Dr Ivana Barbaric

School of Biosciences

Senior Lecturer in Stem Cell Biology

i.barbaric@sheffield.ac.uk
+44 114 222 3645
E225b, Alfred Denny Building

Full contact details

Dr Ivana Barbaric
School of Biosciences
E225b
Alfred Denny Building
Western Bank
Sheffield
S10 2TN
Profile
  • 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

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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Journal articles

All publications

Journal articles

Chapters

Conference proceedings papers

  • 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
Grants
  • Medical Research Council
  • UK Regenerative Medicine Platform
  • The Royal Society
Teaching activities

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
  • 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