Neha Khanna
Research Mentor(s): Eliza Tsou
Mentor Department: Internal Medicine
Authors: Neha Khanna, Alyssa Rosek, Olesya Plazyo, Johann Gudjosson, Eliza Pei-Suen Tsou, Dinesh Khanna
Session: Session 5 (2:00pm – 2:50pm)
Presentation Type: Poster 96
Abstract
Systemic sclerosis (Scleroderma, SSc) is a chronic autoimmune disorder that affects connective tissues, resulting in an overproduction of collagen. This leads to the thickening and hardening of the skin. In its limited form, SSc primarily affects the skin and underlying tissues, while in its diffuse form, it impacts internal organs such as the heart, lungs, and kidneys. Although the exact cause of SSc remains unclear, there is currently no cure. Existing treatments address symptoms but do not target the underlying causes of the disease. Therefore, developing therapies that focus on these underlying mechanisms is crucial. Our research centers on the Hippo pathway, a key regulator of cell proliferation, apoptosis, and stemness. This pathway involves interactions between the transcriptional co-activators YAP/TAZ and the TEAD family of transcription factors to regulate gene expression. In addition, VGLL3 acts as a coactivator by binding to TEADs. We have previously identified dysregulation of this pathway in SSc, with elevated transcriptional activity of YAP/TAZ proteins in SSc fibroblasts contributing to fibrosis. We also discovered that Verteporfin, a YAP inhibitor, can impede fibrosis in SSc. To deepen our understanding of the Hippo pathway’s impact on SSc fibrosis, we propose that targeting specific transcription factors or coactivators within this pathway will provide insights into its role in SSc. Our study focuses on TEAD1-4 and VGLL3 in SSc fibroblasts to evaluate their contributions to fibrosis. We plan to knock down these factors in SSc fibroblasts and assess changes in gene expression and cell functions like proliferation and migration. Our methods include tissue culture, quantitative PCR, proliferation assays, and scratch wound assays. Upon completing this project, we expect to gain valuable insights into the roles of specific Hippo pathway mediators in SSc fibrosis and clarify the contributions of each protein within this context. Our study aims to uncover the mechanistic involvement of the Hippo pathway, potentially leading to the development of more targeted therapies for SSc patients. In addition, these findings could have implications for treating other fibrotic diseases.
