Natalia Gromak

R-Loop Biology in Health and Disease

Our research focuses on understanding the mechanisms of gene regulation in humans in health and disease. In particular, we study non-canonical RNA/DNA structures, called R-loops. These are three-stranded structures formed during transcription and composed of an RNA/DNA hybrid and a displaced single-stranded DNA. R-loops are formed in all living organisms where they play important biological roles. Dysregulation of R-loops is associated with several human diseases, including cancer and neurodegeneration. We are investigating the molecular mechanisms underlying R-loop functions in humans.

In the laboratory, we want to understand the mechanisms underlying regulation of physiological and pathological R-loops in human cells using genome-wide and gene-specific molecular, biochemical and cell biology approaches.

We are investigating the molecular basis of neurodegenerative diseases, associated with pathological R-loops. We study Friedreich ataxia and Fragile X syndrome, two of fifty human diseases with expansion of small nucleotide sequences. It is currently not known how the (GAA)n expansion in frataxin (FXN) gene and the (CGG)n expansion in FMR1 gene leads to their transcriptional repression, resulting in human diseases. We discovered that R-loops are formed in Friedreich ataxia and Fragile X disorders and promote formation of repressive chromatin on the expanded alleles, leading to FXN and FMR1 transcriptional repression.

The results generated in this project will help us to uncover the molecular mechanisms underlying R-loop functions in healthy human cells and also provide a better understanding of the pathology of R-loop-associated human diseases. In the long term, these findings are essential for the development of new therapeutic approaches for cancer and neurodegenerative disorders.

Scientists interested in our work are welcome to contact Natalia Gromak for more details.

Group members

  • Natalia Gromak (Group leader)
  • Chiara Beghe (Postdoc)
  • Martine Palma (Postdoc)
  • Helena Harpham (PhD student)
  • Martha Buhmann (PhD student)
  • Jasmine Barberic (Undergraduate student)
  • Ella Wilczyk (Undergraduate student)

Selected Publications

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Available student projects