J. (Julie) Nonnekens, PhD

Bio

Julie Nonnekens
Associate professor and principal investigator

Julie Nonnekens received her MSc in Biotechnology at Wageningen University in 2009. She obtained her PhD in cancer biology with the focus on DNA repair mechanisms at the University of Toulouse (France) in 2013. Following, she was a postdoc at the Hubrecht Institute working on ribosome biogenesis in cancer and longevity. In 2014 Julie joined the Erasmus MC Departments of Radiology & Nuclear Medicine and Molecular Genetics and is now Associate Professor.

The research of her group bridges the interests of both departments in the field of DNA damage repair mechanisms and nuclear medicine to study the radiation biology of targeted radionuclide anticancer treatment to ultimately optimize treatment regimens.

 See more on the Nonnekens Lab | research laboratory 

Julie has received several (young investigator) awards and is principal investigator on various research grants including the prestigious ERC starting grant.

She is chair of the Netherlands Society of Radiobiology and co-founder of the European working group on Radiobiology of Molecular Radionuclide Therapy. 

Research

Targeted Radionuclide Therapies (TRT) are transforming the treatment landscape for patients with metastatic cancers. These therapies involve delivering radiolabeled compounds directly to cancer cells by targeting specific tumor markers, such as cell surface receptors. Once bound, the radionuclides emit ionizing radiation that damages the DNA of cancer cells, ultimately leading to their death.

While TRT is increasingly used in clinical practice, treatment outcomes vary. Some patients experience excessive toxicity due to overtreatment, while others see little benefit due to undertreatment. This highlights a critical need to optimize and personalize TRT approaches.

Our goal is to enhance the effectiveness of TRT by deepening our understanding of its radiobiological mechanisms: the biological effects of ionizing radiation at the cellular and tissue levels. This knowledge can guide the development of more effective treatment regimens and potentially shift TRT from a primarily palliative option to a curative one.

Our Focus Areas:

• Cellular effects of TRT in both tumor and healthy tissues
• Radiobiology of different radiation qualities, exploring how various types of ionizing radiation affect biological systems
• Radiosensitization strategies to enhance the therapeutic impact of radionuclide treatments

Our Research Tools and Models:

• In vitro systems: 2D cultured cancer cells for detailed mechanistic studies
• In vivo models: Xenografted mice to evaluate treatment efficacy and toxicity in a physiological context
• Clinical relevance: Analysis of patient-derived samples to connect laboratory findings with real-world outcomes
• Advanced imaging and analysis:
  • Cellular assays and immunohistochemistry on human and mouse tissues
  • Confocal live-cell microscopy for dynamic cellular observations
  • Small animal imaging techniques including SPECT, MRI, and optical imaging
  • Computational modeling and data analysis to simulate and interpret biological responses

This integrated approach allows us to investigate TRT from multiple perspectives (molecular, cellular, and systemic) ultimately aiming to personalize and improve cancer treatment outcomes. For more information:  Nonnekens Lab

Selected publications

• J. Nonnekens, M. van Kranenburg, C.E.M.T. Beerens, M. Suker, M. Doukas, C.H.J. van Eijck, M. de Jong, D.C. van Gent. Potentiation of Peptide Receptor Radionuclide Therapy by the PARP Inhibitor Olaparib. Theranostics 2016; 6(11):1821-1832.
  This publication shows the design of RPT combined with a DNA-damage repair inhibitor, which is contributing to a new way of treating patients with RPT. I based this improved treatment regimen on the fundamental DNA repair information obtained in my laboratory. At the moment, >8 different clinical trials have been initiated worldwide based on my findings. Excitingly, I am PI of our own phase I Proof-of-Concept trial based on this work for which we have acquired public funding and patient inclusion is starting in the coming months.
• Feijtel D, Doeswijk GN, Verkaik NS, Haeck JC, Chicco D, Angotti C, Konijnenberg MW, de Jong M, Nonnekens J. Intra-tumoral somatostatin receptor 2 heterogeneity confers differential radionuclide therapy response in preclinical neuroendocrine tumor models. Theranostics 2021; 11(2):491-505.
  In this publication we describe radiobiological factors influencing RPT. We show for the first time that tumor heterogeneity within and between tumor models affects TRT efficacy and provide a molecular basis for designing re-treatment strategies.
• Ruigrok EAM, van Vliet N, Dalm SU, de Blois E, van Gent DC, Haeck JC, de Ridder C, Stuurman D, Konijnenberg MW, van Weerden WM, de Jong M, Nonnekens J. Extensive preclinical evaluation of lutetium-177 labeled PSMA-specific tracers for prostate cancer radionuclide therapy. Eur J Nucl Med Mol Imaging. 2021;48:1339-1350.
  In this publication, we have unraveled various radiobiological parameters of RPT to provide preclinical evidence for the most efficient and least toxic tracer. In 2019, this work was nominated for the Marie Curie prize. This prestigious European prize by the European Association of Nuclear Medicine provides great visibility in the nuclear medicine community and highlights the importance of our work when selecting the most optimal treatment modality for RPT.
• Tamborino G, De Saint-Hubert M, Struelens L, Seoane DC, Ruigrok EAM, Aerts A, van Cappellen WA, de Jong M, Konijnenberg MW, Nonnekens J. Cellular dosimetry of [177Lu]Lu-DOTA-[Tyr3]octreotate radionuclide therapy: the impact of modeling assumptions on the correlation with in vitro cytotoxicity. EJNMMI Phys. 2020 Feb 10;7(1):8.
  This is the first joint publication from my collaboration with the SCK-CEN in Belgium. Here, we prove that biological input is trivial in performing optimal dosimetric calculations and it is paving way for new (collaborative) studies into biology-driven dosimetry. Two follow-up studies on DNA damage modelling and in vivo dosimetry have recently been published as well.
• Ruigrok EAM, Tamborino G, de Blois E, Roobol SJ, Verkaik N, de Saint-Hubert M, Konijnenberg MW, van Weerden WM, de Jong M, Nonnekens J. In vitro dose effect relationships of actinium-225- and lutetium-177-labeled PSMA-I&T. Eur J Nucl Med Mol Imaging. 2022 May 12. doi: 10.1007/s00259-022-05821-w.In this publication, we compare for the first time the biological effectiveness of alpha and beta-RPT for prostate cancer treatment that are currently being employed in the clinic. We found a 4-fold increased effectiveness of alpha-RPT compared to beta-RPT with the same radiation dose. This work can help in the future when selecting the best treatment option in clinical practice.

All publications:

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• MSc Infection and Immunity,
• MSc Molecular Medicine,
• BSc Nanobiology,
• BSc Medicine,
• BSc Radiotherapy,
• Medical residents
• Radiotherapy

Grants

The radiobiology of radionuclide therapy group