Core 3 - Epigenomics Core

Project Summary – Core 3 – Epigenomics Core Broad Institute The overall goal of the core is to study the key features of epigenetic features in myeloma and improve our understanding of global gene regulation to deploy novel therapeutics that target key epigenomic factors. Cells and cell states can be defined by their gene expression programs, and tumor cells commonly have deregulated gene expression programs. This core will perform epigenomic analyses on clinical samples from Projects 1 as well as preclinical samples in Project 2, 3 and 4 at bulk and single cell level. Specifically, samples will be obtained from patients enrolled on the previous clinical trial (IFM/DFCI 2009) and the newer IFM-2020-02 trial (evaluating an MRD-based therapeutic algorithms at time of diagnosis and at relapse) in Project 1. In each case, tumor cells will be isolated in Core 2 using well established procedures. This core will perform analysis for epigenetic regulatory factors. The core has capabilities to perform ATAC-seq, MINT ChIP-seq using low cell number (5000 cells; van Galen et al, Molecular Cell 2016 Jan;61(1):1-11), perform single-cell multi-omics (Ma et al, Cell, 2020, 183, 1103–1116.e20) as well as adopt innovative variations specifically needed to answer questions. The core will help with analysis of the generated data and accurately chart maps of epigenetic modifications and related chromatin structures in myeloma. It will work with Core 5 to help integrate these results with other genomic correlates.