A5014243012- Cancer-related molecular mechanisms research
- Neurogenesis and neuroplasticity mechanisms
- Glioma Diagnosis and Treatment
- MicroRNA in disease regulation
- Epigenetics and DNA Methylation
- Single-cell and spatial transcriptomics
- Neuroscience and Neuropharmacology Research
- Neural dynamics and brain function
- Hippo pathway signaling and YAP/TAZ
- RNA Research and Splicing
- RNA modifications and cancer
- Advanced Fluorescence Microscopy Techniques
- Genetics, Aging, and Longevity in Model Organisms
- Microtubule and mitosis dynamics
- Cancer-related gene regulation
- Histone Deacetylase Inhibitors Research
- Cell Image Analysis Techniques
- Ubiquitin and proteasome pathways
- Cancer Genomics and Diagnostics
- Genomics and Chromatin Dynamics
- RNA regulation and disease
- PI3K/AKT/mTOR signaling in cancer
- Neonatal and fetal brain pathology
- Neuroinflammation and Neurodegeneration Mechanisms
- Photoreceptor and optogenetics research
Cincinnati Children's Hospital Medical Center
2019-2023
Children's Hospital & Medical Center
2022
University of Tennessee at Chattanooga
2020
Massachusetts Institute of Technology
2016-2019
Institute of Cognitive and Brain Sciences
2017
University of Alabama
2008-2009
Abstract MYC-driven medulloblastomas are highly aggressive childhood brain tumors, however, the molecular and genetic events triggering MYC amplification malignant transformation remain elusive. Here we report that mutations in CTDNEP1, a CTD nuclear-envelope-phosphatase, most significantly enriched recurrent alterations medulloblastomas, define high-risk subsets with poorer prognosis. Ctdnep1 ablation promotes of murine cerebellar progenitors into Myc -amplified resembling their human...
Abstract Glioblastoma (GBM) is the most common and aggressive primary brain tumor, but mechanisms underlying tumor growth progression remain unclear. The protein arginine methyltransferases (PRMTs) regulate a variety of biological processes, however, their roles in GBM are not fully understood. In this study, our functional analysis gene expression networks revealed that among PRMT family PRMT3 was significantly enriched both low-grade gliomas. Higher predicted poorer overall survival rate...
<ns4:p>Oligodendrocytes are the critical cell types giving rise to myelin nerve sheath enabling efficient transmission in central nervous system (CNS). Oligodendrocyte precursor cells differentiate into mature oligodendrocytes and maintained throughout life. Deficits generation, proliferation, or differentiation of these their maintenance have been linked neurological disorders ranging from developmental neurodegenerative diseases limit repair after CNS injury. Understanding regulation...
Abstract Ten-eleven translocation (TET) proteins, the dioxygenase for DNA hydroxymethylation, are important players in nervous system development and diseases. However, their role myelination remyelination after injury remains elusive. Here, we identify a genome-wide locus-specific hydroxymethylation landscape shift during differentiation of oligodendrocyte-progenitor cells (OPC). Ablation Tet1 results stage-dependent defects oligodendrocyte (OL) mouse brain. The mice lacking lineage develop...
Neuronal hyperactivity induces memory deficits in Alzheimer's disease. However, how disrupts is unclear. Using vivo synaptic imaging the mouse visual cortex, we show that structural excitatory-inhibitory synapse imbalance apical dendrites favors early amyloidosis. Consistent with this, natural images elicit neuronal these mice. Compensatory changes maintain activity homeostasis disrupt functional connectivity and increase population sparseness such a small fraction of neurons dominates...
Abstract Malignant gliomas such as glioblastoma are highly heterogeneous with distinct cells of origin and varied genetic alterations. It remains elusive whether the specific states neural cell lineages differentially susceptible to alterations during malignant transformation. Here, an analysis The Cancer Genome Atlas databases revealed that comutations PTEN TP53 most significantly enriched in human high-grade gliomas. Therefore, we selectively ablated Pten Trp53 different progenitors...
Line-scanning temporal focusing microscopy (LineTFM) is capable of imaging biological samples more than 10 times faster two-photon laser point-scanning (TPLSM), while achieving nearly the same lateral and axial spatial resolution. However, image contrast taken by LineTFM lower that TPLSM because severely influenced tissue scattering. To reject scattered photons, we implemented using both structured illumination uniform combined with HiLo post-processing algorithm, called HiLL...
The oligodendrocyte (OL) lineage transcription factor Olig2 is expressed throughout oligodendroglial development and essential for progenitor specification differentiation. It was previously reported that deletion of enhanced the maturation myelination immature OLs accelerated remyelination process. However, by analyzing multiple conditional KO mouse lines (male female), we conclude has opposite effect required OL remyelination. We found in driven an OL-expressing Plp1 promoter resulted...
Medulloblastoma (MB) is the most common malignant pediatric brain tumor, however, mechanisms underlying tumorigenesis in different MB subgroups remain incompletely understood. Although previous studies of predisposition have been conducted tertiary referral centers primarily Caucasian cohorts, it not unclear clear whether there exist population-specific genetic alterations MBs. In this study, we investigated contribution genomic and transcriptomic to risk Chinese population (designated as...
The chromatin remodeler CHD8 represents a high-confidence risk factor in autism, multistage progressive neurologic disorder, however the underlying stage-specific functions remain elusive. In this study, by analyzing Chd8 conditional knock-out mice (male and female), we find that controls cortical neural stem/progenitor cell (NSC) proliferation survival stage-dependent manner. Strikingly, inducible genetic deletion reveals is required for production fitness of transit-amplifying intermediate...
Abstract The nerve-cell cytoskeleton is essential for the regulation of intrinsic neuronal activity. For example, migration defects are associated with microtubule regulators, such as LIS1 and dynein, well actin including Rac GTPases integrins, have been thought to underlie epileptic seizures in patients cortical malformations. However, it plausible that post-developmental functions specific cytoskeletal regulators contribute more transient nature aberrant activity could be masked by...
Simultaneous, high-resolution imaging across a large number of synaptic and dendritic sites is critical for understanding how neurons receive integrate signals. Yet, functional that targets submicrometer-sized locations poses significant technical challenges. We demonstrate new parallelized approach to address such questions, increasing the signal-to-noise ratio by an order magnitude compared previous approaches. This selective access multifocal multiphoton microscopy uses spatial light...
The nematode, Caenorhabditis elegans, has become an expedient model for studying neurotransmission. C. elegans is unique among animal models, as the anatomy and connectivity of its nervous system been determined from electron micrographs refined by pharmacological assays. In this video, we describe how two complementary neural stimulants, acetylcholinesterase inhibitor, called aldicarb, a gamma-aminobutyric acid (GABA) receptor antagonist, pentylenetetrazole (PTZ), may be employed to...
Diffuse intrinsic pontine glioma (DIPG) is a pediatric lethal high-grade brainstem with no effective therapies. OLIG2 (oligodendrocyte transcription factor 2) was reported to be critical for the growth of DIPG cell line CCHMC-DIPG-1. Surprisingly, we found that CCHMC-DIPG-1 cells express little and exhibit mesenchymal phenotype, which raised question regarding role in cells.We evaluated function different lines through molecular genetic approaches performed transcriptomic genomic landscape...
The nematode, Caenorhabditis elegans, has become an expedient model for studying neurotransmission. C. elegans is unique among animal models, as the anatomy and connectivity of its nervous system been determined from electron micrographs refined by pharmacological assays. In this video, we describe how two complementary neural stimulants, acetylcholinesterase inhibitor, called aldicarb, a gamma-aminobutyric acid (GABA) receptor antagonist, pentylenetetrazole (PTZ), may be employed to...
Abstract Progenitor heterogeneity and identities underlying tumor initiation relapse in medulloblastomas, the most common malignant pediatric brain tumor, remain elusive. Here, by utilizing single-cell analysis at different stages of tumorigenesis, we demonstrated a developmental hierarchy diverse progenitor pools sonic hedgehog (SHH)-medulloblastomas. Unexpectedly, identified Olig2-expressing progenitors as transit-amplifying cells onset tumorigenesis. Although Olig2+ become quiescent...