Represents Grant table in the DB

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    "data": [
        {
            "type": "Grant",
            "id": "15686",
            "attributes": {
                "award_id": "1R21AG093333-01",
                "title": "Platelet-MLKL role in S100 Release with Age and Infection",
                "funder": {
                    "id": 4,
                    "ror": "https://ror.org/01cwqze88",
                    "name": "National Institutes of Health",
                    "approved": true
                },
                "funder_divisions": [
                    "National Institute on Aging (NIA)"
                ],
                "program_reference_codes": [],
                "program_officials": [
                    {
                        "id": 32534,
                        "first_name": "HONGWEI",
                        "last_name": "GAO",
                        "orcid": "",
                        "emails": "",
                        "private_emails": "",
                        "keywords": null,
                        "approved": true,
                        "websites": null,
                        "desired_collaboration": null,
                        "comments": null,
                        "affiliations": []
                    }
                ],
                "start_date": "2025-05-15",
                "end_date": "2027-04-30",
                "award_amount": 460625,
                "principal_investigator": {
                    "id": 32535,
                    "first_name": "Milka",
                    "last_name": "Koupenova",
                    "orcid": "",
                    "emails": "",
                    "private_emails": "",
                    "keywords": null,
                    "approved": true,
                    "websites": null,
                    "desired_collaboration": null,
                    "comments": null,
                    "affiliations": []
                },
                "other_investigators": [],
                "awardee_organization": {
                    "id": 790,
                    "ror": "",
                    "name": "UNIV OF MASSACHUSETTS MED SCH WORCESTER",
                    "address": "",
                    "city": "",
                    "state": "MA",
                    "zip": "",
                    "country": "United States",
                    "approved": true
                },
                "abstract": "Advanced age is a single risk factor for developing serious complications from infections with respiratory viruses such as influenza, SARS-CoV-2 or RSV. These complications are reflected in thrombotic outcomes including microthrombosis, myocardial infarction and pulmonary embolism. The actual cause and mechanisms of these thrombotic outcomes remains elusive. Pathogen spreading and crossover of these viruses into the circulation is regulated by various mechanisms, some of which involve lytic programmed cell death pathways such as necroptosis executed by membrane channels formed by oligomerized phosho-Mixed Lineage Kinase Domain Like Pseudokinase (MLKL). Platelets express MLKL, have a plethora of immune-sensing viral receptors and are the major blood component responsible for thrombotic outcomes. We have shown that respiratory viral RNA can be found in circulating platelets from influenza patients and preliminary result support channel formation. In this proposal, we hypothesize that platelet-pMLKL channel formation, mediated by influenza, leads to cytoplasmic S100 content release and contributes to immunothrombosis with age. We propose to test this hypothesis with the following aims: 1. Determine the MLKL-specific platelet content release and whether platelets undergo necroptosis as a result of influenza and (or) age, and 2. Determine the contribution of age to MLKL-activation and immunothrombotic aggregates during infection. The proposed studies are central to elucidating mechanisms that may increase immunothrombotic risk and adverse cardiovascular outcomes beyond classical platelet activation, with advanced age, and provide a basis for novel and targeted treatments for prevention.",
                "keywords": [
                    "2019-nCoV",
                    "Acute",
                    "Age",
                    "Aging",
                    "Agonist",
                    "Antiplatelet Drugs",
                    "Apoptosis",
                    "Biochemical",
                    "Blood",
                    "Blood Platelets",
                    "COVID-19 patient",
                    "Cardiovascular system",
                    "Cell membrane",
                    "Cell surface",
                    "Cells",
                    "Cessation of life",
                    "Circulation",
                    "Coagulation Process",
                    "Complex",
                    "Complication",
                    "Cytoplasm",
                    "Cytoplasmic Granules",
                    "DNA",
                    "Elderly",
                    "Electron Microscopy",
                    "Event",
                    "Extravasation",
                    "Goals",
                    "Human",
                    "Immune",
                    "Immunity",
                    "Individual",
                    "Infection",
                    "Inflammation",
                    "Inflammation Mediators",
                    "Inflammatory",
                    "Influenza",
                    "Ion Channel",
                    "Knockout Mice",
                    "Lead",
                    "Leukocytes",
                    "Link",
                    "Lytic",
                    "Mediating",
                    "Membrane",
                    "Modeling",
                    "Molecular",
                    "Morphology",
                    "Mus",
                    "Myocardial Infarction",
                    "Older Population",
                    "Organ",
                    "Outcome",
                    "P-Selectin",
                    "Pathogenicity",
                    "Pathway interactions",
                    "Patients",
                    "Phase",
                    "Phosphotransferases",
                    "Platelet Activation",
                    "Population",
                    "Prevention",
                    "Process",
                    "Proteins",
                    "Pulmonary Embolism",
                    "RIPK1 gene",
                    "Research",
                    "Research Proposals",
                    "Risk",
                    "Risk Factors",
                    "Role",
                    "Serotonin",
                    "Stains",
                    "Surface",
                    "Testing",
                    "Thrombosis",
                    "Time",
                    "Viral",
                    "Viral Antigens",
                    "Viral Respiratory Tract Infection",
                    "Virus",
                    "Virus Receptors",
                    "age related",
                    "beta-n-acetylhexosaminidase",
                    "cytokine",
                    "design",
                    "disulfide bond",
                    "high risk",
                    "human old age (65+)",
                    "immune function",
                    "immunothrombosis",
                    "improved",
                    "influenza infection",
                    "inhibitor",
                    "mouse model",
                    "neutrophil",
                    "novel",
                    "pathogen",
                    "respiratory",
                    "respiratory virus",
                    "therapy design",
                    "thromboinflammation",
                    "thrombotic",
                    "viral RNA"
                ],
                "approved": true
            }
        },
        {
            "type": "Grant",
            "id": "15715",
            "attributes": {
                "award_id": "2515249",
                "title": "Collaborative Research: The mechanics of respiratory particle production in the larynx during phonation",
                "funder": {
                    "id": 3,
                    "ror": "https://ror.org/021nxhr62",
                    "name": "National Science Foundation",
                    "approved": true
                },
                "funder_divisions": [
                    "Engineering (ENG)",
                    "FD-Fluid Dynamics"
                ],
                "program_reference_codes": [],
                "program_officials": [
                    {
                        "id": 573,
                        "first_name": "Ron",
                        "last_name": "Joslin",
                        "orcid": null,
                        "emails": "",
                        "private_emails": null,
                        "keywords": "[]",
                        "approved": true,
                        "websites": "[]",
                        "desired_collaboration": "",
                        "comments": "",
                        "affiliations": []
                    }
                ],
                "start_date": "2025-05-15",
                "end_date": null,
                "award_amount": 355114,
                "principal_investigator": {
                    "id": 3709,
                    "first_name": "Andrea",
                    "last_name": "Ferro",
                    "orcid": null,
                    "emails": "",
                    "private_emails": "",
                    "keywords": null,
                    "approved": true,
                    "websites": null,
                    "desired_collaboration": null,
                    "comments": null,
                    "affiliations": []
                },
                "other_investigators": [
                    {
                        "id": 32593,
                        "first_name": "Sumona",
                        "last_name": "Mondal",
                        "orcid": "",
                        "emails": "",
                        "private_emails": "",
                        "keywords": null,
                        "approved": true,
                        "websites": null,
                        "desired_collaboration": null,
                        "comments": null,
                        "affiliations": []
                    },
                    {
                        "id": 32594,
                        "first_name": "Shantanu",
                        "last_name": "Sur",
                        "orcid": "",
                        "emails": "",
                        "private_emails": "",
                        "keywords": null,
                        "approved": true,
                        "websites": null,
                        "desired_collaboration": null,
                        "comments": null,
                        "affiliations": []
                    }
                ],
                "awardee_organization": {
                    "id": 597,
                    "ror": "https://ror.org/03rwgpn18",
                    "name": "Clarkson University",
                    "address": "",
                    "city": "",
                    "state": "NY",
                    "zip": "",
                    "country": "United States",
                    "approved": true
                },
                "abstract": "Infectious disease transmission, as highlighted by the COVID-19 pandemic, exacts a severe toll on the physical and psychological well-being, economic development, and health of the global community. To better understand how airborne diseases are spread, this project will determine how speaking generates microscopic respiratory particles that can release infectious pathogens into the surrounding air. Although actions like coughing and sneezing produce high numbers of respiratory particles, these events are not as common as speaking. In comparison, speaking produces particles continuously that results in large quantities of particles being expelled from the mouth over time. The rates at which individuals produce respiratory particles when speaking vary widely among people for unknown reasons.  This project will answer this conundrum by performing experiments using both human subjects and physical models of phonation, with the goal of discovering how the mechanics of speaking influences how respiratory particles are produced. This approach will unlock new ways to understand aerosol generation in the vocal tract and how it affects airborne transmission of infectious diseases. Large-scale community outreach efforts through a university sponsored innovation fair (ImagineRIT) will transmit project findings to an interested public.    The objective of this project is to elucidate the underlying mechanisms of aerosolized particle generation during phonation and their implications for the transmission of airborne pathogens. The multidisciplinary approach will utilize experimental models and human measurements to quantify the relationship between the biomechanical processes of speech and the mechanics of respiratory particle production. The project will explore how variations in the rheological properties of the respiratory tract lining fluid and the biomechanical actions at the physiological sites of particle generation contribute to the observed heterogeneity in aerosol production rates among individuals. This research is critically important due to the potential for asymptomatic speech-driven transmission of viruses, as evidenced during the COVID-19 pandemic. Findings from this work will inform the development of evidence-based strategies for mitigating infection risk and will have broad application to public health policies regarding airborne diseases. The multi-disciplinary approach of the research plan will also provide a unique educational and training environment for two graduate students and three undergraduates that will participate in the work plan. Research findings will also be incorporated into existing classroom curricula at both the undergraduate and graduate level.    This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.",
                "keywords": [],
                "approved": true
            }
        },
        {
            "type": "Grant",
            "id": "15685",
            "attributes": {
                "award_id": "1R01HL174310-01A1",
                "title": "Multi-scale characterization of antigen-polymerized immune complexes underlying thrombotic pathologies triggered by adenoviral-vectored vaccines",
                "funder": {
                    "id": 4,
                    "ror": "https://ror.org/01cwqze88",
                    "name": "National Institutes of Health",
                    "approved": true
                },
                "funder_divisions": [
                    "National Heart Lung and Blood Institute (NHLBI)"
                ],
                "program_reference_codes": [],
                "program_officials": [
                    {
                        "id": 32532,
                        "first_name": "RONALD Q",
                        "last_name": "WARREN",
                        "orcid": "",
                        "emails": "",
                        "private_emails": "",
                        "keywords": null,
                        "approved": true,
                        "websites": null,
                        "desired_collaboration": null,
                        "comments": null,
                        "affiliations": []
                    }
                ],
                "start_date": "2025-05-01",
                "end_date": "2029-02-28",
                "award_amount": 601677,
                "principal_investigator": {
                    "id": 32533,
                    "first_name": "IGOR A",
                    "last_name": "KALTASHOV",
                    "orcid": "",
                    "emails": "",
                    "private_emails": "",
                    "keywords": null,
                    "approved": true,
                    "websites": null,
                    "desired_collaboration": null,
                    "comments": null,
                    "affiliations": []
                },
                "other_investigators": [],
                "awardee_organization": {
                    "id": 200,
                    "ror": "https://ror.org/0072zz521",
                    "name": "University of Massachusetts Amherst",
                    "address": "",
                    "city": "",
                    "state": "MA",
                    "zip": "",
                    "country": "United States",
                    "approved": true
                },
                "abstract": "Immunothrombosis is a critical element of intravascular immunity, but its dysregulation or malfunction leads to a range of thrombotic disorders including stroke and disseminated intravascular coagulation. The massive vaccination campaign during the recent COVID-19 pandemic brought to light a novel immunothrombotic pathology, a relatively rare but extremely dangerous side effect of adenoviral (Ad) vectored vaccines, which is now known as vaccine-induced immune thrombotic thrombocytopenia (VITT). Although COVID-19 is no longer a global health threat, the close association of VITT with a specific delivery vector raises the specter of other Ad- vectored vaccines also eliciting this deadly side effect, a grave prospect given the popularity of this platform. VITT has been linked to the emergence of autoantibodies recognizing a cognate chemokine, platelet factor 4 (PF4), but the specific mechanism underlying this pathology remains elusive. Understanding its molecular mechanism and etiology is critical for addressing the currently unmet need to design rational therapeutic and prophylactic strategies targeting VITT. It will also go a long way towards filling the gaps in understanding the delicate interplay between the beneficial and deleterious effects of immunothrombosis and provide the urgently needed ammunition to suppress the latter without sacrificing the former. We will use a combination of experimental and modeling tools to study VITT emergence and progression on different scales, ranging from micro- (formation of platelet-activating immune complexes) to macroscale (thrombi formation). We have already obtained a complete amino acid sequence of the pathogenic VITT antibody and produced its recombinant copy (RVT1) in quantities sufficient for both biophysical and biological investigations. On the microscale, we will use mass spectrometry and other biophysical tools to study the architecture and biological properties of the immune complexes composed of PF4 and RVT1. On the macro-scale, we will use these complexes to study thrombi initiation and formation using in vitro models based on microfluidic devices mimicking vascular environments relevant for VITT pathogenesis (e.g., cerebral venous vasculature). Bridging the micro- and macro-scales will allow us to elucidate the detailed mechanism of VITT progression by understanding how the disease outcome is modulated by the physical and biochemical properties of its molecular triggers. It will also provide a unique opportunity to address another enigmatic feature of VITT - its frequent localization within the cerebral venous sinuses. Lastly, correlating the amino acid sequences of the pathogenic antibodies and the germline sequences for a set of VITT patients will reveal the etiology of this disease, enabling the design of effective prophylactic and monitoring strategies. The proposed research will be carried out by an interdisciplinary team comprising chemists and biophysicists (Dr. Kaltashov's lab at UMass-Amherst), hematologists and molecular biologists (Dr. Nazy's lab at McMaster University School of Medicine) and biomedical engineers (Dr. Jiménez' lab at UMass-Amherst).",
                "keywords": [
                    "Address",
                    "Adenovirus Vector",
                    "Adenoviruses",
                    "Amino Acid Sequence",
                    "Antibodies",
                    "Antigen-Antibody Complex",
                    "Antigens",
                    "Architecture",
                    "Autoantibodies",
                    "Binding",
                    "Biochemical",
                    "Biological",
                    "Biomedical Engineering",
                    "Biophysics",
                    "Blood",
                    "Blood Platelets",
                    "Blood Vessels",
                    "COVID-19",
                    "COVID-19 pandemic",
                    "COVID-19 vaccination",
                    "Complex",
                    "Dangerousness",
                    "Disease",
                    "Disease Outcome",
                    "Disseminated Intravascular Coagulation",
                    "Elements",
                    "Endothelial Cells",
                    "Endothelium",
                    "Engineering",
                    "Environment",
                    "Epitopes",
                    "Etiology",
                    "Genetic",
                    "Germ Lines",
                    "Hematologist",
                    "Idiopathic Thrombocytopenic Purpura",
                    "Immune",
                    "Immunity",
                    "In Vitro",
                    "Innate Immune Response",
                    "Investigation",
                    "Link",
                    "Mass Spectrum Analysis",
                    "Microfluidic Microchips",
                    "Microfluidics",
                    "Microscopic",
                    "Modeling",
                    "Molecular",
                    "Monitor",
                    "Monoclonal Antibodies",
                    "Mutation",
                    "N-Glycosylation Site",
                    "Neutrophil Activation",
                    "PF4 Gene",
                    "Pathogenesis",
                    "Pathogenicity",
                    "Pathology",
                    "Patients",
                    "Phenotype",
                    "Physiological",
                    "Platelet Activation",
                    "Polymers",
                    "Polysaccharides",
                    "Predisposition",
                    "Property",
                    "Proteins",
                    "Recombinants",
                    "Research",
                    "Research Personnel",
                    "Role",
                    "Signal Transduction",
                    "Stroke",
                    "Surface",
                    "Techniques",
                    "Therapeutic",
                    "Thrombocytopenia",
                    "Thrombosis",
                    "Thrombus",
                    "Universities",
                    "Vaccination",
                    "Vaccines",
                    "Variant",
                    "Work",
                    "antigen binding",
                    "biophysical tools",
                    "cerebral vein",
                    "chemokine",
                    "crosslink",
                    "delivery vehicle",
                    "design",
                    "genetic predictors",
                    "global health",
                    "glycosylation",
                    "hemodynamics",
                    "immunothrombosis",
                    "in vitro Model",
                    "individual patient",
                    "medical schools",
                    "novel",
                    "pathogen",
                    "physical property",
                    "preservation",
                    "prevent",
                    "prophylactic",
                    "rational design",
                    "recruit",
                    "shear stress",
                    "side effect",
                    "stoichiometry",
                    "thrombogenesis",
                    "thrombotic",
                    "tool",
                    "vaccine trial",
                    "vector vaccine",
                    "venous sinus"
                ],
                "approved": true
            }
        },
        {
            "type": "Grant",
            "id": "15690",
            "attributes": {
                "award_id": "1S10OD036396-01A1",
                "title": "BD FACSAria Fusion cell sorter",
                "funder": {
                    "id": 4,
                    "ror": "https://ror.org/01cwqze88",
                    "name": "National Institutes of Health",
                    "approved": true
                },
                "funder_divisions": [
                    "NIH Office of the Director"
                ],
                "program_reference_codes": [],
                "program_officials": [
                    {
                        "id": 32542,
                        "first_name": "JEFFREY O",
                        "last_name": "SPECTOR",
                        "orcid": "",
                        "emails": "",
                        "private_emails": "",
                        "keywords": null,
                        "approved": true,
                        "websites": null,
                        "desired_collaboration": null,
                        "comments": null,
                        "affiliations": []
                    }
                ],
                "start_date": "2025-05-01",
                "end_date": "2026-04-30",
                "award_amount": 490899,
                "principal_investigator": {
                    "id": 32543,
                    "first_name": "ZACK Z.",
                    "last_name": "WANG",
                    "orcid": "",
                    "emails": "",
                    "private_emails": "",
                    "keywords": null,
                    "approved": true,
                    "websites": null,
                    "desired_collaboration": null,
                    "comments": null,
                    "affiliations": []
                },
                "other_investigators": [],
                "awardee_organization": {
                    "id": 344,
                    "ror": "https://ror.org/00za53h95",
                    "name": "Johns Hopkins University",
                    "address": "",
                    "city": "",
                    "state": "MD",
                    "zip": "",
                    "country": "United States",
                    "approved": true
                },
                "abstract": "Project Summary: We propose the acquisition of a BD FACSAria Fusion cell sorter from BD Biosciences to serve as a crucial instrument for the Ross Flow Cytometry Core (RFCC) in Johns Hopkins University (JHU) School of Medicine (SOM). This 4-laser (Violet 405nm, Blue 488nm, Yellow-Green 561nm, and Red 640nm) model with 16 fluorescent detectors and a fully integrated Class II biosafety cabinet will significantly enhance the research capabilities of the users with NIH funded projects. The current cell sorter, a BD FACSAria IIu with 3 lasers and biosafety cabinet at the RFCC, has limited technical capabilities and declining reliability. It is failing to meet the sorting requirements for advanced research projects. Having served for over two decades, it has reached its End-of-Life stage without manufactory upgrade and coverages. The proposed instrument addresses the pressing and unmet needs of 22 user groups within JHU SOM, spanning diverse research areas with mostly NIH-funded projects or some from other federal funding agencies. These users rely on cell sorter as a critical tool in their research endeavors. The benefits of the Fusion sorter over the current Aria IIu include: 1) the inclusion of a biosafety cabinet enables biosafety level-2 cell sorting with enhanced precautions during sorting operations; 2) the 4 lasers and ample fluorescent detectors reduce spectral overlap, facilitating multi-color panel design; 3) the Yellow-Green laser can optimally excite some unique fluorescent proteins and fluorochromes; 4) improved index sorting into multi-well plates; 5) temperature controls both input and output chambers to improve cell viability and gene stability; 6) easy aseptic setup and cleaning procedures ensure sterile sorting; 7) the well- established cell sorter offers increased reproducibility and expanded capabilities; 8) Conventional sorter easily and simply handle panels with fluorescent protein. The RFCC, under the administration and management of Department of Medicine in SOM, is oversighted by an advisory committee that provides recommendations for successful installation and management of the Fusion cell sorter. For the past 5 years, including COVID pandemic period, the RFCC has provided over 4,750 hours of cell sorting services to about 270 users from JHU SOM and local research community. However, the current BD FACSAria IIu, upgraded from Aria I in 2012 and addition of violet laser in 2015, no longer has a service contract from BD since the end of 2023. With its inability to have further upgrades of lasers, detectors and other parts, as well as timely repair, it is incapable of fulfilling advanced sorting projects. Although expensive high-end cell sorter, especially spectral sorters, are available, the proposed Fusion cell sorter is vital and cost-effective to maintaining a fully functional flow core facility. It should be sufficient to enable innovative researches across a wide range of sorting experiments, from sorting cells expressing fluorescent proteins to deep immunophenotyping, cellular research, genomic research, and other high-performance, high-throughput applications.",
                "keywords": [
                    "Address",
                    "Advisory Committees",
                    "Area",
                    "Biological Sciences",
                    "COVID-19 pandemic",
                    "Cell Separation",
                    "Cell Survival",
                    "Cell fusion",
                    "Cells",
                    "Color",
                    "Communities",
                    "Contract Services",
                    "Core Facility",
                    "Ensure",
                    "Flow Cytometry",
                    "Fluorochrome",
                    "Funding",
                    "Funding Agency",
                    "Genes",
                    "Genomics",
                    "Hour",
                    "Immunophenotyping",
                    "Lasers",
                    "Medicine",
                    "Modeling",
                    "Output",
                    "Performance",
                    "Procedures",
                    "Proteins",
                    "Recommendation",
                    "Reproducibility",
                    "Research",
                    "Research Project Grants",
                    "Services",
                    "Sorting",
                    "Sterility",
                    "Temperature",
                    "United States National Institutes of Health",
                    "Universities",
                    "Viola",
                    "cost effective",
                    "design",
                    "detector",
                    "end of life",
                    "experimental study",
                    "improved",
                    "indexing",
                    "innovation",
                    "instrument",
                    "medical schools",
                    "operation",
                    "repaired",
                    "tool"
                ],
                "approved": true
            }
        },
        {
            "type": "Grant",
            "id": "15687",
            "attributes": {
                "award_id": "1F31AI179181-01A1",
                "title": "Multidisciplinary studies on overcoming SARS-CoV-2 main protease drug resistance and on fitness costs",
                "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": "2025-05-01",
                "end_date": "2028-04-30",
                "award_amount": 48974,
                "principal_investigator": {
                    "id": 32537,
                    "first_name": "Grace",
                    "last_name": "Neilsen",
                    "orcid": "",
                    "emails": "",
                    "private_emails": "",
                    "keywords": null,
                    "approved": true,
                    "websites": null,
                    "desired_collaboration": null,
                    "comments": null,
                    "affiliations": []
                },
                "other_investigators": [],
                "awardee_organization": {
                    "id": 265,
                    "ror": "https://ror.org/03czfpz43",
                    "name": "Emory University",
                    "address": "",
                    "city": "",
                    "state": "GA",
                    "zip": "",
                    "country": "United States",
                    "approved": true
                },
                "abstract": "The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused a global pandemic since first emerging in 2019. Since, Pfizer, Inc. (USA) developed Paxlovid™, an FDA-approved antiviral containing the protease inhibitor nirmatrelvir (NIR) that has seen moderate success in treating SARS-CoV-2 infections. The main protease (Mpro) of SARS-CoV-2 cleaves the viral polyproteins to release proteins essential for replication. NIR mimics the Mpro consensus sequence, thus covalently blocking Mpro activity and viral replication. However, resistance mutations to NIR have started to develop as its use increases globally. Understanding how such substitutions confer resistance and balance the impacts on fitness will enable the strategic design of the next generation of Mpro inhibitors. My preliminary data and published experiments have identified drug resistance mutations (DRMs) in Mpro that confer significant resistance to NIR including E166V. Further, I have demonstrated that the E166V substitution remains susceptible to GC376, a feline coronavirus protease inhibitor, and PF-00835231, developed during the SARS-CoV-1 epidemic. E166V also severely decreases viral fitness and requires compensatory mutations such as L50F to rescue fitness. Despite this fitness cost, E166V and L50F/E166V were both observed in patients treated with Paxlovid™ during the clinical trial, and recent case studies also identified the L50V/E166V combination. It is unclear how E166V decreases fitness and why mutations at Leu50 restore fitness. Structural work from other labs and my preliminary data indicate Mpro forms an active homodimer with the N-terminus from the opposite protomer interacting with Glu166. Loss of these interactions due to the E166V mutation are likely to disrupt Mpro dimerization and, consequently, activity. Of note, dimerization has not been studied in the context of drug resistance, and the role of Leu50 mutations in restoring fitness is poorly understood. Building upon my previous work, I will analyze E166V and L50V/E166V using virological, biophysical, and structural techniques. The goal of my project is to characterize mechanisms of NIR resistance, determine how DRMs impact Mpro activity and fitness, and investigate strategies for overcoming NIR resistance. I hypothesize that DRMs alter the intermolecular interactions in the active site resulting in decreased binding of inhibitors and Mpro dimer formation. Aim 1 will characterize the effect of the selected substitutions on Mpro resistance to NIR, GC376, PF-00835231, and a novel inhibitor shown to inhibit E166V Mpro (NIP-22c) using a virus-like particle (VLP) assay (Aim 1.1) and elucidate the mechanism of and strategies for overcoming NIR resistance using biochemical (Aim 1.2) and crystallographic studies (Aim 1.3). Aim 2 will investigate the effect of E166V and L50V on viral replication efficiency in cells (Aim 2.1) and on Mpro dimerization in vitro using biochemical methods (Aim 2.2). This project will provide valuable insights into mechanisms of drug resistance, impacts on viral fitness, and strategies for overcoming NIR-resistant SARS-CoV-2 Mpro informing the design of next-generation antivirals targeting Mpro and future development of pan-coronavirus antivirals. Completing this project will train me in techniques and skills essential for my future career as an independent scientist.",
                "keywords": [
                    "2019-nCoV",
                    "Active Sites",
                    "Affect",
                    "Affinity",
                    "Anti-viral Agents",
                    "Anti-viral resistance",
                    "Appearance",
                    "Binding",
                    "Biochemical",
                    "Biological Assay",
                    "Biology",
                    "Biophysics",
                    "COVID-19",
                    "COVID-19 treatment",
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                    "Cessation of life",
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                    "FDA approved",
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                    "Link",
                    "Long COVID",
                    "Methods",
                    "Molecular",
                    "Molecular Conformation",
                    "Molecular Sieve Chromatography",
                    "Mutation",
                    "Patients",
                    "Paxlovid",
                    "Peptide Hydrolases",
                    "Pharmaceutical Preparations",
                    "Polyproteins",
                    "Positioning Attribute",
                    "Predisposition",
                    "Protease Inhibitor",
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                    "SARS-CoV-2 infection",
                    "SARS-CoV-2 protease",
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                    "Virus Replication",
                    "Virus-like particle",
                    "Work",
                    "World Health Organization",
                    "X-Ray Crystallography",
                    "antiviral drug development",
                    "breakthrough infection",
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                    "covalent bond",
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                    "insight",
                    "intermolecular interaction",
                    "light scattering",
                    "molecular dynamics",
                    "multidisciplinary",
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                    "novel",
                    "pandemic disease",
                    "resistance mechanism",
                    "resistance mutation",
                    "skills",
                    "success",
                    "targeted treatment",
                    "variants of concern",
                    "viral fitness",
                    "viral rebound"
                ],
                "approved": true
            }
        },
        {
            "type": "Grant",
            "id": "15688",
            "attributes": {
                "award_id": "1R35GM156452-01",
                "title": "From humans and eukaryotes to viruses and pathogens; how transition metals shape catalysis and allostery",
                "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": 32538,
                        "first_name": "MILJAN",
                        "last_name": "SIMONOVIC",
                        "orcid": "",
                        "emails": "",
                        "private_emails": "",
                        "keywords": null,
                        "approved": true,
                        "websites": null,
                        "desired_collaboration": null,
                        "comments": null,
                        "affiliations": []
                    }
                ],
                "start_date": "2025-05-01",
                "end_date": "2030-02-28",
                "award_amount": 502043,
                "principal_investigator": {
                    "id": 32539,
                    "first_name": "Maria-Eirini",
                    "last_name": "Pandelia",
                    "orcid": "",
                    "emails": "",
                    "private_emails": "",
                    "keywords": null,
                    "approved": true,
                    "websites": null,
                    "desired_collaboration": null,
                    "comments": null,
                    "affiliations": []
                },
                "other_investigators": [],
                "awardee_organization": {
                    "id": 280,
                    "ror": "https://ror.org/05abbep66",
                    "name": "Brandeis University",
                    "address": "",
                    "city": "",
                    "state": "MA",
                    "zip": "",
                    "country": "United States",
                    "approved": true
                },
                "abstract": "Metalloproteins play a crucial but poorly understood role in how viruses manipulate their hosts and how key cellular processes are regulated in eukaryotes, parasites, and viruses. Our proposed research program for the next five years aims to bridge the existing knowledge gap about how metal ions affect the function of enzymes that are at the nexus of host-pathogen interface, immune response, and dNTP homeostasis. Our strategy is a conceptualization of our ideas about how metal ions tune activity and regulation of two important enzyme super- families: viral proteases and SAMHD1 dNTPases.  Viral proteases. Viral polyprotein complexes enclose proteases that not only release the non-structural proteins required for replication of the viral genome but also harbor moonlighting activities that intercept host protein function, ultimately derailing immune defense. A number of viral proteases coordinate an essential for function metallocofactor in a putative Zinc-finger motif that is located far from the proteolytic active site. We propose that this metallocofactor is an Fe-S cluster and that this center is a common but unrecognized element in viral proteases. We aim to dissect the metal-dependent activities of four proteases from viruses for which efficient treatments are lacking: the PLpro from Sars-Cov(2), the Nsp1α from the Porcine Reproductive and Respiratory Syndrome Virus, the putative cysteine protease (PCP) from the Hepatitis E Virus, and the 2Apro from Enterovirus 71 (hand-foot-mouth disease). Based on our results that these proteases interchangeably coordinate [4Fe-4S] clusters or Zn2+, we propose a revision of the well-accepted paradigm of Zn utilization in this class of enzymes. Our studies promise to resolve the apparent Fe-S cluster/Zn dilemma in viral proteases by establishing: i) the in vivo physiological cofactor and ii) the biological relevance of this metal binding promiscuity.  SAMHD1 dNTPases. Sterile Alpha Motif and HD-domain containing protein 1 (SAMHD1) is the only hydrolase in humans that catalyzes the breakdown of cellular deoxynucleotides (dNTPs). SAMHD1 also occurs in phylogenetically diverse organisms, such as viruses, plants, and human pathogens. This proposal exposes significant conceptual and methodological gaps about how SAMHD1 dNTPases have evolved to regulate dNTP levels essential for organism fitness. In this respect our studies promise to delineate, for the first time, molecular and chemical details that govern SAMHD1 catalysis in the human enzyme as well as the untapped pool of eukaryotic and viral orthologs. In this proposal we will: i) establish the role of Fe and Mn in activation and catalysis of human SAMHD1, ii) map the functional repertoire of newly identified SAMHD1 orthologs, and iii) shed light into the evolutionary and functional diversification of SAMHD1 dNTPases. The projected outcome will broadly provide a molecular paradigm for dNTP regulation in plants, fungi and parasites that remains entirely unexplored.",
                "keywords": [
                    "Active Sites",
                    "Affect",
                    "Binding",
                    "Biological",
                    "Caspase",
                    "Catalysis",
                    "Cell Physiology",
                    "Chemicals",
                    "Complex",
                    "Elements",
                    "Enterovirus 71",
                    "Enzymes",
                    "Eukaryota",
                    "Evolution",
                    "Hand  Foot and Mouth Disease",
                    "Hepatitis E virus",
                    "Homeostasis",
                    "Human",
                    "Hydrolase",
                    "Immune",
                    "Immune response",
                    "Intercept",
                    "Ions",
                    "Knowledge",
                    "Life",
                    "Light",
                    "Maps",
                    "Metalloproteins",
                    "Metals",
                    "Methodology",
                    "Molecular",
                    "Nonstructural Protein",
                    "Organism",
                    "Orthologous Gene",
                    "Outcome",
                    "Parasites",
                    "Pathogenesis",
                    "Peptide Hydrolases",
                    "Phylogenetic Analysis",
                    "Physiological",
                    "Plants",
                    "Play",
                    "Polyproteins",
                    "Porcine respiratory and reproductive syndrome virus",
                    "Proteins",
                    "Regulation",
                    "Research",
                    "Role",
                    "SAM Domain",
                    "SARS coronavirus",
                    "Shapes",
                    "Structure",
                    "Time",
                    "Transition Elements",
                    "Viral",
                    "Viral Genome",
                    "Virus",
                    "Virus Replication",
                    "Work",
                    "Zinc Fingers",
                    "cofactor",
                    "fitness",
                    "fungus",
                    "human pathogen",
                    "in vivo",
                    "pathogen",
                    "programs",
                    "protein function",
                    "virus host interaction"
                ],
                "approved": true
            }
        },
        {
            "type": "Grant",
            "id": "15684",
            "attributes": {
                "award_id": "1F30DA062497-01",
                "title": "Molecular and Functional Characterization of Transcriptionally Defined Subpopulations of VTA Dopamine Neurons",
                "funder": {
                    "id": 4,
                    "ror": "https://ror.org/01cwqze88",
                    "name": "National Institutes of Health",
                    "approved": true
                },
                "funder_divisions": [
                    "National Institute on Drug Abuse (NIDA)"
                ],
                "program_reference_codes": [],
                "program_officials": [
                    {
                        "id": 32530,
                        "first_name": "YU",
                        "last_name": "LIN",
                        "orcid": "",
                        "emails": "",
                        "private_emails": "",
                        "keywords": null,
                        "approved": true,
                        "websites": null,
                        "desired_collaboration": null,
                        "comments": null,
                        "affiliations": []
                    }
                ],
                "start_date": "2025-05-01",
                "end_date": "2027-10-31",
                "award_amount": 42856,
                "principal_investigator": {
                    "id": 32531,
                    "first_name": "Natalie Dalton",
                    "last_name": "Fitzgerald",
                    "orcid": "",
                    "emails": "",
                    "private_emails": "",
                    "keywords": null,
                    "approved": true,
                    "websites": null,
                    "desired_collaboration": null,
                    "comments": null,
                    "affiliations": []
                },
                "other_investigators": [],
                "awardee_organization": {
                    "id": 612,
                    "ror": "https://ror.org/008s83205",
                    "name": "University of Alabama at Birmingham",
                    "address": "",
                    "city": "",
                    "state": "AL",
                    "zip": "",
                    "country": "United States",
                    "approved": true
                },
                "abstract": "Substance use disorder is a complex neurobiological disease characterized by a loss of control over drug-taking and drug-seeking behaviors. Further exacerbated by the COVID-19 pandemic, the rate of drug-related overdoses and subsequent deaths has increased dramatically over the past decade, surpassing 107,000 in 2022. All drugs of abuse increase dopamine (DA) transmission within the nucleus accumbens (NAc) from DA projections from the ventral tegmental area (VTA). While the presence of tyrosine hydroxylase (Th) has long been used to identify DA neurons, more recent studies have revealed remarkable heterogeneity among VTA DA neurons, with some neurons co-expressing markers for both DA and glutamate (Glut) transmission that are similarly Th+. However, the role of DA-only compared to combinatorial cells in substance use disorder is currently unknown. Using single nucleus RNA sequencing to comprehensively profile the VTA, we previously identified unique markers for these two subpopulations of DA neurons. Slc26a7, a gene that encodes an anion transporter, serves as a selective marker for combinatorial neurons that harbor expression of genes implicated in both Glut and DA synthesis and neurotransmission. Likewise, the GTP cyclohydrolase Gch1 was identified as a marker for DA-only neurons. Using a fluorescent in situ hybridization protocol, I validated these findings showing the Slc26a7 marks DA+/Glut+ cells while Gch1 marks DA+/Glut- cells. I have shown unique induction of the neuronal activity marker Fos in Slc26a7+ cells in the VTA 1 hour following cocaine, but not fentanyl, experience; this same response was not observed in Gch1+ cells, suggesting a difference in response to cocaine between these two distinct DA neuron populations. These results suggest that two subpopulations of DAergic cells in the VTA respond to cocaine in unique ways and may in turn drive distinct downstream effects and behavioral responses to cocaine. Following these findings, I hypothesize that differences in cellular targets and neurophysiology confer distinct behavioral roles of DA subpopulations. Using these selective markers, I have designed and generated novel adeno-associated viruses (AAVs) to both express distinct fluorophores and manipulate the neurons in a cell-type specific way. Using these AAVs, this project aims to take a multidisciplinary approach to rigourously investigate and determine any differences in cell types through the following aims: (1) Characterize anatomical and cellular localization of projections, (2) Determine neurophysiological differences, and (3) Determine the role of combinatorial cells in behavior. The proposed studies will deepen our understanding of the role of these combinatorial cells in SUD, providing avenues for therapeutic exploration for a disease largely lacking treatment options. Under this award, I will master behavioral paradigms and electrophysiology, techniques that will aid my success as a physician-scientist.",
                "keywords": [
                    "Anatomy",
                    "Anions",
                    "Award",
                    "Axon",
                    "Behavior",
                    "Behavioral",
                    "Behavioral Assay",
                    "Behavioral Paradigm",
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                    "Brain",
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                    "Cells",
                    "Cessation of life",
                    "Chronic",
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                    "Communities",
                    "Complex",
                    "Comprehension",
                    "Data",
                    "Dependovirus",
                    "Disease",
                    "Dopamine",
                    "Drug Addiction",
                    "Drug usage",
                    "ERG gene",
                    "Electrophysiology (science)",
                    "Exposure to",
                    "Family",
                    "Fellowship",
                    "Female",
                    "Fentanyl",
                    "Fluorescent in Situ Hybridization",
                    "Future",
                    "GTP Cyclohydrolase",
                    "Gene Expression",
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                    "Immediate-Early Genes",
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                    "Medial",
                    "Messenger RNA",
                    "Midbrain structure",
                    "Molecular",
                    "Neurobiology",
                    "Neurons",
                    "Neurotransmitters",
                    "Nucleus Accumbens",
                    "Overdose",
                    "Pathway interactions",
                    "Pattern",
                    "Pharmaceutical Preparations",
                    "Physicians",
                    "Physiological",
                    "Population",
                    "Positive Reinforcements",
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                    "Protocols documentation",
                    "RNA",
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                    "activity marker",
                    "addiction",
                    "behavioral response",
                    "cell type",
                    "cellular targeting",
                    "cocaine exposure",
                    "cocaine use",
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                    "dopaminergic neuron",
                    "drug of abuse",
                    "drug reinforcement",
                    "drug reward",
                    "drug seeking behavior",
                    "experience",
                    "fluorophore",
                    "in vivo Model",
                    "insight",
                    "interdisciplinary approach",
                    "male",
                    "mesolimbic system",
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                    "neurotransmission",
                    "neurotransmitter release",
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                    "single nucleus RNA-sequencing",
                    "skills",
                    "success",
                    "targeted treatment",
                    "transmission process",
                    "vesicular glutamate transporter 2"
                ],
                "approved": true
            }
        },
        {
            "type": "Grant",
            "id": "15692",
            "attributes": {
                "award_id": "1R01CA293906-01A1",
                "title": "Engineered Lipid Nanoparticles and Microgel Matrix to Program Th1/Th2 Immune Response",
                "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": 32545,
                        "first_name": "MARCO",
                        "last_name": "CARDONE",
                        "orcid": "",
                        "emails": "",
                        "private_emails": "",
                        "keywords": null,
                        "approved": true,
                        "websites": null,
                        "desired_collaboration": null,
                        "comments": null,
                        "affiliations": []
                    }
                ],
                "start_date": "2025-04-25",
                "end_date": "2030-03-31",
                "award_amount": 630781,
                "principal_investigator": {
                    "id": 32546,
                    "first_name": "Hai-Quan",
                    "last_name": "Mao",
                    "orcid": "",
                    "emails": "",
                    "private_emails": "",
                    "keywords": null,
                    "approved": true,
                    "websites": null,
                    "desired_collaboration": null,
                    "comments": null,
                    "affiliations": []
                },
                "other_investigators": [],
                "awardee_organization": {
                    "id": 344,
                    "ror": "https://ror.org/00za53h95",
                    "name": "Johns Hopkins University",
                    "address": "",
                    "city": "",
                    "state": "MD",
                    "zip": "",
                    "country": "United States",
                    "approved": true
                },
                "abstract": "The overall objectives of this study are to (1) develop mRNA lipid nanoparticle (LNP) formulations capable of eliciting dual or biased Type 1 T helper (Th1) and/or Type 2 T helper (Th2) immune responses via a machine learning-aided screening platform, (2) engineer mRNA LNP- loaded microgels as an immunostimulatory niche in vivo to recruit and transfect host immune cells and potentiate antigen-specific immune responses, and (3) demonstrate the efficacy and safety of this new LNP-based vaccine platform in murine cancer models. The success of mRNA COVID-19 vaccines utilizing lipid nanoparticle (LNP) delivery has underscored the potential of mRNA LNP-based cancer vaccines in advancing immunotherapy by training the immune system to respond effectively to tumor antigens. To maximize their potency in eliciting robust immune responses for cancer immunotherapy, it is important to engineer effective approaches for systematic programming of immune activation profile via optimization of LNP compositions and improving delivery for mRNA LNP vaccines. Our preliminary data have demonstrated that LNP compositions and helper lipid structure influence the polarization of immune activation, and LNPs with dual Th1-plus-Th2 activation profile yielded the most potent antitumor efficacy in mouse tumor models. In addition, a candidate mRNA LNP vaccine loaded into a nanofiber-based microgel matrix, which facilitated recruitment and retention of host immune cells, enhanced antigen presentation, and elicited equally strong anti-tumor response with a single dose compared to a standard three-dose immunization regimen. In this proposed study, we will first optimize LNP composition for efficient transfection of antigen-encoding mRNA into antigen-presenting cells (APCs) and non-APCs via an machine learning-guided, iterative design-build-screen/test-learn process, and evaluate antigen presentation, and immune activation profiles in vivo; then develop an LNP-incorporated nanofiber microgel matrix termed LiNx as an immunostimulatory niche for recruitment of host immune cells and assess gene delivery efficiency and immune response profiles; and finally demonstrate the therapeutic efficacy and biosafety of the optimized LNPs and LiNx in suppressing tumor growth in therapeutic models of melanoma, lymphoma, and colon carcinoma in mice, as well as an orthotopic, immunoquiescent, pancreatic cancer mouse model. The innovation in this study lies in programming the immune activation profile generated by mRNA LNP vaccine by tunning cell-preferential transfection activity of LNPs and engineering an immunostimulatory niche using a nanofiber microgel matrix to recruit and retain host immune cells and deliver LNP vaccines, thus potentiating the therapeutic efficacy against cancer. Findings from this study can inspire rational design of new mRNA-based immunotherapies for the treatment of cancer and other diseases.",
                "keywords": [
                    "Acceleration",
                    "Advanced Malignant Neoplasm",
                    "Antibodies",
                    "Antibody Response",
                    "Antigen Presentation",
                    "Antigen-Presenting Cells",
                    "Antigens",
                    "Antitumor Response",
                    "Bone Marrow",
                    "CD4 Positive T Lymphocytes",
                    "CD8-Positive T-Lymphocytes",
                    "COVID-19 vaccine",
                    "Cancer Model",
                    "Cancer Vaccines",
                    "Cells",
                    "Chemicals",
                    "Colon Carcinoma",
                    "Cytotoxic T-Lymphocytes",
                    "Data",
                    "Dendritic Cells",
                    "Development",
                    "Disease",
                    "Dose",
                    "Engineering",
                    "Formulation",
                    "Fostering",
                    "Gel",
                    "Gene Delivery",
                    "Gene Expression",
                    "Helper-Inducer T-Lymphocyte",
                    "Hydrogels",
                    "IL2 gene",
                    "Immune",
                    "Immune checkpoint inhibitor",
                    "Immune response",
                    "Immune system",
                    "Immunization",
                    "Immunologic Stimulation",
                    "Immunophenotyping",
                    "Immunotherapy",
                    "Injectable",
                    "Injections",
                    "Interferon Type II",
                    "Kinetics",
                    "Learning",
                    "Lipids",
                    "Lymphoma",
                    "Machine Learning",
                    "Malignant Neoplasms",
                    "Malignant neoplasm of pancreas",
                    "Mediating",
                    "Melanoma",
                    "Memory B-Lymphocyte",
                    "Messenger RNA",
                    "Methods",
                    "Modeling",
                    "Molecular",
                    "Mus",
                    "PD-1 inhibitors",
                    "Pancreatic Ductal Adenocarcinoma",
                    "Pilot Projects",
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                    "Property",
                    "Regimen",
                    "Role",
                    "Safety",
                    "Signal Transduction",
                    "Site",
                    "Subcutaneous Injections",
                    "T-Cell Activation",
                    "Testing",
                    "Therapeutic",
                    "Time",
                    "Toxic effect",
                    "Training",
                    "Transfection",
                    "Treatment Efficacy",
                    "Treatment-related toxicity",
                    "Tumor Antigens",
                    "Vaccines",
                    "anti-PD1 antibodies",
                    "cancer immunotherapy",
                    "cancer therapy",
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                    "high throughput screening",
                    "immune activation",
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                    "lipid nanoparticle",
                    "lipid structure",
                    "lymph nodes",
                    "mRNA delivery",
                    "mRNA immunotherapy",
                    "mRNA lipid nano particle vaccine",
                    "mouse model",
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                    "nanoparticle delivery",
                    "novel strategies",
                    "programs",
                    "rational design",
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                    "success",
                    "synergism",
                    "treatment effect",
                    "tumor",
                    "tumor growth",
                    "vaccine platform"
                ],
                "approved": true
            }
        },
        {
            "type": "Grant",
            "id": "15645",
            "attributes": {
                "award_id": "2449371",
                "title": "I-Corps: Translation Potential of a Handheld Standoff Photothermal Spectroscopy System for Real-time Indication of Viral Epidemics",
                "funder": {
                    "id": 3,
                    "ror": "https://ror.org/021nxhr62",
                    "name": "National Science Foundation",
                    "approved": true
                },
                "funder_divisions": [
                    "Technology, Innovation and Partnerships (TIP)",
                    "I-Corps"
                ],
                "program_reference_codes": [],
                "program_officials": [
                    {
                        "id": 31316,
                        "first_name": "Jaime A.",
                        "last_name": "Camelio",
                        "orcid": null,
                        "emails": "",
                        "private_emails": "",
                        "keywords": null,
                        "approved": true,
                        "websites": null,
                        "desired_collaboration": null,
                        "comments": null,
                        "affiliations": []
                    }
                ],
                "start_date": "2025-04-15",
                "end_date": null,
                "award_amount": 50000,
                "principal_investigator": {
                    "id": 32149,
                    "first_name": "Thomas",
                    "last_name": "Thundat",
                    "orcid": null,
                    "emails": "",
                    "private_emails": "",
                    "keywords": null,
                    "approved": true,
                    "websites": null,
                    "desired_collaboration": null,
                    "comments": null,
                    "affiliations": []
                },
                "other_investigators": [],
                "awardee_organization": {
                    "id": 422,
                    "ror": "",
                    "name": "SUNY at Buffalo",
                    "address": "",
                    "city": "",
                    "state": "NY",
                    "zip": "",
                    "country": "United States",
                    "approved": true
                },
                "abstract": "This I-Corps project is focused on the development of an innovative. non-invasive, diagnostic tool for viral infections. The technology is able to provide rapid, accurate, and real-time detection of influenza, respiratory syncytial virus, and COVID-19. The tool's portability ensures that it can be widely distributed, making it accessible in a variety of healthcare settings, including clinics, hospitals, and in remote areas with limited medical infrastructure. By enabling early and precise diagnosis, this tool can improve patient outcomes, reduce the spread of infectious diseases, and alleviate the burden on healthcare systems. Furthermore, its scalability and low manufacturing costs position it as a viable option for mass production and global distribution, addressing urgent public health needs.    This I-Corps project utilizes experiential learning coupled with a first-hand investigation of the industry ecosystem to assess the translation potential of the technology. This solution is based on the development of a method to determine multiple pathological conditions simultaneously. The solution detects the infrared signatures produced by the resonant excitation of certain molecules using a tunable source. This approach achieves a limit of detection that is orders of magnitude higher than available nanosensors. By applying machine learning techniques to analyze the nanomechanical infrared response profile, multiple pathological conditions can be identified simultaneously. This device is capable of continuous miniaturization, making it portable and affordable for widespread deployment.    This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.",
                "keywords": [],
                "approved": true
            }
        },
        {
            "type": "Grant",
            "id": "15675",
            "attributes": {
                "award_id": "1R01EB037031-01",
                "title": "Point-of-care DNA diagnostics from raw samples",
                "funder": {
                    "id": 4,
                    "ror": "https://ror.org/01cwqze88",
                    "name": "National Institutes of Health",
                    "approved": true
                },
                "funder_divisions": [
                    "National Institute of Biomedical Imaging and Bioengineering (NIBIB)"
                ],
                "program_reference_codes": [],
                "program_officials": [
                    {
                        "id": 32518,
                        "first_name": "KRISTIN HEDGEPATH",
                        "last_name": "GILCHRIST",
                        "orcid": "",
                        "emails": "",
                        "private_emails": "",
                        "keywords": null,
                        "approved": true,
                        "websites": null,
                        "desired_collaboration": null,
                        "comments": null,
                        "affiliations": []
                    }
                ],
                "start_date": "2025-04-05",
                "end_date": "2029-03-31",
                "award_amount": 257807,
                "principal_investigator": {
                    "id": 32519,
                    "first_name": "Robert M",
                    "last_name": "Cooper",
                    "orcid": "",
                    "emails": "",
                    "private_emails": "",
                    "keywords": null,
                    "approved": true,
                    "websites": null,
                    "desired_collaboration": null,
                    "comments": null,
                    "affiliations": []
                },
                "other_investigators": [],
                "awardee_organization": {
                    "id": 760,
                    "ror": "https://ror.org/0168r3w48",
                    "name": "University of California, San Diego",
                    "address": "",
                    "city": "",
                    "state": "CA",
                    "zip": "",
                    "country": "United States",
                    "approved": true
                },
                "abstract": "The proposed project will develop living biosensors for detecting and analyzing DNA at the single- base level, without requiring sample purification or any equipment. DNA is the prime information carrier for life, and DNA analysis provides valuable information for, e.g., diagnosing microbial infections or tracking disease outbreaks. Many techniques exist for detecting and analyzing DNA, but these generally require processing steps to extract and purify samples, and most require expensive equipment and significant training and expertise. This proposal will transfer that complexity into the biosensor itself, harnessing functions that evolved into living bacteria over billions of years to pull DNA out of raw samples, analyze it, and produce easily read output. The biosensors will pull in DNA using natural competence, and analyze it with single-base precision using their endogenous CRISPR-Cas system. Upon detecting a target sequence, the living biosensors will release thousands of signal molecules that can be detected using a lateral flow assay, similar to a consumer pregnancy or Covid-19 test. Several target DNA sequences will be used for demonstrations: urinary tract pathogens, E. coli, and Salmonella. The target uropathogens are difficult to diagnose with standard culture tests. Using single-base sequence analysis, the biosensors will subtype E. coli as likely pathogenic or likely commensal. A similar strategy will be employed to detect single-base mutations responsible for the majority of fluoroquinolone-resistant Salmonella isolates. DNA biosensing will be demonstrated in clinically relevant human samples, without the extensive purification required by other methods. The result will be a hybrid living biosensor / lateral flow assay that requires minimal sample preparation, produces rapid results, and can achieve single-base resolution. The biosensors developed in this project could find applications any time DNA monitoring is needed that is inexpensive, requires minimal sample preparation, equipment, and expertise, or takes place at the point of care. Examples include clinical diagnostics, monitoring disease outbreaks for public health, or environmental monitoring, with particular benefits where resources are limited.",
                "keywords": [
                    "Antibiotic Resistance",
                    "Architecture",
                    "Bacteria",
                    "Base Sequence",
                    "Binding",
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                    "Biological Assay",
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                    "COVID-19 test",
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                    "Clustered Regularly Interspaced Short Palindromic Repeats",
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                    "point-of-care diagnostics",
                    "screening",
                    "tumor"
                ],
                "approved": true
            }
        }
    ],
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