A5071295536- Microtubule and mitosis dynamics
- Ubiquitin and proteasome pathways
- Genomics and Chromatin Dynamics
- Photosynthetic Processes and Mechanisms
- Cellular transport and secretion
- Cell Image Analysis Techniques
- Advanced Fluorescence Microscopy Techniques
- Chromosomal and Genetic Variations
- Mitochondrial Function and Pathology
- HIV Research and Treatment
- Genetics and Neurodevelopmental Disorders
- Chromatin Remodeling and Cancer
- DNA Repair Mechanisms
- HIV/AIDS drug development and treatment
- Epigenetics and DNA Methylation
- Nuclear Structure and Function
- Cancer-related Molecular Pathways
- Neurogenesis and neuroplasticity mechanisms
- Gene Regulatory Network Analysis
- Cancer-related gene regulation
- Image Processing Techniques and Applications
- Histone Deacetylase Inhibitors Research
- Advanced Electron Microscopy Techniques and Applications
- Single-cell and spatial transcriptomics
- Melanoma and MAPK Pathways
University of Wisconsin–Madison
2018-2025
University of Wisconsin Carbone Cancer Center
2021-2025
Madison Group (United States)
2025
Colorado State University
2025
University of Iowa
2023
University of North Carolina at Chapel Hill
2013-2018
University of North Carolina Health Care
2017
National Institute of Genetics
2008-2014
The Graduate University for Advanced Studies, SOKENDAI
2011
During meiosis, homologous chromosome (homolog) pairing is promoted by several layers of regulation that include dynamic movement and meiotic recombination. However, the way in which homologs recognize each other remains a fundamental issue biology. Here, we show homolog recognition or association initiates upon entry into prophase before axis assembly double-strand break (DSB) formation. This develops tight only during after Intriguingly, ability to retained Sun1 knockout spermatocytes,...
The constitutive centromere-associated network (CCAN) proteins are central to kinetochore assembly. To define the molecular architecture of this critical network, we sought determine full complement CCAN components and their relationships. This work identified a centromere protein S (CENP-S)–containing subcomplex that includes new CENP-X. Both CENP-S– CENP-X–deficient chicken DT40 cells viable but show abnormal mitotic behavior based on live cell analysis. Human HeLa depleted for CENP-X also...
Abstract The Ndc80 complex, which mediates end-on attachment of spindle microtubules, is linked to centromeric chromatin in human cells by two inner kinetochore proteins, CENP-T and CENP-C. Here quantify their relative contributions recruitment, we combine measurements protein copy number with selective depletion assays. This approach reveals about 244 complexes per (∼14 microtubule), 215 CENP-C, 72 only 151 Ndc80s as part the KMN network (1:1:1 Knl1, Mis12 complexes). Each molecule recruits...
The kinetochore forms a dynamic interface with microtubules from the mitotic spindle. Live-cell light microscopy–based observations on structural changes within suggest that molecular rearrangements occur upon microtubule interaction. However, source of these is still unclear. In this paper, we analyze vertebrate ultrastructure by immunoelectron microscopy (EM) in presence or absence tension spindle microtubules. We found inner region defined CENP-A, CENP-C, CENP-R, and C-terminal domain...
To define the molecular architecture of kinetochore in vertebrate cells, we measured copy number eight proteins that link microtubules (MTs [kMTs]) to centromeric DNA. We used a fluorescence ratio method and chicken DT40 cell lines which endogenous loci encoding analyzed were deleted complemented using integrated green fluorescent protein fusion transgenes. For mean 4.3 kMTs at metaphase, per kMT is between seven nine for members MT-binding KNL-1/Mis12 complex/Ndc80 complex network. It was...
Fluorescence microscopy is a powerful approach for studying subcellular dynamics at high spatiotemporal resolution; however, conventional fluorescence techniques are light-intensive and introduce unnecessary photodamage. Light-sheet (LSFM) mitigates these problems by selectively illuminating the focal plane of detection objective using orthogonal excitation. Orthogonal excitation requires geometries that physically limit numerical aperture (NA), thereby limiting both light-gathering...
The centromere regulates proper chromosome segregation, and its dysfunction is implicated in chromosomal instability (CIN). However, relatively little known about how occurs cancer. Here, we define the consequences of phosphorylation by cyclin E1/CDK2 on a conserved Ser18 residue centromere-associated protein CENP-A, an essential histone H3 variant that specifies identity. hyperphosphorylation cells occurred upon loss FBW7, tumor suppressor whose inactivation leads to CIN. This event CENP-A...
Subunits of the chromatin remodeler SWI/SNF are most frequently disrupted genes in cancer. However, how post-translational modifications (PTM) subunits elicit epigenetic dysfunction remains unknown. Arginine-methylation BAF155 by coactivator-associated arginine methyltransferase 1 (CARM1) promotes triple-negative breast cancer (TNBC) metastasis. Herein, we discovered dual roles methylated-BAF155 (me-BAF155) promoting tumor metastasis: activation super-enhancer-addicted oncogenes recruiting...
Spindle assembly checkpoint proteins have been thought to reside in the peripheral corona region of kinetochore, distal microtubule attachment sites at outer plate. However, recent biochemical evidence indicates that are closely linked core kinetochore site comprised Knl1–Mis12–Ndc80 (KMN) complexes/KMN network. In this paper, we show Knl1–Zwint1 complex is required recruit Rod–Zwilch–Zw10 (RZZ) and Mad1–Mad2 complexes kinetochore. Consistent with this, nanometer-scale mapping RZZ,...
The widespread use of fluorescence microscopy has prompted the ongoing development tools aiming to improve resolution and quantification accuracy for study biological questions. Current calibration images face issues with usability/user experience, lack automation, comprehensive multidimensional measurement/correction capabilities. Here, we developed 3D-Speckler, a versatile, high-throughput image analysis software that can provide fluorescent puncta measurements such as 2D/3D particle size,...
Virion Infectivity Factor (Vif) of the Human Immunodeficiency Virus type 1 (HIV-1) targets and degrades cellular APOBEC3 proteins, key regulators intrinsic innate antiretroviral immune responses, thereby facilitating HIV-1 infection. While Vif’s role in degrading APOBEC3G is well-studied, Vif also known to cause cell cycle arrest, but detailed nature effects on has yet be delineated. In this study, we employed high-temporal single-cell live imaging super-resolution microscopy monitor...
Virion Infectivity Factor (Vif) of the Human Immunodeficiency Virus type 1 (HIV-1) targets and degrades cellular APOBEC3 proteins, key regulators intrinsic innate antiretroviral immune responses, thereby facilitating HIV-1 infection. While Vif’s role in degrading APOBEC3G is well-studied, Vif also known to cause cell cycle arrest, but detailed nature effects on has yet be delineated. In this study, we employed high-temporal resolution single-cell live imaging super-resolution microscopy...
Abstract Microtubule-targeting agents (MTAs) have been successfully translated from basic research into clinical therapies and widely used as first- second-line chemotherapy drugs for various cancers. However, current MTAs exhibit positive responses only in subsets of patients are often accompanied by side effects due to their impact on normal cells. This underscores an urgent need develop novel therapeutic strategies that enhance MTA efficacy while minimizing toxicity tissues. In this...