Washington University in St. Louis (WU)
My research investigates oncogenic gain-of-function (GOF) mutations in cancer, focusing specifically on the transcription factor Nuclear Factor Erythroid 2-Related Factor 2 (NRF2). NRF2 is frequently mutated in various cancers, including Head and Neck Squamous Cell Carcinoma (HNSCC). During oxidative stress, NRF2 forms a heterodimer with a small musculoaponeurotic fibrosarcoma (sMaf) family protein to transactivate Antioxidant Response Element (ARE) containing genes, supporting cell survival. However, when mutated, NRF2 levels increase within tumors, leading to resistance to multiple types of cancer therapy.
The goal of my research is to identify the interactome of sMaf proteins both before and after NRF2 activation. By understanding these protein interactions, we aim to uncover crucial factors that support NRF2 target gene expression and contribute to its oncogenic effects in therapeutic resistance.