Professor Jus St John
NHMRC Grant-Funded Researchr E
School of Biomedicine
Faculty of Health and Medical Sciences
My group's research focuses on how the nuclear and mitochondrial genomes interact during development in order that the cells, tissues and organs of the resultant offspring function efficiently. To do this, we employ a number of assisted reproductive technologies that are either used clinically or are at various stages of development or validation. We are applying the knowledge we accumulate from this work to develop reproductive strategies for women that suffer from repeated failed fertilisation outcome or embryo developmental arrest; and for those who are carriers of severe mitochondrial disorders that are at risk of having affected children.
Research Focus One: Understanding the role of oocyte mitochondrial DNA (mtDNA) in development outcomes.
We undertake this area of research using porcine oocytes and generate embryos and offspring through in vitro fertilisation (IVF), nuclear transfer (NT) cytoplasmic transfer (CT), and mitochondrial supplementation (mICSI). This enables us to determine how the nuclear and mitochondrial genomes interact following fertilisation and at different stages during development; and how mtDNA segregation, transmission and replication are normally regulated, as is the case following IVF, and perturbed as these mechanisms are violated by NT and CT.
We are currently funded by the NHMRC (Development Grant) to generate pig models using a new assisted reproductive technology that we have been developing, which involves supplementing oocytes deficient in mtDNA with genetically identical populations of mtDNA. This technology is known as mICSI, and our published data suggest that mICSI enhances embryo quality and overcomes the predisposition of poor quality oocytes to give rise to diabetes and obesity. The grant will determine whether supplementing eggs at the time of fertilisation with genetically identical mtDNA is safe practice. Furthermore, we are also funded through an NHMRC Project Grant to determine the mechanisms associated with mICSI.
We have also previously generated a derivation of another assisted reproductive technology, namely cloning or somatic cell nuclear transfer (SCNT), that ensures cloned embryos inherit their mtDNA from the population present in the oocyte only, as is the case following natural conception, and not from the somatic cell as well. This technology, known as mito-SCNT, improves embryo quality and developmental outcomes and overcomes the problem of embryos and offspring inheriting two populations of mtDNA. The outcomes from his work have allowed us to commence work on Mitochondrial Donation, a derivative of NT, that has been proposed as an assisted reproductive technology to prevent offspring from inheriting mtDNA disease. Again, we are undertaking this work in a pig model, which is funded by an NHMRC Ideas Grant.
Research Focus Two: Defining the role of the mtDNA set point in early development.
In recent years, we have discovered the ‘mtDNA set point’, which is a key developmental milestone that naïve (pluripotent) cells must acquire in order to initiate and complete their differentiation into mature cell types. The mtDNA set point is characterised by cells expressing pluripotent markers and having very low mtDNA copy number, which are both regulated by the epigenetic status of the nuclear genome. Furthermore, we have shown that key nuclear-encoded mtDNA replication factors are DNA methylated in a tissue specific manner that accounts for cell-specific mtDNA copy number, which requires the establishment of the mtDNA set point early during development. Our studies have also shown that failure to establish the mtDNA set point results in developmental failure and is a key characteristic of tumour-initiating cells. In addition, by depleting tumour-initiating cells of their mtDNA, we have shown that the incidence of tumour formation is significantly reduced (glioblastoma mutiforme and osteosarcoma) or prevented (multiple myeloma), as these cells re-establish the mtDNA set point and undergo differentiation and, therefore, do not form tumours.
We use and derive embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and tumour-initiating cell lines and tumours to perform these studies. These models allow us to focus on molecular mechanisms and to identify the specific windows during differentiation/development when these events manifest and then to confirm and characterise these events through, for example, targeted gene knockdown and overexpression.
Research Focus Three: Determining how mtDNA haplotypes influence phenotype.
Recent outcomes from our research program have shown that mtDNA halpotypes influence livestock phenotypes, such as meat quality and lifetime daily gains in pigs, and reproductive efficiencies in pigs and cattle. Using stem cells models, we have been able to demonstrate that mtDNA haplotypes induce phenotypic changes through modulation of DNA methylation patterns that, in turn, affect chromosomal gene expression patterns. Using tumour cells, we have also demonstrated differences in the onset and progression of tumours based on mtDNA haplotype alone.
CURRENT RESEARCH PROJECTS AVAILABLE FOR STUDENTS:
RESEARCH PROJECT 1: Identifying variants in the mitochondrial genome predictive of oocyte quality.
Project description: A number of mitochondrial DNA variants have been identified in oocytes. However, their affect and role have yet to be properly defined, especially in oocytes from offspring derived from assisted reproductive technologies that perturb the maternal only transmission of mitochondrial DNA. Using next generation sequencing and bioinformatics tools, this project will focus on identifying variants in the mitochondrial genome that are predictive of oocyte quality and whether an oocyte will progress to fertilise and develop into an embryo. Using an experimental model of pig oocyte in vitro maturation, you will learn how to harvest oocytes from ovaries; culture these immature oocytes to a mature stage; and fertilise them using in vitro fertilisation protocols. After preparing fertilised and failed to fertilise oocyte samples for next generation mitochondrial DNA sequencing technology, you will learn to apply bioinformatics tools to identify and quantify variants that are associated with good and poor oocyte quality. These outputs will then be tested in: i) a larger cohort of oocytes from commercial breeding populations and matched to data associated with economic breeding values; and ii) oocytes derived from offspring that were generated from assisted reproductive technologies that result in two populations of mitochondrial DNA being transmitted.
Projects available for:Honours / HDR / Masters / Mphil / PhD
Location: AHMS (Adelaide Health & Medical Sciences Building, North Tce) – Levels 5 and 6.
Research project start: Semester 1 and 2
Special requirements: Vaccination required.
RESEARCH PROJECT 2: Identifying global DNA methylation patterns associated in the preimplantation embryo.
Project description: With the introduction of more invasive assisted reproductive technologies into animal breeding programs and their potential implementation into human clinical IVF, we need to understand how and when they modify the epigenome during early development, especially technologies that perturb the balance between the nuclear and mitochondrial genomes. DNA methylation is a key epigenetic mechanism that regulates gene expression during early development. Using a porcine oocyte and embryo in vitro model, next generation bisulfite DNA sequencing and bioinformatics tools, this project will focus on mapping the DNA methylation profiles of oocytes and early embryos to define the waves of DNA methylation prior to and post-embryonic genome activation, the time point when the early embryo initiates its own global transcription. You will learn how to harvest oocytes from ovaries; culture these immature oocytes to a mature stage; and fertilise them using in vitro fertilisation protocols. After preparing fertilised oocyte and embryo samples for next generation bisulfite DNA sequencing, you will learn to apply bioinformatics tools to map regions of DNA methylation across the whole genome and validate the findings. These outputs will then be tested against embryos generated from other assisted reproductive technologies to determine how these technologies impact on the DNA methylation profiles of the developing embryo.
Projects available for: Third Year / Honours / HDR / Masters / Mphil / PhD
Location: AHMS (Adelaide Health & Medical Sciences Building, North Tce) – Levels 5 and 6.
Research project start: Semester 1 and 2
Special requirements: Vaccination required.
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Appointments
Date Position Institution name 2019 - ongoing Professor University of Adelaide 2009 - 2019 Professor and Centre Head Hudson Institute of Medical Research 2007 - 2009 Professor of Reproductive Biology University of Warwick 2000 - 2007 Lecturer University of Birmingham -
Language Competencies
Language Competency German Can read, write, speak, understand spoken and peer review -
Education
Date Institution name Country Title 1999 University of Birmingham United Kingdom PhD 1995 University of Sheffield United Kingdom BSc (Hons) -
Research Interests
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Journals
Year Citation 2023 McIlfatrick, S., O'Leary, S., Okada, T., Penn, A., Nguyen, V. H. T., McKenny, L., . . . St. John, J. C. (2023). Does supplementation of oocytes with additional mtDNA influence developmental outcome?. iScience, 26(2), 105956-1-105956-27.
Scopus1 WoS1 Europe PMC12023 Okada, T., McIlfatrick, S., & St. John, J. C. (2023). Mitochondrial DNA Deficiency and Supplementation in Sus scrofa Oocytes Influence Transcriptome Profiles in Oocytes and Blastocysts. International Journal of Molecular Sciences, 24(4), 1-26.
Scopus3 WoS2 Europe PMC12023 Okada, T., Penn, A., & St. John, J. C. (2023). Mitochondrial DNA Supplementation of Oocytes Has Downstream Effects on the Transcriptional Profiles of Sus scrofa Adult Tissues with High mtDNA Copy Number. International Journal of Molecular Sciences, 24(8), 7545.
Scopus12022 Okada, T., Sun, X., McIlfatrick, S., & St. John, J. C. (2022). Low guanine content and biased nucleotide distribution in vertebrate mtDNA can cause overestimation of non-CpG methylation. NAR Genomics and Bioinformatics, 4(1), 1-17.
Scopus12022 Azumah, R., Hummitzsch, K., Hartanti, M. D., St John, J. C., Anderson, R. A., & Rodgers, R. J. (2022). Analysis of upstream regulators, networks, and pathways associated with the expression patterns of Polycystic Ovary Syndrome candidate genes during fetal ovary development. Frontiers in Genetics, 12, 762177-1-762177-16.
Scopus4 WoS5 Europe PMC42022 Okada, T., McIlfatrick, S., Hin, N., Aryamanesh, N., Breen, J., & St John, J. C. (2022). Mitochondrial supplementation of Sus scrofa metaphase II oocytes alters DNA methylation and gene expression profiles of blastocysts. Epigenetics and Chromatin, 15(1), 20 pages.
Scopus8 WoS7 Europe PMC42022 Towarnicki, S. G., Youngson, N. A., Corley, S. M., St John, J. C., Melvin, R. G., Turner, N., . . . Ballard, J. W. O. (2022). Ancestral dietary change alters the development of Drosophila larvae through MAPK signalling. Fly, 16(1), 299-311.
Scopus2 WoS1 Europe PMC22022 St John, J. C., Okada, T., Andreas, E., & Penn, A. (2022). The role of mtDNA in oocyte quality and embryo development. Molecular Reproduction and Development, 90(7), 621-633.
Scopus7 WoS4 Europe PMC62021 St. John, J. C. (2021). Epigenetic Regulation of the Nuclear and Mitochondrial Genomes: Involvement in Metabolism, Development, and Disease. Annual Review of Animal Biosciences, 9(1), 203-224.
Scopus1 WoS1 Europe PMC12020 Kapetanovic, R., Afroz, S. F., Ramnath, D., Lawrence, G. M. E. P., Okada, T., Curson, J. E. B., . . . Sweet, M. J. (2020). Lipopolysaccharide promotes Drp1-dependent mitochondrial fission and associated inflammatory responses in macrophages. Immunology and Cell Biology, 98(7), 528-539.
Scopus43 WoS38 Europe PMC262020 Towarnicki, S. G., Youngson, N. A., Corley, S. M., St John, J. C., Turner, N., Morris, M. J., & Ballard, J. W. O. (2020). Ancestral dietary change alters development of <i>Drosophila</i> larvae through MAPK signalling.
2019 St John, J., Makanji, Y., Johnson, J., Tsai, T. -S., Lagondar, S., Rodda, F., . . . Temple-Smith, P. (2019). The transgenerational effects of oocyte mitochondrial supplementation. Scientific Reports, 9(1), 6694-1-6694-12.
Scopus11 WoS12 Europe PMC82019 St John, J. C. (2019). Genomic balance: two genomes establishing synchrony to modulate cellular fate and function. Cells, 8(11), 1-14.
Scopus8 WoS9 Europe PMC62019 St John, J. C. (2019). Mitochondria and female germline stem cells−a mitochondrial DNA perspective. Cells, 8(8), 852-1-852-15.
Scopus12 WoS9 Europe PMC122019 Poulton, J., Steffann, J., Burgstaller, J., McFarland, R., Arbeithuber, B., Bengoa, J., . . . Wells, D. (2019). 243rd ENMC international workshop: Developing guidelines for management of reproductive options for families with maternally inherited mtDNA disease, Amsterdam, the Netherlands, 22-24 March 2019. NEUROMUSCULAR DISORDERS, 29(9), 725-733.
WoS9 Europe PMC72018 Sun, X., Vaghjiani, V., Jayasekara, W. S. N., Cain, J. E., & St John, J. C. (2018). The degree of mitochondrial DNA methylation in tumor models of glioblastoma and osteosarcoma.. Clinical epigenetics, 10(1), 157.
Scopus26 WoS26 Europe PMC212018 Sun, X., & St John, J. C. (2018). Modulation of mitochondrial DNA copy number in a model of glioblastoma induces changes to DNA methylation and gene expression of the nuclear genome in tumours. Epigenetics and Chromatin, 11(1), 53-1-53-18.
Scopus27 WoS23 Europe PMC202018 St John, J. C., & Tsai, T. -S. (2018). The association of mitochondrial DNA haplotypes and phenotypic traits in pigs.. BMC genetics, 19(41), 1-12.
Scopus16 WoS14 Europe PMC72018 Tsai, T. -S., & St John, J. C. (2018). The effects of mitochondrial DNA supplementation at the time of fertilization on the gene expression profiles of porcine preimplantation embryos.. Molecular reproduction and development, 85(6), 490-504.
Scopus17 WoS15 Europe PMC92018 Sun, X., Johnson, J., & St John, J. (2018). Global DNA methylation synergistically regulates the nuclear and mitochondrial genomes in glioblastoma cells. Nucleic Acids Research, 46(12), 5977-5995.
Scopus37 WoS37 Europe PMC312018 Tsai, T., Tyagi, S., & St John, J. (2018). The molecular characterisation of mitochondrial DNA deficient oocytes using a pig model. Human Reproduction, 33(5), 942-953.
Scopus19 WoS15 Europe PMC122018 Srirattana, K., & St John, J. (2018). Additional mitochondrial DNA influences the interactions between the nuclear and mitochondrial genomes in a bovine embryo model of nuclear transfer. Scientific Reports, 8(1), 17 pages.
Scopus20 WoS18 Europe PMC122018 St John, J. C., Srirattana, K., Tsai, T. S., & Sun, X. (2018). The mitochondrial genome: How it drives fertility. Reproduction, Fertility and Development, 30(1), 118-139.
Scopus6 WoS5 Europe PMC32017 Lee, W. T., Sun, X., Tsai, T. S., Johnson, J. L., Gould, J. A., Garama, D. J., . . . St John, J. C. (2017). Mitochondrial DNA haplotypes induce differential patterns of DNA methylation that result in differential chromosomal gene expression patterns. Cell Death Discovery, 3(1), 1-11.
Scopus30 WoS29 Europe PMC192017 Srirattana, K., & St John, J. C. (2017). Manipulating the mitochondrial genome to enhance cattle embryo development. G3 : Genes, Genomes, Genetics, 7(7), 2065-2080.
Scopus18 WoS17 Europe PMC102017 Vaghjiani, V., Cain, J. E., Lee, W., Vaithilingam, V., Tuch, B. E., & St John, J. C. (2017). Modulation of Mitochondrial DNA Copy Number to Induce Hepatocytic Differentiation of Human Amniotic Epithelial Cells. Stem Cells and Development, 26(20), 1505-1519.
Scopus2 WoS2 Europe PMC12017 Tsai, T., Johnson, J., White, Y., & St John, J. (2017). The molecular characterization of porcine egg precursor cells. Oncotarget, 8(38), 63484-63505.
Scopus9 WoS10 Europe PMC92017 Srirattana, K., McCosker, K., Schatz, T., & St John, J. C. (2017). Cattle phenotypes can disguise their maternal ancestry. BMC Genetics, 18(59), 11 pages.
Scopus20 WoS17 Europe PMC72016 Sun, X., & John, J. C. S. (2016). The role of the mtDNA set point in differentiation, development and tumorigenesis. Biochemical Journal, 473(19), 2955-2971.
Scopus36 WoS30 Europe PMC182016 Tsai, T., & St John, J. C. (2016). The role of mitochondrial DNA copy number, variants, and haplotypes in farm animal developmental outcome. Domestic Animal Endocrinology, 56, S133-S146.
Scopus13 WoS12 Europe PMC52016 Lee, W. T. Y., & St. John, J. C. (2016). Mitochondrial DNA as an initiator of tumorigenesis. Cell Death and Disease, 7(3), 2 pages.
Scopus9 WoS8 Europe PMC62016 Cagnone, G., Tsai, T. S., Srirattana, K., Rossello, F., Powell, D. R., Rohrer, G., . . . St John, J. C. (2016). Segregation of naturally occurring mitochondrial DNA variants in a mini-pig model. Genetics, 202(3), 931-944.
Scopus20 WoS20 Europe PMC152016 Tsai, T., Rajasekar, S., & St John, J. (2016). The relationship between mitochondrial DNA haplotype and the reproductive capacity of domestic pigs (Sus scrofa domesticus). BMC Genetics, 17(1), 67.
Scopus34 WoS32 Europe PMC182016 St John, J. C., Tsai, T. S., & Cagnone, G. L. M. (2016). Mitochondrial DNA supplementation as an enhancer of female reproductive capacity. Current Opinion in Obstetrics and Gynecology, 28(3), 211-216.
Scopus4 WoS4 Europe PMC32016 Cagnone, G. L. M., Tsai, T. S., Makanji, Y., Matthews, P., Gould, J., Bonkowski, M. S., . . . John, J. C. S. (2016). Restoration of normal embryogenesis by mitochondrial supplementation in pig oocytes exhibiting mitochondrial DNA deficiency. Scientific Reports, 6(1), 1-15.
Scopus66 WoS55 Europe PMC392016 St John, J. C. (2016). Mitochondrial DNA copy number and replication in reprogramming and differentiation. Seminars in Cell and Developmental Biology, 52, 93-101.
Scopus45 WoS35 Europe PMC262016 Johnson, J., Lee, W., Frazier, A. E., Vaghjiani, V., Laskowski, A., Rodriguez, A. L., . . . St John, J. C. (2016). Deletion of the Complex I Subunit NDUFS4 Adversely Modulates Cellular Differentiation. Stem Cells and Development, 25(3), 239-250.
Scopus7 WoS7 Europe PMC42016 Lee, W. T. Y., Cain, J. E., Cuddihy, A., Johnson, J., Dickinson, A., Yeung, K. Y., . . . St John, J. C. (2016). Mitochondrial DNA plasticity is an essential inducer of tumorigenesis. Cell Death Discovery, 2(1), 11 pages.
Scopus26 WoS26 Europe PMC202015 Lee, W., Johnson, J., Gough, D. J., Donoghue, J., Cagnone, G. L. M., Vaghjiani, V., . . . St John, J. C. (2015). Mitochondrial DNA copy number is regulated by DNA methylation and demethylation of POLGA in stem and cancer cells and their differentiated progeny. Cell Death and Disease, 6(2), e1664.
Scopus79 WoS74 Europe PMC542015 Lee, W. T. Y., & John, J. S. (2015). The control of mitochondrial DNA replication during development and tumorigenesis. Annals of the New York Academy of Sciences, 1350(1), 95-106.
Scopus39 WoS34 Europe PMC212015 Henry, B. A., Loughnan, R., Hickford, J., Young, I. R., St John, J. C., & Clarke, I. (2015). Differences in mitochondrial DNA inheritance and function align with body conformation in genetically lean and fat sheep. Journal of Animal Science, 93(5), 2083-2093.
Scopus10 WoS10 Europe PMC72015 Wu, L., Russell, D., Wong, S., Chen, M., Tsai, T., St John, J., . . . Robker, R. (2015). Mitochondrial dysfunction in oocytes of obese mothers: transmission to offspring and reversal by pharmacological endoplasmic reticulum stress inhibitors. Development, 142(4), 681-691.
Scopus204 WoS184 Europe PMC1272015 St John, J. C. (2015). The mitochondrion, its genome and their contribution to well-being and disease. Molecular Human Reproduction, 21(1), 1-2.
Scopus5 WoS2 Europe PMC52014 St John, J., Srirattana, K., & Clarke, I. (2014). Modifying the mitochondrial genome to enhance animal production. Australasian Biotechnology, 24(3), 61. 2014 Yeung, K. Y., Dickinson, A., Donoghue, J. F., Polekhina, G., White, S. J., Grammatopoulos, D. K., . . . St John, J. C. (2014). The identification of mitochondrial DNA variants in glioblastoma multiforme. Acta Neuropathologica Communications, 2(1), 1.
Scopus45 WoS45 Europe PMC532014 Sobinoff, A. P., Sutherland, J. M., Beckett, E. L., Stanger, S. J., Johnson, R., Jarnicki, A. G., . . . Mclaughlin, E. A. (2014). Damaging legacy: Maternal cigarette smoking has long-term consequences for male offspring fertility. Human Reproduction, 29(12), 2719-2735.
Scopus42 WoS41 Europe PMC252014 St John, J. (2014). The control of mtDNA replication during differentiation and development. Biochimica et Biophysica Acta - General Subjects, 1840(4), 1345-1354.
Scopus80 WoS73 Europe PMC532014 Nagley, P., St John, J., Gabriel, K., & McKenzie, M. (2014). Mitochondrial research in Australia: A major player in worldwide trends. Biochimica et Biophysica Acta - General Subjects, 1840(4), 1225-1226.
2014 Mckenzie, M., Chiotis, M., Hroudová, J., Lopez Sanchez, M., Lim, S., Cook, M., . . . Trounce, I. (2014). Capture of somatic mtDNA point mutations with severe effects on oxidative phosphorylation in synaptosome cybrid clones from human brain. Human Mutation, 35(12), 1476-1484.
Scopus12 WoS12 Europe PMC82014 Lee, T., Clarke, I., St John, J., Young, I., Leury, B., Rao, A., . . . Henry, B. (2014). High cortisol responses identify propensity for obesity that is linked to thermogenesis in skeletal muscle. FASEB Journal, 28(1), 35-44.
Scopus15 WoS15 Europe PMC92013 Dickinson, A., Yeung, K. Y., Donoghue, J., Baker, M. J., Kelly, R. D., McKenzie, M., . . . St John, J. C. (2013). The regulation of mitochondrial DNA copy number in glioblastoma cells. Cell Death and Differentiation, 20(12), 1644-1653.
Scopus98 WoS97 Europe PMC762013 Kelly, R. D. W., Rodda, A. E., Dickinson, A., Mahmud, A., Nefzger, C. M., Lee, W., . . . St John, J. C. (2013). Mitochondrial DNA haplotypes define gene expression patterns in pluripotent and differentiating embryonic stem cells. Stem Cells, 31(4), 703-716.
Scopus61 WoS63 Europe PMC432013 Kelly, R. D. W., Sumer, H., McKenzie, M., Facucho-Oliveira, J., Trounce, I. A., Verma, P. J., & St John, J. C. (2013). The Effects of Nuclear Reprogramming on Mitochondrial DNA Replication. Stem Cell Reviews and Reports, 9(1), 1-15.
Scopus44 WoS39 Europe PMC282013 John, J. S. (2013). A tribute to somatic cell reprogrammers. Molecular Human Reproduction, 19(2), 55-56.
2012 Kelly, R. D. W., Mahmud, A., McKenzie, M., Trounce, I. A., & St John, J. C. (2012). Mitochondrial DNA copy number is regulated in a tissue specific manner by DNA methylation of the nuclear-encoded DNA polymerase gamma A. Nucleic Acids Research, 40(20), 10124-10138.
Scopus145 WoS129 Europe PMC1072012 St John, J. C. (2012). Transmission, inheritance and replication of mitochondrial DNA in mammals: Implications for reproductive processes and infertility. Cell and Tissue Research, 349(3), 795-808.
Scopus24 WoS22 Europe PMC102011 Rae, P. C., Kelly, R. D., Egginton, S., & St John, J. C. (2011). Angiogenic potential of endothelial progenitor cells and embryonic stem cells. Vascular Cell, 3(1), 15 pages.
Scopus32 WoS30 Europe PMC192011 Sanchez-Partida, L., Kelly, R., Sumer, H., Lo, C., Aharon, R., Holland, M., . . . John St, J. (2011). The generation of live offspring from vitrified oocytes. PLoS ONE, 6(6), e21597.
Scopus18 WoS14 Europe PMC102011 Jiang, Y., Kelly, R., Peters, A., Fulka, H., Dickinson, A., Mitchell, D. A., & St. John, J. C. (2011). Interspecies somatic cell nuclear transfer is dependent on compatible mitochondrial DNA and reprogramming factors. PLoS ONE, 6(4), 12 pages.
Scopus44 WoS27 Europe PMC192011 Kelly, R. D. W., & St. John, J. C. (2011). Role of mitochondrial DNA replication during differentiation of reprogrammed stem cells. International Journal of Developmental Biology, 54(11-12), 1659-1670.
Scopus16 WoS11 Europe PMC112010 St John, J. C., & Campbell, K. H. S. (2010). The battle to prevent the transmission of mitochondrial DNA disease: Is karyoplast transfer the answer. Gene Therapy, 17(2), 147-149.
Scopus16 WoS15 Europe PMC82010 St. John, J. C., Facucho-Oliveira, J., Jiang, Y., Kelly, R., & Salah, R. (2010). Mitochondrial DNA transmission, replication and inheritance: A journey from the gamete through the embryo and into offspring and embryonic stem cells. Human Reproduction Update, 16(5), 488-509.
Scopus214 WoS191 Europe PMC1412010 Lee, J. H., Peters, A., Fisher, P., Bowles, E. J., St. John, J. C., & Campbell, K. H. S. (2010). Generation of mtDNA homoplasmic cloned lambs. Cellular Reprogramming, 12(3), 347-355.
Scopus28 WoS21 Europe PMC152009 Fulka, J., Loi, P., Ptak, G., Fulka, H., & John, J. S. (2009). Hope for the mammoth?. Cloning and Stem Cells, 11(1), 1-3.
Scopus7 WoS7 Europe PMC92009 Facucho-Oliveira, J. M., & John St., J. C. (2009). The relationship between pluripotency and mitochondrial DNA proliferation during early embryo development and embryonic Stem Cell differentiation. Stem Cell Reviews and Reports, 5(2), 140-158.
Scopus199 WoS179 Europe PMC1402009 Taylor, R. A., Wang, H., Wilkinson, S. E., Richards, M. G., Britt, K. L., Vaillant, F., . . . Risbridger, G. P. (2009). Lineage enforcement by inductive mesenchyme on adult epithelial stem cells across developmental germ layers. Stem Cells, 27(12), 3032-3042.
Scopus24 WoS26 Europe PMC192008 Fulka, J., Fulka, H., St John, J., Galli, C., Lazzari, G., Lagutina, I., . . . Loi, P. (2008). Cybrid human embryos - warranting opportunities to augment embryonic stem cell research. Trends in Biotechnology, 26(9), 469-474.
Scopus5 WoS5 Europe PMC32008 Bowles, E. J., Tecirlioglu, R. T., French, A. J., Holland, M. K., & St. John, J. C. (2008). Mitochondrial DNA transmission and transcription after somatic cell fusion to one or more cytoplasts. Stem Cells, 26(3), 775-782.
Scopus41 WoS34 Europe PMC232008 St John, J. C., Armstrong, L., Minger, S. L., & Campbell, K. H. S. (2008). Law should recognize value of interspecies embryos [1]. Nature, 451(7179), 627.
Scopus5 WoS6 Europe PMC32007 St John, J., & Lovell-Badge, R. (2007). Human-animal cytoplasmic hybrid embryos, mitochondria, and an energetic debate. Nature Cell Biology, 9(9), 988-992.
Scopus26 WoS19 Europe PMC152007 Bowles, E. J., Lee, J. H., Alberio, R., Lloyd, R. E. I., Stekel, D., Campbell, K. H. S., & St. John, J. C. (2007). Contrasting effects of in vitro fertilization and nuclear transfer on the expression of mtDNA replication factors. Genetics, 176(3), 1511-1526.
Scopus50 WoS48 Europe PMC362007 St John, J. C., Bowles, E. J., & Amaral, A. (2007). Sperm mitochondria and fertilisation.. Society of Reproduction and Fertility supplement, 65, 399-416.
Scopus21 Europe PMC112007 Spikings, E. C., Alderson, J., & St. John, J. C. (2007). Regulated mitochondrial DNA replication during oocyte maturation is essential for successful porcine embryonic development. Biology of Reproduction, 76(2), 327-335.
Scopus212 WoS194 Europe PMC1422007 Amaral, A., Ramalho-Santos, J., & St John, J. C. (2007). The expression of polymerase gamma and mitochondrial transcription factor A and the regulation of mitochondrial DNA content in mature human sperm. Human Reproduction, 22(6), 1585-1596.
Scopus112 WoS100 Europe PMC672007 Facucho-Oliveira, J. M., Alderson, J., Spikings, E. C., Egginton, S., & St. John, J. C. (2007). Mitochondrial DNA replication during differentiation of murine embryonic stem cells. Journal of Cell Science, 120(22), 4025-4034.
Scopus234 WoS228 Europe PMC1852007 Fulka, J., Fulka, H., & St. John, J. C. (2007). Transmission of mitochondrial DNA disorders: Possibilities for the elimination of mutated mitochondria. Cloning and Stem Cells, 9(1), 47-50.
Scopus8 WoS6 Europe PMC52006 Spikings, E. C., Alderson, J., & St. John, J. C. (2006). Transmission of mitochondrial DNA following assisted reproduction and nuclear transfer. Human Reproduction Update, 12(4), 401-415.
Scopus63 WoS60 Europe PMC342006 Poulton, J., Kennedy, S., Oakeshott, P., & St John, J. (2006). Nuclear transfer to prevent mitochondrial DNA diseases. Lancet, 368(9538), 841.
Scopus9 WoS7 Europe PMC22006 Santos, T. A., El Shourbagy, S., & St. John, J. C. (2006). Mitochondrial content reflects oocyte variability and fertilization outcome. Fertility and Sterility, 85(3), 584-591.
Scopus314 WoS292 Europe PMC2032006 Lloyd, R. E., Lee, J. H., Alberio, R., Bowles, E. J., Ramalho-Santos, J., Campbell, K. H. S., & St. John, J. C. (2006). Aberrant nucleo-cytoplasmic cross-talk results in donor cell mtDNA persistence in cloned embryos. Genetics, 172(4), 2515-2527.
Scopus59 WoS54 Europe PMC392006 St John, J. C., Amaral, A., Bowles, E., Oliveira, J. F., Lloyd, R., Freitas, M., . . . Ramalho-Santos, J. (2006). The analysis of mitochondria and mitochondrial DNA in human embryonic stem cells.. Methods in molecular biology (Clifton, N.J.), 331, 347-374.
Scopus46 Europe PMC382006 El Shourbagy, S. H., Spikings, E. C., Freitas, M., & St. John, J. C. (2006). Mitochondria directly influence fertilisation outcome in the pig. Reproduction, 131(2), 233-245.
Scopus265 WoS246 Europe PMC1822005 Fleming, C., Maldjian, A., Da Costa, D., Rullay, A. K., Haddleton, D. M., St John, J., . . . Davis, B. G. (2005). A Carbohydrate-Antioxidant Hybrid Polymer Reduces Oxidative Damage in Spermatozoa and Enhances Fertility. Nature Chemical Biology, 1(5), 270-274.
Scopus65 WoS59 Europe PMC182005 St. John, J. C., Moffatt, O., & D'Souza, N. (2005). Aberrant heteroplasmic transmission of mtDNA in cloned pigs arising from double nuclear transfer. Molecular Reproduction and Development, 72(4), 450-460.
Scopus36 WoS30 Europe PMC222005 St John, J. C., & Alderson, J. (2005). Stem-cell banking: The size of the task. Lancet, 366(9502), 1991-1992.
Scopus2 WoS1 Europe PMC22005 St. John, J. C., Ramalho-Santos, J., Gray, H. L., Petrosko, P., Rawe, V. Y., Navara, C. S., . . . Schatten, G. P. (2005). The expression of mitochondrial DNA transcription factors during early cardiomyocyte in vitro differentiation from human embryonic stemn cells. Cloning and Stem Cells, 7(3), 141-153.
Scopus208 WoS185 Europe PMC1552005 St. John, J. C., Jokhi, R. P., & Barratt, C. L. R. (2005). The impact of mitochondrial genetics on male infertility. International Journal of Andrology, 28(2), 65-73.
Scopus96 WoS74 Europe PMC602004 St. John, J. C., & Schatten, G. (2004). Paternal mitochondrial DNA transmission during nonhuman primate nuclear transfer. Genetics, 167(2), 897-905.
Scopus65 WoS51 Europe PMC322004 St. John, J. C., Lloyd, R. E. I., Bowles, E. J., Thomas, E. C., & El Shourbagy, S. (2004). The consequences of nuclear transfer for mammalian foetal development and offspring survival. A mitochondrial DNA perspective. Reproduction, 127(6), 631-641.
Scopus72 WoS59 Europe PMC402004 Mital, D., White, D. J., & St John, J. C. (2004). Mitochondrial DNA and sperm quality in patients on antiretroviral therapy - Response [3]. AIDS, 18(6), 963.
Scopus4 WoS4 Europe PMC22004 Barratt, C. L. R., St. John, J. C., & Afnan, M. (2004). Clinical challenges in providing embryos for stem-cell initiatives. Lancet, 364(9429), 115-118.
Scopus21 WoS17 Europe PMC122004 St John, J. C., Lloyd, R., & El Shourbagy, S. (2004). The potential risks of abnormal transmission of mtDNA through assisted reproductive technologies. Reproductive BioMedicine Online, 8(1), 34-44.
Scopus30 WoS23 Europe PMC112003 Payne, C., St. John, J. C., Ramalho-Santos, J., & Schatten, G. (2003). LIS1 Association with Dynactin is Required for Nuclear Motility and Genomic Union in the Fertilized Mammalian Oocyte. Cell Motility and the Cytoskeleton, 56(4), 245-251.
Scopus17 WoS16 Europe PMC122002 Perkins, J., St. John, J., & Ahmed, A. (2002). Modulation of trophoblast cell death by oxygen and EGF. Molecular Medicine, 8(12), 847-856.
Scopus25 WoS24 Europe PMC212002 St. John, J. C. (2002). Ooplasm donation in humans: The need to investigate the transmission of mitochondrial DNA following cytoplasmic transfer. Human Reproduction, 17(8), 1954-1958.
Scopus46 WoS42 Europe PMC262001 White, D. J., Mital, D., Taylor, S., & John, J. C. S. (2001). Sperm mitochondrial DNA deletions as a consequence of long term highly active antiretroviral therapy. AIDS, 15(8), 1061-1062.
Scopus55 WoS39 Europe PMC242001 St. John, J. C., Jokhi, R. P., & Barratt, C. L. R. (2001). Men with oligoasthenoteratozoospermia harbour higher numbers of multiple mitochondrial DNA deletions in their spermatozoa, but individual deletions are not indicative of overall aetiology. Molecular Human Reproduction, 7(1), 103-111.
Scopus88 WoS74 Europe PMC522000 John, J. C. S., & De Jonge, C. J. (2000). A hypothesis for transmission of paternal mitochondrial DNA. Reproductive Medicine Review, 8(1), 73-85.
Scopus62000 St. John, J. C., Sakkas, D., & Barratt, C. L. R. (2000). A role for mitochondrial DNA and sperm survival. Journal of Andrology, 21(2), 189-199.
Scopus56 WoS57 Europe PMC322000 Ahmed, A., Rahman, M., Zhang, X., Acevedo, C. H., Nijjar, S., Rushton, I., . . . St. John, J. (2000). Induction of Placental Heme Oxygenase-1 Is Protective Against TNFα-induced Cytotoxicity and Promotes Vessel Relaxation. Molecular Medicine, 6(5), 391-409.
Scopus140 WoS132 Europe PMC992000 St John, J., Sakkas, D., Dimitriadi, K., Barnes, A., Maclin, V., Ramey, J., . . . De Jonge, C. (2000). Failure of elimination of paternal mitochondrial DNA in abnormal embryos. Lancet, 355(9199), 200.
Scopus81 WoS71 Europe PMC421999 St. John, J. C. (1999). Incorporating molecular screening techniques into the modern andrology laboratory. Journal of Andrology, 20(6), 692-701.
Scopus9 WoS4 Europe PMC11999 Sakkas, D., Mariethoz, E., & St. John, J. C. (1999). Abnormal sperm parameters in humans are indicative of an abortive apoptotic mechanism linked to the fas-mediated pathway. Experimental Cell Research, 251(2), 350-355.
Scopus302 WoS251 Europe PMC1611997 St. John, J. C., Cooke, I. D., Barratt, C. L. R., & Johns, D. R. (1997). Mitochondrial mutations and male infertility [2]. Nature Medicine, 3(2), 124-125.
Scopus59 WoS68 Europe PMC291997 St John, J. C., Barratt, C. L. R., Brenner, C. A., Scott, J., & Cohen, J. (1997). Use of anucleate donor oocyte cytoplasm in recipient eggs (multiple letters) [16]. Lancet, 350(9082), 961-962.
Scopus2 WoS12 Europe PMC9- St. John, J. C. (n.d.). Mitochondrial
<scp>DNA</scp>
: Fate of the Paternal Mitochondrial Genome.
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Books
Year Citation 2013 St. John, J. C. (2013). Mitochondrial DNA, mitochondria, disease and stem cells. J. C. St. John (Ed.), Humana Press.
2007 St John, J. C. (2007). Preface (Vol. 77). Elsevier.
2007 Bowles, E. J., Campbell, K. H. S., & St. John, J. C. (2007). Nuclear Transfer: Preservation of a Nuclear Genome at the Expense of Its Associated mtDNA Genome(s) (Vol. 77). J. C. StJohn (Ed.), ELSEVIER ACADEMIC PRESS INC.
Scopus46 WoS36 Europe PMC24 -
Book Chapters
Year Citation 2019 Srirattana, K., & St John, J. (2019). Transmission of Dysfunctional Mitochondrial DNA and Its Implications for Mammalian Reproduction. In P. Sutovsky (Ed.), Cellular and Molecular Basis of Mitochondrial Inheritance (Vol. 231, pp. 75-103). Switzerland: Springer Nature.
Scopus12 WoS11 Europe PMC52016 Cagnone, G., Vaghjiani, V., Lee, W., Sun, C., Johnson, J., Yeung, K. Y., & St John, J. C. (2016). Analysis of the mitochondrial DNA and its replicative capacity in induced pluripotent stem cells. In K. Turksen, & A. Nagy (Eds.), Induced Pluripotent Stem (iPS) Cells: Methods and Protocols (Vol. 1357, pp. 231-267). New York; USA: Springer.
Scopus2 Europe PMC22016 Sun, X., Lee, W., Vaghjiani, V., & St John, J. C. (2016). Analysis of mitochondrial DNA copy number and its regulation through DNA methylation of POLGA. In M. McKenzie (Ed.), Mitochondrial DNA: Methods and Protocols (Vol. 1351, pp. 131-141). New York; USA: Springer.
Scopus5 Europe PMC32015 Lee, W., Kelly, R. D. W., Yeung, K. Y., Cagnone, G., McKenzie, M., & St John, J. C. (2015). Analysis of mitochondrial DNA in induced pluripotent and embryonic stem cells. In P. J. Verma, & H. Sumer (Eds.), Cell Reprogramming: Methods and Protocols (Vol. 1330, pp. 219-252). New York; USA: Springer.
Scopus3 Europe PMC12013 Yeung, K. Y., Dickinson, A., & St. John, J. C. (2013). The Role of Mitochondrial DNA in Tumorigenesis. In Mitochondrial DNA, Mitochondria, Disease and Stem Cells (pp. 119-155). Humana Press.
Scopus12013 Facucho-Oliveira, J., Kulkarni, T., Machado-Oliveira, G., & St. John, J. C. (2013). From Pluripotency to Differentiation: The Role of mtDNA in Stem Cell Models of Mitochondrial Diseases. In Mitochondrial DNA, Mitochondria, Disease and Stem Cells (pp. 87-118). Humana Press.
2013 St. John, J. C. (2013). Mitochondrial DNA: Its Transmission from Gametes and Embryos. In Principles of Cloning: Second Edition (pp. 429-439). Elsevier.
Scopus12013 Kelly, R. D. W., Mahmud, A., & St. John, J. C. (2013). Assisted Reproductive Technologies: The Potential to Prevent the Transmission of Mutant mtDNA from One Generation to the Next. In Mitochondrial DNA, Mitochondria, Disease and Stem Cells (pp. 157-183). Humana Press.
2012 St. John, J. C., & Campbell, K. H. S. (2012). The consequences of reprogramming a somatic cell for mitochondrial DNA transmission, inheritance and replication. In Nuclear Reprogramming and Stem Cells (pp. 83-97). Humana Press.
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Conference Papers
Year Citation 2014 St John, J. C. (2014). SUPPLEMENTING OOCYTES WITH AUTOLOGOUS MITOCHONDRIA ENHANCES FERTILIZATION OUTCOMES.. In FERTILITY AND STERILITY Vol. 102 (pp. E330). Honolulu, HI: ELSEVIER SCIENCE INC.
2009 St. John, J. C. (2009). mtDNA and sperm function. In Systems Biology in Reproductive Medicine Vol. 55 (pp. 17-18). 2008 Fulka, H., St. John, J. C., Fulka, J., & Hozák, P. (2008). Chromatin in early mammalian embryos: Achieving the pluripotent state. In Differentiation Vol. 76 (pp. 3-14). England: ELSEVIER SCI LTD.
Scopus50 WoS43 Europe PMC292004 Ramalho-Santos, J., Sammak, P., Chong, K. Y., Qidwai, H., Rawe, V. Y., St John, J. C., & Schatten, G. (2004). Membrane trafficking and organelle dynamics in undifferentiated embryonic stem cells: Endomembrane biogenesis and expansion coupled with differentiation.. In BIOLOGY OF REPRODUCTION (pp. 216-217). Univ British Columbia, Vancouver, CANADA: SOC STUDY REPRODUCTION. 2002 St. John, J. C. (2002). The transmission of mitochondrial DNA following assisted reproductive techniques. In Theriogenology Vol. 57 (pp. 109-123). FOZ DO IGUACU, BRAZIL: ELSEVIER SCIENCE INC.
Scopus42 WoS39 Europe PMC282000 O'Connell, M., St John, J. C., McClure, N., Steele, E. K., & Lewis, S. E. M. (2000). A comparison of mitochondrial DNA deletions in proximal epididymal and testicular spermatozoa in males with obstructive azoospermia. In HUMAN REPRODUCTION Vol. 15 (pp. 114-115). OXFORD UNIV PRESS. 1999 Barratt, C. L. R., St John, J. C., & Afnan, M. (1999). Genetic testing of the male.. In C. Gagnon (Ed.), MALE GAMETE: FROM BASIC SCIENCE TO CLINICAL APPLICATIONS (pp. 397-405). MONTREAL, CANADA: CACHE RIVER PRESS.
WoS11998 Barratt, C. L. R., & St John, J. C. (1998). Diagnostic tools in male infertility. In Human Reproduction Vol. 13 (pp. 51-61). THESSALONIKI, GREECE: OXFORD UNIV PRESS.
Scopus13 WoS9 Europe PMC31997 St John, J. C., Cooke, I. D., & Barratt, C. L. R. (1997). The Use of Long PCR to detect multiple deletions in the mitochondrial DNA of human testicular tissue from azoospermic and severe oligozoospermic patients. In C. Barratt, C. DeJonge, D. Mortimer, & J. Parinaud (Eds.), GENETICS OF HUMAN MALE FERTILITY (pp. 333-347). COLLIOURE, FRANCE: EDITIONS EDK.
WoS61997 StJohn, J. C., Jokhi, R. P., Barratt, C. L. R., & Cooke, I. D. (1997). The effects of mitochondrial dysfunction on sperm motility. In HUMAN REPRODUCTION Vol. 12 (pp. P11). OXFORD UNIV PRESS. -
Conference Items
Year Citation 2014 Chang, J. R., Chang, C. W., Chao, S. J., Cheng, A., Dai, K., Lee, J. T., . . . Yang, C. P. (2014). Preface. Poster session presented at the meeting of Geotechnical Special Publication.
2021 – 2025 NHMRC Ideas Grant (GNT2000723), Understanding the benefits and limitations of metaphase II spindle transfer (St. John J) $1,629,373.
2019 – 2022: NHMRC Project Grant (GNT1160106), Understanding how mitochondrial DNA contributes to embryo development (St. John J) $669,790
2018 – 2020: NHMRC Development Grant (GNT1136065), Improving oocyte mitochondrial DNA copy number to enhance female reproductive capacity (St. John J, McKenzie W, Western P, Rombauts L) $670,867.20.
2017 – 2018: The Winston Foundation (WF1), Developing a canine in vitro maturation culture system (St. John J) $42,000
2016 – 2018: OvaScience Inc. Waltham, USA. Renewal Grant, Safety of Mitochondrial Transfer (St. John J) $600,000.
2016 – 2019: ARC Discovery Grant(DP160102575), Diet influences the selective advantage of mitochondrial DNA mutations (Ballard B, St. John J, Smyth G) $313,600.00
2015 – 2017: NHMRC Project Grant(GNT1079309) - Metabolic and molecular basis of embryo signalling (Lane M, St. John J, Zander-Fox D) $397,077.00
2014 – 2016: Australian Mitochondrial Disease Foundation- Preventing the transmission of mutant mitochondrial DNA (St. John J) $25,000
2013 – 2016: OvaScience Inc- Determining the safety of homologous mitochondrial transfer in a mini-pig model (St. John J) $1,250,000
2013 – 2015: NHMRC Project Grant(GNT1041471) - Understanding mitochondrial DNA segregation and transmission (CIA - St. John J; Trounce I) $492,863
2013 – 2015: Zwart Estate- The role of mtDNA variants in glioblastoma (St. John J) $133,131
2013 – 2016: Australian Pork Limited- Defining the role of mitochondrial DNA in pig fertility (St. John J) $92,637
2013 – 2014: Johnston Estate- The generation of stem cell models of mtDNA disease (St. John J) $170,000
2012 – 2014: NHMRC Project Grant(GNT1022222) - Understanding the pathogenesis of mitochondrial disease using iPS cells (Thorburn D, St. John J, Frazier A, Nisbet D, White S) $618,675
2011: Marian and EH Flack Trust- Funding to purchase a High Resolution Melting Curve Analysis Machine(White S, Western P, St. John J, Watkins DN) $30,000.
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Committee Memberships
Date Role Committee Institution Country 2019 - 2020 Member Mitochondrial Donation Expert Working Committee National Health and Medical Research Council Australia 2018 - 2021 Member Embryo Research Licencing Committee National Health and Medical Reseach Council Australia
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