Antibody-mediated clearance of an ER-resident aggregate that causes glaucoma.

Recombinant antibodies are a promising class of therapeutics to treat protein misfolding associated with neurodegenerative diseases, and several antibodies that inhibit aggregation are approved or in clinical trials to treat Alzheimer's disease. Here, we developed antibodies targeting the aggregation-prone β-propeller olfactomedin (OLF) domain of myocilin, variants of which comprise the strongest genetic link to glaucoma and cause early onset vision loss for several million individuals worldwide. Mutant myocilin aggregates intracellularly in the endoplasmic reticulum (ER).

Display of Native SARS-CoV-2 Spike on Mammalian Cells to Measure Antibody Affinity and ADCC.

COVID-19 pandemic led to the rapid development of antibody-based therapeutics and vaccines targeting the SARS-CoV-2 spike protein. Several antibodies have been instrumental in protecting vulnerable populations, but their utility was limited by the emergence of spike variants with diminished susceptibility to antibody binding and neutralization. Moreover, these spike variants exhibited reduced neutralization by polyclonal antibodies in vaccinated individuals.

P2 purinergic receptor expression and function in tumor-related immune cells.

P2 purinergic receptor expression is dysregulated in multiple cancer subtypes and is associated with worse outcomes. Studies identify roles for P2 purinergic receptors in tumor cells that drive disease aggressiveness. There is also sufficient evidence that P2 purinergic receptor expression within the tumor microenvironment (TME) is critical for disease initiation and progression.

Structure-based design of a soluble human cytomegalovirus glycoprotein B antigen stabilized in a prefusion-like conformation.

Human cytomegalovirus (HCMV) glycoprotein B (gB) is a class III membrane fusion protein required for viral entry. HCMV vaccine candidates containing gB have demonstrated moderate clinical efficacy, but no HCMV vaccine has been approved. Here, we used structure-based design to identify and characterize amino acid substitutions that stabilize gB in its metastable prefusion conformation.