A5070164462- Pluripotent Stem Cells Research
- Liver physiology and pathology
- Liver Disease Diagnosis and Treatment
- Pancreatic function and diabetes
- CRISPR and Genetic Engineering
- Organ Transplantation Techniques and Outcomes
- Renal and related cancers
- Liver Disease and Transplantation
- Insect Resistance and Genetics
- Animal Genetics and Reproduction
- Drug Transport and Resistance Mechanisms
- Lipid metabolism and disorders
- Ubiquitin and proteasome pathways
- 3D Printing in Biomedical Research
- Drug-Induced Hepatotoxicity and Protection
- Liver Diseases and Immunity
- Endoplasmic Reticulum Stress and Disease
- Sirtuins and Resveratrol in Medicine
- Tissue Engineering and Regenerative Medicine
- Pediatric Hepatobiliary Diseases and Treatments
- Pharmacogenetics and Drug Metabolism
- Alcohol Consumption and Health Effects
University of Pittsburgh
2009-2024
Children's Hospital of Pittsburgh
2009-2020
McGowan Institute for Regenerative Medicine
2009-2015
University of Pittsburgh Medical Center
2015
In the classical form of α1-antitrypsin deficiency (ATD), aberrant intracellular accumulation misfolded mutant Z (ATZ) in hepatocytes causes hepatic damage by a gain-of-function, "proteotoxic" mechanism. Whereas some ATD patients develop severe liver disease (SLD) that necessitates transplantation, others with same genetic defect completely escape this clinical phenotype. We investigated whether induced pluripotent stem cells (iPSCs) from individuals or without SLD could model these...
Hepatocyte transplantation has the potential to cure inherited liver diseases, but its application is impeded by a scarcity of donor livers. Therefore, we explored whether hepatocyte-like cells (iHeps) differentiated from human induced pluripotent stem (iPSCs) could ameliorate diseases. iPSCs reprogrammed skin fibroblasts were iHeps, which transplanted into livers uridinediphosphoglucuronate glucuronosyltransferase-1 (UGT1A1)-deficient Gunn rats, model Crigler-Najjar syndrome 1 (CN1), where...
Metabolic-dysfunction-associated steatotic liver disease (MASLD), which affects 30 million people in the US and is anticipated to reach over 100 by 2030, places a significant financial strain on healthcare system. There presently no FDA-approved treatment for MASLD despite its public health significance burden. Understanding connection between point mutations, enzymes, important comprehending drug toxicity healthy or diseased individuals. Multiple genetic variations have been linked...
Hepatocyte nuclear factor 4 alpha (HNF4α) is a transcription that plays critical role in hepatocyte function, and HNF4α‐based reprogramming corrects terminal liver failure rats with chronic disease. In the livers of patients advanced cirrhosis, HNF4α RNA expression levels decrease as hepatic function deteriorates, protein found cytoplasm. These findings could explain impaired degenerative this study, we analyzed localization pathways involved post‐translational modification human hepatocytes...
A.S.-G is an inventor on a patent application that describes the use of transcription factors to treat chronic liver failure (US20140249209).E.N.T. and A.S.-G., are inventors provisional related methods enhance hepatic functions in human failing livers
Hepatocyte transplantation has been used to treat liver disease. The availability of cells for these procedures is quite limited. Human embryonic stem (hESCs) and induced pluripotent (hiPSCs) may be a useful source hepatocytes basic research if efficient effective differentiation protocols were developed problems with tumorigenicity could overcome. Recent evidence suggests that the cell origin affect hiPSC differentiation. Thus, hiPSCs generated from differentiate back more efficiently than...
The only definitive therapy for end‐stage liver disease is whole‐organ transplantation. success of this intervention severely limited by the complexity surgery, cost patient care, need long‐term immunosuppression, and shortage donor organs. In rodents humans, degeneration hepatocyte function associated with disruption liver‐specific transcriptional network a nearly complete loss promoter P1‐driven nuclear factor 4‐alpha (P1‐HNF4α) activity. Re‐expression HNF4α2 , predominant P1‐HNF4α,...
In the classical form of α1-antitrypsin deficiency, a misfolded variant Z accumulates in endoplasmic reticulum liver cells and causes cell injury by gain-of-function proteotoxicity sub-group affected homozygotes but relatively little is known about putative modifiers. Here, we carried out genomic sequencing uniquely family with an index case failure 2 homozygous siblings minimal or no disease. Their sequences were compared to well-characterized cohorts without disease, then candidate...
Primary biliary cholangitis (PBC) and primary sclerosing (PSC), the most common types of cholestatic liver disease (CLD), result in enterohepatic obstruction, bile acid accumulation, hepatotoxicity. The mechanisms by which hepatocytes respond to cope with CLD remain largely unexplored. This study includes characterization isolated from explanted livers patients PBC PSC. We examined expression hepatocyte-specific genes, intracellular (BA) levels, oxidative stress primary-human-hepatocytes...
Acute hepatic failure is associated with high morbidity and mortality for which the only definitive therapy liver transplantation. Some fraction of those who undergo emergency transplantation have been shown to recover native function when transplanted an auxiliary graft that leaves part intact. Thus, could averted development use some form support. The costs developing testing support systems be dramatically reduced by availability a reliable large animal model therapeutic window allows...
Although the underlying cause may vary across countries and demographic groups, liver disease is a major of morbidity mortality globally. Orthotopic transplantation only definitive treatment for failure but limited by lack donor livers. The development drugs that prevent progression generation alternative constructs could help alleviate burden disease. Bioengineered livers containing human induced pluripotent stem cell (iPSC)-derived cells are being utilized to study identify test potential...