The Scleroderma Research Foundation’s Postdoctoral Fellowship program funds grants aimed at focusing talented young investigators on specific research questions in the nation’s top laboratories. It has become a central element to the overall research effort, leveraging the momentum of SRF core research projects and bringing bright young scientists to scleroderma research. The SRF endeavors to support their interest in dedicating their early careers to scleroderma research—ideally providing the tools, relationships and knowledge that will allow them to become the next generation of leaders in the field.
The SRF has funded Postdoctoral Fellows in the laboratories of nationally respected senior scientists Dr. Laurie Glimcher, Harvard School of Public Health; Dr. Stephen Schwartz, University of Washington; and microarray pioneers Dr. Patrick O. Brown, Stanford University School of Medicine and Dr. David Botstein, Princeton University.
The SRF is proud of our many Fellowship Program successes and continues to look for opportunities to enhance this valuable program, which extends the reach of our scientific objectives—improved therapies and a cure for scleroderma patients.
Postdoctoral Fellowships in Action
Genomic Approach to Characterize the Circulating Soluble Factors in Scleroderma Pathogenesis
Sponsoring Investigator: Patrick O. Brown, MD, PhD
Postdoctoral Fellow: Ashley Chi, MD, PhD
Stanford University School of Medicine
Dr. Chi suspected that abnormalities in the blood of scleroderma patients may account for systemic involvement of the disease, beyond the skin. He proposed a novel method to test his hypothesis, by exposing normal cells to scleroderma blood samples and observing the changes using state-of-the-art DNA microarray technology. In his pilot study, Dr. Chi found that blood from scleroderma patients can convert healthy cells to "scleroderma-like" cells. Dr. Chi extended this method to test other cell types and initiated studies to characterize and identify the factors that change the normal cells. Dr. Chi’s method expected to provide a powerful way to understand scleroderma and lead to better diagnosis and treatment.
Dr. Chi, now an Assistant Professor of Molecular Genetics and Microbiology at the Duke Institute for Genome Sciences and Policy continues to explore the use of DNA microarrays and other genomic tools to enhance our understanding of human diseases.
Analysis of Expression in Scleroderma Monocytes
Sponsoring Investigator: Stephen Schwartz, MD, PhD
Postdoctoral (Senior) Fellow: Azin Agah, PhD
University of Washington
Dr. Agah’s goal was to use microarray analysis to evaluate unique gene expression patterns of monocytes isolated from scleroderma patients. Monocytes are white blood cells that are important to the body’s defense system. Further, she hoped to identify differences in scleroderma monocyte gene expression patterns that correlated with patterns seen in diabetes, atherosclerosis, and others. Here, the sets of genes uniting different disease states could be valuable for exploring possible shared disease mechanism(s).
Dr. Agah, Assistant Professor of Biomedical Sciences is continuing her research into inflammation induced angiogenesis, tissue repair and regeneration, matricellular proteins; scleroderma, fibrosis and extracellular matrix remodeling at the Department of Biomedical Sciences at the University of South Alabama.
The Function of the Transcription Factor T-Bet in Scleroderma
Sponsoring Investigator: Laurie Glimcher, MD
Postdoctoral Fellow: Jingsong Wang, MD
Harvard School of Public Health
Dr. Wang studied the role of a protein—the transcription factor T-bet—as a master regulator of factors that contribute to fibrosis in scleroderma. Early experiments have shown that T-bet represses production of TGF-beta, a protein involved in collagen production. Dr. Wang studied, in more molecular detail, the relationship between T-bet and TGF-beta and the effects of increasing T-bet activity in the setting of scleroderma for possible therapeutic value. In addition, he explored the finding of a strong genetic association among groups of scleroderma patients related to T-bet.
Dr. Wang is now a Director, Discovery Medicine & Clinical Pharmacology, at Bristol-Myers Squibb Co. In his current role, he serves as Exploratory Development Team leader where he oversees a clinical development program with multiple assets targeting several diseases and directs early to mid-stage clinical studies in Immunology Therapeutic Area. Dr. Wang is also an Adjunct Assistant Professor of Medicine at University of Pennsylvania, and an attending physician at the Hospital of The University of Pennsylvania and continues to commit his attention to biotechnology and autoimmune diseases.
A Gene Expression Map of Scleroderma
Sponsoring Investigator: David Botstein, PhD
Postdoctoral Fellow: Michael Whitfield, PhD
Stanford University Medical School, Department of Genetics and Biochemistry
Dr. Michael Whitfield joined the Department of Genetics at Stanford under the direction of Dr. David Botstein, long-time member of the Foundation’s Scientific Advisory Board. He began his fellowship by studying genome-wide gene expression patterns in fibroblasts, endothelial cells and smooth muscle cells using powerful new DNA microarray technology. Dr. Whitfield’s goal was “the characterization of the patterns of gene expression that are present in tissue affected by scleroderma and how those patterns differ from those found in unaffected tissue.” His work provided a ‘molecular portrait’ of the genes that are on or off in tissues affected by scleroderma and allowed for the ability to determine which cell types are involved in order to characterize the “molecular architecture” of the disease. Early results found a clear difference that could be measured consistently and accurately using microarray technology.
Dr. Whitfield is now Assistant Professor of Genetics at Dartmouth Medical School and continues his work with gene expression mapping in his own lab, funded in part by a grant from the SRF.. As a result of his ongoing work with microarray technology, he is now able to distinguish samples from patients with diffuse disease from patients with limited disease solely by examining the gene expression profiles generated from biopsy samples. He also has some promising preliminary data to indicate that elevated or depressed expression of groups of genes may be predictive of certain disease complications such as the severity of skin hardness and Raynaud’s phenomenon. Clearly, the ability to “type” scleroderma and provide information about possible complications would be immensely valuable to physicians and would inform their treatment decisions.
As Dr. Whitfield’s research to establish scleroderma’s molecular architecture continues to progress, it is his hope to provide more information about the pathogenesis of the disease and to create a system or model in the laboratory that mirrors what is observed in the skin biopsies used for testing potential therapeutic agents. Dr. Whitfield enjoys fruitful collaborations with a number of investigators who are studying the fibrotic and autoimmune aspects of scleroderma, including SRF investigators Dr. Laurie Glimcher at Harvard and Dr. Fred Wigley at Johns Hopkins. The Scleroderma Research Foundation is pleased to have provided support to Dr. Whitfield since the inception of his career and will continue to play a vital role in assisting his ability to shed valuable insight into scleroderma.
Sponsoring Investigator: Fredrick M. Wigley, MD
Postdoctoral Fellow: Laura K. Hummers, MD
Johns Hopkins University School of Medicine
In caring for scleroderma patients, one striking feature is the marked heterogeneity of patients’ clinical manifestations and prognosis. A dilemma encountered frequently is determining the “activity” of disease and differentiating activity from damage. Attempts have been made to identify clinical markers of disease severity and activity. It is clear, however, that patients can have ongoing disease activity prior to the onset of clinical symptoms. Based on the many studies providing evidence that the microvasculature is the primary site of disturbance in scleroderma, Dr. Laura Hummers’ aim was to investigate potential biomarkers of vascular disease activity in scleroderma. One area of investigation focused on endothelial cells, which are thought to be involved in the key events in scleroderma pathogenesis. In addition, collaborating with Drs. Antony Rosen and Livia Casciola-Rosen, she helped to further their investigation on the role of granzymes in the pathogenesis of vascular disease. Dr. Hummers worked to correlate these potential markers of disease activity with specific clinical markers of vascular disease such as Raynaud’s intensity, the evolution of pulmonary hypertension and unique events such as renal crisis.
Dr. Hummers continues her commitment to scleroderma at the Johns Hopkins Scleroderma Center. She is a physician-scientist whose research focuses on properties of blood that could help predict outcomes for patients with scleroderma. She is also interested in understanding the natural course of the disease and developing new treatment paradigms for scleroderma. She has a special interest in a rare disease called scleromyxedema.