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Geneticists Hunt for Scleroderma Triggers
October 30, 2009Hanover, N.H.-At its most benign, the autoimmune disease scleroderma can discolor parts of the skin of its sufferers. At its most pernicious, it can thicken and harden their skin, their blood vessels, and their internal organs before, in many cases, killing them.
In all its forms, scleroderma gives Dartmouth geneticist Michael Whitfield, his graduate students, and his postdoctoral researchers a sense of urgency in their search for the triggers of the chronic condition. In a study that the Journal of Investigative Dermatology published in its October 2009 edition, Whitfield's team reports a closer connection between a gene profile for the profibrotic pathway TGF-beta and a tendency in some scleroderma sufferers to develop lung problems. Jennifer Sargent, who recently earned her Ph.D. in molecular and cellular biology from DMS, is lead author of the study, which analyzed the previously-identified TGF-beta pathway signature in skin biopsies from patients and healthy control subjects from around the country.
"The finding that a gene signature expressed in skin is associated with the occurrence of lung disease is surprising and to our knowledge is previously unreported," the report says. "ILD [interstitial lung disease] is the leading cause of death among patients with dSSc [diffuse systemic sclerosis]. . . . Recent work has developed tools and methods for diagnosis, staging, and characterization of ILD in dSSc patients; however, biomarkers that reliably predict who will develop lung complications before they become symptomatic would be beneficial."
In collaboration with M. Kari Connolly, a professor of dermatology at the University of California-San Francisco, Whitfield, an associate professor of genetics at DMS, and his researchers began creating a map of skin to profile the molecular behavior of genes in scleroderma in 2001.
For the current study, he received support from the Scleroderma Research Foundation, as well as a biomedical research award to Dartmouth from the Howard Hughes Medical Institute.
"Several different pathways likely contribute to the gene expression subsets in scleroderma, and each subset may need to be treated differently," Whitfield says, before adding, "We're getting inquiries from rheumatologists and companies that are looking at drug trials."
In 2008, with DMS postdoctoral fellow Ausra Milano as lead author, Whitfield's group profiled gene expression to divide scleroderma patients into different categories. Those findings prompted Sargent, who participated in the 2008 study, to start mapping the genetic pathways that the disease follows in the subset of patients with the most severe cases. She will continue her experiments as a postdoctoral fellow with Whitfield, before going to work at the National Institutes of Health in January of 2010.
Dartmouth College
In collaboration with M. Kari Connolly, a professor of dermatology at the University of California-San Francisco, Whitfield, an associate professor of genetics at DMS, and his researchers began creating a map of skin to profile the molecular behavior of genes in scleroderma in 2001.
For the current study, he received support from the Scleroderma Research Foundation, as well as a biomedical research award to Dartmouth from the Howard Hughes Medical Institute.
"Several different pathways likely contribute to the gene expression subsets in scleroderma, and each subset may need to be treated differently," Whitfield says, before adding, "We're getting inquiries from rheumatologists and companies that are looking at drug trials."
In 2008, with DMS postdoctoral fellow Ausra Milano as lead author, Whitfield's group profiled gene expression to divide scleroderma patients into different categories. Those findings prompted Sargent, who participated in the 2008 study, to start mapping the genetic pathways that the disease follows in the subset of patients with the most severe cases. She will continue her experiments as a postdoctoral fellow with Whitfield, before going to work at the National Institutes of Health in January of 2010.
Dartmouth College
Scleroderma Current Events and Scleroderma News RSSDrug could provide first treatment for scleroderma
Investigators have identified a drug that is currently approved to treat certain types of cancer, Gleevec, that could provide the first treatment for scleroderma, a chronic connective tissue disease for which a treatment has remained elusive.
BUSM researchers identify better laser for treating facial spider veins
Researchers from Boston University School of Medicine (BUSM) have concluded that the 940nm wavelength laser is superior for treating facial spider veins (telangiectasias) as compared to the 532nm wavelength laser.
Endothelin-Related Drugs Benefit Patients With Pulmonary Hypertension
Recent research to block the effects of endothelin, a powerful substance that constricts blood vessels and stimulates cell growth, has led to successful treatment of pulmonary arterial hypertension and provides hope for treating other chronic diseases.
International conference on endothelin
One of the most intriguing developments in recent medical science is the discovery of the human chemical endothelin (ET).
Survival instincts propel 'difficult patient' to insist on quality care
Michelle Mayer had to become a "difficult patient" before she could get her physicians to accurately diagnose the disease that was destroying her health.
Dartmouth researchers discover gene signatures for scleroderma
Distinct genetic profiles can discern different groups of patients with scleroderma, a vexing autoimmune disease in which the body turns against itself, Dartmouth Medical School researchers report.
UCSF marks a milestone with 500th transplant in heart and lung program
UCSF marked a milestone this week with the 500th procedure in its Thoracic Transplant Program, which specializes in transplantation of the heart and lung.
Researchers show that fibrosis can be stopped, cured and reversed
University of California, San Diego researchers have proven in animal studies that fibrosis in the liver can be not only stopped, but reversed.
Scleroderma Outlook Improves as Survival Increases
Individuals with scleroderma are living significantly longer today, compared with 30 years ago, and the physicians who treat this rare disease of connective tissue hope the newer drugs now on the market may extend lives even further.
Green tea may help prevent autoimmune diseases
Green tea may help protect against autoimmune disease, Medical College of Georgia researchers say.
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