A5023437779- RNA Research and Splicing
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Genomics and Chromatin Dynamics
- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- Blood disorders and treatments
- Retinoids in leukemia and cellular processes
- Cancer, Hypoxia, and Metabolism
- Cancer Research and Treatments
- RNA Interference and Gene Delivery
- Cleft Lip and Palate Research
- Head and Neck Surgical Oncology
- Ocular Oncology and Treatments
- Immunodeficiency and Autoimmune Disorders
- Virus-based gene therapy research
- Genetics, Bioinformatics, and Biomedical Research
- Origins and Evolution of Life
- Hydrogels: synthesis, properties, applications
- CRISPR and Genetic Engineering
- Protein Degradation and Inhibitors
- Plant Molecular Biology Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- 3D Printing in Biomedical Research
- Cancer-related gene regulation
Massachusetts Institute of Technology
2008-2025
Allen Institute
2009-2025
Koch Institute for Integrative Cancer Research At MIT
2009-2022
Stanford University
2013-2016
Mutation of the RB-1 and p53 tumor suppressors is associated with development human osteosarcoma. With goal generating a mouse model this disease, we used conditional transgenic strains to inactivate Rb and/or specifically in osteoblast precursors. The resulting Rb;p53 double mutant (DKO) animals are viable but develop early onset osteosarcomas complete penetrance. These tumors display many characteristics osteosarcomas, including being highly metastatic. We established cell lines from DKO...
The retinoblastoma protein gene RB-1 is mutated in one-third of human tumors. Its product, pRB (retinoblastoma protein), functions as a transcriptional coregulator many fundamental cellular processes. Here, we report nonnuclear role for apoptosis induction via pRB's direct participation mitochondrial apoptosis. We uncovered this activity by finding that potentiated TNFα-induced even when translation was blocked. This proapoptotic function highly BAX-dependent, suggesting apoptosis, and...
Biomolecular condensates are implicated in core cellular processes such as gene regulation and ribosome biogenesis. Although the architecture of biomolecular is thought to rely on collective interactions between many components, it unclear how required for their formation emerge during evolution. Here, we show that structure evolution a recently emerged condensate, nucleolar fibrillar center (FC), explained by single self-assembling scaffold, TCOF1. TCOF1 necessary form FC, structurally...
Shwachman-Diamond syndrome (SDS) is characterized by neutropenia, exocrine pancreatic insufficiency, and bony abnormalities with an increased risk of myeloid neoplasia. Almost all cases SDS result from biallelic mutations in SBDS. SBDS interacts EFL1 to displace EIF6 the 60S ribosomal subunit. Released permits assembly large small subunits cytoplasm. Decreased levels due haploinsufficiency or missense which lead decreased protein expression may provide a somatic genetic rescue anti-leukemic...
Protein synthesis during vertebrate embryogenesis is driven by ribosomes of two distinct origins: maternal synthesized oogenesis and stored in the egg, somatic ribosomes, produced developing embryo after zygotic genome activation (ZGA). In zebrafish, these ribosome types are expressed from different genomic loci also differ their ribosomal RNA (rRNA) sequence. To characterize this dual system further, we examined expression patterns rRNAs adult tissues. We found that not only but...
Protein synthesis during vertebrate embryogenesis is driven by ribosomes of two distinct origins: maternal synthesized oogenesis and stored in the egg, somatic ribosomes, produced developing embryo after zygotic genome activation (ZGA). In zebrafish, these ribosome types are expressed from different genomic loci also differ their ribosomal RNA (rRNA) sequence. To characterize this dual system further, we examined expression patterns rRNAs adult tissues. We found that not only but...
Low complexity regions (LCRs) play a role in variety of important biological processes, yet we lack unified view their sequences, features, relationships, and functions. Here, use dotplots dimensionality reduction to systematically define LCR type/copy relationships create map sequence space capable integrating features By defining across the proteome, provide insight into how type copy number contribute higher order assemblies, such as importance K-rich for assembly nucleolar protein RPA43...
Calmodulin inhibitors rescue erythropoiesis and p53-dependent phenotypes of Diamond-Blackfan anemia.
Abstract The composition and organization of the cell surface determine how cells interact with their environment. Traditionally, glycosylated transmembrane proteins were thought to be major constituents external plasma membrane. Here, we provide evidence that a group RNA binding (RBPs) are present on living cells. These RBPs (csRBPs) precisely organize into well-defined nanoclusters enriched for multiple RBPs, glycoRNAs, clustering can disrupted by extracellular RNase addition....
Protein synthesis during vertebrate embryogenesis is driven by ribosomes of two distinct origins: maternal synthesized oogenesis and stored in the egg, somatic ribosomes, produced developing embryo after zygotic genome activation (ZGA). In zebrafish, these ribosome types are expressed from different genomic loci also differ their ribosomal RNA (rRNA) sequence. To characterize this dual system further, we examined expression patterns rRNAs adult tissues. We found that not only but...
Shwachman-Diamond syndrome (SDS) is characterized by exocrine pancreatic insufficiency, neutropenia, and skeletal abnormalities. Biallelic mutations in SBDS, which encodes a ribosome maturation factor, are found 90% of SDS cases. Sbds–/– mice embryonic lethal. Using CRISPR/Cas9 editing, we created sbds-deficient zebrafish strains. Sbds protein levels progressively decreased became undetectable at 10 days postfertilization (dpf). Polysome analysis revealed 80S ribosomes. Homozygous mutant...