5145 Terasaki Life Sciences
|Associate Professor, Molecular, Cell, and Developmental Biology, Biological Chemistry|
|Member, Bioinformatics GPB Home Area, Cell & Developmental Biology GPB Home Area, Gene Regulation GPB Home Area, Molecular Pharmacology GPB Home Area, themes|
Because uncontrolled cell division is so dangerous for an organism, cells must know not only when to divide, but also when not to. Cell division arrest prevents tumors and maintains the proper form of tissues. Many cells must also retain the ability to start dividing again when conditions are right, e.g., when the organism must grow, or a damaged tissue must be repaired. A cell in such a temporary, non-dividing state is said to be quiescent. Quiescence is a common state for many somatic cells, including fibroblasts, lymphocytes, hematopoietic stem cells, and even dormant tumor cells. Failure to appropriately regulate the transition between quiescence and proliferation underlies several common and lethal disorders, such as cancer, fibrosis and autoimmune diseases. Yet, despite its prevalence and medical importance, and in stark contrast to our detailed understanding of cell proliferation, we know remarkably little about quiescence. My research has focused on understanding the molecular basis of quiescence. While the commonly-held perception of quiescence is as a sleepy or default state, my research suggests that quiescence is an active and highly regulated process. My laboratory has used sophisticated technologies and computational approaches to understand the cellular networks that underlie quiescence. We have applied next generation sequencing, mass spectrometry proteomics and mass spectrometry metabolomics to generate high-quality datasets defining the characteristics of proliferating and quiescent cells. We have also developed computational and algorithmic approaches for analyzing and interpreting these datasets. As one example, we used a metabolomics-based strategy to define the metabolic changes in quiescent compared with proliferating fibroblasts, and discovered an important survival pathway for the quiescent cells. This work led to the identification of specific small molecules and combinations of small molecules that selectively target either proliferating or quiescent fibroblasts for apoptotic cell death. Our goals are to translate these findings to understanding the changes that occur during tumor dormancy. We are also applying similar approaches to understand the changes that occur when fibroblasts become activated to cancer-associated fibroblasts.
Evertts Adam G, Manning Amity L, Wang Xin, Dyson Nicholas J, Garcia Benjamin A, Coller Hilary A H4K20 methylation regulates quiescence and chromatin compaction. Molecular biology of the cell. 2013; .
Coller Hilary A, Coller Hilary A Introducing the systems biology of cell state regulation section of Physiological Genomics. Physiological genomics. 2013; 45(11): 407-8.
Jiang Peng, Singh Mona, Coller Hilary A Computational assessment of the cooperativity between RNA binding proteins and microRNAs in transcript decay. PLoS computational biology. 2013; 9(5): e1003075.
Evertts Adam G, Zee Barry M, Dimaggio Peter A, Gonzales-Cope Michelle, Coller Hilary A, Garcia Benjamin A Quantitative dynamics of the link between cellular metabolism and histone acetylation. The Journal of biological chemistry. 2013; 288(17): 12142-51.
Suh Eric J, Remillard Matthew Y, Legesse-Miller Aster, Johnson Elizabeth L, Lemons Johanna Ms, Chapman Talia R, Forman Joshua J, Kojima Mina, Silberman Eric S, Coller Hilary A A microRNA network regulates proliferative timing and extracellular matrix synthesis during cellular quiescence in fibroblasts. Genome biology. 2012; 13(12): R121.
Evertts Adam G, Coller Hilary A Back to the origin: reconsidering replication, transcription, epigenetics, and cell cycle control. Genes & cancer. 2012; 3(11-12): 678-96.
Legesse-Miller Aster, Raitman Irene, Haley Erin M, Liao Albert, Sun Lova L, Wang David J, Krishnan Nithya, Lemons Johanna M S, Suh Eric J, Johnson Elizabeth L, Lund Benjamin A, Coller Hilary A Quiescent fibroblasts are protected from proteasome inhibition-mediated toxicity. Molecular biology of the cell. 2012; 23(18): 3566-81.
Valcourt James R, Lemons Johanna M S, Haley Erin M, Kojima Mina, Demuren Olukunle O, Coller Hilary A Staying alive: metabolic adaptations to quiescence. Cell cycle. 2012; 11(9): 1680-96.
Ventura-Clapier Rene, Coller Hilary A A step toward systems metabolomics. Physiological genomics. 2012; 44(7): 383-5.
Waldron Levi, Coller Hilary A, Huttenhower Curtis Integrative approaches for microarray data analysis. Methods in molecular biology. 2012; 802(4): 157-82.
Wang David J, Legesse-Miller Aster, Johnson Elizabeth L, Coller Hilary A Regulation of the let-7a-3 promoter by NF-kB. PloS one. 2012; 7(2): e31240.
Coller Hilary A Cell biology. The essence of quiescence. Science. 2011; 334(6059): 1074-5.
Guo Jessie Yanxiang, Chen Hsin-Yi, Mathew Robin, Fan Jing, Strohecker Anne M, Karsli-Uzunbas Gizem, Kamphorst Jurre J, Chen Guanghua, Lemons Johanna M S, Karantza Vassiliki, Coller Hilary A, Dipaola Robert S, Gelinas Celine, Rabinowitz Joshua D, White Eileen Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis. Genes & development. 2011; 25(5): 460-70.
Lemons Johanna M S, Feng Xiao-Jiang, Bennett Bryson D, Legesse-Miller Aster, Johnson Elizabeth L, Raitman Irene, Pollina Elizabeth A, Rabitz Herschel A, Rabinowitz Joshua D, Coller Hilary A Quiescent fibroblasts exhibit high metabolic activity. PLoS biology. 2010; 8(10): e1000514.
Wellen Kathryn E, Lu Chao, Mancuso Anthony, Lemons Johanna M S, Ryczko Michael, Dennis James W, Rabinowitz Joshua D, Coller Hilary A, Thompson Craig B The hexosamine biosynthetic pathway couples growth factor-induced glutamine uptake to glucose metabolism. Genes & development. 2010; 24(24): 2784-99.
Forman Joshua J, Coller Hilary A The code within the code: microRNAs target coding regions. Cell cycle. 2010; 9(8): 1533-41.
Ward Patrick S, Patel Jay, Wise David R, Abdel-Wahab Omar, Bennett Bryson D, Coller Hilary A, Cross Justin R, Fantin Valeria R, Hedvat Cyrus V, Perl Alexander E, Rabinowitz Joshua D, Carroll Martin, Su Shinsan M, Sharp Kim A, Levine Ross L, Thompson Craig B The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. Cancer cell. 2010; 17(3): 225-34.
Sang Liyun, Roberts James M, Coller Hilary A Hijacking HES1: how tumors co-opt the anti-differentiation strategies of quiescent cells. Trends in molecular medicine. 2010; 16(1): 17-26.
Huttenhower Curtis, Mutungu K Tsheko, Indik Natasha, Yang Woongcheol, Schroeder Mark, Forman Joshua J, Troyanskaya Olga G, Coller Hilary A Detailing regulatory networks through large scale data integration. Bioinformatics. 2009; 25(24): 3267-74.
Sang Liyun, Coller Hilary A Fear of commitment: Hes1 protects quiescent fibroblasts from irreversible cellular fates. Cell cycle. 2009; 8(14): 2161-7.
Huttenhower Curtis, Haley Erin M, Hibbs Matthew A, Dumeaux Vanessa, Barrett Daniel R, Coller Hilary A, Troyanskaya Olga G Exploring the human genome with functional maps. Genome research. 2009; 19(6): 1093-106.
Legesse-Miller Aster, Elemento Olivier, Pfau Sarah J, Forman Joshua J, Tavazoie Saeed, Coller Hilary A let-7 Overexpression leads to an increased fraction of cells in G2/M, direct down-regulation of Cdc34, and stabilization of Wee1 kinase in primary fibroblasts. The Journal of biological chemistry. 2009; 284(11): 6605-9.
Sudo Hiroko, Li-Sucholeiki Xiao-Cheng, Marcelino Luisa A, Gruhl Amanda N, Herrero-Jimenez Pablo, Zarbl Helmut, Willey James C, Furth Emma E, Morgenthaler Stephan, Coller Hilary A, Ekstrom Per O, Kurzweil Ray, Gostjeva Elena V, Thilly William G Fetal-juvenile origins of point mutations in the adult human tracheal-bronchial epithelium: absence of detectable effects of age, gender or smoking status. Mutation research. 2008; 646(1-2): 25-40.
Coller Hilary A, Kruglyak Leonid Genetics. It's the sequence, stupid!. Science. 2008; 322(5900): 380-1.
Forman Joshua J, Legesse-Miller Aster, Coller Hilary A A search for conserved sequences in coding regions reveals that the let-7 microRNA targets Dicer within its coding sequence. Proceedings of the National Academy of Sciences of the United States of America. 2008; 105(39): 14879-84.
Sang Liyun, Coller Hilary A, Roberts James M Control of the reversibility of cellular quiescence by the transcriptional repressor HES1. Science. 2008; 321(5892): 1095-100.
Pollina Elizabeth A, Legesse-Miller Aster, Haley Erin M, Goodpaster Tracy, Randolph-Habecker Julie, Coller Hilary A Regulating the angiogenic balance in tissues. Cell cycle. 2008; 7(13): 2056-70.
Goodpaster Tracy, Legesse-Miller Aster, Hameed Meera R, Aisner Seena C, Randolph-Habecker Julie, Coller Hilary A An immunohistochemical method for identifying fibroblasts in formalin-fixed, paraffin-embedded tissue. The journal of histochemistry and cytochemistry. 2008; 56(4): 347-58.
Coller Hilary A, Forman Joshua J, Legesse-Miller Aster "Myc'ed messages": myc induces transcription of E2F1 while inhibiting its translation via a microRNA polycistron. PLoS genetics. 2007; 3(8): e146.
Miller Daniel L, Myers Chad L, Rickards Brenden, Coller Hilary A, Flint S Jane Adenovirus type 5 exerts genome-wide control over cellular programs governing proliferation, quiescence, and survival. Genome biology. 2007; 8(4): R58.
Huttenhower Curtis, Flamholz Avi I, Landis Jessica N, Sahi Sauhard, Myers Chad L, Olszewski Kellen L, Hibbs Matthew A, Siemers Nathan O, Troyanskaya Olga G, Coller Hilary A Nearest Neighbor Networks: clustering expression data based on gene neighborhoods. BMC bioinformatics. 2007; 8(8): 250.
Coller Hilary A What's taking so long? S-phase entry from quiescence versus proliferation. Nature reviews. Molecular cell biology. 2007; 8(8): 667-70.
Munger Joshua, Bajad Sunil U, Coller Hilary A, Shenk Thomas, Rabinowitz Joshua D Dynamics of the cellular metabolome during human cytomegalovirus infection. PLoS pathogens. 2006; 2(12): e132.
Zheng Weiming, Khrapko Konstantin, Coller Hilary A, Thilly William G, Copeland William C Origins of human mitochondrial point mutations as DNA polymerase gamma-mediated errors. Mutation research. 2006; 599(1-2): 11-20.
Coller Hilary A, Sang Liyun, Roberts James M A new description of cellular quiescence. PLoS biology. 2006; 4(3): e83.
Coller Hilary A, Khrapko Konstantin, Herrero-Jimenez Pablo, Vatland Janice A, Li-Sucholeiki Xiao-Cheng, Thilly William G Clustering of mutant mitochondrial DNA copies suggests stem cells are common in human bronchial epithelium. Mutation research. 2005; 578(1-2): 256-71.
Smith Laura L, Coller Hilary A, Roberts James M Telomerase modulates expression of growth-controlling genes and enhances cell proliferation. Nature cell biology. 2003; 5(5): 474-9.
Coller Hilary A, Bodyak Natalya D, Khrapko Konstantin Frequent intracellular clonal expansions of somatic mtDNA mutations: significance and mechanisms. Annals of the New York Academy of Sciences. 2002; 959(5): 434-47.