Schroeder Lab

We investigate the role of the Epidermal Growth Factor Receptor (EGFR) in cancer and immune modulation. EGFR is an oncogene commonly investigated for its role as a tyrosine kinase and driver of signal transduction, but it also has extensive non-kinase-dependent functions. We focus on the alterations in EGFR trafficking and direct roles as a transcription co-factor that occur during cellular stress. Cellular stress is a common occurrence during cancer progression, and we are evaluating how reactive oxygen species, aberrant growth signaling and loss of cell adhesion can contribute to changes in EGFR trafficking and function. When exposed to cellular stress environments, EGFR alters its localization and interactions with oncogenes such as MUC1 and Src, trafficking proteins such as Sorting Nexin 1 (SNX1) and transcription factors. We are currently investigating the mechanisms by which cellular stress drives these interactions and how normal and transformed cells modulate EGFR function under conditions of stress.

Through these studies, we recently discovered that EGFR is a regulator of the immune microenvironment in breast cancer. While investigating the role of EGFR in the nucleus as a transcription cofactor, we found that blocking nuclear EGFR induces a transcriptional change that promotes the recruitment and activation of Natural Killer cells against breast cancer. Natural Killer cells are immune cells exquisitely capable of targeting and eradicating metastasis when activated. Current studies in the lab are designed to investigate the ability of targeting nuclear EGFR to activate Natural Killer cells to treat metastatic breast cancer. 

When we identify novel cancer-specific functions of EGFR, we then develop peptide-based therapeutics to target those functions. Our goal is to develop therapies that are cancer-specific and have no impact on normal tissues. To this end, we have created three different peptide-based therapeutics to block these cancer-specific functions of EGFR. Our first therapeutic, PMIP, inhibits the interaction between EGFR and MUC1. Our second therapeutic, SAH-EJ1, promotes the inactive multimerization of EGFR, erbB2 and erbB3, preventing downstream function. Our third therapeutic, cSNX1.3, inhibits the interaction between EGFR and SNX1. Each of these therapeutic peptides effectively treat EGFR-dependent breast cancers, and we are currently working towards the clinical translation of cSNX1.3.