A5077042737- Autophagy in Disease and Therapy
- Lysosomal Storage Disorders Research
- Endoplasmic Reticulum Stress and Disease
- Viral Infectious Diseases and Gene Expression in Insects
- Cellular transport and secretion
- CRISPR and Genetic Engineering
- Nanoparticles: synthesis and applications
- Advanced Nanomaterials in Catalysis
- Calcium signaling and nucleotide metabolism
- Bacterial Genetics and Biotechnology
- RNA Interference and Gene Delivery
- Transgenic Plants and Applications
- Parkinson's Disease Mechanisms and Treatments
- Gene Regulatory Network Analysis
- Biochemical and Structural Characterization
- Bacteriophages and microbial interactions
- Lipid Membrane Structure and Behavior
- Click Chemistry and Applications
- RNA and protein synthesis mechanisms
- Virus-based gene therapy research
- Ubiquitin and proteasome pathways
- Protein Degradation and Inhibitors
- Chemical Synthesis and Analysis
- Monoclonal and Polyclonal Antibodies Research
- Nanopore and Nanochannel Transport Studies
Rice University
2016-2025
University of Pittsburgh
2013
The University of Texas at Austin
2004-2008
Scripps Research Institute
2008
Baylor College of Medicine
2004
This work examines the effect of nanocrystal diameter and surface coating on reactivity cerium oxide nanocrystals with H2O2 both in chemical solutions cells. Monodisperse were formed organic solvents from decomposition precursors, subsequently phase transferred into water using amphiphiles as nanoparticle coatings. Quantitative analysis antioxidant capacity CeO2-x gas chromatography a luminol test revealed that 2 mol reacted every mole cerium(III), suggesting reaction proceeds via...
Loss-of-function diseases are often caused by destabilizing mutations that lead to protein misfolding and degradation. Modulating the innate homeostasis (proteostasis) capacity may rescue of native folding mutated variants, thereby ameliorating disease phenotype. In lysosomal storage disorders (LSDs), a number highly prevalent alleles have missense do not impair enzyme's catalytic activity but destabilize its structure, resulting in degradation misfolded protein. Enhancing cellular enables...
Aggregation of α-synuclein (α-syn) is associated with the development a number neurodegenerative diseases, including Parkinson's disease (PD). The formation α-syn aggregates results from aberrant accumulation misfolded and insufficient or impaired activity two main intracellular protein degradation systems, namely ubiquitin-proteasome system autophagy-lysosomal pathway. In this study, we investigated role transcription factor EB (TFEB), master regulator pathway, in preventing human...
Cerium oxide nanoparticles (nanoceria) are widely used in a variety of industrial applications including UV filters and catalysts. The expanding commercial scale production use ceria have inevitably increased the risk release nanoceria into environment as well human exposure. biomedical is also being currently investigated because its recently characterized antioxidative properties. In this study, we impact on lysosome-autophagy system, main catabolic pathway that activated mammalian cells...
2-Hydroxypropyl-β-cyclodextrin (HPβCD) is a Food and Drug Administration-approved excipient used to improve the stability bioavailability of drugs. Despite its wide use as drug delivery vehicle recent approval clinical trial evaluate potential for treatment cholesterol storage disorder, cellular pathways involved in adaptive response that activated upon exposure HPβCD are still poorly defined. Here, we show cell with results activation transcription factor EB, master regulator lysosomal...
Lysosomal storage disorders are often caused by mutations that destabilize native folding and impair trafficking of secretory proteins. We demonstrate endoplasmic reticulum (ER)-associated degradation (ERAD) prevents mutated lysosomal enzymes in patient-derived fibroblasts from two clinically distinct disorders, namely Gaucher Tay-Sachs disease. Prolonging ER retention via ERAD inhibition enhanced folding, trafficking, activity these unstable enzyme variants. Furthermore, combining with...
Protein aggregation is the hallmark of a number neurodegenerative diseases including Parkinson's and Huntington's diseases. There significant interest in understanding molecular mechanisms involved self-association fibrillization monomeric soluble proteins into insoluble deposits vivo vitro. Probes with novel properties, such as red-shifted emission, large Stokes shifts, high photostability, are desirable for variety protein studies. To respond to increasing need aggregation–responsive...
A number of engineered nanoparticles induce autophagy, the main catabolic pathway that regulates bulk degradation cytoplasmic material by lysosomes. Depending on specific physico-chemical properties nanomaterial, however, nanoparticle-induced autophagy may have different effects cell physiology, ranging from enhanced autophagic to blockage flux. To investigate molecular mechanisms underlying impact nanoparticle charge nature response, we tested polystyrene (50 nm) with neutral, anionic, and...
Misfolding and aggregation of α-synuclein (α-syn) is associated with the development a number neurodegenerative diseases including Parkinson's disease (PD). Analyses post mortem tissues revealed presence molecular chaperones within α-syn aggregates, suggesting that play role in misfolding aggregation. In fact, inhibition chaperone activity aggravates toxicity, overexpression chaperones, particularly 70-kDa heat shock protein (Hsp70), protects against α-syn-induced toxicity. this study, we...
We report the use of an array microcantilevers to measure specific binding Salmonella peptides derived from phage display libraries. Selectivity these phage-derived for spp. and other pathogens (Listeria monocytogenes Escherichia coli) are compared with a commercially available anti-Salmonella antibody antimicrobial peptide alamethicin. A Langmuir isotherm model was applied determine affinity constants pathogens. One particular peptide, MSal 020417, demonstrated higher than is able...
Oral colonic drug delivery systems (CDDSs) are oftentimes associated with a short duration of action and poor tissue specificity. To address these challenges, we engineered an oral prodrug that leverages the engraftment semi-permanence gut commensals to create long-acting depot. We show two synthetic stem peptide probes can be stereoselectively incorporated onto surface bacteria in C57BL/6 mice following administration. then consisting budesonide, corticosteroid otherwise limiting side...
Abstract Manipulation of biomacromolecules is ideally achieved through unique and bioorthogonal chemical reactions genetically encoded, naturally occurring functional groups. The toolkit methods for site‐specific conjugation limited by selectivity concerns a dearth groups with orthogonal reactivity. We report that pyroglutamate amide N−H bonds exhibit copper‐catalyzed Chan–Lam coupling at pyroglutamate‐histidine dipeptide sequences. residue readily incorporated into proteins interest natural...
In the Escherichia coli periplasm, formation of protein disulfide bonds is catalyzed by DsbA and DsbC. a monomer that maintained in fully oxidized state membrane enzyme DsbB, whereas DsbC dimer kept reduced second protein, DsbD. Although catalytic regions are composed structurally homologous thioredoxin motif domains, serves only as an oxidase vivo , catalyzes reduction isomerization also exhibits significant chaperone activity. To reconcile distinct activities DsbA, we constructed series...
Protein function is typically studied and engineered by modulating protein levels within the complex cellular environment. To achieve fast, targeted, predictable control of without genetic manipulation target, we developed a technology for post-translational depletion based on bifunctional molecule (NanoDeg) consisting antigen-binding fragment from Camelidae species heavy-chain antibody (nanobody) fused to degron signal that mediates degradation through proteasome. We provide...
Monitoring the aggregation of proteins within cellular environment is key to investigating molecular mechanisms underlying formation off-pathway protein assemblies associated with development disease and testing therapeutic strategies prevent accumulation non-native conformations. It remains challenging, however, couple events pathogenesis a genetic circuits monitor their progression in quantitative fashion using synthetic biology tools. To link propensity target expression an easily...
Gaucher's disease is caused by deficiency of lysosomal glucocerebrosidase (GC) activity and accumulation GC substrate, glucosylceramide. A number point mutations in encoding gene have been reported to destabilize the enzyme native structure, resulting protein misfolding degradation. Particularly, L444P variant, often associated with neuropathic manifestations disease, severely destabilized immediately degraded, complete loss enzymatic activity. In addition, glucosylceramide causes Ca2+...
Gaucher's disease (GD) is characterized by loss of lysosomal glucocerebrosidase (GC) activity. Mutations in the gene encoding GC destabilize protein's native folding leading to ER-associated degradation (ERAD) misfolded enzyme. Enhancing cellular capacity remodeling proteostasis network promotes and activity mutated variants. However, modulators reported so far, including ERAD inhibitors, trigger stress lead induction apoptosis. We show herein that lacidipine, an L-type Ca2+ channel blocker...