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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

van Dijk Nick

Nick van Dijk

PhD student, MD

Experience

During my research internship at the University of Maastricht I examined the impact of tumor immune-suppressive conditions on NK cell cytotoxicity inMultiple Myeloma. After finishing medical school  I worked as an internal medicine resident for one year to gain more clinical experience.

Since January 2017 I work in the Michiel van der Heijden group as a MD/PhD on improving immunotherapy in urothelial cancer. My goal is to better understand
immune-inhibitory processes in the tumor-microenvironment to optimize immunotherapy treatment and improve patient outcome.

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van Dorp

Jeroen van Dorp

PhD student

Experience

After obtaining my medical degree at the Erasmus Medical Centre in Rotterdam, I continued as a master student in the Molecular Medicine program, doing my internship in the group of Guido Jenster, in the department of Urology in Rotterdam. Here, I focused on the onset of metastases in prostate cancer.

The focus of my Ph.D. project is to unravel the interplay between chemotherapy and immunotherapy in urothelial cancer. We aim to find chemotherapy-induced changes that influence the effect of immunotherapy to further improve patient outcome.

 

 

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Gil Jiminez

Alberto Gil Jimenez

PhD student

Experience

I hold a BSc in Physics and Chemistry from the Autonomous University of Barcelona since 2016. Subsequently, I obtained a MSc in Bioinformatics and Systems Biology (UvA-VU) in 2018.

After graduating, I joined The Hyve (IT consultancy) as a Bioinformatician, in which I worked with an open-source community based on healthcare data focused towards clinical applications.

In April 2019, I started a PhD in Computational Biology at the group of Michiel van der Heijden under a close collaboration with Lodewyk Wessels' group. In the project, I will use bioinformatics approaches to better understand the effect and treatment response of chemo- and immunotherapies in bladder cancer. The ultimate goal is to translate the gained knowledge into novel therapeutic strategies to treat bladder cancer patients. 

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Palit, Sander (web).jpg

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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Experience

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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

  • 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 MS

    Link to PubMed
  • The Cancer Immunogram as a Framework for Personalized Immunotherapy in Urothelial Cancer

    Eur Urol. 2018 Sep 28

    van Dijk N, Funt SA, Blank CU, Powles T, Rosenberg JE, van der Heijden MS

    link to PubMed
 
 

Recent publications View All Publications

  • Management of the penile squamous cell carcinoma patient after node positive radical inguinal lymph node dissection: current evidence and future prospects

    Curr Opin Urol. 2019 Dec 27

    de Vries HM, Ottenhof SR, van der Heijden MS, Pos FJ, Horenblas S, Brouwer OR

    link to PubMed
  • TLE3 loss confers AR inhibitor resistance by facilitating GR-mediated human prostate cancer cell growth

    Elife. 2019 Dec 19;8

    Palit SA, Vis D, Stelloo S, Lieftink C, Prekovic S, Bekers E, Hofland I, Šuštić T, Wolters L, Beijersbergen R, Bergman AM, Győrffy B, Wessels LF, Zwart W, van der Heijden MS

    link to PubMed
 

Contact

  • Office manager

    Patty Lagerweij

  • E-mail

    p.lagerweij@nki.nl

  • Telephone Number

    +31 20 512 6973

Lagerweij, Patty.jpg

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