A5083867613- Genetics and Neurodevelopmental Disorders
- Microtubule and mitosis dynamics
- Epigenetics and DNA Methylation
- Neurogenesis and neuroplasticity mechanisms
- Cellular Mechanics and Interactions
- Genomics and Chromatin Dynamics
- Neuroscience and Neuropharmacology Research
- RNA Research and Splicing
- Ubiquitin and proteasome pathways
- Axon Guidance and Neuronal Signaling
- Protein Kinase Regulation and GTPase Signaling
- Cancer-related gene regulation
- Cancer-related molecular mechanisms research
- Endoplasmic Reticulum Stress and Disease
- RNA and protein synthesis mechanisms
- Cell Adhesion Molecules Research
- Mitochondrial Function and Pathology
- interferon and immune responses
- Autism Spectrum Disorder Research
- Gene Regulatory Network Analysis
- RNA modifications and cancer
- Neuroinflammation and Neurodegeneration Mechanisms
- Signaling Pathways in Disease
- Cell death mechanisms and regulation
- Hedgehog Signaling Pathway Studies
Rockefeller University
2008-2025
Cold Spring Harbor Laboratory
1998-2005
Stony Brook University
2004
Massachusetts Institute of Technology
1998
The AF-6 protein is a multidomain that contains two potential Ras-binding domains within its N terminus. Because of this feature, has been isolated in both two-hybrid and biochemical approaches postulated to be Ras-effector protein. Herein, we show it specifically the first domain mediates interaction Ras-related Rap1A can associate with motif even more efficiently than oncogenic Ha-, K-, N-Ras GTPases. We further demonstrate Ras Rap1 interact full-length vivo mammalian cells fraction...
Understanding how oncogenic transformation sensitizes cells to apoptosis may provide a strategy kill tumor selectively. We previously developed cell-free system that recapitulates oncogene dependent as reflected by activation of caspases, the core apoptotic machinery. Here, we show this requires identified apoptosis-promoting complex consisting caspase-9, APAF-1, and cytochrome c . As predicted in vitro system, preventing caspase-9 blocked drug-induced sensitized E1A, an adenoviral oncogene....
During normal cerebellar development, the remarkable expansion of granule cell progenitors (GCPs) generates a population neurons that outnumbers total neuronal cerebral cortex, and provides model for identifying signaling pathways may be defective in medulloblastoma. While many studies focus on promote growth GCPs, critical unanswered question concerns identification block mitogenic stimulation induce early steps differentiation. Here we identify WNT3 as novel suppressor GCP proliferation...
CNS cortical histogenesis depends on polarity signaling pathways that regulate cell adhesion and motility. Here we report conditional deletion of the Rho GTPase Cdc42 in cerebellar granule precursors (GCPs) results abnormalities foliation revealed by iDISCO clearing methodology, a loss columnar organization proliferating GCPs external germinal layer (EGL), disordered parallel fiber molecular (ML), failure to extend leading process form neuron-glial junction during migration along Bergmann...
Developing neurons undergo a progression of morphological and gene expression changes as they transition from neuronal progenitors to mature neurons. Here we used RNA-seq H3K4me3 H3K27me3 ChIP-seq analyze how chromatin modifications control in specific type CNS neuron: the mouse cerebellar granule cell (GC). We found that proliferating GC (GCPs), H3K4me3/H3K27me3 bivalency is common at genes undergoes dynamic correlate with during migration circuit formation. Expressing fluorescent sensor...
Significance The conserved proteasome-binding protein PI31 serves as an adapter to couple proteasomes with cellular motors mediate their transport distal tips of neurons where breakdown occurs. We generated global and conditional knockout mouse strains show that this is required for homeostasis, its inactivation in disrupts synaptic structures long-term survival. This work establishes a critical role local degradation the maintenance neuronal architecture, circuitry, function. Because...
Alternative polyadenylation (APA) regulates mRNA translation, stability, and protein localization. However, it is unclear to what extent APA these processes uniquely in specific cell types. Using a new technique, cTag-PAPERCLIP, we discovered significant differences between the principal types of mouse cerebellar neurons, Purkinje granule cells, as well proliferating differentiated cells. Transcripts that differed comparisons were enriched key neuronal functions many coding sequence addition...
Spontaneous and sensory-evoked activity sculpts developing circuits. Yet, how these patterns intersect with cellular programs regulating the differentiation of neuronal subtypes is not well understood. Through electrophysiological in vivo longitudinal analyses, we show that C-X-C motif chemokine ligand 14 (Cxcl14), a gene previously characterized for its association tumor invasion, expressed by single-bouquet cells (SBCs) layer I (LI) somatosensory cortex during development. Sensory...
ABSTRACT Alternative polyadenylation (APA) regulates mRNA translation, stability, and protein localization. However, it is unclear to what extent APA these processes uniquely in specific cell types. Using a new technique, cTag-PAPERCLIP, we discovered significant differences between the principal types of mouse cerebellar neurons, Purkinje granule cells, as well proliferating differentiated cells. Transcripts that differed comparisons were enriched key neuronal functions many coding sequence...
Abstract Proteasome-mediated degradation of intracellular proteins is essential for cell function and survival. The proteasome-binding protein PI31 (Proteasomal Inhibitor 31kD) promotes 26S assembly functions as an adapter proteasome transport in axons. As localized synthesis especially critical neurons, we generated a conditional loss spinal motor neurons (MNs) cerebellar Purkinje cells (PCs). A cKO these caused axon degeneration, neuronal progressive neurological dysfunction. For both MNs...
Developing neurons undergo a progression of morphological and gene expression changes as they transition from neuronal progenitors to mature, multipolar neurons. Here we use RNA-seq H3K4me3 H3K27me3 ChIP-seq analyze how chromatin modifications control in specific type CNS neuron, the mouse cerebellar granule cell (GC). We find that proliferating GC (GCPs), H3K4me3/H3K27me3 bivalency is common at genes undergoes dynamic correlate with during migration circuit formation. Expressing fluorescent...