Areas of expertise

Edwin Cuppen is professor of Human Genetics. He is an expert in DNA sequencing and applies next-generation sequencing for both research and diagnostic purposes. He is a pioneer in personalized genomics, carrying his genome not only in his own cells, but also on his iPad.

In 2005, Edwin Cuppen received a European Young Investigators Award and in 2013, he was awarded a prestigious NWO Vici grant for dissecting the molecular mechanisms behind and functional consequences of structural variation in genomes. In his current work he combines experimental methods, including next-generation DNA sequencing technology and other -omics techniques, with patient cohort and cellular model systems and integrative bioinformatic approaches to understand the effects of genetic variation under normal and disease conditions like cancer and congenital disease.

He is also one of the initiators of the nationally operating Center for Personalized Cancer Treatment, and director of a national large scale sequencing center, the Hartwig Medical Foundation, in Amsterdam. These national collaborations aim for the stratification of cancer patients towards targeted treatments based on DNA measurements of the tumor and to bring these developments to all cancer patients in The Netherlands in a timely and responsible manner.

Research program / group

The Cuppen group is a translational research group that investigates the causes and consequences of genetic variation. Variation in DNA sequences can have a large impact on disease or disease susceptibility, for example resulting in congenital disease or cancer. In recent years new technologies have emerged that allow us to determine the complete DNA sequence of individuals. We are using the latest DNA sequencing technologies for studying the basis of specific human diseases. Interpretation of alterations at the single base letter and structural level in both protein-coding and regulatory domains is one of the main challenges that we address using systematic integrative experimental and computational approaches. Furthermore, we are studying the origin and mechanisms by which de novo genetic variation is induced.

Our research is performed in a highly collaborative fashion both within the group and with other research groups and clinical laboratories and researchers on a local, national and international level. These collaborations are important for translating fundamental knowledge into clinical practice and routine diagnostics.


Our main fundamental research questions are:

  • What are the mutation rates and processes in healthy cells in different tissues during the process of aging?
  • How do these mutations contribute to disease and aging and what are the mechanisms that protect normal cells from disfunctioning?
  • How do mutations contribute to tumor characteristics including response to treatment?
  • What are the causes of complex structural variation (SVs)
  • What are the consequences of complex SVs on genome/gene function in congenital disease


We address these questions utilizing several stem cell-based technologies, including organoids and patient-derived induced pluripotent stem cells. The effects of single nucleotide variants and structural variants are determined by sequencing-based technologies such as RNA-seq, Chip-seq etcetera. Such data-sets are integrated and analyzed in the context of large bodies of public data by bioinformaticians and computational scientists to dissect putative mechanism and define hypotheses on potential causal relationships. We envision that these approaches will contribute to increasing fundamental biological knowledge, improving diagnostics and the development of personalized medicine.

The Cuppen group also supports education and training in genomics and bioinformatics.


Group members

  • Edwin Cuppen, PI
  • Arne van Hoeck, postdoc
  • Bastiaan van der Roest, technician
  • Chris de Witte, PhD student
  • Ellen Stelloo, postdoc
  • Ewart Kuijk, postdoc
  • Ies Nijman, postdoc
  • José Espejo Valle-Inclan, PhD student
  • Judith Vlaar, PhD student
  • Luan Nguyen, PhD student
  • Lisanne de la Fonteijne, technician
  • Nicolle Besselink, technician
  • Sander Boymans, bioinformatician
  • Sharon Christensen, PhD student
  • Robin Geene, technician
  • Roel Janssen, technician

Key publications

  • Blokzijl F, de Ligt J, Jager M, Sasselli V, Roerink S, Sasaki N, Huch M, Boymans S, Kuijk E, Prins P, Nijman IJ, Martincorena I, Mokry M, Wiegerinck CL, Middendorp S, Sato T, Schwank G, Nieuwenhuis EE, Verstegen MM, van der Laan LJ, de Jonge J, IJzermans JN, Vries RG, van de Wetering M, Stratton MR, Clevers H, Cuppen E*, van Boxtel R (2016). Tissue-specific mutation accumulation in human adult stem cells during life. Nature 538(7624):260-264. (IF = 38.6)
  • Prins P, de Ligt J, Tarasov A, Jansen RC, Cuppen E, Bourne PE (2015). Toward effective software solutions for big biology. Nature Biotechnol. 33(7):686-7

  • Rat Genome Sequencing and Mapping Consortium (2013). From sequence to phenotype variation in the laboratory rat. Writing group: Baud A, Hermsen R, Guryev V, Gauguier D, Stridh P, Olsson T, Holmdahl R, Graham D, McBride MW, Foroud T, Fernandez-Teruel A, Hubner N, Cuppen E, Mott R, Flint J. Sequencing group: Hermsen R, Hummel O, Lansu N, Patone G, Ruzius FP, de Bruijn E, Hauser H, Atanur SS, Aitman TJ, Flicek P, Adams DJ, Keane T, Saar K, Hubner N, Guryev V, Cuppen E. Nature Genetics, 45:767-775
  • Kettleborough RNW*, Busch-Nentwich EM*, Harvey SA*, Dooley CM, de Bruijn E, van Eeden F, Sealy I, White RJ, Herd C, Nijman IJ, Fényes F, Mehroke S, Scahill C, Gibbons R, Wali N, Carruthers S, Hall A, Yen J, Cuppen E*, Stemple DL* (2013). A systematic genome-wide analysis of zebrafish protein-coding gene function. Nature, 496:494–497
  • Kloosterman WP, Tavakoli-Yaraki M, van Roosmalen MJ, van Binsbergen E, Renkens I, Duran K, Ballarati L, Vergult S, Giardino D, Hansson K, Ruivenkamp CA, Jager M, van Haeringen A, Ippel EF, Haaf T, Passarge E, Hochstenbach R, Menten B, Larizza L, Guryev V, Poot M, Cuppen E (2012). Constitutional chromothripsis rearrangements involve clustered double-stranded DNA breaks and nonhomologous repair mechanisms. Cell Reports 1:648-55
  • Harakalova M, van Harssel JJ, Terhal PA, van Lieshout S, Duran K, Renkens I, Amor DJ, Wilson LC, Kirk EP, Turner CL, Shears D, Garcia-Minaur S, Lees MM, Ross A, Venselaar H, Vriend G, Takanari H, Rook MB, van der Heyden MA, Asselbergs FW, Breur HM, Swinkels ME, Scurr IJ, Smithson SF, Knoers NV, van der Smagt JJ, Nijman IJ, Kloosterman WP, van Haelst MM, van Haaften G, Cuppen E. (2012). Dominant missense mutations in ABCC9 cause Cantú syndrome. Nature Genetics 44:793-6.


Link to full list of publications

More contact information

Visiting address:
Center for Molecular Medicine, UMC Utrecht
STR. 2.201
Universiteitsweg 100
3584 CG Utrecht
The Netherlands

Monique van Schaick,
+31 (0)88 75 68312

Detailed CV