NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Anxiety Disorders;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Dementia;Mental Health;Mental Illness;Neurodegenerative;Neurosciences;Post-Traumatic Stress Disorder (PTSD)

ORG_CITY: CHICAGO

ORG_NAME: UNIVERSITY OF CHICAGO

PHR: NARRATIVE Learning impairments and memory confusion are symptoms of many connected neurological disorders (major depression, anxiety and post-traumatic stress disorders, schizophrenia, autism, Alzheimer’s disease or temporal lobe epilepsy) that also show disorganization of a brain center critical for memory specificity: the dentate gyrus. The goal of the proposed research is to determine how the dentate gyrus normally works to limit confusion by measuring the activity of its input and output neurons in mice forming and recalling memories of similar experiences. Uncovering the brain computations underlying normal memory storage and retrieval will offer new avenues and targets to treat memory impairments in numerous conditions.

PI_NAMEs: MADAR, ANTOINE DAVID (contact)

PROGRAM_OFFICER_NAME: PINARD, COURTNEY ROSE

PROJECT_TERMS: Address;Alzheimer's Disease;Anatomy;Animals;Anxiety;Anxiety Disorders;Area;autism spectrum disorder;Axon;Behavioral;Brain;Brain region;Calcium;Cells;Code;Cognition Disorders;cognitive function;Computer Models;conditioned fear;Confusion;Data Set;Dendrites;dentate gyrus;Discrimination;Disease;Doctor of Philosophy;entorhinal cortex;Environment;Episodic memory;Event;experience;experimental study;Familiarity;Freezing;Fright;Goals;Hippocampus;Image;Impairment;in vivo;in vivo evaluation;Individual;Inherited;Investigation;Knowledge;Learning;Major Depressive Disorder;mathematical model;Measures;Memory;memory consolidation;memory encoding;Memory impairment;memory recall;memory retrieval;Mental Depression;Methods;Mus;Neocortex;Nervous System Disorder;neural;Neurologic;neuronal cell body;Neurons;novel;Output;Parahippocampal Gyrus;Pathologic;Pattern;Phase;Physiology;Play;Population;post-traumatic stress;Post-Traumatic Stress Disorders;prevent;Process;Reporting;Research;Research Project Grants;Research Proposals;Resolution;Retrieval;Role;Schizophrenia;Slice;Source;spatiotemporal;Specificity;Stimulus;Stressful Event;Symptoms;Temporal Lobe Epilepsy;Testing;theories;therapy design;Training;Transfection;Transgenic Mice;two-photon;Viral;virtual environment;Work

PROJECT_TITLE: The role of dentate gyrus input-output computations in episodic memory


ADMINISTERING_IC: VA

ARRA_FUNDED: N

FUNDING_MECHANISM: OTHERS

IC_NAME: Veterans Affairs

ORG_CITY: CHARLESTON

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: RALPH H JOHNSON VA MEDICAL CENTER

ORG_STATE: SC

PHR: Depression is a leading cause of disability worldwide and is more commonly seen in individual’s post-spinal cord injury (SCI) than in the general population. Depression post-SCI impacts an individuals’ quality of life and recovery. It has been reported that among Veterans with an SCI, those without depression live longer than those with depression. Thus, depression must be treated appropriately. Repetitive transcranial magnetic stimulation (rTMS) is an FDA-approved treatment for depression, but dosing is based on a motor response in the thumb. Over half of individuals with SCI have some degree of arm or hand impairment, so these individuals might not be eligible for rTMS, or they may receive the wrong dose. [This study proposes secondary data analysis of a completed trial and a clinical trial in individuals with depression post-SCI to assess the anti-depressant effect of a novel technique to dose rTMS that does not require a motor response.] By gaining a better understanding of the application of rTMS for depression post-SCI, we aim to advance the rehabilitative care of Veterans.

PI_NAMEs: VANDERWERKER, CATHERINE JEFFERSON (contact)

PROJECT_TERMS: Address;Amputees;Anatomy;anti-depressive agents;antidepressant effect;arm;associated symptom;Award;Caregivers;Clinical;Clinical effectiveness;Clinical Practice Guideline;Clinical Trials;cohort;comorbid depression;Computer Models;cost;Data;data acquisition;Data Analyses;Dedications;depressive symptoms;design;Development;disability;Dose;dose individualization;effective therapy;Effectiveness;effectiveness evaluation;electric field;Eligibility Determination;Enrollment;Environment;evidence based guidelines;Evidence based treatment;Exclusion;Exposure to;Family;FDA approved;Foundations;functional improvement;Funding;Future;General Population;Goals;Hamilton Rating Scale for Depression;hand dysfunction;health care service utilization;Health system;Image;Impairment;improved;Individual;injury recovery;Institution;Intervention;Left;Magnetic Resonance Imaging;Major Depressive Disorder;Medical;Medical center;Medicine;Mental Depression;Mental disorders;Mentors;Methods;Modeling;mortality;Motor;motor impairment;MRI Scans;multi-site trial;Neurobiology;neurological rehabilitation;neuropsychiatric disorder;neuropsychiatry;neuroregulation;noninvasive brain stimulation;novel;Outcome Measure;Outcome Study;Paralysed;Patient Outcomes Assessments;patient population;Physiologic pulse;placebo group;Placebos;Population;Prefrontal Cortex;Prevalence;primary outcome;Protocols documentation;psychosocial;Publishing;Quadriplegia;Quality of life;Randomized;Recommendation;Recovery;Rehabilitation Outcome;Rehabilitation therapy;rehabilitative care;repetitive transcranial magnetic stimulation;Reporting;Research;Research Personnel;Resources;response;Rest;Safety;Sampling;skills;South Carolina;Spinal Cord;Spinal cord injury;Techniques;Thumb structure;Time;Tissues;Training;Transcranial magnetic stimulation;treatment effect;trial planning;United States Department of Veterans Affairs;United States National Institutes of Health;Universities;Update;Upper Extremity;Veterans;Veterans Health Administration;Work

PROJECT_TITLE: Evaluating a Novel Method to Determine the rTMS Dose Needed for Treating Depression After Spinal Cord Injury

STUDY_SECTION_NAME: Career Development Program - Panel I[RRD8]


ADMINISTERING_IC: MH

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Anxiety Disorders;Brain Disorders;Genetics;Human Genome;Mental Health;Mental Illness;Pediatric;Prevention;Serious Mental Illness

ORG_CITY: CHAPEL HILL

ORG_DEPT: GENETICS

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: Project Narrative  Obsessive-compulsive disorder (OCD) is a neuropsychiatric condition that causes enormous human suffering and is thought to result from a complex interplay of genetic and the environmental factors. Our goal in this study is to learn more about what precise genetic factors influence an individuals risk for OCD. We propose to do this by resequencing the protein coding portion of the genome in a large number of OCD subjects and matched controls.

PI_NAMEs: CROWLEY, JAMES JOSEPH (contact)

PROGRAM_OFFICER_NAME: PEVSNER, JONATHAN ABRAM

PROJECT_TERMS: Adolescent;Affect;analytical method;Area;Attention deficit hyperactivity disorder;autism spectrum disorder;Awareness;Biological;Biology;Bipolar Disorder;case control;cell type;Child;Chronic;Clinical;Code;Collaborations;Collection;comorbidity;Complex;Copy Number Polymorphism;Country;Data;Data Set;Detection;Development;Disease;disorder risk;DNA;DNA Resequencing;Environmental Risk Factor;Etiology;exome;exome sequencing;follow-up;Functional disorder;gene discovery;Gene Dosage;Gene Expression;Genes;Genetic;genetic architecture;Genetic Risk;genetic risk factor;Genetic Variation;Genome;genome-wide;Genotype;Gilles de la Tourette syndrome;Goals;Human;improved;Individual;Inherited;insertion/deletion mutation;Intellectual functioning disability;Knowledge;Learning;Mental disorders;method development;Methods;Molecular;Molecular Target;Neurodevelopmental Disorder;neuropsychiatry;new therapeutic target;non-genetic;Norway;novel;Nucleotides;Obsessive compulsive behavior;Obsessive-Compulsive Disorder;Outcome;Parents;Pathway interactions;Peptide Sequence Determination;phenotypic data;Play;Population;power analysis;Prevention strategy;Price;Proteins;psychiatric comorbidity;Psychiatric Diagnosis;psychiatric genomics;Psychiatrist;Public Health;Publishing;Research;Risk;risk variant;Role;Sampling;Schizophrenia;Site;skills;societal costs;Specificity;Sweden;System;Tic disorder;tic related;transmission process;Variant

PROJECT_TITLE: 2/2 Rare Genetic Variation and Risk for Obsessive Compulsive Disorder

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-PSE-B(02)]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Cancer;Emerging Infectious Diseases;Genetics;HIV/AIDS;Hematology;Infectious Diseases;Lymphatic Research;Lymphoma;Rare Diseases

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: Kaposi’s sarcoma-associated herpesvirus (KSHV) is an AIDS-associated pathogen and the most common cause of cancer in untreated AIDS patients. This proposal investigates the impact of the RNA- sensing cell intrinsic immune system on KSHV infection. Defining mechanisms by which KSHV is recognized by the immune system, as well as how KSHV combats its recognition, will provide fundamental knowledge regarding how KSHV interacts with the host cell.

PI_NAMEs: KARIJOLICH, JOHN  (contact)

PROGRAM_OFFICER_NAME: PARK, EUN-CHUNG

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;anti-cancer;antiviral drug development;B-Lymphocytes;Binding;Biogenesis;Cancer Etiology;Cells;chemical property;Chemicals;Cyclic GMP;cytosolic receptor;Data;Defect;Defective Viruses;Disease;Disease Progression;DNA;domain mapping;endonuclease;Enzymes;Etiology;experimental study;Family;gammaherpesvirus;genetic information;Germ Lines;Herpesviridae Infections;HIV;Host Defense;Human Herpesvirus 8;Immune;Immune response;Immune system;Immunocompromised Host;Immunosuppression;in vivo;Individual;Infection;Interferons;Kaposi Sarcoma;Knowledge;Life Cycle Stages;Ligands;Link;Lymphoproliferative Disorders;Lytic;Lytic Phase;Malignant Neoplasms;Mediating;Modification;Molecular;Molecular Structure;Multicentric Angiofollicular Lymphoid Hyperplasia;Nucleic Acids;Oncogenic;Organism;Outcome;pathogen;Pathway interactions;Patients;Pattern;Pattern recognition receptor;Plasma Cells;posttranscriptional;primary effusion lymphoma;Production;Proteins;receptor;receptor binding;Regulation;response;Ribonucleases;RNA;RNA Binding;RNA Helicase;RNA Viruses;Role;sensor;Shapes;Signal Transduction;Testing;TLR9 gene;Transcription Process;transcriptome;transcriptomics;Untranslated RNA;Vaccine Therapy;Variant;Viral;Viral Cancer;viral RNA;Virus

PROJECT_TITLE: Cell Intrinsic Immune Control of KSHV

STUDY_SECTION: VIRA

STUDY_SECTION_NAME: Virology - A Study Section[VIRA]


ORG_NAME: VETERANS HEALTH ADMINISTRATION

PHR: Current lung cancer screening eligibility guidelines use only age and smoking history, were developed in a civilian population and miss the majority of Veterans who develop lung cancer. Veterans suffer from lung cancer at higher rates than the rest of the United States population and have unique exposures due to their military service. This proposal will define Veteran-specific lung cancer risk factors, develop a screening eligibility model for Veterans and compare that model to current eligibility risk models and criteria. We will use linked Department of Defense and VA Electronic Health Records to discover novel phenotypes associated with lung cancer risk. We will then build a Veteran-specific lung cancer screening model using standard, machine and deep learning methods and compare it to existing screening models. With nationally recognized leaders in machine learning, Veteran’s health data, lung cancer screening modeling, and health services research, we are uniquely positioned to use artificial intelligence to improve lung cancer screening for Veterans.

PI_NAMEs: GROGAN, ERIC L (contact)

PROJECT_TERMS: Age;agent orange;Artificial Intelligence;Asbestos;Biometry;burn pit;Calibration;cancer diagnosis;cancer risk;Carcinogens;Caring;Chronic Obstructive Pulmonary Disease;Clinical Data;Clinical Services;Data;Databases;deep learning;Department of Defense;Early Diagnosis;Early treatment;Electronic Health Record;Eligibility Determination;Epidemiology;Exposure to;Future;General Population;Goals;Guidelines;hazard;Health;health data;Health Services Research;high risk population;HIV;Hydrocarbons;improved;Individual;Informatics;Ionizing radiation;Link;low socioeconomic status;Lung;lung cancer screening;Machine Learning;machine learning method;Malignant neoplasm of lung;Malignant Neoplasms;Methods;military service;model development;Modeling;mosaic;novel;Pattern;Phenotype;Population;Positioning Attribute;pulmonary function;Race;Radiology Specialty;Recording of previous events;Reporting;Rest;Rheumatoid Arthritis;Risk;Risk Factors;screening;screening guidelines;Services;Signal Transduction;Smoke;Smoker;Smoking;Smoking Behavior;Smoking History;Subgroup;Text;text searching;Time;Tobacco use;United States;United States Department of Veterans Affairs;United States Preventative Services Task Force;Veterans

PROJECT_TITLE: Creating a Veteran's specific risk model to improve lung cancer screening


ADMINISTERING_IC: DC

ED_INST_TYPE: ORGANIZED RESEARCH UNITS

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Hearing Loss;Neurosciences

ORG_CITY: DETROIT

ORG_DEPT: MISCELLANEOUS

ORG_NAME: WAYNE STATE UNIVERSITY

ORG_STATE: MI

PHR: Narrative  Ototoxicity is one of the major side effects of cisplatin, a widely used anti-cancer drug. Cisplatin- induced nitration and downregulation of LMO4, a molecular adaptor protein, appears to mediate its ototoxic effects. The characterization of the regulatory role of LMO4 nitration in cisplatin-mediated ototoxicity is expected to reveal the biological significance of this novel molecular mechanism and facilitate the development of effective therapeutic approaches to prevent the ototoxic effects of cisplatin.

PI_NAMEs: JAMESDANIEL, SAMSON  (contact)

PROGRAM_OFFICER_NAME: FREEMAN, NANCY

PROJECT_TERMS: Acquired Deafness;Adaptor Signaling Protein;Adverse effects;analog;Anti-Inflammatory Agents;anticancer activity;Antineoplastic Agents;Apoptosis;Apoptotic;Attenuated;Auditory;Binding;Biological;Cancer Patient;catalyst;CBA/J Mouse;Cell Death;Cell Death Inhibition;Cell Survival;Cisplatin;cisplatin induced hearing loss;Clinical;clinically relevant;Cochlea;CRISPR/Cas technology;cytotoxicity;Data;Development;Dose Limiting;Down-Regulation;Drug Targeting;effective intervention;Epithelial Cells;Eye;Foundations;Genes;Genetic Transcription;Goals;Hair Cells;hearing impairment;Hearing Protection;Induction of Apoptosis;Inflammatory;innovation;Intervention;Kidney;Knock-out;Knowledge;lactacystin;LIM Domain;Link;Mass Spectrum Analysis;Mediating;Messenger RNA;Modeling;Modification;Molecular;Mus;mutant;new therapeutic target;Nitrates;nitration;novel;novel therapeutic intervention;Oral;Organ;Organ of Corti;otoprotectant;ototoxicity;Outcome;overexpression;Oxidative Stress;Oxidative Stress Induction;Pancreas;Pathway interactions;Patients;permanent hearing loss;Peroxonitrite;pharmacologic;Phosphorylation;Play;Predisposition;prevent;promoter;Protein Inhibition;protein protein interaction;Proteins;Proteomics;Reporting;Repression;Research;response;Role;SCID Mice;Sensory;side effect;Signal Pathway;Signal Transduction;Signaling Protein;Site-Directed Mutagenesis;STAT protein;STAT1 gene;STAT3 gene;Stress;Testing;Therapeutic;therapeutically effective;translational applications;Treatment Efficacy;Treatment Protocols;Ubiquitination

PROJECT_TITLE: Targeting nitrative stress for treatment of cisplatin ototoxicity

STUDY_SECTION: AUD

STUDY_SECTION_NAME: Auditory System Study Section[AUD]


NIH_SPENDING_CATS: Anxiety Disorders;Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Biomedical Imaging;Brain Disorders;Clinical Research;Mental Health;Mental Illness;Neurosciences;Pediatric;Serious Mental Illness

ORG_DEPT: PSYCHIATRY

PHR: PROJECT NARRATIVE Obsessive compulsive disorder (OCD) is a common and chronically disabling disorder in youth, and there is a pressing need for studies that shed light on its functional neurobiology. Our proposed combination of innovative multi-modal functional imaging applications (¹H fMRS and fMRI) will identify dysfunction related to brain glutamate modulation and network dynamics facilitating a better understanding of specifics of this dysfunctional neurobiology. The resultant advances in mechanistic understanding are expected to motivate more effective and precise treatments for this severe form of childhood psychopathology.

PI_NAMEs: DIWADKAR, VAIBHAV A.;ROSENBERG, DAVID R (contact);STANLEY, JEFFREY A

PROGRAM_OFFICER_NAME: THOMAS, LAURA ANDERSON

PROJECT_TERMS: Address;Adolescence;Adrenal Cortex Hormones;Age;Anterior;Anxiety;anxiety symptoms;Apical;Architecture;Automobile Driving;Award;Behavior;Biochemistry;Brain;brain dysfunction;causal model;Childhood;Chronic;cingulate cortex;Clinical;clinical predictors;clinically relevant;cognitive control;comorbidity;Complex;compulsion;Corpus striatum structure;Cross-Sectional Studies;Data;density;design;Diagnostic;Dimensions;Disabling;Disease;disease classification;Dorsal;dorsal visual stream;Early Intervention;Equilibrium;Functional disorder;Functional Imaging;Functional Magnetic Resonance Imaging;Glutamates;Grant;Graph;hemodynamics;Image;Impairment;in vivo;innovation;Intervention;Investigation;Knowledge;Magnetic Resonance Spectroscopy;Measures;Mediating;Motor;motor control;Movement;Multimodal Imaging;multimodality;network dysfunction;network models;neural;Neurobiology;neurochemistry;neuroimaging;Neurons;neuropathology;novel;Obsession;Obsessive-Compulsive Disorder;Onset of illness;Participant;Periodicals;phenomenological models;precision medicine;Process;Psychopathology;Research Design;response;Role;sample fixation;Sampling;Science;Services;Severities;Signal Transduction;Specificity;Stimulus;Structure;Symptoms;Synapses;Task Performances;Thalamic structure;Theoretical model;Time Series Analysis;Titrations;Universities;Work;Youth

PROJECT_TITLE: Multimodal Investigation of Excitatory/Inhibitory Imbalances and Network Dysfunction Related to Motor Control in OCD Youth: ÃÂ¹H fMRS and fMRI Applications

STUDY_SECTION: CPDD

STUDY_SECTION_NAME: Child Psychopathology and Developmental Disabilities Study Section[CPDD]


NIH_SPENDING_CATS: Antimicrobial Resistance;Biotechnology;Clinical Research;Genetics;Infectious Diseases;Malaria;Orphan Drug;Rare Diseases;Vector-Borne Diseases

ORG_CITY: LA JOLLA

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

ORG_STATE: CA

PHR: Project Narrative Antimalarial drugs may lose their effectiveness when the parasites that cause malaria become resistant to the drugs. We seek to better understand how this happens with a goal of developing more effective antimalarial drugs.

PI_NAMEs: GOLDBERG, DANIEL E.;WINZELER, ELIZABETH A (contact);WIRTH, DYANN F

PROGRAM_OFFICER_NAME: JOY, DEIRDRE A

PROJECT_TERMS: acquired drug resistance;Address;African American;Alleles;Anti-malarial drug resistance;Anti-malarials;Asian Americans;assay development;Back;bioinformatics pipeline;Biological Assay;Biology;Biotin;candidate selection;candidate validation;Chemicals;Clinical;Clinical Research;Clinical Trials;clinically relevant;conditional knockout;cost;Cryoelectron Microscopy;Data;Data Set;design;Development;Disease;drug candidate;Drug Costs;drug development;drug discovery;Drug resistance;drug resistance development;Drug Targeting;Drug Tolerance;effective therapy;Effectiveness;Equation;Event;Evolution;experimental study;Exposure to;fitness;fungus;Gene Mutation;gene product;Genes;Genetic;Genome;genome sequencing;Geography;Goals;GPT gene;improved;In Vitro;in vitro Assay;Infectious Agent;innovation;knock-down;Knowledge;Label;Laboratories;large datasets;Lead;Machine Learning;Malaria;Mediating;Mediator;Methodology;Methods;Modernization;Multi-Drug Resistance;Mutation;novel;novel therapeutics;Parasite resistance;Parasites;pathogen;pathogenic bacteria;Pharmaceutical Preparations;Plasmodium falciparum;Play;pre-clinical;preclinical development;preclinical study;predictive modeling;pressure;Probability;protein function;Proteins;Proteomics;Reproducibility;Research;Resistance;resistance allele;resistance gene;resistance mechanism;resistance mutation;resistant Plasmodium falciparum;resistome;Resolution;Risk;Role;Series;small molecule inhibitor;South American;Structure;success;Testing;Time;trafficking;whole genome

PROJECT_TITLE: Defining the resistome in P. falciparum: evolution and mechanism

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-AIDC-V(02)]


ORG_CITY: SEATTLE

ORG_NAME: FRED HUTCHINSON CANCER CENTER

ORG_STATE: WA

PHR: PROJECT NARRATIVE HIV-1 remains a substantial public health burden: antiretroviral therapy (ART) is capable of suppressing virus, but not curing infected individuals. Chimeric antigen receptor (CAR) T-cell gene therapies have induced long term remission in cancer patients, but must address inherent challenges to enable long-term ART-free remission in people living with HIV (PLWH). Our goal in this project is to increase the potency, durability, and feasibility of CAR-T cell therapies for HIV-1 in the nonhuman primate model, in support of future clinical studies in PLWH.

PI_NAMEs: PARHIZ, HAMIDEH ;PETERSON, CHRISTOPHER W (contact)

PROGRAM_OFFICER_NAME: POON, BETTY

PROJECT_TERMS: Address;Alleles;Animal Model;Animals;anti-PD-1;Antibodies;Antigens;antiretroviral therapy;Autologous;B lymphoid malignancy;B-Lymphocytes;Bar Codes;Benchmarking;Berlin;Biological Assay;Biology;cancer cell;Cancer Patient;CAR T cell therapy;CCR5 gene;CD4 Positive T Lymphocytes;Cell Communication;cell immortalization;Cell Line;Cell Physiology;Cell surface;Cell Therapy;Cells;chimeric antigen receptor;chimeric antigen receptor T cells;Chromosomal translocation;Clinic;Clinical Research;clinical translation;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;COVID-19 vaccination;COVID-19 vaccine;CRISPR/Cas technology;CTLA4 gene;curative treatments;Data;Developing Countries;Disease;Disease remission;Dose;env Gene Products;Environment;Event;exhaustion;Experimental Designs;experimental study;Extracellular Domain;FDA approved;Future;gene therapy;gene-editing approach;Genes;genotoxicity;Goals;Graft-Versus-Tumor Induction;Hematologic Neoplasms;Hematopoietic Neoplasms;Hematopoietic stem cells;high risk;HIV;HIV therapy;HIV-1;Homologous Transplantation;Immune;immune checkpoint;immune checkpoint blockade;in vivo;Individual;Infection;interest;Interruption;K-562;K562 Cells;Knowledge;latent HIV reservoir;Learning;Leukemic Cell;lipid nanoparticle;Liquid substance;London;Lymphoma cell;Macaca mulatta;Malignant - descriptor;Malignant Neoplasms;manufacturing process;Messenger RNA;Modeling;Modification;Molecular;mRNA lipid nano particle vaccine;nanoparticle delivery;Nature;New York;next generation;nonhuman primate;novel;Pathway interactions;Patients;PD-1 blockade;Persons;Pfizer-BioNTech COVID-19 vaccine;Phase I Clinical Trials;Plasma;Population Study;prevent;Procedures;programmed cell death protein 1;programs;Property;Public Health;Recrudescences;Refractory;Reporting;Research Design;Resistance;Safety;safety assessment;Series;single-cell RNA sequencing;SIV;Solid Neoplasm;stable cell line;success;Supplementation;Supporting Cell;T-Lymphocyte;Technology;Time;trafficking;tumor;Validation;Viral;Viral Antigens;Viral Envelope Proteins;Viral Load result;viral rebound;Viral reservoir;Virus

PROJECT_TITLE: Developing Durable, Env-Boosted CAR T Cells for HIV Cure

STUDY_SECTION: HIVD

STUDY_SECTION_NAME: HIV Immunopathogenesis and Vaccine Development Study Section[HIVD]


ORG_CITY: BALTIMORE

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

ORG_STATE: MD

PHR: Narrative Defense of the host against pathogens involves multiple cell types which must coordinate their actions across time and space. Here we propose to study a new mechanism which allows immune cells at the initial site of a pathogen infection to warn and prepare far away tissues for a possible attack.

PI_NAMEs: SINGH, NEVIL JOHN (contact)

PROGRAM_OFFICER_NAME: LEITNER, WOLFGANG W

PROJECT_TERMS: Acute;acute infection;Adaptive Immune System;Affect;Bacteria;Bacterial Infections;Biological;Cell secretion;cell type;Cells;Chronic;Clinic;Clinical;clinical development;Clinical Treatment;co-infection;Communication;cytokine;Data;Dendritic Cells;Disease;Disease Resistance;Distal;Distant;Ensure;Focal Infection;Future;Growth;Health;Homeostasis;Host Defense;Host resistance;host-microbe interactions;Immune;Immune response;Immunity;Immunization;Immunologics;immunopathology;immunoregulation;improved;Individual;Infection;Innate Immune System;innovation;insight;Interleukin-12;interleukin-23;Intuition;Knowledge;Lead;Measures;Mediating;Microbe;microbial;Modeling;Modification;Molecular;monomer;mutant;Myeloid Cells;Natural Killer Cells;novel strategies;oral infection;Organ;Organism;Parasites;Parasitic infection;pathogen;Pathway interactions;Phase;Physiological;Porphyromonas gingivalis;Prevention;Primary Infection;Process;Production;Proteins;Publishing;Resistance;response;Role;Signal Transduction;Site;Skin;Stromal Cells;System;Systemic disease;T-Lymphocyte;Therapeutic;therapeutic target;Therapeutic Uses;Time;Tissues;vaccination strategy;vaccine development;Vaccines;Work

PROJECT_TITLE: Mechanisms coordinating the local and systemic resistance to pathogens

STUDY_SECTION: IHD

STUDY_SECTION_NAME: Immunity and Host Defense Study Section[IHD]


NIH_SPENDING_CATS: Autoimmune Disease;Digestive Diseases;Inflammatory Bowel Disease;Microbiome;Prevention

ORG_CITY: SAINT LOUIS

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Project Narrative Events in early life involving the gut microbiota can have an important impact on immune development altering the risk of immune related disorders. For example, it has been reported that the route of delivery, feeding, hygiene, and antibiotics, in early life can modify the risk of inflammatory bowel disease and allergic outcomes later in life. This proposal seeks greater understanding of the gut commensal bacteria that impact immune development and address whether the extent of this interaction dictates durable immune homeostasis and resistance from pathologic immune outcomes in later life. These data on physiologic immune development may inform on risk of developing inflammatory bowel disease or other immune conditions in humans.

PI_NAMEs: HSIEH, CHYI S (contact);NEWBERRY, RODNEY D

PROGRAM_OFFICER_NAME: HUDSPETH, KELLY

PROJECT_TERMS: Address;Adult;Affect;Allergic;Antibiotics;Antigen Presentation;Antigen-Presenting Cells;antigen-specific T cells;Antigens;Bacteria;Bacterial Antigens;Bacterial Infections;Bacterial Translocation;Biological;Bypass;CD4 Positive T Lymphocytes;Cells;Colitis;Colon;commensal bacteria;commensal microbes;Data;Development;Disease;Distant;Event;feeding;Future;Generations;Genetic;Germ-Free;Goblet Cells;Growth;gut bacteria;gut homeostasis;gut microbiota;Helicobacter;Homeostasis;Human;Hygiene;Immune;immune function;immune health;Immune response;Immune system;Immune System Diseases;Immunologic Stimulation;In Vitro;in vivo;Individual;Infection;Inflammatory Bowel Diseases;Inflammatory Response;Intestines;Knowledge;Laboratories;Lactobacillus;Lamina Propria;late life;Life;Lymphoid Tissue;Measures;Mediating;mesenteric lymph node;Methods;Microbe;microbial;microbiota;Mus;Nature;old mice;Outcome;Pathologic;Pathology;Pathway interactions;Pattern;Peripheral;pharmacologic;Phase;Phenotype;Physiological;Population;Predisposition;prevent;Reagent;Regulatory T-Lymphocyte;Reporting;Reproducibility;Resistance;response;Risk;Risk Factors;Role;Route;Severities;single-cell RNA sequencing;Small Intestines;System;T cell response;T-cell receptor repertoire;T-Lymphocyte;Testing;Time;Transgenic Mice;Transgenic Organisms;Weaning

PROJECT_TITLE: Immune interactions with commensal microbes in early life

STUDY_SECTION: DHMI

STUDY_SECTION_NAME: Digestive System Host Defense, Microbial Interactions and Immune and Inflammatory Disease Study Section[DHMI]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Clinical Research;Hematology;Lung

ORG_CITY: BOSTON

ORG_NAME: BETH ISRAEL DEACONESS MEDICAL CENTER

ORG_STATE: MA

PHR: Project Narrative Blood clotting that occurs in large arteries causes heart attacks and stroke, while clotting in small vessels can cause organ failure in the setting of infection. Current therapies to treat these thrombotic diseases are complicated by bleeding and recurrent clotting. We have identified a new layer of control of blood clotting mediated by thiol isomerases and will study the role of these enzymes in thrombus formation to identify better diagnostic and therapeutic approaches for the management of common, life-threatening clotting events.

PI_NAMEs: FLAUMENHAFT, ROBERT C (contact)

PROGRAM_OFFICER_NAME: GOLDBERG, ILANA GRACE

PROJECT_TERMS: Active Sites;Alveolus;Animals;antagonist;Arteries;ATF6 gene;biomarker identification;Blocking Antibodies;Blood coagulation;Blood Platelets;Blood Vessels;Cells;Chemicals;Circulation;Clinical Trials;Coagulation Process;Cysteine;Cytosol;Data;Diabetes Mellitus;Diagnostic;Disease;Disulfides;Dyslipidemias;Endoplasmic Reticulum;Endothelial Cells;Endothelium;Environment;Enzymes;Evaluation;Event;experimental study;extracellular;Family;Gene Modified;Genetic;Hemorrhage;Human;Hydrogen Peroxide;Impairment;in vivo;Infection;Inflammation;Inflammatory Response;inhibitor;Isomerase;knock-down;Life;Lung;Lung infections;Malignant Neoplasms;Mediating;Membrane Proteins;Modeling;Modification;Molecular;Molecular Conformation;mouse model;Mus;mutant;Mutation Analysis;Myocardial Infarction;neutralizing antibody;novel;Organ failure;oxidant stress;Oxidants;oxidation;Oxidation-Reduction;Oxidative Stress;Pathway interactions;Patients;phase 2 study;Platelet Activation;pneumocyte;Post-Translational Protein Processing;Production;programs;Property;prophylactic;Protein Disulfide Isomerase;protein function;Proteins;Proteomics;Pulmonary Inflammation;Reaction;receptor;Recurrence;Regulation;response;Role;sensor;single-molecule FRET;SKIL gene;small molecule;small molecule inhibitor;Stroke;Structure;Sulfhydryl Compounds;Testing;Text;Therapeutic;therapeutic development;therapeutic target;Thrombosis;thrombotic;Thrombus;Translating;Validation

PROJECT_TITLE: Thiol Isomerases and Oxidant Stress in Thrombus Formation

STUDY_SECTION: HTBT

STUDY_SECTION_NAME: Hemostasis, Thrombosis, Blood Cells and Transfusion Study Section[HTBT]


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Biotechnology;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Hematology;Human Genome;Racial and Ethnic Minority Health Research

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF WASHINGTON

PHR: PROJECT NARRATIVE This project will lead to improved insight into the genetic basis of hematologic traits and red blood cell disorders. Finding the risk factors and causes of these disorders or traits will lead to new insights into why they occur, and, potentially, how they can be treated. Our project will create a renewable resource for the scientific community for research into human red blood cell production and how this goes awry in disease.

PI_NAMEs: REINER, ALEXANDER P (contact)

PROGRAM_OFFICER_NAME: QASBA, PANKAJ

PROJECT_TERMS: Achievement;Address;Admixture;African;African American;African ancestry;Anemia;Architecture;Asian Americans;Asian ancestry;Atlases;Award;Base Sequence;biobank;Biological;Biology;Blood;Blood Cells;causal variant;Cell Lineage;Cells;Chromatin;Chromosome Mapping;Clinical;clinical translation;Communities;Complex;computerized tools;Copy Number Polymorphism;COVID-19 severity;COVID-19 susceptibility;Data;Data Set;Disease;DNA copy number;East Asian;Ensure;epigenomics;Erythrocytes;Erythrocytoses;ethnic diversity;European;exome;Frequencies;functional genomics;Funding;Gene Frequency;Genes;Genetic;genetic architecture;genetic association;Genetic Risk;genetic variant;Genetic Variation;Genome;genome resource;genome wide association study;genome-wide analysis;genomic locus;Genomic Segment;genomic tools;Genomics;global health;Goals;Grant;health equity;Hematocrit procedure;Hematological Disease;Hematology;Hematopoiesis;Hematopoietic;Hemoglobin;Heterogeneity;Hispanic;Hispanic Populations;Human;human disease;improved;indexing;Individual;insight;Investigation;Joints;Knowledge;Latino Population;Maps;Methods;Minor;Mitochondria;Mitochondrial DNA;Modeling;multi-ethnic;Multiomic Data;National Heart, Lung, and Blood Institute;Native Americans;next generation;Non-Malignant;novel;Outcome;Penetrance;Phase;Phenotype;pleiotropism;Polygenic Traits;Population;population based;Production;Public Health;rare variant;Red Blood Cell Count;Research;Resources;Risk;Risk Factors;Sample Size;SARS-CoV-2 infection;single cell genomics;Single Nucleotide Polymorphism;Stroke;success;trait;Trans-Omics for Precision Medicine;transcriptome sequencing;Untranslated RNA;Update;Validation;Variant;Venous;whole genome;Width;Work;X Chromosome

PROJECT_TITLE: Next generation functional genomics of hematology traits

STUDY_SECTION: GHD

STUDY_SECTION_NAME: Genetics of Health and Disease Study Section[GHD]


ADMINISTERING_IC: ES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

ORG_CITY: SITKA

ORG_NAME: SITKA TRIBE OF ALASKA

ORG_STATE: AK

PHR: The Knowledge Warding Against Toxin Levels Center for Oceans and Human Health is a multi-site, transdisciplinary consortium led by Sitka Tribe of Alaska and including Tribal Organization, university, and non- academic partners to characterize paralytic shellfish poisoning risks and related issues in the Gulf of Alaska as the world undergoes rapid environmental change.

PI_NAMEs: FELDPAUSCH, JEFF  (contact);GRIBBLE, MATTHEW O.

PROGRAM_OFFICER_NAME: DZIERLENGA, ANIKA LIN

PROJECT_TERMS: Address;Adult;advanced system;Advisory Committees;Alaska;Alaska Native;Area;burden of illness;career;Chemicals;Climate;climate change;climate impact;Communication;Communities;Community Developments;community engagement;Community Surveys;computer game;Consultations;Coupled;Data;dietary;Dietary Practices;Direct Costs;Directories;Disease;Ensure;environmental change;Environmental Health;Epidemiology;Epistemology;equity, diversity, and inclusion;Evaluation;Event;experimental study;Faculty;Food Safety;game development;Generations;Government;harmful algal blooms;Harvest;Health;health disparity;High Pressure Liquid Chromatography;Hour;Human;Ice Cream;Indigenous;Infrastructure;innovation;insight;Interview;invention;Knowledge;Laboratories;Location;Medical;meetings;member;Mentored Clinical Scientist Development Program;Mentors;Methods;minority health disparity;Modeling;Oceanography;Oceans;Outcome;Output;outreach;Paralysed;Poisoning;Process;programs;Progress Reports;Public Health;public health emergency;Reporting;Research;Resources;Risk;Risk Management;Running;Sampling;Science;Scientist;sea level rise;Secure;Series;Services;Shellfish;Site;social;Social Environment;Social Sciences;Strategic Planning;success;Surveys;synergism;System;Techniques;Testing;testing services;Toxic effect;Toxicology;Toxin;tribal Nation;tribal organization;Tribally Based Participatory Research;Tribes;undergraduate student;Universities;Update;Voice;ward;web site;webinar

PROJECT_TITLE: Knowledge Warding Against Toxin Levels

STUDY_SECTION_NAME: Special Emphasis Panel[ZES1 LKB-K (P)]


NIH_SPENDING_CATS: American Indian or Alaska Native;Climate-Related Exposures and Conditions;Health Disparities and Racial or Ethnic Minority Health Research;Racial and Ethnic Minority Health Research

PI_NAMEs: FELDPAUSCH, JEFF  (contact)

PROJECT_TERMS: Academia;Action Research;Administrator;Advisory Committees;Alabama;Alaska;Alaska Native;American Indians;authority;Biological Sciences;Biometry;Businesses;Communication;community based participatory research;community building;community center;Community Health;Community of Practice;Community Services;Complement;data sharing;Development;Directories;diversity and equity;Earth science;Education;Ensure;Environmental Health;Epidemiologist;Epidemiology;Epistemology;equity, diversity, and inclusion;Evaluation;Event;experience;Feedback;Fostering;Government;Grant;hackathon;harmful algal blooms;Health;Human;Indigenous;Institution;interest;Knowledge;Leadership;meetings;member;Mentors;Methodology;Native Americans;news;Oceanography;Oceans;outreach;peer;Policies;programs;Progress Reports;Public Health;recruit;Research;Resource Sharing;Resources;responsible research conduct;Running;Scientist;Secure;Self Assessment;Series;Specialist;Students;success;System;tool;Toxin;Training;Tribes;United States National Institutes of Health;Universities;Update;virtual;ward;web site

PROJECT_TITLE: Knowledge Warding Against Toxin Levels, Administrative Core


NIH_SPENDING_CATS: American Indian or Alaska Native;Arctic;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Pediatric;Racial and Ethnic Minority Health Research;Rural Health

PI_NAMEs: ELLWANGER, GRACE  (contact)

PROJECT_TERMS: Active Learning;Alabama;Alaska;Alaska Native;Area;Career Choice;career preparation;Communities;community engagement;community involvement;Community Participation;continuing medical education;Data;Data Analyses;data sharing;Economic Development;Education;Educational Assessment;Educational Materials;Educational workshop;Effectiveness;Employee;Ensure;experience;Feedback;Food;Goals;Harvest;Health;Healthcare;Human;Information Centers;interest;K-12 Education;Knowledge;marine;Medical Staff;member;Methodology;Oceans;outreach;Paralysed;Physician Executives;Poison;Poisoning;Program Effectiveness;programs;remote communities;Research Personnel;Resources;response;Risk;Running;Rural;Rural Community;Safety;Schools;Science;Shellfish;Specialist;summer research;Symptoms;Toxin;Training;tribal community;tribal organization;Tribes;university student;Voice;ward;Work;Workforce Development;Youth

PROJECT_TITLE: Knowledge Warding Against Toxin Levels, Community Engagement Core


PI_NAMEs: WHITEHEAD, CHRIS  (contact)

PROJECT_TERMS: advanced analytics;Air;Alaska;analytical method;Biological Assay;Collaborations;Communities;community engagement;Consumption;Core Facility;Data;Data Analyses;Data Element;data management;Data Set;Education and Outreach;Ensure;Environmental Science;Event;Food;food security;harmful algal blooms;Harvest;Health;Health Personnel;Health Professional;High Pressure Liquid Chromatography;Hour;Human;innovation;Intake;Internships;Knowledge;laboratory facility;Laboratory Research;Leadership;Measures;member;Methods;Monitor;National Oceanic and Atmospheric Administration;oceanic research;Paralysed;Pattern;Phytoplankton;Poisoning;Process;programs;receptor binding;Reporting;Research;Research Personnel;Research Project Grants;Research Support;Resources;Risk;Role;Running;Sampling;Sea;Services;Shellfish;Site;Temperature;Testing;Tissues;Toxic effect;Toxin;Training;tribal community;tribal leader;Tribes;Universities;ward;Water;water sampling;web page

PROJECT_TITLE: Knowledge Warding Against Toxin Levels, Facility Core


PI_NAMEs: HARLEY, JOHN  (contact)

PROJECT_TERMS: absorption;Acidity;Address;Affect;Air;Alaska;Alaska Native;Alaskan;analytical method;Biological Assay;Carbon Dioxide;career;Clams;Climate;climate adaptation;climate change;Collaborations;Communities;Complex;Consumption;Data;Data Analyses;Data Collection;Data Set;Dinophyceae;Ensure;Equipment;experience;exposed human population;Exposure to;Fishes;food security;Future;future climate scenario;Future Generations;Goals;harmful algal blooms;Harvest;Health;High Pressure Liquid Chromatography;Human;In Situ;in vivo;Individual;invention;Knowledge;Laboratories;Machine Learning;Mammals;marine;Measurement;Measures;Methodology;Methods;Modeling;Monitor;novel;ocean acidification;ocean ecosystems;oceanic research;Oceanography;Oceans;Output;Paralysed;Pattern;Phase;Phytoplankton;Poisoning;Population;predictive modeling;Process;Production;programs;receptor binding;remote sensing;Reporting;Reproducibility of Results;Research;Research Personnel;Research Project Grants;Resources;response;Risk;Role;Safety;sample archive;Sampling;Sea;Seasons;Shellfish;shellfish toxicity;Source;spatiotemporal;Statistical Methods;Surface;Symptoms;Techniques;Temperature;Testing;Time trend;Toxic effect;Toxic Environmental Substances;Toxicokinetics;Toxin;trend;tribal community;Tribes;Uncertainty;ward;Work

PROJECT_TITLE: Changing Oceans Affect Shellfish Toxins


NIH_SPENDING_CATS: Climate-Related Exposures and Conditions;Foodborne Illness;Natural Products;Nutrition

PI_NAMEs: WEBSTER, THOMAS F (contact)

PROJECT_TERMS: Address;Age;Agreement;Agriculture;Alaska;Alaskan;Analytical Chemistry;authority;Binding;Biological;Biological Assay;Cessation of life;Chemicals;climate change;Communities;community burden;Complex Mixtures;Consumption;Core Facility;Data;design;detection limit;Diet;Ensure;Environmental Health;European;experimental study;Food;Food Safety;food security;Geography;Goals;Habits;Harvest;Head;Health;High Pressure Liquid Chromatography;Human;Hunger;improved;In Vitro;in vivo;indexing;Individual;Knowledge;large datasets;Leadership;Link;Measurement;Measures;member;Methods;Modeling;Mus;Neurons;nutrition;oceanic research;Oceanography;Oceans;Paralysed;Personal Satisfaction;Phytoplankton;Poisoning;programs;Public Health;receptor binding;Research;Resources;response;Risk;Risk Assessment;Sampling;Saxitoxin;Sea;Seafood;Seasons;Shellfish;shellfish toxicity;Sodium Channel;Statistical Methods;Sum;Surface;Sustainable Development;synergism;Temperature;Testing;Time;Toxic effect;Toxin;Tribes;United Nations;ward

PROJECT_TITLE: Toxicity of saxitoxin congener mixtures in shellfish from Southeast Alaska


NIH_SPENDING_CATS: American Indian or Alaska Native;Arctic;Basic Behavioral and Social Science;Behavioral and Social Science;Climate-Related Exposures and Conditions;Clinical Research;Foodborne Illness;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Nutrition;Prevention;Racial and Ethnic Minority Health Research;Rural Health;Social Determinants of Health

PI_NAMEs: WICKLIFFE, JEFFREY KIRK (contact)

PROJECT_TERMS: Acute;Address;Affect;Alaska;Alaska Native;Alaskan;Area;Attention;Authorization documentation;Behavioral;Butter;Case Study;Cessation of life;Chemical Warfare Agents;Chemical Weapons;Chemicals;Clams;Classification;Climate;climate change;climate zone;climate-related health;Collaborations;Communities;community center;community engagement;Community Surveys;Consumption;Core Facility;Coupled;cultural values;Data;design;Development;Diet;dietary;Dietary intake;Dietary Practices;Dimensions;Disease;Disparity;Eating;Environmental Health;Epidemiology;Ethnography;Evaluation;Exclusion;experience;Exposure to;Face;Fishes;Food;food security;Frequencies;Future;Geography;Harm Reduction;Harvest;Health;health disparity;health equity;Health protection;holistic approach;Household;Human;improved;Individual;Informed Consent;instrument;Internet;Interview;Island;Knowledge;Measures;Medical;member;Methodology;Methods;Minority Groups;Modeling;Monitor;Names;Nature;non-Native;ocean acidification;oceanic research;Oceanography;Outcome;Paralysed;Participant;pattern perception;Perception;Persons;Poison;Poisoning;Population;population survey;preference;Prevalence;prevent;professor;programs;Psychology;Public Health;Qualitative Research;Questionnaires;racial health disparity;racial population;Recontacts;recruit;remote communities;Research;Research Methodology;resilience;Risk;Risk Assessment;risk perception;Running;Rural Community;Sample Size;Sampling;Saxitoxin;Shellfish;Site;Sociology;Stroke;success;Surveys;symposium;System;Testing;theories;Time;Toxic Environmental Substances;Toxicology;Toxin;Tribes;Voice;ward;water quality;Work

PROJECT_TITLE: Living and Eating in Intertidal Nature: Community-driven shellfish consumption evaluation


ORG_CITY: COLUMBIA

ORG_NAME: UNIVERSITY OF MISSOURI-COLUMBIA

PHR: PROJECT NARRATIVE Type 1 diabetes (T1D) is a chronic autoimmune disorder that affects more than 1% of population worldwide. Insulin as a standard treatment has major long-term complications; therefore, the development of novel approaches to prevent and treat T1D is a significant therapeutic goal. The primary objective of this proposal is to develop an immunomodulatory protocol that prevents the rejection of pancreatic allogeneic islets for the treatment of T1D. If effective, this approach will have immediate and important implications for the use of allogeneic islets for the treatment of T1D in humans.

PI_NAMEs: SHIRWAN, HAVAL  (contact)

PROGRAM_OFFICER_NAME: KEHN, PATRICIA J

PROJECT_TERMS: adaptive immune response;adaptive immunity;Adult;Adverse effects;Affect;Allogenic;allograft rejection;Antigens;Apoptosis;Autoantigens;Autoimmune;Autoimmune Diseases;Biological Response Modifiers;Blood;blood glucose regulation;C57BL/6 Mouse;Cadaver;CD47 gene;Cells;Cessation of life;Chemicals;Child;Chronic;chronic autoimmune disease;Clinical;clinical practice;Clinical Treatment;Clinical Trials;Coagulation Process;Complement;Data;design;Development;diabetic;Diabetic mouse;Eating;effector T cell;efficacy evaluation;Engineering;Engraftment;FOXP3 gene;Goals;graft function;Graft Rejection;Graft Survival;Health Care Costs;Homologous Transplantation;Human;humanized mouse;IL2RA gene;Immune;immune clearance;Immunity;immunoreaction;immunoregulation;Immunosuppression;Inbred BALB C Mice;Inbred NOD Mice;Inflammatory;Inflammatory Response;Infusion procedures;Innate Immune Response;innovation;Insulin;Insulin-Dependent Diabetes Mellitus;islet;Islets of Langerhans;Islets of Langerhans Transplantation;Leucocytic infiltrate;Liver;Mediating;Medical;Methods;Modeling;monocyte;mouse model;Natural Immunity;neutrophil;new technology;nonhuman primate;novel;novel strategies;Outcome;Pancreas;Pathway interactions;Phagocytes;Phagocytosis;Platelet Activation;Play;Population;Portal vein structure;post-transplant;prevent;Prevention;Proteins;Prothrombin;Protocols documentation;Reaction;Recombinant Proteins;Regimen;Regulatory T-Lymphocyte;response;Role;Route;SHPS-1 protein;Signal Transduction;standard care;Stimulus;Streptavidin;Structure of beta Cell of islet;Surface;Testing;Therapeutic;Thrombin;Thrombomodulin;Thromboplastin;thrombotic;Translating;Translations;transplant model;Transplantation;Treatment Protocols;Work

PROJECT_TITLE: A novel immunomodulatory approach to overcome innate and adaptiveimmune barriers to islet transplantation

STUDY_SECTION: TTT

STUDY_SECTION_NAME: Transplantation, Tolerance, and Tumor Immunology Study Section[TTT]


ADMINISTERING_IC: CA

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Cancer;Digestive Diseases;Immunization;Immunotherapy;Orphan Drug;Pancreatic Cancer;Rare Diseases;Vaccine Related

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: Project narrative Immunotherapy activates a patient's immune system to detect and kill cancer cells by recognizing the mutated proteins they express, called neoantigens. In this proposal, we investigate what these neoantigen look like to our immune system and how this information can be used to improve neoantigen-targeted cancer vaccines.

PI_NAMEs: HUFF, AMANDA L (contact)

PROGRAM_OFFICER_NAME: JAKOWLEW, SONIA B

PROJECT_TERMS: Address;Affinity;Alleles;Amino Acids;antigen binding;Antigen Presentation;Antigen Targeting;antigen-specific T cells;Antigens;Binding;Biological Assay;biophysical properties;Biophysics;Cancer Burden;cancer cell;cancer immunotherapy;Cancer Patient;cancer subtypes;cancer type;cancer vaccination;Cancer Vaccines;Cells;Characteristics;chemotherapy;Clinical;clinical application;clinical translation;Codon Nucleotides;cohort;Complex;computational pipelines;computational platform;Computer Models;Computer software;cytotoxic;Data;Data Set;design;Development;Epitopes;Excision;exome sequencing;Generations;Histocompatibility Antigens Class I;HLA Antigens;Human;Immune system;immunogenic;immunogenicity;Immunotherapy;improved;KRAS2 gene;KRASG12D;Libraries;Ligands;Malignant Neoplasms;Measurement;Mechanics;Modeling;Modification;Mutate;Mutation;neoantigen vaccine;neoantigens;novel;Operative Surgical Procedures;Pancreatic Ductal Adenocarcinoma;Patient-Focused Outcomes;Patients;Peptide Vaccines;Peptides;Peripheral Blood Mononuclear Cell;personalized cancer vaccines;Population;Privatization;Prognosis;protein aminoacid sequence;Proteins;rational design;refractory cancer;Resistance;response;Somatic Mutation;Structural Models;Structure;Survival Rate;T cell response;T-Cell Activation;T-Cell Receptor;T-Lymphocyte;Testing;Therapeutic;therapeutic vaccine;Treatment outcome;tumor;Tumor Antigens;vaccine candidate;Vaccines

PROJECT_TITLE: Structural modeling of neoantigen presentation for rational design of heteroclitic neoepitope vaccines


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Mental Health;Pediatric

ORG_CITY: CINCINNATI

ORG_NAME: CINCINNATI CHILDRENS HOSP MED CTR

ORG_STATE: OH

PHR: PROJECT NARRATIVE Sluggish cognitive tempo (SCT) symptoms, characterized by excessive daydreaming, slowed thinking, and mental confusion and fogginess, are distinct from other psychopathologies and associated with functional impairment. SCT symptoms are also strongly associated with internalizing symptoms and suicide risk, yet the absence of rigorous longitudinal research makes the directionality, mechanisms, and vulnerabilities of this association unknown. Findings from this study will advance theoretical models of SCT, position SCT within broader models of psychopathology, and provide avenues for targeted clinical assessment and treatment.

PI_NAMEs: BECKER, STEPHEN P (contact)

PROGRAM_OFFICER_NAME: PACHECO, JENNIFER LYNN

PROJECT_TERMS: Accounting;Adolescence;Adolescent;Advanced Development;Age;Anxiety;associated symptom;Attention deficit hyperactivity disorder;Behavioral;Behavioral inhibition;Behavioral Symptoms;Child;Clinical;Clinical assessments;Clinical Treatment;Cognitive;cognitive change;cognitive process;Communities;Complex;Confusion;Cross-Sectional Studies;Data;Daydreams;design;Development;Diagnostic;Dimensions;early adolescence;Early identification;emerging adult;Failure;Feeling suicidal;Functional impairment;Goals;informant;Link;Loneliness;Measures;Mediating;Mental Depression;Mental disorders;Methods;Modeling;National Institute of Mental Health;Outcome;Parents;Participant;Patient Self-Report;peer;Physiological;Positioning Attribute;prospective;Psychopathology;Punishment;recruit;Research;Research Domain Criteria;rumination;Sampling;School-Age Population;Self Efficacy;social;Social Environment;suicidal risk;Sympathetic Nervous System;symptomatology;Symptoms;System;teacher;Temperament;Testing;Theoretical model;Thinking;Time;Withdrawal;Youth

PROJECT_TITLE: Longitudinal Examination of Sluggish Cognitive Tempo and Internalizing Psychopathology in Adolescence


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: MILWAUKEE

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

ORG_STATE: WI

PHR: PROJECT NARRATIVE All cell types use changes in Ca2+ concentration to control their physiology, and regulated activation of intracellular Ca2+ channels plays a key role in cellular Ca2+ homeostasis. One important family of intracellular Ca2+-permeable channels - two-pore channels (TPCs) - reside within endosomes and lysosomes where they mediate Ca2+ release in response to the second messenger nicotinic acid adenine dinucleotide phosphate (NAADP). Here, our team has identified a long sought, key component in NAADP activation of TPCs, and we will define how activation of the TPC complex is physiologically regulated.

PI_NAMEs: MARCHANT, JONATHAN S (contact);PATEL, SANDIP ;SLAMA, JAMES T

PROGRAM_OFFICER_NAME: CHAO, CHIEN-CHUNG

PROJECT_TERMS: Ablation;ADP Ribose Transferases;ADP ribosylation;Affinity;analog;Architecture;Binding;Binding Sites;Cations;Cell Physiology;cell type;Cells;Cellular biology;Characteristics;Complex;Coronavirus;CRISPR/Cas technology;Cues;design;Disease;Endoplasmic Reticulum;Endosomes;Epitopes;Eukaryotic Cell;Event;Exhibits;Family;Family member;Functional disorder;Goals;high resolution imaging;Homeostasis;Homologous Gene;Human;imaging approach;insight;Ion Channel;Jupiter;Ligands;Link;live cell imaging;Lysosomes;Malignant Neoplasms;Maps;Mediating;member;Membrane;Microtubules;Molecular;Molecular Analysis;molecular domain;mutant;NAADP;Nature;non-alcoholic fatty liver disease;novel;novel therapeutic intervention;Nucleotides;Obesity;Parkinson Disease;Pathogenicity;Pathologic;Pathology;Pathway interactions;Patients;Permeability;Pharmaceutical Chemistry;pharmacologic;Phosphate-Binding Proteins;Physiological;Physiology;Play;Protein Isoforms;Proteins;Recombinants;Regulation;Research;Resolution;response;Role;Second Messenger Systems;Signal Pathway;Signal Transduction;Site;small molecule;Tankyrase;Testing;Therapeutic;tool;trafficking;tumor;Virus Diseases;Work

PROJECT_TITLE: Functional architecture of intracellular Ca2+ signals

STUDY_SECTION: MIST

STUDY_SECTION_NAME: Molecular and Integrative Signal Transduction Study Section[MIST]


NIH_SPENDING_CATS: American Indian or Alaska Native;Clinical Research;Diabetes;Genetics;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Machine Learning and Artificial Intelligence;Nutrition;Prevention;Racial and Ethnic Minority Health Research

ORG_CITY: NEW YORK

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: NARRATIVE Increasing evidence supports the role of arsenic exposure in diabetes development. We will evaluate novel epitranscriptomic mechanisms linking arsenic to diabetes and metabolic dysfunction in American Indian communities. This study can provide insight into novel pathways of arsenic related diabetes, identify prevention interventions, and inform recommendations for arsenic levels in water and food.

PI_NAMEs: KUPSCO, ALLISON ;MASON, CHRISTOPHER EDWARD;NAVAS-ACIEN, ANA  (contact)

PROGRAM_OFFICER_NAME: TYSON, FREDERICK L

PROJECT_TERMS: Adult;Affect;Albuminuria;American Indian community;American Indian Population;Arizona;Arsenic;Beta Cell;Biological;Blood;Blood Cells;blood glucose regulation;Cause of Death;Cellular Stress;Childhood;Clinical;Clinical Data;Clinical Markers;cohort;Data;design;Development;diabetes control;Diabetes Mellitus;diabetes mellitus therapy;Disputes;DNA Methylation;Elderly man;Environmental Pollutants;epigenomics;epitranscriptome;epitranscriptomics;Exposure to;fat mass and obesity-associated protein;Fingerprint;follow-up;Food;Functional disorder;Funding;Future;Gene Expression;Gene Expression Regulation;Genes;Genetic Transcription;Glucose;Glycosylated Hemoglobin;Heart;Hepatic;histone modification;Human;Immune response;Individual;Inflammation;Infrastructure;insight;Insulin;Insulin Resistance;Intervention;Investments;Joints;Life;Link;Lipids;Liver;Longitudinal Studies;Machine Learning;Measures;Mendelian randomization;Messenger RNA;Metabolic dysfunction;Metabolic Marker;Metabolic syndrome;Modification;multidimensional data;Names;Non-Insulin-Dependent Diabetes Mellitus;novel;Oklahoma;Oxidative Stress Induction;Participant;Pathogenesis;Pathway interactions;Phenotype;phenotypic data;Pilot Projects;Plasma;Play;Population;Prevalence;Preventive;preventive intervention;Process;Proteins;Reader;Recommendation;Research;Resources;response;Risk;RNA;RNA Stability;Role;Schedule;Serum;Severities;Shapes;South Dakota;statistical and machine learning;System;systemic inflammatory response;Testing;Tissues;toxicant;Transcript;Translations;United States;Visit;Water;Whole Blood

PROJECT_TITLE: The Epitranscriptome as a Novel Mechanism of Arsenic-Induced Diabetes.

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-PSE-F(02)]


NIH_SPENDING_CATS: Aging

ORG_CITY: ANN ARBOR

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PI_NAMEs: NUNEZ, GABRIEL  (contact)

PROGRAM_OFFICER_NAME: DONG, GANG

PROJECT_TERMS: Actins;Alzheimer's Disease;Atherosclerosis;Bacterial Toxins;Biochemical;biological systems;CASP1 gene;Development;Diabetes Mellitus;Disease;Event;Gouty Arthritis;Grant;IL18 gene;In Vitro;in vivo;Inflammasome;Inflammation;Inflammatory;insight;Interleukin-1 beta;Link;Mediating;Molecular;Motor;Natural Immunity;novel therapeutic intervention;Particulate Matter;Pathogenesis;Phosphorylation;Phosphotransferases;prevent;Proteins;response;Role;Signal Transduction;Silicosis;Stimulus

PROJECT_TITLE: Cryopyrin/NLRP3 Signaling in Inflammation and Innate Immunity

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


NIH_SPENDING_CATS: Biotechnology;Bipolar Disorder;Brain Disorders;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Mental Health;Mental Illness;Neurosciences;Prevention;Racial and Ethnic Minority Health Research;Schizophrenia;Serious Mental Illness;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: PROJECT NARRATIVE Serious mental illness, including schizophrenia and bipolar disorder are common, complex and debilitating psychiatric disorders that carry considerable morbidity, mortality, and personal and societal cost. The overarching goal of our proposal is to leverage multiscale genomics and other functional omics (gene expression and epigenome regulation) data and perform fine mapping to detect and validate causal variants, transcripts and regulatory sequences in serious mental illness. The proposed work will bridge the gap in understanding the link among the effects of risk variants on enhancer activity and transcript expression at the gene- and isoform-level, thus illuminating at least some of the molecular mechanisms that underlie serious mental illness and providing new targets for future therapeutic development.

PI_NAMEs: ROUSSOS, PANAGIOTIS  (contact)

PROGRAM_OFFICER_NAME: PEVSNER, JONATHAN ABRAM

PROJECT_TERMS: Affect;African ancestry;Biological;Biological Assay;Bipolar Disorder;Brain;Brain Diseases;brain tissue;Catalogs;causal variant;cell type;Cells;Clustered Regularly Interspaced Short Palindromic Repeats;Cohort Studies;Complex;Consensus;CRISPR interference;Data;Detection;Diagnostic;East Asian;Enhancers;Epigenetic Process;epigenome;epigenomics;European ancestry;excitatory neuron;Female;Future;Gene Expression;Genes;Genetic;Genetic Risk;genetic risk factor;genetic variant;Genome;genome editing;genome wide association study;genome-wide;genome-wide analysis;genomic locus;Genomics;Goals;Human;human data;human induced pluripotent stem cells;Induced pluripotent stem cell derived human neuron;inhibitory neuron;insight;Latino Population;Learning;Libraries;Link;Linkage Disequilibrium;male;Maps;Mediating;Mental disorders;Meta-Analysis;Methods;Modeling;Molecular;Morbidity - disease rate;mortality;multi-ethnic;Neurons;novel;novel strategies;Nucleic Acid Regulatory Sequences;Organ;Participant;Pathway interactions;Phenotype;Population;promoter;Protein Isoforms;psychiatric genomics;Quantitative Trait Loci;Regulation;Regulatory Element;Reporter;resilience;Risk;risk variant;Sampling;Schizophrenia;schizophrenia risk;severe mental illness;societal costs;South Asian;Specificity;statistics;Testing;therapeutic development;Tissues;trait;Transcript;transcriptomics;Untranslated RNA;Validation;Variant;Work

PROJECT_TITLE: Multiethnic genomic epigenomic and transcriptomic fine-mapping and functional validation analysis of schizophrenia and bipolar disorder risk loci


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Clinical Research;Genetics;Infectious Diseases;Malaria;Rare Diseases;Vector-Borne Diseases

ORG_CITY: SAN FRANCISCO

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: Project Narrative Improved malaria surveillance techniques that offer higher resolution information about local and regional malaria epidemiology will be necessary to more efficiently target malaria control interventions as we work toward malaria elimination. Parasite DNA and host antibodies present in biological samples collected as part of routine surveillance activities can offer useful information about malaria burden that is not captured by routine surveillance metrics – however, there is limited data on how to best apply molecular data to improve malaria surveillance. This project hopes to fill that gap by providing an understanding of which markers are most useful to enhance routine surveillance data at the community level by appropriately risk stratifying sub-national regions over space and time.

PI_NAMEs: BRIGGS, JESSICA  (contact)

PROGRAM_OFFICER_NAME: MCGUGAN, GLEN C

PROJECT_TERMS: Africa South of the Sahara;Age;Antibodies;Antibody Response;Award;Beds;Biological;Biometry;Biostatistical Methods;burden of illness;career;Catchment Area;Child;cohort;Collaborations;Communicable Diseases;Communities;Country;Cross-Sectional Studies;Data;deep sequencing;density;Diagnostic;Diagnostic tests;Disease Surveillance;DNA;Epidemiologic Methods;Epidemiologist;Epidemiology;experience;Funding;Generations;Genetic;Genomics;Goals;Health;Health care facility;Health Services Accessibility;Immunity;improved;Incidence;Individual;Infrastructure;Insecticides;Intervention;Laboratory Scientists;Link;Malaria;Measurement;Measures;Mentored Patient-Oriented Research Career Development Award;Mentorship;Methods;Microscopy;model building;Modeling;Molecular;Morbidity - disease rate;mortality;novel;Outcome;Parasites;Pathway interactions;Persons;Plasmodium falciparum;Population;Population Surveillance;Positioning Attribute;Prevalence;programs;Public Health;Public Health Practice;Randomized;Rapid diagnostics;Research;Research Priority;Resolution;response;Risk;risk stratification;Sampling;serological marker;Serology;Serology test;Site;skills;Statistical Models;surveillance data;Surveillance Methods;surveillance network;Surveys;Techniques;Testing;Time;Training;Translating;transmission process;Uganda;United States National Institutes of Health;Validation;vector control;Work

PROJECT_TITLE: Improving the accuracy of malaria surveillance with serology and parasite genetic data

STUDY_SECTION: MID

STUDY_SECTION_NAME: Microbiology and Infectious Diseases Advisory Committee[MID]


NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Data Science;Genetics;Human Genome;Mental Health;Mental Illness;Neurosciences;Prevention;Schizophrenia;Serious Mental Illness

ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: Recent studies have identified genetic risk for many psychiatric diseases, but the biological effects of many of these risk factors is currently unknown. This project will map these genetic risk elements to proteins, potentially identifying causal pathologies in these diseases.

PI_NAMEs: DEVLIN, BERNIE ;MACDONALD, MATTHEW L (contact);TRINIDAD, JONATHAN

PROJECT_TERMS: Adult;Affect;Anterior;Autopsy;Binding;Biological;Brain;Brain region;brain tissue;Bypass;causal variant;Cell model;cell type;Cells;Chromosome Mapping;cingulate cortex;Code;cohort;Communities;Data;Data Set;Development;Disease;disorder risk;DNA;Dorsal;Elements;experimental study;Genes;Genetic Risk;Genetic Transcription;Genetic Variation;Genome Mappings;genome wide association study;Genomics;glycosylation;Goals;Human;Individual;insight;Investigation;Knowledge;Lateral;learning strategy;Link;Maps;Mass Spectrum Analysis;Measures;Mental disorders;Messenger RNA;Methods;Modeling;Multiomic Data;multiple omics;neural;Neurons;novel;Pathology;Pathway interactions;Pattern;Phosphorylation;Post-Translational Protein Processing;Prefrontal Cortex;Protein Analysis;protein expression;Protein Isoforms;Proteins;proteogenomics;Proteome;Proteomics;Quantitative Trait Loci;Regulation;Resources;Ribosomes;Risk;Risk Factors;risk variant;RNA;Sample Size;Set protein;severe mental illness;Single Nucleotide Polymorphism;Site;SNP genotyping;Specificity;Testing;Tissues;tool;Transcript;transcriptome;transcriptome sequencing;transcriptomics;translational impact;Ubiquitination;Untranslated RNA;Variant

PROJECT_TITLE: Fine-Mapping Genome-Wide Associated Loci using Multi-omics Data to Identify Mechanisms Affecting Serious Mental Illness


ORG_CITY: CORAL GABLES

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

ORG_STATE: FL

PHR: PROJECT NARRATIVE Changes in physiologic pH, particularly acidotic signals, accompany a variety of biological processes and clinical pathologies. The goal of our proposed research program is to pursue an in-depth understanding of how these pH signals regulate the biology and pharmacology of G protein-coupled receptors (GPCRs), the largest and most therapeutically targeted class of transmembrane receptors in the human genome. The three program areas of this proposal will identify pH-selective agonists, inhibitors, modulators, drugs, and conformationally-selective nanobody probes for regulating and studying numerous human GPCRs.

PI_NAMEs: ISOM, DANIEL  (contact)

PROGRAM_OFFICER_NAME: LEWIS, MECHELLE MAYLEBEN

PROJECT_TITLE: pH regulation of cell surface receptors

STUDY_SECTION: MRAC

STUDY_SECTION_NAME: Maximizing Investigators' Research Award C Study Section[MRAC]


NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Genetics;Human Genome;Mental Health;Mental Illness;Neurosciences;Prevention;Serious Mental Illness

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: NARRATIVE This research project will advance human health by identifying risk genes and biological mechanisms that could affect individuals’ genetic vulnerability to a wide array of psychiatric disorders. Understanding of this shared genetic basis is central to decipher the etiologic and nosologic relationships of psychiatric disorders. The clinical and pharmaceutical impact of this study is also particularly high and will lead to the prioritization of genetic targets that could yield most broad and profound impact transcending traditional diagnostic boundaries.

PI_NAMEs: LEE, PHIL H. (contact)

PROJECT_TERMS: Affect;Alcohol dependence;analytical method;Anorexia Nervosa;Anxiety Disorders;Attention deficit hyperactivity disorder;autism spectrum disorder;base;bioinformatics resource;Biological;Biological Process;Bipolar Disorder;Brain;Cell Differentiation process;Cells;Characteristics;chromatin remodeling;Clinical;clinical diagnostics;Code;Collaborations;Communities;comorbidity;Computer software;Data;Data Analyses;Development;Diagnosis;Diagnostic;Disease;Etiology;functional genomics;Gene Expression;Gene set enrichment analysis;Genes;Genetic;genetic analysis;Genetic Diseases;Genetic Predisposition to Disease;Genetic Risk;Genetic study;genome resource;genome wide association study;genome-wide;genomic locus;Genomics;Gilles de la Tourette syndrome;Goals;Health;Heterogeneity;histone modification;Human;improved;Individual;insight;Knowledge;life span;Maps;Mental Depression;Mental disorders;method development;Methods;Molecular;nervous system development;neuropsychiatric disorder;novel;Pathogenicity;Pathway interactions;Persons;Pharmacologic Substance;Phenotype;Play;pleiotropism;Post-Traumatic Stress Disorders;Prevalence;Prevention;psychiatric genomics;Psychopathology;Public Health;Research;Research Personnel;Research Project Grants;Resolution;Resources;Risk;risk variant;Role;Schizophrenia;secondary analysis;sex;Shapes;simulation;Structure;success;Symptoms;Testing;Time;Transcend;Transcriptional Regulation;transcriptomics;Variant;Work

PROJECT_TITLE: Comprehensive analysis of genetic pleiotropy in eleven neuropsychiatric disorders

STUDY_SECTION: MNG

STUDY_SECTION_NAME: Molecular Neurogenetics Study Section[MNG]


ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Influenza;Lung;Pneumonia;Pneumonia and Influenza;Prevention

ORG_CITY: GAINESVILLE

ORG_DEPT: DENTISTRY

ORG_NAME: UNIVERSITY OF FLORIDA

PHR: NARRATIVE The proposal seeks to investigate the role of the influenza-induced pathogenic IL-17 response in the nasopharynx, leading to the transition of colonizing Streptococcus pneumoniae (Spn) into a pathogen. We hypothesize that the nasopharyngeal IL-17 response contributes to influenza-mediated hyper-inflammation and dysregulated barrier integrity in the nasopharynx, which allows colonizing Spn to outgrow and disseminate/invade to sterile tissues, establishing disease. The proposed research plan will lead to the development of an IL-17-based, novel interventional approach to mitigate inflammation and Spn pathogenesis during a co-infection with influenza virus.

PI_NAMEs: KHAN, NADEEM  (contact)

PROGRAM_OFFICER_NAME: UPADHYAY, MEENU MISHRA

PROJECT_TERMS: Adoptive Transfer;Adult;Age;Air;Antibodies;Bacteria;Blood;Blood Circulation;burden of illness;Cell Culture Techniques;Cells;Child;clinically significant;co-infection;Data;Development;Disease;Epithelial Cells;Epithelium;experimental study;Flow Cytometry;Future;Gene Expression Profile;Generations;Genetic Transcription;Human;IL17 gene;Immune;improved;In Vitro;in vivo;Inflammation;Inflammatory;Inflammatory Response;Influenza;Influenza A virus;influenzavirus;Intervention;Invaded;Knock-out;Knockout Mice;Liquid substance;loss of function;Lung;Lymphoid Cell;Mediating;Medical;Meningitis;Modeling;Mus;Nasopharynx;novel;Otitis Media;pathogen;Pathogenesis;pathogenic bacteria;Pathogenicity;Phenotype;Pneumococcal Infections;Pneumococcal vaccine;Pneumonia;Population;prevent;Prevention;receptor;Receptor Signaling;Regulation;Reporter;Research;Research Proposals;Resistance;respiratory;response;Risk Factors;Role;Sepsis;Serotyping;Signal Transduction;Sinusitis;Sorting;Source;Sterility;Streptococcus pneumoniae;Structure;success;Surface;Testing;therapy design;Tissues;transcription factor;transcriptome;vaccine access;Vaccines

PROJECT_TITLE: Pathogenic role of IL-17 response in Streptococcus pneumoniae nasopharyngeal pathogenesis during an influenza virus co-infection

STUDY_SECTION: HIBP

STUDY_SECTION_NAME: Host Interactions with Bacterial Pathogens Study Section[HIBP]


NIH_SPENDING_CATS: Antimicrobial Resistance;Clinical Research;Dissemination and Implementation Research;Infectious Diseases;Precision Medicine

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: PROJECT NARRATIVE Antibiotics are one of the most common interventions for critically ill patients; however, antibiotic resistance is on the rise and few new medications are currently in development. Immediate innovative solutions are needed to preserve and improve the effectiveness of existing drugs. We propose a series of studies to develop more accurate, individualized-dosing models for anti-pseudomonal beta-lactam antibiotics, designed to improve the treatment of infections and limit the development of bacterial resistance.

PI_NAMEs: BARRETO, ERIN FRAZEE (contact)

PROGRAM_OFFICER_NAME: SASTALLA, INKA I

PROJECT_TERMS: Achievement;Acute Renal Failure with Renal Papillary Necrosis;Adopted;Adult;Antibiotic Resistance;Antibiotic Therapy;Antibiotics;Bacterial Antibiotic Resistance;bacterial resistance;beta-Lactams;Bioinformatics;Biological Assay;Biological Markers;Blood specimen;Censuses;Cessation of life;Characteristics;Classification;Clinic;Clinical;clinical practice;clinical translation;cohort;Coupled;Creatinine;Critical Illness;design;Development;dissemination science;Dose;dose individualization;Drug Kinetics;effective therapy;Effectiveness;effectiveness/implementation trial;Electronics;enhancing factor;Equilibrium;Ethnography;Face;falls;Fluid Balance;Future;Goals;Health;high risk;implementation science;improved;improved outcome;individual variation;Infection;informatics infrastructure;Infusion procedures;innovation;insight;Intensive Care Units;Intervention;Interview;K-Series Research Career Programs;Kidney;Laboratories;Legal patent;Life;Marketing;Mentorship;Minimum Inhibitory Concentration measurement;Mission;Modeling;Monitor;multidisciplinary;mutant;National Institute of Allergy and Infectious Disease;neurotoxicity;novel;Organism;Outcome;Overdose;pathogen;Patient Care;patient oriented research;Patients;Pharmaceutical Preparations;pharmacokinetic model;Population;post gamma-globulins;predictive modeling;predictive tools;Predisposition;preservation;Prevention;prospective;Protocols documentation;Provider;Public Health;real world application;Records;Regimen;Renal function;Research;Research Personnel;Residual state;Resistance;Resistance development;Resources;Risk;Safety;Sampling;Series;Shock;Site;skills;standard care;success;Surveys;Testing;Time;tool;Toxic effect;Training;treatment duration;Treatment Failure;Treatment Protocols;United States;user-friendly;Vancomycin;Vertebral column;Work

PROJECT_TITLE: Beta-lactam individualization for critically ill patients

STUDY_SECTION_NAME: Microbiology and Infectious Diseases B Research Study Section[MID-B]


NIH_SPENDING_CATS: Antimicrobial Resistance;Autoimmune Disease;Biodefense and Related Countermeasures;Clinical Research;Digestive Diseases;Emerging Infectious Diseases;Infectious Diseases;Inflammatory Bowel Disease;Microbiome;Pediatric

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

PHR: PROJECT NARRATIVE C. difficile infections (CDI) and inflammatory bowel disease (IBD) are on the rise in children and commonly co- exist. This proposal seeks to better understand the determinants and sequelae of CDI and C. difficile colonization in children with IBD. Knowledge of these factors and their interactions can then be used in clinical settings to improve the treatment and outcomes associated with C. difficile in pediatric IBD patients.

PI_NAMEs: NICHOLSON, MARIBETH RUTH (contact)

PROGRAM_OFFICER_NAME: RANALLO, RYAN

PROJECT_TERMS: 16S ribosomal RNA sequencing;Abdominal Pain;Acute;adaptive immune response;advanced system;anti-toxin;antibiotic-associated diarrhea;Antibodies;Antibody titer measurement;Award;bacterial community;bile acid metabolism;Bile Acids;Biochemical;Biological;Biometry;Blood Transfusion;career;career development;Categories;Cessation of life;Charge;Child;Childhood;Chronic;Chronic Disease;Clinical;clinical care;Clinical Investigator;Clinical Research;Clostridium;Clostridium difficile;Communicable Diseases;Data;Development;Diagnosis;Diarrhea;Disease;Enrollment;Enzyme-Linked Immunosorbent Assay;experience;Feces;Flare;follow-up;Frequencies;Functional disorder;Future;Gastroenteritis;Gastrointestinal tract structure;Germination;Goals;Guidelines;gut microbiome;Home;Hospitalized Child;host microbiome;Hour;Immune;Immune response;Immunoglobulin A;Immunoglobulin G;Immunoglobulin M;Immunologics;improved;Incidence;Individual;Infection;Inflammation;Inflammatory Bowel Diseases;infliximab;Infusion procedures;insight;Knowledge;Laboratories;Leadership;Length of Stay;Mass Spectrum Analysis;Mediator;Mentors;Metabolic;Metabolism;metagenomic sequencing;microbial;microbiome analysis;Molecular;multidisciplinary;observational cohort study;Outcome;Outcome Assessment;Parenteral Nutrition;pathogen;Pathway interactions;Patients;Pediatric Hospitals;pediatric patients;Prevalence;Proline;prospective;Pseudomembranous Colitis;Recommendation;Recovery;Recurrent disease;Reporting;Research;Role;Sampling;Science;Serum;stool sample;Structure;Symptoms;Systems Biology;Techniques;Testing;Time;Toxin;Training;translational approach;treatment and outcome;Uncertainty;United States;Work;young adult

PROJECT_TITLE: Immune, Microbial, and Metabolic Factors that Impact Clostridioides difficile and Inflammatory Bowel Disease in Children


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Childhood Injury;Clinical Research;Genetics;Mental Health;Mental Illness;Neurosciences;Pediatric;Suicide

PHR: Project Narrative. This study will examine short-term or proximal biological risk profiles for suicidal behavior in stress response and inflammatory pathways, peripherally and in the brain, and examine familial and nonfamilial biological mechanisms underlying suicidal behavior in young adults at acute risk. This study will improve our understanding of familial and nonfamilial biological mechanisms for suicidal behavior to better separate long- term and short-term risk biological phenotypes, which will help guide risk detection and novel just-in-time approaches.

PI_NAMEs: MELHEM, NADINE M. (contact)

PROGRAM_OFFICER_NAME: WIJTENBURG, SARAH ANDREA

PROJECT_TERMS: Accident and Emergency department;Acute;Admission activity;Age;aged;Autoreceptors;Binding;Biological;biological adaptation to stress;Blood specimen;Brain;Cause of Death;Cells;Chronic;Chronic stress;Clinical;Clinical Data;clinical risk;Complex;cytochrome c;cytochrome c oxidase;cytokine;Detection;Event;Family history of;Feeling suicidal;follow-up;Frequencies;Funding;Future;Genes;glial activation;Hair;high risk;Hospitals;Hydrocortisone;hypothalamic-pituitary-adrenal axis;improved;indexing;Inflammation;Inflammatory;Insula of Reil;Interleukin-6;Knowledge;Kynurenine;Ligands;Longitudinal Studies;Machine Learning;Measures;Messenger RNA;Methods;Mitochondria;Mitochondrial DNA;mitochondrial dysfunction;Mood Disorders;Near-Infrared Spectroscopy;Neurocognitive;neuroinflammation;novel;offspring;Outpatients;oxidation;Parents;Pathogenesis;Pathway interactions;Patients;Peripheral;peripheral blood;Phenotype;Plasma;Positron-Emission Tomography;predicting response;Production;psychiatric inpatient;psychosocial;Recording of previous events;recruit;Reporting;resilience;Respiration;response;Risk;Risk Behaviors;Risk Factors;Salivary;Sampling;Serotonin;Severities;Site;social stress;Stress;suicidal;suicidal adolescent;suicidal behavior;suicidal risk;Suicide;Suicide attempt;Time;TNF gene;transmission process;Tryptophan;Universities;Work;young adult;Youth

PROJECT_TITLE: 1/2 Inflammation and Stress Response in Familial and Nonfamilial Youth Suicidal Behavior

STUDY_SECTION: NPAS

STUDY_SECTION_NAME: Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section[NPAS]


NIH_SPENDING_CATS: Biotechnology;Climate-Related Exposures and Conditions;Clinical Research;Clinical Trials and Supportive Activities;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Effects of Household Energy Combustion;Health Effects of Indoor Air Pollution;Lung;Prevention;Social Determinants of Health;Tobacco;Women's Health Research

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: PROJECT NARRATIVE This career development award is focused on developing the necessary skills, through mentored training, to independently investigate sex specific effects of air pollutants on respiratory health. This project will significantly enhance understanding of sex specific regulation of respiratory immune function in response to wood smoke exposure using in vivo and translational models with immediate human relevance. Increasing our understanding of differential respiratory immune responses in males and females to air pollutants will potentially identify new targets for preventative measure development or treatments against adverse responses and will decrease the burden on public health.

PI_NAMEs: REBULI, MEGHAN ELIZABETH (contact)

PROGRAM_OFFICER_NAME: NADADUR, SRIKANTH

PROJECT_TERMS: Address;Adverse effects;air filter;Air Pollutants;Air Pollution;airway immune response;airway obstruction;analysis pipeline;Area;asthma exacerbation;Bioenergetics;Biological Response Modifiers;Biology;Biomass;Breathing;bronchial epithelium;career;career development;Cell Culture Techniques;Cell Physiology;Cessation of life;Chemicals;Chronic Obstructive Pulmonary Disease;cigarette smoke;climate change;Clinical Research;Clinical Trials;Communication;cooking;Coughing;Data;defense response;design;Development;Disease;Educational workshop;Electronic cigarette;epidemiology study;Epithelial Cells;Epithelium;Estrogens;Exposure to;Extramural Activities;Female;Funding;Future;Gene Expression;Gene Proteins;Genetic;Genomics;global health;Goals;Gonadal Steroid Hormones;Grant;Health Policy;Heating;Hormonal;Hormone Receptor;hormone regulation;Host Defense;Human;Immune;immune function;Immune response;Immune system;immunoregulation;Impairment;In Vitro;in vivo;Inflammation;inflammatory marker;Inflammatory Response;Inhalation;Investigation;K-Series Research Career Programs;Knowledge;Laboratories;Link;Lung;Macrophage;Magnetic Resonance Imaging;male;Measures;Mediating;men;Mentors;Mentorship;Modification;novel;Ozone;particle;particle exposure;Particulate Matter;Physiological;Physiology;pollutant;Predisposition;premature;Prevention;Preventive measure;programs;Protein Analysis;Public Health;pulmonary function;Pulmonary Function Test/Forced Expiratory Volume 1;Pulmonary Inflammation;Randomized;receptor;Regulation;Reporting;Research;Research Personnel;respiratory;Respiratory Disease;respiratory health;Respiratory Mucosa;Respiratory physiology;response;Sampling;Severities;sex;Sex Bias;Sex Differences;skill acquisition;skills;Source;Spirometry;Sputum;Structure of mucous membrane of nose;Surface;Techniques;Testing;tobacco products;toxicant;Training;translational model;Viral;Wildfire;Woman;wood smoke;Work

PROJECT_TITLE: Impact of sex on respiratory response to wood smoke exposure


NIH_SPENDING_CATS: Autoimmune Disease;Brain Disorders;Genetics;Multiple Sclerosis;Neurodegenerative;Neurosciences

PHR: The immune system maintains a careful balance between protecting the body from infectious pathogens and the collateral damage that may arise as a result of too much inflammation, particularly autoimmunity. Interleukin (IL)-17 is an important mediator of immune inflammation and protects against various microorganisms. However, an overabundance of IL-17 signaling contributes to the pathogenesis of autoimmunity. Antibodies that block IL-17 are now approved for psoriasis, but this treatment may put patients at risk for developing infections. Although we know quite a bit about which cells make IL-17, the molecular process of IL-17 signaling through its receptor is poorly defined. This proposal focuses on how the regulation of IL-17-driven mRNA expression occurs at a molecular level and how this serves to control autoimmune pathology.

PI_NAMEs: GAFFEN, SARAH L (contact)

PROGRAM_OFFICER_NAME: GUERAU, MIREIA

PROJECT_TERMS: Address;Antibodies;Attention;Autoimmune;Autoimmune Diseases;Autoimmunity;Binding;Biological;Biological Markers;Biological Models;Biological Response Modifiers;Blocking Antibodies;Bone Marrow;CCAAT-Enhancer-Binding Proteins;Cell Cycle Kinetics;cell type;Cells;Chimera organism;clinical efficacy;Data;Development;Diabetes Mellitus;Diagnostic;Disease;Drug Targeting;Epithelium;Equilibrium;Evaluation;Event;Exhibits;Experimental Autoimmune Encephalomyelitis;Foundations;Gene Expression;Genes;Genetic Transcription;Glomerulonephritis;Goals;IL17 gene;Immune response;Immune system;immunopathology;Impairment;in vivo;Infection;Inflammation;Inflammatory;interest;Interleukin-6;Interleukins;LCN2 gene;Lead;Link;Lymphocyte;Mediating;Mediator;member;Mesenchymal;Messenger RNA;microorganism;Modeling;Molecular;mRNA Expression;mRNA Stability;mRNA Translation;Multiple Sclerosis;Mus;novel;pathogen;Pathogenesis;Pathogenicity;Pathologic;Pathology;Pathway interactions;Patients;posttranscriptional;pre-clinical;Process;Production;Protein Family;Proteins;Psoriasis;receptor;Refractory;Regulation;Resistance;Risk;RNA-Binding Proteins;Role;Signal Induction;Signal Transduction;Signal Transduction Induction;Signaling Molecule;System;T-Lymphocyte;Therapeutic;therapeutic target;Thermogenesis;Tissues;Transcript;transcription factor;Translations;γδ T cells

PROJECT_TITLE: Molecular Mechanisms of IL-17-dependent autoimmune signaling

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IMM-H(02)]


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Osteoporosis

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Osteoclasts are critical cells for resorbing bone under homeostatic conditions but that also contribute to pathogenic bone loss under inflammatory conditions. Regulation of osteoclast maturation by externally- triggered metabolic switching may represent an important avenue for disease mitigation that require further study.

PI_NAMEs: CHOI, YONGWON  (contact)

PROGRAM_OFFICER_NAME: CHEN, FAYE H

PROJECT_TERMS: Affect;Biological;Biological Assay;bone;bone loss;bone resorbing activity;Bone Resorption;bone strength;Cell Surface Receptors;Cells;clinically relevant;Colitis;Complex;Coupled;Data;dextran sulfate sodium induced colitis;Disease;DLG4 gene;Enzymes;experimental study;Future;Genetic Transcription;Glycolysis;Homeostasis;Human;Immunoglobulins;Inflammation;Inflammatory;inflammatory bone loss;inhibitor;JAK2 gene;Link;Mass Spectrum Analysis;Mediating;member;Metabolic;Metabolism;Mind;Modeling;Modification;Molecular;Mus;mutant;Myelogenous;Nature;novel;Osteoblasts;Osteoclasts;Osteogenesis;Pathogenicity;Pathway interactions;Patients;Phenotype;Phosphorylation;Phosphotransferases;Polyubiquitination;prevent;Process;Pyruvate Kinase;Regulation;Role;Scaffolding Protein;Signal Pathway;Signal Transduction;small molecule;SRC gene;src-Family Kinases;Testing;Therapeutic;TRAF6 gene;Validation

PROJECT_TITLE: IgSF11 Signaling Controls Osteoclast Maturation and Pathogenic Bone Loss

STUDY_SECTION: SBDD

STUDY_SECTION_NAME: Skeletal Biology Development and Disease Study Section[SBDD]


NIH_SPENDING_CATS: Biotechnology;Gene Therapy;Genetics

ORG_CITY: RICHMOND

ORG_DEPT: PHYSIOLOGY

ORG_NAME: VIRGINIA COMMONWEALTH UNIVERSITY

ORG_STATE: VA

PHR: PROJECT NARRATIVE This work will provide insights into the molecular mechanism by which AAV Rep proteins mediate site-specific integration and genome packaging. A complete understanding of this process is crucial to improve the current AAV based gene therapy vectors, generate vectors with novel specificities and with higher capacities.

PI_NAMEs: ESCALANTE, CARLOS R (contact)

PROGRAM_OFFICER_NAME: SAKALIAN, MICHAEL

PROJECT_TERMS: Binding;Binding Sites;Biochemical;Biological Assay;Biophysics;Capsid;Complex;Coupled;Cryoelectron Microscopy;Data;Dependovirus;DNA;DNA Binding;DNA Binding Domain;DNA biosynthesis;endonuclease;Esterification;Event;experimental study;Family;Funding;gene therapy;Gene Transduction Agent;Generations;Genetic Conjugation;Genome;Goals;helicase;Human Genome;improved;in vivo;insight;integration site;Kinetics;Length;Life;Life Cycle Stages;Mediating;melting;Methodology;Methods;Molecular;Nature;novel;Organism;particle;Phase;Play;Process;Property;Proteins;Reaction;reconstruction;Replication Origin;Resolution;Role;Single-Stranded DNA;Site;site-specific integration;Specificity;stem;stoichiometry;structural biology;structural determinants;Structure;System;Testing;Time;Transcriptional Regulation;Transgenes;vector;Viral Packaging;Virus;Work;X-Ray Crystallography

PROJECT_TITLE: Structural and Mechanistic Insights into AAV Rep Mediated Site-Specific Integration and Packaging

STUDY_SECTION: MSFC

STUDY_SECTION_NAME: Macromolecular Structure and Function C Study Section[MSFC]


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Biotechnology;Clinical Research;Emerging Infectious Diseases;Immunization;Immunotherapy;Infectious Diseases;Prevention

ORG_CITY: CHICAGO

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: NARRATIVE Antibiotic-resistant Staphylococcus aureus (MRSA) persistently colonize humans, which represents the key risk factor for community- and hospital-acquired infections with poor clinical outcomes. Capitalizing on new insights into S. aureus immune evasion, this proposal combines the skills of three investigators to generate human monoclonal antibodies that neutralize staphylococcal protein A (SpA), resist bacterial interference with antibody effector functions and promote opsonophagocytic killing of MRSA. Preclinical testing will identify antibodies with product profiles of 1) promoting broad spectrum antibody responses against MRSA, 2) clearing S. aureus from colonized individuals, 3) inducing persistent immunity to colonization and invasive disease, and 4) improving the outcome of MRSA bloodstream infections.

PI_NAMEs: MISSIAKAS, DOMINIQUE M. (contact);WANG, LAI-XI

PROGRAM_OFFICER_NAME: XU, ZUOYU

PROJECT_TERMS: American;Amino Acid Substitution;Animal Experiments;Antibiotic Resistance;Antibiotic Therapy;Antibiotics;Antibodies;Antibody Response;Antibody Suppression;Antibody Therapy;B Cell Proliferation;B-Cell Activation;B-Cell Antigen Receptor;B-Lymphocytes;Bacteria;Bacterial Interference;Binding;Blood;Clinical;Communities;community-level factor;Complement 1q;crosslink;Cultured Cells;Disease;Engineering;Excision;Gastrointestinal tract structure;Generations;Genus staphylococcus;Glycoengineering;glycosylation;Half-Life;Hospitals;Human;Human Engineering;human monoclonal antibodies;IgG1;Immune;Immune Evasion;Immunity;Immunoglobulin binding proteins;Immunoglobulin G;Immunoglobulin Idiotypes;Immunoglobulin M;Immunoglobulins;Immunotherapeutic agent;improved outcome;in vivo;Individual;Infection;insight;intravenous administration;Ligands;methicillin resistant Staphylococcus aureus;methicillin susceptible Staphylococcus aureus;Monoclonal Antibodies;Morbidity - disease rate;mortality;Mucous Membrane;Mus;Nasopharynx;neutralizing monoclonal antibodies;Nosocomial Infections;novel therapeutics;Outcome;Patient Admission;Plasma;Pre-Clinical Model;Preclinical Testing;prevent;Production;Proteins;Recurrence;Recurrent disease;Relapse;Reporting;research clinical testing;Research Personnel;Resistance;Risk Factors;Sepsis;Serum;skills;standard of care;Staphylococcal Protein A;Staphylococcus aureus;Staphylococcus aureus infection;Superantigens;Surface Antigens;Testing;Tissues;Treatment Failure;vaccine development;Variant

PROJECT_TITLE: Antibody therapy of MRSA colonization and infection

STUDY_SECTION_NAME: Immunity and Host Defense Study Section[IHD]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Bioengineering;Biomedical Imaging;Brain Disorders;Clinical Research;Dementia;Neurodegenerative;Neurosciences;Prevention

ORG_CITY: KANSAS CITY

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: UNIVERSITY OF KANSAS MEDICAL CENTER

ORG_STATE: KS

PHR: Project Narrative Statistical methods used in agreement studies contain fundamental flaws that hinder the complete development and understanding of biomarkers and diagnostic tests. As we have entered into an era where neuroimaging biomarkers are warranted for use in the diagnostic strategy of Alzheimer’s disease, these statistical methods have never been more important. This project develops a novel statistical methodology for evaluating inter- and intra-rater agreement upon which diagnostic tests and biomarkers are evaluated, and, in doing so, will identify clinical, provider and neuroimaging features important for obtaining an Alzheimer’s disease diagnosis.

PI_NAMEs: MCKENZIE, KATELYN A (contact)

PROGRAM_OFFICER_NAME: LUO, YUAN

PROJECT_TERMS: Adopted;Affect;Agreement;Algorithms;Alzheimer disease prevention;Alzheimer's Disease;Alzheimer's disease diagnosis;Alzheimer's disease model;Alzheimer’s disease biomarker;Award;base;Biological Markers;biomarker development;biomarker performance;Brain imaging;career;Characteristics;Clinical;Clinical Research;clinical training;Communities;Complex;Data;Data Collection;Data Set;Dementia;Dependence;design;Development;Diagnosis;Diagnostic;diagnostic biomarker;diagnostic strategy;Diagnostic tests;Disease;Disease Progression;Doctor of Philosophy;Enrollment;Environment;Evaluation;evaluation/testing;Exercise;Experimental Designs;flexibility;Foundations;Funding;Future;Goals;Growth;Histologic;Image;imaging biomarker;improved;in silico;Literature;Measures;Medical;Medicine;Methodology;Methods;Modeling;neuroimaging;neuroimaging marker;novel;novel diagnostics;novel marker;Physicians;pre-doctoral;predictive modeling;Prevalence;Prevention program;Probability;programs;Provider;Recommendation;recruit;Research;Research Design;Research Training;Risk Adjustment;Risk Factors;Sampling;Science;Sensitivity and Specificity;simulation;Source;Statistical Methods;success;Testing;tool;Training;United States National Institutes of Health

PROJECT_TITLE: Statistical developments for biomarker and diagnostic test evaluation with applications to Alzheimer's disease


NIH_SPENDING_CATS: Aging;Arthritis;Bioengineering;Biotechnology;Genetics;Human Genome;Osteoarthritis;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

PHR: PROJECT NARRATIVE Osteoarthritis (OA) is the most common joint disorder in the United States, but the mechanisms leading to OA are still unclear. To better understand the influence of genetic and environmental factors on OA pathogenesis, this research will use a large panel of differentiated human chondrocytes to identify inter-individual variation in gene expression and epigenetic responses to biomechanical strain treatments that induce OA phenotypes. This work will yield insight into the genetic basis of how biomechanical stress contributes to human OA and may inform efforts to screen for and treat this disorder.

PI_NAMEs: HUNG, ANTHONY  (contact)

PROGRAM_OFFICER_NAME: WILLIAMS, JOHN

PROJECT_TERMS: Abbreviations;Accounting;Affect;arthropathies;articular cartilage;Biochemical;Biological;Biology;Biomechanics;Bone structure;cartilage cell;Cell Culture Techniques;Cell Line;Cells;Chondrocytes;Chromatin;Chronic;Complex;Data;Degenerative polyarthritis;Development;disability;Disease;Disease Progression;Disparity;DNA Methylation;Environmental Risk Factor;Epigenetic Process;experimental study;gene environment interaction;Gene Expression;Gene Expression Profile;Gene Expression Regulation;Genes;Genetic;genetic association;Genetic Transcription;Genetic Variation;genome wide association study;genomic locus;Genomics;Genotype-Tissue Expression Project;Health;Heritability;Heterogeneity;Homeostasis;Human;human induced pluripotent stem cells;improved;In Vitro;in vitro Model;Individual;Individual Differences;induced pluripotent stem cell;insight;inter-individual variation;joint inflammation;joint loading;Joints;Link;Maps;Measures;mechanical load;Mediating;Mentors;Methods;Modeling;molecular phenotype;Nature;Onset of illness;Pain;Pathogenesis;Pathway interactions;Pattern;Periodicity;Phenotype;Pilot Projects;Process;Publishing;Quantitative Trait Loci;Replacement Arthroplasty;Research;Resort;response;Risk;risk variant;Sampling;single-cell RNA sequencing;skills;Specificity;Stimulus;Stress;Structure;subchondral bone;System;Testing;Time;tissue culture;Tissue-Specific Gene Expression;Tissues;transcriptome sequencing;Trauma;Treatment Protocols;United States;Variant;Work

PROJECT_TITLE: Determing the genetic basis of responses to biomechanical strain in an in vitro model of osteoarthritis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F08-M(20)L]


ORG_CITY: OKLAHOMA CITY

ORG_NAME: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR

ORG_STATE: OK

PHR: Aging and obesity are the most significant risk factors for the development of type 2 diabetes and metabolic disease. In this proposal, we test the hypothesis that age-dependent changes in a key regulator of glucose metabolism leads to changes in adipocyte function that increase the risk of disease. Completion of this work will enhance our understanding of how adipocyte biology changes over the lifespan.

PI_NAMEs: OLSON, ANN LOUISE (contact)

PROGRAM_OFFICER_NAME: FU, YI-PING

PROJECT_TERMS: 6-Phosphofructo-2-kinase;6-Phosphofructokinase;Acceleration;adipocyte biology;adipocyte differentiation;Adipocytes;adipokines;adiponectin;Adipose tissue;Adolescence;Age;age related;age related changes;age-related disease;aged;Aging;anaerobic glycolysis;animal old age;Animals;Biological Assay;blood glucose regulation;Caloric Restriction;Catecholamines;Data;Development;diabetes risk;disorder risk;Down-Regulation;Enzymes;Excision;experimental study;Fasting;feeding;Fructose;Fructose-2,6-bisphosphatase;Functional disorder;Glucose;glucose metabolism;glucose production;glucose uptake;glucose-regulated proteins;GLUT 4 protein;Glycolysis;Goals;Grant;Growth;healthy aging;HK2 gene;Homeostasis;Hormones;Human;Insulin;insulin sensitivity;insulin signaling;Intervention;Knock-out;Laboratories;life span;lipid metabolism;Lipids;Lipolysis;Maintenance;Measurement;Mediating;Metabolic;Metabolic Diseases;Metabolism;Modeling;Molecular;Non-Insulin-Dependent Diabetes Mellitus;Obesity;Obesity associated disease;old mice;Oxidation-Reduction;Pathway interactions;Peptides;Phosphoric Monoester Hydrolases;Phosphotransferases;Physiological;Play;postnatal;Preparation;Prevalence;Production;protein expression;Protein Isoforms;Publishing;Pyruvate;Regulation;Research;Research Project Grants;Risk;Risk Factors;Role;Signal Transduction;SLC2A1 gene;Source;stem cells;Testing;Tissues;Up-Regulation;uptake;Weight Gain;Work

PROJECT_TITLE: Does age-dependent PFKFB3 down-regulation alter adipose tissue function

STUDY_SECTION: CMAD

STUDY_SECTION_NAME: Cellular Mechanisms in Aging and Development Study Section[CMAD]