A5080005941- Hippo pathway signaling and YAP/TAZ
- Glioma Diagnosis and Treatment
- Phagocytosis and Immune Regulation
- Cell Adhesion Molecules Research
- Erythrocyte Function and Pathophysiology
- Kruppel-like factors research
- Pluripotent Stem Cells Research
- MicroRNA in disease regulation
- Cancer Cells and Metastasis
- Epigenetics and DNA Methylation
- Parkinson's Disease Mechanisms and Treatments
- Nerve injury and regeneration
- Neuroinflammation and Neurodegeneration Mechanisms
- Extracellular vesicles in disease
- CRISPR and Genetic Engineering
- Neuroscience and Neural Engineering
- Protein Degradation and Inhibitors
- Conducting polymers and applications
- RNA Research and Splicing
- Genetic Neurodegenerative Diseases
- CAR-T cell therapy research
- RNA Interference and Gene Delivery
- Lanthanide and Transition Metal Complexes
- Nuclear Receptors and Signaling
- PARP inhibition in cancer therapy
Kennedy Krieger Institute
2016-2025
Johns Hopkins Medicine
2008-2024
Johns Hopkins University
2015-2024
Taizhou People's Hospital
2020
Nantong University
2020
Wake Forest University
2019
Forest Institute
2019
Charlottesville Medical Research
2019
John Wiley & Sons (United States)
2019
Moser (Czechia)
2017
Intracerebral hemorrhage (ICH) causes high mortality and morbidity, but our knowledge of post-ICH neuronal death related mechanisms is limited. In this study, we first demonstrated that ferroptosis, a newly identified form cell death, occurs in the collagenase-induced ICH model mice. We found administration ferrostatin-1, specific inhibitor prevented reduced iron deposition induced by hemoglobin organotypic hippocampal slice cultures (OHSCs). Mice treated with ferrostatin-1 after exhibited...
The tyrosine kinase c-Met promotes the formation and malignant progression of multiple cancers. It is well known that hyperactivation increases tumorigenicity tumor cell resistance to DNA damaging agents, properties associated with tumor-initiating stem cells. However, a link between signaling and/or maintenance neoplastic cells has not been previously identified. Here, we show activated functional in glioblastoma (GBM) neurospheres enriched for expression/function correlates marker...
Abstract Glioblastoma (GBM) stem cells (GSC) are a subpopulation of tumor that display stem-like characteristics (stemness) and play unique roles in propagation, therapeutic resistance, recurrence. Therapeutic targets GSCs focus increasing interest to improve GBM therapy. Here we report the hyaluronan-mediated motility receptor (HMMR) is highly expressed tumors, where it supports self-renewal tumorigenic potential GSCs. HMMR silencing impairs GSC inhibits expression markers regulators....
Abstract Pathologic α-synuclein (α-syn) spreads from cell-to-cell, in part, through binding to the lymphocyte-activation gene 3 (Lag3). Here we report that amyloid β precursor-like protein 1 (Aplp1) interacts with Lag3 facilitates binding, internalization, transmission, and toxicity of pathologic α-syn. Deletion both Aplp1 eliminates loss dopaminergic neurons accompanying behavioral deficits induced by α-syn preformed fibrils (PFF). Anti-Lag3 prevents internalization PFF disrupting...
The ligands of mitochondrial translocator protein (TSPO) have been widely used as diagnostic biomarkers for glioma. However, the true biological actions TSPO in vivo and its role glioma tumorigenesis remain elusive.
Abstract Glioblastomas (GBM) are highly infiltrated by myeloid-derived innate immune cells that contribute to the immunosuppressive nature of brain tumor microenvironment (TME). CD47 has been shown mediate evasion, as CD47–SIRPα axis prevents phagocytosis macrophages and other myeloid cells. In this study, we established homozygous deletion (CD47−/−) in human mouse GBM investigated impact eliminating "don't eat me" signal on growth tumor–TME interactions. knockout (KO) did not significantly...
While carbon dots (C-dots) have been extensively investigated pertaining to their fluorescent, phosphorescent, electrochemiluminescent, optoelectronic, and catalytic features, inherent chemical exchange saturation transfer magnetic resonance imaging (CEST MRI) properties are unknown. By virtue of hydrophilicity abundant exchangeable protons hydroxyl, amine, amide anchored on the surface, we report here that C-dots can be adapted as effective diamagnetic CEST (diaCEST) MRI contrast agents. As...
A subset of stem-like cells in glioblastoma (GBM; GSC) underlies tumor propagation, therapeutic resistance, and recurrence. Immune evasion is critical for GSCs to carry out these functions. However, the molecular mechanisms employed by escape antitumor immunity remain largely unknown. The reprogramming transcription factors Oct4 Sox2 function as core multipotency play an essential role formation maintenance GSCs, but roles GSC immune have not been well explored. Here we examine how Oct4/Sox2...
Dentatorubral-pallidoluysian atrophy (DRPLA) is a progressive neurodegenerative disease caused by polyglutamine expansion within the Atrophin-1 protein. To study mechanism of this and to test potential therapeutic methods, we established Atro-118Q transgenic mice, which express in neurons mutant human protein that contains an expanded stretch 118 glutamines. Consistent with results from previous studies on mice expressed 65 glutamines, exhibited several phenotypes are commonly seen DRPLA...
Abstract Background Missense mutations and multiplications of the α-synuclein gene cause autosomal dominant familial Parkinson's disease (PD). α-Synuclein protein is also a major component Lewy bodies, hallmark pathological inclusions PD. Therefore, plays an important role in pathogenesis sporadic To model α-synuclein-linked vivo , transgenic mouse models have been developed that express wild-type or mutant human from variety neuronal-selective heterologous promoter elements. These exhibit...
Tumor-initiating stem cells (alternatively called cancer cells, CSCs) are a subpopulation of tumor that plays unique roles in propagation, therapeutic resistance, and recurrence. It is becoming increasingly important to understand the molecular signaling regulates self-renewal differentiation CSCs. Transcription factors critical for regulation normal neopolastic cells. Here, we examined expression function Krüppel-like family transcription (KLFs) human glioblastoma (GBM)-derived neurosphere...
Altered DNA methylation status is associated with human diseases and cancer; however, the underlying molecular mechanisms remain elusive. We previously identified many transcription factors, including Krüppel-like factor 4 (KLF4), as sequence-specific readers that preferentially recognize methylated CpG (mCpG), here we report biological function of mCpG-dependent gene regulation by KLF4 in glioblastoma cells. show promotes cell adhesion, migration, morphological changes, all which are...
Spinal cord motor neurons (MNs) from human iPS cells (iPSCs) have wide applications in disease modeling and therapeutic development for amyotrophic lateral sclerosis (ALS) other MN-associated neurodegenerative diseases. We need highly efficient MN differentiation strategies generating iPSC-derived models that closely recapitulate the genetic phenotypic complexity of ALS. An important application these is to understand molecular mechanisms action FDA-approved ALS drugs only show modest...
Abstract The spread of prion‐like protein aggregates is a common driver pathogenesis in various neurodegenerative diseases, including Alzheimer's disease (AD) and related Tauopathies. Tau pathologies exhibit clear progressive spreading pattern that correlates with severity. Clinical observation combined complementary experimental studies has shown preformed fibrils (PFF) are seeds propagate pathology by entering cells templating misfolding aggregation endogenous Tau. While several cell...
Lymphocyte activation gene 3 (LAG3) is a key receptor involved in the propagation of pathological proteins Parkinson disease (PD). This study investigates role neuronal LAG3 mediating binding, uptake, and alpha-synuclein (aSyn) preformed fibrils (PFFs). Using conditional knockout mice human induced pluripotent stem cells-derived dopaminergic (DA) neurons, we demonstrate that expression critical for pathogenic aSyn propagation. Our results show absence significantly reduces pathology,...
Abstract Human pluripotent stem cells (PSCs) are a promising cell resource for various applications in regenerative medicine. Highly efficient approaches that differentiate human PSCs into functional lineage-specific neurons critical modeling neurological disorders and testing potential therapies. Proneural transcription factors crucial drivers of neuron development hold promise driving highly neuronal conversion PSCs. Here, we study the functions proneural factor Atoh1 differentiation We...
Abstract Proneural transcription factors (TFs) drive highly efficient differentiation of pluripotent stem cells to lineage-specific neurons. However, current strategies mainly rely on genome-integrating viruses. Here, we used synthetic mRNAs coding two proneural TFs (Atoh1 and Ngn2) differentiate induced (iPSCs) into midbrain dopaminergic (mDA) Atoh1 Ngn2 with defined phosphosite modifications led higher more stable protein expression, neuron conversion, as compared wild-type proteins. Using...
We evaluate the feasibility of using a biological sample's transcriptome to predict its genome-wide regulatory element activities measured by DNase I hypersensitivity (DH). develop BIRD, Big Data Regression for predicting DH, handle this high-dimensional problem. Applying BIRD Encyclopedia DNA Elements (ENCODE) data, we found that large extent gene expression predicts and information useful prediction is contained in whole rather than limited element's neighboring genes. show applications...
Abstract Glioblastoma (GBM) is the most aggressive primary brain tumor. In addition to being genetically heterogeneous, GBMs are also immunologically heterogeneous. However, whether differences in immune microenvironment driven by genetic driver mutation unexplored. By leveraging versatile RCAS/ tv‐a somatic gene transfer system, we establish a mouse model for Classical GBM introducing EGFRvIII expression Nestin ‐positive neural stem/progenitor cells adult mice. Along with our previously...
ATRX inactivation occurs with IDH1R132H and p53 mutations in over 80% of Grades II/III astrocytomas. It is believed that loss contributes to oncogenesis by dysregulating epigenetic telomere mechanisms but effects on anti-glioma immunity have not been explored. This paper examines how the malignant immunosuppressive phenotypes IDH1R132H/p53mut glioma cells xenografts.Isogenic astrocytoma (+/-IDH1R132H/+/-ATRXloss) were established p53mut cell lines using lentivirus encoding...
Krüppel-like factor 4 (KLF4) is a zinc finger transcription critical for the regulation of many cellular functions in both normal and neoplastic cells. Here, using human glioblastoma cells, we investigated KLF4's effects on cancer cell metabolism. We found that forced KLF4 expression promotes mitochondrial fusion induces dramatic changes morphology. To determine impact these following, analyzed how alters metabolism, including glucose uptake, glycolysis, pentose phosphate pathway, oxidative...