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Identification Of Sars-cov-2 Host Factors Using Genome Wide Crispr Screens Chris Vulpe MD, PhD Professor, Center for Environmental and Human Toxicology University of Florida |
The COVID-19 pandemic has resulted in 153 million infections and 3.2 million deaths as of May 2021. While effective vaccines are being administered globally, there is still a great need for antiviral therapies as potentially antigenically distinct SARS-CoV-2 variants continue to emerge across the globe. Viruses require host factors at every step in their life cycle, representing a rich pool of candidate targets for antiviral drug design. To identify host factors that promote SARS-CoV-2 infection with potential for broad-spectrum activity across the coronavirus family, we carried out a collaborative effort with Dr. Michel Norris and Dr. Stephanie Karst to perform genome-scale CRISPR knockout screens in two cell lines (Vero E6 and HEK293T ectopically expressing ACE2) with SARS-CoV-2 and the common cold-causing human coronavirus OC43. We identified multiple genes and functional pathways that have been previously reported to promote human coronavirus replication as well as novel genes and pathways. Of note, host factors involved in cell cycle regulation were enriched in our screens as were several key components of the programmed mRNA decay pathway. We identified novel candidate antiviral compounds targeting a number of factors revealed by our screens. Our studies substantiate and expand the growing body of literature focused on understanding key human coronavirus-host cell interactions and exploit that knowledge for rational antiviral drug development.
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Interrogating Microglia As A Critical Mediator Of Pfos-induced Neurotoxicity Jessica Plavicki Manning Assistant Professor of Pathology and Laboratory Medicine Brown University |
Per- and Polyfluoroalkyl Substances (PFAS) are a class of global toxicants that are resistant to environmental degradation. Exposure to perfluorooctane sulfonate (PFOS), a prevalent PFAS congener, dampens adaptive immune responses in children. However, it is not known whether PFOS exposure affects the development and function of microglia, the resident innate immune cells in the brain. Using a single cell image analysis pipeline, we found that PFOS exposure produced a rounded, activated microglia morphology in developing zebrafish. PFOS-exposed embryos exhibited a heightened microglial response to brain injury. The exacerbated responses were not due to changes in inflammatory cytokine signaling or an increase in cell death; therefore, we examined other factors in the microenvironment that may modulate microglial development and behavior. Using the photoconvertible calcium indicator CaMPARI, we observed increased neural activity following PFOS exposure. The observed increase may reflect aberrant connectivity associated with the failure of microglia to refine neural networks. Alternatively, the increase in neuronal firing may drive the observed activated microglial phenotypes and alter microglial response to injury. Using optogenetics, we were able to induce a ramified, less activated state in microglia and rescue the exacerbated microglial response to brain injury. We are currently conducting experiments to determine if neural silencing is sufficient to rescue the altered microglial morphology in PFOS-exposed embryos and the microglial response to brain injury.
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New Technologies To Measure Environmental Exposures And Influences On Human Health Perry Hystad College of Public Health and Human Sciences Oregon State University |
Identifying and preventing environmental causes of disease requires estimating long-term personal exposures. Most environmental exposures do not have valid biomarkers and studies therefore rely on external exposure assessment methods. Approaches are split broadly into methods for modeling exposures for large populations versus measuring exposures for small populations. New technologies and resulting big data offer tremendous opportunity for unifying these approaches and improving long-term personal exposure prediction at scales needed for population-based research. In this presentation I will provide examples from ongoing research projects, such as: (1) leveraging existing individual time-activity data from Google Location History to estimate long-term environment exposures; (2) integrating image-based deep learning models to assess environmental exposures; and (3) applying new air pollution sensors to large epidemiological studies. I will make the case that a multi-disciplinary approach is needed to combine these types of technologies to improve personal exposure measures, enhance epidemiological research, and identify new prevention opportunities.
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Uncertain times call for uncertain measures: Challenges in Modern Dose Response Analysis Ian Moran Graduate Research Fellow PI: Kim Anderson |
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Identifying mechanisms for toxicant-induced epigenetic change: towards “bench to community” translation of environmental epigenetics Caren Weinhouse, PhD, MPH Oregon Institute of Occupational Health Sciences Oregon Health & Science University |
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How Should We Approach Forming Representative Mixtures? Briana Rivera Graduate Research Fellow Oregon State University |
Diesel exhaust suppresses adult neurogenesis, induces microglial activation, and increases levels of neurodegenerative markers Dr. Jacki Coburn Postdoc Fellow Oregon State University |
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Trichloroethylene Cometabolic Degradation by Pseudomonas mendocina KR1Trichloroethylene Cometabolic Degradation by Pseudomonas mendocina KR1 Alyssa Saito GRA, CBEE PI: Lewis Semprini |
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Silicone pet tags associate tris(1,3-dichloro-2-isopropyl) phosphate exposures with feline hyperthyroidism Carolyn Poutasse PhD Candidate PI: Kim Anderson |
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Macrophage Matters in Air Particulate Matter Induced Cardiometabolic Diseases Xiaoquan Rao, PhD Assistant Professor, Oregon Institute of Occupational Health Sciences Oregon Health & Science University |
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PAHs, PCBs, and PFASs in stormwater: one sorbent to rule them all Bethany Parker Graduate Research Assistant, Chemistry PIs: Staci Simonich, Jennifer Field |
