Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=3&sort=-end_date
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-end_date", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1392&sort=-end_date", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=4&sort=-end_date", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=2&sort=-end_date" }, "data": [ { "type": "Grant", "id": "15615", "attributes": { "award_id": "1R01AI183624-01A1", "title": "BATF as an inducible regulator of natural killer cell expansion and effector function", "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": 12151, "first_name": "AARON MICHAEL", "last_name": "Joffe", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-02-01", "end_date": "2030-01-31", "award_amount": 550375, "principal_investigator": { "id": 32112, "first_name": "BARBARA L.", "last_name": "KEE", "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": "Project Summary: Natural killer (NK) cells exist in a chronically “primed” state that facilitates rapid cytokine production, chemokine-mediated dendritic cell and macrophage recruitment, and direct target elimination. These cells play a pivotal role in protection against -herpesviruses and coronaviruses, and in the immune response against metastatic tumors and leukemia. Emerging evidence supports an important role for NK cells in the initiation of the immune response against some solid tumors. While NK cell survival and function can be suppressed in the tumor microenvironment, these cells can be restored by environmental manipulation or checkpoint blockade therapy. These findings raise the possibility that NK cells, if manipulated appropriately, could have therapeutic benefits in multiple disease contexts including in solid tumors. Therefore, a comprehensive understanding of the mechanisms controlling NK cell survival, proliferation, and effector function in different disease contexts is needed. In this grant, we present preliminary data identifying BATF as a transcription factor induced by the proinflammatory cytokine IL-12, which is responsible for the priming of NK cells during their development and for NK cell expansion in response to viral infection. We will test the consequences of altered BATF expression, both loss and gain of function, on NK cell maturation and anti-tumor immunity (Aim 1) and the NK cell response to viral infection (Aim 2). We propose a comprehensive characterization of BATF target genes and the impact of BATF on chromatin accessibility, histone modification, and functional output. Taken together, these studies will provide a broad view of the requirements for BATF and the potential for modulating BATF or its target genes for therapeutic intervention in anti-viral and anti-tumor immune responses.", "keywords": [ "Activated Natural Killer Cell", "Address", "CD8-Positive T-Lymphocytes", "Cell Maturation", "Cell Physiology", "Cell Proliferation", "Cell Survival", "Cells", "Chromatin", "Chronic", "Clinical", "Coronavirus", "Cytomegalovirus Infections", "Data", "Dendritic Cells", "Dendritic cell activation", "Development", "Disease", "ETS1 gene", "Environment", "Family", "Gene Expression", "Gene Expression Profiling", "Genes", "Genetic Transcription", "Germ Lines", "Goals", "Grant", "Herpesviridae", "IL18 gene", "IRF4 gene", "Immune", "Immune response", "Inflammatory", "Interleukin-12", "Knowledge", "Ligands", "Macrophage", "Major Histocompatibility Complex", "Mediating", "Memory", "Modeling", "Murid herpesvirus 1", "Mus", "Natural Killer Cells", "Neoplasm Metastasis", "Output", "Pathogenicity", "Phase", "Play", "Production", "Proliferating", "Property", "Repression", "Role", "Series", "Signal Pathway", "Signal Transduction", "Solid Neoplasm", "Stress", "Testing", "Therapeutic", "Therapeutic Intervention", "Transcription Factor AP-1", "Transcriptional Activation", "Transgenic Organisms", "Tumor Immunity", "Viral", "Virus", "Virus Diseases", "anti-tumor immune response", "antiviral immunity", "chemokine", "constitutive expression", "cytokine", "gain of function", "histone modification", "immune checkpoint blockade", "leukemia", "loss of function", "nuclear factors of activated T-cells", "programs", "protein expression", "receptor", "recruit", "response", "transcription factor", "tumor", "tumor microenvironment" ], "approved": true } }, { "type": "Grant", "id": "15612", "attributes": { "award_id": "1U54AG089326-01", "title": "Biospecimen Analysis", "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": [], "start_date": "2025-02-01", "end_date": "2030-01-31", "award_amount": 796905, "principal_investigator": { "id": 20884, "first_name": "Suman Ranjan", "last_name": "Das", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 456, "ror": "https://ror.org/05dq2gs74", "name": "Vanderbilt University Medical Center", "address": "", "city": "", "state": "TN", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 456, "ror": "https://ror.org/05dq2gs74", "name": "Vanderbilt University Medical Center", "address": "", "city": "", "state": "TN", "zip": "", "country": "United States", "approved": true }, "abstract": "The Biospecimen Analysis Core (BAC) of our Vanderbilt-coordinated human Virome Characterization Center (V2C2) is designed to enable the composition and complexity of a host-contextualized human virome (replicating and integrated) to be rapidly and cost-effectively generated with high-quality across multiple tissue types. In Aim 1, the BAC will receive and characterize the virome across a range of biospecimen types from our Biospecimen Collection Core (BCC). This process will include viral sequencing (whole metagenomics/metatranscriptomic sequencing), validation studies (digital PCR and capture-based methods, among them), and host response characterization, including tropism studies (via bulk and single-cell RNA-seq approaches, in vitro infection studies) and assessments of host inflammatory state (targeted proteomics). In Aim 2, the BAC will establish standard operating procedures for metadata, analytics, and quality control and assessment, including consortium-wide benchmarking and reproducibility of critical assays to investigate and limit variability from the collection point to the final analysis. The BAC will synergize with all other V2C2 cores via (1) scientific counsel to the administrative core and the wider HVP on the development of new technologies based on HVP results to enable viral screening at the epidemiologic scale; (2) enabling collaborative projects with other HVP efforts (e.g., tropism studies with Functional Interactions projects; RFA-RM-23-017), augmenting essential human translational biology in the HVP. Our BCC has several fundamental strengths that ensure success, including: (1) leadership structure with extensive expertise in large epidemiologic efforts: Dr. Simon Mallal (a renowned physician-scientist who works on viral-host co-evolution and genetic interactions, Director of the Vanderbilt VANTAGE sequencing core), Dr. Jane Freedman (a leader in sequencing and proteomics and large NIH studies, including Common Fund efforts), and Dr. Suman Das (a human molecular virologist with extensive experience in methods development and discovery in human virology), all of whom have a track-record of collaboration in large NIH-funded human studies; (2) deep expertise in viral sequencing: Dr. Das and Mallal have sequenced many classes of human viruses (e.g., influenza, RSV, HIV, HCV, HBV, EBV, enteroviruses, rotavirus, norovirus, Ebola, Zika, coronaviruses, resulting in >400K Genbank accessions); (3) expertise in methods development in metagenomics: in this process, they have developed many new laboratory and computational methods enabling capture of the human virome (replicating eukaryotic RNA/DNA viruses and phages) and host integration; (5) rapid assessment of host response characteristics (including mucosal immunity, relation with other commensal microbial flora, and emerging types for characterization [e.g., extracellular vesicles, platelets, proteomics]); (6) large, NIH-funded core laboratory structures that enable cost-efficient BAC conduct (e.g., NHLBI TOPMed 2.0 Core; Vanderbilt resources led PD Mallal/PI Das). Successful completion will provide HVP with a comprehensive host-viral characterization for consortium-wide integration.", "keywords": [ "Adult", "Architecture", "Bacteriophages", "Benchmarking", "Biological Assay", "Biological Markers", "Biology", "Blood Platelets", "Cell Culture Techniques", "Cells", "Characteristics", "Child", "Child Health", "Collaborations", "Collection", "Communicable Diseases", "Communication", "Computing Methodologies", "Coronavirus", "Counseling", "DNA Sequencing Facility", "DNA Viruses", "Data", "Data Analyses", "Data Coordinating Center", "Development", "Ebola", "Ensure", "Enterovirus", "Epidemiology", "Funding", "Genbank", "Genetic", "Genome", "Genomics", "Goals", "HIV", "Health", "Hepatitis B Virus", "Hepatitis C virus", "High-Throughput Nucleotide Sequencing", "Human", "Human Genome", "Human Herpesvirus 4", "Immune response", "In Vitro", "Infection", "Inflammatory", "Influenza", "Institution", "Investments", "Laboratories", "Leadership", "Meta-Analysis", "Metadata", "Metagenomics", "Methods", "Mission", "Molecular", "Mucosal Immunity", "National Heart Lung and Blood Institute", "Norovirus", "Organoids", "Outcome", "Physicians", "Procedures", "Process", "Proteomics", "Quality Control", "RNA", "Reporting", "Reproducibility", "Resolution", "Resources", "Rotavirus", "Sampling", "Scientist", "Site", "Source", "Specific qualifier value", "Standardization", "Structure", "Techniques", "Tissues", "Trans-Omics for Precision Medicine", "Tropism", "United States National Institutes of Health", "Validation", "Viral", "Virus", "Work", "ZIKA", "biobank", "cost", "cost efficient", "data submission", "design", "digital", "experience", "extracellular", "extracellular vesicles", "human virome", "integration site", "interoperability", "metagenomic sequencing", "metatranscriptomics", "method development", "microbial", "microbial host", "microbiota", "multiple omics", "new technology", "screening", "single-cell RNA sequencing", "success", "synergism", "validation studies", "virology", "virome" ], "approved": true } }, { "type": "Grant", "id": "15606", "attributes": { "award_id": "1R01HL171387-01A1", "title": "Analyzing effectiveness of ongoing natural experiments in telehealth", "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": 26847, "first_name": "ALISON GWENDOLYN MARY", "last_name": "Brown", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-03-01", "end_date": "2029-12-31", "award_amount": 705383, "principal_investigator": { "id": 32102, "first_name": "Mark J", "last_name": "Pletcher", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32103, "first_name": "Steven Michael", "last_name": "Smith", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 158, "ror": "https://ror.org/02y3ad647", "name": "University of Florida", "address": "", "city": "", "state": "FL", "zip": "", "country": "United States", "approved": true }, "abstract": "Uncontrolled blood pressure (BP) is the most prevalent modifiable risk for cardiovascular disease (CVD) and disorders directly influencing CVD (e.g., diabetes, chronic kidney disease, etc.). Along with many other aspects of U.S. healthcare, management of uncontrolled BP was severely disrupted during the COVID- 19 pandemic. In response, many health systems rapidly accelerated implementation of new technologies, including telehealth visits for BP control and support for self-monitoring with home-based measurement of BP. Anecdotally, new BP control technologies and strategies have been implemented differentially with wide variation in timing and degree of utilization, but systematic analyses showing the extent and variability of implementation across sites are lacking. Meanwhile, substantial and variable backsliding in BP control rates across health systems was documented at the onset of the pandemic, and it is unclear how much of the variability is driven by differential implementation of new BP-related technologies and strategies. To learn from this unprecedented natural experiment and help guide the US healthcare enterprise towards more effective and equitable practices for management of BP control, we propose a mixed methods comparative effectiveness analysis. We will leverage our nationally scoped PCORnet Blood Pressure Control Laboratory (BPCL) – designed fundamentally for efficient surveillance of BP control and related process metrics using electronic health record (EHR) data – to develop and validate process metric queries that track implementation of new BP-related technologies & strategies, field these queries along with our previously developed metrics, extract trend results and individual patient-level data from participating sites, and conduct descriptive and causal inference analyses to decipher successful patterns of care for uncontrolled BP. And, we will conduct a positive deviance analysis with mixed methods approach to assess residual variability in BP control across clinics and learn from clinics with unexplained excellence. Our specific aims are to: 1) evaluate time trends and disparities in utilization of BP-related telehealth and home BP monitoring; 2) estimate causal effects of telehealth implementation on BP control and related metrics in hypertension management; and, 3) identify clinics with unexplained resilience in BP control and use mixed methods to analyze potential mechanisms and opportunities for dissemination of effective, scalable practices. As we have done in prior work, we will test for effect heterogeneity across important subgroups (sex, race, ethnicity) and place special emphasis on BP control in non-Hispanic Black patients, for whom disparities are historically largest. Findings from these aims will be discussed with stakeholders via webinar including a panel of frontline clinicians and leaders from positive deviant clinical sites, and disseminated via conference presentations and publications.", "keywords": [ "Abbreviations", "Acceleration", "Age", "American", "Blood Pressure", "COVID-19 pandemic", "Cardiovascular Diseases", "Caring", "Chronic Kidney Failure", "Clinic", "Code", "Consolidated Framework for Implementation Research", "Data", "Data Collection", "Diabetes Mellitus", "Disparity", "Effectiveness", "Electronic Health Record", "Equity", "Ethnic Origin", "Feedback", "Health Care", "Health system", "Heterogeneity", "Home", "Home Blood Pressure Monitoring", "Hypertension", "Interview", "Laboratories", "Learning", "Measurable", "Measurement", "Measures", "Methods", "Monitor", "Natural experiment", "Not Hispanic or Latino", "Outcome", "Outcomes Research", "Patient-Focused Outcomes", "Patients", "Patterns of Care", "Physiologic Monitoring", "Practice Management", "Process", "Publications", "Race", "Recommendation", "Residual state", "Rural", "Site", "Site Visit", "Standardization", "Subgroup", "Technology", "Testing", "Time trend", "Variant", "Visit", "Work", "black patient", "blood pressure control", "cardiovascular disorder risk", "clinical research site", "comparative effectiveness analysis", "data modeling", "design", "deviant", "health care settings", "hypertension control", "improved", "individual patient", "modifiable risk", "new technology", "novel strategies", "pandemic disease", "pandemic disruption", "partial recovery", "patient subsets", "pre-pandemic", "preventable death", "resilience", "response", "sex", "symposium", "technology validation", "telehealth", "trend", "webinar" ], "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": "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": "15630", "attributes": { "award_id": "1R01AI182308-01A1", "title": "Integrated Host/Microbe (IHM) Metagenomics of the Lower Airway to Diagnose PediatricRespiratory Infections, Identify Etiologic Pathogens, and Predict Outcomes", "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": 8282, "first_name": "Inka I", "last_name": "Sastalla", "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": 781129, "principal_investigator": { "id": 32132, "first_name": "Charles", "last_name": "Langelier", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32133, "first_name": "PETER M", "last_name": "MOURANI", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 768, "ror": "https://ror.org/043mz5j54", "name": "University of California, San Francisco", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Lower respiratory tract infection (LRTI) leads to more deaths each year than any other type of infection and disproportionately affects children. The past three years have seen record pediatric hospitalizations due to RSV, influenza, and SARS-CoV-2, highlighting the burden of LRTI in this vulnerable demographic. LRTI remains diagnostically challenging in children due to high rates of viral/bacterial co-infections, noninfectious syndromes that mimic LRTI, frequent incidental pathogen carriage, and the limitations of existing clinical diagnostics. As a result, accurate and timely LRTI diagnosis is difficult to achieve in pediatric critical care, leading to the inappropriate use of empirical antibiotics, the emergence of resistant pathogens, and adverse patient outcomes. Respiratory infections involve a dynamic relationship among three key features: pathogens, the airway microbiome, and the host immune response. However, existing clinical tests rely primarily on pathogen detection, limiting their diagnostic and prognostic utility. Our group has pioneered integrated host/microbe (IHM) metagenomic next generation sequencing (mNGS) methods that enable accurate, culture-independent LRTI diagnosis by simultaneously assessing all three key LRTI features from a single tracheal aspirate sample. Here, we propose a prospective, multicenter cohort study of 400 critically ill children with acute respiratory failure requiring mechanical ventilation that is designed to validate and extend the IHM diagnostic we developed. Aim 1 will independently validate the performance of our existing IHM LRTI diagnostic classifier in distinguishing LRTI from non-infectious acute respiratory conditions and in identifying likely etiologic pathogens. Aim 2 will develop a novel host gene expression classifier specifically for bacterial LRTI rule-out, which would reduce unnecessary antibiotic use in a principled manner. For both Aims 1 and 2, we will additionally develop parsimonious host-based PCR versions of the classifiers for rapid, point-of-care LRTI diagnosis and bacterial LRTI rule-out where mNGS capacity is unavailable. Finally, Aim 3 will develop novel IHM classifiers to predict LRTI outcomes, including prolonged mechanical ventilation and persistent acute respiratory distress syndrome (ARDS), which can facilitate prioritization of resources and intensive interventions to the highest-risk patients. This study promises to address the unmet need for accurate molecular LRTI diagnostics that detect emerging pathogens, enable judicious antimicrobial treatment, and predict outcomes in critically ill children. Our multidisciplinary team of translational scientists with experience in innovative metagenomic approaches is well- positioned to accomplish the study goals. The results of this study will directly inform the design of a future clinical trial evaluating the impact of IHM diagnostics on clinical management and patient outcomes.", "keywords": [ "2019-nCoV", "Acute", "Acute Respiratory Distress Syndrome", "Acute respiratory failure", "Address", "Affect", "Antibiotic Therapy", "Antibiotics", "Area Under Curve", "Bacterial Infections", "Biological Markers", "Biological Testing", "COVID-19 pandemic", "Cessation of life", "Child", "Childhood", "Clinical", "Clinical Management", "Clinical Trials", "Cohort Studies", "Communicable Diseases", "Critical Care", "Critically ill children", "Data", "Decision Making", "Detection", "Diagnosis", "Diagnostic", "Diagnostic tests", "Early identification", "Elements", "Enrollment", "Enterovirus", "Epidemiology", "Etiology", "Future", "Gene Expression", "Genetic Transcription", "Goals", "Hospitalization", "Immune response", "Infection", "Influenza", "Innovative Therapy", "Intervention", "Intubation", "Lower Respiratory Tract Infection", "Mechanical ventilation", "Medical center", "Medicine", "Metagenomics", "Methods", "Microbe", "Molecular", "Morbidity - disease rate", "Outcome", "Pathogen detection", "Patient-Focused Outcomes", "Patients", "Performance", "Positioning Attribute", "Preparation", "Prognosis", "Prospective cohort study", "Randomized Controlled Trials", "Reporting", "Resistance", "Resource Allocation", "Resources", "Respiratory Tract Infections", "Sampling", "Scientist", "Specimen", "Syndrome", "Testing", "Trachea", "Translational Research", "Validation", "Viral", "accurate diagnostics", "adjudication", "antimicrobial", "aspirate", "clinical application", "clinical care", "clinical diagnostics", "clinical investigation", "co-infection", "cohort", "design", "diagnostic assay", "diagnostic value", "emerging pathogen", "experience", "high risk", "improved", "infection management", "innovation", "lung microbiome", "machine learning method", "metagenomic sequencing", "microbial", "microbiome", "mortality", "multidisciplinary", "next generation sequencing", "novel", "novel diagnostics", "outcome prediction", "pathogen", "pathogenic microbe", "point of care", "prevent", "prognostic", "prognostic assays", "prognostic value", "prospective", "recruit", "respiratory", "respiratory microbiome", "respiratory pathogen", "secondary analysis", "success", "translational scientist" ], "approved": true } }, { "type": "Grant", "id": "15635", "attributes": { "award_id": "1R01CA285395-01A1", "title": "Resolution of inflammation in chemical-induced cancer", "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": 22996, "first_name": "THOMAS K.", "last_name": "HOWCROFT", "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": 749474, "principal_investigator": { "id": 31455, "first_name": "Dipak", "last_name": "Panigrahy", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 31456, "first_name": "Charles Nicholas", "last_name": "Serhan", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 32137, "first_name": "Hooman Henry", "last_name": "Rashidi", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 771, "ror": "https://ror.org/04drvxt59", "name": "Beth Israel Deaconess Medical Center", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "While exposure to toxic environmental chemicals can mutate DNA, causing cancer, the underlying non- genotoxic mechanisms that support malignant transformation remain largely uncharacterized. Transformed cells require growth factors to support and stimulate them in carcinogenesis, resulting in hyperinflammation and a cytokine storm. A paradigm shift is emerging in understanding the resolution of acute inflammation as an active biochemical process with our discovery of novel specialized pro-resolving mediators (SPMs), such as resolvins, and endogenous resolution programs. At nanogram doses, SPMs stimulate macrophage-mediated clearance of debris and counter-regulate pro-inflammatory cytokine (e.g., TNFα) production without immune suppression. Despite approaches to block systemic inflammation, there are no “pro-resolving” therapies for cancer treatment. Furthermore, the impact of carcinogens on eicosanoids and pro-resolving lipid media- tors, both critical regulators of the initiation and resolution of inflammation, is completely unknown. In response to NOSI-20-018 “Promoting Fundamental Research in Inflammation Resolution,” this proposal focuses on ad- vancing our recent results indicating that stimulating the resolution of inflammation prevents carcingogen- induced tumor growth by counter-regulating cytokine storms. Therefore, the overarching theme of this pro- posal is to elucidate the underlying processes of failed resolution of inflammation initiated by environmental chemicals. We will rely on a set of established experimental systems, including genetic and pharmacological manipulation of SPMs and their receptors in animal models and macrophage studies. In Specific Aim 1, we will profile lipid autacoid mediators, including eicosanoids (PGs, LTs) and SPMs, as well as cytokines to test our innovative hypothesis that environmental chemicals trigger dysregulation of SPMs that leads to an uncon- trolled cytokine & eicosanoid storm. We will evaluate pro-resolving lipid mediators as interventional targets in chemical-induced cancer. We will elucidate cellular, intracellular, and receptor-mediated pro-resolving and anti-tumor mechanisms of resolvins. In Specific Aim 2, the mechanisms that mediate failed resolution of in- flammation in chemical-induced cancer will be investigated. These studies will complement Specific Aim 3 in a multi-pronged approach that will evaluate SPM analog mimetics and humanized nano-pro-resolving medi- cines (NPRMs) carrying SPM cargo as novel targeted treatment approaches to prevent chemical-induced can- cer. These studies will offer new animal models to evaluate toxic chemicals and novel therapies to counter cancer. We will then connect our preclinical findings to clinical disease phenotypes using a new computational framework to understand failed resolution of inflammation in chemical-induced cancers. As SPMs are safe and effective in inflammatory disorders, the proposed studies shall provide the basis for rapid translation of resolution-directed treatments in humans as a new direction to prevent and/or reduce cancers that arise from environmental carcinogens.", "keywords": [ "Acute", "Aflatoxin B1", "Agonist", "Animal Model", "Animals", "Anti-Inflammatory Agents", "Apoptotic", "Autacoids", "Biochemical Process", "CD59 Antigen", "Cancer Control", "Cancer Etiology", "Cancer Patient", "Carcinogens", "Cell Death Induction", "Chemical Stimulation", "Chemicals", "Clinical", "Complement", "Cytotoxic Chemotherapy", "DNA", "Data", "Disease", "Dose", "Eicosanoids", "Environmental Carcinogens", "Environmental and Occupational Exposure", "Event", "Excision", "Exposure to", "Failure", "Family", "Genetic", "Growth Factor", "Homeostasis", "Human", "Human body", "Immunosuppression", "Inflammation", "Inflammation Mediators", "Inflammatory", "Intervention", "Laboratories", "Lipids", "Machine Learning", "Macrophage", "Malignant - descriptor", "Malignant Neoplasms", "Mediating", "Mediator", "Medicine", "Micrometastasis", "Molecular", "Mutate", "Necrosis", "Occupational", "Pathologic", "Phagocytosis", "Poison", "Preclinical data", "Prevention", "Process", "Production", "Recurrent tumor", "Research Personnel", "Resolution", "Risk Factors", "Role", "Severity of illness", "Signal Transduction", "System", "TNF gene", "Testing", "Time", "Toxic effect", "Toxin", "Translations", "Treatment Efficacy", "analog", "cancer initiation", "cancer therapy", "carcinogenesis", "cell transformation", "chemotherapy", "combat", "computer framework", "cytokine", "cytokine release syndrome", "disease phenotype", "environmental chemical", "fundamental research", "innovation", "lipid mediator", "lipidome", "mimetics", "nano", "neoplastic cell", "novel", "novel strategies", "novel therapeutics", "pharmacologic", "prevent", "programs", "receptor", "response", "systemic inflammatory response", "targeted treatment", "tumor", "tumor growth", "tumor progression", "tumorigenesis" ], "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": "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": "15634", "attributes": { "award_id": "1R01DK141612-01", "title": "Hodgkin’s Lymphoma-induced Nephrotic Syndrome", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)" ], "program_reference_codes": [], "program_officials": [ { "id": 22545, "first_name": "KEVIN E", "last_name": "Chan", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-01-01", "end_date": "2029-11-30", "award_amount": 343650, "principal_investigator": { "id": 32136, "first_name": "Eduardo", "last_name": "Molina Jijon", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 804, "ror": "https://ror.org/01j7c0b24", "name": "Rush University Medical Center", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true }, "abstract": "/ ABSTRACT (max 30 lines) Hodgkin Lymphoma (HL) is a malignant condition most prevalent in adolescents and young adults (3 new cases per 100,000 individuals per year). About 0.5 to 1% of HL patients develop nephrotic syndrome (NS). Hodgkin Reed–Sternberg (HRS) cells, representing about 1% of the tumor bulk, release cytokines and soluble proteins into the circulation that may reach the kidney where they trigger the development of NS. Published evidence in literature shows the presence of a ZHX2 hypomorph (ZHX2hypo/hypo) state in the tumor in HL, and several HRS cell lines are also known to have a ZHX2hypo/hypo state. The PI recently showed that Rhinovirus cytokine storm cocktails, a model for common cold induced MCD relapse, induce glomerular injury and albuminuria selectively in ZHX2hypo/hypo BALB/cJ and Zhx2flox/flox; NPHS2 promoter cre+/+ mice. The PI showed that the ZHX2hypo/hypo state is a key genomic defect in Minimal Change Disease (MCD) and some Focal Segmental Glomerulosclerosis (FSGS) patients. Preliminary data generated by the PI show a ZHX2hypo/hypo state and the presence of the same insertion at Chr8: 122,533,694 in the L-1236 HRS cell line and in some patients with HL that develop NS. When this insertion found in HL patients is replicated in cultured human podocytes using CRISPR/Cas9 editing, it triggers a ZHX2hypo/hypo state. When cytokines and soluble proteins present in the supernatant of the L-1236 HL cell line are injected into ZHX2hypo/hypo state and control mice, they trigger development of albuminuria only in ZHX2hypo/hypo state mice. The PI generated a cytokine HL cocktail replicating the secreted cytokine and soluble proteins profile of L-1236 cells and successfully induced albuminuria only in ZHX2hypo/hypo state mice. The PI identified the threshold nephritogenic dose 1X of the HL cocktail that induces significant histological glomerular injury and albuminuria in ZHX2hypo/hypo state mice. Hypothesis: A combination of cytokines and soluble proteins released by HRS cells induce glomerular injury and albuminuria in ZHX2hypo/hypo mice to mimic HL related NS. Depleting selected cytokines or soluble proteins alone or in combination, with antibodies, will improve glomerular injury and albuminuria in HL. In Specific Aim 1, injection of HL cell supernatant or HL cytokine cocktail to replicate the phenomenon of HL- induced glomerular injury and albuminuria in ZHX2hypo/hypo mice. Cell signaling in CRISPR-edited ZHX2hypo/hypo human podocytes will be studied. The contribution of IL-4Rα and other identified major components of the cocktail will be investigated. In Specific Aim 2, xenotransplant of HRS cells into immunodeficient NSG mice in a ZHX2hypo/hypo background to develop a new rodent model of HL and study the development of NS. In Specific Aim 3, treatment of HL-related glomerular injury and albuminuria by anti-cytokines antibodies (single or in combination) or their receptors blockage (alternative strategy) will be assessed for therapeutic response in ZHX2hypo/hypo BALB/cJ mice injected with HL cocktail and the new tumor HL mice model.", "keywords": [ "Adolescent and Young Adult", "Albuminuria", "Antibodies", "B-Lymphocytes", "BALB/cJ Mouse", "Blood", "CCL17 gene", "CCL2 gene", "CRISPR/Cas technology", "CXCL10 gene", "CXCR3 gene", "Cell Line", "Cell Lineage", "Cell Nucleus", "Cells", "Chronic", "Circulation", "Clustered Regularly Interspaced Short Palindromic Repeats", "Common Cold", "Culture Media", "Data", "Defect", "Development", "Disease", "Dose", "Focal and Segmental Glomerulosclerosis", "Genetic", "Genomic DNA", "Genomics", "Histologic", "Hodgkin Disease", "Human", "IL6ST gene", "Inbred BALB C Mice", "Incidence", "Individual", "Injections", "Injury", "Integrins", "Intercellular adhesion molecule 1", "Interferon Type II", "Interleukin-13", "Interleukin-6", "Kidney", "Lesion", "Literature", "LoxP-flanked allele", "Lymphoma cell", "Malignant - descriptor", "Modeling", "Mus", "Nephrotic Syndrome", "Nuclear", "Patients", "Proteins", "Publishing", "RANTES", "RNA Splicing", "Recurrent disease", "Reed-Sternberg Cells", "Rhinovirus", "Rodent Model", "Signal Pathway", "Signal Transduction", "Source", "TNF gene", "TNFRSF1A gene", "Therapeutic", "Tissue Inhibitor of Metalloproteinase-1", "Tumor Necrosis Factor-Beta", "Xenograft procedure", "atopy", "cytokine", "cytokine release syndrome", "experimental study", "immunodeficiency", "improved", "kidney biopsy", "mouse model", "neoplastic cell", "podocyte", "prevent", "promoter", "receptor", "treatment response", "tumor" ], "approved": true } } ], "meta": { "pagination": { "page": 3, "pages": 1392, "count": 13920 } } }