Ruihua Chen
Bristol Myers Squibb, USA
Title: A high throughput platform for the identification of inhibitors of integrin-mediated TGFβ activation
Biography
Biography: Ruihua Chen
Abstract
Integrins and Transforming Growth Factor beta (TGFβ) regulate multiple cellular processes including adhesion, migration, proliferation, extracellular matrix (ECM) homeostasis and epithelial-mesenchymal transition. Integrin–mediated TGFβ activation has been indicated in pathological conditions including fibrogenesis and immune suppression. Macrophages are a major cellular source of TGFβ. Alteration of macrophage phenotypes and aberrant activation of TGFβ lead to several fibrotic and immune diseases therefore inhibitors of TGF-β activation have potential values in multiple therapeutic areas. We have developed de novo Homogenous Time Resolved Fluorescence 1536-well binding assays using multiple integrins to identify inhibitors and to support mechanism of action studies. Further, we have developed a high throughput Detroit 562 cell co-culture assay to measure TGFβ activation. In conjunction with these studies, we have also utilized a macrophage polarization model and developed cytokine and mRNA profiling assays to explore potential pharmacodynamic and/or disease biomarkers. These studies offer a novel platform to identify novel inhibitors of TGF beta signaling associated with specific subsets of integrins.