Function and Dysfunction of Myocilin in Glaucoma: New Insight from Proteomics

Raquel Lieberman, PhD
Georgia Institute of Technology (Atlanta, GA)

Co-Principal Investigators

Matthew Torres, PhD
Georgia Institute of Technology
Year Awarded:
2016
Grant Duration:
July 1, 2016 to June 30, 2018
Disease:
Glaucoma
Award Amount:
$75,000
Grant Reference ID:
G2016027
Award Type:
Standard
Award Region:
US Southeastern
Raquel Lieberman, PhD

Identification of Myocilin Posttranslational Modifications and Binding Partners Under Static and Glaucoma-Relevant Mechanical Stretch

Summary

Myocilin, a protein molecule associated with two specific forms of glaucoma, is expressed at high levels in the very same eye tissue that appears to malfunction and contribute to ocular hypertension-- the most common risk factor—in other types of glaucoma. To this day, the normal function of myocilin in the eye tissue and elsewhere in the body remains unknown. We will use knowledge of the myocilin structure and modern proteomics techniques to identify changes in myocilin and interacting partners under distinct glaucoma-relevant environments. This research will help clarify myocilin function and will lead to new targets for novel anti-glaucoma therapies.

Details

The aim of this research is to comprehend molecular changes in myocilin under experimental conditions in the lab that mimic glaucoma. Myocilin is closely associated with several forms of glaucoma, including early-onset inherited open angle glaucoma, and steroid-induced glaucoma. Myocilin is also expressed at relatively high levels in the eye tissue called the trabecular meshwork (TM). Dysfunction of the TM is believed to bring about elevated ocular pressure, the most common glaucoma risk factor leading to retinal degeneration and vision loss. We will use modern high resolution mass spectrometry techniques to investigate changes in myocilin isolated from the eye-derived cells that maintain the TM tissue. Results of our experiments will provide new insight into glaucoma-relevant changes that will lead to a better understanding of myocilin-associated glaucoma as well the identification of novel targets for anti-glaucoma therapies more generally.   

About the Researcher

Raquel L. Lieberman received her bachelor of science degree in chemistry from the Massachusetts Institute of Technology in 1998, and her doctoral degree in chemistry from Northwestern University in Chicago (2005), where she worked with Prof. Amy C. Rosenzweig on biophysical and structural studies of an intramembrane metalloenzyme. After conducting postdoctoral work with Prof. Michael S. Wolfe (Center for Neurological Diseases, Harvard Medical School) and Prof. Gregory A. Petsko (Brandeis) where she expanded to molecular aspects of protein misfolding, she joined the faculty in the School of Chemistry and Biochemistry at Georgia Institute of Technology and is currently an associate professor. Research projects in Dr. Lieberman’s lab focus on molecular aspects of proteins implicated in misfolding disorders.

Personal Story

My resolve to studying protein misfolding was solidified after learning that a close friend of mine, who suffers from the lysosomal storage disorder Gaucher Disease, is alive today because of enzyme replacement therapy. She was one of the three children on the original trial for Cerezyme™ (imiglucerase), a man-made form of an enzyme that occurs naturally in the body, and she continues to take this medication today. It is her courage as an eight-year-old, and the commitment of her family to move from South Africa to Maryland in the hopes of a cure for their child, that motivates me every day in my work to combat human disease.

Don't miss out.
Receive research updates, inspiring stories, and expert advice
Please enter your first name.
Please enter your last name.
Keep me informed about: *
Please select at least one.
You must select at least one disease category.