Epigenomics of Mutant p53

Icahn School Of Medicine At Mount Sinai, New York NY

Investigators

Abstract

PROJECT SUMMARY The primary objective of Core 1, “Epigenomics of mutant p53” is to provide state-of-the-art transcriptomic and epigenomic experimental approaches, next generation sequencing (NGS) expertise, computational analysis and bioinformatic tools for data visualization, and integration of large ‘omic datasets across all Projects of this PPG. Core 1 will also establish a reference epigenome for key experimental systems shared across Projects. Generation of chromatin states and complete transcriptomes will serve this PPG to develop novel hypotheses and enhance our understanding of mutant p53 enrichment patterns genome-wide. Importantly, Core 1 will standardize genomics techniques to ensure the highest quality data that can be directly compared across Projects. Core 1 will also manage the central data hub GOGO53 (Guardian Of the Genome Omics) through standardized bioinformatic analysis across all Projects. The Core will provide: 1) state-of-the art epigenomic studies to identify regulatory elements and transcription factor networks operating in the context of WT and mutant p53 (ATAC-seq, ChIP-seq, CUT&RUN/TAG), 2) integrated transcriptomic and epigenomic data to reveal direct (vs. indirect) target genes and identify altered p53 networks, 3) single cell technologies for transcript (scRNA-seq) and epigenetic (scATAC-seq) analyses, and 4) creation and maintenance of GOGO53, an interactive web-based platform to allow integration of all datasets across all Projects available to PPG users. These aims will apply to each Project individually, yet simultaneously promote synergy between the various mechanisms of p53 being investigated. This, in turn, will facilitate an in-depth understanding of the epigenetic and transcriptional mechanisms regulating aberrant oncogenic programs of mutant p53. In addition, the core will provide statistical support for all NGS-related studies, computational resource management, and training. Core 1 will be spearheaded by Dr. Emily Bernstein (Professor, Icahn School of Medicine at Mount Sinai), together with co-investigator Dr. Dan Hasson (Associate Professor, ISMMS) and Lead Bioinformatician Dr. Deniz Demircioglu (Assistant Professor, ISMMS). Dr. Bernstein has 20 years of experience in chromatin biology and >15 years in cancer biology; Dr. Hasson has >10 years of experience in epigenomic experimental approaches and computational genomics including designing computational pipelines, complex data analysis, and interpreting data across numerous biological contexts; Dr. Demircioglu has extensive experience in developing bioinformatic pipelines for NGS data analysis in the context of cancer. This strong and dedicated team, all located on the same floor at ISMMS, will work closely together to provide first-rate service to this P01.