A5035759204- Cancer Cells and Metastasis
- Renal and related cancers
- Digestive system and related health
- 3D Printing in Biomedical Research
- Pluripotent Stem Cells Research
- Single-cell and spatial transcriptomics
- RNA modifications and cancer
- Liver physiology and pathology
- Advanced biosensing and bioanalysis techniques
- Nanoparticle-Based Drug Delivery
- RNA Interference and Gene Delivery
- biodegradable polymer synthesis and properties
- Neonatal Respiratory Health Research
- Liver Disease Diagnosis and Treatment
- Pharmacogenetics and Drug Metabolism
- Diet and metabolism studies
- Cancer Genomics and Diagnostics
- Angiogenesis and VEGF in Cancer
- Genetics, Aging, and Longevity in Model Organisms
- Congenital heart defects research
- Hydrogels: synthesis, properties, applications
- Metabolomics and Mass Spectrometry Studies
- Genetic factors in colorectal cancer
- Birth, Development, and Health
- MicroRNA in disease regulation
University of Michigan
2018-2023
Michigan Medicine
2021-2023
University at Buffalo, State University of New York
2017
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...
Organs are composed of diverse cell types that traverse transient states during organogenesis. To interrogate this diversity human development, we generate a single-cell transcriptome atlas from multiple developing endodermal organs the respiratory and gastrointestinal tract. We illuminate states, transcription factors, organ-specific epithelial stem mesenchyme interactions across lineages. implement as high-dimensional search space to benchmark pluripotent (hPSC)-derived intestinal...
Drug-induced liver injury (DILI), both intrinsic and idiosyncratic, causes frequent morbidity, mortality, clinical trial failures post-approval withdrawal. This suggests an unmet need for improved in vitro models DILI risk prediction that can account diverse host genetics other factors. In this study, we evaluated the utility of human organoids (HLOs) high-throughput organ-on-chip system.
Pluripotent-stem-cell-derived human intestinal organoids (HIOs) model some aspects of development and disease, but current culture methods do not fully recapitulate the diverse cell types complex organization intestine are reliant on 3D extracellular matrix or hydrogel systems, which limit experimental control translational potential for regenerative medicine. We describe suspension as a simple, low-maintenance method culturing HIOs promoting in vitro differentiation an organized serosal...
Epithelial organoids derived from intestinal tissue, called enteroids, recapitulate many aspects of the organ in vitro and can be used for biological discovery, personalized medicine, drug development. Here, we interrogated cell signaling environment within developing human intestine to identify niche cues that may important epithelial development homeostasis. We identified an EGF family member, EPIREGULIN (EREG), which is robustly expressed crypt. Enteroids generated grown standard culture...
NOTCH signaling is a key regulator involved in maintaining intestinal stem cell (ISC) homeostasis and for balancing differentiation. Using single-cell transcriptomics, we observed that OLFM4, target gene present ISCs, first expressed at 13 weeks post-conception the developing human intestine increases over time. This led us to hypothesize requirement acquired across development. To test this, established series of epithelium-only organoids (enteroids) from different developmental stages used...
The intestinal epithelium is often a site of pathology, such as in inflammatory bowel disease (IBD), and its maintenance highly modulated by interactions with the microenvironment. However, systematic understanding how myriad niche cues impact distinct epithelial cell types diseased context still lacking. To address this gap, we first benchmarked diverse human colonic organoid injury models against IBD tissue, established disease-relevant model inflammation using TNFɑ, IFNɣ, IL1β. Using...
Abstract Complex three‐dimensional in vitro organ‐like models, or organoids, offer a unique biological tool with distinct advantages over two‐dimensional cell culture systems, which can be too simplistic, and animal complex may fail to recapitulate human physiology pathology. Significant progress has been made driving stem cells differentiate into different organoid types, though several challenges remain. For example, many models suffer from high heterogeneity, it difficult fully...
MicroRNAs (miRNAs) are important post-transcriptional gene regulators controlling cellular lineage specification and differentiation during embryonic development, including the gastrointestinal system. However, miRNA-mediated regulatory mechanisms involved in early development of human small intestine (SI) remains underexplored. To explore candidate roles for miRNAs prenatal SI humans, we used a multi-omic analysis strategy directed model that programs pluripotent stem cells toward lineage.
Summary 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...
Summary Epithelial organoids derived from intestinal tissue, also referred to as mini-intestines or mini-guts, recapitulate many aspects of the organ in vitro and can be used for biological discovery, personalized medicine, drug development. Murine represent a homeostatic system that balances stem cell maintenance within crypt-like compartment differentiation villus-like 1–3 . However, this balance spatial organization has not been achieved with human 4 Here, we leverage single RNA-seq data...
SUMMARY Human pluripotent stem cell (hPSC)-derived intestinal organoids (HIOs) generated using directed differentiation lack some cellular populations found in the native organ, including vasculature. Using single RNA sequencing (scRNAseq), we have identified a transient population of endothelial cells (ECs) present early HIO that are lost over time culture. Here, developed method to enhance co-differentiation and maintenance ECs within HIOs (vHIOs). Given known possess organ specific gene...
Abstract MicroRNAs (miRNAs) are important post-transcriptional gene regulators in organ development. To explore candidate roles for miRNAs prenatal SI lineage specification humans, we used a multi-omic analysis strategy directed differentiation model that programs human pluripotent stem cells toward the lineage. We leveraged small RNA-seq to define changing miRNA landscape, and integrated chromatin run-on sequencing (ChRO-seq) genes subject significant regulation across different stages of...
ABSTRACT Background and Aims Drug-induced liver injury (DILI), both intrinsic idiosyncratic, causes frequent morbidity, mortality, clinical trial failures post-approval withdrawal. This suggests an unmet need for improved in vitro models DILI risk prediction that can account diverse host genetics other factors. In this study, we evaluated the utility of human organoids (HLOs) high-throughput organ-on-chip system. Methods HLOs were derived from 3 separate iPSC lines benchmarked on two...