Centre for Inflammation Research

Dr Douglas Gibson

My research focuses on understanding how hormones control macrophage function in the womb and how this might affect women's reproductive health.

Dr Douglas Gibson

Sir Henry Dale Fellow

  • Centre for Inflammation Research

Contact details

Group Members

  • Erin Brown - MSc by Research student
  • Jo Mulligan - MRC Precision Medicine PhD student

Background

Endometrial repair is essential for women's reproductive health. One in three women in the UK will suffer from a reproductive health problem1 such as polycystic ovarian syndrome (3.5 million), heavy menstrual bleeding (3.5 million) or endometriosis (1.5 million). These common disorders cause debilitating, lifechanging symptoms and are associated with dysregulated endometrial repair. We need to understand how endometrial repair is regulated in order to develop new therapies for women's reproductive health disorders.

Each month, the endometrium must repair following menstruation in order to maintain healthy function and ensure ongoing fertility. Macrophages are essential mediators of tissue repair, but we lack fundamental knowledge about how they are regulated in the endometrium. Although there is consensus that macrophages are necessary for endometrial repair, their nature, origins, and the environmental factors that control their behaviour remain poorly understood thereby limiting our understanding of their function.

Androgens are important for controlling endometrial function, but excess androgens are detrimental to repair. We have previously shown that androgens delay wound healing, reduce re-epithelialisation, and prolong bleeding in mice undergoing simulated menses2. In other tissues, such as the skin, androgens regulate macrophage function during repair by altering their turnover and phenotype but it is not known if this occurs in the endometrium.

We aim to understand how macrophages are regulated in the endometrium, how their function may be altered in response to androgens, and how this can impact on women's reproductive health.

1Public Health England, 2018194, 2018

2Cousins FL, Kirkwood PM, Murray AA, Collins F, Gibson DA, Saunders PTK. Androgens regulate scarless repair of the endometrial "wound" in a mouse model of menstruation. FASEB Journal, 2016 30 (8), pp. 2802-2811.

Research Overview

We use fate-mapping techniques, transcriptomics analysis, multiparameter flow cytometry and immunohistochemistry in order to characterise cell populations that are required for endometrial repair. We combine these approaches with pharmacological and genetic modulation of androgen action in order to understand how androgens affect repair.

Confocal images of mouse endometrium
Confocal images of mouse endometrium

Biographical Profile

I obtained my undergraduate degree in Pharmacology from the University of Edinburgh before undertaking a PhD at the MRC Human Reproductive Sciences Unit with Professor Philippa Saunders examining the role of estrogen signalling in the endometrium. I undertook postdoctoral training at the MRC Centre for Reproductive Health and then the MRC Centre for Inflammation Research where I discovered that local hormone signalling within the endometrium was required for establishment of pregnancy in women.

In 2013, I published a landmark study which was the first to identify that local biosynthesis of oestrogens occurs within the endometrium during early pregnancy remodelling (Gibson et al 2013) and went on to show that this directly affects the function of uterine natural killer cells by increasing cell migration and promoting vascular remodelling (Gibson et al 2015). These studies led to a paradigm shift in our understanding of early pregnancy remodelling and specifically how temporal and spatial changes that are required for pregnancy are controlled by local hormone action. I went on to identify that androgens also play a key role regulating endometrial receptivity (Gibson et al 2016) and, in further studies, found that the decline in circulating androgen precursors that occurs in older women may contribute to lower fertility (Gibson et al 2018). These studies attracted significant media attention (The Times, The Sun, The Daily Mail) and were recognised by the award of the Society for Endocrinology Early Career Lecture Prize (2018) and the Society for Reproduction and Fertility New Investigator Award 2020.

In July 2020, I was awarded a Royal Society and Wellcome Trust Sir Henry Dale Fellowship to establish my own laboratory in Edinburgh investigating the impact of androgens on macrophage function during endometrial tissue repair.

  • Gibson, D.A. et al. Journal of Clinical Endocrinology and Metabolism, 2013, 98 (11), pp. E1802-E1806.
  • Gibson, D.A. et al. Human Reproduction, 2015, 30 (6), pp. 1290-1301.
  • Gibson, D.A. et al. Scientific Reports, 2016, 6, art. no. 19970.
  • Gibson, D.A. et al.. Fertility and Sterility, 2018. 109(4), pp. 728-734.e2

Honours and Awards

  • 2020  - Wellcome-Beit Prize
  • 2019  - Society for Reproduction and Fertility New Investigator Award
  • 2018  - Society for Endocrinology Early Career Prize lecture
  • 2018 - Winner of ‘Future of Pharmacology’ competition – Pharmacology Futures conference
  • 2018 - Research paper ‘The impact of 27-hydroxycholesterol on endometrial cancer proliferation’ featured on cover of Endocrine Related Cancer.
  • 2018  -Scottish Crucible Leadership and Development Programme
  • 2017 - Society for Reproductive Investigation (SRI)-Pfizer President’s Presenter’s Award
  • 2016 - Best New Investigator poster award, SRI meeting, Montreal, Canada.
  • 2015 - International Award for Best Abstract by Region. Society for Study of Reproduction meeting, Puerto Rico, USA.
  • 2014 - Society for Reproduction and Fertility Postdoctoral Scientist Prize

Alumni

Justine Vaccaro – Society for Endocrinology funded visiting MSc student, currently R&D intern at MIT spin-off company.

Phoebe Kirkwood – PhD student, currently MRC transition fellow in Professor Saunders' lab.

Public Engagement

Society for Reproduction and Fertility public engagement committee, organiser ‘Sex in three cities’ Public lecture series, Endometriosis awareness (invited speaker ‘Endometriosis Research Now!’ Patient day 2019), Society for Endocrinology Media ambassador and blog contributor, Editorial board The Endocrinologist Magazine.

Other Responsibilities

  • 2019-2021 - Program Organising Committee; Fertility annual meeting
  • 2018 -Guest Editor, Molecular and Cellular Endocrinology. Androgens Special Issue 2018
  • 2018 - Conference organising committee Androgens 2018
  • 2017 - Conference organising committee Reproductive Immunology 2017
  • 2017 to present - Editorial board – Endocrinologist magazine
  • 2017 to present - BSI Inflammation Affinity Group
  • 2016-2020 - Society for Reproduction and Fertility (SRF) Council
  • 2014-2018 - Chair of Postdoctoral Society

Collaborators

External

Internal

Publications

Bain CC, Gibson DA, et al. Rate of replenishment and microenvironment contribute to the sexually dimorphic phenotype and function of peritoneal macrophages. Science Immunology 2020. DOI:10.1126/sciimmunol.abc4466.

Gibson DA, Esnal-Zufiaurre A, Bajo-Santos C, Collins F, Critchley HOD, Saunders PTK. Profiling the expression and function of ER46 in human endometrial tissues and uterine NK cells. Human Reproduction 2020,Volume 35, Issue 3.  

Gibson DA, Collins F, Cousins FL, Esnal Zufiaurre A, Saunders PTK. The impact of 27-hydroxycholesterol on endometrial cancer proliferation. Endocrine Related Cancer 2018,25(4),p.381-391.  

Cousins FL, Kirkwood PM, Saunders PTK, Gibson DA. Evidence for a dynamic role for mononuclear phagocytes during endometrial repair and remodelling. Scientific Reports 2016;6;36748.  

Gibson DA, Simitsidellis I, Cousins FL, Critchley HOD, Saunders PTK. Intracrine Androgens Enhance Decidualization and Modulate Expression of Human Endometrial Receptivity Genes. Scientific Reports 2016, 6, art. no. 19970.

View all 28 publications on Research Explorer

Funding

  • Wellcome Trust
  • Medical Research Council
  • Tenovus Scotland
  • Royal Society of Edinburgh

More information on funding at Douglas Gibson's Research Explorer profile.