Drexel University College of Medicine

Our work focuses on understanding the cellular function of sigma1 receptors (Sigma1) in normal and pathophysiological conditions. Our research goals are: (1) to elucidate the role of Sigma1 in cell growth and survival by investigating its functions in endoplasmic reticulum protein homeostasis; and (2) to evaluate the Sigma1 system as a therapeutic target in cancer.

Sigma1 is an integral membrane protein with primarily endoplasmic reticulum (ER) localization in tumor cells. Growing evidence suggests that Sigma1 antagonists may be effective anti-tumor agents. However, the mechanisms of these Sigma1 antagonist-mediated actions are unclear. We propose that Sigma1 functions as an ER chaperone that regulates tumor cell survival and growth by modulating response to ER stress and by contributing to protein homeostasis (the balance of synthesis, folding, maturation, transport, and degradation of functional and defective proteins). We use pharmacological, biochemical, and cellular experimental approaches to investigate how sigma1 receptor-ligand interactions modulate receptor function to influence ER protein homeostasis. Our current projects address questions regarding cellular responses to Sigma1 receptor-ligand binding: from ligand-mediated changes in Sigma1 protein-protein interactions to the characterization of antagonist-induced ER stress associated signaling pathways.