A5075035041- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer-related gene regulation
- RNA modifications and cancer
- Extracellular vesicles in disease
- Alzheimer's disease research and treatments
- Cancer-related molecular mechanisms research
- Amyotrophic Lateral Sclerosis Research
- Esophageal Cancer Research and Treatment
- Sphingolipid Metabolism and Signaling
- Head and Neck Cancer Studies
- Lysosomal Storage Disorders Research
- Muscle Physiology and Disorders
- Epigenetics and DNA Methylation
- Circular RNAs in diseases
- Autophagy in Disease and Therapy
- Neurogenesis and neuroplasticity mechanisms
- S100 Proteins and Annexins
- Adipose Tissue and Metabolism
- Bioinformatics and Genomic Networks
- Tryptophan and brain disorders
- Oral microbiology and periodontitis research
- Calcium signaling and nucleotide metabolism
- Cellular transport and secretion
- Salivary Gland Disorders and Functions
- Nerve injury and regeneration
Johns Hopkins Medicine
2023-2024
Johns Hopkins University
2023-2024
Central South University
2020-2023
Third Xiangya Hospital
2020-2023
Second Xiangya Hospital of Central South University
2020-2021
Emory University
2020
Guangxi Maternal and Child Health Hospital
2018
Abstract Heterozygous, loss-of-function mutations in the granulin gene ( GRN ) encoding progranulin (PGRN) are a common cause of frontotemporal dementia (FTD). Homozygous neuronal ceroid lipofuscinosis-11 (CLN11), lysosome storage disease. PGRN is secreted glycoprotein that can be proteolytically cleaved into seven bioactive 6 kDa granulins. However, it unclear how deficiency and granulins causes neurodegeneration. To gain insight mechanisms FTD pathogenesis, we utilized Tandem Mass Tag...
Alpha-synuclein aggregates (α-synAgg) are pathological hallmarks of Parkinson's disease (PD) and other synucleinopathies that induce microglial activation immune-mediated neurotoxicity, but the molecular mechanisms α-synAgg-induced immune poorly defined. We performed quantitative proteomics by mass spectrometry coupled with PCR, immunohistochemical functional validations studies to define characteristics alpha synuclein mediated activation. In mouse microglia, α-synAgg induced robust...
Abstract Background Cognitive decline in Alzheimer’s disease (AD) is associated with hyperphosphorylated tau (pTau) propagation between neurons along synaptically connected networks, part via extracellular vesicles (EVs). EV biogenesis triggered by ceramide enrichment at the plasma membrane from neutral sphingomyelinase2 (nSMase2)-mediated cleavage of sphingomyelin. We report, for first time, that human expression elevates brain ceramides and nSMase2 activity. Methods To determine...
Skeletal muscle suffers atrophy and weakness with aging. Denervation, oxidative stress, mitochondrial dysfunction are all proposed as contributors to age-associated loss, but connections between these factors have not been established. We examined contractility, function, intracellular calcium transients (ICTs) in muscles of mice throughout the life span define their sequential relationships. performed same measures analyzed neuromuscular junction (NMJ) morphology postnatal deletion neuronal...
Peripheral nerve injuries (PNIs) represent a significant clinical challenge, particularly in elderly populations where axonal remyelination and regeneration are impaired. Developing therapies to enhance these processes is crucial for improving PNI repair outcomes. Glutamate carboxypeptidase II (GCPII) neuropeptidase that plays pivotal role modulating glutamate signaling through its enzymatic cleavage of the abundant neuropeptide N-acetyl aspartyl (NAAG) liberate glutamate. Within PNS, GCPII...
Abstract Background Cognitive decline in Alzheimer’s disease (AD) is associated with prion-like tau propagation between neurons along synaptically connected networks, part via extracellular vesicles (EV). EV biogenesis triggered by ceramide enrichment at the plasma membrane from neutral sphingomyelinase2(nSMase2)-mediated cleavage of sphingomyelin. We report, for first time, that expression triggers an elevation brain ceramides and nSMase2 activity. Methods To determine therapeutic benefit...
Alzheimer’s disease(AD) progression correlates with the propagation of hyperphosphorylated Tau (pTau) from entorhinal cortex to hippocampus and neocortex. Neutral sphingomyelinase2(nSMase2) is critical in biosynthesis extracellular vesicles (EVs), which play a role pTau propagation. We recently conjugated DPTIP, potent nSMase2 inhibitor, hydroxyl-PAMAM-dendrimer nanoparticles can improve brain delivery. showed that dendrimer-conjugated-DPTIP (D-DPTIP) robustly inhibited spread an AAV-pTau...
The progression of Alzheimer's disease (AD) correlates with the propagation hyperphosphorylated tau (pTau) from entorhinal cortex to hippocampus and neocortex. Neutral sphingomyelinase2 (nSMase2) is critical in biosynthesis extracellular vesicles (EVs), which play a role pTau propagation. We recently conjugated DPTIP, potent nSMase2 inhibitor, hydroxyl-PAMAM-dendrimer nanoparticles that can improve brain delivery. showed dendrimer-conjugated DPTIP (D-DPTIP) robustly inhibited spread an...
Background KIAA1199 is a recently identified novel gene that upregulated in various human cancers with poor survival, but its role and the underlying mechanisms laryngeal squamous cell carcinoma (LSCC) remain unknown. Here, we collected tissues from 105 cases of LSCC to investigate relationships between protein expression clinical factors. Methods Western blotting real-time quantitative PCR (RT-PCR) were used for detect mRNA tissue. Immunohistochemistry (IHC) staining was KIAA1199. Patient...
Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor of head and neck. Screening target genes for therapy one the focuses cancer research, with proto-oncogene suppressor gene as breakthrough. It has become an urgent need to find related treatment prognosis LSCC.This study aims explore role Lin28B C-myc in LSCC by detecting expressions these two proteins analyze correlation between expression clinicopathological features LSCC.
Age-related loss of muscle mass and strength (Sarcopenia) significantly impairs quality life in the elderly, yet lacks effective treatments. We previously demonstrated that inhibition GCPII delayed function decline neuromuscular junction (NMJ) denervation an amyotrophic lateral sclerosis (ALS) animal model. As sarcopenia shares NMJ deterioration with ALS, we tested potent inhibitor 2-(phosphonomethyl)-pentanedioic acid (2-PMPA) aging mice, found it also preserved integrity. By...
Abstract Background Cognitive decline associated with Alzheimer’s disease (AD) correlates hyperphosphorylated tau (pTau) propagating between neurons along networks connected by synapses. It has been hypothesized this transcellular transmission occurs partially extracellular vesicles (EVs). Both genetic and pharmacological inhibition of nSMase2 found to inhibit EV biogenesis pTau propagation. However, the lack suitable inhibitors for clinical development a challenge. In our lab, highly...
Abstract Background Mounting evidence correlates the propagation of hyperphosphorylated tau (pTau) along synaptically connected networks in brain with progressive cognitive decline Alzheimer’s Disease (AD). Recent findings have highlighted extracellular vesicle (EV)s enabling transcellular transmission pathological and identified partial inhibition EV biogenesis via small‐molecule inhibitors nSMase2 as a potential therapeutic avenue. However, there are no suitable compounds for clinical...
Mutations in the GRN gene, which encodes progranulin (PGRN) protein, are one of most common causes Frontotemporal dementia (FTD) and cause disease through haploinsufficiency PGRN. PGRN is composed 7.5 repeating domains termed granulins (GRNs 1–7) that joined by linker regions. We have recently found processed into ~6kDa GRNs within lysosome, where we hypothesize they critical for lysosome homeostasis (Holler et al, eNeuro , 2017 Aug 18;4(4)). However, molecular mechanisms caused decreased...
Abstract Background Mutations in the GRN gene, encoding progranulin (PGRN) protein, are a common cause of Frontotemporal dementia (FTD) and induce haploinsufficiency PGRN. PGRN is composed 7.5 repeating domains called granulins (GRNs 1‐7). processed into GRNs within lysosome, where we hypothesize they critical for lysosome homeostasis function. However, it unclear how decreased levels lysosomal PGRN/GRNs FTD, Alzheimer’s disease, related neurodegenerative disorders. Methods We performed...