This component of our research program comprises two principle projects focused on: (1) Metabolism. Define the role of Sigma1 in cancer cell lipid metabolism and metabolic rewiring that enables tumor adaptation and development of resistance. (2) Tumor microenvironment (TME). Here, we investigate the role of Sigma1 in the regulation of immune checkpoint molecules, secretion of immune modulatory cytokine, and production and composition of exosomes and other extracellular vesicles (EVs).

Here, we use in vitro, ex vivo, and in vivo experimental models to define how small molecule Sigma1 modulators regulate Sigma1 activity in prostate cancer cells. (1) The first project is pharmacological mechanism of action focused and aims to define at the molecular, biochemical, and cellular level how drugs that target Sigma1 work to suppress tumor growth, proliferation, and survival. (2) The second project aims to confirm on target mechanism of action in vivo using mouse models of cancer, including standard tumor xenograft and cancer patient derived tumor xenograft models. 

Our translational cancer research program includes a drug discovery platform which has produced a novel drug-like small molecule Sigma1 modulator series. An emerging paradigm in precision medicine is the co-development of cancer drugs with predictive biomarkers that can optimize treatment efficacy in selected patient populations. Biomarker-guided therapy can also inform synergistic drug combinations that bypass or delay treatment resistance. We are exploring biomarkers to serve as companion diagnostic tools for precision treatment approaches that will enable the identification of patients most likely to benefit from this new class of cancer drugs.