Discovering Novel Rho GEF Inhibitors for Cancer Treatment

 

Trainee:

Lauren Parker

Parker

Research Mentor:

Dr. Adrienne Cox, PhD

Cox

Clinical Co-Mentor;

Dr. JenJen Yeh, MD

yeh
Project Description

Rho family GTPases act as signaling nodes within the cell to regulate cytoskeletal changes, adhesion, cell cycle, apoptosis, and polarity. GTPases are activated by guanine nucleotide exchange factors (GEFs). Rho GTPases and their GEFs are overexpressed in a multitude of cancers, and work by our lab and others have shown Rho GTPases and their GEFs to be necessary and sufficient for cellular transformation, tumorigenesis, invasion, and metastasis. This makes Rho GEFs promising targets for anticancer drugs.

We are currently working to identify inhibitors of Rho GEFs, determine the specificity of these inhibitors for different classes of Rho GTPases, and test the ability of these compounds to inhibit cellular transformation, migration, and invasion. In the future we plan to test the effects of these compounds on patient derived xenografts. We will also examine the mechanism of action of the compounds in greater detail. In this way we hope to identify compounds that can be used clinically in treatment of a variety of cancers.