A5031265292- Microtubule and mitosis dynamics
- Chromosomal and Genetic Variations
- Cancer Genomics and Diagnostics
- Fungal and yeast genetics research
- Evolution and Genetic Dynamics
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- Genomic variations and chromosomal abnormalities
- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- Photosynthetic Processes and Mechanisms
- Cancer-related Molecular Pathways
- Plant Molecular Biology Research
- Bioinformatics and Genomic Networks
- Advanced biosensing and bioanalysis techniques
- Protein Degradation and Inhibitors
- Genomics and Phylogenetic Studies
- Biofuel production and bioconversion
- Ethics and Legal Issues in Pediatric Healthcare
- Yeasts and Rust Fungi Studies
- Genomics, phytochemicals, and oxidative stress
- ATP Synthase and ATPases Research
- Lipid metabolism and biosynthesis
- Renal and related cancers
- Genetics, Aging, and Longevity in Model Organisms
Institute of Medical Biology
2012-2023
Agency for Science, Technology and Research
2010-2023
Nanyang Technological University
2015-2021
Stowers Institute for Medical Research
2007-2012
University of Milano-Bicocca
2005-2009
University of Missouri–Kansas City
2007
Genomic instability (GIN) is a hallmark of cancer cells that facilitates the acquisition mutations conferring aggressive or drug-resistant phenotypes during evolution. Chromosomal (CIN) form GIN involves frequent cytogenetic changes leading to in chromosome copy number (aneuploidy). While both CIN and aneuploidy are common characteristics cells, their roles tumor initiation progression unclear. On one hand, known provide genetic variation allow adapt changing environments such as nutrient...
Gut microbes live in symbiosis with their hosts, but how mutualistic animal-microbe interactions emerge is not understood. By adaptively evolving the opportunistic fungal pathogen Candida albicans mouse gastrointestinal tract, we selected strains that only had lost main virulence program also protected new hosts against a variety of systemic infections. This protection was independent adaptive immunity, arose as early single day postpriming, dependent on increased innate cytokine responses,...
Recent studies in cancer cells and budding yeast demonstrated that aneuploidy, the state of having abnormal chromosome numbers, correlates with elevated instability (CIN), i.e. propensity gaining losing chromosomes at a high frequency. Here we have investigated ploidy- chromosome-specific determinants underlying aneuploidy-induced CIN by observing karyotype dynamics fully isogenic aneuploid strains ploidies between 1N 2N obtained through random meiotic process. The exhibited various levels...
Chromosome segregation relies on centromeres, yet their repetitive DNA is often prone to aberrant rearrangements under pathological conditions. Factors that maintain centromere integrity prevent centromere-associated chromosome translocations are unknown. Here, we demonstrate the importance of centromere-specific histone H3 variant CENP-A in safeguarding replication alpha-satellite repeats structural aneuploidy. Rapid removal S phase, but not other cell-cycle stages, caused accumulation R...
Abstract Aneuploidy is a hallmark of cancer with tissue-specific prevalence patterns that suggest it plays driving role in initiation and progression. However, the contribution aneuploidy to tumorigenesis depends on both cellular genomic contexts. Whole-genome duplication (WGD) common macroevolutionary event occurs more than 30% human tumors early tumorigenesis. Although have undergone WGD are reported be permissive aneuploidy, remains unknown whether also affects patterns. Here we analyzed...
Chromosomal instability (CIN), a high rate of chromosome loss or gain, is often associated with poor prognosis and drug resistance in cancers. Aneuploid, including near-polyploid, cells contain an abnormal number chromosomes exhibit CIN. The post-mitotic cell fates following generation different degrees mis-segregation aneuploidy are unclear. Here we used inducers, nocodazole reversine, to create levels aneuploidy. A higher extent aneuploid near-polyploid given population led senescence....
Highlights•Culture on 3T3 cells enables long-term self-renewal of human pancreatic progenitors•Proliferation requires EGF, FGF10, retinoic acid, and inhibition Notch TGF-β•Cultured progenitors upregulate genes required for mitosis telomere maintenance•Pancreatic duct β-like are generated in vitro vivoSummaryPluripotent stem have been proposed as an unlimited source β studying treating diabetes. However, the long, multi-step differentiation protocols used to generate functional inevitably...
Tetraploidization, or genome doubling, is a prominent event in tumorigenesis, primarily because cell division polyploid cells error-prone and produces aneuploid cells. This study investigates changes gene expression evoked acute adapted tetraploid their effect on cell-cycle progression. Acute polyploidy was generated by knockdown of the essential regulator cytokinesis anillin, which resulted failure formation binucleate cells, chemical inhibition Aurora kinases, causing abnormal mitotic exit...
The spatial organization of the genome is enigmatic. Direct evidence physical contacts between chromosomes and their visualization at nanoscale resolution has been limited. We used superresolution microscopy to demonstrate that ribosomal DNA (rDNA) can form linkages chromosomes. observed rDNA in many different human cell types demonstrated anaphase. are coated by transcription factor UBF formation depends on UBF, indicating they regularly occur transcriptionally active loci. Overexpression...
Recombinant protein production in the methylotrophic yeast Pichia pastoris largely relies on integrative vectors. Although stability of integrated expression cassettes is well appreciated for most applications, availability reliable episomal vectors this host would represent a useful tool to expedite cloning and high-throughput screening, ameliorating also relatively high clonal variability reported transformants from caused by off-target integration P. genome. Recently, heterologous...
Abstract In many eukaryotic organisms cytokinesis is driven by a contractile actomyosin ring (CAR) that guides membrane invagination. What triggers CAR constriction at precise time of the cell cycle fundamental question. budding yeast assembled via septin scaffold division site. A Hippo-like kinase cascade, Mitotic Exit Network (MEN), promotes mitotic exit and cytokinesis, but whether how these two processes are independently controlled MEN poorly understood. Here we show critical function...
The distinct states of pluripotency in the pre- and post-implantation embryo can be captured vitro as naive primed pluripotent stem cell cultures, respectively. study application state remains hampered, particularly humans, partially due to current culture protocols relying on extraneous undefined factors such feeders. Here we performed a small-molecule screen identify compounds that facilitate chemically defined establishment maintenance human feeder-independent embryonic (FINE) cells....
The spindle assembly checkpoint (SAC) coordinates mitotic progression with sister chromatid alignment. In mitosis, the machinery accumulates at kinetochores, which are scaffolds devoted to microtubule capture. protein Mad2 (mitotic arrest deficient 2) adopts two conformations: open (O-Mad2) and closed (C-Mad2). C-Mad2 forms when binds its target Cdc20 or kinetochore receptor Mad1. When unbound these ligands, folds as O-Mad2. HeLa cells, an essential interaction between C- O-Mad2 conformers...
Understanding how cells acquire genetic mutations is a fundamental biological question with implications for many different areas of biomedical research, ranging from tumor evolution to drug resistance. While karyotypic heterogeneity hallmark cancer cells, few causing chromosome instability have been identified in genomes, suggesting nongenetic origin this phenomenon. We found that vitro exposure karyotypically stable human colorectal cell lines environmental stress conditions triggered wide...