Endometriosis

Objectives: Conduct a comprehensive characterization of endometriosis heterogeneity in patients undergoing surgery (clinical, psychological, lifestyle, chemical, biological and microbiological dimensions).

Leaders: German Cano-Sancho, Sarah Le Vigouroux & Michel Neunlist

Objective: Establish comprehensive clinical data and biocollection in the same patients undergoing surgery through questionnaires, sampling (blood, urine, feces, vaginal swap, peritoneal fluid, endometriosis lesions, endometrial biopsy) and imaging (MRI and surgery videos).

Leaders: Elodie Chantalat, Krystel Nyangoh Timoh & German Cano-Sancho

Objective: Characterize the differential steroidome of endometriotic lesions, metabolome, inflammatory mediators such as cytokines and chemical organic exposome in systemic and local microenvironments.

Leader: German Cano-Sancho

Objective: Characterize the vaginal and intestinal microbiomes and identify the existence of microbiota signature of patients responding to treatment.

Leaders: Samuel Alizon & Michel Neunlist

Objective: Conduct a comprehensive inventory of lesions and endometriosis sub-types using accurate MRI and surgical annotated imaging to build the largest endometriosis surgical database (annotated surgical videos, pelvic and brain MRIs and biological data integrating pre-, intra- and post-operative information).

Leader: Krystel Nyangoh Timoh

Objective: Characterize psychological, lifestyle and gain insight into the chemical, microbiological and diet determinants by improving knowledge of the temporal and causal relationships between endometriosis symptoms (particularly pain), biological and chemical markers (microbiome, nature of the lesions, environment), psychological outcomes (affects, chronic fatigue, social relations, coping) and the lifestyle (physical activity, dietary habits) of those affected.

Leader: Sarah Le Vigouroux

Objective: Identify molecular commonalities and discrimination patterns among endometriotic lesions and their microenvironment based on location, severity or other clinical manifestations, in order to 1) create an unbiased cell atlas of the lesions, the endometrium, and the surrounding peritoneal fluid, and 2) identify novel gene targets for the development of therapeutic strategies.

Leaders: Fatima Mechta-Grigoriou & Françoise Lenfant

Objective: Perform an in-depth characterization of selected pathways (e.g. genes that have been linked to hormone signaling) to shed light on their involvement in normal menstrual cycling and their links with endometriosis development, subtypes and severity of symptoms.

Leaders: Agnès Bernet & Andreas Schedl

Objectives: Better understand endometrial physiology and endometriosis pathophysiology and its consequences in the numerous biological systems it affects: steroid hormone response, immune function, neuroendocrine system, intestinal/gut function, and endometrial stromal function.

Leaders: Ludivine Doridot, Françoise Lenfant & Vincent Prévot

Objective: Dissect the mechanisms of hormone actions within the endometrial cells/tissue and in the hypothalamus and delineate the role of this signaling pathway in endometrium physiology and endometriosis by 1) assessing steroid hormone response and signaling in patient-derived organoids, human endometrial and endometriotic cells, mouse endometrium and hypothalamus tissues.

Leaders: Françoise Lenfant & Andreas Schedl

Objective: Obtain a precise picture on the impact of endometriosis and its subtype on immune cell function by studying it in immune cells either isolated  or in combination with endometrial 3D models, and evaluate the impact of Netrin-1, a secreted protein involved in angiogenesis and inflammation, and NP137, an antibody against this protein.

Leader: Ludivine Doridot

Objective: Characterize the role of hypothalamic tanycytes and identify novel gene targets in a surgically-induced endometriosis mouse model, including Netrin-1, which may also play a major role in the innervation and neo-angiogenesis of endometriotic lesions in the periphery.

Leader: Vincent Prévot

Objective: Provide a deep understanding of the roles of mesenchymal cells in endometriosis by determining how the stromal compartment promotes the development of endometriosis in patients, and testing the impact of molecular candidates on the identity, plasticity and spatial organization of distinct cell populations (epithelial, stromal, immune and endothelial cells).

Leader: Fatima Mechta-Grigoriou

Objective: Better understand pathophysiological mechanisms underlying Irritable Bowel Syndrome (IBS)-like symptoms in patients with endometriosis by analyzing in particular the contribution of the gut microbiota and Tryptophane derivatives (e.g. indoles – known to be involved in IBS) to alterations of bowel transit and visceral pain.

Leader: Michel Neunlist

Objectives: Bridge the gap between molecular research and clinical practice by giving the foundation to develop precision diagnostic tools and personalized interventions based on comprehensive data integration

Leaders: Samuel Alizon, Krystel Nyangoh Timoh & Agnès Bernet

Objective: Co-construct a means of improving communication about surgery with patients, and demonstrate the efficacy of three procedures: 1) surgery, 2) combining psychological process and adapted physical activity, and 3) studying the effectiveness on psychological experience and lifestyle of an intervention by testing the new NP137 therapy (this intervention is carried out outside the consortium).

Leaders: Sarah Le Vigouroux, Krystel Nyangoh Timoh & Agnès Bernet

Objective: Test new therapies using preclinical approaches that can quickly lead to innovative clinical trials.

Leaders: Agnès Bernet & Vincent Prévot

Objective: Develop and validate advanced data integration and analytical models that enhance the understanding of surgical outcomes in endometriosis treatment to perform personalized treatment strategies and improve predictive models for surgical success and long-term patient results.

Leaders: Samuel Alizon, Adrien Bartoli & Krystel Nyangoh Timoh