Soutenance publique de thèse de doctorat en sciences biologiques - Karim Bouhjar
Study of treatment -induced senescence (TIS) in head and neck squamous cell carcinoma (HNSCC) according to the HPV status
Date : 19/11/2026 15:00 - 19/11/2026 18:00
Lieu : Centre Hospitalier de l'Université de Montréal (CHUM) - Salle A.01.9209.B - 1000 R. Saint-Denis, Montréal, QC H2X 0C1
Orateur(s) : Karim Bouhjar
Organisateur(s) : Carine Michiels
Jury
- Prof. Anne-Catherine HEUSKIN (UNamur), Présidente
- Prof. Carine MICHIELS (UNamur), Secrétaire
- Prof. Francis RODIER (UMontreal)
- Prof. Yves POUMAY (UNamur)
- Prof. Anabelle DECOTTIGNIES (UCLouvain)
- Prof. Marc THERRIEN (UMontreal)
- Prof. Sue YOM (UCSF)
Résumé
Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous malignancy in which human papillomavirus (HPV) status strongly influences therapeutic response. HPV+ tumors generally show greater sensitivity to treatment, whereas HPV- tumors are associated with poorer prognosis and increased resistance. This thesis investigated how HPV status shapes cellular adaptation to therapeutic stress, with a particular focus on therapy-induced senescence (TIS), autophagy and MMS19.
HPV- HNSCC cells developed a senescence-like phenotype following cisplatin or x-ray irradiation, whereas HPV+ cells showed limited induction. Silencing of the viral oncogenes E6 and E7 in HPV+ cells increased this phenotype, indicating that HPV actively modulates treatment-induced cellular responses. Proteomic analyses further identified autophagy- and lysosome-related pathways as major features distinguishing HPV- from HPV+ cells. Autophagy inhibition predominantly impaired proliferation and clonogenic survival in HPV- cells, supporting an HPV-dependent autophagy–senescence axis involved in treatment adaptation.
The second part of this thesis identified MMS19, a component of the cytosolic iron–sulfur cluster assembly machinery, as a potential determinant of HPV- HNSCC resistance. MMS19 was associated with poorer clinical outcome, while its silencing impaired proliferation and clonogenic survival, particularly in HPV- cells.
Together, these findings identify autophagy-dependent remodeling and MMS19-associated genome maintenance as potential vulnerabilities contributing to therapeutic resistance in HPV- HNSCC.
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