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Principal Investigator: Kiesha Wilson
Organization: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
Fiscal Year: 2022
Award: $100,000
Funding agency: National Institute of General Medical Sciences
PROJECT SUMMARY/ABSTRACT
The virus, SARS-CoV-2 has caused COVID-19 and claimed the lives of over 240,000 Americans and
1,270,000 people worldwide. Severe cases of the disease leads to Acute Respiratory Distress
Syndrome (ARDS), sepsis and can be fatal due to pulmonary inflammation and destruction of the
epithelial and endothelial cell lining. Understanding the mechanisms behind these diseases is vital to
develop effective preventive and therapeutic strategies. Staphylococcus enterotoxin B (SEB)-induced
ARDS mimics the cytokine storm, sepsis and multiple organ failure presented in patients with severe
COVID-19. It has been shown that the superantigen structure and sequence associated with the spike
protein of the SARS-CoV-2 is similar to that of SEB. This SEB-induced ARDS model also results in
various presentations of severity of illness in mice of different genetic backgrounds, as does COVID-
19 in humans. When C3H/HeJ mice are treated with SEB, their survival rate drops to 0%. In our study,
we found that Cannabidiol (CBD) administration following SEB treatment, led to 100% survival
indefinitely. Initial evaluation of whole single cell sequencing data comparing lungs from naïve with
SEB-induced ARDS mice illustrated that there was an increase in neutrophils, inflammatory
macrophages and pro-inflammatory cytokines (IL-1β and TNF-α) as well as a loss in lung epithelial
cells. To characterize the mechanism by which CBD treatment led to amelioration of the inflammatory
response, microRNA expression analysis was done that showed a significant decrease in expression
of miR-124-3p in SEB-treated group which is directly associated with upregulation of TNF-α and IL-1β
expression as well as macrophage activation gene, Cebp. We hypothesized that CBD attenuates SEB-
induced ARDS by miRNA dysregulation in lung-infiltrating cells, specifically by inducing miR-124-3p
which downregulates Cebp expression resulting in reduced activation of macrophages. Aim 1 will
elucidate the role of resident and monocyte-derived macrophages in disease and the effect CBD on
those subpopulations. Aim 2 will elucidate whether CBD affects Cebp expression and the effects that
miR-124-3p has on manifestation of disease. Aim 3 will determine the epigenetic factors regulating
expression of miR-124-3p. This study will explore CBD as a potential therapeutic for ARDS and/or
sepsis induced not only by SEB but other pathogens such as SARS-CoV-2. The K99R00 will provide
opportunities associated with Career Development and training in –omics approaches and biostatistics.
Taken together, my mentors, advisory committee, consultant, and research environment at the
University of South Carolina will nurture my successful transition to an Independent Investigator.
Terms: <(TNF)-α><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV S protein><2019-nCoV spike glycoprotein><2019-nCoV spike protein><9-ene-Tetrahydrocannabinol><ARDS><Acute Respiratory Distress><Acute Respiratory Distress Syndrome><Address><Adult ARDS><Adult RDS><Adult Respiratory Distress Syndrome><Advisory Committees><Affect><Alveolar><Alveolar Macrophages><American><Amino Acid Sequence><Anti-Inflammatories><Anti-Inflammatory Agents><Anti-inflammatory><Antiinflammatories><Antiinflammatory Agents><Apoptotic><Assay><Attenuated><B cell differentiation factor><B cell stimulating factor 2><B-Cell Differentiation Factor><B-Cell Differentiation Factor-2><B-Cell Stimulatory Factor-2><BCDF><BSF-2><BSF2><Bacteria><Basal Transcription Factor><Basal transcription factor genes><Beta Proprotein Interleukin 1><Bioassay><Biologic Assays><Biologic Models><Biological Assay><Biological Markers><Biological Models><Biometrics><Biometry><Biostatistics><Blood Neutrophil><Blood Polymorphonuclear Neutrophil><Blood monocyte><C-EBP alpha><C-EBP α><C-EBPalpha><C-EBPα><C3H/HeJ Mouse><CCAAT-Enhancer-Binding Protein-alpha><CCAAT-Enhancer-Binding Protein-α><CD14><CD14 gene><CD16><CD16B><COVID infected patient><COVID patient><COVID positive patient><COVID-19><COVID-19 S protein><COVID-19 infected patient><COVID-19 patient><COVID-19 positive patient><COVID-19 spike glycoprotein><COVID-19 spike protein><COVID-19 virus><COVID19><COVID19 S protein><COVID19 patient><COVID19 positive patient><COVID19 spike glycoprotein><COVID19 spike protein><COVID19 virus><CRISPR approach><CRISPR based approach><CRISPR method><CRISPR methodology><CRISPR technique><CRISPR technology><CRISPR tools><CRISPR-CAS-9><CRISPR-based method><CRISPR-based technique><CRISPR-based technology><CRISPR-based tool><CRISPR/CAS approach><CRISPR/Cas method><CRISPR/Cas technology><CRISPR/Cas9><CRISPR/Cas9 technology><CV-19><CV19><CXCL9><CXCL9 gene><Cachectin><Cannabidiol><Cannabinoids><Cannabis><Cas nuclease technology><Cell Body><Cells><Cellular Infiltration><Characteristics><Chemotactic Cytokines><Clinical><Clustered Regularly Interspaced Short Palindromic Repeats approach><Clustered Regularly Interspaced Short Palindromic Repeats method><Clustered Regularly Interspaced Short Palindromic Repeats methodology><Clustered Regularly Interspaced Short Palindromic Repeats technique><Clustered Regularly Interspaced Short Palindromic Repeats technology><CoV-2><CoV2><Coronaviridae><Coronavirus><DNA><Da Nang Lung><Data><Delta-9-Tetrahydrocannabinol><Deoxyribonucleic Acid><Disease><Disorder><Drops><Edodekin Alfa><Endothelial Cells><Environment><Epigenetic><Epigenetic Change><Epigenetic Mechanism><Epigenetic Process><Epithelial Cells><Evaluation><FCGR3B><FCGR3B gene><Fc Receptor III-1><Fc gamma IIIb receptor><Fc-Gamma RIII-Beta><Fc-Gamma RIIIB><FcRIIIB><Gene Activation><Gene Expression><Gene Transcription><General Transcription Factor Gene><General Transcription Factors><Genes><Genetic><Genetic Transcription><HPGF><Hepatocyte-Stimulating Factor><Homologous Chemotactic Cytokines><Human><Humig><Hybridoma Growth Factor><Hypoxia><Hypoxic><IFN-beta 2><IFNB2><IL-1><IL-1 beta><IL-1 β><IL-1-b><IL-12><IL-1β><IL-23><IL-6><IL1><IL1-Beta><IL1-β><IL12><IL1B Protein><IL1F2><IL1β><IL6 Protein><IgG Fc Receptor IIIB><Immune><Immunes><Immunochemical Immunologic><Immunologic><Immunological><Immunologically><Immunologics><Infection><Inflammatory><Inflammatory Response><Inhalation><Inhaling><Intercrines><Interleukin 1beta><Interleukin I><Interleukin-1><Interleukin-1 beta><Interleukin-12><Interleukin-1β><Interleukin-6><Investigators><Liquid substance><Low Affinity IgG Fc Receptor IIIB><Low Affinity Immunoglobulin Gamma Fc Region Receptor III-B><Lung><Lung Inflammation><Lung Respiratory System><Lymphocyte-Stimulating Hormone><MGI-2><MIG Gene><MOF syndrome><Macrophage Activation><Macrophage Cell Factor><Macrophage-Derived TNF><Marijuana><Marrow Neutrophil><Marrow monocyte><Mediating><Mentors><Mice><Mice Mammals><Micro RNA><MicroRNAs><Model System><Modeling><Modern Man><Monocyte-Derived TNF><Mononuclear><Multiple Organ Dysfunction Syndrome><Multiple Organ Failure><Murine><Mus><Myeloid Differentiation-Inducing Protein><Mφ><NKSF><Natural Killer Cell Stimulatory Factor><Network Analysis><Neutrophilic Granulocyte><Neutrophilic Leukocyte><Overdose><Oxygen Deficiency><Pathway Analysis><Patients><Persons><Phagocytosis><Plants><Plasmacytoma Growth Factor><Play><Plethysmography><Pneumonitis><Polymorphonuclear Cell><Polymorphonuclear Leukocytes><Polymorphonuclear Neutrophils><Preinterleukin 1 Beta><Preventative strategy><Prevention strategy><Preventive><Preventive strategy><Primary Protein Structure><Property><Public Health><Pulmonary Inflammation><Pulmonary Macrophages><Quantitative RTPCR><Quantitative Reverse Transcriptase PCR><RNA Expression><Receptor Protein><Reporter><Research><Research Personnel><Researchers><Role><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 S protein><SARS-CoV-2 infected patient><SARS-CoV-2 patient><SARS-CoV-2 positive patient><SARS-CoV-2 spike glycoprotein><SARS-CoV-2 spike protein><SARS-CoV2><SARS-CoV2 S protein><SARS-CoV2 spike glycoprotein><SARS-CoV2 spike protein><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><SCYB9><SEB superantigen><SIS cytokines><Sepsis><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 S protein><Severe acute respiratory syndrome coronavirus 2 spike glycoprotein><Severe acute respiratory syndrome coronavirus 2 spike protein><Severe acute respiratory syndrome related corona virus 2><Severity of illness><Shock Lung><Site><South Carolina><Staining method><Stains><Staphylococcal Enterotoxin B><Stiff lung><Structure><Superantigens><Survival Rate><T Helper Factor><TNF><TNF A><TNF Alpha><TNF gene><TNF-α><TNFA><TNFα><Task Forces><Testing><Tetrahydrocannabinol><Therapeutic><Toxin><Training><Transcription><Transcription Factor Proto-Oncogene><Transcription factor genes><Trauma><Tumor Necrosis Factor><Tumor Necrosis Factor-alpha><Universities><Up-Regulation><Upregulation><Virus><Wuhan coronavirus><advisory team><alveolar destruction><antiinflammatory><attenuation><base><bio-markers><biologic marker><biomarker><blood infection><bloodstream infection><cannabinergic><cannabinoidergic><career development><cell type><chemoattractant cytokine><chemokine><corona virus><corona virus disease 2019><coronavirus disease 2019><coronavirus disease 2019 S protein><coronavirus disease 2019 infected patient><coronavirus disease 2019 patient><coronavirus disease 2019 positive patient><coronavirus disease 2019 spike glycoprotein><coronavirus disease 2019 spike protein><coronavirus disease 2019 virus><coronavirus disease infected patient><coronavirus disease patient><coronavirus disease positive patient><coronavirus disease-19><coronavirus disease-19 patient><coronavirus disease-19 virus><coronavirus infectious disease-19><coronavirus patient><crg-10><cytokine><cytokine release syndrome><cytokine storm><delta(1)-THC><delta(1)-Tetrahydrocannabinol><delta(9)-THC><delta(9)-Tetrahydrocannabinol><disease severity><fluid><hCoV19><in silico><in vivo><insight><interferon beta 2><interleukin-23><life-threatening COVID><life-threatening COVID-19><life-threatening SARS-CoV-2><life-threatening coronavirus disease><life-threatening coronavirus disease 2019><life-threatening severe acute respiratory syndrome coronavirus 2><liquid><lung function><lymphocyte activating factor><macrophage><marihuana><miRNA><miRNAs><migration><monocyte><multiorgan failure><multiple organ system failure><myeloid cell development><nCoV2><neutrophil><pandemic><pandemic disease><pathogen><patient infected with COVID><patient infected with COVID-19><patient infected with SARS-CoV-2><patient infected with coronavirus disease><patient infected with coronavirus disease 2019><patient infected with severe acute respiratory syndrome coronavirus 2><patient with COVID><patient with COVID-19><patient with COVID19><patient with SARS-CoV-2><patient with coronavirus disease><patient with coronavirus disease 2019><patient with severe acute respiratory distress syndrome coronavirus 2><phytocannabinoid><promoter><promotor><protein sequence><protein structure><protein structures><proteins structure><pulmonary><pulmonary function><qRTPCR><receptor><sedative><serious COVID><serious COVID-19><serious SARS-CoV-2><serious coronavirus disease><serious coronavirus disease 2019><serious severe acute respiratory syndrome coronavirus 2><severe COVID><severe COVID-19><severe COVID19><severe SARS-CoV-2><severe acute respiratory syndrome coronavirus 2 infected patient><severe acute respiratory syndrome coronavirus 2 patient><severe acute respiratory syndrome coronavirus 2 positive patient><severe coronavirus disease><severe coronavirus disease 19><severe coronavirus disease 2019><severe severe acute respiratory syndrome coronavirus 2><single cell sequencing><social role><staph enterotoxin B><staphylococcus enterotoxin B><super antigen SEB><therapeutic agent development><therapeutic development><transcription factor><wet lung><Δ(1)-THC><Δ(1)-tetrahydrocannabinol><Δ(9)-THC><Δ(9)-tetrahydrocannabinol><Δ-9-tetrahydrocannabinol><Δ9-tetrahydrocannabinol>