A5046722897- Neuroinflammation and Neurodegeneration Mechanisms
- Mosquito-borne diseases and control
- interferon and immune responses
- Chemokine receptors and signaling
- Viral Infections and Vectors
- Immunotherapy and Immune Responses
- Neurogenesis and neuroplasticity mechanisms
- Complement system in diseases
- Sphingolipid Metabolism and Signaling
- Multiple Sclerosis Research Studies
- Immune Response and Inflammation
- Long-Term Effects of COVID-19
- Systemic Lupus Erythematosus Research
- Tryptophan and brain disorders
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- HIV Research and Treatment
- Immune cells in cancer
- Barrier Structure and Function Studies
- Extracellular vesicles in disease
- Lipid Membrane Structure and Behavior
- Malaria Research and Control
- Infectious Encephalopathies and Encephalitis
- RNA regulation and disease
- Cytomegalovirus and herpesvirus research
Western University
2024-2025
Washington University in St. Louis
2015-2024
Center for Neuro-Oncology
2024
Cooperative Trials Group for Neuro-Oncology
2023
Institute of Neuroimmunology of the Slovak Academy of Sciences
2023
Bipar
2007-2023
Keele University
2023
Indiana University
2023
Johns Hopkins University
2023
Indiana University School of Medicine
2023
The vast majority of brain tumors in adults exhibit glial characteristics. Brain children are diverse: Many have neuronal characteristics, whereas others features. Here we show that activation the G i protein-coupled receptor CXCR4 is critical for growth both malignant and tumors. Systemic administration antagonist AMD 3100 inhibits intracranial glioblastoma medulloblastoma xenografts by increasing apoptosis decreasing proliferation tumor cells. This reflects ability to reduce extracellular...
Monocyte recruitment to the central nervous system (CNS) is a necessary step in development of pathologic inflammatory lesions experimental autoimmune encephalomyelitis (EAE), murine model multiple sclerosis. chemoattractant protein (MCP)-1, potent agonist for directed monocyte migration, has been implicated pathogenesis EAE. Here we report that deficiency CC chemokine receptor (CCR)2, MCP-1, confers resistance EAE induced with peptide derived from myelin oligodendrocyte glycoprotein 35–55...
The activation and entry of antigen-specific CD8(+) T cells into the central nervous system is an essential step towards clearance West Nile virus (WNV) from infected neurons. molecular signals responsible for directed migration virus-specific their cellular sources are presently unknown. Here we demonstrate that in response to WNV infection, neurons secrete chemokine CXCL10, which recruits effector via receptor CXCR3. Neutralization or a genetic deficiency CXCL10 leads decrease CXCR3(+)...
COVID-19 has resulted in more than 120 million cases and 2.6 deaths to date.Respiratory gastrointestinal symptoms are accompanied by short-and long-term neuropsychiatric (NPs) brain sequelae.Some patients present with anosmia, cognitive attention deficits (ie, fog), new-onset anxiety, depression, psychosis, seizures, even suicidal behavior. 1,2These before, during, after respiratory unrelated insufficiency, 1 suggesting independent damage.Follow-ups conducted Germany the United Kingdom found...
Multiple sclerosis is characterized by inflammatory demyelination and irreversible axonal injury leading to permanent neurological disabilities. Diffusion tensor imaging demonstrates an improved capability over standard magnetic resonance differentiate axon from myelin pathologies. However, the increased cellularity vasogenic oedema associated with inflammation cannot be detected or separated axon/myelin diffusion imaging, limiting its clinical applications. A novel basis spectrum capable of...
<h3>Background</h3> B cells are implicated in the pathogenesis of multiple sclerosis. A beneficial effect B-cell depletion using rituximab has been shown, but complete mechanism action for this drug is unclear. <h3>Objective</h3> To determine relationship between T and changes cerebrospinal fluid (CSF) chemokine levels with rituximab, a monoclonal antibody that targets CD20. <h3>Design</h3> Phase 2 trial as an add-on therapy. <h3>Setting</h3> The John L. Trotter Multiple Sclerosis Center,...
The blood-brain barrier (BBB) protects the central nervous system (CNS) by restricting passage of molecules and microorganisms. Despite this barrier, however, fungal pathogen Cryptococcus neoformans invades brain, causing a meningoencephalitis that is estimated to kill over 600,000 people annually. Cryptococcal infection begins in lung, experimental evidence suggests host phagocytes play role subsequent dissemination, although remains ill defined. Additionally, disparate approaches have been...
Pattern recognition receptor (PRR) detection of pathogen-associated molecular patterns (PAMPs), such as viral RNA, drives innate immune responses against West Nile virus (WNV), an emerging neurotropic pathogen. Here we demonstrate that WNV PAMPs orchestrate endothelial to via competing cytokine signals at the blood-brain barrier (BBB), a multicellular interface with highly specialized brain cells normally prevents pathogen entry. While Th1 cytokines increase permeability barriers, type I...
Interferon-λ signaling tightens the blood-brain barrier and limits ability of West Nile virus to infect central nervous system in mice.
The development of an effective vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent disease 2019 (COVID-19), is a global priority. Here, we compare protective capacity intranasal and intramuscular delivery chimpanzee adenovirus-vectored encoding prefusion stabilized spike protein (chimpanzee adenovirus [ChAd]-SARS-CoV-2-S) in Golden Syrian hamsters. Although immunization with ChAd-SARS-CoV-2-S induces robust spike-protein-specific antibodies...
The chemokine SDF-1α (CXC12) and its receptor CXCR4 have been shown to play a role in the development of normal cerebellar cytoarchitecture. We report here that both induces chemotactic responses granule precursor cells enhances cell proliferative Sonic hedgehog. Chemotactic are greater obtained from cerebella animals first postnatal week, coinciding with observed vivo peak expression. activation neuronal differs leukocytes SDF-1α-induced calcium flux is activity dependent, requiring...
During development of the nervous system, neural progenitors arise in proliferative zones, then exit cell cycle and migrate away from these zones. Here we show that migration cerebellar granule cells out their zone, external layer (EGL), is impaired Bdnf–/– mice. The reason for BDNF directly acutely stimulates migration. Purified defects initiation along glial fibers Boyden chamber assays. This phenotype can be rescued by exogenous BDNF. Using time-lapse video microscopy find motogenic as it...
Abstract The inflammatory response in the CNS begins with movement of leukocytes across blood-brain barrier a multistep process that requires cells to pass through perivascular space before entering parenchyma. molecular mechanisms orchestrate this are not known. chemokine CXCL12 is highly expressed throughout by microendothelial under normal conditions, suggesting it might play role maintaining barrier. We tested hypothesis setting experimental autoimmune encephalomyelitis (EAE) using...
Multiple sclerosis is a neurodegenerative disease characterized by episodes of autoimmune attack oligodendrocytes leading to demyelination and progressive functional deficits. Because many patients exhibit recovery in between demyelinating episodes, understanding mechanisms responsible for repair damaged myelin critical developing therapies that promote remyelination prevent progression. The chemokine CXCL12 developmental molecule known orchestrate the migration, proliferation,...
Loss of CXCL12, a leukocyte localizing cue, from abluminal surfaces the blood–brain barrier occurs in multiple sclerosis (MS) lesions. However, mechanisms and consequences reduced CXCL12 abundance remain unclear. Here, we show that activation CXCR7, which scavenges is essential for entry via endothelial barriers into central nervous system (CNS) parenchyma during experimental autoimmune encephalomyelitis (EAE), model MS. CXCR7 expression on increased EAE at sites inflammatory infiltration....