Raquel Lieberman
Georgia Institute of Technology, GA·Biochemistry
Glaucoma is a leading cause of blindness. It affects about 70 million people, and roughly 10% of patients still lose their sight despite treatment.
- Fields
Biochemistry
Chemistry
Biophysics
- Topics
glaucoma
myocilin
trabecular meshwork
- Grants
- 2 known grants, through Jun 2029
What they work on
- Screen the baker's yeast gene-deletion library for strains that survive toxic mutant myocilin, to find cellular pathways that make cells vulnerable to this glaucoma protein.
- Determine how protective gene deletions found in yeast reduce mutant myocilin toxicity, following up on preliminary proteostasis hits (genes that help keep proteins properly folded) and on new hits from the full screen.
- Run a high-throughput screen in the yeast model for small molecules that rescue cells from mutant myocilin, as leads for preventing drainage-tissue cell death in glaucoma.
- Track how myocilin's olfactomedin (OLF) domain, the part that forms fibers, starts to clump, using hydrogen-deuterium exchange mass spectrometry and NMR on normal and variant proteins.
- Compare the end-point structures of OLF aggregates with known amyloids using solid-state NMR, and test whether intermediate aggregates are toxic to cells.
- Evaluate common full-length myocilin variants for experimental signs of disease-causing behavior, to clarify which variants may contribute to glaucoma.
More about the research
Most cases involve high pressure inside the eye. That pressure builds when the trabecular meshwork, the eye's fluid drainage tissue, stops working properly. Mutations in myocilin, a protein made in large amounts by trabecular meshwork cells, cause an inherited, early-onset form of glaucoma. Mutant myocilin cannot leave the cell. It piles up in the endoplasmic reticulum (ER), the compartment where proteins are folded, and it kills the drainage cells. Current treatments only lower eye pressure. The lab studies how myocilin misfolds and why misfolded myocilin is toxic, with the goal of laying the groundwork for therapies that target the cause of the disease.
Why it matters
People with inherited, early-onset glaucoma caused by myocilin mutations could benefit from therapies that stop drainage-tissue cells from dying, rather than only lowering eye pressure. The work aims to identify genes, pathways and small-molecule leads that protect these cells. It also aims to clarify how myocilin forms amyloid, which could inform new ways to diagnose and treat this form of glaucoma. Because many myocilin variants tend to misfold, the findings may also apply to a broader group of glaucoma patients.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Weiming Mao
Indiana University-Purdue University-Indianapolis, IN·Pharmacology
Test whether activating canonical Wnt signaling prevents steroid-induced high eye pressure in mice, using Wnt reporter mice and conditional knockout mice that lack β-catenin, the pathway's key protein.
Daniel Gewirth
University at Buffalo, NY·Biochemistry
Produce Grp94, the ER chaperone of the hsp90 family, with controlled glycosylation at each of its sequons (sugar-attachment sites), using the lab's in-cell expression system.
Qinglian Liu
Virginia Commonwealth University, VA·Biochemistry
Determine the in vivo role of Hsp110 holdase activity (keeping unfolded proteins from clumping) in protein folding, using the selective inhibitor 2H and the genetics of the yeast Saccharomyces cerevisiae.
The school
Georgia Institute of Technology: 50 labs on PI Pages, $1.5B a year on research, 572 research doctorates a year.
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