Profile
Our laboratory focuses on unravelling how transposable elements contribute to human cancers. About half of the human genome is derived from transposons and their genetic remnants. Although most transposons are currently inactive, a small fraction among them, mainly retrotransposons LINE-1, Alu and SVA elements are still mobile. Other retrotransposons include human endogenous retroviruses that are not mobile, however, they contain functional promoters and splice sites that can cause aberrant expression or structural changes to nearby genes. Retrotransposons are epigenetically silenced in normal cells, however, cancer cells exhibit widespread expression of retrotransposons along with a global loss of DNA methylation. We are interested in deciphering how retrotransposon silencing is lost in various human cancers. In addition, we are interested in understanding how derepressed retrotransposons alter the regulation and structure of nearby genes. These studies will be crucial in understanding tumour properties such as chemoresistance and help in developing targeted immunotherapeutic approaches.
Current Focus Areas
Understanding how the epigenetic repression of retrotransposons is lost in human cancers and how that contributes to tumorigenesis. We are currently studying this in breast cancer and pancreatic neuroendocrine cancers. We use integrative wet-lab and computational approaches to identify aberrant retrotransposon expression and epigenetic silencing mechanisms controlling their expression.
Selected Publications
Das S, Senapati P, Chen Z, Reddy MA, Ganguly R, Lanting LL, Mandi V, Bansal A, Leung A, Zhang S, Jia Y, Wu X, Schones, DE, Natarajan R. (2017) Regulation of Angiotensin II Actions by Enhancers and Super-enhancers in Vascular Smooth Muscle Cells. Nature Communications; 13;8(1):1467.
Senapati P, Kato H, Lee M, Leung A, Thai C, Sanchez A, Gallagher EJ, LeRoith D, Seewaldt VL, Ann DK, Schones DE. (2019) Hyperinsulinemia promotes aberrant histone acetylation in triple-negative breast cancer. Epigenetics & Chromatin; 12(1):44.
Senapati P, Bhattacharya A, Das S, Dey S, Sudarshan D, Shyla G, Vishwakarma J, Sudevan S, Ramachandran R, Maliekal TT, Kundu TK. (2022) Histone chaperone Nucleophosmin regulates transcription of key genes involved in oral tumorigenesis. Molecular and Cellular Biology; 42(2):e0066920.
Senapati P, Miyano M, Basam M, Sayaman RW, Leung A, LaBarge MA, Schones DE. (2023) Loss of epigenetic suppression of retrotransposons with oncogenic potential in aging mammary luminal epithelial cells. Genome Res; 33(8):1229-1241.
Shin H, Leung A, Costello KR, Senapati P, Kato H, Schones DE. (2023) Glucose-regulated O-GlcNAcylation of DNMT1 inhibits DNA methyltransferase activity and maintenance of genomic methylation. Elife; 12:e85595.