"Engineering Effector Proteins as Modulators of Cell Signaling Pathways for Breast Cancer Therapy"

Julie A. Champion, Ph.D.
Assistant Professor
Tanner Junior Faculty Fellow
School of Chemical & Biomolecular Engineering
Georgia Tech

Abstract
Bacterial pathogens trigger cell death by a variety of mechanisms, including injection of effector proteins. Effector proteins have great potential as anti-cancer agents because they efficiently subvert a variety of eukaryotic signaling pathways involved in cancer development, drug resistance, and metastasis. In this talk, I will discuss our use of YopJ, an effector from Yersinia pestis, as a potential breast cancer therapeutic. In breast cancer, MAPK and NFκB pathways are known to be dysregulated. YopJ down-regulates MAPK and NFκB pathways to induce cell death in specific cell types and we seek to exploit this infection-enabling protein for therapeutic use. We engineered YopJ to self-assemble into protein nanoparticles to efficiently deliver protein to cells, replacing the need for the pathogen secretion mechanism for effector delivery to host cells. YopJ nanoparticles induced dose and time-dependent death in multiple breast cancer cell lines. Treatment with sub-lethal doses of nanoparticles was still seen to be beneficial as well, decreasing metastasis-related behaviors and MAPK signaling. YopJ nanoparticles demonstrate the potential of engineered effector proteins as breast cancer therapeutics.