A5029117087- interferon and immune responses
- Cytokine Signaling Pathways and Interactions
- Cancer Mechanisms and Therapy
- Neuroscience and Neuropharmacology Research
- Immune cells in cancer
- Pancreatic and Hepatic Oncology Research
- Ion channel regulation and function
- Neural dynamics and brain function
- MicroRNA in disease regulation
- HIV Research and Treatment
- Chromatin Remodeling and Cancer
- Parkinson's Disease Mechanisms and Treatments
- Epigenetics and DNA Methylation
- HIV/AIDS Research and Interventions
- RNA modifications and cancer
- Pancreatitis Pathology and Treatment
- Virus-based gene therapy research
- Genetic Neurodegenerative Diseases
- Cancer Cells and Metastasis
- Neurological disorders and treatments
- Neurotransmitter Receptor Influence on Behavior
- Influenza Virus Research Studies
- Autophagy in Disease and Therapy
- Histone Deacetylase Inhibitors Research
- Cytomegalovirus and herpesvirus research
Zhejiang University
2007-2025
State Key Laboratory of Diagnosis and Treatment of Infectious Diseases
2015-2025
Shandong University
2024-2025
National Clinical Research Center for Digestive Diseases
2024-2025
First Affiliated Hospital Zhejiang University
2021-2025
National Center for Infectious Diseases
2024
University of California, Los Angeles
2012-2023
University of California System
2016
Los Angeles City College
2016
Broad Center
2012
Loss-of-function mutations in parkin are the major cause of early-onset familial Parkinson's disease. To investigate pathogenic mechanism by which loss function causes disease, we generated a mouse model bearing germline disruption parkin. Parkin–/– mice viable and exhibit grossly normal brain morphology. Quantitative vivo microdialysis revealed an increase extracellular dopamine concentration striatum parkin–/– mice. Intracellular recordings medium-sized striatal spiny neurons showed that...
Pancreatic ductal adenocarcinoma (PDAC) is almost uniformly fatal; however, some improvement in overall survival has been achieved with the introduction of nanocarriers that deliver irinotecan or paclitaxel. Although it generally assumed rely principally on abnormal leaky vasculature for tumor access, a transcytosis transport pathway regulated by neuropilin-1 (NRP-1) recently reported. NRP-1-mediated can be triggered cyclic tumor-penetrating peptide iRGD. In KRAS-induced orthotopic PDAC...
To carry out an integrative profile of human pancreatic ductal adenocarcinoma (PDAC) to identify prognosis-significant genes and their related pathways.
Abstract The electrophysiological properties of distinct subpopulations striatal medium‐sized spiny neurons (MSSNs) were compared using enhanced green fluorescent protein as a reporter gene for identification expressing dopamine D1 and D2 receptor subtypes in mice. Whole‐cell patch‐clamp recordings slices revealed that passive membrane similar cells. All MSSNs displayed hyperpolarized resting potentials but the threshold firing action was lower than neurons. In voltage clamp, frequency...
Overexpression or mutation of α-synuclein (α-Syn), a protein associated with presynaptic vesicles, causes familial forms Parkinson's disease in humans and is also sporadic the disease. We used vivo microdialysis, tissue content analysis, behavioral assessment, whole-cell patch clamp recordings from striatal medium-sized spiny neurons (MSSNs) slices to examine dopamine transmission dopaminergic modulation corticostriatal synaptic function mice overexpressing human wild-type α-Syn under Thy1...
Introduction Pancreatic ductal adenocarcinoma (PDAC) is projected to rise the second leading cause of U.S. cancer-related deaths by 2020. Novel therapeutic targets are desperately needed. MicroRNAs (miRs) small noncoding RNAs that function suppressing gene expression and dysregulated in cancer. miR-21 overexpressed PDAC tumor cells (TC) associated with decreased survival, chemoresistance invasion. Dysregulation miR regulatory networks tumor-associated fibroblasts (TAFs) have not been...
This work determines the invasive potential of pancreatic cancer cells, and its relationship to deformability using three independent mechanotyping methods.
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer due in part to lack of robust cytotoxic or molecular-based therapies. Recent studies investigating ligand-mediated Wnt/β-catenin signaling have highlighted its importance pancreatic initiation and progression, as well potential therapeutic target PDAC. The small-molecule ICG-001 binds cAMP-responsive element binding (CREB)-binding protein (CBP) disrupt interaction with β-catenin inhibit CBP function coactivator...
Trigeminal mesencephalic (Mes V) neurons are critical components of the circuits controlling oral-motor activity. The possibility that they can function as interneurons necessitates a detailed understanding factors their soma excitability. Using whole-cell patch-clamp recording, in vitro , we investigated development ionic mechanisms responsible for previously described subthreshold membrane oscillations and rhythmical burst discharge Mes V from rats ages postnatal day (P) 2–12. We found...
The functional and biophysical properties of a persistent sodium current (I(NaP)) previously proposed to participate in the generation subthreshold oscillations burst discharge mesencephalic trigeminal sensory neurons (Mes V) were investigated brain stem slices (rats, p7-p12) using whole cell patch-clamp methods. I(NaP) activated around -76 mV peaked at -48 mV, with V1/2 -58.7 mV. Ramp voltage-clamp protocols showed that undergoes time- as well voltage-dependent inactivation recovery from...
Abstract Huntington's disease (HD) is characterized by loss of striatal γ‐aminobutyric acid (GABA)ergic medium‐sized spiny projection neurons (MSSNs), whereas some classes interneurons are relatively spared. Striatal provide most the inhibitory synaptic input to MSSNs and use GABA as their neurotransmitter. We reported previously alterations in glutamatergic activity R6/2 R6/1 mouse models HD. In present study, we used whole‐cell voltage clamp recordings examine GABAergic currents from...
Huntington disease (HD) is a neurodegenerative disorder caused by an expanded CAG tract in the HD gene. Polyglutamine expansion of huntingtin (htt) results early, progressive loss medium spiny striatal neurons, as well cortical neurons that project to striatum. Excitotoxicity has been postulated play key role selective vulnerability HD. Early excitotoxic neuropathological changes observed human brain include increased quinolinate (QUIN) concurrent with proliferative such spine density and...
Neurons in the primary visual cortex receive subliminal information originating from periphery of their receptive fields (RF) through a variety cortical connections. In cat cortex, long-range horizontal axons have been reported to preferentially bind distant columns similar orientation preferences, whereas feedback connections higher areas provide more diverse functional input. To understand role these lateral interactions, it is crucial characterize effective connectivity and tuning...
Pancreatic ductal adenocarcinoma (PDAC) has a characteristically dense stroma comprised predominantly of cancer-associated fibroblasts (CAF). CAFs promote tumor growth, metastasis, and treatment resistance. This study aimed to investigate the molecular changes functional consequences associated with chemotherapy PDAC CAFs. Chemoresistant immortalized (R-CAF) were generated by continuous incubation in gemcitabine. Gene expression differences between treatment-naïve (N-CAF) R-CAFs compared...
Seizures in cortical dysplasia (CD) could be from cytomegalic neurons and balloon cells acting as epileptic ‘pacemakers’, or abnormal neurotransmission. This study examined these hypotheses using vitro electrophysiological techniques to determine intrinsic membrane properties spontaneous glutamatergic GABAergic synaptic activity for normal-pyramidal neurons, 67 neocortical sites originating 43 CD patients (ages 0.2–14 years). Magnetic resonance imaging (MRI),...
Subthreshold sodium currents are important in sculpting neuronal discharge and have been implicated production and/or maintenance of subthreshold membrane oscillations burst generation mesencephalic trigeminal neurons (Mes V). Moreover, recent data suggest that, some CNS neurons, resurgent contribute to high-frequency discharge. In the present study, we sought determine more directly participation these during Mes V electrogenesis using action potential-clamp method. postnatal day 8-14 rats,...
Summary: Cortical dysplasia (CD), a frequent pathological substrate of pediatric epilepsy surgery patients, has number similarities with immature cortex, such as reduced Mg 2+ sensitivity N‐methyl‐D‐aspartate (NMDA) receptors and the persistence subplate‐like neurons undifferentiated cells. Because γ‐aminobutyric acid (GABA) is main neurotransmitter in early cortical development, we hypothesized increased GABA receptor‐mediated synaptic function CD tissue. Infrared videomicroscopy whole‐cell...
Pancreatic cysts are a group of lesions with heterogeneous malignant potential. Currently, there no reliable biomarkers to aid in cyst diagnosis and classification. The objective this study was identify potential microRNA (miR) endoscopically acquired pancreatic fluid that could be used distinguish between benign, premalignant, cysts.A list candidate miRs developed using whole-genome expression array analysis cancer (pancreatic ductal adenocarcinoma) nonmalignant samples overlapped existing...
The sudden outbreak of the severe acute respiratory syndrome–coronavirus (SARS-CoV-2) has spread globally with more than 1,300,000 patients diagnosed and a death toll 70,000. Current genomic survey data suggest that single nucleotide variants (SNVs) are abundant. However, no mutation been directly linked functional changes in viral pathogenicity. We report characterizations 11 patient-derived isolates. observed diverse mutations these isolates, including 6 different spike glycoprotein (S...
Purine nucleoside phosphorylase (PNP) enables the breakdown and recycling of guanine nucleosides. PNP insufficiency in humans is paradoxically associated with both immunodeficiency autoimmunity, but mechanistic basis for these outcomes incompletely understood. Here, we identify two immune lineage-dependent consequences inactivation dictated by distinct gene interactions. During T cell development, synthetically lethal downregulation dNTP triphosphohydrolase SAMHD1. This interaction requires...
A defining histopathologic feature of Taylor-type cortical dysplasia (CD) is the presence cytomegalic neurons and balloon cells. Most appear to be pyramidal-shaped glutamatergic. The present study demonstrates GABAergic interneurons in a subset pediatric patients with severe CD. Cortical tissue samples from children mild, severe, non-CD pathologies were examined using morphologic electrophysiologic techniques. By vitro slices, cells characteristics consistent found 6 10 Biocytin labeling...
Abstract α‐Synuclein (α‐Syn) is a presynaptic protein implicated in Parkinson's disease (PD). Mice overexpressing human wildtype (WT) α‐Syn under the Thy1 promoter show high levels of cortical and subcortical regions, exhibit progressive sensorimotor anomalies, as well non‐motor abnormalities are considered models pre‐manifest PD there little evidence early loss dopaminergic (DA) neurons. We used whole‐cell patch clamp recordings from visually identified striatal medium‐sized spiny neurons...
Significance Pancreatic cancer is notoriously treatment resistant. These tumors rely on lysosome-dependent recycling pathways to generate substrates for metabolism, which are inhibited by chloroquine (CQ) and its derivatives. However, clinical efficacy of CQ as a monotherapy or combined with standard-of-care regimens has been limited. Using an unbiased kinome screen, we identify replication stress induced vulnerability due impaired de novo nucleotide biosynthesis find that combination...
We determine that type I interferon (IFN) response biomarkers are enriched in a subset of pancreatic ductal adenocarcinoma (PDAC) tumors; however, actionable vulnerabilities associated with IFN signaling have not been systematically defined. Integration phosphoproteomic analysis and chemical genomics synergy screen reveals activates the replication stress kinase ataxia telangiectasia Rad3-related protein (ATR) PDAC cells sensitizes them to ATR inhibitors. triggers cell-cycle arrest S-phase,...
Abstract Despite their small number, fast‐spiking (FS) GABAergic interneurons play a critical role in controlling striatal output by mediating cortical feed‐forward inhibition of medium‐sized spiny (MS) projection neurons. We have examined the functional development FS and inputs, expression three molecular markers, dorsolateral rat striatum between postnatal days (P)12–14 19–23, time major corticostriatal synaptogenesis. were visualized with infrared differential interference contrast...