A5091597289- CRISPR and Genetic Engineering
- DNA Repair Mechanisms
- Genomics and Chromatin Dynamics
- Microtubule and mitosis dynamics
- Ubiquitin and proteasome pathways
- Marine Invertebrate Physiology and Ecology
- Developmental Biology and Gene Regulation
- Pancreatic and Hepatic Oncology Research
- Cancer-related Molecular Pathways
- Marine Ecology and Invasive Species
- Cancer Genomics and Diagnostics
- Bacterial Genetics and Biotechnology
- Genomic variations and chromosomal abnormalities
- Protein Degradation and Inhibitors
- Renal cell carcinoma treatment
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Phagocytosis and Immune Regulation
- Renal and related cancers
- RNA modifications and cancer
- Marine Sponges and Natural Products
- Photosynthetic Processes and Mechanisms
- Sphingolipid Metabolism and Signaling
- Cognitive Abilities and Testing
Memorial Sloan Kettering Cancer Center
2016-2024
University Medical Center Utrecht
2022-2024
Oncode Institute
2021-2024
Utrecht University
2010-2024
The Netherlands Cancer Institute
2014-2016
Kettering University
2016
Pacific Biosciences (United States)
2012
University of Hawaii System
2011-2012
University of Hawaiʻi at Mānoa
2010-2012
Survival rates of cancer patients vary widely within and between malignancies. While genetic aberrations are at the root all cancers, individual genomic features cannot explain these distinct disease outcomes. In contrast, intra-tumour heterogeneity (ITH) has potential to elucidate pan-cancer survival biology that drives prognosis. Unfortunately, a comprehensive effective framework measure ITH across cancers is missing. Here, we introduce scalable chromosomal copy number (CNH) predicts...
Abstract Programmed DNA double-strand break (DSB) formation is a crucial feature of meiosis in most organisms. DSBs initiate recombination-mediated linking homologous chromosomes, which enables correct chromosome segregation meiosis. are generated on axes by heterooligomeric focal clusters DSB-factors. Whereas DNA-driven protein condensation thought to assemble the DSB-machinery, its targeting poorly understood. We uncover mice that efficient biogenesis DSB-machinery requires seeding axial...
achaete-scute homologs (ash) regulate neural development in all bilaterian model animals indicating that they represent a component of the ancestral neurogenic pathway. We test this by investigating four ash genes during basal metazoan, cnidarian sea anemone Nematostella vectensis. Spatiotemporal expression early embryo and larval stages suggests neurogenesis. More specifically, NvashA is co-expressed with embryonic ectoderm. Knockdown results decreased eight markers, including six novel...
Meiotic DNA double-strand breaks (DSBs) initiate homologous recombination and are crucial for ensuring proper chromosome segregation. In mice, ANKRD31 recently emerged as a regulator of DSB timing, number, location, with particularly important role in targeting DSBs to the pseudoautosomal regions (PARs) sex chromosomes. interacts multiple proteins, including conserved essential DSB-promoting factor REC114, so it was hypothesized be modular scaffold that "anchors" other proteins together...
Sister chromatid separation creates a sudden loss of tension on kinetochores, which could, in principle, re-activate the spindle checkpoint anaphase. This so-called "anaphase problem" is probably avoided by timely inactivation cyclin B1-Cdk1, may prevent sensing Aurora B kinase from destabilizing kinetochore-microtubule interactions as they lose However, exactly how re-activation prevented remains unclear. Here, we investigated different degrees B1 stabilization affected metaphase and Cells...
Nek2A is a presumed APC/CCdc20 substrate, which, like cyclin A, degraded in mitosis while the spindle checkpoint active. Cyclin A prevents proteins from binding to Cdc20 and recruited APC/C prometaphase. We found that avoid stabilization by different ways. First, enhancing mitotic complex (MCC) formation nocodazole treatment inhibited degradation of geminin disappeared at normal rate. Secondly, depleting effectively stabilized but not Nek2A. Nevertheless, destruction critically depended on...
Summary Programmed DNA double-strand break (DSB) formation is a unique meiotic feature that initiates recombination-mediated linking of homologous chromosomes, thereby enabling chromosome number halving in meiosis. DSBs are generated on axes by heterooligomeric focal clusters DSB-factors. Whereas DNA-driven protein condensation thought to assemble the DSB-machinery, its targeting poorly understood. We discovered mice efficient biogenesis DSB-machinery requires seeding axial IHO1 platforms,...
Sex chromosomes in males share only a diminutive homologous segment, the pseudoautosomal region (PAR), wherein meiotic double-strand breaks (DSBs), pairing, and crossing over must occur for correct segregation. How cells ensure PAR recombination is unknown. Here we delineate cis-and trans-acting factors that control ultrastructure make hottest area of DSB formation male mouse genome. Prior to formation, chromosome axes elongate, sister chromatids separate, DSB-promoting hyperaccumulate....
Hyperactivation of WNT signaling is a well-established hallmark cancer. Various epithelial cancers express high levels WNT7B and WNT10A that are not commonly expressed during tissue homeostasis, but rather associate with development regeneration. Although increased WNT7B/10A expression correlates aggressive disease lower patient survival rates, the mechanism by which these WNTs influence cancer progression remains unknown. Here, we use patient-derived organoids to show tumor-intrinsic drives...
Meiotic DNA double-strand breaks (DSBs) initiate homologous recombination and are crucial for ensuring proper chromosome segregation. In mice, ANKRD31 recently emerged as a regulator of DSB timing, number, location, with particularly important role in targeting DSBs to the pseudoautosomal regions (PARs) sex chromosomes. interacts multiple proteins, including conserved essential DSB-promoting factor REC114, so it was hypothesized be modular scaffold that "anchors" other proteins together...
In Birt-Hogg-Dubé (BHD) syndrome, germline loss-of-function mutations in the Folliculin (FLCN) gene lead to an increased risk of renal cancer. To address how FLCN inactivation affects cellular kinase signaling pathways, we analyzed comprehensive phosphoproteomic profiles FLCNPOS and FLCNNEG human tubular epithelial cells (RPTEC/TERT1). total, 15,744 phosphorylated peptides were identified from 4329 proteins. INKA analysis revealed that loss alters activity numerous kinases, including...
Double-strand breaks (DSBs) initiate the homologous recombination that is crucial for meiotic chromosome pairing and segregation. Here we unveil mouse ANKRD31 as a lynchpin governing multiple aspects of DSB formation. Spermatocytes lacking have altered locations fail to target DSBs sex chromosomes’ pseudoautosomal regions (PAR). They also delayed/fewer sites but, paradoxically, more DSBs, suggesting dysregulation. Unrepaired failures—stochastic on autosomes, nearly absolute X Y—cause arrest...
Abstract E2F transcription factors control the oscillating expression pattern of multiple target genes during cell cycle. Activator E2Fs, E2F1-3, induce an upswing targets, which is essential for G1-to-S phase transition, whereas atypical E2F7 and E2F8, mediate a downswing same targets late S, G2, M phase. Expression E2Fs induced by but it unknown how are inactivated in timely manner. Using molecular assays, time lapse microscopy, flow cytometry we now demonstrate that E2F8 substrates...