A5004632950- Cystic Fibrosis Research Advances
- RNA and protein synthesis mechanisms
- Endoplasmic Reticulum Stress and Disease
- Pancreatitis Pathology and Treatment
- Advanced biosensing and bioanalysis techniques
- ATP Synthase and ATPases Research
- Legume Nitrogen Fixing Symbiosis
- RNA regulation and disease
- Neonatal Respiratory Health Research
- Phagocytosis and Immune Regulation
- Ion channel regulation and function
- RNA modifications and cancer
- RNA Research and Splicing
- Bacterial Genetics and Biotechnology
- Neuroscience and Neuropharmacology Research
- Respiratory viral infections research
- Cancer, Lipids, and Metabolism
- Photoreceptor and optogenetics research
- Heat shock proteins research
- Drug Transport and Resistance Mechanisms
- Robotics and Sensor-Based Localization
- Pediatric Hepatobiliary Diseases and Treatments
- Physiological and biochemical adaptations
- RFID technology advancements
- Fungal and yeast genetics research
Cystic Fibrosis Foundation
2018-2024
Kyung Hee University
2013-2021
Oregon Health & Science University
2015
Yonsei University
2008-2014
Catholic Kwandong University
2012
In cells, biosynthetic machinery coordinates protein synthesis and folding to optimize efficiency minimize off-pathway outcomes. However, it has been difficult delineate experimentally the mechanisms responsible. Using fluorescence resonance energy transfer, we studied cotranslational of first nucleotide-binding domain from cystic fibrosis transmembrane conductance regulator. During synthesis, occurred discretely via sequential compaction N-terminal, α-helical, α/β-core subdomains. Moreover,...
Abstract Premature termination codons (PTCs) are responsible for 10–15% of all inherited disease. PTC suppression during translation offers a promising approach to treat variety genetic disorders, yet small molecules that promote read-through have yielded mixed performance in clinical trials. Here we present high-throughput, cell-based assay identify anticodon engineered transfer RNAs (ACE-tRNA) which can effectively suppress in-frame PTCs and faithfully encode their cognate amino acid. In...
Abstract Protein misfolding causes a wide spectrum of human disease, and therapies that target are transforming the clinical care cystic fibrosis. Despite this success, however, very little is known about how disease-causing mutations affect de novo folding landscape. Here we show inherited, located within first nucleotide-binding domain (NBD1) fibrosis transmembrane conductance regulator (CFTR) have distinct effects on nascent polypeptides. Two these (A455E L558S) delay compaction NBD1...
During acute pancreatitis, protease-activated receptor 2 (PAR2) can be activated by interstitially released trypsin. In the mild form of PAR2 activation exerts local protection against intrapancreatic damage, whereas, in severe mediates some systemic complications. This study aimed to identify molecular mechanisms PAR2-mediated protective effects damage. A pancreatitis was induced an intraperitoneal injection caerulein (40 μg/kg) rats. Effects on damage and mitogen-activated protein (MAP)...
Herein, apoptotic mechanism of Moracin D was explored in prostate cancer cells association with peroxisome proliferator-activated receptor gamma (PPAR-γ)-related signaling involved lipid metabolism. augmented cytotoxicity and sub G1 population PC3 DU145 cells, while were more susceptible to than cells. attenuated the expression caspase-3, poly (ADP-ribose) polymerase (PARP), B-cell lymphoma 2 (Bcl-2), lymphoma-extra-large (Bcl-xL) Consistently, significantly number terminal deoxynucleotidyl...
The ubiquitous ribosome-associated complex (RAC) is a chaperone that spans ribosomes, making contacts near both the polypeptide exit tunnel and decoding center, position prime for sensing coordinating translation folding. Loss of RAC known to result in growth defects sensitization translational osmotic stresses. However, physiological substrates mechanism(s) by which involved responding specific stresses higher eukaryotes remain obscure. data presented here uncover an essential function...
Abstract Background Nonsense or Premature Termination Codon (PTC) mutations of the CFTR gene are pathogenic and found in ∼10% North American people with cystic fibrosis. PTC induce Nonsense-Mediated mRNA Decay (NMD), leading to a substantial (∼80-90%) reduction full-length mRNA. This is key contributor mutation-related pathology. Various approaches evade NMD preserve impacted transcript have been explored but not progressed clinical development, leaving significant hurdle for readthrough...
Genetic mutations cause a wide spectrum of human disease by disrupting protein folding, both during and after synthesis. Transient de-novo folding intermediates therefore represent potential drug targets for pharmacological correction disorders. Here we develop FRET-based high-throughput screening (HTS) assay in 1,536-well format capable identifying small molecules that interact with nascent polypeptides correct genetic, cotranslational defects. Ribosome chain complexes (RNCs) containing...
ABSTRACT Premature termination codons (PTCs) are responsible for 10-15% of all inherited disease. PTC suppression during translation offers a promising approach to treat variety genetic disorders, yet small molecules that promote read-through have yielded mixed performance in clinical trials. We present high-throughput, cell-based assay identify nti c odon e ngineered transfer RNAs (ACE-tRNA) which can effectively suppress in-frame PTCs and faithfully encode their cognate amino acid. In...
The ubiquitous ribosome-associated complex (RAC) is a chaperone that spans ribosomes, making contact near both the polypeptide exit tunnel and decoding center, position prime for coordination of translation folding. Loss RAC results in growth defects sensitization to translational stress. mechanism responding specific stresses remains obscure. Data presented here uncover an essential function mammalian unfolded protein response (UPR), coupling inositol-requiring 1α (IRE1α) branch...