Natalia Gromak

At Trinity, I tutor first year Biomedical students on ‘Genes and Molecules’ and Medical students on ‘Biochemistry and Medical Genetics’ courses. I tutor second-year medical students in Principles of Pathology and second-year Biomedical Sciences students in Human Molecular Biology. I also give lectures and tutorials in the ‘Molecular Pathology’ option for the Final Honours School (FHS) students in ‘Human molecular biology and disease’ theme.

My teaching for graduate students includes MSc courses in Applied Cancer Science.

I have also supervised undergraduate extended essays, Part II (Masters) Biochemistry students and DPhil research students in my group.

I began my research career in Cambridge, where I studied for a doctorate in Biochemistry, focusing on alternative RNA splicing. I subsequently worked as a Post-Doctoral Fellow in the Sir William Dunn School of Pathology, University of Oxford, investigating co-regulation of transcription and RNA processing. I became an independent group leader in 2011, funded by the Royal Society University Research Fellowship. Before joining Trinity college, I have been a Tutor in Biochemistry in St John’s college for 19 years. In 2023 I was awarded MRC Senior Research Fellowship to continue our work on R-loops.

My research aims to uncover the mechanisms of gene regulation in humans in health and disease. In particular, I am interested in non-canonical RNA/DNA structures, called R-loops. These structures are formed during transcription in all living organisms where they play important biological roles. However, dysregulation of R-loops is associated with pathology of several human diseases, including cancer and neurodegeneration.

We are investigating the molecular basis of neurodegenerative diseases, associated with pathological R-loops. We study Friedreich ataxia and Fragile X syndrome, two of forty 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 lead to FXN and FMR1 transcriptional repression.

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. 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

Cristini A, Tellier M, Constantinescu F, Accalai C, Albulescu LO, Heiringhoff R, Bery N, Sordet O, Murphy S, Gromak N. ‘RNase H2, mutated in Aicardi-Goutières syndrome, resolves co-transcriptional R-loops to prevent DNA breaks and inflammation’. Nature Communications 26;13(1) (2022) :2961

Abakir A, Giles TC, Cristini A, et al Klungland A, Gromak N* and Ruzov A*. ‘N6-methyladenosine Regulates the Stability of RNA:DNA Hybrids in Human Cells’, Nature Genetics 52(1) (2020): 48-55

Cristini A, Groh M, Kristiansen MS, Gromak N. ‘RNA/DNA Hybrid Interactome Identifies DXH9 as a Molecular Player in Transcriptional Termination and R-Loop-Associated DNA Damage’ Cell Reports 23(6) (2018):1891-1905

Kotsantis P, Marques Silva L, Irmscher S, Jones RM, Folkes L, Gromak N*, Petermann E*. ‘Increased Global Transcription Activity as a Mechanism of Replication Stress in Cancer’. Nature Communications 11;7 (2016):13087

Groh M, Lufino M, Wade-Martins R, Gromak N. ‘R-loops formed over expanded repeats cause transcriptional silencing in Friedreich ataxia and Fragile X syndrome’ PLoS Genetics 1;10(5) (2014) :e1004318

Skourti-Stathaki K, Proudfoot NJ and Gromak N. ‘Human senataxin resolves RNA/DNA hybrids formed at transcriptional pause sites to promote Xrn2-dependent termination’ Molecular Cell 42 (2011): 794-805