Research in this laboratory aims to better understand the role of ion channels in cell survival, cancer, and in the response to chemotherapy. Dr. Miller’s lab is also utilizing a drug discovery approach to identify a TRPM2 (ion channel) inhibitor that can be used as a novel anti-cancer agent in clinical trials.
Our research studies the role of ion channels in cell survival, cancer and in the response to chemotherapy. Ion channels are pores on the surface of the cells through which ions like calcium and sodium enter a cell. This dramatically affects many processes within cells including the energy production in the powerhouse of the cell, the mitochondria, and production of reactive oxygen species (R0S) which are toxic to cells at high concentrations.
TRPM2 depletion results in increased mitochondrial ROS.
TRPM2 and Ion Channels in Cancer
Ion channels are proteins located in the plasma membrane that arrange themselves to form passageways or pores that extend from one side of the membrane to the other. These passageways, or ion channels, are able to open and close in response to chemical or mechanical signals. Individual ion channels are specific to particular ions, thus allowing only a single type of ion to pass through them.
Research in this lab focuses primarily on one particular ion channel known as Transient Receptor Potential Cation Channel Subfamily M Member 2, or TRPM2 for short. Permeable to calcium, sodium and potassium, this ion channel is activated by oxidative stress and confers susceptibility to cell death. Notably, and of interest to us as cancer researchers, TRPM2 is highly expressed in many cancers, including neuroblastoma. Expression of the TRPM2 ion channel serves to protect the viability of neuroblastoma, glioblastoma, AML and other cancers as well. Thus finding a way to deplete or turn off TRPM2 in cancer cells could provide us new treatment avenues to pursue in our fight against neuroblastoma and other childhood cancers.