A5040778831- Microtubule and mitosis dynamics
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Chromosomal and Genetic Variations
- Marine Invertebrate Physiology and Ecology
- Pluripotent Stem Cells Research
- Digestive system and related health
- Cell Image Analysis Techniques
- Single-cell and spatial transcriptomics
- Cellular Mechanics and Interactions
- RNA and protein synthesis mechanisms
- Hippo pathway signaling and YAP/TAZ
- Protein Structure and Dynamics
- Advanced NMR Techniques and Applications
- Biomedical and Engineering Education
- Erythrocyte Function and Pathophysiology
- Genetics, Aging, and Longevity in Model Organisms
- Biomedical Ethics and Regulation
- Cancer Cells and Metastasis
- 3D Printing in Biomedical Research
- Genomic variations and chromosomal abnormalities
- Bacterial Genetics and Biotechnology
- Gastrointestinal Bleeding Diagnosis and Treatment
- Aerogels and thermal insulation
- Interdisciplinary Research and Collaboration
Howard Hughes Medical Institute
2017-2024
University of California, San Francisco
2017-2024
Harvard University
2021-2024
Harvard Stem Cell Institute
2023
Whitehead Institute for Biomedical Research
2014-2018
Massachusetts Institute of Technology
2014-2018
Princeton University
2011
Lawrence Livermore National Laboratory
1995
Abstract Maintaining centromere identity relies upon the persistence of epigenetic mark provided by histone H3 variant, protein A (CENP-A), but molecular mechanisms that underlie its remarkable stability remain unclear. Here, we define contributions each three candidate CENP-A nucleosome-binding domains (two on CENP-C and one CENP-N) to using gene replacement rapid degradation. Surprisingly, most conserved domain, motif, is dispensable. Instead, conferred unfolded central domain folded...
Cell division is essential to expand, shape, and replenish epithelia. In the adult small intestine, cells from a common progenitor intermix with other lineages, whereas cell progeny in many epithelia form contiguous patches. The mechanisms that generate these distinct patterns of are poorly understood. Using light sheet confocal imaging intestinal organoids, we show lineages intersperse during cytokinesis, when elongated interphase insert between apically displaced daughters. Reducing...
Bridging knowledge gaps could enable regenerative therapy.
A central challenge of synthetic biology is to enable the growth living systems using parts that are not derived from nature, but designed and synthesized in laboratory. As an initial step toward achieving this goal, we probed ability a collection >106 de novo proteins provide biological functions necessary sustain cell growth. Our was drawn combinatorial library 102-residue sequences, by binary patterning polar nonpolar residues fold into stable 4-helix bundles. We capacity function vivo...
The key player in directing proper chromosome segregation is the macromolecular kinetochore complex, which mediates DNA-microtubule interactions. Previous studies testing individual genes documented examples of their overexpression tumors relative to normal tissue, leading proposals that up-regulation specific may promote tumor progression. However, components do not function isolation, and previous did comprehensively compare expression behavior components. Here we analyze full range human...
Cells rely on a diverse array of engulfment processes to sense, exploit, and adapt their environments. Among these, macropinocytosis enables indiscriminate rapid uptake large volumes fluid membrane, rendering it highly versatile strategy. Much the molecular machinery required for has been well established, yet how this process is regulated in context organs organisms remains poorly understood. Here, we report discovery extensive outer epithelium cnidarian Hydra vulgaris. Exploiting Hydra’s...
Abstract A key aspect of nutrient absorption is the exquisite division labor across length small intestine, with individual classes micronutrients taken up at different positions. For millennia, intestine was thought to comprise three segments indefinite borders: duodenum, jejunum, and ileum. By examining fine-scale longitudinal segmentation mouse human intestines, we identified transcriptional signatures upstream regulatory factors that define five domains absorption, distinct from...
Abstract Cell proliferation is critical for maintaining the absorptive, protective and regenerative functions of small intestine throughout adulthood. Interphase nuclei are positioned near basal surface intestinal epithelium, but during mitosis, chromosomes located apically. The molecular basis apical-basal DNA positioning its consequences tissue homeostasis poorly understood. Here, we image pharmacologically perturb these behaviors in live murine organoids. We find that apical movements...
Summary The Mad1-Mad2 heterodimer is the catalytic hub of spindle assembly checkpoint (SAC), which controls mitosis through a multi-subunit anaphase inhibitor, mitotic complex (MCC) [1, 2]. first catalyzes MCC at interphase nuclear pores [3], then migrates to kinetochores envelope breakdown (NEBD) and resumes until bipolar attachment complete There significant debate about factor(s) involved in targeting higher eukaryotes [4-9]. Through gene editing live-cell imaging, we found that human...
CRISPR/Cas9 technology has revolutionized the production of animal models by reducing experimental timelines, slashing costs and streamlining gene editing, leading to a rapid expansion in number unique for study human disease function. However, most non-model animals, many which are important cancer aging research, remain recalcitrant genome engineering due our limited understanding their reproductive biology. Many wild rodents that transmit diseases particularly challenging engineer low...
Abstract Cells rely on a diverse array of engulfment processes to sense, exploit, and adapt their environments. Macropinocytosis is versatile example such process, allowing for the indiscriminate rapid uptake large volumes fluid membrane. Much molecular machinery essential macropinocytosis has been well established. However, most these studies relied tissue culture models, leaving regulation this process within context organs organisms unresolved. Here, we report that large-scale occurs in...