A5011303065- RNA and protein synthesis mechanisms
- Metalloenzymes and iron-sulfur proteins
- Monoclonal and Polyclonal Antibodies Research
- Bacterial Genetics and Biotechnology
- Celiac Disease Research and Management
- CRISPR and Genetic Engineering
- Bacteriophages and microbial interactions
- Protein purification and stability
- Glycosylation and Glycoproteins Research
- Asymmetric Hydrogenation and Catalysis
- Peptidase Inhibition and Analysis
- DNA and Nucleic Acid Chemistry
- Organometallic Complex Synthesis and Catalysis
- Trypanosoma species research and implications
- Protein Structure and Dynamics
- Metal complexes synthesis and properties
- Analytical Chemistry and Chromatography
- Lysosomal Storage Disorders Research
- Nanocluster Synthesis and Applications
- Inorganic Chemistry and Materials
- Kawasaki Disease and Coronary Complications
- Circadian rhythm and melatonin
- Microscopic Colitis
- Transgenic Plants and Applications
- Liquid Crystal Research Advancements
Second Affiliated Hospital of Jilin University
2025
Denali Therapeutics (United States)
2021-2024
Liaoning University
2024
Chinese Academy of Sciences
1998-2021
Tianjin Institute of Industrial Biotechnology
2021
AstraZeneca (United States)
2019-2021
Baylor College of Medicine
1997-2009
Shanghai Institute of Ceramics
2009
Lexicon Pharmaceuticals (United States)
2008
Institute of Biophysics
2006-2008
Celiac Sprue, a widely prevalent autoimmune disease of the small intestine, is induced in genetically susceptible individuals by exposure to dietary gluten. A 33-mer peptide was identified that has several characteristics suggesting it primary initiator inflammatory response gluten Sprue patients. In vitro and vivo studies rats humans demonstrated stable toward breakdown all gastric, pancreatic, intestinal brush-border membrane proteases. The reacted with tissue transglutaminase, major...
Two recently identified immunodominant epitopes from α-gliadin account for most of the stimulatory activity dietary gluten on intestinal and peripheral T lymphocytes in patients with celiac sprue. The proteolytic kinetics peptides containing these were analyzed vitro using soluble proteases bovine porcine pancreas brush-border membrane vesicles adult rat intestine. We showed that proline-glutamine-rich are exceptionally resistant to enzymatic processing. Moreover, as estimated residual...
Dietary gluten proteins from wheat, rye, and barley are the primary triggers for immuno-pathogenesis of Celiac Sprue, a widespread immune disease small intestine. Recent molecular structural analyses representative proteins, most notably α- γ-gliadin have improved our understanding these pathogenic mechanisms. In particular, based on properties 33-mer peptide, generated α-gliadin under physiological conditions, link between digestive resistance inflammatory character has been proposed. Here,...
Prolyl endopeptidases have potential for treating coeliac sprue, a disease of the intestine caused by proteolytically resistant peptides from proline-rich prolamins wheat, barley and rye. We compared properties three similar bacterial prolyl endopeptidases, including known enzymes Flavobacterium meningosepticum (FM) Sphingomonas capsulate (SC) novel enzyme Myxococcus xanthus (MX). These were interrogated with reference chromogenic substrates, as well two related gluten (PQPQLPYPQPQLP...
Persistent hyperinsulinemic hypoglycemia of infancy is caused by inappropriate and excessive secretion insulin. Although the disease rare in outbred communities (approximately 1 case per 50,000 persons), incidence approximately 2500 inbred Arabic which there a familial (autosomal recessive) form disease. The most commonly presents with severe few hours after birth, although some cases present several weeks or months. Some patients have response to treatment diazoxide somatostatin, but others...
Bile acids are potentially toxic compounds and their levels of hepatic production, uptake export tightly regulated by many inputs, including circadian rhythm. We tested the impact disrupting peripheral clock on integral steps bile acid homeostasis.
Delivery of biotherapeutics across the blood-brain barrier (BBB) is a challenge. Many approaches fuse to platforms that bind transferrin receptor (TfR), brain endothelial cell target, facilitate receptor-mediated transcytosis BBB. Here, we characterized pharmacological behavior two distinct TfR-targeted fused iduronate 2-sulfatase (IDS), lysosomal enzyme deficient in mucopolysaccharidosis type II (MPS II), and compared relative exposures functional activities both mouse models. IDS...
Prolyl endopeptidases (PEPs) are a unique class of serine proteases with considerable therapeutic potential for the treatment celiac sprue. The crystal structures two didomain PEPs have been solved in alternative configurations, thereby providing insights into mode action these enzymes. structure Sphingomonas capsulata PEP, and refined to 1.8-A resolution, revealed an open configuration active site. In contrast, inhibitor-bound PEP from Myxococcus xanthus was crystallized (1.5-A resolution)...
Two members of the angiopoietin-like family proteins, ANGPTL3 and ANGPTL4, have been shown to play important roles in modulating lipoprotein metabolism body. Both proteins were found suppress lipase (LPL) activity vitro as well vivo. However, their mechanisms inhibition remained poorly understood. Using enzyme kinetic analysis with purified recombinant we key mechanistic differences between ANGPTL4. reduced LPL catalytic but did not significantly alter its self-inactivation rate. In...
Monoclonal antibodies (mAbs) are complex molecular structures. They often prone to development challenges particularly at high concentrations due undesired solution properties such as reversible self-association, viscosity, and liquid–liquid phase separation. In addition formulation optimization, applying protein engineering can provide an alternative mitigation strategy. Protein during the discovery great benefits optimize properties, resulting in improved developability profiles. Here, we...
Antibodies are an important class of therapeutics that have significant clinical impact for the treatment severe diseases. Computational tools to support antibody drug discovery been developing at increasing rate over last decade and typically rely upon a predetermined co-crystal structure bound antigen structural predictions. Here, we show example successful in silico affinity maturation hybridoma derived antibody, AB1, using just homology model fragment variable region protein-protein...
Abstract Although the first generation of immunotherapies for Alzheimer’s disease (AD) are now clinically approved, amyloid-related imaging abnormalities (ARIA) remain a major safety problem this class drugs. Here, we report an antibody transport vehicle (ATV) targeting transferrin receptor (TfR) brain delivery amyloid beta (Aý) antibodies that significantly reduced ARIA-like lesions and improved plaque target engagement in mouse model deposition. Asymmetrical Fc mutations (ATV cisLALA )...
The immunoglobulin Fc region is a homodimer consisted of two sets CH2 and CH3 domains has been exploited to generate two-arm protein fusions with high expression yields, simplified purification processes extended serum half-life. However, attempts one-arm fusion proteins monomeric Fc, one set domains, are often plagued challenges such as weakened binding FcRn or partial monomer formation. Here, we demonstrate the generation stable IgG4 unique combination mutations at CH3-CH3 interface using...
Abstract The influence of vinyl ester/styrene network structure on thermal and mechanical properties was investigated. crosslink density the resins altered by changing molecular weight ester oligomer varying amount styrene used during crosslinking reaction leading to variations in both physical chemical composition polymeric networks. glass transition temperatures polymers were found increase systematically with increasing without additional as determined from differential scanning...
The hyperthermophilic Ssh10b from Sulfolobus shibatae is a member of the Sac10b family, which has been postulated to play role in chromosomal organization Archaea. capable significantly constraining negative DNA supercoils at elevated temperatures. In this study, solution structure dimeric P62A mutant ([P62A]Ssh10b) was determined by multidimensional NMR spectroscopy. backbone 15N dynamics, H/D exchange with and without denaturant GdmSCN, chemical thermal denaturation experiments were...
Targeted strategies to deliver and retain drugs kidneys are needed improve drug accumulation efficacy in a myriad of kidney diseases. These delivery systems show potential for improving the therapeutic windows acting kidney. Biodistribution antibody-based therapeutics vivo is governed by several factors including binding affinity, size, valency. Investigations how biophysical biochemical properties biologics enable them overcome biological barriers reach therefore interest. Although renal...