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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

Code Description Percentage
060199 Biochemistry and Cell Biology not elsewhere classified 50
111499 Paediatrics and Reproductive Medicine not elsewhere classified 50

Professional Experience

Academic appointment

Dates Title Organisation / Department
1/02/2012 - 1/04/2015 Fellow - ARC University of Newcastle
School of Biomedical Sciences and Pharmacy
Australia
1/01/2011 - 1/12/2013 Fellow - UON University 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For publications that are currently unpublished or in-press, details are shown in italics.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)

Year Citation Altmetrics Link
2013 Jones KT, Lane SIR, Holt JE, 'Start and Stop Signals of Oocyte Meiotic Maturation', Oogenesis, Springer, London 183-193 (2013) [B1]
DOI 10.1007/978-0-85729-826-3_13
Co-authors Keith Jones
2013 Holt JE, Lane SIR, Jones KT, 'The Control of Meiotic Maturation in Mammalian Oocytes', Gametogenesis, Academic Press, San diego 207-226 (2013) [B1]
DOI 10.1016/B978-0-12-416024-8.00007-6
Citations Scopus - 9Web of Science - 9
Co-authors Keith Jones

Journal article (18 outputs)

Year Citation Altmetrics Link
2014 Sadeqzadeh 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)
DOI 10.1016/j.yexcr.2014.02.012
Co-authors Rick Thorne, Matt Dun
2014 Sadeqzadeh 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... [more]

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.

DOI 10.1016/j.yexcr.2014.02.012
Citations Scopus - 1Web of Science - 1
Co-authors Matt Dun, Rick Thorne
2014 Camlin 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 fa... [more]

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.

DOI 10.1016/j.taap.2014.10.010
Co-authors Eileen Mclaughlin
2014 Holt 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]
DOI 10.1242/dev.104828
Citations Scopus - 1Web of Science - 1
Co-authors Keith Jones, Eileen Mclaughlin
2014 Yun 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, ... [more]

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.

DOI 10.4161/cc.28897
Citations Scopus - 4Web of Science - 3
Co-authors Eileen Mclaughlin, Keith Jones
2013 Merriman 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]
DOI 10.1095/biolreprod.112.104786
Citations Scopus - 4Web of Science - 4
Co-authors Eileen Mclaughlin, Keith Jones
2013 Holt 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 environmen... [more]

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.

DOI 10.1007/978-1-62703-191-2-6
Citations Scopus - 1
Co-authors Keith Jones
2012 Holt 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]
Citations Scopus - 10Web of Science - 10
Co-authors Keith Jones
2012 Seah 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-authors Keith Jones
2011 Holt 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]
DOI 10.1242/dev.059022
Citations Scopus - 18Web of Science - 16
Co-authors Keith Jones
2010 Jones KT, Holt JE, 'BubR1 highlights essential function of Cdh1 in mammalian oocytes', Cell Cycle, 9 1029-1030 (2010) [C3]
Co-authors Keith Jones
2010 Holt 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]
DOI 10.1242/dev.047555
Citations Scopus - 31Web of Science - 26
Co-authors Keith Jones
2009 Holt JE, Jones KT, 'Control of homologous chromosome division in the mammalian oocyte', Molecular Human Reproduction, 15 139-147 (2009) [C1]
DOI 10.1093/molehr/gap007
Citations Scopus - 31Web of Science - 31
Co-authors Keith Jones
2007 Holt 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]
DOI 10.2174/138920207782446151
Citations Scopus - 9Web of Science - 10
2006 Holt 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]
DOI 10.1016/j.ygeno.2005.08.015
Citations Scopus - 3Web of Science - 3
Co-authors Eileen Mclaughlin, John Aitken, Shaun Roman
2006 Curry 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]
DOI 10.1016/j.ygeno.2005.10.007
Citations Scopus - 2Web of Science - 2
Co-authors Eileen Mclaughlin, John Aitken, Ben Curry
2006 Holt 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]
DOI 10.1016/j.ydbio.2006.02.012
Citations Scopus - 47Web of Science - 44
Co-authors Shaun Roman, John Aitken, Eileen Mclaughlin
2004 Blackmore 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]
DOI 10.1095/biolreprod.104.028779
Citations Scopus - 26Web of Science - 25
Co-authors John Aitken, Eileen Mclaughlin
Show 15 more journal articles

Conference (8 outputs)

Year Citation Altmetrics Link
2010 Hopkins 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-authors Keith Jones, Eileen Mclaughlin
2009 Jones 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-authors Keith Jones
2007 Gunter 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-authors Shaun Roman, John Aitken, Eileen Mclaughlin
2006 Fraser 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-authors Shaun Roman, John Aitken, Eileen Mclaughlin
2006 Holt 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-authors Eileen Mclaughlin, Shaun Roman, John Aitken
2005 Holt 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]
Co-authors John Aitken, Eileen Mclaughlin, Shaun Roman
2004 Holt 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-authors Shaun Roman, John Aitken, Eileen Mclaughlin
2003 Holt JE, Aitken RJ, Roman SD, McLaughlin EA, 'Gene expression in the activating mammalian ovarian follicle', ComBio Combined Conference Abstracts, Melbourne (2003) [E3]
Co-authors John Aitken, Eileen Mclaughlin, Shaun Roman
Show 5 more conferences
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Grants and Funding

Summary

Number of grants 13
Total funding $1,390,694

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


20143 grants / $485,121

miRNA regulation of sperm maturation $383,447

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

Funding body NHMRC (National Health & Medical Research Council)
Project Team Associate Professor Brett Nixon, Professor Eileen McLaughlin, Doctor Janet Holt
Scheme Project Grant
Role Investigator
Funding Start 2014
Funding Finish 2014
GNo G1300125
Type Of Funding Aust Competitive - Commonwealth
Category 1CS
UON Y

JuLI Stage $71,674

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

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

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Ms Kate Redgrove, Doctor Janet Holt, Professor Eileen McLaughlin, Associate Professor Brett Nixon
Scheme Bridging Grant
Role Investigator
Funding Start 2014
Funding Finish 2014
GNo G1301333
Type Of Funding Grant - Aust Non Government
Category 3AFG
UON Y

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 body University of Newcastle - Faculty of Health and Medicine
Project Team Doctor Janet Holt
Scheme Travel Grant
Role Lead
Funding Start 2013
Funding Finish 2013
GNo G1300895
Type Of Funding Internal
Category INTE
UON Y

20122 grants / $705,000

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

Funding body: ARC (Australian Research Council)

Funding body ARC (Australian Research Council)
Project Team Doctor Janet Holt
Scheme Discovery Early Career Researcher Award (DECRA)
Role Lead
Funding Start 2012
Funding Finish 2012
GNo G1100556
Type Of Funding Aust Competitive - Commonwealth
Category 1CS
UON Y

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

Funding body: ARC (Australian Research Council)

Funding body ARC (Australian Research Council)
Project Team Doctor Janet Holt
Scheme Discovery Projects
Role Lead
Funding Start 2012
Funding Finish 2012
GNo G1100078
Type Of Funding Aust Competitive - Commonwealth
Category 1CS
UON Y

20115 grants / $163,478

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

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Doctor Janet Holt
Scheme Research Fellowship
Role Lead
Funding Start 2011
Funding Finish 2011
GNo G1100163
Type Of Funding Internal
Category INTE
UON Y

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

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

Funding body NHMRC (National Health & Medical Research Council)
Project Team Professor 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
Scheme Equipment Grant
Role Investigator
Funding Start 2011
Funding Finish 2011
GNo G1100028
Type Of Funding Other Public Sector - Commonwealth
Category 2OPC
UON Y

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

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Doctor Janet Holt
Scheme Fellowship Grant
Role Lead
Funding Start 2011
Funding Finish 2011
GNo G1100395
Type Of Funding Internal
Category INTE
UON Y

IMPLEN NanoPhotometer pearl$10,000

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

Funding body NHMRC (National Health & Medical Research Council)
Project Team Conjoint 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
Scheme Equipment Grant
Role Investigator
Funding Start 2011
Funding Finish 2011
GNo G1100030
Type Of Funding Other Public Sector - Commonwealth
Category 2OPC
UON Y

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 body University of Newcastle - Faculty of Health and Medicine
Project Team Doctor Janet Holt
Scheme Travel Grant
Role Lead
Funding Start 2011
Funding Finish 2011
GNo G1100939
Type Of Funding Internal
Category INTE
UON Y

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 body University of Newcastle - Faculty of Health and Medicine
Project Team Doctor Janet Holt
Scheme Travel Grant
Role Lead
Funding Start 2010
Funding Finish 2010
GNo G1000768
Type Of Funding Internal
Category INTE
UON Y
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Research Supervision

Number of supervisions

Completed4
Current3

Total current UON EFTSL

PhD0.7

Current Supervision

Commenced Level of Study Research Title / Program / Supervisor Type
2014 PhD Role of microenvironment in endometrial cancer progression, metastasis and drug resistance
Medical Science, Faculty of Health and Medicine, The University of Newcastle
Co-Supervisor
2013 PhD The Impact of Maternal Ageing and Chemotoxicants on Female Fertility
Biological Sciences, Faculty of Science and Information Technology, The University of Newcastle
Principal Supervisor
2013 PhD Endometrial Stem/Progenitor Cells in Endometrial Regeneration, Carcinogenesis and Aging
Medical Science, Faculty of Health and Medicine, The University of Newcastle
Co-Supervisor

Past Supervision

Year Level of Study Research Title / Program / Supervisor Type
2015 PhD Susceptibility of Mammalian Oocytes to Chromosome Segregation Errors with Maternal Aging
Human Biology, Faculty of Health and Medicine, The University of Newcastle
Principal Supervisor
2013 PhD Role of Fzr1 in Embryogenesis
Human Biology, Faculty of Health and Medicine, The University of Newcastle
Co-Supervisor
2012 PhD Control of Chromosome Segregation in Mouse Oocytes
Human Biology, Faculty of Health and Medicine, The University of Newcastle
Co-Supervisor
2012 Masters Characterisation of an Oocyte Specific Knockout Model of Cdh1
Human Biology, Faculty of Health and Medicine, The University of Newcastle
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

Email janet.holt@newcastle.edu.au
Phone (02) 49854484

Office

Room LS2.39
Building Life Sciences Building
Location Callaghan
University Drive
Callaghan, NSW 2308
Australia
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