A5040115644- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- CAR-T cell therapy research
- Single-cell and spatial transcriptomics
- Immune Cell Function and Interaction
- Nuclear Structure and Function
- Immunotherapy and Immune Responses
- Molecular Biology Techniques and Applications
- Cancer Genomics and Diagnostics
- Congenital heart defects research
- Epigenetics and DNA Methylation
- T-cell and B-cell Immunology
- Receptor Mechanisms and Signaling
- Nanowire Synthesis and Applications
- RNA and protein synthesis mechanisms
- Pluripotent Stem Cells Research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Cardiac Fibrosis and Remodeling
- Geriatric Care and Nursing Homes
- Histone Deacetylase Inhibitors Research
- Tissue Engineering and Regenerative Medicine
- Ultrasound Imaging and Elastography
- TGF-β signaling in diseases
- Machine Learning in Healthcare
- Chromosomal and Genetic Variations
Ludwig Cancer Research
2020-2023
University of California, San Diego
2020-2023
National Cancer Institute
2015-2019
National Institutes of Health
2015-2019
Center for Cancer Research
2015-2019
Aurora Health Care
2015
University of Wisconsin–Madison
2014
Current catalogs of regulatory sequences in the human genome are still incomplete and lack cell type resolution. To profile activity gene elements diverse types tissues body, we applied single-cell chromatin accessibility assays to 30 adult tissue from multiple donors. We integrated these datasets with previous data 15 fetal reveal status open for ∼1.2 million candidate cis-regulatory (cCREs) 222 distinct comprised >1.3 nuclei. used maps delineate cell-type-specificity cCREs systematically...
A human heart cell type–specific cis-regulatory element atlas reveals gene regulatory mechanisms of cardiovascular diseases.
Abstract T cell senescence and exhaustion are major barriers to successful cancer immunotherapy. Here we show that miR-155 increases CD8 + antitumor function by restraining functional through epigenetic silencing of drivers terminal differentiation. enhances Polycomb repressor complex 2 (PRC2) activity indirectly promoting the expression PRC2-associated factor Phf19 downregulation Akt inhibitor, Ship1. orchestrates a transcriptional program extensively shared with restrain sustain responses....
Patients with idiopathic fibrosis (IPF) have poor long-term survival as there are limited diagnostic/prognostic tools or successful therapies. Remodeling of the extracellular matrix (ECM) has been implicated in IPF progression; however, structural consequences on collagen architecture not received considerable attention. Here, we demonstrate that second harmonic generation (SHG) and multiphoton fluorescence microscopy can quantitatively differentiate normal human tissues. For SHG analysis,...
Remodeling of the extracellular matrix has been implicated in ovarian cancer. To quantitate remodeling, we implement a form texture analysis to delineate collagen fibrillar morphology observed second harmonic generation microscopy images human normal and high grade malignant tissues. In learning stage, dictionary "textons"—frequently occurring features that are identified by measuring image response filter bank various shapes, sizes, orientations—is created. By calculating representative...
Abstract Topologically associating domains (TAD) and insulated neighborhoods (INs) have been proposed to constrain enhancer-promoter communications enable cell-type specific transcription programs, but recent studies show that disruption of TADs INs resulted in relatively mild changes gene expression profiles. To better understand the role chromatin architecture dynamic contacts lineage-specific expression, we utilized auxin-inducible degron system acutely deplete CTCF, a key factor involved...
SUMMARY Current catalogs of regulatory sequences in the human genome are still incomplete and lack cell type resolution. To profile activity gene elements diverse types tissues body, we applied single chromatin accessibility assays to 25 distinct tissue from multiple donors. The resulting maps comprising ∼500,000 nuclei revealed status open for over 750,000 candidate cis -regulatory (cCREs) 54 types. We further delineated type-specific tissue-context dependent programs, developmental stage...
ABSTRACT Matrix remodeling outcomes largely dictate patient survival post myocardial infarction. Moreover, human-restricted noncoding regulatory elements have been shown to worsen fibrosis, but their mechanism of action remains elusive. Here, we demonstrate, using induced pluripotent stem cell-derived cardiac fibroblasts (iCFs), that inflammatory ligands abundant in the heart after infarction activate AP-1 transcription factor signaling pathways resulting fibrotic responses. This observed...
Abstract IL-13 is predominantly a Th2-derived cytokine that displays variety of effects on inflammatory and stromal cells. Receptors for are expressed by several cancers including prostate carcinoma. Although expression was previously positively correlated with human cancer, there no studies validate the functional contribution during cancer progression. In this study, we examined importance tumor progression using Transgenic Adenocarcinoma Mouse Prostate [TRAMP] model cancer. Il13-deficient...
Texture analyses are successfully applied to SHG imaging microscopy data discriminate the structural changes in collagen organization extracellular matrix ex vivo human normal ovarian and malignant tissues.
ABSTRACT Background Cis -regulatory elements such as enhancers and promoters are crucial for directing gene expression in the human heart. Dysregulation of these can result many cardiovascular diseases that major leading causes morbidity mortality worldwide. In addition, genetic variants associated with disease risk enriched within cis elements. However, location activity individual cardiac cell types remains to be fully defined. Methods We performed single nucleus ATAC-seq RNA-seq define a...
Abstract As we age, structural changes contribute to progressive decline in organ function, which the heart acts through poorly characterized mechanisms. Utilizing rapidly aging fruit fly model with its significant homology human cardiac proteome, found that cardiomyocytes exhibit loss of Lamin C (mammalian A/C homologue) age. Unlike other tissues and laminopathies, observe decreasing nuclear size, while stiffness increases. Premature genetic reduction phenocopies aging’s effects on nucleus,...
Background: A prognostication predictive model incorporated into the electronic health record (EHR) may be useful in assisting care team accurately predicting mortality and used appropriately allocating palliative services.
Abstract Lymphodepleting regimens are employed prior to adoptive immunotherapy augment the antitumor efficacy of transferred T cells by removing endogenous homeostatic cytokine sinks. These conditioning modalities, however, often associated with severe toxicities. We found that miR-155 enabled B16 melanoma-specific CD8+ mediate profound responses in lymphoreplete hosts were not potentiated immune-ablation. enhanced cell responsiveness limited amounts γc cytokines restraining expression Akt...
Introduction: Cardiac performance depends on proper function of the extracellular matrix, cytoskeleton and nucleus to regulate systolic contraction diastolic relaxation. As we age, mechanical properties these structures change, but their influence tissue-level is unclear. Nuclear Lamins (Lam), intermediate filaments that underly nuclear envelope, change in expression localization with leading irregularly shaped nuclei. Mutations LamA/C can cause premature aging cardiomyopathy whether Lamin...