Our current research interests are focused towards two main directions:
1. The exploration of fibroblast diversity within the synovial membrane through lineage tracing approaches and molecular dissection of their profiles during development and in the course of Rheumatoid-like and Psoriatic-like modeled disease.
We have set forth the hypothesis that different types of SFs function for maintaining homeostasis or fueling disease by their expansion, differential sensitivity to inflammatory stimuli and compromised cell competition leading to irreversible changes in the cellular composition of the synovial membrane and unresolved inflammation in the joint. Our goal involves the molecular and functional characterization of synovial subpopulations in chronic murine arthritides (rheumatoid-like: hTNFtg mouse and psoriatic-like: A20Znf7 mutant mice) employing single-cell omic techniques and SF subset-specific genetic targeting in vivo and ex vivo.
2. The signaling pathways affecting the different types of cellular demise in synovial fibroblasts and their effect in the outcome of modeled arthritic diseases by employing functional genetic approaches.
Following previous observations of the lab, Our goal is to revert inflammatory profile and death resistance of SFs by modifying TNF-signaling components, such as RIPK1 and Cyld. Both molecules are mainly involved in NFkB and death responses downstream of TNF. We are currently investigating the role of the regulatory phosphorylation-based mechanisms in RIPK1 kinase activity and as well as the role of the scaffolding properties of RIPK1 operating in SFs in TNF-mediated disease, by employing SF-specific targeting of RIPK1 protein and enzymatic activity either alone or in combination with the RIPK1 signalling regulators. In parallel, we also explore the SF-specific role of cyld in arthritis both in vivo and ex vivo.