A5082921381- Neuroinflammation and Neurodegeneration Mechanisms
- Cell Image Analysis Techniques
- Single-cell and spatial transcriptomics
- Neurological Disease Mechanisms and Treatments
- Advanced Fluorescence Microscopy Techniques
- Inflammation biomarkers and pathways
- Long-Term Effects of COVID-19
- Immune cells in cancer
- 3D Printing in Biomedical Research
- Infectious Encephalopathies and Encephalitis
- Alzheimer's disease research and treatments
- Advanced Neural Network Applications
- Acute Ischemic Stroke Management
- Extracellular vesicles in disease
- Amino Acid Enzymes and Metabolism
- Immune Response and Inflammation
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Advanced Proteomics Techniques and Applications
- interferon and immune responses
- Biomedical Text Mining and Ontologies
- Bioinformatics and Genomic Networks
- Cancer Cells and Metastasis
- Medicinal Plants and Neuroprotection
- Advanced biosensing and bioanalysis techniques
- S100 Proteins and Annexins
Helmholtz Zentrum München
2019-2025
Ludwig-Maximilians-Universität München
2019-2025
Munich Cluster for Systems Neurology
2025
Yale University
2022
Xiamen University
2016-2021
Triggering Receptor Expressed on Myeloid cells 2 (TREM2), which is expressed myeloid including microglia in the CNS, has recently been identified as a risk factor for Alzheimer's disease (AD). TREM2 transmits intracellular signals through its transmembrane binding partner DNAX-activating protein 12 (DAP12). Homozygous mutations inactivating or DAP12 lead to Nasu–Hakola disease; however, how AD risk-conferring variants increase not clear. To elucidate signaling pathways underlying reduced...
The bone marrow in the skull is important for shaping immune responses brain and meninges, but its molecular makeup among bones relevance human diseases remain unclear. Here, we show that mouse has most distinct transcriptomic profile compared with other states of health injury, characterized by a late-stage neutrophil phenotype. In humans, proteome analysis reveals distinct, differentially expressed neutrophil-related pathways unique synaptic protein signature. 3D imaging demonstrates...
Efficient and accurate nanocarrier development for targeted drug delivery is hindered by a lack of methods to analyze its cell-level biodistribution across whole organisms. Here we present Single Cell Precision Nanocarrier Identification (SCP-Nano), an integrated experimental deep learning pipeline comprehensively quantify the targeting nanocarriers throughout mouse body at single-cell resolution. SCP-Nano reveals tissue distribution patterns lipid nanoparticles (LNPs) after different...
Abstract Whole-body imaging of mice is a key source information for research. Organ segmentation prerequisite quantitative analysis but tedious and error-prone task if done manually. Here, we present deep learning solution called AIMOS that automatically segments major organs (brain, lungs, heart, liver, kidneys, spleen, bladder, stomach, intestine) the skeleton in less than second, orders magnitude faster prior algorithms. matches or exceeds quality state-of-the-art approaches human...
ABSTRACT Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has been associated mainly with a range of neurological symptoms, including brain fog and tissue loss, raising concerns about virus’s potential chronic impact on central nervous system. In this study, we utilized mouse models human post-mortem tissues to investigate presence distribution SARS-CoV-2 spike protein in skull-meninges-brain axis. Our results revealed...
Abstract Automated detection of specific cells in three-dimensional datasets such as whole-brain light-sheet image stacks is challenging. Here, we present DELiVR, a virtual reality-trained deep-learning pipeline for detecting c-Fos + markers neuronal activity cleared mouse brains. Virtual reality annotation substantially accelerated training data generation, enabling DELiVR to outperform state-of-the-art cell-segmenting approaches. Our available user-friendly Docker container that runs with...
SARS-CoV-2 infection is associated with long-lasting neurological symptoms, although the underlying mechanisms remain unclear. Using optical clearing and imaging, we observed accumulation of spike protein in skull-meninges-brain axis human COVID-19 patients, persisting long after viral clearance. Further, biomarkers neurodegeneration were elevated cerebrospinal fluid from COVID proteomic analysis skull, meninges, brain samples revealed dysregulated inflammatory pathways...
Mutation of Triggering receptor expressed on myeloid cells 2 (TREM2) impairs the response microglia to amyloid-β (Aβ) pathology in Alzheimer's disease (AD), although mechanism governing TREM2-regulated recruitment Aβ plaques remains unresolved. Here, we confirm that TREM2 mutation attenuates microglial migration. Then, using Trem2-/- mice and an R47H variant mouse model for AD generated this study, show deficiency or AD-associated results inhibition FAK Rac1/Cdc42-GTPase signaling critical...
Triggering receptor expressed on myeloid cells-2 (TREM2) and colony-stimulating factor 1 (CSF1R) are crucial molecules for microgliopathy, which is characterized by microglia dysfunction has recently been proposed as the neuropathological hallmark of neurological disorders. TREM2 CSF1R receptors primarily in brain modulate microglial activation survival. They thought to be close physical proximity. However, whether there a direct interaction between these remains elusive. Moreover,...
Epilepsy is a common neurological disease with recurrent seizures and neurobehavioral comorbidities, including cognitive impairment psychiatric disorders.Recent studies suggest that L-3-n-butylphthalide (NBP), an extract from the seeds of Apiumgraveolens Linn (Chinese celery), ameliorates dysfunction in ischemia and/or Alzheimer's (AD) animal models. However, little known about role NBP epilepsy associated comorbidities. Here, using pilocarpine-induced chronic epileptic mouse model, we found...
<b><i>Objective(s):</i></b> Neuroinflammation is an important contributor to the development of seizures and epilepsy. Micro-RNA-155 (miR-155) plays a critical role in immunity inflammation. This study aims explore function miR-155 miR-155-mediated inflammation <b><i>Methods:</i></b> About 8-week-old male C57BL/6 mice were administered intraperitoneal injection (i.p.) kainic acid (KA) (15 mg/kg) or saline. The KA group developing acute seizure...
SUMMARY The meninges of the brain are an important component neuroinflammatory response. Diverse immune cells move from calvaria marrow into dura mater via recently discovered skull-meninges connections (SMCs). However, how bone is different other bones and whether it contributes to human diseases remain unknown. Using multi-omics approaches whole mouse transparency we reveal that highly heterogeneous across body. harbors most distinct molecular signature with hundreds differentially...
Frontotemporal dementia includes a large spectrum of neurodegenerative disorders. SQSTM1, coding for p62 protein, plays vital role in the pathogenesis FTD. Here, we report case female patient with SQSTM1 mutation S224X, who was 59 years old when she initially exhibited memory decline, mild personality changes, and subtle atrophy frontal/temporal lobes magnetic resonance imaging (MRI). Genetic testing revealed nonsense gene (S224X), resulting premature termination protein synthesis predicted...
SUMMARY Spatial molecular profiling of complex tissues is essential to investigate cellular function in physiological and pathological states. However, methods for analysis biological specimens imaged 3D as a whole are lacking. Here, we present DISCO-MS, technology combining whole-organ imaging, deep learning-based image analysis, ultra-high sensitivity mass spectrometry. DISCO-MS yielded qualitative quantitative proteomics data indistinguishable from uncleared samples both rodent human...
Background: Protein Phosphatase 2A (PP2A) is an important and ubiquitously expressed serine threonine phosphatase in brain.Structurally, it composed of catalytic (C), scaffold (A) regulatory (B) subunits.It plays a critical role regulation many cellular processes has been implicated various neurological disorders including major depressive disorder (MDD).MDD the most common mental affecting up to 17% population USA.To date, limited information available related PP2A interactome.To dissect...