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.
Jiang P, Singh M, Coller HA., "Computational assessment of the cooperativity between RNA binding proteins and MicroRNAs in Transcript Decay", PLoS Comput Biol, 9 (5): e1003075.- (2013) [link].
Introducing the systems biology of cell state regulation section of physiological genomics, "Coller, H.A", Physiological Genomics, 45 (11): 407-408 (2013) .
Evertts, A., Zee, B.M., DiMaggio, P.A., Gonzales-Cope, M., Coller, H.A. and Garcia, B.A., "Quantitative dynamics of the link between cellular metabolism and histone acetylation", Journal of Biological Chemistry, 288 (17): -12151 (2013) .
Klionsky et al., "Guidelines for the use and interpretation of assays for monitoring autophagy", Autophagy, 8 (4): 445-544 (2013) .
Sang, L. and Coller, H.A., "Fear of commitment: Hes1 protects quiescent fibroblasts from irreversible cellular fates", Cell Cycle, 8 (14): 2161-2167 (2013) .
Coller, H.A. and Kruglyak, L., "It's the sequence, stupid!", Science, 322 (5900): 380-381 (2013) .
Evertts AG, Coller HA., "Back to the origin: reconsidering replication, transcription, epigenetics, and cell cycle control", Genes Cancer, 3 (11-12): 678-696 (2012) [link].
Suh, E.J., Remillard, M.Y., Legesse-Miller, A., Johnson, E.L. Lemons, J.M.S., Chapman, T.R., Forman, J.J., Kojima, M., Silberman, E.S., and Coller, H.A., "A microRNA network regulates proliferative timing and extracellular matrix synthesis during cellular quiescence in fibroblasts", Genome Biology, 13 (12): R121- (2012) .
Legesse-Miller, A., Raitman, I., Haley, E.M., Liao, A., Sun, L., Wang, D.J., Suh, E.J., Johnson, E.L., Lund, B., and Coller, H.A., "Quiescent fibroblasts are protected from proteasome inhibition-mediated toxicity", Molecular Biology of the Cell, 23 (18): 3566-3581 (2012) .
Jiang, P., and Coller, H.A. (2012), "Functional interactions between microRNAs and RNA binding proteins", microRNA, 1 (1): 70-79 (2012) .