The Georgiou Lab is currently working on the discovery and development of protein therapeutics by capitalizing on state of the art protein engineering and directed evolution technologies. Work in the group includes: (1) Methods for discovering and increasing the potency of therapeutic antibodies; (2) Novel antibody therapeutics that activate the adaptive immune system to kill cancer cells; (3) Engineering of human therapeutic enzymes for the treatment of a variety of malignancies; (4) Design of proteolytic enzymes that cleave and inactivate disease targets; (5) Molecular signatures of the immune responses in disease states. In addition, the group is also interested on a number of issues related to the mechanism of protein biogenesis in bacteria.
Protein Engineering
Together with Professor Brent L. Iverson, Chemistry and Biochemistry, University of Texas, Austin we have developed a number of complementary technologies for the isolation of ligand-binding proteins and enzymes from very large libraries of mutants expressed in bacteria. We have used these and other relevant technologies for the engineering of novel therapeutic antibodies and enzymes.
Currently main areas of study include:
1) The discovery and production of IgG antibodies using bacteria.
2) Development of antibodies with improved therapeutic properties.
3) Development of specific therapeutic antibodies for cancer and inflammation.
4) Engineering of humanized enzymes that can catalyze therapeutically important reactions without eliciting adverse immune responses.
Protein Biogenesis
In the cell protein synthesis occurs in the cytoplasm. Newly synthesized proteins may fold into their final three dimensional conformation, be exported from the cytoplasm so that they can be localized in other subcellular compartments, or, in some instances, subjected to degradation. We are particularly interested in the processes that dictate protein folding and export across the cytoplasmic membrane of E.coli. Studies from our group have resulted not only in mechanistic advances but have also led the foundation for better protein expression technologies that have been licensed to more than half a dozen biotechnology and pharmaceutical companies.
Current projects include:
1) Oxidative protein folding and the formation of disulfide bonds in bacteria.
2) The mechanism of the Twin Arginine Transporter (TaT) pathway of protein secretion.
3) Biogenesis of membrane proteins.
4) Engineering the redox state of E.coli.