Dr Ivana Barbaric
School of Biosciences
Senior Lecturer in Stem Cell Biology

+44 114 222 3645
Full contact details
School of Biosciences
E225b
Alfred Denny Building
Western Bank
Sheffield
S10 2TN
- Profile
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- 2019 – present: Senior Lecturer in Stem Cell Biology, Centre for Stem Cell Biology, School of Biosciences, University of Sheffield.
- 2014–2018: Lecturer in Stem Cell Biology, Centre for Stem Cell Biology, Department of Biomedical Science, University of Sheffield.
- 2013–2014: Research Fellow, Department of Materials Science and Tissue Engineering, University of Sheffield.
- 2006–2013: Post-doctoral Research Associate, Department of Biomedical Science, University of Sheffield. Research Advisor: Professor Peter Andrews.
- 2002–2006: DPhil, Wolfson College, University of Oxford. Supervisor: Professor Stephen Brown.
- Research interests
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Research in my group is focused on the basic biology of human pluripotent stem cells (hPSCs). HPSCs have the ability to self-renew indefinitely and to differentiate into any cell type. Thus, they hold great promise for the use in regenerative medicine and drug discovery. However, fulfilling the therapeutic and pharmaceutical potential of stem cells hinges on our ability to efficiently differentiate them towards a desired cell type. Furthermore, the cells must pose no safety risk upon transplantation into humans. This issue has been brought into focus by recognition that hPSCs acquire genetic changes upon prolonged culture, which mirror the changes found in human cancers. My group is researching the genetic stability of hPSCs, the extrinsic and intrinsic cues that govern the stem cell fates, and using hPSCs for disease modelling and drug discovery.
Stem Cell Biology and Engineering
Overview
Research in my group is focused on the basic biology of human pluripotent stem cells (hPSCs). HPSCs have the ability to self-renew indefinitely and to differentiate into any cell type. Thus, they hold great promise for the use in regenerative medicine and drug discovery. However, fulfilling the therapeutic and pharmaceutical potential of stem cells hinges on our ability to efficiently differentiate them towards a desired cell type. Furthermore, the cells must pose no safety risk upon transplantation into humans.
This issue has been brought into focus by recognition that hPSCs acquire genetic changes upon prolonged culture, which mirror the changes found in human cancers. My group is researching: (i) the genetic stability of hPSCs, (ii) the extrinsic and intrinsic cues that govern the stem cell fates, and (iii) using hPSCs for disease modelling and drug discovery.
Genetic stability of human pluripotent stem cells
HPSCs can acquire genetic changes in culture, some of which increase their growth rate and cloning efficiency. The genetic changes observed during prolonged culture are mostly non-random, with the gain of material from chromosomes 1, 12, 17, 20 and X particularly frequent. The non-random nature of genetic changes implies that they confer the growth advantage to variant cells, presumably by affecting the molecular mechanisms that control the balance between self-renewal, differentiation and apoptosis. However, the processes that lead to the generation of mutations and the subsequent selection of variant cells remain unclear. Our research aims to reveal the molecular mechanisms of genetic change in hPSCs and establish the processes that select for the growth of mutant cells. The results of these studies should pinpoint the mechanisms of genetic changes in hPSCs and instruct future hPSC maintenance to minimise the occurrence of variant cells. They may also provide a model to study the causes and consequences of chromosomal aberrations in human congenital disorders and cancer.
Determining the extrinsic and intrinsic cues that govern the stem cell fates
Understanding the mechanisms that influence the stem cell fate determination is the key to developing efficient maintenance and differentiation strategies of hPSCs. In collaboration with colleagues from the Faculty of Engineering, we are exploring approaches to manipulate stem cell fates by controlled delivery of morphogens (collaborator: Professor Daniel Coca, Department of Automatic Control and Systems Engineering, The University of Sheffield) or manipulating the substrate on which the cells grow (collaborator: Department of Materials Science, Dr Fred Claeyssens).
Given the importance of mitochondria for multiple essential cellular processes, such as energy metabolism and apoptosis, we posited that mitochondrial dynamics can influence hPSC fate decisions. Hence, to explore intrinsic mechanisms impacting the stem cell fates, in collaboration with Dr Tristan Rodriguez (Imperial College London), we are investigating the effects of mitochondrial dynamics on hPSC fate determination.
HPSC-based disease modelling and drug discovery
A significant bottleneck in disease modelling and drug discovery is the lack of suitable humanized models for sensitive and reliable assessment of disease phenotypes. The dual ability of hPSCs to self-renew and to differentiate makes them an ideal source of cells for disease modelling and drug discovery applications, whereby undifferentiated cells could be expanded and directed to differentiate into a cell type of interest. The advent of genome editing technologies, particularly CRISPR/Cas9, allows for the introduction and/or correction of disease-causing mutations in order to investigate the disease phenotype. We are using this approach to model diseases, in particular amyotrophic lateral sclerosis (ALS) and Charcot Marie Tooth Disease (CMT) (Collaborator: Dr Andy Grierson, Sheffield Institute for Translational Neuroscience, The University of Sheffield).
- Publications
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Show: Featured publications All publications
Featured publications
Journal articles
- Genetically variant human pluripotent stem cells selectively eliminate wild-type counterparts through YAP-mediated cell competition. Developmental Cell. View this article in WRRO
- Nucleosides rescue replication-mediated genome instability of human pluripotent stem cells. Stem Cell Reports, 14(6), 1009-1017. View this article in WRRO
- Anti-apoptotic Mutations Desensitize Human Pluripotent Stem Cells to Mitotic Stress and Enable Aneuploid Cell Survival. Stem Cell Reports, 12(3), 557-571. View this article in WRRO
- Identification and Single-Cell Functional Characterization of an Endodermally Biased Pluripotent Substate in Human Embryonic Stem Cells. Stem Cell Reports, 10(6), 1895-1907. View this article in WRRO
- Assessment of established techniques to determine developmental and malignant potential of human pluripotent stem cells. Nature Communications, 9. View this article in WRRO
- Detecting Genetic Mosaicism in Cultures of Human Pluripotent Stem Cells.. Stem Cell Reports, 7(5), 998-1012. View this article in WRRO
- Aneuploidy in pluripotent stem cells and implications for cancerous transformation.. Protein Cell, 5(8), 569-579. View this article in WRRO
- 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
All publications
Journal articles
- Assessing cell competition in human pluripotent stem cell (hPSC) cultures. Current Protocols, 2. View this article in WRRO
- DRP1 levels determine the apoptotic threshold during embryonic differentiation through a mitophagy-dependent mechanism.. Dev Cell.
- Genetically variant human pluripotent stem cells selectively eliminate wild-type counterparts through YAP-mediated cell competition. Developmental Cell. View this article in WRRO
- Fitness selection in human pluripotent stem cells and interspecies chimeras: Implications for human development and regenerative medicine.. Developmental Biology, 476, 209-217.
- Nanopore sequencing indicates that tandem amplification of chromosome 20q11.21 in human pluripotent stem cells is driven by break induced replication. Stem Cells and Development.
- Defining the signalling determinants of a posterior ventral spinal cord identity in human neuromesodermal progenitor derivatives. Development, 148(6). View this article in WRRO
- Low rates of mutation in clinical grade human pluripotent stem cells under different culture conditions. Nature Communications, 11(1). View this article in WRRO
- Generation and trapping of a mesoderm biased state of human pluripotency. Nature Communications, 11(1).
- Retinoic Acid Accelerates the Specification of Enteric Neural Progenitors from In-Vitro-Derived Neural Crest. Stem Cell Reports.
- Nucleosides rescue replication-mediated genome instability of human pluripotent stem cells. Stem Cell Reports, 14(6), 1009-1017. View this article in WRRO
- Anti-apoptotic Mutations Desensitize Human Pluripotent Stem Cells to Mitotic Stress and Enable Aneuploid Cell Survival. Stem Cell Reports, 12(3), 557-571. View this article in WRRO
- Rapid PCR Assay for Detecting Common Genetic Variants Arising in Human Pluripotent Stem Cell Cultures. Current Protocols in Stem Cell Biology. View this article in WRRO
- Stem cell culture conditions and stability: a joint workshop of the PluriMes Consortium and Pluripotent Stem Cell Platform. Regenerative medicine, 14(3), 243-255. View this article in WRRO
- Science-based assessment of source materials for cell-based medicines: report of a stakeholders workshop. Regenerative Medicine, 13(8), 935-944. View this article in WRRO
- Identification and Single-Cell Functional Characterization of an Endodermally Biased Pluripotent Substate in Human Embryonic Stem Cells. Stem Cell Reports, 10(6), 1895-1907. View this article in WRRO
- Assessment of established techniques to determine developmental and malignant potential of human pluripotent stem cells. Nature Communications, 9. View this article in WRRO
- Regenerative medicine: Advances from developmental to degenerative diseases. Advances in Experimental Medicine and Biology, 1007, 225-239. View this article in WRRO
- Erratum to: Loss of plakoglobin promotes cell-cell contact, increased invasion and breast cancer cell dissemination in vivo.. Breast Cancer Research, 19.
- Preclinical imaging methods for assessing the safety and efficacy of regenerative medicine therapies. npj Regenerative Medicine, 2(1). View this article in WRRO
- Detecting Genetic Mosaicism in Cultures of Human Pluripotent Stem Cells.. Stem Cell Reports, 7(5), 998-1012. View this article in WRRO
- Aneuploidy in pluripotent stem cells and implications for cancerous transformation.. Protein Cell, 5(8), 569-579. View this article in WRRO
- 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
- Karyotypically abnormal human ESCs are sensitive to HDAC inhibitors and show altered regulation of genes linked to cancers and neurological diseases.. Stem Cell Res, 11(3), 1022-1036.
- Loss of plakoglobin promotes decreased cell-cell contact, increased invasion, and breast cancer cell dissemination in vivo.. Breast Cancer Res, 14(3), R86. View this article in WRRO
- Rediscovering pluripotency: from teratocarcinomas to embryonic stem cells. Cardiff, 10-12 October 2011.. Int J Dev Biol, 56(4), 197-206.
- Pinacidil enhances survival of cryopreserved human embryonic stem cells.. Cryobiology, 63(3), 298-305.
- High-content screening for chemical modulators of embryonal carcinoma cell differentiation and survival.. J Biomol Screen, 16(6), 603-617.
- High-content screening of small compounds on human embryonic stem cells.. Biochem Soc Trans, 38(4), 1046-1050.
- A mutation in the mitochondrial fission gene Dnm1l leads to cardiomyopathy.. PLoS Genet, 6(6), e1001000. View this article in WRRO
- Novel regulators of stem cell fates identified by a multivariate phenotype screen of small compounds on human embryonic stem cell colonies.. Stem Cell Res, 5(2), 104-119. View this article in WRRO
- Culture of murine embryonic stem cells.. Methods Mol Biol, 561, 161-184.
- An ENU-induced mutation in the Ankrd11 gene results in an osteopenia-like phenotype in the mouse mutant Yoda.. Physiol Genomics, 32(3), 311-321.
- Appearances can be deceiving: phenotypes of knockout mice.. Brief Funct Genomic Proteomic, 6(2), 91-103.
- Spectrum of ENU-induced mutations in phenotype-driven and gene-driven screens in the mouse.. Environ Mol Mutagen, 48(2), 124-142.
- Mutation at the Evi1 locus in Junbo mice causes susceptibility to otitis media.. PLoS Genet, 2(10), e149. View this article in WRRO
- Acquired genetic changes in human pluripotent stem cells: origins and consequences. Nature Reviews Molecular Cell Biology.
- Human pluripotent stem cells as tools for high-throughput and high-content screening in drug discovery. International Journal of High Throughput Screening, 1-1. View this article in WRRO
Chapters
- Characterizing the Genetic Stability of Human Naïve and Primed Pluripotent Stem Cells In Rugg-Gunn P (Ed.), Human Naïve Pluripotent Stem Cells (pp. 267-284). Humana Press (part of Springer Nature)
- Human Embryonic Stem Cell Characterization: Similarities and Differences between Cell Lines and Sources, Stem Cells (pp. 1-22). WORLD SCIENTIFIC
- Human embryonic stem cell characterization: Similarities and differences between cell lines and sources, Stem Cells: From Bench to Bedside, Second Edition (pp. 1-22).
Conference proceedings papers
- View this article in WRRO
- Genetic models of bone disease using ENU mutagenesis. BONE, Vol. 44 (pp S19-S19)
- Genetically variant human pluripotent stem cells selectively eliminate wild-type counterparts through YAP-mediated cell competition. Developmental Cell. View this article in WRRO
- Grants
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- Medical Research Council
- UK Regenerative Medicine Platform
- The Royal Society
- Teaching activities
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Teaching experience
Postgraduate Certificate in Learning and Teaching from the University of Sheffield (Fellow of The Higher Education Academy, FHEA)
Undergraduate and postgraduate taught modules:
Level 3:
- BMS354 Principles of Regenerative Medicine and Tissue Engineering (Coordinator)
- BMS382 Stem Cell Biology
- Practical and Dissertation Modules
Masters (MSc):
- BMS6398 Principles of Regenerative Medicine and Tissue Engineering (Coordinator)
- BMS6056 Stem Cell Biology
- Professional activities
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- Education Academy (FHEA)
- Executive Editor of Biochemistry and Biophysics Reports (Elsevier)
- Member of the International Stem Cell Initiative Genetics and Epigenetics Study Group
- Committee member of the EuroStemCell, a European infrastructure for stem cell research communication and engagement