PROJECT SUMMARY / ABSTRACT Dr. Minmin Liu and the Unit Director, Dr. Peter A. Jones, have closely collaborated since 2012, resulting in a significant number of high-quality publications that have had a major impact on the field of cancer epigenetics. Dr. Liu possesses a strong foundation in biomedical sciences, covering biochemistry, microbiology, immunology, molecular biology, structural biology, genetics, and epigenetics. Her skill set includes a diverse range of techniques crucial for the proposed study, including the use of next-generation sequencing for epigenome research. In addition to her wet-lab expertise, she is proficient in computational and bioinformatics tools for genomic and epigenomic data analysis. Dr. Liu's unique qualifications, extensive research background, specialized expertise, and proven scientific contributions make her an exceptional asset to the team. The objective of this proposal is to support Dr. Liu's career development as a research specialist to continue making significant contributions to Dr. Jones' established research program, funded by the NCI. Dr. Liu is currently addressing the following questions: 1) Does DNMT3A2 overexpression contribute to carcinogenesis? 2) How does de novo methylation occur in a nucleosomal context? 3) What are the potential biological roles of hemimethylation? The aims of her future studies are to identify novel protein isoforms for epigenetic modifiers and study their roles during tumorigenesis, as well as to explore the role of hemimethylation in both stem cell development and cancer. These projects will provide new insights into how the abnormal epigenome is shaped in cancer and will lead to the development of novel methods for measuring genome-wide hemimethylation. This award will provide Dr. Liu with the freedom and security to advance her research in cancer epigenetics and support the research program of the Jones group.