Ivan Merelli
STAFF
Project
VEXAS
Unraveling molecular targets of myeloid-driven inflammation in VEXAS syndrome
Name
Unraveling molecular targets of myeloid-driven inflammation in VEXAS syndrome
Acronym
VEXAS
Location
Segrate
Start Date
2023
End Date
2026
Funder
Ministero dell'Università e della Ricerca
Partners
San Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan, Italy University La Sapienza, Rome, Italy
VEXAS syndrome is a recently discovered autoinflammatory disease caused by a somatic mutation affecting UBA1. Despite its increasing incidence, the mechanisms triggering inflammation remain unknown and treatment is often ineffective. Recently, we revealed that myeloid cells in VEXAS display remarkable changes in cellular energy metabolism (“immunometabolic activation”). We hypothesise that this is a key driver sustaining inflammation in VEXAS. The aim is to investigate this mechanism and determine the therapeutic potential of its targeted inhibition. We will study primary myeloid cells from VEXAS patients, also developing in vitro and in vivo disease models. Access to biological samples and collaboration with leaders in the field of gene editing allow us to carry forward this ambitious project. This study will unveil key mechanisms sustaining inflammation in VEXAS and test innovative treatment strategies for this currently incurable disease.
Publications
- Molteni R, Fiumara M, Campochiaro C, Alfieri R, Pacini G, Licari E, Tomelleri A, Diral E, Varesi A, Weber A, Quaranta P, Albano L, Gaddoni C, Basso-Ricci L, Stefanoni D, Alessandrini L, Degl’Innocenti S, Sanvito F, Bergonzi GM, Annoni A, Panigada M, Cantoni E, Canarutto D, Xie SZ, D’Alessandro A, Di Micco R, Aiuti A, Ciceri F, De Luca G, Dagna L, Matucci-Cerinic M, Merelli I, Cenci S, Scala S, Cavalli G, Naldini L, Ferrari S. Mechanisms of hematopoietic clonal dominance in VEXAS syndrome. Nat Med. 2025 Jun;31(6):1911-1924. doi: 10.1038/s41591-025-03623-9
