After training as a clinician, Jan Molenaar decided to focus completely on molecular translational research. His aim is to bridge the gap between novel molecular findings and clinical treatment in pediatric cancer. He was offered the opportunity to start his own research group within the department of Oncogenomics at the AMC. In 2011, Jan became a KWF fellow and obtained a Principal Investigator (PI) position in the AMC in 2012. From 2016 on, he will lead an independent research group as PI in the Princes Máxima Center for pediatric oncology. In 2016 Jan received a Vidi and an ERC Start grant to further support his research.
Our group currently consists of 1 Post doc, 6 PhD students, 4 technicians and 1 student. The focus is on the identification of potential new therapeutic targets for neuroblastoma and efficient in-vitro and in-vivo validation of targeted compounds. We have used high-throughput analysis and a variety of molecular biological techniques to identify multiple new oncogenes and aberrations in neuroblastoma. To get full insight in the molecular genetic aberrations in neuroblastoma, we recently performed Whole Genome Sequencing for over 300 samples. For further validation of new target genes we have developed an in-vivo system using Tumor Initiating Cells from primary tumor samples and bone marrow metastasis. We have performed in-vitro and in-vivo validations for Survivin (YM155), BCl2 (ABT199), CDK2 (AT7519), BRAF (Dabrafenib), EZH2 (GSK126), DNA-PK (NU7026), MTH1 (TH588) and MEK (Cobimetinib). Clinical trial proposals are currently being discussed with Astex (AT7519), Abbott (ABT199) and Roche (Cobimetinib).
We will use the knowledge and infrastructure that we obtained in neuroblastoma research to set up an evidence-based precision medicine program. We have initiated the iTHER (individualized therapy) project in which we will perform biological characterization of all relapsed pediatric tumors for which no curative treatment options are available. Patients will then be assigned to the best fitting trial based on the molecular profile of their tumor.
- TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors. Valentijn LJ, Koster J, Zwijnenburg DA, Hasselt NE, van Sluis P, Volckmann R, van Noesel M, George RE, Tytgat GAM, Molenaar JJ, Versteeg R. Nat Genet. 2015
- Relapsed neuroblastomas show frequent RAS-MAPK pathway mutations. Eleveld TF, Oldridge DA, V Bernard, J Koster, LC Daage, SJ Diskin, L Schild, N Bentahar, A Bellini, M Chicard, E Lapouble, V Combaret, P Legoix-Né, J Michon, TJ Pugh, LS Hart, JA Rader, EF Attiyeh, JS Wei, S Zhang, A Naranjo, JM Gastier-Foster, MD Hogarty, MA. Smith, JM Guidry Auvil. TBK Watkins, DA Zwijnenburg, ME Ebus, P v Sluis, A Hakkert, E v Wezel, CE vd Schoot, EM Westerhout, JH Schulte, GA Tytgat, MEM Dolman, , I Janoueix-Lerosey, DS Gerhard, HN Caron, O Delattre, J Khan, R Versteeg, G Schleiermacher, Molenaar JJ (corr. author), Maris JM. Nat Genet. 2015
- Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes. Molenaar JJ, Koster J, Zwijnenburg DA, van Sluis P, Valentijn LJ, van der Ploeg I, Hamdi M, van Nes J, Westerman BA, van Arkel J, Ebus ME, Haneveld F, Lakeman A, Schild L, Molenaar P, Stroeken P, van Noesel MM, Ora I, Santo EE, Caron HN, Westerhout EM, Versteeg R. Nature. 2012. Feb 22;483(7391):589-93.
- Genome sequencing of pediatric medulloblastoma links catastrophic DNA rearrangements with TP53 mutations. Rausch T, Jones DT, Zapatka M, Stütz AM, Zichner T, Weischenfeldt J, Jäger N, Remke M, Shih D, Northcott PA, Pfaff E, Tica J, Wang Q, Massimi L, Witt H, Bender S, Pleier S, Cin H, Hawkins C, Beck C, von Deimling A, Hans V, Brors B, Eils R, Scheurlen W, Blake J, Benes V, Kulozik AE, Witt O, Martin D, Zhang C, Porat R, Merino DM, Wasserman J, Jabado N, Fontebasso A, Bullinger L, Rücker FG, Döhner K, Döhner H, Koster J, Molenaar JJ, Versteeg R, Kool M, Tabori U, Malkin D, Korshunov A, Taylor MD, Lichter P, Pfister SM, Korbel JO. Cell. 2012. Jan 20;148(1-2):59-71.
- LIN28B induces neuroblastoma and enhances MYCN levels via let-7 suppression. Molenaar JJ, Domingo-Fernández R, Ebus ME, Lindner S, Koster J, Drabek K, Mestdagh P, van Sluis P, Valentijn LJ, van Nes J, Broekmans M, Haneveld F, Volckmann R, Bray I, Heukamp L, Sprüssel A, Thor T, Kieckbusch K, Klein-Hitpass L, Fischer M, Vandesompele J, Schramm A, van Noesel MM, Varesio L, Speleman F, Eggert A, Stallings RL, Caron HN, Versteeg R, Schulte JH. Nat Genet. 2012. Nov;44(11):1199-206.
- Jan Molenaar, PI
- Emmy Dolman, post doc
- Thomas Eleveld, PhD
- Laurel Bate-Eya, PhD
- Anne Hakkert, PhD
- Nil Schubert, PhD
- Waleed Hassan, PhD
- Lindy Vernooij, PhD
- Marli Serbanescu, technician
- Linda Schild, technician
- Bianca Koopmans, technician
- Lindy Alles, technician