My research is aimed towards understanding the molecular basis of diseases such as repeat expansion disorders and cancer. The goal of my research is to dissect the DNA replication in human cells at the endogenous locus in vivo to identify defects, which could lead to genomic instability.

Several inherited human neurological and muscular disorders like Friedreich’s ataxia (FRDA), fragile X syndrome (FXS), myotonic dystrophy (DM1), Huntington’s disease and spinocerebellar ataxia type 7 (SCA7) are caused by a trinucleotide repeat expansion. The mechanism leading to repeat instability is still not known and there is currently no cure for these repeat expansion diseases. One goal of my research is to dissect the DNA replication program at the endogenous disease locus and find molecular components driving repeat expansion in human cells. Therefore we are using a unique technique, called single-molecule analysis of replicated DNA (SMARD), which allows us to visualize the DNA replication at the endogenous genomic locus in human cells at single DNA molecule level. Using SMARD we revealed an altered replication program in FXS human embryonic stem cells (hESCs) and in FRDA induced pluripotent stem cells (iPSCs). In addition we found that stalled replication forks are driving GAA repeat expansion in FRDA cells. It is important to understand how repeat expansion occurs in the native chromosomal context for the development of effective therapeutic treatments to prevent repeat expansions in patients with diseases like FRDA and FXS. 

Errors in the DNA replication process are also linked to genomic alterations and cancer. The replication could be hindered through difficult to replicate DNA sequences, which would lead to incomplete and incorrect DNA synthesis and induce DNA breaks as well as mutations. My current research is aimed to analyze DNA replication defects causing genomic instability in cancer-prone and reprogrammed cells to prevent genomic instability leading to tumorigenesis.