Search Result Details

This page shows the details of why an item matched the keywords from your search.
One or more keywords matched the following properties of Duncan, Stephen
overview Research in the Duncan laboratory focuses on liver development and disease using mice and induced pluripotent stem cells (iPSCs) as model systems. 1) Molecular mechanisms underlying liver development Development of a simple two-cell embryo to a complex multicellular organism is a highly dynamic procedure requiring orchestrated cell movements and multiple interactions between cells and their surroundings. As cells differentiate, not only do they receive extra-cellular signals they secrete and display signals of their own, thereby defining the makeup of their local environments. The result of these intercellular communications is the controlled differentiation of populations of progenitor cells to produce novel cell types. The repertoire of genes expressed by the cell defines the phenotype. Gene transcription therefore plays a critical role in regulating cell fate. To comprehend the molecular mechanisms controlling embryonic development my laboratory is, therefore, attempting to understand how transcription factors interact with extracellular signaling mechanisms to drive cell differentiation. Most organs are a complex array of different cell types and tissues, all of which dynamically interact to regulate organogenesis. Tissue complexity can make it challenging to measure the contribution of a specific transcription factor to overall organ or tissue development. However, the liver, in which 80% of the cells are hepatocytes, offers an attractive and relatively simple system in which to study the role of transcription factors during morphogenesis and development. In the laboratory, we use transgenic and knockout mice and genetically modified iPSCs to uncover the mechanisms through which transcription factors and cell signaling molecules are required to drive liver development. 2) Using pluripotent stem cells to study inborn errors of hepatic metabolism The liver has vital endocrine and exocrine functions that regulate a diverse array of metabolic activities. Although specific forms of inborn errors of hepatic metabolism are relatively rare, cumulatively they are common and without treatment are often fatal. To date, a liver transplant can treat the most severe hepatic metabolic deficiencies. Unfortunately, the number of available donor livers is limited, and demand for transplant-quality livers continues to increase. With donor livers being scarce, it has been proposed that cell transplant therapy may offer an alternative to an organ transplant. One source of hepatocytes for transplant could be human iPSCs. Several projects in the laboratory, therefore, focus on generating functional hepatocytes from iPSCs. Metabolic liver disease can also often be treated using small molecules or biologics that, in general, have an established track record of success. With this in mind, we are developing a platform that will facilitate the efficient identification of treatments for rare inborn errors of hepatic metabolism. We propose to 1) establish human pluripotent stem cells harboring genetic variants associated with disease in patients, 2) differentiate the stem cells to hepatocytes and examine whether genetic variations recapitulate the disease in culture, 3) establish assays that are compatible with moderate to high throughput screening to identify existing drugs that could be repurposed to correct the pathophysiology of the disease, and 4) establish the efficacy and safety of lead drugs using humanized animal models and human trials.
One or more keywords matched the following items that are connected to Duncan, Stephen
Item TypeName
Concept Basic Helix-Loop-Helix Transcription Factors
Concept COUP Transcription Factor II
Concept GATA6 Transcription Factor
Concept STAT3 Transcription Factor
Concept GATA4 Transcription Factor
Concept Octamer Transcription Factor-3
Concept Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Concept Transcription Factors
Concept GATA5 Transcription Factor
Concept STAT1 Transcription Factor
Academic Article Sall4 overexpression blocks murine hematopoiesis in a dose-dependent manner.
Academic Article Epicardial GATA factors regulate early coronary vascular plexus formation.
Academic Article Pancreas-specific deletion of mouse Gata4 and Gata6 causes pancreatic agenesis.
Academic Article A cell surfaceome map for immunophenotyping and sorting pluripotent stem cells.
Academic Article Endoplasmic reticulum-tethered transcription factor cAMP responsive element-binding protein, hepatocyte specific, regulates hepatic lipogenesis, fatty acid oxidation, and lipolysis upon metabolic stress in mice.
Academic Article The transcription factor cyclic AMP-responsive element-binding protein H regulates triglyceride metabolism.
Academic Article GATA factors regulate proliferation, differentiation, and gene expression in small intestine of mature mice.
Academic Article Transcriptional control of hepatocyte differentiation.
Academic Article The transcription factor GATA-6 regulates pathological cardiac hypertrophy.
Academic Article Foxa1 functions as a pioneer transcription factor at transposable elements to activate Afp during differentiation of embryonic stem cells.
Academic Article GATA4 is essential for jejunal function in mice.
Academic Article Loss of both GATA4 and GATA6 blocks cardiac myocyte differentiation and results in acardia in mice.
Academic Article Cardiomyocyte GATA4 functions as a stress-responsive regulator of angiogenesis in the murine heart.
Academic Article Development of the mammalian liver and ventral pancreas is dependent on GATA4.
Academic Article A threshold of GATA4 and GATA6 expression is required for cardiovascular development.
Academic Article Generation of mice harbouring a conditional loss-of-function allele of Gata6.
Academic Article Transcriptional regulation of the human hepatic lipase (LIPC) gene promoter.
Academic Article Cardiac-specific deletion of Gata4 reveals its requirement for hypertrophy, compensation, and myocyte viability.
Academic Article Generation of embryos directly from embryonic stem cells by tetraploid embryo complementation reveals a role for GATA factors in organogenesis.
Academic Article GATA6 is essential for embryonic development of the liver but dispensable for early heart formation.
Academic Article Retinoic acid, hypoxia, and GATA factors cooperatively control the onset of fetal liver erythropoietin expression and erythropoietic differentiation.
Academic Article The MODY1 gene HNF-4alpha regulates selected genes involved in insulin secretion.
Academic Article GATA4 is essential for formation of the proepicardium and regulates cardiogenesis.
Academic Article Progression of HCC in mice is associated with a downregulation in the expression of hepatocyte nuclear factors.
Academic Article Hepatocyte nuclear factor 4alpha controls the development of a hepatic epithelium and liver morphogenesis.
Academic Article HNF4: a central regulator of hepatocyte differentiation and function.
Academic Article The orphan nuclear receptor HNF4alpha determines PXR- and CAR-mediated xenobiotic induction of CYP3A4.
Academic Article Mechanisms controlling early development of the liver.
Academic Article Generation of a conditionally null allele of hnf4alpha.
Academic Article An efficient method to successively introduce transgenes into a given genomic locus in the mouse.
Academic Article Transcriptional regulation of liver development.
Academic Article Mammalian hepatocyte differentiation requires the transcription factor HNF-4alpha.
Academic Article Impaired glucose homeostasis and neonatal mortality in hepatocyte nuclear factor 3alpha-deficient mice.
Academic Article In situ hybridization with 33P-labeled RNA probes for determination of cellular expression patterns of liver transcription factors in mouse embryos.
Academic Article Regulation of a transcription factor network required for differentiation and metabolism.
Academic Article The maturity-onset diabetes of the young (MODY1) transcription factor HNF4alpha regulates expression of genes required for glucose transport and metabolism.
Academic Article Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis.
Academic Article STAT signaling is active during early mammalian development.
Academic Article Murine gastrulation requires HNF-4 regulated gene expression in the visceral endoderm: tetraploid rescue of Hnf-4(-/-) embryos.
Academic Article Disruption of the HNF-4 gene, expressed in visceral endoderm, leads to cell death in embryonic ectoderm and impaired gastrulation of mouse embryos.
Academic Article Expression of transcription factor HNF-4 in the extraembryonic endoderm, gut, and nephrogenic tissue of the developing mouse embryo: HNF-4 is a marker for primary endoderm in the implanting blastocyst.
Academic Article GATA6 defines endoderm fate by controlling chromatin accessibility during differentiation of human-induced pluripotent stem cells.
Search Criteria
  • Transcription Factors