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Laboratorium voor Reproductieve Genomica

 

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Group leader: Thierry Voet

Thierry Voet graduated in 1998 as Bio-engineer in Cell and Gene Biotechnology at the K.U.Leuven. In 2003, he obtained a Ph.D. at the Faculty of Medicine of the same university. During his Ph.D. and part of his postdoctoral research at the Department of Human Genetics (K.U.Leuven) he developed human artificial chromosomes as tools for transgenesis and analysis of mammalian mitosis and meiosis. For the latter he worked in close collaboration with the laboratory of Dr. Harry Scherthan (Max Planck Institute of Molecular Genetics, Berlin, Germany) for approximately two years. In 2007, he joined the SymBioSys team (Department of Human Genetics, K.U.Leuven) as a postdoctoral researcher. He mainly co-developed methods for SNP- and DNA copy number profiling of single human cells. Application of this technology to single human blastomeres led to a publication in Nature Medicine in 2009: "Chromosome instability is common in human cleavage stage embryos". As of October 1st 2009, he became Tenure Track professor at the Department of Human Genetics (K.U.Leuven) and started the Laboratory of Reproductive Genomics.

Thierry Voet is part of the ‘Genomics Core Facility of KU/UZ-Leuven’ for support of (1) developed single cell genomics strategies and (2) high resolution DNA-microarray analyses.

Research interests

My research focuses on (1) the development and applications of technologies for single cell genomics, (2) the unravelment of the mechanisms of embryonic chromosome instability and its impact on human variation and infertility and (3) the identification of genetic variants causing human infertility.

  • Development of single cell genomics At the moment, we are world-leaders in the development and application of single cell DNA-array technology which allows to type SNPs, Mb-sized DNA copy number variants (CNVs) and haplotypes in single human cells. We are currently developing technology to detect Kb-sized CNVs as well as balanced structural variation (inversions, insertions, translocations) in single cells to answer specific biological questions. The developed technology and data analysis pipeline will be invaluable for genome analyses of embryos and tumors.
  • Unravelment of the causal mechanisms of chromosome instability at early (human) embryogenesis Our data suggest that whole chromosome mal-segregation, chromosome breakage, fusion and centric fission occur frequently during early human embryogenesis (Vanneste et al., Nature Medicine 2009). We aim to identify and study the causal molecular mechanisms in human and animal model embryos.
  • Genetic causes of human infertility We aim to uncover the genetic variants causal for (1) cleavage failure of human fertilized oocytes and (2) (male) infertility in general. This will be achieved by novel DNA-microarray, massive parallel sequencing and bio-informatic technologies.

Keywords

Single cell genomics – Chromosome instability – Mitosis – Meiosis – Genomic analyses of embryos – Genetic causes of infertility – Human genetic variation – Human artificial chromosomes

Key publications

  • Vanneste E*, Voet T*, Le Caignec C, Ampe M, Konings P, Melotte C, Debrock S, Amyere M, Vikkula M, Schuit F, Fryns JP, Verbeke G, D'Hooghe T, Moreau Y, Vermeesch JR°. Chromosome instability is common in human cleavage-stage embryos. Nat Med. 2009 May;15(5):577-83.
  • Vanneste E*, Voet T*, Melotte C, Debrock S, Sermon K, Staessen C, Liebaers I, Fryns JP, D'Hooghe T, Vermeesch JR°. What next for preimplantation genetic screening? High mitotic chromosome instability rate provides the biological basis for the low success rate. Hum Reprod. 2009 Nov;24(11):2679-82.
  • Voet T*,°, Vanneste E, Peeters H, Konings P, Moreau Y, Fryns JP, D’Hooghe T, Legius E, Vermeesch JR. Genome-wide haplotyping of single cells. Submitted.
  • Dar M*,°, Giesler T, Richardson R, Cai C, Cooper M, Lavasani S, Kille P, Voet T, Vermeesch J. Development of a novel ozone- and photo-stable HyPer5 red fluorescent dye for array CGH and microarray gene expression analysis with consistent performance irrespective of environmental conditions. BMC Biotechnol. 2008 Nov 12;8:86.
  • Pawlinski R*, Tencati M, Holscher T, Pedersen B, Voet T, Tilley RE, Marynen P, Mackman N°. Role of cardiac myocyte tissue factor in heart hemostasis. J Thromb Haemost. 2007 Aug;5(8):1693-700.
  • Voet T*, Schoenmakers E*, Carpentier S, Labaere C and Marynen P. Controlled transgene dosage and PAC mediated transgenesis in mice using a chromosomal vector. Genomics, 2003 Dec;82(6):596-605.
  • Voet T*, Liebe B*, Labaere C, Marynen P and Scherthan H. Telomere-independent homologue pairing and checkpoint escape of accessory ring chromosomes in male mouse meiosis. J Cell Biol. 2003 Sep 1;162(5):795-808.
  • Voet T*, Vermeesch J*, Carens A, Durr J, Labaere C, Duhamel H, David G, Marynen P. Efficient Male and Female Germline Transmission of a Human Chromosomal Vector in Mice. Genome Res 2001 Jan;11(1):124-136

 

Research team

 

Parveen Kumar
PhD student


parveen.dabas@student.kuleuven.be

 

Niels Van der Aa
PhD student

016347992
niels.vanderaa@med.kuleuven.be

 

Thierry Voet
Group leader


Thierry.Voet@med.kuleuven.be

 

Masoud Zamani Esteki
PhD student

01647991
masoud.zamaniesteki@uzleuven.be