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Dr Janet Holt

ARC DECRA Fellow

School of Biomedical Sciences and Pharmacy (Human Physiology)

Career Summary

Biography

Dr Holt completed her PhD at the University of Newcastle 2002-2006 investigating gene expression in the developing mammalian ovary. Post-doctoral research areas have included nuclear signalling in the developing mammalian testis and currently, control of meiosis and molecular mechanisms underlying aneuploidy in the mammalian female gamete.

Research Expertise
- Egg quality and the ageing ovary - Meiosis regulation in the male and female gamete - Molecular mechanisms leading to aneuploidy in the egg








Qualifications

  • PhD, University of Newcastle
  • Bachelor of Science (Biotechnology)(Honours), University of Newcastle

Keywords

  • Reproductive Medicine
  • meiosis
  • oocytes

Fields of Research

CodeDescriptionPercentage
060199Biochemistry and Cell Biology not elsewhere classified50
111499Paediatrics and Reproductive Medicine not elsewhere classified50

Professional Experience

UON Appointment

DatesTitleOrganisation / Department
21/07/2008 - 19/12/2008Casual AcademicUniversity of Newcastle
School of Environmental and Life Sciences
Australia

Academic appointment

DatesTitleOrganisation / Department
1/02/2012 - 1/04/2015Fellow - ARCUniversity of Newcastle
School of Biomedical Sciences and Pharmacy
Australia
1/01/2011 - 1/12/2013Fellow - UONUniversity of Newcastle
School of Biomedical Sciences and Pharmacy
Australia
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Publications

For publications that are currently unpublished or in-press, details are shown in italics.


Chapter (2 outputs)

YearCitationAltmetricsLink
2013Jones KT, Lane SIR, Holt JE, 'Start and Stop Signals of Oocyte Meiotic Maturation', Oogenesis, Springer, London 183-193 (2013) [B1]
DOI10.1007/978-0-85729-826-3_13
Co-authorsKeith Jones
2013Holt JE, Lane SIR, Jones KT, 'The Control of Meiotic Maturation in Mammalian Oocytes', Gametogenesis, Academic Press, San diego 207-226 (2013) [B1]
DOI10.1016/B978-0-12-416024-8.00007-6Author URL
CitationsScopus - 8Web of Science - 8
Co-authorsKeith Jones

Journal article (18 outputs)

YearCitationAltmetricsLink
2014Sadeqzadeh E, De Bock CE, Wojtalewicz N, Holt JE, Smith ND, Dun MD, et al., 'Furin processing dictates ectodomain shedding of human FAT1 cadherin', Experimental Cell Research, 323 41-55 (2014)
DOI10.1016/j.yexcr.2014.02.012
Co-authorsRick Thorne, Matt Dun
2014Sadeqzadeh E, De Bock CE, Wojtalewicz N, Holt JE, Smith ND, Dun MD, et al., 'Furin processing dictates ectodomain shedding of human FAT1 cadherin', Experimental Cell Research, 323 41-55 (2014) [C1]

Fat1 is a single pass transmembrane protein and the largest member of the cadherin superfamily. Mouse knockout models and in vitro studies have suggested that Fat1 influences cell polarity and motility. Fat1 is also an upstream regulator of the Hippo pathway, at least in lower vertebrates, and hence may play a role in growth control. In previous work we have established that FAT1 cadherin is initially cleaved by proprotein convertases to form a noncovalently linked heterodimer prior to expression on the cell surface. Such processing was not a requirement for cell surface expression, since melanoma cells expressed both unprocessed FAT1 and the heterodimer on the cell surface. Here we further establish that the site 1 (S1) cleavage step to promote FAT1 heterodimerisation is catalysed by furin and we identify the cleavage site utilised. For a number of other transmembrane receptors that undergo heterodimerisation the S1 processing step is thought to occur constitutively but the functional significance of heterodimerisation has been controversial. It has also been generally unclear as to the significance of receptor heterodimerisation with respect to subsequent post-translational proteolysis that often occurs in transmembrane proteins. Exploiting the partial deficiency of FAT1 processing in melanoma cells together with furin-deficient LoVo cells, we manipulated furin expression to demonstrate that only the heterodimer form of FAT1 is subject to cleavage and subsequent release of the extracellular domain. This work establishes S1-processing as a clear functional prerequisite for ectodomain shedding of FAT1 with general implications for the shedding of other transmembrane receptors. © 2014.

DOI10.1016/j.yexcr.2014.02.012
CitationsScopus - 1Web of Science - 1
Co-authorsMatt Dun, Rick Thorne
2014Camlin NJ, McLaughlin EA, Holt JE, 'Through the smoke: Use of in vivo and in vitro cigarette smoking models to elucidate its effect on female fertility', Toxicology and Applied Pharmacology, 281 266-275 (2014) [C1]

A finite number of oocytes are established within the mammalian ovary prior to birth to form a precious ovarian reserve. Damage to this limited pool of gametes by environmental factors such as cigarette smoke and its constituents therefore represents a significant risk to a woman's reproductive capacity. Although evidence from human studies to date implicates a detrimental effect of cigarette smoking on female fertility, these retrospective studies are limited and present conflicting results. In an effort to more clearly understand the effect of cigarette smoke, and its chemical constituents, on female fertility, a variety of in vivo and in vitro animal models have been developed. This article represents a systematic review of the literature regarding four of experimental model types: 1) direct exposure of ovarian cells and follicles to smoking constituents' in vitro, 2) direct exposure of whole ovarian tissue with smoking constituents in vitro, 3) whole body exposure of animals to smoking constituents and 4) whole body exposure of animals to cigarette smoke. We summarise key findings and highlight the strengths and weaknesses of each model system, and link these to the molecular mechanisms identified in smoke-induced fertility changes.

DOI10.1016/j.taap.2014.10.010
Co-authorsEileen Mclaughlin
2014Holt JE, Pye V, Boon E, Stewart JL, Garcia-Higuera I, Moreno S, et al., 'The APC/C activator FZR1 is essential for meiotic prophase I in mice', DEVELOPMENT, 141 1354-U327 (2014) [C1]
DOI10.1242/dev.104828Author URL
CitationsScopus - 1Web of Science - 1
Co-authorsKeith Jones, Eileen Mclaughlin
2014Yun Y, Holt JE, Lane SIR, McLaughlin EA, Merriman JA, Jones KT, 'Reduced ability to recover from spindle disruption and loss of kinetochore spindle assembly checkpoint proteins in oocytes from aged mice', Cell Cycle, 13 1938-1947 (2014) [C1]

Currently, maternal aging in women, based on mouse models, is thought to raise oocyte aneuploidy rates, because chromosome cohesion deteriorates during prophase arrest, and Sgo2, a protector of centromeric cohesion, is lost. Here we show that the most common mouse strain, C57Bl6/J, is resistant to maternal aging, showing little increase in aneuploidy or Sgo2 loss. Instead it demonstrates significant kinetochore-associated loss in the spindle assembly checkpoint protein Mad2 and phosphorylated Aurora C, which is involved in microtubule-kinetochore error correction. Their loss affects the fidelity of bivalent segregation but only when spindle organization is impaired during oocyte maturation. These findings have an impact clinically regarding the handling of human oocytes ex vivo during assisted reproductive techniques and suggest there is a genetic basis to aneuploidy susceptibility. © 2014 Landes Bioscience.

DOI10.4161/cc.28897
CitationsScopus - 3Web of Science - 2
Co-authorsEileen Mclaughlin, Keith Jones
2013Merriman JA, Lane SIR, Holt JE, Jennings PC, Garcia-Higuera I, Moreno S, et al., 'Reduced Chromosome Cohesion Measured by Interkinetochore Distance Is Associated with Aneuploidy Even in Oocytes from Young Mice', Biology of Reproduction, 88 31-31 (2013) [C1]
DOI10.1095/biolreprod.112.104786
CitationsScopus - 4Web of Science - 4
Co-authorsEileen Mclaughlin, Keith Jones
2013Holt JE, Lane SIR, Jones KT, 'Time-lapse epifluorescence imaging of expressed cRNA to cyclin B1 for studying meiosis i in mouse oocytes', Methods in Molecular Biology, 957 91-106 (2013) [C2]

The first meiotic division of mammalian oocytes physiologically occurs in the ovary in the hours preceding ovulation. Fortunately, oocytes removed from their follicular environment will readily undergo this process in culture. Their large size, optical transparency, and efficiency in translating exogenous cRNA make mouse oocytes very amenable to study this process in detail using fluorescence imaging-based techniques. Here we describe the process of microinjecting cRNA to proteins of interest that have been coupled to a fluorescent protein using cyclin B1 as an example. © 2013 Springer Science+Business Media, LLC.

DOI10.1007/978-1-62703-191-2-6
CitationsScopus - 1
Co-authorsKeith Jones
2012Holt JE, Lane SI, Jennings PC, Garcia-Higuera I, Moreno S, Jones KT, 'APC FZR1 prevents nondisjunction in mouse oocytes by controlling meiotic spindle assembly timing', Molecular Biology of the Cell, 23 3970-3981 (2012) [C1]
CitationsScopus - 9Web of Science - 9
Co-authorsKeith Jones
2012Seah KYM, Holt JE, Garcia-Higuera I, Moreno S, Jones KT, 'The APC activator fizzy-related-1 (FZR1) is needed for preimplantation mouse embryo development', Journal of Cell Science, 125 6030-6037 (2012) [C1]
Co-authorsKeith Jones
2011Holt JE, Tran SM-T, Stewart JL, Minahan KL, Garcia-Higuera I, Moreno S, Jones KT, 'The APC/C activator FZR1 coordinates the timing of meiotic resumption during prophase I arrest in mammalian oocytes', Development, 138 905-913 (2011) [C1]
DOI10.1242/dev.059022
CitationsScopus - 18Web of Science - 16
Co-authorsKeith Jones
2010Jones KT, Holt JE, 'BubR1 highlights essential function of Cdh1 in mammalian oocytes', Cell Cycle, 9 1029-1030 (2010) [C3]
Co-authorsKeith Jones
2010Holt JE, Stewart JL, Jones KT, 'Spatial regulation of APC(Cdh1)-induced cyclin B1 degradation maintains G2 arrest in mouse oocytes', Development, 137 1297-1304 (2010) [C1]
DOI10.1242/dev.047555
CitationsScopus - 31Web of Science - 26
Co-authorsKeith Jones
2009Holt JE, Jones KT, 'Control of homologous chromosome division in the mammalian oocyte', Molecular Human Reproduction, 15 139-147 (2009) [C1]
DOI10.1093/molehr/gap007
CitationsScopus - 31Web of Science - 30
Co-authorsKeith Jones
2007Holt JE, Jans DA, Ly-Huynh JD, Efthymiadis A, Hime GR, Loveland KL, Jans DA, 'Regulation of Nuclear Import During Differentiation: The IMP alpha gene family and spermatogenesis', Current Genomics, 8 323-334 (2007) [C1]
DOI10.2174/138920207782446151
CitationsScopus - 9Web of Science - 9
2006Holt JE, Roman SD, Aitken RJ, McLaughlin EA, 'Identification and characterization of a novel Mt-retrotransposon highly represented in the female mouse germline', Genomics, 87 490-499 (2006) [C1]
DOI10.1016/j.ygeno.2005.08.015
CitationsScopus - 3Web of Science - 3
Co-authorsEileen Mclaughlin, John Aitken, Shaun Roman
2006Curry BJ, Holt JE, McLaughlin EA, Aitken RJ, 'Characterization of structure and expression of the Dzip1 gene in the rat and mouse', Genomics, 87 275-285 (2006) [C1]
DOI10.1016/j.ygeno.2005.10.007
CitationsScopus - 2Web of Science - 2
Co-authorsJohn Aitken, Eileen Mclaughlin
2006Holt JE, Jackson A, Roman SD, Aitken RJ, Koopman PA, McLaughlin EA, 'CXCR4/SDF1 interaction inhibits the primordial to primary follicle transition in the neonatal mouse ovary', Developmental Biology, 293 449-460 (2006) [C1]
DOI10.1016/j.ydbio.2006.02.012
CitationsScopus - 47Web of Science - 44
Co-authorsEileen Mclaughlin, John Aitken, Shaun Roman
2004Blackmore DG, Baillie LR, Holt JE, Dierkx LM, Aitken RJ, McLaughlin EA, 'Biosynthesis of the Canine Zona Pellucida Requires the Integrated Participation of Both Oocytes and Granulosa Cells', Biology of Reproduction, 71 661-668 (2004) [C1]
DOI10.1095/biolreprod.104.028779
CitationsScopus - 25Web of Science - 24
Co-authorsJohn Aitken, Eileen Mclaughlin
Show 15 more journal articles

Conference (8 outputs)

YearCitationAltmetricsLink
2010Hopkins LA, Pye VJ, Fraser BA, Holt JE, Jones KT, McLaughlin EA, 'The Role of Fizzy Related 1 in Male Meiosis', Reproduction, Fertility and Development, Sydney (2010) [E3]
Co-authorsEileen Mclaughlin, Keith Jones
2009Jones KT, Weaver J, Holt JE, 'The mechanism by which fizzy-related (Fzr1) controls pro-phase 1 arrest in mouse oocytes', Biology of Reproduction, Pittsburgh, PA (2009) [E3]
Co-authorsKeith Jones
2007Gunter KM, Fraser BA, Holt JE, Stanger SJ, Aitken RJ, Roman SD, McLaughlin EA, 'CXCR4/SDF1 interaction in the neonatal mouse testes', 7th Hunter Cellular Biology Meeting. Program, Hunter Valley, NSW (2007) [E3]
Co-authorsShaun Roman, John Aitken, Eileen Mclaughlin
2006Fraser BA, Holt JE, Andrew J, Roman SD, Stanger SJ, Aitken RJ, et al., 'CXCR4/SDF1 Interactionin the Embryonic and Neonatal Mpise Testes', Abstracts, Brisbane Convention Centre, QLD, Australia (2006) [E3]
Co-authorsShaun Roman, Eileen Mclaughlin, John Aitken
2006Holt JE, Andrew J, Roman SD, Stanger SJ, Aitken RJ, Peter K, McLaughlin EA, 'CXCR4/SDF-1 interaction in the embryonic and neonatal mouse tests', Book of Abstracts, Chicago, Illinois (2006) [E3]
Co-authorsJohn Aitken, Shaun Roman, Eileen Mclaughlin
2005Holt JE, Aitken RJ, Roman SD, McLaughlin E, 'Use of RNA interference for the functional analysis of genes involved in ovarian development', MECHANISMS OF DEVELOPMENT (2005) [E3]
Author URL
Co-authorsJohn Aitken, Eileen Mclaughlin, Shaun Roman
2004Holt JE, Aitken RJ, Roman SD, McLaughlin EA, 'Expression of the Chemokine CXCL12 and its receptor CXCR4 in the activating Mammalian Ovarian follicle', Reproduction, Fertility and Development, Sydney (2004) [E3]
Co-authorsShaun Roman, John Aitken, Eileen Mclaughlin
2003Holt JE, Aitken RJ, Roman SD, McLaughlin EA, 'Gene expression in the activating mammalian ovarian follicle', ComBio Combined Conference Abstracts, Melbourne (2003) [E3]
Co-authorsJohn Aitken, Eileen Mclaughlin, Shaun Roman
Show 5 more conferences
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Grants and Funding

Summary

Number of grants12
Total funding$1,319,020

Click on a grant title below to expand the full details for that specific grant.


20142 grants / $413,447

miRNA regulation of sperm maturation $383,447

Funding body: NHMRC (National Health & Medical Research Council)

Funding bodyNHMRC (National Health & Medical Research Council)
Project TeamAssociate Professor Brett Nixon, Professor Eileen McLaughlin, Doctor Janet Holt
SchemeProject Grant
RoleInvestigator
Funding Start2014
Funding Finish2014
GNoG1300125
Type Of FundingAust Competitive - Commonwealth
Category1CS
UONY

The Role of the GTPase Dynamin in the Female Germline$30,000

Funding body: Hunter Medical Research Institute

Funding bodyHunter Medical Research Institute
Project TeamMs Kate Redgrove, Doctor Janet Holt, Professor Eileen McLaughlin, Associate Professor Brett Nixon
SchemeBridging Grant
RoleInvestigator
Funding Start2014
Funding Finish2014
GNoG1301333
Type Of FundingGrant - Aust Non Government
Category3AFG
UONY

20132 grants / $35,595

The Annual Scientific Meeting of the Endocrine Society of Australia and Society of Reproductive Biology, Sydney 25-28 August 2013.$595

Funding body: University of Newcastle - Faculty of Health and Medicine

Funding bodyUniversity of Newcastle - Faculty of Health and Medicine
Project TeamDoctor Janet Holt
SchemeTravel Grant
RoleLead
Funding Start2013
Funding Finish2013
GNoG1300895
Type Of FundingInternal
CategoryINTE
UONY

20122 grants / $705,000

Regulation of germ cell number and quality by Fizzy-Related protein$375,000

Funding body: ARC (Australian Research Council)

Funding bodyARC (Australian Research Council)
Project TeamDoctor Janet Holt
SchemeDiscovery Early Career Researcher Award (DECRA)
RoleLead
Funding Start2012
Funding Finish2012
GNoG1100556
Type Of FundingAust Competitive - Commonwealth
Category1CS
UONY

The control of chromosome division during female meiosis$330,000

Funding body: ARC (Australian Research Council)

Funding bodyARC (Australian Research Council)
Project TeamDoctor Janet Holt
SchemeDiscovery Projects
RoleLead
Funding Start2012
Funding Finish2012
GNoG1100078
Type Of FundingAust Competitive - Commonwealth
Category1CS
UONY

20115 grants / $163,478

2010 Research Fellowship - PRCRS (DECRA 1/3/2012)$121,978

Funding body: University of Newcastle

Funding bodyUniversity of Newcastle
Project TeamDoctor Janet Holt
SchemeResearch Fellowship
RoleLead
Funding Start2011
Funding Finish2011
GNoG1100163
Type Of FundingInternal
CategoryINTE
UONY

Eppendorf mastercycler pro with thermomixer comfort and 5430R centrifuge$15,000

Funding body: NHMRC (National Health & Medical Research Council)

Funding bodyNHMRC (National Health & Medical Research Council)
Project TeamProfessor Eileen McLaughlin, Professor Peter Lewis, Professor Adam McCluskey, Conjoint Professor Keith Jones, Associate Professor Brett Nixon, Doctor Shaun Roman, Doctor Jennette Sakoff, Doctor Ian Grainge, Doctor Janet Holt, Doctor Xiao Yang
SchemeEquipment Grant
RoleInvestigator
Funding Start2011
Funding Finish2011
GNoG1100028
Type Of FundingOther Public Sector - Commonwealth
Category2OPC
UONY

Mechanisms underlying the incidence of aneuploidy in mammalian eggs$15,000

Funding body: University of Newcastle

Funding bodyUniversity of Newcastle
Project TeamDoctor Janet Holt
SchemeFellowship Grant
RoleLead
Funding Start2011
Funding Finish2011
GNoG1100395
Type Of FundingInternal
CategoryINTE
UONY

IMPLEN NanoPhotometer pearl$10,000

Funding body: NHMRC (National Health & Medical Research Council)

Funding bodyNHMRC (National Health & Medical Research Council)
Project TeamConjoint Associate Professor Murray Cairns, Associate Professor Paul Tooney, Professor Alan Brichta, Emeritus Professor John Rostas, Emeritus Professor Patricia Michie, Conjoint Professor Keith Jones, Professor Ulli Schall, Associate Professor Phillip Dickson, Doctor Frederick Walker, Doctor Rick Thorne, Doctor Chris Dayas, Doctor Nikki Verrills, Doctor Janet Holt, Doctor Severine Roselli, Doctor Kathryn Skelding, Doctor Jude Weidenhofer, Associate Professor Liz Milward, Doctor Charles De Bock, Doctor Julie Merriman-Jones, Doctor Jing Qin Wu, Doctor Bing Liu, Mr Dan Johnstone, Ms Belinda Goldie, Doctor Natalie Beveridge
SchemeEquipment Grant
RoleInvestigator
Funding Start2011
Funding Finish2011
GNoG1100030
Type Of FundingOther Public Sector - Commonwealth
Category2OPC
UONY

EMBO Meiosis Meeting, Hotel Ariston and Congress Centre, Cappacio, Italy, 17 - 21 September 2011$1,500

Funding body: University of Newcastle - Faculty of Health and Medicine

Funding bodyUniversity of Newcastle - Faculty of Health and Medicine
Project TeamDoctor Janet Holt
SchemeTravel Grant
RoleLead
Funding Start2011
Funding Finish2011
GNoG1100939
Type Of FundingInternal
CategoryINTE
UONY

20101 grants / $1,500

Cold Springs Harbor Germ Cell Conference, Cold Spring Harbor Laboratory, NT, USA, 5 - 9 October 2010$1,500

Funding body: University of Newcastle - Faculty of Health and Medicine

Funding bodyUniversity of Newcastle - Faculty of Health and Medicine
Project TeamDoctor Janet Holt
SchemeTravel Grant
RoleLead
Funding Start2010
Funding Finish2010
GNoG1000768
Type Of FundingInternal
CategoryINTE
UONY
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Research Supervision

Current Supervision

CommencedResearch Title / Program / Supervisor Type
2014Investigating Genetic Alteration in Pathogenesis of Urine Endometrial Cancers
Medical Science, Faculty of Health and Medicine
Co-Supervisor
2013The Impact of Maternal Ageing and Chemotoxicants on Female Fertility
Biological Sciences, Faculty of Science and Information Technology
Principal Supervisor
2013Endometrial Stem/Progenitor Cells in Endometrial Regeneration, Carcinogenesis and Aging
Medical Science, Faculty of Health and Medicine
Co-Supervisor

Past Supervision

YearResearch Title / Program / Supervisor Type
2015Susceptibility of Mammalian Oocytes to Chromosome Segregation Errors with Maternal Aging
Human Biology, Faculty of Health and Medicine
Principal Supervisor
2013Role of Fzr1 in Embryogenesis
Human Biology, Faculty of Health and Medicine
Co-Supervisor
2012Control of Chromosome Segregation in Mouse Oocytes
Human Biology, Faculty of Health and Medicine
Co-Supervisor
2012Characterisation of an Oocyte Specific Knockout Model of Cdh1
Human Biology, Faculty of Health and Medicine
Co-Supervisor
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Dr Janet Holt

Position

ARC DECRA Fellow
School of Biomedical Sciences and Pharmacy
Faculty of Health and Medicine

Focus area

Human Physiology

Contact Details

Emailjanet.holt@newcastle.edu.au
Phone(02) 49854484

Office

RoomLS2.39
BuildingLife Sciences Building
LocationCallaghan
University Drive
Callaghan, NSW 2308
Australia
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