Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1419&sort=principal_investigator
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=principal_investigator", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1424&sort=principal_investigator", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1420&sort=principal_investigator", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1418&sort=principal_investigator" }, "data": [ { "type": "Grant", "id": "15912", "attributes": { "award_id": "1F32AI191492-01", "title": "RANKL regulation of human B cell responses", "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": 32556, "first_name": "TIMOTHY A", "last_name": "GONDRE-LEWIS", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-07-01", "end_date": "2026-06-30", "award_amount": 88360, "principal_investigator": { "id": 44355, "first_name": "Jonathan J", "last_name": "Kotzin", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2627, "ror": "", "name": "UNIVERSITY OF PENNSYLVANIA", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true }, "abstract": "Improved understanding of B cell biology may uncover therapies that will restore immune tolerance in autoimmune disease with minimal safety risk. Tumor necrosis factor (TNF) superfamily members are key regulators of B cell biology, and blockade of several of these pathways has shown significant clinical benefit in autoimmunity with minimal infectious risk. For example, B cell activating factor (BAFF)-blockade provides benefit in lupus, a proliferation-inducing ligand (APRIL)-blockade provides benefit in IgA nephropathy, CD40L-blockade shows promise in Sjogren’s disease, and all these therapies are well-tolerated. TNF superfamily member receptor activator of NF-κB (RANK), and its ligand RANKL, are highly expressed by memory B cell subsets. Human genetic variation in RANK is associated with the autoantibody-mediated disease myasthenia gravis. In mice, transient blockade of RANKL increases the quantity of antigen-specific vaccine titers. Yet, the impact of RANKL on human humoral immunity remains unknown. Understanding RANK-RANKL B cell control in humans may identify a new pathway to augment antibody responses to vaccination or dampen autoantibody responses in autoimmunity with limited safety risk. To address this gap in knowledge, I captured the in vivo human experiment by collecting plasma and peripheral blood mononuclear cells from individuals receiving denosumab, an FDA approved RANKL-blocking antibody commonly used in the treatment of osteoporosis, and matched controls following Covid-19 booster vaccination. I observed a significant increase in Covid-specific IgG responses, total IgG1, and autoantibody formation to numerous self-antigens in individuals receiving RANKL- blockade. As RANK signaling can induce FAS in osteoclasts and FAS expression in B cells is a critical negative regulator of T cell-dependent B cell responses, I hypothesize that blockade of RANKL broadly increases human B cell responses to vaccination and self-antigen by impairing B cell FAS-mediated apoptosis. This hypothesis will be tested through the following 3 aims: 1) Determine the impact of RANKL-blockade on humoral and cellular immunity to recent Covid and influenza vaccination versus remote tetanus vaccination, 2) Define the site of impaired B cell tolerance and the pattern of autoantibodies following RANKL-blockade, and 3) Test the impact of RANKL-blockade on FAS-mediated B cell survival in vitro and in vivo. Collectively, these studies will address the existing knowledge gap of RANKL control of human B cell responses and may provide the foundation to target RANK-RANKL to tune human humoral immunity.", "keywords": [ "Active Immunization", "Address", "Age", "Antibodies", "Antibody Response", "Antigens", "Apoptosis", "Apoptotic", "Autoantibodies", "Autoantigens", "Autoimmune Diseases", "Autoimmunity", "B-Cell Activation", "B-Lymphocyte Subsets", "B-Lymphocytes", "B-cell receptor repertoire sequencing", "Bioinformatics", "Biology", "Blocking Antibodies", "CD95 Antigens", "COVID-19 booster", "COVID-19 vaccination", "Cell Survival", "Cells", "Cellular Immunity", "Cellular Immunology", "Cellular biology", "Clinical", "Collaborations", "Coombs' Test", "Data", "Defect", "Disease", "Distant", "Emigrant", "Enzyme-Linked Immunosorbent Assay", "Erythrocytes", "Exclusion", "FDA approved", "Flow Cytometry", "Foundations", "Gene Expression Profiling", "Genetic Variation", "Germ Lines", "Human", "Human Genetics", "Humoral Immunities", "IGA Glomerulonephritis", "IgG1", "Immune", "Immune Tolerance", "Immunity", "Immunoglobulin G", "Immunology", "Impairment", "In Vitro", "Indirect Immunofluorescence", "Individual", "Influenza vaccination", "Knowledge", "Ligands", "Lupus", "Measures", "Mediating", "Memory B-Lymphocyte", "Mentors", "Mus", "Myasthenia Gravis", "Osteoclasts", "Osteoporosis", "Pathway interactions", "Patients", "Pattern", "Peripheral Blood Mononuclear Cell", "Phage ImmunoPrecipitation Sequencing", "Pharmaceutical Preparations", "Phenotype", "Physicians", "Plasma", "Proliferating", "Regulation", "Research", "Risk", "Role", "SARS-CoV-2 variant", "Safety", "Sampling", "Scientist", "Secondary Immunization", "Signal Transduction", "Site", "Sjogren's Syndrome", "Specificity", "T-Lymphocyte", "TNF gene", "TNFSF11 gene", "TNFSF5 gene", "TNFSF6 gene", "Techniques", "Testing", "Tetanus", "Time", "Vaccination", "Vaccines", "Work", "absorption", "autoreactivity", "bisphosphonate", "cohort", "experience", "experimental study", "genetic variant", "improved", "in vivo", "insight", "lens", "member", "neutralizing antibody", "novel", "peripheral tolerance", "receptor", "receptor binding", "response", "skills", "standard of care" ], "approved": true } }, { "type": "Grant", "id": "15913", "attributes": { "award_id": "1R21AI194204-01", "title": "Notch regulation of airway epithelial-immune cell cross-talk in SARS-CoV-2 infection", "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": 32599, "first_name": "MICHELLE MARIE", "last_name": "ARNOLD", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-07-09", "end_date": "2027-06-30", "award_amount": 448688, "principal_investigator": { "id": 44356, "first_name": "Susan", "last_name": "Kovats", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 44357, "first_name": "Matthew Stuart", "last_name": "Walters", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 3399, "ror": "", "name": "OKLAHOMA MEDICAL RESEARCH FOUNDATION", "address": "", "city": "", "state": "OK", "zip": "", "country": "United States", "approved": true }, "abstract": "Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of COVID-19. Infection with SARS-CoV-2 begins in epithelial cells of the upper airways, which triggers multiple antiviral responses that activate myeloid immune cells, coordinate the early innate immune response, and limit viral spread. Notably, our understanding of the cell signaling mechanisms that regulate early epithelial-immune cell interactions and induction of tissue pathology during SARS-CoV-2 infection of the human airway remains limited. To investigate these processes, we have developed a novel in vitro all human 3D model of the upper airways (HUA) composed of layers of primary differentiated airway epithelial cells expressing ACE2, lung fibroblasts in a collagen matrix, and pulmonary endothelial cells, with myeloid cells present in each layer. SARS-CoV-2 infection of the HUA model results in virus replication and induction of an immune response reminiscent of in vivo infection, and the presence of myeloid cells limits viral replication. Therefore, we will use the HUA model to perform kinetic studies of the mechanisms by which human airway cells interact to regulate virus-host interactions, inflammation, and tissue pathology associated with SARS-CoV-2. We will focus on the Notch pathway, which acts via direct cell- to-cell signaling to regulate airway epithelial cell fate decisions as well as myeloid cell maintenance, Toll-like receptor signaling, pro-inflammatory polarization, and antiviral functions. However, the mechanisms by which Notch signaling regulates airway epithelial-myeloid cell interactions during SARS-CoV-2 infection remain unknown. Our preliminary analyses showed that airway epithelial cells and myeloid cells express multiple Notch ligands and receptors in uninfected HUA models, suggesting that the Notch pathway will mediate bidirectional crosstalk during the airway response to infection. We will test the central hypothesis that Notch receptor signaling in myeloid cells regulates their pro-inflammatory phenotype, thereby promoting the host innate antiviral immune response and contributing to airway epithelial cell damage and remodeling during SARS-CoV-2 infection. Using lentivirus vectors and inducible expression systems, we will attenuate expression of individual Notch ligands and receptors in a cell-type specific and temporal manner. Following SARS-CoV-2 infection, we will quantify the impact of reducing Notch signaling activity on virus replication, myeloid cell phenotypes, the host immune response, and airway epithelial remodeling. The data collected in this study will advance our understanding of the mechanisms that regulate airway epithelial-immune cell interactions during SARS-CoV-2 infection and may identify candidate therapeutic targets in the Notch pathway to enhance antiviral immunity and reduce epithelial injury and remodeling in the upper airway.", "keywords": [ "2019-nCoV", "ACE2", "Address", "Anti-viral Response", "Anti-viral Therapy", "Attenuated", "COVID-19", "COVID-19 treatment", "Cell Communication", "Cell Differentiation process", "Cell Maintenance", "Cell Separation", "Cells", "Cessation of life", "Collagen", "Data", "Dendritic Cells", "Endothelial Cells", "Environment", "Epithelial Cells", "Epithelium", "Fibroblasts", "Gene Modified", "Human", "Immune", "Immune response", "In Vitro", "Individual", "Infection", "Inflammation", "Inflammatory", "Innate Immune Response", "Kinetics", "Lentivirus Vector", "Ligands", "Lung", "Macrophage", "Maintenance", "Mediating", "Membrane", "Modeling", "Myelogenous", "Myeloid Cells", "NOTCH1 gene", "Notch Signaling Pathway", "Pathology", "Pathway interactions", "Phenotype", "Play", "Process", "Receptor Signaling", "Regulation", "Role", "SARS-CoV-2 infection", "Shapes", "Signal Transduction", "Structure of parenchyma of lung", "System", "Testing", "Tissue Model", "Tissues", "Toll-like receptors", "Viral", "Viral Physiology", "Virus", "Virus Activation", "Virus Replication", "airway epithelium", "antiviral immunity", "candidate identification", "cell injury", "cell type", "epithelial injury", "human disease", "in vivo", "inducible gene expression", "lung injury", "lung microvascular endothelial cells", "lung repair", "monocyte", "notch protein", "novel", "pandemic disease", "post SARS-CoV-2 infection", "pulmonary", "receptor", "respiratory infection virus", "respiratory virus", "response", "single-cell RNA sequencing", "therapeutic target", "three-dimensional modeling", "virus host interaction" ], "approved": true } }, { "type": "Grant", "id": "15914", "attributes": { "award_id": "1K99CA293268-01A1", "title": "Deciphering the Transcriptomic Basis of Chemo Fog", "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": 44358, "first_name": "MICHAEL K", "last_name": "SCHMIDT", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-07-01", "end_date": "2027-06-30", "award_amount": 135513, "principal_investigator": { "id": 44359, "first_name": "Jonathan D", "last_name": "Lee", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3370, "ror": "", "name": "BETH ISRAEL DEACONESS MEDICAL CENTER", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "CANDIDATE: My long-term career objective is to lead an independent research program dedicated to improving the efficacy of cancer treatments and the post-treatment experiences of cancer survivors. This proposed research represents a convergence of my research experiences: to elucidate the transcriptional mechanisms underpinning cognitive impairment induced by cancer therapies, a critical issue affecting cancer survivors. In preparation for this transition to independence, I have curated a training plan encompassing four key objectives: (1) acquiring essential skills, (2) forging strategic scientific collaborations, (3) honing professional development, and (4) ensuring a seamless transition to independence. This proposal serves as a blueprint for my future research career in the field of cancer biology. RESEARCH: Chemotherapy, despite its life-saving potential, often leads to debilitating side effects such as cognitive impairment, significantly diminishing the quality of life for cancer survivors. Multiple studies have identified disturbances in brain cell homeostasis upon chemotherapy treatment, including neuronal death, disrupted myelination, and activated microglia. However, the transcriptional regulation governing these changes remains largely unclear. My early postdoctoral research revealed substantial transcriptional overlaps shared among various forms of cognitive impairment, including aging, Alzheimer's disease, and severe COVID-19. Yet, whether this transcriptional overlap, and more crucially, its regulatory mechanisms, extend to chemotherapy-induced cognitive impairment (CICI) remains unknown. Through comparative analysis of brain transcriptomic profiles of mice upon systemic chemotherapy treatment and other forms of cognitive impairment, I have identified candidate transcription factor drivers of CICI. This proposal will test the hypothesis that transcriptomic states (Aim 1) and key underlying transcription factor regulators (Aim 2) can be manipulated to modify CICI behaviors in mice (Aim 3). These investigations will illuminate the transcriptional underpinnings of cognitive impairment induced by chemotherapy, offering new insights into potential therapeutic strategies to ameliorate or reverse this debilitating side effect. ENVIRONMENT: The Harvard Medical School community provides an optimal setting for me to achieve my training and research objectives while successfully transitioning to an independent faculty position. My mentors, Dr. Frank Slack and Dr. Clifford Woolf, are global leaders in RNA biology and neuroscience, respectively. Additionally, I have assembled an advisory committee comprising three established scientists—Drs. Rosalind Segal, Winston Hide, and Marcia Haigis—with pertinent expertise and strong commitment to mentorship. Their support will be invaluable in guiding my research endeavors and facilitating my path toward independence. Combined with the intellectually rich and resource-abundant communities of BIDMC and BCH, this mentorship team will foster an ideal environment, enabling me to effectively execute the proposed research and transition to independence.", "keywords": [ "Advisory Committees", "Affect", "Aftercare", "Aging", "Alzheimer's Disease", "Applications Grants", "Attention", "Behavior", "Behavioral Assay", "Binding", "Biology", "Brain", "Cancer Biology", "Cancer Patient", "Cancer Survivor", "Candidate Disease Gene", "Chromatin", "Cisplatin", "Cognition Disorders", "Collaborations", "Communities", "Data Set", "Dedications", "Development", "Dose", "Ensure", "Environment", "Exhibits", "Faculty", "Female", "Fogs", "Folic Acid Antagonists", "Fostering", "Gene Expression Profile", "Genes", "Genetic Transcription", "Genomics", "Grant", "Homeostasis", "Human", "Impaired cognition", "Impairment", "Injections", "Investigation", "Lead", "Life", "Light", "Machine Learning", "Malignant Neoplasms", "Manuscripts", "Maps", "Memory", "Mentors", "Mentorship", "Methods", "Methotrexate", "Microglia", "Mining", "Modeling", "Mus", "Neurons", "Neuropathy", "Neurosciences", "Phase", "Physiology", "Positioning Attribute", "Postdoctoral Fellow", "Preparation", "Proteomics", "Quality of life", "RNA", "Research", "Resources", "Scientist", "Survival Rate", "Systems Biology", "Testing", "Therapeutic", "Therapeutic Intervention", "Time", "Training", "Transcriptional Regulation", "Treatment Side Effects", "United States National Institutes of Health", "Work", "adenovirus mediated delivery", "aging brain", "behavioral impairment", "behavioral phenotyping", "biological sex", "brain cell", "cancer survival", "cancer therapy", "candidate identification", "carcinogenesis", "career", "chemobrain", "chemotherapeutic agent", "chemotherapy", "chromatin protein", "cofactor", "cognitive function", "cohort", "comparative", "crosslink", "experience", "forging", "glial activation", "improved", "information processing", "insight", "invention", "knock-down", "male", "medical schools", "myelination", "neuro-oncology", "neuron loss", "personalized medicine", "programs", "quality of life for cancer survivors", "quality of life improvement", "scaffold", "severe COVID-19", "short hairpin RNA delivery", "side effect", "skills", "therapy development", "transcription factor", "transcriptome sequencing", "transcriptomic profiling", "transcriptomics", "treatment strategy" ], "approved": true } }, { "type": "Grant", "id": "15915", "attributes": { "award_id": "1R21AI187633-01A1", "title": "Develop novel iNOS/NO inhibitors for mitigating inflammatory cell death, ARDS, and MODS", "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": 32860, "first_name": "KENTNER L", "last_name": "SINGLETON", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-07-07", "end_date": "2027-06-30", "award_amount": 385625, "principal_investigator": { "id": 44360, "first_name": "Yuguo", "last_name": "Lei", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 833, "ror": "", "name": "PENNSYLVANIA STATE UNIVERSITY, THE", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true }, "abstract": "Many causes can trigger excessive production of inflammatory cytokines (i.e., cytokine storm). Elevated circulating cytokines induce extensive cell death (i.e., inflammatory cell death) that causes severe organ injuries, eventually leading to acute respiratory distress syndrome (ARDS) and multi-organ dysfunction (MODS). Patients with ARDS and MODS have extremely high mortality (~46%). There is an unmet clinical need for novel therapeutics capable of inhibiting inflammatory cell death to mitigate ARDS and MODS. Recent studies find that the excessive expression of inducible Nitric Oxide Synthase (iNOS) and over-production of nitric oxide (NO) play a critical role in inflammatory cell death. Therefore, inhibiting iNOS/NO represents a promising therapeutic approach. Hydrogen sulfide (H2S), a gaseous signaling molecule in our body, is known for its capability to inhibit iNOS and quench NO. However, due to its gaseous nature, its therapeutic application is limited by the challenge of administering a precise dose into the target cells sustainably. Preliminary studies developed five polymeric micelles containing H2S donating-anethole dithiolethione (ADT) groups to overcome the problem. The micelles enter cells via endocytosis and release H2S upon oxidation by reactive oxygens species (ROS) inside cells. The release rate can be controlled by changing the polymer design. The micelles have no significant cytotoxicity. In a proof-of-concept study, the micelles effectively inhibited cytokine-induced cell death. In short, the data show that the micelles are promising drug candidates. This project proposes systematically evaluating their therapeutic potential using vitro and mouse models, with the goal of gathering robust evidence to support their advancement into full drug development. The hypothesis is that the micelles can effectively mitigate iNOS/NO, inflammatory cell death, ARDS, and MODS. Aim 1 will test the hypothesis that micelles can mitigate iNOS/NO activity and inflammatory cell death in vitro. Aim 2 will test the hypothesis that micelles can mitigate cytokine storm, inflammatory cell death, organ injury, and mortality in mouse models. This project will collect essential efficacy/potency data, identify the most promising candidates, and provide valuable insights into polymer structure-property relationships to optimize these candidates further. The work is significant, as it has the potential to lead to novel therapeutics for managing ARDS and MODS, conditions responsible for ~11 million deaths annually. In terms of innovation, this is the first to investigate H₂S as an iNOS/NO inhibitor to reduce inflammatory cell death, cytokine storms, ARDS, and MODS. The micelle design is also highly innovative, enabling sustained, targeted, and ROS-responsive intracellular delivery of H₂S - a combination of features currently unmatched by any existing technology.", "keywords": [ "Acute Respiratory Distress Syndrome", "Address", "Affect", "Cell Death", "Cell Death Induction", "Cells", "Cessation of life", "Clinical", "Data", "Death Rate", "Dose", "Endocytosis", "Endothelial Cells", "Epithelial Cells", "Face", "Functional disorder", "Goals", "Hydrogen Sulfide", "Hydrophobicity", "In Vitro", "Inflammatory", "Macrophage", "Micelles", "NOS2A gene", "Nature", "Nitric Oxide", "Nitric Oxide Synthetase Inhibitor", "Organ", "Patients", "Play", "Polyethylene Glycols", "Polymers", "Pre-Clinical Model", "Production", "Property", "Reactive Oxygen Species", "Role", "Signaling Molecule", "Structure", "Syndrome", "Technology", "Testing", "Therapeutic", "Tissues", "Work", "cell type", "copolymer", "cytokine", "cytokine release syndrome", "cytotoxicity", "design", "dithiolethione", "drug candidate", "drug development", "hydrophilicity", "improved", "in vitro Model", "inducible gene expression", "innovation", "insight", "monocyte", "morpholine", "mortality", "mouse model", "novel", "novel therapeutics", "organ injury", "overexpression", "oxidation", "response", "self assembly" ], "approved": true } }, { "type": "Grant", "id": "15916", "attributes": { "award_id": "1R21AI187071-01", "title": "Long-lived highly differentiated monocyte-derived cells (LDMs) activate lung-resident CD8+ T cell memory", "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": 44361, "first_name": "HALONNA R", "last_name": "KELLY", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-07-07", "end_date": "2027-06-30", "award_amount": 415250, "principal_investigator": { "id": 44362, "first_name": "KIHONG", "last_name": "LIM", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2634, "ror": "", "name": "UNIVERSITY OF ROCHESTER", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "The lung, as it is constantly challenged, has a unique immune system, much of which is still underappreciated. Respiratory viral infection, including influenza and SARS-CoV-2, is among the worst burdens of disease worldwide and in the US, and especially viral pneumonia is one of the leading causes for irreversible tissue damage and death. Importantly, immune responses of the lung to the viral infection determine the outcome of these viral illnesses, so better understanding of the lung immunology is warranted. CD8+ T cells are the most important immune effector against viral infection of the respiratory organs because they significantly reduce virus burden and spread by eliminating infected cells. But T cell immunity is not an autonomous system and innate immune cells are required for the T cells to be functional. In the lung, dendritic cells (DCs) and macrophages play such regulatory roles in general. I had previously demonstrated that tissue- infiltrated monocytes are also important for efficient T cell immune responses during influenza infection of the lung and trachea, adding to the knowledge of innate immune regulation of T cell responses. Now I have strong evidence that the monocytes infiltrating into the lung during influenza virus infection further differentiate into a novel myeloid cell type, long-lived highly differentiated monocyte-derived cell (LDM), and the LDM cells persist in the lung for many months since recovery from the infection. I also obtained preliminary, but significant, data indicating that those LDM cells are a key regulator of lung-resident memory T cell (TRM). TRM is an effective cytolytic immune effector to protect hosts from recurrent infection, however current understanding of regulatory mechanisms for lung-resident T cell memory remains insufficient. We will address an unsolved issue in this field–how lung TRM is regulated by innate immunity. In Aim 1, it will be tested if LDM, not conventional DCs, activates lung TRM upon recurrent influenza infection using a LDM depletion mouse model that I newly developed. In Aim 2, I will investigate the mechanism(s) by which the LDM activates TRM. Through rechallenge of virus-immune mice with viral antigens, reconstituted in vitro cell assays and reporter assays that distinguish cytokine signals and TCR activation signal, it will be determined if the LDM is a lung-resident antigen presenting cell (APC) type for TRM activation. In Aim 3, to corroborate evidence that the LDM promotes TRM activation, interaction, migration and tissue localization of LDM and TRM in the lung will be investigated using cutting-edge lung imaging technologies.", "keywords": [ "2019-nCoV", "Antigen Presentation", "Antigen-Presenting Cells", "Biological Assay", "CD8-Positive T-Lymphocytes", "Cause of Death", "Cells", "Cellular Assay", "Cellular Immunity", "Cessation of life", "Communicable Diseases", "Cytokine Signaling", "Cytotoxic T-Lymphocytes", "Data", "Dendritic Cells", "Development", "Human", "Image", "Imaging technology", "Immune", "Immune response", "Immune system", "Immunity", "Immunologic Memory", "Immunology", "In Vitro", "Infection", "Infiltration", "Influenza", "Knowledge", "Lung", "Lung immune response", "Lung infections", "Macrophage", "Mediating", "Medical", "Memory", "Mus", "Myeloid Cells", "Natural Immunity", "Nature", "Organ", "Outcome", "Phenotype", "Play", "Pneumonia", "Population", "Recovery", "Recurrence", "Reporter", "Role", "Science", "Signal Transduction", "System", "T cell differentiation", "T cell response", "T memory cell", "T-Cell Activation", "T-Lymphocyte", "TCR Activation", "Testing", "Time", "Tissues", "Trachea", "Viral", "Viral Antigens", "Viral Pneumonia", "Viral Respiratory Tract Infection", "Virus", "Virus Diseases", "Vulnerable Populations", "burden of illness", "cell type", "chemokine", "cytokine", "cytotoxic CD8 T cells", "effective therapy", "immune function", "immunoregulation", "improved", "influenza infection", "lung imaging", "migration", "monocyte", "mouse model", "neutrophil", "novel", "novel vaccines", "pathogen", "reconstitution", "recruit", "recurrent infection", "respiratory", "respiratory infection virus", "respiratory virus", "response", "tissue resident memory T cell", "tool" ], "approved": true } }, { "type": "Grant", "id": "15918", "attributes": { "award_id": "1R21AI194052-01", "title": "Development of siRNA-peptide libraries for delivery screening", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 32536, "first_name": "DIPANWITA", "last_name": "BASU", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-07-09", "end_date": "2027-06-30", "award_amount": 506000, "principal_investigator": { "id": 44363, "first_name": "IAN JOHN", "last_name": "MACRAE", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 745, "ror": "", "name": "SCRIPPS RESEARCH INSTITUTE, THE", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Viral infections pose a major public health concern, affecting millions and contributing significantly to global mortality, as evidenced by the COVID-19 pandemic, which cut short over 7 million lives worldwide. The success of mRNA vaccines during this pandemic showcased the power of nucleic acid therapeutics in combating emerging viral threats. However, vaccines rely on the adaptive immune response, requiring time to mount protection and unable to treat ongoing infections. Small interfering RNAs (siRNAs) represent a promising class of nucleic acid therapeutics with the potential to overcome these limitations. siRNAs induce gene silencing by directly degrading targeted RNAs, offering rapid action and adaptability to emerging viral strains. These properties make siRNAs attractive for treating viral infections, with positive indications in models for many viruses on NIAID’s priority list, including Dengue Fever, Ebola, Hepatitis, Herpes, Human Papillomavirus, Influenza, Respiratory Syncytial Virus (RSV), Smallpox, West Nile Virus, and Zika Virus. Despite demonstrated efficacy in tissue culture and model systems, clinical translation of siRNAs is hampered by challenges in efficient delivery to target tissues. While the development of GalNAc-siRNA conjugates has led to FDA-approved liver-targeted therapies, scalable methods for screening siRNA delivery strategies in tissues beyond the liver are lacking. This proposal aims to address these limitations by developing high-throughput technologies for generating and screening siRNA-peptide conjugates—a novel approach to improving delivery efficiency and overcoming key bottlenecks of cellular uptake, endosomal escape, and siRNA activation. In Aim 1, we will adapt mRNA display, an established method for creating diverse mRNA-protein libraries, to synthesize compact siRNA-peptide conjugates. By encoding each peptide's amino acid sequence within its conjugated siRNA nucleotide sequence, we will create libraries with millions of variants, enabling high-throughput functional screening. In Aim 2, we will evaluate the functionality of these siRNA-peptide conjugates using biochemistry and small RNA sequencing (sRNA-seq) to identify those that successfully load into Argonaute 2 (Ago2), the enzyme that mediates silencing directed by siRNAs. This method allows for a direct, highly sensitive assessment of delivery efficiency and quantitative identification of the most promising siRNA conjugates for further development. Completion of this project will establish new technologies for high-throughput siRNA conjugate screening, facilitating the discovery of efficient delivery strategies for siRNA-based antiviral therapeutics across diverse biological contexts. This will significantly impact the treatment of viral infections, providing a pathway toward developing siRNA therapies that can rapidly respond to emerging viral threats, treat chronic infections, and protect vulnerable populations such as immunocompromised individuals. This work aligns with NIAID’s mission to combat infectious diseases through innovative therapeutics and the development of broadly applicable antiviral treatments.", "keywords": [ "Address", "Affect", "Amino Acid Sequence", "Anti-viral Agents", "Automobile Driving", "Base Sequence", "Biochemistry", "Biological", "Biological Assay", "Biological Models", "COVID-19 pandemic", "Cells", "Chemicals", "Code", "Communicable Diseases", "Complex", "Cyclic Peptides", "Cytoplasm", "Data", "Dengue Fever", "Development", "Disease", "Diversity Library", "Ebola", "Elements", "Endosomes", "Enzymes", "Event", "FDA approved", "Future", "Gene Silencing", "Generations", "Genes", "Goals", "Hepatitis", "High-Throughput Nucleotide Sequencing", "Human Papillomavirus", "Immunocompromised Host", "Individual", "Infection", "Influenza", "Intervention", "Lead", "Libraries", "Liver", "Mediating", "Messenger RNA", "Methodology", "Methods", "Mission", "Modeling", "Modern Medicine", "National Institute of Allergy and Infectious Disease", "Pathway interactions", "Peptide Library", "Peptides", "Property", "Proteins", "Public Health", "RNA", "RNA Degradation", "RNA vaccine", "Research", "Respiratory syncytial virus", "Small Interfering RNA", "Small RNA", "Smallpox", "Testing", "Therapeutic", "Time", "Tissue Model", "Tissues", "Vaccines", "Variant", "Viral", "Virus", "Virus Diseases", "Vulnerable Populations", "West Nile virus", "Work", "Zika Virus", "adaptive immune response", "chronic infection", "clinical translation", "combat", "detection method", "experimental study", "functional group", "high throughput screening", "high throughput technology", "improved", "in vivo", "innovation", "insight", "knock-down", "mortality", "new technology", "novel", "novel strategies", "nucleic acid-based therapeutics", "pandemic disease", "prophylactic", "protein aminoacid sequence", "screening", "siRNA delivery", "success", "targeted treatment", "therapeutic RNA", "tissue culture", "transcriptome sequencing", "unnatural amino acids", "uptake" ], "approved": true } }, { "type": "Grant", "id": "15919", "attributes": { "award_id": "1R03AI185905-01A1", "title": "Modeling and validating dynamic accessibility to healthcare with system science approach", "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": 32873, "first_name": "MISRAK", "last_name": "GEZMU", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-07-25", "end_date": "2027-06-30", "award_amount": 137064, "principal_investigator": { "id": 44364, "first_name": "Liang", "last_name": "Mao", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2642, "ror": "", "name": "UNIVERSITY OF FLORIDA", "address": "", "city": "", "state": "FL", "zip": "", "country": "United States", "approved": true }, "abstract": "In public health sciences, people’s accessibility to healthcare determines how easily they can reach and utilize health services. For researchers and policy makers, modeling and measuring accessibility to healthcare is key to narrowing disparities and achieving health equality. Each year, a plethora of research efforts aim to model, estimate, and map geographic disparities in healthcare accessibility, informing targeted interventions in underserved areas. These studies have predominantly adopted either a travel cost-based approach or supply- demand approach to measure accessibility. Both approaches are population-based and temporally static, assuming uniformity among individuals and disregarding temporal factors. The derived accessibility measures fail to account for temporal variations, as well as heterogenous individuals and their interactions. To address these limitations, I will propose new conceptual frameworks to model and validate accessibility to healthcare using a system science approach. This two-year small project will study people’s access to healthcare in a dynamic and social system that involves complex interactions among individuals, as well as interactions between individuals and the environment (e.g., transportation network and health facilities). I will pioneer two models in system science, namely the system dynamics model and the agent-based model, to represent this system. I will implement these two types of models in the state of Florida in the context of recent ‘triplepidemic’ (flu, RSV and COVID) during 2022-23 season, and attempt to validate the model results. This study will contribute to the literature by adding a time dimension, individuals’ heterogeneity, and their social networks to the models of healthcare accessibility. Additionally, this study will investigate a novel method to validate healthcare accessibility models, addressing a persistent gap in existing research. Researchers and policy makers can use the newly developed tools to better monitor dynamics of healthcare accessibility and to mitigate health disparities more precisely with spatio-temporally dependent intervention.", "keywords": [ "Address", "Adopted", "Area", "COVID-19", "Communities", "Complex", "Differential Equation", "Dimensions", "Disease Outbreaks", "Disparity", "Environment", "Epidemic", "Florida", "Government", "Health", "Health Care", "Health Care Facility", "Health Sciences", "Household", "Individual", "Intervention", "Literature", "Maps", "Measures", "Methods", "Modeling", "Monitor", "Persons", "Policies", "Policy Maker", "Population", "Public Health", "Reduce health disparities", "Research", "Research Personnel", "Science", "Seasons", "Social Network", "System", "Time", "Transportation", "Travel", "Variant", "cost", "design", "dynamic system", "experimental study", "flu", "geographic disparity", "health care availability", "health care disparity", "health care model", "health disparity", "health equality", "health service use", "improved", "individual variation", "metropolitan", "novel", "population based", "social", "spatiotemporal", "tool", "underserved area" ], "approved": true } }, { "type": "Grant", "id": "15920", "attributes": { "award_id": "1R01HD114790-01A1", "title": "Health Outcomes of Youth Who Experience Caregiver Death", "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": 44281, "first_name": "VALERIE", "last_name": "MAHOLMES", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-07-24", "end_date": "2030-03-31", "award_amount": 569563, "principal_investigator": { "id": 44365, "first_name": "Dylan B.", "last_name": "Jackson", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 44366, "first_name": "Terrinieka Williams", "last_name": "Powell", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2615, "ror": "", "name": "JOHNS HOPKINS UNIVERSITY", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "Each year, over two million US youth experience the death of a caregiver before the age of 18 (hereafter referred to as caregiver death). Given the syndemic of COVID-19, the opioid crisis, and gun violence, rates of caregiver death among US children are likely to remain elevated or increase in the next decade. US non-Hispanic Black children are three times more likely to experience parent death than White children. Bereaved youth (i.e., who experienced a caregiver death) are vulnerable to adverse emotional and behavioral health (EBH) outcomes, such as higher risks of depression, anxiety, substance use, and suicidality. The goal of this research is to identify opportunities for improving EBH outcomes among bereaved youth. Three knowledge gaps must be filled to achieve this goal. First, we need to evaluate caregiver death in the context of other co-occurring adverse experiences. Second, we need to understand how the caregiving context mediates the relationship between caregiver death and EBH outcomes. Third, we need to learn from the lived experiences of bereaved young people. In addition to our multidisciplinary investigative team with relevant content and methodological expertise, an Advisory Board of bereaved young adults and grief professionals will be developed to inform this research. Guided by a Life Course Framework and Multidimensional Grief Theory, we will use a convergent mixed-method design to achieve three aims and fill the identified knowledge gaps: 1) Assess associations between caregiver death and EBH outcomes in the context of adverse childhood expereinces among young adults from the Future of Families and Child Wellbeing Study (N = ~2900); 2) Determine the extent to which the caregiving context (i.e., material hardship and parental monitoring) mediates the relationship between caregiver death and EBH outcomes; 3) Identify diverse strategies to support bereaved youth using longitudinal survey data and lived experiences (i.e., life history interviews with 80 young adults and consensus building with our Advisory Board). Achieving these aims will improve our ability develop tailored, family-centered interventions, practices and policies that support bereaved youth across sociodemographic groups. Ultimately, study findings will inform theory-driven and data-informed recommendations for future research, practice, and policies to improve EBH outcomes for the growing number of bereaved young people.", "keywords": [ "Adverse effects", "Adverse event", "Affect", "Age", "Anxiety", "Bereavement", "Black race", "COVID-19", "Caregivers", "Cessation of life", "Characteristics", "Child", "Child Health", "Child Welfare", "Childhood", "Consensus", "Data", "Development", "Dimensions", "Emotional", "Ethnic Origin", "Exhibits", "Family", "Family member", "Future", "Gender", "Goals", "Grief reaction", "Health", "Intervention", "Interview", "Joints", "Knowledge", "Learning", "Life Cycle Stages", "Lived experience", "Longitudinal Surveys", "Mediating", "Mental Depression", "Mental disorders", "Methodology", "Methods", "Not Hispanic or Latino", "Outcome", "Parents", "Persons", "Policies", "Policy Maker", "Public Health", "Reaction", "Recommendation", "Research", "Research Personnel", "Schools", "Shapes", "Symptoms", "Translating", "Voice", "Youth", "behavioral health", "caregiving", "comparison group", "data centers", "design", "experience", "gun violence", "high risk", "improved", "life history", "multidisciplinary", "opioid epidemic", "parental monitoring", "post-traumatic stress", "prevent", "racial difference", "sociodemographic group", "substance use", "suicidal", "syndemic", "theories", "transition to adulthood", "young adult" ], "approved": true } }, { "type": "Grant", "id": "15921", "attributes": { "award_id": "1R21AI188078-01A1", "title": "Elucidating the role of the SARS-CoV-2 ORF9b protein in virus replication", "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": 32891, "first_name": "MARY KATHERINE BRADFORD", "last_name": "PLIMACK", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-07-23", "end_date": "2027-06-30", "award_amount": 217337, "principal_investigator": { "id": 44367, "first_name": "Mohsan", "last_name": "Saeed", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 860, "ror": "", "name": "BOSTON UNIVERSITY MEDICAL CAMPUS", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "Highly pathogenic human coronaviruses encode an array of accessory proteins that are crucial for their virulence, enabling them to effectively manipulate cellular machinery and subvert host defenses. Our research proposal is centered on the SARS-CoV-2 accessory protein, ORF9b, which is known to amplify viral virulence in vivo, yet its specific roles during viral infection remain to be elucidated. Transfection studies suggest that ORF9b prevents innate immune induction by hindering the assembly of the MAVS signalosome, a finding that awaits confirmation in the context of actual SARS-CoV-2 infection. The investigation of ORF9b in virus-infected cells has traditionally been hampered by its integrated localization within the nucleocapsid gene, complicating efforts to manipulate ORF9b without unintentionally interfering in the nucleocapsid functionality. We have successfully overcome this challenge by strategically relocating the ORF9b sequence away from the nucleocapsid gene, creating a SARS-CoV-2 variant that produces native ORF9b levels and replicates as efficiently as the wild-type virus. This engineered virus provides a strong platform for exploring ORF9b functions during infection without unintended impact on the nucleocapsid gene. Further advancing our methodology, we tagged ORF9b in its new locale with an HA tag and TurboID, setting the stage for pioneering investigations of ORF9b networks in SARS-CoV-2-infected cells. Our extensive validation of these viral variants confirmed their ability to replicate comparably to the unmodified virus while preserving the native characteristics of ORF9b. We will employ these advanced tools to rigorously examine the impact of ORF9b phosphorylation on SARS- CoV-2 replication and the protein’s specific functions (Aim 1). Additionally, we will generate a detailed, time- resolved interaction map of ORF9b, uncovering its evolving interactions during infection (Aim 2). Achieving these goals will provide significant insights into the biological mechanisms of ORF9b and enhance our understanding of SARS-CoV-2 pathogenesis. This foundational work will also set the stage for extending similar methodologies to other viral proteins, vastly improving our knowledge of the coronaviral biology and aiding in the identification of new prophylactic and therapeutic avenues.", "keywords": [ "2019-nCoV", "Affect", "Affinity", "Affinity Chromatography", "Attenuated", "Binding", "Biological", "Biology", "Cell Physiology", "Cells", "Characteristics", "Coronavirus", "Disease Progression", "Engineering", "Exhibits", "Foundations", "Genes", "Goals", "Host Defense", "Host Defense Mechanism", "Immune", "Infection", "Interferons", "Investigation", "Knowledge", "Label", "Life Cycle Stages", "Locales", "Maps", "Methodology", "Mitochondria", "Modernization", "Molecular", "Molecular Biology", "Molecular Target", "Mutation", "Nucleocapsid", "Pathogenesis", "Pathogenicity", "Phase", "Phosphoproteins", "Phosphorylation", "Phosphorylation Site", "Phosphotransferases", "Process", "Proteins", "Readiness", "Recombinants", "Research", "Research Proposals", "Ribosomes", "Role", "SARS-CoV-2 infection", "SARS-CoV-2 pathogenesis", "SARS-CoV-2 variant", "Scanning", "Signal Transduction", "System", "Systems Biology", "Techniques", "Testing", "Therapeutic", "Time", "Transfection", "Vaccines", "Validation", "Variant", "Viral", "Viral Pathogenesis", "Viral Proteins", "Virulence", "Virulence Factors", "Virus", "Virus Diseases", "Virus Replication", "Work", "coronavirus vaccine", "design", "future pandemic", "gene function", "human coronavirus", "improved", "in vivo", "innovation", "insight", "mimetics", "preservation", "prevent", "prophylactic", "tool" ], "approved": true } }, { "type": "Grant", "id": "15924", "attributes": { "award_id": "1R21AI190938-01", "title": "Identification and enrichment of signature regions of antimicrobial resistant pathogen genomes for wastewater disease surveillance", "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": 32875, "first_name": "INKA I", "last_name": "SASTALLA", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-07-24", "end_date": "2027-06-30", "award_amount": 421673, "principal_investigator": { "id": 44369, "first_name": "Lauren", "last_name": "Stadler", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3400, "ror": "", "name": "RICE UNIVERSITY", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "Antimicrobial resistance is recognized as a global public health threat that makes infections more difficult to treat and increases the risk of other medical procedures. Global and local surveillance of antimicrobial resistance is critical to understanding transmission of resistant pathogens, detecting the emergence of resistance mechanisms, and mitigating the spread of resistant pathogens. Wastewater surveillance represents a powerful, resource-efficient, and comprehensive approach for population-level surveillance of infectious diseases. It has been widely applied to track COVID-19 and other respiratory virus levels in communities, as well as identify circulating variants. However, wastewater surveillance of antimicrobial resistant pathogens has not been widely implemented because of specific challenges that limit its actionability (i.e., the direct use of the surveillance data to inform public health action). This is because antimicrobial resistance is ubiquitous in the environment and even clinically-important antibiotic resistance genes (ARGs) are abundant and widespread in wastewater. Thus, previous approaches that quantified ARGs generated information that was not specific to antimicrobial resistant pathogens. This proposal focuses on the development of foundational computational tools and laboratory methods necessary to identify and detect signature regions of antimicrobial resistant pathogens for wastewater surveillance. Signature regions are defined as genomic regions that are conserved in a pathogen strain but not found in neighboring strains or other genomes. We propose to develop a genomic language model approach to identify signature regions of target antimicrobial resistant pathogens. This will be integrated with a fully automated design pipeline for quantitative assay design. On the wet lab side, we will use microdroplet encapsulation of wastewater microbes to do high-throughput enrichment and isolation of antimicrobial resistant bacteria. This approach will enable sensitive and specific detection of antimicrobial resistant pathogens by encapsulating individual cells and assaying them for signature regions using digital droplet PCR. The proposed computational and laboratory tools will result in software and wet lab methodologies that can be used by public health laboratories and wastewater surveillance programs for specific and sensitive antimicrobial resistance monitoring. Software, assays, and protocols will be made publicly available and can also be applied for other pathogen targets. Advancing the actionability of antimicrobial resistance wastewater monitoring has the potential to enable the prediction of outbreaks, forecast hospitalizations, guide treatment decisions, understand transmission, and evaluate mitigation strategies for antimicrobial resistant infections.", "keywords": [ "2019-nCoV", "Adoption", "Antibiotic Resistance", "Antimicrobial Resistance", "Behavior", "Biological Assay", "COVID-19", "Cells", "Circulation", "Cities", "Classification", "Clinical", "Communicable Diseases", "Communities", "Complement", "Complex", "Computer software", "Computing Methodologies", "Death Rate", "Decision Making", "Detection", "Development", "Disease Surveillance", "Emulsions", "Encapsulated", "Environment", "Extended spectrum Beta lactamase producing Escherichia coli", "Extended-spectrum β-lactamase", "Genes", "Genome", "Genomic Segment", "Genomics", "Goals", "Health", "Health Care Costs", "Health Care Facility", "Health Care Systems", "Hospitalization", "Hospitals", "Individual", "Infection", "Influenza", "Intervention", "Klebsiella pneumoniae", "Knowledge", "Laboratories", "Language", "Length of Stay", "Literature", "Medical", "Methodology", "Methods", "Microbe", "Microfluidics", "Mobile Genetic Elements", "Modeling", "Monitor", "Outcome", "Pathogenicity", "Patient Care", "Persons", "Plasmids", "Population", "Prevalence", "Procedures", "Protocols documentation", "Pseudomonas aeruginosa", "Public Health", "Reporting", "Research", "Resistance", "Resources", "Respiratory syncytial virus", "Risk", "Sampling", "Sensitivity and Specificity", "Side", "Surveillance Program", "Technology", "Vancomycin Resistance", "Vancomycin resistant enterococcus", "Vancomycin-resistant S. aureus", "Variant", "Virus", "antimicrobial resistant infection", "antimicrobial resistant pathogen", "bacterial resistance", "carbapenem resistance", "carbapenemase", "clinical care", "clinical risk", "community transmission", "computational pipelines", "computerized tools", "design", "detection limit", "droplet digital PCR", "genomic signature", "improved", "metagenomic sequencing", "methicillin resistant Staphylococcus aureus", "microbial community", "microbial host", "outbreak prediction", "pathogen", "pathogen genome", "public health intervention", "resistance gene", "resistance mechanism", "resistant strain", "respiratory virus", "surveillance data", "tool", "transmission process", "wastewater monitoring", "wastewater samples", "wastewater surveillance" ], "approved": true } } ], "meta": { "pagination": { "page": 1419, "pages": 1424, "count": 14236 } } }