# Neuroimmune communication as a driver of lesion formation and macrophage colonization of the omentum in endometriosis-associated pain > **NIH NIH K99** · BOSTON CHILDREN'S HOSPITAL · 2024 · $254,610 ## Abstract PROJECT SUMMARY/ABSTRACT Endometriosis is a painful gynecological inflammatory disease that affects up to 15% of people born with a uterus. While effective for a fraction of patients, current therapies such as hormones and NSAIDs present several side effects. Therefore, new medical therapies and targets that provide long-term benefit are still needed. Here, we propose to validate drugs that block neuroimmune communication as well as macrophage-targeting drugs as novel, non-hormonal, and non-opioid approaches for the treatment of endometriosis-associated pain. The project also addresses a previous unknown mechanism by which CGRP contributes to a pro-endometriosis phenotype in macrophages and pinpoints a nociceptor-responsive macrophage population that drives omental colonization for subsequent pain and lesion formation in endometriosis. My preliminary data show that nociceptor to macrophage signaling via CGRP/RAMP1 contributes lesion formation and endometrial cell growth. However, the mechanisms by which CGRP programs (re)macrophages to a pro-endometriosis phenotype is not known. Therefore, we will (Aim 1) identify the inflammatory mediators released and the signaling pathways activated in macrophages upon CGRP stimulation using bulk RNAseq analysis. I will further use FDA approved drugs such as pexidartinib to the measure the effect of macrophage-targeting in my mouse model. I also have preliminary data showing that Maresin-1 (MaR1) a pro-resolving lipid mediator reduces pain and stimulates efferocytosis by macrophages. I will next determine the mechanisms by which MaR1 resolves pain and inflammation in endometriosis. For that, I will perform scRNAseq of MaR1-treated mice at different timepoints to understand the dynamics and mechanism of pain resolution during endometriosis. I also have preliminary scRNAseq data showing that endometriosis completely changes the immune cell landscape in the peritoneal cavity with a decrease in the macrophages that migrate to the omentum. Therefore, during my R00 phase (Aim 2) I will determine the extent to which neuroimmune communication drives omental colonization by macrophages as well as pinpoint the nociceptor-responsive population of macrophages in the omentum that is responsible for endometriosis pain and lesion formation. I will then use transgenic mice to deplete that macrophage population to determine the extent to which those cells contribute to pain and lesion formation. To reach these long-term goals, I have outlined a detailed career development plan, which will provide me with the technical and leadership skills to establish a successful research laboratory. The K99 phase of research will be conducted under the excellent co-mentorship of Drs. Michael Rogers and Clifford Woolf. My Research Advisory Committee and collaborator are leading experts in neuroimmune communication (Dr. Chiu), endometriosis (Dr. Missmer), and pharmacology of pain and neuroimmune communication (Dr. Cunha). This K99/R00 award w... ## Key facts - **NIH application ID:** 10864635 - **Project number:** 1K99HD115239-01 - **Recipient organization:** BOSTON CHILDREN'S HOSPITAL - **Principal Investigator:** Victor Fattori - **Activity code:** K99 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $254,610 - **Award type:** 1 - **Project period:** 2024-07-15 → 2025-06-30 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10864635 ## Citation > US National Institutes of Health, RePORTER application 10864635, Neuroimmune communication as a driver of lesion formation and macrophage colonization of the omentum in endometriosis-associated pain (1K99HD115239-01). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10864635. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*