The Chen laboratory investigates the molecular, biological, and therapeutic potential of WEE1 in esophageal adenocarcinoma (EAC). The hypothesis is that smoking-induced aberrant overexpression of WEE1 provides a full pro-survival advantage to cancer cells. Targeting the WEE1 could be a novel therapeutic approach in EAC. Dr. Chen's study is significant and can positively impact not only by revealing a novel molecular WEE1 signaling axis but also because of its translational components. The translational studies include 1. identifying potential therapeutic response biomarkers using RNA-seq in 3 best versus three worst WEE1 inhibitors (MK1775) PDX responders. 2. determining the potential therapeutic efficacy of MK1775 as a single agent or in combination with FDA-approved anti-cancer drugs in pre-clinical settings predicted by complex computational therapeutics approach using SynergySeq. The integrated molecular, functional, and translational approaches are expected to provide a novel understanding of EAC's biology and molecular basis. The results can lay the foundation for evidence-based therapy and swiftly be translated to improve EAC patients' therapy and prognosis.