Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=4&sort=-award_id
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-award_id", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1397&sort=-award_id", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=5&sort=-award_id", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=3&sort=-award_id" }, "data": [ { "type": "Grant", "id": "11456", "attributes": { "award_id": "7R21HD105907-03", "title": "The impact of COVID-19 on child maltreatment-related medical encounters and system responses using linked administrative data", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)" ], "program_reference_codes": [], "program_officials": [ { "id": 27515, "first_name": "LEAH KAYE", "last_name": "Gilbert", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-03-01", "end_date": "2023-06-30", "award_amount": 252121, "principal_investigator": { "id": 24277, "first_name": "Rebecca", "last_name": "Rebbe", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 152, "ror": "https://ror.org/03taz7m60", "name": "University of Southern California", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 817, "ror": "", "name": "UNIV OF NORTH CAROLINA CHAPEL HILL", "address": "", "city": "", "state": "NC", "zip": "", "country": "United States", "approved": true }, "abstract": "Project Summary/Abstract: With schools and daycare facilities closed and unemployment rates soaring due to the COVID- 19 pandemic, experts worry not only that the incidence of child maltreatment has increased but that that new or recurrent cases of maltreatment have gone undetected because two-thirds of reports to child protective services (CPS) are made by professionals. Linked administrative data (i.e., records collected for the provision of services, including health and child protection) can overcome the challenges of relying solely on CPS reports by joining the CPS database with medical records. Medical records have been identified as a useful data source for measuring child maltreatment. The objective of this application is to determine if and how the COVID-19 pandemic has impacted the incidence of child maltreatment-related medical encounters and the system responses to diagnosed cases of maltreatment. The rationale is maltreatment has significant identified impacts on children and if maltreatment has increased during this time, it will be important to allocate resources to address this detrimental form of trauma. The proposed study will take advantage of a natural experiment to focus on two specific aims: 1) Compare the incidence rates of child maltreatment-related medical encounters, before and during COVID-19; and 2) Determine the social and legal interventions/system responses to diagnosed medical encounters of child maltreatment before and during the pandemic. For the first aim, an interrupted time series will be used to identify the frequency of diagnosed maltreatment in primary care, emergency department, and hospitalization medical encounters. For the second aim, interrupted time series and logistic regression will be used to determine the percentage and likelihood of diagnosed maltreatment-related medical encounters being reported to CPS. The proposed research is innovative because it uses data from multiple sources and includes several types of medical encounters. The proposed research is significant because maltreatment is highly consequential but difficult to measure. Results will identify with robust empirical evidence if the pandemic COVID-19 has increased the incidence and severity of child maltreatment-related medical encounters and changed the social and legal interventions in response to such medical encounters. Ultimately, such knowledge has the potential to identify how community-level events impact child maltreatment, informing public policy, resource allocation, professional training, and future research.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "10467", "attributes": { "award_id": "7R21GM142011-02", "title": "Novel organic-ion-based technology for long-term virus preservation at ambient temperature", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of General Medical Sciences (NIGMS)" ], "program_reference_codes": [], "program_officials": [ { "id": 22244, "first_name": "MICHAEL", "last_name": "SAKALIAN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-01-01", "end_date": "2023-12-31", "award_amount": 155018, "principal_investigator": { "id": 23638, "first_name": "Scott F", "last_name": "Michael", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1267, "ror": "https://ror.org/05tc5bm31", "name": "Florida Gulf Coast University", "address": "", "city": "", "state": "FL", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 23639, "first_name": "Arsalan", "last_name": "Mirjafari", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 1935, "ror": "", "name": "COLLEGE AT OSWEGO", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "PROJECT SUMMERY Most currently available vaccines, especially live and mRNA-based COVID-19 vaccines, are temperature sensi- tive and require stringent cold-chain maintenance, entailing their storage and distribution at recommended tem- peratures from production to administration. This necessity imposes the most prohibitive barrier to global im- munization programs, particularly in developing countries, accounting for up to 80% of the cost delivery. Thus, there is a critical need for a technology to provide cost-effective and long-term ambient temperature storage for viral samples without requiring cold chain or complicated sample recovery protocols. This proposal aims to develop an organic-ion platform for long-term storage of viruses at ambient tem- perature to potentially reduce costs in the face of growing needs for new vaccines and avoid labor-intensive maintenance associated with current biobanking technology. Ionic liquids (ILs) organic salts comprised entirely of ions offer a well-suited platform on which the properties can be altered by the selection of ions, enabling the tunable design of solvents/media for virus stabilization. We hypothesize that the solutions of proposed ILs with ca. 20 wt% water may prevent hydrolytic and enzymatic degradation of viral genomes and protein capsids, providing a reliable approach to preserve viruses. We will use a bacteriophage from the myovirus family as an example of a naked protein particle and dengue virus as an example of a lipid-enveloped particle. First, we will develop a thoughtfully conceived library of novel ILs through systematic variations of heterocyclic cations and kosmotropic anions, and judicious incorporation of two functionalities (NH3+ and SO2F) into the IL structures. Structural variability will be achieved by pairing new genre of biocompatible cations and anions. Second, we will examine their effectiveness for stabilizing viruses by evaluating their structural integrity, thermostability, and shelf-life from six months and four year. We will monitor changes in viral secondary structure, thermal denatur- ation, and particle morphology. Last, we will study their empirical structure-activity relationships to gain compre- hensive understanding of binding characteristics and molecular mechanisms of interactions between the viral particles and the targeted aqueous ionic solvents via simulation, crystallographic, and spectroscopic methods. This project will provide a viable solution for ambient temperature preservation of viruses for extended periods (potentially for decades) by developing the virusILwater matrices that are stable towards hydrolytic and enzymatic degradation. Another important feature of the proposed approach is that these nucleic acid-ILs solutions can be directly amplified by PCR without being subjected to prior extraction, purification or quantifica- tion. This approach has the merit of simplicity, which makes the process of ambient temperature storage and distribution profoundly efficient, increases the stability of biosamples for prolonged time, reduces operational costs and carbon footprint, and improves logistics for viruses and virus-based technologies. Summery", "keywords": [ "Accounting", "Acids", "Affect", "Ammonium", "Anions", "Bacteriophages", "Base Pairing", "Benign", "Binding", "Biological Assay", "Buffers", "COVID-19", "COVID-19 vaccine", "Capsid Proteins", "Carbon", "Cations", "Characteristics", "Circular Dichroism Spectroscopy", "Cold Chains", "Cryopreservation", "DNA", "Dengue Virus", "Developing Countries", "Development", "Differential Scanning Calorimetry", "Effectiveness", "Electrostatics", "Enzymes", "Exhibits", "Family", "Fluorides", "Formulation", "Freezing", "Future", "Goals", "Hydration status", "Hydrogen Bonding", "Hydrolysis", "Ions", "Knowledge", "Libraries", "Life", "Lipid Bilayers", "Lipids", "Liquid substance", "Logistics", "Lytic", "Maintenance", "Medicine", "Messenger RNA", "Methods", "Mind", "Modeling", "Molecular", "Monitor", "Morphology", "Names", "Nature", "Nucleic Acid Vaccines", "Nucleic Acids", "Outcome", "Polymerase Chain Reaction", "Procedures", "Process", "Production", "Property", "Proteins", "Protocols documentation", "Quantitative Structure-Activity Relationship", "Recombinant Proteins", "Recovery", "Resource-limited setting", "Resources", "Reverse Transcription", "Roentgen Rays", "Salts", "Sampling", "Savings", "Scanning", "Scientist", "Solvents", "Structure", "Structure-Activity Relationship", "Techniques", "Technology", "Temperature", "Time", "Toxicology", "Transmission Electron Microscopy", "Transportation", "Vaccination", "Vaccines", "Variant", "Viral", "Viral Genome", "Viral Proteins", "Virus", "Virus-like particle", "Water", "aqueous", "base", "biobank", "biomaterial compatibility", "cost", "cost effective", "cytotoxicity", "design", "fighting", "flu", "functional group", "global health", "improved", "light scattering", "liquid formulation", "neglect", "novel", "novel vaccines", "nucleic acid stability", "pandemic disease", "particle", "preservation", "prevent", "programs", "rational design", "simulation", "solute", "stressor", "technology development", "thermostability", "vaccination outcome", "vaccine access", "vaccine distribution", "water diffusion" ], "approved": true } }, { "type": "Grant", "id": "3383", "attributes": { "award_id": "7R21ES032762-03", "title": "The External Exposome and COVID-19 Severity", "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": [ { "id": 10747, "first_name": "Yuxia", "last_name": "Cui", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2021-12-15", "end_date": "2023-07-31", "award_amount": 232702, "principal_investigator": { "id": 10749, "first_name": "Jiang", "last_name": "Bian", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 10751, "first_name": "Hui", "last_name": "Hu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 891, "ror": "https://ror.org/04b6nzv94", "name": "Brigham and Women's Hospital", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "The 2019 novel coronavirus disease (COVID-19) is a global pandemic with severe medical and socioeconomic consequences. Young adults without any underlying health conditions can still develop severe COVID-19 disease, and there are racial and ethnic disparities in COVID-19 hospitalization and mortality rates which cannot be explained by age and underlying health conditions alone. Risk factors of severe COVID-19 beyond older age and underlying health conditions are large unknown. There are large overlaps between the currently known risk factors of severe COVID-19 and the health conditions that are affected by environmental exposures, and emerging evidence suggested that long-term environmental exposures may be important determinants of COVID-19 severity. Traditional environmental epidemiological studies usually examine environmental factors separately without considering “the totality of the external environment”. Such studies are not only time consuming as they examine individual exposures separately, but more importantly, cannot account for confounding by co-exposures. The external exposome is an ideal framework to identify novel exposures associated with severe COVID-19 as it can systematically and efficiently screen thousands of environmental exposures. In this project, we will leverage a unique real-world data (RWD) resource – OneFlorida – a large repository of linked electronic health records (EHR), claims and vital statistics data, covering more than 60% of Floridians, contributing to the national Patient-Centered Clinical Research Network (PCORnet). Building on our prior work on the external exposome, we will expand our existing external exposome database to include additional factors that may impact COVID-19 outcomes through a systematic analysis of literature and resources. We aim to (1) develop phenotyping algorithms for identifying a COVID-19 cohort and their severity and extracting associated individual-level risk factors from the OneFlorida real-world data, and (2) identify external exposome factors associated with severe COVID-19, examine how the external exposome contributes to racial and ethnic disparities in severe COVID-19, and build predictive models of severe COVID-19 with external exposome factors. This study will fill important knowledge gaps by providing timely information to understand how environmental exposures may impact COVID-19 severity that will improve identifications of high-risk COVID-19 patients and inform the design of future precision interventions. Our approach and initial results for Florida can (1) be readily scaled up to a multi-state study through PCORnet and (2) answer other novel questions such as the external exposome’s contribution to geographic disparities in COVID-19 outcomes.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "14790", "attributes": { "award_id": "7R21EB034085-02", "title": "Implantable real-time troponin biosensor for early diagnosis of silent cardiac injuries", "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": 27406, "first_name": "SHAWN PATRICK", "last_name": "Mulvaney", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-08-01", "end_date": "2025-07-31", "award_amount": 422987, "principal_investigator": { "id": 28116, "first_name": "ZHENGUO", "last_name": "LIU", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 28117, "first_name": "XIANGQUN", "last_name": "ZENG", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 1049, "ror": "", "name": "UNIVERSITY OF MISSOURI-COLUMBIA", "address": "", "city": "", "state": "MO", "zip": "", "country": "United States", "approved": true }, "abstract": "Cardiovascular disease is the leading cause of death in the United States. Among them, silent heart attack, also known as silent myocardial infarction (SMI) that occurs without apparent symptoms, accounts for approximately half of the total number of heart attacks. When cardiac myocytes are damaged, cardiac troponin (cTn), a component of the heart muscle, is released into circulation. Currently, blood cTn is routinely measured in patients suspected of having Acute Myocardial Infarction (AMI). However, SMI is often undiagnosed until it is too late, although SMI causes similar level of damage to the heart as symptomatic typical AMI. We hypothesize that an implantable cTn sensor providing a real-time and continuous data on the blood levels of cTn will allow a timely diagnosis at the very time when a SMI occurs to a subject, enabling timely treatment. For an in vivo biosensor, the sensing reactions not only need to be sensitive and selective to the analyte but also need to be self-sustaining for a long time in complex physiological conditions. This requires that the sensing reactions can be self- regenerating while at the same time developing a signal related to the analytes. Currently there is no cTn sensors that can be operated in real-time and continuously. We propose to use a radically new biosensor approach to develop highly sensitive, specific, and self-sustaining biosensors based on our years of research and innovations in 1) uniquely designed peptide mimotope biosensing interface for label-free affinity based electrochemical biosensor; 2) the unique properties of bifunctional Pd/Au bimetallic substrate electrode for sensing interface self- regeneration; and 3) miniaturized, low cost and real-time electrochemical sensor platform. Peptide mimotopes, in lieu of antibodies, when immobilized on the surface via self-assemble monolayer (SAM) can significantly reduce the structural variability, retain biological activity, and minimize or eliminate non-specific adsorption from interfering proteins and provide real-time, highly sensitive and selective detection of protein antigens in human blood samples. In addition, our multifunctional bimetallic nanostructured Pd/Au electrode will allow the formation of stable and robust peptide SAM on gold (Au) as well as controlled rapid regeneration of the protein complex using palladium (Pd) chemistry to induce rapid local pH change. We have two research Aims to develop and validate this novel biosensing technology: 1. Develop self-regenerable electrochemical cTn biosensor for real-time detection of cTn; 2. Develop miniaturized implantable cTn biosensor and validate its in vivo sensing using rat cardiac ischemia model. Successful completing these Aims will validate the capability of our cTn biosensor for real-time, sensitive and selective sensing of cTn in vivo for early detection and monitoring of SMI. The sensor will have great potential in the diagnosis and monitoring of a variety of other forms of heart injuries including (but not limited to) viral myocarditis (such as myocardial injury related to COVID-19 infection), drug-induced cardiac toxicities, and radiation-induced cardiac injuries. The biosensor methods developed can also be applied to many other implantable real-time sensing applications.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "11473", "attributes": { "award_id": "7R21CA267955-02", "title": "A New Approach to Modulating CAR T Cell Activity", "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": [ { "id": 27524, "first_name": "MARCO", "last_name": "Cardone", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-09-23", "end_date": "2024-05-31", "award_amount": 186104, "principal_investigator": { "id": 23874, "first_name": "Ulrike", "last_name": "Lorenz", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 908, "ror": "https://ror.org/0153tk833", "name": "University of Virginia", "address": "", "city": "", "state": "VA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 827, "ror": "", "name": "WASHINGTON UNIVERSITY", "address": "", "city": "", "state": "MO", "zip": "", "country": "United States", "approved": true }, "abstract": "Chimeric antigen receptor (CAR) T cells targeting CD19 are highly effective in children with refractory/relapsed acute lymphoblastic leukemia (ALL), including those with primary refractory or CNS disease. Current CAR T cell therapies infuse patients with T cells constitutively expressing CARs, which are not susceptible to any controllable regulation. Cytokine release syndrome (CRS) and CAR-associated neurotoxicity (CAN), both of which can be fatal, arise from uncontrolled CAR T cell activation and expansion. While a few pharmacological management approaches have been attempted to overcome this issue, they are often suboptimal. In addition, chronic B-cell aplasia from persistent CD19 CAR T cells requires monthly infusions of immunoglobulin, which is burdensome and expensive, especially for pediatric patients facing potentially a lifetime need. Here, we propose to develop a system for controllable CAR T cells that can be turned on and off as needed. We have previously demonstrated that exogenous expression of the tyrosine phosphatase SHP-1 acts as a negative regulator to dampen T cell activation. Recently, we have developed an inducible and reversible protein degradation system for SHP-1 by adapting the plant Auxin-induced degron (AID) system for T cells. Combining these two tools in Aim 1, we propose to develop CD19 CAR T cells that will be kept basally dormant through overexpression of SHP-1. However, upon administration of Auxin, the CAR T cells can be temporarily and reversibly activated through the degradation of SHP-1. As the doses of Auxin sufficient to activate the AID system had no significant toxicities in humans, we do not foresee a problem translating this system into the clinic. In Aim 2, we will examine the efficacy of this novel CAR T cell system in a murine model of ALL. In Aim 3, we will expand the studies to test whether this regulatable CAR T cells system can control and/or limit CAR T cell-associated toxicities using a muring model of ALL, CRS and neurotoxicity. Such an exogenously regulatable CAR T cell system may provide clinicians a tool to avoid/limit severe CRS and CAN, and allow repopulation of the B-cell compartment after a sufficient treatment course. This approach will greatly enhance the safety of CD19 CAR T cells and is likely applicable to CARs for other malignancies, including solid tumors, where on-target, off-tissue cytotoxicity is more problematic.", "keywords": [ "Acute Lymphocytic Leukemia", "Admission activity", "Adolescent", "Adult", "Auxins", "B lymphoid malignancy", "B-Lymphocytes", "B-cell precursor acute lymphoblastic leukemia cell", "Beauty", "Brain Edema", "CAR T cell therapy", "CD19 gene", "Cell Compartmentation", "Central Nervous System Diseases", "Characteristics", "Chemotherapy and/or radiation", "Child", "Chronic", "Clinic", "Clinical", "Clinical Data", "Clinical Trials", "Confusion", "Development", "Diagnosis", "Dose", "Effector Cell", "Face", "Fever", "Future", "Goals", "Heart Rate", "Hematopoietic Stem Cell Transplantation", "High Dose Chemotherapy", "Hispanic", "Human", "Hypotension", "Immune", "Immunoglobulins", "In Vitro", "Incidence", "Infusion procedures", "Length of Stay", "Life", "Long-Term Survivors", "Malignant Neoplasms", "Medical", "Medication Management", "Medicine", "Modeling", "Morbidity - disease rate", "Mus", "Neurologic", "Neurotoxicity Syndromes", "PTPN6 gene", "Patients", "Pharmaceutical Preparations", "Plant Growth Regulators", "Plants", "Prevention", "Property", "Protein Tyrosine Phosphatase", "Proteins", "Refractory", "Refractory Disease", "Regulation", "Relapse", "Resolution", "Risk", "Safety", "Savings", "Seizures", "Signal Transduction", "Solid Neoplasm", "Specificity", "System", "T-Cell Activation", "T-Lymphocyte", "Technology", "Testing", "Tissues", "Toxic effect", "Translating", "Work", "Xenograft procedure", "attenuation", "base", "cancer diagnosis", "cancer immunotherapy", "chemotherapy", "chimeric antigen receptor", "chimeric antigen receptor T cells", "cytokine release syndrome", "cytotoxicity", "efficacy evaluation", "experience", "in vivo", "leukemia", "mortality risk", "mouse model", "neoplastic cell", "neurotoxicity", "novel", "novel strategies", "overexpression", "pediatric patients", "pre-clinical", "prevent", "protein degradation", "public health relevance", "side effect", "tool", "young adult" ], "approved": true } }, { "type": "Grant", "id": "15429", "attributes": { "award_id": "7R21AI175883-02", "title": "What Precursors Become Lung-Resident CD4 Memory that Protect Against Respiratory Infections or Cause Lung Pathology?", "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": 31609, "first_name": "Hariharan", "last_name": "Subramanian", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-11-22", "end_date": "2025-10-31", "award_amount": 123405, "principal_investigator": { "id": 29185, "first_name": "Priyadharshini", "last_name": "Devarajan", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1415, "ror": "", "name": "STATE UNIVERSITY NEW YORK STONY BROOK", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "What Precursors Become Lung-Resident CD4 Memory that Protect Against Respiratory Infections or Cause Lung Pathology? Respiratory viruses such as SARS-CoV1, Influenza and recently SARS-CoV2 (COVID-19) have caused the major pandemics in the 21st century and influenza causes high levels of death from yearly circulating outbreaks. T cells can target internal viral proteins, that mutate less frequently. Thus, T cell memory induced by previous vaccination or infection can still be effective against emerging mutant viral strains. Tissue resident memory (TRM) cells, that develop in the lung are at the first line of defense of our adaptive immune response against respiratory infections because of their location. However, lung CD8 TRM, which are most- studied, are short- lived. The few studies that have examined lung CD4 TRM suggest that they may decay less rapidly. We know relatively little about lung CD4 TRM longevity and mechanisms of function, though they are known to protect against many respiratory infections such Influenza, Sendai, B.pertussis, pneumococcal pneumonia and tuberculosis infections. Moreover, we know little about the CD4 effectors that are precursors to the lung CD4 TRM. If CD4 lung TRM are longer-lived, they might compensate over the long-term for the rapid decline in CD8 lung TRM, thus making them good vaccine targets to provide strong more durable immunity. A majority of the CD4 and CD8 T cells in human lung express TRM features, so it is vital to understand their impact when they are reactivated during an immune response, both their positive effect on protection against pathogens and negative effects on lung function and tissue damage. In many respiratory infections such as influenza and COVID-19 there is also potential for severe lung damage leading to poor prognosis. We show that cytotoxic CD4 T cells, that are resident effectors in the lung and that contribute to damage, can be precursors oflung CD4 TRM. Thus, it is vital that we learn how CD4 TRM can both protect and cause lung pathology on reactivation, especially if they are maintained long-term. Here, we propose to identify the precursors of CD4 lung TRM from CD4 lung effectors, and better define their protective and pathogenic potentials. We will phenotypically and molecularly characterize the CD4 TRM formed from subsets of lung CD4 effectors. We will study their longevity and their maintenance via mechanisms such as homeostatic proliferation and recruitment from circulation. Finally, we will study in detail their functional mechanisms of eliciting protection vs those causing lung immunopathology by direct cytolysis, inflammation and helper function. Understanding mechanisms/conditions driving protection and pathology by CD4 TRM will enable design of interventions like vaccines and immunotherapies, that favor the development of protection while minimizing pathology. Identifying precursor CD4 effectors that give rise to protective CD4 TRM will also allow us to finetune vaccine approaches that drive generation of those CD4 effector subsets. In future studies, we will use the knowledge gained here, to identify transcriptional networks that regulate the development of CD4 TRM from CD4 effectors and naïve CD4.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "11907", "attributes": { "award_id": "7R21AI173596-02", "title": "Improving mRNA vaccines with extracellular vesicle-associated immunogens", "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": 6908, "first_name": "JENNIFER L.", "last_name": "Gordon", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-11-09", "end_date": "2024-10-31", "award_amount": 189627, "principal_investigator": { "id": 21748, "first_name": "Michael R.", "last_name": "Farzan", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1472, "ror": "", "name": "SCRIPPS FLORIDA", "address": "", "city": "", "state": "FL", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 798, "ror": "https://ror.org/00dvg7y05", "name": "Boston Children's Hospital", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "The central hypothesis of this proposal is that the efficacy of mRNA vaccines that deliver membrane-anchored immunogens can be improved by localizing the immunogen to extracellular vesicles (EVs, small membrane- limited structures shed by eukaryotic cells). Our rationale is that EVs provide a natural scaffold for immunogen multimerization while also enabling membrane-bound antigens to access antigen presenting cells, both local to the site of injection, and in the draining lymph node. To localize immunogens to EVs and promote EV shedding we propose two complimentary approaches. In Aim 1, we will append a viral “late domain” to the carboxy terminus of our immunogen. Viral late domains are small protein domains, usually associated with a matrix or capsid protein, used by enveloped viruses to facilitate budding and egress. We have found that these domains can act out of context; fusing a late domain from feline immunodeficiency virus Gag to a SARS-CoV-2 spike protein immunogen caused the immunogen to re- localize to EVs and improved its immunogenicity nearly two-fold. We will expand this work by testing late domains from other viruses for their ability to promote EV localization and/or production. We will thoroughly characterize these EVs to determine correlates of vaccine immunogenicity. In Aim 2, we will modify our immunogens to overcome the activity of the host anti-viral restriction factor BST-2 (a.k.a. tetherin). Tetherin inhibits viral egress by “tethering” budding enveloped viruses to the host cell membranes and also inhibits the release of EVs by the same mechanism. Therefore, we will explore strategies for antagonizing tetherin in order to promote release of our immunogen-laden EVs. Enveloped viruses have evolved different strategies for tetherin evasion that we will attempt to incorporate into our immunogen designs. Indeed, we have identified a portion of the SARS-CoV-2 spike protein that we suspect is responsible for tetherin antagonism. Incorporating this S protein domain into our immunogen dramatically increases the amount of immunogen recovered from EV fractions of tissue culture supernatants. We will also explore similar strategies based on tetherin resistance mechanisms from other viruses. Finally, in Aim 3, promising immunogen design strategies in the context of different viral envelope protein immunogens (SARS-CoV-2, influenza A virus, HIV) will be compared in mice. These tests will allow us to establish correlations between the behavior of our vaccine immunogens in tissue culture (quantity and characteristics of the EVs, cytoxicity, etc.) and performance of the vaccine in vivo and determine if our modifications universally improve vaccine efficacy, or if particular immunogen designs are better suited for specific viral antigens.", "keywords": [ "2019-nCoV", "Acting Out", "Adenovirus Vector", "Animals", "Antibody Formation", "Antibody Response", "Antibody titer measurement", "Antigen-Presenting Cells", "Antigens", "Behavior", "COVID-19", "COVID-19 vaccine", "Capsid Proteins", "Carrier Proteins", "Cell Fraction", "Cell Line", "Cell membrane", "Cells", "Characteristics", "Communicable Diseases", "DNA", "Data", "Development", "Dose", "Effectiveness", "Eukaryotic Cell", "Feline Immunodeficiency Virus", "Fluzone", "Formulation", "Glycoproteins", "HIV", "HIV-1", "Hemagglutinin", "Human", "Immune", "Improve Access", "Influenza A virus", "Injections", "Interferons", "Membrane", "Messenger RNA", "Modification", "Molecular Conformation", "Mus", "Nonstructural Protein", "Patients", "Performance", "Preparation", "Production", "Proteins", "RNA vaccine", "Recombinants", "Reporting", "Resistance", "Route", "SARS-CoV-2 spike protein", "Sampling", "Serum", "Site", "Structure", "Subunit Vaccines", "Tail", "Tertiary Protein Structure", "Testing", "Transfection", "Translating", "Vaccinated", "Vaccines", "Viral", "Viral Antigens", "Viral Envelope Proteins", "Viral Matrix Proteins", "Viral Proteins", "Viral Vaccines", "Virus", "Virus Diseases", "Work", "adaptive immunity", "antagonist", "antigen binding", "antigen test", "cellular transduction", "chicken egg", "design", "draining lymph node", "efficacy testing", "empowerment", "env Gene Products", "exosome", "experimental study", "extracellular vesicles", "immunogenic", "immunogenicity", "improved", "in vivo", "influenza virus vaccine", "interest", "iterative design", "lipid nanoparticle", "manufacturing process", "microvesicles", "panacea", "pathogen", "prevent", "process optimization", "resistance mechanism", "response", "scaffold", "success", "tissue culture", "vaccine delivery", "vaccine efficacy", "vaccine immunogenicity", "vaccine platform", "vector vaccine" ], "approved": true } }, { "type": "Grant", "id": "11588", "attributes": { "award_id": "7R21AI168808-02", "title": "Development of a rapid multiplex CRISPR-based testing pathway for tuberculosis and COVID-19", "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": 7856, "first_name": "Karen A.", "last_name": "Lacourciere", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-05-12", "end_date": "2024-04-30", "award_amount": 193004, "principal_investigator": { "id": 7857, "first_name": "Padmapriya", "last_name": "Banada", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 925, "ror": "", "name": "RBHS-NEW JERSEY MEDICAL SCHOOL", "address": "", "city": "", "state": "NJ", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 7858, "first_name": "Cameron Amadeus", "last_name": "Myhrvold", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 7859, "first_name": "Yingda Linda", "last_name": "Xie", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 1856, "ror": "", "name": "RUTGERS BIOMEDICAL AND HEALTH SCIENCES", "address": "", "city": "", "state": "NJ", "zip": "", "country": "United States", "approved": true }, "abstract": "Tuberculosis (TB) and COVID-19 (COVID) are currently the deadliest pathogens worldwide, with 1.4 million TB and 2.5 million COVID deaths annually, both perpetuated by potential transmission from undiagnosed, asymptomatic infection. In the many TB-COVID co-endemic populations in Asia, sub-Saharan Africa, South America, and Eastern Europe, there is a critical need for widespread, active, symptom-agnostic screening of TB and COVID to control transmission and reduce morbidity and mortality. However, the simultaneous burden of COVID and TB poses enormous stress on these health care systems with severely limited bandwidth and resources for active case finding and surveillance. Consequently, around 400 thousand more TB deaths are estimated in the next 5 years compared to prior years as a direct consequence of COVID. Beyond their global co-prevalence and potential for asymptomatic transmission, TB and COVID’s overlapping clinical signs and symptoms, risk factors, and shared respiratory transmission pathways allow for a combined rapid screening approach that can detect both infections using one sample and testing pathway. This would enable i) more wide-spread screening, ii) at higher efficiency – fewer individuals need to be screened to detect one TB or COVID infected individual. We propose to leverage our existing TB and COVID non-invasive samples (eg. sputum, concentrated saliva, oral swabs), common processing methods and a novel point-of-care compatible CRISPR-Cas 13 COVID diagnostic system (SHINE) to pilot a streamlined approach to simultaneously screen for TB and COVID. Specifically, to develop this combined screening strategy, we will pursue the following aims: 1) transition a point-of-care CRISPR platform for multiplex screening of TB and COVID, and 2) optimize co-extraction methods from TB and COVID sputum and sputum specimens. These complementary aims will contribute independent value to enable streamlined testing and control of both COVID and TB, and are adaptable towards rapid, multiplex screening and surveillance of future pandemics.", "keywords": [ "2019-nCoV", "Africa South of the Sahara", "Asia", "Biological Assay", "COVID diagnostic", "COVID-19", "COVID-19 assay", "COVID-19 patient", "Cause of Death", "Cessation of life", "Chemicals", "Clinical", "Clustered Regularly Interspaced Short Palindromic Repeats", "Communicable Diseases", "DNA", "Detection", "Development", "Diagnostic", "Eastern Europe", "Evaluation", "Health Resources", "Healthcare Systems", "Individual", "Infection", "Methods", "Morbidity - disease rate", "Mycobacterium tuberculosis", "Nucleic Acids", "Oral", "Pathway interactions", "Patients", "Performance", "Phase", "Population", "Prevalence", "Property", "Protocols documentation", "Public Health", "RNA", "Rapid screening", "Research Personnel", "Resource-limited setting", "Resources", "Risk Factors", "Saliva", "Sampling", "Signs and Symptoms", "South America", "Specimen", "Sputum", "Stress", "Swab", "Symptoms", "Technical Expertise", "Technology", "Testing", "Tuberculosis", "Validation", "Work", "case finding", "coronavirus disease", "cost", "detection limit", "diagnostic platform", "future pandemic", "mortality", "novel", "pandemic pathogen", "pathogen", "point of care", "prototype", "rapid technique", "respiratory", "respiratory pathogen", "saliva sample", "screening", "transmission process", "tuberculosis diagnostics" ], "approved": true } }, { "type": "Grant", "id": "2811", "attributes": { "award_id": "7R21AI164080-02", "title": "Understanding how the MERS Coronavirus protein ORF4b interactions with importin alpha modulate innate immunity", "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": 8363, "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": "2021-07-01", "end_date": "2023-06-30", "award_amount": 186654, "principal_investigator": { "id": 8364, "first_name": "Christopher F", "last_name": "Basler", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 625, "ror": "https://ror.org/04a9tmd77", "name": "Icahn School of Medicine at Mount Sinai", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "The Middle East respiratory syndrome coronavirus (MERS-CoV), is a highly pathogenic, zoonotic, non-segmented, positive-sense RNA virus related to the severe acute respiratory syndrome coronavirus (SARS CoV) and SARS-CoV-2 that can spread from person to person. The potential threat posed by zoonotic coronaviruses is demonstrated by the emergence of SARS-CoV-2 and the subsequent COVID-19 pandemic. Because MERS CoV remains a threat, an understanding of mechanisms of MERS CoV replication, particularly as these related to pathogenesis and therapeutic development, remains critical. ORF4b (4b) is notable among the MERS CoV accessory proteins because it strongly localizes to the nucleus, despite virus replication occurring in the cytoplasm, and it exerts innate immune evasion functions. These include inhibition of interferon beta (IFNβ) and IFNλ production and inhibition of NF-κB-dependent cytokine production. The 4b protein also inhibits the 2’, 5’ oligoadenylate synthetase (OAS)-RNase L pathway, an activity attributed to its C-terminal phosphodiesterase domain. ORF4b is a nuclear protein and both transfection- and infection-based assays indicate that mutation of the apparent ORF4b nuclear localization signal (NLS) impairs affects inhibition of innate immune evasion functions. One notable study found that 4b blocks NF-ĸB-dependent responses and this correlated with the capacity of 4b to outcompete the p65 subunit of NF-ĸB for IMPA3 binding. We have undertaken X ray crystallography studies of the 4b-IMPA interaction. Our Preliminary Data demonstrate that 4b has uniquely bypassed canonical rules of NLS recognition and does not contain a Lys residue at a binding site formerly thought to be critical for NLS function. Further, the proposed specificity of 4b for IMPA3 is not fully supported by our data. We found that the NLS region of 4b binds IMPA2 and with an interface that is more extensive than IMPA3. Thus, the specificity that has been proposed is unlikely to be mediated by this simple interaction interface. Furthermore, if 4b is able to bind a greater range of IMPA isoforms than had previously been proposed, this MERS-CoV protein is likely to be able to competitively inhibit the nuclear import of other innate immune transcription factors such as IRF3 and STAT1. Consistent with such a model, Preliminary Data of crystal structures of the p50 NF-κB NLS bound to IMPA2 and IMPA3 demonstrate that these regions overlap with MERS ORF4b. Based on these observations, we propose to solve structures of full-length and NLS peptides of MERS- CoV and bat Merbecovirus ORF4b proteins in complex with nuclear receptor IMPA isoforms and define interaction interfaces. .This will provide a structural basis for the specificity of ORF4b binding and nuclear import. To compare the structural data obtained for ORF4b and IMPAs, we will determine the structures of IMPA isoforms in complex with NF-κB to establish a structural basis for the immune evasion. Finally. we will test the hypothesis that ORF4b inhibits NF-κB signaling and IFN production by competing for p50-IMPA interaction in transfection-based and virus infection studies.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "10215", "attributes": { "award_id": "7R21AI163282-02", "title": "DiagnosDisk - a highly sensitive point-of-care test for detecting SARS-CoV-2antigen in saliva", "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": "2022-02-01", "end_date": "2023-05-31", "award_amount": 134168, "principal_investigator": { "id": 11756, "first_name": "James", "last_name": "Lai", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 159, "ror": "https://ror.org/00cvxb145", "name": "University of Washington", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1896, "ror": "https://ror.org/00q09pe49", "name": "National Taiwan University of Science and Technology", "address": "", "city": "", "state": "TW-TPQ", "zip": "", "country": "TAIWAN", "approved": true }, "abstract": "SARS-CoV-2, a global pandemic, has caused more than 6 million infections and 180,000 deaths in the United States alone during the past 7 months. Both the WHO and CDC emphasize the need for point-of-care (POC) tests to expand diagnosis of acute infections to control the pandemic (i.e. isolating infected individuals). The current gold standard test for diagnosing acute SARS-CoV-2 infection is reverse transcriptase polymerase chain reaction (RT-PCR) with nasopharyngeal samples. The assay is highly sensitive, but requires well-trained personnel for sample collection and locations with specialized equipment. Therefore, the turnaround time varies from one to few days, delaying isolation, contact tracing, and medical attention. These challenges can be addressed with lateral flow immunoassays (LFIA) to detect viral antigens in self-collected saliva samples. Compared to nasopharyngeal specimens, studies have demonstrated that assays with saliva samples are more consistent and the saliva itself may contain higher viral load. However, existing LFIA for detecting salivary antigens exhibit poor sensitivity (≤ 40%) caused by the use of small sample volumes and sample dilution. To achieve timely and accurate screening of suspected COVID-19 cases, this project aims to develop a rapid assay for detecting SARS-CoV-2 antigens in saliva with high sensitivity to meet WHO's target product profile. We hypothesize that using ≥500 µL saliva as the assay sample can significantly improve the sensitivity because a larger specimen volume provides more analytes for detection. The new test will employ temperature-responsive polymer-antibody conjugates in conjunction with DiagnosDisk, a novel flow-through assay device. The approach is innovative in in using enriched saliva specimens for more consistent assay results, enhancing antigen detection by scaling up the saliva specimen volume, and adopting the well- developed sandwich immunoassay for DiagnosDisk with temperature-responsive polymer reagents that simplify the design while maximizing the sensitivity. We will employ polymer-antibody conjugates that efficiently isolate analytes in saliva (Aim 1) and fabricate the DiagnosDisk device to accommodate larger volume saliva specimens to improve the detection limit (Aim 2). The sensitivity of the new rapid assay, which combines polymer-antibody conjugates and DiagnosDisk, will be evaluated using saliva specimens from COVID-19 positive and negative patients (Aim 3).", "keywords": [ "2019-nCoV", "Acute", "Address", "Adopted", "Antibodies", "Antigens", "Biological Assay", "Blood Plasma Volume", "COVID-19", "COVID-19 detection", "COVID-19 pandemic", "COVID-19 patient", "COVID-19 screening", "Centers for Disease Control and Prevention (U.S.)", "Cessation of life", "Contact Tracing", "Coupling", "Data", "Deposition", "Detection", "Development", "Devices", "Diagnosis", "Early Diagnosis", "Enzyme-Linked Immunosorbent Assay", "Equipment", "Evaluation", "Exhibits", "Goals", "Gold", "Gold Colloid", "Human Resources", "Hydrophobicity", "Image", "Immunoassay", "Individual", "Infection", "Lateral", "Location", "Malaria", "Measures", "Membrane", "Noise", "Nucleocapsid", "Patients", "Plasma", "Polymers", "Precipitation", "Prostate-Specific Antigen", "Proteins", "Reagent", "Reverse Transcriptase Polymerase Chain Reaction", "SARS coronavirus", "SARS-CoV-2 antigen", "SARS-CoV-2 infection", "SARS-CoV-2 negative", "SARS-CoV-2 positive", "Saliva", "Salivary", "Sampling", "Scanning", "Sensitivity and Specificity", "Signal Transduction", "Specimen", "Temperature", "Testing", "Time", "Training", "United States", "Viral Antigens", "Viral Load result", "Virus", "Visual", "acute infection", "antibody conjugate", "antigen binding", "antigen detection", "design", "detection assay", "detection limit", "hydrophilicity", "improved", "innovation", "medical attention", "novel", "pandemic disease", "point of care testing", "rapid test", "saliva sample", "salivary assay", "sample collection", "scale up", "screening", "success", "viral RNA" ], "approved": true } } ], "meta": { "pagination": { "page": 4, "pages": 1397, "count": 13961 } } }