A5041244583- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- MicroRNA in disease regulation
- Cell Adhesion Molecules Research
- RNA Research and Splicing
- Cancer-related Molecular Pathways
- Glioma Diagnosis and Treatment
- Cellular Mechanics and Interactions
- RNA Interference and Gene Delivery
- Cellular transport and secretion
- PARP inhibition in cancer therapy
- BRCA gene mutations in cancer
- Cancer Research and Treatments
- Protease and Inhibitor Mechanisms
- Genomics and Chromatin Dynamics
- Ubiquitin and proteasome pathways
- Epigenetics and DNA Methylation
- RNA and protein synthesis mechanisms
- Circular RNAs in diseases
Stanford University
2018-2025
Whitehead Institute for Biomedical Research
2023
Howard Hughes Medical Institute
2023
Massachusetts Institute of Technology
2023
Harvard University
2016-2022
Dana-Farber Cancer Institute
2022
Long noncoding RNAs (lncRNAs) have been implicated in numerous cellular processes including brain development. However, the vivo expression dynamics and molecular pathways regulated by these loci are not well understood. Here, we leveraged a cohort of 13 lncRNA-null mutant mouse models to investigate spatiotemporal lncRNAs developing adult transcriptome alterations resulting from loss lncRNA loci. We show that several differentially expressed both time space, with some presenting highly...
The Linc-p21 locus, encoding a long non-coding RNA, plays an important role in p53 signaling, cell-cycle regulation, and tumor suppression. However, despite extensive study, confusion exists regarding its mechanism of action: is activity driven by the transcript acting trans, cis, or underlying functional enhancer? Here, using knockout mouse model massively parallel enhancer assay, we delineate elements at this locus. We observe that, even tissues with no detectable transcript, deletion...
MicroRNAs (miRNAs) pair to sites in mRNAs direct the degradation of these RNA transcripts. Conversely, certain transcripts can particular miRNAs. This target-directed miRNA (TDMD) requires ZSWIM8 E3 ubiquitin ligase. Here, we report function mouse embryo. Zswim8 −/− embryos were smaller than their littermates and died near time birth. highly penetrant perinatal lethality was apparently caused by a lung sacculation defect attributed failed maturation alveolar epithelial cells. Some mutant...
Collagens are the most abundant proteins in body and comprise basement membranes stroma through which cancerous invasion occurs; however, a pro-neoplastic function for mutant collagens is undefined. Here we identify COL11A1 mutations 66 of 100 cutaneous squamous cell carcinomas (cSCCs), second common U.S. cancer, concentrated triple helical region known to produce trans-dominant collagens. Analysis other collagen genes found that they mutated across epithelial malignancies. Knockout impairs...
Abstract KRAS receives and relays signals at the plasma membrane (PM) where it transmits extracellular growth factor to downstream effectors. SNORD50A/B were recently found bind inhibit its tumorigenic action by unknown mechanisms. proximity protein labeling was therefore undertaken in wild-type knockout cells, revealing that RNAs shape composition of proteins proximal KRAS, notably inhibiting SNARE vesicular transport SNAP23, SNAP29, VAMP3. To remain enriched on PM, undergoes cycles...
Abstract MicroRNAs (miRNAs) pair to sites in mRNAs direct the degradation of these RNA transcripts. Conversely, certain transcripts can particular miRNAs. This target-directed miRNA (TDMD) requires ZSWIM8 E3 ubiquitin ligase. Here, we report function mouse embryo. Zswim8 −/− embryos were smaller than their littermates and died near time birth. highly penetrant perinatal lethality was apparently caused by a lung sacculation defect attributed failed maturation alveolar epithelial cells. Some...
Abstract TP53 is the most frequently mutated tumor suppressor with somatic alterations found in approximately 50% of all human cancers. In remaining wild-type (WT) tumors, functional inactivation p53 pathway may be achieved through a variety other mechanisms, including gene deletion, epigenetic silencing, and/or prominent negative regulators, MDM2/MDM4 and PPM1D. These block activity lead to uncontrolled cell proliferation oncogenesis majority cancers, highly aggressive, universally fatal...
Abstract A majority of high grade gliomas retain a wild-type TP53 gene and are amenable to strategies for activation the pathway inhibit tumor growth. The interaction between p53 MDM2 has served as target such currently in clinical trials glioblastoma. As effects resistance mechanisms inhibition (MDM2i) remain poorly understood glioma, we performed genomic transcriptomic analyses patient-derived models better characterize sensitive tumors identify putative biomarkers drug response. Treatment...