A5024226423- Neonatal Respiratory Health Research
- Congenital Diaphragmatic Hernia Studies
- Fibroblast Growth Factor Research
- Congenital heart defects research
- Renal and related cancers
- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- Cystic Fibrosis Research Advances
- Congenital Anomalies and Fetal Surgery
- Tracheal and airway disorders
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Medical Imaging and Pathology Studies
- Kruppel-like factors research
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Wnt/β-catenin signaling in development and cancer
- Infant Nutrition and Health
- Connexins and lens biology
- Machine Learning in Bioinformatics
- RNA modifications and cancer
- Digestive system and related health
- Immune Response and Inflammation
- Barrier Structure and Function Studies
- Ethics and Legal Issues in Pediatric Healthcare
- Respiratory Support and Mechanisms
- Genetic Syndromes and Imprinting
UCLA Medical Center
2020-2025
Harbor–UCLA Medical Center
2020-2025
University of California, Los Angeles
2023-2024
The Lundquist Institute
2022-2024
IST Research
2023
Children's Hospital of Los Angeles
2011-2020
University of Southern California
2010-2019
APLA Health
2013
Giessen School of Theology
2012
Infection et inflammation
2010
The lung mesenchyme consists of a widely heterogeneous population cells that play crucial roles during development and homeostasis after birth. These belong to myogenic, adipogenic, chondrogenic, neuronal other lineages. Yet, no clear hierarchy for these lineages has been established. We have previously generated novel Fgf10(iCre) knock-in mouse line allows lineage tracing Fgf10-positive postnatally. Using mice, we hereby demonstrate the presence two waves Fgf10 expression embryonic...
Lung morphogenesis relies on a number of important processes, including proximal-distal patterning, cell proliferation, migration and differentiation, as well epithelial-mesenchymal interactions. In mouse lung development, SOX2 + cells are localized in the proximal epithelium, whereas SOX9 present distal epithelium. We show that, human lung, expression these transcription factors differs, that during pseudoglandular stage epithelial progenitors at tips coexpress SOX9. This double-positive...
Lipid-containing alveolar interstitial fibroblasts, or simply lipofibroblasts, are increasingly recognized as an important component of the epithelial stem-cell niche in rodent lung. Although lipofibroblasts were initially believed to merely assist type 2 cells surfactant production during neonatal life, recent evidence suggests that these indispensable for survival and growth stem adult life. Despite increasing interest lipofibroblast biology, little is known about their cellular origin...
Rationale Premature infants exposed to oxygen are at risk for bronchopulmonary dysplasia (BPD), which is characterised by lung growth arrest. Inflammation important, but the mechanisms remain elusive. Here, we investigated inflammatory pathways and therapeutic targets in severe clinical experimental BPD. Methods results First, transcriptomic analysis with silico cellular deconvolution identified a lung-intrinsic M1-like-driven cytokine pattern newborn mice after hyperoxia. These findings...
During embryonic development, appropriate dorsoventral patterning of the trachea leads to formation periodic cartilage rings from ventral mesenchyme and continuous smooth muscle dorsal mesenchyme. In this work, we have investigated role two crucial morphogens, fibroblast growth factor 10 sonic hedgehog, in periodically alternating cartilaginous non-cartilaginous domains Using a combination gain- loss-of-function approaches for FGF10 SHH, demonstrate that precise spatio-temporal patterns...
Canonical Wnt signaling plays multiple roles in lung organogenesis and repair by regulating early progenitor cell fates: investigation has been enhanced canonical reporter mice, TOPGAL, BATGAL Axin2LacZ. Although widely used, it remains unclear whether these reporters convey the same information about signaling. We therefore compared beta-galactosidase expression patterns of mice whole embryo versus isolated prenatal lungs. To determine if varied further during repair, we analyzed...
Abstract Fibroblast growth factor (FGF) signaling plays an important role in lung organogenesis. Over recent decades, FGF development has been extensively studied animal models. However, little is known about the expression, localization, and functional roles of ligands during human fetal development. Therefore, we aimed to determine expression function several receptors Using situ hybridization (ISH) RNA sequencing, assessed their distribution native lung. Human explants were treated with...
Alveolar type 2 (AT2) cells are heterogeneous cells, with specialised AT2 subpopulations within this lineage exhibiting stem cell properties. However, the existence of quiescent, immature that activated during lung regeneration is unknown.
Rodent incisors regenerate throughout the lifetime of animal owing to presence epithelial and mesenchymal stem cells in proximal region tooth. Enamel, hardest component tooth, is continuously deposited by cell-derived ameloblasts exclusively on labial, or outer, surface The that are ameloblast progenitors reside structures called cervical loops at base incisors. Previous studies have suggested FGF10, acting mainly through fibroblast growth factor receptor 2b (FGFR2b), crucial for development...
Fibroblast growth factor 10 (Fgf10) is a key regulator of diverse organogenetic programs during mouse development, particularly branching morphogenesis. Fgf10-null mice suffer from lung and limb agenesis as well cecal colonic atresia are thus not viable. To date, the Mlcv1v-nLacZ-24 transgenic strain (referred to Fgf10LacZ), which carries LacZ insertion 114 kb upstream exon 1 Fgf10 gene, has been only allow transient lineage tracing Fgf10-positive cells. Here, we describe novel Fgf10Cre-ERT2...
Rationale The lung mesenchyme gives rise to multiple distinct lineages of cells in the mature respiratory system, including smooth muscle airway and vasculature. However, a thorough understanding specification mesenchymal cell diversity human is lacking. Methods We completed single-cell RNA sequencing analysis fetal tissues. Canonical correlation analysis, clustering, cluster marker gene identification t-distributed stochastic neighbour embedding representation was performed Seurat. Cell...
This study demonstrates that FGF10/FGFR2b signaling on distal epithelial progenitor cells, via ß-catenin/EP300, controls, through a comprehensive set of developmental genes, morphogenesis, and differentiation. Fibroblast growth factor (FGF) 10 FGF receptor 2b (FGFR2b) is mandatory during early lung development as the deletion either ligand or leads to agenesis. However, this drastic phenotype previously hampered characterization primary biological activities, immediate downstream targets...
The lung alveolus is lined with alveolar type 1 (AT1) and 2 (AT2) epithelial cells. During alveologenesis, increasing demand associated expanding numbers met by proliferating progenitor AT2s (pAT2). Little information exists regarding the identity of this population their niche microenvironment. We show that during Hedgehog-responsive PDGFRa(+) progenitors (also known as SCMFs) are a source secreted trophic molecules maintain unique pAT2 population. SCMFs in turn maintained TGFβ signaling....
Millions of teeth are saved each year by root canal therapy. Although current treatment modalities offer high levels success for many conditions, an ideal form therapy might consist regenerative approaches in which diseased or necrotic pulp tissues removed and replaced with healthy tissue to revitalize teeth. Melanocortin peptides (α-MSH) possess anti-inflammatory properties acute chronic inflammatory models. Our recent studies have shown that α-MSH covalently coupled poly-l-glutamic acid...
Wnt signaling has been implicated in promoting somatic cell reprogramming. However, its molecular mechanisms remain unknown. Here we report that Wnt/β-catenin enhances iPSCs induction at the early stage of The augmented reprogramming induced by β-catenin is not due to increased total population or activation c-Myc. In addition, interacts with factors Klf4, Oct4, and Sox2, further enhancing expression pluripotency circuitry genes. These studies reveal novel underlying regulation cells signaling.
Cell polarity, mitotic spindle orientation and asymmetric division play a crucial role in the self-renewal/differentiation of epithelial cells, yet little is known about these processes molecular programs that control them embryonic lung distal epithelium. Herein, we provide first evidence epithelium polarized with characteristic perpendicular cell divisions. Consistent findings, orientation-regulatory proteins Insc, LGN (Gpsm2) NuMA, fate determinant Numb are asymmetrically localized...
Fibroblast growth factors (FGFs) are a family of conserved peptides that play an important role in the development, homeostasis, and repair processes many organ systems, including gastrointestinal tract. All four FGF receptors several ligands present intestine. They roles controlling cell proliferation, differentiation, epithelial restitution, stem maintenance. Several FGFs have also been proven to be protective against diseases such as inflammatory bowel or aid regeneration after intestinal...
Intestinal epithelial cell renewal relies on the right balance of migration, proliferation, differentiation, and apoptosis. cells consist absorptive secretory lineage. The latter is comprised goblet, Paneth, enteroendocrine cells. Fibroblast growth factor 10 (FGF10) plays a central role in survival, differentiation several organs. expression pattern FGF10 its receptors both human mouse intestine their small have yet to be investigated. First, we analyzed FGF10, FGFR1, FGFR2, ileum throughout...
Cell shedding from the intestinal villus is a key element of tissue turnover, essential to maintain health and homeostasis. However, signals regulating this process are not well understood. We asked whether controlled by epidermal growth factor receptor (EGFR), an important driver differentiation. In 3D ileal enteroid culture cell models (MDCK, IEC-6, IPEC-J2 cells), extrusion events were suppressed EGF, as determined direct counting released cells or rhodamine-phalloidin labeling condensed...