- Renal and related cancers
- Cancer Cells and Metastasis
- Neonatal Respiratory Health Research
- Digestive system and related health
- Congenital Diaphragmatic Hernia Studies
- Pluripotent Stem Cells Research
- Tissue Engineering and Regenerative Medicine
- 3D Printing in Biomedical Research
- Pancreatic function and diabetes
- Single-cell and spatial transcriptomics
- Genetics and Neurodevelopmental Disorders
- Ubiquitin and proteasome pathways
- SARS-CoV-2 and COVID-19 Research
- Cancer-related Molecular Pathways
- Cancer Research and Treatments
- Gut microbiota and health
- Congenital heart defects research
- Fibroblast Growth Factor Research
- COVID-19 Clinical Research Studies
- Wnt/β-catenin signaling in development and cancer
- Gastrointestinal motility and disorders
- Tracheal and airway disorders
- Congenital gastrointestinal and neural anomalies
- Pancreatic and Hepatic Oncology Research
- Cancer-related gene regulation
University of Michigan
2016-2025
A. Alfred Taubman Health Care Center
2024
Michigan Medicine
2017-2023
Michigan United
2019-2023
Organogenesis (United States)
2013-2022
University Gastroenterology
2022
University of North Carolina at Chapel Hill
2021
North Carolina State University
2021
Magyar Agrár- és Élettudományi Egyetem
2021
Tufts University
2021
Recent breakthroughs in 3-dimensional (3D) organoid cultures for many organ systems have led to new physiologically complex vitro models study human development and disease. Here, we report the step-wise differentiation of pluripotent stem cells (hPSCs) (embryonic induced) into lung organoids. By manipulating developmental signaling pathways hPSCs generate ventral-anterior foregut spheroids, which are then expanded organoids (HLOs). HLOs consist epithelial mesenchymal compartments lung,...
This study identifies and characterizes retinal stem cells (RSCs) in early postnatal to seventh-decade human eyes. Different subregions of eyes were dissociated cultured by using a clonal sphere-forming assay. The derived only from the pars plicata plana ciliary margin, at frequency approximately 1:500. To test for long-term self-renewal, both sphere assay monolayer passaging used. By single assay, primary spheres replated, individual demonstrated 100% with giving rise one or more new each...
ABSTRACT Clostridium difficile is the leading cause of infectious nosocomial diarrhea. The pathogenesis C. infection (CDI) results from interactions between pathogen, intestinal epithelium, host immune system, and gastrointestinal microbiota. Previous studies host-pathogen interaction in CDI have utilized either simple cell monolayers or vivo models. While much has been learned by utilizing these approaches, little known about direct bacterium with a complex epithelium. Here, we asked if...
The canonical Wnt pathway is necessary for gut epithelial cell proliferation, and aberrant activation of this causes intestinal neoplasia. We report a novel mechanism by which the Sox family transcription factors regulate signaling pathway. found that some proteins antagonize while others enhance β-catenin/T-cell factor (TCF) activity. Sox17, expressed in normal epithelium but exhibits reduced expression neoplasia, antagonistic to signaling. When overexpressed SW480 colon carcinoma cells,...
Significance Human mutations in SOX9 lead to several congenital disorders, including campomelic dysplasia. Babies born with this condition often die of respiratory distress; however, defects lung development have thus far not been reported mouse models. Here, we report that epithelial-specific deletion Sox9 leads developmental abnormalities the during branching morphogenesis. We demonstrate plays multiple roles epithelium, balancing proliferation and differentiation regulating extracellular...
Human intestinal organoids (HIOs) are a tissue culture model in which small intestine-like is generated from pluripotent stem cells.By carrying out unsupervised hierarchical clustering of RNA-sequencing data, we demonstrate that HIOs most closely resemble human fetal intestine.We observed genes involved digestive tract development enriched both intestine and compared to adult tissue, whereas related function Paneth cell host defense expressed at higher levels intestine.Our study also...
The current study aimed to understand the developmental mechanisms regulating bud tip progenitor cells in human fetal lung, which are present during branching morphogenesis, and use this information induce a progenitor-like population from pluripotent stem (hPSCs) vitro. We identified cues that maintained isolated lung epithelial vitro induced three-dimensional hPSC-derived organoids with tip-like domains. Bud domains could be isolated, expanded, as nearly homogeneous population. Molecular...
Human intestinal organoids (HIOs) represent a powerful system to study human development and are promising candidates for clinical translation as drug-screening tools or engineered tissue. Experimental control use of HIOs is limited by growth in expensive poorly defined tumor-cell-derived extracellular matrices, prompting investigation synthetic ECM-mimetics HIO culture. Since possess an inner epithelium outer mesenchyme, we hypothesized that adhesive cues provided the matrix may be...
Human pluripotent stem cell (hPSC) derived tissues often remain developmentally immature in vitro, and become more adult-like their structure, cellular diversity function following transplantation into immunocompromised mice. Previously we have demonstrated that hPSC-derived human lung organoids (HLOs) resembled fetal tissue vitro (<xref ref-type="bibr" rid="bib10">Dye et al., 2015</xref>). Here show HLOs required a bioartificial microporous poly(lactide-co-glycolide) (PLG)...
Significance Since its emergence in China December 2019, SARS-CoV-2 has caused a global pandemic. Repurposing of FDA-approved drugs is promising strategy for identifying rapidly deployable treatments COVID-19. Herein, we developed pipeline quantitative, high-throughput, image-based screening infection human cells that led to the identification several and clinical candidates with vitro antiviral activity.