Philippa Saunders' group are exploring the mechanisms responsible for sex steroids 'master regulators' of health impacts on repair, regeneration and cell replication in both healthy and diseased reproductive and other tissues.
Sex steroids are synthesised and secreted by the gonads and adrenals as well as peripheral tissues, eg adipose and skin. Local concentrations of steroids are also modulated within target tissues, a feature of human tissues known as 'intracrinology' which has been implicated in development of cancers. Steroids can regulate tissue function by binding to receptors that function as ligand activated transcription factors within the nucleus with cell-specific effects dependent upon recruitment of a 'cocktail' of co-factors. Steroid receptors including those that recognise oestrogens may also participate in membrane-initiated steroid signaling (MISS) pathways which are typically rapid and thought to be important for vascular function. Sex steroids have both direct and indirect effects on immune cells and inflammatory processes.
Reproductive tissues in both men and women display remarkable properties of resilience and repair that are regulated by steroids. During a women's reproductive life the endometrium found within the luminal portion of the uterus (womb) retains a remarkable degree of developmental plasticity that allows it to adapt to the challenges imposed by the menstrual cycle and pregnancy. During each menstrual cycle the luminal portion of the tissue is shed at menses, an event that is immediately preceded by a marked inflammatory response characterized by increased numbers of immune cells and a 'perfect storm' of cytokines and prostaglandins. Remarkably, repair of the surface 'wound' is both rapid and scarless; this is followed by rapid regeneration of stromal and epithelial compartments accompanied by active angiogenesis. We have developed a mouse model of endometrial wound healing that mimics the events during the human menstrual cycle [see slide summary of the model]. The results from our recent studies have revealed dynamic changes in the phenotype and location of monocytes/macrophages (see picture opposite - click link below for larger version).
Women's health disorders including heavy periods, endometrial cancer and endometriosis all have their origins in endometrial malfunction. We are working closely with clinical colleagues to improve both diagnosis and treatment of these disorders that affect many millions of women and their families. These initiatives have included the development of a substantial resource of human tissues and primary cells, formation of an Endometriosis Centre, funding from Pharma and funding for several clinical trials.
Further information on our work:
I obtained a PhD from the University of Cambridge and then undertook postdoctoral fellowships at the University of Florida and the Institute of Zoology in London. After coming to Edinburgh I established an independent research group within the MRC Human Reproductive Sciences Unit exploring the mechanisms that underlie steroid-dependent impacts on reproductive health in men and women. I served as Head of the University Centre for Reproductive Biology from 2007-2011 and Inaugural Director of the MRC Centre for Reproductive Health (2011-2012). In 2012 I was appointed as Dean of Postgraduate Research for the College of Medicine and Veterinary Medicine.
Medical Research Council
Academy of Medical Sciences
Society for Endocrinology
Royal Society of London
2013- Ithus. Spin Out Company. (co-founders Andrew Horne, Philippa Saunders, Erin Greaves). Pump priming from Bioquarter £25,000 (Bioquarter champion Mike Finnen)
Chair, Public Talk at the Edinburgh Science Festival April 2014
Chair UoE Public lecture series 'Our Changing World'
Speaker, Public Talk Edinburgh Science Festival April 2012 'Sex steroids: bodies, babies and brains'