Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=2&sort=start_date
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=start_date", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1392&sort=start_date", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=3&sort=start_date", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=start_date" }, "data": [ { "type": "Grant", "id": "7689", "attributes": { "award_id": "1ZIADK075023-12", "title": "Structural study of the HIV1 gp41 coat protein", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)" ], "program_reference_codes": [], "program_officials": [], "start_date": null, "end_date": null, "award_amount": 995227, "principal_investigator": { "id": 23487, "first_name": "Adriaan", "last_name": "Bax", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1600, "ror": "https://ror.org/00adh9b73", "name": "National Institute of Diabetes and Digestive and Kidney Diseases", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1600, "ror": "https://ror.org/00adh9b73", "name": "National Institute of Diabetes and Digestive and Kidney Diseases", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "The envelope glycoprotein gp41 mediates the process of membrane fusion that enables entry of the HIV-1 virus into the host cell. Strong lipid affinity of the ectodomain suggests that its heptad repeat regions play an active role in destabilizing membranes by directly binding to the lipid bilayers and thereby lowering the free-energy barrier for membrane fusion. In such a model, immediately following the shedding of gp120, the N-heptad and C-heptad helices dissociate and melt into the host cell and viral membranes, respectively, pulling the destabilized membranes into juxtaposition, ready for fusion. Post-fusion, reaching the final 6-helix bundle (6HB) conformation then involves competition between intermolecular interactions needed for formation of the symmetric 6HB trimer and the membrane affinity of gp41's ectodomain, including its membrane-proximal regions. Our solution NMR study of the structural and dynamic properties of three constructs containing the ectodomain of gp41 with and without its membrane-proximal regions suggests that these segments do not form inter-helical interactions until the very late steps of the fusion process. Interactions between the polar termini of the heptad regions, which are not associating with the lipid surface, therefore may constitute the main driving force initiating formation of the final post-fusion states. The absence of significant intermolecular ectodomain interactions in the presence of dodecyl phosphocholine and bicelles consisting of DMPC and dihexanoyl phosphatidylcholine suggested the importance of trimerization of gp41s transmembrane helix to prevent complete dissociation of the trimer during the course of fusion. The membrane proximal external region (MPER) of HIV-1 gp41 contains epitopes for at least four broadly neutralizing antibodies. Depending on solution conditions and construct design, different structures have been reported for this segment. We have found that in aqueous solution the MPER fragment (gp160 residues 660-674) exists in a monomer-trimer equilibrium with an association constant in the micro-molar range. Thermodynamic analysis revealed that the association is exothermic, more favorable in D2O than H2O, and increased with ionic strength, indicating hydrophobically driven intermolecular interactions. Circular dichroism, 13C chemical shifts, NOE, and hydrogen exchange rates revealed that MPER undergoes a structural transition from predominately unfolded monomer at low concentrations to an alpha-helical trimer at high concentrations. This result has implications for antibody recognition of MPER prior to and during the process where gp41 switches from a pre-hairpin intermediate to its post-fusion 6-helical bundle state. Preliminary experiments applied to the ecto-domain of the Spike protein of SARS-CoV-2 indicate this protein contains a three-helical N-terminal heptad repeat (NHR) that is considerably more stable than the corresponding region of gp41, and the propensity for the C-terminal heptad (CHR) repeat albeit lower than that of NHR, is also substantially higher than for the CHR of gp41, whereas the propensity to trimerize for its membrane proximal region is substantially lower. Work has been submitted for publication but remains under review.", "keywords": [ "2019-nCoV", "Affinity", "Antibodies", "Binding", "C-terminal", "Capsid Proteins", "Cell membrane", "Cells", "Chemicals", "Circular Dichroism", "Detergents", "Dissociation", "Ebola", "Epitopes", "Equilibrium", "Free Energy", "Glycoproteins", "HIV Envelope Protein gp120", "HIV-1", "Hemagglutinin", "Hydrogen", "Hydrophobicity", "Influenza", "Ionic Strengths", "Lecithin", "Lipid Bilayers", "Lipids", "Mediating", "Membrane", "Membrane Fusion", "Micelles", "Modeling", "Molecular Conformation", "N-terminal", "Phosphorylcholine", "Play", "Process", "Property", "Proteins", "Publications", "Reporting", "Role", "Structure", "Surface", "Tertiary Protein Structure", "Thermodynamics", "Transmembrane Domain", "Viral", "Viral Fusion Proteins", "Virus", "Work", "aqueous", "biophysical techniques", "design and construction", "driving force", "experimental study", "gp160", "influenzavirus", "intermolecular interaction", "melting", "monomer", "neutralizing antibody", "prevent" ], "approved": true } }, { "type": "Grant", "id": "7699", "attributes": { "award_id": "1ZIAES103345-01", "title": "SARS-CoV-2 Studies", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Environmental Health Sciences (NIEHS)" ], "program_reference_codes": [], "program_officials": [], "start_date": null, "end_date": null, "award_amount": 438205, "principal_investigator": { "id": 23493, "first_name": "DOUGLAS", "last_name": "BELL", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1605, "ror": "https://ror.org/00j4k1h63", "name": "National Institute of Environmental Health Sciences", "address": "", "city": "", "state": "NC", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1605, "ror": "https://ror.org/00j4k1h63", "name": "National Institute of Environmental Health Sciences", "address": "", "city": "", "state": "NC", "zip": "", "country": "United States", "approved": true }, "abstract": "Smoking, Immune Senescence and COVID-19 morbidity. The general approach is to prospectively establish a bank of cryopreserved PBMCs from smokers and nonsmokers before any COVID-19 exposure and use CyTOF to analyze detailed immune profiles. Subjects will return for second post-COVID-19 pandemic visit to provide a second blood sample for analysis. The focus is primarily on immune profiles compared with COVID-19 incidence (or levels of morbidity) in smokers. As seen in Figure 2, there is a large variance in CD16+CD8+ T cell frequency among smokers. We hypothesize that senescent CD16+CD8+ T cells will be higher in smokers who develop COVID-19 or who have more severe morbidity. Specific Aims and Experimental Plans Specific Aim 1. Establish CyTOF immune profiles in 60 smokers and 60 matched nonsmokers who are COVID-19 negative and will be followed up on and recalled after the COVID-19 pandemic has subsided. Specific Aim 2. Compare immune profiles determined from a post-COVID-19 visit to the pre-COVID-19 negative sample. COVID-19 Diagnostics. Aim 1. Develop cDNA library methods for SARS-CoV-2 and host cells suitable for Next Generation sequencing.", "keywords": [ "2019-nCoV", "Bar Codes", "Blood specimen", "CD8-Positive T-Lymphocytes", "COVID-19", "COVID-19 pandemic", "Cells", "Communicable Diseases", "Cryopreservation", "Diagnostic", "Disease Outbreaks", "FCGR3B gene", "Frequencies", "Genetic Transcription", "Goals", "Guide RNA", "Healthcare Systems", "Immune", "Immune System Diseases", "Incidence", "Infection", "Methods", "Morbidity - disease rate", "Peripheral Blood Mononuclear Cell", "Predisposition", "Premature aging syndrome", "Regulatory T-Lymphocyte", "Sampling", "Screening procedure", "Severe Acute Respiratory Syndrome", "Smoker", "Smoking", "T-Lymphocyte Subsets", "Viral", "Visit", "cDNA Library", "follow-up", "high risk", "indexing", "mortality", "next generation sequencing", "non-smoker", "prospective", "response", "screening", "senescence" ], "approved": true } }, { "type": "Grant", "id": "7698", "attributes": { "award_id": "1ZICAI001226-03", "title": "Center for Human Immunology", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [], "start_date": null, "end_date": null, "award_amount": 3460631, "principal_investigator": { "id": 23492, "first_name": "Yasmine", "last_name": "Belkaid", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1540, "ror": "https://ror.org/043z4tv69", "name": "National Institute of Allergy and Infectious Diseases", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1540, "ror": "https://ror.org/043z4tv69", "name": "National Institute of Allergy and Infectious Diseases", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "In response to the SARS-CoV-2 pandemic we have made the technologies and platforms at CHI available for characterization of COVID-19 patient samples, as a priority ahead of our ongoing collaborative studies. By early April we had completed adaptation of our transcriptomic and flow cytometry platforms, and operating procedures, to begin analysing peripheral blood from Covid-19 patients. CHI began receiving samples from Northern Italy and CITE-Seq was performed for more than 100 samples in close collaboration with the Tsang lab. BCR sequencing and scATAC seq was performed for a subset of these, and proteomic analysis was obtained for all of the samples by outsourcing this work at SomaLogic. 27-color flow cytometry phenotyping was also performed by CHI to validate the novel CITE-seq platform. Further, CHIs automated pipeline was used to isolate high quality RNA from PAXgene samples of 200 Covid-19 samples, to be used for both RNA-Seq at CHI as well as distribution to the Goldbach-Mansky lab. Together these efforts have contributed to initial immune characterization of acutely infected Covid-19 patients. We hope these platforms can now be applied to new cohorts becoming available which are able to address questions such as variation in the outcomes of infection. In addition to this COVID work CHI has continued to advance its previous studies that comprise 25 active collaborations across 8 Institutes and the Clinical Center. These are divided into 3 stages: initiation/sample collection (12 studies), assay (8 studies), and analysis/write up (5 studies). These all comprise multi-modal high-dimensional immune phenotyping of primary human samples. The current studies include characterizing immune changes in vaccine trials (malaria, HSV), clinical intervention trials (lupus, CHAPLE), and cohort studies of rare diseases (mitochondrial dysfunction). One of the new studies added is an exciting collaboration with Kevin Hall at NIDDK to characterize immune differences after periods of highly controlled diet changes. The monoclonal antibody therapy study of CHAPLE disease patients, with Mike Lenardo, is an example of how high dimensional phenotyping can lead to better understanding of patient pathology, and may inform use of a nascent therapy. The proteomic changes we observed give basic biology insight into, in this case, CD55 function and the mechanisms of complement inhibition, and this work is under review at Nature Immunology. Studies published this year included an integrated proteomic and cellular phenotyping analysis of maternal peripheral blood in longitudinally sampled human pregnancies, and characterization of changes in peripheral blood during treatment of healthy subjects with statins, and obese individuals undergoing a clinical trial of colchicine treatment. To support CHIs mission we continue to develop wet-lab and computational infrastructure. For single cell sequencing technologies using the 10x platform, we have expanded the number of protein antigens measured in CITE-Seq, and developed scATAC-seq approaches with greater throughput and lower cost. CITE-Seq, in particular, led to a high-profile finding characterizing variation in baseline immune states that predicts immune responses (see section Scientific Advances). For flow cytometry, on a new Cytek Aurora we have validated a 27 color cytometry for broad immune phenotyping, as well as a 33 color T cell focused panel run after PMA stimulation to detect cells primed for production of characteristic cytokines or transcription factors. For flow cytometry analysis we are applying methods to enable conventionally gated populations to be recognized and interrogated using high dimensional parameters, to help overcome the difficulties of interpreting unbiased clustering of high dimensional data. For mass cytometry analysis we are finalising a package that uses high dimensional observations to discriminate only the subset of cells that respond in ex vivo stimulation assays, such as our mass cytometry assay that quantifies phosphorylation of 10 intracellular proteins, in addition to 20 cell phenotype markers, in response to 12 in vitro stimulation conditions. CHI also provides fee-for-service access to assays not otherwise accessible to NIH researchers. The SomaLogic proteomic assay has been run for over 1000 samples, for 8 investigators, in the last year. This included human and murine samples from serum, plasma, cerebrospinal fluid, bronchioalveolar lavage fluid, and tissue homogenates. We continue to monitor alternative platforms and have run tests on O-Link that is offering increasingly high parameter antibody based analysis, although currently plan to transition our SomaLogic platform from the current 1.3k antigen panel to an analysis of 4.5k antigens.", "keywords": [ "2019-nCoV", "Acute", "Address", "Antibodies", "Antigens", "Behavior", "Biological", "Biological Assay", "Biology", "Bronchoalveolar Lavage", "COVID-19", "Cells", "Cerebrospinal Fluid", "Characteristics", "Clinical", "Clinical Trials", "Cohort Studies", "Colchicine", "Collaborations", "Color", "Complement", "Computer Analysis", "Computer Models", "Coupled", "Cytometry", "Data", "Development", "Diet", "Disease", "Fee-for-Service Plans", "Flow Cytometry", "Goals", "Health", "Health Services Accessibility", "Human", "Immune", "Immune response", "Immunity", "Immunologic Monitoring", "Immunology", "Immunotherapy", "In Vitro", "Individual", "Infection", "Institutes", "Intervention", "Intervention Trial", "Italy", "Laboratories", "Lead", "Leadership", "Link", "Liquid substance", "Lupus", "Malaria", "Measures", "Methods", "Mission", "Modeling", "Monitor", "Monoclonal Antibody Therapy", "Mus", "National Institute of Allergy and Infectious Disease", "National Institute of Diabetes and Digestive and Kidney Diseases", "Nature", "Obesity", "Outcome", "Outsourcing", "Pathology", "Patients", "Phenotype", "Phosphorylation", "Plasma", "Population", "Pregnancy", "Procedures", "Production", "Proteins", "Proteomics", "Publishing", "RNA", "Rare Diseases", "Research Personnel", "Resources", "Review Committee", "Running", "Sampling", "Scientific Advances and Accomplishments", "Serum", "Services", "Simplexvirus", "System", "T-Lymphocyte", "Technology", "Testing", "Tissues", "Training", "United States National Institutes of Health", "Vaccination", "Variant", "Work", "Writing", "base", "clinical application", "clinical center", "cohort", "collaborative approach", "computer infrastructure", "coronavirus disease", "cost", "cytokine", "data mining", "data modeling", "design", "high dimensionality", "insight", "microbiome", "microbiome research", "microbiota", "mitochondrial dysfunction", "multidimensional data", "multimodality", "novel", "pandemic disease", "peripheral blood", "phenotypic biomarker", "programs", "recruit", "response", "sample collection", "single cell sequencing", "tool", "transcription factor", "transcriptome sequencing", "transcriptomics", "vaccine trial" ], "approved": true } }, { "type": "Grant", "id": "7727", "attributes": { "award_id": "1ZICES103326-04", "title": "NIEHS Cryo-EM Core Facility", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Environmental Health Sciences (NIEHS)" ], "program_reference_codes": [], "program_officials": [], "start_date": null, "end_date": null, "award_amount": 2904674, "principal_investigator": { "id": 23521, "first_name": "Mario", "last_name": "Borgnia", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1605, "ror": "https://ror.org/00j4k1h63", "name": "National Institute of Environmental Health Sciences", "address": "", "city": "", "state": "NC", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1605, "ror": "https://ror.org/00j4k1h63", "name": "National Institute of Environmental Health Sciences", "address": "", "city": "", "state": "NC", "zip": "", "country": "United States", "approved": true }, "abstract": "During FY2020, the Cryo-EM Core continued to collaborate with regional researchers through the Molecular Microscopy Consortium. The high productivity of the past year is reflected in the number of publications that resulted from over two dozen collaborations. This year we had our first Regional Symposium in cryo-EM organized by NIEHS, Duke and UNC. The symposium featured over 20 speakers and was attended by over 100 local scientists. Most of the work presented in the symposium was performed in collaboration with Core personnel in the context of the Molecular Microscopy Consortium. At the onset of the COVID-19 pandemic, we had been actively collaborating with Dr. Priyamvada Acharya at the Duke Human Vaccine Institute and with Dr. Eric Freed at NCI-Frederick on various structural questions involving the main viral antigen of HIV, the envelope glycoprotein Env. In response, we rapidly repurposed our structural virology pipelines to study the analogous SARS-CoV-2 S-protein. This prompted additional collaborations in the IRP, most notably an effort to map the binding sites of nanobodies developed by the group of Dr. Matt Hall at NCATS. We are also collaborating with others at NIEHS to solve the structure of a variety of SARS-CoV-2 non-structural proteins. The collaborations of the Cryo-EM Core have also grown in the NIH Intramural Program. In addition to ongoing work with colleagues at NCI, through the first half of FY2020 we have discussed a series of prospective collaborative projects with other ICs. These include both providing access to current technologies in single particle cryo-EM as well as the development of new capabilities in cryo-electron tomography and in situ structure determination. The interactions led to the organization of an intramural consortium between NIEHS, NCATS, NIA, NIBIB and NIDA for the purchase of a state of the art 300 keV TFS Titan Krios cryo-electron microscope which is expected to be operational at NIEHS by the spring of 2021.", "keywords": [ "2019-nCoV", "Binding Sites", "COVID-19 pandemic", "Collaborations", "Complex", "Core Facility", "Cryo-electron tomography", "Cryoelectron Microscopy", "Crystallization", "Development", "Electron Microscope", "Electron Microscopy", "Ensure", "Goals", "HIV Antigens", "Human", "Human Resources", "In Situ", "Institutes", "Intramural Research Program", "Macromolecular Complexes", "Maps", "Membrane Proteins", "Methods", "Microscopy", "Mission", "Molecular", "Molecular Structure", "National Institute of Biomedical Imaging and Bioengineering", "National Institute of Drug Abuse", "National Institute of Environmental Health Sciences", "Nonstructural Protein", "Nuclear Magnetic Resonance", "Preparation", "Process", "Productivity", "Proteins", "Publications", "Research", "Research Personnel", "Resolution", "Scientist", "Series", "Specimen", "Structural Biologist", "Structure", "Techniques", "Technology", "Titan", "Training", "United States National Institutes of Health", "Vaccines", "Viral Antigens", "Work", "X-Ray Crystallography", "collaborative environment", "env Glycoproteins", "image processing", "macromolecule", "nanobodies", "new technology", "novel strategies", "particle", "prospective", "response", "structural biology", "symposium", "tool", "virology" ], "approved": true } }, { "type": "Grant", "id": "7724", "attributes": { "award_id": "1ZIAHG200394-07", "title": "Insights into Sickle Cell Trait and Sickle Cell Disease", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Human Genome Research Institute (NHGRI)" ], "program_reference_codes": [], "program_officials": [], "start_date": null, "end_date": null, "award_amount": 284538, "principal_investigator": { "id": 23514, "first_name": "Vence L", "last_name": "Bonham", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1614, "ror": "https://ror.org/00baak391", "name": "National Human Genome Research Institute", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1614, "ror": "https://ror.org/00baak391", "name": "National Human Genome Research Institute", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "GOAL: SYSTEMATIC REVIEW OF CLINICAL COMPLICATIONS OF SICKLE CELL TRAIT (SCT) For Aim 1: A systematic review of published original research articles between January 1970 and June 30, 2018 that reported an association between SCT and clinical outcomes of interest were reviewed by an expert working group. We followed standard procedures for systematic reviews and reported results according to Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines. The study excluded: 1) non-English language research articles; 2) research articles that reported exclusively on patients with sickle cell disease, in vitro cells, or nonhuman animals; 3) research articles that solely examined physiological mechanisms, laboratory parameters, or had no information on clinical outcomes; 4) prevalence studies, case reports, case series, meeting abstracts, editorials and commentaries; and 5) systematic reviews and review articles after their bibliographies had been reviewed for previously unidentified articles.) Of 7,083 screened studies, 41 met inclusion criteria. There was strong evidence for a positive association between SCT and risk for pulmonary embolism, proteinuria, and chronic kidney disease. There was moderately strong evidence for a positive association between SCT and exertional rhabdomyolysis and for a null association between SCT and deep venous thrombosis, heart failure/cardiomyopathy, stroke, and pediatric height/weight. Absolute risks for the thromboembolism and rhabdomyolysis complications were small. There were either insufficient data or low strength of evidence regarding associations for the remaining 15 clinical outcomes reported in these studies. See Naik RP. et al., Clinical Outcomes Associated With Sickle Cell Trait, Annals of Internal Medicine. 169, 619 (2018). GOAL: EXPLORING THE GENOMIC AND ENVIRONMENTAL CONTRIBUTIONS TO SICKLE CELL DISEASE AND LEG ULCERS Aim 2: The study of leg ulcers in sickle cell disease is ongoing. As of September 1, 2019, we have recruited 235 participants. We have increased our accrual goal for the skin microbiome study up to 250 participants. We will recruit and sample participants with active ulcers, currently with a healed leg ulcer, and those with no previous history of leg ulcers. Additionally, we will compare a previously published microbiome dataset from diabetic foot ulcers to SCD leg ulcers to identify microbial signatures (similarities or differences) that exist in the microbial communities present in the different ulcers, which may be important in the healing process. Aim 3: We will conduct a cross-sectional study to investigate, resilience, stress, social function, health behaviors, and quality of life indicators for each participant with the goal of identifying environmental (i.e. social, physical, and psychosocial) factors that may impact sickle cell disease and the formation and healing of leg ulcers. Aim 4: We will conduct genomic sequencing to seek to identify the role of genetic modifiers in patients with and without leg ulcers. Specifically, we will conduct whole genome sequencing in the participants to study the genetic factors responsible for variation in leg ulceration in our patient population. Aim 5: We will develop and evaluate a return of genomic results program for INSIGHTS study participants. We will conduct an ethnographic study to collect longitudinal data to examine study participants that receive genomics results and assess health behaviors and treatment decisions over time. We predict that the population of study participants that are most in need of support in addressing unexpected genomic results will be low-income and under-insured individuals. GOAL: EXAMINE COVID-19 PANDEMIC IMPACTS INDIVIDUALS LIVING with SICKLE CELL DISEASE Aim 6 and 7: We will survey and conduct interviews to understand how the COVID-19 pandemic impacts individuals living with SCD, with a focus on the major physical and psychosocial facets of their disease referenced above including the presentation of pain, health care utilization, and social and behavioral health. We are particularly interested in how disease severity, pain frequency and severity, frequency and quality of healthcare services, emotional distress, sleep disturbance, perceived stress, and resilience affect the overall psychosocial well-being of individuals living with SCD during this current pandemic.", "keywords": [ "Accounting", "Address", "Affect", "African", "African American", "American", "Anemia", "Animals", "Arabs", "Behavior Therapy", "Bibliography", "COVID-19 pandemic", "Cardiomyopathies", "Case Series", "Case Study", "Cells", "Cessation of life", "Childhood", "Chronic Kidney Failure", "Clinical", "Codon Nucleotides", "Complication", "Cross-Sectional Studies", "Data", "Data Set", "Deep Vein Thrombosis", "Diabetic Foot Ulcer", "Disease", "Erythrocyte Membrane", "Ethnography", "Etiology", "Exertion", "Frequencies", "Genes", "Genetic", "Genetic study", "Genomic approach", "Genomics", "Goals", "Guidelines", "Health", "Health behavior", "Heart failure", "Height", "Hemolysis", "Hemolytic Anemia", "Hispanics", "Hospitalization", "Impairment", "In Vitro", "Incidence", "Individual", "Internal Medicine", "Interview", "Laboratories", "Leg", "Leg Ulcer", "Low income", "Mutation", "Nature", "Organ", "Outcome", "Pain", "Participant", "Patients", "Personal Satisfaction", "Physical environment", "Physiological", "Point Mutation", "Population", "Predisposition", "Prevalence Study", "Procedures", "Process", "Proteinuria", "Psychosocial Factor", "Public Policy", "Published Comment", "Publishing", "Pulmonary Embolism", "Quality of life", "Recording of previous events", "Recurrence", "Reporting", "Research", "Resistance", "Resources", "Rhabdomyolysis", "Risk", "Role", "Sampling", "Severities", "Severity of illness", "Sickle Cell", "Sickle Cell Anemia", "Sickle Cell Trait", "Sleep disturbances", "Social Environment", "Social Functioning", "Social Sciences", "Stress", "Stroke", "Surveys", "Symptoms", "Thromboembolism", "Time", "Ulcer", "Underinsured", "United States", "Variant", "Weight", "Well in self", "behavioral health", "beta Globin", "carrier testing", "clinical care", "comorbidity", "design", "editorial", "emotional distress", "genome sequencing", "healing", "health care quality", "health care service", "health care service utilization", "improved", "inclusion criteria", "insight", "interest", "meeting abstracts", "microbial", "microbial community", "microbiome", "microbiome research", "nonEnglish language", "offspring", "pandemic disease", "patient population", "perceived stress", "premature", "programs", "psychosocial", "recruit", "research study", "resilience", "screening program", "skin microbiome", "social", "southeast Asian", "stress resilience", "systematic review", "whole genome", "working group" ], "approved": true } }, { "type": "Grant", "id": "7682", "attributes": { "award_id": "1ZIEBC011384-10", "title": "Anatomic Pathology Residency Program", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Cancer Institute (NCI)" ], "program_reference_codes": [], "program_officials": [], "start_date": null, "end_date": null, "award_amount": 852774, "principal_investigator": { "id": 23485, "first_name": "Frederic", "last_name": "Barr", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1601, "ror": "", "name": "DIVISION OF BASIC SCIENCES - NCI", "address": "", "city": "", "state": "", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1601, "ror": "", "name": "DIVISION OF BASIC SCIENCES - NCI", "address": "", "city": "", "state": "", "zip": "", "country": "United States", "approved": true }, "abstract": "Residents in the Anatomic Pathology Residency Program contribute to the clinical research program of the NCI and the NIH. Through their efforts as anatomic pathology residents in training, they help illuminate the pathological changes associated initial presentation and therapy of both neoplastic and non-neoplastic diseases and explore new techniques to improve diagnosis of these diseases. These residents are critical to the patient care activities of the NCI and the NIH, and contribute to the diagnosis and management of disease, especially COVID-19 this year. Residents have also contributed to publications dealing with characterization, diagnosis, and pathogenesis of a number of disease entities.", "keywords": [ "Accreditation", "Anatomy", "Area", "Autopsy", "Biological Assay", "COVID-19", "Case Study", "Clinical", "Clinical Research", "Clinical Trials", "Clonality", "Communicable Diseases", "Consult", "Consultations", "Cytopathology", "DNA Methylation", "DNA analysis", "Diagnosis", "Diagnostic", "Digestive System Disorders", "Disease", "Disease Management", "Educational process of instructing", "Enrollment", "Etiology", "Exposure to", "Extramural Activities", "Flow Cytometry", "Fluorescent in Situ Hybridization", "Functional disorder", "Funding", "Gene Mutation", "Genes", "Genetic study", "Hematopathology", "Institutes", "Investigation", "Kidney Diseases", "Laboratories", "Learning", "Lymphoid", "Malignant Neoplasms", "Medicine", "Mission", "Molecular Genetics", "Mutation", "Oncology", "Outcome", "Pathogenesis", "Pathologic", "Pathology", "Patient Care", "Patients", "Philosophy", "Play", "Protocols documentation", "Publications", "Research", "Research Activity", "Research Training", "Residencies", "Role", "Services", "Surgical Pathology", "Techniques", "Tissues", "Training", "Training Programs", "United States National Institutes of Health", "base", "cancer therapy", "clinical center", "disease diagnosis", "epidemiology study", "experience", "improved", "insight", "molecular diagnostics", "neoplastic", "nervous system disorder", "neuropathology", "next generation sequencing", "novel", "programs", "recruit", "research clinical testing", "soft tissue", "urologic" ], "approved": true } }, { "type": "Grant", "id": "7697", "attributes": { "award_id": "1ZIAAI001306-01", "title": "tissue tropism of coronavirus", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [], "start_date": null, "end_date": null, "award_amount": 41824, "principal_investigator": { "id": 23492, "first_name": "Yasmine", "last_name": "Belkaid", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1540, "ror": "https://ror.org/043z4tv69", "name": "National Institute of Allergy and Infectious Diseases", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1540, "ror": "https://ror.org/043z4tv69", "name": "National Institute of Allergy and Infectious Diseases", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "The COVID-19 condition caused by the novel coronavirus SARS-CoV-2 is an active, existential global health threat. A substantial fraction of those infected exhibit no symptoms, while others progress to severe illness resulting in multi-organ failure and death. The factors dictating whether an infected subject will progress to develop symptoms or will experience asymptomatic infection remains poorly understood. Using experimental models, work that we and others have conducted over the past few years revealed that the ability of a given microbe to cause disease can be highly contextual. Indeed, numerous factors can contribute to pathogen-induced morbidity or mortality including age, microbiota, nutritional status as well as co-infection or previous infections. Our combined laboratories have pioneered the development of murine models of infectious diseases and developed novel tools to track microbial tropism, tissue specific pathologies and immune responses to pathogens. Using models of murine coronavirus infection, this proposal aims at addressing the circumstances controlling anti-viral immunity and pathogenicity.", "keywords": [ "Acute", "Address", "Age", "COVID-19", "Cessation of life", "Coronavirus", "Coronavirus Infections", "Development", "Disease", "Exhibits", "Experimental Models", "Failure", "Family", "Goals", "Immune response", "Immunity", "Infection", "Intestines", "Intranasal Administration", "Laboratories", "Lung", "Microbe", "Modeling", "Morbidity - disease rate", "Murine hepatitis virus", "Mus", "Nutritional status", "Organ", "Pathogenicity", "Pathology", "Pulmonary Inflammation", "RNA Viruses", "Research Personnel", "Respiratory Signs and Symptoms", "Symptoms", "Tissues", "Tropism", "Virus", "Work", "antiviral immunity", "co-infection", "experience", "global health", "human disease", "infectious disease model", "member", "microbial", "microbiota", "mortality", "mouse model", "novel", "novel coronavirus", "nutrition", "pathogen", "tissue tropism", "tool" ], "approved": true } }, { "type": "Grant", "id": "7694", "attributes": { "award_id": "1ZIAEY000306-26", "title": "Role of Protein Interactions in Retina Development and Function", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Eye Institute (NEI)" ], "program_reference_codes": [], "program_officials": [], "start_date": null, "end_date": null, "award_amount": 728296, "principal_investigator": { "id": 23489, "first_name": "SOFIA P", "last_name": "BECERRA", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1611, "ror": "https://ror.org/03wkg3b53", "name": "National Eye Institute", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1611, "ror": "https://ror.org/03wkg3b53", "name": "National Eye Institute", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "A study on the role of the PNPLA2 gene in the regulation of oxidative stress damage of RPE was completed. Oxidative stress-mediated injury of the retinal pigment epithelium (RPE) can precede progressive retinal degeneration and ultimately lead to blindness (e.g., age-related macular degeneration). The RPE expresses the PNPLA2 gene and produces its protein product PEDF-R. We showed that transient PNPLA2 overexpression decreases dead-cell proteolytic activity and that synthetic peptides derived from a central region of PEDF-R efficiently protect ARPE-19 and pig primary RPE cells from oxidative stress. We evaluated the effect of loss of PNPLA2 in RPE cells undergoing oxidative stress and found that loss of PNPLA2 conferred increased resistance to cells when subjected to oxidative stress. The molecular pathways triggered by PEDF that are involved in retinal survival activity was reviewed. PEDF is involved in signal transduction cascades necessary for protection of the retina. The interaction between PEDF and retinal cells elicits neuroprotective effects in vitro and in vivo. The direct substrates and signaling mechanisms involved in the survival response derived from such interaction were summarized. Three semi-automated cell-based protocols to identify retinoprotective factors with two retinal cell lines, rat R28 cells and mouse 661W cells were described in detail. In these protocols, cells are induced to undergo death by photo-oxidation stress, growth factor depletion or cytotoxicity with sodium iodate. PEDF, an established neurotrophic factor for retinal cells, was used as a positive control. These protocols will prove useful in high-throughput quantitative screening of potential retinoprotective factors. The polarized RPE releases PEDF in an apicolateral fashion. We determined the levels of PEDF released by polarized iPSC-derived RPE attached to porous membranes in transwells (in collaboration with the laboratory of V. Canto-Soler). The media from the basal and apical compartments were subjected to western blotting and ELISA using specific antibodies to human PEDF. Photoreceptor outer segments were isolated from bovine retina. Cells exposed to photoreceptor outer segments were assayed for phagocytosis, by following ingestion and degradation of the outer segments. Western blots of cell lysates using specific antibodies to rhodopsin were performed to determine ingestion of outer segments by the cells. The levels of a byproduct of POS degradation, beta-hydroxybutyrate, were measured in the media of the cells. The role of PEDF-R in the phagocytosis of photoreceptor outer segments continued to be investigated. The PNPLA2 gene was transiently silenced in the ARPE-19 cell line using siScramble and siPNPLA2 oligonucleotide duplexes. mRNA and protein levels of fatty acid metabolism related genes ACAD9 (acyl-CoA dehydrogenase family member 9), CPT1C (carnitine palmitoyltransferase 1C), and FASN (fatty acid synthase) were measured in PEDF-R-deficient cells challenged with photoreceptor outer segments. Cell viability of ARPE-19 cells incubated with bromoenol lactone, a phospholipase inhibitor was measured. The effects of bromoenol lactone on the degradation of photoreceptor outer segments, as well as the secretion of the ketone body beta-hydroxybutyrate were determined. PEDF-R protein levels following photoreceptor outer segments addition were measured. Total phospholipids and fatty acids were determined from cell lysates of transiently transfected cells challenged with photoreceptor outer segments (collaboration with the laboratory of MP Agdaba). An in vitro model of cultured primary retinal neurons was used to examine intracellular signaling stimulated by exogenous additions of PEDF peptide fragments. The newborn rat retinal cells in culture die spontaneously in the absence of trophic factors. CRX immunostaining was performed to identify photoreceptor cells. We performed mitochondrial assays using Mitotracker, and quantification of the changes in mitochondrial membrane potential in live cells by flow cytometry, microplate spectrophotometry and fluorescent microscopy using tetramethylrhodamine, ethyl ester (TMRE). Results show that PEDF peptides protected photoreceptor precursors from apoptosis, preserved mitochondrial function and promoted polarization of opsin enhancing their developmental process, as well as induced neurite outgrowth in amacrine neurons. These effects were abolished by an enzymatic inhibitor of the PEDF-R, or receptor-derived peptides that block ligand/receptor interactions. While all the activities were specifically conferred by short peptide fragments (17 amino acid residues) derived from the PEDF neurotrophic domain, no effects were triggered by peptides from the PEDF antiangiogenic region. The mRNA levels of Bcl2 gene were determined in cells treated with and without effectors. Protein extracts from cells treated with and without PEDF were obtained for large-scale study of proteins. The effects of PEDF and derived peptides on regulation of Bcl2, Bax and RAC1 proteins were examined by western blotting of the rat primary cultures treated with and without the effectors. We continued to purify large amounts of recombinant human PEDF protein versions from conditioned media of stably transfected Hek.Ebna 293 cells with PEDF expression plasmids. Cells expressing for full length human PEDF and versions with single point alterations at H105A were cultured at large scale and secreted proteins in their serum free media were collected, concentrated and dialyzed (collaboration with Y. Shiloachs laboratory). The proteins were purified using a two-step ion-exchange chromatography. The purified PEDF protein combined with a peptide fragment of the ectodomain of PEDF-R was used in high-throughput crystallization screening (collaboration with V Sagar in G. Wistows laboratory). Recombinant PEDF-R versions were produced in E. coli cells induced with isopropyl - d-1-thiogalactopyranoside. The recombinant PEDF-R versions overproduced in bacteria were insoluble and solubilization studies were performed using urea. Conditions for overproduction, solubilization with urea and purification by ion exchange column chromatography were optimized. PEDF-R variants retained the ability to bind PEDF. Mammalian-derived recombinant PEDF and bacterially derived recombinant PEDF-R can be produced and purified in large amounts for use in structural and biological studies. A proposal to investigate the effects of PEDF and its derived peptides to inhibit the hallmark of COVID-19 cytokine storm, in particular regulation of the IL-6 gene and the IL-6 protein levels and its consequences in the context of COVID-19, was prepared and submitted to ITAC. Another proposal in collaboration with R Star, NIDDK, to study PEDF as biomarker for intervention in COVID-16 during cytokine storm was also prepared and submitted to ITAC.", "keywords": [ "Age related macular degeneration", "Amino Acids", "Angiogenesis Inhibitors", "Animal Model", "Antibodies", "Apical", "Apoptosis", "BCL-2 Protein", "BCL2 gene", "Bacteria", "Bax protein", "Binding", "Biological", "Biological Assay", "Biological Markers", "Blindness", "COVID-19", "Carnitine Palmitoyltransferase I", "Cattle", "Cell Extracts", "Cell Line", "Cell Survival", "Cells", "Cessation of life", "Choroidal Neovascularization", "Collaborations", "Column Chromatography", "Corneal Neovascularization", "Crystallization", "Development", "Developmental Process", "Enzyme-Linked Immunosorbent Assay", "Escherichia coli", "Esters", "Exposure to", "Eye", "FASN gene", "Family", "Family member", "Family suidae", "Fatty Acids", "Fatty-acid synthase", "Flow Cytometry", "Genes", "Growth Factor", "Human", "Hydrolysis", "IL6 gene", "In Vitro", "Incubated", "Ingestion", "Inherited", "Injury", "Interest Group", "Interleukin-6", "Intervention", "Ion Exchange", "Ion-Exchange Chromatography Procedure", "Ketone Bodies", "Laboratories", "Lactones", "Lead", "Length", "Ligands", "Light", "Link", "Lipase", "Longevity", "Maintenance", "Mammals", "Measures", "Mediating", "Membrane", "Membrane Potentials", "Messenger RNA", "Microscopy", "Mitochondria", "Molecular", "Mus", "National Institute of Diabetes and Digestive and Kidney Diseases", "Neoplasm Metastasis", "Neurites", "Neuronal Differentiation", "Neurons", "Newborn Infant", "Oligonucleotides", "Opsin", "Oxidative Regulation", "Oxidative Stress", "Pathway interactions", "Peptide Fragments", "Peptides", "Phagocytosis", "Phospholipase", "Phospholipases A", "Phospholipids", "Photoreceptors", "Plasmids", "Proteins", "Protocols documentation", "Rattus", "Recombinants", "Regulation", "Research", "Resistance", "Retina", "Retinal Degeneration", "Retinal Neovascularization", "Rhodopsin", "Role", "Serpin Superfamily", "Serum-Free Culture Media", "Signal Transduction", "Spectrophotometry", "Stress", "Structure", "Structure of retinal pigment epithelium", "Triglycerides", "Urea", "Variant", "Western Blotting", "Work", "acyl-CoA dehydrogenase", "base", "beta-Hydroxybutyrate", "coronavirus disease", "cytokine release syndrome", "cytotoxicity", "fatty acid metabolism", "in vitro Model", "in vivo", "induced pluripotent stem cell", "inhibitor/antagonist", "member", "mitochondrial membrane", "neuronal survival", "neurotrophic factor", "overexpression", "oxidatio" ], "approved": true } }, { "type": "Grant", "id": "7706", "attributes": { "award_id": "1ZIABC011941-01", "title": "Studies of the SARS-CoV-2 Spike Protein", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Cancer Institute (NCI)" ], "program_reference_codes": [], "program_officials": [], "start_date": null, "end_date": null, "award_amount": 512699, "principal_investigator": { "id": 23500, "first_name": "JAY A", "last_name": "BERZOFSKY", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1601, "ror": "", "name": "DIVISION OF BASIC SCIENCES - NCI", "address": "", "city": "", "state": "", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1601, "ror": "", "name": "DIVISION OF BASIC SCIENCES - NCI", "address": "", "city": "", "state": "", "zip": "", "country": "United States", "approved": true }, "abstract": "This project just began in April, 2020, during the COVID-19-induced closure of NIH labs, with very few people allowed to work, so it is very early ( 3 months) and progress is limited on each of the above sub-studies. In vitro studies in macaque bronchioalveolar lavage cells: So far, we have seen some effects in vitro on these cells of stimulating them with recombinant spike protein to affect expression of ACE2 and of interferons, that may play a role in infection. Little effect was seen on other cytokine or chemokine production. This work is in progress. In vivo vaccine studies in macaques: the animals have been primed IM with spike in different adjuvants and boosted systemically with spike in nanoparticles. Some T cell responses have been induced by the different regimens, and serum and BAL fluid for antibody responses have been collected and are being assayed. It is too soon to determine which regimen is more immunogenic. If we can arrange a challenge at a BSL3 facility that can handle the virus (being negotiated), we hope to challenge the animals with SARS-CoV-2 to measure vaccine efficacy and correlate that with different immune responses. In vivo studies in mice: ACE2-transgenic mice have been ordered but their shipment was delayed until the end of July. In wild type B6 mice, we have immunized with recombinant spike protein in several different adjuvants to determine the best formulation. That work is in progress. The DNA vaccine with spike protein coupled to a chemokine is being constructed and that work is in progress. Human cell lines: We have received the immortalized human lung epithelial cell lines, that express ACE2, from John Minna at UTSW, as well as some of his non-small-cell lung cancer cell lines that also express ACE2. We have just obtained (mid-July) an antibody to ACE2 that we will use to verify expression. These lines have now been thawed and are being grown up, but no results of planned studies to stimulate with spike protein have been obtained yet. We intend to measure production of chemokines, cytokines, and other factors that may affect the COVID-19 disease course, as noted above.", "keywords": [ "2019-nCoV", "Adjuvant", "Affect", "Animal Model", "Animals", "Antibodies", "Antibody Response", "Binding", "Bioinformatics", "Biological Assay", "Bronchoalveolar Lavage", "COVID-19", "Cancer cell line", "Cell Line", "Cells", "Clinical Trials", "Coupled", "DNA Vaccines", "Dendritic Cells", "Disease", "Electroporation", "Engineering", "Epithelial Cells", "Epitopes", "Formulation", "Human", "Human Cell Line", "Immune", "Immune response", "Immunize", "In Vitro", "Industrialization", "Infection", "Interferons", "Liquid substance", "Lung", "Macaca", "Malignant neoplasm of lung", "Measures", "Mediation", "Medical center", "Methods", "Modeling", "Morbidity - disease rate", "Mucosal Immunity", "Mucous Membrane", "Mus", "Natural Immunity", "Non-Small-Cell Lung Carcinoma", "Phase", "Play", "Production", "Proteins", "Recombinants", "Regimen", "Respiratory Mucosa", "Role", "Route", "SIV Vaccines", "Serum", "Ships", "Site", "Structure of respiratory epithelium", "T cell response", "Texas", "Transgenic Mice", "United States National Institutes of Health", "Universities", "Vaccines", "Vascular Endothelial Cell", "Viral", "Viral Vaccines", "Virus", "Work", "biosafety level 3 facility", "chemokine", "cytokine", "immunogenic", "immunogenicity", "immunopathology", "in vivo", "mucosal vaccine", "nanoparticle", "neutralizing antibody", "nonhuman primate", "preclinical study", "receptor", "receptor binding", "response", "vaccine candidate", "vaccine efficacy", "vaccine trial", "viral transmission" ], "approved": true } }, { "type": "Grant", "id": "7717", "attributes": { "award_id": "1ZIAAG000778-04", "title": "The role of immune cells in Alzheimer's disease", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Aging (NIA)" ], "program_reference_codes": [], "program_officials": [], "start_date": null, "end_date": null, "award_amount": 528921, "principal_investigator": { "id": 23510, "first_name": "Arya", "last_name": "Biragyn", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1613, "ror": "https://ror.org/049v75w11", "name": "National Institute on Aging", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1613, "ror": "https://ror.org/049v75w11", "name": "National Institute on Aging", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "The role of B cells in Alzheimer's disease (AD) remains poorly understood even though we and others showed their benefit as producers of antibody that help to eliminate neurotoxic beta-amyloid depositions (Ab plaques) (Olkhanud et al, Vaccine, 2011). About 6 years ago, we have hypothesized that B cells could also be promoting AD because they upregulate expression of inflammatory factors together with the onset of AD in 3xTgAD mice. We tested this possibility in 3 different mouse models of AD, such as 3xTgAD, APP/PS1 and 5xFAD mice, utilizing complementing experimental strategies. First, we generated B-cell deficient (BKO) mice that develop AD in young and old age, 2xTgAD and 3xTgAD mice by crossing BKO mice with 2xTgAD and 3xTgAD mice, respectively. The loss of B cells in these mice almost completely reversed the AD symptoms despite expression of AD-promoting transgenes. Compared to age/sex-matched B-cell sufficient littermates, 2xTgAD/BKO and 3xTgAD/BKO mice exhibited reduced anxiety and improved memory deficits. Both 2xTgAD/BKO and 3xTgAD/BKO mice contained significantly fewer Ab-plaques in the brain subiculum than their age- and sex-matched littermates. The over activated microglia, another hallmark of AD pathology, in both mice without B cells was also markedly reduced. To confirm this finding, we also transiently depleted B cells from the circulation of mice with AD, such as 3xTgAD, APP/PS1 and 5xFAD mice, by injecting CD20-targeting antibody. The B-cell depletion indeed significantly delayed AD symptoms in all three types of mice. Overall, for the first time we demonstrate that B cells play pathogenic role in AD and, importantly, their transient depletion from the circulation can delay AD onset. The paper, which we recently submitted for publication, came back for revision. Due to the COVID-19 quarantine, we had to terminate experiments and cull essential AD mice, precluding a proper addressing the editor and reviewers comments. We therefore expect to finalize this paper by middle of 2021. Despite this, we have played the key roles in successful completion of 2 papers from our collaborators on Ad and AD-like symptoms in Down syndrome.", "keywords": [ "APP-PS1", "Address", "Age", "Aging", "Alzheimer&apos", "s Disease", "Alzheimer&apos", "s disease model", "Alzheimer&apos", "s disease pathology", "Antibodies", "Anxiety", "B-Lymphocytes", "Back", "Blood Circulation", "Brain", "COVID-19", "Cells", "Complement", "Disease", "Down Syndrome", "Exhibits", "Goals", "Immune", "Inflammatory", "MS4A1 gene", "Memory impairment", "Microglia", "Mus", "Onset of illness", "Paper", "Pathogenicity", "Play", "Publications", "Published Comment", "Quarantine", "Role", "Symptoms", "Testing", "Therapeutic", "Time", "Transgenes", "Vaccines", "abeta deposition", "experimental study", "improved", "mouse model", "neurotoxic", "sex" ], "approved": true } } ], "meta": { "pagination": { "page": 2, "pages": 1392, "count": 13920 } } }