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Molecular Carcinogenesis: Michiel van der Heijden

VanDerHeijden

Michiel van der Heijden MD Ph.D.Group leader

About Michiel van der Heijden

Urogenital carcinogenesis

Molecular pathways that are specifically activated in cancer cells provide targets for new and more effective cancer treatments, so-called targeted therapies.
Michiel van der Heijden aims to advance the development of targeted therapies for treating cancer, with a specific focus on bladder cancer. For patients with advanced disease, new therapeutic approaches are urgently needed. Michiel and his group are searching for novel molecular targets, as well as mechanisms of drug resistance and biomarkers that can guide therapy. Through the large number of bladder cancer patients at the adjacent Antoni van Leeuwenhoek hospital, their discoveries can be rapidly translated into the clinic.

 

Research Interests

One of our main interests is to find new ways in which molecular alterations in cancer in general, and bladder cancer in particular, can be targeted by cancer drugs. Also, we aim to explain why resistance develops to molecularly targeted drugs. Although many bladder cancers appear similar under the microscope, some are highly sensitive to cisplatin and others are resistant. Despite a clear difference in biological behaviour, little is known about the molecular differences between cancers that respond well to platinum-based chemotherapy and cancers that do not. We aim to molecularly define these two groups of bladder cancers and search for potentially actionable mutations in these patients.

In addition, we are currently helping to develop a next-generation sequencing assay that can be used for clinical analysis of mutations in cancer patients. This assay will include approximately 175 genes relevant to cancer and should be able to reveal various types of genetic aberrations (mutations, amplifications, translocations). We expect this assay to become part of clinical diagnostics in the course of 2014.

In our research, we collaborate closely with the group of Rene Bernards, department of molecular carcinogenesis. The Bernards group uses advanced molecular technologies to find molecular pathways that play an important role in the sensitivity to several cancer drugs and has pioneered the use of siRNA-based functional genetic screens to find modulators of sensitivity to various drugs.

Co-workers

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Sander Palit

PhD student

Experience

After obtaining my Bachelor of Applied Sciences degree in Biochemistry, I graduated from the Medical Biology Master program at the Radboud University in Nijmegen. During my Master, I focused on cancer-related research.

In June 2015, I joined the group of Dr. Michiel van der Heijden to focus on prostate cancer. The majority of prostate cancers are driven by deregulated androgen receptor (AR) function, and virtually all of these cancers initially respond to androgen deprivation therapy (ADT). However, most patients develop metastatic castration-resistant prostate cancer (mCRPC) that is unresponsive to ADT. The importance of continued AR signaling in mCRPC is illustrated by the efficacy of novel AR-directed drugs such as abiraterone and enzalutamide. Unfortunately, patients develop resistance to these drugs and invariably succumb to the disease.

Within my project, I am interested in the molecular mechanisms of resistance of mCRPC to abiraterone and enzalutamide. Through functional genetic approaches we aim to identify genes that control drug responses, with the ultimate goal to identify effective drug combinations that can be translated to targeted therapies for the treatment of mCRPC.

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Vessies, D.

Daan Vessies

Technician

Experience

After having studied Life Science & Technology at Leiden University and Delft Technical University, I worked at the Genomics Core Facility (Ron Kerkhoven group) for two years. Here I worked on a project that aimed to incorporate capture hybridization sequencing of tumour biopsy DNA into a clinical setting.

 

After this I started working in a collaborative project between the Michiel van der Heijden group and the Clinical Laboratory. In this project I develop methods (ddPCR and NGS-based) to investigate circulating tumour DNA from blood plasma.

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Van der Vos, Kristan

Kristan van der Vos

Postdoctoral Fellow

Experience

I obtained my PhD in the lab of Paul Coffer (Utrecht University) studying the PI3K-Akt-FOXO pathway. After graduating in 2010, I moved to Boston where I investigated the potential of circulating extracellular vesicles as a source of biomarkers in glioblastoma (Massachusetts General Hospital/Harvard Medical School).

In 2014 I joined the NKI to work under supervision of Michiel van der Heijden and René Bernards. My projects focus on understanding the emergence of therapy resistance in bladder cancer. We aim to identify prognostic biomarkers by epigenetic profiling and by analyzing the longitudinal kinetics of tumor mutations in biofluids.

 

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Daniel Vis

Postdoctoral Fellow

Experience

My academic background is in medical biology and computer science. I have had an IT company for five years that designed software for training purposes. I hold a PhD from the University of Amsterdam in data-analysis studying endocrine dynamics and the detection of events and rhythms. Along with  work on mega-variate model validation and non-linear (mixed) modeling.

In the following post-doc at UMCU I focused on dynamic systems and challenge tests in particular. Currently I work on identifying predictive models for personalized treatments for the Center for Personalized Cancer Treatments (CPCT) using NextGenSequencing, cell line panels, and (in-house) clinical data.

 

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Research updates View All Updates

  • Veni subsidie from NWO

    30-7-2013

     

    Publication on NKI website
  • KWF/Alpe d'Huzes grant

    Michiel van der Heijden received a KWF/Alpe d'Huzes grant of1.250.000 for his project on resistance against abirateron and enzalutamide, two novel drugs against prostate cancer. We aim to establish how resistance against these anti-hormonal drugs arises and what can be done against it.

    We will also develop a blood test on DNA from the tumor (ctDNA) that can be used to determine when a tumor starts to develop resistance and by which genetic mechanism.

    This project is a collaboration with Andre Bergman (NKI) and researchers from the Erasmus University Rotterdam and the Center for Personalized Cancer Treatment (CPCT)

Key publications View All Publications

  • Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial

    Lancet. 2016 Mar 4.

    Rosenberg JE, Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A, Dawson N, O'Donnell PH, Balmanoukian A, Loriot Y, Srinivas et al.

    link to PubMed
  • ERBB2 Mutations Characterize a Subgroup of Muscle-invasive Bladder Cancers with Excellent Response to Neoadjuvant Chemotherapy

    Eur Urol. 2015 Jan 27

    Groenendijk FH, de Jong J, Fransen van de Putte EE, Michaut M, Schlicker A, Peters D, Velds A, Nieuwland M, van den Heuvel MM, Kerkhoven et al.

    link to PubMed
 
 

Recent publications View All Publications

  • A Functional Genetic Screen Identifies the Phosphoinositide 3-kinase Pathway as a Determinant of Resistance to Fibroblast Growth Factor Receptor Inhibitors in FGFR Mutant Urothelial Cell Carcinoma

    Eur Urol. 2017 Jan 17

    Wang L, Šuštić T, Leite de Oliveira R, Lieftink C, Halonen P, van de Ven M, Beijersbergen RL, van den Heuvel MM, Bernards R, van der Heijden...

    Link to PubMed
  • Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial

    Lancet. 2016 Dec 7

    Balar AV, Galsky MD, Rosenberg JE, Powles T, Petrylak DP, Bellmunt J, Loriot Y, Necchi A, Hoffman-Censits J, Perez-Gracia JL, Dawson NA,...

    lijk to PubMed
 

Contact

  • Office manager

    Patty Lagerweij

  • E-mail

    p.lagerweij@nki.nl

  • Telephone Number

    +31 20 512 6973

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