Shujian “Scott” Lin
Stimulating Anti-Viral Signaling in HGSC via EHMT1/2 Inhibition
Abstract
Ovarian cancer is the 5th leading cause of cancer death in women. While ovarian cancer responds to the immune system, current immunotherapy has been clinically ineffective. A promising mechanism for inducing immune activation against tumors is “viral mimicry”. By inducing aberrant double-stranded RNA expression, drugs can cause tumor cells to activate anti-viral responses that recruit immune cells. This results in tumor killing. We identified EHMT1/2, methyltransferase, as a potential target to induce viral mimicry in HGSC. EHMT1/2 is elevated in multiple models of ovarian cancer and is correlated to worsened patient outcomes. We have shown that inhibiting EHMT1/2 in mouse models of ovarian cancer leads to tumor regression and improved survival. In this project, we aim to determine the key innate immune pathways that EHMT1/2 uses to induce viral mimicry and identify other RNA-sensing receptors that can sensitize HGSC to the immune system.
The PhRMA Foundation Predoctoral Fellowship will help fund my efforts in discovering new molecular targets against treatment-resistant ovarian cancer. It is an incredible training opportunity to advance my career as a future physician-scientist.
