- Traumatic Brain Injury and Neurovascular Disturbances
- Traumatic Brain Injury Research
- RNA and protein synthesis mechanisms
- Mitochondrial Function and Pathology
- Metabolomics and Mass Spectrometry Studies
- Neuroscience and Neuropharmacology Research
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Cardiac Arrest and Resuscitation
- Monoclonal and Polyclonal Antibodies Research
- S100 Proteins and Annexins
- Viral Infections and Outbreaks Research
- Alzheimer's disease research and treatments
- RNA Research and Splicing
- Immunotoxicology and immune responses
- Virus-based gene therapy research
- T-cell and B-cell Immunology
- RNA modifications and cancer
- Immune Cell Function and Interaction
- SARS-CoV-2 and COVID-19 Research
- interferon and immune responses
- Inflammatory Bowel Disease
- Dementia and Cognitive Impairment Research
- Advanced biosensing and bioanalysis techniques
- Neurological Disease Mechanisms and Treatments
- Alcoholism and Thiamine Deficiency
Scripps Research Institute
2017-2025
University of Florida
2022-2024
Scripps (United States)
2021-2024
The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology
2023-2024
Broad Institute
2024
Jupiter Medical Center
2023
Roskamp Institute
2012-2021
Scripps Health
2021
The Open University
2011-2020
James A. Haley Veterans' Hospital
2014-2017
Traumatic brain injury (TBI) is a recognized risk factor for later development of neurodegenerative disease. However, the mechanisms contributing to neurodegeneration following TBI remain obscure.In this study, we have utilized novel mild (mTBI) model examine chronic neurobehavioral and neuropathological outcomes single repetitive mTBI at time points from 6 18 months injury.Our results reveal that 6, 12, after injury, animals exposed learning impairments when compared their sham controls...
Concussion or mild traumatic brain injury (mTBI) represents the most common type of injury. However, in contrast with moderate severe injury, there are currently few non-invasive experimental studies that investigate cumulative effects repetitive mTBI using rodent models. Here we describe and compare behavioral pathological consequences a mouse model single (s-mTBI) (r-mTBI, five injuries given at 48 h intervals) administered by an electromagnetic controlled impactor. Our results reveal is...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein mediates infection of cells expressing angiotensin-converting enzyme (ACE2). ACE2 is also the viral receptor SARS-CoV (SARS-CoV-1), a related that emerged in 2002–2003. Horseshoe bats (genus Rhinolophus ) are presumed to be original reservoir both viruses, and SARS-like coronavirus, RaTG13, closely SARS-CoV-2, has been identified one horseshoe-bat species. Here we characterize ability S-protein...
Abstract Target occupancy is often insufficient to elicit biological activity, particularly for RNA, compounded by the longstanding challenges surrounding molecular recognition of RNA structures small molecules. Here we studied patterns between a natural-product-inspired small-molecule collection and three-dimensionally folded structures. Mapping these interaction landscapes across human transcriptome defined structure–activity relationships. Although RNA-binding compounds that bind...
Exposure to repetitive concussion, or mild traumatic brain injury (mTBI), has been linked with increased risk of long-term neurodegenerative changes, specifically chronic encephalopathy (CTE). To date, preclinical studies largely have focused on the immediate aftermath mTBI, no literature lifelong consequences mTBI in these models. This study provides first account neurobehavioral and histological providing unique insight into constellation evolving ongoing pathologies late survival.Male...
Reprogramming known medicines for a novel target with activity and selectivity over the canonical is challenging. By studying binding interactions between RNA folds small-molecule mining resultant dataset across human RNAs, we identified that Dovitinib, receptor tyrosine kinase (RTK) inhibitor, binds precursor to microRNA-21 (pre-miR-21). Dovitinib was rationally reprogrammed pre-miR-21 by using it as an recognition element in chimeric compound also recruits RNase L induce RNA's catalytic...
Phospholipid (PL) abnormalities are observed in the cerebrospinal fluid of patients with traumatic brain injury (TBI), suggesting their role TBI pathology. Therefore, PL levels were examined a mouse model that received 1.8 mm deep controlled cortical impact or craniectomy only (control). The rotarod and Barnes maze acquisition probe tests performed within 2 wk after injury, another test 3 mo postinjury. Liquid chromatography/mass spectrometry analyses on lipid extracts from several regions...
Gulf War Illness (GWI) is a chronic multisymptom illness with central nervous system component such as memory deficits, neurological, and musculoskeletal problems. There are ample data that demonstrate exposure to (GW) agents, pyridostigmine bromide (PB) pesticides permethrin (PER), were key contributors the etiology of GWI post deployment Persian GW. In current study, we examined consequences acute (10 days) PB PER in C57BL6 mice. Learning tests performed at 18 days 5 months post-exposure....
Abstract Background In addition to experiencing traumatic events while deployed in a combat environment, there are other factors that contribute the development of posttraumatic stress disorder ( PTSD ) military service members. This study explored contribution genetics, childhood prior trauma, psychological, cognitive, and deployment following deployment. Methods Both pre‐ postdeployment data on 231 458 soldiers were analyzed. Postdeployment assessments occurred within 30 days from...
In the military population, there is high comorbidity between mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD) due to inherent risk of psychological trauma associated with combat. These disorders present long-term neurological dysfunction remain difficult diagnose their overlapping clinical presentation. Therefore, we performed cross-sectional analysis blood samples from demographically matched soldiers (total, n = 120) mTBI, PTSD, mTBI+PTSD those who were...
This study was designed to explore the influence of apolipoprotein E (APOE) on blood phospholipids (PL) in predicting preclinical Alzheimer's disease (AD).Lipidomic analyses were also performed from an AD mouse model expressing human APOE isoforms (EFAD) and five mutations 195 cognitively normal participants, 23 who converted mild cognitive impairment (MCI)/AD within 3 years.APOE ε4-carriers converting MCI/AD had high arachidonic acid (AA)/docosahexaenoic (DHA) ratios PL compared ε4 non-ε4...
Repetitive mild traumatic brain injury (r-mTBI) results in neuropathological and biochemical consequences the human visual system. Using a recently developed mouse model of r-mTBI, with control mice receiving repetitive anesthesia alone (r-sham) we assessed effects on retina optic nerve using histology, immunohistochemistry, proteomic lipidomic analyses at 3 weeks post injury. Retina tissue was used to determine retinal ganglion cell (RGC) number, while examined for cellularity, myelin...
Abstract Rhes (Ras homolog enriched in the striatum), a multifunctional protein that regulates striatal functions associated with motor behaviors and neurological diseases, can shuttle from cell to via formation of tunneling-like nanotubes (TNTs). However, mechanisms by which mediates diverse remain unclear. is small GTPase family member contains unique C-terminal Small Ubiquitin-like Modifier (SUMO) E3-like domain promotes SUMO post-translational modification proteins (SUMOylation)...
Gulf War Illness (GWI) is a chronic multisymptom illness with central nervous system component that includes memory impairment as well neurological and musculoskeletal deficits. Previous studies have shown in the First Persian conflict (1990-1991) exposure to (GW) agents, such pyridostigmine bromide (PB) permethrin (PER), were key contributors etiology of GWI. For this study, we used our previously established mouse model GW agent (10 days PB+PER) undertook an extensive lifelong...