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2018 Scientific Report

  • Text
  • Institute
  • Biology
  • Methylation
  • Molecular
  • Mechanisms
  • Epigenetic
  • Michigan
  • Vari
  • Scientific

Center for Epigenetics

Center for Epigenetics SCOTT ROTHBART, Ph.D. Dr. Rothbart earned a Ph.D. in pharmacology and toxicology from Virginia Commonwealth University in 2010. He joined VARI in April 2015 as an Assistant Professor. RESEARCH INTERESTS The long-term goal of my research program is to define molecular mechanisms regulating chromatin modification signaling. Through a multidisciplinary and collaborative research program, we hope to translate basic knowledge of epigenetic mechanisms into therapeutic benefits. STAFF Evan Cornett, Ph.D. Bradley Dickson, Ph.D. Alison Lanctot, Ph.D. Amy Nelson Kevin Shaw, B.S. Rochelle Tiedemann, Ph.D. STUDENTS We are keen on understanding the complex relationship between DNA methylation and histone post-translational modifications (PTMs); these are two key epigenetic regulators of genome accessibility, interaction, and function. Within this broad framework, we ask 1) how are the writers and erasers of chromatin modifications regulated? 2) how do nuclear proteins and their complexes interface with (i.e., read) epigenetic marks to perform their chromatin regulatory functions? and 3) how does deregulation of chromatin signaling contribute to human diseases like cancer? We fabricate histone peptide microarrays in my lab as an integral part of our effort to characterize the complex interactions of proteins with the DNA and histone components of chromatin. We use this platform extensively to characterize the reader, writer, and eraser activities of chromatin regulators and also the behavior of antibodies that recognize histones and their PTMs. We are also developing new functional proteomics techniques to study the writers, erasers, and readers of lysine methylation signaling. Our studies are providing crucial systems-level information for the construction of lysine methylation signaling networks, are aiding drug discovery and development efforts, and are improving our understanding of lysine methylation function in human health and disease. Christine Ausherman Robert Vaughan, B.S. Philip Versluis 28 | VAN ANDEL RESEARCH INSTITUTE SCIENTIFIC REPORT

HUI SHEN, Ph.D. Dr. Shen earned her Ph.D. at the University of Southern California in genetic, molecular, and cellular biology. She joined VARI in September 2014 as an Assistant Professor. STAFF Huihui Fan, Ph.D. Hongbo Liu, Ph.D. Amy Nelson Wanding Zhou, Ph.D. RESEARCH INTERESTS The laboratory focuses on the epigenome and its interaction with the genome in various diseases, with a specific emphasis on cancers of women and cross-cancer comparisons. We use bioinformatics as a tool to understand the etiology, cell of origin, and epigenetic mechanisms of disease and to devise better approaches for cancer prevention, detection, therapy, and monitoring. We have extensive experience with genome-scale DNA methylation profiles in primary human samples, and we have made major contributions to epigenetic analysis within The Cancer Genome Atlas (TCGA). DNA methylation is ideally suited for deconstructing heterogeneity among cell types within a tissue sample. In cancer research, this approach can be used for cancer cell clonal evolution studies or for quantifying normal cell infiltration and stromal composition. The latter can provide insights into the tumor microenvironment, and in noncancer studies it can be a useful tool for accurately estimating cell populations and providing insights into lineage structures and population shifts in disease. In addition, we are interested in translational applications of epigenomic technology. To this end, we bring markers emerging from our bioinformatics analysis into clinical assay development, marker panel assembly, and optimization, with the ultimate goal of clinical testing and validation. VAN ANDEL RESEARCH INSTITUTE SCIENTIFIC REPORT | 29

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