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Leendert Looijenga

11A. Normal and aberrant germ cell development

The project bridges the exciting and developing scientific domains of fertility, oncology and regenerative medicine. Germ cell tumors are on these crossroads, and allow investigations related to genomic (in)stability, regulation of pluripotency, toxicology and clinical treatment efficacy.

Various in vitro and in vivo models  have been generated and are currently explored (e.g. CRISPR-Cas9 based genetic modulations). These are proven to be highly informative to investigate the underlying mechanisms related to both normal and malignant germ cell development. The impact of the Looijenga group has been demonstrated based on adaptation of the WHO classification of germ cell tumors (Looijenga and Oosterhuis, Nature Reviews Cancer 2005 and 2019), identification and effort to clinical implementation of microRNA371a-3p in a clinical setting (Salvatori et al., Stem Cell Reports 2018; Almstrup et al., Nat Rev Urol. 2020), and identification of a novel mechanism of cisplatin resistance (Timmerman et al., J Clin Oncol. 2022).

The PhD candidate will be trained in understanding the underlying mechanisms regarding normal as well as aberrant germ cell development, in which molecular- as well as cell-biological laboratory approaches will be applied. These will include CRISPR-Cas9 based modulations as well as application of novel organoid-based culture methods. In addition, the candidate will be trained in bioinformatics for multi-omics evaluations based on both in-house generated as well as publicly domain available data sets. The secondments will be an exciting combination of  visiting a highly experienced clinical environment in close interaction with a well-known scientific research institute (Bratislava) as well as visiting a commercial company related to detection of RNA targets based on a unique non-PCR based method (Granada). This program will allow the candidate to obtain a broad know how and set of technical skills relevant in the context of a future career in developmental biology, (translational) oncology, toxicology and regenerative medicine.

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