Our group applies experimental and computational genomics approaches to study the extent, functional impact, as well as mutational and evolutionary origins of genetic variants, particularly genomic structural variants (SVs). SVs, which include copy-number variants (e.g. deletions/duplications) and balanced inversions, represent the least well-studied form of genetic variation, despite their net effect on the human genome (in terms of affected basepairs), which is higher than the effect of single nucleotide polymorphisms.

Major objectives of the lab include to decipher the origin and impact of SVs in healthy individuals and disease states, specifically in cancer. Our activities in international consortia, including the 1000 Genomes Project and the International Cancer Genome Consortium (ICGC), facilitate pursuing these objectives. We are particularly interested in understanding a cellular process in which massive SVs form in a single catastrophic event, termed chromothripsis - a crucial event during the development of a particular childhood brain tumor subtype (Rausch et al. Cell 2012). We envision that breakthroughs in the genetic variation field will pave the way towards novel medical applications, enabling specific personalized treatments following detailed assessment of patient genome sequences.

Heidelberg: While prostate cancer is the most common cancer in elderly Western men it also, but more rarely, strikes patients younger than 50. In the context of the International Cancer Genome Consortium we have led a study discovering that such early-onset prostate cancers are triggered by a different mechanism from that which causes the disease at a later age. These findings are published in Cancer Cell.