Lung cancer is the leading cause of cancer-related deaths worldwide, with non-small cell lung cancer (NSCLC) accounting for 85% of all lung cancer cases. Lung adenocarcinoma (LUAD), the most common subtype of NSCLC, is associated with high mortality rates, particularly due to the development of chemotherapy resistance. In addition, Cisplatin, a cornerstone of chemotherapy for LUAD often has significant side effects. Recent work from the lab of Yvonne Janssen-Heininger, PhD, has shown that a significant percentage of LUAD samples have high levels of glutathione S-transferase P (GSTP). These high levels of GSTP have been linked to poor survival, indicating GSTP may be a promising target for therapeutic intervention. 

But what is GSTP and why does it matter for cancer cell survival? Cancer cells thrive in an elevated oxidative environment and are very adept at adjusting their metabolism to cope with oxidative stress. One mechanism by which cancer cells protect themselves from oxidative stress is by increasing production of glutathione (GSH), an essential antioxidant that helps detoxify reactive oxygen species (ROS) found in oxidative environments. Increased levels of GSH have also been shown to play a role in inactivating and excreting Cisplatin, contributing to Cisplatin resistance in LUAD. In addition. GSH controls the process of protein glutathionylation, which leads to alterations in protein structure and function. GSTP, catalyzes the glutathionylation reaction and has been shown to contribute to chemotherapy resistance. 

Reem Aboushousha, PhD, a faculty scientist in the Janssen-Heininger lab, was recently awarded a Parker B. Francis Fellowship from the Francis Family Foundation. The new funding will enable her to study the role of GSTP and S-glutathionylation in chemotherapy resistance in LUAD. Dr. Aboushousha will investigate how GSTP-mediated glutathionylation of key proteins contributes to elevated glutathione levels and enhances tumor cell survival in an oxidative environment. The research will explore potential therapeutic strategies to target GSTP and sensitize LUAD cells to Cisplatin, with the goal of overcoming chemotherapy resistance and improving patient outcomes. With high rates of lung cancer in Vermont and Northern New York, findings from this study could directly benefit patients in the University of Vermont Cancer Center (UVMCC) catchment area. 

The Parker B. Francis Fellowship is awarded to candidates with a strong aptitude in research and who are transitioning from post-doctoral trainee to independent investigator. The fellowship will support three years of funding for Dr. Aboushousha. The fellowship was made possible with support from the Center for Biomedical Shared Resources (Microscopy Imaging Center, VBRN Proteomics, and Flow Cytometry and Small Particle Detection Facility) and a UVMCC pilot grant.