Researcher Profile

Researcher Profile

Barbara Miller, MD

Barbara Miller, MD

Four Diamonds Endowment Fund Christopher Millard Chair for Pediatric Cancer Research and Professor, Department of Pediatrics
Professor, Department of Biochemistry and Molecular Biology
Division of Hematology and Oncology
Scientific Program:Experimental Therapeutics
Disease Teams:
Pediatric Cancer
bam11@psu.edu
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Research Interests

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. 

  • Erythropoietin
  • Calcium
  • Erythroblasts
  • Erythroid Precursor Cells
  • Fetal Hemoglobin
  • Transient Receptor Potential Channels
  • Oxidative Stress
  • Genes
  • Growth
  • Globins
  • Cell Death
  • Neoplasms

Clinical Trials

A Phase 2 Study of Reduced Therapy for Newly Diagnosed Average-RiskWNT-Driven Medulloblastoma Patients

Recent Publications

2019

Miller, B 2019, 'TRPM2 in Cancer', Cell Calcium, vol. 80, pp. 8-17. https://doi.org/10.1016/j.ceca.2019.03.002
Miller, B, Wang, JF, Song, J, Zhang, XQ, Hirschler-Laszkiewicz, I, Santhanam, S, Tomar, D, Rajan, S, Feldman, AM, Madesh, M, Sheu, SS & Cheung, JY 2019, 'Trpm2 enhances physiological bioenergetics and protects against pathological oxidative cardiac injury: Role of Pyk2 phosphorylation', Journal of Cellular Physiology, vol. 234, no. 9, pp. 15048-15060. https://doi.org/10.1002/jcp.28146

2018

Dower, CM, Bhat, N, Gebru, MT, Chen, L, Wills, CA, Miller, B & Wang, H-G 2018, 'Targeted inhibition of ULK1 promotes apoptosis and suppresses tumor growth and metastasis in neuroblastoma', Molecular cancer therapeutics, vol. 17, no. 11, pp. 2365-2376. https://doi.org/10.1158/1535-7163.MCT-18-0176
Hirschler-Laszkiewicz, I, Chen, S, Bao, L, Wang, J, Zhang, XQ, Santhanam, S, Keefer, K, Madesh, M, Cheung, JY & Miller, B 2018, 'The human ion channel TRPM2 modulates neuroblastoma cell survival and mitochondrial function through Pyk2, CREB, and MCU activation', American Journal of Physiology - Cell Physiology, vol. 315, no. 4, pp. C571-C586. https://doi.org/10.1152/ajpcell.00098.2018

2017

Cheung, JY & Miller, B 2017, 'Transient Receptor Potential-Melastatin Channel Family Member 2: Friend or Foe', Transactions of the American Clinical and Climatological Association, vol. 128, pp. 308-329.

2016

Bao, L, Chen, S, Conrad, K, Keefer, K, Abraham, T, Lee, JP, Wang, JF, Zhang, XQ, Hirschler-Laszkiewicz, I, Wang, H-G, Dovat, S, Gans, B, Madesh, M, Cheung, JY & Miller, B 2016, 'Depletion of the human ion channel TRPM2 in neuroblastoma demonstrates its key role in cell survival through modulation of mitochondrial reactive oxygen species and bioenergetics', Journal of Biological Chemistry, vol. 291, no. 47, pp. 24449-24464. https://doi.org/10.1074/jbc.M116.747147
Shakerley, NL, Chandrasekaran, A, Trebak, M, Miller, B & Melendez, JA 2016, 'Francisella tularensis catalase restricts immune function by impairing TRPM2 channel activity', Journal of Biological Chemistry, vol. 291, no. 8, pp. 3871-3881. https://doi.org/10.1074/jbc.M115.706879
Katsnelson, MA, Lozada-Soto, KM, Russo, HM, Miller, B & Dubyak, GR 2016, 'NLRP3 inflammasome signaling is activated by low-level lysosome disruption but inhibited by extensive lysosome disruption: Roles for K+ efflux and Ca2+ influx', American Journal of Physiology - Cell Physiology, vol. 311, no. 1, pp. C83-C100. https://doi.org/10.1152/ajpcell.00298.2015
Miller, B & Cheung, JY 2016, 'TRPM2 protects against tissue damage following oxidative stress and ischaemia–reperfusion', Journal of Physiology, vol. 594, no. 15, pp. 4181-4191. https://doi.org/10.1113/JP270934

2015

Hoffman, NE, Miller, B, Wang, JF, Elrod, JW, Rajan, S, Gao, E, Song, J, Zhang, XQ, Hirschler-Laszkiewicz, I, Santhanam, S, Koch, WJ, Feldman, AM, Madesh, M & Cheung, JY 2015, 'Ca2+ entry via Trpm2 is essential for cardiac myocyte bioenergetics maintenance', American Journal of Physiology - Heart and Circulatory Physiology, vol. 308, no. 6, pp. H637-H650. https://doi.org/10.1152/ajpheart.00720.2014

Clinical Trials Search


Children (age < 18 years)
Adults (age >= 18 years)