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The Ray lab seeks to provide molecular-level insights into the mechanisms of post-translational protein modifications (PTMs) driving cancer progression and therapy resistance. We utilize clinical and preclinical models and combine with advanced genomic, proteomic, and biochemical approaches to identify molecular mediators of gastrointestinal (GI) cancers. Our ongoing research revealing novel roles of interferon stimulated gene 15 (ISG15), a ubiquitin like (UBL) protein, causing therapy resistance in esophageal adenocarcinoma (EAC), one of the fastest growing cancers in the Western World with a 5-year survival below 20%. During this presentation, we will focus on discussing our mechanistic insight how ISG15 is exerting pleotropic effects by (i) activating DNA damage repair (DDR) pathways to cause radioresistance; and (ii) causing T-cell anergy to dampen immunotherapy efficacy, thus promoting EAC progression. |