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null Nada Jabado, OC, MD, PhD

Senior Scientist, RI-MUHC, Glen site

Child Health and Human Development Program

Centre for Translational Biology

Professor, Department of Pediatrics, Faculty of Medicine and Health Sciences, McGill University

Department of Pediatrics, Division of Hematology, MUHC

 

Keywords

pediatric brain tumors • gliomas • astrocytomas • epigenetics • next generation sequencing

Research Focus

My research focuses on brain tumors, the leading cause of cancer-related mortality and morbidity in the pediatric years. Our main focus is pediatric and young adult astrocytomas, a deadly group of brain tumors. My group established that pediatric high-grade astrocytomas (HGA) are molecularly and genetically distinct from adult tumors. We identified a new molecular mechanism driving pediatric HGA, namely recurrent somatic driver mutations in the tail of histone 3 variants (H3.3 and H3.1). These mutations lead to aminoacid substitutions at key residues and are tightly correlated with a distinct global DNA methylation pattern, neuroanatomical and age specificities. We aim to identify events affected downstream of each mutation, and validate targets in our new models to better advise the use of experimental or pipeline drug(s) that could be rapidly translated into clinical trials.

Selected Publications

Click on Pubmed to see my current publications list

  • Khazaei S, Chen CCL, Andrade AF, Kabir N, Azarafshar P, Morcos SM, França JA, Lopes M, Lund PJ, Danieau G, Worme S, Adnani L, Nzirorera N, Chen X, Yogarajah G, Russo C, Zeinieh M, Wong CJ, Bryant L, Hébert S, Tong B, Sihota TS, Faury D, Puligandla E, Jawhar W, Sandy V, Cowan M, Nakada EM, Jerome-Majewska LA, Ellezam B, Gomes CC, Denecke J, Lessel D, McDonald MT, Pizoli CE, Taylor K, Cocanougher BT, Bhoj EJ, Gingras AC, Garcia BA, Lu C, Campos EI, Kleinman CL, Garzia L, Jabado N. Single substitution in H3.3G34 alters DNMT3A recruitment to cause progressive neurodegeneration. Cell. 2023 Mar 16;186(6):1162-1178.e20. doi: 10.1016/j.cell.2023.02.023. PMID: 36931244.

  • Jessa S, Mohammadnia A, Harutyunyan AS, Hulswit M, Varadharajan S, Lakkis H, Kabir N, Bashardanesh Z, Hébert S, Faury D, Vladoiu MC, Worme S, Coutelier M, Krug B, Faria Andrade A, Pathania M, Bajic A, Weil AG, Ellezam B, Atkinson J, Dudley RWR, Farmer JP, Perreault S, Garcia BA, Larouche V, Blanchette M, Garzia L, Bhaduri A, Ligon KL, Bandopadhayay P, Taylor MD, Mack SC, Jabado N, Kleinman CL. K27M in canonical and noncanonical H3 variants occurs in distinct oligodendroglial cell lineages in brain midline gliomas. Nat Genet. 2022 Dec;54(12):1865-1880. doi: 10.1038/s41588-022-01205-w. Epub 2022 Dec 5. PMID: 36471070.

  • Chen CCL, Deshmukh S, Jessa S, Hadjadj D, Lisi V, Andrade AF, Faury D, Jawhar W, Dali R, Suzuki H, Pathania M, A D, Dubois F, Woodward E, Hébert S, Coutelier M, Karamchandani J, Albrecht S, Brandner S, De Jay N, Gayden T, Bajic A, Harutyunyan AS, Marchione DM, Mikael LG, Juretic N, Zeinieh M, Russo C, Maestro N, Bassenden AV, Hauser P, Virga J, Bognar L, Klekner A, Zapotocky M, Vicha A, Krskova L, Vanova K, Zamecnik J, Sumerauer D, Ekert PG, Ziegler DS, Ellezam B, Filbin MG, Blanchette M, Hansford JR, Khuong-Quang DA, Berghuis AM, Weil AG, Garcia BA, Garzia L, Mack SC, Beroukhim R, Ligon KL, Taylor MD, Bandopadhayay P, Kramm C, Pfister SM, Korshunov A, Sturm D, Jones DTW, Salomoni P, Kleinman CL, Jabado N. Histone H3.3G34-Mutant Interneuron Progenitors Co-opt PDGFRA for Gliomagenesis. Cell. 2020 Dec 10;183(6):1617-1633.e22. doi: 10.1016/j.cell.2020.11.012. Epub 2020 Nov 30. PMID: 33259802.

  • Papillon-Cavanagh S, Lu C, Gayden T, Mikael LG, Bechet D, Karamboulas C, Ailles L, Karamchandani J, Marchione DM, Garcia BA, Weinreb I, Goldstein D, Lewis PW, Dancu OM, Dhaliwal S, Stecho W, Howlett CJ, Mymryk JS, Barrett JW, Nichols AC, Allis CD, Majewski J, Jabado N. Impaired H3K36 methylation defines a subset of head and neck squamous cell carcinomas. Nat Genet. 2017 Feb;49(2):180-185. doi: 10.1038/ng.3757. Epub 2017 Jan 9. PMID: 28067913.

  • Schwartzentruber J, Korshunov A, Liu XY, Jones DT, Pfaff E, Jacob K, Sturm D, Fontebasso AM, Quang DA, Tönjes M, Hovestadt V, Albrecht S, Kool M, Nantel A, Konermann C, Lindroth A, Jäger N, Rausch T, Ryzhova M, Korbel JO, Hielscher T, Hauser P, Garami M, Klekner A, Bognar L, Ebinger M, Schuhmann MU, Scheurlen W, Pekrun A, Frühwald MC, Roggendorf W, Kramm C, Dürken M, Atkinson J, Lepage P, Montpetit A, Zakrzewska M, Zakrzewski K, Liberski PP, Dong Z, Siegel P, Kulozik AE, Zapatka M, Guha A, Malkin D, Felsberg J, Reifenberger G, von Deimling A, Ichimura K, Collins VP, Witt H, Milde T, Witt O, Zhang C, Castelo-Branco P, Lichter P, Faury D, Tabori U, Plass C, Majewski J, Pfister SM, Jabado N. Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature. 2012 Jan 29;482(7384):226-31. doi: 10.1038/nature10833. Erratum in: Nature. 2012 Apr 5;484(7392):130. PMID: 22286061.