A5030660240- Neuroinflammation and Neurodegeneration Mechanisms
- Multiple Sclerosis Research Studies
- CAR-T cell therapy research
- Pituitary Gland Disorders and Treatments
- Amyotrophic Lateral Sclerosis Research
- Glioma Diagnosis and Treatment
- Esophageal Cancer Research and Treatment
- Toxin Mechanisms and Immunotoxins
- T-cell and Retrovirus Studies
- Acute Ischemic Stroke Management
- Neurogenesis and neuroplasticity mechanisms
- CRISPR and Genetic Engineering
- Immune Cell Function and Interaction
- Neurogenetic and Muscular Disorders Research
- Cytomegalovirus and herpesvirus research
- Immune cells in cancer
- HIV Research and Treatment
- interferon and immune responses
- Chromosomal and Genetic Variations
- Immune Response and Inflammation
- Animal Disease Management and Epidemiology
- Vector-Borne Animal Diseases
- RNA Research and Splicing
- Cytokine Signaling Pathways and Interactions
- Cancer-related molecular mechanisms research
National Institutes of Health
2015-2025
National Institute of Neurological Disorders and Stroke
2015-2025
Oxford University Press (United Kingdom)
2020
Office of Extramural Research
2012-2019
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.
To perform a meta-analysis of randomized, blinded, multiple sclerosis (MS) clinical trials, to test the hypothesis that efficacy immunomodulatory disease-modifying therapies (DMTs) on MS disability progression is strongly dependent age.We performed literature search with pre-defined criteria and extracted relevant features from 38 trials assessed DMTs progression. We fit linear regression, weighted for trial sample size, duration, examine age has defining effect therapeutic DMTs.More than...
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...
Patients with nodding syndrome have autoantibodies to leiomodin-1 that are neurotoxic and cross-react proteins of the parasitic worm Onchocerca volvulus .
An elevated human T cell lymphotropic virus 1 (HTLV)-1 proviral load (PVL) is the main risk factor for developing HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in HTLV-1 infected subjects, and a high cerebrospinal fluid (CSF) to peripheral blood mononuclear (PBMC) PVL ratio may be diagnostic of condition. However, standard method quantification PVL-real-time PCR-has multiple limitations, including increased inter-assay variability compartments with low numbers, such as...
BACKGROUND. Cerebral malaria (CM) accounts for nearly 400,000 deaths annually in African children. Current dogma suggests that CM results from infected RBC (iRBC) sequestration the brain microvasculature and resulting sequelae. Therapies targeting these events have been unsuccessful; findings experimental models suggest CD8+ T cells drive disease pathogenesis. However, data largely ignored because corroborating evidence humans is lacking. This work fills a critical gap our understanding of...
Genome-wide CRISPR screens have transformed our ability to systematically interrogate human gene function, but are currently limited a subset of cellular phenotypes. We report novel pooled screening approach for wider range and subtle subcellular Machine learning convolutional neural network models trained on the phenotype be queried. then utilizes cells stably expressing dCas9-KRAB (CRISPRi), photoactivatable fluorescent protein (PA-mCherry), lentiviral guide RNA (gRNA) pool. Cells screened...
Abstract Glioblastoma multiforme is the most common primary malignant brain tumor and despite treatment with surgery, radiation, chemotherapy, median survival of patients glioblastoma ∼1 year. explants cell lines have been reported to overexpress interleukin-13 receptor α2 subunit (IL13Rα2) relative nonneoplastic brain. Based on this finding, a recombinant cytotoxin composed IL13 ligand truncated form Pseudomonas aeruginosa exotoxin A (IL13-PE38QQR) was developed for targeted tumors. In...
Infection with JC virus (JCV) may lead to development of demyelinating progressive multifocal leukoencephalopathy in patients multiple sclerosis (MS) who are treated natalizumab.To determine whether mononuclear cells circulation from MS natalizumab harbor JCV DNA.In this prospective investigation, we enrolled 49 the Clinical Center for Multiple Sclerosis at The University Texas Southwestern Medical and 18 healthy volunteers. We drew 120-mL blood samples 26 baseline approximately 3-month...
Efficient and homogeneous in vitro generation of peripheral sensory neurons may provide a framework for novel drug screening platforms disease models touch pain. We discover that, by overexpressing NGN2 BRN3A, human pluripotent stem cells can be transcriptionally programmed to differentiate into surprisingly uniform culture cold- mechano-sensing neurons. Although such neuronal subtype is not found mice, we identify molecular evidence its existence ganglia. Combining BRN3A programming with...
Several viruses can infect the mammalian nervous system and induce neurological dysfunction. Adoptive immunotherapy is an approach that involves administration of antiviral T cells has shown promise in clinical studies for treatment peripheral virus infections humans such as cytomegalovirus (CMV), Epstein-Barr (EBV), adenovirus, among others. In contrast, clearance neurotropic particularly challenging because central (CNS) relatively intolerant immunopathological reactions. Therefore, it...
Skin color patterns are ubiquitous in nature, impact social behavior, predator avoidance, and protection from ultraviolet irradiation. A leading model system for vertebrate skin patterning is the zebrafish; its alternating blue stripes yellow interstripes depend on light-reflecting cells called iridophores. It was suggested that zebrafish's pattern arises a single type of iridophore migrating differentially to interstripes. However, here we find iridophores do not migrate between but instead...
Significance Human endogenous retroviruses (HERV) were incorporated into the genome over millions of years but are mostly inactive. HERV-K subtype HML-2 is most recently and its incidental expression occurs in a variety pathological conditions. However, physiological role not understood. We discovered that envelope protein this virus plays critical early embryonic development. It expressed at high levels on surface pluripotent stem cells signals via direct binding to CD98HC, leading...
Biomarkers aid diagnosis, allow inexpensive screening of therapies, and guide selection patient-specific therapeutic regimens in most internal medicine disciplines. In contrast, neurology lacks validated measurements the physiological status, or dysfunction(s) cells central nervous system (CNS). Accordingly, patients with chronic neurological diseases are often treated a single disease-modifying therapy without understanding drivers disability. Therefore, using multiple sclerosis (MS) as an...
The application of allele-specific gene editing tools can expand the therapeutic options for dominant genetic conditions, either via correction or allelic inactivation in situations where haploinsufficiency is tolerated. Here, we used allele-targeted CRISPR-Cas9 guide RNAs (gRNAs) to introduce inactivating frameshifting indels at an SNV
TDP-43 mislocalization and pathology occurs across a range of neurodegenerative diseases, but the pathways that modulate in neurons are not well understood. We generated Halo-TDP-43 knock-in iPSC line performed genome-wide CRISPR interference FACS-based screen to identify modifiers levels neurons. A meta-analysis our publicly available screens identified both specific hits present multiple screens, latter likely responsible for generic protein level maintenance. BORC, complex required...
TDP-43 mislocalization and pathology occurs across a range of neurodegenerative diseases, but the pathways that modulate in neurons are not well understood. We generated Halo-TDP-43 knock-in iPSC line performed genome-wide CRISPR interference FACS-based screen to identify modifiers levels neurons. A meta-analysis our publicly available screens identified both specific hits present multiple screens, latter likely responsible for generic protein level maintenance. BORC, complex required...