A5023524466- Pediatric Hepatobiliary Diseases and Treatments
- Liver physiology and pathology
- Developmental Biology and Gene Regulation
- Organ Transplantation Techniques and Outcomes
- Liver Disease Diagnosis and Treatment
- Lung Cancer Treatments and Mutations
- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- Pancreatic function and diabetes
- Wnt/β-catenin signaling in development and cancer
- Gallbladder and Bile Duct Disorders
- Drug Transport and Resistance Mechanisms
- Cancer Cells and Metastasis
- Cytokine Signaling Pathways and Interactions
- Cancer-related Molecular Pathways
- Congenital Anomalies and Fetal Surgery
- Pluripotent Stem Cells Research
- Renal and related cancers
- Ubiquitin and proteasome pathways
- Clinical Nutrition and Gastroenterology
- Genetic and Kidney Cyst Diseases
- HER2/EGFR in Cancer Research
- Retinal Development and Disorders
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Diabetes and associated disorders
Cincinnati Children's Hospital Medical Center
2013-2024
University of Cincinnati Medical Center
2016-2024
University of Cincinnati
2013-2024
Vanderbilt University
2008-2015
Medical Center Hospital
2014
Vanderbilt University Medical Center
2006-2012
Johannes Gutenberg University Mainz
2012
Foundation for Human Potential
2011
University of Palermo
2010
Washington University in St. Louis
2000-2007
ABSTRACT Delta and Notch are required for partitioning of vein intervein cell fates within the provein during Drosophila metamorphosis. We find that these is dependent on Delta-mediated signalling from 22 to 30 hours after puparium formation at 25°C. Within provein, expressed more highly in central cells (presumptive cells) lateral cells). Accumulation presumptive activity constitutive receptor represses accumulation cells. When protein expression elevated ectopically cells, complementary...
Mutations in the epidermal growth factor receptor (EGFR) are most common actionable genetic abnormalities yet discovered lung cancer. However, targeting these mutations with kinase inhibitors is not curative advanced disease and has to demonstrate an impact on potentially curable, early-stage disease, some data suggesting adverse outcomes. Here, we report that treatment of EGFR-mutated cancer cell lines erlotinib, while showing robust death, enriches ALDH(+) stem-like cells through...
Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic worldwide. While it is well-accepted that inflammation central to NAFLD pathogenesis, immune pathway(s) orchestrating progression are poorly defined. Notably, IL-17RA signaling, via IL-17A, plays an important role in obesity-driven pathogenesis. However, of IL-17F, another ligand, pathogenesis not been examined. Further, cell types expressing and producing ligands have Here, IL-17RA-/-, IL-17A-/-, IL-17F-/-...
The four highly conserved Notch receptors receive short-range signals that control many biological processes during development and in adult vertebrate tissues. involvement of Notch1 signaling tissue self-renewal is less clear, however. We developed a novel genetic approach N(1)IP-CRE (Notch1 Intramembrane Proteolysis) to follow, at high resolution, the descendents cells experiencing activation mouse. By combining with loss-of-function analysis, patterns were correlated function development,...
Alagille syndrome, a chronic hepatobiliary disease, is characterized by paucity of intrahepatic bile ducts (IHBDs). To determine the impact Notch signaling specifically on IHBD arborization, we studied influence both gain and loss function intact three-dimensional structure using series mutant mouse models resin casting method. Impaired in bipotential hepatoblast progenitor cells (BHPCs) dose-dependently decreased density peripheral IHBDs, whereas activation Notch1 results an increased...
JAGGED1 mutations cause Alagille syndrome, comprising a constellation of clinical findings, including biliary, cardiac and craniofacial anomalies. Jagged1, ligand in the Notch signaling pathway, has been extensively studied during biliary development. However, role development is poorly understood. Patients with syndrome have midface hypoplasia giving them characteristic 'inverted V' facial appearance. This study design determines requirement Jagged1 cranial neural crest (CNC) cells, which...
Objective— Calcific aortic valve disease (CAVD) is a significant cardiovascular disorder, and controversy exists as to whether it primarily dystrophic or osteogenic process in vivo. In this study, we sought clarify the mechanism of CAVD by assessing genetic mutation, Notch1 heterozygosity, which leads with 100% penetrance humans. Approach Results— Murine immortalized +/− interstitial cells (AVICs) were isolated expanded vitro. Molecular signaling wild-type AVICs compared identify changes...
Vascular endothelial growth factor (VEGF) is crucial for vascular development in several organs. However, the specific contribution of epithelial-VEGF signaling liver has not been tested. We used a mouse model to specifically delete Vegf from epithelial lineages during midgestational and assessed cell identities architectures tissues. find that without epithelial-derived VEGF, zonal hepatocyte are altered. also decreased portal vein hepatic artery branching coincident with an increase...
The potential for intrahepatic bile duct (IHBD) regeneration in patients with insufficiency diseases is poorly understood. Notch signaling and Hnf6 have each been shown to be important the morphogenesis of IHBDs mice. One congenital pediatric liver disease characterized by reduced numbers IHBDs, Alagille syndrome, associated mutations components. Therefore, we investigated whether cell plasticity could contribute IHBD mice disruptions Hnf6. We studied a mouse model epithelial cell–specific...
Notch signaling and hepatocyte nuclear factor–6 (HNF–6) are two genetic factors known to affect lineage commitment in the bipotential hepatoblast progenitor cell (BHPC) population. A interaction involving HNF–6 mice has been inferred through separate experiments showing that both BHPC specification bile duct morphogenesis. To define between an vivo mouse model, we examined effects of BHPC–specific loss alone within background recombination signal binding protein immunoglobulin kappa J...
Background and Aims Alagille syndrome (ALGS) is a multisystem developmental disorder characterized by bile duct (BD) paucity, caused primarily haploinsufficiency of the Notch ligand jagged1. The course liver disease highly variable in ALGS. However, genetic basis for ALGS phenotypic variability unknown. Previous studies have reported decreased expression transcription factor SOX9 (sex determining region Y‐box 9) late embryonic neonatal livers Jag1 ‐deficient mice. Here, we investigated...
BiliQML is the first comprehensive machine-learning platform for biliary form analysis in whole slide histopathological images. This provides clinical and basic science researchers with a novel tool improved quantification characterization of tract disorders.
In the past decade we have witnessed an epidemic of obesity in developed countries. Therefore, understanding mechanisms involved regulation body weight is becoming increasingly important goal shared by public and scientific community. The key to fat deposition adipocyte, a specialized cell that plays critical role energy balance appetite regulation. Much our knowledge adipogenesis comes from studies using preadipocytic lines provided information regarding molecular control adipocyte...
Abnormal Notch signaling in humans results Alagille syndrome, a pleiotropic disease characterized by paucity of intrahepatic bile ducts (IHBDs). It is not clear how IHBD develops as consequence atypical signaling, whether developmental lack duct formation, post-natal branching and elongation or an inability to maintain formed ducts. Previous studies have focused on the role development, demonstrated dosage requirement for proper formation. In this study, we use resin casting X-ray...
Abstract γ‐Secretase is a lipid‐embedded, intramembrane‐cleaving aspartyl protease that cleaves its substrates twice within their transmembrane domains (TMD): once near the cytosolic leaflet (at S3/ɛ) and again in middle of TMD S4/γ). To address whether this unusual process occurs two independent or interdependent steps, we investigated how mutations at S3/ɛ site Notch1‐based impact proteolysis. We demonstrate such greatly inhibit not only γ‐secretase‐mediated cleavage S3 but also S4, on...
Hepatoblastoma, the most common pediatric liver cancer, consists of epithelial mixed embryonal/fetal (EMEF) and pure fetal histologic subtypes, with latter exhibiting a more favorable prognosis. Few embryonal histology markers that yield insight into biologic basis for this prognostic discrepancy exist. CBP/P-300 interacting transactivator 1 (CITED1), transcriptional co-activator, is expressed in self-renewing nephron progenitor population developing kidney broadly its malignant analog,...
In organs, the correct architecture of vascular and ductal structures is indispensable for proper physiological function, formation maintenance these a highly regulated process. The analysis complex, 3-dimensional has greatly depended on either 2-dimensional examination in section or dye injection studies. These techniques, however, are not able to provide complete quantifiable representation they intended elucidate. Alternatively, nature plastic resin casts generates permanent snapshot...