Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1392&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=1405&sort=principal_investigator", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1393&sort=principal_investigator", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1391&sort=principal_investigator" }, "data": [ { "type": "Grant", "id": "15618", "attributes": { "award_id": "1R01MH135844-01A1", "title": "Harnessing smartphones for real-time detection of affective disturbance and future depression risk in adolescents", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Mental Health (NIMH)" ], "program_reference_codes": [], "program_officials": [ { "id": 23085, "first_name": "Eric Rousseau", "last_name": "Murphy", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-02-01", "end_date": "2029-11-30", "award_amount": 759581, "principal_investigator": { "id": 32116, "first_name": "Christian Anthony", "last_name": "Webb", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 844, "ror": "https://ror.org/01kta7d96", "name": "McLean Hospital", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "Negative affective (NA) states (e.g., high sadness, anger, and anxiety) increase substantially during adolescence, which may heighten risk for the onset of affective disorders, in particular major depressive disorder (MDD), which surges during the adolescent years. Over the past decade, affective disturbances and MDD have been rising in adolescents, and the COVID-19 pandemic has only exacerbated this alarming trend. As a result, the Surgeon General and national pediatric organizations (American Academy of Pediatrics, American Academy of Child and Adolescent Psychiatry, and Children’s Hospital Association) recently declared a national state of emergency for youth mental health. Accordingly, there is an acute need to develop personalized data-driven approaches to predict and ultimately interrupt states of markedly high NA as they occur in the daily lives of teens. In addition to the immediate benefits of alleviating acute states of affective distress, reducing the frequency and duration of episodes of high NA may serve to reduce the risk of depression onset in youth. Relevant in this context, the majority (88%) of U.S. teens own a smartphone, which can continuously and unobtrusively measure behaviors predictive of affective disturbance, including activity levels, location, phone use, sleep, and proxies of social interaction. In addition, smartphone data may also predict risk of MDD onset. The ability to prospectively predict MDD prior to its onset would have important clinical implications for the early identification of – and targeted deployment of interventions for – at-risk youth, which is strongly aligned with the NIMH Strategic Plan. To address these gaps, adolescents ages 12-16 (the age range corresponding to the largest developmental increase in depression) will complete repeated ecological momentary assessment (EMA) surveys of NA (i.e., assessing different negative emotional states) over 30 days. During this period, smartphone sensors and a wrist-worn actigraphy band will collect data on activity levels, location, phone/screen use, calls/texts and estimates of relevant sleep variables (e.g., sleep onset, offset, and duration). The project has two aims. First, a personalized machine learning approach recently developed by the study team will test the accuracy of predicting states of high NA in the daily lives of teens from these passively derived features (Aim 1). The ability to accurately predict states of high NA at the individual level could ultimately inform the development of highly scalable and personalized smartphone-delivered interventions matched to the current affective state (e.g., high sadness vs. anger) of a given teen. Second, during a follow-up phase, participants will be contacted every 6 months to assess changes in symptoms, along with bursts of passive sensor data collection and EMA. Machine learning analyses will test whether passive data, in combination with affect dynamics, predict subject-specific risk of future depression onset with sufficiently high sensitivity and specificity to be clinically useful (Aim 2). To the extent that a data-driven approach could be developed to predict individual risk of future depression onset, it could ultimately inform the development and delivery of individualized, targeted, and timely prevention efforts.", "keywords": [ "16 year old", "Academy", "Accelerometer", "Acute", "Address", "Adolescence", "Adolescent", "Adolescent Psychiatry", "Affect", "Affective", "Age", "American", "Anger", "Anhedonia", "Anxiety", "Behavioral", "COVID-19 pandemic", "Cellular Phone", "Characteristics", "Child Psychiatry", "Childhood", "Clinical", "Collaborations", "Data", "Data Collection", "Depressed mood", "Detection", "Development", "Distress", "Doctor of Philosophy", "Early identification", "Ecological momentary assessment", "Emergency Situation", "Emotional disorder", "Emotions", "Exercise", "Frequencies", "Funding", "Future", "Global Positioning System", "Goals", "Grant", "Individual", "Infrastructure", "Interruption", "Intervention", "Location", "Machine Learning", "Major Depressive Disorder", "Measures", "Mental Depression", "Mental Health", "Metadata", "Mood Disorders", "National Institute of Mental Health", "Onset of illness", "Participant", "Pediatric Hospitals", "Pediatrics", "Persons", "Phase", "Prevalence", "Prevention", "Proxy", "Psychiatry", "Research", "Risk", "Risk Reduction", "Sensitivity and Specificity", "Severities", "Sleep", "Social Interaction", "Strategic Planning", "Surgeon", "Surveys", "Symptoms", "Technology", "Teenagers", "Telephone", "Testing", "Text", "Time", "Wrist", "Youth", "actigraphy", "affective disturbance", "anxiety symptoms", "behavior prediction", "child depression", "depressive symptoms", "emotional distress", "emotional experience", "experience", "follow-up", "innovation", "machine learning algorithm", "mindfulness", "negative affect", "negative emotional state", "novel strategies", "personalized predictions", "predictive modeling", "prospective", "risk prediction", "rumination", "sensor", "sensor data", "single episode major depressive disorder", "sleep onset", "stressor", "trend" ], "approved": true } }, { "type": "Grant", "id": "15619", "attributes": { "award_id": "1R01HL171220-01A1", "title": "Mitochondrial deubiquitinase USP30 regulates cell metabolism-mediated miRNA biogenesis and microvascular inflammation", "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": "2025-02-01", "end_date": "2028-11-30", "award_amount": 678803, "principal_investigator": { "id": 32117, "first_name": "Yutong", "last_name": "Zhao", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 778, "ror": "", "name": "OHIO STATE UNIVERSITY", "address": "", "city": "", "state": "OH", "zip": "", "country": "United States", "approved": true }, "abstract": "Acute inflammatory diseases are life-threatening health conditions that are most often caused by bacterial or viral infection such as Pseudomonas aeruginosa- or SARS-CoV-2-induced acute respiratory distress syndrome (ARDS) and sepsis. ARDS and sepsis-related mortality remains at unexpectedly high levels due to lack of effective pharmacotherapies. Hence, a new therapeutic strategy for ARDS and sepsis is needed. Microvascular inflammation and barrier disruption play critical roles in the pathogenesis of acute inflammatory diseases. A mitochondrial de-ubiquitinating enzyme, USP30, plays a vital role in regulation of mitochondrial outer membrane protein homeostasis. USP30 has been considered as a potential target for treating Parkinson’s disease and cancers; however, the role of USP30 in microvascular endothelial cells (ECs) and acute inflammatory diseases has not been reported. In our preliminary data, we discovered that inhibiting USP30 diminished EC dysfunction and reduced the severity of experimental lung injury. Mechanistically, we discovered a non-canonical pathway of USP30 that links MAT2A stability, the S- adenosylmethionine (SAM) cycle, DNA methylation, miRNA-30a-5p synthesis. Based on our comprehensive preliminary data, we hypothesize that inhibiting USP30 preserves EC function by modulating intracellular signaling cascades implicated in MAT2A stability, SAM production, DNA methylation, and miR-30a-5p expression. We propose testing the hypothesis with the following Specific Aims: Aim 1 is to determine if USP30 in the endothelium is a potential target for treatment of acute lung injury. We will determine if inhibiting EC USP30 diminishes leukocyte cell adhesion to EC and transendothelial migration and preserves EC barrier integrity. Further, we will determine if depletion of USP30 in endothelial cells reduces severity of pseudomonas aeruginosa- or sepsis-induced experimental lung injury. Aim 2 is to determine the molecular mechanisms by which inhibiting USP30 destabilizes MAT2A, decreases the SAM production, and increases miR-30a-5p. We will determine if inhibiting USP30- induced miR-30a-5p occurs through modulation of MAT2A stability in the SAM cycle, reduction of SAM production and pri-miR-30 promoter methylation. Further, we will determine if miR-30a-5p regulates USP30 inhibition-mediated MDM2, MLC, and NFAT5 downregulation. Aim 3 is to determine if the protective effect of USP30 inhibition occurs through modulating miR-30a-5p expression. We will determine if USP30 inhibition preserves EC function by modulating miR-30a-5p expression in HLMVECs. Further, we will determine if EC USP30 depletion reduces severity of experimental lung injury through modulating miR- 30a-5p expression by using a cutting-edge RNA nanoparticle technology. Comprehensive understanding of mitochondrial de-ubiquitinating enzyme inhibition-induced changes of cell metabolisms and EC function is important for development of new therapeutic targets for treatment of acute inflammatory diseases.", "keywords": [ "Acute", "Acute Lung Injury", "Attenuated", "Azacitidine", "Bacterial Infections", "Biogenesis", "COVID-19/ARDS", "Cell Adhesion", "Cell Physiology", "Cellular Metabolic Process", "DNA Methylation", "Data", "Deubiquitinating Enzyme", "Development", "Disease", "Down-Regulation", "Endothelial Cells", "Endothelium", "Enzyme Inhibition", "Enzymes", "Extravasation", "Functional disorder", "Genes", "Health", "Human", "Inflammation", "Inflammatory", "Leukocytes", "Life", "Link", "Lipopolysaccharides", "Liquid substance", "MDM2 gene", "Malignant Neoplasms", "Mediating", "Methylation", "MicroRNAs", "Microvascular Dysfunction", "Mitochondria", "Molecular", "Multiple Organ Failure", "Mus", "Myosin Light Chains", "Outer Mitochondrial Membrane", "Parkinson Disease", "Pathogenesis", "Pathway interactions", "Pharmacotherapy", "Plasma", "Play", "Production", "Proteins", "Pseudomonas aeruginosa", "Pulmonary Inflammation", "RNA", "Regulation", "Reporting", "Role", "S-Adenosylhomocysteine", "S-Adenosylmethionine", "Scheme", "Sepsis", "Severities", "Signal Transduction", "System", "Technology", "Testing", "Tissues", "Transfection", "Vascular Cell Adhesion Molecule-1", "Vascular Endothelial Cell", "Virus Diseases", "inhibitor", "interstitial", "knock-down", "lung injury", "lung microvascular endothelial cells", "methionine adenosyltransferase", "migration", "mortality", "nanoparticle", "new therapeutic target", "novel therapeutic intervention", "preservation", "promoter", "protective effect", "proteostasis", "sepsis induced ARDS", "targeted treatment", "ubiquitin isopeptidase", "vascular inflammation" ], "approved": true } }, { "type": "Grant", "id": "15620", "attributes": { "award_id": "1K23AI180356-01A1", "title": "Post-Infectious Dysautonomia: Insights into Clinical Phenotypes and Disease Pathogenesis", "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": 6125, "first_name": "Timothy A.", "last_name": "Gondre-Lewis", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-01-01", "end_date": "2029-12-31", "award_amount": 198720, "principal_investigator": { "id": 32118, "first_name": "Brittany Lee", "last_name": "Adler", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 344, "ror": "https://ror.org/00za53h95", "name": "Johns Hopkins University", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "Dysautonomia, or autonomic nervous system dysfunction, is a common and disabling post-infectious syndrome that can occur following COVID-19 and Lyme disease. Dysautonomia accounts for many of the symptoms in Post-Acute Sequelae of COVID-19 (PASC, also called Long COVID) and Post-Treatment Lyme Disease (PTLD, also called Chronic Lyme). Dysautonomia has a wide variety of manifestations, including POTS (Postural orthostatic tachycardia syndrome), gastrointestinal dysmotility, interstitial cystitis, and neuropathic pain. A small- fiber neuropathy is also often present. The mechanisms of dysautonomia in patients with PASC and PTLD are not well understood. A subset of patients with dysautonomia have ganglionic acetylcholine receptor (gAchR) autoantibodies and often respond to immunomodulatory therapy with intravenous immunoglobulin (IVIG), implicating autoimmune destruction of small nerve fibers as a potential mechanism of dysautonomia. Some patients without gAchR antibodies still respond to IVIG, suggesting that some autoantibodies remain to be discovered. This project will leverage the clinical resources of the Johns Hopkins post-Acute COVID Clinic, the Lyme Disease Research Center, and the POTS Clinic to identify patients with post-infectious dysautonomia. Patients with confirmed PASC and PTLD dysautonomia will prospectively undergo objective autonomic testing in the Autonomic Lab, histopathological examination of small-fiber nerve density on skin biopsy, and clinical phenotyping using patient-reported outcome measures. In Aim 1, we will identify distinct clinical subgroups using unbiased latent variable cluster analysis. In Aim 2, we will determine the clinical significance of small-fiber neuropathy in post-infectious dysautonomia by investigating the association with disease severity, and will correlate clinical outcomes with changes in nerve fiber density over time. In Aim 3, we will perform immunoprecipitation and mass spectrometry to identify novel autoantibodies targeting the sympathetic ganglia in post-infectious dysautonomia. This Award will help the candidate, who is currently an Assistant Professor at Johns Hopkins University, develop her career as an independent physician-scientist with a focus on dysautonomia. Throughout the Award period, she will enhance her clinical research and biostatistical skills through hands-on experience and formal coursework. A key focus of the proposal is for Dr. Adler to refine her skills in autonomic testing and learn how to perform transcranial doppler ultrasound which is currently being integrated into the Autonomic Lab and will be a key skill that she will utilize throughout her research career. She has assembled an exceptional mentorship team that each provides complementary skills to ensure the success of this project, and includes experts in autonomic neuroscience and peripheral neuropathies, PASC and PTLD, immunology and autoantibody discovery, and biostatistics. With the guidance of her mentorship team, the candidate will develop an independent translational research program and a track-record that will lead to a successful R01 application.", "keywords": [ "Acute", "Affect", "Aftercare", "Autoantibodies", "Autoantigens", "Autonomic Dysfunction", "Autonomic nervous system", "Award", "Biological Markers", "Biometry", "Borrelia burgdorferi", "COVID-19", "COVID-19 pandemic", "Cell Death", "Cerebrum", "Cholinergic Receptors", "Chronic", "Clinic", "Clinical", "Clinical Research", "Clinical Trials", "Cluster Analysis", "Cognitive", "Cutaneous", "Data", "Disabling", "Disease", "Disease Marker", "Disease Progression", "Dizziness", "Dysautonomias", "Ensure", "Enzyme-Linked Immunosorbent Assay", "Evaluation", "Fatigue", "Fc Receptor", "Fiber", "Functional disorder", "Heart Rate", "Immunologic Markers", "Immunology", "Immunoprecipitation", "Immunotherapeutic agent", "Infection", "Interstitial Cystitis", "Intervention", "Intravenous Immunoglobulins", "Laboratories", "Learning", "Left", "Life", "Long COVID", "Lyme Disease", "Mass Spectrum Analysis", "Measurable", "Mediating", "Mentorship", "Nerve", "Nerve Fibers", "Neurons", "Neuropathy", "Neurosciences", "Outcome", "Outcome Measure", "Pain Measurement", "Pathogenesis", "Pathogenicity", "Pathologic", "Pathway interactions", "Patient Outcomes Assessments", "Patients", "Perfusion", "Peripheral Nervous System Diseases", "Persons", "Phenotype", "Physicians", "Post-Acute Sequelae of SARS-CoV-2 Infection", "Postural Orthostatic Tachycardia Syndrome", "Prevalence", "Questionnaires", "Radioimmunoprecipitation Assay", "Recording of previous events", "Research", "Resources", "Schools", "Scientist", "Severities", "Severity of illness", "Subgroup", "Sweat Glands", "Sympathetic Ganglia", "Symptom Burden", "Symptoms", "Syndrome", "Testing", "Therapeutic", "Tilt-Table Test", "Time", "Transcranial Doppler Ultrasonography", "United States", "Universities", "Vasomotor", "Vinculin", "Work", "acute infection", "autoimmune pathogenesis", "calponin", "career", "clinical phenotype", "clinically significant", "cohort", "density", "disabling symptom", "disorder subtype", "experience", "gastrointestinal", "hemodynamics", "histopathological examination", "immunomodulatory therapies", "immunoregulation", "improved", "insight", "motility disorder", "nerve damage", "novel", "painful neuropathy", "pathogenic autoantibodies", "patient subsets", "patient variability", "persistent symptom", "professor", "prospective", "rate of change", "skills", "skin biopsy", "success", "translational research program" ], "approved": true } }, { "type": "Grant", "id": "15621", "attributes": { "award_id": "1R21AI185033-01A1", "title": "Role of APOBEC3B in the Innate Immune Response", "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": 7389, "first_name": "Halonna R.", "last_name": "Kelly", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-01-02", "end_date": "2026-12-31", "award_amount": 228435, "principal_investigator": { "id": 32119, "first_name": "Remi", "last_name": "Buisson", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 971, "ror": "", "name": "UNIVERSITY OF CALIFORNIA-IRVINE", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "The APOBEC3 enzymes are a family of cytosine deaminases that convert cytosine to uracil on DNA or RNA and function as a vital part of mammals’ innate immune system. They provide an innate immune barrier against DNA and RNA viruses, retroviruses, retrotransposons, and other viral pathogens by inducing mutations in the virus genomes to stop their replication and protect cell integrity. APOBEC3 enzymes have evolved different preferences for DNA or RNA sequences and structures to fight against diverse viruses that cells may encounter. Many viruses, such as HIV-1, hepatitis B virus, and SARS-CoV-2, have been found to accumulate APOBEC- driven hypermutations in their genomes. However, mutations induced by APOBEC3 enzymes are a double- edged sword, as a high level of mutations blocks viral replication by inducing lethal alterations, but a lower level of mutations promotes virus evolution and the production of new viral variants with improved features, allowing them to escape cell defense mechanisms. Remarkably, APOBEC3 enzymes also protect cells against viruses through non-canonical pathways without mutating their genomes, suggesting that APOBEC3 enzymes have evolved other mechanisms to inhibit viruses without promoting their evolution, transcending the simple model of APOBEC3s inducing mutations in viral genomes to stop their replication. Yet, the different mechanisms by which APOBEC3 members suppress viral infection without editing their genomes are still poorly understood. Our goal is to identify novel APOBEC3B anti-viral functions that do not require their deaminase activity. We hypothesize that APOBEC3B RNA binding activity is critical in suppressing RNA virus replication by acting as a viral RNA sensor to promote the activation of the innate immune response. Our preliminary results showed that APOBEC3B promotes PKR activity after different types of RNA virus infections. Based on these results, we propose to 1) explain how APOBEC3B modulates the PKR signaling pathway to promote translation arrest, and 2) determine whether APOBEC3B suppresses RNA virus replication. This study will reveal for the first time that APOBEC3B is critical to protecting our cells against RNA virus infection without editing their genomes alongside its function against DNA viruses and retroviruses. The long-term goal resulting from this study is the development of therapeutic strategies to suppress RNA virus replication by exploiting APOBEC3B antiviral activity.", "keywords": [ "2019-nCoV", "ADAR1", "Affect", "Asthma", "Binding", "C-terminal", "Cells", "Chronic Obstructive Pulmonary Disease", "Chronic lung disease", "Cystic Fibrosis", "Cytoprotection", "Cytosine", "Cytosine deaminase", "DNA", "DNA Sequence", "DNA Viruses", "Deaminase", "Deamination", "Defense Mechanisms", "Disease", "Enzymes", "Evolution", "Family", "Future", "Genes", "Genome", "Goals", "HIV-1", "Health", "Hepatitis B Virus", "Human poliovirus", "Immune", "Immune response", "Induced Mutation", "Infection", "Innate Immune Response", "Innate Immune System", "Interstitial Lung Diseases", "Knowledge", "Lung", "Lung infections", "Mammals", "Measles", "Mediating", "Modeling", "Mutate", "Mutation", "N-terminal", "Outcome", "Pathogenesis", "Pathway interactions", "Patients", "Predisposition", "Production", "RNA", "RNA Binding", "RNA Sequences", "RNA Virus Infections", "RNA Viruses", "Regulation", "Research", "Respiratory syncytial virus", "Retrotransposon", "Retroviridae", "Role", "Signal Pathway", "Single-Stranded DNA", "Structure", "Time", "Transcend", "Translational Repression", "Translations", "Uracil", "Variant", "Viral", "Viral Genome", "Viral Physiology", "Viral Proteins", "Virus", "Virus Diseases", "Virus Replication", "disease transmission", "fighting", "improved", "influenzavirus", "member", "novel", "pathogen", "pathogenic virus", "preference", "prevent", "protein activation", "protein kinase R", "respiratory", "respiratory aerosol", "respiratory virus", "response", "sensor", "therapeutic development", "viral RNA", "viral detection" ], "approved": true } }, { "type": "Grant", "id": "15622", "attributes": { "award_id": "1R01NS140610-01", "title": "Neural Mechanisms of Fatigue in Post-Acute Sequela of SARS-CoV-2", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Neurological Disorders and Stroke (NINDS)" ], "program_reference_codes": [], "program_officials": [ { "id": 10999, "first_name": "Vicky R", "last_name": "Whittemore", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-01-01", "end_date": "2029-12-31", "award_amount": 654367, "principal_investigator": { "id": 32120, "first_name": "Vikram S", "last_name": "Chib", "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": "Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) and has led to a global pandemic, infecting more than 760 million people worldwide. Although COVID-19 was initially described as a respiratory disease, there is growing evidence that SARS-CoV-2 impacts the nervous system and causes impairments that may last long after the acute phase of the disease. This spectrum of persistent symptoms is called Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) or Long COVID. Physical fatigue is one of the most common symptoms associated with PASC, yet there is a limited understanding of its behavioral and neural mechanisms. Neuroinflammation is thought to be a primary contributor to feelings of fatigue in many neurological disorders, including PASC, and brain blood-brain barrier (BBB) injury is a hallmark of neuroinflammation. Despite the potential links between PASC, BBB dysfunction, and fatigue, their relationship has yet to be studied. To this end, we will use a combination of experiments in human participants, computational modeling of behavior, and neuroimaging. The central hypothesis of this proposal is that individuals with PASC will have increased BBB permeability from COVID infection, which disrupts neural processing of effort, resulting in increased feelings of physical fatigue. Aim 1 will determine the relationship between BBB permeability and neural and behavioral representations of effort assessment in individuals with PASC suffering from fatigue. We will collect measures of BBB permeability in PASC patients, have them make assessments of effort, and scan their brains with fMRI while they make these judgments. This data will allow us to study how disruptions in effort assessment are related to COVID-19-induced changes in BBB permeability, and their influence on the neural representations of effort. In Aim 2, we will investigate how BBB permeability influences individuals with PASC's immediate response to bouts of fatiguing exertion and the underlying neural processes. We will have individuals perform bouts of fatiguing exertion and simultaneously scan their brains with fMRI. This data will allow us to study how individuals with PASC's feelings of fatigue (and associated neural activity) evolve, and how COVID-induced increases in BBB permeability mediate these changes. In Aim 3 we will evaluate how BBB permeability changes through the time course of PASC and how these changes are related to behavioral and neural representations of fatigue. Over the course of a year, we will collect measures of BBB permeability in individuals with PASC and have them assess their levels of effort exertion and perform effort-based decision-making tasks while scanned with fMRI. In sum, our proposed studies will provide an understanding of the neurobiological mechanisms of fatigue in PASC. This knowledge will eventually provide candidate mechanisms to target with pharmacological intervention and inform rehabilitative care for those individuals suffering from symptoms of fatigue in PASC.", "keywords": [ "2019-nCoV", "Acute", "Attention", "Behavior", "Behavioral", "Behavioral Mechanisms", "Blood - brain barrier anatomy", "Blood brain barrier dysfunction", "Brain", "COVID-19", "Clinical", "Computer Models", "Data", "Decision Making", "Disease", "Exertion", "Exhibits", "Fatigue", "Feeling", "Functional Magnetic Resonance Imaging", "Functional disorder", "Health", "Human", "Impairment", "Individual", "Injury", "Judgment", "Knowledge", "Link", "Long COVID", "Magnetic Resonance Imaging", "Mathematics", "Measures", "Mediating", "Methods", "Nervous System", "Nervous System Disorder", "Neurologic Symptoms", "Participant", "Patients", "Persons", "Pharmacotherapy", "Phase", "Physical Efforts", "Physical assessment", "Population", "Post-Acute Sequelae of SARS-CoV-2 Infection", "Process", "Psyche structure", "Reporting", "Respiratory Disease", "Rest", "SARS-CoV-2 infection", "Scanning", "Speed", "Symptoms", "Testing", "Time", "associated symptom", "behavior influence", "blood-brain barrier permeabilization", "common symptom", "cost", "executive function", "experimental study", "improved", "information processing", "innovation", "laboratory experiment", "neural", "neurobiological mechanism", "neuroimaging", "neuroinflammation", "neuromechanism", "novel", "pandemic disease", "persistent symptom", "rehabilitative care", "response" ], "approved": true } }, { "type": "Grant", "id": "15623", "attributes": { "award_id": "1R13CA298641-01", "title": "2025 RNA Nanotechnology Gordon Research Conference and Seminar", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Cancer Institute (NCI)" ], "program_reference_codes": [], "program_officials": [ { "id": 32121, "first_name": "YALI", "last_name": "FU", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-01-01", "end_date": "2025-12-31", "award_amount": 5000, "principal_investigator": { "id": 32122, "first_name": "Dolores", "last_name": "Di Vizio", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 226, "ror": "https://ror.org/05rad4t93", "name": "Gordon Research Conferences", "address": "", "city": "", "state": "RI", "zip": "", "country": "United States", "approved": true }, "abstract": "This R13 application requests partial funding to support the upcoming Gordon Research Conference (GRC) on RNA Nanotechnology, which will be held in Ventura, CA on Jan 5–10, 2025, and the associated Gordon Research Symposium (GRS), to precede it on Jan 4–5. The meeting will be co-chaired by Dolores Di Vizio and Mark Bathe, who served as the co-vice chairs of the third GRC in January 2023, elected in 2019 at the same GRC Meeting. Vice-chairs are Nils Walter and Alissa Weaver. RNA nanotechnology continues to grow as an important field, with active research being carried out to elucidate fundamental principles of, and develop innovative approaches to, the design and construction of RNA assemblies for diagnostic, therapeutic, and structural applications in biotechnology and medicine. The pace of discovery and innovation in RNA nanotechnology has significantly accelerated in the past two years with the success of the mRNA vaccines that helped mitigate the spread of COVID19, which has spurred major research activity in other forms of mRNA vaccines including principally also cancer vaccines. RNA nanotechnology is built on the unique properties of RNA, including its structural versatility, its known biological functions, its ease of production and functionalization, and its programmability, which altogether make it an ideal platform on which to build self-assembling architectures with a variety of functional attributes for biomedical applications. This GRC focuses on linking fundamental studies of RNA sequence, modifications, and structure to self-assembly and packaging to inform translational studies using RNA nanotechnology in therapeutics and diagnostics with in situ characterization. The 2025 meeting will cover a range of topics in nine sessions. Sessions on Structure-based Elucidation of RNA Function, RNA Therapeutics, RNA Modifications, RNA Delivery, RNA Imaging & Characterization \"In Situ\", RNA Immunology, RNA Cargo Selection, Transport, and Processing, RNA-based Diagnostics and Biomarkers, and RNA Synthetic Biology will feature cutting-edge research on the molecular basis of nucleic acid architectures and modifications, design and characterization of RNA for cancer vaccines and therapeutics, and biophysical approaches to study and predict RNA function. Sessions on RNA cargo selection in extracellular vesicles, RNA immunology, and RNA therapeutics will provide perspectives on the discovery, isolation, and application of RNA from extracellular vesicles and learnings from viruses with an emphasis on translational aspects of natural and synthetic RNAs in cancer diagnostics and therapeutics. The 2025 conference will continue to emphasize robust representation of women and minority scientists. The invited speakers and discussion leaders will include a mix of established researchers in the field and outstanding junior-level investigators from around the world. The meeting will be advertised to a diverse audience to include early career and under-represented minority scientists in the RNA nanotechnology and related fields. A Power Hour will feature topics of diversity, inclusion, and opportunity for under-represented scientists.", "keywords": [ "Academia", "Acceleration", "Address", "Architecture", "Area", "Base Pairing", "Bathing", "Biological Assay", "Biological Markers", "Biological Process", "Biology", "Biophysics", "Biotechnology", "COVID-19", "Cancer Diagnostics", "Cancer Vaccines", "Characteristics", "Chemicals", "Chemistry", "Collaborations", "Collection", "Communication", "Communities", "Computational Biology", "Dedications", "Development", "Diagnosis", "Diagnostic", "Disease", "Drug Industry", "Early Diagnosis", "Engineering", "Ensure", "Environment", "Feedback", "Free Energy", "Funding", "Future", "Genetic Transcription", "Genome", "Government", "Growth", "Hour", "Image", "Immunology", "In Situ", "Knowledge", "Learning", "Link", "Malignant Neoplasms", "Medicine", "Messenger RNA", "Modification", "Molecular", "Nanostructures", "Nanotechnology", "Nucleic Acids", "Participant", "Postdoctoral Fellow", "Principal Investigator", "Production", "Productivity", "Property", "Proteins", "RNA", "RNA Sequences", "RNA chemical synthesis", "RNA delivery", "RNA vaccine", "Reporting", "Request for Applications", "Research", "Research Activity", "Research Personnel", "Role", "Schedule", "Scientist", "Screening for cancer", "Structure", "Technology", "Therapeutic", "Time", "Translating", "Underrepresented Minority", "Untranslated RNA", "Vaccines", "Vertebral column", "Virus", "Woman", "Work", "base", "biophysical techniques", "biotypes", "cancer biomarkers", "career", "clinical application", "clinical diagnostics", "design", "design and construction", "drug development", "extracellular", "extracellular vesicles", "fundamental research", "graduate student", "innovation", "interdisciplinary collaboration", "interest", "meetings", "minority scientist", "new growth", "novel", "novel therapeutics", "preclinical trial", "programs", "rational design", "self assembly", "success", "supportive environment", "symposium", "synthetic biology", "therapeutic RNA", "translational applications", "translational approach", "translational potential", "translational study", "undergraduate student" ], "approved": true } }, { "type": "Grant", "id": "15624", "attributes": { "award_id": "1R01MH135862-01A1", "title": "The neuroimmune mechanism of SARS-CoV-2 on synaptic transmission and plasticity", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Mental Health (NIMH)" ], "program_reference_codes": [], "program_officials": [ { "id": 31795, "first_name": "Leonardo H", "last_name": "Tonelli", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-01-10", "end_date": "2028-11-30", "award_amount": 384772, "principal_investigator": { "id": 32123, "first_name": "Jianyang", "last_name": "Du", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 847, "ror": "", "name": "UNIVERSITY OF TENNESSEE HEALTH SCI CTR", "address": "", "city": "", "state": "TN", "zip": "", "country": "United States", "approved": true }, "abstract": "Given the current global COVID-19 pandemic, as well as documented challenges in long-COVID health burdens among people of lower socioeconomic backgrounds, understanding the cellular and molecular mechanisms responsible for SARS-CoV-2-induced neurological disorders is of fundamental importance. We recently developed a mouse SARS-CoV-2 infection model (SARS2-N501YMA30) showing alteration in mice behaviors fourteen days post-infection, allowing us to study long-term behavioral changes caused by SARS-CoV-2. Four days after the virus infection, we detected SARS-CoV-2 genomic RNA in brain tissues. In addition, SARS-CoV-2 dsRNA was detected exclusively within neurons, along with vigorous microglia activation. These data together with previous works might implicate the involvement of brain immune cells, such as microglia. Also, these preliminary data suggest a novel mechanism of SARS-CoV-2 infection- induced behavioral changes in mice. Thus, the goal of this proposal is to elucidate the mechanisms by which SARS-CoV-2 modulates neuronal activity in mice. This proposal describes three distinct aims to reach this goal. The first aim focuses on determining whether SARS2-N501YMA30 infection induces neuronal hyperactivity in mice. The second aim will determine how SARS2-N501YMA30 activates microglia via microglia-neuron interaction. The third aim will determine how microglia activation excites surrounding excitatory neurons in response to SARS2-N501YMA30 infection. Uncovering the cellular and molecular mechanisms by which SARS-CoV-2 alters neuronal activity through regulating neuron-microglia interaction will facilitate the development of therapeutic strategies to minimize long-COVID suffering, health disparity, and mortality from the COVID-19 pandemic.", "keywords": [ "2019-nCoV", "ACE2", "Affect", "American", "Animal Model", "Animals", "Anxiety", "Astrocytes", "Behavior", "Behavioral", "Biological Assay", "Brain", "C57BL/6 Mouse", "COVID-19", "COVID-19 burden", "COVID-19 detection", "COVID-19 mortality", "COVID-19 pandemic", "Cells", "Central Nervous System", "Data", "Death Rate", "Double-Stranded RNA", "Electrophysiology (science)", "Excitatory Postsynaptic Potentials", "Exhibits", "Foundations", "Goals", "Health Care Systems", "Human", "Hyperactivity", "Immune", "Infection", "Inflammatory", "Long COVID", "Long-Term Effects", "Longitudinal Studies", "Mental Depression", "Microglia", "Modeling", "Molecular", "Mus", "Natural Resistance", "Nervous System Disorder", "Neuroimmune system", "Neuroimmunomodulation", "Neurons", "Neurotropism", "Outcome", "Perfusion", "Persons", "Play", "Post-Acute Sequelae of SARS-CoV-2 Infection", "Process", "Production", "Proteins", "Recombinants", "Recovery", "SARS-CoV-2 infection", "SARS-CoV-2 spike protein", "Scientist", "Serial Passage", "Slice", "Symptoms", "Synaptic Transmission", "Synaptic plasticity", "Syndrome", "Tail Suspension", "Time", "Virulent", "Virus Diseases", "Work", "behavior test", "brain tissue", "current pandemic", "cytokine", "excitatory neuron", "forced swim test", "genomic RNA", "glial activation", "health disparity", "improved", "in vivo", "mortality", "mouse model", "novel", "novel therapeutic intervention", "overexpression", "patch clamp", "response", "socioeconomics", "therapeutic development", "therapeutic target" ], "approved": true } }, { "type": "Grant", "id": "15625", "attributes": { "award_id": "1K08HL177422-01", "title": "Using novel RNA therapy to understand the role of fibrinogen in thromboinflammation in acute and chronic venous thrombosis", "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": 32124, "first_name": "CRYSTAL DARLEANE-ROBIN", "last_name": "Hill-Pryor", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-01-01", "end_date": "2029-12-31", "award_amount": 151523, "principal_investigator": { "id": 32125, "first_name": "Mitchell R", "last_name": "Dyer", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 700, "ror": "https://ror.org/00qqv6244", "name": "Medical College of Wisconsin", "address": "", "city": "", "state": "WI", "zip": "", "country": "United States", "approved": true }, "abstract": "Deep venous thrombosis (DVT) is a major cause of short and long-term morbidity and mortality. Despite the use of gold-standard anticoagulation therapies for the prevention and treatment of DVT, such as heparins and direct oral anticoagulants (DOACs), the incidence of DVT remains high in certain at-risk populations such as trauma patients and patients who suffer from chronic inflammatory diseases. Furthermore, current therapies have increased risks of bleeding. 40-70% of patients develop Post Thrombotic Syndrome (PTS) due to the extensive nature of the clot or poor clot resolution resulting in chronic thrombosis and vein wall scarring. Clinically, there are few treatments for PTS, which is characterized by pain, leg swelling, and ulcer formation. At the cellular level, the development and subsequent resolution of thrombus occurs through a complex interplay between the coagulation system and inflammation. Fibrinogen is the most abundant protein in circulation that is involved in the process of thrombus formation and resolution. The fibrin matrix serves as a platform for cellular infiltration, thrombus growth, and can result in dense clots resistant to lysis. Inadequate clot resolution and vein wall scarring, processes that are in part regulated by matrix metalloproteases (MMPs), lead to chronic DVT. The proposed aims of this project will investigate the role of fibrinogen in thromboinflammation in post-traumatic and acute DVT and the interplay between fibrinogen and MMPs in thrombus resolution and vein wall remodeling/fibrosis. To address these aims we will use novel RNA therapy to reduce circulating levels of fibrinogen. We have developed small interfering RNA (siRNA) directed against fibrinogen messenger RNA (mRNA) that can be delivered into cells using lipid nanoparticles (LNPs). Within the cell, the siRNA is released from the LNP and induces degradation of the target mRNA, preventing translation of the protein product. I will use LNPs similar to those used in the COVID-19 mRNA vaccines as a delivery platform, which naturally accumulate in the liver after intravenous injection, where fibrinogen is synthesized. We will use the LNP-RNA therapy in models of rodent and swine thrombosis to provide rigorous pre-clinical data. We hypothesize that fibrinogen plays a central role in regulating inflammatory cell infiltration in the developing thrombus and in regulating the activity of MMPs to promote thrombus resolution and vein wall healing. Through selective control of fibrinogen levels using a highly specific approach, targeting fibrinogen is not expected to increase the risk of bleeding. These studies will provide mechanistic insights into the role of fibrinogen in regulating thromboinflammation in settings of acute and chronic venous thrombosis. I have assembled a mentorship team with expertise in RNA therapy, LNP biochemistry, and coagulation biology that will oversee my successful completion of the proposed studies and development of the professional and scientific skills to transition to independence.", "keywords": [ "Acute", "Address", "Age", "Animal Model", "Anticoagulants", "Anticoagulation", "Automobile Driving", "Biochemistry", "Biological", "Biology", "Blood Coagulation Factor", "Blood Platelets", "COVID-19", "Cell Physiology", "Cells", "Cellular Infiltration", "Chronic", "Cicatrix", "Circulation", "Clinical", "Coagulation Process", "Complex", "Cytolysis", "Deep Vein Thrombosis", "Deposition", "Development", "Encapsulated", "Endothelium", "Environmental Risk Factor", "Event", "Family suidae", "Fibrin", "Fibrinogen", "Fibrinolysis", "Fibrosis", "Goals", "Grant", "Growth", "Health Care Costs", "Hemorrhage", "Hemostatic Agents", "Hemostatic function", "Heparin", "Hospitalization", "Incidence", "Individual", "Inferior vena cava structure", "Infiltration", "Inflammation", "Inflammatory", "Injury", "Innate Immune System", "Knowledge", "Lead", "Leg", "Leukocytes", "Liver", "Mediating", "Mentors", "Mentorship", "Messenger RNA", "Metalloproteases", "Modeling", "Morbidity - disease rate", "Multiple Trauma", "Mus", "Nature", "Operative Surgical Procedures", "Oral", "Pain", "Patients", "Plasma", "Play", "Populations at Risk", "Postphlebitic Syndrome", "Preclinical data", "Pregnancy", "Prevention", "Prevention therapy", "Process", "Prophylactic treatment", "Proteins", "Pulmonary Embolism", "Quality of life", "RNA", "RNA vaccine", "Recurrence", "Research Personnel", "Resistance", "Resolution", "Risk", "Rodent Model", "Role", "Small Interfering RNA", "Smoking", "Swelling", "System", "Tail", "Technology", "Thrombosis", "Thrombus", "Training", "Translations", "Trauma", "Trauma patient", "Ulcer", "Veins", "Venous Thrombosis", "Work", "chronic inflammatory disease", "efficacy evaluation", "extracellular", "healing", "immune activation", "improved", "insight", "intravenous injection", "lipid nanoparticle", "mortality", "mouse model", "neutrophil", "novel", "patient population", "porcine model", "preservation", "prevent", "release factor", "scaffold", "skills", "therapeutic RNA", "thromboinflammation", "thrombotic", "tool", "venous thromboembolism", "von Willebrand Factor" ], "approved": true } }, { "type": "Grant", "id": "15626", "attributes": { "award_id": "1R01HL171013-01A1", "title": "Modulation of Acute Lung Injury by Type I Interferon Signaling", "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": 22653, "first_name": "EMMANUEL FRANCK", "last_name": "Mongodin", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-01-01", "end_date": "2028-11-30", "award_amount": 690626, "principal_investigator": { "id": 32126, "first_name": "Brian T", "last_name": "Emmer", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 770, "ror": "", "name": "UNIVERSITY OF MICHIGAN AT ANN ARBOR", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "The proliferation of type 2 alveolar (AT2) cells is a critical step in the regeneration of the alveolar epithelium after acute lung injury, but the molecular pathways that regulate this process are unclear. Our preliminary findings strongly suggest that a specific host defense response, type I interferon (IFN-I) signaling, inhibits the proliferation of AT2 cells. We performed a high-throughput CRISPR screen, unexpectedly finding that despite its canonical antiviral properties, IFN-I signaling actually reduced the fitness of SARS-CoV-2- infected respiratory epithelial cells by restricting their proliferation after the initial peak of viral replication and cytopathic effect. We furthermore found that IFN-I signaling was not only necessary but sufficient for this antiproliferative response, and that it was also present in AT2 cells derived from induced pluripotent stem cells. Although IFN-I signaling has been implicated in driving lung pathology during SARS-CoV-2 infection in vivo, the underlying basis for this effect is unknown. Our in vitro data forms the foundation of our central hypothesis that IFN-I signaling promotes acute lung injury of diverse causes by inhibiting AT2 cellular proliferation during alveolar regeneration. In Aim 1, we will identify the molecular effectors that link IFN-I signaling activation to cell cycle arrest in respiratory epithelial cells. In Aim 2, we will determine whether inhibition of AT2 proliferation and alveolar regeneration is responsible for the pathogenic effect of IFN-I signaling in a mouse model of SARS- CoV-2 infection. In Aim 3, we will determine the potential of IFN-I signaling in AT2 cells to modulate alveolar regeneration after noninfectious acute lung injury. Together, these studies will clarify the fundamental biology of IFN-I signaling in the alveolar epithelium and facilitate our long-term objective of developing new disease- modifying treatments for acute lung injury and the acute respiratory distress syndrome.", "keywords": [ "2019-nCoV", "Acute Lung Injury", "Acute Respiratory Distress Syndrome", "Affect", "Alveolar", "Alveolar Cell", "Attenuated", "Automobile Driving", "Biology", "CDKN1A gene", "COVID-19", "COVID-19 treatment", "CRISPR screen", "Cell Cycle", "Cell Cycle Arrest", "Cell Death", "Cell Proliferation", "Cells", "Clinical", "Complex", "Data", "Development", "Disease", "Epithelial Cells", "Exhibits", "Foundations", "Genetic Predisposition to Disease", "Genetic Screening", "Goals", "Host Defense", "Human", "IFNAR1 gene", "IFNAR2 gene", "Immune response", "Impairment", "In Vitro", "Infection", "Interferon Type I", "JAK1 gene", "Link", "Lung Diseases", "Mediating", "Mediator", "Modeling", "Molecular", "Mus", "Natural regeneration", "Outcome", "Pathogenicity", "Pathway interactions", "Patients", "Pharmaceutical Preparations", "Process", "Proliferating", "Property", "Pulmonary Pathology", "Recovery", "Role", "SARS-CoV-2 infection", "Severities", "Signal Induction", "Signal Transduction", "Sterility", "TYK2", "Testing", "Treatment Efficacy", "Viral", "Virus Diseases", "Virus Receptors", "Virus Replication", "Work", "airway epithelium", "alveolar epithelium", "arm", "cell type", "defense response", "fitness", "improved", "in vivo", "in vivo regeneration", "induced pluripotent stem cell", "inhibitor", "insight", "mouse model", "pathogenic virus", "pre-clinical", "receptor", "receptor expression", "response", "severe COVID-19", "targeted treatment", "therapeutic target" ], "approved": true } }, { "type": "Grant", "id": "15627", "attributes": { "award_id": "1R43GM157920-01", "title": "Three-Dimensional Spatio-Temporal Control of Lipid Nanoparticle Manufacturing for Improved Nucleic Acid Delivery", "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": 31602, "first_name": "Sailaja", "last_name": "Koduri", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-01-01", "end_date": "2025-06-30", "award_amount": 306873, "principal_investigator": { "id": 32127, "first_name": "Po-Lun", "last_name": "Feng", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2551, "ror": "", "name": "OSEM FLUIDICS INC", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "The COVID-19 pandemic has established the importance of nucleic acid-based lipid nanoparticles (LNPs) for the future of global health. The benefits of lipid nanoparticles are multifaceted as they protect sensitive pharmaceutical payloads from enzymatic degradation and allow for the modification of solubility, release kinetics, and bioavailability. While chemical formulation of LNPs has been widely explored, the effects of manufacturing—specifically microfluidics processing—are not currently well-understood. This knowledge gap presents challenges in the production of intricate nanoparticle structures, which require specialized microfluidic systems that produce well-defined and reproducible flow configurations. The proposed research focuses on developing 3D-printed channel architectures to precisely control LNP structure and properties to enhance transfection efficiency without modifying their chemical composition. Aim 1 involves designing, simulating, and testing various 3D channel architectures to manipulate flow conditions and tailor LNP properties. Aim 2 focuses on structural determination via SAXS and CryoTEM, and assesses the impact of LNP structures on mRNA transfection efficiency through in vitro transfection studies. Aim 3 will demonstrate the therapeutic- and disease-agnostic design workflow by robustly encapsulating siRNA and pDNA. This project aims to overcome the limitations of current LNP manufacturing methods which are constrained by fixed geometries and limited control over LNP assembly processes. Development of our enabling technology will offer an additional process parameter - channel architecture, for tuning LNP properties and structure in a rapid and customizable manner that is broadly applicable.", "keywords": [ "3-Dimensional", "3D Print", "Acceleration", "Address", "Affect", "Architecture", "Biological Availability", "COVID-19", "COVID-19 pandemic", "COVID-19 vaccine", "Characteristics", "Chemicals", "Chemistry", "Cholesterol", "Complex", "Development", "Devices", "Disease", "Encapsulated", "Formulation", "Foundations", "Future", "Gene Delivery", "Gene Expression", "Geometry", "Image", "In Vitro", "Kinetics", "Knowledge", "Lipids", "Liquid substance", "Messenger RNA", "Methods", "Microfabrication", "Microfluidic Microchips", "Microfluidics", "Modality", "Modification", "Nucleic Acids", "Outcome", "Pharmacologic Substance", "Phase", "Process", "Production", "Property", "Reproducibility", "Research", "Research Personnel", "Roentgen Rays", "Route", "SARS-CoV-2 spike protein", "Series", "Small Interfering RNA", "Solubility", "Structure", "System", "Technology", "Testing", "Therapeutic", "Time", "Transfection", "United States National Institutes of Health", "clinically relevant", "cost", "design", "experimental study", "fabrication", "fluid flow", "global health", "improved", "in vivo", "innovation", "interest", "lipid nanoparticle", "mRNA lipid nano particle vaccine", "manufacture", "manufacturing systems", "millimeter", "nanoparticle", "novel", "novel therapeutics", "nucleic acid delivery", "nucleic acid structure", "nucleic acid-based therapeutics", "operation", "particle", "pre-clinical", "prevent", "spatiotemporal", "therapeutic development", "tool" ], "approved": true } } ], "meta": { "pagination": { "page": 1392, "pages": 1405, "count": 14046 } } }