Barbara Miller, MD - Penn State Cancer Institute
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Barbara Miller, MD
Division of Hematology and Oncology
Professor Emeritus, Department of Biochemistry and Molecular Biology
Dr. Barbara Miller is internationally recognized for her work on the superfamily of TRP ion channels. Her lab is currently studying an ion channel called TRPM2. This channel is found on many cell types and has an important role in cell proliferation and survival. Dr. Miller’s lab recently demonstrated that TRPM2 channels are highly expressed in neuroblastoma, the most common pediatric solid tumor outside the brain, as well as other cancers including melanoma, lung, breast cancer and leukemia.
Full-length TRPM2 channels allow ion (calcium/sodium) entry into a cell. The channel isoform TRPM2-S (S for short), which is missing the pore, inhibits ion entry through the channel. Using mouse models, Dr. Miller’s lab found that neuroblastomas expressing full-length TRPM2 channels grow much larger than tumors in which TRPM2 is inhibited, either by depleting it by cutting it out with a technique called CRISPR or by inhibiting it with the short isoform, TRPM2-S, that has no pore function.
Leukemia growth is also significantly reduced by TRPM2 inhibition. Inhibition of calcium entry through TRPM2 reduces energy production in both neuroblastoma and leukemia, increases the levels of harmful oxidants (ROS), blocks the growth of tumors and leukemia and increases sensitivity to chemotherapy.
Research currently focuses on better understanding the mechanisms through which TRPM2 modulates cell growth and survival through cellular bioenergetics, and new projects are underway to study its role in metastasis and leukemia. Dr. Miller’s lab is utilizing a drug discovery approach to identify a TRPM2 inhibitor that can be used as a novel anti-cancer agent in clinical trials.
- Transient Receptor Potential Channels
- Erythroid Precursor Cells
- Ion Channels
- Oxidative Stress
- Fetal Hemoglobin
- Cell Survival