Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1384&sort=-program_reference_codes
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-program_reference_codes", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1405&sort=-program_reference_codes", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1385&sort=-program_reference_codes", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1383&sort=-program_reference_codes" }, "data": [ { "type": "Grant", "id": "11566", "attributes": { "award_id": "5R21CA261775-02", "title": "A Practical Approach to Tumor-Specific Aptamers for B-Cell Hematologic Malignancies", "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": 23826, "first_name": "Tawnya C", "last_name": "Mckee", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-05-01", "end_date": "2025-04-30", "award_amount": 188415, "principal_investigator": { "id": 23827, "first_name": "Qiao", "last_name": "Lin", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 922, "ror": "", "name": "COLUMBIA UNIV NEW YORK MORNINGSIDE", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 922, "ror": "", "name": "COLUMBIA UNIV NEW YORK MORNINGSIDE", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "Personalized medicine will greatly improve the effectiveness of cancer care; however, the development of practically attainable patient-specific strategies has remained challenging. One unique opportunity exists with B cell-derived malignancies, which often express surface immunoglobulins (sIgs) with variable regions (idiotypes, Ids) within their B-cell receptors (BCRs). As malignant cells originate from a single clone, such sIg-Id molecules are specific to the tumor and unique to each patient. Targeting sIg-Ids can hence enable personalized disease identification and treatment strategies. Early studies using patient-specific anti-sIg-Id antibodies yielded promising results but were deemed unsustainable. A technology to generate personalized ligands in a time- efficient and cost-effective manner remains an unmet need in sIg-Id-based diagnostics and therapeutics. Aptamers, i.e., single-stranded oligonucleotides that specifically bind to biological targets, offer an attractive solution to this unmet need. Aptamers are isolated from a randomized oligonucleotide library via an in vitro process known as SELEX, which is traditionally labor-intensive, time-consuming (up to a month), and impractical for personalized aptamer generation. In contrast, we have developed a microfluidic platform, called microSELEX (μSELEX), which has been used to isolate aptamers for protein biomarkers, including Id regions of monoclonal antibodies from patients with multiple myeloma and COVID-19. Given a monoclonal protein from a patient sample, the platform is capable of rapidly isolating personalized anti-Id aptamers within ~10 hours. We propose to explore time-efficient and cost-effective μSELEX isolation of patient-specific DNA aptamers targeting sIg-Ids of tumor B cells for B-cell hematologic malignancies. We will first establish an optimal μSELEX protocol using B cell-derived cell lines, then isolate anti-sIg aptamers against tumor B cells obtained from peripheral blood samples of B cell lymphoma patients, and finally demonstrate noninvasive peripheral blood- based monitoring of minimal residual disease by using the aptamers to detect circulating tumor B cells. In addition to enabling timely identification of minimal residual disease for more precise clinical decision making, anti-sIg-Id aptamers can also be used as therapeutic ligands to enable personalized and precisely targeted therapy for more effective disease treatment. Such personalized aptamers can hence potentially lead to transformative changes in the care of patients with B-cell hematologic malignancies.", "keywords": [ "Affinity", "Antibodies", "B lymphoid malignancy", "B-Cell Antigen Receptor", "B-Cell Lymphomas", "B-Cell Neoplasm", "B-Lymphocytes", "Behavior", "Binding", "Biochemical", "Biological", "Blood specimen", "COVID-19", "Cancer Diagnostics", "Cell Line", "Cell surface", "Cells", "Chronic Lymphocytic Leukemia", "Classification", "Clinical", "Consumption", "DNA", "Detection", "Development", "Devices", "Diagnostic", "Disease", "Disease remission", "Effectiveness", "Evolution", "Generations", "Hematologic Neoplasms", "Hour", "Immunoglobulin Idiotypes", "Immunoglobulins", "In Vitro", "Ions", "Libraries", "Ligands", "Magic", "Magnetic nanoparticles", "Malignant - descriptor", "Malignant Neoplasms", "Mantle Cell Lymphoma", "Medicine", "Methods", "Microfluidics", "Monitor", "Monoclonal Antibodies", "Multiple Myeloma", "Nucleic Acids", "Oligonucleotides", "Patient Care", "Patients", "Precision therapeutics", "Process", "Proteins", "Protocols documentation", "Randomized", "Reagent", "Residual Neoplasm", "Residual state", "Sampling", "Specificity", "Surface Immunoglobulins", "Tars", "Technology", "Therapeutic", "Time", "Tin", "Translations", "aptamer", "cancer care", "cancer cell", "clinical decision-making", "cohort", "cost effective", "cross reactivity", "improved", "innovation", "nanoparticle", "neoplastic cell", "novel", "peripheral blood", "personalized medicine", "personalized therapeutic", "protein biomarkers", "response", "targeted treatment", "treatment strategy", "tumor" ], "approved": true } }, { "type": "Grant", "id": "11567", "attributes": { "award_id": "5R01AG076541-02", "title": "Project on EHR-Integrated Lifestyle Interventions for Adults Aged Fifty and Older (PIVOT)", "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": 27534, "first_name": "Elise", "last_name": "Rice", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-05-15", "end_date": "2027-04-30", "award_amount": 651752, "principal_investigator": { "id": 22236, "first_name": "Thomas George", "last_name": "Kannampallil", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 163, "ror": "https://ror.org/02mpq6x41", "name": "University of Illinois at Chicago", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 23830, "first_name": "Jun", "last_name": "Ma", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 23831, "first_name": "Elizabeth Mary", "last_name": "Venditti", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 163, "ror": "https://ror.org/02mpq6x41", "name": "University of Illinois at Chicago", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true }, "abstract": "Obesity and cardiometabolic comorbidities are leading chronic conditions among middle-aged and older adults. During the COVID-19 pandemic unhealthy lifestyle habits seem to worsen to a greater degree in those with multiple chronic conditions, promoting weight gain and further widening health disparities. Middle to older aged adults with underlying multimorbid conditions, especially minorities, are particularly vulnerable to the secondary health effects of the pandemic and are the target population for this study. This study capitalizes on our decades-long translational research on the efficacious Diabetes Prevention Program (DPP) and DPP-based Group Lifestyle Balance (GLB) interventions; our extensive experience in using electronic health records (EHR) for patient identification and monitoring; and our partnerships with multisector stakeholders in digital health and wellness solutions. This multisite clinical trial uses a 2-stage sequential randomization design to test the adaptive and nonadaptive augmentation of an EHR-integrated, validated base (GLB video) intervention using problem solving treatment (PST), a proven behavior therapy. English/Spanish speaking adults (N=1029), ≥50 years with a body mass index ≥27 and ≥1 cardiometabolic conditions, will be randomized at baseline to base intervention or waitlist control. Responders to the base intervention, defined by ≥3% weight loss at 6 weeks, will continue the base intervention; participants with <3% weight loss or missing weight data (i.e., nonresponders) will be re-randomized to continue the base intervention alone or augmented with PST coaching via videoconference. Waitlist participants will be re-randomized after a 12-week control period to receive the base or the augmented intervention, but without tailoring based on early weight loss. The base intervention will use EHR-integrated delivery of the self-directed GLB videos, 1 per week for 12 weeks, followed by digital behavior change and motivational messages. The augmented intervention includes base intervention + PST videoconference coaching. All participants will receive a tablet, wireless weight scale, and wearable activity tracker and will be followed for 52 weeks after baseline randomization. Aim 1 is to demonstrate intervention effects on weight loss, behavior change, and patient-reported outcomes. We hypothesize: (1) the augmented intervention will be more effective than the base intervention both among early nonresponders to the base intervention (adaptive) and among participants in the waitlist group (nonadaptive) at 52 weeks; (2) the adaptive augmented intervention will be more efficacious than the base intervention and more efficacious than the waitlist control group at 12 weeks. Aim 2 is to identify predictors of clinically significant (5%) weight loss for individual patients, using sociodemographic, clinical and behavioral engagement characteristics. The proposed interventions are poised to have immediate and widespread impact on access, reach, delivery, effectiveness, scalability and sustainability. This study, if successful, will point the way toward an inexpensive, scalable intervention that would likely be adopted by insurers.", "keywords": [ "Acceleration", "Accelerometer", "Adopted", "Adult", "Age", "Aging", "Behavior", "Behavior Therapy", "Behavioral", "Body Weight Changes", "Body Weight decreased", "Body mass index", "COVID-19 pandemic", "COVID-19 pandemic effects", "Characteristics", "Chronic", "Clinical", "Control Groups", "Data", "Development", "Effectiveness", "Elderly", "Electronic Health Record", "Equilibrium", "Frequencies", "Future", "Goals", "Habits", "Health", "Health system", "Improve Access", "Incidence", "Individual", "Insurance Carriers", "Intervention", "Life Style", "Machine Learning", "Measures", "Minority", "Modeling", "Monitor", "Motivation", "Multi-Institutional Clinical Trial", "Obesity", "Outcome", "Overweight", "Participant", "Patient Outcomes Assessments", "Patients", "Personal Satisfaction", "Physical activity", "Prevalence", "Problem Solving", "Public Health", "Quality of life", "Randomized", "Research", "Secondary to", "Self Direction", "Sequential Multiple Assignment Randomized Trial", "Sleep", "Surveys", "System", "Tablets", "Target Populations", "Techniques", "Testing", "Translational Research", "Treatment Efficacy", "Unhealthy Diet", "United States National Institutes of Health", "Waiting Lists", "Weight", "Weight Gain", "Work", "adaptive intervention", "adult obesity", "aged", "aging population", "base", "behavior change", "behavior measurement", "behavioral health intervention", "burden of illness", "cardiometabolism", "care delivery", "clinical predictors", "clinically significant", "comorbidity", "design", "diabetes prevention program", "digital", "digital health", "digital healthcare", "effectiveness evaluation", "electronic data", "experience", "health care delivery", "health disparity", "human old age (65+)", "individual patient", "innovation", "intervention effect", "lifestyle intervention", "middle age", "multi-site trial", "multiple chronic conditions", "novel strategies", "pandemic impact", "patient health information", "physical inactivity", "point of care", "predictive modeling", "prevent", "primary outcome", "programs", "psychosocial", "recruit", "remote health care", "response", "sociodemographics", "success", "therapy development", "trial design", "unhealthy lifestyle", "wearable device", "weight loss intervention", "wireless" ], "approved": true } }, { "type": "Grant", "id": "11568", "attributes": { "award_id": "5F31MH130274-02", "title": "Assessing the Impact of COVID-19-Related Distancing and Clinical Service Disruptions on the HIV Epidemic in the United States", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Mental Health (NIMH)" ], "program_reference_codes": [], "program_officials": [ { "id": 6810, "first_name": "Susannah", "last_name": "Allison", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-05-01", "end_date": "2024-04-30", "award_amount": 47694, "principal_investigator": { "id": 23832, "first_name": "Laura M", "last_name": "Mann", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 265, "ror": "https://ror.org/03czfpz43", "name": "Emory University", "address": "", "city": "", "state": "GA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 265, "ror": "https://ror.org/03czfpz43", "name": "Emory University", "address": "", "city": "", "state": "GA", "zip": "", "country": "United States", "approved": true }, "abstract": "With over 1.2 million Americans currently living with Human Immunodeficiency Virus (HIV), and nearly 40,000 new infections every year, HIV remains a major public health challenge in the United States. HIV risk is not uniform across the US population: approximately 70% of infections occur among gay, bisexual, and other men who have sex with men (MSM), and certain racial/ethnic groups experience higher HIV risk. HIV transmission remains high despite recent advancements in biomedical prevention and treatment partly because of disparities in access to these measures. Economic and social disruptions from the COVID-19 global pandemic have exacerbated these disparities and created new challenges in HIV control, disrupting access to HIV prevention and clinical care services and prompting major behavioral changes (including reductions in sexual activity, “sexual distancing”). These changes may dramatically impact the trajectory of the US HIV epidemic. There have been reports of decreased HIV diagnoses during the pandemic, but these estimates may be an artifact of reduced screening rather than decreased transmission and are therefore unreliable. Enumerating HIV transmission is critical for the provision of HIV prevention interventions; a better understanding of how the COVID-19 pandemic has affected and will continue to affect HIV dynamics of US MSM is urgently required. Increased transmission due to service disruptions may be offset by sexual distancing, but this depends on the temporal patterns and demographic distribution of these changes. Transmission may also be mitigated by interventions that address clinical disruptions (e.g., telehealth and other home-based HIV medical services). Our overarching hypotheses are: 1) COVID-19-related changes in sexual behavior and service disruptions have varied among US MSM in magnitude and timing by demographic factors, 2) these changes will alter HIV incidence across the pandemic era, and 3) targeted home-based HIV medical care retention interventions can curtail the impact of clinical care disruptions on HIV transmission. In AIM 1, we will triangulate data from two independent longitudinal studies of US MSM to describe the temporal patterns and demographic distribution of sexual distancing and HIV service disruptions. In AIM 2, we will use a network-based HIV transmission model to disentangle changes in HIV transmission versus screening to estimate HIV incidence among US MSM during and after the COVID-19 pandemic. In AIM 3, we will use a transmission model to determine the epidemiologic impact of targeted home-based HIV care retention interventions in a high burden jurisdiction. The findings of this project will both inform HIV surveillance efforts and guide the development of targeted HIV prevention programs. With this research and training program, the applicant will gain a multidisciplinary skill set combining epidemiologic methods, network science, and infectious disease modeling, while advancing our knowledge of HIV dynamics in the COVID era. This unique training will provide the technical skillset needed for the applicant to become a successful independent researcher and infectious disease epidemiologist.", "keywords": [ "AIDS prevention", "Address", "Affect", "American", "Area", "Behavior", "Behavioral", "Bisexual", "Black Populations", "COVID-19", "COVID-19 impact", "COVID-19 pandemic", "Caring", "Clinical", "Clinical Services", "Communicable Diseases", "Complex", "Data", "Demographic Factors", "Development", "Economics", "Epidemic", "Epidemiologic Methods", "Epidemiologist", "Epidemiology", "Ethnic Population", "Funding", "Gays", "Goals", "HIV", "HIV Infections", "HIV diagnosis", "HIV risk", "HIV-2", "Home", "Incidence", "Infection", "Intervention", "Knowledge", "Longitudinal Studies", "Measures", "Medical", "Mentors", "Modeling", "Monitor", "Morphologic artifacts", "Network-based", "Pattern", "Persons", "Population", "Prevalence", "Prevention", "Prevention program", "Prevention strategy", "Public Health", "Reporting", "Research", "Research Personnel", "Safe Sex", "Science", "Services", "Sex Behavior", "Shapes", "Signal Transduction", "Social Distance", "Socialization", "Southeastern United States", "Statistical Models", "Target Populations", "Technical Expertise", "Training", "Training Programs", "United States", "United States National Institutes of Health", "Variant", "Viral Load result", "antiretroviral therapy", "behavior change", "care systems", "clinical care", "coronavirus disease", "experience", "future pandemic", "high risk", "infectious disease model", "mathematical model", "men who have sex with men", "multidisciplinary", "pandemic disease", "pandemic preparedness", "pre-exposure prophylaxis", "preventive intervention", "programs", "racial population", "remote intervention", "screening", "service utilization", "sexual risk behavior", "skills", "social", "telehealth", "tool", "transmission process", "treatment program", "treatment strategy" ], "approved": true } }, { "type": "Grant", "id": "11569", "attributes": { "award_id": "5R03NS127075-02", "title": "MiRNA-based Therapeutics for SARS-CoV-2 S1 mediated neuroinflammation and beta-amyloid production", "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": 6896, "first_name": "WILLIAM PATRICK", "last_name": "Daley", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-05-01", "end_date": "2024-04-30", "award_amount": 74750, "principal_investigator": { "id": 23833, "first_name": "Eleni", "last_name": "Markoutsa", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 235, "ror": "https://ror.org/032db5x82", "name": "University of South Florida", "address": "", "city": "", "state": "FL", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 235, "ror": "https://ror.org/032db5x82", "name": "University of South Florida", "address": "", "city": "", "state": "FL", "zip": "", "country": "United States", "approved": true }, "abstract": "There is ample evidence that SARS-CoV-2, the causative agent of COVID-19, causes neurological symptoms but there is insufficient evidence that the virus can directly infect the brain. It has been suggested that neurological symptoms might be due to additional factors such as cytokine storm, neuroimmune stimulation, and systemic SARS-CoV-2 infection, rather than by direct CNS damage caused by the virus. The S protein is the main antigenic component of SARS- CoV-2 structural protein and its proteolytic processing allows the S1 subunit to dissociate, which then triggers the S2 subunit rearrangement that is required for fusion. Also, TLR4 is the most important member of the TLR family for pathogen recognition and helps to provide first line defense against infections through inflammatory factors induction. Herein, we propose to test the hypothesis that the cleaved S1 subunit itself enters the brain parenchyma causing neuroinflammation and b-amyloid accumulation and TLR4-targeted microRNA(s) can inhibit these processes. This hypothesis will be tested in two specific aims. First, we will test if S1 directly interacts with TLR4 in microglia and initiates immune responses that leads to excessive activation of the pathway, which disrupts immune homeostasis and results in chronic brain inflammation and b-amyloid accumulation. Second, we will test the role of specific miRNAs, selected using bioinformatics prediction tools, in regulating the S1-initiated neuroinflammation. After experimental validation of miRNA targets, specific miRNAs will be enriched in exosomes and tested for their ability to end the positive feedback loop between inflammation and b-amyloid production. The results are expected to provide mechanistic insights into the COVID-19 effects on neuroinflammation and dementia and lead to the development of miRNA therapeutics against covid-induced regulatory loop between inflammation and b-amyloid production.", "keywords": [ "2019-nCoV", "Abeta synthesis", "Algorithms", "Alzheimer&apos", "s disease risk", "Amyloid", "Amyloid deposition", "Astrocytes", "Attenuated", "Bioinformatics", "Biological Assay", "Brain", "COVID-19", "COVID-19 impact", "COVID-19 survivors", "COVID-19 therapeutics", "Cells", "Central Nervous System", "Cerebrospinal Fluid", "Cessation of life", "Chronic", "Data", "Dementia", "Development", "Dissociation", "Down-Regulation", "Encephalitis", "Family", "Feedback", "Future", "Genes", "Homeostasis", "Human", "Immune", "Immune response", "Immune signaling", "Infection", "Inflammation", "Inflammation Mediators", "Inflammatory", "Inflammatory Response", "Interleukin-6", "Intranasal Administration", "Light", "Long-Term Effects", "Luciferases", "MAP Kinase Gene", "MAPK1 gene", "MAPK8 gene", "Measures", "Mediating", "MicroRNAs", "Microglia", "Mus", "NF-kappa B", "Neuroimmune", "Neurologic Symptoms", "Pathway interactions", "Persons", "Process", "Production", "Proteins", "Proteolytic Processing", "Quantitative Reverse Transcriptase PCR", "Regulation", "Reporter", "Respiratory Signs and Symptoms", "Role", "SARS-CoV-2 infection", "Signal Pathway", "Signal Transduction", "Stains", "Structural Protein", "TLR4 gene", "TNF gene", "Testing", "Therapeutic Intervention", "Time", "Transcript", "Validation", "Viral Proteins", "Virus", "Work", "bioinformatics tool", "brain parenchyma", "coronavirus therapeutics", "cytokine", "cytokine release syndrome", "effectiveness validation", "engineered exosomes", "exosome", "experimental study", "glial activation", "high risk", "in vitro testing", "in vivo", "in vivo evaluation", "innovation", "insight", "member", "neuroinflammation", "novel", "p38 Mitogen Activated Protein Kinase", "pandemic disease", "pathogen", "predictive tools", "therapeutic miRNA", "viral RNA" ], "approved": true } }, { "type": "Grant", "id": "11570", "attributes": { "award_id": "5R21AI159303-02", "title": "Targeting macrophages to reduce the combined injury effects of radiation and virus exposure", "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": 23834, "first_name": "Thomas A.", "last_name": "Winters", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-05-05", "end_date": "2024-04-30", "award_amount": 154000, "principal_investigator": { "id": 23835, "first_name": "BRIAN", "last_name": "MARPLES", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 464, "ror": "https://ror.org/022kthw22", "name": "University of Rochester", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 464, "ror": "https://ror.org/022kthw22", "name": "University of Rochester", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "PROJECT SUMMARY/ABSTRACT: Pneumonitis and fibrosis occur after oncologic lung radiotherapy (RT) or TBI conditioning for BMT. The sustained production of inflammatory cytokines, dysregulated macrophage activation and perpetual ROS generation are considered molecular mediators of these events. SARS-CoV-2- confirmed patients experience lower respiratory tract illness, dyspnea and peripheral fibrosis, along with production of proinflammatory cytokines from recruited immune cells; events that indicate the lungs are susceptible to SARS-CoV-2 infection, with old age and comorbidities also identified as predisposing conditions. Therefore, both high-dose RT and viral infection promote proinflammatory microenvironments in the lung, the recruitment of macrophage populations and cytokine signaling; suggesting a commonality to mechanisms of pulmonary fibrosis that involve a ‘cytokine storm’. In support of this, we reported preliminary data that lung- targeted RT, alone or combined with TBI, increased mortality and fibrosis from influenza virus A (HKx31 (H3N2)) and exacerbated infection risks in radiation-sensitive organs. Since both local microenvironmental alterations and innate immune cell recruitment were implicated, we now hypothesize that lung radiation produces long- term changes in the lung microenvironment that affect immune responses to respiratory viral pathogens. We will investigate the immediate (<24h) mechanistic interactions responsible for long-term lung injury (>26 wks) caused by combined exposures to focal lung RT followed by virus, and vice versa, using 3D precision cut lung slices and mouse models. The overall goal is to develop molecular-based protective/mitigating strategies. Aim 1.1: To investigate how prior lung irradiation of C57BL/6 and C3H mice, and dose-dependent radiation- induced lung injury, affects sensitivity and susceptibility to virus infection using Influenza and murine corona viral strains to model SARS-CoV-2 infection. Also, to investigate how persistent or latent lung injury from the first insult impacts the sensitivity to the second insult by varying the time interval between the two insults. Aim 1.2: To investigate how viral infection and the viral-induced ‘cytokine storm’ alters lung radiosensitivity, and the temporal progression through radiation-induced pneumonitis and fibrosis. Aged mice will also be used to determine how age- and weight-related co-morbidity factors exacerbate the risk for combined pulmonary injury. Aim 1.3: Use human 3D lung slice cultures to investigate how viral infection alters mechanisms of RT-induced DNA DSB repair, and the impact on cell lethality. Aim 2: To determine if mitigating inflammation and/or oxidative stress in the lungs with antioxidants AEOL-10150 and NaI, or preventing the aberrant recruitment and activation of infiltrating macrophages at sites of pulmonary injury by targeting the CD200 receptor, will mitigate risks for combined radiation and viral exposures. These studies will be significant because they model the relationship between radiation damage and viral infectivity in the lung, and offer the potential for molecular-targeted mitigation for RT and combined viral injury.", "keywords": [ "2019-nCoV", "3-Dimensional", "Acute", "Acute Respiratory Distress Syndrome", "Address", "Affect", "Age", "Alveolar", "Alveolar Macrophages", "Animals", "Anti-Inflammatory Agents", "Antioxidants", "Body Weight decreased", "Breathing", "CD 200", "COVID-19 patient", "COVID-19 susceptibility", "Cancer Patient", "Cells", "Chronic", "Clinical", "Clinical Trials", "Complement", "Coronavirus", "Cytokine Signaling", "DNA", "Data", "Diffuse", "Dose", "Dyspnea", "Elderly", "Epithelial", "Event", "Exposure to", "Female", "Fibrosis", "Generations", "Goals", "Grant", "Heart", "Histopathology", "Human", "Immune", "Immune response", "Immunomodulators", "Impairment", "Inbred C3H Mice", "Infection", "Infiltration", "Inflammation", "Inflammatory", "Inflammatory Infiltrate", "Influenza", "Influenza A Virus H1N1 Subtype", "Influenza A Virus H3N2 Subtype", "Influenza A virus", "Injury", "Lower respiratory tract structure", "Lung", "Macrophage Activation", "Malignant neoplasm of lung", "Measures", "Mediating", "Mediator", "Modeling", "Molecular", "Molecular Target", "Morbidity - disease rate", "Murine hepatitis virus", "Mus", "Organ", "Oxidative Stress", "Pathogenicity", "Pathology", "Patients", "Peripheral", "Phase", "Phenotype", "Plasma", "Pleural effusion disorder", "Population", "Predisposition", "Process", "Production", "Proteins", "Puerto Rico", "Pulmonary Fibrosis", "Pulmonary Inflammation", "Pulmonary Pathology", "Radiation", "Radiation Pneumonitis", "Radiation Tolerance", "Radiation induced damage", "Radiation therapy", "Recombinants", "Recovery", "Regulation", "Reporting", "Resolution", "Risk", "SARS-CoV-2 infection", "Severities", "Signal Transduction", "Site", "Slice", "Targeted Radiotherapy", "Testing", "Time", "Tumor-infiltrating immune cells", "Viral", "Viral Load result", "Virulence", "Virus", "Virus Diseases", "Weight", "Whole-Body Irradiation", "age related", "aged", "biobank", "cellular targeting", "chemokine", "clinically relevant", "comorbidity", "conditioning", "cytokine", "cytokine release syndrome", "epithelial injury", "experience", "fibrogenesis", "human old age (65+)", "immunoregulation", "infection risk", "influenza virus strain", "influenzavirus", "irradiation", "lung injury", "macrophage", "male", "mortality", "mouse model", "novel", "pathogen", "pathogenic virus", "pneumonitis and fibrosis", "prevent", "pulmonary function", "radiation effect", "radiation risk", "radiation-induced lung injur" ], "approved": true } }, { "type": "Grant", "id": "11571", "attributes": { "award_id": "5R21AI161470-02", "title": "Creation and Validation of cell-based screening systems for SARS-CoV-2 drug targets", "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": 6115, "first_name": "DIPANWITA", "last_name": "Basu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-05-06", "end_date": "2024-04-30", "award_amount": 199375, "principal_investigator": { "id": 7011, "first_name": "THOMAS", "last_name": "MELENDY", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 856, "ror": "", "name": "STATE UNIVERSITY OF NEW YORK AT BUFFALO", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 856, "ror": "", "name": "STATE UNIVERSITY OF NEW YORK AT BUFFALO", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "Project Summary/Abstract: Effective antivirals are sorely needed against SARS CoV-2 (CoV2), and coronaviruses (CoV) in general. Screening systems for drugs targeting CoV2 enzymes usually involve screening against purified enzymes. This can be technically challenging, and the vast majority of inhibitors identified ultimately lack utility as antivirals because: they may not be transported into and retained in cells, altered within cells such that they no longer inhibit the target effectively, or exhibit off-target effects that preclude their use as therapeutics. Using predicted drugs directly in viral infection assays can exhibit off-target effects against the host cell or other viral proteins and can be difficult to distinguish within the context of the viral infection (the inhibition of CoV2 infection by hydroxychloroquine is one such example). Ideally screens for viral enzymes isolate the enzyme from the viral infection, but evaluate function within human cells. We have constructed vectors for expression of four wild-type CoV2 proteins, and unique biosensors, to evaluate function of two CoV2 enzymatic functions, the CoV Main Protease and the CoV RNA-dependent RNA polymerase complex. We are completing assay validation and beginning to use the assays to evaluate the few known inhibitors of these enzymes. The protease assay will be converted to a stable cell line for large scale screening programs. The transfection assays will be evaluated using both established and experimental 3CL and RdRpC inhibitors, and 128 FDA- approved drugs that we have predicted target these enzymes, to validate the usefulness of these screening assays. Drugs that show inhibition of activity will be quantified using dose-response analysis in the cell-based assays, and subsequently analyzed for inhibition of CoV2 infection of cultured human lung cells across a similar dose-response range. Following validation, vectors and/or stable cells lines for the cell-based drug screening systems will be made readily available to other researchers, such as NIH’s NCATS, who are currently seeking CoV antiviral agents.", "keywords": [ "2019-nCoV", "Amino Acids", "Antiviral Agents", "Appearance", "Biological Assay", "Biosensor", "COVID-19", "COVID-19 vaccine", "Cell Line", "Cells", "Chymase", "Code", "Complex", "Coronavirus", "Development", "Disease Outbreaks", "Dose", "Drug Screening", "Drug Targeting", "Economics", "Enzyme Inhibition", "Enzyme Inhibitor Drugs", "Enzymes", "Exhibits", "FDA approved", "Firefly Luciferases", "Fluorescence", "Future", "Genomic DNA", "Health", "Human", "Hydroxychloroquine", "Individual", "Infection", "Libraries", "Luciferases", "Lung", "Messenger RNA", "National Center for Advancing Translational Sciences", "Peptide Hydrolases", "Pharmaceutical Preparations", "Plasmids", "Point Mutation", "Polyproteins", "Proteins", "RNA Polymerase Inhibitor", "RNA-Directed RNA Polymerase", "Recovery", "Renilla Luciferases", "Research Personnel", "Ribonucleic Acid Regulatory Sequences", "SARS-CoV-2 antiviral", "SARS-CoV-2 infection", "SARS-CoV-2 inhibitor", "Series", "Site", "System", "Testing", "Therapeutic", "Transfection", "Translating", "Uncertainty", "United States National Institutes of Health", "Vaccines", "Validation", "Viral", "Viral Genome", "Viral Physiology", "Viral Proteins", "Virus Diseases", "antiviral drug development", "coronavirus antiviral", "design", "enzyme activity", "expression vector", "improved", "in vitro activity", "inhibitor", "novel coronavirus", "pandemic coronavirus", "red fluorescent protein", "resistant strain", "response", "screening", "screening program", "stable cell line", "vaccine acceptance", "vector", "zoonotic coronavirus" ], "approved": true } }, { "type": "Grant", "id": "11572", "attributes": { "award_id": "3U19AI171413-01S1", "title": "UTMB-Novartis Alliance for Pandemic Preparedness", "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": 27535, "first_name": "Ping", "last_name": "Chen", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-05-16", "end_date": "2025-04-30", "award_amount": 18849015, "principal_investigator": { "id": 27536, "first_name": "Thierry", "last_name": "Diagana", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 7025, "first_name": "VINEET D", "last_name": "MENACHERY", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 851, "ror": "", "name": "UNIVERSITY OF TEXAS MED BR GALVESTON", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true } ] } ], "awardee_organization": { "id": 851, "ror": "", "name": "UNIVERSITY OF TEXAS MED BR GALVESTON", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "OVERALL – ABSTRACT Pandemic prevention and preparedness is a major scientific and societal priority that requires sustained and forward looking investments across governmental, non-governmental, academic and private sectors to develop an arsenal of countermeasures against the existential threat of viral pandemics. Combining world-leading BSL3/4 capabilities at University of Texas of Medical Branch (UTMB) and state-of-the art drug discovery technologies at Novartis, the UTMB Novartis Alliance for Pandemic Preparedness (UNAPP), is a unique and innovative partnership that brings together the multi-disciplinary expertise required to deliver high quality antiviral drug candidates. Enabled by world-leading virologists and seasoned drug hunters, UNAPP will aggressively prosecute a portfolio of 5 projects aiming to discover orally available, safe, and effective drugs against coronaviruses, flavivirus and henipavirus, three major classes of viruses with pandemic potential. The projects portfolio combines approaches targeting well validated drug targets, such as the RNA- dependent RNA polymerases and viral proteases, as well as phenotypic screening, which will allow for the discovery of clinical drug candidates and novel targets that will advance our fundamental understanding of the biology of those viruses. Four scientific Cores—Virology, High-Throughput Biology, Drug Discovery and Translational Research Cores—will provide technological and scientific expertise to support Project Teams and implement the scientific strategy toward novel antiviral drugs. The UNAPP will be governed by an Administrative Core which will be co-led by the PIs, Dr. Pei-Yong Shi and Dr. Thierry Diagana, who have a long track-record of successfully working together. Both PIs have led multiple productive collaborations focused on translational impact and combining public, private and non-governmental organizations. The Administrative Core will provide integrated decision making in scientific, operational, financial, intellectual property protection, and communication. In collaboration with all project and Core leaders, as well as with external input from a Scientific Advisory Board and NIH program officers, they will ensure that the projects portfolio leverages the full spectrum of technologies and capabilities residing in all four scientific Cores, capturing synergies across projects through cross-learning and efficient deployment of platforms relevant to multiple viruses. Because of the unique complementarity of the scientific Cores and the remarkable synergies of the project portfolio, we fully expect that the UNAPP will yield exceptional productivity and deliver all the proposed objectives: (1) Deliver 3 IND-ready candidates and 3 Development Candidates, (2) advance antiviral research, and (3) train next-generation drug hunters.", "keywords": [ "2019-nCoV", "Academia", "Air", "Antiviral Agents", "Biology", "COVID-19", "COVID-19 assay", "COVID-19 pandemic", "Cells", "Cessation of life", "Clinical", "Collaborations", "Communicable Diseases", "Communication", "Complex", "Coronavirus", "Data", "Decision Making", "Dengue", "Development", "Diagnostic", "Drug Targeting", "Education", "Emerging Technologies", "Ensure", "Faculty", "Family", "Flavivirus", "Foundations", "Future", "Generations", "Goals", "Hendra Virus", "Henipavirus", "Home", "Human", "Humanities", "Industry", "Infection", "Institution", "Intellectual Property", "Investments", "Laboratories", "Learning", "Libraries", "Life", "Machine Learning", "Marketing", "Medical", "Medicine", "Membrane Proteins", "Mentors", "Middle East Respiratory Syndrome Coronavirus", "Nipah Virus", "Nongovernmental Organizations", "Nucleosides", "Nucleotides", "Oral", "Peptide Hydrolases", "Pharmaceutical Preparations", "Pharmacologic Substance", "Phase I Clinical Trials", "Phenotype", "Polymerase", "Population Density", "Postdoctoral Fellow", "Predisposition", "Private Sector", "Privatization", "Probability", "Process", "Productivity", "Protease Inhibitor", "Quantitative Structure-Activity Relationship", "RNA-Directed RNA Polymerase", "Rationalization", "Research", "Research Activity", "Research Project Grants", "Resistance", "SARS-CoV-2 inhibitor", "Seasons", "Serotyping", "Spanish flu", "Technology", "Texas", "Training", "Translational Research", "Travel", "United States National Institutes of Health", "Universities", "Vaccines", "Viral", "Virus", "biosafety level 4 facility", "clinical candidate", "clinical investigation", "combat", "drug candidate", "drug discovery", "economic cost", "inhibitor", "innovation", "mortality", "multidisciplinary", "new technology", "next generation", "novel", "pandemic disease", "pandemic potential", "pandemic preparedness", "prevent pandemics", "programs", "public health relevance", "public-private partnership", "recruit", "response", "role model", "screening", "student training", "success", "synergism", "translational impact", "viral pandemic", "virology" ], "approved": true } }, { "type": "Grant", "id": "11573", "attributes": { "award_id": "5R21AI158230-02", "title": "Activation of inflammatory programmed cell death by SARS-CoV-2", "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": 26918, "first_name": "Michelle Marie", "last_name": "Arnold", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-05-01", "end_date": "2024-04-30", "award_amount": 220625, "principal_investigator": { "id": 7127, "first_name": "Andrew Atwell", "last_name": "Oberst", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 159, "ror": "https://ror.org/00cvxb145", "name": "University of Washington", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 159, "ror": "https://ror.org/00cvxb145", "name": "University of Washington", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true }, "abstract": "Programmed cell death is an ancient and effective defense mechanism against intracellular infection: activation of cellular suicide in response to intracellular pathogens eliminates pathogens’ replicative niches and exposes them to immune-mediated killing. However, when these responses occur incorrectly or overexuberantly, they can cause tissue destruction and exacerbate inflammation. Work from many groups including our own has shown that infection of the lung with RNA viruses can trigger cell death via the inflammatory process termed “necroptosis.” Our preliminary data confirm that infection of cells of the lung epithelium with SARS-CoV-2 leads to their death by necroptosis. These findings, along with additional preliminary data contained within the proposal, lead us to hypothesize that cell death by necroptosis is a key early response to infection of the lung with SARS-CoV-2. We further hypothesize that while a measured necroptotic response helps to eliminate SARS-CoV-2 virus, excessive necroptosis in the lung can lead to detrimental inflammatory pathology. We will test these hypotheses by focusing on three Aims: First, we will carry out detailed immunological and pathological profiling of SARS-2 infected mice lacking key components of necroptotic signaling. Next, we will use a mouse model developed in our lab to experimentally induce necroptosis in the alveolar epithelium in conjunction with SARS-2 infection. Finally, we will use human lung slices to assess cell death responses to SARS-2 infection in intact human tissue.", "keywords": [ "2019-nCoV", "Acute Respiratory Distress Syndrome", "Adaptive Immune System", "Address", "Affect", "Antigens", "Apoptosis", "Architecture", "Attention", "Atypical lymphocyte", "Autoimmunity", "COVID-19", "COVID-19 mortality", "COVID-19 patient", "COVID-19/ARDS", "Cell Death", "Cell Death Induction", "Cell Death Process", "Cell membrane", "Cells", "Cessation of life", "Clinical", "Coagulation Process", "Cytolysis", "Data", "Defense Mechanisms", "Disease", "Epithelial", "Epithelial Cells", "Event", "Functional disorder", "Future", "Genetic Transcription", "Heterogeneity", "Hour", "Human", "Hyperactivity", "Illness Days", "Image", "Immune", "Immune response", "Immune system", "Immunofluorescence Immunologic", "Immunologics", "Infection", "Inflammation", "Inflammatory", "Inflammatory Response", "Innate Immune System", "Lung", "Lung infections", "Lymphocyte", "Lymphocyte Activation", "Measures", "Mediating", "Morphology", "Mus", "Nature", "Pathologic", "Pathology", "Patients", "Phosphotransferases", "Process", "Production", "Publications", "RIPK1 gene", "RIPK3 gene", "RNA Viruses", "Reaction", "Respiratory Tract Infections", "Role", "SARS-CoV-2 infection", "Severities", "Signal Pathway", "Signal Transduction", "Slice", "Suicide prevention", "System", "Testing", "Tissues", "Viral", "Virus", "Virus Diseases", "Virus Replication", "Work", "adaptive immune response", "alveolar epithelium", "antiviral immunity", "autoreactivity", "cell suicide", "chemokine", "cytokine", "cytokine release syndrome", "human tissue", "immune activation", "inhibitor", "molecular marker", "mouse model", "pandemic disease", "pathogen", "post SARS-CoV-2 infection", "preservation", "recruit", "response", "severe COVID-19", "single cell sequencing", "suicidal morbidity" ], "approved": true } }, { "type": "Grant", "id": "11574", "attributes": { "award_id": "5R44HD105529-03", "title": "OvaReady: An automated microfluidic oocyte retrieval and denudation device expanding access to IVF", "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": 27537, "first_name": "NEELAKANTA", "last_name": "RAVINDRANATH", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-05-01", "end_date": "2024-04-30", "award_amount": 815410, "principal_investigator": { "id": 23847, "first_name": "Ismail Emre", "last_name": "Ozkumur", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1651, "ror": "", "name": "AUTOIVF, INC.", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1651, "ror": "", "name": "AUTOIVF, INC.", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "In the United States, the total number of In-vitro Fertilization (IVF) clinics has stayed relatively stagnant through the past decade, and the IVF-cycles per million women remains significantly lower than in other developed countries. The greatest challenge for widespread use of IVF include its high cost, driven by the need for complex and expensively equipped IVF laboratories and highly-trained embryologists. An IVF laboratory costs approximately $2 million to build, which has the effect of confining IVF laboratories to high-density population areas, causing geographic inaccessibility. The high cost and accessibility of IVF treatment is the leading reason why couples are unable to undergo and/or delay IVF treatment. Additionally, demand for fertility preservation through egg banking is rapidly increasing, but again the requirement of conducting the egg collection in fully equipped facilities and cost stand as significant hurdles to broader adoption. Our goal is to automate various functions within an embryology lab to decrease the cost and improve the overall accessibility of IVF and egg banking. This will be achieved by reducing the equipment and personnel requirements so as to pave the way towards de-centralization of IVF. Our technology will facilitate processing of gametes at basic satellite clinics prior to them being transferred to central embryology laboratories or long-term storage facilities. We propose to develop and commercialize a novel technique for preparation of human oocytes towards preservation or assisted fertilization, to address both the accessibility and cost limitations. OvaReady, an automated system that will utilize microfluidic devices to collect Cumulus-Oocyte-Complexes (COCs) from follicular fluid aspirate (FFA) and denude them, will enable a one-touch preparation of vitrification or ICSI-ready eggs. OvaReady will utilize innovative microfluidic technology with hardware and software controls, to enable automated isolation of oocytes from FFA. Performing egg denudation in a closed and integrated system will limit exposure of the eggs to deviations in temperature and pH, therefore improving safety, reliability, and efficiency of the IVF treatment by removing inter-/intra-operator variability. A further benefit, more applicable to today’s COVID environment, is that it will limit the operator exposure to potentially harmful agents in FFA. In our preliminary study, we demonstrate a proof of principle microfluidic platform that conducts rapid denudation of mouse oocytes from the COC, while maintaining their viability. In the proposed work, we will build on this innovation and integrate the following functions: COC collection from follicular fluid aspirate; denudation, washing, concentration of eggs to an appropriate handling volume for freezing, transport or insemination. Through this Fast-Track application, we propose and plan to complete the following aims in this order: Develop COC isolation unit and integrate with denudation unit; develop rest of the microfluidic design and generate recipe for reliable egg preparation; transfer microfluidic design to scaled-up manufacturing to achieve reliable performance; demonstrate success of the automated workflow with preparation of human oocytes.", "keywords": [ "Address", "Adoption", "Age", "Area", "Automobile Driving", "Blood Cells", "Cattle", "Clinic", "Collection", "Complex", "Computer software", "Couples", "Cryopreservation", "Decentralization", "Developed Countries", "Development", "Devices", "Embryology", "Environment", "Equipment", "Exposure to", "Fertilization", "Fertilization in Vitro", "Follicular Fluid", "Freezing", "Germ Cells", "Goals", "Growth", "Health Services Accessibility", "Human", "Human Resources", "Hyaluronidase", "Injections", "Insemination", "Institutional Review Boards", "Intracytoplasmic Sperm Injections", "Laboratories", "Liquid substance", "Marketing", "Methods", "Microfluidic Microchips", "Microfluidics", "Molds", "Mus", "Oocytes", "Patients", "Performance", "Phase", "Population Density", "Preparation", "Production", "Recipe", "Rest", "Safety", "Sampling", "Small Business Innovation Research Grant", "System", "Systems Integration", "Techniques", "Technology", "Temperature", "Training", "United States", "Woman", "Work", "access restrictions", "aspirate", "commercialization", "coronavirus disease", "cost", "design", "egg", "fertility preservation", "geographic inaccessibility", "improved", "infertility treatment", "innovation", "manufacturing scale-up", "microfluidic technology", "novel", "oocyte retrieval", "parallelization", "pregnant", "preservation", "procedure cost", "process optimization", "prototype", "scale up", "success" ], "approved": true } }, { "type": "Grant", "id": "11575", "attributes": { "award_id": "5R44AI165188-02", "title": "Live Cell Fluorescent Assays for SARS-CoV-2 protease activity and COVID-19 Drug Discovery", "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": 6115, "first_name": "DIPANWITA", "last_name": "Basu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-05-13", "end_date": "2024-04-30", "award_amount": 300000, "principal_investigator": { "id": 7258, "first_name": "THOMAS E", "last_name": "HUGHES", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 878, "ror": "", "name": "MONTANA MOLECULAR, LLC", "address": "", "city": "", "state": "MT", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 27538, "first_name": "Anne Marie", "last_name": "Quinn", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 878, "ror": "", "name": "MONTANA MOLECULAR, LLC", "address": "", "city": "", "state": "MT", "zip": "", "country": "United States", "approved": true }, "abstract": "STATEMENT The SARS-CoV-2 virus depends upon two proteases for replication, 3CLpro and PLpro. If one or both of these proteases can be blocked, COVID-19 infection can be effectively treated. Montana Molecular makes and sells live cell, fluorescent biosensor assays for disease research and drug discovery. In response to the COVID-19 pandemic, Montana Molecular applied its expertise and background in live cell assay development to build fluorescent biosensors for the SARS-CoV-2 main protease, 3CLpro. The prototype sensor described in this proposal demonstrates feasibility. Direct to Phase II support is requested here to speed the development of even brighter, more sensitive assays for the 3CLpro and PLpro proteases. These assays can be used in high throughput screening for compounds that inhibit the protease, and engage with their target in living, human cells. 406-539-7399 366 Gallatin Park Drive Suite A Bozeman, MT 59715", "keywords": [ "2019-nCoV", "Biological", "Biological Assay", "Biosensor", "COVID-19", "COVID-19 assay", "COVID-19 pandemic", "COVID-19 therapeutics", "COVID-19 treatment", "Cells", "Cellular Assay", "Coronavirus", "Development", "Dimerization", "Disease", "Drug Screening", "Enzymes", "Fluorescence", "Goals", "Health", "Hour", "Human", "Image", "Immunohistochemistry", "Incubated", "Intercalated Cell", "Libraries", "Liquid substance", "Measurable", "Measurement", "Methods", "Microscopy", "Molecular", "Montana", "Noise", "Nonstructural Protein", "Peptide Hydrolases", "Personal Satisfaction", "Pharmaceutical Preparations", "Phase", "Protease Inhibitor", "Proteins", "Reader", "Reporting", "Research", "SARS-CoV-2 genome", "SARS-CoV-2 infection", "SARS-CoV-2 protease", "Signal Transduction", "Site", "Speed", "Testing", "Time", "Translating", "Viral", "Virus", "Virus Replication", "assay development", "cell type", "combat", "design", "drug discovery", "high throughput screening", "inhibitor", "lead optimization", "prototype", "response", "screening", "sensor", "targeted treatment", "tool", "vector" ], "approved": true } } ], "meta": { "pagination": { "page": 1384, "pages": 1405, "count": 14046 } } }