Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1405&sort=other_investigators
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=other_investigators", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1405&sort=other_investigators", "next": null, "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1404&sort=other_investigators" }, "data": [ { "type": "Grant", "id": "11881", "attributes": { "award_id": "1S21MD018975-01", "title": "PREDICT (Precision Medicine, Education, Data Informatics and Community Translation) Institute", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Minority Health and Health Disparities (NIMHD)" ], "program_reference_codes": [], "program_officials": [ { "id": 6103, "first_name": "Nancy Lynne", "last_name": "Jones", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-07-06", "end_date": "2028-05-31", "award_amount": 2000000, "principal_investigator": { "id": 27778, "first_name": "Kathleen B.", "last_name": "Kennedy", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 23397, "first_name": "Christopher", "last_name": "Williams", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1594, "ror": "https://ror.org/04dzpzw79", "name": "National Health Promotion Associates", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true } ] } ], "awardee_organization": { "id": 487, "ror": "https://ror.org/0085d9t86", "name": "Xavier University of Louisiana", "address": "", "city": "", "state": "LA", "zip": "", "country": "United States", "approved": true }, "abstract": "Xavier University of Louisiana seeks support from the NIH National Institute on Minority Health and Health Disparities to complement the research infrastructure in the College of Pharmacy through a new initiative. The proposed initiative will establish the Precision Medicine, Education, Data Informatics, and Community Translation (PREDICT) Institute, a comprehensive programmatic initiative creating a holistic and replicable framework for the utilization of electronic health data and community translation to affect the decision- making process to improve health outcomes. The Institute will extend the technical research exchange (TREX) program at Xavier to include training of current and future underrepresented researchers on health informatics best practices to diversify the research workforce and leverage community-based approaches to enhance clinical research efforts in vulnerable populations. This request comes at both a challenging and opportunistic time where an awareness of health disparities was heightened and, in some instances, exacerbated by the COVID-19 pandemic. The use of population health and bioinformatics data are potential tools useful in collective approaches required to achieve health equity. The Specific Aims of the PREDICT Institute are: Specific Aim #1: To enhance the existing Xavier health informatics infrastructure by increasing capacity for data acquisition, data warehousing, data access, data analytics, and technical assistance necessary for addressing health outcomes in minority communities. Specific Aim #2: To strengthen the research and outreach infrastructure of the university to promote community-engaged translational/clinical research and health promotion to mitigate health disparities. Specific Aim #3: To develop a diverse, highly competitive research workforce through the implementation of training/mentoring programs for students, postdoctoral residents/fellows, and early-stage/mid-career faculty (PREDICT scholars).", "keywords": [ "Address", "Affect", "Awareness", "Bioinformatics", "COVID-19 pandemic", "Clinical Research", "Communities", "Complement", "Data", "Data Analytics", "Decision Making", "Education", "Future", "Health", "Health Promotion", "Informatics", "Infrastructure", "Louisiana", "Mentors", "National Institute on Minority Health and Health Disparities", "Outcome", "Pharmacy facility", "Postdoctoral Fellow", "Process", "Public Health Informatics", "Reduce health disparities", "Research", "Research Infrastructure", "Research Personnel", "Students", "Time", "Training", "Translations", "United States National Institutes of Health", "Universities", "Vulnerable Populations", "college", "data access", "data acquisition", "data warehouse", "eHealth", "health data", "health disparity", "health equity", "improved", "informatics infrastructure", "mid-career faculty", "minority communities", "outreach", "population health", "precision medicine", "programs", "tool", "translational engagement" ], "approved": true } }, { "type": "Grant", "id": "14983", "attributes": { "award_id": "5S21MD018975-02", "title": "PREDICT (Precision Medicine, Education, Data Informatics and Community Translation) Institute", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Minority Health and Health Disparities (NIMHD)" ], "program_reference_codes": [], "program_officials": [ { "id": 6103, "first_name": "Nancy Lynne", "last_name": "Jones", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-07-06", "end_date": "2028-05-31", "award_amount": 2000000, "principal_investigator": { "id": 27778, "first_name": "Kathleen B.", "last_name": "Kennedy", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 23397, "first_name": "Christopher", "last_name": "Williams", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1594, "ror": "https://ror.org/04dzpzw79", "name": "National Health Promotion Associates", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true } ] } ], "awardee_organization": { "id": 487, "ror": "https://ror.org/0085d9t86", "name": "Xavier University of Louisiana", "address": "", "city": "", "state": "LA", "zip": "", "country": "United States", "approved": true }, "abstract": "Xavier University of Louisiana seeks support from the NIH National Institute on Minority Health and Health Disparities to complement the research infrastructure in the College of Pharmacy through a new initiative. The proposed initiative will establish the Precision Medicine, Education, Data Informatics, and Community Translation (PREDICT) Institute, a comprehensive programmatic initiative creating a holistic and replicable framework for the utilization of electronic health data and community translation to affect the decision- making process to improve health outcomes. The Institute will extend the technical research exchange (TREX) program at Xavier to include training of current and future underrepresented researchers on health informatics best practices to diversify the research workforce and leverage community-based approaches to enhance clinical research efforts in vulnerable populations. This request comes at both a challenging and opportunistic time where an awareness of health disparities was heightened and, in some instances, exacerbated by the COVID-19 pandemic. The use of population health and bioinformatics data are potential tools useful in collective approaches required to achieve health equity. The Specific Aims of the PREDICT Institute are: Specific Aim #1: To enhance the existing Xavier health informatics infrastructure by increasing capacity for data acquisition, data warehousing, data access, data analytics, and technical assistance necessary for addressing health outcomes in minority communities. Specific Aim #2: To strengthen the research and outreach infrastructure of the university to promote community-engaged translational/clinical research and health promotion to mitigate health disparities. Specific Aim #3: To develop a diverse, highly competitive research workforce through the implementation of training/mentoring programs for students, postdoctoral residents/fellows, and early-stage/mid-career faculty (PREDICT scholars).", "keywords": [], "approved": true } }, { "type": "Grant", "id": "8776", "attributes": { "award_id": "1R01EB031510-01", "title": "A SARS-CoV-2 NFC ePAD Biosensor", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Biomedical Imaging and Bioengineering (NIBIB)" ], "program_reference_codes": [], "program_officials": [ { "id": 22599, "first_name": "TATJANA", "last_name": "Atanasijevic", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2021-09-13", "end_date": "2023-09-12", "award_amount": 988864, "principal_investigator": { "id": 24577, "first_name": "DAVID S", "last_name": "DANDY", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 323, "ror": "https://ror.org/03k1gpj17", "name": "Colorado State University", "address": "", "city": "", "state": "CO", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 4432, "first_name": "Charles S", "last_name": "Henry", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 323, "ror": "https://ror.org/03k1gpj17", "name": "Colorado State University", "address": "", "city": "", "state": "CO", "zip": "", "country": "United States", "approved": true } ] }, { "id": 23399, "first_name": "Brian", "last_name": "Geiss", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 323, "ror": "https://ror.org/03k1gpj17", "name": "Colorado State University", "address": "", "city": "", "state": "CO", "zip": "", "country": "United States", "approved": true } ] } ], "awardee_organization": { "id": 323, "ror": "https://ror.org/03k1gpj17", "name": "Colorado State University", "address": "", "city": "", "state": "CO", "zip": "", "country": "United States", "approved": true }, "abstract": "The current SARS-CoV-2 outbreak has begun to reshape how we think about and use diagnostic assays for preventing the spread of infectious diseases. Early diagnostic efforts specific to SARS focused almost solely on detecting the virus using nucleic acid amplification tests; more recently detection of circulating antibodies using ELISA to complete serological screening. While these techniques can provide accurate results, they require laboratory facilities and equipment, creating a significant delay between sampling and results. Rapid diagnostic tests in the form of lateral flow assays have appeared more recently but so far have lacked the sensitivity and selectivity to be useful for slowing disease spread. Another challenge with current approaches is that they require different molecular approaches for different markers making creation of a single test that can determine if an individual is or has been infected is challenging. As a result, there is a clear and pressing need to develop a single sensing platform that can quantitatively detect ng/mL levels of both viral antigens produced during infection and circulating antibodies at the point-of-care from blood, saliva, or nasal swabs that can be used by essentially anyone with little or no training. The goal of this project is to create a simple, inexpensive, and deployable electrochemical paper-based analytical device (ePAD) for detecting SARS-CoV-2 antigens and antibodies in blood, saliva, and nasopharyngeal swabs. Our device will combine three innovative components: a label-free electrochemical biosensor, a disposable near field communication (NFC) potentiostat, and a self-powered microfluidic device that performs complex sample preparation steps without user intervention. This system, the NFC-ePAD, will allow a user to literally add sample and press a button on the sensor and then place their phone on the unit to initiate the measurement. The phone activates the sensor and reports the results to the user. To achieve our goal, we are collaborating with colleagues at Chulalongkorn University and Silicon Craft™ in Thailand. Our aims are 1) demonstrate a sensitive label-free biosensor for circulating SARS-CoV-2 nucleocapsid protein and anti-spike receptor binding domain (RBD) antibodies, 2) create a self-power microfluidic device for sample processing, and 3) validate the system using deidentified, banked clinical samples. Once developed, the system will provide a fast, simple, and easy-to-use platform for healthcare providers and individuals alike to rapidly determine the infection and immune status of potential COVID-19 patients.", "keywords": [ "2019-nCoV", "Antibodies", "Antigens", "Archives", "Biological Assay", "Biosensor", "Blood", "Blood specimen", "Buffers", "COVID-19", "COVID-19 detection", "COVID-19 diagnostic", "COVID-19 outbreak", "COVID-19 patient", "Cessation of life", "Clinical", "Collaborations", "Communicable Diseases", "Communication", "Complex", "Detection", "Development", "Devices", "Diagnostic", "Diagnostic tests", "Disease", "Disease Outbreaks", "Electrodes", "Enzyme-Linked Immunosorbent Assay", "Generations", "Goals", "Gold", "Guidelines", "Health Personnel", "Human", "Individual", "Infection", "Infectious Diseases Research", "Institutional Review Boards", "Intervention", "Label", "Laboratories", "Location", "Measurement", "Measures", "Methods", "Microfluidic Microchips", "Modification", "Molecular", "Nucleic Acid Amplification Tests", "Nucleocapsid", "Nucleocapsid Proteins", "Paper", "Patients", "Performance", "Preparation", "Procedures", "Process", "Quarantine", "Rapid diagnostics", "Reagent", "Reporting", "Risk", "SARS-CoV-2 antigen", "Saliva", "Sampling", "Sensitivity and Specificity", "Serology", "Severe Acute Respiratory Syndrome", "Silicon", "Surface", "Surface Tension", "System", "Techniques", "Technology", "Telephone", "Testing", "Thailand", "Training", "Translating", "United States", "Universities", "Viral", "Viral Antigens", "Virus", "antibody detection", "base", "cost effective", "diagnostic assay", "diagnostic platform", "healthy aging", "immunological status", "improved", "innovation", "laboratory equipment", "laboratory facility", "lateral flow assay", "nasal swab", "nasopharyngeal swab", "point of care", "prevent", "receptor binding", "screening", "sensor", "waiver" ], "approved": true } }, { "type": "Grant", "id": "7605", "attributes": { "award_id": "1R21AI158335-01", "title": "Mechanisms and functional implications of SARS-CoV-2 mRNA capping and modification.", "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": [ { "id": 6011, "first_name": "Erik J.", "last_name": "Stemmy", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2020-09-01", "end_date": "2022-08-31", "award_amount": 407060, "principal_investigator": { "id": 23399, "first_name": "Brian", "last_name": "Geiss", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 323, "ror": "https://ror.org/03k1gpj17", "name": "Colorado State University", "address": "", "city": "", "state": "CO", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 23400, "first_name": "Jeffrey", "last_name": "Wilusz", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 323, "ror": "https://ror.org/03k1gpj17", "name": "Colorado State University", "address": "", "city": "", "state": "CO", "zip": "", "country": "United States", "approved": true }, "abstract": "SARS-CoV-2 must cap and methylate its mRNAs to ensure their stability, translatability, and avoid detection by host innate immune mechanism as non-self transcripts. The process of RNA capping, therefore, is pivotal to the success of a SARS-CoV-2 infection. It also represents a key contributor to the molecular mechanisms of pathogenesis as well as a very attractive target for the development of antiviral therapeutics. However, there are three key knowledge gaps that have slowed progress in our understanding of this important area of coronavirus molecular biology that will be addressed in this proposal. First, the identity of the guanylyltransferase (GTase), the centerpiece of the viral RNA capping machinery that transfers GTP to the 5' end of the nascent transcript, is unknown. We will use a two-pronged strategy of complementary molecular and biochemical approaches to address this glaring gap in our understanding of SARS-CoV-2 mRNA capping mechanisms, laying the foundation for the development of capping-targeted antivirals. Second, while RNA capping is a regulated process and uncapped RNAs play an influential role in the biology of other positive sense RNA viral infections, it is not known if RNA capping is a regulated or a default event in coronaviruses. We will determine if uncapped RNAs are produced by SARS-CoV-2 in order to establish the foundation for a role of regulated capping and non-coding viral transcripts in SARS-CoV-2 infections. Finally, every cellular mRNA that begins with a terminal adenosine has that residue 2'O methylated at the ribose ring as well as N6 methylated on the adenosine base (m6Am). The strong conservation of this m6Am modification indicates its importance in cell biology, an assertation recently confirmed with data suggesting that the modification increases translatability and facilitates recognition of the transcript as `self'. Interestingly, SARS-CoV-2 and other coronaviruses all initiate their transcripts with an A residue, but it is not known whether that A residue contains an m6A modification. In the final part of this project, we will determine the m6A modification status of the terminal 5' A residue of SARS-CoV-2 mRNAs and investigate the role that the modification (or lack thereof) plays in the biology of coronaviral transcripts. Collectively these studies will provide important new insights into the molecular biology of SARS-CoV-2 and open up avenues for the development of broad-spectrum anti- coronaviral therapeutics.", "keywords": [ "2019-nCoV", "Address", "Adenosine", "Antiviral Agents", "Area", "Attention", "Biochemical", "Biological", "Biology", "Cell physiology", "Cells", "Cellular biology", "Coronavirus", "DNA Polymerase II", "Data", "Defense Mechanisms", "Detection", "Development", "Ensure", "Enzymes", "Event", "Family", "Foundations", "Future", "Gene Expression", "Generations", "Genetic Transcription", "Genetic Translation", "Genome", "Genomics", "Glare", "Guanosine", "Guanosine Triphosphate", "Immunologic Surveillance", "Immunoprecipitation", "Infection", "Influentials", "Knowledge", "Label", "Lysine", "Mass Spectrum Analysis", "Messenger RNA", "Methylation", "Modification", "Molecular", "Molecular Biology", "Mutation Analysis", "Open Reading Frames", "Pathogenesis", "Play", "Process", "Property", "Proteins", "RNA", "RNA Caps", "RNA Stability", "RNA Virus Infections", "RNA Viruses", "RNA metabolism", "RNA methylation", "RNA replication", "Regulation", "Replicon", "Ribose", "Role", "SARS coronavirus", "Structure", "System", "Therapeutic", "Transcript", "Transfection", "Translation Initiation", "Untranslated RNA", "Viral", "Viral Genes", "Viral Pathogenesis", "Viral Proteins", "Virus", "Virus Diseases", "Virus Replication", "Work", "base", "drug development", "guanylyltransferase", "innate immune mechanisms", "innate immune sensing", "insight", "mRNA Stability", "mRNA capping", "novel", "novel therapeutics", "novel vaccines", "nucleotidyltransferase", "success", "therapeutic development", "vaccine development", "viral RNA", "virus host interaction" ], "approved": true } }, { "type": "Grant", "id": "7606", "attributes": { "award_id": "3UL1TR002537-03S3", "title": "The University of Iowa Clinical and Translational Science Award", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Center for Advancing Translational Sciences (NCATS)" ], "program_reference_codes": [], "program_officials": [ { "id": 21379, "first_name": "SOJU", "last_name": "Chang", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2018-03-30", "end_date": "2023-02-28", "award_amount": 98933, "principal_investigator": { "id": 23401, "first_name": "Marlan R", "last_name": "Hansen", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 220, "ror": "https://ror.org/036jqmy94", "name": "University of Iowa", "address": "", "city": "", "state": "IA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 23402, "first_name": "Patricia", "last_name": "Winokur", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 220, "ror": "https://ror.org/036jqmy94", "name": "University of Iowa", "address": "", "city": "", "state": "IA", "zip": "", "country": "United States", "approved": true }, "abstract": "The Institute for Clinical and Translational Science (ICTS) at the University of Iowa (UI) was established by the Board of Regents to realize three objectives – first, to lead the development of translational science at the UI; second, to advance translational science as a distinct academic discipline; and third, to disseminate capacities in translational science across the State of Iowa. This mandate enabled us to tackle large problems affecting translational science that required institutional solutions, such as transforming regulatory processes for human subjects research, developing an informatics infrastructure for integrating electronic medical record and other health care data, establishing bi-directional relationships with community organizations, and revitalizing the pipeline of well trained clinical and translational researchers. Iowa is a rural state, which brings special health care needs and challenges. We have used these rural considerations as a catalyst for driving our approach to clinical and translational research pushing our teams to develop strategies to engage rural populations of all ages and backgrounds and to create new approaches that overcome the geographic barriers in a rural state. We are capitalizing on our established community practice networks of family physicians, clinics, school nurses and pharmacists. We utilize e Health/ e Learning platforms in novel ways and will test the efficacy of these new methods of engagement. As we move research “Beyond Our Borders,” we have created methods to capture real-time, real-life data from the home and to correlate this environmentally specific, comprehensive data to human performance. The ICTS is engaging with other CTSA hubs and national CTR systems to empirically test different approaches and to develop the evidence base of proven strategies for accelerating translation that can be more broadly disseminated. Though distance and rurality drive our approaches, the strategies that we develop are simply new and potentially better ways to generate broad representation and improved participation by patients, healthcare teams and academicians. Through our local, state and national partnerships, UI and the ICTS are poised to move clinical and translational discovery rapidly into healthcare practice in a variety of clinical settings.", "keywords": [ "Affect", "Age", "Area", "Artificial Intelligence", "Automobile Driving", "Award", "COVID-19", "Caring", "Center for Translational Science Activities", "Clinic", "Clinical", "Clinical Data", "Clinical Research", "Clinical Sciences", "Clinical and Translational Science Awards", "Clinics and Hospitals", "Communities", "Community Practice", "Computerized Medical Record", "Data", "Data Element", "Data Set", "Data Sources", "Development", "Discipline", "Disease", "E-learning", "Emergency Situation", "Family Physicians", "Future", "Genomics", "Geography", "Goals", "Health", "Health system", "Healthcare", "Home environment", "Human", "Human Subject Research", "Image", "Infrastructure", "Institutes", "Institutional Review Boards", "Iowa", "Knowledge", "Lead", "Life", "Longevity", "Machine Learning", "Medical Care Team", "Methods", "Mission", "Modeling", "Outcome", "Patient Participation", "Patients", "Performance", "Pharmaceutical Preparations", "Pharmacists", "Phenotype", "Positioning Attribute", "Process", "Research", "Research Personnel", "Research Project Grants", "Resources", "Rural", "Rural Health", "Rural Population", "School Nursing", "Services", "System", "Testing", "Time", "Training", "Transfer Agreement", "Translational Research", "Translations", "Universities", "Work", "base", "biomedical informatics", "catalyst", "clinical decision support", "cohort", "collaborative approach", "community organizations", "coronavirus disease", "data acquisition", "data enclave", "data exchange", "data resource", "data sharing", "data warehouse", "efficacy testing", "evidence base", "health management", "improved", "informatics infrastructure", "innovation", "interest", "member", "novel", "novel strategies", "pandemic disease", "phenotypic data", "programs", "rurality", "social determinants", "support tools", "translational scientist" ], "approved": true } }, { "type": "Grant", "id": "7611", "attributes": { "award_id": "3RF1AG056318-01A1S1", "title": "Capturing the molecular complexity of Alzheimer's disease through the lens of RNA binding proteins", "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": [ { "id": 21374, "first_name": "LISA A.", "last_name": "Opanashuk", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2018-06-01", "end_date": "2023-03-31", "award_amount": 410947, "principal_investigator": { "id": 23404, "first_name": "Hu", "last_name": "Li", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 860, "ror": "", "name": "BOSTON UNIVERSITY MEDICAL CAMPUS", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 23405, "first_name": "Benjamin L", "last_name": "Wolozin", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 860, "ror": "", "name": "BOSTON UNIVERSITY MEDICAL CAMPUS", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "Neuritic plaques and neurofibrillary tangles are the hallmark pathologies of Alzheimer's disease (AD), but the presence individual tangles or plaques is not sufficient to predict degeneration; 45% of the elderly with plaques and tangles lack cognitive loss or dementia. We have recently identified a new type of molecular pathology in AD that derives from the aggregation of RNA binding proteins (RBPs), forming RNA-protein complexes, which are termed RNA granules. Microtubule associated protein tau (MAPT) binds to RBPs, co-localizes with RBPs in RNA granules, and RBPs increase MAPT misfolding /aggregation. Importantly, reducing the RBP TIA1 delays progression of tauopathy, despite increased MAPT aggregation. We hypothesize that variation in the composition of MAPT complexes (soluble or insoluble) and RNA granule complexes represent critical determinants of the molecular heterogeneity of AD and other tauopathies, and identify particular pathways that uniquely contribute to each type of disease. We will apply systems biology approaches that integrate information from proteomics and RNA metabolism to identify key proteins in each complex that are associated with neurodegeneration, and then test the roles of these proteins/genes experimentally. Throughout this proposal we will use unbiased studies (e.g., proteomic and RNAseq) combined with the systems biology algorithms to model context-dependent information flows to identify key molecular interactions and pathways regulating pathology, neurodegeneration and neuroprotection. Aim 1 will determine whether the RBP TIA1 directs the biochemical and functional properties of MAPT aggregation. We have discovered that reducing the RBP TIA1 delays disease progression in PS19 P301S MAPT mice despite producing more aggregation. We will elucidate the mechanisms by which TIA1 reduction produces neuroprotection using both in vitro molecular studies, and use unbiased “omic” studies (mass spectrometry and RNAseq). We will apply the systems biology algorithms to quantify key gene-gene interactions and pathways, and identify those pathways that parallel the human condition. Aim 2 will determine how MAPT and RBP complexes vary with cognitive decline in humans. We will use mass spectrometry and RNAseq to determine how the composition of complexes of MAPT, TIA1 and other key RBPs varies among human cases exhibiting neuritic plaques and neurofibrillary tangles with or without cognitive decline. Aim 3 will determine whether RBPs direct the strain of MAPT and resulting pathologies that are propagated in vitro and in vivo. We will characterize propagation of tauopathy for MAPT aggregates from PS19, PS19xTIA1+/--mice, as well as human cases exhibiting MAPT pathology with and without cognitive decline. The resulting mice will be analyzed as described in Aim 1.", "keywords": [ "Algorithms", "Alzheimer&apos", "s Disease", "Alzheimer&apos", "s disease pathology", "Appearance", "Binding", "Biochemical", "Bioinformatics", "Brain", "Code", "Complex", "Cytoplasmic Granules", "Data", "Dementia", "Disease", "Disease Progression", "Elderly", "Engineering", "Evolution", "Excision", "Exhibits", "Gene Proteins", "Genes", "Heat shock proteins", "Heterogeneity", "Human", "Impaired cognition", "In Vitro", "Individual", "MAPT gene", "Mass Spectrum Analysis", "Mediating", "Membrane", "Modeling", "Molecular", "Mus", "Nerve Degeneration", "Neurofibrillary Tangles", "Neurologic", "Organelles", "Pathologic", "Pathology", "Pathway interactions", "Patients", "Pattern", "Phenotype", "Physiological", "Process", "Property", "Proteins", "Proteomics", "Publishing", "RNA", "RNA metabolism", "RNA-Binding Proteins", "Regulation", "Research", "Role", "Senile Plaques", "Structure", "Symptoms", "System", "Systems Biology", "Tauopathies", "Testing", "Toxic effect", "Transcript", "Transgenic Model", "Translations", "Variant", "Work", "base", "biological adaptation to stress", "gene interaction", "human disease", "in vivo", "in vivo evaluation", "knock-down", "lens", "molecular pathology", "neuroprotection", "neurotoxicity", "protein complex", "receptor", "response", "stress granule", "tau Proteins", "tau aggregation", "transcriptome sequencing" ], "approved": true } } ], "meta": { "pagination": { "page": 1405, "pages": 1405, "count": 14046 } } }