A5102938140- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- Monoclonal and Polyclonal Antibodies Research
- RNA and protein synthesis mechanisms
- Cell Adhesion Molecules Research
- Biochemical and Structural Characterization
- Lysosomal Storage Disorders Research
- Metal complexes synthesis and properties
- Cellular transport and secretion
- Trypanosoma species research and implications
- Alzheimer's disease research and treatments
- Bacteriophages and microbial interactions
- Angiogenesis and VEGF in Cancer
- Metabolism and Genetic Disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Carbohydrate Chemistry and Synthesis
- Sinusitis and nasal conditions
- HIV Research and Treatment
- Cancer-related Molecular Pathways
- CRISPR and Genetic Engineering
- Mycobacterium research and diagnosis
- Epigenetics and DNA Methylation
- HIV/AIDS drug development and treatment
- RNA Interference and Gene Delivery
- Thermal Analysis in Power Transmission
Northwell Health
2023-2025
Denali Therapeutics (United States)
2018-2024
Codexis (United States)
2021-2023
Stanford University
2005-2016
Albert Einstein College of Medicine
1997-2008
University of Southern California
2007
Massachusetts Institute of Technology
2000-2002
Yeshiva University
1999
George Washington University
1999
Children's National
1999
Engineering human IgG1 Fc binding to a brain endothelial cell–enriched receptor allows enhanced exposure of biotherapeutics in multiple species.
An enzyme transport vehicle enables brain delivery of lysosomal enzymes across the blood-brain barrier in mice.
The ε4 allele of the apolipoprotein E (APOE) gene is strongest genetic risk factor for late-onset Alzheimer's disease (AD) and greatly influences development amyloid-β (Aβ) pathology. Our current study investigated potential therapeutic effects anti-human APOE antibody HAE-4, which selectively recognizes human that co-deposited with Aβ in cerebral amyloid angiopathy (CAA) parenchymal In addition, we tested whether HAE-4 provoked brain hemorrhages, a component amyloid-related imaging...
The apolipoprotein E E4 allele of the APOE gene is strongest genetic factor for late-onset Alzheimer disease (LOAD). There compelling evidence that apoE influences (AD) in large part by affecting amyloid β (Aβ) aggregation and clearance; however, molecular mechanism underlying these findings remains largely unknown. Herein, we tested whether anti–human antibodies can decrease Aβ pathology mice producing both human apoE4, investigated effects. We utilized APPPS1-21 crossed to apoE4-knockin...
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 )...
Exposure of young spinach seedlings (Spinacia oleracea L. cv Bloomsdale) to 5 degrees C leads an increase in the synthesis several 79-kilodalton proteins that are present leaf tissue grown at 20 C. Protein sequence analyses and immunological cross-reactivity indicate this group belongs 70-kilodalton heat-shock family. Steady-state transcript levels protein increased two- threefold within 1 day, but immunoblot suggest steady-state concentration only gradually accumulates low temperature. It...
Quenched autoligation (QUAL) probes are a class of self-reacting nucleic acid that give strong fluorescence signal in the presence fully complementary RNAs and selectivity against single nucleotide differences solution. Here, we describe experiments designed to test whether QUAL can discriminate between bacterial species by detection small their 16S rRNA sequences. Probes were introduced into live cells using amounts detergent, thus eliminating need for fixation, was monitored both...
Significant cross-talk exists between receptors that mediate angiogenesis, such as VEGF receptor-2 (VEGFR2) and α v β 3 integrin. Thus, agents inhibit both would have important therapeutic potential. Here, we used an antagonistic ligand a molecular scaffold to engineer dual-specific proteins bound VEGFR2 integrin with antibody-like affinities inhibited angiogenic processes in vitro vivo. Mutations were introduced into single-chain (scVEGF) retained binding, but prevented receptor...
Recently, a truncated form of the agouti-related protein (AgRP), 4-kDa cystine-knot peptide human origin, was used as scaffold to engineer mutants that bound α<sub>v</sub>β<sub>3</sub> integrin with high affinity and specificity. In this study, we evaluated potential engineered integrin-binding AgRP peptides for use cancer imaging agents in living subjects. <b>Methods:</b> Engineered were prepared by solid-phase synthesis folded vitro purified reversed-phase high-performance liquid...
The results presented describe the effects of various spectator ligands, attached to a platinum 1,2-intrastand d(GpG) cross-link in duplex DNA, on binding high mobility group box (HMGB) domains and TATA-binding protein (TBP). In addition cisplatin-modified 15-base pair DNA probes modified by [Pt(1R,2R-diaminocyclohexane)](2+), cis-[Pt(NH(3))(cyclohexylamine)](2+), [Pt(ethylenediamine)](2+), cis-[Pt(NH(3))(cyclobutylamine)](2+), cis-[Pt(NH(3))(2-picoline)](2+) were examined. Electrophoretic...
cis-trans-cis-Ammine(cyclohexylamine)diacetatodichloroplatinum(IV) is an oral analog of the platinum anti-cancer drug cisplatin that currently in phase III clinical trials. Its active form, {Pt(ammine)(cyclohexylamine)}2+, binds to DNA similarly cisplatin, forming intra- and interstrand cross-links between adjacent purine bases. Since {Pt(ammine)(cyclohexylamine)}2+ contains two different ligands, it can form isomeric 1,2-d(GpG) intrastrand cross-links. Here we report 2.4-Å resolution x-ray...
Abstract Background The MRSA nasal PCR is a screening tool that may help decrease the use of antimicrobials. as test has shown high negative predictive value associated with various infections - including pneumonia, intra-abdominal infections, wounds, and bacteremia. Despite this, been under-utilized for purposes deescalating antibiotics targeting MRSA. Odds Ratios Methods This was retrospective, observational, single-center cohort study within Northwell Health system, approved by...
This study examines in vivo the role and functional interrelationships of components regulating exit from G1 resting phase into DNA synthetic (S) cell cycle. Our approach made use several key experimental attributes developing mouse lens, namely its strong dependence on pRb maintenance postmitotic state, down-regulation cyclins D E up-regulation p57(KIP2) inhibitor lens fiber compartment, ability to target transgene expression this compartment. These provide an ideal context which examine...
A truncated form of the Agouti-related protein (AgRP), a member cystine-knot family, has shown promise as scaffold for engineering novel peptides with new molecular recognition properties. In this study, we replaced constrained six amino acid loop in AgRP nine containing an Arg–Gly–Asp integrin motif, and randomized neighboring residues to create library ∼20 million variants. We displayed mutants fusions on surface yeast used high-throughput fluorescence-activated cell sorting (FACS) isolate...
Fabry disease is caused by a deficiency of α-galactosidase A (GLA) leading to the lysosomal accumulation globotriaosylceramide (Gb3) and other glycosphingolipids. patients experience significant damage heart, kidney, blood vessels that can be fatal. Here we apply directed evolution generate more stable GLA variants as potential next generation treatments for disease. GLAv05 GLAv09 were identified after screening than 12,000 through 8 rounds evolution. Both exhibit increased stability at both...
Cystine-knot miniproteins (knottins) are promising molecular scaffolds for protein engineering applications. Members of the knottin family have multiple loops capable displaying conformationally constrained polypeptides recognition. While previous studies illustrated potential knottins with modified loop sequences, a thorough exploration into tolerated lengths and sequence space scaffold has not been performed. In this work, we used Ecballium elaterium trypsin inhibitor II (EETI) as model...