Gregory C. Rogers, PhD

Professor, Cellular and Molecular Medicine
Associate Head, Faculty Development
Professor, BIO5 Institute
Professor, Cancer Biology GIDP
Professor, Genetics GIDP
Professor, Molecular and Cellular Biology

BA Biology, University of Rochester PhD Cell and Developmental Biology, University of California, Davis Postdoctoral Researcher, Albert Einstein College of Medicine Postdoctoral Researcher, University of North Carolina, Chapel Hill

Research Interests: 

I. Regulation of Centriole Duplication. Errors in chromosome segregation during cell division can result in the production of aneuploid daughter cells. This is particularly devastating during development, as aneuploidy is an underlying cause of miscarriage, birth defects, and cancers. During cell division, the accurate transmission of replicated chromosomes depends on the assembly of a bipolar spindle which is facilitated by the presence of centrioles, tiny organelles that help generate and organize spindle microtubules. Normally cells contain a single centriole pair, each duplicating only once prior to entering cell division. However, these mother centrioles have the capacity to assemble multiple daughters simultaneously. If cells assemble excess daughter centrioles (known as centriole amplification), then multipolar spindle assembly can ensue, leading to chromosomal instability (CIN) and increased risk for miscarriage/birth defects and cancer. How cells control centriole copy number is unclear. My lab uses the fruit fly Drosophila melanogaster as a model system to study the mechanisms that underlie centrioles duplication and function.

II. Centrosome instability in prostate cancer (PCa). We study centrosome aberrations as a major causal factor in promoting CIN in PCa. Unlike many cancers, PCa does not harbor signature mutations in key oncogenes and tumor-suppressor genes. Instead, primary prostate tumors display wide-spread CIN which may be a 'driver' of tumorigenesis in this organ. Our study of centrosomes in PCa (Wang et al., Oncogene, 2020) (1) is the first to provide a mechanism for the cause of CIN in early prostate tumors. (2) Centrosomes are frequently overduplicated (amplified) in many types of cancer, promoting both CIN and tumorigenesis. However, the opposite condition, centrosome loss has never been reported in any cancer. This is surprising because mitotic spindles are still able to form in the absence of centrosomes and these are error prone, producing identical types of CIN. Thus, one would expect that centrosome loss would be observed in cancer. Ours is the first study to show centrosome loss in any human cancer. (3) We discovered that centrosome loss is sufficient to transform cells and promote invasive tumor formation in a mouse xenograft model, producing tumors that have classic features of malignant and high grade primary human prostate carcinoma - the first demonstration that centrosome loss has oncogenic potential. Interestingly, in contrast to primary tumors, aggressive metastatic-derived PCa cells display centrosome amplification. Thus, like chromosomes, centrosomes appear to display instability as their numbers fluctuate during cancer progression. Notably, molecular alterations that promote centrosome loss or amplification are unknown. Our goals are to: (1) Determine the molecular mechanisms that underlie centrosome loss and amplification during PCa progression. (2) Test whether centrosome loss is an early 'driver' event and, through further CIN, cells transition to genotypes that trigger centrosome amplification, leading to malignant transformation. (3) Since CIN is observed in many cancers, we are interested in determining whether centrosome instability is a ubiquitous oncogenic feature of lesions, whether precancerous, benign, or metastatic.

Molecular Medicine Grad Program: 
Yes

Bibliography

2024

Ryniawec, J. M., A. Amoiroglou, and G. C. Rogers, "Generating CRISPR-edited clonal lines of cultured S2 cells.", Biol Methods Protoc, vol. 9, issue 1, pp. bpae059, 2024. PMCID: PMC11357795  PMID: 39206452

2023

Jensen, C. C., A. N. Clements, H. Liou, L. E. Ball, J. R. Bethard, P. R. Langlais, R. K. Toth, S. S. Chauhan, A. L. Casillas, S. R. Daulat, et al., "PIM1 phosphorylates ABI2 to enhance actin dynamics and promote tumor invasion.", J Cell Biol, vol. 222, issue 6, 2023 Jun 05. PMCID: PMC10103708  PMID: 37042842
Duan, T., S. Thyagarajan, A. Amoiroglou, G. C. Rogers, and P. K. Geyer, "Analysis of a rare progeria variant of Barrier-to-autointegration factor in Drosophila connects centromere function to tissue homeostasis.", Cell Mol Life Sci, vol. 80, issue 3, pp. 73, 2023 Feb 26. PMCID: PMC9968693  PMID: 36842139
Ryniawec, J. M., D. W. Buster, L. K. Slevin, C. J. Boese, A. Amoiroglou, S. M. Dean, K. C. Slep, and G. C. Rogers, "Polo-like kinase 4 homodimerization and condensate formation regulate its own protein levels but are not required for centriole assembly.", Mol Biol Cell, pp. mbcE22120572, 2023 May 10. PMID: 37163316

2022

Ryniawec, J. M., M. R. Coope, E. Loertscher, V. Bageerathan, D. de Oliveir Pessoa, N. A. Warfel, A. E. Cress, M. Padi, and G. C. Rogers, "GLUT3/SLC2A3 Is an Endogenous Marker of Hypoxia in Prostate Cancer Cell Lines and Patient-Derived Xenograft Tumors.", Diagnostics (Basel), vol. 12, issue 3, 2022 Mar 10. PMCID: PMC8946944  PMID: 35328229
Ryniawec, J. M., and G. C. Rogers, "Balancing the scales: fine-tuning Polo-like kinase 4 to ensure proper centriole duplication.", Genes Dev, vol. 36, issue 11-12, pp. 647-649, 2022 Jun 01. PMCID: PMC9296006  PMID: 35835509

2021

Ryniawec, J. M., and G. C. Rogers, "Centrosome instability: when good centrosomes go bad.", Cell Mol Life Sci, vol. 78, issue 21-22, pp. 6775-6795, 2021 Nov. PMCID: PMC8560572  PMID: 34476544
Boese, C. J., A. Amoiroglou, and G. C. Rogers, "Centrosome duplication", Encyclopedia of Biological Chemistry, 3rd, vol. 5, 2021.

2020

Mahadevan, D., and G. C. Rogers, "Janus Face of Drug-Induced Tetraploidy in Non-Hodgkin Lymphoma.", Trends Cancer, 2020 04 01. PMID: 32291237
McLamarrah, T. A., S. K. Speed, J. M. Ryniawec, D. W. Buster, C. J. Fagerstrom, B. J. Galletta, N. M. Rusan, and G. C. Rogers, "A molecular mechanism for the procentriole recruitment of Ana2.", J Cell Biol, vol. 219, issue 2, 2020 02 03. PMID: 31841145

2019

Wang, M., G. C. Rogers, and A. E. Cress, "Immunofluorescence-based Determination of Centrosome Number in Tissue Samples.", Bio Protoc, vol. 9, issue 20, pp. e3396, 2019 Oct 20. PMCID: PMC7854016  PMID: 33654897
Patrón, L. A., K. Nagatomo, D. Tyler Eves, M. Imad, K. Young, M. Torvund, X. Guo, G. C. Rogers, and K. E. Zinsmaier, "Cul4 ubiquitin ligase cofactor DCAF12 promotes neurotransmitter release and homeostatic plasticity.", J Cell Biol, 2019 01 22. PMID: 30670470
Wang, M., B. S. Knudsen, R. B. Nagle, G. C. Rogers, and A. E. Cress, "A method of quantifying centrosomes at the single-cell level in human normal and cancer tissue.", Mol Biol Cell, vol. 30, issue 7, pp. 811-819, 2019 03 21. PMID: 30699045
Gambarotto, D., C. Pennetier, J. M. Ryniawec, D. W. Buster, D. Gogendeau, A. Goupil, M. Nano, A. Simon, D. Blanc, V. Racine, et al., "Plk4 Regulates Centriole Asymmetry and Spindle Orientation in Neural Stem Cells.", Dev Cell, vol. 50, issue 1, pp. 11-24.e10, 2019 07 01. PMID: 31130353
Wang, M., R. B. Nagle, B. S. Knudsen, A. E. Cress, and G. C. Rogers, "Centrosome loss results in an unstable genome and malignant prostate tumors.", Oncogene, 2019 09 02. PMID: 31477840

2018

McLamarrah, T. A., D. W. Buster, B. J. Galletta, C. J. Boese, J. M. Ryniawec, N. Ann Hollingsworth, A. E. Byrnes, C. W. Brownlee, K. C. Slep, N. M. Rusan, et al., "An ordered pattern of Ana2 phosphorylation by Plk4 is required for centriole assembly.", J Cell Biol, vol. 217, issue 4, pp. 1217-1231, 2018 Apr 02. PMCID: PMC5881488  PMID: 29496738
Xie, S., J. B. Reinecke, T. Farmer, K. Bahl, I. Yeow, B. J. Nichols, T. A. McLamarrah, N. Naslavsky, G. C. Rogers, and S. Caplan, "Vesicular trafficking plays a role in centriole disengagement and duplication.", Mol Biol Cell, vol. 29, issue 22, pp. 2622-2631, 2018 Nov 01. PMCID: PMC6249839  PMID: 30188792
Boese, C. J., J. Nye, D. W. Buster, T. A. McLamarrah, A. E. Byrnes, K. C. Slep, N. M. Rusan, and G. C. Rogers, "Asterless is a Polo-like kinase 4 substrate that both activates and inhibits kinase activity depending on its phosphorylation state.", Mol Biol Cell, vol. 29, issue 23, pp. 2874-2886, 2018 Nov 15. PMCID: PMC6249866  PMID: 30256714

2017

Wang, M., R. B. Nagle, B. S. Knudsen, G. C. Rogers, and A. E. Cress, "A basal cell defect promotes budding of prostatic intraepithelial neoplasia.", J Cell Sci, 2017 01. PMCID: PMC5394777  PMID: 27609833

2016

Galletta, B. J., C. J. Fagerstrom, T. A. Schoborg, T. A. McLamarrah, J. M. Ryniawec, D. W. Buster, K. C. Slep, G. C. Rogers, and N. M. Rusan, "A centrosome interactome provides insight into organelle assembly and reveals a non-duplication role for Plk4.", Nat Commun, vol. 7, pp. 12476, 2016. PMID: 27558293

2015

Klebba, J. E., D. W. Buster, T. A. McLamarrah, N. M. Rusan, and G. C. Rogers, "Autoinhibition and relief mechanism for Polo-like kinase 4.", Proc Natl Acad Sci U S A, vol. 112, issue 7, pp. E657-66, 2015 Feb 17. PMCID: PMC4343128  PMID: 25646492
Wallace, H. A., J. E. Klebba, T. Kusch, G. C. Rogers, and G. Bosco, "Condensin II Regulates Interphase Chromatin Organization Through the Mrg-Binding Motif of Cap-H2.", G3 (Bethesda), vol. 5, issue 5, pp. 803-17, 2015 May. PMCID: PMC4426367  PMID: 25758823
Nguyen, H. Q., J. Nye, D. W. Buster, J. E. Klebba, G. C. Rogers, and G. Bosco, "Drosophila casein kinase I alpha regulates homolog pairing and genome organization by modulating condensin II subunit Cap-H2 levels.", PLoS Genet, vol. 11, issue 2, pp. e1005014, 2015. PMCID: PMC4344196  PMID: 25723539
Klebba, J. E., B. J. Galletta, J. Nye, K. M. Plevock, D. W. Buster, N. A. Hollingsworth, K. C. Slep, N. M. Rusan, and G. C. Rogers, "Two Polo-like kinase 4 binding domains in Asterless perform distinct roles in regulating kinase stability.", J Cell Biol, vol. 208, issue 4, pp. 401-14, 2015 Feb 16. PMCID: PMC4332252  PMID: 25688134
Bozler, J., H. Q. Nguyen, G. C. Rogers, and G. Bosco, "Condensins exert force on chromatin-nuclear envelope tethers to mediate nucleoplasmic reticulum formation in Drosophila melanogaster.", G3 (Bethesda), vol. 5, issue 3, pp. 341-52, 2015 Mar. PMCID: PMC4349088  PMID: 25552604

2014

Galletta, B. J., R. X. Guillen, C. J. Fagerstrom, C. W. Brownlee, D. A. Lerit, T. L. Megraw, G. C. Rogers, and N. M. Rusan, "Drosophila pericentrin requires interaction with calmodulin for its function at centrosomes and neuronal basal bodies but not at sperm basal bodies.", Mol Biol Cell, vol. 25, issue 18, pp. 2682-94, 2014 Sep 15. PMCID: PMC4161505  PMID: 25031429
Nye, J., D. W. Buster, and G. C. Rogers, "The use of cultured Drosophila cells for studying the microtubule cytoskeleton.", Methods Mol Biol, vol. 1136, pp. 81-101, 2014. PMID: 24633795
Skwarek, L. C., S. L. Windler, G. de Vreede, G. C. Rogers, and D. Bilder, "The F-box protein Slmb restricts the activity of aPKC to polarize epithelial cells.", Development, vol. 141, issue 15, pp. 2978-83, 2014 Aug. PMCID: PMC4197664  PMID: 25053431

2013

Buster, D. W., S. G. Daniel, H. Q. Nguyen, S. L. Windler, L. C. Skwarek, M. Peterson, M. Roberts, J. H. Meserve, T. Hartl, J. E. Klebba, et al., "SCFSlimb ubiquitin ligase suppresses condensin II-mediated nuclear reorganization by degrading Cap-H2.", J Cell Biol, vol. 201, issue 1, pp. 49-63, 2013 Apr 1. PMCID: PMC3613687  PMID: 23530065
Klebba, J. E., D. W. Buster, A. L. Nguyen, S. Swatkoski, M. Gucek, N. M. Rusan, and G. C. Rogers, "Polo-like kinase 4 autodestructs by generating its Slimb-binding phosphodegron.", Curr Biol, vol. 23, issue 22, pp. 2255-61, 2013 Nov 18. PMCID: PMC3844517  PMID: 24184097
Smith, H. F., M. A. Roberts, H. Q. Nguyen, M. Peterson, T. A. Hartl, X-J. Wang, J. E. Klebba, G. C. Rogers, and G. Bosco, "Maintenance of interphase chromosome compaction and homolog pairing in Drosophila is regulated by the condensin cap-h2 and its partner Mrg15.", Genetics, vol. 195, issue 1, pp. 127-46, 2013 Sep. PMCID: PMC3761296  PMID: 23821596
Brownlee, C. W., and G. C. Rogers, "Show me your license, please: deregulation of centriole duplication mechanisms that promote amplification.", Cell Mol Life Sci, vol. 70, issue 6, pp. 1021-34, 2013 Mar. PMID: 22892665

2012

Mennella, V., B. Keszthelyi, K. L. McDonald, B. Chhun, F. Kan, G. C. Rogers, B. Huang, and D. A. Agard, "Subdiffraction-resolution fluorescence microscopy reveals a domain of the centrosome critical for pericentriolar material organization.", Nat Cell Biol, vol. 14, issue 11, pp. 1159-68, 2012 Nov. PMCID: PMC3767400  PMID: 23086239
Slevin, L. K., J. Nye, D. C. Pinkerton, D. W. Buster, G. C. Rogers, and K. C. Slep, "The structure of the plk4 cryptic polo box reveals two tandem polo boxes required for centriole duplication.", Structure, vol. 20, issue 11, pp. 1905-17, 2012 Nov 7. PMCID: PMC3496063  PMID: 23000383
Roberts, D. M., M. I. Pronobis, K. M. Alexandre, G. C. Rogers, J. S. Poulton, D. E. Schneider, K-C. Jung, D. J. McKay, and M. Peifer, "Defining components of the ß-catenin destruction complex and exploring its regulation and mechanisms of action during development.", PLoS One, vol. 7, issue 2, pp. e31284, 2012. PMCID: PMC3281067  PMID: 22359584

2011

Brownlee, C. W., J. E. Klebba, D. W. Buster, and G. C. Rogers, "The Protein Phosphatase 2A regulatory subunit Twins stabilizes Plk4 to induce centriole amplification.", J Cell Biol, vol. 195, issue 2, pp. 231-43, 2011 Oct 17. PMCID: PMC3198173  PMID: 21987638

2010

Buster, D. W., J. Nye, J. E. Klebba, and G. C. Rogers, "Preparation of Drosophila S2 cells for light microscopy.", J Vis Exp, issue 40, 2010. PMCID: PMC3153891  PMID: 20543772
Rogers, G. C., "Spindle assembly: more than just microtubules.", Curr Biol, vol. 20, issue 8, pp. R364-6, 2010 Apr 27. PMID: 21749958
Taylor, S. M., K. R. Nevis, H. L. Park, G. C. Rogers, S. L. Rogers, J. G. Cook, and V. L. Bautch, "Angiogenic factor signaling regulates centrosome duplication in endothelial cells of developing blood vessels.", Blood, vol. 116, issue 16, pp. 3108-17, 2010 Oct 21. PMCID: PMC2974614  PMID: 20664058

2009

Rath, U., G. C. Rogers, D. Tan, M. Ana Gomez-Ferreria, D. W. Buster, H. J. Sosa, and D. J. Sharp, "The Drosophila kinesin-13, KLP59D, impacts Pacman- and Flux-based chromosome movement.", Mol Biol Cell, vol. 20, issue 22, pp. 4696-705, 2009 Nov. PMCID: PMC2777100  PMID: 19793918
Rusan, N. M., and G. C. Rogers, "Centrosome function: sometimes less is more.", Traffic, vol. 10, issue 5, pp. 472-81, 2009 May. PMID: 19192251
Rogers, G. C., N. M. Rusan, D. M. Roberts, M. Peifer, and S. L. Rogers, "The SCF Slimb ubiquitin ligase regulates Plk4/Sak levels to block centriole reduplication.", J Cell Biol, vol. 184, issue 2, pp. 225-39, 2009 Jan 26. PMCID: PMC2654306  PMID: 19171756

2008

Hall, J. R., H. O. Lee, B. D. Bunker, E. S. Dorn, G. C. Rogers, R. J. Duronio, and J. Gowen Cook, "Cdt1 and Cdc6 are destabilized by rereplication-induced DNA damage.", J Biol Chem, vol. 283, issue 37, pp. 25356-63, 2008 Sep 12. PMCID: PMC2533066  PMID: 18617514
Rogers, G. C., N. M. Rusan, M. Peifer, and S. L. Rogers, "A multicomponent assembly pathway contributes to the formation of acentrosomal microtubule arrays in interphase Drosophila cells.", Mol Biol Cell, vol. 19, issue 7, pp. 3163-78, 2008 Jul. PMCID: PMC2441692  PMID: 18463166
Rogers, S. L., and G. C. Rogers, "Culture of Drosophila S2 cells and their use for RNAi-mediated loss-of-function studies and immunofluorescence microscopy.", Nat Protoc, vol. 3, issue 4, pp. 606-11, 2008. PMID: 18388942

2007

Zhang, D., G. C. Rogers, D. W. Buster, and D. J. Sharp, "Three microtubule severing enzymes contribute to the "Pacman-flux" machinery that moves chromosomes.", J Cell Biol, vol. 177, issue 2, pp. 231-42, 2007 Apr 23. PMCID: PMC2064132  PMID: 17452528
Kim, H., S-C. Ling, G. C. Rogers, C. Kural, P. R. Selvin, S. L. Rogers, and V. I. Gelfand, "Microtubule binding by dynactin is required for microtubule organization but not cargo transport.", J Cell Biol, vol. 176, issue 5, pp. 641-51, 2007 Feb 26. PMCID: PMC2064022  PMID: 17325206

2005

Rogers, G. C., S. L. Rogers, and D. J. Sharp, "Spindle microtubules in flux.", J Cell Sci, vol. 118, issue Pt 6, pp. 1105-16, 2005 Mar 15. PMID: 15764594
Mennella, V., G. C. Rogers, S. L. Rogers, D. W. Buster, R. D. Vale, and D. J. Sharp, "Functionally distinct kinesin-13 family members cooperate to regulate microtubule dynamics during interphase.", Nat Cell Biol, vol. 7, issue 3, pp. 235-45, 2005 Mar. PMID: 15723056

2004

Rogers, G. C., S. L. Rogers, T. A. Schwimmer, S. C. Ems-McClung, C. E. Walczak, R. D. Vale, J. M. Scholey, and D. J. Sharp, "Two mitotic kinesins cooperate to drive sister chromatid separation during anaphase.", Nature, vol. 427, issue 6972, pp. 364-70, 2004 Jan 22. PMID: 14681690