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Welcome to the Lieberman Lab at Georgia Tech!
We are interested in the molecular details of how cells survive by recognizing and responding to intracellular signals. Eukaryotic cells employ several mechanisms to maintain homeostasis, and if these systems are mis-regulated, changes in metabolite concentrations or protein production/folding eventually lead to a host of diseases. In addition, some of these pathways exist in and are exploited by bacterial pathogens and viruses to gain entry into eukaryotic cells. We seek to understand the details of structure, function, and mechanism of proteins involved in these highly regulated pathways, focusing on enzymes that perform hydrolysis reactions in an unexpected chemical environment: within lipid membrane or near the surface of membranes. In the long term, we hope to identify small molecule inhibitors to modulate these activities and prevent diseases associated with aberrant signaling behavior.
Our methods focus on protein crystallography, biochemical and biophysical characterization, in silico modeling, and drug design.
Our research falls into two categories:
- Protein Misfolding and Trafficking
- Intramembrane proteolysis
- Development of Glucose Regulated Protein 94-Selective Inhibitors based on the BnIm and Radamide Scaffold.
- Increased Fab thermoresistance via VH-targeted directed evolution.
- Structural and biophysical characterization of an epitope-specific engineered Fab fragment and complexation with membrane proteins: implications for co-crystallization.
- Structural basis for misfolding in myocilin-associated glaucoma.