A5028573253- Spaceflight effects on biology
- Effects of Radiation Exposure
- Radiation Therapy and Dosimetry
- Gut microbiota and health
- High Altitude and Hypoxia
- Neuroinflammation and Neurodegeneration Mechanisms
- Health, Environment, Cognitive Aging
- Clostridium difficile and Clostridium perfringens research
- Anesthesia and Neurotoxicity Research
- Mitochondrial Function and Pathology
- Probiotics and Fermented Foods
- Medical and Biological Ozone Research
- DNA Repair Mechanisms
- Polar Research and Ecology
- Carcinogens and Genotoxicity Assessment
- Microbial Community Ecology and Physiology
- Toxoplasma gondii Research Studies
- Multiple Sclerosis Research Studies
- Neurogenesis and neuroplasticity mechanisms
- Genetics, Aging, and Longevity in Model Organisms
- Viral Infectious Diseases and Gene Expression in Insects
- Dermatology and Skin Diseases
- Bone Metabolism and Diseases
- Single-cell and spatial transcriptomics
- Apelin-related biomedical research
Ames Research Center
2018-2024
National Aeronautics and Space Administration
2022
Universities Space Research Association
2018-2019
Icahn School of Medicine at Mount Sinai
2018
Center for Innovation
2018
University of California, San Diego
2018
City University of New York
2018
The Graduate Center, CUNY
2018
University of California, San Francisco
2016-2018
Stanford Medicine
2016
Significance We have experimentally investigated the immunoregulatory effects of human gut microbiota in multiple sclerosis (MS). identified specific bacteria that are associated with MS and demonstrated these regulate T lymphocyte-mediated adaptive immune responses contribute to proinflammatory environment vitro vivo. Thus, our results expand knowledge microbial regulation immunity may provide a basis for development microbiome-based therapeutics autoimmune diseases.
There is emerging evidence that the commensal microbiota has a role in pathogenesis of multiple sclerosis (MS), putative autoimmune disease CNS. Here, we compared gut microbial composition 34 monozygotic twin pairs discordant for MS. While there were no major differences overall profiles, found significant increase some taxa such as Akkermansia untreated MS twins. Furthermore, most notably, when transplanted to transgenic mouse model spontaneous brain autoimmunity, twin-derived induced...
Spaceflight induces molecular, cellular and physiological shifts in astronauts poses myriad biomedical challenges to the human body, which are becoming increasingly relevant as more humans venture into space
TGFβ is both neuroprotective and a key immune system modulator likely to be an important target for future stroke therapy. The precise function of increased TGF-β1 after unknown its pleiotropic nature means that it may convey signal, orchestrate glial scarring or as regulator. We therefore investigated the time course cell-specificity signaling stroke, whether pattern altered by gender aging.We performed distal middle cerebral artery occlusion strokes on 5 18 month old reporter mice get...
Astrocytes limit inflammation after CNS injury, at least partially by physically containing it within an astrocytic scar the injury border. We report here that transforming growth factor-beta (TGFβ) signaling is a second, distinct mechanism astrocytes utilize to neuroinflammation. TGFβs are anti-inflammatory and neuroprotective cytokines upregulated subacutely stroke, during clinically accessible time window. have previously demonstrated signal astrocytes, neurons microglia in stroke border...
Abstract The balance between controlling infection and limiting inflammation is particularly precarious in the brain because of its unique vulnerability to toxic effects inflammation. Astrocytes have been implicated as key regulators neuroinflammation CNS infections, including with Toxoplasma gondii, a protozoan parasite that naturally establishes chronic mice humans. In toxoplasmosis, astrocytes are critical growth. They secrete proinflammatory cytokines physically encircle parasites....
To determine the effects of disease-modifying therapies, glatiramer acetate (GA) and dimethyl fumarate (DMF), on gut microbiota in patients with MS.Participants relapsing MS who were either treatment-naive or treated GA DMF recruited. Peripheral blood mononuclear cells immunophenotyped. Bacterial DNA was extracted from stool, amplicons targeting V4 region bacterial/archaeal 16S rRNA gene sequenced (Illumina MiSeq). Raw reads clustered into Operational Taxonomic Units using GreenGenes...
Prostaglandin E 2 (PGE ), a potent lipid signaling molecule, modulates inflammatory responses through activation of downstream G-protein coupled EP 1–4 receptors. Here, we investigated the cell-specific in vivo function PGE its E-prostanoid (EP2) receptor murine innate immune systemically and CNS. In , systemic administration lipopolysaccharide (LPS) resulted broad induction cytokines chemokines plasma that was significantly attenuated EP2-deficient mice. Ex stimulation peritoneal...
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by adaptive and innate immune dysregulation. Recent work has revealed moderate alteration gut microbial communities in subjects with MS experimental, induced models. However, a mechanistic understanding linking observed changes microbiota presence still missing. Chloroform-resistant, spore-forming bacteria, which primarily belong to classes Bacilli Clostridia phylum Firmicutes, have been shown...
We have identified and validated a spaceflight-associated microRNA (miRNA) signature that is shared by rodents humans in response to simulated, short-duration long-duration spaceflight. Previous studies miRNAs regulate rodent responses spaceflight low-Earth orbit, we confirmed the expression of these proposed reacting simulated conditions. Moreover, astronaut samples from NASA Twins Study signatures miRNA sequencing, single-cell RNA sequencing (scRNA-seq), assay for transposase accessible...
A comprehensive understanding of spaceflight factors involved in immune dysfunction and the evaluation biomarkers to assess in-flight astronaut health are essential goals for NASA. An elevated neutrophil lymphocyte ratio (NLR) is a potential biomarker candidate, as leukocyte differentials altered during spaceflight. In reduced gravity environment space, rodents astronauts displayed NLR granulocyte ratios (GLR), respectively. To simulate microgravity using two well-established ground-based...
Radiation-induced foci (RIF) are nuclear puncta visualized by immunostaining of proteins that regulate DNA double-strand break (DSB) repair after exposure to ionizing radiation. RIF a standard metric for measuring DSB formation and in clinical, environmental space radiobiology. The time course dose dependence their has great potential predict vivo responses radiation, predisposition cancer probability adverse reactions radiotherapy. However, increasing complexity experimentally...
Stroke is the leading cause of long-term disability in United States, yet no drugs are available that proven to improve recovery. Brain-derived neurotrophic factor stimulates neurogenesis and plasticity, processes implicated stroke It binds both tropomyosin-related kinase B p75 neurotrophin receptors. However, brain-derived not a feasible therapeutic agent, small molecule exists can reproduce its binding We tested hypothesis (LM22A-4) selectively targets would promote functional recovery...
Abstract Spaceflight introduces a combination of environmental stressors, including microgravity, ionizing radiation, changes in diet and altered atmospheric gas composition. In order to understand the impact each component on astronauts it is important investigate potential influences isolation. Rodent spaceflight experiments involve both standard vivarium cages animal enclosure modules (AEMs), which are used house rodents spaceflight. Ground control AEMs engineered match environment. There...
With the development of transcriptomic technologies, we are able to quantify precise changes in gene expression profiles from astronauts and other organisms exposed spaceflight. Members NASA GeneLab GeneLab-associated analysis working groups (AWGs) have developed a consensus pipeline for analyzing short-read RNA-sequencing data spaceflight-associated experiments. The includes quality control, read trimming, mapping, quantification steps, culminating detection differentially expressed genes....
Abstract Impairment of the central nervous system (CNS) poses a significant health risk for astronauts during long-duration space missions. In this study, we employed an innovative approach by integrating single-cell multiomics (transcriptomics and chromatin accessibility) with spatial transcriptomics to elucidate impact spaceflight on mouse brain in female mice. Our comparative analysis between ground control spaceflight-exposed animals revealed alterations essential processes including...
Deep space exploration will require real-time, minimally invasive monitoring of astronaut health to mitigate the potential impairments caused by radiation and microgravity. Genotoxic stress in humans can be monitored quantifying amount DNA double-strand breaks (DSBs) immune cells from a simple finger prick. In cohort 674 healthy donors, we show that endogenous level DSBs increases with age latent cytomegalovirus infection. To map range human responses radiation, then study DSB induction...
We present a comprehensive comparative analysis on the repair of radiation-induced DNA damage ex vivo in 15 strains mice, including 5 inbred reference and 10 collaborative-cross strains, both sexes, totaling million skin fibroblast cells imaged by three-dimensional highthroughput conventional microscopy. Non-immortalized primary fibroblasts derived from 76 mice were subjected to increasing doses low- high-LET radiation (X rays; 350 MeV/n 40Ar; 600 56Fe), which are relevant carcinogenesis...
Central nervous system (CNS) damage by galactic cosmic ray radiation is a major health risk for human deep space exploration. Simulated rays or their components, especially high Z-high energy particles such as 56Fe ions, cause neurodegeneration and neuroinflammation in rodent models. CNS can be partially mediated the blood-brain barrier, which regulates systemic interactions between rest of body. Astrocytes are cellular regulators barrier permeability that also modulate neuronal health....