My group studies how RNA-mediated mechanisms, in particular long noncoding RNAs, regulate cell division and how dysregulation of these processes leads to genome instability and cancer.
A high-content RNAi screen reveals multiple roles for long noncoding RNAs in cell division. Nat Commun (2020) 11(1):1851. PMID: 32296040
Specificity of RNAi, LNA and CRISPRi as loss-of-function methods in transcriptional analysis. Nucleic Acids Res (2018) 46(12):5950-5966. PMID: 29860520
The neural RNA-binding protein Musashi 1 regulates human brain size and drives Zika virus replication. Science (2017) 357(6346):83-88. PMID: 28572454
Transcriptional silencing of long noncoding RNA GNG12-AS1 uncouples its transcription and product-related function. Nature Communications (2016) 7:10406. PMID: 26832224
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.
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.
A high-content RNAi screen reveals multiple roles for long noncoding RNAs in cell division Stojic L, Lun ATL, Mascalchi P et al. Nature Communications (2020) 11(7)
Erratum: “Aging increases cell-to-cell transcriptional variability upon immune stimulation”(Science(2020)366:6472 (eaba3487)Doi:10.1126/science.aah4115) Martinez-Jimenez CP, Eling N, Chen HC et al. Science (2019) 366(7)
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(7) 5950-5966
SAM68 is required for regulation of pumilio by the NORAD long noncoding RNA Tichon A, Perry RBT, Stojic L et al. Genes and Development (2018) 32(7) 70-78
Neurodevelopmental protein Musashi-1 interacts with the Zika genome and promotes viral replication Chavali PL, Stojic L, Meredith LW et al. Science (2017) 357(7) 83-88
Aging increases cell-to-cell transcriptional variability upon immune stimulation Martinez-Jimenez CP, Eling N, Chen HC et al. Science (2017) 355(7) 1433-1436
Successful transmission and transcriptional deployment of a human chromosome via mouse male meiosis Ernst C, Pike J, Aitken SJ et al. eLife (2016) 5(7)
What lies beneath the epigenetic signatures associated with breast cancer and how do we find out? Murrell A, Stojic L, Niemczyk M BREAST CANCER RESEARCH AND TREATMENT (2016) 159(11) 190-190
Transcriptional silencing of long noncoding RNA GNG12-AS1 uncouples its transcriptional and product-related functions Stojic L, Niemczyk M, Orjalo A et al. Nature Communications (2016) 7(7)
5-hydroxymethylcytosine marks promoters in colon that resist DNA hypermethylation in cancer Uribe-Lewis S, Stark R, Carroll T et al. Genome Biology (2015) 16(7)For additional publications, please click here
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.