Dual functions of WDR11 in the pathogenesis of hypogonadotrophic hypogonadism

Lead Research Organisation: St George's University of London
Department Name: Inst of Medical & Biomedical Education

Abstract

Disorders of sexual development are one of the most common human birth defects affecting up to 3% of the population. Delayed or absent puberty, insufficient sex hormone production and malformation of reproductive organs - clinically termed as hypogonadotrophic hypogonadism - subsequently lead to infertility. Reproductive dysfunction is a major public health issue affecting up to 15% of couples worldwide and includes infertility, spontaneous abortion and stillbirth. Hypogonadism is the most severe form of infertility. Somewhat surprisingly, nearly 30% of infertile couples have unexplained infertility with apparently normal reproductive organs (eugonadal infertility). Pregnancy rates have improved for these patients using ovulation inducing agents along with artificial insemination or in vitro fertilisation. However, this has opened up a potential risk of transmitting abnormal genes to the next generation. In order to provide best clinical treatment and expert counselling, a better understanding of the genetics of infertility is essential.

Although some of the key genes required for the onset of puberty and development of the gonads (testis and ovary) have been identified, the underlying causes and mechanisms of the majority of infertility cases remain unexplained. This is because genes responsible for sexual development and fertility are often difficult to identify by conventional genetic studies within families, as they affect the reproductive capacity of the individual, and the sexual dysfunction is often under-recognized. Thus investigation of the genetic basis of infertility represents a major challenge in reproductive science and medicine.

To ensure normal reproductive function, proper development and coordination of the hypothalamus-pituitary-gonads (HPG axis) is essential. The key factor that regulates the HPG axis is gonadotrophin releasing hormone (GnRH) which is released by specialised neurons in the brain. Timely release of GnRH is critical for the onset of puberty and subsequent sexual maturation; thus misregulation of the function and release of GnRH will cause delayed or absent puberty, and infertility. Primordial germ cells (PGCs) are the founders of sperm and egg. Mis-regulation of PGC development during the early embryonic stage can also result in infertility due to an insufficient number of sperm or eggs present in the gonads at birth.

We have recently identified that a relatively unknown gene WDR11 is mutated in at least two forms of human reproductive disorders, Kallmann Syndrome (KS) and normosmic idiopathic hypogonadotrophic hypogonadism (nHH). These are genetic disorders defined by absent or delayed puberty and infertility, often accompanied by several other malformations in the body such as loss of sense of smell, cleft palate and kidney dysfunctions. How the mutation of WDR11 causes the disease is not known. We hypothesise that WDR11 regulates the function of GnRH neurons and PGCs. This project aims to investigate the role of WDR11 and the molecular mechanisms it may regulate during the developmental process of GnRH neurons and PGCs, defects of which may cause the clinical condition of KS/nHH.

We will employ genetically engineered mouse models that allow us to monitor the proper development of GnRH and PGCs in live embryos. Human and mouse cells in culture will also be used to study the molecular and cellular mechanisms of WDR11 and its interacting partner EMX1 that regulates gene expression. Our study will reveal new genetic basis of infertility, thus helping provide better clinical treatment, prognosis and management of the patients, as well as more accurate genetic screening and counselling.

Technical Summary

Reproductive failure occurs in 10-15% of all couples and nearly 30% of them have unexplained infertility. Defects in the hypothalamic-pituitary-gonadal axis are likely to underlie a significant proportion of the aetiologies in these patients, but a critical barrier to proper diagnosis and treatment is the lack of understanding of the specific mechanisms of impairment. WDR11 gene was identified by positional cloning from normosmic hypogonadotrophic hypogonadism (nHH) and Kallmann syndrome (KS) patients. The mechanism of how WDR11 regulates reproductive function is not known, except that WDR11 mutations interfere with its binding to EMX1. Based on the findings of human mutations, we hypothesise that it will affect GnRH neuron migration and/or regulate GnRH secretion or action. Recently, several genes have been shown to affect not only hypothalamic function, but also directly affect gonadal function. In fact, our preliminary data suggests that WDR11 be one such protein that affects the migration of primordial germ cells (PGCs), resulting in primary gonadal defects. We hypothesise that WDR11 is important for normal hypothalamic function and PGC migration. To test this hypothesis, we will determine the phenotype of the Wdr11 KO mouse and confirm the effects of WDR11 deficiency on the development and establishment of GnRH neurons and PGCs. We will also investigate the role of WDR11 on the migratory behaviour of PGCs using Stella-GFP transgenic mouse that allows purification and live monitoring of PGCs. We will also determine the molecular mechanisms of WDR11 and EMX1 in human and mouse cell lines and test the potential involvement of Hedgehog signal pathway. These studies will reveal novel insights into the function of WDR11 in the regulation of GnRH neuronal migration and establishment of PGCs in the gonads, disruptions of which underlie human reproductive disorders.

Planned Impact

Approximately 10-15% of all couples suffer from infertility and nearly 30% of infertile couples have unexplained infertility. Disorder of sexual development is one of the most common human birth defects affecting upto 3% of the population and remains as the main contributing factor of infertility. Kallmann Syndrome (KS) and normosmic idiopathic hypogonadotropic hypogonadism (nHH) are estimated to affect 1/4000 to 1/10,000 males and can be 2-5 time more prevalent in females. However, this figure might be an underestimate with potentially broader demographic of undiagnosed individuals with milder and isolated symptoms. Our study will directly contribute to the improved diagnosis of KS/nHH, which is often delayed and difficult due to complex and overlapping clinical symptoms. Identifying dual effects of WDR11 upon the hypothalamus and gonad are important because this information could help determine the underlying mechanisms for those who do not respond to current gonadotrophin treatment. These findings will also be relevant to eugonadal (normal) infertility patients, who could have a combination of hypothalamic and gonadal defects. Moreover, if WDR11 causes primordial germ cell (PGC) migration defects, contributing to the primary gonadal defects, it will have a significant impact on the current categorisation and management of the disease, underpinning "stratified medicine", thus potentially influences the clinical practices, health economics and public perceptions.

Definitive diagnosis and genetic counselling in the context of assisted pregnancies are central to the long-term prognosis of fertility. Although pregnancy rates have improved for patients with unexplained infertility, these treatments may be costly and result in multiple births. In addition, our study will allow better ante- and neo-natal care and pre-pubertal treatment which can improve some of the congenital defects in these patients and their future reproductive functions. It will also contribute to improve other neonatal health issues such as midline defects and sensori-neural abnormalities which are associated with KS.

Germ cells are pluripotential stem cells that can be induced to differentiate into multiple types of precursor cells highly resembling embryonic stem cells. Therefore, a better understanding of germ cell biology will enhance clinical application of stem cell technology. Defects in PGC migration underlie not only infertility but also other human disorders including childhood germ cell tumours (one of the most common neonatal tumours) that are thought to be derived from the extra-gonadal germ cells that failed to undergo proper migration into the genital ridges and were not removed by apoptosis. Therefore, the mechanisms we have already started to investigate are likely to have a considerable impact in understanding germ cell behaviour during development and in postnatal life.

Therefore, the proposed work will have substantial benefits towards the UK competitiveness and contribution to quality of life, as it will allow more accurate diagnosis and tailored treatments, improving patient management, thus reduce healthcare cost. There will be a direct link with the health care industry through stem cell applications, eventually contributing to the country's economy.

Finally, the postdoctoral fellow and the named research technician (50% post) will develop expertise in a wide-range of techniques, ranging from in vivo experimentation to cell and molecular biology. The clinical collaborations will enable them to develop significant insight for successful medical research. In particular, the named technician, Ji-Young Lee, has already showed significant potential and capacity, generating novel preliminary data using the embryo slice culture techniques, thus this grant will provide a critical opportunity for her development in academic research career.
 
Title Journal cover image of the EMBO Reports 
Description An image from our research was selected as the cover image of the EMBO Reports Volume 19, Issue 2, published on 01 February 2018. 
Type Of Art Image 
Year Produced 2018 
Impact Our research is now internationally recognised, as evidenced by several requests from research groups who want to collaborate on the WDR11 gene and ciliopathy-related mutation studies. I also received several new contacts from students who want to take research internships in my lab. The Imaging Facility at St. George's University of London is recognised for the high quality of images they produced and now our cover image is displayed on the wall of the facility. 
URL http://embor.embopress.org/content/19/2.cover-expansion
 
Description Generation of rare disease educational materials
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact I am an active member of the COST GnRH Network Action (BM1105), an international consortium of physician/researchers from 28 countries, working on the elucidation of the neuroendocrine control of human reproduction. This consortium, funded by the European Cooperation in Science and Technology (COST) under the Biomedicine and Molecular Biosciences domain, during 04/2012 - 04/2016 (http://www.gnrhnetwork.eu/hhn_home/hhncost.htm). In 2017, I have produced a Korean translation version of the KS/CHH patient education material, which was a part of the coordinated effort of generating patient education material in 9 different languages.
URL http://www.gnrhnetwork.eu/hhn_home/hhncost.htm
 
Description International collaboration agreement between Biochemical Society and KSBMB
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a advisory committee
Impact I was a member of advisory board for the Korean Society for Biochemistry and Molecular Biology (KSBMB) to facilitate the International Cooperation Agreement between the two societies. The have exchaged an MOU (memorandum of understanding) for collaborative opportunities which are mutually beneficial in the delivery of strategic objectives and strengthening links between the scientific communities.
URL http://www.biochemistry.org/Membership/InternationalAssociateMembership.aspx
 
Description Invited speaker, Assisted Conception Unit, Guy's and St Thomas NHS Foundation Trust, London, UK
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Influenced training of practitioners or researchers
 
Description Invited speaker, St. George's Hospital Trust, Clinical Genetics
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Influenced training of practitioners or researchers
 
Description Primary ciliary dyskinesia (PCD) Medical Board Meeting
Geographic Reach National 
Policy Influence Type Influenced training of practitioners or researchers
URL http://pcdsupport.org.uk
 
Description COST Action BM1105: Joint Scientific Meeting and Training School
Amount € 752 (EUR)
Organisation European Cooperation in Science and Technology (COST) 
Sector Public
Country Belgium
Start 03/2016 
End 03/2016
 
Description COST GnRH Network
Amount € 1,030 (EUR)
Organisation European Cooperation in Science and Technology (COST) 
Sector Public
Country Belgium
Start 04/2015 
End 04/2015
 
Description Faircourt Capital Charity
Amount $60,000 (USD)
Funding ID 12923-12 
Organisation Faircourt Capital Limited 
Sector Private
Country United Kingdom
Start 06/2018 
End 05/2019
 
Description MCS Research Institute Funding
Amount £6,970 (GBP)
Organisation Wellcome Trust 
Department Wellcome Trust Strategic Award
Sector Charity/Non Profit
Country United Kingdom
Start 04/2017 
End 06/2017
 
Description MCS Research Institute Funding
Amount £7,000 (GBP)
Organisation Wellcome Trust 
Department Wellcome Trust Strategic Award
Sector Charity/Non Profit
Country United Kingdom
Start 06/2017 
End 09/2017
 
Description St George's Research Bridging Fund Scheme for Research Institute Staff
Amount £11,214 (GBP)
Organisation St George's University of London 
Sector Academic/University
Country United Kingdom
Start 03/2019 
End 05/2019
 
Description St George's Research Bridging Fund Scheme for Research Institute Staff
Amount £13,100 (GBP)
Organisation Wellcome Trust 
Department Wellcome Trust Strategic Award
Sector Charity/Non Profit
Country United Kingdom
Start 03/2018 
End 05/2018
 
Title Stella-WDR11 hybrid mouse line 
Description We generated a new hybrid transgenic mouse line 
Type Of Material Model of mechanisms or symptoms - mammalian in vivo 
Year Produced 2016 
Provided To Others? No  
Impact This is a novel transgenic model system which allows the investigation of WDR11 function in primordial germ cell development. We have generated live imaging and tracking data of migrating germ cells in vivo. This contributes to 3R by refining and reducing the number of mouse embryos required to obtain the novel information. We are currently preparing a manuscript. 
 
Title Human WDR11 variant sequencing data 
Description We have validated the rare sequence variants of WDR11 initially identified by whole exome sequencing. 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
Impact The clinicians treating the patients have been informed. The patients and their family will be given genetic counselling based on this information. 
URL https://decipher.sanger.ac.uk/ddd#overview
 
Title KS/CHH patient exome sequencing database 
Description Whole exome sequencing of the genomic DNA from 200 patients. We will continue sequencing more samples. 
Type Of Material Database/Collection of data 
Year Produced 2014 
Provided To Others? No  
Impact This database will provide the overall genetic information of patients which will aid the identification of new genes and molecular mechanisms underlying the disease. The candidate genes will also be confirmed and verified based on the experimental data generated from our group. 
 
Title Mouse phenotype database 
Description Deciphering the Mechanisms of Developmental Disorders (DMDD) is a systematic screen of knockout mouse lines, carrying out detailed imaging and morphological phenotyping of the resulting embryos and placentas. Data derived for each knockout line is freely available to the scientific community in a custom online resource. The DMDD database links gene identity with detailed morphological phenotypes, and will ultimately evolve to include transcriptional profiles in an attempt to correlate between morphological and molecular phenotypes. Insights gained from DMDD data will shed light on the origins of human developmental disorders. 
Type Of Material Database/Collection of data 
Provided To Others? No  
Impact The WDR11 gene knockout data with consequences that mimic aspects of human congenital abnormalities (in particular human ciliopathy spectrum disorders), as well as identifying novel associations between WDR11 and the Hedgehog signal pathway regulation which affects the differentiation of embryonic tissues and structures in both human and mouse. 
URL https://dmdd.org.uk/
 
Description Analysis of pituitary phenotypes 
Organisation University College London
Department Institute of Child Health
Country United Kingdom 
Sector Academic/University 
PI Contribution We provide the data on phenotype analysis of knockout mouse, as well as the cellular and molecular evidence to support the hypothesis.
Collaborator Contribution They helped with protocols for expression analysis of genes in the knockout mouse embryos and other advice on mouse colony management and pituitary gland development markers.
Impact He was an author on our manuscript. EMBO Rep. 2018 Feb;19(2):269-289. doi: 10.15252/embr.201744632
Start Year 2014
 
Description Analysis of zebrafish knockout model 
Organisation St George's University of London
Department Molecular and Clinical Sciences Research Institute
Country United Kingdom 
Sector Hospitals 
PI Contribution We provided the phenotypic and molecular data from our investigation of knockout mice and cellular analysis in vitro to support the establishment of zebrafish models.
Collaborator Contribution Zebsolution generated a zebrafish model using morpholinos and CRISPR approaches and analysed the phenotypes of the mutant fish lines.
Impact We produced a manuscript together. EMBO Rep. 2018 Feb;19(2):269-289. doi: 10.15252/embr.201744632
Start Year 2015
 
Description Generation of WDR11 knockout mouse 
Organisation Kumamoto University
Country Japan 
Sector Academic/University 
PI Contribution We have analysed the phenotypes of the knockout mouse they have generated. We include them as co-authors in our manuscript.
Collaborator Contribution They have generated a knockout mouse line and provide the live animals on the bases of a non-commercial academic collaboration. They confirmed the germ-line transmission of the embryonic stem cell, genotype analysis and preliminary phenotyping.
Impact EMBO Rep. 2018 Feb;19(2):269-289. doi: 10.15252/embr.201744632.
Start Year 2014
 
Description Identification of novel WDR11 mutations in neurodevelopmental disorders with mental retardation and autism 
Organisation Hamad bin Khalifa University
Country Qatar 
Sector Academic/University 
PI Contribution We generated functional assays using physiologically relevant cell model systems to test the activity of the rare variants of WDR11gene. We validated the sequence variants in the patient pedigrees, confirming the genetic basis of the disease. We include these novel findings in our publications, with the collaborators as co-authors.
Collaborator Contribution Performed clinical diagnosis of many patients through a long-term recruitment project (with ethics approvals and consents), analysed the patients' DNA samples, obtained the exome sequencing data, identified rare sequence variants of WDR11 gene so that it can be used in our functional assays.
Impact Still ongoing.
Start Year 2017
 
Description Identification of unusal clinical phenotype association of Kallmann syndrome and lymphodema 
Organisation St George's Hospital
Country United Kingdom 
Sector Hospitals 
PI Contribution We found a rare case of Kallmann syndrome patient with lymphodema. After contacting the corresponding clinicians in St. George's Hospital Trust, we confirmed the genotypes of the patient and their family to establish the genotype/phenotype correlation and validated the activity and function of the rare gene variant in cell model systems. These studies confirmed the genetic basis of the disease and defined the nature of mutation (loss/gain of function).
Collaborator Contribution The collaborators are mainly clinical geneticists who initially diagnosed the patient, obtained the patient/families' consent for research and collected their DNA or tissue samples. They analysed the DNA samples by whole-exome sequencing and deposited the results on the Deciphering Developmental Disorders project.
Impact These investigations ended due to lack of funding.
Start Year 2019
 
Description Imaging analysis of mouse embryos 
Organisation Francis Crick Institute
Department Mill Hill Laboratory
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution We have provided the phenotypic data of WDR11 knockout mouse and the embryo samples.
Collaborator Contribution They have analysed the mouse embryos using high-resolution episcopic microscopy and generated a 3-dimensional modelling.
Impact We published a manuscript together. EMBO Rep. 2018 Feb;19(2):269-289. doi: 10.15252/embr.201744632
Start Year 2015
 
Description Rare disease educational materials for congenital hypogonadotropic hypogonadism 
Organisation European Cooperation in Science and Technology (COST)
Department European Network on Brain Malformations
Country Belgium 
Sector Public 
PI Contribution I have produced the Korean translation version of the patient education material.
Collaborator Contribution They have formed a consortium of clinicians and nurses and coordinated the project of generating patient education material in 9 different languages.
Impact The project has produced a manuscript titled "Developing and evaluating rare disease educational materials co-created by expert clinicians and patients: the paradigm of congenital hypogonadotropic hypogonadism". Orphanet J Rare Dis. 2017 Mar 20;12(1):57. doi: 10.1186/s13023-017-0608-2
Start Year 2015
 
Description Role of WDR11 and ciliogenesis in primordial germ cell development 
Organisation Cincinnati Children's Hospital Medical Center
Country United States 
Sector Hospitals 
PI Contribution We established the mouse embryo slice culture which allows the monitoring of migratory behaviour of primordial germ cells by live imaging. Using this technique, we identified that WDR11-defective mouse embryos show delayed migration of primordial germ cells which could be dependent on the Hedgehog signal pathway. We are currently investigating the molecular mechanisms underlying this phenomenon.
Collaborator Contribution Professor Christopher Wylie has invited me to his lab and taught me the protocol for live imaging embryo slice culture technique to study primordial germ cell migration and gonadal development.
Impact The data we generated was included as preliminary data for the grant application, and the study on the role of WDR11 in primordial germ cells development is a part of the proposed study in the grant. Some of the data generated by using this technique are published in a manuscript soon.
Start Year 2014
 
Description Undiagnosed patients with WDR11 variant 
Organisation Birmingham Women's Hospital
Country United Kingdom 
Sector Hospitals 
PI Contribution We found patients with rare WDR11 variants who have been undiagnosed so far due to lack of genetic information. Through our collaboration with the corresponding clinicians we confirmed the genotype of these patients and their family to establish a correlation of the clinical phenotypes with the genetic mutation. We also conducted functional screening of the genetic mutations using in vitro assays to confirm the loss of normal activities.
Collaborator Contribution The clinicans have obtained the patient's consent for research and publication of the data, and collected their clinical samples (blood, saliva, skin biopsy). They sent us the extracted DNA for sequence analysis. The skin fibroblast culture was generated and established in the cytogenetics laboratory to be used for our studies. In some cases, they generated the mutant constructs and sent us for functional analysis.
Impact The investigation is still ongoing. Once the clinical data are validated, we will publish a manuscript which will be a multi-disciplinary effort (human clinical genetics, animal models, imaging, cell biology, bioinformatics)
Start Year 2016
 
Description Undiagnosed patients with WDR11 variant 
Organisation Helsinki University Hospital
Country Finland 
Sector Hospitals 
PI Contribution We found patients with rare WDR11 variants who have been undiagnosed so far due to lack of genetic information. Through our collaboration with the corresponding clinicians we confirmed the genotype of these patients and their family to establish a correlation of the clinical phenotypes with the genetic mutation. We also conducted functional screening of the genetic mutations using in vitro assays to confirm the loss of normal activities.
Collaborator Contribution The clinicans have obtained the patient's consent for research and publication of the data, and collected their clinical samples (blood, saliva, skin biopsy). They sent us the extracted DNA for sequence analysis. The skin fibroblast culture was generated and established in the cytogenetics laboratory to be used for our studies. In some cases, they generated the mutant constructs and sent us for functional analysis.
Impact The investigation is still ongoing. Once the clinical data are validated, we will publish a manuscript which will be a multi-disciplinary effort (human clinical genetics, animal models, imaging, cell biology, bioinformatics)
Start Year 2016
 
Description Undiagnosed patients with WDR11 variant 
Organisation Leeds General Infirmary
Country United Kingdom 
Sector Hospitals 
PI Contribution We found patients with rare WDR11 variants who have been undiagnosed so far due to lack of genetic information. Through our collaboration with the corresponding clinicians we confirmed the genotype of these patients and their family to establish a correlation of the clinical phenotypes with the genetic mutation. We also conducted functional screening of the genetic mutations using in vitro assays to confirm the loss of normal activities.
Collaborator Contribution The clinicans have obtained the patient's consent for research and publication of the data, and collected their clinical samples (blood, saliva, skin biopsy). They sent us the extracted DNA for sequence analysis. The skin fibroblast culture was generated and established in the cytogenetics laboratory to be used for our studies. In some cases, they generated the mutant constructs and sent us for functional analysis.
Impact The investigation is still ongoing. Once the clinical data are validated, we will publish a manuscript which will be a multi-disciplinary effort (human clinical genetics, animal models, imaging, cell biology, bioinformatics)
Start Year 2016
 
Description Undiagnosed patients with WDR11 variant 
Organisation The Wellcome Trust Sanger Institute
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution We found patients with rare WDR11 variants who have been undiagnosed so far due to lack of genetic information. Through our collaboration with the corresponding clinicians we confirmed the genotype of these patients and their family to establish a correlation of the clinical phenotypes with the genetic mutation. We also conducted functional screening of the genetic mutations using in vitro assays to confirm the loss of normal activities.
Collaborator Contribution The clinicans have obtained the patient's consent for research and publication of the data, and collected their clinical samples (blood, saliva, skin biopsy). They sent us the extracted DNA for sequence analysis. The skin fibroblast culture was generated and established in the cytogenetics laboratory to be used for our studies. In some cases, they generated the mutant constructs and sent us for functional analysis.
Impact The investigation is still ongoing. Once the clinical data are validated, we will publish a manuscript which will be a multi-disciplinary effort (human clinical genetics, animal models, imaging, cell biology, bioinformatics)
Start Year 2016
 
Description WDR11 MUTATIONS IN PITUITARY STALK INTERRUPTION SYNDROME 
Organisation Children's Hospital of Philadelphia
Country United States 
Sector Hospitals 
PI Contribution We conducted functional assays to test the loss of biological activities caused by WDR11 mutation associated with a rare clinical case. We generated the mutant constructs and performed two different in vitro assays. This work has produced a manuscript currently under revision.
Collaborator Contribution They have conducted a whole exome sequencing of a rare syndromic patient and identified a novel mutation of WDR11. They have mostly prepared the manuscript with our input and submitted the final manuscript.
Impact a manuscript titled "DIGENIC INHERITANCE OF PROKR2 AND WDR11 MUTATIONS IN PITUITARY STALK INTERRUPTION SYNDROME AND HORMONE DEFICIENCIES" is published. J Clin Endocrinol Metab. 2017 Jul 1;102(7):2501-2507. doi: 10.1210/jc.2017-00332
Start Year 2016
 
Description 27th MAMMALIAN GENETICS AND DEVELOPMENT WORKSHOP 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The Mammalian Genetics and Development Workshop is an annual meeting covering the genetics and development of mammals. Meetings are based on the submitted abstracts, and usually include diverse topics ranging from mammalian development. My postdoc fellow was selected for an oral presentation and there were more than 20 short talks covering various aspects of developmental biology.
Year(s) Of Engagement Activity 2015,2016
URL https://www.ucl.ac.uk/ich/research/developmental-biology-cancer/DBCmeetings/MGDW/mgw_workshop/
 
Description Bio Korea in Europe Symposium (Biochemical Society funded) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The meeting aimed to bring together Korean and European scientists working in various fields of Biomedical Sciences, following the recent initiative of International Associate Membership agreement between the Biochemical Society and the Korean Society for Biochemistry and Molecular Biology (KSBMB) to encourage scientific communication and strengthen the global networks between Korea and Europe. Representatives of KSBMB as well as the Korean Academy of Science and Technology (KAST), Korea Institute of Science and Technology (KIST-Europe) and Yonsei University gave short presentations introducing their organisational structures and activities, along with a representative (Head of Membership Engagement), representing the Biochemical Society.
Year(s) Of Engagement Activity 2017
 
Description COST Action BM1105: Joint Scientific Meeting & Training School 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Over 100 clinical practitioners and researchers attended for this research conference in Budapest, Hungary. This led to international collaborations and exchange of reagents, and an invitation to contribute to a manuscript titled "Developing and evaluating rare disease educational materials co-created by expert clinicians and patients: the paradigm of congenital hypogonadotrophic hypogonadism" which is just accepted for publication in Orphanet Journal of Rare Diseases.
Year(s) Of Engagement Activity 2014,2015,2016
URL http://gnrh.koki.hu/
 
Description COST2015 GnRH Network 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact We (including my postdoctoral research fellow and a PhD student) have presented two posters and participated in the Working Group committee and Scientific Training Workshops. It has led to many further inquiries of the data, offers of collaborations, and invitation for journal reviewers.
Year(s) Of Engagement Activity 2014,2015,2016
URL http://www.gnrhnetwork.eu/hhn_home/hhn-cost/hhn-costaboutcost.htm
 
Description ENDO2015 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I have presented a poster at ENDO2015, an international research conference, which is the biggest in the field. Many clinical and scientific researchers came to see my poster and sparked discussions afterwards, leading to exchange of reagents and international collaboration ideas.
Year(s) Of Engagement Activity 2015
URL https://www.endocrine.org/meetings/endo-annual-meeting/endo-2015#/nav/
 
Description EU Korea Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Europe-Korea Conference on Science and Technology (EKC) is to bring together Korean scientists and engineers working in Europe and in Korea and European scientists and engineers interested in collaborating with Korean nationals. Particular emphasis is given to develop friendship and to exchange useful knowledge and bright ideas for the promotion of science and technology in service of the human being and the society. EKC was established in 2007.
Year(s) Of Engagement Activity 2017
URL http://ekc2017.org/
 
Description Image Resource Facility Re-launch event, St George's, Universtiy of London 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact A new imaging facility has launched with upgrades of equipment and highlighted the research project that produced significant outputs. Our group regularly use the facility with funding from Research Councils and University, therefore I was invited to present our work, and how it increased the use and application of the technology and equipment of the facility. The talk was appreciated by the financial supervisors and other stakeholders of the university.
Year(s) Of Engagement Activity 2018
 
Description Interview for Women in Science Media promotion by a journal publisher 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact I was recently highlighted among 23 female corresponding authors with cover studies in EMBO family journals, as EMBO Press recently celebrated Women in Science week. This was a follow up on our research publication in EMBO Reports, which was the cover story and also in the journal's top 20 most downloaded papers in 2018.
Year(s) Of Engagement Activity 2020
URL https://twitter.com/emboreports/status/1227283115954991104
 
Description Invited speaker at the Institute of Child Health, UCL 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact I was invited to give a seminar presentation at the Cilia research group section of the Institute of Child Health, UCL. Researchers at various levels (students, research fellows, clinicians) from 4 different research groups were attending as well as their group leaders (PIs), mainly working on ciliopathy disorders and gene therapies. We discussed the potential grant application with multi-centre collaborations.
Year(s) Of Engagement Activity 2019
 
Description Korean Neuroendocrine Society Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Over 100 clinical practitioners and researchers attended for this research conference in Seoul, Korea. This led to a collaboration with the industry (Novartis) and an invitation to write a review manuscript which was published in 2015.
Year(s) Of Engagement Activity 2014
 
Description Korean-Scandinavian Scientists and Engineers Association BT Workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Korean-Scandinavian Scientists and Engineers Association is a 5 year-old non-profit organisation officially registered in Stockholm, Sweden. It is open for individuals residing in the Scandinavian countries (Denmark, Norway, Sweden) who are engaged in science, engineering or a related field. Eminent scientists and government officials from Korea also participated.This workshop was co-organised by Korean Federation of Science and Technology Societies, founded in 1966.
Year(s) Of Engagement Activity 2016
 
Description Primary ciliary dyskinesia (PCD) Family Support Group event 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact I am invited to attend the Primary Ciliary Dyskinesia (PCD) family support group event and fundraising. PCD patients and families gather across the country and share their experiences and hear the recent progress in the treatment and diagnosis of the disease. There is also fundraising event.
Year(s) Of Engagement Activity 2020
URL http://pcdsupport.org.uk
 
Description Rare Disease Day Lecture and Networking Event Cambridge 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact Jointly hosted by NIHR Rare Diseases Translational Research Collaboration and Cambridge Rare Disease Network.
Cambridge Rare Disease Network is a newly established charity working to build a regional community and address the unmet needs of rare disease patients, their families and the professionals who work with them. This was the first time my research group (postdoctoral fellow and PhD student) met these people in person, who are living with rare congenital disorders. It gave them much motivation and pride in doing their research as they want to make difference in these people's lives.
Year(s) Of Engagement Activity 2017
URL http://camraredisease.org/index.php/about/
 
Description Science Media Center Introduction to the News Media Event (Royal College of Obs and Gyn) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact A panel discussion with journalists from diverse media (newspapers, TV, Freelance journalists) and listed to other scientists experience with media. I have now joined the Science Media Center expert database. I have also joined the Progress Educational Trust and BioNews network.
Year(s) Of Engagement Activity 2018
URL https://www.progress.org.uk/
 
Description Society for Endocrinology and British Endocrine Society Annual Conference, Brighton, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I gave an oral presented at the Society for Endocrinology and British Endocrine Society Annual Conference. Over 1000 people including clinicians, nurses, researchers, students, industry partners from national and international hospitals, universities and research institutes.Our study not only increases the current knowledge about the pathogenesis of the disease, but may also help young patients obtain a more accurate diagnosis by prompting healthcare practitioners to consider alternative strategies for improved diagnosis, management and treatment. Early and accurate diagnosis of young patients can alleviate and prevent many of the potential endocrinopathies and metabolic disorders in their adolescences and adult life. This also has an economic impact on patients by preventing expensive treatments which will not work on them.
Year(s) Of Engagement Activity 2019
URL https://www.endocrine-abstracts.org/ea/0065/ea0065oc6.4
 
Description St. George's Hospital Trust, Clinical genetics seminar 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact I was invited to give a presentation at the St. George's Hospital Clinical Genetics Seminar. I have established collaborations with clinical genetics regarding patients with novel WDR11 mutations and an unusual case of association of Kallmann syndrome and lymphodema. The work is currently ongoing.
Year(s) Of Engagement Activity 2019
 
Description Understanding Animal Research - Debates and Arguments: Arguing science in the media and beyond 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Third sector organisations
Results and Impact Training workshop managed by Understanding Animal Research.
Year(s) Of Engagement Activity 2017
URL http://www.understandinganimalresearch.org.uk/
 
Description Understanding Animal Research - Opening Up: Engaging the public on animal research 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Training workshop managed by Understanding Animal Research - I have signed up as a member of speakers to give a talk at local schools and general public when needed.
Year(s) Of Engagement Activity 2017
URL http://www.understandinganimalresearch.org.uk/
 
Description William Harvey Research Institute, QMUL 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact I was invited to give a departmental seminar at the William Harvey Research Institute, Queen Mary University of London. After the seminar, I have met two researchers who have common interest on the project and we discussed collaboration ideas. Following up discussions with exchange of research materials are still ongoing.
Year(s) Of Engagement Activity 2018