The increased demand for protein production associated with aberrant growth and metabolism as well as survival under stressful microenvironment conditions render cancer cells particularly dependent on factors that maintain protein homeostasis (the balance of synthesis, folding, maturation, transport, and degradation of proteins). Due to deregulation of processes that drive cancer cell growth and survival, cancer cells are prone to constant accumulation of mis-folded proteins and mis-assembled protein complexes, and thus constant proteotoxic stress. Together, these increase the burden on the protein homeostasis regulatory apparatus of cancer cells. This stress phenotype is a hallmark of many solid tumors and presents a point of vulnerability. The support machinery that maintains protein homeostasis, including scaffolding proteins and molecular chaperones, is responsible for processing excess and mis-folded proteins in hyperactive cancer cells and represents a novel family of potential drug targets.
Sigma1 is a unique ligand-operated integral membrane scaffolding protein present primarily on the endoplasmic reticulum (ER) in cancer cells. Growing evidence suggests that certain small molecule Sigma1 modulator compounds (ligands that positively or negatively modulate Sigma1 mediated effects) cancer cell protein homeostasis and may be effective tumor growth and metastasis inhibiting agents. Our lab is investigating the mechanisms underlying these Sigma1 modulator actions. We use pharmacological, biochemical, cellular, proteomic, and transcriptomic experimental approaches to investigate the functional consequences of Sigma1 protein-ligand interactions in cancer cells.
We conduct mechanism focused, early drug discovery and experimental therapeutics research, and our goals are to:
- Understand the role of Sigma1 in cancer cell protein homeostasis.
- Investigate Sigma1 as a drug target in cancer.
- Discover novel therapeutic agents and approaches to pharmacologically control aspects of Sigma1 mediated protein homeostasis.
News & Announcements
Dr. Oyer Wins STAT News Wunderkind Award
STAT — a Boston-based national publication focused on science and health news — has named Halley Oyer, PhD, one of the "brightest young minds in life science." Read more.
Dr. Kim Publishes Sigma Protein Text
Felix Kim, PhD, is the co-author of Sigma Proteins: Evolution of the Concept of Sigma Receptors, which was e-published in October 2017 by Springer. The text is a part of the Handbook of Experimental Pharmacology book series.
Back to Top