Dr Ivana Barbaric
Lecturer in Stem Cell Biology
Telephone: +44(0) 114 222 3645
Brief career history
My lab focuses on understanding the mechanisms that control pluripotent stem cell self-renewal and commitment to differentiation. In particular, we investigate the molecular basis of aneuploidy in hPSCs and study how such genetic changes may perturb the normal control of stem cell fate and enhance their ability to grow in culture.
Stem Cell Biology and Engineering
Our research is focused on investigating the causes and consequences of genetic changes in human pluripotent stem cells (hPSCs), and studying how signals from the stem cells microenvironment affect their fate decisions, patterning and how inappropriate signals lead to genetic changes that mimic cancer. Assurance of genetic stability of hPSCs is pivotal for their eventual safe use in regenerative medicine, but hPSCs can adapt to life in culture by acquiring non-random genetic changes that render them more robust and easier to grow, akin to cancer cells. In our work we are elucidating the molecular mechanisms that underlie the maintenance of the integrity of the hPSC genome, and how disruption of these mechanisms can lead to undesired genetic changes. The reduction of selection pressures on hPSCs in vitro requires an understanding of the native stem cell microenvironment and recapitulating it in culture. Using interdisciplinary approaches, we are creating artificial stem cell niches to mimic embryogenesis in vitro.
In a Royal Society-funded project, we are using the controlled delivery of morphogens to study signalling that underlies the primitive streak patterning from hPSCs. In a Sheffield Science Gateway-funded project we are collaborating with National Physics Laboratory and Kirkstall Ltd. on creating synthetic polymer scaffolds to identify mechanical and chemical cues that influence stem cell fate decisions. This research may offer new routes to engineering stem cell niches and understanding mechanisms that influence stem cell fate decision and patterning.
Human pluripotent stem cells have the potential to create all of the cell types within the body. Therefore, they may provide a useful source of cells for cellular therapies. However, the main prerequisite for such applications is an efficient and reproducible production of specialised cell types from stem cells and ensuring that they are safe to use in therapies. Our work aims to define the molecular mechanisms and external cues that govern stem cell fates as a necessary step towards their safe and reliable clinical use.
Postgraduate Certificate in Learning and Teaching from the University of Sheffield (Fellow of The Higher Education Academy, FHEA)
Undergraduate and postgraduate taught modules:
Postgraduate PhD Opportunity
Integrity of mitochondrial DNA in human pluripotent stem cells and implications for regenerative medicine
Human Pluripotent Stem Cells (hPSCs) have the ability to produce cells of all tissues within the body. They can provide a valuable tool for modelling human disease, as well as a potential source of differentiated cells for use in regenerative medicine and drug discovery. In order to fulfil the therapeutic potential of hPSCs it is important to ensure their genome is free of any potentially deleterious mutations that could either impair the function of the hPSC-derived differentiated derivatives or give rise to malignant phenotypes upon transplantation in vivo. Recurrent genetic changes have been noted in the nuclear genome of hPSCs that appear to confer selective growth advantage to the variant cells. Less understood is the appearance and role of mutations in the mitochondrial genome of hPSCs.
This project will focus on investigating the extent of mitochondrial DNA instability, molecular mechanisms that underpin mutation generation and the functional consequences of the mutations on hPSC phenotype and behaviour. Techniques will include a range of molecular and cellular biology methods, including hPSC culture, genetic manipulation of hPSC using CRISPR/Cas9, flow cytometry and live cell imaging.
For further information about this project and how to apply, see our PhD Opportunities page:
- Baker D, Hirst AJ, Gokhale PJ, Juarez MA, Williams S, Wheeler M, Bean K, Allison TF, Moore HD, Andrews PW & Barbaric I (2016) Detecting Genetic Mosaicism in Cultures of Human Pluripotent Stem Cells.. Stem Cell Reports, 7(5), 998-1012. View this article in WRRO
- Na J, Baker D, Zhang J, Andrews PW & Barbaric I (2014) Aneuploidy in pluripotent stem cells and implications for cancerous transformation.. Protein Cell, 5(8), 569-579. View this article in WRRO
- Barbaric I, Biga V, Gokhale PJ, Jones M, Stavish D, Glen A, Coca D & Andrews PW (2014) Time-Lapse Analysis of Human Embryonic Stem Cells Reveals Multiple Bottlenecks Restricting Colony Formation and Their Relief upon Culture Adaptation. Stem Cell Reports, 3(1), 142--155. View this article in WRRO