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Barbara Miller, MD

Barbara Miller, MD

Four Diamonds Endowment Fund Christopher Millard Chair for Pediatric Cancer Research and Professor Emeritus, Department of Pediatrics
Division of Hematology and Oncology
Professor Emeritus, Department of Biochemistry and Molecular Biology
Scientific Program:Next-Generation Therapies
Disease Teams:
Cancer Institute, Pediatric Cancer Team
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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
  • Transient Receptor Potential Channels
  • Erythroblasts
  • Erythroid Precursor Cells
  • Ion Channels
  • Oxidative Stress
  • Fetal Hemoglobin
  • Genes
  • Neuroblastoma
  • Cell Survival
  • Neoplasms

Clinical Trials

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

Recent Publications


Zong, P, Feng, J, Yue, Z, Li, Y, Wu, G, Sun, B, He, Y, Miller, B, Yu, AS, Su, Z, Xie, J, Mori, Y, Hao, B & Yue, L 2022, 'Functional coupling of TRPM2 and extrasynaptic NMDARs exacerbates excitotoxicity in ischemic brain injury', Neuron, vol. 110, no. 12, pp. 1944-1958.e8.
Beattie, K, Jiang, H, Gautam, M, MacVittie, MK, Miller, B, Ma, M, Liu, Q & Luo, W 2022, 'TRPC3 Antagonizes Pruritus in a Mouse Contact Dermatitis Model', Journal of Investigative Dermatology, vol. 142, no. 4, pp. 1136-1144.
Hirschler-Laszkiewicz, I, Festa, F, Huang, S, Moldovan, GL, Nicolae, C, Dhoonmoon, A, Bao, L, Keefer, K, Chen, SJ, Wang, HG, Cheung, JY & Miller, BA 2022, 'The human ion channel TRPM2 modulates cell survival in neuroblastoma through E2F1 and FOXM1', Scientific reports, vol. 12, no. 1, 6311.
Bao, L, Festa, F, Hirschler-Laszkiewicz, I, Keefer, K, Wang, HG, Cheung, JY & Miller, BA 2022, 'The human ion channel TRPM2 modulates migration and invasion in neuroblastoma through regulation of integrin expression', Scientific reports, vol. 12, no. 1, 20544.


Miller, BA & Schaffer, JE 2021, Receptors: Hematopoietin receptors. in Encyclopedia of Biological Chemistry: Third Edition. vol. 6, Elsevier, pp. 162-167.


Li, Y, Liao, Z, Luo, H, Benyoucef, A, Kang, Y, Lai, Q, Dovat, S, Miller, B, Chepelev, I, Li, Y, Zhao, K, Brand, M & Huang, S 2020, 'Alteration of CTCF-associated chromatin neighborhood inhibits TAL1-driven oncogenic transcription program and leukemogenesis', Nucleic acids research, vol. 48, no. 6, pp. 3119-3133.
Rao, P, Segel, JE, McGregor, LM, Lengerich, EJ, Drabick, JJ & Miller, B 2020, 'Attendance at National Cancer Institute and Children's Oncology Group Facilities for Children, Adolescents, and Young Adults with Cancer in Pennsylvania: A Population-Based Study', Journal of Adolescent and Young Adult Oncology, vol. 9, no. 1, pp. 47-54.
Liu, Z, Grant, CN, Sun, L, Miller, BA, Spiegelman, VS & Wang, HG 2020, 'Expression patterns of immune genes reveal heterogeneous subtypes of high-risk neuroblastoma', Cancers, vol. 12, no. 7, 1739, pp. 1-16.
Gebru, MT, Atkinson, JM, Young, MM, Zhang, L, Tang, Z, Liu, Z, Lu, P, Dower, CM, Chen, L, Annageldiyev, C, Sharma, A, Kawasawa, YI, Zhao, Z, Miller, BA, Claxton, DF & Wang, HG 2020, 'Glucocorticoids enhance the antileukemic activity of FLT3 inhibitors in FLT3-mutant acute myeloid leukemia', Blood, vol. 136, no. 9, pp. 1067-1079.
Chen, SJ, Bao, L, Keefer, K, Shanmughapriya, S, Chen, L, Lee, J, Wang, JF, Zhang, XQ, Hirschler-Laszkiewicz, I, Merali, S, Merali, C, Imamura, Y, Dovat, S, Madesh, M, Cheung, JY, Wang, HG & Miller, BA 2020, 'Transient receptor potential ion channel TRPM2 promotes AML proliferation and survival through modulation of mitochondrial function, ROS, and autophagy', Cell Death and Disease, vol. 11, no. 4, 247.


Miller, BA 2019, 'TRPM2 in Cancer', Cell Calcium, vol. 80, pp. 8-17.
Bao, L, Festa, F, Freet, CS, Lee, JP, Hirschler-Laszkiewicz, IM, Chen, SJ, Keefer, KA, Wang, HG, Patterson, AD, Cheung, JY & Miller, BA 2019, 'The Human Transient Receptor Potential Melastatin 2 Ion Channel Modulates ROS Through Nrf2', Scientific reports, vol. 9, no. 1, 14132.
Miller, BA, Wang, JF, Song, J, Zhang, XQ, Hirschler-Laszkiewicz, I, Shanmughapriya, 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.