Professor Sarah Robertson

Biography/ Background

Current Appointments

• NHMRC Principal Research Fellow
  
• Co-Director Research Centre for Reproductive Health
  
• Research Program Leader, Reproductive Immunology Research Group
  
• Editor-in-Chief of the Journal of Reproductive Immunology (2009-ongoing)
• Fellow of the Society for Reproductive Biology (2011-ongoing)
• Council member, International Society for Immunology of Reproduction
  
• Representative for ISIR on International Union of Immunological Societies
  
• Editorial Board member, Reproduction (2008-ongoing)

 

Reproductive Immunology Research Group

Professor Sarah Robertson, PhD: NHMRC Principal Research Fellow
David Sharkey, PhD: Research Associate
John Schjenken, PhD: Research Associate
Kerrilyn Diener, PhD: NHMRC Early Career Fellow
Camilla Dorian, BSc: Research Officer

Students
Vicki Nisenblat, MD: PhD student
Mohammed Zaheid Johan, BSc: PhD student
Peck-Yin Chin (Loretta), BSc; PhD student
Jelmer Prins, MD: PhD student
Siti Mariam Noor Din, BSc; PhD Student
Xuan (Sally) Sun, BSc: PhD Student

Close collaborators
Louise Hull, MBBS, PhD: Clinical Lecturer
Wendy Ingman, PhD: Research Fellow

Past Appointments

• Treasurer, Society for Reproductive Biology (2006-2009)
  
• Chair, XI International Congress for Reproductive Immunology (2009-2010)
  
• Board member, Bio Innovation SA (2001-2010)
  
• Advisory Board member, Mater Medical Research Institute (2008-2009)
  
• Editorial Board member, Biology of Reproduction (2007-2010)
  
• Member, NHMRC Council (2003-2006)
  
• Member of the Research Committee of the NHMRC (2003-2006)   

Awards & Achievements

• AWT Edwards Orator, Australian Health and Medical Research Congress (2012)

• Robinson Institute Director's Award (2012)

• NHMRC Academy Member (2011-)

• Fellow of the Society for Reproductive Biology (2011-)

• Society for Reproductive Biology RCRH Award for Excellence in Reproductive Biology Research (2008)

• Award for Excellence in Postgraduate Research Supervision from the School of Paediatrics and Reproductive Health, University of Adelaide (2011)

• Award for Outstanding Mentorship of ECRs from the Discipline of Obstetrics and Gynaecology, University of Adelaide (2008)

• J Christian Herr Award of the American Society for Reproductive Immunology for Excellence in Reproductive Immunology Research (2005)

• Young Tall Poppy Science Award of the Australian Institute of Policy and Science (2000)

Research Interests

Research in the Reproductive Immunology group centres on three related themes:
• The roles of cytokines and leukocytes in the events of embryo development during early pregnancy.
• The impact of the maternal immune response on success and quality of embryo implantation, placental development and reproductive outcome.
• Male seminal fluid signalling in the female reproductive tract and significance for reproductive events and immunity to sexually transmitted infection.

Research projects

1. Role of seminal fluid signalling in the female reproductive tract

We are interested in the female genital tract response to insemination, and its significance in fertility and reproductive tract health. Seminal fluid has a profound effect on the female tract immune environment and is a key factor in establishing local immune adaptations that allow receptivity to pregnancy. This is mediated by paternal transplantation antigens also shared by the conceptus, as well as immune-deviating cytokines that promote immune tolerance as opposed to rejection. Importantly the immune changes induced by seminal fluid can impact infection with sexually transmitted infections such as HIV and Chlamydia, as well as progression of tumorigenesis and potentially other disease states including endometriosis. We aim to unravel the molecular identity of the sperm and seminal plasma signalling molecules, and characterise the nature of the cytokine and chemokine response and ensuing inflammatory events elicited in the female tissues. The physiological consequences of the female tract response for fertility and embryo development, as well as infection and immune defence, are studied.

2. Uterine leukocytes and the immune response to pregnancy.

Antigen presenting cells (APCs) are essential for initiating immune tolerance for pregnancy and uterine immune responses to infection. Uterine macrophages and dendritic cells are master regulators of tolerance to paternal alloantigens, through generating regulatory T cells that prevent maternal immune rejection of the conceptus. Our current projects using T-cell transgenic models aim to investigate the cytokine regulation and role of professional and non-professional APCs in unique mechanisms for processing paternal MHC antigens at the outset of pregnancy. Additionally, these cells have tissue remodelling functions and communicate with epithelial cells and stromal cells to impact endometrial receptivity for blastocyst implantation. Immune-deviating cytokines including TGFb, IL-10 and IL-6 contribute to these events and their significance is being evaluated in null mutant mouse models.

3. Seminal fluid and reproductive health in women

In women, seminal fluid induces cellular changes and an induction of inflammatory cytokines similar to the response in mice and other animals. The cytokine and chemokine regulation of the cervical and uterine response in women can be modelled in in vitro experiments, where we are aiming to identify the nature of the active signalling factors in human seminal fluid. We are now seeking to investigate the influence of seminal fluid on fertility in women, and to examine the relationship between the seminal fluid content of individual signalling components and fertility status in men. This work has implications for our understanding of the immune response to STDs such as HIV, as well as for reproductive processes.

4. Role of reproductive tract cytokines in embryo development and fertility.

Cytokines originating from the oviduct and uterine epithelium act to regulate the development of the embryo as it traverses the reproductive tract prior to implantation. Through effects on the timing and extent of cell proliferation and differentiation, cytokines synchronise embryo growth with the maternal changes that lead to uterine receptivity. Our studies indicate an important role for GM-CSF in promoting optimal blastocyst development, implantation and placental development, and in programming metabolic health in offspring. In humans, GM-CSF promotes development of healthy blastocysts and application of this discovery to improve implantation success in human IVF is now the subject of clinical trials. Our current studies are exploring the mechanisms through which GM-CSF and other maternal tract cytokines influence gene expression and developmental programming in embryos.

Research Funding

Our work is funded by:

• NHMRC Project Grants
• NHMRC Fellowship (Sarah Robertson)

• GAPPS / Gates Foundation
• Canadian Institutes of Health Research

Publications

Publications and citation metrics as listed on Google Scholar

Publications and citation metrics as listed on ISI Web of Knowledge 

Selected publications (2005-2012) from 120 refereed articles, reviews and book chapters published since 1990:

Fung KY, Mangan NE, Cumming H, Horvat JC, Mayall JR, Stifter S, De Weerd N, Roisman LC, Rossjohn J, Robertson SA, Schjenken JR, Parker B, Gargett C, Nguyen HPT, Carr DJ, Hansbro PM, Hertzog PJ (2013) Interferon epsilon is a novel, innate cytokine that protects the reproductive tract from viral and bacterial infection. Science 339: 1088-1092.

Ziebe S, Loft A, Povlsen BB, Erb K, Agerholm I, Aasted M, Gabrielsen A, Hnida C, Zobel DP, Munding B, Bendz SH, Robertson SA. (2013) A randomized clinical trial to evaluate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) in embryo culture medium for in vitro fertilization. Fertility and Sterility (accepted for publication, Dec 2012).

Sun X, Robertson SA, Ingman WV (2013) Regulation of epithelial cell turnover and macrophage phenotype by epithelial cell-derived transforming growth factor beta1 in the mammary gland. Cytokine (accepted for publication, Dec 2012).

Sharkey DJ, Macpherson AM, Tremellen KP, Mottershead DG, Gilchrist RB, Robertson SA (2012). TGF-beta mediates proinflammatory seminal fluid signaling in human cervical epithelial cells. Journal of Immunology. 189:1024-1035.

Sharkey DJ, Tremellen KP, Jasper MJ, Gemzell-Danielsson K, Robertson SA (2012). Seminal fluid induces leukocyte recruitment and cytokine and chemokine mRNA expression in the human cervix after coitus. Journal of Immunology 188, 2445-2454.

Hull ML, Johan MZ, Hodge WL, Robertson SA, Ingman WV (2012). Host-derived TGFB1 deficiency suppresses lesion development in a mouse model of endometriosis. American Journal of Pathology 180, 880-887.

Prins JR, Gomez-Lopez N, Robertson SA (2012). Interleukin-6 in pregnancy and gestational disorders. Journal of Reproductive Immunology 95, 1-14.

Aitken RJ, Jones KT, Robertson SA (2012). Reactive oxygen species and sperm function--in sickness and in health. Journal of Andrology 33:1096-1106

Nakamura H, Jasper MJ, Hull ML, Aplin JD, Robertson SA (2012). Macrophages regulate expression of alpha1,2-fucosyltransferase genes in human endometrial epithelial cells. Molecular Human Reproduction 18, 204-215.

Robertson SA (2012) Regulatory T cells in the corpus luteum - new players in fertility control? Biology of Reproduction 86, 26.

Guerin LR, Bromfield JJ, Prins JR, Moldenhauer LM, Hayball JD, Robertson SA (2011). Seminal fluid regulates accumulation of FOXP3+ regulatory T cells in the pre-implantation mouse uterus through both expanding the FOXP3+ cell pool and CCL19-mediated recruitment. Biology of Reproduction 85: 397-408

O'Leary S, Armstrong DT, Robertson SA (2011) Transforming growth factor-β (TGFβ) in porcine seminal plasma. Reproduction, Fertility and Development 23: 748-758

Robertson SA, Chin PY, Glynn DJ, Thompson JG (2011) Peri-conceptual cytokines--setting the trajectory for embryo implantation, pregnancy and beyond. American Journal of Reproductive Immunology 66 Suppl 1:2-10

Wu Y, Lousberg EL, Moldenhauer LM, Hayball JD, Robertson SA, Coller JK, Watkins LR, Somogyi AA, Hutchinson MR (2011) Attenuation of microglial and IL-1 signaling protects mice from acute alcohol-induced sedation and/or motor impairment. Brain, Behavior, and Immunity Suppl 1: S155-64

Jasper MJ, Care AS, Sullivan B, Ingman WV, Aplin JD, Robertson SA (2011). Macrophage-derived LIF and IL1B regulate alpha(1,2)fucosyltransferase 2 (Fut2) expression in mouse uterine epithelial cells during early pregnancy. Biology of Reproduction 84: 179–188

Lousberg EL, Diener KR, Fraser CK, Phipps S, Foster PS, Chen W, Uematsu S, Akira S, Robertson SA, Brown MP, Hayball JD (2011). Antigen-specific T-cell responses to a recombinant fowlpox 1 virus are dependent on MyD88 and IL-18 and independent of TLR7- and TLR9-mediated innate immune recognition. Journal of Virology 85: 3385-96

Chua AC, Hodson LJ, Moldenhauer LM, Robertson SA, Ingman WV (2010) Dual roles for macrophages in ovarian cycle-associated development and remodelling of the mammary gland epithelium. Development 137: 4229-38

Moldenhauer LM, Keenihan SN, Hayball JD and Robertson SA (2010) GM-CSF is an essential regulator of antigen presenting competence in uterine dendritic cells during early pregnancy in mice. Journal of Immunology 185: 7085-96

Moldenhauer LM, Hayball JD, Robertson SA (2010) Utilising T cell receptor transgenic mice to define mechanisms of maternal T cell tolerance in pregnancy. Journal of Reproductive Immunology  87: 1-13

Robertson SA, Christiaens I, Dorian C, Zaragoza DB, Care AS, Schuurmans A, Olson DM (2010) Interleukin-6 is an essential determinant of on-time parturition in the mouse. Endocrinology 151: 3996-4006

Lloyd ML, Papadimitriou JM, O’Leary S, Robertson SA, Shellam GR (2010) Immunoglobulin to zona pellucida 3 mediates ovarian damage and infertility after contraceptive vaccination in mice.  Journal of Autoimmunity 35: 77-85

Robertson SA (2010) Immune regulation of conception and embryo implantation-all about quality control? Journal Reproductive Immunology 85: 51-57

Ingman WV, McGrath LM, Breed WG, Musgrave IF, Robker RL, Robertson SA (2010) The mechanistic basis for sexual dysfunction in male transforming growth factor beta1 null mutant mice. Journal Andrology 31: 95-107.

Robertson SA, Guerin LR, Moldenhauer LM, Hayball JD (2009). Activating T regulatory cells for tolerance in early pregnancy - the contribution of seminal fluid. Journal Reproductive Immunology 83(1-2):109-16.

Chin PY, Macpherson AM, Thompson JG, Lane M, Robertson SA (2009). Stress response genes are suppressed in mouse preimplantation embryos by granulocyte-macrophage colony-stimulating factor (GM-CSF).Human Reproduction 24(12):2997-3009.

Ingman WV, Robertson SA (2009). The essential roles of TGFB1 in reproduction. Cytokine Growth Factor Review 20(3):233-9.

Moldenhauer LM, Diener KR, Brown MP, Hayball JD, Robertson SA (2009) Cross-presentation of male seminal fluid antigens elicits T cell activation to initiate the female immune response to pregnancy. Journal of Immunology 182(12):8080-93.

Guerin L, Prins J, Robertson SA (2009) Regulatory T cells and immune tolerance in pregnancy – a new target for infertility treatment?  Human Reproduction Update 15(5):517-35.

 

Sferruzzi-Perri AN, Macpherson AM, Roberts CT, Robertson SA  (2009) Csf2 null mutation alters placental gene expression and trophoblast glycogen cell and giant cell differentiation in mice. Biology of Reproduction 81(1):207-21.

 

Robertson SA, Guerin LR, Bromfield JJ, Branson KM, Ahlström AC, Care AS (2009) Seminal fluid drives expansion of the CD4⁺CD25⁺ T regulatory cell pool and induces tolerance to paternal alloantigens in mice. Biology of Reproduction 80(1):1036-45.

 

Ohlsson Teague EMC, Van der Hoek KH, Van der Hoek MB, Perry N, Wagaarachchi P, Robertson SA, Print CG, Hull ML (2009). MicroRNA-regulated pathways associated with endometriosis. Molecular Endocinology 23: 265-275

 

O’Leary S, Lloyd M, Shellam GR, Robertson SA (2008). Immunization with recombinant murine cytomegalovirus expressing murine zona pellucida 3 causes permanent infertility in BALB/c mice due to follicle depletion and ovulation failure. Biology of Reproduction 79: 849-860.

 

Ingman WI, Robertson SA (2008) The effect of TGFb1 null mutation on mammary gland development in mice – systemic and epithelial effects. Biology of Reproduction 79: 711-717.

 

Robertson SA (2007) GM-CSF regulation of embryo development and pregnancy Cytokine and Growth Factor Reviews 18: 287-298.

 

Ingman WI, Robertson SA (2007) TGFb1 null mutation causes infertility in male mice associated with testosterone deficiency and sexual dysfunction. Endocrinology 148(8): 4032-4043.

 

Sharkey DJ, Macpherson AM, Tremellen KP, Robertson SA (2007) Seminal plasma differentially regulates inflammatory cytokine gene expression in human cervical and vaginal epithelial cells.  Molecular Human Reproduction 13: 491-501.

 

Jasper MJ, Tremellen KP and Robertson SA (2007) Reduced endometrial IL-6 expression in recurrent miscarriage. Journal of Reproductive Immunology 73: 74-84.

 

Robertson SA, Skinner RJ, Care AS (2007) Interleukin-10 regulates inflammatory cytokine synthesis to protect against LPS-induced abortion and fetal growth restriction in mice. Biology of Reproduction 76:738-48.

 

Ingman WI, Robker RL, Woittiez K, Robertson SA (2006) Null mutation in TGFb1 disrupts ovarian function causing impaired folliculogenesis, oocyte incompetence and early embryo arrest. Endocrinology 147: 835-45.

 

Jasper MJ, Tremellen KP and Robertson SA (2006) Primary unexplained infertility is associated with reduced expression of the T-regulatory cell transcription factor Foxp3 in endometrial tissue. Molecular Human Reproduction 12: 301-8.

 

O’Leary S, Jasper MJ, Robertson SA and Armstrong DT (2006) Seminal plasma regulates ovarian progesterone production, leukocyte recruitment and follicular cell responses in the pig. Reproduction 132: 147-58.

 

Robertson SA, Care AS, Skinner RJ (2006) Essential role for interleukin-10 in resistance to LPS-induced preterm labour in mice. Journal of Immunology 177: 4888-96.

 

Sjoblom C, Roberts CT, Wikland M, Robertson SA (2005) GM-CSF alleviates adverse consequences of embryo culture on placental morphogenesis and fetal growth.  Endocrinology 146: 2142-53.

 

Robertson SA (2005) Seminal plasma and male factor signalling in the female reproductive tract.  Cell and Tissue Research 322:43-52.

 

Patents

 

Robertson SA and Tremellen KP (1998), Luminis Pty Ltd (owner). IPN WO 98/39021 “Treatment and diagnosis of infertility using TGFß”. International Publication Date 11 September 1998. Claiming priority from PO5508 dated 6 March 1997.

 

Robertson SA, Sjöblom C and Wikland MF (1999), Luminis Pty Ltd and Fertilitetscentrum AB (co-owners) IPN WO 99/67364 “Method and medium for in vitro culture of human embryos”. International Publication Date 29 December 1999.  Claiming priority from PP4212 dated 19 June 1998.

 

Robertson SA, Sharkey D, Glynn D and Tremellen KP (2003), University of Adelaide (owner). IPN WO 2004/026333 “Treatment and diagnosis of an infertility condition by measuring or inhibiting interferong” filed 20 Sept 2003, International Publication Date 1 April 2004.  Claiming priority from PP2002951531 filed 20 Sept 2002.

 

 

 

Expertise for Media Contact

Categories	Fertility & reproduction
Expertise	reproductive biology and function; infertility (implantation failure, recurrent spontaneous abortion, uterine receptivity); embryo (in vitro culture, growth factors, IVF); Pregnancy (immunology of pregnancy, early pregnancy, embryo implantation, insemination and pregnancy, animal models)
Notes	Alt phone: (08) 8303 5100

Entry last updated: Tuesday, 5 Mar 2013