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.
We will develop experimental and computational approaches to study epigenetic regulation in human cancers. We will reveal mechanisms underlying cancer development and progression. The written critiques and criteria scores of individual reviewers are provided in essentially unedited form in the Critique section below. Please note that these critiques and criteria scores were prepared prior to the meeting and may not have been revised subsequent to any discussions at the review meeting. The Resume and Summary of Discussion section above summarizes the final opinions of the committee.
|Gao, Shuai; Gao, Yanfei; He, Housheng Hansen et al. (2016) Androgen Receptor Tumor Suppressor Function Is Mediated by Recruitment of Retinoblastoma Protein. Cell Rep 17:966-976|
|Xu, Han; Xu, Kexin; He, Housheng H et al. (2016) Integrative Analysis Reveals the Transcriptional Collaboration between EZH2 and E2F1 in the Regulation of Cancer-Related Gene Expression. Mol Cancer Res 14:163-72|
|He, Housheng Hansen; Meyer, Clifford A; Hu, Sheng'en Shawn et al. (2014) Refined DNase-seq protocol and data analysis reveals intrinsic bias in transcription factor footprint identification. Nat Methods 11:73-8|
|Cai, Changmeng; He, Housheng Hansen; Gao, Shuai et al. (2014) Lysine-specific demethylase 1 has dual functions as a major regulator of androgen receptor transcriptional activity. Cell Rep 9:1618-27|