A5100747457- Alzheimer's disease research and treatments
- MicroRNA in disease regulation
- Parkinson's Disease Mechanisms and Treatments
- Single-cell and spatial transcriptomics
- Autophagy in Disease and Therapy
- Mass Spectrometry Techniques and Applications
- Neuroinflammation and Neurodegeneration Mechanisms
- CRISPR and Genetic Engineering
- Advanced biosensing and bioanalysis techniques
- Genomics and Chromatin Dynamics
- Lysosomal Storage Disorders Research
- Atherosclerosis and Cardiovascular Diseases
- RNA modifications and cancer
- Nuclear Receptors and Signaling
- Cleft Lip and Palate Research
- Mitochondrial Function and Pathology
- Microtubule and mitosis dynamics
- Genetics and Neurodevelopmental Disorders
- Bioinformatics and Genomic Networks
- Protein Kinase Regulation and GTPase Signaling
- Advanced Proteomics Techniques and Applications
- Neuroscience and Neuropharmacology Research
- Autism Spectrum Disorder Research
- Protein Structure and Dynamics
- Galectins and Cancer Biology
Icahn School of Medicine at Mount Sinai
2018-2025
Binzhou University
2017-2025
Binzhou Medical University
2017-2025
Beibu Gulf University
2025
Allen Institute for Brain Science
2018-2023
Regenerative Medicine Institute
2023
Center for High Pressure Science & Technology Advanced Research
2023
Johns Hopkins University
2021-2022
Pediatrics and Genetics
2022
Sanofi (United States)
2019-2022
Three major molecular subtypes of Alzheimer’s disease are identified, cross-validated, and characterized across 1543 individuals.
Parkinson's disease (PD) has been attributed to a combination of genetic and nongenetic factors. We studied set monozygotic twins harboring the heterozygous glucocerebrosidase mutation (GBA N370S) but clinically discordant for PD. applied induced pluripotent stem cell (iPSC) technology PD modeling using twins' fibroblasts evaluate dissect contributions. Utilizing fluorescence-activated sorting, we obtained homogenous population "footprint-free" iPSC-derived midbrain dopaminergic (mDA)...
To explore the developmental reorganization of three-dimensional genome brain in context neuropsychiatric disease, we monitored chromosomal conformations differentiating neural progenitor cells. Neuronal and glial differentiation was associated with widespread remodeling contact map included interactions anchored common variant sequences that confer heritable risk for schizophrenia. We describe cell type-specific connectomes composed schizophrenia variants their distal targets, which...
Heterozygous mutations in GBA, the gene encoding lysosomal enzyme glucosylceramidase beta/β-glucocerebrosidase, comprise most common genetic risk factor for Parkinson disease (PD), but mechanisms underlying this association remain unclear. Here, we show that GbaL444P/WT knockin mice, L444P heterozygous Gba mutation triggers mitochondrial dysfunction by inhibiting autophagy and priming, two steps critical selective removal of dysfunctional mitochondria autophagy, a process known as mitophagy....
The most common genetic risk factors for Parkinson’s disease (PD) are a set of heterozygous mutant (MT) alleles the GBA1 gene that encodes β-glucocerebrosidase (GCase), an enzyme normally trafficked through ER/Golgi apparatus to lysosomal lumen. We found half GCase in lysosomes from postmortem human GBA-PD brains was present on surface and this mislocalization depends pentapeptide motif used target cytosolic protein degradation by chaperone-mediated autophagy (CMA). MT at inhibits CMA,...
The cellular complexity of the human brain is established via dynamic changes in gene expression throughout development that mediated, part, by spatiotemporal activity cis-regulatory elements (CREs). We simultaneously profiled and chromatin accessibility 45,549 cortical nuclei across six broad developmental time points from fetus to adult. identified cell type-specific domains which highly correlated with expression. Differentiation pseudotime trajectory analysis indicates at CREs precedes...
Dysregulated autophagy may lead to the development of disease. Role and diagnostic potential microRNAs that regulate in cardiac hypertrophy have not been evaluated. A rat model was established using transverse abdominal aortic constriction (operation group). Cardiomyocyte enhanced rats from operation group, compared with those sham group. Moreover, group showed up-regulation beclin-1 (an autophagy-related gene), down-regulation miR-30 tissue. The effects inhibition over-expression gene on...
Abstract Stem cell therapy can be used to repair and regenerate damaged hearts tissue; nevertheless, the low survival rate of transplanted cells limits their therapeutic efficacy. Recently, it has been proposed that exosomes regulate multiple cellular processes by mediating communication among cells. The following study investigates whether injured cardiomyocytes-derived (cardiac exosomes) affect bone marrow mesenchymal stem (BMSCs) in infarcted heart. To mimic harsh microenvironment heart...
Alzheimer's disease (AD) is marked by the coordinated emergence of disease-associated cell states across multiple types. Here, we first performed a meta-analysis single-nucleus transcriptomic (snRNAseq) data from 869 brains diverse decedents, confirming critical role an SLC38A2 high SMTN CACNA1D astrocyte subset, Astrocyte 10 (Ast10), in AD and aging-related cognitive decline. We then investigated signaling drivers Ast10's aging brain, focusing on interactions among microglial astrocytic...
Trophic factor withdrawal induces cell death by mechanisms that are incompletely understood.Previously we reported of interleukin-7 (IL-7) or IL-3 produced a rapid intracellular alkalinization, disrupting mitochondrial metabolism and activating the protein Bax.We now observe this novel alkalinization pathway is mediated pH regulator NHE1, as shown requirement for sodium, blocking pharmacological inhibitors use an NHE1-deficient line, altered phosphorylation NHE1.Alkalinization also required...
An alternative method to enzymatic digestion for protein identification by mass spectrometry has been developed that is based on chemical cleavage formic acid. This was tested gel-purified apomyoglobin and BSA, as well unknown proteins cofractionate with Ty1-virus-like particles from Saccharomyces cerevisiae. Cleavage at aspartyl residues found be efficient specific, this specificity of lent itself easily database searches. Parallel digestions using trypsin were also performed. The acid...
Parkinson's disease (PD), one of the most devastating neurodegenerative brain disorders, is characterized by progressive loss dopaminergic neurons in substantia nigra (SN) and deposits α-synuclein aggregates. Currently, pharmacological interventions for PD remain inadequate. The cell necroptosis executor protein MLKL (Mixed-lineage kinase domain-like) involved various diseases, including inflammatory bowel diseases; however, its precise role remains unclear. Here, we investigated...
Protein kinase C (PKC)-theta, a member of the 'novel' subfamily PKC isoforms, is singular importance in transducing signals T-lymphocytes. Since understanding regulatory phosphorylation novel PKCs fragmentary and inconsistent with findings for 'classical' we investigated three potential sites on PKC-theta; activation loop (Thr(538)), turn motif (Ser(676)) hydrophobic (Ser(695)). Combined evidence from phospho-specific antisera MS demonstrates at all sites. Unlike its closest paralogue,...
IgA nephropathy (IgAN), characterized by mesangial IgA1 deposits, is a leading cause of renal failure worldwide. IgAN pathogenesis involves circulating hypogalactosylated complexed with soluble Fc receptor I (sCD89) and/or anti-hypogalactosylated-IgA1 autoantibodies, but no specific treatment available for IgAN. The absence and CD89 homologs in the mouse has precluded vivo proof-of-concept studies therapies targeting IgA1. However, α1KI‑CD89Tg model IgAN, which expresses human CD89, allows...
Crocin has been reported to have multiple bioactivities. However, the effect of crocin administration on caecal ligation and puncture (CLP)-induced sepsis remains unknown.We investigated effects CLP-induced in mice underlying mechanism action.Five experimental groups (n = 10) BALB/c were used: control, CLP (normal saline) + (50, 100 250 mg/kg, 30 min prior CLP). Mice sacrificed 24 h after CLP. Liver, kidney lung histopathology, indicator levels, apoptotic status, pro-inflammatory cytokines...
Apomorphine (APO), a potent D1/D2 dopamine receptor agonist, is currently used as an antiparkinsonian drug. We have shown previously that APO stimulates synthesis and release of multiple trophic factors, such brain-derived neurotrophic factor (BDNF) glial cell line-derived (GDNF), in both mesencephalic striatal neurons, thereby effectively preventing dopaminergic neuron loss vitro. The present study was designed to investigate the effects on fibroblast growth factor-2 (FGF-2) expression...
<italic>In situ</italic>surface functionalization by reactant molecules (thiourea) is feasible to engineer MoS<sub>2</sub>surfaces with rich amino groups, leading facile antigen immobilization and thus selective recognition of cancer cells.