A5017626758- Glycosylation and Glycoproteins Research
- SARS-CoV-2 and COVID-19 Research
- Animal Virus Infections Studies
- Evolution and Genetic Dynamics
- Protein Structure and Dynamics
- Peptidase Inhibition and Analysis
- Monoclonal and Polyclonal Antibodies Research
- Glaucoma and retinal disorders
- CRISPR and Genetic Engineering
- Signaling Pathways in Disease
- Click Chemistry and Applications
- Cancer Research and Treatments
- Genetic Associations and Epidemiology
- Biochemical and Structural Characterization
- Bacteriophages and microbial interactions
- COVID-19 Clinical Research Studies
- Innovative Microfluidic and Catalytic Techniques Innovation
- SARS-CoV-2 detection and testing
- Retinal Diseases and Treatments
- Ubiquitin and proteasome pathways
- Retinal Development and Disorders
- Biochemical and Molecular Research
- Microbial Metabolic Engineering and Bioproduction
The University of Texas at Austin
2021-2024
Rutgers, The State University of New Jersey
2019-2022
Quantitative BioSciences
2021
Michigan State University
2017-2019
University of Colorado Boulder
2019
To address the ongoing SARS-CoV-2 pandemic and prepare for future coronavirus outbreaks, understanding protective potential of epitopes conserved across variants lineages is essential. We describe a highly conserved, conformational S2 domain epitope present only in prefusion core β-coronaviruses: apex residues 980–1006 flexible hinge. Antibody RAY53 binds native hinge MERS-CoV spikes on surface mammalian cells mediates antibody-dependent cellular phagocytosis cytotoxicity against spike...
Abstract Our lack of total understanding the intricacies how enzymes behave has constrained our ability to robustly engineer substrate specificity. Furthermore, mechanisms natural evolution leading improved or novel specificities are not wholly defined. Here we generate near-comprehensive single-mutation fitness landscapes comprising >96.3% all possible single nonsynonymous mutations for hydrolysis activity an amidase expressed in E. coli with three different substrates. For selections,...
ABSTRACT Three pathogenic human coronaviruses have emerged within the last 20 years, with SARS-CoV-2 causing a global pandemic. Although therapeutic antibodies targeting spike currently focus on poorly conserved receptor-binding domain, essential neutralizing epitopes more S2 domain may provide broader protection. We report an antibody binding epitope in pre-fusion core of MERS-CoV, SARS-CoV and domains. Antibody 3A3 binds conformational ~2.5 nM affinity neutralizes from SARS-CoV, variants...
It is incompletely understood how biophysical properties like protein stability impact molecular evolution and epistasis. Epistasis defined as specific when a mutation exclusively influences the phenotypic effect of another mutation, often at physically interacting residues. In contrast, nonspecific epistasis results influenced by large number nonlocal mutations. As most mutations are pleiotropic, in vivo folding probability-governed basal stability-is thought to determine activity-enhancing...
Confining the activity of a designed protein to specific microenvironment would have broad-ranging applications, such as enabling cell type-specific therapeutic action by enzymes while avoiding off-target effects. While many natural are synthesized inactive zymogens that can be activated proteolysis, it has been challenging redesign any chosen enzyme similarly stimulus responsive. Here, we develop massively parallel computational design, screening, and next-generation sequencing-based...
Recombinant antibodies are a promising class of therapeutics to treat protein misfolding associated with neurodegenerative diseases, and several that inhibit aggregation approved or in clinical trials Alzheimer's disease. Here, we developed targeting the aggregation-prone β-propeller olfactomedin (OLF) domain myocilin, variants which comprise strongest genetic link glaucoma cause early onset vision loss for million individuals worldwide. Mutant myocilin aggregates intracellularly endoplasmic...
Recombinant antibodies with well-characterized epitopes and known conformational specificities are critical reagents to support robust interpretation reproducibility of immunoassays across biomedical research. For myocilin, a protein prone misfolding that is associated glaucoma an emerging player in other human diseases, currently available unable differentiate among the numerous disease-associated states. This fundamentally constrains efforts understand connection between myocilin...
Abstract It is incompletely understood how biophysical properties like protein stability impact molecular evolution and epistasis. Epistasis defined as specific when a mutation exclusively influences the phenotypic effect of another mutation, often at physically interacting residues. By contrast, nonspecific epistasis results influenced by large number non-local mutations. As most mutations are pleiotropic, in vivo folding probability – governed basal thought to determine activity-enhancing...
Most chemotherapy targets dividing cells, rather than just tumor cells. This causes the failure of chemotherapy, as dosing limited by side-effects leads to drug resistance and relapse. One strategy overcome this, referred Directed Enzyme Prodrug Therapy (DEPT), involves administration an inactive prodrug that is activated a foreign enzyme at site. targeting can be achieved using mechanisms include tumor-directed antibodies or viruses. Clinical trials have demonstrated effectiveness DEPT, but...
Abstract Confining the activity of a designed protein to specific microenvironment would have broad-ranging applications, such as enabling cell type-specific therapeutic action by enzymes while avoiding off-target effects. While many natural are synthesized inactive zymogens that can be activated proteolysis, it has been challenging re-design any chosen enzyme similarly stimulus-responsive. Here, we develop massively parallel computational design, screening, and next-generation...