A5009669109- Extracellular vesicles in disease
- MicroRNA in disease regulation
- Autophagy in Disease and Therapy
- Immune Cell Function and Interaction
- Phagocytosis and Immune Regulation
- Neonatal Respiratory Health Research
- IL-33, ST2, and ILC Pathways
- Immune cells in cancer
- Medical Imaging and Pathology Studies
- RNA modifications and cancer
- Immunotherapy and Immune Responses
- Congenital Diaphragmatic Hernia Studies
- RNA Research and Splicing
- T-cell and B-cell Immunology
- Genetics and Neurodevelopmental Disorders
- Cannabis and Cannabinoid Research
- Tuberculosis Research and Epidemiology
- RNA Interference and Gene Delivery
- Pulmonary Hypertension Research and Treatments
- Genomic variations and chromosomal abnormalities
- Adipokines, Inflammation, and Metabolic Diseases
- Genomics and Chromatin Dynamics
- Calcium signaling and nucleotide metabolism
- Mycobacterium research and diagnosis
- Cancer, Hypoxia, and Metabolism
Vanderbilt University Medical Center
2019-2025
Vanderbilt University
2024
University of California, San Francisco
2013-2019
Duke University
2008-2014
Duke Medical Center
2006-2010
Duke University Hospital
2006-2010
Crescent University
2008
Macroautophagy (hereafter referred to as autophagy) is a well-conserved intracellular degradation process. Recent studies examining cells lacking the autophagy genes Atg5 and Atg7 have demonstrated that plays essential roles in cell survival during starvation, innate clearance of microbial pathogens, neural maintenance. However, role T lymphocyte development not known. Here, we demonstrate autophagosomes form primary mouse lymphocytes. By generating Atg5−/− chimeric mice, found...
Macroautophagy plays an important role in the regulation of cell survival, metabolism, and lysosomal degradation cytoplasmic material. In immune system, autophagy contributes to clearance intracellular pathogens, MHCII cross-presentation endogenous Ags, as well survival. We others have demonstrated that occurs T lymphocytes their cellular function, including survival proliferation. Here we show essential gene Atg7 is required a cell-intrinsic manner for mature primary lymphocytes. also find...
Macroautophagy (herein autophagy) is an evolutionarily conserved process, requiring the gene ATG5, by which cells degrade cytoplasmic constituents and organelles. Here we show that ATG5 required for efficient B cell development maintenance of B-1a numbers. Deletion in lymphocytes using Cre-LoxP technology or repopulation irradiated mice with ATG5-/- fetal liver progenitors resulted a dramatic reduction B-1 peritoneum. exhibited significant defect at pro- to pre-B transition, although...
Macroautophagy (hereafter referred to as autophagy) is an evolutionarily conserved intracellular bulk degradation pathway that plays critical roles in eliminating pathogens, presenting endogenous Ags, and regulating T lymphocyte survival proliferation. In this study, we have investigated the role of autophagy endoplasmic reticulum (ER) compartment lymphocytes. We found ER content expanded mature autophagy-related protein (Atg) 7-deficient Atg7-deficient cells stimulated through TCR display...
Mammalian cells release a heterogeneous array of extracellular vesicles (EVs) that contribute to intercellular communication by means the cargo they carry. To resolve EV heterogeneity and determine if is partitioned into select populations, we developed method named "EV Fingerprinting" discerns distinct vesicle populations using dimensional reduction multiparametric data collected quantitative single-EV flow cytometry. were found be discernible combination membrane order size, both which...
MicroRNAs (miRNAs) exert powerful effects on immunity through coordinate regulation of multiple target genes in a wide variety cells. Type 2 innate lymphoid cells (ILC2s) are tissue sentinel mediators allergic inflammation. We established the physiological requirements for miRNAs ILC2 homeostasis and immune function compared global miRNA repertoire resting activated ILC2s T helper type (TH2) After exposure to natural allergen papain, mice selectively lacking miR-17∼92 cluster displayed...
Extracellular RNAs (exRNAs) can be released by numerous cell types in vitro, are often protected within vesicles, and modify recipient function. To determine how the composition cellular sources of exRNAs extracellular vesicles (EVs) that carry them change vivo during tissue inflammation, we analyzed bronchoalveolar lavage fluid (BALF) from mice before after lung allergen challenge. In lung, microRNAs (ex-miRNAs) had a was highly correlated with airway-lining epithelium. Using type-specific...
Determining how alveoli are formed and maintained is critical to understanding lung organogenesis regeneration after injury. To study the cellular dynamics of this stage development, we have used scanned oblique-plane illumination microscopy living slices observe alveologenesis in real time at high resolution over several days. Contrary prevailing notion that occurs by airspace subdivision via ingrowing septa, find form ballooning epithelial outgrowth supported contracting mesenchymal ring...
Transcription factors (TFs) and microRNAs (miRNAs) are fundamental regulators of gene expression, cell state, biological processes. This study investigated whether a small subset TFs miRNAs could accurately predict genome-wide expression. We analyzed 8895 samples across 31 cancer types from The Cancer Genome Atlas identified 28 miRNA TF clusters using unsupervised learning. Medoids these differentiate tissues origin with 92.8% accuracy, demonstrating their relevance. developed...
Extracellular vesicles (EVs) are membrane-bound particles secreted by cells with emerging roles in intercellular communication during tissue homeostasis and disease. Although EVs abundant respiratory biofluids, their cellular sources, critical cargos, functions the airway remain poorly understood. To determine how EV populations changed fluids a chronic inflammatory response, nasal were assayed 23 control participants 22 Aspirin-Exacerbated Respiratory Disease (AERD). Nasal lining fluid from...
Abstract Th17 cell responses orchestrate immunity against extracellular pathogens but also underlie autoimmune disease pathogenesis. In this study, we uncovered a distinct and critical role for miR-18a in limiting differentiation. was the most dynamically upregulated microRNA of miR-17–92 cluster activated T cells. deficiency enhanced CCR6+ RAR-related orphan receptor (ROR)γt+ differentiation vitro increased number tissue cells expressing CCR6, RORγt, IL-17A airway inflammation models vivo....
First identified as a pathway for nutrient recovery during periods of starvation, the role autophagy has expanded to clearance "toxic" intracellular material including ubiquitin-positive protein aggregates, damaged organelles well microbial pathogens in various cell types. We have examined development and function adaptive immune system. Genes encoding machinery are expressed T lymphocytes, occurs primary CD4+ CD8+ cells. By generating fetal liver chimeric mice, we found that thymocyte is...
Identifying molecular circuits that control adipose tissue macrophage (ATM) function is necessary to understand how ATMs contribute homeostasis and obesity-induced insulin resistance. In this study, we find mice with a myeloid-specific knockout of the miR-23-27-24 clusters microRNAs (miRNAs) gain less weight on high-fat diet but exhibit worsened glucose tolerance. Analysis from these shows selectively reduced numbers proliferation recently reported subset lipid-associated CD9+Trem2+...
Adequate mass and function of adipose tissues (ATs) play essential roles in preventing metabolic perturbations. The pathological reduction ATs lipodystrophy leads to an array diseases. Understanding the underlying mechanisms may benefit development effective therapies. Several cellular processes, including autophagy vesicle trafficking, collectively maintain AT homeostasis. Here, we investigated impact adipocyte-specific deletion lipid kinase phosphatidylinositol 3-kinase catalytic subunit...
Extracellular vesicles (EVs) are secreted lipid-enclosed particles that have emerged as potential biomarkers and therapeutic agents in lung disease, including bronchopulmonary dysplasia (BPD), a leading complication of preterm birth. Many unanswered questions remain about the content cargo EVs premature infants their role development. To characterize during human development, tracheal aspirates were collected from neonates between 22 35 wk gestational age analyzed via nanoparticle tracking...
Myeloid cells are critical for systemic inflammation, microbial control, and organ damage during sepsis. MicroRNAs small noncoding RNAs that can dictate the outcome of The role myeloid-based expression microRNA-21 (miR-21) in sepsis is inconclusive. In this study, we show enhanced miR-21 both peritoneal macrophages neutrophils from septic C57BL/6J mice, deletion locus myeloid (miR-21Δmyel mice) animal survival, decreased bacterial growth, damage. Resistance to was associated with a reduction...