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Looijenga group

Investigation of the origin and underlying mechanism(s) of clinical behavior of the various types of human germ cell tumors with the goal to facilitate optimal (early) diagnosis and treatment by identification and application of clinically relevant (molecular) biomarkers. This will result in development of the most effective treatment of these young patients based on optimal risk stratification with limited side effects, both on the short and long term. This is approached using generation and investigation of both (published) high throughput datasets an well as development and characterization of clinically relevant model systems.  In addition, pre-clinical studies are performed to investigate methods to increase the change of fertility preservation of prepubertal patients undergoing high risk gonadotoxic treatment because of the diagnosis cancer. 

Group leader: Prof. dr. Leendert Looijenga
Phone +31 (0) 88 972 5211
Email L.Looijenga@prinsesmaximacentrum.nl

Germ Cell Tumors (GCT) are historically considered to be highly heterogeneous and complex, both regarding origin, histological constitution as well as clinical behavior. Investigations on normal developmental processes related to germ cell and gonadal formation and maturation combined with integrated and omics-based studies on germ cell tumors, stimulated novel and clinically relevant insights. This resulted in a modified classification system, currently recommended by the WHO (World Health Organization), including application of diagnostic tools. Current studies will further elucidate the mechanism(s) responsible for their origin and clinical behavior, including their overall sensitivity to systematic treatment and the exceptional resistance. This will allow optimal treatment of the individual patient with minimal (long term) side effects. Moreover, the knowlegde regarding the normal germ cell development will be applied in the development of pre-clinical spermatogonial stem cell propagation methods to increase the change of successfull fertility preservation in prepubertal cancer patients undergoing high risk gonadatoxic treatment. 

"Understanding developmental biological processes amplify identification of the clinically relevant pathogenetic changes in human germ cell tumors as well as prepubertal fertility preservation." Prof. dr. Leendert Looijenga - Group leader

Informative liquid biopsy biomarkers are highly instructive for the diagnosis and follow-up of patients with a malignant germ cell tumor. Currently the proteins AFP and hCG and to a lesser extend LDH are applied and found to be relevant in a clinical setting. However, they have significant limitations due to false negative and positive findings. We demonstrated that a defined (embryonic) set of small noncoding RNA (i.e., microRNAs) in combination with RASSF1AM are highly informative as serum/plasma and cerebrospinal fluid molecular biomarker for malignant germ cell tumors. In addition, these miRNAs are informative to detect undifferentiated (and potentially malignant) elements in Induced Pluripotent Stem Cell (IPSC) and Embryonic Stem Cell (ESC) derivatives, potentially used for regenerative medicine. Current studies are performed to clinically implement the embryonic miRNA and RASSF1AM as molecular biomarkers for the optimal diagnosis and treatment of patients with germ cell tumors. In addition, it is investigated whether a similar approach will also be applicable for other cancer types as well.  Moreover, knowlegde is generated to develop an in vitro method for spermatogonial stem cell propagation to allow fertility preservation in male prepubertal cancer patients undergoing high risk gonadotoxic treatment. The underlying mechanism(s) of platin-based chemotherapy is investigated using both pre-clinical laboratory model systems, as well as (publically available and own generated) high throughput datasets of both proven treatment sensitive as well as resistance GCT samples. 

Our mission: All pediatric and young adult patients with a GCT need to be diagnosed, treated and followed-up using the most informative and updated tools to generate the highest treatment efficacy with no or limited side effects to ensure long term quality of life. Prepuberal cancer patients undergoing high risk gonadotoxic treatment need to benefit for the possibilities for fertility preservation. 

Our vision: Multi-modal developmental biology-based research will generate clinically relevant tools to improve lifelong care of pediatric and young adult GCT patients, and endepth opur possibilities to develop effective and safe regenerative medicine tools, including fertility preservation.  

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About our group
Our team consists of a multidisciplinary group of scientists in various phases of their development, including an experienced technician (Ad Gillis), a postdoc (Thomas Eleveld), and the following PhD students: Sruthi Sriram (Fertility Preservation), Sanne Hillenius (Regenerative Medicine), Ferd Janssen (Liquid Biopsies), Camilla Perosa (Platin Resistance and Biomarkers), Caroline Hulsker (Surgery). Dr. Annelies Mavinkurve-Groothuis (pediatric oncologist) is associate group leader. A close collaboration exist with the group of Professor Daniela Salvatori (Prof. Veterinary Medicine, Utrecht), related to (in)stability of pluripotent stem cells used for regenerative medicine (PhD students Joaquin Montilla-Rojo and Marnix van Soest). In this context a collaboration exists as well with the group of Prof. Eelco de Koning (LUMC). On average three students are trained within the group.

Looijenga group

Prof. dr. (PhD) Leendert Looijenga Group Leader (50%) and Manager Director Research (50%)
Ing. Ad Gillis Technician
Marit Buiting Research technician
Thomas Eleveld Postdoc
Sanne Hillenius PhD student
Ferd Janssen PhD student
Joaquin Montilla Rojo PhD student
Camilla Perosa PhD student
Marnix van Soest PhD student
Sruthi Sriram PhD student
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