Friday, April 26, 2024
4/26/2024
ABSTRACT Systemic sclerosis (SSc; Scleroderma) is a connective tissue disease of unknown etiology that is associated with significant morbidity and mortality. It has long been presumed that SSc likely results from environmental triggers, although these environmental insults have not been identified. The gold standard for assessing the role of environmental and inherited genetic effects on the development of a disease is the study of twins. A cross sectional study of twins with SSc we conducted several years ago showed a comparable concordance for disease of approximately 5% in monozygotic (MZ) and dizygotic (DZ) twins. We propose to conduct a follow-up study of the twin cohort to determine longitudinal concordance for disease, ANA status, and autoantibody presence. Since epigenetic regulation has emerged as an important mechanism mediating gene expression and the manifestation of a disease phenotype, we will also compare the DNA methylation profile of twins longitudinally. One of the factors we recently implicated in dermal fibrosis in SSc is estrogen. Our findings show that estrogen levels are elevated in Caucasian patients with diffuse cutaneous (dc)SSc and identified clinical features of disease associated with elevated estrogen levels. Since dcSSc is more severe in African Americans (AA), we now propose to measure estrogen levels in post-menopausal AA women and men of similar age with dcSSc and identify correlates with clinical features of the disease. Our findings will significantly advance our understanding of disease pathogenesis in SSc, propel progress in the field, and importantly provide new avenues for research for mentees to facilitate their research and allow them to establish their own independent research programs. These mentees will be integral participants in my program throughout the award period. I will mentor junior physician investigators in the assessment of SSc in patients and the absence of disease in healthy twins, evaluation of Raynaud phenomenon, detection of autoantibodies, obtaining informed consent, banking and use of clinical samples, examination of DNA methylation profiles, measurement of estrogen, and identification of associations with clinical variables. The mentoring goals of this application also include mentoring junior clinician investigators in patient-oriented research, grantsmanship, manuscript writing, responsible conduct of research, entrepreneurship and innovation, and career development. My reputation as an excellent mentor coupled with the collaborative and supportive environment at the Medical University of South Carolina, the resources available at the institution and via the CTSA, and the resources of the Division of Rheumatology P30 CCCR, provide the perfect environment for attracting and training successful clinician investigators. My ultimate goal is to ensure a pipeline of well-trained clinical investigators who will continue the mission of treating patients and identifying the cause and cure for Scleroderma and related diseases.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
