A5054443948- Immune Cell Function and Interaction
- Immune Response and Inflammation
- Single-cell and spatial transcriptomics
- Asthma and respiratory diseases
- Cell Image Analysis Techniques
- Eosinophilic Disorders and Syndromes
- Immune cells in cancer
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Dermatology and Skin Diseases
- Epigenetics and DNA Methylation
- T-cell and B-cell Immunology
- Cancer-related gene regulation
- Urticaria and Related Conditions
- Molecular Biology Techniques and Applications
- Adrenal Hormones and Disorders
- Digital Imaging for Blood Diseases
- MicroRNA in disease regulation
- Genetics and Neurodevelopmental Disorders
- Medical Image Segmentation Techniques
- Contact Dermatitis and Allergies
- CAR-T cell therapy research
- Advanced Electron Microscopy Techniques and Applications
- Acute Myeloid Leukemia Research
- S100 Proteins and Annexins
- Hemoglobinopathies and Related Disorders
National Institute of Arthritis and Musculoskeletal and Skin Diseases
2020-2025
National Institutes of Health
2018-2025
National Institute of Allergy and Infectious Diseases
2018-2019
Children's Nutrition Research Center at Baylor College of Medicine
2013-2015
University of Tulsa
2004
University of Oklahoma
2004
Glucocorticoids remain the most widely used immunosuppressive and anti-inflammatory drugs, yet substantial gaps exist in our understanding of glucocorticoid-mediated immunoregulation. To address this, we generated a pathway-level map transcriptional effects glucocorticoids on nine primary human cell types. This analysis revealed that response to is highly type dependent, terms individual genes pathways affected, as well magnitude direction regulation. Based these data given their importance...
Neutrophils are the most abundant leukocytes in human blood and essential components of innate immunity. Until recently, neutrophils were considered homogeneous transcriptionally inactive cells, but both concepts being challenged. Single-cell RNA sequencing (scRNA-seq) offers an unbiased view cells along a continuum transcriptional states. However, use scRNA-seq to characterize has proven technically difficult, explaining part paucity published single-cell data on neutrophils. We have found...
DNA methylation is an epigenetic mechanism central to development and maintenance of complex mammalian tissues, but our understanding its role in intestinal limited.We use whole genome bisulfite sequencing, find that differentiation mouse colonic stem cells epithelium not associated with major changes methylation. However, we detect extensive dynamic their progeny during the suckling period, suggesting postnatal this cell population. We increases at 3' CpG islands (CGIs) correlate...
Significance Despite clear differences in female and male immunity that may contribute to variations response infections predisposition cancer autoimmunity, the exact mechanisms drive this stark contrast remain insufficiently characterized. Neutrophils play essential roles homeostasis disease, but little is known about how sex modulate their phenotype function. Using transcriptomic functional approaches, we report healthy young adult females have an activated/mature neutrophil profile...
Cancer has long been viewed as a genetic disease; however, epigenetic silencing the result of aberrant promoter DNA methylation is frequently associated with cancer development, suggesting an component to disease. Nonetheless, it remained unclear whether epimutation (an change in regulation) can induce tumorigenesis. Here, we exploited functionally validated cis-acting regulatory element and devised strategy developmentally regulated genomic targeting methylation. We used this system target...
During development, a small but significant number of CpG islands (CGIs) become methylated. The timing developmentally programmed CGI methylation and associated mechanisms transcriptional regulation during cellular differentiation, however, remain poorly characterized. Here, we used genome-wide DNA microarrays to identify epigenetic changes human embryonic stem cell (hESC) differentiation. We discovered group CGIs with developmental genes that gain after hESCs differentiate. Conversely,...
Deep learning is rapidly becoming the technique of choice for automated segmentation nuclei in biological image analysis workflows. In order to evaluate feasibility training nuclear models on small, custom annotated datasets that have been augmented, we designed a computational pipeline systematically compare different model architectures and strategies. Using this approach, demonstrate transfer tuning parameters, such as composition, size, preprocessing dataset, can lead robust models,...
Abstract Neutrophils are the most abundant leukocytes in human blood and essential components of innate immunity. Until recently, neutrophils were considered homogeneous transcriptionally inactive cells, but both concepts being challenged. To date, have been characterized based on discrete parameters including cell-surface markers, buoyancy, maturation status, or tissue localization. Single-cell RNA sequencing (scRNA-seq) offers an unbiased view cells along a continuum transcriptional...
Abstract Glucocorticoids are first-line agents for the treatment of many eosinophil-associated disorders; however, their effects on human eosinophils remain poorly understood. To gain an unbiased, genome-wide view early transcriptional glucocorticoids in vivo , RNA sequencing was performed purified blood obtained before and 30, 60, 120 minutes after administration a single dose oral prednisone (1 mg/kg) to three unrelated healthy subjects with hypereosinophilia unknown significance. The...
Topical corticosteroids (TCS) are first-line therapies for numerous skin conditions. Steroid Withdrawal (TSW) is a controversial diagnosis advocated by patients with prolonged TCS exposure who report severe systemic reactions upon treatment cessation. However, to date there have been no systematic clinical or mechanistic studies distinguish TSW from other eczematous disorders.
Abstract Background Topical glucocorticoids (more commonly termed topical corticosteroids; TCS) are first line therapy for management of numerous skin conditions. Steroid Withdrawal (TSW) is a controversial diagnosis advocated by patients with prolonged TCS exposure who report severe systemic reactions upon treatment cessation. Although the disease may be confused eczematous disorders or dismissed outright, there have been no systematic clinical mechanistic studies to either refute support...
The paper presents a novel method to detect and count dead live hepatocytes (liver cells) within clusters. new distinguishes single cells from clusters in digital microscopic images based on cell shape rather than size. shows an improvement when compared earlier algorithm, especially where have varying sizes.
Glucocorticoids are the cornerstone of immunosuppressive and anti-inflammatory therapy in humans, yet mechanisms glucocorticoid immunoregulation toxicity remain unclear. The response to glucocorticoids is highly cell type-dependent, so translating results from different experimental systems into a better understanding effects humans would benefit rapid access high-quality data on by types. We introduce GCgx, web application that allows investigators quickly visualize changes transcript...
Abstract Deep learning is rapidly becoming the technique of choice for automated segmentation nuclei in biological image analysis workflows. In order to evaluate feasibility training nuclear models on small, custom annotated datasets that have been augmented, we designed a computational pipeline systematically compare different model architectures and strategies. Using this approach, demonstrate transfer tuning parameters, such as composition, size pre-processing dataset, can lead robust...
Measurement of gene expression at the single-cell level has advanced study transcriptional regulation programs in healthy and disease states. In particular, approaches have shed light on high heterogeneity individual cells, both baseline response to experimental or environmental perturbations. We developed a method for high-content imaging (HCI)-based quantification relative changes transcript abundance human primary immune cells validated its performance under multiple conditions...
Abstract Neutrophils are the most abundant circulating immune cell in humans and primates, they play a central role inflammation innate immunity. Glucocorticoids (GCs) cornerstone of anti-inflammatory immunosuppressive therapies. While GCs known to induce neutrophilia, little is about underlying kinetics or molecular mechanisms. To better define GC-induced we studied healthy human volunteers rhesus macaques, found that neutrophilia peaks within 4 hours GC infusion lasts beyond 72 hours. Flow...
Abstract Glucocorticoids (GCs) have been the cornerstone of immunosuppressive therapies for past 70 years, yet mechanisms by which they regulate human immunity remain poorly understood. Specifically, there remains a need direct insight into how GCs functions T cells. We previously demonstrated that response to in humans is highly cell type-dependent. In this project, we combine high-throughput techniques study effects on CD4+ and CD8+ cells, vivo vitro. As part clinical 20 healthy...
Abstract Neutrophils play central roles in immunity and inflammation. Glucocorticoids (GCs) are the cornerstone of anti-inflammatory immunosuppressive therapy. While GCs trigger an acute rise circulating neutrophils, little is known about mechanisms by which modulate neutrophil biology. We studied response 9 primary human cells to vitro treatment with GCs. Surprisingly, neutrophils were transcriptionally most responsive cell type, they express proportionally glucocorticoid receptor (GR)...
Abstract Glucocorticoids (GCs) are the most commonly used anti-inflammatory and immunosuppressive drugs. However, of work on this class drugs has focused their relationship to coding genome. It been demonstrated in recent years that non-coding genes can play important biological roles. Thus, we performed total RNA-seq small-RNA-seq 9 primary human cell types: B cells, CD4+ T monocytes, neutrophils, endothelial fibroblasts, myoblasts, osteoblasts, preadipocytes, treated vitro with GC...