A5021331883- Neonatal Respiratory Health Research
- Congenital Diaphragmatic Hernia Studies
- Tracheal and airway disorders
- Neuroscience of respiration and sleep
- Developmental Biology and Gene Regulation
- Genetics, Aging, and Longevity in Model Organisms
- Respiratory viral infections research
- Cancer-related gene regulation
- Single-cell and spatial transcriptomics
- Renal and related cancers
- Cleft Lip and Palate Research
- Hippo pathway signaling and YAP/TAZ
- Connective tissue disorders research
- Fibroblast Growth Factor Research
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Respiratory and Cough-Related Research
- Voice and Speech Disorders
- Pluripotent Stem Cells Research
- Congenital limb and hand anomalies
- Lung Cancer Diagnosis and Treatment
- Heart Rate Variability and Autonomic Control
- Health, Environment, Cognitive Aging
- Inhalation and Respiratory Drug Delivery
- Mitochondrial Function and Pathology
University of California, San Diego
2018-2025
Universidad Católica Santo Domingo
2020
University of Wisconsin–Madison
2008-2019
Gladstone Institutes
2014
Howard Hughes Medical Institute
2011
The lung is constantly exposed to environmental atmospheric cues. How it senses and responds these cues poorly defined. Here, we show that Roundabout receptor (Robo) genes are expressed in pulmonary neuroendocrine cells (PNECs), a rare, innervated epithelial population. Robo inactivation mouse results an inability of PNECs cluster into sensory organoids triggers increased neuropeptide production upon exposure air. Excess neuropeptides lead increase immune infiltrates, which turn remodel the...
Respiratory failure associated with COVID-19 has placed focus on the lungs. Here, we present single-nucleus accessible chromatin profiles of 90,980 nuclei and matched transcriptomes 46,500 in non-diseased lungs from donors ~30 weeks gestation,~3 years years. We mapped candidate
The human lung plays vital roles in respiration, host defense, and basic physiology. Recent technological advancements such as single-cell RNA sequencing genetic lineage tracing have revealed novel cell types enriched functional properties of existing lung. time has come to take a new census. Initiated by members the NHLBI-funded LungMAP Consortium aided experts biology community, we synthesized current data into comprehensive practical cellular census Identities normal are captured...
Lung growth to its optimal size at birth is driven by reiterative airway branching followed differentiation and expansion of alveolar cell types. How this elaborate coordinated with the constraint chest poorly understood. Here we investigate role Hippo signaling, a cardinal pathway in organ control. Unexpectedly, found that epithelial loss kinase genes Lats1 Lats2 (Lats1/2) leads striking reduction lung due an early arrest morphogenesis. This defect accompanied abnormalities polarity,...
Known as the gas exchange organ, lung is also critical for responding to aerosol environment in part through interaction with nervous system. The diversity and specificity of innervating neurons remain poorly understood. Here, we interrogated cell body location molecular signature projection pattern sensory neurons. Retrograde tracing from coupled whole tissue clearing highlighted primarily vagal ganglia. Centrally, they project specifically nucleus solitary tract brainstem. Peripherally,...
Previous studies have implicated fibroblast growth factor receptor 1(FGFR1) in limb development. However, the precise nature and complexity of its role not been defined. Here, we dissect Fgfr1 function mouse by conditional inactivation using two different Cre recombinase-expressing lines. Use T (brachyury)-cre line led to all bud mesenchyme (LBM) cells during initiation. This mutant reveals FGFR1 phases In a nascent bud, promotes length proximodistal (PD) axis while restricting dimensions...
In the trachea and bronchi of mouse, airway smooth muscle (SM) cartilage are localized to complementary domains surrounding epithelium. Proper juxtaposition these tissues ensures a balance elasticity rigidity that is critical for effective air passage. It unknown how this tissue complementation established during development. Here we dissect developmental relationship between by genetically disrupting SM formation (through Srf inactivation) or Sox9 assessing impact on remaining lineage. We...
The mesothelium is a squamous monolayer that ensheathes internal organs, lines the body cavity, and diaphragm. It serves as protective barrier, coated in glycocalyx, secretes lubricants to facilitate tissue movement. How forms poorly understood. Here, we investigate Myrf , transcription factor gene expressed mesothelium, because it carries variants patients with Congenital Diaphragmatic Hernia (CDH), disorder affects diaphragm, lung, other organs. In mice, inactivation of early organogenesis...
Coordination of the cell cycle with developmental events is crucial for generation tissues during development and their maintenance in adults. Defects that coordination can shift balance fates devastating clinical effects. Yet our understanding molecular mechanisms integrating core regulators remains its infancy. This work focuses on interplay between Caenorhabditis elegans germline. Key control germline stem cells (GSCs) to self-renew or begin differentiation: FBF RNA–binding proteins...
Significance An average human lung is composed of 14 million airway tips, conducting air to 300 gas-exchange units. organ such complex architecture nevertheless constructed with robust precision, the result a largely stereotypical branching sequence. Although regulation at transcript level known be critical, how control protein may play role remains poorly understood. The function ubiquitin proteasome system in has primarily been studied pathological settings adult. Here, we show that...
SUMMARY Respiratory failure is the leading cause of COVID-19 death and disproportionately impacts adults more than children. Here, we present a large-scale snATAC-seq dataset (90,980 nuclei) human lung, generated in parallel with snRNA-seq (46,500 nuclei), from healthy donors ~30 weeks, ~3 years age. Focusing on genes implicated SARS-CoV-2 cell entry, observed an increase proportion alveolar epithelial cells expressing ACE2 TMPRSS2 adult compared to young lungs. Consistent expression...
Germ cell specification as sperm or oocyte is an ancient fate decision, but its molecular regulation poorly understood. In Caenorhabditis elegans, the FOG-1 and FOG-3 proteins behave genetically terminal regulators of specification. Both are homologous to well-established RNA regulators, suggesting that specify post-transcriptionally. We predicted FOG-3, fate, might regulate a battery gamete-specific differentiation genes. Here we test prediction by exploring on genomic scale messenger RNAs...
ABSTRACT Congenital laryngeal webs result from failure of vocal fold separation during development in utero. Infants present with life-threatening respiratory problems at birth, and extensive lifelong difficulties breathing voicing. The molecular mechanisms that instruct formation are rarely studied. Here, we show, for the first time, conditional inactivation gene encoding β-catenin primitive laryngopharyngeal epithelium leads to folds, which approximates gross phenotype webbing. These...