Professor Ivana Barbaric

School of Biosciences

Professor of Stem Cell Biology

Photo of Ivana Barbaric, Senior Lecturer in Stem Cell Biology
Profile picture of Photo of Ivana Barbaric, Senior Lecturer in Stem Cell Biology
i.barbaric@sheffield.ac.uk
+44 114 222 3645

Full contact details

Professor Ivana Barbaric
School of Biosciences
E225b
Alfred Denny Building
Western Bank
Sheffield
S10 2TN
Profile
  • 2023 - present: Professor of Stem Cell Biology, Centre for Stem Cell Biology, School of Biosciences, University of Sheffield.
  • 2019 – 2022: 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

Research in my group is focused on the genetic stability of human pluripotent stem cells (hPSCs) and implications of genetic changes arising in hPSCs for regenerative medicine applications. We also use hPSCs as a model for understanding the causes and consequences of aneuploidy on early human development. Finally, my lab is also using hPSCs for human disease modelling and therapeutic discovery.

Genetic stability of human pluripotent stem cells: implications for safety and efficacy of regenerative medicine applications

The ability of human pluripotent stem cells (hPSC) to self-renew and to differentiate into any cell type of the human body has led to the development of regenerative medicine strategies for treatment of previously incurable diseases and injuries. Clinical trials for regenerative medicine of various conditions, including macular degeneration, Parkinson’s disease and spinal cord injury using hPSC-derived differentiated cells are currently underway or on the horizon. However, a significant safety concern that stands to seriously jeopardise a successful translation of hPSC-based therapies is the takeover of cultures by genetically abnormal 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, 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.

The causes and consequences of aneuploidy in human pluripotent stem cells

Mammalian development requires multiple, rapid cell divisions in order to support the growth and morphogenesis of the developing embryo. Given the limited number of early embryonic cells within the embryo that give rise to all cells in the adult body, errors occurring during cell division (mitotic errors) in these cells could have devastating consequences, from congenital defects to embryonic lethality. Yet, despite the pivotal importance of preserving genome integrity during early embryogenesis, embryonic cells are particularly prone to mitotic errors. It remains unclear what makes early embryonic cells susceptible to mitotic errors and what is the fate of aneuploid cells during development.

Early human embryogenesis is experimentally inaccessible, but hPSCs represent a unique and powerful tool for studying otherwise intractable stages of development. We have recently demonstrated that the high frequency of mitotic errors characteristic of early embryos is also evident upon in vitro culture of hPSCs (Zhang et al., 2019 Stem Cell Reports 12:557; Halliwell et al., 2020 Stem Cell Reports 14:1009), indicating that the susceptibility to mitotic errors is an intrinsic property of early embryonic cells and that hPSC provide a good platform for determining the mechanistic basis of these errors. In our current work we are addressing the molecular mechanisms governing a high incidence of mitotic errors in hPSCs and are working to understand the impact of aneuploidy on the developmental potential of hPSCs.

HPSC-based disease modelling and therapeutic 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 Charcot Marie Tooth Disease (CMT) and Osteogenesis imperfecta to study disease mechanisms. Our models also provide us with a platform for testing small molecules and gene therapy approaches in a human cell-based model in vitro.
 

Publications

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Journal articles

All publications

Journal articles

Chapters

Conference proceedings papers

  • Stavish D, Price C & Barbaric I (2019) The implications of genetic variants on human pluripotent stem cell characteristics. HUMAN GENE THERAPY, Vol. 30(8) (pp A18-A18) RIS download Bibtex download
  • Halliwell JA, Barbaric I & Andrews PW (2019) Mechanisms that lead to genetic instability in human pluripotent stem cells. HUMAN GENE THERAPY, Vol. 30(8) (pp A18-A19) RIS download Bibtex download
  • Price C & Barbaric I (2019) Mechanisms of selective advantage in cultures of human pluripotent stem cells. HUMAN GENE THERAPY, Vol. 30(8) (pp A27-A27) RIS download Bibtex download
  • Barbaric I (2017) Genetic changes in human pluripotent stem cells: implications for basic biology and regenerative medicine. HUMAN GENE THERAPY, Vol. 28(8) (pp A8-A9) View this article in WRRO RIS download Bibtex download
  • Brown SDM, Esapa CT, Barbaric I, Hough T, Brown M, Croucher P, Head R, Chan C, Crane E, Cox R , Cheeseman M et al (2009) Genetic models of bone disease using ENU mutagenesis. BONE, Vol. 44 (pp S19-S19) RIS download Bibtex download

Preprints

Grants
  • Medical Research Council
  • UK Regenerative Medicine Platform
  • Muscular Dystrophy UK
  • EU Horizon2020
  • The Royal Society
  • Sheffield Children's NHS Trust
  • Canadian Institute for Health Research
Teaching activities

Undergraduate and postgraduate taught modules:
Level 3:

  • BMS354 Principles of Regenerative Medicine and Tissue Engineering (Coordinator)
  • BMS382 Stem Cell Biology
  • Practical and Dissertation Modules (BIS303)

Masters (MSc):

  • BMS6398 Principles of Regenerative Medicine and Tissue Engineering (Coordinator)
  • BMS6056 Stem Cell Biology
  • Practical and Dissertation Modules (BIS404-401, BMS51005-BMS61006)
Professional activities and memberships
  • Member of the MRC Molecular and Cellular Medicine Board (2022)
  • Co-chair of the Working group on Genomic characterisation of hPSC within the ISSCR Task Force on Standards in Stem Cell Research (2021 – present)
  • Member of the Steering Committee of the International Stem Cell Initiative (2021 – present)
  • Board member of the British Society for Cell and Gene Therapy (2019 – present) and the BSGCT EDI lead (2022 – present)
  • Member of the Executive Team of the Pluripotent and Engineered Stem Cell Hub (2018 –present)
  • Member of the EuroGCT Consortium (2020 – present)
  • Co-lead for the Mechanistic Neurobiology theme within the Neuroscience Institute Executive Team at the University of Sheffield (2020 – present)
  • Co-Director of the INSIGNEO Biomechanics, Biomaterials and Cell Engineering theme (2022 – present)
  • Member of the Scientific Advisory Board for WiCell (USA) (2022 – present)
  • Member of the Scientific Advisory Board for Broken Strings Ltd (UK) (2021 – present)