Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=4&sort=-principal_investigator
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-principal_investigator", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1405&sort=-principal_investigator", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=5&sort=-principal_investigator", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=3&sort=-principal_investigator" }, "data": [ { "type": "Grant", "id": "15765", "attributes": { "award_id": "1R21HD118668-01", "title": "Effects of a natural experiment on maternal and infant health", "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": 32834, "first_name": "JUANITA JEANNE", "last_name": "CHINN", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-01", "end_date": "2027-07-31", "award_amount": 446000, "principal_investigator": { "id": 32835, "first_name": "Tim Allen", "last_name": "Bruckner", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32836, "first_name": "Claire E", "last_name": "Margerison", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2633, "ror": "", "name": "HENRY FORD HEALTH + MICHIGAN STATE UNIVERSITY HEALTH SCIENCES", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "Rates of adverse maternal and infant health outcomes (e.g., preterm delivery, severe maternal morbidity, and mortality) in the United States (US) substantially outpace other high-income nations and are unacceptably high among women identifying as Black, American Indian, or Alaska Native and those living in rural areas. Municipalities and states across the US have begun implementing cash transfer programs, many targeted to pregnant women or families, with the objective of improving maternal and infant health through poverty reduction. Yet, evidence about the impact of cash transfers (i.e., intentional monetary transfers to individuals or households) on maternal and infant health in the US is decidedly mixed. A temporary expansion of the US Child Tax Credit (CTC) that led to an unprecedented 35% reduction in child poverty in 2021 offers an ideal natural experiment with which to test the impact of receiving monthly cash transfers during pregnancy on maternal and infant health. Surprisingly, our own preliminary ecological study indicated that the 2021 CTC expansion preceded an unexpected increase in low birth weight (LBW) among births to women likely to have received the CTC.17 This work calls into question the straightforward assumption that cash transfers in the US (such as the CTC) would improve infant health. The overall goal of this proposal is to thus examine the impact of cash transfers during pregnancy on maternal and infant health and health disparities in the US. The specific aims of this proposal are to 1) Estimate impacts of receiving CTC monthly payments during pregnancy on maternal and infant health, and 2) Determine whether impacts of receiving CTC monthly payments during pregnancy on maternal and infant health differ by race/ethnicity, socioeconomic status, or rurality. Exploiting, as a natural experiment, the unexpected and temporary monthly CTC payments received by ~40% of pregnant women between July and December of 2021, we will construct a simulated instrument to estimate individual-level impacts of the CTC expansion during pregnancy on maternal and infant health, and we will use rigorous methods to account for other health, social, policy, and economic changes during the COVID-19 pandemic. We will use two high-quality survey and administrative datasets (i.e., US Natality data and the Pregnancy Risk Assessment Monitoring System survey) to assess maternal and infant health measures plausibly impacted by cash transfers. Our study team, with 15 years of collaboration and expertise in maternal health, impacts of cash transfers on health, and the proposed methods and datasets, is ideally poised to achieve our goal. Our proposal responds directly to an NICHD Notice of Special Interest. Achieving these aims will increase understanding of how cash transfers impact maternal and infant health and will inform development of ongoing programs and policies, including local cash transfer pilot projects and future changes to the CTC and other tax credits.", "keywords": [ "Address", "Affect", "Age", "Alaska Native", "American", "American Indian", "Birth", "Black race", "COVID-19 pandemic", "Child", "Collaborations", "Data", "Data Set", "Development", "Economics", "Eligibility Determination", "Ethnic Origin", "Ethnic Population", "Face", "Family", "Future", "Goals", "Health", "Health Benefit", "Household", "Income", "Individual", "Infant Health", "Knowledge", "Literature", "Low Birth Weight Infant", "Maternal Health", "Measures", "Mental Health", "Methods", "Monitor", "Municipalities", "National Institute of Child Health and Human Development", "Natural experiment", "Outcome", "Persons", "Pilot Projects", "Policies", "Population", "Pregnancy", "Pregnant Women", "Premature Birth", "Prenatal care", "Productivity", "Quasi-experiment", "Race", "Research", "Resources", "Risk Assessment", "Role", "Rural", "Shock", "Socioeconomic Status", "Surveys", "System", "Taxes", "Testing", "United States", "Variant", "Woman", "Work", "adverse outcome", "care utilization", "child poverty", "federal policy", "health disparity", "improved", "innovation", "instrument", "interest", "low socioeconomic status", "member", "mortality", "pandemic disease", "payment", "poverty reduction", "programs", "racial difference", "racial minority population", "rural area", "rural dwellers", "rurality", "safety net", "severe maternal morbidity", "smoking during pregnancy", "social", "socioeconomics", "theories", "unemployment insurance" ], "approved": true } }, { "type": "Grant", "id": "15764", "attributes": { "award_id": "1R21AI187979-01A1", "title": "Development of a stable mRNA prophylactic vaccine against SARS-CoV-2 omicron variant", "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": 32831, "first_name": "JENNIFER L", "last_name": "GORDON", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-18", "end_date": "2027-07-31", "award_amount": 161500, "principal_investigator": { "id": 32832, "first_name": "Yongbin", "last_name": "Liu", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32833, "first_name": "Junhua", "last_name": "Mai", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2632, "ror": "", "name": "METHODIST HOSPITAL RESEARCH INSTITUTE", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "Infectious disease remains one of the leading causes of illness and mortality worldwide. The recent coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) led to widespread illness and death, disrupting public health and economy. It has been successfully mitigated thanks to the development and global application of the novel messenger RNA (mRNA) vaccine technology. While mRNA vaccines have offered significant protection, the high mutation rate of SARS-CoV-2 necessitates ongoing development of updated vaccines to combat new variants. While mRNA vaccines have shown remarkable effectiveness against COVID-19 by stimulating both humoral and cellular immune responses, the main limitation lies in the inherent instability of mRNAs at normal conditions without protection. Therefore, current mRNA and mRNA formulations require ultralow temperatures for storage and transportation. Recognizing the instability challenge, we proposed to develop a novel “RNA-plex” technology, which uses an “carrier-base” polymer to bind to mRNA molecules, preventing them from degradation in fridge or room temperature during storage. It significantly reduces the transportation and distribution costs, and makes mRNA vaccines more accessible globally, especially in areas with limited cold chain facilities. Notably, this mRNA protection technology can universally shield various mRNAs, is compatible with multiple delivery systems, and significantly enhances mRNA translation in cells, suggesting its promising potential for diverse therapeutic and research applications. In this proposal, we will apply this mRNA stabilization technology named “RNA-plex” in the development of stable and efficient vaccines for SARS-CoV-2 prevention. Specifically, we will optimize the composition and formulation of RNA-plex to maximize its protective efficacy for SARS-CoV-2 omicron variant spike protein mRNA. Next, we will apply it in preparing prophylactic lipid nanoparticle (LNP) mRNA vaccines with high stability, enhanced antigen translation efficiency, and superior vaccination effectiveness compared to conventional approaches against emerging viral threats, using the recent SARS-CoV-2 omicron variant XBB.1.5 as a proof-of-principle model. Specific Aims: Aim 1. Stabilization of SARS-CoV-2 omicron variant mRNA using RNA-plex technology and develop an LNP mRNA vaccine. Aim 2. Evaluate the efficacy of LNP-RNA-plex vaccine in eliciting immune responses and protection against SARS-CoV-2 Omicron variant.", "keywords": [ "2019-nCoV", "Address", "Adverse effects", "Affect", "Algorithms", "Animal Model", "Antibody titer measurement", "Antigens", "Area", "Aspartate", "B-Lymphocytes", "Base Composition", "Behavior", "Binding", "Biological", "Biological Assay", "Biology", "COVID-19", "COVID-19 pandemic", "COVID-19 vaccine", "Cells", "Cessation of life", "Charge", "Circular Dichroism", "Codon Nucleotides", "Cold Chains", "Communicable Diseases", "Complex", "Cryopreservation", "Dependence", "Development", "Differential Scanning Calorimetry", "Dissociation", "Effectiveness", "Electrostatics", "Endosomes", "Ensure", "Enzyme-Linked Immunosorbent Assay", "Formulation", "Glutamates", "Goals", "Hydrogen Bonding", "Hydrolysis", "Immune response", "Immunization", "Individual", "Infrastructure", "K-18 conjugate", "Knowledge", "Length", "Logistics", "Messenger RNA", "Methods", "Modality", "Modeling", "Modification", "Mutation", "Names", "Nucleotides", "Outcome", "Performance", "Phosphorus", "Poly(A) Tail", "Polymers", "Prevention", "Preventive vaccine", "Proteins", "Public Health", "RNA", "RNA Degradation", "RNA Sequences", "RNA Stability", "RNA vaccine", "Research", "Ribonucleases", "Ribose", "Ribosomal Frameshifting", "Ribosomes", "SARS-CoV-2 B.1.1.529", "Structure", "Surface Plasmon Resonance", "System", "T cell response", "Techniques", "Technology", "Temperature", "Testing", "Therapeutic", "Toxic effect", "Transgenic Mice", "Translations", "Transportation", "Update", "Vaccination", "Vaccines", "Variant", "Viral", "Western Blotting", "base", "biodegradable polymer", "booster vaccine", "circular RNA", "cold temperature", "combat", "compare effectiveness", "cost", "design", "efficacy evaluation", "hydroxyl group", "improved", "in vivo monitoring", "innovation", "lipid nanoparticle", "mRNA delivery", "mortality", "mouse model", "novel", "nucleobase", "phrases", "preservation", "prevent", "prophylactic", "protective efficacy", "success", "therapeutic RNA", "translation assay", "vaccine access", "vaccine efficacy", "vaccine formulation", "vaccine platform" ], "approved": true } }, { "type": "Grant", "id": "15762", "attributes": { "award_id": "1K08AI193077-01", "title": "Impact of Spatial and Social Determinants on Invasive Fungal Infection Risk", "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": 32829, "first_name": "DONA", "last_name": "LOVE", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-01", "end_date": "2030-07-31", "award_amount": 197640, "principal_investigator": { "id": 32830, "first_name": "Lucy", "last_name": "Li", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2615, "ror": "", "name": "JOHNS HOPKINS UNIVERSITY", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": ": Invasive fungal infections (IFIs) are a growing public health challenge, leading to over 1.5 million deaths each year worldwide. Contextual factors are believed to be critical components of IFI risk as evidenced by historical fungal outbreaks associated with specific geographic distributions and ecological disruptions. Certain communities are thought to be particularly vulnerable with greater exposure to high-risk contextual factors, leading to higher rates of and worse outcomes from IFIs. In addition, socioeconomic status may impact IFI outcomes, due to delays in diagnosis, access to care, and quality of care. However, prior studies of IFI epidemiology have focused primarily on host factors without adequately considering the uneven distribution of hazards and their spatiotemporal trends related to socioeconomic factors. The objective of this proposal is to assess the impact of social determinants on IFI risk by leveraging a national data source, the National COVID Cohort Collaborative, and a more granular hospital system electronic-health medical records data source. In Aim 1, we will determine neighborhood-level contextual and socioeconomic predictors of IFIs. In Aim 2, we will examine the association between individual socioeconomic status factors and clinical outcomes of IFIs. This work will advance our understanding of the spatial and social determinants of IFI risk and outcomes as well as provide a robust training platform for the award recipient, Dr. Lucy Li. Through both research and career development training, Dr. Li will acquire essential skills in large data analysis, including advanced methods in spatial science and social factors research, time series analyses, and risk prediction modeling. Dr. Li will then be well positioned to be an independent clinical investigator focused on IFIs in at-risk populations with an expertise in integrating spatial and social factors data into population health analyses.", "keywords": [ "Address", "Affect", "Air", "Allergic", "American", "Area", "Asthma", "Award", "COVID-19", "Caring", "Censuses", "Cessation of life", "Clinical", "Clinical Investigator", "Clinical Research", "Communities", "Community Surveys", "Computerized Medical Record", "Data", "Data Analyses", "Data Commons", "Data Sources", "Databases", "Diagnosis", "Dimensions", "Disease", "Disease Outbreaks", "Education", "Electronic Health Record", "Employment Status", "Epidemiology", "Equation", "Ethnic Origin", "Exposure to", "Geographic Distribution", "Geographic Locations", "Health Services Accessibility", "Health system", "Hospitalization", "Hospitals", "Housing", "Immunocompetent", "Immunocompromised Host", "Incidence", "Income", "Individual", "Infection", "Insurance Coverage", "Integration Host Factors", "International Classification of Disease Codes", "Intervention", "Length of Stay", "Logistic Regressions", "Longitudinal trends", "Measures", "Mentors", "Methods", "Molds", "Mycoses", "Neighborhoods", "Organ", "Outcome", "Outcome Assessment", "Patients", "Pattern", "Persons", "Play", "Population", "Populations at Risk", "Positioning Attribute", "Public Health", "Quality of Care", "Race", "Research", "Resolution", "Risk", "Risk Factors", "Science", "Seasons", "Shapes", "Site", "Socioeconomic Factors", "Socioeconomic Status", "Source", "System", "Time Series Analysis", "Training", "United States", "Weather", "Work", "Yeasts", "adjudication", "career", "career development", "clinical care", "clinical risk", "cohort", "contextual factors", "design", "electronic medical record system", "fungus", "hazard", "high risk", "improved", "indexing", "infection risk", "low socioeconomic status", "mortality", "multilevel analysis", "patient screening", "population health", "primary outcome", "research and development", "risk prediction", "risk prediction model", "secondary outcome", "skills", "social determinants", "social factors", "social vulnerability", "socioeconomics", "spatial epidemiology", "spatial integration", "spatial relationship", "spatiotemporal", "statistics", "time use", "trend" ], "approved": true } }, { "type": "Grant", "id": "15759", "attributes": { "award_id": "1R01AI175536-01A1", "title": "ACE2 immunodecoys for long-lasting immunoprophylaxis against sarbecovirus and merbecoviruses that target human ACE2", "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": 32536, "first_name": "DIPANWITA", "last_name": "BASU", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-18", "end_date": "2029-07-31", "award_amount": 2937578, "principal_investigator": { "id": 32825, "first_name": "Samuel", "last_name": "Lai", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32826, "first_name": "RAYMOND J", "last_name": "PICKLES", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2628, "ror": "", "name": "UNIV OF NORTH CAROLINA CHAPEL HILL", "address": "", "city": "", "state": "NC", "zip": "", "country": "United States", "approved": true }, "abstract": "While vaccines are readily available for SARS-CoV-2, there continues to be significant demand for prophylaxis that are potent and not at risk for viral escape to better protect vulnerable populations. In addition, there is emerging evidence that a number of bat sarbecoviruses and merbecoviruses can use human ACE2 (hACE2) as an entry receptor to infect human cells. Thus, there is also a need to advance effective immunoprophylaxis to protect against such zoonotic coronaviruses with pandemic potential. We have previously advanced an ACE2-immunodecoy as treatment for SARS-CoV-2 infections. Instead of the common approach pursued by many investigators to affinity mature ACE2 to enhance binding to SARS-CoV-2 Spike, we instead sought to optimize the linkage between the extracellular fragment of human ACE2 and IgG1-Fc (ALFc) to promote improved bivalent binding to SARS-CoV-2 Spike. Similar to other ACE2- decoys, ALFc is not susceptible to viral escape. Unlike other ACE2-decoys, the preservation of the full human ACE2 sequence means ALFc is likely active against all ACE2-targeted viruses. We have demonstrated that ALFc maintains picomolar activity (comparable to many of the previous leading monoclonal antibodies that received emergency use authorization) against all variants of SARS-CoV-2, and is highly effective in a hamster challenge model. Importantly, the ALFc has outstanding bioprocessing attributes, including stability at high concentrations and exceptional productivity using cGMP CHO production cell line. These attributes have led the U.S. Army to select ALFc to be advanced into clinical development over other ACE2 decoys; GMP materials for clinical trials and GLP tox studies are currently underway, and a Phase 1 clinical study is planned for 2H 2025. In this proposal, we build on the success of ALFc as an inhaled therapy to establish the efficacy of ALFc as a systemic immunoprophylaxis that can prevent severe pulmonary disease in vulnerable populations. Specifically, the ALFc currently in development possess wildtype IgG1-Fc. For sustained immunoprophylaxis lasting >6-9 months, it is essential to utilize Fc with enhanced affinity to FcRn, such as YTE, LS and DHS mutations. In this proposal, we will first produce and characterize ALFcYTE, ALFcLS and ALFcDHS(Aim 1). We will evaluate their activity against a panel of hACE2-targeting viruses, including emerging bat sarbecoviruses and merbecoviruses, using both pseudotyped alphavirus vectors in cell-lines (BSL-2) and infectious virus clones in well-differentiated cultures of human airway epithelial cells (BSL-3) (Aim 2). Finally, we evaluate the ability of ALFc to protect against infectious clones of SARS-CoV-2 and SHC014-CoV challenge in human ACE2 transgenic mice (Aim 3). Successful completion of these studies will likely advance an intervention for providing immunoprophylaxis against future SARS-CoV-2 variants as well as other hACE2-targeted coronaviruses with pandemic potential.", "keywords": [ "2019-nCoV", "ACE2", "Adult", "Affinity", "Allergic Reaction", "Alpha Virus", "Antibodies", "Binding", "Binding Proteins", "Biodistribution", "Biological Products", "COVID-19 pandemic", "COVID-19 treatment", "Cell Culture Techniques", "Cell Line", "Cells", "Chiroptera", "Circulation", "Clinical Research", "Clinical Trials", "Coronavirus", "Coronavirus Infections", "Cyclic GMP", "Data", "Development", "Dose", "Drug Kinetics", "Engineering", "Epithelial Cells", "Escape Mutant", "Evolution", "Excipients", "FDA Emergency Use Authorization", "Future", "Hamsters", "Human", "IgG1", "Immunocompromised Host", "Individual", "Infant", "Infection", "Inhalation", "Inhalation Therapy", "Intervention", "Length", "Link", "Literature", "Lung", "Lung Diseases", "Macaca", "Macaca mulatta", "Marketing", "Measures", "Merbecovirus", "Modeling", "Molecular Conformation", "Monoclonal Antibodies", "Mus", "Mutate", "Mutation", "Nebulizer", "Nose", "Parents", "Passive Immunization", "Phase", "Prevention", "Production", "Productivity", "Prophylactic treatment", "Proteins", "RNA vaccine", "Recording of previous events", "Research Personnel", "Risk", "SARS coronavirus", "SARS-CoV-2 infection", "SARS-CoV-2 spike protein", "SARS-CoV-2 variant", "Sarbecovirus", "Serum", "Temperature", "Testing", "Therapeutic", "Transgenic Mice", "Transgenic Organisms", "Vaccines", "Variant", "Viral", "Virus", "Virus Diseases", "Vulnerable Populations", "Work", "Zoonoses", "aerosolized", "airway epithelium", "bioprocess", "clinical development", "clinical material", "design", "extracellular", "flexibility", "immunoprophylaxis", "improved", "in vitro Model", "in vivo", "manufacture", "melting", "mutant", "neonatal Fc receptor", "pandemic coronavirus", "pandemic potential", "preservation", "prevent", "pulmonary", "receptor", "receptor binding", "success", "vector", "zoonotic coronavirus" ], "approved": true } }, { "type": "Grant", "id": "15758", "attributes": { "award_id": "1R01HL180743-01", "title": "Putting Implementation into context to advance the management of mechanically ventilated patients.", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Heart Lung and Blood Institute (NHLBI)" ], "program_reference_codes": [], "program_officials": [ { "id": 32823, "first_name": "SHAHNAZ", "last_name": "KHAN", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-15", "end_date": "2029-05-31", "award_amount": 748970, "principal_investigator": { "id": 32824, "first_name": "Meeta Prasad", "last_name": "Kerlin", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2627, "ror": "", "name": "UNIVERSITY OF PENNSYLVANIA", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true }, "abstract": "Over one million Americans undergo invasive mechanical ventilation (IMV) annually in intensive care units (ICUs). A few interventions have improved patient-centered outcomes in IMV patients, including sedation minimization, corticosteroid administration in selected patients, and low tidal volume ventilation and prone positioning in the subgroup patients with acute respiratory distress syndrome (ARDS). However, variability exists across ICUs in processes of care, clinical outcomes, and resource utilization. ICUs are highly complex interprofessional environments, and knowledge gaps remain regarding how contextual elements influence implementation determinants in different ICUs. The coronavirus disease 2019 (COVID-19) pandemic created unprecedented surges of patients requiring IMV and catalyzed rapid and dynamic changes in critical care delivery, facilitating some evidence-based practices after many years of persistently low penetration, and impeding others. Furthermore, new evidence, such as corticosteroids for COVID-19 and pneumonia, may have later influenced practice changes for IMV patients more broadly. Thus, this major disruption in critical care delivery is a unique opportunity to gain new knowledge about implementation in the ICU context. The overall objective of this proposal is to better understand the interplay between contextual factors and intervention features in care delivery for IMV patients. Guided by implementation frameworks, we will employ state-of-the-art causal inference methods and innovative qualitative approaches to conduct three specific aims: (1) Quantify penetration of four evidence-based treatments – sedation minimization, corticosteroid administration, low tidal volume ventilation, and prone positioning – over time among IMV patients and specific subgroups; (2) Develop a novel conceptual model of ICU implementation incorporating relationships between determinants and contextual elements; and (3) Apply implementation mapping to create adaptable menus to facilitate evidence-based practices. We will apply state-of-the-art causal inference methods to analyze a diverse, multicenter retrospective cohort of IMV patients admitted to more than 30 ICUs in 16 hospitals before, during, and after the height of the COVID-19 pandemic. In addition, we will use cutting-edge qualitative techniques and implementation research frameworks and will engage an array of stakeholders to develop implementation menus for each treatment that not only provide strategies to promote utilization of evidence- based treatments but also guidance for tailoring those strategies to different contexts. This project will advance the science of care delivery in a high-stakes setting by increasing the evidence regarding how contextual elements interact with treatment characteristics in critical care delivery. It will generate direct preliminary data for future implementation studies to test strategies to promote evidence-based care of IMV patients. Finally, it will create a conceptual model with potential application to delivery of critical care interventions in different ICU contexts more broadly.", "keywords": [ "Acute Respiratory Distress Syndrome", "Adherence", "Adrenal Cortex Hormones", "Advocate", "American", "COVID-19", "COVID-19 pandemic", "Caring", "Characteristics", "Clinical", "Communities", "Complex", "Consolidated Framework for Implementation Research", "Critical Care", "Data", "Effectiveness", "Elements", "Environment", "Evidence based intervention", "Evidence based practice", "Evidence based treatment", "Familiarity", "Focus Groups", "Height", "Hospitals", "Intensive Care Units", "Interruption", "Intervention", "Interview", "Knowledge", "Life", "Literature", "Maps", "Mechanical ventilation", "Methodology", "Methods", "Modeling", "Morbidity - disease rate", "Natural experiment", "Nurses", "Outcome", "Patient Admission", "Patient Care", "Patient Selection", "Patient-Focused Outcomes", "Patients", "Pattern", "Penetration", "Phase", "Physicians", "Pneumonia", "Process", "Prone Position", "Publications", "Qualitative Methods", "Resources", "Respiratory Failure", "Retrospective cohort", "Role", "Safety", "Science", "Sedation procedure", "Sepsis", "Service delivery model", "Structure", "Subgroup", "Surveys", "Syndrome", "Techniques", "Testing", "Tidal Volume", "Time", "Time Series Analysis", "Trauma", "Treatment outcome", "Vulnerable Populations", "acceptability and feasibility", "alternative treatment", "aspirate", "care delivery", "community acquired pneumonia", "comparative", "contextual factors", "evidence base", "future implementation", "high risk", "implementation determinants", "implementation framework", "implementation process", "implementation protocol", "implementation science", "implementation strategy", "implementation study", "improved", "improved outcome", "innovation", "mortality", "novel", "pandemic disease", "patient subsets", "respiratory", "rural area", "suburb", "ventilation" ], "approved": true } }, { "type": "Grant", "id": "15757", "attributes": { "award_id": "1R01HD114714-01A1", "title": "Bone age determination for the 21st Century: Using AI to broaden and diversify a 60-year-old gold standard and overcome reader bias", "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": 21091, "first_name": "KAREN", "last_name": "WINER", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-01", "end_date": "2030-04-30", "award_amount": 448280, "principal_investigator": { "id": 32820, "first_name": "Anouck", "last_name": "Girard", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32821, "first_name": "JOSEPHINE Z", "last_name": "KASA-VUBU", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 32822, "first_name": "Niko Albert", "last_name": "Kaciroti", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2626, "ror": "", "name": "UNIVERSITY OF MICHIGAN AT ANN ARBOR", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "/ Abstract Bone age (BA) is a measure of maturation of a child’s skeleton, and, as such, a key clinical indicator of growth used by pediatricians and pediatric endocrinologists. As a person’s body ages, from birth through childhood, puberty, and adulthood, the size and shape of the bones of the skeleton change. Growth plates, initially wide open, fuse progressively in childhood. The BA is meant to be the “average” age at which the skeleton reaches a certain degree of maturation. In combination with other measures, it can be used to predict future adult height and detect possible growth disorders or abnormal pubertal maturation. The estimation of BA with a radiological image of the left hand and wrist describes the degree of maturation of a child’s skeleton. The most commonly available standards for the BA estimation, such as the Greulich and Pyle (G&P) Atlas (1959) and the Tanner-Whitehouse method, involve visual inspection of X-ray images of the person’s left hand and wrist, followed by its comparison with the set of reference images. This manual inspection is not only time- consuming, but subjective, and the estimation among radiologists may vary depending upon experience / expertise. Moreover, the data collected in these approaches is outdated: the current population of the United States has been much reshaped in the last 60 years, due to a larger number of children of international ancestry and a nutritional environment, particularly during the COVID pandemic, that has resulted in an obesity pandemic that affects the growth and rate of physical maturation of children. Thus, there is a need to renovate these bone age standards such that the reference is representative of the current population and develop an AI-assisted system for the accurate prediction of bone age. Moreover, the research team for the proposed project will develop an adjustment factor to incorporate the BMI Z-score for more clinical relevance of the AI- assisted outcome. The proposed technical approach is three-pronged. Specific Aim 1 is to establish a database for BA assessment in children that addresses racial and ethnic disparities and reduces spacing between available standards. Specific Aim 2 is to develop and validate an AI-assisted classification system for BA readings from the X-ray images. Finally, Specific Aim 3 is to enhance BA determination by an adjustment factor reflecting the impact of BMI Z-score on skeletal maturation. In support of all three aims, a web designer will build and deploy a web application capable of incorporating the AI algorithm for the adjusted Bone Age determination with qualitative data provided by users.", "keywords": [ "Address", "Adoption", "Adrenal Gland Diseases", "Adult", "Affect", "Age", "Anxiety", "Artificial Intelligence enhanced", "Atlases", "Automobile Driving", "Birth", "Black race", "Body mass index", "COVID-19 pandemic", "Child", "Child Health", "Childhood", "Chronology", "Classification", "Clinical", "Computerized Medical Record", "Consultations", "Consumption", "Data", "Databases", "Decision Making", "Elements", "Endocrinologist", "Environment", "Epiphysial cartilage", "Ethnic Origin", "European ancestry", "Evaluation", "FDA approved", "Fostering", "Future", "Growth", "Growth Disorders", "Hand", "Health", "Health Care Costs", "Height", "Hormonal", "Image", "International", "Internet", "Left", "Link", "Machine Learning", "Manuals", "Marketing", "Measures", "Medical", "Methods", "Michigan", "North America", "Nutritional", "Obesity", "Obesity Epidemic", "Ohio", "Outcome", "Pattern", "Performance", "Persons", "Population", "Precocious Puberty", "Predisposition", "Procedures", "Puberty", "Race", "Radiology Specialty", "Reader", "Reading", "Research", "Roentgen Rays", "Sampling", "Selection Bias", "Shapes", "Skeletal bone", "Skeleton", "Societies", "Somatotropin", "Specialist", "Standardization", "System", "Technology", "Testing", "Time", "Underweight", "United States", "Universities", "Variant", "Visual", "Weight", "Wrist", "X-Ray Medical Imaging", "artificial intelligence algorithm", "bone age", "boys", "care providers", "clinical practice", "clinically relevant", "cost", "database expansion", "ethnic disparity", "experience", "girls", "health disparity", "infancy", "innovation", "novel", "novel strategies", "obesity in children", "pandemic disease", "pediatrician", "racial disparity", "racial diversity", "radiological imaging", "radiologist", "skeletal maturation", "stem", "tool", "web app", "young adult" ], "approved": true } }, { "type": "Grant", "id": "15756", "attributes": { "award_id": "1R01AI190195-01", "title": "The Impact of Systemic Immunosuppression on RSV Antibody Generation and Effector Functions After Vaccination", "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": 21312, "first_name": "SONNIE", "last_name": "KIM", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-01", "end_date": "2030-07-31", "award_amount": 775187, "principal_investigator": { "id": 32819, "first_name": "Andrew Hoover", "last_name": "Karaba", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2615, "ror": "", "name": "JOHNS HOPKINS UNIVERSITY", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "Immunosuppressed persons (ISPs) have a nearly 40% risk of hospitalization if infected with respiratory syncytial virus (RSV). Recently, novel RSV vaccines based on the prefusion F protein of the virus were found to be effective at reducing RSV disease, but these were not tested in high-risk ISPs. Owing to immunosuppression, ISPs often develop attenuated antibody responses to vaccines and require either additional doses or different formulations to achieve protective levels of antibodies. Antibodies against prefusion F are associated with protection from RSV disease and thought to be central to the protection afforded by RSV vaccines. Our preliminary data indicate that, among ISPs, the antibody response to RSV vaccines is heterogeneous, with many ISPs demonstrating minimal or no response. However, the nature of this decreased response (i.e. unrecognized antibody epitopes and impact on neutralizing and non-neutralizing functions) remains unknown. Furthermore, the influence of specific immunosuppressive medications and the type of vaccine received (adjuvanted vs. unadjuvanted) is undetermined. To protect this high-risk group from this common and often devastating infection, a comprehensive understanding of the antibody response to these vaccines by ISPs is necessary and will improve vaccine recommendations, design, and medication management. The proposed research will address these uncertainties by systematically studying the antibody response to novel RSV vaccines in a national observational cohort of ISPs, comparing the responses to those of healthy participants (HPs). This national cohort of highly engaged ISPs was critical in our previous successful efforts to define the effects of immunosuppression on SARS-CoV-2 vaccination, and we will leverage this opportunity to discern the impact of immunosuppression on antibody responses to RSV vaccines. We will accomplish this by quantifying the prefusion F and neutralizing antibody response longitudinally in these groups and determining the impact of vaccine type (adjuvanted vs. unadjuvanted), type of immunosuppressive medication, and demographic factors (Aim 1). Additionally, we will study the entire viral antibody epitope landscape before and after vaccination using innovative DNA barcoded-protein technology to identify key gaps in epitope recognition, measure the impact of pre-existing immunity on vaccine responses, and correlate specific epitope responses with antibody function (Aim 2). Finally, the researchers will measure the effect of immunosuppression and vaccine adjuvant on antibody subtype, subclass, and non-neutralizing functions using a systems serology approach (Aim 3). The investigators’ established productive collaborative relationships, extensive experience studying antibody responses in high-risk and/or immunosuppressed populations, and this cohort of ISPs provide the ideal circumstances to provide critical knowledge that promises to be directly applicable to improving RSV vaccine responses in this high-risk group and inform future vaccine design for immunosuppressed persons.", "keywords": [ "Adjuvant", "Antibodies", "Antibody Formation", "Antibody Response", "Attenuated", "Autoimmune Diseases", "Bar Codes", "COVID-19 vaccination", "COVID-19 vaccine", "Cells", "Clinical", "Clinical Trials", "Complement Activation", "Complex", "DNA", "Data", "Demographic Factors", "Disease", "Dose", "Enzyme-Linked Immunosorbent Assay", "Epitopes", "Formulation", "Future", "Generations", "Goals", "Hospitalization", "Immune response", "Immune signaling", "Immunity", "Immunocompromised Host", "Immunoglobulin A", "Immunoglobulin G", "Immunoglobulin M", "Immunologics", "Immunosuppression", "Individual", "Infection", "Innate Immune System", "Knowledge", "Measures", "Medication Management", "Modeling", "Molecular", "Nature", "Older Population", "Participant", "Peptides", "Persons", "Pharmaceutical Preparations", "Play", "Population", "Process", "Productivity", "Proteins", "Recommendation", "Regimen", "Research", "Research Personnel", "Respiratory Syncytial Virus Infections", "Respiratory Syncytial Virus Vaccines", "Respiratory syncytial virus", "Risk", "Role", "Serology", "Solid", "System", "Technology", "Testing", "Toxic effect", "Uncertainty", "Vaccination", "Vaccine Adjuvant", "Vaccine Design", "Vaccines", "Viral", "Viral Antibodies", "Viral Proteins", "Virus", "Virus Diseases", "antibody-dependent cell cytotoxicity", "attenuation", "cohort", "design", "disorder prevention", "experience", "high risk", "high risk population", "immune activation", "immunogenicity", "immunosuppressed", "improved", "in vitro Model", "indexing", "innovation", "machine learning model", "neutralizing antibody", "novel", "organ transplant recipient", "pathogen", "pharmacologic", "response", "self assembly", "vaccine access", "vaccine immunogenicity", "vaccine response" ], "approved": true } }, { "type": "Grant", "id": "15754", "attributes": { "award_id": "1U01AI186939-01", "title": "Mitigation of multi-organ delayed effects of acute radiation exposure (DEARE) with ACE2 agonist diminazene aceturate.", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "NIH Office of the Director" ], "program_reference_codes": [], "program_officials": [ { "id": 32816, "first_name": "CARMEN I", "last_name": "RIOS", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-11", "end_date": "2030-07-31", "award_amount": 546000, "principal_investigator": { "id": 32817, "first_name": "Heather A", "last_name": "Himburg", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2624, "ror": "", "name": "MEDICAL COLLEGE OF WISCONSIN", "address": "", "city": "", "state": "WI", "zip": "", "country": "United States", "approved": true }, "abstract": "With the advent of hematopoietic growth factors for mitigation of acute radiation syndrome (ARS), victims of nuclear or radiological events will be more likely to survive ARS but also at greater risk for the development of a range of late multi-organ toxicities collectively referred to as the delayed effects of acute radiation exposure (DEARE). To date, there are no FDA-approved medical countermeasures (MCMs) for the treatment of DEARE. This application to RFA-AI-23-059 (Development of Candidate Radiation/Nuclear MCMs) proposes to address this unmet need and will focus on the unmet need for MCMs against two life-threatening subsyndromes of DEARE: radiation pneumonitis and nephropathy. Here, we propose to screen three candidate MCMs which target the non-canonical, alternative renin angiotensin system (RAS). As a counterbalance to the canonical RAS, the alternative RAS has broad tissue-protective function by promoting vasodilation, reducing inflammation, and reducing fibrosis. For these reasons, several recent and ongoing clinical trials are evaluating alternative RAS activators for the treatment of severe COVID-19. Data from our lab and others also supports the potential for alternative RAS activation in the treatment of radiation toxicities. Our laboratory has shown diminazene aceturate (DIZE) a small molecule agonist of the alternative RAS pathway promotes survival in rat models of ARS and DEARE. Important to this application, DIZE treatment also mitigated injury to the lung and kidney as evidenced by improved survival during the sub-syndromes of lung and kidney DEARE. Based on these data, we hypothesize the alternative RAS pathway can be targeted pharmacologically to mitigate radiation-induced multi-organ DEARE. Here, we propose a stepwise approach to targeting three key players in the alternative RAS pathway: angiotensin converting enzyme 2 (ACE2), Ang(1-7), and the Mas receptor (MasR). Each Aim of this application will target one of these players using the following lead candidate therapies: DIZE (ACE2 activator), TXA127 (synthetic Ang(1-7)), and BIO101 (MasR activator). We will evaluate the efficacy of the candidate MCMs in an established rat DEARE model which recapitulates the anticipated human sequelae of acute and delayed toxicities. For each candidate MCM, the primary outcome measure will be mitigation of all-cause mortality, which is the clinically relevant endpoint for FDA approval under the Animal Rule.", "keywords": [ "ACE2", "Acceleration", "Acute", "Acute Respiratory Distress Syndrome", "Address", "Adult", "Agonist", "Anti-Inflammatory Agents", "Antiinflammatory Effect", "Antioxidants", "Binding", "Body System", "Bone Marrow", "COVID-19", "Clinical Research", "Clinical Trials", "Data", "Development", "Dose", "Exposure to", "FDA approved", "Fibrosis", "G-Protein-Coupled Receptors", "Generations", "Goals", "Hematopoietic", "Hematopoietic Cell Growth Factors", "Homeostasis", "Human", "Hypoxia", "In Vitro", "Inflammation", "Injury", "Investigation", "Ischemic Stroke", "Kidney", "Kidney Diseases", "Laboratories", "Life", "Lung", "Modeling", "Nuclear", "Nuclear Accidents", "Oral Administration", "Organ", "Outcome Measure", "Pathway interactions", "Peptide Signal Sequences", "Phase I/II Clinical Trial", "Play", "Population", "Radiation", "Radiation Accidents", "Radiation Injuries", "Radiation Pneumonitis", "Radiation Toxicity", "Radiation exposure", "Rattus", "Recovery", "Renin-Angiotensin System", "Reproducibility", "Respiratory Failure", "Risk", "Rodent Model", "Signal Transduction", "Testing", "Therapeutic Uses", "Time", "Tissues", "Toxic effect", "Vasodilation", "Vasodilator Agents", "Work", "animal rule", "clinical investigation", "clinically relevant", "efficacy evaluation", "experience", "improved", "in vivo Model", "irradiation", "lead candidate", "mass casualty", "medical countermeasure", "mortality", "multiorgan injury", "nuclear countermeasure", "pharmacologic", "pre-clinical", "preclinical study", "primary outcome", "programs", "protective effect", "radiation mitigation", "radiation mitigator", "receptor", "response", "severe COVID-19", "small molecule", "stroke patient", "subcutaneous", "therapeutic target" ], "approved": true } }, { "type": "Grant", "id": "15753", "attributes": { "award_id": "1R21ES038077-01", "title": "Project Firestorm: Assessing Respiratory and Mental Health Impacts of Wildland-Urban Interface Fires and Long-Term Toxic Exposures", "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": 32812, "first_name": "ASHLINN KO", "last_name": "QUINN", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-25", "end_date": "2027-08-24", "award_amount": 456500, "principal_investigator": { "id": 32813, "first_name": "FRANK D.", "last_name": "GILLILAND", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32814, "first_name": "Daniel", "last_name": "Soto", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 32815, "first_name": "Jennifer Beth", "last_name": "Unger", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2622, "ror": "", "name": "UNIVERSITY OF SOUTHERN CALIFORNIA", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "/ ABSTRACT The Los Angeles firestorms in January 2025 burned over 50,000 acres, destroyed over 16,000 homes and other structures, and displaced over 150,000 Los Angeles County residents. Most importantly, the fires have significantly impacted air quality across the Los Angeles Basin. The fires released high levels of fine particulate matter, VOCs, CO, NOx, and ozone precursors, exacerbating respiratory and cardiovascular conditions for those throughout Los Angeles. These findings stress the need to study long-term health impacts of wildland- urban interface (WUI) wildfire smoke. The acute and longer-term health effects of exposures from these catastrophic wildfires have yet to be defined. A better understanding of WUI) fire-related exposures and the health impacts is an urgent public health priority for Los Angeles. We will collect biological samples from affected individuals and analyze home dust, surface contaminants and outdoor soil and ash over time. After a wildfire it is critical to assess exposure levels and characterize the composition of toxins before home clean-up and environmental factors, such as wind and rain, alter its distribution or concentrations. We propose to conduct Project Firestorm, a rapid study to quantify the health effects of the wildfires. We will leverage an existing cohort of over 9,000 USC faculty, staff, and students who participated in a longitudinal COVID-19 study in 2021-2022. These participants, most of whom live in or around Los Angeles, have completed surveys about their physical and mental health and sociodemographics, providing an essential baseline assessment. The participants have signed consent forms giving their permission to be recontacted for future studies, enabling us to launch the study quickly without extensive recruitment time. We will recontact these participants and invite them to complete a survey about the effects of the fires on physical, mental, and financial health over the next year. From those who complete the survey (N=approximately 3000), we will recruit and collect more detailed data from a sample of 200 participants--100 who lived near the fires (fire-adjacent) and 100 who live over 15 miles away from the burn site (fire-distant). These participants will provide health outcome data on respiratory and other key outcomes, hair samples, wear silicone bracelets for VOC measurements, and samples of their house dust, surface wipes and yard soil for analysis, in February-March 2025 and again in February-March 2026. We will analyze (1) differences between fire-adjacent and fire-distant participants at baseline, and (2) change over a one-year period among fire-affected households and more distant households. Findings will guide public health interventions, long-term remediation efforts, and strategies to mitigate the WUI fires’ health impacts.", "keywords": [ "Acute", "Adult", "Affect", "Air", "Anxiety", "Area", "Aromatic Polycyclic Hydrocarbons", "Arsenic", "Authorization documentation", "Biological", "Burn injury", "COVID-19", "Cadmium", "Carbon Black", "Carbon Monoxide", "Cardiovascular system", "Characteristics", "Chemical Burns", "Communities", "Consent", "Consent Forms", "Consumption", "County", "Data", "Dioxins", "Disasters", "Distant", "District of Columbia", "Dose", "Environmental Risk Factor", "Environmental Wind", "Evaluation", "Event", "Exposure to", "Faculty", "Financial Hardship", "Fire - disasters", "Flame Retardants", "Funding", "Future", "Hair", "Health", "High Prevalence", "Home", "House Dust", "Household", "Individual", "Intervention", "Investigation", "Lead", "Lead levels", "Longitudinal Studies", "Los Angeles", "Measurement", "Measures", "Mental Depression", "Mental Health", "Mercury", "Metals", "National Institute of Environmental Health Sciences", "Nitrogen Oxides", "Outcome", "Ozone", "Participant", "Particulate Matter", "Pattern", "PhenX Toolkit", "Physical assessment", "Policies", "Polychlorinated Biphenyls", "Positioning Attribute", "Post-Traumatic Stress Disorders", "Protocols documentation", "Psyche structure", "Public Health", "Rain", "Readiness", "Recontacts", "Reporting", "Research", "Respiratory Signs and Symptoms", "Risk", "Sampling", "Silicones", "Site", "Smoke", "Soil", "Standardization", "Stress", "Structure", "Students", "Surface", "Surveys", "Testing", "Time", "Toxicant exposure", "Toxin", "Wildfire", "Wrist", "air monitoring", "coarse particles", "cohort", "design", "exposed human population", "fine particles", "health data", "improved", "persistent organic pollutants", "phthalates", "physical conditioning", "physical symptom", "pollutant", "psychological symptom", "public health intervention", "public health priorities", "recruit", "remediation", "respiratory", "respiratory health", "sociodemographics", "tool", "toxic metal", "volatile organic compound", "wristband" ], "approved": true } }, { "type": "Grant", "id": "15752", "attributes": { "award_id": "1DP2CA311214-01", "title": "Harnessing natural killer cells for cellular immunotherapy against solid tumors", "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": 32810, "first_name": "LILLIAN S", "last_name": "KUO", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-06", "end_date": "2028-07-31", "award_amount": 1457050, "principal_investigator": { "id": 32811, "first_name": "Wilfredo F", "last_name": "Garcia-Beltran", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2623, "ror": "", "name": "MASSACHUSETTS GENERAL HOSPITAL", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "Despite recent advances in cancer therapy, cancer remains the second leading cause of death in the United States. The field of cancer immunotherapy has evolved to meet this challenge, but there is an ongoing need for treating metastatic and treatment-resistant solid tumors, particularly those of lung, breast, prostate, and colorectal origin. Cellular immunotherapies, such as chimeric antigen receptor (CAR) T-cell therapy, have shown success in treating blood cancers. However, they remain ineffective against solid tumors, and are often fraught with inherent toxicities such as cytokine release syndrome and attack of healthy tissues. In light of these challenges, this proposal aims to harness natural killer (NK) cells, which have broad anti-tumor activity and a superior safety profile, to generate CAR NK-cell therapy as an effective immunotherapy against solid tumors. CAR NK-cell therapy has recently shown remarkable success against blood cancers but remains challenging for use in solid tumors. The tumor microenvironment employs immune-evasive mechanisms to subvert NK-cell killing and limits their infiltration and survival. Our research proposal will address these obstacles by leveraging high-throughput, sequencing-based functional screens and innovative synthetic biology approaches that will shed light on fundamental NK-cell biology and enhance CAR NK-cell infiltration and killing of solid tumors. We will implement a genome-wide CRISPR screen in primary human NK cells to identify negative regulators (‘innate immune checkpoints’) of NK-cell cytotoxicity. Subsequently, we will identify homing and survival signals in tumor- infiltrating immune cells by mining single-cell RNA-sequencing databases. We will then introduce these genes into NK cells to enhance their infiltration and survival in in-vitro and in-vivo models of the tumor microenvironment. Finally, we will perform a high-throughput CARpool screen to simultaneously assess hundreds of NK cell-tailored CARs designed with native NK cell-receptor signaling machinery to maximize CAR NK-cell functioning. In summary, this proposed research introduces several innovative approaches to study fundamental NK-cell biology and engineer NK-cell based immunotherapies against solid tumors. Our project is poised to uncover new targets in NK cells for 'innate immune checkpoint blockade' as well as create the next-generation of CAR NK- cell therapy for treating metastatic and treatment-resistant cancers. Ultimately, we will establish a pipeline of technologies that can be applied to many cancer types in order to broaden the scope of immunotherapies against cancer and transform patient care to mitigate the devastating impact of this disease.", "keywords": [ "Biomedical Engineering", "Breast", "CAR T cell therapy", "CRISPR screen", "Cancer Etiology", "Cause of Death", "Cell Physiology", "Cell Therapy", "Cells", "Cellular biology", "Cellular immunotherapy", "Cessation of life", "Colorectal", "Colorectal Cancer", "Disease", "Effectiveness", "Genes", "Goals", "Hematopoietic Neoplasms", "Homing", "Human", "Immune", "Immune Evasion", "Immunotherapy", "In Vitro", "Infiltration", "Light", "Lung", "Malignant Breast Neoplasm", "Malignant Neoplasms", "Malignant neoplasm of lung", "Malignant neoplasm of prostate", "Methods", "Mining", "Molecular and Cellular Biology", "NK cell therapy", "Natural Killer Cells", "Patient Care", "Patients", "Prostate", "Quality of life", "Receptor Signaling", "Research", "Research Proposals", "Resistance", "Safety", "Signal Transduction", "Solid Neoplasm", "Technology", "Tissues", "Toxic effect", "Tumor-infiltrating immune cells", "United States", "cancer immunotherapy", "cancer therapy", "cancer type", "cell killing", "chimeric antigen receptor", "chimeric antigen receptor natural killer cells", "cytokine release syndrome", "cytotoxicity", "design", "engineered NK cell", "genome-wide", "immune checkpoint blockade", "improved", "in vivo Model", "innate immune checkpoint", "innovation", "molecular sequence database", "next generation", "refractory cancer", "single-cell RNA sequencing", "success", "synthetic biology", "tumor", "tumor microenvironment" ], "approved": true } } ], "meta": { "pagination": { "page": 4, "pages": 1405, "count": 14046 } } }