Barbaric, Ivana, Professor

Professor Ivana Barbaric

School of Biosciences

Professor of Stem Cell Biology

Photo of Ivana Barbaric, Senior Lecturer in Stem Cell Biology

i.barbaric@sheffield.ac.uk
+44 114 222 3645

E225b, Alfred Denny Building

Full contact details

Professor Ivana Barbaric
School of Biosciences
E225b
Alfred Denny Building
Western Bank
��«Ӱҵ
S10 2TN

Profile

2023 - present: Professor of Stem Cell Biology, Centre for Stem Cell Biology, School of Biosciences, University of ��«Ӱҵ.
2019 – 2022: Senior Lecturer in Stem Cell Biology, Centre for Stem Cell Biology, School of Biosciences, University of ��«Ӱҵ.
2014–2018: Lecturer in Stem Cell Biology, Centre for Stem Cell Biology, Department of Biomedical Science, University of ��«Ӱҵ.
2013–2014: Research Fellow, Department of Materials Science and Tissue Engineering, University of ��«Ӱҵ.
2006–2013: Post-doctoral Research Associate, Department of Biomedical Science, University of ��«Ӱҵ. 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

Show: Featured publications All publications

Featured publications

Journal articles

Price CJ, Stavish D, Gokhale PJ, Stevenson BA, Sargeant S, Lacey J, Rodriguez TA & Barbaric I (2021) . Developmental Cell.
Halliwell JA, Frith TJR, Laing O, Price CJ, Bower OJ, Stavish D, Gokhale PJ, Hewitt Z, El-Khamisy SF, Barbaric I & Andrews PW (2020) . Stem Cell Reports, 14(6), 1009-1017.
Zhang J, Hirst AJ, Duan F, Qiu H, Huang R, Ji Y, Bai L, Zhang F, Robinson D, Jones M , Li L et al (2019) . Stem Cell Reports, 12(3), 557-571.
Allison TF, Smith AJH, Anastassiadis K, Sloane-Stanley J, Biga V, Stavish D, Hackland J, Sabri S, Langerman J, Jones M , Plath K et al (2018) . Stem Cell Reports, 10(6), 1895-1907.
Allison TF, Andrews PW, Avior Y, Barbaric I, Benvenisty N, Bock C, Brehm J, Bruestle O, Damjanov I, Elefanty A , Felkner D et al (2018) . Nature Communications, 9.
Baker D, Hirst AJ, Gokhale PJ, Juarez MA, Williams S, Wheeler M, Bean K, Allison TF, Moore HD, Andrews PW & Barbaric I (2016) . Stem Cell Reports, 7(5), 998-1012.
Na J, Baker D, Zhang J, Andrews PW & Barbaric I (2014) . Protein Cell, 5(8), 569-579.
Barbaric I, Biga V, Gokhale PJ, Jones M, Stavish D, Glen A, Coca D & Andrews PW (2014) . Stem Cell Reports, 3(1), 142--155.

All publications

Journal articles

Stavish D, Price CJ, Gelezauskaite G, Alsehli H, Leonhard KA, Taapken SM, McIntire EM, Laing O, James BM, Riley JJ , Zerbib J et al (2024) . Stem Cell Reports.
Saldana-Guerrero IM, Montano-Gutierrez LF, Boswell K, Hafemeister C, Poon E, Shaw LE, Stavish D, Lea RA, Wernig-Zorc S, Bozsaky E , Fetahu IS et al (2024) . Nature Communications, 15(1).
Beltran-Rendon C, Price CJ, Glen K, Stacey A, Barbaric I & Thomas RJ (2024) . Cytotherapy.
Ludwig TE, Andrews PW, Barbaric I, Benvenisty N, Bhattacharyya A, Crook JM, Daheron LM, Draper JS, Healy LE, Huch M , Inamdar MS et al (2023) . Stem Cell Reports, 18(9), 1744-1752.
Saldana-Guerrero IM, Montano-Gutierrez LF, Hafemeister C, Stavish D, Shaw LE, Fetahu IS, Wenninger-Weinzierl A, Sturtzel C, Souilhol C, Tarelli S , Shoeb MR et al (2023) . Cancer Research, 83(7_Supplement), 3542-3542.
Vitillo L, Anjum F, Hewitt Z, Stavish D, Laing O, Baker D, Barbaric I & Coffey P (2023) . Stem Cell Reports, 18(3), 782-797.
Andrews PW, Barbaric I, Benvenisty N, Draper JS, Ludwig T, Merkle FT, Sato Y, Spits C, Stacey GN, Wang H & Pera MF (2022) . Cell Stem Cell, 29(12), 1624-1636.
Steventon‐Jones V, Stavish D, Halliwell JA, Baker D & Barbaric I (2022) . Current Protocols, 2(11).
Price CJ & Barbaric I (2022) . Current Protocols, 2.
Pernaute B, Pérez-Montero S, Sánchez Nieto JM, Di Gregorio A, Lima A, Lawlor K, Bowling S, Liccardi G, Tomás A, Meier P , Sesaki H et al (2022) . Dev Cell.
Price CJ, Stavish D, Gokhale PJ, Stevenson BA, Sargeant S, Lacey J, Rodriguez TA & Barbaric I (2021) . Developmental Cell.
Wu J & Barbaric I (2021) . Developmental Biology, 476, 209-217.
Halliwell J, Baker D, Judge K, Quail MA, Oliver K, Betteridge E, Skelton J, Andrews PW & Barbaric I (2021) . Stem Cells and Development.
Wind M, Gogolou A, Manipur I, Granata I, Butler L, Andrews PW, Barbaric I, Ning K, Guarracino MR, Placzek M & Tsakiridis A (2021) . Development, 148(6).
Thompson O, von Meyenn F, Hewitt Z, Alexander J, Wood A, Weightman R, Gregory S, Krueger F, Andrews S, Barbaric I , Gokhale PJ et al (2020) . Nature Communications, 11(1).
Stavish D, Böiers C, Price C, Frith TJR, Halliwell J, Saldaña-Guerrero I, Wray J, Brown J, Carr J, James C , Barbaric I et al (2020) . Nature Communications, 11(1).
Frith TJR, Gogolou A, Hackland JOS, Hewitt ZA, Moore HD, Barbaric I, Thapar N, Burns AJ, Andrews PW, Tsakiridis A & McCann CJ (2020) . Stem Cell Reports.
Halliwell JA, Frith TJR, Laing O, Price CJ, Bower OJ, Stavish D, Gokhale PJ, Hewitt Z, El-Khamisy SF, Barbaric I & Andrews PW (2020) . Stem Cell Reports, 14(6), 1009-1017.
Zhang J, Hirst AJ, Duan F, Qiu H, Huang R, Ji Y, Bai L, Zhang F, Robinson D, Jones M , Li L et al (2019) . Stem Cell Reports, 12(3), 557-571.
Laing O, Halliwell J & Barbaric I (2019) . Current Protocols in Stem Cell Biology.
Stacey GN, Andrews P, Barbaric I, Boiers C, Chandra A, Cossu G, Csontos L, Frith TJR, Halliwell JA, Hewitt Z , McCall M et al (2019) . Regenerative medicine, 14(3), 243-255.
Stacey G, Andrews P, Asante C, Barbaric I, Barry J, Bisset L, Braybrook J, Buckle R, Chandra A, Coffey P , Crouch S et al (2018) . Regenerative Medicine, 13(8), 935-944.
Allison TF, Smith AJH, Anastassiadis K, Sloane-Stanley J, Biga V, Stavish D, Hackland J, Sabri S, Langerman J, Jones M , Plath K et al (2018) . Stem Cell Reports, 10(6), 1895-1907.
Allison TF, Andrews PW, Avior Y, Barbaric I, Benvenisty N, Bock C, Brehm J, Bruestle O, Damjanov I, Elefanty A , Felkner D et al (2018) . Nature Communications, 9.
Blair NF, Frith TJR & Barbaric I (2017) . Advances in Experimental Medicine and Biology, 1007, 225-239.
Holen I, Whitworth J, Nutter F, Evans A, Brown HK, Lefley DV, Barbaric I, Jones M & Ottewell PD (2017) . Breast Cancer Research, 19.
Scarfe L, Brillant N, Kumar JD, Ali N, Alrumayh A, Amali M, Barbellion S, Jones V, Niemeijer M, Potdevin S , Roussignol G et al (2017) . npj Regenerative Medicine, 2(1).
Baker D, Hirst AJ, Gokhale PJ, Juarez MA, Williams S, Wheeler M, Bean K, Allison TF, Moore HD, Andrews PW & Barbaric I (2016) . Stem Cell Reports, 7(5), 998-1012.
Na J, Baker D, Zhang J, Andrews PW & Barbaric I (2014) . Protein Cell, 5(8), 569-579.
Barbaric I, Biga V, Gokhale PJ, Jones M, Stavish D, Glen A, Coca D & Andrews PW (2014) . Stem Cell Reports, 3(1), 142--155.
Lund RJ, Emani MR, Barbaric I, Kivinen V, Jones M, Baker D, Gokhale P, Nykter M, Lahesmaa R & Andrews PW (2013) . Stem Cell Res, 11(3), 1022-1036.
Holen I, Whitworth J, Nutter F, Evans A, Brown HK, Lefley DV, Barbaric I, Jones M & Ottewell PD (2012) . Breast Cancer Res, 14(3), R86.
Barbaric I & Harrison NJ (2012) . Int J Dev Biol, 56(4), 197-206.
Barbaric I, Jones M, Buchner K, Baker D, Andrews PW & Moore HD (2011) . Cryobiology, 63(3), 298-305.
Barbaric I, Jones M, Harley DJ, Gokhale PJ & Andrews PW (2011) . J Biomol Screen, 16(6), 603-617.
Barbaric I, Gokhale PJ & Andrews PW (2010) . Biochem Soc Trans, 38(4), 1046-1050.
Ashrafian H, Docherty L, Leo V, Towlson C, Neilan M, Steeples V, Lygate CA, Hough T, Townsend S, Williams D , Wells S et al (2010) . PLoS Genet, 6(6), e1001000.
Barbaric I, Gokhale PJ, Jones M, Glen A, Baker D & Andrews PW (2010) . Stem Cell Res, 5(2), 104-119.
Barbaric I & Dear TN (2009) . Methods Mol Biol, 561, 161-184.
Barbaric I, Perry MJ, Dear TN, Rodrigues Da Costa A, Salopek D, Marusic A, Hough T, Wells S, Hunter AJ, Cheeseman M & Brown SDM (2008) . Physiol Genomics, 32(3), 311-321.
Barbaric I & Dear TN (2007) Optimizing screening and mating strategies for phenotype-driven recessive N-ethyl-N-nitrosourea screens in mice.. J Am Assoc Lab Anim Sci, 46(6), 44-49.
Barbaric I, Miller G & Dear TN (2007) . Brief Funct Genomic Proteomic, 6(2), 91-103.
Barbaric I, Stewart M, Wells S & Dear TN (2007) A new coat color mouse line for testing germline transmission of embryonic stem cells while retaining an inbred genetic background.. J Am Assoc Lab Anim Sci, 46(3), 37-40.
Barbaric I, Wells S, Russ A & Dear TN (2007) . Environ Mol Mutagen, 48(2), 124-142.
Parkinson N, Hardisty-Hughes RE, Tateossian H, Tsai H-T, Brooker D, Morse S, Lalane Z, MacKenzie F, Fray M, Glenister P , Woodward A-M et al (2006) . PLoS Genet, 2(10), e149.
Vales JP & Barbaric I () . BioEssays.
De Santis E, Faruqui N, Russell CT, Noble JE, Kepiro IE, Hammond K, Tsalenchuk M, Ryadnov EM, Wolna M, Frogley MD , Price CJ et al () . ACS Applied Materials & Interfaces.
Halliwell J, Barbaric I & Andrews PW () . Nature Reviews Molecular Cell Biology.
Barbaric I, Allison T, Powles-Glover N, Biga V & Andrews P () . International Journal of High Throughput Screening, 1-1.

Chapters

Baker D & Barbaric I (2022) In Rugg-Gunn P (Ed.), Human Naïve Pluripotent Stem Cells (pp. 267-284). Humana Press (part of Springer Nature)
Harrison NJ, Barbaric I & Andrews PW (2010) , Stem Cells (pp. 1-22). WORLD SCIENTIFIC
Harrison NJ, Barbaric I & Andrews PW (2010) , Stem Cells: From Bench to Bedside, Second Edition (pp. 1-22).

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)
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)
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)
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)
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) . BONE, Vol. 44 (pp S19-S19)

Preprints

Stanton A, Aydin S, Skelly DA, Stavish D, Leonhard K, Taapken S, McIntire E, Pankratz M, Czechanski A, Ludwig T , Choi T et al (2024) , Cold Spring Harbor Laboratory.
Wing T, Price CJ, Stavish D, Laing O, Riley JJ, Lam A, Oh S, Atlasi Y & Barbaric I (2023) , Cold Spring Harbor Laboratory.
Stavish D, Price CJ, Gelezauskaite G, Leonhard KA, Taapken SM, McIntire EM, Laing O, James BM, Riley JJ, Zerbib J , Baker D et al (2023) , Cold Spring Harbor Laboratory.
Saldana-Guerrero IM, Montano-Gutierrez LF, Hafemeister C, Stavish D, Shaw LE, Fetahu IS, Wenninger-Weinzierl A, Sturtzel C, Souilhol C, Tarelli S , Shoeb MR et al (2022) , Cold Spring Harbor Laboratory.
Butler L, Adamson KI, Johnson SL, Jestice LH, Price CJ, Stavish D, Pooranachandran N, Malicki JJ, Tsakiridis A, Grierson AJ & Barbaric I () , Cold Spring Harbor Laboratory.
Halliwell JA, Baker D, Judge K, Quail MA, Oliver K, Betteridge E, Skelton J, Andrews PW & Barbaric I () , Cold Spring Harbor Laboratory.
Wind M, Gogolou A, Manipur I, Granata I, Butler L, Andrews PW, Barbaric I, Ning K, Guarracino MR, Placzek M & Tsakiridis A () .
Price CJ, Stavish D, Gokhale PJ, Sargeant S, Lacey J, Rodriguez TA & Barbaric I () .
Halliwell JA, Frith TJR, Laing O, Price CJ, Bower OJ, Stavish D, Gokhale PJ, Hewitt Z, El-Khamisy SF, Barbaric I & Andrews PW () , Cold Spring Harbor Laboratory.
Pernaute B, Sánchez Nieto JM, Pérez-Montero S, di Gregorio A, Lima A, Lawlor K, Bowling S, Liccardi G, Tomás A, Meier P , Rutter GA et al () , Cold Spring Harbor Laboratory.
Frith TJR, Gogolou A, Hackland JOS, Barbaric I, Thapar N, Burns AJ, Andrews PW, Tsakiridis A & McCann CJ () .
Stavish D, Böiers C, Price C, Frith TJR, Halliwell J, Barbaric I, Brown J, Carr J, James C, Andrews PW & Enver T () , Cold Spring Harbor Laboratory.
Price CJ, Stavish D, Gokhale PJ, Sargeant S, Lacey J, Rodriguez TA & Barbaric I () .

Grants

Medical Research Council
UK Regenerative Medicine Platform
Muscular Dystrophy UK
EU Horizon2020
The Royal Society
��«Ӱҵ 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 ��«Ӱҵ (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)

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School of Biosciences

School of Biosciences

Professor Ivana Barbaric

Featured publications

Journal articles

All publications

Journal articles

Chapters

Conference proceedings papers

Preprints

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