Research Program

The best way to help people living with scleroderma is to fund the most promising research aimed at improved therapies and a cure.

Research is the cornerstone of the Scleroderma Research Foundation’s existence. Only from continued investment in top quality medical research will discoveries be made to help people living with scleroderma and improve their quality of life. To that end, we press forward with finding, funding and facilitating the most promising research projects at institutions around the world.

The Scleroderma Research Foundation (SRF) funds research aimed at understanding scleroderma pathogenesis (disease development), identifying markers for disease progression, developing new and more relevant animal models for scleroderma and developing new therapies. Through generous donations, the SRF awards research grants totaling more than $1,000,000 annually and is the largest nonprofit source of funds for scleroderma research.

Our core projects are aimed at understanding how the immune system and vasculature malfunction, how fibrosis begins and progresses as well as the interrelationships among these facets of the disease. Research relating to disease mechanisms provides a basis for identifying new therapeutic targets and the SRF actively promotes the exploration of new therapies.

The Foundation continues to focus significant energy on developing animal models that mimic aspects of scleroderma. These models will allow researchers to ask questions that cannot be asked in human studies and will complement experiments done with human tissue. Additionally, the SRF funds research aimed at identifying scleroderma biomarkers. Effective biomarkers could be used for early diagnosis, predicting and monitoring disease progression and assessing response to therapies.

The Scleroderma Research Foundation is dedicated to fostering the creation and continued success of Scleroderma Clinical Centers of Excellence. At these Centers, physicians representing many different specialties, such as rheumatology, pulmonology, cardiology, gastroenterology and dermatology are dedicated to clinical research and the care of scleroderma patients. Patients receive integrated care at the Centers and because all of the specialists are present and work closely together, standards of scleroderma care can be advanced. The Centers are also critical for training the next generation of scleroderma physicians and clinical investigators. Physicians and clinical investigators at the Centers play an integral role in other research projects funded by the SRF by providing vital clinical expertise.

With the expert guidance of our esteemed Scientific Advisory Board, our research projects are evaluated annually at the SRF Scientific Workshop, where intensive review and discussion of the next critical steps take place. The workshop is a forum for leading scientists from inside and outside the SRF program to provide new perspectives on the search for a cure, while promoting synergy among investigators and advancing the growing understanding of scleroderma.

Understanding of scleroderma at the cellular and molecular level is increasing thanks in part to partnerships the SRF has facilitated. Increasingly, SRF-funded scientists are exploring new opportunities that will translate laboratory advances into effective therapies to help patients live longer, fuller lives.

The Scleroderma Research Foundation is leading the scleroderma research effort by:

  • Promoting collaboration and cross-institutional cooperation among scientists in a variety of disciplines, through a strategic, integrated program.
  • Attracting promising new scientists to scleroderma research, through its Postdoctoral Fellowship Program.
  • Promoting and maintaining Scleroderma Centers of Excellence, such as the Scleroderma Center at Johns Hopkins University.
  • Bringing new experts, technology and forward thinking to the field of scleroderma research.
 
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Research News

M10, a caspase cleavage product of the hepatocyte growth factor receptor, interacts with Smad2 and demonstrates antifibrotic properties in vitro and in vivo.

Author: Atanelishvili I, Shirai Y, Akter T, Buckner T, Noguchi A, Silver RM, Bogatkevich G
Date Published: April-2016
Source: Translational Research

Hepatocyte growth factor receptor, also known as cellular mesenchymal-epithelial transition factor (c-MET, MET), is an important antifibrotic molecule that protects various tissues, including lung, from injury and fibrosis. The intracellular cytoplasmic tail of MET contains a caspase-3 recognition motif "DEVD-T" that on cleavage by caspase-3 generates a 10-amino acid peptide, TRPASFWETS, designated as "M10". M10 contains at its N-terminus the uncharged amino acid proline (P) directly after a cationic amino acid arginine (R) which favors the transport of the peptide through membranes. M10, when added to cell culture medium, remains in the cytoplasm and nuclei of cells for up to 24 hours.

Esophageal dilatation and interstitial lung disease in systemic sclerosis: a cross-sectional study

Author: C. Richardson, R. Agrawal, J. Lee, O. Almagor, R. Nelson, J. Varga, M. Cuttica, J. D′Amico Dematte, R. Chang, M. Hinchcliff,
Date Published: February-2016
Source: Science Direct

A patulous esophagus on high-resolution computed tomography (HRCT) of the thorax is frequently observed in patients with systemic sclerosis (SSc). Microaspiration has been purported to play a role in the development and progression of SSc interstitial lung disease (ILD), but studies examining the role of microaspiration in SSc-ILD have yielded conflicting results. This study was conducted to determine the association between esophageal diameter and SSc-ILD.

Integrated long non-coding RNA analyses identify novel regulators of epithelial-mesenchymal transition in the mouse model of pulmonary fibrosis

Author: Hao Sun, Junjie Chen, Wenyi Qian, Jiang Kang, Jun Wang, Lei Jiang, Li Qiao, Wei Chen and Jinsong Zhang
Date Published: January-2016
Source: Journal of Cellular and Molecular Medicine

Idiopathic pulmonary fibrosis (IPF) is a chronic fatal lung disease characterized by aberrant accumulation of fibroblast population and deposition of extra cellular matrix. Increasing evidence support that epithelial-mesenchymal transition (EMT) of alveolar epithelial cells is a critical process in the pathogenesis of IPF. Although delivery of bleomycin to induce acute lung injury is the most well-studied animal model of pulmonary fibrosis, there is considerable interest to pursue other models to understand the common and/or specific pathological mechanisms. In this study, we established a mouse model of pulmonary injury and progressive interstitial fibrosis via intraperitoneal injection of paraquat, a widely used herbicide known to cause pulmonary fibrosis in human.

CD4+ Group 1 Innate Lymphoid Cells (ILC) Form a Functionally Distinct ILC Subset That Is Increased in Systemic Sclerosis

Author: Florence Roan, Thomas A. Stoklasek, Elizabeth Whalen, Jerry A. Molitor, Jeffrey A. Bluestone, Jane H. Buckner and Steven F. Ziegler
Date Published: January-2016
Source: The Journal of Immunology

Innate lymphoid cells (ILC) are a heterogeneous group of cellular subsets that produce large amounts of T cell–associated cytokines in response to innate stimulation in the absence of Ag. In this study, we define distinct patterns of surface marker and cytokine expression among the ILC subsets that may further delineate their migration and function. Most notably, we found that the subset previously defined as group 1 ILC (ILC1) contains CD4+ CD8−, CD4− CD8+, and CD4− CD8− populations.

Treprostinil iontophoresis improves digital blood flow during local cooling in systemic sclerosis

Author: Florence Gaillard-Bigot, Matthieu Roustit, Sophie Blaise, et al
Date Published: January-2016
Source: Microcirculation

Severe Raynaud's syndrome and digital ulcers are the most prevalent manifestations of systemic sclerosis (SSc) peripheral microvascular disease. We tested whether treprostinil iontophoresis on the finger pad of patients with SSc would improve digital blood flow during hand cooling.

News for Patients

Predictors of long-term outcomes in patients treated with riociguat for pulmonary arterial hypertension: data from the PATENT-2 open-label, randomised, long-term extension trial

Author: Patricia Inacio
Date Published: April-2016
Source: Scleroderma News

Researchers recently discovered a natural molecule, the M10 peptide, that can significantly decrease fibrosis in a mouse model of scleroderma. The study, “M10, a caspase cleavage product of the hepatocyte growth factor receptor, interacts with Smad2 and demonstrates antifibrotic properties in vitro and in vivo,” was published in the journal Translational Research. Systemic sclerosis, also known as scleroderma, is a chronic systemic autoimmune disease characterized by excessive deposition of collagen, leading to fibrosis in several organs, which can ultimately result in organ failure. Effective treatments targeting fibrosis in systemic sclerosis patients are lacking.

Predictors of long-term outcomes in patients treated with riociguat for pulmonary arterial hypertension: data from the PATENT-2 open-label, randomised, long-term extension trial

Author: H. Ghofrani, F. Grimminger, E. Grünig, Y. Huang, et al
Date Published: April-2016
Source: The Lancet

Pulmonary arterial hypertension is a chronic disease associated with poor long-term outcomes. Identifying predictors of long-term outcome in pulmonary arterial hypertension is important to assess disease severity and guide treatment. We investigate associations between efficacy parameters and long-term outcomes in patients with pulmonary arterial hypertension receiving riociguat in the PATENT-2 study. We also present safety and efficacy data from the final data cutoff of PATENT-2, where most patients had received at least 2 years of riociguat treatment.

Predictors of long-term outcomes in patients treated with riociguat for pulmonary arterial hypertension: data from the PATENT-2 open-label, randomised, long-term extension trial

Author: H. Ghofrani, F. Grimminger, E. Grünig, Y. Huang, et al
Date Published: April-2016
Source: The Lancet

Pulmonary arterial hypertension is a chronic disease associated with poor long-term outcomes. Identifying predictors of long-term outcome in pulmonary arterial hypertension is important to assess disease severity and guide treatment. We investigate associations between efficacy parameters and long-term outcomes in patients with pulmonary arterial hypertension receiving riociguat in the PATENT-2 study. We also present safety and efficacy data from the final data cutoff of PATENT-2, where most patients had received at least 2 years of riociguat treatment.

Prediction of improvement in skin fibrosis in diffuse cutaneous systemic sclerosis: a EUSTAR analysis

Author: Rucsandra Dobrota, Britta Maurer1, Nicole Graf, Suzana Jordan, Carina Mihai, Otylia Kowal-Bielecka, Yannick Allanore, Oliver Distler
Date Published: March-2016
Source: Annals of the Rheumatic Diseases

Improvement of skin fibrosis is part of the natural course of diffuse cutaneous systemic sclerosis (dcSSc). Recognising those patients most likely to improve could help tailoring clinical management and cohort enrichment for clinical trials. In this study, we aimed to identify predictors for improvement of skin fibrosis in patients with dcSSc.

Large Scleroderma Study Offers Genetic Map, Identifies Patients at Risk for Pulmonary Hypertension

Author: Margarida Azevdeo
Date Published: April-2016
Source: Scleroderma News Today

A research team with scientists from the University of Granada in Spain and the Spanish National Research Council (CSIC) has carried out the largest scleroderma study to date, creating a complete genetic map of the disease with the genetic analysis of more than 5,000 patients.

Ways to Give

There are many ways that you can support the work of the Scleroderma Research Foundation. We are grateful for your commitment to helping the SRF fund research that will result in improved therapies and, ultimately, a cure.

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