Research

Every time a cell divides, it must accurately duplicate and transmit the genetic material to new daughter cells. Mistakes during cell division can lead to genome instability, a driving force in cancer evolution that contributes to tumour heterogeneity and drug resistance. Although protein-mediated mechanisms are well described, the biological and regulatory function of RNA-based mechanisms in genome stability, and in particular the contribution of long noncoding RNAs (lncRNAs), is largely unknown.

LncRNAs are very heterogenous group of noncoding transcripts that can regulate gene expression through different mechanisms. Over 50,000 lncRNA loci have been annotated in the human genome but the functional role for the majority of the lncRNAs is still unknown. My lab is interested in understanding the role of lncRNAs in regulation of cell division and maintenance of genome stability. Since lncRNAs are also deregulated in different types of cancer, there is an unmet need to understand how these RNA molecules contribute to known hallmarks of cancer.

Current projects:

• What are the mechanisms underlying the functions of lncRNA regulatory networks in control of cell division and genome stability;
• What is the impact of lncRNA dysregulation on genome instability in cancer.

Our research is highly interdisciplinary and combines functional cell biology, genomics, imaging and proteomics. We currently focus on kidney and lung cancer in order to understand how lncRNA dysregulation contribute to genome instability in cancer. By working closely with clinician scientists, we also aim to reveal whether lncRNA regulatory mechanisms might have clinical relevance. Our ultimate goal is to develop new RNA-based strategies that can improve diagnosis and treatment of cancer patients.

Visit the Stojic laboratory website here.

Other Activities

• QMUL Epigenetics Hub
• BCI RNA Cancer Hub
• British Society of Cell Biology
• Biochemical Society
• Genetics Society
• RNA Society

Major Funding

• 2023-2024: The Royal Society Research Grant, £62,000
• 2021-2027: Cancer Research UK (CRUK) Career Establishment Award, “Understanding the role of long noncoding RNAs in genome stability and cancer”, £982,428
• 2021-2023: The Academy of Medical Science (AMS) Springboard Award, £99,934
• 2021-2023: AIRC Fellowship for Abroad €120,000
• 2019-2022: Barts Charity

Recent Publications

TREX reveals proteins that bind to specific RNA regions in living cells Dodel M, Guiducci G, Dermit M et al. Nature Methods (2024) 21(10) 423-434

CCT3-LINC00326 axis regulates hepatocarcinogenic lipid metabolism Søndergaard JN, Sommerauer C, Atanasoai I et al. Gut (2022) 71(10) 2081-2092

Long Noncoding RNAs at the Crossroads of Cell Cycle and Genome Integrity Guiducci G, Stojic L Trends in Genetics (2021) (1)

Tuning the Expression of Long Noncoding RNA Loci with CRISPR Interference Stojic L (2020) 2161(10) 1-16

Erratum for the Report: “Aging increases cell-to-cell transcriptional variability upon immune stimulation” by C. P. Martinez-Jimenez, N. Eling, H.-C. Chen, C. A. Vallejos, A. A. Kolodziejczyk, F. Connor, L. Stojic, T. F. Rayner, M. J. T. Stubbington, S. A. Teichmann, M. de la Roche, J. C. Marioni, D. T. Odom Science (2019) 366(10) eaba3487

A high-content RNAi screen reveals multiple roles for long noncoding RNAs in cell division Stojic L, Lun ATL, Mascalchi P et al. (10) 709030

Spotlight On Early Career Researchers: an interview with Lovorka Stojic Communications Biology 2(10) 204

Specificity of RNAi, LNA and CRISPRi as loss-of-function methods in transcriptional analysis Stojic L, Lun ATL, Mangei J et al. Nucleic Acids Research (2018) 46(10) gky437-

SAM68 is required for regulation of Pumilio by the NORAD long noncoding RNA Tichon A, Perry RB-T, Stojic L et al. Genes & Development (2018) 32(10) 70-78

Specificity of RNAi, LNA and CRISPRi as loss-of-function methods in transcriptional analysis Stojic L, Lun A, Mangei J et al. (10) 234930

Team

• Giulia Guiducci
• Alice Coomer

• Parnia Babei

Biography

After receiving my undergraduate degree in Molecular Biology from the University of Zagreb (Croatia), I completed my PhD at the Institute of Molecular Cancer Research, University of Zurich (Switzerland). During my PhD with Prof Josef Jiricny, I discovered the mechanism through which DNA repair and DNA damage checkpoints maintain genome stability. I was awarded an EMBO Long-Term Fellowship and joined the lab of Prof Valerio Orlando (Dulbecco Telethon Institute, Italy), where I identified a signalling pathway regulating the activities of chromatin-modifying enzymes.

I then moved to Cambridge (UK) and started my second postdoctoral position at the Cancer Research UK Cambridge Institute (CRUK CI) under joint supervision of Drs Adele Murrell, Fanni Gergely and Duncan Odom. At the CRUK CI, I investigated how long noncoding RNAs (lncRNAs) and RNA binding proteins coordinate gene regulation during the cell cycle and in viral replication. By integrating functional cell biology, genomics and proteomics, I identified new functions of lncRNAs controlling cell division and genome stability.

In October 2019 I started my own research programme at the Barts Cancer Institute. My group is focused on understanding the role of RNA-mediated mechanisms, in particular lncRNAs, in genome stability and cancer.