National Scleroderma Foundation Announces 2025 Research Grant Awardees

The National Scleroderma Foundation is excited to announce its 2025 Scleroderma Research Grant awardees. The National Scleroderma Foundation fosters development of innovative, high-quality research by new and established investigators in fields related to scleroderma. To accomplish this goal, we provide funding for new and established investigators based on investigator-directed topics.

2025 Grant Award Recipients

Chen, Yen Tzu, PhD

Brain boost program to improve cognitive function in people with systemic sclerosis: A pilot randomized controlled trial
University of Michigan
New Investigator Award

Scleroderma (or systemic sclerosis) is a rare autoimmune disease that can make life difficult for patients, not just because of physical discomfort and limitations, but also due to cognitive dysfunction like problems with attention, planning, and short-term memory. Up to 8 out of 10 people with scleroderma experience these cognitive difficulties, which make everyday tasks and work much harder, also worsening pain, fatigue, and psychological symptoms. Current treatments for scleroderma do not specifically help with cognitive difficulties. Therefore, this study is designed to test whether an 8-week online educational group-based program tailored to people with scleroderma can help improve cognitive function and well-being. This program will teach cognitive strategies and lifestyle modifications to help participants manage cognitive challenges, along with online brain
games to boost cognitive abilities. The study will involve 66 people with scleroderma, who will either be randomly assigned to an online comprehensive cognitive program or to waitlist control. Their progress will be checked at baseline, week 8, and at 3- and 6-month follow-ups. Cognitive function will be assessed by both objective cognitive assessments and self-reported surveys. The proposed research has the potential to improve cognitive function and well-being that lead to better care for people with scleroderma.

Herzog, Erica L., MD, PhD

Marta Marx Fund for the Eradication of Scleroderma Award

Nerve-Fibroblast Interactions in Scleroderma ILD
Yale University
Established Investigator Award

It is not known how the sympathetic overactivity seen in Scleroderma contributes to interstitial lung disease (SScILD). This process may be linked to a type of cell called “myofibroblasts” that contribute to the scar formation that is often called “fibrosis.” We have recently identified a functional connection between sympathetic nerves and myofibroblasts that express a neurotransmitter receptor called ADRA1D. This axis is present in fibrotic mouse models of in samples from people with SSc-ILD. Our application will explore the impact of this discovery. In aim 1 we will evaluate whether SSc-ILD lung fluids and tissues are enriched for sympathetic neurotransmitters and ADRA1D+ myofibroblasts, respectively. We will also study whether ADRA1D+ expression contributes to scar forming properties of SSc-ILD lung fibroblasts. In aim 2 we will use mouse models to find out if sympathetic nerves are required for lung fibrosis, and how ADRA1D+ myofibroblasts are involved. If successful, this project could lead to treatments that could improve the health of people living with SSc-ILD.

Jarvis, James, N, MD

Mark Flapan Award

Mechanistic Studies of Genetic Risk Scleroderma
University of Washington
Established Investigator Award

We’re learning a lot about genetic risk for scleroderma/systemic sclerosis (SSc), but we still need to learn more to be able to use that information help us understand the disease process(es), guide clinical care, and to make drug trials more informative. At the same time, we know this can be done, because people in cancer fand other fields are already doing it. At the present time, we only know the regions of the genome where risk is exerted. We don’t know the genetic variants that actually cause risk. There’s a lot to sort through, because there are more than 13,000 genetic variants in the regions that are known to confer risk for SSc. Not knowing the variants that cause risk makes it hard to know the genes that are affected, and we need to know that to make genetic information clinically useful. Earlier studies from our group show that there are more than 500 of these so-called “target
gene” candidates. We need to whittle this number down, because these genes and processes that are affected by the risk-causing genetic variants are very likely also unsuspected targets for new therapies. Our project is directed at identifying the true drivers of genetic risk and the genes affected by those drivers. Someday, in the near future, we hope to be able to say to our patients, “You have genetic variants a, b, and c. These variants affect genes X, Y and Z. Therefore, the best medication for you is…” Our strategy is to test all 13,019 variants in the SSc genetic risk regions for the efficiency with which they activate a model (“reporter”) gene. Using data we have already generated, we can further sift the candidate variants, and, using another data set we’ve already generated, identify the affected genes. Based on our work in juvenile arthritis, we expect to reduce to number of high-risk variants from 13,019 to 50-80, and the number of affected genes from 500 to 35-45. While further sifting will still be required, we will have reduced the task to workable numbers of genes and variants and be prepared for a range of studies to move individualized therapies from a theoretical concept to standard medical practice.

Lammi, Mathew, MD MSCR

Quantitative CT scanning to examine the pulmonary vascular effects
of mycophenolate and nintedanib in patients with scleroderma
Johns Hopkins University
Established Investigator Award

Scleroderma, also known as systemic sclerosis, is a serious autoimmune disease that causes inflammation and scar tissue formation in the skin and organs inside the body, especially the lungs. Lung disease is patients with scleroderma can either involve the lung tissue (“interstitial lung disease”) and/or blood vessels (“pulmonary hypertension”). Two medications commonly used for interstitial lung disease in patients with scleroderma, mycophenolate (Cellcept ®) and nintedanib (Ofev ®), help improve lung function but also appear to improve blood vessel function. The ability of these medications to improve lung blood vessel function has never been tested in people with scleroderma. In this study, we will investigate the effect of mycophenolate and nintedanib on lung blood vessel function in patients with scleroderma by using a new test to image the lungs, called
quantitative CT scanning. This technique can automatically measure the size and distribution of blood vessels in the lung that are not able to be seen on standard CT scanning. We hope that by using this exciting new technique to image the lung blood vessels we will be able to uncover new ways to treat the pulmonary vascular disease that many patients with scleroderma suffer from.

Odell, Ian, Douglas, MD, PhD

Regulation of fibroblast metabolism by EGFR during skin fibrosis
Yale Univeristy
New Investigator Award

Fibrosis that occurs in scleroderma has high oxidative stress and dysregulated metabolism. It is unclear what causes these findings and whether they can be therapeutically targeted. EGFR is a receptor on fibroblasts highly linked to scleroderma fibrosis that can act as an oxidative sensor and regulator of cell metabolism. In this application, we propose to study how EGFR functions as an oxidative sensor in fibrosis and the metabolic consequences that determine fibrosis severity. To accomplish these goals, we generated a mutant mouse that lacks the oxidative sensor in EGFR and will test whether these mice have different fibrotic responses in mouse models of scleroderma. Using experimental techniques that allow us to see which modifications occur on the EGFR oxidative sensor, we will test the effects of different EGFR activating proteins on EGFR modifications and associate those with metabolic consequences in fibroblasts. By understanding how EGFR senses oxidative stress and regulates the metabolism of cells in scleroderma, we will gain insight into fundamental disease processes and potential new therapeutic strategies.

Pioli, Patricia A, PhD

Walter and Marie Coyle Award

The Role of Paracrine WNT5A in Immuno-metabolic Regulation of SSc Macrophage Activation
Dartmouth College
Established Investigator Award

Autoimmune systemic sclerosis (SSc) is a chronic disease characterized by vasculopathy, immune dysfunction, and fibrosis. Our prior work demonstrates that fibroblasts, which secrete excess extracellular matrix that mediates fibrosis, and macrophages, a white blood cell that regulates inflammation and fibroblast activation, communicate through release of secreted vesicles known as exosomes, which contain nucleic acids (RNA and DNA) and proteins. Coordinated interaction between these two cell types results in mutual activation, culminating in the production of excess collagen and inflammation. Although we have shown that exosomes from SSc fibroblasts cause macrophages to become activated, the specific cargo carried by exosomes that underlies this activation is unknown. In new studies, we now have shown that SSc fibroblast-derived exosomes contain high
levels of the signaling protein WNT5A. Significantly, WNT5A has been shown to induce macrophage activation by changing energy usage pathways. Therefore, we hypothesize that WNT5A derived from SSc fibroblasts causes macrophages to become pro-fibrotic in SSc by changing metabolic programming. Studies in this proposal will investigate the molecular mechanism by which this occurs.

The National Scleroderma Foundation is the leading nonprofit supporter of peer-reviewed, scleroderma research to discover the cause, understand the mechanism, and overcome scleroderma forever. Since its inception, the Foundation has committed over $33 million for scleroderma research, which continues as a priority of our mission. Funding levels are variable and based on the most promising research proposals. Current research investment exceeds $1.5 million annually.

Our Peer-Review Research Grant Funding Program has earned a unique place in the field of scleroderma research. It is respected by medical researchers and by government health agencies such as National Institutes of Health (NIH) and National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). The program is administered by the National Scleroderma Foundation’s Board of Directors and staff and is guided by the Foundation’s Peer Research Review Committee. This committee, composed of scleroderma medical experts from around the world, helps determine which proposals will be funded each year by reading, critiquing, and ranking all applications.

The 2026 research grant application cycle will begin in April 2025. For more information on the grant program, visit the Grant Opportunities page on the Foundation’s website.