Carolyn Phillips
Center, Institute & Lab Affiliations
- USC Norris Comprehensive Cancer Center, Member of the Genomic and Epigenomic Regulation Program
Education
- Ph.D. Molecular and Cell Biology, University of California – Berkeley, 2007
- B.S. Biological Sciences, University of California – Davis, 2001
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- Marion Abbe Fellow of the Damon Runyon Cancer Research Foundation, Massachusetts General Hospital and Harvard Medical School , 2008 – 2014
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Summary Statement of Research Interests
Small RNA pathways protect the genome against foreign RNAs, such as viruses, in addition to regulating many endogenous RNAs, including aberrant transcripts, pseudogenes, and non-coding regions. The Phillips lab uses genetics, cell biology, and biochemistry to understand how RNA silencing pathways modulate gene expression and maintain genome integrity. Small RNAs are generally ~20-30 nucleotides in length and associate with an Argonaute protein. There are three major classes of small RNAs – microRNAs (miRNAs), small-interfering RNAs (siRNAs), and Piwi-interacting RNAs (piRNAs), which are defined by their mode of biogenesis, protein cofactors, and mechanism of action. We and others have identified a group of genes (the mutator class) that are required for RNA interference (RNAi), transposon silencing, and production of endogenous siRNAs (endo-siRNAs) in the nematode, C. elegans. The mutator genes act downstream of primary siRNAs (produced by the endoribonuclease, Dicer) and piRNAs, and are required for the production of 22-nt “secondary” siRNAs. Our research will have important implications in the understanding of how RNA silencing pathways inhibit transposon movement and repress aberrant RNAs to prevent deleterious gene mutations that can result in infertility, birth defects, as well cancer and other diseases.
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Book Chapters
- Phillips, C. M., McDonald, K. L., Dernburg, A. F. (2009). Cytological analysis of meiosis in Caenorhabditis elegans. (Vol. 558) pp. 171-95. Methods in molecular biology (Clifton, N.J.). PubMed Web Address
Journal Article
- Chen, S., Phillips, C. M. (2024). HRDE-2 drives small RNA specificity for the nuclear Argonaute protein HRDE-1. Nature communications. Vol. 15 (1), pp. 957. PubMed Web Address
- Chen, S., Phillips,Chen, C. M., Phillips, C. M. (2024). Silencing of a NRDE-3 transgene in C. elegans germ cells and early embryos is mediated by the RNAi pathway. microPublication biology. Vol. 2024 PubMed Web Address
- Uebel, C. J., Rajeev, S., Phillips, C. M. (2023). Caenorhabditis elegans germ granules are present in distinct configurations and assemble in a hierarchical manner. Development (Cambridge, England). Vol. 150 (24) PubMed Web Address
- Phillips, C. M., Updike,Phillips, D. L., Updike, D. L. (2022). Germ granules and gene regulation in the Caenorhabditis elegans germline. Genetics. Vol. 220 (3) PubMed Web Address
- Schreier, J., Dietz, S., Boermel, M., Oorschot, V., Seistrup, A. S., de, A. M., Bronkhorst, A. W., Nguyen, D. A., Phillis, S., Gleason, E. J., L’Hernault, S. W., Phillips, C. M., Butter, F., Ketting,Schreier, R. F., Dietz, S., Boermel, M., Oorschot, V., Seistrup, A. S., de, A. M., Bronkhorst, A. W., Nguyen, D. A., Phillis, S., Gleason, E. J., L’Hernault, S. W., Phillips, C. M., Butter, F., Ketting, R. F. (2022). Membrane-associated cytoplasmic granules carrying the Argonaute protein WAGO-3 enable paternal epigenetic inheritance in Caenorhabditis elegans. Nature cell biology. Vol. 24 (2), pp. 217-229. PubMed Web Address
- Nguyen, D. A., Phillips,Nguyen, C. M., Phillips, C. M. (2021). Arginine methylation promotes siRNA-binding specificity for a spermatogenesis-specific isoform of the Argonaute protein CSR-1. Nature communications. Vol. 12 (1), pp. 4212. PubMed Web Address
- Uebel, C. J., Manage, K. I., Phillips,Uebel, C. M., Manage, K. I., Phillips, C. M. (2021). SIMR foci are found in the progenitor germ cells of C. elegans embryos. microPublication biology. Vol. 2021 PubMed Web Address
- Rogers, A. K., Phillips,Rogers, C. M., Phillips,Rogers, C. M., Phillips, C. M. (2020). A Small-RNA-Mediated Feedback Loop Maintains Proper Levels of 22G-RNAs in C. elegans. Cell reports. Vol. 33 (3), pp. 108279. PubMed Web Address
- Uebel, C. J., Agbede, D., Wallis, D. C., Phillips, C. M. (2020). Mutator Foci Are Regulated by Developmental Stage, RNA, and the Germline Cell Cycle in Caenorhabditis elegans. G3 (Bethesda, Md.). Vol. 10 (10), pp. 3719-3728. PubMed Web Address
- Rogers, A. K., Phillips, C. M. (2020). RNAi pathways repress reprogramming of C. elegans germ cells during heat stress. Nucleic acids research. Vol. 48 (8), pp. 4256-4273. PubMed Web Address
- Manage, K. I., Rogers, A. K., Wallis, D. C., Liebel, C. J., Anderson, D. C., Nguyen, D. A., Arca, K., Brown, K. C., Rodrigues, R. J., de Albuquerque, B. F., Ketting, R. F., Montgomery, T. A., Phillips, C. M. (2020). A tudor domain protein, SIMR-1, promotes siRNA production at piRNA-targeted mRNAs in C. elegans. ELIFE. Vol. 9, pp. e56731. PubMed Web Address
- Rogers, A. K., Phillips, C. M. (2020). Disruption of the mutator complex triggers a low penetrance larval arrest phenotype. microPublication biology. Vol. 2020 PubMed Web Address
- Wallis, D. C., Nguyen, D. A., Uebel, C. J., Phillips, C. M. (2019). Visualization and Quantification of Transposon Activity in Caenorhabditis elegans RNAi Pathway Mutants. G3 (Bethesda, Md.). Vol. 9 (11), pp. 3825-3832. PubMed Web Address
- Winkenbach, L. P., Doser, R., Reed, K. J., Pasquinelli, A. E., Phillips, C. M., Claycomb, J. M. (2019). Todos Santos small RNA symposium. RNA biology. pp. 1-5. PubMed Web Address
- Svendsen, J. M., Reed, K. J., Vijayasarathy, T., Montgomery, B. E., Tucci, R. M., Brown, K. C., Marks, T. N., Nguyen, D. A., Phillips, C. M., Montgomery, T. A. (2019). henn-1/HEN1 Promotes Germline Immortality in Caenorhabditis elegans. Cell reports. Vol. 29 (10), pp. 3187-3199.e4. PubMed Web Address
- Uebel, C. J., Phillips, C. M. (2019). Phase-separated protein dynamics are affected by fluorescent tag choice. microPublication biology. PubMed Web Address
- Uebel, C. J., Anderson, D. C., Mandarino, L. M., Manage, K. I., Aynaszyan, S., Phillips, C. M. (2018). Distinct regions of the intrinsically disordered protein MUT-16 mediate assembly of a small RNA amplification complex and promote phase separation of Mutator foci. PLoS genetics. Vol. 14 (7), pp. e1007542. PubMed Web Address
- Wan, G., Fields, B. D., Spracklin, G., Shukla, A., Phillips, C. M., Kennedy, S. (2018). Spatiotemporal regulation of liquid-like condensates in epigenetic inheritance. Nature. Vol. 557 (7707), pp. 679-683. PubMed Web Address
- Phillips, C. M., Brown, K. C., Montgomery, B. E., Ruvkun, G., Montgomery, T. A. (2015). piRNAs and piRNA-Dependent siRNAs Protect Conserved and Essential C. elegans Genes from Misrouting into the RNAi Pathway. Developmental cell. Vol. 34 (4), pp. 457-65. PubMed Web Address
- Phillips, C. M., Montgomery, B. E., Breen, P. C., Roovers, E. F., Rim, Y. S., Ohsumi, T. K., Newman, M. A., van, J. C., Ketting, R. F., Ruvkun, G., Montgomery, T. A. (2014). MUT-14 and SMUT-1 DEAD box RNA helicases have overlapping roles in germline RNAi and endogenous siRNA formation. Current biology : CB. Vol. 24 (8), pp. 839-44. PubMed Web Address
- Phillips, C. M., Montgomery, T. A., Breen, P. C., Ruvkun, G. (2012). MUT-16 promotes formation of perinuclear mutator foci required for RNA silencing in the C. elegans germline. Genes & development. Vol. 26 (13), pp. 1433-44. PubMed Web Address
- Montgomery, T. A., Rim, Y. S., Zhang, C., Dowen, R. H., Phillips, C. M., Fischer, S. E., Ruvkun, G. (2012). PIWI associated siRNAs and piRNAs specifically require the Caenorhabditis elegans HEN1 ortholog henn-1. PLoS genetics. Vol. 8 (4), pp. e1002616. PubMed Web Address
- Zhang, C., Montgomery, T. A., Gabel, H. W., Fischer, S. E., Phillips, C. M., Fahlgren, N., Sullivan, C. M., Carrington, J. C., Ruvkun, G. (2011). mut-16 and other mutator class genes modulate 22G and 26G siRNA pathways in Caenorhabditis elegans. Proceedings of the National Academy of Sciences of the United States of America. Vol. 108 (4), pp. 1201-8. PubMed Web Address
- Sato, A., Isaac, B., Phillips, C. M., Rillo, R., Carlton, P. M., Wynne, D. J., Kasad, R. A., Dernburg, A. F. (2009). Cytoskeletal forces span the nuclear envelope to coordinate meiotic chromosome pairing and synapsis. Cell. Vol. 139 (5), pp. 907-19. PubMed Web Address
- Phillips, C. M., Meng, X., Zhang, L., Chretien, J. H., Urnov, F. D., Dernburg, A. F. (2009). Identification of chromosome sequence motifs that mediate meiotic pairing and synapsis in C. elegans. Nature cell biology. Vol. 11 (8), pp. 934-42. PubMed Web Address
- Phillips, C. M., Dernburg, A. F. (2006). A family of zinc-finger proteins is required for chromosome-specific pairing and synapsis during meiosis in C. elegans. Developmental cell. Vol. 11 (6), pp. 817-29. PubMed Web Address
- Phillips, C. M., Wong, C., Bhalla, N., Carlton, P. M., Weiser, P., Meneely, P. M., Dernburg, A. F. (2005). HIM-8 binds to the X chromosome pairing center and mediates chromosome-specific meiotic synapsis. Cell. Vol. 123 (6), pp. 1051-63. PubMed Web Address
- MacQueen, A. J., Phillips, C. M., Bhalla, N., Weiser, P., Villeneuve, A. M., Dernburg, A. F. (2005). Chromosome sites play dual roles to establish homologous synapsis during meiosis in C. elegans. Cell. Vol. 123 (6), pp. 1037-50. PubMed Web Address
- Collins-Schramm, H. E., Phillips, C. M., Operario, D. J., Lee, J. S., Weber, J. L., Hanson, R. L., Knowler, W. C., Cooper, R., Li, H., Seldin, M. F. (2002). Ethnic-difference markers for use in mapping by admixture linkage disequilibrium. American journal of human genetics. Vol. 70 (3), pp. 737-50. PubMed Web Address