The Scleroderma, Fibrosis and Autoinflammatory Disease Program supports studies of basic, translational, and pre-clinical studies on scleroderma, fibrosis, and autoinflammatory diseases.
Scleroderma is an autoimmune rheumatic disease without an available curative therapy. It is a heterogenous and complex disease that can be categorized as localized scleroderma (morphea) and systemic scleroderma (SSc). One major clinical manifestation is dermal fibrosis, yet it often involves fibrosis in internal organs or tissues leading ultimately to fatality. Fibrosis, a progressive scarring and hardening of tissues and exaggerated wound healing process, is also associated with other autoimmune rheumatic diseases.
This program supports research on:
- The elucidation of molecular and cellular mechanisms of pathogenesis and pathophysiology, identification of unique genomic and proteomic signatures, and translational and pre-clinical research on diagnostic and therapeutic development for scleroderma and fibrosis in autoimmune rheumatic diseases.
- Unveiling the mechanisms of pathogenesis, identifying causative environmental and genetic risk factors, developing translational models for diagnosis and treatment for AID.
- Dysregulated immune responses resulting in impaired inflammation resolution and development of chronic inflammation plays a pivotal role in the pathogenesis of scleroderma and fibrotic rheumatic diseases. Research on not only immune cells but also non-immune cells (e.g. fibroblasts, endothelium, pericytes, and adipocytes) or the cross-talk among these cells will be supported to delineate the immunological mechanism of fibrosis and scleroderma.
- Autoinflammatory diseases (AID). In general, AID is caused by the defect or dysregulation in the innate immune system, and distinctively different from autoimmune diseases due to the lack of a primary pathogenic role for the adaptive immune system (e.g. autoreactive T-cells or autoantibody production).
- Heightened Inflammasome and IL-1 signaling pathways are known to be the main drivers for the severe and life-threatening systematic inflammation (or flare) seen in AID. However, pathological dysregulation of stress-sensing pathways (e.g. ER stress) or cross-talk with interferon pathways also contribute to the pathogenesis, suggesting that rheumatic diseases share common autoinflammatory components. This portfolio supports research on unveiling the mechanisms of pathogenesis, identifying causative environmental and genetic risk factors, developing translational models for diagnosis and treatment for AID.