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2016 Scientific Report

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PETER W. LAIRD, PH.D. Dr. Laird earned his Ph.D. in 1988 from the University of Amsterdam with Piet Borst. Dr. Laird was a faculty member at the University of Southern California from 1996 to 2014, where he was Skirball-Kenis Professor of Cancer Research and directed the USC Epigenome Center. He joined VARI as a Professor in September 2014. STAFF KELLY FOY, B.S. TOSHINORI HINOUE, PH.D. KWANGHO LEE, PH.D. ZHOUWEI ZHANG, M.S. WANDING ZHOU, PH.D. STUDENT NICOLE VANDER SCHAAF, B.S. RESEARCH INTERESTS Our goal is to develop a detailed understanding of the molecular basis of human disease, with a particular emphasis on the role of epigenetics in cancer. Cancer is often considered to have a primarily genetic basis, with contributions from germline variations in risk and somatically acquired mutations, rearrangements, and copy number alterations. However, it is clear that nongenetic mechanisms can exert a powerful influence on cellular phenotype, as evidenced by the marked diversity of cell types within our bodies, which virtually all contain an identical genetic code. This differential gene expression is controlled by tissue-specific transcription factors and variations in chromatin packaging and modification, which can provide stable phenotypic states governed by epigenetic, not genetic, mechanisms. It seems intrinsically likely that an opportunistic disease such as cancer would take advantage of such a potent mediator of cellular phenotype. Our laboratory is dedicated to understanding how epigenetic mechanisms contribute to the origins of cancer and how to translate this knowledge into more-effective cancer prevention, detection, treatment, and monitoring. We use a multidisciplinary approach in our research, relying on mechanistic studies in model organisms and cell cultures, clinical and translational collaborations, genome-scale and bioinformatic analyses, and epidemiological studies to advance our understanding of cancer epigenetics. In recent years, we participated in the generation and analysis of high-dimensional epigenetic data sets, including the production of all epigenomic data for The Cancer Genome Atlas (TCGA) and the application of next-generation sequencing technology to single-base-pair-resolution, whole-genome DNA methylation analysis. We are leveraging this epigenomic data for translational applications and hypothesis testing in animal models. A major focus of our laboratory is to develop mouse models for investigating epigenetic mechanisms and drivers of cancer and to develop novel strategies for single-cell epigenomic analysis. 36 Van Andel Research Institute | Scientific Report

RECENT PUBLICATIONS Cancer Genome Atlas Research Network. 2016. Comprehensive molecular characterization of papillary renal-cell carcinoma. New England Journal of Medicine 374(2): 135–145. Ceccarelli, Michele, Floris P. Barthel, Tathiane M. Malta, Thais S. Sabedot, Sofie R. Salama, Bradley A. Murray, Olena Morozova, Yulia Newton, Arnie Radenbaugh, et al. 2016. Molecular profiling reveals biologically discrete subsets and pathways of progression in diffuse glioma. Cell 164(3): 550–563. Levine, A. Joan, Amanda I. Phipps, John A. Baron, Daniel D. Buchanan, Dennis J. Ahnen, Stacey Cohen, Noralane M. Lindor, Polly A. Newcomb, Christophe Rosty, et al. 2016. Clinicopathological risk factor distributions for MLH1 promoter region methylation in CIMP positive tumors. Cancer Epidemiology, Biomarkers and Prevention 25(1): 68–75. Ryland, Katherine E., Allegra G. Hawkins, Daniel J. Weisenberger, Vasu Punj, Scott C. Borinstein, Peter W. Laird, Jeffrey R. Martens, and Elizabeth R. Lawlor. 2016. Promoter methylation analysis reveals that SCNA5 ion channel silencing supports Ewing sarcoma cell proliferation. Molecular Cancer Research 14(1): 26–34. Cancer Genome Atlas Research Network. 2015. The molecular taxonomy of primary prostate cancer. Cell 163(4): 1011–1025. Ciriello, Giovanni, Michael L. Gatza, Andrew H. Beck, Matthew D. Wilkerson, Suhn K Rhie, Alessandro Pastore, Hailei Zhang, Michael McLellan, Christina Yau, et al. 2015. Comprehensive molecular portraits of invasive lobular breast cancer. Cell 163(2): 506–519. CENTER FOR EPIGENETICS 37

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