblast immune compartments. identify tumor-specific subset CST1 + myofibroblasts with prognostic...
Heat stress affects epigenetic gene silencing in Arabidopsis. To test for a mechanistic involvement of regulation heat-stress responses, we analyzed the heat tolerance mutants defective DNA methylation, histone modifications, chromatin-remodeling, or siRNA-based pathways. Plants deficient NRPD2, common second-largest subunit RNA polymerases IV and V, Rpd3-type deacetylase HDA6 were hypersensitive to exposure. Microarray analysis demonstrated that NRPD2 have independent roles transcriptional...
Objective- Three distinct human monocyte subsets have been identified based on the surface marker expression of CD14 and CD16. We hypothesized that monocytes were likely more heterogeneous in composition. Approach Results- used high dimensionality mass cytometry together with FlowSOM clustering algorithm to accurately identify define blood healthy subjects those coronary artery disease (CAD). To study behavior functionality newly defined subsets, we performed RNA sequencing, transwell...
The regulation of gene expression is mediated at the transcriptional level by enhancer regions that are bound sequence-specific transcription factors (TFs). Recent studies have shown in vivo binding sites single TFs differ between developmental or cellular contexts. How this context-specific encoded cis -regulatory DNA sequence has, however, remained unclear. We computationally dissect TF Drosophila , Caenorhabditis elegans mouse, and human find distinct combinations motifs for partner...
Oesophageal squamous cell carcinoma (OSCC) and adenocarcinoma (OAC) are distinct cancers in terms of a number clinical epidemiological characteristics, complicating the design trials biomarker developments. We analysed 1048 oesophageal tumour-germline pairs from both subtypes, to characterise their genomic features, biological significance.
Significance Glioblastoma (GBM) cells develop intrinsic or acquired insensitiveness to BET bromodomain inhibitors (BBIs) yet persistent protein dependency. Selective degradation of proteins by a next-generation chemical compound undermines the dependency and exerts superior antineoplastic effects over inhibition bromodomain. Given significant difference between in GBM cells, chemically induced serves as promising strategy overcome anticipated clinical BBIs resistance.
The human fallopian tube harbors the cell of origin for majority high-grade serous "ovarian" cancers (HGSCs), but its cellular composition, particularly epithelial component, is poorly characterized. We perform single-cell transcriptomic profiling around 53,000 individual cells from 12 primary specimens to map their major types. identify 10 subpopulations with diverse transcriptional programs. Based on signatures, we reconstruct a trajectory whereby secretory differentiate into ciliated via...
Summary: Research on precancers, as defined at-risk tissues and early lesions, is of high significance given the effectiveness intervention. We discuss need for risk stratification to prevent overtreatment, an emphasis role genetic epigenetic aging when considering risk, importance integrating macroenvironmental factors with molecules cells in lesions normal developing effective intervention health policy strategies.
Neutrophils are rapidly recruited to sites of infection and critical for pathogen clearance. Therapeutic use primary neutrophils has been limited, as they have a short lifespan not amenable genetic manipulation. Human induced pluripotent stem cells (iPSCs) can provide robust source infusion genetically tractable. However, current work indicated that dampened intracellular signaling limits iPSC-derived neutrophil (iNeutrophil) cellular activation antimicrobial response. Here, we show protein...
Abstract Epigenetic changes of gene expression can potentially be reversed by developmental programs, genetic manipulation, or pharmacological interference. However, a case transcriptional silencing, originally observed in tetraploid Arabidopsis thaliana plants, created an epiallele resistant to many mutations inhibitor treatments that activate other suppressed genes. This raised the question about molecular basis this extreme stability. A combination forward and reverse genetics drug...
We have previously reported that transgenic Arabidopsis plants overexpressing the wheat dehydrin DHN-5 show enhanced tolerance to osmotic stresses. In order understand mechanisms through which exerts this effect, we performed transcriptome profiling using Affymetrix ATH1 microarray. Our data an altered expression of 77 genes involved mainly in transcriptional regulation, cellular metabolism, stress and signaling. Among up-regulated genes, identified those are known be stress-related genes....
Fallopian tube secretory epithelial cells (FTSECs) are likely the main precursor cell type of high-grade serous ovarian cancers (HGSOCs), but these tumors may also arise from surface (OSECs). We profiled global landscapes gene expression and active chromatin to characterize molecular similarities between OSECs (n = 114), FTSECs 74), HGSOCs 394). A one-class machine learning algorithm predicts that most derive FTSECs, with particularly high FTSEC scores in mesenchymal-type (padj < 8 × 10−4)....
Abstract Purpose: We investigated whether in human head and neck squamous cell carcinoma (HNSCC) high levels of expression stress keratin 17 (K17) are associated with poor survival resistance to immunotherapy. Experimental Design: the role K17 regulating both tumor microenvironment immune responsiveness HNSCC using a syngeneic mouse model, MOC2. MOC2 gives rise immunologically cold tumors that resistant immune-checkpoint blockade (ICB). engineered multiple, independent knockout (KO) lines...