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Grant of Fertility Innovation

Louise Glover

LGlover

Dr. Louise Glover

 

Dr. Louise Glover is Research and Development Co-ordinator at Merrion Fertility Clinic, Dublin and Adjunct Assistant Professor at the School of Biochemistry and Immunology, Trinity College Dublin, Ireland. Dr. Glover acquired both her BSc degree and PhD at the Conway Institute of Biomolecular and Biomedical Sciences, University College Dublin in Ireland. Following her doctoral studies, Dr. Glover completed her post-doctoral training at Massachusetts General Hospital and Harvard Medical School, and was subsequently appointed to faculty positions of Instructor (2008-2011) and Assistant Professor (2011-2016) at the University of Colorado, USA, where her research focused on regulation of the innate immune response at mucosal tissue surfaces.

 

Throughout her career to date, Dr. Glover has been the recipient of grant awards from several prestigious funding bodies, such as the US National Institutes of Health and the Department of Veterans Affairs, and has served in the role of Principal Investigator and Co-investigator in various international projects. For her strong focus on translational and biomedical research, Dr. Glover has received a number of accolades, including the 2011 Young Investigator Award, CCFA, and the 2013 Junior Faculty Award for Basic/Translational Research, Department of Medicine at University of Colorado.

 

Dr. Glover holds active memberships in the Irish Fertility Society, the European Society of Human Reproduction and Embryology and the Health Research Board Clinical Research Coordination Ireland (CRCI). In addition to authoring over forty internationally published, peer-reviewed articles, Dr. Glover acts as a peer reviewer for several high impact journals in the field of mucosal immunology. Dr. Glover has also served on a number of international grant review panels, and has received invitations to speak and chair at international conferences, workshops and seminars.

 

Project: Antimicrobial peptides in endometrial immune-microbe crosstalk: Predictive biomarkers of optimal endometrial receptivity

 

The close relationship between mammalian hosts and commensal microbes is the product of millions of years of co-evolution, and is fundamentally a symbiotic one. Omnipresent microbes at mucosal surfaces have been shown to promote development and priming of the host immune system, and protect against growth of pathogenic invasive bacteria. The human uterine cavity and maternal-foetal interface have both traditionally been considered sterile environments. However, microbial sequencing technologies have now revealed that the female reproductive tract, including the uterus, co-exists with microbial species. Recent seminal work has shown that microbial community architecture in the endometrium can in fact impact reproductive success. Microbiome sequencing is now likely to be incorporated into clinical infertility testing, along with personalised anti-microbial or probiotic treatments in an attempt to impact fertility. We must now re-evaluate our understanding of immune regulation at the maternal-embryo interface as a coordinated interaction between both maternal and bacterially-derived factors. Understanding how uterine innate immune responses are regulated by endometrial commensal bacteria, and how this affects reproductive success, will be critical for the development of novel treatment strategies in assisted reproduction. Antimicrobial peptides (AMPs) are highly conserved innate immune factors. Ubiquitously expressed among all biological kingdoms, AMPs are short peptides that have broad antibacterial activity and diverse roles in immune function, cellular repair and development. AMPs are primarily secreted by epithelial cells, the primary cellular barrier at mucosal surfaces. Similar to other mucosal sites, the endometrium expresses a unique AMP subset that is functionally tailored to this tissue, including defensins, elafin, SLPI and MIP-3a. While their role in modulating immune responses to luminal microbiota at other mucosal surfaces (e.g. gastrointestinal tract) has garnered marked interest of late, the function of AMPs in human fertility, endometrial receptivity and implantation remains poorly understood. Defining the AMP signature and microbial landscape of a functional, receptive endometrium has the strong potential to lead to novel predictive tests and clinical interventions for women with infertility and peri-implantation disorders, to increase success rates of treatment and to reduce the number of ART cycles required to achieve live birth.

 

To this end, our study objectives are to elucidate the influence of microbial ligands on endometrial AMP production and examine the relationship between AMP levels, endometrial microbiota and ART reproductive outcomes. This work will shed significant light on the endometrial immune microenvironment in patients who can successfully conceive and carry a pregnancy to term, and in those who cannot. By identifying a targeted biomarker panel of AMP immune factors to help define optimal endometrial receptivity, this study has the potential to profoundly impact the care of patients with recurrent implantation failure and to shape healthcare training guidelines in the field of ART, and may further provide a biological basis for embryo implantation failure.