{"paper_id":"8140f4a3-faf9-4512-a60f-f024476d25ec","body_text":"MultiMENDo MultiMENDo \nAdobe Stock: Generated with AI © Kawarina\nMultiMENDo at \nmidpoint: a researcher’s \nreflections on progress \nand purpose \nThis five-year project, which began in \nMay 2023, has now reached its mid-\npoint. This article provides an update on \nits progress and shares the coordinator’s \npersonal reflections on the journey so far.\nThe aims of the  \nMultiMENDo project\nThe MultiMENDo project has two clear \nobjectives:\n1. Find diagnostic biomarkers and/or \nprognostic biomarker candidates for \nendometriosis in menstrual blood.\n2. Establish a relevant 3D model from \nmenstrual blood cells to investigate \nnew therapeutic approaches for \nendometriosis.\nThe setting up of the \nobservational clinical study \nto collect menstrual blood\nIn order to collect menstrual blood from \nwilling participants, whether affected by \nendometriosis or not, a clinical study with \nclear objectives had to be established. T o \nachieve this, the coordinator received \nsupport from the INSERM clinical \nresearch department. Following the \nprovided template, the coordinator had \nto understand what was expected and \nhow to design a clinical research protocol. \nThis proved challenging and took longer \nthan anticipated. Once the protocol \nand additional documentation were \nwritten, the whole file was submitted to \nan ethics committee. Their feedback led \nto a few minor changes, but also to a \njustification for not implementing some \nof their recommendation. Indeed, some \nsuggestions were not relevant in the \ncontext of menstrual blood collection—\nfor example requiring participants to \nwear gloves during collection, which is \nnot something they normally do when \nmanaging their menstrual hygiene, \nor concerns about the bacterial \ncontamination of the sample (something \nthat cannot be avoided in the context of \nan intra-vaginal collection with the use of \na menstrual cup).\nFinally, the clinical study was validated, \nand since July 2024, we have had an \nongoing clinical trial (NCT06245512) \nallowing the recruitment of willing \nparticipants.\nThe recruitment started slowly, and \nwe did not attempt to accelerate it \nright away, as we needed to fine-\ntune the menstrual blood processing \nwithin the lab (more on that in the next \nparagraph). Once we were confident \nwith this processing, we used several \nchannels to improve the enrolment \nrate (for example, we talk about the \nstudy in university courses related to \nendometriosis, we made a LinkedIn post \nabout our ongoing research and clinical \nstudy which led to more than 50 000  \nimpressions, 25 000 members reached, \nmore than 230 reposts—notably by a \npatient’s association). So far, we have \nalready included more than 50 women \nwho provided one to three samples (this \nnumber has doubled since May 2025, \nindicating a significant improvement \nin the recruitment rate). As the goal \nis to enrol 250 participants, most of \nwhom are affected by endometriosis, \nwe are progressing well; however, we \nstill have some way to go. We allowed \nfor several menstrual blood collections \nper patient (up to three samples) to \nrefine the protocols with the first \nsamples and still be able to analyse each \npatient appropriately, and to assess \nthe potential stability of the measured \nparameters over time. This is important \nin order to design rigorous and useful \ntools for endometriosis care.\nThe menstrual blood \nprocessing: a challenge\nWhile this was not unexpected, the \nquality and quantity of the samples \nwere quite heterogeneous between \nparticipants. We have not yet been able \nto assess potential predictive factors \nfor this heterogeneity. However, we \nare collecting data to identify such \nfactors and refine the method for \ncollecting this overlooked biological \nfluid in reproducible and standardised \nconditions. Furthermore, we are trying \nto design a protocol that is as simple \nand rapid as possible in order to boost \nits potential usefulness in future clinical \npractice, while adapting to the observed \nheterogeneity of the samples. However, \nsince we don’t know which part of the \nsample will be the most useful (for \nexample, a specific cell type or the cell-\nfree portion), we are trying to extract \nas much information as possible from \nthese samples.\nUpdate on the transcriptomic \ndata from menstrual blood\nThe first single-cell proteogenomics \ndatasets that we generated were of \npoor quality, so we had to optimise our \nprotocols and identify key factors to \nknow when a sample is usable or not. \nFollowing this initial setback, we made \nprogress and successfully generated our \nfirst good-quality datasets of single-cell \nThe MultiMENDo project is an ERC-funded research \nproject led by Ludivine Doridot, Associate Professor at \nINSERM and Université Paris Cité, realised at Institut \nCochin in Paris, France.\n172\n 173\nDISSEMINATION DISSEMINATION\n\n\nMultiMENDo \nproteogenomics from the menstrual \nblood of women with and without \nendometriosis. We could detect the \nexpected cell types and are currently \ndiving into the data to identify the most \npromising biomarkers, while expanding \nthe number of assessed patients. In \nparallel, for the major cell populations, \nwe set apart enriched cell type fractions \nin order to perform bulk RNAseq. This \nwill complement the single-cell data and \nhopefully facilitate a more cost-effective \nvalidation of the identified biomarkers.\nUpdate on the 3D culture \nmodels from menstrual blood\nConcerning the establishment of 3D \nmodels (notably organoids with epithelial \ncells), we are able to obtain successful \ncultures for most of the menstrual \nblood samples. We are currently mostly \ncryopreserving them in order to use a \nstandardised protocol on a reasonable \nset of samples from women with and \nwithout endometriosis. In parallel, we \nare cryopreserving stromal and immune \ncells to construct a complex model that \nexamines how cells interact and defines \nnew therapeutic approaches.\nIn parallel with these organoids, we began \ndeveloping an endometrium-on-chip \nmodel that provides a more controlled \nstructure and environment for modelling \nthe endometrium.\nPersonal perspectives on \nobtaining the funding and \ncoordinating this project\nThe obtained funding is an European \nResearch Council (ERC) Starting Grant \n(StG), awarded to early-career researchers \nwithin ten years of completing a PhD. \nThis eligibility window can be extended \nby up to 18 months in the event of \npregnancy or maternity leave; a provision \nI could have benefited from with my two \nchildren, but did not actually need, as my \nPhD was obtained in 2013. I responded \nto the 2022 call (submitting my written \napplication in January 2022 and attending \nan interview in September 2022).\nBefore submitting my application, I \nspent several years getting started. I had \ninitially sought national funding (ANR \nJCJC), however, my application was not \nsuccessful. The amount available through \nthe ERC calls allowed me to aim higher \nand design a more ambitious project. \nHowever, I had to convince myself to go \nfor it. The testimonials I had heard during \ninformation sessions on these calls had \nrather discouraged me, giving me the \nimpression that I wasn’t up to the task. \nLittle by little, my project matured, and \nthe objectives became clearer. \nThe first projects I participated in or led \nin my laboratory resulted in publications. \nI also obtained initial funding through \nan internal call for projects at Université \nParis Cité (emergence call), which \nenabled me to launch the first single-\ncell transcriptomic manipulations and \nbecome more comfortable with the \ntechnological aspects of my project. All \nof this gave me the confidence I needed. \nThen I worked hard and read extensively \nto position the project in relation to the \nliterature, emphasising the limitations of \nprevious studies and how my proposal \nwould go further or complement them \nby offering a new perspective. I also had \nnumerous discussions to gather the views \nof people from diverse backgrounds, \nincluding doctors and researchers (both \nyoung and not so young), as well as \nadministrative staff with a background \nin biology. And although I sometimes \nthought, “This feedback isn’t relevant \nbecause this person doesn’t really \nunderstand the subject,” I forced myself \nto take all the feedback into account, to \nquestion myself, to tell myself, “If this \nperson didn’t understand, it’s because I’m \nnot being clear enough.” \nI also received advice from previous \nlaureates (a big thank you to Leila Périé and \nCamille Berthelot), whose feedback on \ntheir experiences and some more specific \nadvice on my project helped me improve \nboth the project and the application. \nT o accomplish all this, I worked on \nmy application for approximately four \nmonths, albeit not full-time, but with a \nsignificant investment of time (one day \na week at the beginning, three days a \nweek at the end). These intermittent \nwork sessions allowed me to take a step \nback and reread my work with a ‘fresh’ \nperspective. I also received support from \nmy institution (Université Paris Cité) for \nthe budgetary part and feedback on the \nscientific part, as well as the curriculum \npart (thanks, Elise Viola).\nIn June, I received notification of a \nvideoconference audition scheduled for \nSeptember. The task was to present the \nfive-year project in eight minutes flat. \nI considered taking a training course \ndesigned to prepare candidates for these \ninterviews, but after discussing the cost \nand actual benefits with my institution, \nwe decided against it. Once again, the \nhelp and advice of previous laureates \nproved invaluable (another thank you \nto Camille Berthelot). I had two mock \ninterviews organised by my institution \n(thank you, Giuliana Victoria!) and a group \nof national institutions, with former \nlaureates or jury members as evaluators. \nI also organised a dozen other rehearsals \nwith everyone around me (researchers, \ndoctors, administrators). I recorded a \nversion, and some friends shared it with \ntrusted Anglo-Saxon researchers. And \nhere too, I forced myself to listen and take \nnotes of all the feedback, some of which \nmight even seem contradictory, so it \nwasn’t necessarily a matter of integrating \nit as suggested by these selected jurors, \nbut rather an effort to clarify, to take a \nstep back from the comments, to find a \nway to emphasise certain points. I also \nnoted and prepared responses to all \nthe questions that had been asked of \nme during these rehearsals. I was very \nstressed before the interview, but I had \nprepared as well as I possibly could. \nThe interview itself was intense, with \na panel of about 15 people remotely \nsitting in front of me. The eight-minute \npresentation went well. I knew every \nword by heart and had worked on my \nspeech so that every idea and every \ndetail was essential and flowed clearly. \nIt was the questions that worried me. \nI was asked about ten questions that \nfocused on my mastery of the different \naspects of the project: my knowledge \nof the field from a clinical point of \nview (endometriosis and its subtypes), \nstatistics and bioinformatics tools, \nand my technical skills in cell biology \n(particularly organoids). I also had an \nopen question on a subject outside my \nfield of expertise (the microbiome) and \nthe possibility of incorporating this \ndimension into the project. I had to \ndefend the project and the way I had \ndesigned it, demonstrating that I had \nthought beyond the defined project (and \nconsidered potential collaborations, \nsuch as studying the microbiome, for \nexample). At the end of the interview, I \nwas sure I had not convinced the jury. \nThe announcement that the funding \nhad been granted a few weeks later \ncame as a big surprise to me. As I truly \nbelieved in this project, I had already \nstarted working on a resubmission (due \nin October), trying to consolidate all the \nproject’s limitations. These reflections \nhave already enabled me to improve \nthe project, and I was ultimately able to \nincorporate some of them.\nThe project took longer than expected \nto get off the ground, mainly due to \nadministrative procedures, despite the \nrequest to postpone the start of the \nproject by several months in order to \nmove forward with the procedures for \nsetting up the clinical study. There were, \ntherefore, moments of doubt during the \nfirst period, as it was impossible to obtain \nthe biological samples of menstrual blood \nfor over a year, which was the cornerstone \nof the project. However, thanks to the \ngood relations and collaboration with the \nclinical team at Cochin Hospital, we were \nable to make progress on the technical \ndevelopments. I feel extremely fortunate \nto work in an environment where \nresearchers and clinician-researchers \nwork hand in hand. Nevertheless, this \ndelay caused a setback in the project’s \nprogress, and other developments took \nplace in the meantime. \nThe project is now making great strides, \nand it is exciting to see the theory put into \npractice. The first experiments are nearing \ncompletion, and data are being generated \nand analysed. Additionally, numerous \ncollaborations have been established, \nallowing me to broaden my vision and \nintegrate new dimensions into my \nresearch. This journey has been enriching, \nbut it has not been smooth sailing. It is \nalso a great responsibility. Doubt remains, \nand it is easy to put pressure on ourselves \nto prove that the jury was right to place \ntheir trust in us. This helps us grow as \nresearchers and opens up many new \nhorizons. However, the difficulty now \nlies in realising that we cannot pursue \neverything, even if we have wide interests \nand a lot of curiosity, which must always \nremain a driving force.\nAmong the major projects I have chosen \nto get involved in, there is a rather local \nand multidisciplinary initiative focus on \nwomen’s health: the Institute for Women \nand Interdisciplinary Research in Science \nand Health (iWISH) at Université Paris \nCité, which provides an integrated view \nof women’s health with many covered \ntopics (https:/ /iwish.u-pariscite.fr/),\nand a nationwide initiative focused on \nendometriosis: the InEndo consortium \nof the women’s and couples’ health \npriority research programme (https:/ /\npepr-sante-femmes-et-couples.fr/en/\nendometriosis/).\nPROJECT SUMMARY\nThe MultiMENDo project focuses on \nendometriosis, a gynaecological disorder \naffecting approximately 10% of women \nof childbearing age. This complex disease \nis notably associated with chronic pelvic \npain and infertility, leading to a reduced \nquality of life. There is a huge diagnostic \ndelay and a lack of curative therapies. \nThe project aims to find diagnostic and \nprognostic biomarkers and investigate new \ntherapeutic approaches using menstrual \nblood, a relevant and easily accessible yet \noverlooked biological fluid.\nPROJECT LEAD PROFILE\nLudivine Doridot is a researcher at INSERM \n(French National Institute of Health and \nMedical Research) and an Associate \nProfessor at Université Paris Cité (Paris, \nFrance). She obtained her PhD in Genetics \nfrom Université Paris Descartes in 2013 for \nher studies on preeclampsia, a hypertensive \ndisease of pregnancy. She then performed \na postdoc in Beth Israel Deaconess Medical \nCenter, a Harvard-affiliated hospital in \nBoston (USA), where she studied genetic-\nenvironment interaction in the context of \nmetabolic syndrome. Since 2017, she has \nfocused on endometriosis and reproductive \nimmunology.\nPROJECT CONTACTS\nLudivine Doridot\nBatiment Gustave Roussy, 4ème étage\n22 rue Mechain, 75014 Paris, France\nludivine.doridot@inserm.fr \nhttps:/ /institutcochin.fr/en/\nresearch-project/endometriosis-\nphysiopathology-pregnancy-\nimmunomodulatory-treatments \n/ludivine-doridot/\nFUNDING\nThis project has received funding from the \nEuropean Research Council (ERC) under the \nEuropean Union’s Horizon 2020 research and \ninnovation programme under grant agreement \nNo. 101078556.\nViews and opinions expressed are, however, those of the author(s) \nonly and do not necessarily reflect those of the European Union or \nthe ERC. Neither the European Union nor the granting authorities \ncan be held responsible for them.\n174\n 175\nDISSEMINATION DISSEMINATION","source_license":"CC0","license_restricted":false}