Liver cancer is the third most common cause of cancer-related deaths globally, and patients with liver cancer currently have limited treatment options, including tumor ablation and liver transplant. More than half of the liver cancer cases have mutations in regulators of genome structure, which play a crucial role in cellular differentiation and development by controlling gene expression patterns. Lysine Methyl Transferases 2d (KMT2d) is one of the most frequently mutated regulators. However, we do not fully understand how changes in the KMT2d can drive liver cancer. In this project, I will investigate the mechanism in which KMT2d influences liver development as well as induces liver cancer from normal liver cells using organs that mimic human livers. Moreover, discovering its interaction partners, such as transcription factors that function in turning on and off genes, will provide more comprehensive mechanistic insight into the roles of KMT2d in liver formation and health. This study will advance fundamental knowledge for future research on the liver’s developmental biology and provide promising alternative therapeutic avenues for liver cancer.