Project 4 - PI Varga

CURRENT MCRC PROJECT
Genetic polymorphisms of TGF-ß associated with systemic sclerosis (SSc)

Scleroderma or systemic sclerosis (SSc) is a chronic autoimmune disease that affects predominantly postwomen. Fibrosis in multiple organs is a hallmark of the disease and accounts for substantial morbidity and mortality. The cause is unknown and there is no effective disease modifying therapy. TGF-ß plays a key role in inducing fibrosis and has been implicated in the pathogenesis of SSc. THG-ß signals via two membrane receptors and downstream Smad signaling pathways to induce the transcription of collagen and smooth muscle actin genes. Our team of investigators including Drs Pasche, Varga and Hinchcliff hypothesized that genetic variations in the TGF-ß pathway may be a risk factor for the development of SSc.  The project merges basic discoveries identified in the laboratory of Dr. Boris Pasche on SNPs in TGF-ß receptor alleles associated with cancer with the clinical databases and registry of SSc patients at Northwestern. The expectation is that identifying specific genetic polymorphisms that are risk factors for SSc provides new insight into SSc pathogenesis. Moreover, identifying specific SSc endophenotypes associated with distinct genetic polymorphisms in the TGF-ß signaling axis might also aid in a pathomechanism-based patient classification and risk stratification, leading ultimately toward personalized medicine.