A5010150893- Neuroinflammation and Neurodegeneration Mechanisms
- Traumatic Brain Injury and Neurovascular Disturbances
- Cancer Treatment and Pharmacology
- Stress Responses and Cortisol
- Tryptophan and brain disorders
- Pain Mechanisms and Treatments
- Immune Cell Function and Interaction
- Histone Deacetylase Inhibitors Research
- Peripheral Neuropathies and Disorders
- Anesthesia and Neurotoxicity Research
- Multiple Myeloma Research and Treatments
- Neonatal and fetal brain pathology
- Memory and Neural Mechanisms
- S100 Proteins and Annexins
- Genetics, Aging, and Longevity in Model Organisms
- Nicotinic Acetylcholine Receptors Study
- Neuroscience and Neuropharmacology Research
- Spaceflight effects on biology
- T-cell and B-cell Immunology
- Traumatic Brain Injury Research
- interferon and immune responses
- Glioma Diagnosis and Treatment
- Microtubule and mitosis dynamics
- Atomic and Subatomic Physics Research
- Advanced NMR Techniques and Applications
University of California, San Francisco
2017-2024
Neurological Surgery
2017-2024
Altos Labs
2022-2024
Bay Institute
2023
American Physical Therapy Association
2017-2022
University of Denver
2021-2022
The University of Texas MD Anderson Cancer Center
2014-2022
Institute of Neuroimmunology of the Slovak Academy of Sciences
2016
Loyola University Chicago
2009-2014
University of Chicago
2010-2014
Significance Traumatic brain injury (TBI) is a leading cause of long-term neurological disability and affects an ever-growing population. Currently, there are no effective treatments for patients suffering from chronic TBI-induced cognitive impairments. Here, we found that suppression the integrated stress response (ISR) with drug-like small-molecule inhibitor, ISRIB, rescued cognition in two TBI mouse models, even when administered weeks after injury. Consistent behavioral results, ISRIB...
Chemotherapy-induced peripheral neuropathy (CIPN), characterized by pain and numbness in hands feet, is a common side effect of cancer treatment. In most patients, symptoms CIPN subside after treatment completion. However, substantial subgroup, persists long into survivorship. Impairment resolution pathways may explain persistent CIPN. We investigated the contribution T cells endogenous interleukin (IL)-10 to Paclitaxel-induced mechanical allodynia was prolonged T-cell-deficient (Rag1 −/− )...
Chemotherapy-induced peripheral neuropathy (CIPN) characterized by loss of sensory sensitivity and pain in hands feet is the major dose-limiting toxicity many chemotherapeutics. At present, there are no FDA-approved treatments for CIPN. The anti-diabetic drug metformin most widely used prescription world improves glycemic control diabetes patients. There some evidence that enhances efficacy cancer treatment. aim this study was to test hypothesis protects against chemotherapy-induced...
Chemotherapy-induced peripheral neuropathy is one of the most common dose-limiting side effects cancer treatment. Currently, there no Food and Drug Administration-approved treatment available. Histone deacetylase 6 (HDAC6) a microtubule-associated whose function includes regulation α-tubulin-dependent intracellular mitochondrial transport. Here, we examined effect HDAC6 inhibition on established cisplatin-induced neuropathy. We used novel inhibitor ACY-1083, which shows 260-fold selectivity...
With increased life expectancy, age-associated cognitive decline becomes a growing concern, even in the absence of recognizable neurodegenerative disease. The integrated stress response (ISR) is activated during aging and contributes to age-related brain phenotypes. We demonstrate that treatment with drug-like small-molecule ISR inhibitor ISRIB reverses activation brain, as indicated by decreased levels activating transcription factor 4 (ATF4) phosphorylated eukaryotic translation initiation...
Traumatic brain injury (TBI) is of particular concern for the aging community since there both increased incidence TBI and decreased functional recovery in this population. In addition, strongest environmental risk factor development Alzheimer’s disease other dementia-related neurodegenerative disorders. Critical changes that affect cognition take place over time following initial insult. Our previous work identified immune system activation as a key contributor to cognitive deficits...
Understanding the endogenous mechanisms regulating resolution of pain may identify novel targets for treatment chronic pain. Resolution chemotherapy-induced peripheral neuropathy (CIPN) after completion depends on CD8+ T cells and IL-10 produced by other cells. Using Rag2-/- mice lacking B adoptive transfer Il13-/- cells, we showed that producing IL-13 were required CIPN. Intrathecal administration anti-IL-13 delayed CIPN reduced production dorsal root ganglion macrophages. Depleting local...
Microglia are the main immune component in brain that can regulate neuronal health and synapse function. Exposure to cosmic radiation cause long-term cognitive impairments rodent models thereby presenting potential obstacles for astronauts engaged deep space travel. The mechanism/s how induces deficits currently unknown. We find temporary microglia depletion, one week after radiation, prevents development of memory deficits. Gene array profiling reveals acute depletion alters late...
Chemotherapy-induced peripheral neuropathy (CIPN), a debilitating major side effect of cancer treatment, is characterized by pain and sensory loss in hand feet. Platinum-based chemotherapeutics like cisplatin frequently induce CIPN. The molecular mechanism underlying these neurotoxic symptoms incompletely understood there are no preventive or curative interventions. We hypothesized that acts as cellular stressor triggers p53 accumulation at mitochondria, leading to mitochondrial dysfunction...
Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer treatment. It the most frequent cause dose reduction or treatment discontinuation in patients treated for with commonly used drugs including taxanes and platinum-based compounds. No FDA-approved treatments CIPN are available. In rodents, represented by mechanical allodynia association retraction intraepidermal nerve fibers. The mechanism chemotherapy-induced neurotoxicity unclear, but it has been established...
Traumatic brain injury (TBI) is a leading cause for neurological disabilities world-wide. TBI occurs most frequently among the elderly population, and survivors suffer from reduced recovery poorer quality of life. The effect age on pathophysiology still poorly understood. We previously established that peripherally-derived monocytes (CCR2+) infiltrate injured contribute to chronic TBI-induced cognitive deficits in young animals. Furthermore, was shown amplify monocyte infiltration acutely...
Traumatic brain injury (TBI) is one of the leading causes long-term neurological disability in world. Currently, there are no therapeutics for treating deleterious consequences trauma; this part due to a lack complete understanding cellular processes that underlie TBI-related pathologies. Following TBI, microglia, resident immune cells, turn into "reactive" state characterized by production inflammatory mediators contribute development cognitive deficits. Utilizing multimodal,...
Space radiation affects memory in male and not female mice, it is dependent on the innate immune system response.
Abstract Background Tau is aberrantly acetylated in various neurodegenerative conditions, including Alzheimer’s disease, frontotemporal lobar degeneration (FTLD), and traumatic brain injury (TBI). Previously, we reported that reducing tau by pharmacologically inhibiting p300-mediated acetylation at lysine 174 reduces pathology improves cognitive function animal models. Methods We investigated the therapeutic efficacy of two different antibodies specifically target on (ac-tauK174). treated...
Traumatic brain injury (TBI) has long been identified as a precipitating risk factor for higher-order cognitive deficits associated with the frontal and prefrontal cortices (PFC). In addition, mild repetitive TBI (rTBI), in particular, is being steadily recognized to increase of neurodegenerative disease. Thus, further understanding how rTBI changes pathophysiology lead impairment warranted. The current models lack knowledge regarding chronic functions underlying neuronal physiology,...
Complex alterations in cerebral energetic metabolism arise after traumatic brain injury (TBI). To date, methods allowing for metabolic evaluation are highly invasive, limiting our understanding of impairments associated with TBI pathogenesis. We investigated whether 13C MRSI hyperpolarized (HP) [1-13C] pyruvate, a non-invasive imaging method, could detect changes controlled cortical (CCI) mice (n = 57). Our results show that HP lactate-to-pyruvate ratios were increased the injured cortex at...
Mild repetitive traumatic brain injury (rTBI) induces chronic behavioral and cognitive alterations increases the risk for dementia. Currently, there are no therapeutic strategies to prevent or mitigate deficits associated with rTBI. Previously we developed an animal model of rTBI that recapitulates observed in humans. We now report results increase risk-taking behavior male but not female mice. This phenotype is activation integrated stress response cell-specific synaptic type A subtype...
Traumatic brain injury (TBI) is a major public health problem. Despite considerable research deciphering pathophysiology, precision therapies remain elusive. Here, we present large-scale data sharing and machine intelligence approaches to leverage TBI complexity. The Open Data Commons for (ODC-TBI) community-centered repository emphasizing Findable, Accessible, Interoperable, Reusable publication with persistent identifiers. Importantly, the ODC-TBI implements of individual subject data,...
Exposure to galactic cosmic rays (GCR) poses an obstacle successful deep space missions, including missions the Moon or Mars. Previously, we and others have identified chronic cognitive impairments associated with GCR in rodent model systems. The persistent loss previously reported is indicative of global changes different regions brain, prefrontal cortex hippocampus. It has been shown that both these brain are involved social functions. Here demonstrate four months after a single exposure...
Interplanetary space travel poses many hazards to the human body. To protect astronaut health and performance on critical missions, there is first a need understand effects of deep hazards, including ionizing radiation, confinement, altered gravity. Previous studies rodents exposed single such stressor document significant deficits, but our study investigate possible cumulative synergistic impacts simultaneous gravity behavior cognition. Our cohort was divided between 6-month-old female male...