Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1392&sort=start_date
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=start_date", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1405&sort=start_date", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1393&sort=start_date", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1391&sort=start_date" }, "data": [ { "type": "Grant", "id": "15598", "attributes": { "award_id": "1R01ES037151-01", "title": "Multi-component INTERLUNG intervention to protect lung health in Nepal", "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": 11803, "first_name": "Claudia L", "last_name": "Thompson", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-03-19", "end_date": "2030-02-28", "award_amount": 893525, "principal_investigator": { "id": 9093, "first_name": "William", "last_name": "Checkley", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 265, "ror": "https://ror.org/03czfpz43", "name": "Emory University", "address": "", "city": "", "state": "GA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 344, "ror": "https://ror.org/00za53h95", "name": "Johns Hopkins University", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "Chronic respiratory diseases (CRDs) remain the third leading cause of death worldwide and their incidence is increasing. In 2019, it was estimated that 455 million people worldwide live with a CRD such as asthma, COPD, and chronic bronchitis. CRDs are responsible for 4 million deaths and 103.5 million disability-adjusted life years lost each year. The development and severity of CRDs is attributed to both environmental exposures and infectious causes. Individuals who live in densely populated cities in low- and middle-income countries (LMICs) are disproportionately affected by high levels of ambient particulate matter, indoor exposure to allergens, dust and tobacco smoke, and a high incidence of viral and bacterial infections. Therefore, to have a meaningful impact on the incidence and severity of CRDs, and prevent further lung function decline, a multi- component evidence-based intervention targeting multiple risk factors is needed. We seek to test the implementation and effectiveness of a tailored multi-component evidence-based intervention following a community health worker (CHW)-driven chronic care delivery model to protect lung health over a 40-month period using a Type I hybrid implementation-effectiveness randomized controlled trial in Bhaktapur, Nepal. The multi-component intervention will consist of: reducing environmental risk factors by targeting tobacco smoking through CHW-delivered messaging and education on smoking prevention and smoking cessation, and targeting indoor and ambient air pollution exposures by providing households with HEPA-indoor air purifiers and vacuum cleaners and encourage masking outdoors with N95 respirators when e-notified about days with high ambient air pollution; reducing infectious risks through an CHW-led vaccine campaign for annual influenza, COVID and pneumococcal vaccine in all eligible participants and household members; encouraging use of surgical masks in indoor public spaces during the peak winter season or at home when there are sick household contacts; and, improving physiologic health by encouraging physical activity through CHW- monitored pedometer goals. Aligned with the Consolidated Framework for Implementation Research, we will first conduct human-centered design workshops with community members and healthcare practitioners to tailor the multi-component intervention. We will then screen and identify 800 index participants aged ≥ 9 years (with a pre-bronchodilator FEV1/FVC Z-score ≤ 10th percentile and chronic cough or wheeze (i.e., at-risk participants). We will enroll index participants and household members and assign half of the households to the adapted intervention. Controls will be asked to continue usual care practices. We will evaluate the effect of the intervention on pre-bronchodilator FEV1 Z-score (primary outcome), respiratory symptoms, and evaluate implementation outcomes. We seek to facilitate scale-up of a multi-component intervention that responds to the real-world implementation context to protect lung health in Nepal and other LMICs.", "keywords": [ "Adherence", "Adopted", "Adoption", "Affect", "Air Pollution", "Allergens", "Asthma", "Bacterial Infections", "Behavior", "Bronchodilator Agents", "COVID-19 vaccine", "Cause of Death", "Censuses", "Cessation of life", "Chronic", "Chronic Bronchitis", "Chronic Care", "Chronic Obstructive Pulmonary Disease", "Cities", "Communities", "Community Health Aides", "Consolidated Framework for Implementation Research", "Coughing", "Data", "Development", "Dust", "Education", "Educational workshop", "Effectiveness", "Enrollment", "Environmental Exposure", "Environmental Risk Factor", "Evidence based intervention", "Exposure to", "Future", "Goals", "Government Officials", "Hand", "Health", "Health Care", "Health system", "Home", "Household", "Household Air Pollution", "Hygiene", "Incidence", "Individual", "Indoor Air Pollution", "Inhalation", "Intervention", "Lateral", "Lower respiratory tract structure", "Masks", "Modeling", "Monitor", "N95 mask", "Nepal", "Notification", "Participant", "Particulate Matter", "Perception", "Persons", "Physical activity", "Physiological", "Pneumococcal vaccine", "Policies", "Process", "Pulmonary Function Test/Forced Expiratory Volume 1", "Quality of life", "Questionnaires", "Recommendation", "Research", "Resources", "Respiratory Signs and Symptoms", "Respiratory Tract Infections", "Risk", "Risk Factors", "Seasons", "Self Efficacy", "Self Management", "Service delivery model", "Severities", "Smoking Prevention", "Social outcome", "Spirometry", "Testing", "Tobacco", "Tobacco smoke", "Tobacco smoking behavior", "Vaccination", "Vaccines", "Vacuum", "Viral", "Virus Diseases", "Wheezing", "World Health Organization", "aged", "ambient air pollution", "chronic care model", "chronic respiratory disease", "comparison control", "disability-adjusted life years", "effectiveness-implementation RCT", "effectiveness/implementation hybrid", "eligible participant", "experience", "high efficiency particulate air filter", "human centered design", "implementation context", "implementation evaluation", "implementation outcomes", "implementation science", "improved", "indexing", "indoor air", "indoor exposure", "influenza virus vaccine", "intervention effect", "intervention mapping", "life span", "low and middle-income countries", "lung health", "member", "multi-component intervention", "multidisciplinary", "nicotine replacement", "pedomet" ], "approved": true } }, { "type": "Grant", "id": "15604", "attributes": { "award_id": "1R21AI183320-01A1", "title": "Altered protein structures and neoepitopes in lupus neutrophils from dysregulated splicing of messenger RNA", "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": 8447, "first_name": "Jeffrey S.", "last_name": "Rice", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-03-21", "end_date": "2027-02-28", "award_amount": 256808, "principal_investigator": { "id": 32100, "first_name": "Tomas M", "last_name": "Mustelin", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 159, "ror": "https://ror.org/00cvxb145", "name": "University of Washington", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true }, "abstract": "The goal of our research is to better define the molecular mechanisms cause and perpetuate systemic lupus erythematosus (SLE). Based on our discovery that transcripts from a large number of genes are spliced differently in neutrophils from SLE patients compared to neutrophils from healthy donors or COVID-19 patients, we propose a novel hypothesis of SLE pathogenesis, namely that dysregulated mRNA splicing in SLE granulocytes can affect their function and generate (neo)autoantigens not seen by the immune system before. We propose to expand and substantiate the analysis of altered mRNA splicing and begin to search for its cause(s). We will define how specific it is to SLE, understand the relation of altered splicing to sex, age, disease activity, type I interferons, and patient heterogeneity. Our work will also embark on the quest to elucidate why mRNA slicing is dysregulated in SLE. Next, we propose to explore the consequences of altered mRNA splicing in SLE. Although we have high confidence in the alignment of RNAseq reads to support all the splicing events we detect, and the transcripts are present at good read counts, it needs to be demonstrated that at least some are translated into altered proteins. We will continue to use targeted LC-MS/MS to find evidence for those with novel amino acid sequences. The proteolytic processing into antigenic peptides presented on MHC seen by T cells will then be explored. We know the MHC haplotypes of all our donors from the RNAseq data, so can match putative neoepitopes with the right MHC. Our work will clarify whether the production of novel, and perhaps individual, neo-autoantigens are a feature of SLE. If so, the production of such antigenic peptides would drive an immune response against the specific cell type that produces them (rather than all cells expressing the gene), adding a new element of tissue or cell linage-targeting to the autoimmune response. This model also introduces a new avenue for the development of therapeutics: modulating mRNA splicing to eliminate the production of neo-autoantigens. This will only be possible once the mechanism(s) underpinning abnormal splicing have been elucidated.", "keywords": [ "2019-nCoV", "Adaptive Immune System", "Address", "Affect", "Affinity", "Age", "Alleles", "Amino Acid Sequence", "Antigens", "Arginine", "Autoantigens", "Autoimmune Responses", "Autoimmunity", "Behavior", "Binding", "Biological", "COVID-19 patient", "Categories", "Cells", "Computer Analysis", "Data", "Databases", "Dermatomyositis", "Disease", "Disproportionately impacts women", "Elements", "Embryo", "Epitopes", "Event", "Genes", "Goals", "Haplotypes", "Heterogeneity", "Immune", "Immune response", "Immune system", "Individual", "Interferon Type I", "Lupus", "Malignant Neoplasms", "Mass Spectrum Analysis", "Messenger RNA", "Modeling", "Molecular", "Mutation", "Nature", "Nonsense-Mediated Decay", "Organ", "Pathogenesis", "Patients", "Peptides", "Pharmaceutical Preparations", "Post-Translational Protein Processing", "Process", "Production", "Protein Isoforms", "Proteins", "Proteolytic Processing", "Public Health", "RNA Splicing", "RNA Messenger Splicing", "RNA-Binding Proteins", "Race", "Reporting", "Research", "Retroelements", "Rheumatoid Arthritis", "Sampling", "Site", "Sjogren&apos", "s Syndrome", "Slice", "Spliced Genes", "Structure", "Systemic Lupus Erythematosus", "T-Lymphocyte", "Testing", "Tissues", "Transcript", "Translating", "Translations", "Western Blotting", "Work", "anti-tumor immune response", "cell type", "density", "disorder control", "experimental study", "granulocyte", "individual patient", "mRNA Transcript Degradation", "monocyte", "nanomolar", "neutrophil", "novel", "patient subsets", "protein structure", "sex", "therapeutic development", "transcriptome sequencing" ], "approved": true } }, { "type": "Grant", "id": "15646", "attributes": { "award_id": "2422986", "title": "PFI (MCA): Integration of Protein Engineering and Electrochemical Biosensors for Virus Detection", "funder": { "id": 3, "ror": "https://ror.org/021nxhr62", "name": "National Science Foundation", "approved": true }, "funder_divisions": [ "Unknown", "Special Projects" ], "program_reference_codes": [], "program_officials": [ { "id": 2267, "first_name": "Samir M.", "last_name": "Iqbal", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-04-01", "end_date": null, "award_amount": 331189, "principal_investigator": { "id": 32150, "first_name": "Karin", "last_name": "Chumbimuni-Torres", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 173, "ror": "", "name": "The University of Central Florida Board of Trustees", "address": "", "city": "", "state": "FL", "zip": "", "country": "United States", "approved": true }, "abstract": "This Partnerships for Innovation – Mid Career Advancement (PFI-MCA) project is focused on the development of a new, affordable technology to test for viruses with high accuracy. The project innovation is in the use of stable enzymes that can be stored at room temperature without requiring cold environments. The enzymes, combined with an electrochemical biosensor and microfluidics technology, will create a portable, affordable platform for virus detection in resource-limited environments. This technology can impact areas like health diagnostics, national security, and food safety. The research is multidisciplinary as it integrates chemistry, biology, and engineering. The project will give students hands-on experience in research scientific fields. The commercial impact of this technology will be important since it has potential to develop technology for virus detection that will be low cost and portable so it can be used anywhere and can supplement virus outbreak surveillance. This project will also translate the technology to manufacturing and commercialization. This project employs protein engineering to make stable enzymes that can be stored at room temperature without requiring cold environments. These enzymes are used to perform isothermal amplification of a virus fragment for posterior detection with electrochemical biosensors. By combining these two technologies, the project will develop a virus detection platform that works even in areas with limited resources, making it more accessible and cost-effective. The recent pandemic has shown the urgent need for affordable and quick virus detection methods. Currently, the most common virus detection method, Reverse Transcriptase Polymerase Chain Reaction, is expensive, requires special equipment and trained staff, and is mostly available in large labs, which makes it hard to use in areas with limit resources. This project aims to develop a more affordable and practical solution by using protein engineering to create stable, cost-effective enzymes that can be used with Nucleic Acid Sequence-Based Amplification technique at a single temperature. The enzymes, combined with an electrochemical biosensor and microfluidics technology, will create a portable, affordable platform for virus detection in resource-limited environments. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15647", "attributes": { "award_id": "2525962", "title": "Conference: International Symposium on the Infectious Diseases of Bats:Fourth International Symposium on the Infectious Diseases of Bats (BatID 2025), Chicago, IL", "funder": { "id": 3, "ror": "https://ror.org/021nxhr62", "name": "National Science Foundation", "approved": true }, "funder_divisions": [ "Unknown", "Symbiosis Infection & Immunity" ], "program_reference_codes": [], "program_officials": [ { "id": 2558, "first_name": "Joanna", "last_name": "Shisler", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-04-01", "end_date": null, "award_amount": 14868, "principal_investigator": { "id": 26531, "first_name": "Cara", "last_name": "Brook", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 289, "ror": "https://ror.org/024mw5h28", "name": "University of Chicago", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true }, "abstract": "This award supports the Fourth International Symposium on the Infectious Diseases of Bats (‘BatID 2025’), an international conference which brings together researchers from the disparate fields of virology, immunology, biochemistry, ecology, physiology, and genetics to investigate the role of bats as unique pathogen hosts. Bats are natural reservoir hosts for several high profile emerging human pathogens—including SARS-related coronaviruses, the likely precursors to the COVID-19 pandemic—yet they demonstrate limited pathology upon infection with viruses that cause extreme disease in non-bat (including human) hosts. Studying the mechanisms by which bats avoid disease from infection offers opportunities to translate bat-inspired immunological approaches into human disease therapeutics. This meeting offers opportunities for early career trainees, particularly graduate students and postdoctoral scholars, to share ideas and research findings with experts across this wide-ranging and interdisciplinary field. The meeting also aims to facilitate conversation between bat ecologists and conservationists with those engaged in more molecular approaches to understanding bat infectious disease to reconcile bats’ roles as major pathogen reservoirs. BatID 2025 is organized around three major conference objectives: (1) to disseminate research on the unique role of bats as pathogen hosts, (2) to foster collaborations and expand the field of bat infectious disease research, and (3) to identify a priority future research agenda in the study of bat infectious diseases. The first objective highlights this meeting’s utility as a research-sharing forum that welcomes representatives from disparate disciplines, who may not closely follow research outputs from other fields. The second objective seeks to turn this idea exchange into action by fostering collaborations among attendees, this year with a particular emphasis on recruiting participants and speakers who have not previously attended this meeting. Finally, the third objective seeks to organize the community around future research goals through an open discussion at the end of the two-day program. As an output, the Conference Organizing Committee will produce a peer-reviewed ‘Conference Proceedings’ article (to be led by junior researcher attendees) that shares these goals with the broader scientific community. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15648", "attributes": { "award_id": "2439345", "title": "CAREER: Intelligent Biomarker Analysis based on Wearable Distributed Computing", "funder": { "id": 3, "ror": "https://ror.org/021nxhr62", "name": "National Science Foundation", "approved": true }, "funder_divisions": [ "Unknown", "CAREER: FACULTY EARLY CAR DEV" ], "program_reference_codes": [], "program_officials": [ { "id": 12587, "first_name": "Juan", "last_name": "Li", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 340, "ror": "", "name": "North Dakota State University Fargo", "address": "", "city": "", "state": "ND", "zip": "", "country": "United States", "approved": true } ] } ], "start_date": "2025-04-01", "end_date": null, "award_amount": 503930, "principal_investigator": { "id": 32151, "first_name": "Juan", "last_name": "Patarroyo", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1024, "ror": "", "name": "University of Puerto Rico Mayaguez", "address": "", "city": "", "state": "PR", "zip": "", "country": "United States", "approved": true }, "abstract": "Some of the challenges associated with wearable technologies are the limitation on computational power, battery capacity, data privacy, user interface design, and the need for seamless integration into user lifestyles without causing discomfort. These challenges limit the on-device implementation of machine learning methods, which are suitable for classifying and estimating medical conditions based on the biomarkers sensed by the wearable devices. This research addresses these problems by developing a scheme that distributes the computational load of machine-learning models across wearable devices. Results from this research contribute to deploying advanced health monitoring tools for in-home care of frail populations, such as post-COVID patients. This is aligned with the NSF mission to promote the progress of science and advance national health. The development of this project involves multidisciplinary efforts from computer science, bioengineering, and electrical engineering, as well as educational activities with the participation of students from underrepresented groups. This project focuses on developing a wearable sensor network scheme with distributed and interconnected computing capabilities. As an application case, the wearable computing sensor network is aimed at biomechanics analysis for frail populations. The research plan is geared toward creating an advanced scheme of wearable devices to improve power consumption, data privacy, and computational performance for advanced health monitoring and analysis. To fulfill the strict requirements of size, computational load, and energy consumption, a novel distributed machine learning architecture is designed and deployed on each wearable sensor using field programmable gate arrays. The deployed architecture is a simplified version of the parallel-computing architecture found in commercial graphics processing units, which have been demonstrated to be suitable for machine-learning applications. In addition, this architecture contains additional hardware components for estimating missing data, synchronization, and addressing communication errors between the devices. This project addresses realistic challenges in biomedical and wearable technologies research, including (i) segmenting and training machine learning models considering the nature of biomechanical data and wearable inertial sensors without affecting accuracy, (ii) modeling a lightweight computer architecture for performing distributed machine learning inference in real time, (iii) estimating detailed body motion dynamics using a reduced amount of inertial sensors, and (iv) integrating reliable and state-of-the-art data analytics environments for efficient real-time analysis and visualization. The education plan tackles three major areas: (i) research training and competitive experiences for graduate and undergraduate students in the areas of computer science, computer architecture, and health-related areas, (ii) course development in topics related to edge computing, real-time systems, and machine learning applications to healthcare, and (iii) outreach to K-12 students and professionals by the introduction of competitive activities. Most of the students and contributors for this project are Hispanic, and this project supports broader access to and training in cutting-edge research in computational applications. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15674", "attributes": { "award_id": "1I01BX006818-01", "title": "Regulation of T cell immunity", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2025-04-01", "end_date": "2029-03-31", "award_amount": null, "principal_investigator": { "id": 32517, "first_name": "John T", "last_name": "Chang", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2485, "ror": "https://ror.org/00znqwq11", "name": "VA San Diego Healthcare System", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Background and Innovation: Mortality from infectious diseases remains the second leading cause of death worldwide, a fact highlighted by 4 years of a global pandemic, making the understanding of host responses, development of new vaccines, and improving existing vaccines important priorities of biomedical research. Memory T cells mediate protection from reinfection with previously encountered pathogens, and a large number of these cells, termed tissue-resident memory cells (TRM), do not recirculate throughout the body, reside within tissues, and provide essential sentinel protection at body surfaces. Using a murine infection model that is well established in the field for studying CD8 TRM, this application will investigate the context- and tissue-specific roles of the transcription factor Foxo1. Conceptual innovations include the study of Foxo1, the role of which is poorly understood in TRM biology. Technical innovations include the use of numerous cutting- edge approaches, including Cellular Indexing of Transcriptomes and Epitopes (CITE-seq) which enables proteomic and transcriptomic (scRNA-seq) analyses in the same single-cells, to identify consequences of Foxo1-deficiency in TRM. Bioinformatic innovations include the application of Taiji, a state-of-the-art bioinformatic analysis algorithm integrating transcriptomic and epigenomic data, to reveal Foxo1-transcription factor networks and identify putative regulatory factors and pathways controlled by Foxo1. Significance and Impact to Veterans Healthcare: Infectious diseases have a substantial public health and economic burden on the Veteran population. These include diseases for which we have vaccines, such as SARS-CoV-2 and influenza, as well as diseases that we do not yet have vaccines for, such as Hepatitis C (HCV) and HIV. A major gap in knowledge is that current vaccines generate neutralizing antibodies but do not generate a robust memory T cell response, including TRM, which are crucial for optimal protection at barrier surfaces. Another gap in knowledge is a comprehensive molecular understanding of the tissue-specific requirements for the generation and persistence of TRM, which will be addressed by this project. This research will address the VHA/ORD research priority of exploring fundamental biologic principles in pre-clinical models with the ultimate goal of improving the well-being of the nation’s Veterans specifically in the area of infectious diseases. Path to translation/implementation: Current vaccination regimens aim to generate protective antibodies but do not generate TRM. A detailed understanding of regulatory programs and transcriptional networks that govern T cell adaptation to tissues and barrier sites must be gained in order to provide the foundation and rational scientific basis to develop “tissue-tailored” immune responses. In this way, immune cells that promote or regulate inflammation can be transcriptionally engineered for trafficking to, retention in, and function within a particular tissue. Next steps to move this research along the translational pathway will involve testing whether modulation of Foxo1-mediated pathways enhances vaccine-generated immune memory.", "keywords": [ "2019-nCoV", "Address", "Adoptive Transfer", "Algorithmic Analysis", "Antibodies", "Area", "Bioinformatics", "Biological", "Biology", "Biomedical Research", "Blood", "Body Surface", "CD8-Positive T-Lymphocytes", "CD8B1 gene", "CRISPR/Cas technology", "Categories", "Cause of Death", "Cell Differentiation process", "Cells", "Cellular Indexing of Transcriptomes and Epitopes by Sequencing", "Cellular biology", "Circulation", "Colon", "Communicable Diseases", "Computer Analysis", "Data", "Development", "Disease", "Economic Burden", "Engineering", "Epitopes", "Exhibits", "FOXO1A gene", "Foundations", "Generations", "Genetic", "Genetic Transcription", "Goals", "HIV/HCV", "Health", "Health Care", "Homologous Gene", "Human", "Immune", "Immune response", "Immunity", "Immunologic Memory", "Infection", "Infectious Skin Diseases", "Inflammation", "Influenza", "Integrins", "Kidney", "Knowledge", "Liver", "Lymphocytic choriomeningitis virus", "Lymphoid Tissue", "Maintenance", "Mediating", "Memory", "Modeling", "Molecular", "Morbidity - disease rate", "Mucous Membrane", "Mus", "Neoplasm Metastasis", "Organ", "Pathogenesis", "Pathway interactions", "Personal Satisfaction", "Play", "Population", "Pre-Clinical Model", "Proteins", "Proteomics", "Public Health", "RUNX3 gene", "Regimen", "Repression", "Research", "Research Priority", "Residencies", "Respiratory Mucosa", "Role", "Salivary Glands", "Sentinel", "Site", "Skin", "Small Intestines", "Sphingosine-1-Phosphate Receptor", "Surface", "System", "T cell regulation", "T cell response", "T memory cell", "T-Cell Receptor", "T-Lymphocyte", "Tai Ji", "Tamoxifen", "Testing", "Therapeutic", "Tissue Differentiation", "Tissues", "Transcription Repressor", "Transgenic Organisms", "Translations", "Vaccination", "Vaccines", "Veterans", "adaptive immunity", "chemokine receptor", "design", "epigenomics", "field study", "first responder", "improved", "indexing", "innovation", "military veteran", "mortality", "neutralizing antibody", "novel vaccines", "pandemic disease", "pathogen", "pathogenic microbe", "programs", "response", "trafficking", "transcription factor", "transcriptome", "transcriptomics", "tumor growth" ], "approved": true } }, { "type": "Grant", "id": "15676", "attributes": { "award_id": "1F32HD116425-01A1", "title": "Developing a Biomimetic Lactating Mammary Lobe for Therapeutic Safety", "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": 32520, "first_name": "KATIE MARIE", "last_name": "VANCE", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-04-01", "end_date": "2027-07-31", "award_amount": 76756, "principal_investigator": { "id": 32521, "first_name": "Amy H", "last_name": "Lee", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 210, "ror": "https://ror.org/042nb2s44", "name": "Massachusetts Institute of Technology", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "PROJECT SUMMARY. Breast milk is rich with bioactive components that are critical to an infant’s development. It is highly recommended that infants ingest breast milk; but, fluctuating maternal hormones and substandard post-parturition health directly mediate breast milk production. Maternal ingestion of small molecule drugs further compounds decreased breast milk synthesis and secretion, and adversely compromises breast milk quality. Although the majority of actively breastfeeding women consume medication or receive therapeutics, small drug molecule transport from maternal plasma to synthesized breast milk remains largely unknown. Important strides in understanding pharmacokinetics in milk-producing mammary glands have yet to occur because of the lack of engineered bioinspired mammary lobe systems that mimic complex in vivo signatures— topographical lobule microcurves, spiked levels of lactogenic hormones, cellular landscapes, and mechanically-driven lobe expansion and contraction. The objective of this proposal is to determine if our established microengineered mammary lobe system, which integrates key physiological characteristics, i.) faithfully mirrors multifactorial breast milk synthesis processes and ii.) could be employed as a versatile screening testbed for evaluating drug and therapeutic safety during lactation. The project is based on the central hypothesis that exogenous stimuli that reflect in vivo mechanisms, such as hormone levels, dynamic mechanical lobe stimulation, and passive transport of small drug molecules, will potentiate differential cellular landscape phenotypes and lead to unique content differences in engineered breast milk. This could develop a new in vitro preclinical model that promotes the cognizance of drugs or therapeutics that are safe to ingest or receive during lactation. We believe this contributes to improving important women’s health issues. Our hypothesis will be tested through the following two aims. Aim 1 will develop a 3D mammary lobe model and determine how in vivo relevant parameters alter physical and molecular mammary cell phenotypes, and regulate the secretion of important breast milk components. Aim 2 will investigate the pharmacokinetics of small molecule drugs or therapeutics that passively diffuse into the engineered breast milk. Nicotine or mRNA encoding for SARS-CoV-2 will serve as a model drug or therapeutic, respectively. We will pursue these aims using an innovative combination of analytical and adaptable techniques from engineering and biological sciences. These include the development of a scalable lobe model, by which the application of physiologically relevant stimuli and compartments can mimic breast milk synthesis and drug distribution. The engineering approaches that we leverage will develop foundational resources for the ongoing efforts and research revolving lactation and post-parturition health equity. The expected outcome of this work will highlight the importance of engineering new microsystems for in vivo mimicry. These platforms can facilitate clinical translation of rapid drug and therapeutic safety screening. The results will have a significant positive impact to women and will encourage the ongoing efforts to support women during their breastfeeding journey.", "keywords": [ "2019-nCoV", "3-Dimensional", "Affect", "Air", "Apical", "Biological Sciences", "Biomimetics", "Birth", "Breast Feeding", "COVID-19", "COVID-19 vaccine", "Carrier Proteins", "Caseins", "Cell Polarity", "Cell Proliferation", "Cell-Cell Adhesion", "Cells", "Characteristics", "Chemicals", "Circulation", "Complex", "Consumption", "Cultured Cells", "Cytoskeletal Proteins", "Development", "Diffuse", "Diffusion", "Drug Kinetics", "Drug Modelings", "Engineering", "Enzyme-Linked Immunosorbent Assay", "Excretory function", "Exhibits", "Exposure to", "Gland", "Goals", "Harvest", "Health", "High Pressure Liquid Chromatography", "Hormones", "Human Milk", "In Vitro", "Individual", "Infant", "Infant Development", "Ingestion", "Lactation", "Lipids", "Lobe", "Lobule", "Mammary gland", "Maternal health equity", "Mechanical Stimulation", "Mechanical Stress", "Mechanics", "Mediating", "Membrane", "Messenger RNA", "Milk Proteins", "Mission", "Modeling", "Molds", "Molecular", "Mothers", "Motion", "Nicotine", "Nutrient", "Outcome", "Oxytocin", "Perfusion", "Periodicity", "Pharmaceutical Preparations", "Phenotype", "Physiological", "Plasma", "Pre-Clinical Model", "Pregnancy", "Process", "Prolactin", "Protein Biosynthesis", "Protein Secretion", "Proteins", "Proteomics", "Public Health", "Pump", "RNA vaccine", "Recommendation", "Regulation", "Reporting", "Research", "Resources", "Safety", "Side", "Stains", "Stimulus", "Structure", "Surface", "System", "Techniques", "Testing", "Therapeutic", "Tight Junctions", "United States National Institutes of Health", "Variant", "Ventilator", "Woman", "Women&apos", "s Health", "Work", "clinical translation", "drug distribution", "drug testing", "extracellular vesicles", "health equity", "high throughput screening", "improved", "in vivo", "innovation", "interstitial", "lactogenesis", "lipidomics", "mammary", "maternal vaccination", "mechanical drive", "mechanical properties", "mechanical stimulus", "microsystems", "milk expression", "milk production", "milk secretion", "mimicry", "molecular phenotype", "nicotine use", "passive transport", "pre-clinical", "protein expression", "reconstitution", "screening", "secretory protein", "small molecule", "therapeutic evaluation" ], "approved": true } }, { "type": "Grant", "id": "15677", "attributes": { "award_id": "1I21BX007163-01", "title": "Development of 12-Lipoxygenase Inhibitors for diabetes treatment.", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2025-04-01", "end_date": "2027-03-31", "award_amount": null, "principal_investigator": { "id": 32522, "first_name": "JERRY L.", "last_name": "NADLER", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2157, "ror": "", "name": "VA NORTHERN CALIFORNIA HEALTH CARE SYS", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Approximately 25% of US Veterans have diabetes and the annual mortality rate due to diabetes in Veterans is almost double of the rate in Veterans without diabetes. The presence of diabetes in the Veteran population is an important cause of disability due to complications such as cardiovascular disease, neuropathy, retinopathy, and kidney disease. Recent studies have indicated higher rates of new onset diabetes in Veterans who have had COVID-19 and analysis of Veterans using the Million Veteran Database indicate a growing identification of new onset type 1 diabetes (T1D) in adults. Almost half of the newly diagnosed cases of T1D are adults and there is an unmet medical need to identify treatments to prevent or halt progression of the disease. 12-lipoxygenase (12-LOX) is a lipid-generating enzyme produced by various sites including pancreatic islet beta cells. 12- LOX expression is elevated in obesity, Type 2 diabetes ( T2D) and T1D. We showed that 12-LOX protein is increased in islets of auto-antibody-positive and Type 1 and Type 2 individuals. 12-LOX products are highly pro-inflammatory and reduce pancreatic beta cell function and viability. 12-LOX lipids lead to oxidative and endoplasmic reticulum stress and macrophage activation. Genetic deletion of 12-LOX in mouse models improves insulin signaling and prevents T1D development. We earlier discovered a highly selective 12-LOX inhibitor, ML-355, through a comprehensive screening, followed by iterative medicinal chemistry optimization. ML-355 has been licensed and pre-clinical and phase 1 safety testing has been successfully completed and found to be safe. ML-355 is in a phase 2 clinical trial for intravenous administration for a hematologic indication as the inhibitor is not sufficiently orally bio-available for chronic diabetes use. We recently discovered a new 12-LOX inhibitor, Slug001, which manifests increased potency both in vitro and in rescuing inflamed human islet cells, relative to ML355. We propose to explore this novel structural space with a suite of modifications of Slug001, guided by our computational modeling of ML355 docking. The goal in Aim 1 is to derivatize Slug001 and fill the active site cavity more efficiently so that the inhibitor potency can be increased more than its current 7-fold improvement relative to ML355 and have improved oral bioavailability. The docking model will greatly enhance the identification of promising new inhibitors. Of the six Slug001 lead derivatives, we have already synthesized several and shown that Slug002 is as potent as Slug001 but has better solubility. The completed studies will generate novel inhibitors and a new VA patent. In Aim 1 of the proposal, we will synthesize the new molecules and measure their potency and selectivity. Established methods, comparing potency with docking scores, will allow us to quickly design these derivatives, increase their potency and then subject them to our human diabetic cellular assays established in Aim 2. The derivatives of Slug001 will be screened by the Holman laboratory against the LOX isozymes (5-LOX, 12-LOX, 15-LOX-1, 15-LOX-2) to establish their selectivity. In Aim 2 we will test the efficacy of the inhibitors in a reliable and novel human functional Islet beta cell line and then move to testing in primary cadaveric human pancreatic islets. The testing will utilize using our established and validated assays to test effects on insulin secretion and protection from cytokine mediated damage. Our expectation at the completion of this pilot, is to move the lead compound (s) into a novel in humanized 12-LOX mouse model of T1D that will facilitate rapid translation to clinical testing. The proposed project will provide a new way to address the high rates of adult-onset Type 1 diabetes and complications in the Veteran population.", "keywords": [ "Acceleration", "Active Sites", "Address", "Adult", "Arachidonate 12-Lipoxygenase", "Arachidonate 15-Lipoxygenase", "Beta Cell", "Biological Assay", "Biological Availability", "Blood Vessels", "COVID-19", "Cadaver", "Cardiovascular Diseases", "Cell Line", "Cell Physiology", "Cell Survival", "Cells", "Cellular Assay", "Characteristics", "Chronic", "Computer Models", "Data", "Databases", "Death Rate", "Derivation procedure", "Development", "Diabetes Mellitus", "Disease Progression", "Docking", "Enzymes", "Generations", "Genetic", "Goals", "Health", "Hematology", "Human", "Immune", "In Vitro", "Individual", "Inflammatory", "Injury", "Insulin Resistance", "Insulin-Dependent Diabetes Mellitus", "Islet Cell", "Islets of Langerhans", "Isoenzymes", "Kidney Diseases", "LOX gene", "Laboratories", "Lead", "Legal patent", "Licensing", "Lipids", "Lipoxygenase Inhibitors", "Machine Learning", "Macrophage", "Macrophage Activation", "Measures", "Mediating", "Medical", "Methods", "Modeling", "Modification", "Neuropathy", "Newly Diagnosed", "Non-Insulin-Dependent Diabetes Mellitus", "Obesity", "Oral", "Pathway interactions", "Pharmaceutical Chemistry", "Phase", "Phase II Clinical Trials", "Population", "Proteins", "Retinal Diseases", "Safety", "Site", "Solubility", "Structure of beta Cell of islet", "Testing", "Translations", "Veterans", "blood glucose regulation", "cell injury", "cytokine", "design", "diabetic", "disability", "efficacy testing", "endoplasmic reticulum stress", "expectation", "improved", "in vivo", "in vivo evaluation", "inhibitor", "insulin dependent diabetes mellitus onset", "insulin secretion", "insulin signaling", "intravenous administration", "islet", "islet cell antibody", "military veteran", "mouse model", "non-diabetic", "novel", "novel therapeutics", "post SARS-CoV-2 infection", "pre-clinical", "prevent", "programs", "research clinical testing", "safety testing", "screening", "small molecule inhibitor", "type I and type II diabetes" ], "approved": true } }, { "type": "Grant", "id": "15678", "attributes": { "award_id": "1I01BX006894-01", "title": "NCOA7 deficiency worsens brain damage after stroke", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2025-04-01", "end_date": "2029-03-31", "award_amount": null, "principal_investigator": { "id": 32523, "first_name": "Dandan", "last_name": "Sun", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1477, "ror": "https://ror.org/05eq41471", "name": "Veterans Health Administration", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "Background and Innovation: Lysosomes (with an acidic milieu of pH around 4.5) contain numerous acidic hydrolases for maintaining cellular homeostasis via the degradation of unwanted cellular components. NCOA7 (nuclear receptor coactivator 7), a member of the Tre2/Bub2/Cdc16 (TBC), lysin motif (LysM), domain catalytic (TLDc) protein family, was initially implicated in the oxidative stress as oxidation resistance proteins. However, new research demonstrates that NCOA7 directly binds and modulates vacuolar H+- ATPase (V-ATPase) assembly and activity to control endolysosomal acidification. Our pilot data from SNP- edited, human stem cell-derived endothelial cells have demonstrated that allele-specific binding of the inflammatory transcription factor NF-κB to a common intronic variant SNP rs11154337 in NCOA7 controls gene expression. Namely, we found that a C/C genotype, present in ~25% of the population, promoted lower NCOA7 expression and less lysosomal acidification (Prelim Data). Global Ncoa7 transgenic knockout mice (Ncoa7-/-, KO) are viable up to 18 months of age, with comparable gross brain structure to wild-type littermate (WT). However, upon ischemic stroke, compared to WT mice, we found that Ncoa7 KO mice exhibited worsened ischemic stroke outcomes (higher mortality, worsened blood-brain barrier impairment, increased astrogliosis and microglial activation, and abnormal accumulation of myelin basic protein, MBP) (Prelim Data). Whether the above worsened ischemic stroke outcomes resulted from V-ATPase dysfunction and lysosomal de-acidification remains unknown. In this proposal, we will test our hypotheses: 1). NCOA7 plays an important role in V-ATPase activity and lysosomal function in stroke brain in a cell-specific manner; 2). NCOA7 deficient in neurons and in oligodendrocytes drives lysosomal dysfunction and oxysterol/bile acid- specific inflammation, as well as abnormal cholesterol and MBP accumulation; 3). Post-stroke administration of NCOA7 activator Compound 958 will stimulate NCOA7 activity and reduce stroke brain damage. Significance and Impact to Veterans Healthcare: Cardiovascular diseases such as hypertension and pre- hypertension are common in active US military personnel. Moreover, post-traumatic stress disorder is associated with different cardiovascular and cerebrovascular diseases in older veterans. Collectively, these are well-established risk factors for stroke. The goal of this proposal is to study cellular mechanisms underlying the worsened ischemic stroke outcomes in NCOA7 deficient conditions and to determine whether pharmacological stimulation of NCOA7 is a novel therapeutic strategy for improving acute ischemic stroke outcomes. Therefore, our proposal is closely relevant to Veterans and the VA mission. Path to translation/implementation: completion of this study will directly address our knowledge gap about role of NCOA7 in regulating lysosome function and cholesterol metabolism in the stroke brains. To explore pharmacological tools, utilizing computational modeling, we developed a novel small molecule activator of NCOA7, Compound 958, which reduced pulmonary endothelial immunoactivation and robustly improved survival of a mouse model of acute COVID-19 (Prelim Data). Our findings from this study will reveal potentials of NCOA7 as a therapeutic target for attenuating V-ATPase dysfunction in stroke brain, and efficacy of NCOA7 activator Compound 958 in stroke therapy.", "keywords": [ "Acute", "Address", "Age Months", "Alleles", "Axon", "Bile Acids", "Binding", "Blood - brain barrier anatomy", "Blood Vessels", "Brain", "Brain Diseases", "Brain Injuries", "Cardiovascular Diseases", "Catalytic Domain", "Cause of Death", "Cells", "Cerebral Ischemia", "Cerebrovascular Disorders", "Cholesterol", "Cholesterol Homeostasis", "Computer Models", "Data", "Demyelinations", "Drug Kinetics", "Endothelial Cells", "Endothelium", "Endowment", "Exhibits", "Functional disorder", "Gene Expression", "Generations", "Genotype", "Goals", "Health Care", "Heterozygote", "Homeostasis", "Hydrolase", "Hydrolysis", "Hydroxylation", "Hypertension", "Impairment", "Inflammation", "Inflammatory", "Institute of Medicine (U.S.)", "Ischemic Stroke", "Knockout Mice", "Knowledge", "Lung", "Lysosomes", "Medicine", "Military Personnel", "Mission", "Mus", "Myelin Basic Proteins", "Nerve Degeneration", "Neuroglia", "Neurological outcome", "Neurons", "Nuclear Receptors", "Oligodendroglia", "Oxidative Stress", "Pathogenesis", "Play", "Population", "Post-Traumatic Stress Disorders", "Production", "Protein Family", "Proteins", "Pulmonary Hypertension", "Recovery", "Research", "Resistance", "Risk Factors", "Role", "Scientist", "Sterols", "Stroke", "Structure", "Testing", "Transgenic Organisms", "Translations", "USP6 gene", "Variant", "Vascular Diseases", "Veterans", "acute COVID-19", "astrogliosis", "career", "cholesterol trafficking", "design", "efficacy evaluation", "glial activation", "human stem cell-derived", "improved", "innovation", "lysin", "member", "mortality", "mouse model", "neuron loss", "novel", "novel therapeutic intervention", "oxidation", "pharmacologic", "post stroke", "prehypertension", "professor", "small molecule", "stroke outcome", "stroke recovery", "stroke therapy", "therapeutic target", "tool", "transcription factor", "vacuolar H+-ATPase", "white matter" ], "approved": true } }, { "type": "Grant", "id": "15679", "attributes": { "award_id": "1R01HL176493-01", "title": "Pathogenic Mechanism and Therapeutic Approaches for Exercise Intolerance in Post-Acute Sequelae of COVID-19", "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": 32514, "first_name": "EMMANUEL FRANCK", "last_name": "MONGODIN", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-04-01", "end_date": "2029-01-31", "award_amount": 633045, "principal_investigator": { "id": 32524, "first_name": "Michael G", "last_name": "Risbano", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32525, "first_name": "Lianghui", "last_name": "Zhang", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 848, "ror": "", "name": "UNIVERSITY OF PITTSBURGH AT PITTSBURGH", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true }, "abstract": "Post-acute sequelae of COVID-19 (PASC) is an emerging public health priority with up to 18% prevalence. Noteably, almost 30% patients diagnosed with PASC experence exercise intolerance. This activity limitation continues to negatively impact our workforce, and poses a persistent socialeconimic burden on our society. Our Post-Covid Recovery Clinic, a RECOVERY Vital site, has evaluated exercise intolerant PASC for nearly 4 years. We recently discovered pathophysiologic endotypes that contribute to exercise intolerance in PASC via invasive cardiopulmonary exercise testing (iCPET). Yet, the molecular drivers for this population remain elusive. Four- years after the onset of the pandemic we are left without PASC-defining biomarkers, or targeted therapeutics. Thus, it is crucial to investigate the interconnected molecular and pathophysiologic links in exercise intolerant PASC, a task uniquely within our team’s expertise. Angiotensin-converting enzyme 2 (ACE2) is not just an entry receptor for SARS-CoV-2 but also an enzyme with a protective function through regulation of the renin- angiotensin system. Studies have shown that a high level of plasma ACE2 is associated with an increased risk of SARS-CoV-2-related mortality. Our preliminary data showed that the catalytic activity of increased plasma ACE2 was significantly impaired in the exercise intolerant PASC patients, and closely correlated with reduced exercise capacity as measured by peak oxygen consumption evaluated during iCPET. Furthermore, to study the pathogenic mechanism of exercise intolerance in PASC, we established a novel PASC mouse model. In this model, we observed the persistence of the SARS-CoV-2 RNAs in lung microvascular ECs, impaired ACE2 activity, chronic pulmonary inflammation, along with a significant reduction in exercise capacity. Thus, we hypothesize that dysfunctional ACE2 shed from pulmonary ECs is a major driver for exercise intolerance in PASC and an engineered solube ACE2 with enhanced ACE2 activity will improve exercise capacity of PASC. To test our hypotheses, we will investigate the predictive value of ACE2 activity as a clinical biomarker and assess its association with exercise capacity over 12 months in PASC patients in Aim 1. We will define an engineered soluble ACE2 with enhanced ACE2 activity as an innovative therapeutic intervention to improve exercise capacity and vascular function in the PASC mouse model in Aim 2. Furthermore, we will explore the mechanism of ACE2 dysfunction shed from the pulmonary vasculature in Aim 3. If successful, we will identify a diagnostic and therapeutic paradigm urgently needed for PASC patients experiencing exercise intolerance, and remediate the deficient response to this global public health threat.", "keywords": [ "2019-nCoV", "ACE2", "Acute Lung Injury", "Adult", "Affect", "Binding", "Biological Markers", "Blood Vessels", "COVID-19", "COVID-19 mortality", "COVID-19 patient", "Cardiopulmonary", "Cell surface", "Characteristics", "Chronic", "Circulation", "Clinic", "Clinical assessments", "Data", "Diagnosis", "Diagnostic", "Disease Progression", "Disintegrins", "Endothelial Cells", "Endothelium", "Engineering", "Enzymes", "Exercise", "Exercise Test", "Fatigue", "Functional disorder", "Health", "Impairment", "Inflammation", "Knock-in", "Knockout Mice", "Left", "Link", "Long COVID", "Lung", "Measures", "Medicine", "Metalloproteases", "Modeling", "Molecular", "Outpatients", "Oxygen Consumption", "Pathogenicity", "Pathology", "Patients", "Peptides", "Plasma", "Population", "Post-Acute Sequelae of SARS-CoV-2 Infection", "Predictive Value", "Prevalence", "Proteins", "Public Health", "Pulmonary Inflammation", "Questionnaires", "RNA", "Recovery", "Regulation", "Renin-Angiotensin System", "Risk", "SARS-CoV-2 infection", "Site", "Societies", "Symptoms", "Testing", "Therapeutic", "Therapeutic Intervention", "clinical biomarkers", "clinical infrastructure", "design", "dosage", "endothelial dysfunction", "exercise capacity", "exercise intolerance", "experience", "improved", "innovation", "knock-down", "lung microvascular endothelial cells", "mortality", "mouse model", "novel", "pandemic disease", "post SARS-CoV-2 infection", "post-COVID-19", "public health priorities", "receptor", "remediation", "research clinical testing", "response", "symptom cluster", "targeted treatment", "treatment optimization" ], "approved": true } } ], "meta": { "pagination": { "page": 1392, "pages": 1405, "count": 14046 } } }