The Major Grant is designed to fund projects focused on translational perspectives on lung fibrosis, including the pathogenesis of ILD, the mechanisms of progression, the prediction of response to treatment, the biomarkers of ILD and the outcome measures of ILD.
Major Grant
on ILD
The World Scleroderma Foundation (WSF) is pleased to announce the launch of a Major Grant and invites researchers worldwide to submit their projects for consideration.
This grant aims to support significant research initiatives in the field.
Grant Objectives
Application Process
Phase 01
Letter of Interest (LOI) Submission: Applicants must complete the online application form, detailing their research project and how it aligns with WSF’s objectives.
Application Deadline: April 15, 2025, at midnight (CET).
Review Process: applications will be evaluated by an international selection committee.
Projects selected in this initial phase will be invited to proceed to Phase2.
Important: We strongly encourage applicants to check the WSF website regularly to verify their selection status, as emails may sometimes be filtered into spam folders.
Phase 02
Full Proposal Submission: Selected applicants will submit their final research proposal via the WSF online form, which will be sent by email once they have been selected.
Review Process: Proposals will undergo rigorous evaluation by field experts. Winners will be notified via email and announced on the WSF website. Applicants are advised to regularly check their email inbox and spam folder for updates.
Eligibility Criteria
The Principal Investigator must hold a position at an academic institution or a hospital devoted to SSc care for the duration of the project. The applicant must demonstrate access to the necessary infrastructure to conduct the proposed research.
Institutions or individuals who have received a WSF grant in 2023 or 2024 are not eligible to apply. Selected applicants must sign and return the funding agreement by the deadline communicated by the WSF office. It should be noted that this is a condition for funding and all applicants that will not comply with the deadline will be excluded.
Funding Details
The total available funding is €300,000, awarded to two projects (€150,000 each).Funds must be utilized within three years.
Recipients will be contacted by the WSF Central Office to sign an agreement outlining project milestones and payment details.
The Principal Investigator must present the final or preliminary results at the opening ceremony of the World Congress on Systemic Sclerosis in 2026.
For any questions or further clarifications, please do not hesitate to contact us at info@worldsclerofound.org
The application process closed on Tuesday 15 April 2025 at 11:59 pm CET.
Winning Projects 2024
Project Title: Investigating the role of fibroblast trained immunity in the pathogenesis of systemic sclerosis associated pulmonary fibrosis.
Project Summary: Fibroblasts shift between immunosuppressive and inflammatory states and may be persistently altered by inflammatory stimuli, in a process known as
trained immunity. Trained immunity is classically associated with innate/myeloid cells, interestingly, fibroblasts also exhibit memory-like responses.
Examples include transcriptional and epigenetic modifications, enhanced functional response to subsequent stimuli and metabolic alterations, leading
to negative pathological outcomes. Importantly, how trained immunity in lung fibroblasts influences lung fibrosis development and whether this
process holds therapeutic promise, has not been addressed. Crosstalk between immune cells and fibroblasts drives SSc pathogenesis. Immune-derived
cytokines activate fibroblasts, leading to fibrosis. The NFκB transcription factor cRel/REL orchestrates epigenetic and metabolic changes in immune cells,
implicating this molecule as a putative regulator of trained immunity. Our preliminary data show conditional myeloid cell deletion of cRel reduced
fibrosis in mouse models, suggesting cRel/REL signalling is crucial for fibroblast-immune cell interactions in lung fibrosis. We have shown REL is
constitutively active in SSc patient fibroblasts and is associated with a distinct transcriptional profile linked to fibrosis. Inhibiting REL with IT603 reduced
fibrotic markers in human dermal fibroblasts. Furthermore, SSc-ILD myofibroblasts have elevated REL levels and expression in the lung is localised in
immune cells and fibroblastic foci. Our preliminary findings indicate that trained immunity in lung fibroblasts, driven by cRel/REL, may contribute to lung
fibrosis, representing a potential therapeutic target. This project employs a multifaceted approach integrating transcriptomics, metabolomics, and
spatial analysis to unravel the role of fibroblast trained immunity in lung fibrosis, focusing on translating findings into potential treatments.
Project Title: To B or not to B: the Topoisomerase-1 B cell response and progression of interstitial lung disease in Systemic Sclerosis.
Project Summary: Systemic Sclerosis (SSc) is hallmarked by the presence of different anti-nuclear antibodies, each associated with distinct clinical phenotypes. Antitopoisomerase-1 antibody (ATA)+ SSc patients frequently develop interstitial lung disease (ILD), the leading cause of death in this population. We and others
have demonstrated that ATA of different isotypes associate with disease progression. Moreover, we observed that the frequency of circulating, ATA-IgGsecreting B cells correlate with the extend and severity of ILD. These findings, together with the first reports on the successes of CD19 CAR T-cell therapy in
SSc, indicate that the autoreactive B cell response drives disease activity and the development/progression of ILD. Here, we aim to understand the
contribution of the ATA B cell response to disease, focusing on the development and progression of ILD. Specifically, we will analyze patient ATA clonal
repertoires and their ability to differentiate patients with and without ILD using a novel, ATA-specific mass spectrometry-based IgG1 Fab profiling approach.
Furthermore, ATA-expressing B cells will be phenotypically and functionally analyzed in relation to patient ILD status using spectral flow cytometry. Together,
we expect to define (1) the molecular make-up of ATA and ATA-expressing B cell responses in relation to ILD development, (2) the potential of assessing (the
activity of) the ATA B cell response as biomarker for disease progression and ILD-risk stratification (to be substantiated in subsequent prospective studies),
and (3) possible novel targets rendering the ATA B cell response amenable for therapeutic intervention.
Project Summary: Systemic Sclerosis (SSc) is hallmarked by the presence of different anti-nuclear antibodies, each associated with distinct clinical phenotypes. Antitopoisomerase-1 antibody (ATA)+ SSc patients frequently develop interstitial lung disease (ILD), the leading cause of death in this population. We and others
have demonstrated that ATA of different isotypes associate with disease progression. Moreover, we observed that the frequency of circulating, ATA-IgGsecreting B cells correlate with the extend and severity of ILD. These findings, together with the first reports on the successes of CD19 CAR T-cell therapy in
SSc, indicate that the autoreactive B cell response drives disease activity and the development/progression of ILD. Here, we aim to understand the
contribution of the ATA B cell response to disease, focusing on the development and progression of ILD. Specifically, we will analyze patient ATA clonal
repertoires and their ability to differentiate patients with and without ILD using a novel, ATA-specific mass spectrometry-based IgG1 Fab profiling approach.
Furthermore, ATA-expressing B cells will be phenotypically and functionally analyzed in relation to patient ILD status using spectral flow cytometry. Together,
we expect to define (1) the molecular make-up of ATA and ATA-expressing B cell responses in relation to ILD development, (2) the potential of assessing (the
activity of) the ATA B cell response as biomarker for disease progression and ILD-risk stratification (to be substantiated in subsequent prospective studies),
and (3) possible novel targets rendering the ATA B cell response amenable for therapeutic intervention.
