A5007813039- Ubiquitin and proteasome pathways
- Bacteriophages and microbial interactions
- CAR-T cell therapy research
- Nuclear Receptors and Signaling
- Endoplasmic Reticulum Stress and Disease
- Animal Virus Infections Studies
- SARS-CoV-2 and COVID-19 Research
- Cancer-related Molecular Pathways
- Monoclonal and Polyclonal Antibodies Research
- HIV Research and Treatment
- COVID-19 Clinical Research Studies
- Hepatitis B Virus Studies
- Protein purification and stability
- Cytomegalovirus and herpesvirus research
- Advanced Biosensing Techniques and Applications
- Herpesvirus Infections and Treatments
- Protein Degradation and Inhibitors
- Mitochondrial Function and Pathology
- Glycosylation and Glycoproteins Research
University of California, San Francisco
2021-2025
Hyper-phosphorylated tau accumulates as insoluble fibrils in Alzheimer's disease (AD) and related dementias. The strong correlation between phosphorylated has led to an interest understanding how cellular factors discriminate it from normal tau. Here, we screen a panel of chaperones containing tetratricopeptide repeat (TPR) domains identify those that might selectively interact with We find the E3 ubiquitin ligase, CHIP/STUB1, binds 10-fold more strongly than unmodified presence even...
Carboxyl-terminus of Hsp70-Interacting Protein (CHIP) is an E3 ubiquitin ligase that marks misfolded substrates for degradation. Hyper-activation CHIP has been implicated in multiple diseases, including cystic fibrosis and cancer, suggesting it may be a potential drug target. However, there are few tools available exploring this possibility. Moreover, the best ways inhibiting CHIP's function not obvious, as complex protein composed tetratricopeptide repeat (TPR) domain, U-box coiled-coil...
Abstract In vitro biopanning platforms using synthetic phage display antibody libraries have enabled the identification of antibodies against antigens that were once thought to be beyond scope immunization. Applying these methods challenging targets remains a critical challenge. Here, we present new pipeline, RAPID ( R are A ntibody P hage I solation and D iscrimination), for rare high-affinity targets. uses fluorescent labeled displayed fragment antigen-binding (Fab) isolation binders with...
Viruses are responsible for some of the most deadly human diseases, yet available vaccines and antivirals address only a fraction potential viral pathogens. Here, we provide methodology managing herpesvirus (HHV) infection by covalently inactivating HHV maturational protease via conserved, non-catalytic cysteine (C161). Using cytomegalovirus (HCMV Pr) as model, screened library disulfides to identify molecules that tether C161 inhibit proteolysis, then elaborated hits into irreversible HCMV...
Abstract Background The direct and chaperone‐associated interactions of E3 ubiquitin ligase CHIP with tau in Alzheimer’s disease other tauopathies, regulates turnover, by directly linking it to ubiquitination proteasomal degradation, as well through suppression aggregation. Modulation these CHIP‐driven clearance mechanisms can be an effective treatment strategy. Antigen‐binding antibody fragments (Fabs) are potent tools that highly‐selectively engage target proteins act functional probes or...