Siraad Belcher
Research Mentor(s): Mohammad Amin
Mentor Department: Internal Medicine – Rheumatology
Authors: John Varga
Session: Session 4 (1:00pm – 1:50pm)
Presentation Type: Poster 95
Abstract
Systemic sclerosis (SSc) is a severe autoimmune condition where progressive skin, lung, and vital organ fibrosis leads to organ failure and elevated mortality rates. Despite its severity, the underlying mechanisms of SSc remain poorly understood, and no effective treatment currently exists. Unraveling these mechanisms is crucial for developing targeted therapies that can target fibrosis progression. The continuous activation of fibroblasts into myofibroblasts produces excessive profibrotic factors such as alpha-smooth muscle actin, leading to fibrosis in SSc. The Varga Lab discovered that nicotinamide adenine dinucleotide (NAD) deficiency is a primary driver of myofibroblast activation and fibrosis development. This deficiency is largely caused by the enzyme nicotinamide N-methyltransferase (NNMT), which significantly depletes NAD levels. Our laboratory’s research found that inhibiting NNMT significantly reduces profibrotic factors, highlighting NNMT as a potential therapeutic target for treating SSc and other fibrotic conditions. Our research focuses on mapping the molecular pathways in SSc to determine how NNMT inhibition affects TGF-ß1 treated fibroblasts using foundational laboratory methods such as protein quantification, PCR, Western blotting, and immunofluorescence. Studying the NNMT inhibitor’s effects on profibrotic factors helps improve knowledge of pathogenesis involved in SSc while supporting new treatment development for fibrotic conditions. This project may demonstrate the role of NNMT as a new therapeutic target to treat fibrotic diseases such as SSc.
