A5012270723- Pancreatic function and diabetes
- Neonatal Respiratory Health Research
- Pancreatic and Hepatic Oncology Research
- Cancer Genomics and Diagnostics
- Congenital Diaphragmatic Hernia Studies
- Single-cell and spatial transcriptomics
- Cystic Fibrosis Research Advances
- Renal and related cancers
- Energy Harvesting in Wireless Networks
- Epigenetics and DNA Methylation
- Lung Cancer Treatments and Mutations
- Biomedical Ethics and Regulation
- Cancer Cells and Metastasis
- Viral Infectious Diseases and Gene Expression in Insects
- Cell Image Analysis Techniques
- Fibroblast Growth Factor Research
- Pancreatitis Pathology and Treatment
- Phagocytosis and Immune Regulation
- Esophageal Cancer Research and Treatment
- Diabetes and associated disorders
- Medical Imaging and Pathology Studies
- 3D Printing in Biomedical Research
- Cancer Research and Treatments
- Molecular Biology Techniques and Applications
Technical University of Munich
2024
Helmholtz Zentrum München
2024
Broad Center
2022-2023
Stanford University
2016-2023
University of California, San Francisco
2018-2023
Stratford University
2017
ABSTRACT The critical cellular transitions that govern human pancreas development are largely unknown. We performed large-scale single-cell RNA-sequencing (scRNA-Seq) to interrogate fetal from 8-20 weeks post conception. identified 103 distinct cell types, including four novel endocrine progenitor subtypes displaying unique transcriptional features and differentiation potency. Integration with single-nucleus Assay for Transposase Accessible Chromatin Sequencing (snATAC-Seq) candidate...
ABSTRACT The distal lung contains terminal bronchioles and alveoli that facilitate gas exchange is affected by disorders including interstitial disease, cancer, SARS-CoV-2-associated COVID-19 pneumonia. Investigations of these localized pathologies have been hindered a lack 3D in vitro human culture systems. Further, stem cell identification has impaired quiescence, anatomic divergence from mouse lineage tracing clonogenic culture. Here, we developed robust feeder-free, chemically-defined...
<title>Abstract</title> Human pancreas development remains incompletely understood due to limited sample access constrained by ethical and practical considerations. Here we investigate whether pigs resemble humans in more closely than rodents, as such, offer a valuable alternative large-animal model. As pig organogenesis is unexplored, first annotated developmental hallmarks lineage markers of differentiation morphogenesis throughout the 114-day gestation. Building on this detailed roadmap,...
The molecular links between tissue-level morphogenesis and the differentiation of cell lineages in pancreas remain elusive despite a decade studies. We previously showed that both processes depend on proper lumenogenesis. Rab GTPase Rab11 is essential for epithelial lumen formation vitro, however few studies have addressed its functions vivo none tested requirement pancreas. Here, we show critical development. Co-deletion isoforms Rab11A Rab11B developing pancreatic epithelium (Rab11pancDKO)...
Pancreatic development requires spatially and temporally controlled expression of growth factors derived from mesenchyme. Here, we report that in mice the secreted factor Fgf9 is expressed principally by mesenchyme then mesothelium during early development, subsequently both rare epithelial cells E12.5 onwards. Global knockout gene resulted reduction pancreas stomach size, as well complete asplenia. The number Pdx1+ pancreatic progenitors was reduced at E10.5, proliferation E11.5. Although...
Somatic copy number gains are pervasive across cancer types, yet their roles in oncogenesis insufficiently evaluated. This inadequacy is partly due to spanning large chromosomal regions, obscuring causal loci. Here, we employed organoid modeling evaluate candidate oncogenic loci identified via integrative computational analysis of extreme overlapping with expression dysregulation The Cancer Genome Atlas. Subsets "outlier" candidates were contextually screened as tissue-specific cDNA...
Numerous studies have characterized the existence of cell subtypes, along with their corresponding transcriptional profiles, within developing mouse pancreas. The upstream mechanisms that initiate and maintain gene expression programs across states, however, remain largely unknown. Here, we generate single-nucleus ATAC-Sequencing data murine pancreas perform an integrated, multi-omic analysis both chromatin accessibility RNA to describe landscape at E14.5 E17.5 single-cell resolution. We...
Abstract Cystic fibrosis (CF) is a monogenic autosomal recessive disorder caused by mutations in the Fibrosis Transmembrane Conductance Regulator (CFTR) Cl - channel. CF results multiorgan dysfunction and ultimately mortality from respiratory sequelae. Although pharmacologic approaches have demonstrated efficacy reducing symptoms decline, curative treatment modality remains elusive. Gene therapy, promising strategy, has been limited due to poor correction efficiencies both vitro vivo . Here,...
Pancreatic organogenesis is a complex, multistep process whereby multiple cell types must migrate, proliferate, and differentiate in strict spatiotemporal manner to ultimately form the complete organ. Although pancreatic epithelial well characterized, peripheral nervous system (PNS) innervating organ poorly understood. PNS has been shown be critical formation of other budding exocrine organs, therefore likely plays role pancreas, there dearth information on innervation this developing To...
Abstract We report an in-depth characterization of patient-derived orthotopic xenograft (PDOX) models triple-negative breast cancer (TNBC) regarding their molecular profile at the single cell level, tumor heterogeneity, 3D organoid generation, and ability to generate circulating cells (CTCs). A panel seven TNBC PDOX tumors were grown orthotopically in Nod scid gamma mice used this study. Blood obtained via cardiac puncture from bearing animals was processed on Vortex microfluidic platform,...
SUMMARY Somatic copy number gains are pervasive in many cancer types, yet their roles oncogenesis often poorly explored. This lack of understanding is part due to broad extensions across genomes spanning large chromosomal regions, obscuring causal driver loci. Here we employed a multi-tissue pan-organoid modeling approach validate candidate oncogenic loci identified within pan-cancer TCGA data by the overlap extreme amplifications with expression dysregulation for each gene. The outlier...
77 Background: Genome scale sequencing efforts have identified chromosomal deletions and non-synonymous mutations as putative drivers of gastro-intestinal cancer. There is a need to rapidly validate these in robust models. The culture primary, non-transformed tissues vitro three-dimensional organoids that accurately recapitulate organ structure physiology serves an ideal model for such validation, many other applications biology. Methods: Mouse wild type p53 flox/flox upper digestive tract...
46 Background: Esophageal squamous cell carcinomas remains a particularly intractable disease due to limited therapeutic options as well lack of targeted therapies. The genetic landscape esophageal carcinoma is varied, but common means tumorigenesis in cancers are alterations copy number putative oncogenic loci that result upregulated mRNA. Within this subset with alterations, however, it has been difficult distinguish between driver and passenger mutations using traditional vitro models....
Abstract Numerous studies have characterized the existence of cell subtypes, along with their corresponding transcriptional profiles, within developing mouse pancreas. The upstream mechanisms that initiate and maintain gene expression programs across states, however, remain largely unknown. Here, we generate single-nucleus ATAC-Sequencing data murine pancreas perform an integrated, multi-omic analysis both chromatin accessibility RNA to describe landscape epithelium mesenchyme at E14.5...