"Development of Recombinant Antibodies for Detecting Multiple Conformational States of Glaucoma-associated Myocilin”

Minh Thu "Alice" Ma
Ph.D. Candidate (Lieberman lab)
Georgia Tech

ABSTRACT
Throughout biomedical research, antibodies that recognize well-characterized epitopes are key reagents in the reproducibility and interpretation of immunoassays. Over the past three decades and after the COVID-19 pandemic, monoclonal antibodies have also emerged as a major class of successful clinical drugs. However, no such treatment currently exists for the debilitating eye disease glaucoma, which is the second leading cause of blindness worldwide. The heritable subtype of the most common type of glaucoma, POAG, is associated with the misfolding of the protein myocilin: mutant myocilin aggregates within the eye tissue trabecular meshwork, leading to cell death, severe damage to the optic nerve, and vision loss. Here, we develop recombinant, conformational antibodies that specifically target myocilin for research and therapeutics applications. These novel antibodies supersede existing commercial reagents due to their quality control and biological insight gleaned. Importantly, our antibodies also enable degradation of aggressive disease mutants of myocilin through cellular mechanisms afforded by their unique structural interactions with the protein. These exciting results provide proof of concept that targeted antibodies that ameliorate the insult of mutant myocilin aggregation could be therapeutic, and represent a new paradigm for treating other diseases associated with protein misfolding.

The F. L. "Bud" Suddath and Frances "Lee" Gafford Suddath Fellowship Award was established by family and friends in recognition of Bud Suddath's contributions as a Georgia Tech faculty member and to support Bud and Lee's shared interest in graduate education in the fields of biology, biochemistry and biomedical engineering. The fellowship award is given annually to Georgia Tech Ph.D. students, typically within one year of graduation, who have demonstrated significant achievement in research of fundamental importance in the fields of biology, biochemistry, or biomedical engineering and are working in laboratories affiliated with Georgia Tech's Institute of Bioengineering and Biosciences (IBB).