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Holstege Group

Frank Holstege 

Obtained his PhD from Utrecht University in 1996 for his biochemical analyses of RNA polymerase II promoter opening. EMBO and HFSP fellowships enabled postdoctoral studies at the Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology (MIT) in Cambridge, U.S.A., from 1997-1999. Here, under the supervision of Rick Young, Frank performed pioneering genome-wide analyses of transcription regulatory mechanisms, which he continued in his own group at the University Medical Center Utrecht from 2000 onwards. In 2006, Frank was appointed full professor in Genomics in a newly created Utrecht University Academic Biomedical Center professorship within the Molecular Cancer Research department of the Division of Biomedical Genetics. He received an NWO (Dutch Science Foundation) VIDI grant in 2001 and was elected as EMBO (European Molecular Biology Organisation) member in 2007. In 2010, Frank was the recipient of an NWO VICI award and in 2014 he received an ERC (European Research Council) advanced grant. Frank joined the Princess Máxima Center for Pediatric Oncology in 2016.

Research

The Holstege group studies gene expression genome-wide, in health and in disease. The research ranges from molecular analysis of regulatory mechanisms to the discovery of clinically relevant gene expression patterns. Several members of the group are bioinformaticians and there is a strong collaboration with the Kemmeren group. The group is multidisciplinary and has biochemistry, molecular biology, genetics, bioinformatics, high-throughput biology and genomics expertise, as well as extensive experience with setting up and running infrastructure for large-scale genome-wide analyses including robotic automation and IT aspects.

The most important asset of our lab is the people involved. Members have their own projects and responsibilities. We believe that, by working together, we can achieve both our personal goals and the institute's long-term goal. Individual excellence combined with teamwork are key. Whether you are a prospective Ph.D. student, post-doc, bioinformatician or a Masters student looking for an exciting internship, we invite you to join us. If you are intelligent, ambitious and like to work hard at something that is worthwhile, enjoy a challenge and are interested in performing meaningful science at the highest international level, our lab is an excellent place to test and develop your skills. We offer an environment that is internationally oriented, and where it is fun to work and learn together. We take our work seriously and aim to publish in the best scientific journals because we believe that is where our work belongs. For information regarding internships, send us an e-mail. We also welcome letters of interest and CVs from any prospective Ph.D. student, post-doc, scientific programmer or bioinformatician. Useful past experience is in protein biochemistry, molecular biology, molecular genetics, cell biology, next-generation sequencing approaches and bioinformatics. Previous experience in these subjects is not essential for a successful application. Previous excellence and ambition is.

Key publications

  • Large-scale genetic perturbations reveal regulatory networks and an abundance of gene-specific repressors. Kemmeren P, Sameith K, Pasch LA van de, Benschop JJ, Lenstra TL, Margaritis T, O'Duibhir E, Apweiler E, Wageningen S van, Ko CW, Heesch S van, Kashani MM, Ampatziadis-Michailidis G, Brok MO, Brabers NA, Miles AJ, Bouwmeester D, Hooff SR van, Bakel H van, Sluiters E, Bakker LV, Snel B, Lijnzaad P, Leenen D van, Groot Koerkamp MJ, Holstege FC
    Cell. 2014 Apr 24;157(3):740-52. 
  • Validation of a gene expression signature for assessment of lymph node metastasis in oral squamous cell carcinoma.Hooff, SR van, Leusink FKJ, Roepman P, Baatenburg de Jong RJ, Speel E-JM, Brekel MWM van den, Velthuysen M-LF, Diest PJ van, Es RJJ van, Merkx MAW, Kummer JA, Leemans R, Schuuring E, Langendijk JA, Lacko M, Herdt MJ de, Jansen JC, Brakenhoff RH, Slootweg PJ, Takes RP, Holstege FCPJournal of Clinical Oncology. 2012 Nov 20;30(33):4104-10
  • Two distinct repressive mechanisms for histone 3 lysine 4 methylation through promoting 3’-end antisense transcription. Margaritis T, Oreal V, Brabers N, Maestroni L, Vitaliano-Prunier A, Benschop J, Hooff SR van, Leenen D van, Dargemont C, Géli V, Holstege F PloS Genetics. 2012 Sep;8(9):e1002952 (epub 2012 Sep 20)
  • The specificity and topology of chromatin interaction pathways in yeast. Lenstra TL, Benschop JJ, Kim T, Schulze JM, Brabers NACH, Margaritis T, Pasch LAL van de, Heesch SA van, Brok MO, Groot Koerkamp MJ, Ko CW, Leenen D van, Sameith K, Hooff SR van, Lijnzaad P, Kemmeren P, Hentrich T, Kobor MS, Buratowski S, Holstege FCP Molecular Cell. 2011 May 20;42(4):536-49
  • Functional overlap and regulatory links shape genetic interactions between signaling pathways. Wageningen S van, Kemmeren P, Lijnzaad P, Margaritis T, Benschop JJ, Castro IJ de, Leenen D van, Groot Koerkamp MJ, Ko C, Miles AJ, Brabers NAC, Brok MO, Lenstra TL, Fiedler D, Fokkens L, Aldecoa R, Apweiler E, Taliadouros V, Sameith K, Pasch LAL van de, Hooff SR van, Bakker LV, Krogan NJ, Snel B, Holstege FCP Cell. 2010 Dec 10;143(6):991-1004

Group members

  • Frank Holstege, PI
  • Mariel Brok, research technician
  • Willemijn Breunis, pediatric oncologist/post-doc
  • Marian Groot Koerkamp, research technician
  • Philip Lijnzaad, bioinformatician
  • Thanasis Margaritis, post-doc
  • Wim de Jonge, PhD student
  • Christian Tomuta, PhD student
  • Jeff DeMartino, Masters student

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