KMap
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Primary 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 aneuploidy and increased risk for miscarriage/birth defects and cancer. In normal cells, what limits mother centrioles to assemble only a single daughter is unknown. It is known, however, that Polo-like kinase 4 (Plk4), the conserved master-initiator of centriole assembly, plays a key role in the duplication process. Therefore, a major goal of the Rogers lab is discovering how Plk4 works and how Plk4's activity is regulated.
II. Chromatin Organization during Interphase
During interphase, a cell must organize its chromatin to accommodate the active transcription of genes and -- for those cells progressing through the cell cycle -- the replication of the cell's genome. One aspect of chromatin organization is its degree of compaction: while chromatin clearly undergoes extreme compaction during mitosis, the chromatin within interphase cells is also compacted but at a more moderate level. Importantly, interphase chromatin compaction is required for normal cellular function. In collaboration with Gio Bosco (Dartmouth), my lab is interested in understanding the regulation and physiological significance of interphase chromatin organization, particularly at the level of chromatin compaction.
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Courses
- ATCBAdvanced Topics in Cancer Biology
- CBDCell Biology of Disease
- PCBPrinciples of Cell Biology
- CBCancer Biology
Grants
- Characterizing the Molecular Mechanisms of Centriole Duplication, Growth and Maturation
Principal Investigator (PI)
2020
$1.5M
Active - Integrative Cancer Scholars Training Grant
Multiple Principal Investigator (MPI)
2020
$830.7K
Active - Centrosome Instability as a Mechanism to Promote Localized Prostate Cancer
Principal Investigator (PI)
2019
$2.3M
Active - Centrosome instability as a mechanism to promote localized prostate cancer
Principal Investigator (PI)
2019
$55.6K
Active - Inherent Mechanisms that Govern Centrosome Function and Duplication
Principal Investigator (PI)
2018
$1.0M
- Identifying Molecular Mechanisms that Suppress Centriole Amplification
Principal Investigator (PI)
2015
$1.4M
- Molecular Mechanisms of Centrosome Amplification in Cancer Cells
Principal Investigator (PI)
2013
$50.0K
- Assembling Centrioles: Molecular Biogenesis of an Organelle
Principal Investigator (PI)
2012
$670.6K
- Molecular mechanisms of centrosome amplification in cancer cells
Principal Investigator (PI)
2012
$49.5K
- Molecular mechanisms of centrosome amplification in cancer cells
Principal Investigator (PI)
2011
$50.0K
Publications (93)
Recent
- PIM kinases regulate actin dynamics and tumor cell invasion in hypoxia
2023
- Polo-like kinase 4 homodimerization and condensate formation regulate its own protein levels but are not required for centriole assembly
2023
- Analysis of a rare progeria variant of Barrier-to-autointegration factor in Drosophila connects centromere function to tissue homeostasis
2023
- GLUT3/SLC2A3 is an endogenous marker of hypoxia in prostate epithelial and prostate cancer cells.
2022
- GLUT3/SLC2A3 is an endogenous marker of hypoxia in prostate cancer cell lines and patient-derived xenograft tumors
2022
- GLUT3/SLC2A3 Is an Endogenous Marker of Hypoxia in Prostate Cancer Cell Lines and Patient-Derived Xenograft Tumors. Diagnostics 2022, 12, 676
2022
- Balancing the scales: fine-tuning Polo-like kinase 4 to ensure proper centriole duplication
2022
- Polo-like kinase 4 homodimerization is not required for catalytic activation, autodestruction, or centriole assembly
2021
- Further Reading| Centrosome Duplication
2021
- Centrosome instability: when good centrosomes go bad
2021
- A molecular mechanism for the procentriole recruitment of Ana2
2020
- Janus Face of Drug-Induced Tetraploidy in Non-Hodgkin Lymphoma
2020
- A method of quantifying centrosomes at the single-cell level in human normal and cancer tissue
2019
- Centrosome loss results in an unstable genome and malignant prostate tumors
2019
- Immunofluorescence-based Determination of Centrosome Number in Tissue Samples
2019
- Plk4 regulates centriole asymmetry and spindle orientation in neural stem cells
2019
- Cul4 ubiquitin ligase cofactor DCAF12 promotes neurotransmitter release and homeostatic plasticity
2019
- Centrosome loss and chromosomal instability in prostate tumor progression.
2018
- An ordered pattern of Ana2 phosphorylation by Plk4 is required for centriole assembly
2018
- Vesicular trafficking plays a role in centriole disengagement and duplication
2018
- Integrin alpha 6 beta 4E is an inducible dynamic adhesion splice variant in normal epithelial and endothelial cells that modifies biophysical properties of cell-cell and cell …
2018
- Asterless is a Polo-like kinase 4 substrate that both activates and inhibits kinase activity depending on its phosphorylation state
2018
- A basal cell defect promotes budding of prostatic intraepithelial neoplasia
2017
- A centrosome interactome provides insight into organelle assembly and reveals a non-duplication role for Plk4
2016
- Plk4 phosphorylates Ana2 to block association and inhibit centriole duplication
2016
- A Detailed Centrosome Interactome Reveals A Novel Role Of Plk4 And Provides Insight Into The Mechanisms Of Human Centrosome Disease
2016
- Therapeutic Molecular Targeting of Polo-Like Kinase 4 for Cancer Treatment
2015
- Autoinhibition and relief mechanism for Polo-like kinase 4
2015
- Dual role for the APC/C recognition motif in the master regulator of centriole duplication Plk4.
2015
- Drosophila casein kinase I alpha regulates homolog pairing and genome organization by modulating condensin II subunit Cap-H2 levels
2015
- A Detailed Centrosome Interactome Reveals a Novel Substrate of Plk4
2015
- Two Polo-like kinase 4 binding domains in Asterless perform distinct roles in regulating kinase stability
2015
- Condensins exert force on chromatin-nuclear envelope tethers to mediate nucleoplasmic reticulum formation in Drosophila melanogaster
2015
- Condensins Exert Force on Chromatin-Nuclear Envelope Tethers to Mediate Nucleoplasmic
2015
- Condensin II regulates interphase chromatin organization through the Mrg-binding motif of Cap-H2
2015
- A Highlights from MBoC Selection: Drosophila pericentrin requires interaction with calmodulin for its function at centrosomes and neuronal basal bodies but not at sperm basal …
2014
- Drosophila pericentrin requires interaction with calmodulin for its function at centrosomes and neuronal basal bodies but not at sperm basal bodies
2014
- The use of cultured Drosophila cells for studying the microtubule cytoskeleton
2014
- The F-box protein Slmb restricts the activity of aPKC to polarize epithelial cells
2014
- Cell cycle-dependent regulation of the centriole protein Ana2/STIL
2013
- Maintenance of Interphase Chromosome Compaction and Homolog Pairing in Drosophila Is Regulated by the Condensin Cap-H2 and Its Partner Mrg15
2013
- Polo-like kinase 4 autodestructs by generating its Slimb-binding phosphodegron
2013
- Show me your license, please: deregulation of centriole duplication mechanisms that promote amplification
2013
- SCFSlimb ubiquitin ligase suppresses condensin II-mediated nuclear reorganization by degrading Cap-H2
2013
- The structure of the plk4 cryptic polo box reveals two tandem polo boxes required for centriole duplication
2012
- Structural analysis of Polo-Like Kinase-4's Cryptic Polo Box reveals a novel pair of tandem Polo Box Domains required for centriole assembly.
2012
- Defining components of the ßcatenin destruction complex and exploring its regulation and mechanisms of action during development
2012
- The SCFSlimb ubiquitin-ligase regulates Cap-H2 levels to suppress condensin II-mediated nuclear reorganization.
2012
- Sub-diffraction-resolution fluorescence microscopy reveals a novel domain of the centrosome critical for pericentriolar material organization.
2012
- The SCFSlimb ubiquitin-ligase regulates Cap-H2 levels to control interphase chromosome condensation and spatial organization.
2011
- The Protein Phosphatase 2A regulatory subunit Twins stabilizes Plk4 to induce centriole amplification
2011
- SV40 small tumor antigen exploits PP2A's role in stabilizing Plk4 to induce centriole amplification.
2011
- Polo-like kinase 4 stability is controlled by autophosphorylation of multiple residues within its downstream regulatory element.
2011
- Spindle assembly: more than just microtubules
2010
- Angiogenic factor signaling regulates centrosome duplication in endothelial cells of developing blood vessels
2010
- Preparation of Drosophila S2 cells for light microscopy
2010
- Centrosome function: sometimes less is more
2009
- The Drosophila kinesin-13, KLP59D, impacts Pacman- and Flux-based chromosome movement
2009
- The SCFSlimb ubiquitin ligase regulates Plk4/Sak levels to block centriole reduplication
2009
- A Multicomponent Assembly Pathway Contributes to the Formation of Acentrosomal Microtubule Arrays in Interphase Drosophila Cells
2008
- Culture of Drosophila S2 cells and their use for RNAi-mediated loss-of-function studies and immunofluorescence microscopy
2008
- An InCytes from MBC Selection: A Multicomponent Assembly Pathway Contributes to the Formation of Acentrosomal Microtubule Arrays in Interphase Drosophila Cells
2008
- Microtubule binding by dynactin is required for microtubule organization but not cargo transport
2007
- Three microtubule severing enzymes contribute to the “Pacman-flux” machinery that moves chromosomes
2007
- Functionally distinct kinesin-13 family members cooperate to regulate microtubule dynamics during interphase
2005
- Spindle microtubules in flux (vol 118, pg 1105, 2005)
2005
- Spindle microtubules in flux
2005
- Functionally distinct Kin I kinesins cooperate to regulate microtubule dynamics during interphase
2004
- Two mitotic kinesins cooperate to drive sister chromatid separation during anaphase
2004
- A Kin I-Independent Pacman: Flux Mechanism for Anaphase A
2004
- The chromokinesin, KLP3A, drives mitotic spindle pole separation during prometaphase and anaphase and facilitates chromatid motility
2004
- Inhibition of chromokinesins increases the aneuploid frequency of Drosophila S2 cells
2004
- Peptide inhibitors of cellular proliferation
2003
- Drosophila EB1 is important for proper assembly, dynamics, and positioning of the mitotic spindle
2002
- Dynein
2002
- Identification and characterization of three Kin I family members in Drosophila: Evidence that mitosis in this system involves the coordinated action of functionally distinct …
2002
- The kinesin, KLP3A, contributes to the balance of forces that positions spindle poles and daughter nuclei in Drosophila early embryos
2001
- Mitosis, microtubules, and the matrix
2001
- Three microtubule motors, cytoplasmic dynein, KLP59C, and KLP38B, function cooperatively to position chromosomes relative to spindle poles in Drosophila early embryos
2001
- KLP3A, an interzonal MT motor, is involved in spindle pole positioning and nuclear spacing in Drosophila early embryos
2000
- A Kinesin-Related Protein, Krp180, Positions Prometaphase Spindle Poles during Early Sea Urchin Embryonic Cell Division
2000
- Cytoplasmic dynein is required for poleward chromosome movement during mitosis in Drosophila embryos
2000
- Roles of two homotetrameric kinesins in sea urchin embryonic cell division
2000
- Roles of motor proteins in building microtubule-based structures: a basic principle of cellular design
2000
- Microtubule motors in mitosis
2000
- The functional coordination of three different microtubule-based motors in positioning centrosomes during sea urchin embryogenesis
2000
- Three microtubule-motors, cytoplasmic dynein, KLP59D and KLP38B, function cooperatively to position chromosomes relative to spindle poles in Drosophila early embryos.
2000
- Functional Coordination of Three Mitotic Motors inDrosophila Embryos
2000
- Identification of kinesin-C, a calmodulin-binding carboxy-terminal kinesin in animal (Strongylocentrotus purpuratus) cells
1999
- Cytoplasmic dynein drives sister chromatid separation during anaphase A in Drosophila early embryos.
1999
- Cooperation between three mitotic motors revealed by real-time analysis of Drosophila embryos.
1999
- KRP180, a candidate kinesin-related motor required for early sea urchin embryonic cell division.
1998
- The bimC family of kinesins: essential bipolar mitotic motors driving centrosome separation
1997
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