Tumor hypoxia

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

Principal Investigator

Prof. Carine Michiels

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

PhD students: Karim Bouhjar, Jia-Wei Chen, Camille Huart and Christoph Schifflers

Research projects

  • ONGOING PROTHER-WAL: Proton Therapy Research in Wallonia
  • 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 Investigation of immunological factors contributing to the increased radiosensitivity of HPV-driven compared to HPV-negative head and neck cancer. Ongoing PhD thesis by Christoph Schifflers. Joint PhD programme at UNamur (Prof. Carine Michiels) and German Cancer Research Center DKFZ, Heidelberg (Dr. Angelika Riemer)
  • ONGOING Determination of the genes implicated in intrinsic resistance to proton beam therapy for the treatment of glioblastoma. Ongoing PhD thesis by Jia-Wei Chen. Under the supervision of Prof. Carine Michiels, UNamur, NARILIS.
  • ONGOING Reprogramming tumour-associated macrophages with proton irradiation to boost the effects of immunotherapy in pancreatic cancer. Ongoing PhD thesis by Camille Huart. Under the supervision of Prof. Carine Michiels, UNamur, NARILIS.
  • ONGOING 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. Ongoing PhD thesis by Eléonore Longton. Under co-supervision by Prof. Carine Michiels, UNamur, NARILIS (promoter) and Dr. Jean-François Daisne, CHU UCL Namur, site Sainte-Elisabeth (co-promoter).
  • 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, UNamur, NARILIS (promoter) and Prof. Stéphane Lucas, UNamur, NARILIS (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, NARILIS (promoter) and Prof. Olivier Féron, UCLouvain, IREC (co-promoter).

  • Characterization of the functions of TMEM45A using a loss of function model. Postdoctoral research by Dr. Benjamin Le Calvé. Under the supervision of Prof. Carine Michiels, UNamur, NARILIS

Selected publications

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