Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1391&sort=-approved
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-approved", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1424&sort=-approved", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1392&sort=-approved", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1390&sort=-approved" }, "data": [ { "type": "Grant", "id": "12339", "attributes": { "award_id": "1R35GM150528-01", "title": "Real-time structural and functional studies of SARS-CoV-2 spike proteins", "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": 22244, "first_name": "MICHAEL", "last_name": "SAKALIAN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-09-20", "end_date": "2028-07-31", "award_amount": 389820, "principal_investigator": { "id": 28254, "first_name": "Yi-Chih", "last_name": "Lin", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 972, "ror": "", "name": "UNIVERSITY OF TEXAS AT AUSTIN", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "Abstract: Spike glycoprotein (S-protein) is one of the viral transmembrane proteins on the envelope of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19). S- protein plays a crucial role in mediating the initial entry of viral genome into the host cell by binding to the human angiotensin-converting enzyme 2 (ACE2) and then inducing fusion between the virus envelope and cell membrane. Thus, S-protein is a target of choice for diagnostic and therapeutic assays, including neutralizing monoclonal antibodies (nAbs). To date, the conformations of S-protein and its molecular assemblies with ACE2 and/or nAbs have been mainly determined by structural techniques, including crystallographic and electron microscopic methods. These structural studies allow us to understand the molecular basis underlying viral entry and to further develop treatment and preventive therapeutics for COVID-19. However, these resolved structures are rather “static snapshots” compared to the dynamic nature of proteins in physiological conditions. Due to the technical difficulties, our knowledge about the real-time structural dynamics of S-protein and its real-time interactions with host receptors, nAbs, and the other relevant biomolecules, which may have functional significance, is still very limited. In this proposal, my lab will develop a bio-mimicking reconstitution system and apply a cutting-edge structural imaging technique, high-speed atomic force microscopy (HS-AFM), for real-time observations of S- protein’s structural dynamics in close-to-native environments and under various conditions. We will also develop novel methods to quantitatively characterize the architecture of molecular assemblies comprising S-protein, ACE2 receptor, nAbs, host proteases and enzymes, and biological membranes, which can mediate the membrane fusion and viral entry processes. Specifically, we will identify the “real-time” structural dynamics of S- protein in different states and visualize how the state transitions happen, for example, during ACE2 binding, nAbs attachment, and the structural cleavages in S-protein subunits. My lab will further develop correlated fluorescence microscopy and HS-AFM to study these dynamic events associated with S-protein on the mammalian cell surface. The biophysical and biochemical information acquired in our proposed experiments will provide a comprehensive molecular understanding of the conformational states of S-protein, intermolecular interactions between S-protein and binding molecules (ACE2 and nAbs), the conformational changes in S- protein for initiating membrane fusion processes for viral entry, and how the mammalian cell surface impacts the S-protein. The developed methods here can further apply to the other receptor-mediated membrane fusion systems for cell entry.", "keywords": [ "2019-nCoV", "ACE2", "Architecture", "Atomic Force Microscopy", "Binding", "Biochemical", "Biological", "Biological Assay", "Biophysics", "COVID-19", "COVID-19 therapeutics", "Cell membrane", "Cell surface", "Cells", "Crystallography", "Diagnostic", "Electrons", "Environment", "Enzymes", "Event", "Fluorescence Microscopy", "Glycoproteins", "Human", "Imaging Techniques", "Integral Membrane Protein", "Knowledge", "Mammalian Cell", "Mediating", "Membrane", "Membrane Fusion", "Methods", "Microscopic", "Molecular", "Molecular Conformation", "Nature", "Peptide Hydrolases", "Physiological", "Play", "Preventive", "Process", "Proteins", "Role", "SARS-CoV-2 spike protein", "Speed", "Structure", "System", "Techniques", "Therapeutic", "Time", "Viral", "Viral Genome", "Virus", "Visualization", "experimental study", "intermolecular interaction", "molecular assembly/self assembly", "neutralizing monoclonal antibodies", "novel", "receptor", "reconstitution", "structural imaging", "virus envelope" ], "approved": true } }, { "type": "Grant", "id": "12340", "attributes": { "award_id": "1R21HD115355-01", "title": "Identifying adolescent social media response in real-time: Risk and protective factors for Asian American mental health", "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": 8605, "first_name": "JAMES", "last_name": "GRIFFIN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-09-19", "end_date": "2025-08-31", "award_amount": 542860, "principal_investigator": { "id": 23755, "first_name": "CINDY H", "last_name": "LIU", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 891, "ror": "https://ror.org/04b6nzv94", "name": "Brigham and Women's Hospital", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 23756, "first_name": "Tiffany", "last_name": "Yip", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 891, "ror": "https://ror.org/04b6nzv94", "name": "Brigham and Women's Hospital", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "As of 2022, nearly all (95%) adolescents report using at least one social media (SM) platform daily. Adolescents are prone to engage in social comparison with SM users, which may negatively affect their self-concept (SC). Despite the outsized role of SM on adolescent outcomes, little is known about how SM use impacts SC and ultimately mental health. Furthermore, racial minority adolescents may face additional risks to SC when experiencing indirect or vicarious discrimination experiences, including viewing racial stereotypes on SM. Determining Asian American (AA) adolescent responses to race- based SM content can provide key information on the effects of SM on the psychological adjustment of racial minority youth. AA youth experience the most online bullying compared to other racial/ethnic groups and also reported the largest increase in online victimization and exposure to stereotypic SM content since the start of the COVID-19 pandemic. This R21 proposal involving 135 AA adolescents fulfills a gap in the science of how immediate responses to SM content may affect adolescent SC and subsequent mental health. Naturally occurring, popular or “viral ” posts will be presented as experimental stimuli to reflect either stereotypic or counter-stereotypic portrayals of AAs. SC will be assessed immediately through a series of questions to understand how adolescents view themselves, how they compare themselves to others in the post, and whether they or others might perceive their racial group positively or negatively. The long-term objective is to reveal modifiable targets through the direct assessments of psychological processes, specifically how adolescents feel and interpret the messages from social media posts. With implications for cognitive behavioral therapy and mindfulness- based practices for adolescents, our findings have potential for providing evidence-based anticipatory guidance for parents, clinicians, and communities. Our study has the following aims: Aim 1. To test associations between stereotype and counter stereotype race-related SM content and self-concept (SC) using experimental stimuli, and (b) To investigate how race centrality (whether being Asian American is central to one's identity) moderates the links. Aim 2. To examine the mediation pathways of race-related SM content exposure on mental health and psychological outcomes via SC. Exploratory Aim. To determine how adolescents identify messages in social media content, including the extent they identify racial messaging. The major strengths of this work include the generalizability of findings across SM platforms and enhanced ecological validity through the use of real, viral SM posts, with its selection conducted in collaboration with our youth advisory board of AA teens and other AA consultants. Our approach to assess immediate affective and cognitive response to SM has potential to yield groundbreaking insights on how adolescents learn identity-relevant information online.", "keywords": [ "Adolescent", "Affect", "Affective", "Age", "Algorithms", "American", "Asian", "Asian Americans", "COVID-19 pandemic", "Cellular Phone", "Cognitive", "Cognitive Therapy", "Collaborations", "Communities", "Data", "Development", "Discrimination", "Ethnic Origin", "Ethnic Population", "Exposure to", "Family", "Feeling", "Funding", "Health", "Individual", "Infrastructure", "Intervention", "Learning", "Link", "Mediation", "Mental Health", "National Institute of Mental Health", "Nature", "Outcome", "Parents", "Participant", "Pathway interactions", "Persons", "Process", "Psychological adjustment", "Public Health", "Published Comment", "Race", "Reporting", "Research Personnel", "Risk", "Risk Factors", "Role", "Schools", "Science", "Self Concept", "Series", "Social Network", "Socialization", "Source", "Stereotyping", "Stimulus", "Teenagers", "Testing", "Thinking", "Time", "Victimization", "Violence", "Viral", "Work", "Youth", "anti-Asian", "bullying", "critical period", "distress tolerance", "early adolescence", "ethnic identity", "evidence base", "experience", "innovation", "insight", "marginalization", "mindfulness", "minority children", "negative affect", "novel", "peer", "perceived discrimination", "pressure", "protective factors", "psychologic", "psychological outcomes", "racial minority", "racial population", "racism", "response", "social", "social media", "uptake" ], "approved": true } }, { "type": "Grant", "id": "12341", "attributes": { "award_id": "1R43IP001233-01", "title": "SBIR PA22-176 - RNA aptamers for rapid response to COVID-19 variants", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2023-09-30", "end_date": "2024-03-29", "award_amount": 275482, "principal_investigator": { "id": 28255, "first_name": "Hong Yan", "last_name": "Liu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2085, "ror": "", "name": "DOTQUANT, LLC", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true }, "abstract": "The COVID-19 pandemic caused by SARS-CoV-2 viruses has had an unprecedented disruptive global impact. Although vaccination has been expected to end the spread, the fast mutations have increased the breakthrough infection rates in the fully vaccinated population. RNA viruses are known to have very high rates of mutation and evolution. The high rate of mutation is correlated with virulence modulation and the ability to escape host immunity posting an urgent need for treatments that can keep up with the virus mutations. On the molecular level, spike (S) protein receptor binding domain (RBD) and angiotensin-converting enzyme 2 (ACE2) are key mediators for viral entry, therefore pharmacological disruption of S1 RBD binding to ACE2 could be an effective treatment against SARS-CoV-2. Indeed, neutralization antibodies against the S protein have been developed and are used in clinics. Unfortunately, it is difficult for antibody engineering to keep up with the virus evolution. The Delta variant is twice as contagious as the previous variants, whereas the Omicron variant exhibits more mutations in the spike protein than other variants. These variants have raised CDC's concerns due to the risks of immune escape and increased transmissibility. The need for effective drugs against the fast mutating variants can not be met by antibodies because the production of therapeutic antibodies is time-consuming and costly. In this context, nucleic acid-based aptamers, also known as `chemical antibodies' have the potential to address this challenge. Aptamers are selected using an in vitro chemical combinatorial approach, systematic evolution of ligands by exponential enrichment (SELEX), and offer advantages over antibodies to address the problem of mutating viruses because of the fast selection and chemical production, easy chemical modification, high thermostability, and low immunogenicity. Although RNA aptamer is sensitive to nucleases and renal clearance, 2'-fluoro-pyrimidine modification has significantly increased the resistance nucleases, while multivalent aptamers or conjugation to PEGs can increase aptamer sizes and consequently the circulation time. In our preliminary studies, we have selected a series of RNA aptamers targeting the wild-type SARS-CoV-2 S1RBD protein and invented a proprietary approach to generate chemical-modified serum-stable RNAs at high yield and low cost. The selected aptamers show the universal inhibitory effect to RBD-ACE2 binding for WT and variants (Alpha, Beta, Gamma, and Omicron) but not the Delta variant yet. In this project, we will address the Delta variant and optimize our current aptamers and the new anti-Delta aptamer into a bispecific format (avoid rapid renal clearance). We will reach our goals through the following specific aims:1) Screening and characterization of aptamers against the Delta variant and optimization of aptamers by forming bivalent structures, and 2) Evaluation of the antiviral activity. The antiviral capability will be assessed in pseudovirus as well as live infectious viruses through our established agreement with NIAID. Beyond the specific aptamers, we will establish a platform and our ability for quick responses to virus mutations. In terms of responding to fast-mutating infectious diseases, developing aptamer-based therapeutics as an alternative to antibodies is similar to developing mRNA vaccines over conventional inactivated virus vaccines because both aptamers and mRNAs can be screened/designed quickly.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "12342", "attributes": { "award_id": "1R01GM152745-01", "title": "DMS/NIGMS 2: Integrated Analysis of Fusion Protein Conformational Changes for Virus Entry", "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": 22244, "first_name": "MICHAEL", "last_name": "SAKALIAN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-09-25", "end_date": "2027-07-31", "award_amount": 278687, "principal_investigator": { "id": 28256, "first_name": "Jin", "last_name": "Liu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 306, "ror": "https://ror.org/05dk0ce17", "name": "Washington State University", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true }, "abstract": "Virus infections remain major threats to human health worldwide as demonstrated by COVID-19 pandemic caused by SARS-CoV-2 and its variants. All enveloped viruses must fuse with host membranes to initiate the infection process. Membrane fusion is a critical, but poorly understood biological process that is driven by protein conformational changes. Membrane fusion is a highly complex, multistage and multiscale process, which is difficult to investigate through scale-specific techniques (both experimentally and numerically). In this project, we propose to investigate the structural changes of fusion proteins and virus fusion through a combination of multiscale modeling, machine learning, and complementary experimentation. Because of our decades long experience in working with the herpes simplex virus (HSV), we will utilize the herpesvirus fusogen, gB, a class Ill fusion protein, as a model protein, to elucidate protein conformational changes during virus fusion. The specific research aims are: (1) To delineate the conformational changes of viral fusion proteins, through development of the machine learning facilitated enhanced sampling scheme for fusion proteins and delineation of the sequential conformation changes of gB protein for HSV fusion by a combination of machine learning and experiments; (2) To elucidate membrane fusion driven by viral fusion protein conformational changes, through development of a multiscale model for membrane fusion, assessment of the role of membrane fluidity in fusion and elucidation of the importance of the gB membrane proximal region on gB conformational changes and membrane fusion through combined simulations and experiments. This research will establish experimentally validated, powerful modeling platforms for exploration of the protein conformational changes and will bridge the multiple spatial and temporal scales involved in the fusion process. The machine learning method for enhanced sampling is highly innovative and crucial to capture the large-scale structural (conformational) changes and associated energy profiles of fusion proteins, and to identify the appropriate pathways during the fusion process. The integration of the gradient-based optimization method to the machine learning algorithm is novel to identify the most appropriate reaction coordinates.", "keywords": [ "2019-nCoV", "Acceleration", "Address", "Biological", "Biological Process", "COVID-19 pandemic", "Cell membrane", "Cells", "Chimeric Proteins", "Cholesterol", "Complex", "Computer Models", "Computer Simulation", "Dengue", "Development", "Dimensions", "Endocytosis", "Event", "Exocytosis", "Freedom", "Future", "Grain", "HIV", "Health", "Herpesviridae", "Human", "Infection", "Lipids", "Liquid substance", "Machine Learning", "Measurement", "Membrane", "Membrane Fluidity", "Membrane Fusion", "Methods", "Modeling", "Molecular", "Molecular Conformation", "Monoclonal Antibodies", "Morbidity - disease rate", "National Institute of General Medical Sciences", "Organism", "Pathway interactions", "Process", "Protein Conformation", "Proteins", "Reaction", "Research", "Role", "Sampling", "Scheme", "Simplexvirus", "Solid", "Spanish flu", "Structure", "Surface", "Techniques", "Variant", "Viral", "Viral Fusion Proteins", "Virion", "Virus", "Virus Diseases", "effective intervention", "env Gene Products", "experience", "experimental study", "flexibility", "innovation", "insight", "machine learning algorithm", "machine learning method", "membrane model", "molecular modeling", "mortality", "multi-scale modeling", "multidisciplinary", "mutant", "nanosized", "neural network", "novel", "novel coronavirus", "obligate intracellular parasite", "pathogen", "simulation", "sperm cell", "zygote" ], "approved": true } }, { "type": "Grant", "id": "12343", "attributes": { "award_id": "1R43HL167437-01", "title": "The Development of CSD peptides for the therapeutic treatment of post-acute sequelae of COVID-19 (PACS)", "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": 22454, "first_name": "GUOFEI", "last_name": "Zhou", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-09-15", "end_date": "2024-02-29", "award_amount": 259332, "principal_investigator": { "id": 28257, "first_name": "BreAnne", "last_name": "MacKenzie", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2086, "ror": "", "name": "LUNG THERAPEUTICS, INC.", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "Acute respiratory distress syndrome (ARDS) from SARS-CoV-2 infection activates many lung remodeling pathways observed in Idiopathic Pulmonary Fibrosis (IPF) and reports indicate that symptoms persist for 2 to 12 months or longer in approximately 33% of hospitalized patients. To address this emerging health concern, this proposal aims to 1) develop a translational model for post-acute COVID-19 sequelae (PACS) induced organ fibrosis and to use this model to 2) rigorously assess efficacy of a potentially prophylactic, antifibrotic therapeutic peptides patented and developed by Lung Therapeutics, Inc (LTI). A reduction of Caveolin-1 expression is observed in human fibrotic tissues and histopathology revealed that endogenous CAV-1 protein expression was significantly reduced in 10 unique fatal COVID lungs. Furthermore, CAV-1 RNA was reduced in PACs tissue samples from which cells for this model will be derived. The anti-fibrotic activity of LTI’s patented portfolio of Caveolin-1 scaffolding domain (CSD) peptides is conferred through the 7-amino acid sequence FTTFTVT. The 7-mer was formulated as an inhaled dry powder and is currently undergoing a phase 1 safety, tolerability, and pharmacokinetic study (NCT04233814) as it demonstrated the ability to reverse established fibrosis in multiple in vivo pre-clinical models of dermal, cardiac, and pulmonary fibrosis (PF) and attenuates multiple pro-fibrotic signaling pathways in vitro. However, given that a dose limit of 20mg was observed in this trial, and PACS has been observed to effect other organs aside from the lung as well as systemic vasculature, a more soluble, stable, XR, subcutaneous, injectable version of LTI-03, called LTI-2355. LTI- 2355 has demonstrated robust anti-inflammatory and antifibrotic effects in a variety of human and rodent fibrosis models. Moreover, preliminary PK data on our depot, extended release (XR) formulations indicate that it is stable and available in the lung following a single injection at putative therapeutic dose levels out to 14 to 22 days. Given our experience with the IPF- SCID mouse system, we hypothesize that robust lung fibrosis with possible development of multi-organ fibrosis will develop following intravenous administration of live human pulmonary cells from discarded COVID lung transplants (viral titer negative) into SCID mice. If successfully established, we will not only test three putative extended-release (XR) therapeutic peptides in this novel PACS model, but we will also publish the methods and characteristics of the model, which may potentially become an important tool for testing putative PACS interventional therapeutics. Taken together, we propose to establish a translational mouse model of PACS, and to test three patented LTI-2355-XR formulations via (SC) delivery and compare against efficacy of a control peptide and Nintedanib, the standard of care for IPF, and a current candidate for PACS therapy (PINCER, NCT04856111). Pending efficacious results (composite reduction in pro-inflammatory and pro-fibrotic indicators of at least 40%, a lead candidate will be selected, and a Phase II SBIR will be filed to support further clinical development (PK/PD, toxicology specific to the SC formulation, IND-supporting work). This proposal caters to the aggregate strengths of the team including peptide formulation, expertise in the biochemical assessment of translational mouse models of pulmonary fibrosis, immunology, organ fibrosis, pharmacokinetics, and overall drug development. Finally, this project has strong potential to yield a novel therapy for the treatment of PACS.", "keywords": [ "Acute", "Acute Respiratory Distress Syndrome", "Address", "Amino Acid Sequence", "Animal Model", "Anti-Inflammatory Agents", "Attenuated", "Biochemical", "Biological Assay", "Biological Availability", "Bleomycin", "Blood", "COVID-19", "COVID-19 patient", "COVID-19/ARDS", "Cell model", "Cells", "Characteristics", "Clinical Trials", "Data", "Development", "Dose", "Dose Limiting", "Drug Kinetics", "Dryness", "Fibrosis", "Formulation", "Foundations", "Genetic Models", "Goals", "Harvest", "Health", "Heart", "Histopathology", "Hospitalization", "Human", "Hydroxyproline", "Immunology", "In Vitro", "Infection", "Inflammation", "Inflammatory", "Inhalation", "Injectable", "Injections", "Injury", "Kidney", "Lead", "Legal patent", "Lung", "Lung Transplantation", "Methods", "Modeling", "Molecular Analysis", "Mus", "Nonspecific Interstitial Pneumonia", "Operative Surgical Procedures", "Organ", "Organ Harvestings", "Outcome", "Pathway interactions", "Patients", "Peptides", "Phase", "Pilot Projects", "Post-Acute Sequelae of SARS-CoV-2 Infection", "Powder dose form", "Pre-Clinical Model", "Profibrotic signal", "Public Health", "Publishing", "Pulmonary Fibrosis", "RNA", "Reporting", "Research Contracts", "Rodent", "SARS-CoV-2 infection", "SCID Mice", "Safety", "Signal Pathway", "Slide", "Small Business Innovation Research Grant", "Symptoms", "System", "Tertiary Protein Structure", "Testing", "Therapeutic", "Therapeutic Intervention", "Time", "Tissue Sample", "Tissues", "Toxicology", "Trichrome stain", "Viral", "Work", "attenuation", "caveolin 1", "cell type", "clinical development", "cohort", "comparison control", "coronary fibrosis", "coronavirus disease", "cytokine", "drug development", "efficacy evaluation", "experience", "high risk", "hospital readmission", "idiopathic pulmonary fibrosis", "in vivo", "injured", "interstitial", "intravenous administration", "lead candidate", "mouse model", "nintedanib", "novel", "novel therapeutics", "peptide drug", "prophylactic", "protein expression", "pulmonary symptom", "scaffold", "skin fibrosis", "standard of care", "subcutaneous", "synthetic polymer Bioplex", "tool", "translational model" ], "approved": true } }, { "type": "Grant", "id": "12344", "attributes": { "award_id": "1U18HS029920-01", "title": "Mid-Atlantic Pediatric Long COVID Network:Implementing patient-centered and multi-disciplinary practices to improve pediatric long COVID", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "Agency for Healthcare Research and Quality (AHRQ)" ], "program_reference_codes": [], "program_officials": [ { "id": 22615, "first_name": "Brent", "last_name": "Sandmeyer", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-09-30", "end_date": "2028-09-29", "award_amount": 943814, "principal_investigator": { "id": 28258, "first_name": "Laura A", "last_name": "Malone", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2039, "ror": "", "name": "HUGO W. MOSER RES INST KENNEDY KRIEGER", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "Long COVID can affect many aspects of a child’s physical and mental health. Between 5 and 25% of children with SARS-CoV-2 infection go on to develop long COVID. Persistent health disparities and socioeconomic factors have put certain vulnerable populations at higher risk of infection, morbidity, and mortality from SARS- CoV-2 infection. In pediatrics, children with physical, intellectual, or developmental disabilities (IDDs), children from resource-limited areas (e.g., rural), and children that are uninsured or underinsured are particularly vulnerable populations that have limited access to specialized pediatric clinics for children with COVID-19 sequelae. Even with the successes of the Pediatric Post-COVID-19 Rehabilitation Clinic at the Kennedy Krieger Institute to garner international recognition for its integrated and person-centered multidisciplinary clinic model and substantial research, awareness, and advocacy efforts of the clinical team, there remain critical gaps in long COVID care for children. These gaps include limited integrative healthcare treatments, resources for navigating schooling, and access to timely long COVID care in the community and medical home. There are two arms to this proposal to address these gaps in multi-faceted and independent ways. Arm 1 will involve using an innovative integrative health model of care to expand and strengthen the services of the KKI Pediatric Post-COVID-19 Rehabilitation Clinic. This model can help support children with long lasting persistent or fluctuating symptoms, acknowledging the critical roles schools serve as an important partner in the cultural context of health and in the recovery process of pediatric patients. Arm 2 will involve the development of a novel Pediatric Long COVID Telementoring ECHO (Extension for Community Healthcare Outcomes) Project. The highly experienced clinical team will create provider education on long COVID in typically developing children (TDC) and children with IDD to educate and mentor multidisciplinary community providers through an 8-10 course series that will be adapted annually. In partnership with the Agency for Healthcare Research and Quality, this proposal will achieve the following program objectives: (1) expand and strengthen the current clinic to utilize an innovative integrative healthcare model, (2) provide services to more children with long COVID, (3) expand services offered, (4) strengthen care coordination, (5) implement and share best practices for long COVID management, (6) support the primary care community in long COVID education and management through the Pediatric Long COVID ECHO project, (7) evaluate project success through mixed methods evaluations, and (8) disseminate project findings through community partners. In the end, with this proposal a network of community providers across Maryland and the Mid-Atlantic region will be established that can treat pediatric long COVID early and effectively, providing greater access to care in vulnerable pediatric populations.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "12345", "attributes": { "award_id": "1R01DK134514-01A1", "title": "E-TREAT: Evaluation of Telemedicine for diabetes care in Latinos", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)" ], "program_reference_codes": [], "program_officials": [ { "id": 28259, "first_name": "Nishadi", "last_name": "Rajapakse", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-09-05", "end_date": "2028-05-31", "award_amount": 668936, "principal_investigator": { "id": 28260, "first_name": "Miguel", "last_name": "Marino", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 765, "ror": "https://ror.org/009avj582", "name": "Oregon Health & Science University", "address": "", "city": "", "state": "OR", "zip": "", "country": "United States", "approved": true }, "abstract": "E-TREAT: Evaluation of Telemedicine for diabetes and hypertension care in Latinos Latinos are more likely to have diabetes and hypertension and to face poor outcomes and complications from these diseases. Quality primary care can reduce poor outcomes from these diseases, but primary care services changed drastically in 2020 because of the COVID-19 pandemic. The pandemic shifted many primary care visits from face-to-face visits to telemedicine (telephone and video) visits. It is uncertain how frequently Latino patients with diabetes and hypertension utilized (and continue to utilize) these types of visits, and how this may have affected the services they received for diabetes and hypertension, and how well their diseases were controlled. It is also unknown how various social factors (community economic resources, language barriers, access to broadband internet) might moderate the association of telemedicine on diabetes and hypertension care and control. This study will assess the use of telemedicine (video and telephone visits) vs. in person visits between Latino and non-Hispanic white patients with diabetes and/or hypertension seen at community health centers in the United States over the course of and subsequent to the COVID-19 pandemic. It will also assess the association of telemedicine utilization with the receipt of recommended diabetes and hypertension care services, and assess the potential of social determinants of health to moderate the effectiveness of telemedicine in mitigating disparities in diabetes and hypertension care between Latino populations and non-Hispanic white populations in these patients. Understanding the quality of diabetes and hypertension care delivered via telemedicine among Latinos with diabetes and hypertension and which social determinants of health moderate its effectiveness is critical for healthcare planning and policies around reimbursement and regulations and will have a significant impact on patients, clinicians, policy-makers, and healthcare system leaders and allow for equitable healthcare delivery.", "keywords": [ "Address", "Affect", "COVID-19 pandemic", "Caring", "Chronic Care", "Chronic Disease", "Communities", "Community Health Education", "Community Health Networks", "Data", "Data Set", "Databases", "Decision Making", "Diabetes Mellitus", "Disease", "Disease Outcome", "Disparity", "Drug Prescriptions", "Economics", "Education", "Educational Status", "Effectiveness", "Electronic Health Record", "Ensure", "Equitable healthcare", "Equity", "Evaluation", "Face", "Health Insurance", "Health Services Accessibility", "Health system", "Healthcare", "Healthcare Systems", "Hypertension", "Immigration", "Individual", "Inequity", "Internet", "Knowledge", "Language", "Latino", "Latino Population", "Link", "Managed Care", "Minority Groups", "Monitor", "Morbidity - disease rate", "Neighborhood Health Center", "Not Hispanic or Latino", "Outcome", "Patients", "Persons", "Policies", "Policy Maker", "Population", "Prevention", "Primary Care", "Quasi-experiment", "Recommendation", "Regulation", "Relaxation", "Research Design", "Resources", "Risk", "Services", "Social Distance", "Technology", "Telemedicine", "Telephone", "Training", "United States", "Virus", "Visit", "World Health Organization", "access disparities", "acronyms", "care delivery", "care seeking", "care systems", "comorbidity", "diabetes management", "disparity reduction", "health care availability", "health care delivery", "health inequalities", "improved", "innovation", "member", "mortality", "pandemic disease", "patient oriented", "poor communities", "primary care services", "primary care visit", "risk stratification", "rurality", "safe patient", "screening", "social", "social factors", "social health determinants" ], "approved": true } }, { "type": "Grant", "id": "12346", "attributes": { "award_id": "1OT2OD035605-01", "title": "Partnership to Optimize Equity in Maternal and Infant Health", "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": 28261, "first_name": "Yvonne Owens", "last_name": "Ferguson", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-09-20", "end_date": "2028-09-19", "award_amount": 1124930, "principal_investigator": { "id": 28262, "first_name": "Karen Comer", "last_name": "Matthews", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2087, "ror": "", "name": "DELTA HEALTH ALLIANCE, INC.", "address": "", "city": "", "state": "MS", "zip": "", "country": "United States", "approved": true }, "abstract": "Poor maternal and infant health outcomes are long-standing public health problems particularly in rural, low-income communities of color. Sustainable improvements are needed to address structural barriers and policies which have trapped marginalized populations in generational cycles of insufficient access to care and high rates of maternal and infant mortality and morbidity. This community-led, multisectoral partnership seeks to jointly conduct a community assessment in five rural impoverished counties of the Mississippi Delta, to identify the structural factors that contribute to these negative outcomes. Subsequently we will then develop, implement and evaluate a structural intervention research strategy that will support sustainable health equity improvements in these marginalized communities. Delta Health Alliance, the largest community-based non-profit in Mississippi, has developed this study in partnership with the Center for Community Research and Evaluation, building upon our eight years of experience working together on large and small health and community-engaged research encompassing the full spectrum of qualitative and quantitative methods on projects pertaining to behavioral health, chronic disease, maternal and infant home visitation, nutrition, COVID-19 vaccinations, and teenage pregnancy. This effort is joined by a wide range of partners including local practitioners, social service providers, business leaders, policy advocates, members of faith-based communities, and members of a regional advisory group consisting of representatives of our target population – to capture and directly address the concerns of all parties of interest.", "keywords": [ "Address", "Advocate", "Affect", "Area", "Birth", "Businesses", "COVID-19 vaccination", "Child", "Chronic Disease", "Color", "Communities", "Contraceptive methods", "Country", "County", "Disadvantaged", "Economics", "Elements", "Environment", "Equity", "Evaluation", "Face", "Faith", "Family Planning", "Future", "Geography", "Health", "Health Alliance", "Health Policy", "Health Services Accessibility", "Home visitation", "Incidence", "Infant", "Infant Health", "Insurance Coverage", "Intervention", "Intervention Studies", "Laws", "Legal", "Low income", "Maternal Health", "Maternal Mortality", "Measures", "Medicaid", "Methodology", "Methods", "Minority", "Misinformation", "Mississippi", "Mothers", "Nurse Practitioners", "Outcome", "Personal Satisfaction", "Physicians", "Policies", "Policy Developments", "Policy Maker", "Poverty", "Predisposition", "Pregnancy", "Pregnancy in Adolescence", "Public Health", "Regulation", "Religious Belief", "Reproductive Health", "Research", "Resources", "Rights", "Rural", "Rural Community", "Safety", "Services", "Social Work", "System", "Target Populations", "Training", "Vulnerable Populations", "Woman", "Women&apos", "s Health", "Work", "abortion", "behavioral health", "black women", "community based participatory research", "community center", "community engaged research", "experience", "health care availability", "health care service", "health disparity", "health equity", "improved", "improved outcome", "infant morbidity/mortality", "innovation", "interest", "long-standing disparities", "marginalized community", "marginalized population", "member", "multi-component intervention", "novel", "nutrition", "payment", "policy implication", "postpartum care", "primary care services", "reversible contraceptive", "rural dwellers", "safety net", "service providers", "social", "structural determinants", "unintended pregnancy" ], "approved": true } }, { "type": "Grant", "id": "12347", "attributes": { "award_id": "1R01AG079799-01A1", "title": "Molecular mechanisms of aging and accelerated aging in the human brain", "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": 26177, "first_name": "Maja", "last_name": "Maric", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-09-15", "end_date": "2028-05-31", "award_amount": 841971, "principal_investigator": { "id": 28263, "first_name": "Maria", "last_name": "Mavrikaki", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 771, "ror": "https://ror.org/04drvxt59", "name": "Beth Israel Deaconess Medical Center", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "SUMMARY. This proposal is in response to PAR-21-038: Stephen I. Katz Early Stage Investigator Research Project Grant. Aging is a major risk factor for the development of cognitive deficits and neurodegenerative diseases. Understanding the exact molecular mechanisms of brain aging and accelerated brain aging can lead to the development of novel interventions to delay or potentially reverse brain aging. Environmental factors including viral infections (such as SARS-CoV-2, the virus that caused the COVID-19 pandemic) have been shown to be associated with cognitive decline and accelerated brain aging. However, the exact molecular mechanisms underlying the effects of environmental factors, and specifically COVID-19, on brain aging remain unknown. Our long-term goal is to identify key factors that induce accelerated brain aging, so that therapeutics can be developed to delay or reverse brain aging. The overall objective of this proposal is to identify genes and regulators of gene expression that cause brain aging and accelerated brain aging in COVID-19 patients. Previous research from our group showed that many microRNAs (miRNAs), which are small non-coding RNAs that induce an orchestrated regulation of gene expression, are differentially expressed in the aged mouse brain and regulate aging. Based on those data and our recently published bulk RNA sequencing studies showing molecular signatures of brain aging in COVID-19 patients, our central hypothesis is that dysregulated gene and miRNA expression is an important facet of accelerated brain aging. Previous studies using microarray and bulk RNA sequencing approaches showed that aging induces distinct molecular signatures in the human frontal cortex. While layer enriched expression signatures have been identified in the human frontal cortex, the spatial topography of molecular signatures of aging remain largely unknown. Here, we will utilize state-of-the-art spatial transcriptomic technologies to analyze human frontal cortex sections from healthy individuals across lifespan, as well as frontal cortex sections from COVID-19 patients (and appropriate controls) to identify spatially distinct aging-regulated transcriptomic changes. We will investigate the effects of aging-regulated genes on cellular senescence using in vitro assays. To better understand regulatory mechanisms of aging-regulated gene expression, we will measure the expression of miRNAs in healthy individuals across lifespan and COVID-19 cases on similar frontal cortex sections and we will identify aging-regulated mRNA targets for candidate miRNAs. Finally, we will test the potential of miRNAs to accelerate and delay aging using in vitro assays and in vivo mouse models. These studies are expected to have a significant impact as they will determine novel targets for the development of therapeutics to delay or reverse brain aging and aging-related neuropathology. This proposal is highly relevant to public health and to the NIA’s mission of advancing knowledge on the causes of aging processes and age-associated diseases to extend healthy lifespan.", "keywords": [ "2019-nCoV", "Acceleration", "Adult", "Age", "Aging", "Autopsy", "Binding Sites", "Bioinformatics", "Biological Assay", "Brain", "COVID-19", "COVID-19 impact", "COVID-19 pandemic", "COVID-19 patient", "Cell Aging", "Cognition", "Cognitive deficits", "Coronavirus Infections", "Data", "Development", "Disease", "Environmental Risk Factor", "Functional disorder", "Funding Opportunities", "Gene Expression", "Gene Expression Profile", "Gene Expression Regulation", "Genes", "Genetic Transcription", "Goals", "Human", "Impaired cognition", "In Vitro", "Individual", "Intervention", "Knowledge", "Longevity", "Luciferases", "Maps", "Measures", "Messenger RNA", "MicroRNAs", "Mission", "Molecular", "Molecular Profiling", "Mus", "Neurodegenerative Disorders", "Neurons", "Neurophysiology - biologic function", "Normal tissue morphology", "Phenotype", "Play", "Process", "Public Health", "Publishing", "Recording of previous events", "Regulator Genes", "Reporter", "Research", "Research Personnel", "Research Project Grants", "Risk Factors", "Site-Directed Mutagenesis", "Small RNA", "Spatial Distribution", "Technology", "Testing", "Therapeutic", "Tissues", "Untranslated RNA", "Validation", "Ventilator", "Virus", "Virus Diseases", "adeno-associated viral vector", "age effect", "aged", "aging brain", "cell type", "cognitive function", "differential expression", "frontal lobe", "in vitro Assay", "in vivo", "induced pluripotent stem cell", "mouse model", "neuropathology", "new therapeutic target", "novel", "prevent", "promoter", "response", "senescence", "severe COVID-19", "single-cell RNA sequencing", "therapeutic development", "transcriptome sequencing", "transcriptomics" ], "approved": true } }, { "type": "Grant", "id": "12348", "attributes": { "award_id": "1F31HL170778-01", "title": "Three-dimensional Confocal Microscopy Visualization and AFM-IR Chemical Mapping of Lung Surfactant Monolayer Collapse Morphologies", "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": 20693, "first_name": "Roya", "last_name": "Kalantari", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-09-15", "end_date": null, "award_amount": 43943, "principal_investigator": { "id": 28264, "first_name": "Zachary D", "last_name": "McAllister", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 764, "ror": "https://ror.org/017zqws13", "name": "University of Minnesota", "address": "", "city": "", "state": "MN", "zip": "", "country": "United States", "approved": true }, "abstract": "Neonatal respiratory distress syndrome (NRDS) and acute respiratory distress syndrome (ARDS) afflict upwards of 250,000 Americans every year. NRDS affects premature infants due to their underdeveloped lung’s inability to produce sufficient functional lung surfactant. Animal replacement surfactant treatment options exist for NRDS, although concerns over bio-variability, interspecies disease transmittance, and religious questions over porcine versus bovine derived surfactants remain. ARDS was seen in ~75% of all admitted COVID-19 ICU patients and is currently untreatable leading to a mortality rate of ~40%. ARDS is initiated by lung trauma or disease that leads to inflammation, causing an uncharacteristic increase of the surface tension within the lungs, leading to atelectasis. A deeper understanding of the fundamental structure and limiting behavior of lung surfactant monolayers may be the avenue to suggest new synthetic replacement surfactant treatments that could mitigate the biological concerns in NRDS as well as develop treatment options for patients with ARDS. My group has previously identified that the “collapse” of a monolayer determines the lower surface tension limit during the alveolar area compression accompanying exhalation. The physical and chemical factors that govern collapse may be altered in patients who develop dysfunctional, high surface tension lung surfactant during ARDS. Monolayers of healthy lung surfactant phase separate into domains of a semi-crystalline ordered phase and a disordered liquid phase of varied composition. We hypothesize that this phase separation dictates many of the dynamic and rheological properties of the monolayer that influence collapse. However, there is little direct information on the composition of the different domains in multicomponent lung surfactants. I will address monolayer collapse and phase separation in the following two aims. In Aim 1, I will visualize monolayer collapse structures using the 3-D serial sectioning capabilities of the confocal fluorescence microscope to determine how monolayer domains alter collapse behavior and the minimum surface tension. I have also recently found that collapse behavior changes on curved, alveolar-size interfaces compared to the flat surfaces in a Langmuir trough, and I will use confocal imaging to determine the relationship between collapse morphology and interfacial curvature. Aim 2 is to pioneer infrared-coupled atomic force microscopy (AFM-IR) methods to map the lateral distribution of the chemical species and their local ordering in multicomponent lung surfactant monolayers. I will use AFM-IR to examine the hypothesis that cholesterol concentrates at domain boundaries to lower the line tension while palmitic acid and hexadecanol promote crystallization of dipalmitoylphosphatidylcholine, increasing the fraction of solid phase in the monolayer. Successful completion of this project will provide a detailed description of the two-dimensional chemical distribution in laterally phase separated lung surfactant monolayers and how this phase separation influences the minimum surface tension at monolayer collapse.", "keywords": [ "3-Dimensional", "Acute Respiratory Distress Syndrome", "Admission activity", "Affect", "Air", "Alveolar", "Alveolus", "American", "Animals", "Architecture", "Area", "Atelectasis", "Atomic Force Microscopy", "Behavior", "Biological", "Blood capillaries", "Breathing", "COVID-19", "Cattle", "Chemical Surfactants", "Chemicals", "Cholesterol", "Complex", "Confocal Microscopy", "Coupled", "Crystallization", "Data", "Disease", "Exhalation", "Family suidae", "Fluorescence Microscopy", "Frequencies", "Growth", "Image", "Immune response", "Inflammation", "Lateral", "Life", "Lipase", "Lipids", "Liquid substance", "Lung", "Maps", "Methods", "Minnesota", "Minor", "Modulus", "Morphology", "Neonatal Respiratory Distress", "Palmitic Acids", "Patients", "Phase", "Positioning Attribute", "Premature Infant", "Property", "Proteins", "Pulmonary Surfactants", "Radial", "Religion", "Research", "Resolution", "Route", "Signal Transduction", "Solid", "Spatial Distribution", "Structure", "Surface", "Surface Tension", "Surfactant therapy", "System", "Trauma", "Universities", "Unsaturated Fats", "Visualization", "Water", "Work", "behavior change", "confocal imaging", "fluorescence microscope", "improved", "interfacial", "microscopic imaging", "monolayer", "mortality", "nanometer", "pressure", "prevent", "protein distribution", "respiratory distress syndrome", "segregation", "submicron", "surfactant", "surfactant replacement", "surfactant replacement therapy", "three dimensional structure", "trend", "two-dimensional" ], "approved": true } } ], "meta": { "pagination": { "page": 1391, "pages": 1424, "count": 14236 } } }