The Johns Hopkins University received a $731,451 federal Project Grant award from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847). The 5-year project, commencing on May 1, 2024, aims to define biological drivers promoting early gastroesophageal junction (GEJ) cardia neoplastic evolution and elucidate the crosstalk between lipid metabolism and epigenomic reprogramming. Key research activities include assessing the effects of platelet-activating factor and free fatty acids on GEJ cardia organoid models, and investigating the functional regulation of GEJ cardia chromatin accessibility and activity by the HNF4A transcription factor. This work has the potential to uncover candidate approaches for preventing and intervening in early GEJ cardia neoplastic transformation.