[R03] Modifying bone morphogenetic protein 9 (BMP9) signaling in secondary lymphedema
Ente: National Institute of Arthritis and Musculoskeletal and Skin Diseases
Scadenza: 2028-07-31
Importo max: 151.950 EUR
Paese: US
Descrizione
PROJECT SUMMARY
Secondary lymphedema is a morbid condition affecting over 5 million patients in the United States.
Patients with this condition develop lymphatic retention, which progresses to irreversible subcutaneous
fibroadipose deposition in the affected extremity. As a result, patients experience chronic pain, decreased
mobility and function, open wounds, and overall reduced quality-of-life. In Aim 1, I will examine how loss of
signaling through the bone morphogenetic protein 9 (BMP9) signaling pathway modifies lymphatic function and
maturity in the setting of post-natal lymphatic regeneration which occurs after surgical lymphatic disruption.
Findings from this portion of the proposal will inform our understanding of post-natal lymphatic regeneration,
which is currently incompletely understood. In addition, it may provide insights into the development of mouse
lymphedema models which have longer duration of lymphedema relative to current models. In Aim 2, I will
examine how augmentation of BMP9 modifies lymphatic maturity and function during post-natal lymphatic
regeneration after surgical lymphatic disruption. I will examine a direct method of augmenting BMP9 signaling
through delivery of BMP9 ligand, and a second method to inhibit Endoglin, an inhibitor of BMP9, through
delivery of carotuximab, an anti-Endoglin antibody. Upon completion of this proposal, I will have developed a
strategy to improve upon current models of secondary lymphedema and developed a new avenue for
therapeutic intervention in secondary lymphedema through modification of BMP9 signaling.
Istituzione: BRIGHAM AND WOMEN'S HOSPITAL
PI: Shailesh Agarwal
Progetto: 1R03AR086904-01
Settori: National Institute of Arthritis and Musculoskeletal and Skin Diseases
Vai al bando originale
Registrati gratis su Bandolo per trovare bandi compatibili con la tua azienda.