Carine Michiels

Tumor hypoxia

Understanding the molecular mechanisms of cancer cell resistance to chemotherapy and radiation therapy

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Prof. Carine Michiels ^PhD

UNamur, Department of biology, Laboratory of Cellular and Molecular Biology (URBC) 

Research portal UNamur  |  ORCID  |  ResearchGate

Expertise and research interests

The TumHyp team aims at understanding how cancer cells respond to anti-cancer therapies including radio-, chemo and immunotherapies as well as to targeted nanoparticles. The role of tumor microenvironment, more particularly of endothelial cells, macrophages, inflammation and hypoxia, in tumor growth, response to treatments and metastasis is also investigated.

Together with physicists Prof. Stéphane Lucas and Prof. Anne-Catherine Heuskin (UNamur, NARILIS), Prof. Carine Michiels set up an experienced radiobiology team. This multidisciplinary collaboration connecting biology and physics has the objective to optimize conventional radiation therapy, as well as to achieve a more efficient cancer treatment by combining nanotechnology and protontherapy.

Group members

Postdoc: Dr. François Bulteau

PhD students: Karim Bouhjar, Inès Bouriez, Hortence Parée, Lise Praprzycki, Eloïse Rapport, Manon Van Den Abbeel

Research projects

• ^ONGOING Radiotherapy-induced immunogenicity of cancer cells. Ongoing PhD thesis by Manon Van Den Abbeel (Télévie).

• ^ONGOING Étude intégrée des altérations musculaires causées par l’hypoxie périodique et contribution de la voie de l’adiponectine. Ongoing PhD thesis by Lise Praprzycki. Joint PhD programme at UNamur (Prof. Carine Michiels) and UMons (Prof. Alexandra Tassin).

• ^ONGOING Pathways of senescence induction in keratinocytes and impact of their secretome on the cellular microenvironment. Ongoing PhD thesis by Inès Bouriez. Under co-supervision by Prof. Carine Michiels (promoter) and Prof. Yves Poumay (co-promoter).

• ^ONGOING Development of Personalized Neutron Therapy using Theranostic carriers. Ongoing PhD thesis by Eloïse Rapport. Joint PhD programme at UNamur (promoter: Prof. Carine Michiels) and Institut Jules Bordet, ULB (promoter: Prof. Nick Reynaert | co-promoter: Dr. Sébastien Penninckx).

• ^ONGOING Induction of antitumor immunity in syngeneic mouse models exposed to X-ray vs high LET proton irradiation. Postdoctoral research by Dr. François Bulteau.

• ^ONGOING Study of the pro-senescence response to anti-cancer treatments in head and neck HPV positive cancer. Ongoing PhD thesis by Karim Bouhjar. Joint PhD programme at UNamur (Prof. Carine Michiels) and University of Montreal (Dr. Francis Rodier).

• ^ONGOING Determination of the genes implicated in intrinsic resistance to proton beam therapy for the treatment of glioblastoma. Ongoing PhD theses by Hortence Parée.

• ^ONGOING PROTHER-WAL: Proton Therapy Research in Wallonia

• Study of the immunomodulatory effects of irradiation on human papillomavirus-driven vs. carcinogen-driven head and neck squamous cell carcinoma. PhD thesis defended by Christoph Schifflers on 15/09/2023. Joint PhD programme at UNamur (Prof. Carine Michiels) and German Cancer Research Center DKFZ, Heidelberg (Dr. Angelika Riemer).

• Identification of genes implicated in the resistance to treatment in Glioblastoma: focus on intracellular trafficking pathway. PhD thesis defended by Jia-Wei Chen on 07/09/2023. Under co-supervision by Prof. Carine Michiels (promoter) and Prof. Anne-Catherine Heuskin (co-promoter)

• Combination of X-rays and targeted therapies in head & neck cancers / Tumor macrophage rewiring by proton irradiation in order to boost the anti-PD-L1 immune checkpoint blocker effect. Doctoral research by Eléonore Longton. Under co-supervision by Prof. Carine Michiels, UNamur (promoter) and Dr. Jean-François Daisne, CHU UCL Namur, site Sainte-Elisabeth (co-promoter).

• Deciphering the senescent phenotype induced by radiotherapy, protontherapy and PARP inhibitors in cancer cell lines. PhD thesis defended by Camille Huart on 28/10/2022.

• Contextual synthetic lethality to optimise glioblastoma cell responses to proton and X-ray irradiation: an upscaling approach to study radiosensitisation and radioresistance. Postdoctoral research by Dr. Anne-Catherine Wera. Under co-supervision by Prof. Carine Michiels (promoter) and Prof. Stéphane Lucas (co-promoter).

• How cycling hypoxia initiates endothelial cell-macrophage cooperation to support tumor growth and metastasis. PhD thesis defended by Victor Delprat on 24/08/2021. Under co-supervision by Prof. Carine Michiels, UNamur (promoter) and Prof. Olivier Féron, UCLouvain (co-promoter).

• PACMAN, Peptide-Assisted Cellular Migration Along eNgineered surfaces: Characterization of the migratory phenotype of cancer cells selected on IGDQ-expressing surface. PhD thesis defended by Sophie Ayama on 05/07/2021. Under co-supervision by Prof. Carine Michiels, UNamur (promoter) and Prof. Davide Bonifazi, Cardiff University / Vienna University (co-promoter).

• Characterization of the functions of TMEM45A using a loss of function model. Postdoctoral research by Dr. Benjamin Le Calvé.
  

• Hybrid gold nanoparticles coated with organic polymers and antibodies as a platform for cancer theranostics: cytotoxicity assessment and radiolabeling. PhD thesis defended by Noami Daems on 02/09/2020. PhD thesis at SCK-CEN (Dr. An Aerts and Prof. Sarah Baatout) in collaboration with UNamur, under co-supervision by Prof. Stéphane Lucas (promoter) and Prof. Carine Michiels (co-promoter).

• Characterization of the anticancer properties of new hydroxamate-based histone deactylase inhibitors. PhD thesis defended by Manon Lernoux on 22/11/2019. Under co-supervision by Dr. Michael Schnekenburger, LBMCC, Luxembourg (promoter), Prof. Marc Diederich, Seoul National University (co-promoter) and Prof. Carine Michiels, UNamur (co-promoter).

• Identification of chemosensitizing compounds inhibiting the resistance of taxol induced by TMEM45A protein on MDA-MB-231 cell line. PhD thesis defended by Sébastien Marx on 25/10/2019. Under co-supervision by Prof. Johan Wouters (promoter) and Prof. Carine Michiels (co-promoter).

• Structural and functional characterization of the transmembrane protein 45A (TMEM45A) in triple negative breast cancers. PhD thesis defended by Thomas Dal Maso on 04/10/2019. Under co-supervision by Prof. Johan Wouters (promoter) and Prof. Carine Michiels (co-promoter).

• Role of TMEM45A in cancer resistance to chemotherapy. PhD thesis defended by Kathleen Schmit on 27/03/2019.

• NanoROS: Unravelling the Mechanism of Gold Nanoparticle Radiosensitization in protontherapy. PhD thesis defended by Sébastien Penninckx on 01/03/2019. Under co-supervision by Prof. Stéphane Lucas (promoter) and Prof. Carine Michiels (co-promoter).

• Role of the interactions between tumor cells and endothelial cells or macrophages in radioresistance observed during treatment with rays X, protons or alpha particle. PhD thesis defended Géraldine Genard on 30/05/2018. Under co-supervision by Prof. Carine Michiels (promoter) and Prof. Stéphane Lucas (co-promoter).

Selected publications

Schifflers C, Zottnick S, Förster JD, Kruse S, Yang R, Wiethoff H, Bozza M, Hoppe-Seyler K, Heikenwälder M, Harbottle RP, Michiels C, Riemer AB. Development of an Orthotopic HPV16-Dependent Base of Tongue Tumor Model in MHC-Humanized Mice. Pathogens. 2023 Jan 25;12(2):188.

Ayama-Canden S, Tondo R, Piñeros L, Ninane N, Demazy C, Dieu M, Fattaccioli A, Tabarrant T, Lucas S, Bonifazi D, Michiels C. IGDQ motogenic peptide gradient induces directional cell migration through integrin (αv)β3 activation in MDA-MB-231 metastatic breast cancer cells. Neoplasia. 2022 Jun 25;31:100816.

Delprat V, Huart C, Feron O, Soncin F, Michiels C. The impact of macrophages on endothelial cells is potentiated by cycling hypoxia: Enhanced tumor inflammation and metastasis. Front Oncol. 2022 Sep 28;12:961753.

Huart C, Fransolet M, Demazy C, Le Calvé B, Lucas S, Michiels C, Wéra AC. Taking Advantage of the Senescence-Promoting Effect of Olaparib after X-ray and Proton Irradiation Using the Senolytic Drug, ABT-263. Cancers (Basel). 2022 Mar 12;14(6):1460.

Delprat V, Tellier C, Demazy C, Raes M, Feron O, Michiels C. Cycling hypoxia promotes a pro-inflammatory phenotype in macrophages via JNK/p65 signaling pathway. Sci Rep. 2020 Jan 21;10(1):882.

Daems N, Verlinden B, Van Hoecke K, Cardinaels T, Baatout S, Michiels C, Lucas S, Aerts A. In Vivo Pharmacokinetics, Biodistribution and Toxicity of Antibody-Conjugated Gold Nanoparticles in Healthy Mice. J Biomed Nanotechnol. 2020 Jun 1;16(6):985-996.

Schmit K, Chen JW, Ayama-Canden S, Fransolet M, Finet L, Demazy C, D'Hondt L, Graux C, Michiels C. Characterization of the role of TMEM45A in cancer cell sensitivity to cisplatin. Cell Death Dis. 2019 Dec 4;10(12):919.

Wéra AC, Lobbens A, Stoyanov M, Lucas S, Michiels C. Radiation-induced synthetic lethality: combination of poly(ADP-ribose) polymerase and RAD51 inhibitors to sensitize cells to proton irradiation. Cell Cycle. 2019 Jun 25:1-14.

Marx S, Van Gysel M, Breuer A, Dal Maso T, Michiels C, Wouters J, Le Calvé B. Potentialization of anticancer agents by identification of new chemosensitizers active under hypoxia. Biochem Pharmacol. 2019 Apr;162:224-236.

Penninckx S, Heuskin AC, Michiels C, Lucas S. Thioredoxin Reductase Activity Predicts Gold Nanoparticle Radiosensitization Effect. Nanomaterials (Basel). 2019 Feb 19;9(2).

Genard G, Wera AC, Huart C, Le Calve B, Penninckx S, Fattaccioli A, Tabarrant  T, Demazy C, Ninane N, Heuskin AC, Lucas S, Michiels C. Proton irradiation orchestrates macrophage reprogramming through NFκB signaling. Cell Death Dis. 2018 Jun 27;9(7):728.

Longton E, Schmit K, Fransolet M, Clement F, Michiels C. Appropriate Sequence for Afatinib and Cisplatin Combination Improves Anticancer Activity in Head and Neck Squamous Cell Carcinoma. Front Oncol. 2018 Oct 5;8:432.

ALL PUBLICATIONS

Contact

carine.michiels@unamur.be