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2016 Scientific Report

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STEPHEN B. BAYLIN, M.D.

STEPHEN B. BAYLIN, M.D. Dr. Baylin joined VARI as a Professor in the Center for Epigenetics in January 2015 and is co-leader of the VARI-SU2C Epigenetics Dream Team. He devotes a portion of his time to VARI. His primary appointment is with Johns Hopkins University as the Virginia and D.K. Ludwig Professor of Oncology and Medicine and co-head of Cancer Biology at the Sidney Kimmel Comprehensive Cancer Center. RESEARCH INTERESTS The Van Andel Research Institute–Stand Up To Cancer (VARI-SU2C) Epigenetics Dream Team is a multi-institutional effort to develop new epigenetic therapies against cancer and to move promising therapies to clinical trials. As co-leader, Dr. Baylin oversees the team’s research, which leverages the combined expertise of its members. Epigenetics is the study of how the packaging and modification of DNA influences the genes that are active or kept silent in a particular cell, and it holds untold potential for treating cancer and other diseases. Through a detailed understanding of how normal epigenetic processes work, scientists can identify erroneous epigenetic modifications that may contribute to the development and progression of cancer. Epigenetic therapies, which work by correcting these errors, have the potential to directly treat cancer and to sensitize patients to traditional treatments such as chemotherapy and radiation and to promising new immunotherapy approaches. The VARI-SU2C Epigenetics Dream Team is headquartered at VARI in Grand Rapids, Michigan, and it includes members from Johns Hopkins University, Memorial Sloan Kettering Cancer Center, Fox Chase Cancer Center/Temple University, University of Southern California, and Rigshospitalet/University of Copenhagen. The American Association for Cancer Research (AACR), as SU2C’s scientific partner, reviews projects and provides objective scientific oversight. RECENT PUBLICATIONS Chaiappinelli, Katherine B., Pamela L. Strissel, Alexis Desrichard, Huili Li, Christine Henke, Benjamin Akman, Alexander Hein, Neal S. Rote, Leslie M. Cope, et al. 2015. Inhibiting DNA methylation causes an interferon response in cancer via dsRNA including endogenous retroviruses. Cell 162(5): 961–973. 32 Van Andel Research Institute | Scientific Report

PETER A. JONES, PH.D., D.SC. Dr. Jones received his Ph.D. from the University of London. He joined the University of Southern California in 1977 and served as director of the USC Norris Comprehensive Cancer Center between 1993 and 2011. Dr. Jones joined VARI in 2014 as its Chief Scientific Officer and Director of the Center for Epigenetics. STAFF MINMIN LIU, PH.D. HITOSHI OTANI, PH.D. ROCHELE TIEDEMANN, PH.D. WANDING ZHOU, PH.D. ADJUNCT FACULTY RONALD CHANDLER, JR., PH.D. FEYRUZ RASSOOL, PH.D. RESEARCH INTERESTS Epigenetics may be defined as mitotically heritable changes in gene expression that are not caused by changes in the DNA sequence itself. Epigenetic processes establish the differentiated state of cells and govern how genes are used to allow organs and cells to function correctly and inherit their properties through cell division. In the case of diseases such as cancer, these processes can go wrong, changing the behavior of cells to adverse effect. However, many of these changes are potentially reversible by treatment with drugs. Because epigenetic processes are at the root of biology, they have implications for all of human development and disease. Our laboratory studies the mechanisms by which epigenetic processes become misregulated in cancer and contribute to the disease phenotype. We focus on the role of DNA methylation in controlling the expression of genes during normal development and in cancer. Our work has shifted to a holistic approach in which we are interested in the interactions between processes such as DNA methylation, histone modification, and nucleosomal positioning in the epigenome, and we want to determine how mutations in the genes which modify the epigenome contribute to the cancer phenotype. We have had a long-term interest in the mechanism of action of DNA methylation inhibitors, both in the lab and in the clinic. We are working with several major institutions to bring epigenetic therapies to the forefront of cancer medicine. RECENT PUBLICATIONS Lay, Fides D., Yaping Liu, Theresa K. Kelly, Heather Witt, Peggy J. Farnham, Peter A. Jones, and Benjamin P. Berman. 2015. The role of DNA methylation in directing the functional organization of the cancer epigenome. Genome Research 25(4): 467–477. Roulois, David, Helen Loo Yau, Rajat Singhania, Yadong Wang, Amavaz Danesh, Shu Yi Shen, Han Han, Gangning Liang, Peter A. Jones, et al. 2015. DNA-demethylating agents target colorectal cancer cells by inducing viral mimicry by endogenous transcripts. Cell 162(5): 961–973. Statham, Aaron L., Phillippa C. Taberlay, Theresa K. Kelly, Peter A. Jones, and Susan J. Clark. 2015. Genome-wide nucleosome occupancy and DNA methylation profiling of four human cell lines. Genomics Data 3: 94–96. CENTER FOR EPIGENETICS 33

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