Matei Alexandru Banu

All Publications

• Recurrent ERBB2 alterations are associated with esophageal adenocarcinoma brain metastases. medRxiv : the preprint server for health sciences Lawson, N. M., Ye, L., Cho, C. Y., Zhao, B., Mitchell, T., Martín-Barrio, I., Beernaert, B., Gupta, A., Banu, M., Lissanu, Y., Shaffer, S., Tawbi, H., Li, J., Gule-Monroe, M. K., Alvarez-Breckenridge, C. A., Huse, J. T., Murphy, M. B., Yin, F., Lang, F. F., Parkes, E. E., Weinberg, J. S., Akdemir, K. C. 2025

  Abstract

  Brain metastases in esophageal adenocarcinoma (EAC) patients are associated with poor prognosis and remain understudied. We performed multi-omics analysis with whole-genome sequencing and single-cell spatial transcriptomics on the brain metastases and matched primary tumors. Our analysis identified ERBB2 as a recurrent oncogene in EAC brain metastases, with 9 out of 10 cases harboring amplifications. Single-cell whole-genome and multi-region sequencing revealed that ERBB2 alterations, occur early during disease progression and are associated with monoclonal seeding. Although the median survival in our cohort was 13 months, one patient on HER2 antibody-drug conjugate therapy remains a long-term survivor beyond 34 months. Interestingly, the sole patient without an ERBB2 alteration had JAK2 deletion, high T cell infiltration in the brain lesion, and survived 35 months after immune checkpoint therapy. Our findings have significant clinical implications for the treatment and management of EAC brain metastases.

  View details for DOI 10.1101/2025.02.19.25322558

  View details for PubMedID 40061311

  View details for PubMedCentralID PMC11888521

• Molecular profiling of neuronal extracellular vesicles reveals brain tissue specific signals. medRxiv : the preprint server for health sciences Kalia, V., Jackson, G., Dominguez, R. J., Pinto-Pacheco, B., Bloomquist, T., Furnari, J., Banu, M., Volpert, O., Manz, K. E., Walker, D. I., Pennell, K. D., Canoll, P. D., Bruce, J. N., Eitan, E., Wu, H., Baccarelli, A. A. 2025

  Abstract

  Extracellular vesicles (EVs) released by neurons (nEVs) provide an opportunity to measure biomarkers from the brain circulating in the periphery. No study yet has directly compared molecular cargo in brain tissue to nEVs found in circulation in humans. We compared the levels microRNAs and environmental chemicals because microRNAs are one of the most studied nEV cargoes and offer great potential as biomarkers and environmental chemical load in nEVs is understudied and could reveal levels of chemicals in the brain. To do so, we leveraged matched sets of brain tissue and serum, and isolated serum total EVs and serum nEVs. We also generated and compared metabolomic profiles in a different set of matched serum, serum total EVs, and serum nEVs since metabolite cargo in nEVs is also understudied but could offer potential biomarkers. Highly expressed brain tissue miRNAs showed stronger correlations with nEVs than serum or total EVs. We detected several environmental chemical pollutant classes in nEVs. The chemical pollutant concentrations in nEVs were more strongly correlated with brain tissue levels than those observed between brain tissue and serum or total EVs. We also detected several endogenous metabolite classes in nEVs. Compared to serum and total EVs, there was enrichment of metabolites with known signaling roles, such as bile acids, oleic acid, phosphatidylserine, and isoprenoids. We provide evidence that nEV cargo is closely correlated to brain tissue content, further supporting their utility as a brain liquid biopsy.

  View details for DOI 10.1101/2025.01.23.25320909

  View details for PubMedID 39974146

• 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