Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1384&sort=other_investigators
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=other_investigators", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1424&sort=other_investigators", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1385&sort=other_investigators", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1383&sort=other_investigators" }, "data": [ { "type": "Grant", "id": "8101", "attributes": { "award_id": "1R01CA258297-01", "title": "Precision targeting of T cell cytotoxicity with PET", "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": 22660, "first_name": "LEELA RANI RANI", "last_name": "Avula", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2021-03-01", "end_date": "2026-02-28", "award_amount": 524205, "principal_investigator": { "id": 22661, "first_name": "Rahul", "last_name": "Aggarwal", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 768, "ror": "https://ror.org/043mz5j54", "name": "University of California, San Francisco", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 22581, "first_name": "CHARLES Scott", "last_name": "CRAIK", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 768, "ror": "https://ror.org/043mz5j54", "name": "University of California, San Francisco", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, { "id": 22662, "first_name": "Michael John", "last_name": "Evans", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 22663, "first_name": "Lawrence", "last_name": "Fong", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 768, "ror": "https://ror.org/043mz5j54", "name": "University of California, San Francisco", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "The recent clinical success of inhibitors against immune checkpoint proteins (e.g. CTLA-4, PD-L1), which are thought to stimulate T cell responses against tumors, has revolutionized cancer therapy. Yet even among patients with high tumor mutational burden, only approximately 20-30% of patients achieve deep response, and discerning responders from non-responders is challenging with conventional imaging. On this basis, there is an urgent unmet need to develop biomarkers that distinguish responsive and treatment resistant patients, as well as identify patients at risk for undesired immune related adverse events. We hypothesized that an imaging biomarker capable of selectively measuring the biology that T cells use to impart cytotoxicity might address these unmet needs. Since antitumor T cell cytotoxicity is conferred primarily by the pro-apoptotic serine protease granzyme B, we have developed a peptide-based chemosensor we term “restricted interaction peptide” that enables spatiotemporal measurements of granzyme B proteolytic activity as the enzyme traverses the immunological synapse between T cell and target cell. Upon proteolytic cleavage of the full length, pro-form of the restricted interaction peptide (termed GB1) by granzyme B, a radiolabeled antimicrobial peptide is liberated and undergoes a spontaneous conformational shift that results in stable (and non-toxic) membrane association. We have shown that radiolabeled GB1 detects T cell activation in tumors and normal tissues elicited by systemic immune checkpoint inhibitors. Following on these encouraging preclinical data, we have now assembled a multidisciplinary team to conduct translational studies to evaluate the utility of granzyme B biochemistry as a biomarker. Over three specific aims, we will (1) perform IND enabling studies for 64Cu-GB1, (2) conduct a phase 0 first in human study to determine tracer safety, pharmacokinetics, and dosimetry, and (3) execute a phase I study to determine the accuracy for detection of urothelial and renal cancers undergoing a productive immune response due to treatment with standard of care immune checkpoint inhibitors. If successful, this project will establish a new paradigm for the measurement of T cell cytotoxicity in vivo that could have implications for the clinical management of other problematic human disorders like bacterial or viral (HIV, SARS-CoV) infections. Moreover, the imaging approach is entirely new, and favorable data emerging from this project could motivate further studies to develop restricted interaction peptides to measure the enzymology of other disease associated proteases in vivo with PET.", "keywords": [ "Address", "Adopted", "Apoptotic", "Aspartic Acid", "Bacterial Infections", "Biochemistry", "Biological Markers", "Biology", "Biopsy", "Blood", "CTLA4 gene", "Cancer Model", "Cancer Patient", "Cell membrane", "Cells", "Chemistry", "Clear cell renal cell carcinoma", "Cleaved cell", "Clinic", "Clinical", "Clinical Management", "Data", "Detection", "Disease", "Drug Kinetics", "Enzymatic Biochemistry", "Enzymes", "Exposure to", "Family member", "Female", "Goals", "Granzyme", "HIV", "Hour", "Human", "Image", "Imaging technology", "Immune", "Immune checkpoint inhibitor", "Immune response", "Immune system", "Immunologic Markers", "Infection", "Injections", "Label", "Length", "Malignant neoplasm of urinary bladder", "Measurement", "Measures", "Mediating", "Membrane", "Modeling", "Molecular Conformation", "Mus", "Mutation", "Natural Killer Cell toxicity", "Neoplasm Metastasis", "Normal tissue morphology", "PET/CT scan", "Patients", "Peptide Hydrolases", "Peptides", "Phase", "Phase 0 Study", "Phospholipids", "Positron-Emission Tomography", "Proteins", "Radiolabeled", "Rattus", "Renal carcinoma", "Resistance", "Risk", "Rodent", "SARS coronavirus", "Safety", "Serine Protease", "Site", "Specificity", "Spleen", "T cell response", "T-Cell Activation", "T-Lymphocyte", "Technology", "Time", "Toxic effect", "Tracer", "Tumor Tissue", "Urothelial Cell", "Urothelium", "Viral", "Virus Diseases", "Work", "anti-CTLA-4 therapy", "anti-PD-1", "anti-PD-1/PD-L1", "antimicrobial peptide", "base", "cancer imaging", "cancer therapy", "checkpoint inhibition", "cohort", "combat", "cytotoxicity", "dosimetry", "enzyme activity", "experience", "extracellular", "first-in-human", "human imaging", "human study", "imaging approach", "imaging biomarker", "immune checkpoint", "immune-related adverse events", "immunological synapse", "immunomodulatory therapies", "in vivo", "inhibitor/antagonist", "innovation", "interest", "male", "multidisciplinary", "neoplastic cell", "novel", "phase 1 study", "pre-clinical", "programmed cell death ligand 1", "radiochemical", "radiotracer", "responders and non-responders", "response", "serial imaging", "spatiotemporal", "standard of care", "success", "translational study", "tumor", "uptake" ], "approved": true } }, { "type": "Grant", "id": "6831", "attributes": { "award_id": "5R01CA258297-02", "title": "Precision targeting of T cell cytotoxicity with PET", "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": 22660, "first_name": "LEELA RANI RANI", "last_name": "Avula", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2021-03-01", "end_date": "2026-02-28", "award_amount": 652933, "principal_investigator": { "id": 22661, "first_name": "Rahul", "last_name": "Aggarwal", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 768, "ror": "https://ror.org/043mz5j54", "name": "University of California, San Francisco", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 22581, "first_name": "CHARLES Scott", "last_name": "CRAIK", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 768, "ror": "https://ror.org/043mz5j54", "name": "University of California, San Francisco", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, { "id": 22662, "first_name": "Michael John", "last_name": "Evans", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 22663, "first_name": "Lawrence", "last_name": "Fong", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 768, "ror": "https://ror.org/043mz5j54", "name": "University of California, San Francisco", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "The recent clinical success of inhibitors against immune checkpoint proteins (e.g. CTLA-4, PD-L1), which are thought to stimulate T cell responses against tumors, has revolutionized cancer therapy. Yet even among patients with high tumor mutational burden, only approximately 20-30% of patients achieve deep response, and discerning responders from non-responders is challenging with conventional imaging. On this basis, there is an urgent unmet need to develop biomarkers that distinguish responsive and treatment resistant patients, as well as identify patients at risk for undesired immune related adverse events. We hypothesized that an imaging biomarker capable of selectively measuring the biology that T cells use to impart cytotoxicity might address these unmet needs. Since antitumor T cell cytotoxicity is conferred primarily by the pro-apoptotic serine protease granzyme B, we have developed a peptide-based chemosensor we term “restricted interaction peptide” that enables spatiotemporal measurements of granzyme B proteolytic activity as the enzyme traverses the immunological synapse between T cell and target cell. Upon proteolytic cleavage of the full length, pro-form of the restricted interaction peptide (termed GB1) by granzyme B, a radiolabeled antimicrobial peptide is liberated and undergoes a spontaneous conformational shift that results in stable (and non-toxic) membrane association. We have shown that radiolabeled GB1 detects T cell activation in tumors and normal tissues elicited by systemic immune checkpoint inhibitors. Following on these encouraging preclinical data, we have now assembled a multidisciplinary team to conduct translational studies to evaluate the utility of granzyme B biochemistry as a biomarker. Over three specific aims, we will (1) perform IND enabling studies for 64Cu-GB1, (2) conduct a phase 0 first in human study to determine tracer safety, pharmacokinetics, and dosimetry, and (3) execute a phase I study to determine the accuracy for detection of urothelial and renal cancers undergoing a productive immune response due to treatment with standard of care immune checkpoint inhibitors. If successful, this project will establish a new paradigm for the measurement of T cell cytotoxicity in vivo that could have implications for the clinical management of other problematic human disorders like bacterial or viral (HIV, SARS-CoV) infections. Moreover, the imaging approach is entirely new, and favorable data emerging from this project could motivate further studies to develop restricted interaction peptides to measure the enzymology of other disease associated proteases in vivo with PET.", "keywords": [ "Address", "Adopted", "Apoptotic", "Aspartic Acid", "Bacterial Infections", "Biochemistry", "Biological Markers", "Biology", "Biopsy", "Blood", "CTLA4 gene", "Cancer Model", "Cancer Patient", "Cell membrane", "Cells", "Chemistry", "Clear cell renal cell carcinoma", "Clinic", "Clinical", "Clinical Management", "Data", "Detection", "Disease", "Drug Kinetics", "Enzymatic Biochemistry", "Enzymes", "Exposure to", "Family member", "Female", "Goals", "Granzyme", "HIV", "Hour", "Human", "Image", "Imaging technology", "Immune", "Immune checkpoint inhibitor", "Immune response", "Immune system", "Immunologic Markers", "Infection", "Injections", "Label", "Length", "Malignant neoplasm of urinary bladder", "Measurement", "Measures", "Mediating", "Membrane", "Modeling", "Molecular Conformation", "Mus", "Mutation", "Natural Killer Cell toxicity", "Neoplasm Metastasis", "Normal tissue morphology", "PET/CT scan", "Patients", "Peptide Hydrolases", "Peptides", "Phase", "Phase 0 Study", "Phospholipids", "Positron-Emission Tomography", "Proteins", "Radiolabeled", "Rattus", "Renal carcinoma", "Resistance", "Risk", "Rodent", "SARS coronavirus", "Safety", "Serine Protease", "Site", "Specificity", "Spleen", "T cell response", "T-Cell Activation", "T-Lymphocyte", "Technology", "Time", "Toxic effect", "Tracer", "Tumor Tissue", "Urothelial Cell", "Urothelium", "Viral", "Virus Diseases", "Work", "anti-CTLA-4 therapy", "anti-PD-1", "anti-PD-1/PD-L1", "antimicrobial peptide", "base", "cancer imaging", "cancer therapy", "checkpoint inhibition", "cohort", "combat", "cytotoxicity", "dosimetry", "enzyme activity", "experience", "extracellular", "first-in-human", "human imaging", "human study", "imaging approach", "imaging biomarker", "immune checkpoint", "immune-related adverse events", "immunological synapse", "immunomodulatory therapies", "in vivo", "inhibitor/antagonist", "innovation", "interest", "male", "multidisciplinary", "neoplastic cell", "novel", "phase 1 study", "pre-clinical", "programmed cell death ligand 1", "radiochemical", "radiotracer", "responders and non-responders", "response", "serial imaging", "spatiotemporal", "standard of care", "success", "translational study", "tumor", "uptake" ], "approved": true } }, { "type": "Grant", "id": "8101", "attributes": { "award_id": "1R01CA258297-01", "title": "Precision targeting of T cell cytotoxicity with PET", "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": 22660, "first_name": "LEELA RANI RANI", "last_name": "Avula", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2021-03-01", "end_date": "2026-02-28", "award_amount": 524205, "principal_investigator": { "id": 22661, "first_name": "Rahul", "last_name": "Aggarwal", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 768, "ror": "https://ror.org/043mz5j54", "name": "University of California, San Francisco", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 22581, "first_name": "CHARLES Scott", "last_name": "CRAIK", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 768, "ror": "https://ror.org/043mz5j54", "name": "University of California, San Francisco", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, { "id": 22662, "first_name": "Michael John", "last_name": "Evans", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 22663, "first_name": "Lawrence", "last_name": "Fong", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 768, "ror": "https://ror.org/043mz5j54", "name": "University of California, San Francisco", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "The recent clinical success of inhibitors against immune checkpoint proteins (e.g. CTLA-4, PD-L1), which are thought to stimulate T cell responses against tumors, has revolutionized cancer therapy. Yet even among patients with high tumor mutational burden, only approximately 20-30% of patients achieve deep response, and discerning responders from non-responders is challenging with conventional imaging. On this basis, there is an urgent unmet need to develop biomarkers that distinguish responsive and treatment resistant patients, as well as identify patients at risk for undesired immune related adverse events. We hypothesized that an imaging biomarker capable of selectively measuring the biology that T cells use to impart cytotoxicity might address these unmet needs. Since antitumor T cell cytotoxicity is conferred primarily by the pro-apoptotic serine protease granzyme B, we have developed a peptide-based chemosensor we term “restricted interaction peptide” that enables spatiotemporal measurements of granzyme B proteolytic activity as the enzyme traverses the immunological synapse between T cell and target cell. Upon proteolytic cleavage of the full length, pro-form of the restricted interaction peptide (termed GB1) by granzyme B, a radiolabeled antimicrobial peptide is liberated and undergoes a spontaneous conformational shift that results in stable (and non-toxic) membrane association. We have shown that radiolabeled GB1 detects T cell activation in tumors and normal tissues elicited by systemic immune checkpoint inhibitors. Following on these encouraging preclinical data, we have now assembled a multidisciplinary team to conduct translational studies to evaluate the utility of granzyme B biochemistry as a biomarker. Over three specific aims, we will (1) perform IND enabling studies for 64Cu-GB1, (2) conduct a phase 0 first in human study to determine tracer safety, pharmacokinetics, and dosimetry, and (3) execute a phase I study to determine the accuracy for detection of urothelial and renal cancers undergoing a productive immune response due to treatment with standard of care immune checkpoint inhibitors. If successful, this project will establish a new paradigm for the measurement of T cell cytotoxicity in vivo that could have implications for the clinical management of other problematic human disorders like bacterial or viral (HIV, SARS-CoV) infections. Moreover, the imaging approach is entirely new, and favorable data emerging from this project could motivate further studies to develop restricted interaction peptides to measure the enzymology of other disease associated proteases in vivo with PET.", "keywords": [ "Address", "Adopted", "Apoptotic", "Aspartic Acid", "Bacterial Infections", "Biochemistry", "Biological Markers", "Biology", "Biopsy", "Blood", "CTLA4 gene", "Cancer Model", "Cancer Patient", "Cell membrane", "Cells", "Chemistry", "Clear cell renal cell carcinoma", "Cleaved cell", "Clinic", "Clinical", "Clinical Management", "Data", "Detection", "Disease", "Drug Kinetics", "Enzymatic Biochemistry", "Enzymes", "Exposure to", "Family member", "Female", "Goals", "Granzyme", "HIV", "Hour", "Human", "Image", "Imaging technology", "Immune", "Immune checkpoint inhibitor", "Immune response", "Immune system", "Immunologic Markers", "Infection", "Injections", "Label", "Length", "Malignant neoplasm of urinary bladder", "Measurement", "Measures", "Mediating", "Membrane", "Modeling", "Molecular Conformation", "Mus", "Mutation", "Natural Killer Cell toxicity", "Neoplasm Metastasis", "Normal tissue morphology", "PET/CT scan", "Patients", "Peptide Hydrolases", "Peptides", "Phase", "Phase 0 Study", "Phospholipids", "Positron-Emission Tomography", "Proteins", "Radiolabeled", "Rattus", "Renal carcinoma", "Resistance", "Risk", "Rodent", "SARS coronavirus", "Safety", "Serine Protease", "Site", "Specificity", "Spleen", "T cell response", "T-Cell Activation", "T-Lymphocyte", "Technology", "Time", "Toxic effect", "Tracer", "Tumor Tissue", "Urothelial Cell", "Urothelium", "Viral", "Virus Diseases", "Work", "anti-CTLA-4 therapy", "anti-PD-1", "anti-PD-1/PD-L1", "antimicrobial peptide", "base", "cancer imaging", "cancer therapy", "checkpoint inhibition", "cohort", "combat", "cytotoxicity", "dosimetry", "enzyme activity", "experience", "extracellular", "first-in-human", "human imaging", "human study", "imaging approach", "imaging biomarker", "immune checkpoint", "immune-related adverse events", "immunological synapse", "immunomodulatory therapies", "in vivo", "inhibitor/antagonist", "innovation", "interest", "male", "multidisciplinary", "neoplastic cell", "novel", "phase 1 study", "pre-clinical", "programmed cell death ligand 1", "radiochemical", "radiotracer", "responders and non-responders", "response", "serial imaging", "spatiotemporal", "standard of care", "success", "translational study", "tumor", "uptake" ], "approved": true } }, { "type": "Grant", "id": "6835", "attributes": { "award_id": "1R21MH127992-01A1", "title": "The Community-based ART REtention and Suppression (CARES) App: an innovation to improve patient monitoring and evaluation data in community-based antiretroviral therapy programs in Lilongwe, Malawi", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Mental Health (NIMH)" ], "program_reference_codes": [], "program_officials": [ { "id": 22665, "first_name": "Christopher M.", "last_name": "Gordon", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-01-01", "end_date": "2023-12-31", "award_amount": 183319, "principal_investigator": { "id": 22666, "first_name": "Caryl", "last_name": "Feldacker", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 159, "ror": "https://ror.org/00cvxb145", "name": "University of Washington", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 22667, "first_name": "Hannock Mukoma", "last_name": "Tweya", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 159, "ror": "https://ror.org/00cvxb145", "name": "University of Washington", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true }, "abstract": "Differentiated service delivery (DSD) increases antiretroviral therapy (ART) access in sub-Saharan Africa (SSA) by moving patients out of congested ART clinics to communities for care. Patient outcomes in DSD and traditional clinic-based care appear similar at lower cost. Decreased donor funding, health system constraints, healthcare worker (HCW) shortages, and COVID-related calls to reduce clinic visits, push DSD expansion. But, DSD settings challenge routine patient monitoring and evaluation (M&E) required to ensure quality care, risking viral suppression (VS), scarce resources, and epidemic control. Electronic medical record systems (EMRs) ensure effective patient M&E in compliance with complex guidelines, improving patient outcomes and reducing workload. Yet, despite decades of SSA EMRs investment, EMRs benefits do not extend to low resource/low infrastructure settings where the majority of DSD occurs. How to optimize collection and use of high quality M&E for DSD patient care is a critical implementation research priority. Lighthouse Trust (LT) operates two Ministry of Health (MoH) clinics in Lilongwe, Malawi, with combined >35,000 ART patients. LT’s real-time, point-of-care (POC) EMRs collects complex M&E data and provides decision-making support, ensuring adherence to integrated HIV/TB guidelines that optimize patient and program outcomes. LT’s EMRs scaled to all large MoH ART clinics. LT implements a nurse-led community-based ART program (NCAP), a DSD model to provide ART and rapid assessment to 2400 stable LT patients in the community. LT’s EMRs requires consistent power and server access. Without EMRs, NCAP providers lack embedded prompts and alerts, reducing integrated MoH ART guideline compliance. NCAP M&E is incomplete and burdensome, leaving data gaps that lessen VS monitoring and care continuity. Poor M&E limits NCAP expansion. Therefore, University of Washington’s International Training and Education Center for Health, LT, and Medic seek to leverage a proven, open-source digital health framework to design, deploy, and assess an offline-first, user-centered, battery-operated App, “Community-based ART REtention and Suppression” (CARES). Apps are faster to design, simpler to deploy, cheaper to maintain, and operate without constant connectivity or electricity. CARES brings a POC EMRs-like App to NCAP with real-time benefits for optimal, integrated patient care. CARES captures complete patient M&E data and syncs to facility EMRs, improving data quality while reducing workload. Guided by implementation science, we use a quasi-experimental, interrupted time-series design to assess NCAP patient care, pre- and post-CARES. Mixed-methods evaluate CARES effect on NCAP patient outcomes, data quality, workload, and cost. Aims: 1) Assess how CARES ensures high quality NCAP patient outcomes using RE-AIM to gauge reach, effectiveness, adoption, implementation, and maintenance; and 2) Estimate CARES cost to improve M&E using a systems perspective. We hypothesize that CARES increases NCAP on-time, annual VS testing from 65% to 80% at lower cost. COVID19 raises potential impact of this App to strengthen integrated DSD care provision and to provide M&E evidence on DSD patient and program outcomes.", "keywords": [ "Acquired Immunodeficiency Syndrome", "Adherence", "Adoption", "Africa South of the Sahara", "COVID-19", "Caring", "Clinic", "Clinic Visits", "Collection", "Communities", "Complement", "Complex", "Computerized Medical Record", "Continuity of Patient Care", "Cost Analysis", "Cost Effectiveness Analysis", "Data", "Database Management Systems", "Decision Making", "Development", "Effectiveness", "Electricity", "Emergency Situation", "Ensure", "Epidemic", "Evaluation", "Face", "Funding", "Future", "Gold", "Government", "Guideline Adherence", "Guidelines", "HIV", "HIV/TB", "Health", "Health Personnel", "Health system", "Individual", "Infrastructure", "Intensive Care", "International", "Interruption", "Intervention", "Interview", "Investments", "Maintenance", "Malawi", "Manuals", "Measures", "Methods", "Monitor", "Nurses", "Outcome", "Outpatients", "Patient Care", "Patient Monitoring", "Patient-Focused Outcomes", "Patients", "Persons", "Population", "Program Evaluation", "Provider", "Quality of Care", "Reach Effectiveness Adoption Implementation and Maintenance", "Research Priority", "Resources", "Risk", "Rural", "Series", "Service delivery model", "Site", "System", "Tablets", "Technology", "Testing", "Time", "Time and Motion Studies", "Training and Education", "Treatment Failure", "Trust", "Universities", "Viral", "Washington", "Workload", "antiretroviral therapy", "base", "care delivery", "clinical decision-making", "coronavirus disease", "cost", "cost estimate", "data quality", "design", "digital", "digital health", "falls", "implementation research", "implementation science", "improved", "informant", "innovation", "literacy", "low income country", "mHealth", "open source", "point of care", "pressure", "program costs", "programs", "scale up", "secondary outcome", "service delivery", "therapy outcome", "usability", "user centered design" ], "approved": true } }, { "type": "Grant", "id": "10925", "attributes": { "award_id": "5R21MH127992-02", "title": "The Community-based ART REtention and Suppression (CARES) App: an innovation to improve patient monitoring and evaluation data in community-based antiretroviral therapy programs in Lilongwe, Malawi", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Mental Health (NIMH)" ], "program_reference_codes": [], "program_officials": [ { "id": 22665, "first_name": "Christopher M.", "last_name": "Gordon", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-01-01", "end_date": "2023-12-31", "award_amount": 199090, "principal_investigator": { "id": 22666, "first_name": "Caryl", "last_name": "Feldacker", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 159, "ror": "https://ror.org/00cvxb145", "name": "University of Washington", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 22667, "first_name": "Hannock Mukoma", "last_name": "Tweya", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 159, "ror": "https://ror.org/00cvxb145", "name": "University of Washington", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true }, "abstract": "Differentiated service delivery (DSD) increases antiretroviral therapy (ART) access in sub-Saharan Africa (SSA) by moving patients out of congested ART clinics to communities for care. Patient outcomes in DSD and traditional clinic-based care appear similar at lower cost. Decreased donor funding, health system constraints, healthcare worker (HCW) shortages, and COVID-related calls to reduce clinic visits, push DSD expansion. But, DSD settings challenge routine patient monitoring and evaluation (M&E) required to ensure quality care, risking viral suppression (VS), scarce resources, and epidemic control. Electronic medical record systems (EMRs) ensure effective patient M&E in compliance with complex guidelines, improving patient outcomes and reducing workload. Yet, despite decades of SSA EMRs investment, EMRs benefits do not extend to low resource/low infrastructure settings where the majority of DSD occurs. How to optimize collection and use of high quality M&E for DSD patient care is a critical implementation research priority. Lighthouse Trust (LT) operates two Ministry of Health (MoH) clinics in Lilongwe, Malawi, with combined >35,000 ART patients. LT’s real-time, point-of-care (POC) EMRs collects complex M&E data and provides decision-making support, ensuring adherence to integrated HIV/TB guidelines that optimize patient and program outcomes. LT’s EMRs scaled to all large MoH ART clinics. LT implements a nurse-led community-based ART program (NCAP), a DSD model to provide ART and rapid assessment to 2400 stable LT patients in the community. LT’s EMRs requires consistent power and server access. Without EMRs, NCAP providers lack embedded prompts and alerts, reducing integrated MoH ART guideline compliance. NCAP M&E is incomplete and burdensome, leaving data gaps that lessen VS monitoring and care continuity. Poor M&E limits NCAP expansion. Therefore, University of Washington’s International Training and Education Center for Health, LT, and Medic seek to leverage a proven, open-source digital health framework to design, deploy, and assess an offline-first, user-centered, battery-operated App, “Community-based ART REtention and Suppression” (CARES). Apps are faster to design, simpler to deploy, cheaper to maintain, and operate without constant connectivity or electricity. CARES brings a POC EMRs-like App to NCAP with real-time benefits for optimal, integrated patient care. CARES captures complete patient M&E data and syncs to facility EMRs, improving data quality while reducing workload. Guided by implementation science, we use a quasi-experimental, interrupted time-series design to assess NCAP patient care, pre- and post-CARES. Mixed-methods evaluate CARES effect on NCAP patient outcomes, data quality, workload, and cost. Aims: 1) Assess how CARES ensures high quality NCAP patient outcomes using RE-AIM to gauge reach, effectiveness, adoption, implementation, and maintenance; and 2) Estimate CARES cost to improve M&E using a systems perspective. We hypothesize that CARES increases NCAP on-time, annual VS testing from 65% to 80% at lower cost. COVID19 raises potential impact of this App to strengthen integrated DSD care provision and to provide M&E evidence on DSD patient and program outcomes.", "keywords": [ "Acquired Immunodeficiency Syndrome", "Adherence", "Adoption", "Africa South of the Sahara", "COVID-19", "Caring", "Clinic", "Clinic Visits", "Collection", "Communities", "Complement", "Complex", "Computerized Medical Record", "Continuity of Patient Care", "Cost Analysis", "Cost Effectiveness Analysis", "Data", "Database Management Systems", "Decision Making", "Development", "Effectiveness", "Electricity", "Emergency Situation", "Ensure", "Epidemic", "Evaluation", "Face", "Funding", "Future", "Government", "Guideline Adherence", "Guidelines", "HIV", "HIV/TB", "Health", "Health Personnel", "Health system", "Individual", "Infrastructure", "Intensive Care", "International", "Interruption", "Intervention", "Interview", "Investments", "Maintenance", "Malawi", "Manuals", "Measures", "Methods", "Monitor", "Nurses", "Nursing Assessment", "Outcome", "Patient Care", "Patient Monitoring", "Patient-Focused Outcomes", "Patients", "Persons", "Population", "Printing", "Program Evaluation", "Provider", "Quality of Care", "Quasi-experiment", "Reach Effectiveness Adoption Implementation and Maintenance", "Research Priority", "Resources", "Risk", "Rural", "Series", "Service delivery model", "Site", "System", "Tablets", "Technology", "Testing", "Time", "Time and Motion Studies", "Training and Education", "Treatment Failure", "Trust", "Universities", "Viral", "Washington", "Workload", "antiretroviral therapy", "base", "care delivery", "clinical decision-making", "coronavirus disease", "cost", "cost estimate", "data quality", "data reduction", "design", "digital", "digital health", "falls", "implementation research", "implementation science", "improved", "informant", "innovation", "integrated care", "literacy", "low income country", "mHealth", "open source", "point of care", "pressure", "program costs", "programs", "scale up", "secondary outcome", "service delivery", "therapy outcome", "usability", "user centered design" ], "approved": true } }, { "type": "Grant", "id": "10986", "attributes": { "award_id": "5I01CX002322-02", "title": "Neural and cognitive consequences of COVID-19 survival.", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2021-10-01", "end_date": "2025-09-30", "award_amount": null, "principal_investigator": { "id": 22671, "first_name": "Judith M", "last_name": "Ford", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1522, "ror": "", "name": "VETERANS AFFAIRS MED CTR SAN FRANCISCO", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 22672, "first_name": "Lynn", "last_name": "PULLIAM", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 1522, "ror": "", "name": "VETERANS AFFAIRS MED CTR SAN FRANCISCO", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "The SARS-CoV-2 pandemic has been going on for over a year worldwide, with 115,000,000 confirmed cases and over 2,500,000 deaths (as of Mar 3, 2021). We are seeing people recover from the initial COVID19 infection with complaints of ongoing problems. An increasing number of people are complaining of cognitive deficits and depression/anxiety. Veterans are at a higher risk of COVID19 infection as well as suffering complications due to a number of co-morbidities. Veterans with neurocognitive complications may experience premature aging and neurodegeneration that could manifest as a huge burden for health care. We have brought together two laboratories studying neurocognitive impairment using an EEG, MRI, and behavioral approach as well as laboratory-based data. The Ford lab proposes to query neuropsychological function in Veterans using a computerized internet-based neuropsychological battery, EEG-based measures, functional MRI (connectivity) and structural MRI (gray and white matter volumes, myelin, micro-bleeds). The Pulliam lab has preliminary data to show a continued increase in plasma cytokines in COVID19 survivors. Plasma isolated neuronal enriched extracellular vesicles (nEVs) showed an increase in amyloid beta, neurofilament light and pT181- Tau, all proteins associated with neurodegeneration. The Overall Aim is to determine the extent of the cognitive, clinical, and neurological damage in people recovered from COVID19. The Specific Aims are to: 1) characterize neuropsychological function in COVID19 survivors, 2) assess EEG and MRI data in COVID19 survivors, 3) determine whether peripheral inflammation and markers of neuroinflammation, aging, and neurodegeneration persist in nEVs, and 4) explore relationships between neurodegenerative and inflammatory blood markers and EEG/MRI/NP measures while considering pre-existing co-morbidities and complications of COVID19.", "keywords": [ "Age", "Aging", "Amyloid beta-Protein", "Anxiety", "Attention", "Auditory", "Behavioral", "Biological", "Biological Assay", "Biological Markers", "Blood", "Blood Vessels", "Brain", "Brain imaging", "COVID-19", "COVID-19 complications", "COVID-19 impact", "COVID-19 pandemic", "COVID-19 survivors", "Cells", "Cessation of life", "Clinic", "Clinical", "Cognition", "Cognitive", "Cognitive deficits", "Collaborations", "Data", "Diabetes Mellitus", "Electroencephalography", "Event", "Event-Related Potentials", "Functional disorder", "HIV", "Healthcare", "Impaired cognition", "Infection", "Inflammation", "Inflammatory", "Internet", "Laboratories", "Laboratory Study", "Light", "Lung", "Measures", "Memory", "Mental Depression", "Myelin", "Nerve Degeneration", "Nervous System Trauma", "Neural Cell Adhesion Molecule L1", "Neurocognitive", "Neurocognitive Deficit", "Neurologic", "Neuronal Dysfunction", "Neurons", "Neurophysiology - biologic function", "Neuropsychology", "Obesity", "P300 Event-Related Potentials", "Parents", "Pathologic", "Patient Recruitments", "Peripheral", "Persons", "Pilot Projects", "Plasma", "Precipitation", "Premature aging syndrome", "Proteins", "Psychological Tests", "Reporting", "Rest", "SARS-CoV-2 infection", "SARS-CoV-2 positive", "San Francisco", "Signal Transduction", "Smoking", "Techniques", "Time", "Translating", "Veterans", "Work", "base", "body system", "cell injury", "cognitive function", "comorbidity", "computerized", "cytokine", "experience", "experimental study", "extracellular vesicles", "gray matter", "high risk", "imaging modality", "long-term sequelae", "neurofilament", "neuroimaging", "neuroinflammation", "neurophysiology", "novel coronavirus", "post SARS-CoV-2 infection", "relating to nervous system", "response", "tau Proteins", "white matter" ], "approved": true } }, { "type": "Grant", "id": "6841", "attributes": { "award_id": "1I01CX002322-01A1", "title": "Neural and cognitive consequences of COVID-19 survival.", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2021-10-01", "end_date": "2025-09-30", "award_amount": null, "principal_investigator": { "id": 22671, "first_name": "Judith M", "last_name": "Ford", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1522, "ror": "", "name": "VETERANS AFFAIRS MED CTR SAN FRANCISCO", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 22672, "first_name": "Lynn", "last_name": "PULLIAM", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 1522, "ror": "", "name": "VETERANS AFFAIRS MED CTR SAN FRANCISCO", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "The SARS-CoV-2 pandemic has been going on for over a year worldwide, with 115,000,000 confirmed cases and over 2,500,000 deaths (as of Mar 3, 2021). We are seeing people recover from the initial COVID19 infection with complaints of ongoing problems. An increasing number of people are complaining of cognitive deficits and depression/anxiety. Veterans are at a higher risk of COVID19 infection as well as suffering complications due to a number of co-morbidities. Veterans with neurocognitive complications may experience premature aging and neurodegeneration that could manifest as a huge burden for health care. We have brought together two laboratories studying neurocognitive impairment using an EEG, MRI, and behavioral approach as well as laboratory-based data. The Ford lab proposes to query neuropsychological function in Veterans using a computerized internet-based neuropsychological battery, EEG-based measures, functional MRI (connectivity) and structural MRI (gray and white matter volumes, myelin, micro-bleeds). The Pulliam lab has preliminary data to show a continued increase in plasma cytokines in COVID19 survivors. Plasma isolated neuronal enriched extracellular vesicles (nEVs) showed an increase in amyloid beta, neurofilament light and pT181- Tau, all proteins associated with neurodegeneration. The Overall Aim is to determine the extent of the cognitive, clinical, and neurological damage in people recovered from COVID19. The Specific Aims are to: 1) characterize neuropsychological function in COVID19 survivors, 2) assess EEG and MRI data in COVID19 survivors, 3) determine whether peripheral inflammation and markers of neuroinflammation, aging, and neurodegeneration persist in nEVs, and 4) explore relationships between neurodegenerative and inflammatory blood markers and EEG/MRI/NP measures while considering pre-existing co-morbidities and complications of COVID19.", "keywords": [ "Age", "Aging", "Amyloid beta-Protein", "Anxiety", "Attention", "Auditory", "Behavioral", "Biological", "Biological Assay", "Biological Markers", "Blood", "Blood Vessels", "Brain", "Brain imaging", "COVID-19", "COVID-19 complications", "COVID-19 pandemic", "COVID-19 survivors", "Cells", "Cessation of life", "Clinic", "Clinical", "Cognition", "Cognitive", "Cognitive deficits", "Collaborations", "Data", "Diabetes Mellitus", "Electroencephalography", "Event", "Event-Related Potentials", "Functional Magnetic Resonance Imaging", "Functional disorder", "HIV", "Healthcare", "Impaired cognition", "Infection", "Inflammatory", "Internet", "Laboratories", "Laboratory Study", "Light", "Lung", "Magnetic Resonance Imaging", "Measures", "Memory", "Mental Depression", "Methods", "Myelin", "Nerve Degeneration", "Nervous System Trauma", "Neural Cell Adhesion Molecule L1", "Neurocognitive", "Neurocognitive Deficit", "Neurologic", "Neuronal Dysfunction", "Neurons", "Neurophysiology - biologic function", "Neuropsychology", "Obesity", "P300 Event-Related Potentials", "Parents", "Pathologic", "Patient Recruitments", "Peripheral", "Persons", "Pilot Projects", "Plasma", "Precipitation", "Premature aging syndrome", "Proteins", "Psychological Tests", "Reporting", "Rest", "SARS-CoV-2 infection", "SARS-CoV-2 positive", "San Francisco", "Signal Transduction", "Smoking", "Techniques", "Time", "Translating", "Veterans", "Work", "base", "body system", "cell injury", "cognitive function", "comorbidity", "computerized", "coronavirus disease", "cytokine", "experience", "experimental study", "extracellular vesicles", "gray matter", "high risk", "inflammatory marker", "long-term sequelae", "magnetic resonance imaging/electroencephalography", "neurofilament", "neuroimaging", "neuroinflammation", "neurophysiology", "novel coronavirus", "post-COVID-19", "relating to nervous system", "response", "tau Proteins", "white matter" ], "approved": true } }, { "type": "Grant", "id": "6842", "attributes": { "award_id": "1R21GM146142-01", "title": "Multiomic, mass spectrometry-based analysis of dried blood for deep phenotyping of sepsis", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of General Medical Sciences (NIGMS)" ], "program_reference_codes": [], "program_officials": [ { "id": 22300, "first_name": "XIAOLI", "last_name": "Zhao", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-04-01", "end_date": "2024-03-31", "award_amount": 201250, "principal_investigator": { "id": 22673, "first_name": "Matthew Wolf", "last_name": "Foster", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 246, "ror": "https://ror.org/00py81415", "name": "Duke University", "address": "", "city": "", "state": "NC", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 22674, "first_name": "TIMOTHY J", "last_name": "MCMAHON", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 246, "ror": "https://ror.org/00py81415", "name": "Duke University", "address": "", "city": "", "state": "NC", "zip": "", "country": "United States", "approved": true }, "abstract": "Sepsis, which is characterized by life threatening organ dysfunction caused by an uncontrolled host response to infection, is the leading cause of death in hospitals and is responsible for >250,000 deaths per year in the U.S. at the cost of over $20 billion in patient care. Sepsis has a mortality rate nearing 50% at 2 years, which has profound implications for patients recovering from severe COVID-19, a form of viral sepsis. Because sepsis is a multi-organ disease, the quantification of circulating proteins and metabolites is central to the profiling of sepsis and of its long-term effects, and some such assays (lactate, procalcitonin) have become the standard of care. To date, the majority of studies, and particularly the large number in COVID-19 sepsis, have profiled plasma and serum, which, compared to whole blood is fraught with variability and belies the important roles of the erythrocyte and other cell-types. To this end, biorepositories at Duke University, which are banking samples from COVID- 19 sepsis patients in the intensive care unit (ICU) and in a post-COVID outpatient clinic, have been utilizing volumetric absorptive microsampling (VAMS) on Neoteryx Mitra tips to collect and store whole blood specimens for future ‘omic analyses. The overarching goals of this application are to develop and validate multiomic methods for mass spectrometry-based quantification of proteins and metabolites from Mitra tips that comprehensively profile sepsis pathobiology. In the R21 phase, we will develop and validate mass spectrometry-based methods for the non-targeted quantification of proteins and post-translational modifications (phosphorylation, glycosylation) in whole blood, and for targeted quantification of numerous metabolite classes. We will develop reference materials and standard operating procedures for inter-laboratory translation of these approaches. In the R33 phase, we will analyze proteins, PTMs and metabolites from over 600 patient timepoints from biorepositories containing longitudinal samples in critically ill sepsis and post-COVID-19 cohorts, and we will integrate these data with well-curated clinical datasets. Completion of these aims will establish the utility of blood sampling by VAMS for future sepsis studies and will create a highly curated clinical and deep multiomic dataset for future hypothesis generation.", "keywords": [ "Address", "Adoption", "Affect", "Ambulatory Care Facilities", "Antibiotics", "Bioethics", "Biological Assay", "Biology", "Blood", "Blood specimen", "C-reactive protein", "COVID-19", "Cause of Death", "Cells", "Cessation of life", "Clinical", "Clinical Data", "Clinical Management", "Code", "Collection", "Coupled", "Critical Illness", "Data", "Data Set", "Development", "Devices", "Disease", "Electronic Health Record", "Erythrocytes", "Exhibits", "Functional disorder", "Future", "Generations", "Goals", "Hospitals", "IV Fluid", "Immune response", "Immune signaling", "In Vitro", "Infection", "Intensive Care Units", "Laboratories", "Life", "Liquid Chromatography", "Long-Term Effects", "Mass Spectrum Analysis", "Metabolism", "Methodology", "Methods", "Morbidity - disease rate", "Multiomic Data", "Organ", "Outcome", "Pathway Analysis", "Pathway interactions", "Patient Care", "Patients", "Persons", "Phase", "Phenotype", "Phosphorylation", "Pilot Projects", "Plasma", "Post-Translational Protein Processing", "Preparation", "Procedures", "Proteins", "Proteome", "Proteomics", "Pythons", "Quality Control", "Recovery", "Reporting", "Role", "Sampling", "Sepsis", "Shipping", "Signal Pathway", "Signal Transduction", "Standardization", "Techniques", "Tissues", "Translations", "Universities", "Validation", "Viremia", "Whole Blood", "Work", "base", "biobank", "cell type", "cohort", "cost", "data repository", "demographics", "glycosylation", "high throughput screening", "metabolome", "metabolomics", "mortality", "multidisciplinary", "multiple omics", "novel", "post-COVID-19", "procalcitonin", "protein metabolite", "protein profiling", "septic patients", "severe COVID-19", "stability testing", "standard of care", "tandem mass spectrometry", "translational scientist" ], "approved": true } }, { "type": "Grant", "id": "11608", "attributes": { "award_id": "5R21GM146142-02", "title": "Multiomic, mass spectrometry-based analysis of dried blood for deep phenotyping of sepsis", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of General Medical Sciences (NIGMS)" ], "program_reference_codes": [], "program_officials": [ { "id": 22300, "first_name": "XIAOLI", "last_name": "Zhao", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-04-01", "end_date": "2024-03-31", "award_amount": 237615, "principal_investigator": { "id": 22673, "first_name": "Matthew Wolf", "last_name": "Foster", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 246, "ror": "https://ror.org/00py81415", "name": "Duke University", "address": "", "city": "", "state": "NC", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 22674, "first_name": "TIMOTHY J", "last_name": "MCMAHON", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 246, "ror": "https://ror.org/00py81415", "name": "Duke University", "address": "", "city": "", "state": "NC", "zip": "", "country": "United States", "approved": true }, "abstract": "Sepsis, which is characterized by life threatening organ dysfunction caused by an uncontrolled host response to infection, is the leading cause of death in hospitals and is responsible for >250,000 deaths per year in the U.S. at the cost of over $20 billion in patient care. Sepsis has a mortality rate nearing 50% at 2 years, which has profound implications for patients recovering from severe COVID-19, a form of viral sepsis. Because sepsis is a multi-organ disease, the quantification of circulating proteins and metabolites is central to the profiling of sepsis and of its long-term effects, and some such assays (lactate, procalcitonin) have become the standard of care. To date, the majority of studies, and particularly the large number in COVID-19 sepsis, have profiled plasma and serum, which, compared to whole blood is fraught with variability and belies the important roles of the erythrocyte and other cell-types. To this end, biorepositories at Duke University, which are banking samples from COVID- 19 sepsis patients in the intensive care unit (ICU) and in a post-COVID outpatient clinic, have been utilizing volumetric absorptive microsampling (VAMS) on Neoteryx Mitra tips to collect and store whole blood specimens for future ‘omic analyses. The overarching goals of this application are to develop and validate multiomic methods for mass spectrometry-based quantification of proteins and metabolites from Mitra tips that comprehensively profile sepsis pathobiology. In the R21 phase, we will develop and validate mass spectrometry-based methods for the non-targeted quantification of proteins and post-translational modifications (phosphorylation, glycosylation) in whole blood, and for targeted quantification of numerous metabolite classes. We will develop reference materials and standard operating procedures for inter-laboratory translation of these approaches. In the R33 phase, we will analyze proteins, PTMs and metabolites from over 600 patient timepoints from biorepositories containing longitudinal samples in critically ill sepsis and post-COVID-19 cohorts, and we will integrate these data with well-curated clinical datasets. Completion of these aims will establish the utility of blood sampling by VAMS for future sepsis studies and will create a highly curated clinical and deep multiomic dataset for future hypothesis generation.", "keywords": [ "Address", "Adoption", "Affect", "Ambulatory Care Facilities", "Antibiotics", "Biological Assay", "Biology", "Blood", "Blood specimen", "C-reactive protein", "COVID-19", "Cause of Death", "Cells", "Cessation of life", "Clinical", "Clinical Data", "Clinical Management", "Code", "Collecting Cell", "Collection", "Coupled", "Critical Illness", "Data", "Data Set", "Development", "Devices", "Disease", "Dryness", "Electronic Health Record", "Erythrocytes", "Exhibits", "Functional disorder", "Future", "Generations", "Goals", "Hospitals", "IV Fluid", "Immune response", "Immune signaling", "In Vitro", "Infection", "Intensive Care Units", "Laboratories", "Life", "Liquid Chromatography", "Long-Term Effects", "Mass Spectrum Analysis", "Metabolism", "Methodology", "Methods", "Morbidity - disease rate", "Multiomic Data", "Organ", "Outcome", "Pathway Analysis", "Pathway interactions", "Patient Care", "Patient Selection", "Patients", "Persons", "Phase", "Phenotype", "Phosphorylation", "Pilot Projects", "Plasma", "Post-Translational Protein Processing", "Preparation", "Procedures", "Proteins", "Proteome", "Proteomics", "Pythons", "Quality Control", "Recovery", "Reporting", "Role", "Sampling", "Sepsis", "Serum", "Shipping", "Signal Pathway", "Signal Transduction", "Standardization", "Techniques", "Tissues", "Translations", "Universities", "Validation", "Viremia", "Whole Blood", "Work", "biobank", "cell type", "cohort", "cost", "data integration", "data repository", "demographics", "glycosylation", "high throughput screening", "metabolome", "metabolomics", "mortality", "multidisciplinary", "multiple omics", "novel", "post-COVID-19", "procalcitonin", "protein profiling", "septic patients", "severe COVID-19", "stability testing", "standard of care", "tandem mass spectrometry", "translational approach", "translational scientist" ], "approved": true } }, { "type": "Grant", "id": "10890", "attributes": { "award_id": "5R21AI169548-02", "title": "Development and function of humoral immunity in the Jamaican fruit bat, Artibeus jamaicensis", "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": 8224, "first_name": "Kentner L.", "last_name": "Singleton", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-02-18", "end_date": "2024-01-31", "award_amount": 152000, "principal_investigator": { "id": 22677, "first_name": "Hannah Kim", "last_name": "Frank", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 811, "ror": "", "name": "TULANE UNIVERSITY OF LOUISIANA", "address": "", "city": "", "state": "LA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 22678, "first_name": "William A", "last_name": "Schountz", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 323, "ror": "https://ror.org/03k1gpj17", "name": "Colorado State University", "address": "", "city": "", "state": "CO", "zip": "", "country": "United States", "approved": true } ] } ], "awardee_organization": { "id": 811, "ror": "", "name": "TULANE UNIVERSITY OF LOUISIANA", "address": "", "city": "", "state": "LA", "zip": "", "country": "United States", "approved": true }, "abstract": "Bats host many viruses, seemingly without disease, that cause lethal infections in humans and other non-bat species, including rabies, Marburg fever virus and SARS-related coronaviruses. A greater understanding of the bat immune system – how it responds to viruses, how it differs from the human immune system – could lead to improved approaches for treating or even avoiding infection in humans. The immune response consists of two major branches: the nonspecific innate response and the pathogen-specific adaptive response. Although numerous studies have investigated innate immunity in bats, very little is known about their adaptive immune system. The long-term objective of the proposed research is to enhance understanding of adaptive immunity in bats. A key feature of adaptive immunity is humoral immunity; this immune response is mediated by antibodies, also known as immunoglobulins. The hyper-diverse immunoglobulin repertoire is generated through a combination of gene recombination, DNA insertions and deletions, and somatic mutation of the antibody sequence. While immunoglobulins have been detected in several serological studies of bats, the true extent of the diversity of bat immunoglobulin repertoires, the degree to which bats rely on gene rearrangement vs. somatic mutation to generate these repertoires, how mutation of the immunoglobulins correlates with neutralization of pathogens, or the B cell subsets that arise in response to infection remain unknown. The proposed study will use rabies virus vaccination followed by rabies virus infection in Jamaican fruit bats to generate the most comprehensive understanding of B cell-mediated adaptive immunity in bats to date. Jamaican fruit bats are common across Central and South America, where rabies remains a serious threat, and are naturally infected by rabies virus. This research will use long-read sequencing to characterize the germline genes that provide the starting diversity for the immunoglobulin repertoire. Next generation genomic techniques will be used to track the development of rearranged immunoglobulin repertoires, monitor expansion of specific B cell clones, and quantify the degree of somatic mutation in antigen-exposed antibodies across vaccination and challenge with rabies. Single-cell transcriptomics will be used to characterize the B cell subsets that arise in response to immune challenges, and binding assays and rabies neutralization tests will facilitate an understanding of how antibody maturation correlates with function. Comparison of the immune responses of bats to vaccination and infection will be used to investigate immunity in controlled and natural contexts. This research will provide important information on the adaptive immune system of bats that is currently lacking. These data will provide insight into the differences in immune responses between bats and humans to a shared pathogen and can be used to develop new rabies prevention or intervention approaches. The framework and immunological data generated by this project will also allow for specific investigations of B-cell mediated immunity to any infection.", "keywords": [ "Adaptive Immune System", "Address", "Affinity", "Aliquot", "Animals", "Antibodies", "Antibody Repertoire", "Antibody Response", "Antibody titer measurement", "Antigens", "Avidity", "B-Cell Antigen Receptor", "B-Cell Development", "B-Lymphocyte Subsets", "B-Lymphocytes", "Binding", "Biological Assay", "Blood specimen", "Body Size", "Cell Culture Techniques", "Cells", "Cellular Immunity", "Central America", "Chiroptera", "Clonal Expansion", "Clone Cells", "Communicable Diseases", "Comparative Genomic Analysis", "DNA", "Data", "Development", "Disease", "Exposure to", "Fever", "Frequencies", "Fruit", "Future", "Gene Combinations", "Gene Rearrangement", "Genes", "Genetic", "Genetic Recombination", "Genomic DNA", "Genomics", "Health", "Human", "Humoral Immunities", "Immune", "Immune response", "Immune system", "Immunity", "Immunoglobulin Class Switching", "Immunoglobulin G", "Immunoglobulin Isotypes", "Immunoglobulin Somatic Hypermutation", "Immunoglobulin Switch Recombination", "Immunoglobulins", "Immunologic Memory", "Immunologics", "Individual", "Infection", "Intervention", "Investigation", "Jamaican", "Knowledge", "Malignant Neoplasms", "Marburgvirus", "Measures", "Mediating", "Memory", "Memory B-Lymphocyte", "Monitor", "Mutate", "Mutation", "Natural Immunity", "Neutralization Tests", "Organ", "Organism", "Population", "Prevention", "Public Health", "Rabies", "Rabies virus", "Reagent", "Research", "Research Personnel", "Role", "SARS coronavirus", "Serology", "Somatic Mutation", "South America", "T-Lymphocyte", "Techniques", "Testing", "Time", "Vaccinated", "Vaccination", "Vaccines", "Viral", "Virus", "Virus Diseases", "Zoonoses", "adaptive immunity", "bat-borne", "cell mediated immune response", "cell type", "cohort", "experience", "experimental study", "immunoglobulin receptor", "improved", "insertion/deletion mutation", "insight", "next generation", "pathogen", "peripheral blood", "prevent", "receptor", "response", "transcriptome", "transcriptomics" ], "approved": true } } ], "meta": { "pagination": { "page": 1384, "pages": 1424, "count": 14236 } } }