This is the NIH Pathway to Independence Award (K99/R00) application proposal Epigenetic Regulators in Cancer Development and Progression by Dr. Housheng Hansen He, an experimentally and computationally trained Instructor in the Department of Medical Oncology at Dana-Farber Cancer Institute (DFCI). Dr. He is committed to a research career in Cancer genomics and epigenomics, his long-term goal is to understand mechanisms underlying cancer development and progression, and his short- term goal is to develop genomic approach to investigate the function of epigenetic regulators in cancers. This application includes research plan for the k99 phase and the R00 phase, a letter from Dr. James Griffin, Chair of the Department of Medical Oncology, DFCI, detailing the institutional commitment, and details for Dr. He's career development plan. The proposed research contains three major aims: (1) Develop chromatin dynamics as an effective approach to infer transcription factor binding (K99 phase), (2) Define epigenetic regulator transcription network using chromatin dynamics (K99 phase) and (3) Decipher the role of interactions between noncoding RNAs and the epigenetic regulator LSD1 in prostate cancer development and progression (R00 phase). The proposed K99 phase study is derived from Dr. He's previous research, and the approach will be developed in this phase will be applied to study the mechanism of epigenetic regulation in cancer development and progression in the R00 phase. The career development for Dr. He and accomplishment of the research aims will be facilitated by excellent research and career supporting resources available at DFCI.