A5029019490- Hedgehog Signaling Pathway Studies
- Epigenetics and DNA Methylation
- Liver physiology and pathology
- Cancer-related Molecular Pathways
- Liver Disease Diagnosis and Treatment
- Genetic and Kidney Cyst Diseases
- Chromatin Remodeling and Cancer
- Pancreatic and Hepatic Oncology Research
- Ubiquitin and proteasome pathways
- Pediatric Hepatobiliary Diseases and Treatments
- Tumors and Oncological Cases
- Microtubule and mitosis dynamics
- interferon and immune responses
- Proteoglycans and glycosaminoglycans research
- Immunotherapy and Immune Responses
- Cancer, Hypoxia, and Metabolism
- Immune Cell Function and Interaction
- Genomics and Chromatin Dynamics
- Glycosylation and Glycoproteins Research
- Natural Compounds in Disease Treatment
- Cancer Immunotherapy and Biomarkers
- Cell death mechanisms and regulation
- Hippo pathway signaling and YAP/TAZ
- Digestive system and related health
- Glioma Diagnosis and Treatment
Medical University of South Carolina
2018-2024
Duke University
2013-2019
Duke Medical Center
2012-2016
Foundation for Liver Research
2012
Duke University Hospital
2012
Center for Human Genetics
2012
University of North Carolina at Chapel Hill
2012
Liver repair involves phenotypic changes in hepatic stellate cells (HSCs) and reactivation of morphogenic signaling pathways that modulate epithelial-to-mesenchymal/mesenchymal-to-epithelial transitions, such as Notch Hedgehog (Hh). Hh stimulates HSCs to become myofibroblasts (MFs). Recent lineage tracing studies adult mice with injured livers showed some MFs became multipotent progenitors regenerate hepatocytes, cholangiocytes, HSCs. We studied primary HSC cultures two different animal...
Adult liver regeneration requires induction and suppression of proliferative activity in multiple types cells. The mechanisms that orchestrate the global changes gene expression are required for to change within individual cells, coordinate among different not well understood. Morphogenic signaling pathways active during fetal development, including Hedgehog Hippo/Yes‐associated protein 1 (Yap1), regulate adulthood. Cirrhosis cancer result when these become dysregulated, but relatively...
Smoothened (SMO), a coreceptor of the Hedgehog (Hh) pathway, promotes fibrogenic repair chronic liver injury. We investigated roles SMO+ myofibroblast (MF) in regeneration by conditional deletion SMO α smooth muscle actin (αSMA)+ cells after partial hepatectomy (PH).αSMA-Cre-ER(T2)×SMO/flox mice were treated with vehicle (VEH) or tamoxifen (TMX), and sacrificed 24-96 h post-PH. Regenerating livers analysed for proliferation, progenitors fibrosis qRT-PCR quantitative immunohistochemistry...
Thyroid hormone (TH) is important for tissue repair because it regulates cellular differentiation. Intrahepatic TH activity controlled by both serum levels and hepatic deiodinases. substrate (T4) converted into active (T3) deiodinase 1 (D1) but inactive (rT3) 3 (D3). Although the relative expressions of D1 D3 are known to change during liver injury, cell types signaling mechanisms involved unclear. We evaluated hypothesis that changes in deiodinases result from repair-related activation...
It is unclear why the histology of pediatric and adult nonalcoholic fatty liver disease (NAFLD) sometimes differs. In adults, severity portal inflammation fibrosis correlate with Hedgehog pathway activity. (Hh) signaling regulates organogenesis, but silent in livers until injury reinduces Hh ligand production. During adolescence, development completed children's normally lose cells that produce and/or respond to ligands. We postulated interferes this process by increasing production,...
Hepatocellular carcinoma (HCC) typically develops in cirrhosis, a condition characterized by Hedgehog (Hh) pathway activation and accumulation of Hh-responsive myofibroblasts. Although Hh signaling generally regulates stromal-epithelial interactions that support epithelial viability, the role Hh-dependent myofibroblasts hepatocarcinogenesis is unknown. Here, we used human HCC samples, mouse model, hepatoma cell/myofibroblast cocultures to examine hypothesis modulates myofibroblasts'...
<h3>Objective</h3> The ductular reaction (DR) involves mobilisation of reactive-appearing duct-like cells (RDC) along canals Hering, and myofibroblastic (MF) differentiation hepatic stellate (HSC) in the space Disse. Perivascular stem cell niches produce pleiotrophin (PTN) to inactivate PTN receptor, protein tyrosine phosphatase receptor zeta-1 (PTPRZ1), thereby augmenting phosphoprotein-dependent signalling. We hypothesised that DR is regulated by PTN/PTPRZ1 <h3>Design</h3> PTN-GFP,...
Most children with medulloblastoma (MB) achieve remission, but some face very aggressive metastatic tumors. Their dismal outcome highlights the critical need to advance therapeutic approaches that benefit such high-risk patients. Minnelide, a clinically relevant analog of natural product triptolide, has oncostatic activity in both preclinical and early clinical settings. Despite its efficacy tolerable toxicity, this compound not been evaluated MB. Utilizing bioinformatic dataset integrates...
Background Alcohol consumption promotes hepatocellular carcinoma ( HCC ). The responsible mechanisms are not well understood. Hepatocarcinogenesis increases with age and is enhanced by factors that impose a demand for liver regeneration. Because alcohol hepatotoxic, habitual ingestion evokes recurrent hepatic alcohol‐preferring P ) rat model mimics the level of humans who habitually abuse alcohol. Previously, we showed heavy amplified age‐related hepatocarcinogenesis in rats, over 80%...
SRY (sex determining region Y)-box 2 (SOX2)-labeled cells play key roles in chemoresistance and tumor relapse; thus, it is critical to elucidate the mechanisms propagating them. Single-cell transcriptomic analyses of most common malignant pediatric brain tumor, medulloblastoma (MB), revealed existence astrocytic
Obesity is associated with multiple diseases, but it unclear how obesity promotes progressive tissue damage. Recovery from injury requires repair, an energy-expensive process that coupled to energy availability at the cellular level. The satiety factor, leptin, a key component of sensor matches utilization available supplies. Leptin deficiency signals depletion, whereas activating Hedgehog pathway drives energy-consuming activities. Tissue repair impaired in mice are obese due genetic leptin...
Dysregulation of Sonic hedgehog (SHH) signaling drives the growth distinct cancer subtypes, including medulloblastoma (MB). Such cancers have been treated in clinic with a number clinically relevant SHH inhibitors, majority which target upstream regulator, Smoothened (SMO). Despite considerable efficacy, many these patients develop resistance to drugs, primarily due mutations SMO. Therefore, it is essential identify druggable, components downstream SMO inhibitor resistant cancers. We...
Chronic intermittent hypoxia and hedgehog (Hh) pathway dysregulation are associated with nonalcoholic fatty liver disease (NAFLD) progression. In this study, we determined the relationship between obstructive sleep apnea (OSA)/nocturnal Hh signaling in pediatric NAFLD. Adolescents histologic NAFLD (n = 31) underwent polysomnogram testing, laboratory Sonic (SHh), Indian (IHh), glioblastoma‐associated oncogene 2 (Gli2), keratin 7 (K7), α‐smooth muscle actin (α‐SMA), hypoxia‐inducible factor 1α...
<p>PDF file - 127K, S1. Panc 10.05 cells do not generate functional Hh ligands. S2. Other malignant hepatoma lines can increase MF and glycolytic activity. S3. Summary of metabolism. S4. MF-derived lactate provides energy source for lipogenesis in other lines. S5. Schematic alterations due to release metabolic end products by MF</p>
<p>PDF file - 82K</p>
<p>PDF file - 82K</p>
<p>PDF file - 127K, S1. Panc 10.05 cells do not generate functional Hh ligands. S2. Other malignant hepatoma lines can increase MF and glycolytic activity. S3. Summary of metabolism. S4. MF-derived lactate provides energy source for lipogenesis in other lines. S5. Schematic alterations due to release metabolic end products by MF</p>
Supplementary Figure from A Druggable UHRF1/DNMT1/GLI Complex Regulates Sonic Hedgehog–Dependent Tumor Growth
Supplementary Figure from A Druggable UHRF1/DNMT1/GLI Complex Regulates Sonic Hedgehog–Dependent Tumor Growth