A5086984359- Endoplasmic Reticulum Stress and Disease
- Pancreatic and Hepatic Oncology Research
- RNA modifications and cancer
- Metabolism and Genetic Disorders
- Cancer Genomics and Diagnostics
- Insect Resistance and Genetics
- Viral Infectious Diseases and Gene Expression in Insects
- MicroRNA in disease regulation
- Helicobacter pylori-related gastroenterology studies
- DNA Repair Mechanisms
- Congenital heart defects research
- Liver Disease Diagnosis and Treatment
- Signaling Pathways in Disease
- Circular RNAs in diseases
- Biochemical and Molecular Research
- Caveolin-1 and cellular processes
- Hemophilia Treatment and Research
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Lysosomal Storage Disorders Research
- Calpain Protease Function and Regulation
- Phytase and its Applications
- Cellular transport and secretion
- Hepatitis C virus research
- Adenosine and Purinergic Signaling
- Heat shock proteins research
The University of Texas MD Anderson Cancer Center
2022-2025
Scripps MD Anderson Cancer Center
2024
Telethon Institute Of Genetics And Medicine
2016-2022
Ospedale dei Pellegrini
1972
While pancreatic ductal adenocarcinomas (PDACs) are addicted to KRAS-activating mutations, inhibitors of downstream KRAS effectors, such as the MEK1/2 kinase inhibitor trametinib, devoid therapeutic effects. However, extensive rewiring regulatory circuits driven by attenuation pathway may induce vulnerabilities relevance. An in-depth molecular analysis transcriptional and epigenomic alterations occurring in PDAC cells initial hours after inhibition trametinib unveiled induction endogenous...
Tumors represent ecosystems where subclones compete during tumor growth. While extensively investigated, a comprehensive picture of the interplay clonal lineages dissemination is still lacking. Using patient-derived pancreatic cancer cells, we created orthotopically implanted replica tumors to trace dynamics unperturbed expansion and dissemination. This model revealed multifaceted nature growth, with rapid changes in fitness leading continuous reshuffling architecture alternating dominance...
Significance α1-Antitrypsin deficiency is one of the most common genetic diseases. Homozygous and heterozygous carriers Z allele α1-antitrypsin are susceptible to developing liver fibrosis cirrhosis. In mouse human samples expressing α1-antitrypsin, we found both miR-34b miR-34c up-regulated by activation FOXO3 upon JNK phosphorylation on Ser 574 . Deletion miR-34b/c resulted in early development increased signaling PDGF pathway, a target miR-34b/c. JNK-activated up-regulation also occur...
Protein solubility problems arise in a wide range of applications, from antibody development to enzyme production, and are linked several major disorders, including cataracts Alzheimer's diseases. To assist scientists designing proteins with improved better understand solubility-related diseases, we introduce SOuLMuSiC, computational tool for the fast accurate prediction impact mutations on protein solubility. Our model is based simple shallow artificial neural network that takes as input...
Abstract One of the major risk factors strongly associated with PDAC is pancreatitis and meta-analysis studies have revealed that inflammation pancreas increases relative developing pancreatic cancer by up to 13-fold. During pancreatitis, acinar cells transiently undergo metaplasia known as ductal (ADM). It well in presence activated oncogenes, for example mutated Kras, this metaplastic state can progress into ADM being first step towards tumorigenesis. To understand pathophysiological role...
α 1 ‐Antitrypsin (AAT) deficiency is one of the most common genetic disorders and liver disease due to Z mutant AAT (ATZ) a prototype conformational disorder protein misfolding with consequent aberrant intermolecular aggregation. In present study, we found that livers PiZ transgenic mice expressing human ATZ have altered expression network hepatocyte transcriptional factors, including nuclear factor‐4α, early down‐regulated induces repression expression. Reduced factor‐4α was associated...
Alpha1-antitrypsin deficiency is a genetic disease that can affect both the lung and liver. The vast majority of patients harbor mutation in serine protease inhibitor 1A (SERPINA1) gene leading to single amino acid substitution results an unfolded protein prone polymerization. defciency-related liver therefore caused by gain-of-function mechanism due accumulation mutant Z alpha1-antitrypsin (ATZ) key example induced toxicity. Intracellular retention ATZ triggers complex injury cascade...
α1-Antitrypsin (AAT) encoded by the SERPINA1 gene is an acute-phase protein synthesized in liver and secreted into circulation. Its primary role to protect lung tissue inhibiting neutrophil elastase. The Z allele of encodes a mutant AAT, named ATZ, that changes structure leads its misfolding polymerization, which cause endoplasmic reticulum (ER) stress disease through gain-of-function toxic mechanism. Hepatic retention ATZ results deficiency one most important circulating proteinase...
Abstract It is unclear how cells counteract the potentially harmful effects of uncoordinated DNA replication in context oncogenic stress. Here, we identify WRAD (WDR5/RBBP5/ASH2L/DPY30) core as a modulator pancreatic ductal adenocarcinoma (PDAC) models. Molecular analyses demonstrated that interacts with replisome complex, disruption DPY30 resulting re-replication, damage, and chromosomal instability (CIN) without affecting cancer cell proliferation. Consequently, immunocompetent models,...
Abstract Life-threatening hyperammonemia occurs in both inherited and acquired liver diseases affecting ureagenesis, the main pathway for detoxification of neurotoxic ammonia mammals. Protein O-GlcNAcylation is a reversible nutrient-sensitive post-translational modification using as substrate UDP-GlcNAc, end-product hexosamine biosynthesis pathway. Here we show that increased UDP-GlcNAc during increases protein enhances ureagenesis. Mechanistically, on specific threonine residues catalytic...
The urea cycle and glutamine synthetase (GS) are the two main pathways for waste nitrogen removal their deficiency results in hyperammonemia. Here, we investigated efficacy of liver-specific GS overexpression therapy To achieve hepatic overexpression, generated a helper-dependent adenoviral (HDAd) vector expressing murine under control expression cassette (HDAd-GS). Compared to mice injected with an unrelated reporter gene (HDAd-alpha-fetoprotein), wild-type increased showed reduced blood...
We performed whole exome sequencing in individuals from a family with autosomal dominant gastropathy resembling Ménétrier disease, premalignant gastric disorder epithelial hyperplasia and enhanced EGFR signalling. disease is believed to be an acquired disorder, but its aetiology unknown. In affected members, we found missense p.V742G variant MIB2, gene regulating NOTCH signalling that has not been previously linked human diseases. The segregated the pedigree, highly conserved amino acid...
Abstract Tumors represent ecosystems where subclones compete during tumor growth. While extensively investigated, a comprehensive picture of the interplay clonal lineages dissemination is still lacking. Using patient-derived pancreatic cancer cells, we created orthotopically-implanted replica tumors to trace dynamics unperturbed expansion and dissemination. This model revealed multifaceted nature growth, with rapid changes in fitness leading continuous reshuffling architecture alternating...
A random sample of 582 blood donors from the district Naples, Italy, was examined for electrophoretic pattern red cell 6-phosphogluconate dehydrogenase. This population found to be polymorphic and gene frequency rarest allele (PGDC = 0.018 ± 0.004) similar that described other populations in Europe.
ABSTRACT Alpha-1 antitrypsin (AAT) deficiency is a common genetic disorder with lung and liver involvement. Most patients carry the Z allele in SERPINA1 that encodes mutant AAT (ATZ) forming hepatotoxic polymers. We found CHOP upregulation activation both mouse (PiZ) human livers expressing ATZ. Compared to controls, juvenile PiZ/ Chop -/- mice showed reduction hepatic ATZ transcriptional response endoplasmic reticulum stress, as consequence of CHOP-mediated increase transcription. was...