Dissertation Defense: Darius Gaymon
Candidate Name: Darius Gaymon
Major: Tumor Biology
Advisor: Michael Johnson, Ph.D.
Title: ROS-MEDIATED MATRIPTASE ACTIVATION CONTRIBUTES TO ER-NEGATIVE PROLIFERATION AND MIGRATION AND DIRECTS NAC TREATMENT IN SEVERAL CARCINOMAS
Matriptase is a type-II serine protease that is widely expressed in epithelial tissues and is known to have a role in normal epithelial cell integrity. Matriptase expression and activation are normally tightly regulated by its cognate inhibitor, Hepatocytpe Growth Factor Activator Inhibitor-1, HAI-1, but is often deranged in many cancers and correlates with poor patient prognoses. Matriptase is known to act as an oncogene and has been shown to activate tumor promoting substrates such as uPA, PAR2 and pro-HGF. Matriptase activation correlates universally with inflammatory conditions such as low pH and has been shown to occur as a result of stimulation with compounds such as sphingosine 1-phosphate (S-1P) in A1N4 breast cancer cells. In this thesis, we have shown that EGFR-directed matriptase activation contributes to proliferation and migration in ER-negative breast cancer. We have also shown that matriptase activation returns with Lapatinib resistance in HER2-amplified breast cancer. Finally, we have demonstrated that ROS is central to the mechanism of matriptase activation and have used matriptase activation to direct N-acetyl cysteine (NAC) treatment in several carcinomas. This work is promising for the future clinical use of matriptase as well as the study of matriptase in other ROS-dependent malignancies.
Tuesday, March 12 at 12:00pm to 1:30pm
New Research Building, Auditorium 3970 Reservoir Rd. NW. New Res Bldg Washington, DC. 20057