A5042239870- Protein purification and stability
- Monoclonal and Polyclonal Antibodies Research
- Lipid Membrane Structure and Behavior
- Viral Infectious Diseases and Gene Expression in Insects
- Molecular Sensors and Ion Detection
- Alzheimer's disease research and treatments
- Biosimilars and Bioanalytical Methods
- Advanced biosensing and bioanalysis techniques
- Drug Transport and Resistance Mechanisms
- Heat shock proteins research
- Transgenic Plants and Applications
- Protein Structure and Dynamics
- Endoplasmic Reticulum Stress and Disease
- Microfluidic and Bio-sensing Technologies
- RNA Interference and Gene Delivery
- Cellular transport and secretion
- Microfluidic and Capillary Electrophoresis Applications
- Mineral Processing and Grinding
- Prion Diseases and Protein Misfolding
- Safe Handling of Antineoplastic Drugs
- ATP Synthase and ATPases Research
- Neonatal Respiratory Health Research
- Drug Solubulity and Delivery Systems
- HIV/AIDS Research and Interventions
- HIV-related health complications and treatments
Lonza (Switzerland)
2016-2020
Roche (Switzerland)
2015-2018
Novartis (Switzerland)
2011-2014
Scripps Research Institute
2005-2012
Drugs for Neglected Diseases Initiative
2012
University of Notre Dame
2002-2008
Amyloid is a generally insoluble, fibrous cross-beta sheet protein aggregate. The process of amyloidogenesis associated with variety neurodegenerative diseases including Alzheimer, Parkinson, and Huntington disease. We report the discovery an unprecedented functional mammalian amyloid structure generated by Pmel17. This demonstrates that fundamental nonpathological fold utilized organisms from bacteria to humans. have found Pmel17 templates accelerates covalent polymerization reactive small...
A fluorescent assay based on the chloride-sensitive probe, lucigenin, is developed for monitoring chloride transport into vesicles, and used to compare effectiveness of three steroid-derived transporters.
The activator of Hsp90 ATPase 1, Aha1, has been shown to participate in the chaperone cycle by stimulating low intrinsic activity Hsp90. To elucidate structural basis for stimulation human we have developed novel mass spectrometry approaches that demonstrate N- and C-terminal domains Aha1 cooperatively bind across dimer interface modulate ATP hydrolysis client vivo. Mutations both impair its ability stimulate vitro vivo system folding trafficking wild-type variant (DeltaF508) cystic fibrosis...
Subvisible proteinaceous particles which are present in all therapeutic protein formulations the focus of intense discussions between health authorities, academics and biopharmaceutical companies context concerns that such could promote unwanted immunogenicity via anti-drug antibody formation. In order to provide further understanding subject, this study closely examines specific biological effects may exert on dendritic cells (DCs) as most efficient antigen-presenting cell population...
Crossing the barriers: Membrane transport, a well-established phenomenon for neutral cation receptors such as valinomycin, has been demonstrated anion-binding "cholapods". The cholapods promote chloride efflux from vesicles by an antiport mechanism and mediate anion flow through live cells grown epithelia (see schematic representation).
Chloride transport by a series of steroid-based "cholapod" receptors/carriers was studied in vesicles. The principal method involved preincorporation the cholapods vesicle membranes, and use lucigenin fluorescence quenching to detect inward-transported Cl-. results showed partial correlation between anion affinity activity, that changes at steroidal 7 12 positions affected both properties concert. However, 3-position yielded irregular effects. Among new steroids investigated...
Proteostasis (Balch WE, Morimoto RI, Dillin A, Kelly JW. Adapting proteostasis for disease intervention. Science 2008;319:916–919) refers to the biology that maintains proteome in health and disease. is challenged by most common mutant cystic fibrosis, ΔF508, a chloride channel [the fibrosis transmembrane conductance regulator (CFTR)] exhibits temperature‐sensitive phenotype coupling coatomer complex II (COPII) transport machine exit from endoplasmic reticulum. Whether rescue of export ΔF508...
Protein folding is the primary role of proteostasis network (PN) where chaperone interactions with client proteins determine success or failure reaction in cell. We now address how Phe508 deletion NBD1 domain cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein responsible for impacts binding CFTR cellular chaperones. applied single ion monitoring mass spectrometry (SRM-MS) to quantitatively characterize stoichiometry heat shock (Hsps) intermediates vivo and mapped sites...
A current concern with the use of therapeutic proteins is likely presence aggregates and submicrometer, subvisible, visible particles. It has been proposed that particles may lead to unwanted increases in immune response a possible impact on safety or efficacy. The aim this study was thus evaluate ability subvisible antibody break tolerance an IgG1 transgenic mouse model understand particle attributes might play role process. We investigated immunogenic properties (unfractionated, mixed...
A synthetic receptor, with an ability to bind sodium or potassium chloride as a contact ion-pair, is shown effectively transport either salt across vesicle membranes. Significant observed even when the transporter ∶ phospholipid ratio low 1 2500. Chloride efflux from unilamellar vesicles monitored using selective electrode. Mechanistic studies indicate that facilitated due uncomplexed diffusing into and transporter–salt complex out. Vesicle influx experiments are also reported, where of ions...
The formation of undesired high molecular weight species such as dimers is an important quality attribute for therapeutic monoclonal antibody formulations. Therefore, the thorough understanding mAb dimerization and detailed characterization great interest future pharmaceutical development antibodies. In this work, we focused on analyses different regarding size, surface properties, chemical identity, overall structure localization possible sites. Dimer fractions mAbs were isolated to a...