Bernd Wollnik. Professor of Medical Genetics, Director 

University Medical Center Göttingen. Website

Heinrich-Düker-Weg 12, 37073 Göttingen, Germany

Reseach subject

Next generation sequencing-based identification of causative genes for rare diseases; novel genes/pathways involved in human accelerated-aging syndromes; genomic instability and its role in progeria syndromes & aging

Summary

My group’s key research area is to discover novel genes and elucidate the molecular mechanisms underlying rare congenital syndromes. We focus especially on syndromes associated with primary microcephaly, e.g. Bloom syndrome or Seckel syndrome, and progeroid syndromes, i.e. disorders associated with premature or accelerated aging like, for example, Hallermann-Streiff syndrome or Wiedemann-Rautenstrauch syndrome.

We have established an innovative bioinformatics pipeline and approach for assessing and interpreting next generation sequencing (NGS) data from whole-genome or whole-exome sequencing that brings together scientists and clinicians coming from different backgrounds to identify new causative genes for undiagnosed rare congenital diseases. By deep functional characterization of the involved gene products and molecular pathways, we unravel how they act in fundamental cellular processes such as DNA replication, chromatin structure & remodelling, transcriptional regulation or mitochondrial functions. Our findings expand our knowledge about the pathogenesis of these rare disorders and, at the same time, provide us with important new insights in the processes involved in physiological aging and in common age-related pathologies such as neurodegeneration, heart failure or cancer.

We also use different cellular models and model organisms as well as iPS cells to investigate the role of somatic mutations in genomic instability and changes in gene expression profiles.

Publications

• Gordon CT, Xue S, Yigit G, Filali H, Chen K, Rosin N, Yoshiura KI, Oufadem M, Beck TJ, McGowan R, Magee AC, Altmüller J, Dion C, Thiele H, Gurzau AD, Nürnberg P, Meschede D, Mühlbauer W, Okamoto N, Varghese V, Irving R, Sigaudy S, Williams D, Ahmed SF, Bonnard C, Kong MK, Ratbi I, Fejjal N, Fikri M, Elalaoui SC, Reigstad H, Bole-Feysot C, Nitschké P, Ragge N, Lévy N, Tunçbilek G, Teo AS, Cunningham ML, Sefiani A, Kayserili H, Murphy JM, Chatdokmaiprai C, Hillmer AM, Wattanasirichaigoon D, Lyonnet S, Magdinier F, Javed A, Blewitt ME, Amiel J, Wollnik B, Reversade B. De novo mutations in SMCHD1 cause Bosma arhinia microphthalmia syndrome and abrogate nasal development. Nat Genet (2017) Feb;49(2):249-255. doi: 10.1038/ng.3765
• Harley ME, Murina O, Leitch A, Higgs MR, Bicknell LS, Yigit G, Blackford AN, Zlatanou A, Mackenzie KJ, Reddy K, Halachev M, McGlasson S, Reijns MA, Fluteau A, Martin CA, Sabbioneda S, Elcioglu NH, Altmuller J, Thiele H, Greenhalgh L, Chessa L, Maghnie M, Salim M, Bober MB, Nurnberg P, Jackson SP, Hurles ME, Wollnik B, Stewart GS, and Jackson AP. TRAIP promotes DNA damage response during genome replication and is mutated in primordial dwarfism. Nat Genet (2016), 48(1):36-43.
• Hatzold J, Beleggia F, Herzig H, Altmüller J, Nürnberg P, Bloch W, Wollnik B, Hammerschmidt M. Tumor suppression in basal keratinocytes via dual non-cell-autonomous functions of a Na,K-ATPase beta subunit. eLife (2016), doi: 10.7554/eLife.14277.
• Bögershausen N, Tsai IC, Pohl E, Kiper PÖ, Beleggia F, Percin EF, Keupp K, Matchan A, Milz E, Alanay Y, Kayserili H, Liu Y, Banka S, Kranz A, Zenker M, Wieczorek D, Elcioglu N, Prontera P, Lyonnet S, Meitinger T, Stewart AF, Donnai D, Strom TM, Boduroglu K, Yigit G, Li Y, Katsanis N, Wollnik B. RAP1-mediated MEK/ERK pathway defects in Kabuki syndrome. J Clin Invest (2015), 125(9):3585-99.
• Kalay E, Yigit G, Aslan Y, Brown KE, Li Y, Pohl E, Bicknell L, Kayserili H, Tüysüz B, Nürnberg N, Kiess W, Baessmann I, Buruk K, Kul S, Ikbal M, Taylor MS, Aerts J, Scott C, Dollfuss H, Wieczorek D, Brunner HG, Rauch A, Nürnberg P, Hurles M, Jackson AP, Karagüzel A, Wollnik B. CEP152 is a novel genome-maintenance protein and its disruption causes genomic instability in Seckel syndrome. Nat Genet (2011) 43, 23-26.