A5080479135- Cancer, Hypoxia, and Metabolism
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurogenesis and neuroplasticity mechanisms
- Neuroscience and Neuropharmacology Research
- MicroRNA in disease regulation
- Glioma Diagnosis and Treatment
- Lanthanide and Transition Metal Complexes
- Immune cells in cancer
- Ion channel regulation and function
- HIV Research and Treatment
- Pain Mechanisms and Treatments
- RNA modifications and cancer
- Immune Cell Function and Interaction
- Wnt/β-catenin signaling in development and cancer
- Nuclear Receptors and Signaling
- Single-cell and spatial transcriptomics
- RNA Research and Splicing
- Angiogenesis and VEGF in Cancer
- Ubiquitin and proteasome pathways
- Lipid metabolism and biosynthesis
- Alzheimer's disease research and treatments
- Axon Guidance and Neuronal Signaling
- Pluripotent Stem Cells Research
- interferon and immune responses
- Viral-associated cancers and disorders
National Institute of Neurological Disorders and Stroke
2016-2025
National Institutes of Health
2016-2025
National Institute of Biomedical Imaging and Bioengineering
2010-2024
University North
2023
College of Slavonski Brod
2023
University Hospital of Lausanne
2020
National Cancer Institute
2005-2018
National Heart Lung and Blood Institute
2008-2018
MedStar Georgetown University Hospital
2018
Georgetown University
2018
The Notch family of proteins plays an integral role in determining cell fates, such as proliferation, differentiation, and apoptosis. We show that Notch-1 its ligands, Delta-like-1 Jagged-1, are overexpressed many glioma lines primary human gliomas. Immunohistochemistry a tissue array shows the presence nucleus intracellular domain, indicating activation situ. Down-regulation Notch-1, Delta-like-1, or Jagged-1 by RNA interference induces apoptosis inhibits proliferation multiple lines. In...
Mutations in DJ-1, PINK1 (PTEN-induced putative kinase 1) and parkin all cause recessive parkinsonism humans, but the relationships between these genes are not clearly defined. One event associated with loss of any is altered mitochondrial function. Recent evidence suggests that turnover damaged mitochondria by autophagy might be central to process parkinsonism. Here, we show DJ-1 leads polarization, fragmentation accumulation markers (LC3 punctae lipidation) around human dopaminergic cells....
Human endogenous retrovirus-K is activated in the cortical neurons of patients with amyotrophic lateral sclerosis, and expression viral envelope protein mouse brain reproduces clinical pathological phenotype this disease.
Recent advances in high-field MRI have dramatically improved the visualization of human brain anatomy vivo. Most notably, cortical gray matter, strong contrast variations been observed that appear to reflect local laminar architecture. This has attributed subtle magnetic properties tissue, possibly reflecting varying iron and myelin content. To establish origin this contrast, data from postmortem samples were compared with electron microscopy histological staining for myelin. The results...
Highlights•NDP52 associates with the ULK1 complex through FIP200, facilitated by TBK1•NDP52/TBK1 targets to cargo initiate autophagy in absence of LC3•ULK1 is activated on independently AMPK and mTOR activity•Ectopic recruitment FIP200-binding peptide sufficient degrade cargoSummarySelective recycles damaged organelles clears intracellular pathogens prevent their aberrant accumulation. How kinase targeted during selective autophagic events remains be elucidated. In this study, we used...
Chronic immune activation is a major complication of antiretroviral therapy (ART) for HIV infection and can cause devastating reconstitution inflammatory syndrome (IRIS) in the brain. The mechanism T-cell this population not well understood. We found HIV-Tat protein IL-17–expressing mononuclear cells brain an individual with IRIS. Tat was also present CSF individuals virologically controlled on ART. Hence we examined if could directly activate T cells. transcriptionally dysregulated 94 genes...
The underlying mechanisms by which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to and long-term neurological manifestations remains obscure. We aimed characterize the neuropathological changes in patients with disease 2019 determine pathophysiological mechanisms. In this autopsy study of brain, we characterized vascular pathology, neuroinflammatory cellular humoral immune responses immunohistochemistry. All died during first wave pandemic from March July 2020. were...
The mammalian spinal cord functions as a community of cell types for sensory processing, autonomic control, and movement. While animal models have advanced our understanding cellular diversity, characterizing human biology directly is important to uncover specialized features basic function pathology. Here, we present taxonomy the adult using single-nucleus RNA sequencing with spatial transcriptomics antibody validation. We identified 29 glial clusters 35 neuronal clusters, organized...
During cortical development, embryonic neurons migrate from germinal zones near the ventricle into plate, where they organize layers. Mechanisms that direct neuronal migration may include molecules act as chemoattractants. In rats, GABA, which localizes target destination for migrating neurons, stimulates in vitro. mice, glutamate is highly localized destinations neurons. Glutamate-induced of murine cells was evaluated cell dissociates and slice cultures. dissociates, chemotropic effects...
Glycogen synthase kinase 3 (GSK3), a serine/threonine kinase, is involved in diverse cellular processes ranging from nutrient and energy homeostasis to proliferation apoptosis. Its role glioblastoma multiforme has yet be elucidated. We identified GSK3 as regulator of cell survival using microarray analysis small-molecule genetic inhibitors activity. Various molecular approaches were then used dissect out the mechanisms responsible for inhibition-induced cytotoxicity. show that multiple small...
Viruses have been implicated in the development of neurodegenerative diseases, such as Alzheimer's, Parkinson’s, and multiple sclerosis. Human herpesvirus-6 (HHV-6) is a neurotropic virus that has associated with wide variety neurologic disorders, including encephalitis, mesial temporal lobe epilepsy, Currently, route HHV-6 entry into CNS unknown. Using autopsy specimens, we found frequency DNA olfactory bulb/tract region was among highest brain regions examined. Given this finding,...
Functional NK cell deficiencies are associated with autoimmune diseases, including multiple sclerosis. cells can promote or inhibit adaptive immunity via either cytokine production cytotoxicity toward immature dendritic and activated T cells. In humans, this immunoregulatory role resides in the CD56(bright) subset, which is selectively expanded by daclizumab, a CD25-blocking Ab that suppresses sclerosis-associated inflammation. The objective of study was to investigate molecular mechanisms...
We are interested in the causal interactions between psychological stress and activity within different compartments of immune system. Psychosocial has been reported to not only alter microglia morphology but also produce anxiety-like depressive-like effects by triggering CNS infiltration macrophages from periphery. sought test these phenomena a somewhat standardized model chronic social defeat (SD) stress. used paradigm dyadic home pairing dominant subordinate mice that validated induce...
We examined whether cells of the adaptive immune system retain memory psychosocial stress and thereby alter mood states CNS function in host. Lymphocytes from mice undergoing chronic social defeat or unstressed control were isolated adoptively transferred into naive lymphopenic Rag2 −/− mice. Changes affective behavior, hippocampal cell proliferation, microglial activation states, blood cytokine levels reconstituted stress-naive The receiving lymphocytes defeated donors showed less anxiety,...
Tumor cell invasion is the principal cause of treatment failure and death among patients with malignant gliomas. Connective tissue growth factor (CTGF) has been previously implicated in cancer metastasis various tumors. We explored mechanism CTGF-mediated glioma infiltration examined potential therapeutic targets. Highly infiltrative patient-derived tumor–initiating or tumor stem cells (TIC/TSCs) were harvested used to explore a CTGF-induced signal transduction pathway via luciferase...
Autosomal-dominant missense mutations in LRRK2 (leucine-rich repeat kinase 2) are a common genetic cause of PD (Parkinson's disease). is multidomain protein with and GTPase activities. Dominant found the domains that have these two enzyme activities, including G2019S mutation increases activity 2–3-fold. However, there also variant some populations, G2385R, lies C-terminal WD40 domain acts as risk factor for PD. In present study we show G2385R causes partial loss function deletion C-terminus...