Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1383&sort=principal_investigator
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=principal_investigator", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1397&sort=principal_investigator", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1384&sort=principal_investigator", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1382&sort=principal_investigator" }, "data": [ { "type": "Grant", "id": "15410", "attributes": { "award_id": "1R01AI182177-01", "title": "Armed nanobodies as anti-infectives and anti-tumor agents", "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": 29189, "first_name": "Moriah Jovita", "last_name": "Castleman", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-07-19", "end_date": "2029-05-31", "award_amount": 542900, "principal_investigator": { "id": 32013, "first_name": "Hidde L.", "last_name": "Ploegh", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 798, "ror": "https://ror.org/00dvg7y05", "name": "Boston Children's Hospital", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "A nanobody that recognizes immunoglobulin light chains, conjugated to a molecular entity that recognizes a virus-infected or a cancerous cell, is an effective therapeutic: A single injection of fusion constructs comprising an anti-kappa light chain nanobody (VHHkappa) and zanamivir, a small molecule that targets influenza neuraminidase, protects mice from a lethal challenge with both A- and B-strains of influenza. In the model that established protection by VHHkappa adducts against influenza, the underlying mechanism of action involves antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), but the relative contribution of each is not known. We shall therefore use FcgR common g chain-deficient mice and C3- deficient mice to assess the relative contributions of ADCC and CDC. The generation of Fc constructs of different Ig isotypes and bearing FcR-engagement disabling mutations, similarly modified with zanamivir, will be used to complement this analysis. Having established proof-of-concept for influenza and optimized parameters for elimination of influenza virus- infected cells, we will explore nanobodies that recognize other pathogens (Ebola virus, SARS-CoV-2, HIV) in combination with VHHkappa in a series of collaborative experiments. The agents to be developed may inspire novel immunomodulatory therapeutics, to be used as a stand-alone approach, or in combination with approved drugs. The possibilities of post-exposure prophylaxis against viral infections (Ebola, SARS-CoV-2, HIV) in the absence of pre-existing immunity, deserve particular emphasis. We shall further enhance the activity of the proposed VHHkappa fusions through the generation of the corresponding drug adducts, using cytotoxic drugs such as maytansinoids as compounds that have shown clinical utility. Enveloped viruses (e.g., HIV, SARS-CoV-2) export viral proteins to the surface of the infected cell during budding. Infected cells can thus be distinguished from uninfected cells based on the surface display of viral proteins. We now extend these in vivo observations to fusions of VHHkappa with anti-checkpoint (PD-L1, CTLA-4) nanobodies. We generated maytansinoid-modified VHHkappa fusions with the anti-PD-L1 and anti-CTLA-4 VHHs. Our preliminary data show enhanced anti-tumor activity in the MC38 and B16.F10 mouse tumor models in comparison with commonly used monoclonal antibodies. However, not all such fusions (examples: fusions of VHHkappa with nanobodies that recognize Class II MHC or CD8) have shown the intended depletion efficacy in vivo. This proposal seeks to establish the parameters -including biodistribution and surface expression levels of the targeted molecules- that determine success or failure of VHHkappa fusions. The availability of VHHs that recognize human kappa light chains suggest the possibility of clinical translation of this approach.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15411", "attributes": { "award_id": "1R13AI186420-01", "title": "Mechanisms of RNA Decay", "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": 32014, "first_name": "Patricia M.", "last_name": "Strickler-Dinglasan", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-07-16", "end_date": "2024-11-30", "award_amount": 5000, "principal_investigator": { "id": 32015, "first_name": "Olivia Selfridge", "last_name": "Rissland", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1511, "ror": "", "name": "FEDERATION OF AMER SOC FOR EXPER BIOLOGY", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "A counterbalance to RNA synthesis, RNA degradation is critical for regulating gene expression. The understanding that RNA degradation is critical for gene expression traces back to 1959 when Pardee, Jacob and Monod demonstrated in a historical paper that there had to be an unstable intermediate directing protein synthesis. Groundbreaking research over the past decades led to the identification of a variety of specific and tightly regulated RNA decay pathways and biochemical characterization of the enzymes involved in them, both in eukaryotic and prokaryotic organisms. The clinical applications in the post-transcriptional regulation/RNA field are now being realized with the initial development of Nusinersen/Spinraza® to successfully treat Spinal Muscular Atrophy and the more recent description of Milasin® to treat a single patient through a personalized RNA therapy. Of course, in 2020, RNA burst onto the global stage in a way we could not have predicted with the COVID-19 RNA virus impacting life as we know it across the globe. Who would or could have guessed that RNA could also represent a potential path back to a new normal via the rapid development and deployment of the first mRNA vaccines. All these examples highlight why the FASEB meeting on ‘Mechanisms of RNA Decay’ is timely. This meeting has developed into a unique conference that brings together the leading experts in RNA decay in humans and other metazoan animals, plants, fungi, viruses, and bacteria. This meeting is the 13th is a series of FASEB meetings on this topic where there is a long tradition of sharing key discoveries, building collaborations, and contributing to career development for junior scientists in the field. This meeting, held August 18–22, 2024 in Lisbon, Portugal, is co-organized by three leaders in the RNA decay field, Dr. Olivia Rissland from University of Colorado School of Medicine, USA, Dr. Alicia Bicknell from Moderna Therapeutics, and Dr. Oliver Muhlemann from University of Bern, Switzerland. We propose three specific aims for this meeting: 1) Bringing together the international community working on RNA degradation and providing an intellectually stimulating and mutually supportive forum for the presentation and discussion of the latest advances in the field; 2) Providing an inclusive and friendly environment for establishing collaborations between researchers studying RNA degradation with different approaches and in different organisms; and 3) Encouraging productive interactions between a diverse group of both junior scientists and world leaders in the RNA degradation field. In keeping with the meeting goals, the organizers are committed to inclusive excellence: Among the 28 invited speakers, there are 13 women (46%) and a well-balanced gender ratio will be ensured among the 25 additional oral presentations that will be selected from the submitted abstracts. Also, among the 10 session chairs, six are women. We are excited to include trainee co-chairs, who will be selected from the short-talk presenters. The long-term goal is to continue a successful meeting series that addresses modern and timely topics in RNA decay and strengthens the interactions within a diverse and inclusive community of collaborative scientists and colleagues.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15412", "attributes": { "award_id": "1R21AI185841-01", "title": "Optimization of novel inhibitors of mycolic acid synthesis as TB drug candidates.", "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": 32016, "first_name": "Jim P.", "last_name": "Boyce", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-07-17", "end_date": "2026-06-30", "award_amount": 237288, "principal_investigator": { "id": 32017, "first_name": "Kyle H", "last_name": "Rohde", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32018, "first_name": "Jennifer Marie", "last_name": "Schomaker", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 1475, "ror": "https://ror.org/036nfer12", "name": "University of Central Florida", "address": "", "city": "", "state": "FL", "zip": "", "country": "United States", "approved": true }, "abstract": "Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is responsible for staggering levels of morbidity and mortality, with ~1.7 million deaths and ~10 million new cases each year. The current TB regimens for drug susceptible strains, entailing multidrug cocktails for ≥4 months, leave much to be desired. The cost and logistics of administering standard of care regimens over many months and the inability of many patients to tolerate the debilitating side effects further complicate the clinical control of TB. The lingering negative impacts of the COVID pandemic on TB control efforts and increasing challenge of multidrug-resistant Mtb strains, which have only a ~50% treatment success rate, further highlight the urgent need for better antibiotics to tackle this problem. Even our definition of what “better” means has shifted based on recent appreciation of the heterogeneity of mycobacteria subpopulations that must be eradicated, including replicating and non-replicating bacilli residing both extracellularly and within host cells in diverse microenvironments. Thus, effective drug combinations must not only access mycobacteria within different niches and layers of granulomas but also be able to kill Mtb in many distinct metabolic states while minimizing the emergence of resistance. In order to meet this urgent need for game-changing new treatment options for TB, it is imperative to maintain a robust pipeline of new anti-TB drug candidates with the potential to meet these demanding performance criteria. This project seeks to address this need by building on our recent discovery of a first-in-class series of compounds that kill Mtb via inhibition of a well- validated but underexploited target enzyme essential for cell wall synthesis. Thus far, we have demonstrated sub-micromolar potency, enhanced potency against Mtb within macrophages, high specificity for Mtb, and high selectivity over mammalian cells. We have strong evidence that these compounds act via inhibition of an essential enzyme involved in mycolic acid biosynthesis for which there are currently no viable preclinical candidates. The first major goal of this project is hit-to-lead optimization and elucidation of structure-activity relationships, using whole cell potency and ADME/PK properties as key drivers of compound prioritization. Secondly, we will employ orthogonal approaches to further validate the target and ensure that optimized lead compounds remain on-target. Successful completion of this project will set the stage for subsequent lead optimization and in vivo efficacy studies of a promising new class of cell-wall targeting TB antibiotics.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15413", "attributes": { "award_id": "1UG3AI181797-01", "title": "Coordinating and Data Sharing Center - R&D of Vaccines and Antibodies for Pandemic Preparedness (ReVAMPP)", "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": 32019, "first_name": "ANNE ELIZABETH MAYER", "last_name": "Bridwell", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-07-16", "end_date": "2027-06-30", "award_amount": 7994888, "principal_investigator": { "id": 32020, "first_name": "Sean Thomas", "last_name": "Hanlon", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32021, "first_name": "Gregory D", "last_name": "Sempowski", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 809, "ror": "", "name": "RESEARCH TRIANGLE INSTITUTE", "address": "", "city": "", "state": "NC", "zip": "", "country": "United States", "approved": true }, "abstract": "0BPROJECT SUMMARY/ABSTRACT The global pandemic caused by SARS-CoV-2 highlighted the continual threat of emerging and re-emerging pandemic-potential pathogens and the critical value of coordinated multidisciplinary basic and translational research for pandemic preparedness. There is an urgent need for an integrated collaborative effort to build a robust basic research and translational science portfolio for preparedness against high-risk viral families including Paramyxoviridae, Picornaviridae, and Bunyavirales. The National Institute of Allergy and Infectious Diseases (NIAID) is supporting the development of the Research and Development of Vaccines and Monoclonal Antibodies for Pandemic Preparedness (ReVAMPP) Network to fill this critical gap. The overall goal of this new collaborative Network, consisting of a Coordinating and Data Sharing Center (CDSC) and six to eight Research Centers, is to collaboratively produce generalizable knowledge that enables a rapid response when previously understudied or unknown pathogens emerge. RTI International’s well-established track record implementing large-scale domestic and international coordinating and data management centers, including in the emerging infectious disease ecosystem, makes us well qualified to develop and provide Network governance, communications, and data sharing and analysis as the ReVAMPP CDSC. The overall goal of the RTI-based CDSC is to establish and maintain an integrated Network to accelerate discovery and dissemination of novel vaccine and monoclonal antibody strategies to prepare for the next pandemic outbreak. To accomplish this goal, RTI proposes a CDSC organizational structure, consisting of two interconnected teams under mPIs and a Project Director—an Administration and Leadership Team, and a Data Management and Analysis Team. This structure leverages RTI multidisciplinary experts and will provide ReVAMPP Centers, NIAID, and stakeholders centralized administrative, communication, and operational support for Network-wide activities, while also establishing data sharing and analysis standards and platforms. The Specific Aims of the RTI-based CDSC align with these two teams and will use both established and novel innovative approaches and technologies to (Aim 1) coordinate preparatory vaccine and antibody strategy research by establishing and maintaining ReVAMPP Network governance, administration, and communication; and (Aim 2) accelerate transparent collaborative vaccine and antibody strategy research by developing and maintaining a secure ReVAMPP Network Private Portal that includes centralized resource, data sharing, and reporting systems. This independent, but integrated team of administrators, communicators, and data science experts embedded within the ReVAMPP Network as the CDSC, will coordinate, facilitate, and empower Network investigators and NIAID to proactively prepare to rapidly share information with key stakeholders across the globe when new viral pandemic/outbreaks occur.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15414", "attributes": { "award_id": "1U24AI183849-01", "title": "The Bacterial and Viral Bioinformatics Resource Center (BV-BRC)", "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": 32022, "first_name": "WIRIYA", "last_name": "Rutvisuttinunt", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-07-18", "end_date": "2029-06-30", "award_amount": 3600000, "principal_investigator": { "id": 32023, "first_name": "RICK L.", "last_name": "STEVENS", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 289, "ror": "https://ror.org/024mw5h28", "name": "University of Chicago", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true }, "abstract": "The mission of the NIH/NIAID Bioinformatics Resource Center (BRC) program is to accelerate basic and applied infectious disease research by providing access to cutting edge bioinformatic tools, knowledgebases, and expertise, ensuring that our knowledge of pathogenesis can be translated into diagnostics, therapeutics and a public health response that mitigates the morbidity and mortality resulting from infectious diseases. The current NIH/NIAID-funded Bacterial and Viral Bioinformatics Resource Center (BV-BRC; Contract No. 75N93019C00076) supported this mission by providing a bioinformatics knowledgebase and analysis platform covering all bacterial and viral pathogens. In response to the NIAID notice of funding opportunity, RFA-AI-23- 032, our proposal intends to maintain, improve, and expand the BV-BRC to combat future infectious disease threats, while maintaining our commitment to enhance diversity, equity, inclusion, and accessibility, fostering a more inclusive scientific community, and ensuring equitable access to bioinformatics resources. BV-BRC will support bacteria, archaea, viruses, bacteriophages, as well as metagenomic analyses, with particular emphasis on the microbiomes and viromes related to infectious disease and public health. BV-BRC will continue to support the basic scientific research necessary to understand the biology of these organisms, their pathogenesis, and disease processes; support development of diagnostics and therapeutics to combat pathogenic organisms; and provide a rapid response framework to effectively deal with the inevitable and unpredictable outbreaks and pandemics. To support these overarching goals, we propose to extend and enhance BV-BRC through the following four key elements: 1) Maintain and enhance the BV-BRC knowledgebase to support exponential growth of data and usage and provide integrated access to omics data, metadata, analysis services and visualization tools, private user workspace, and user documentation to allow users to analyze public and private data and share or publish results; 2) Develop innovative tools and technologies to provide comprehensive services for viral and bacterial bioinformatics, metagenomics, drug development, and developing AI-driven natural language-based user interface for interacting with data and tools, with emphasis on improving user experience; 3) Offer critical bioinformatics expertise, outreach, and training to the community, with emphasis on fostering opportunities for students and researchers from minority and underserved communities by providing freely accessible training material and conducting training for instructors from underrepresented institutions, with particular focus on Minority Serving Institutions (MSIs); and 4) Provide cutting-edge support to rapidly respond to emerging needs, outbreaks, and pandemic preparedness by building on the tools and procedures developed during COVID-19 and Mpox pandemics and enhancing them to improve readiness and response to future outbreaks and pandemics.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15417", "attributes": { "award_id": "1R01AI188576-01", "title": "SCH: Improving Early Prediction and Decision-Making for Sepsis with Human-AI Collaboration", "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)", "NIH Office of the Director" ], "program_reference_codes": [], "program_officials": [ { "id": 23983, "first_name": "Nancy L.", "last_name": "Ernst", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-07-17", "end_date": "2028-05-31", "award_amount": 300000, "principal_investigator": { "id": 32024, "first_name": "Jeffrey M", "last_name": "Caterino", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 29277, "first_name": "Ping", "last_name": "Zhang", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 32025, "first_name": "Lace M.", "last_name": "Padilla", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 32026, "first_name": "Dakuo", "last_name": "Wang", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 778, "ror": "", "name": "OHIO STATE UNIVERSITY", "address": "", "city": "", "state": "OH", "zip": "", "country": "United States", "approved": true }, "abstract": "Early prediction and timely decision-making of acute diseases are critical to enabling early intervention and improving clinical outcomes (for example, a sepsis patient may benefit from a 4% higher chance of survival if diagnosed 1 hour earlier). Developing machine learning (ML) models for clinical decision-making on Electronic Health Records (EHRs) presents several significant challenges: 1) existing models are trained mostly on EHR data from intensive care units (ICUs), which are not generalizable for sepsis onsets in emergency rooms and hospital wards; 2) most existing tools simply output prediction result as a risk score, without sufficient explanation or confidence interval for it, which is not trustworthy for physicians; 3) existing systems often ignore the human workflow by neither providing actionable insights to physicians nor enabling interactive explorations from physicians, which limits their clinical usages. To address these challenges, we propose a Human-Centered Artificial Intelligence (HCAI) system to collaborate with human domain experts in the high-stake and high-uncertainty decision-making process. Specifically, we 1) create a deidentified database with complete visits and long-term EHR history for patients with sepsis risk; 2) develop early sepsis risk prediction models with uncertainty quantification and active sensing; 3) design and implement a physician-centered AI prediction module and user interface for early sepsis human-AI decision making; and 4) design and conduct controlled usability evaluations to quantitatively and qualitatively measure the clinical outcome and user satisfaction. This project integrates human-AI collaboration design, novel ML algorithms, and data visualization tools for improving early prediction and decision-making for sepsis, which hold great promise for leading new insights into human-AI systems for clinical decision support. RELEVANCE (See instructions): Sepsis, which can be caused by bacteria, fungi, or in the case of COVID-19, a virus, is a life-threatening condition with high mortality rates and expensive treatment costs. This project will develop a physician- centered deep-learning algorithm to predict sepsis onset and a user interface for effective human-AI collaboration. As a result, this work relates to the mission of the NIAID and will make a relevant public health impact by delivering early, life-saving care to the bedside of sepsis patients, and will lead to a useful clinical decision support tool for physicians.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15418", "attributes": { "award_id": "1R01HL175474-01", "title": "Non-conventional signaling by α5 integrin in blood and endothelial cells", "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": 22468, "first_name": "Deborah", "last_name": "Philp", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-07-15", "end_date": "2028-06-30", "award_amount": 718854, "principal_investigator": { "id": 32027, "first_name": "Jieqing", "last_name": "Zhu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1016, "ror": "", "name": "VERSITI WISCONSIN, INC.", "address": "", "city": "", "state": "WI", "zip": "", "country": "United States", "approved": true }, "abstract": "– Integrins interact with their ligands to induce intracellular signals that mediate cellular activities such as cell adhesion, spreading, and migration, which are the essential cellular activities for the function of blood and endothelial cells. These signaling events are typically mediated by the cytoplasmic tail of integrin β subunit, while the role of α integrin cytoplasmic tail in integrin function remains relatively underexplored. Our research found that the fibronectin receptor integrin α5β1, via its α cytoplasmic tail, is involved in the formation of tunneling nanotubes (TNTs), a novel type of cellular structure for cell-to-cell communication. Remarkably, our research found that the α5β1-mediated TNT formation can be induced by the spike protein of coronavirus SARS- CoV-2. We observed the spike-induced and α5-dependent TNT formation in model cell lines and primary human blood and endothelial cells. Furthermore, we found that α5β1 integrin can mediate the spike-induced proinflammatory response in human blood and endothelial cells, which may contribute to the thrombotic events in COVID-19. TNTs are long actin-rich cell membrane protrusions that have been increasingly recognized as functional subcellular structures for long-distance dynamic intercellular connection. Functioning as conduits between connected cells, TNTs can transport cytoplasmic components like small molecules, proteins, vesicles, and mitochondria intercellularly. Accumulating evidence suggests that TNTs are involved in the progress of many pathological conditions such as cancer, inflammation, and neurodegenerative diseases. Bacteria and virus pathogens also exploit TNTs for cell-to-cell transmission. TNTs can form under cell stress conditions such as inflammation and virus infection. However, the cellular mechanisms regulating TNT formation remain largely unknown. This is mainly because little to nothing is known about the cell surface receptors directly responsible for TNT biogenesis. Our discovery of α5β1 integrin as a functional signaling receptor for TNT formation provides a powerful platform for investigating TNT biology. Mechanistically, we found that both α5β1-mediated TNT formation and proinflammatory response require the participation of α5 cytoplasmic tail, suggesting that these two processes are interconnected events. Moreover, our protein interaction data suggest a direct binding between α5β1 and the spike protein, which is independent of the classical integrin recognition Arg-Gly-Asp (RGD) motif. Based on these promising data, this application aims to elucidate the cellular mechanisms governing the non-conventional signaling function of α5β1 integrin in TNT formation and inflammation in blood and endothelial cells. Multifaced biochemical, biophysical, structural and cell biology approaches will be used to identify intracellular molecules and signaling pathways involved in the α5β1-mediated TNT formation (Aim 1) and inflammation (Aim 2) and to characterize the non-RGD dependent α5β1 and ligand interaction (Aim 3). The outcome of this study will advance both integrin and TNT biology and uncover potential therapeutic targets for modulating TNTs and inflammation in various diseases.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15420", "attributes": { "award_id": "3U01AA026817-05S1", "title": "S-adenosylmethionine treatment in alcoholic cirrhosis", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Alcohol Abuse and Alcoholism (NIAAA)" ], "program_reference_codes": [], "program_officials": [ { "id": 10229, "first_name": "Gary", "last_name": "Murray", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-06-01", "end_date": "2025-08-31", "award_amount": 273786, "principal_investigator": { "id": 32028, "first_name": "Bin", "last_name": "Gao", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32029, "first_name": "Suthat", "last_name": "Liangpunsakul", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 32030, "first_name": "Shelly Chi-Loo", "last_name": "Lu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2527, "ror": "https://ror.org/03eftgw80", "name": "Indiana University Indianapolis", "address": "", "city": "", "state": "IN", "zip": "", "country": "United States", "approved": true }, "abstract": "Alcoholic cirrhosis is a leading cause of morbidity and mortality in the US. One of the key drivers in its pathogenesis is the reduction in hepatic methionine adenosyltransferase 1A (MAT1A) expression resulting in the reduction in hepatic S-adenosylmethionine (SAMe) levels. The reduction in SAMe level leads to several adverse intracellular consequences, which include promoting the inflammatory cascades in immune cells such as macrophages by lipopolysaccharides (LPS), oxidative stress and endoplasmic reticulum (ER) stress. This project involves two academic centers in the United States (Cedars-Sinai Medical Center in Los Angeles and Indiana University Hospital), a research institute in Spain (CIC bioGUNE), and NIAAA intramural liver research scientist (Dr. Bin Gao) to examine SAMe in humans with alcoholic cirrhosis. We proposed a randomized double-blind placebo controlled trial to determine the efficacy of SAMe (1,200 mg/day given in two divided dose) and its mechanistic effects in patients with alcoholic cirrhosis (Child class A and B) in the real world setting. The primary endpoint will be the mortality of any causes between groups. The target enrollment of our clinical trial is 196 participants (176 patients with alcohol-associated cirrhosis and 20 controls). The approval for funding of our study started on September 20, 2019. However, our study was significantly impacted by the COVID-19 pandemic in 2020 and 2021. The administrative hold on research activities due to the pandemic prohibited us to enroll patients as we anticipated. To date, 112 participants (~57%) were enrolled. Our enrollment continues to improve and meet the monthly target enrollment starting around the beginning of Yr 3 of the project (~September 2021, the time when the overall COVID-19 pandemic was improving). Given the trajectory of the enrollment, we anticipated that we should be able to complete our enrollment around August 2026. Our current funding ends on 8/31/24. This supplemental application is to allow us to complete the clinical trial, currently being funded by 1U01AA02681.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15424", "attributes": { "award_id": "1SB1AG087755-01", "title": "Ryan® CompanionBot for Assisting Older Adults with Early-Stage Alzheimer's Disease and Dementia", "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": 32031, "first_name": "DINESH", "last_name": "John", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-03-01", "end_date": "2026-05-31", "award_amount": 1424731, "principal_investigator": { "id": 32032, "first_name": "Mohammad", "last_name": "Mahoor", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2541, "ror": "", "name": "DREAM FACE TECHNOLOGIES, LLC", "address": "", "city": "", "state": "CO", "zip": "", "country": "United States", "approved": true }, "abstract": "The population of Americans age 65 years or older will increase from 58 million in 2021 to 88 million by 2050. By 2050, nearly 14 million older adults are expected to have AD/ADRD. For these individuals, significant care is required, and that care is often provided by family members. A 2022 study estimated that 11 million American family members are providing 16 billion hours of care valued at more than $272 billion. Senior care facilities are another option. The COVID-19 pandemic severely affected senior care facility residents. Despite representing only about 1% of the total population in the U.S., COVID-19 deaths in senior care facilities have made up nearly 40% of total COVID-19 deaths. Senior care facilities often face staffing shortages during and after the pandemic. Currently, 3 in 5 assisted living facilities are concerned that they may have to close due to staffing shortages. The situation with these two caregiving options is alarming; increasing demand for caregivers coupled with short supply has led to higher costs, unfilled needs, and fierce competition for resources. While computer technologies, such as wearable devices, are beginning to partially alleviate the shortage of caregivers, more powerful and personalized tools are needed. To address this urgent need, DreamFace Technologies, LLC invented Ryan® CompanionBot, a novel humanoid socially-assistive robot expertly tailored to the specific needs of older adults with early-stage AD/ADRD. The development of Ryan®, with the support of one NSF and two NIA/NIH SBIR grants, has been informed by 100 customer interviews and several subsequent field tests and clinical trials involving more than 50 older adults with early-stage AD/ADRD. In these tests, Ryan® has effectively delivered companionship, engaging conversations, physical and mental stimulation, daily activity reminders, and valuable assistance to the AD/ADRD-afflicted seniors powered by state-of-the-art artificial intelligence technologies such as facial expression recognition and synthesis, brain games, and empathic conversations while we also learned about several additional capabilities required for commercial success. Furthermore, in the pre-launch phase of the initial version of Ryan®, it has been deployed on a subscription basis at the esteemed senior care facility, Morningstar, which has served as a valuable beta site. In this Commercialization Readiness Pilot (CRP) program, we plan to complete the preparation of Ryan® for full commercialization. Specifically, we will: (1) refine and enhance Ryan®'s software and hardware, making mass manufacturing more efficient and cost-effective while making Ryan®'s operation more robust and easier to adopt by family members, staff, administrators, and caregivers in senior care facilities, (2) develop robust, integrated marketing and sales strategies, (3) develop an Intellectual Property strategy and required privacy policy and legal documents and (4) develop a financing and fundraising strategy for the successful commercialization of Ryan®. Upon the completion of the CRP project, we will have all the essential elements in place for the full commercialization of Ryan® as a transformative solution for senior care, benefiting both individuals diagnosed with early-stage AD/ADRD and caregivers alike.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15425", "attributes": { "award_id": "5G08LM014107-03", "title": "Reading Bees: Adapting and Testing a Mobile App Designed to Empower Families to Read more Interactively with Children in Distinct Geographical and Cultural Contexts", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Library of Medicine (NLM)" ], "program_reference_codes": [], "program_officials": [ { "id": 26724, "first_name": "Meryl", "last_name": "Sufian", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-01-23", "end_date": "2026-07-31", "award_amount": 149693, "principal_investigator": { "id": 32033, "first_name": "John S.", "last_name": "Hutton", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1215, "ror": "", "name": "UT SOUTHWESTERN MEDICAL CENTER", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "Many children arrive at kindergarten unprepared to learn to read, at-risk of falling more behind, with major inequities linked to race, geography and poverty (rates >50%). These are amplified during disruptions such as COVID, when access to information and resources is perturbed. Low proficiency is strongly linked to adverse school, vocational and health outcomes, with estimated costs >$350 billion/year. As parents are a child’s “first and most important teachers,” home reading routines have a large impact on these outcomes. However, there are wide disparities in these between high- and low-resource families, fueled by household stressors, cultural differences, literacy challenges and other factors. Marginalized families also often face barriers to access of reliable literacy-promoting information, programs and resources, worsening disparities. Given trusted access to families when parenting routines are shaped, health providers are poised to help mitigate these barriers, yet guidance tends to be general, inconsistent and can fade-out at home. The objective of the proposed project is to enhance, “localize” and test a new, free mobile app designed to provide reliable shared reading guidance and resources for parents (Reading Bees; RB) in an efficient, engaging way. The rationale is that no similar approach exists, RB is free and designed to enhance existing programs, and there is evidence that its features will be useful and effective. Content is evidence-based and has been co-developed with input from community stakeholders and families from disadvantaged backgrounds. Core principles are clarity, credibility, flexibility (e.g., parents set their own goals), responsiveness (child age, family concerns, ZIP), engaging content (tips, videos, resources) and positive reinforcement (“LitCoin” awards). The long-term goal of this project is to use RB to help improve reading and literacy outcomes. To achieve this, teams in 3 culturally distinct areas (OH, WV, FL) will collaborate in a 3-year project. Content will first be added to address needs in each community: lists of local reading-related resources curated by area stakeholders and a Spanish language version of RB. Enhanced, “localized” RB will then be tested with parents in each area, first through focus groups to gauge usefulness and guide refinement, and then by providing RB to parents (ages 0-6) during clinic visits and measuring use over the next 2 months. Outcome measures involve feasibility, acceptance and useflness. The central hypothesis is that local stakeholders will be engaged by the opportunity to highlight resources in their area; families will rate RB content as useful and use RB often, especially to earn LitCoin awards; and improved access to information and resources will fuel better reading and literacy outcomes. This work is significant and innovative as it involves a tech-enabled, user-centered approach that is scalable within existing pediatric, library and program infrastructure and empowers parents to read more interactively and access reliable information. The expected outcome is that this work will provide vital enhancements to RB, show feasibility and usefulness and provide a flexible, collaborative model to “localize” and scale use of RB into other areas.", "keywords": [], "approved": true } } ], "meta": { "pagination": { "page": 1383, "pages": 1397, "count": 13961 } } }