Matei Alexandru Banu

All Publications

• A cell state-specific metabolic vulnerability to GPX4-dependent ferroptosis in glioblastoma EMBO JOURNAL Banu, M. A., Dovas, A., Argenziano, M. G., Zhao, W., Sperring, C. P., Cuervo Grajal, H., Liu, Z., Higgins, D. O., Amini, M., Pereira, B., Ye, L. F., Mahajan, A., Humala, N., Furnari, J. L., Upadhyayula, P. S., Zandkarimi, F., Nguyen, T. T., Teasley, D., Wu, P. B., Hai, L., Karan, C., Dowdy, T., Razavilar, A., Siegelin, M. D., Kitajewski, J., Larion, M., Bruce, J. N., Stockwell, B. R., Sims, P. A., Canoll, P. 2024

  Abstract

  Glioma cells hijack developmental programs to control cell state. Here, we uncover a glioma cell state-specific metabolic liability that can be therapeutically targeted. To model cell conditions at brain tumor inception, we generated genetically engineered murine gliomas, with deletion of p53 alone (p53) or with constitutively active Notch signaling (N1IC), a pathway critical in controlling astrocyte differentiation during brain development. N1IC tumors harbored quiescent astrocyte-like transformed cell populations while p53 tumors were predominantly comprised of proliferating progenitor-like cell states. Further, N1IC transformed cells exhibited increased mitochondrial lipid peroxidation, high ROS production and depletion of reduced glutathione. This altered mitochondrial phenotype rendered the astrocyte-like, quiescent populations more sensitive to pharmacologic or genetic inhibition of the lipid hydroperoxidase GPX4 and induction of ferroptosis. Treatment of patient-derived early-passage cell lines and glioma slice cultures generated from surgical samples with a GPX4 inhibitor induced selective depletion of quiescent astrocyte-like glioma cell populations with similar metabolic profiles. Collectively, these findings reveal a specific therapeutic vulnerability to ferroptosis linked to mitochondrial redox imbalance in a subpopulation of quiescent astrocyte-like glioma cells resistant to standard forms of treatment.

  View details for DOI 10.1038/s44318-024-00176-4

  View details for Web of Science ID 001299791100003

  View details for PubMedID 39192032

  View details for PubMedCentralID 5937676

• Long-term outcomes of mesial temporal laser interstitial thermal therapy for drug-resistant epilepsy and subsequent surgery for seizure recurrence: a multi-centre cohort study. Journal of neurology, neurosurgery, and psychiatry Youngerman, B. E., Banu, M. A., Khan, F., McKhann, G. M., Schevon, C. A., Jagid, J. R., Cajigas, I., Theodotou, C. B., Ko, A., Buckley, R., Ojemann, J. G., Miller, J. W., Laxton, A. W., Couture, D. E., Popli, G. S., Buch, V. P., Halpern, C. H., Le, S., Sharan, A. D., Sperling, M. R., Mehta, A. D., Englot, D. J., Neimat, J. S., Konrad, P. E., Sheth, S. A., Neal, E. G., Vale, F. L., Holloway, K. L., Air, E. L., Schwalb, J. M., D'Haese, P., Wu, C. 2023

  Abstract

  BACKGROUND: Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a minimally invasive alternative to surgical resection for drug-resistant mesial temporal lobe epilepsy (mTLE). Reported rates of seizure freedom are variable and long-term durability is largely unproven. Anterior temporal lobectomy (ATL) remains an option for patients with MRgLITT treatment failure. However, the safety and efficacy of this staged strategy is unknown.METHODS: This multicentre, retrospective cohort study included 268 patients consecutively treated with mesial temporal MRgLITT at 11 centres between 2012 and 2018. Seizure outcomes and complications of MRgLITT and any subsequent surgery are reported. Predictive value of preoperative variables for seizure outcome was assessed.RESULTS: Engel I seizure freedom was achieved in 55.8% (149/267) at 1year, 52.5% (126/240) at 2 years and 49.3% (132/268) at the last follow-up ≥1year (median 47 months). Engel I or II outcomes were achieved in 74.2% (198/267) at 1year, 75.0% (180/240) at 2 years and 66.0% (177/268) at the last follow-up. Preoperative focal to bilateral tonic-clonic seizures were independently associated with seizure recurrence. Among patients with seizure recurrence, 14/21 (66.7%) became seizure-free after subsequent ATL and 5/10 (50%) after repeat MRgLITT at last follow-up≥1year.CONCLUSIONS: MRgLITT is a viable treatment with durable outcomes for patients with drug-resistant mTLE evaluated at a comprehensive epilepsy centre. Although seizure freedom rates were lower than reported with ATL, this series represents the early experience of each centre and a heterogeneous cohort. ATL remains a safe and effective treatment for well-selected patients who fail MRgLITT.

  View details for DOI 10.1136/jnnp-2022-330979

  View details for PubMedID 37336643