A5101701206- Pancreatic function and diabetes
- Diabetes and associated disorders
- Metabolism, Diabetes, and Cancer
- Diabetes Management and Research
- Genetics and Neurodevelopmental Disorders
- Diet, Metabolism, and Disease
- Microtubule and mitosis dynamics
- Pluripotent Stem Cells Research
- Cellular transport and secretion
- Endoplasmic Reticulum Stress and Disease
- Plant nutrient uptake and metabolism
- Congenital heart defects research
- Mitochondrial Function and Pathology
- FOXO transcription factor regulation
- Pancreatic and Hepatic Oncology Research
- Epigenetics and DNA Methylation
- Neurogenesis and neuroplasticity mechanisms
- Liver physiology and pathology
- Gene expression and cancer classification
- Fibroblast Growth Factor Research
- Adipose Tissue and Metabolism
- Magnesium in Health and Disease
- Diabetes Treatment and Management
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Cancer Genomics and Diagnostics
Vanderbilt University
2016-2025
Vanderbilt University Medical Center
2010-2024
Vanderbilt Health
2024
Nashville Oncology Associates
2019-2023
Second Hospital of Hebei Medical University
2019
Tennessee Valley Authority
2018
Huazhong University of Science and Technology
2015
Harvard University
2003
Howard Hughes Medical Institute
2002
The location and lineage of cells that give rise to endocrine islets during embryogenesis has not been established nor the origin or identity adult islet stem cells. We have employed an inducible Cre-ERTM-LoxP system indelibly mark progeny expressing either Ngn3 Pdx1 at different stages development. results provide direct evidence NGN3+ are progenitors in mice. In addition, we find all three types pancreatic tissue: exocrine, duct. Furthermore, exocrine derived from Pdx1-expressing...
To define genetic pathways that regulate development of the endocrine pancreas, we generated transcriptional profiles enriched cells isolated from four biologically significant stages pancreas development:endoderm before specification, early pancreatic progenitor cells,endocrine and adult islets Langerhans. These analyses implicate new signaling in development, identified sets known novel genes are temporally regulated, as well spatially developing their neighbors. The differential...
Abstract Cre/LoxP‐mediated DNA recombination allows for gene function and cell lineage analyses during embryonic development tissue regeneration. Here, we describe the derivation of a K19 CreERT mouse line in which tamoxifen‐activable CreER T was knocked into endogenous cytokeratin 19 locus. In absence tamoxifen, leaky Cre activity could be detected only less than 1% stomach intestinal epithelial cells, but not pancreatic or hepatic tissues. Tamoxifen administration postnatal animals induced...
Neurog3 (Neurogenin 3 or Ngn3) is both necessary and sufficient to induce endocrine islet cell differentiation from embryonic pancreatic progenitors. Since robust expression has not been detected in hormone-expressing cells, used as an progenitor marker regarded dispensable for the function of differentiated cells. Here we independent lines knock-in reporter mice mRNA/protein-based assays examine mRNA protein are hormone-producing cells at adult stages. Significantly, inactivating insulin...
The adult pancreas is capable of limited regeneration after injury but has no defined stem cell population. types and molecular signals that govern the production new pancreatic tissue are not well understood. Here, we show inactivation SCF-type E3 ubiquitin ligase substrate recognition component Fbw7 induces ductal cells to reprogram into α, δ, β cells. Loss stabilized transcription factor Ngn3, a key regulator endocrine differentiation. induced resemble islet in morphology histology,...
Recent studies have revealed that newly emerging transformed cells are often eliminated from epithelial tissues via cell competition with the surrounding normal cells. This cancer preventive phenomenon is termed defense against (EDAC). However, it remains largely unknown whether and how EDAC diminished during carcinogenesis. In this study, using a mouse model, we show high-fat diet (HFD) feeding substantially attenuates frequency of apical elimination RasV12-transformed intestinal pancreatic...
A critical role of circadian oscillators in orchestrating insulin secretion and islet gene transcription has been demonstrated recently. However, these studies focused on whole islets did not explore the interplay between α-cell β-cell clocks. We performed a parallel analysis molecular properties using mouse model expressing three reporter genes: one labeling α cells, specific for β third monitoring expression. Thus, phase entrainment properties, expression, functional outputs clockworks...
<p dir="ltr"><a href="" target="_blank">Glucolipotoxicity</a>, caused by combined hyperglycemia and hyperlipidemia, results in b-cell failure type 2 diabetes via cellular stress-related mechanisms. Activating transcription factor 4 (Atf4) is an essential effector of stress response. We show here that <i>Atf4</i> expression b-cells minimally required for glucose homeostasis juvenile adolescent mice but it needed function during aging under obesity-related...
Activating mutations in the Kras gene are commonly found some but not all epithelial cancers. In order to understand susceptibility of different tissues Kras-induced tumorigenesis, we introduced one most common mutations, Kras(G12D), broadly tissues. We used a mouse model which G12D mutation is placed endogenous locus controlled by inducible, Cre-mediated recombination expressing cytokeratin 19 including oral cavity, GI tract, lungs, and ducts liver, kidney, pancreas. Introduction Kras(G12D)...
Developmental biology is challenged to reveal the function of numerous candidate genes implicated by recent genome-scale studies as regulators organ development and diseases. Recapitulating organogenesis from purified progenitor cells that can be genetically manipulated would provide powerful opportunities dissect such gene functions. Here we describe systems for reconstructing pancreas development, including islet β-cell α-cell differentiation, single fetal cells. A strict requirement...
The high-mobility group AT-hook 1 (HMGA1) protein is a nuclear architectural factor that can organize chromatin structures. It regulates gene expression by controlling the formation of stereospecific multiprotein complexes called "enhanceosomes" on AT-rich regions target promoters. Previously, we reported defects in HMGA1 caused decreased insulin receptor and increased susceptibility to type 2 diabetes mellitus humans mice. Interestingly, mice with disrupted had significantly smaller islets...
Analysis of MafB −/− mice has suggested that the MAFB transcription factor was essential to islet α- and β-cell formation during development, although postnatal physiological impact could not be studied here because these mutants died due problems in neural development. Pancreas-wide mutant were generated compare significance ( Δpanc ) MafA/B MafAB with deficiencies associated related β-cell-enriched MafA (MafA ). Insulin + cell production activity merely delayed islets until comprehensively...