ADMINISTERING_IC: LM

IC_NAME: NATIONAL LIBRARY OF MEDICINE

NIH_SPENDING_CATS: Bioengineering;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Data Science;Health Services;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Patient Safety

PHR: Narrative The project will yield a highly flexible and effective analytical method for reducing confounding bias in studies that utilize routine-care data to compare effects of medical or surgical treatments. This method will enable researchers to leverage a large amount of patient information recorded in the clinical notes and reports that are contained within electronic health records to adjust for differences in background risks of different comparison groups. Our proposal can improve the quality of evidence based on electronic healthcare data generated in the routine-care settings to better inform patient care and optimal prescribing.

PI_NAMEs: LIN, JOSHUA K (contact)

PROGRAM_OFFICER_NAME: REDDY, GOUTHAM

PROJECT_TERMS: Address;Algorithms;analytical method;care delivery;Clinical;Clinical Research;Code;Cohort Studies;Comparative Effectiveness Research;comparative effectiveness study;comparison control;comparison group;Complex;computerized;Confounding Factors (Epidemiology);Consumption;cost;Data;Data Set;Data Sources;Databases;disease prognosis;disorder risk;eHealth;electronic health database;electronic health information;Electronic Health Record;electronic health record system;Elements;Empirical Research;Ensure;Environment;Evaluation;evidence base;flexibility;Future;health care service utilization;Healthcare;Healthcare Systems;high dimensionality;improved;Influentials;innovation;Knowledge;Knowledge acquisition;Left;Link;Machine Learning;machine learning method;Manuals;Massachusetts;Maximum Likelihood Estimate;Medicaid;Medical;Medicare;Methods;Modeling;Names;Natural Language Processing;North Carolina;novel strategies;operation;Operative Surgical Procedures;Patient Care;Patient-Focused Outcomes;Patients;Pattern;Performance;Physicians;preservation;Probability;Property;Proxy;randomized trial;Randomized, Controlled Trials;Reporting;Research;Research Design;Research Personnel;research study;Risk;Risk Factors;routine care;safety study;scalable algorithms;Semantics;Severities;simulation;sound;Specific qualifier value;Stratification;Structure;Symptoms;System;Techniques;Testing;Texas;Text;Therapeutic;Time;tool;training data;treatment choice;Treatment outcome;unstructured data;Validation;Work

PROJECT_TITLE: Developing scalable algorithms to incorporate unstructured electronic health records for causal inference based on real-world data

STUDY_SECTION_NAME: Biomedical Computing and Health Informatics Study Section[BCHI]


ADMINISTERING_IC: AI

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Rare Diseases;Vector-Borne Diseases

ORG_CITY: SAINT LOUIS

ORG_COUNTRY: UNITED STATES

ORG_DEPT: PATHOLOGY

ORG_FIPS: US

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Project Narrative Arthropod-transmitted viruses belonging to the large Bunyavirales order (such as Oropouche virus (OROV), La Crosse virus (LACV), and Rift Valley fever virus (RVFV)) can cause significant disease outbreaks in humans throughout the world. Our proposed work will define critical host factors for virus entry and identify novel targets that will facilitate pan-bunyavirus therapeutic development. Recent outbreaks and the emerging nature of bunyaviruses due to climate change, coupled with a rising potential of misuse in the form of bioterrorism, underscore the importance of the proposed studies to global health.

PI_NAMEs: AMARASINGHE, GAYA K. (contact);HARTMAN, AMY L

PROGRAM_OFFICER_NAME: ALARCON, RODOLFO M

PROJECT_TERMS: Address;Affinity;Animals;arboviral disease;arthropod-borne;Atherosclerosis;Binding;Biochemical;Biochemistry;Biological;Biology;Bioterrorism;Birds;Brain;Brazil;Bunyavirales;Category A pathogen;Cell Line;Cells;chikungunya;Chikungunya fever;Childhood;climate change;Collaborations;Complement;Complex;Coupled;Culicidae;Data;Dengue;Dengue Fever;Disease;Disease Outbreaks;Disease Outcome;Distant;Drug or chemical Tissue Distribution;Emerging Communicable Diseases;Endocytosis;Epidemic;epidemic preparedness;Excision;Family;Family member;Fever;Frequencies;Genomics;global health;Glycoproteins;Health;Human;Human Biology;human disease;human pathogen;Immunology;In Vitro;in vivo;Infection;innovation;Insecta;Integration Host Factors;Kidney;Knowledge;La Crosse virus;LDL-Receptor Related Protein 1;Ligands;Lipoprotein Receptor;Liver;Low Density Lipoprotein Receptor;Low-Density Lipoproteins;Malignant Neoplasms;Mammals;member;Molecular;mouse model;Mus;National Institute of Allergy and Infectious Disease;Nature;Neurodegenerative Disorders;new therapeutic target;North America;novel;Oropouche virus;Orthobunyavirus;pandemic potential;pathogen;Pathogenesis;Peripheral;Pharmacotherapy;Play;prevent;Productivity;programs;Proteins;Proteomics;receptor;Receptor Cell;Reporting;Reptiles;Research Personnel;Rift Valley fever virus;Role;Route;Sequence Homology;South America;Spleen;structural biology;Structure;Taxonomy;Testing;Therapeutic;therapeutic development;Tissues;Tropism;United States;Vaccines;Validation;validation studies;vector tick;Viral;Viral Encephalitis;Viral Pathogenesis;viral transmission;virology;Virus;Virus Diseases;Virus Replication;virus tropism;Work

PROJECT_TITLE: Characterizing the role of LDL related receptor 1 (Lrp1) as host entry factor for multiple bunyaviruses

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IIDA-S(90)]


ADMINISTERING_IC: CA

ED_INST_TYPE: UNIVERSITY-WIDE

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Colorectal Cancer;Digestive Diseases;Genetics;Human Genome;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: BRONX

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

ORG_STATE: NY

PHR: Narrative The DNA mismatch repair system (MMR) is essential for maintaining the integrity of mammalian genomes and defects in MMR are the cause of the most prevalent cancer syndrome, Lynch syndrome (LS) that is characterized by the development of cancers in the colon, endometrium ovary and other tissues as well as in significant number of sporadic colorectal cancers in humans. We are studying genetically modified mouse lines and human LS patient derived xenograft tumors with mutations in MMR genes to determine the ability of MMR in intestinal stem cells to suppress tumor formation. The goal of our studies is to provide a better understanding of the cellular and molecular mechanisms that underlie MMR-deficient colorectal tumorigenesis and to investigate novel strategies for the prevention and treatment of colorectal cancers with MMR defects.

PI_NAMEs: EDELMANN, WINFRIED  (contact)

PROGRAM_OFFICER_NAME: GHOSH-JANJIGIAN, SHARMISTHA

PROJECT_TERMS: ABCB1 gene;Affect;Alleles;cancer stem cell;Cell Death;chemotherapeutic agent;Clinical;Code;colon cancer cell line;colon cancer patients;Colon Carcinoma;colon tumorigenesis;Colorectal Cancer;colorectal cancer treatment;Colorectal Neoplasms;Cytostatics;cytotoxic;Defect;Development;DNA;efficacy study;efficacy testing;Endometrium;Etiology;Failure;Frameshift Mutation;Gene Expression Profile;Gene Modified;Gene Mutation;gene repair;Genomics;Goals;Hereditary Nonpolyposis Colorectal Neoplasms;Human;Hypersensitivity;Intestinal Neoplasms;intestinal tumorigenesis;Intestines;Knock-in;KRAS2 gene;LGR5 gene;Malignant Neoplasms;mammalian genome;Mismatch Repair;Mismatch Repair Deficiency;Molecular;mouse model;mTOR inhibition;Mus;Mutation;neoplastic cell;novel;novel strategies;Oncogenes;Organoids;Ovary;oxidative DNA damage;Paneth Cells;Pathway interactions;patient derived xenograft model;Patients;Population;pre-clinical;Predisposition;Prevention;Prevention strategy;refractory cancer;repaired;Resistance;resistance mechanism;Resolution;response;Role;SDZ RAD;single-cell RNA sequencing;Sirolimus;Small Intestinal Neoplasm;stem cell biomarkers;stem cell niche;stem cell population;stem cells;Syndrome;System;Testing;Tissues;TP53 gene;treatment response;tumor;tumor growth;Tumor Suppressor Genes;Tumor Suppressor Proteins;tumor xenograft;tumorigenesis;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Analyzing the Hypersensitivity of MMR-deficient Colorectal Cancers to mTOR Inhibition and the Response of Cancer Stem Cells

STUDY_SECTION: CE

STUDY_SECTION_NAME: Cancer Etiology Study Section[CE]


NIH_SPENDING_CATS: Biotechnology;Cancer;Hematology;Immunization;Infectious Diseases;Lymphatic Research;Lymphoma;Neurosciences;Orphan Drug;Prevention;Rare Diseases;Vaccine Related

ORG_CITY: CORAL GABLES

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

ORG_STATE: FL

PHR: PROJECT NARRATIVE Human T cell leukemia virus type-1 (HTLV-1) is a human retrovirus that is the causative agent of a malignant T CD4+ cell lymphoproliferation referred to as Adult T cell leukemia/lymphoma (ATLL), as well as several inflammatory disorders with the most problematic being human myelopathy/tropical spastic paraparesis (HAM/TSP). Remarkable, while millions are affected worldwide, there is no effective vaccine or treatment options to prevent ATL or HAM/TSP afflicted individuals. We thus aim here, to develop a candidate vaccine to prevent and plausibly treat HTLV1-associated disease.

PI_NAMEs: BARBER, GLEN N. (contact)

PROGRAM_OFFICER_NAME: PERLOFF, MARJORIE

PROJECT_TERMS: Adult T-Cell Leukemia/Lymphoma;Affect;Africa;aged;Area;Attenuated;Australia;Binding;bZIP Domain;Caribbean region;CD4 Positive T Lymphocytes;Cell fusion;Cells;Clinical;Communities;Cytotoxic T-Lymphocytes;design;Development;Disease;efficacy testing;Evaluation;Exhibits;experience;Future;genetic regulatory protein;Giant Cells;Glycoproteins;Human;Human T-lymphotropic virus 1;Immune response;Immune system;Immunization;Immunocompetent;immunogenicity;In Vitro;in vivo;Individual;Infection;Inflammatory;insight;Japan;Knowledge;leukemia/lymphoma;Lymphoproliferative Disorders;Malignant - descriptor;Malignant Neoplasms;manufacture;Measures;Mediating;Middle East;mouse model;Mus;mutant;Nerve Tissue;Nervous System;neutralizing antibody;novel;novel vaccines;Oncolytic;Persons;phase I trial;Predisposition;prevent;Prevention;Production;Proliferating;Proteins;receptor;Reporting;Retroviridae;seropositive;South America;Spinal Cord Diseases;Symptoms;tax Gene Products;Taxes;Tertiary Protein Structure;therapeutic vaccine;transcription factor;Tropical Spastic Paraparesis;Tropism;United States;vaccine candidate;Vaccines;vector;vector-based vaccine;Vesicular stomatitis Indiana virus;Viral;Viral Proteins;Viral Vaccines

PROJECT_TITLE: Development of  A HTLV-1 Vaccine

STUDY_SECTION: TTT

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


NIH_SPENDING_CATS: Digestive Diseases;Emerging Infectious Diseases;Hepatitis;Infectious Diseases;Liver Disease

ORG_CITY: COLUMBUS

ORG_NAME: RESEARCH INST NATIONWIDE CHILDREN'S HOSP

ORG_STATE: OH

PHR: PROJECT NARRATIVE HEV is a leading cause of acute hepatitis worldwide and is able to persist in immunocompromised patients re- sulting in increased risk of severe liver diseases. The project will investigate the role of the viral ORF3 protein in the virus envelopment and exit in polarized hepatocyte culture and in a rat model. The study will provide novel insight into the mechanism of HEV infection and pathogenesis.

PI_NAMEs: FENG, ZONGDI  (contact);KAPOOR, AMIT

PROGRAM_OFFICER_NAME: PARK, EUN-CHUNG

PROJECT_TERMS: Acute Hepatitis;Apical;Bile fluid;Biliary;Biogenesis;Biology;Blood Circulation;Capsid;Cell Culture Techniques;Cell Line;Cell Membrane Permeability;Cell Polarity;Cells;Clinical;Complex;Data;Endosomes;Enteral;FDA approved;Feces;Goals;Hepatitis B;Hepatitis E virus;Hepatocyte;hepatoma cell;HepG2;Human;Immunocompromised Host;In Vitro;in vivo Model;Individual;Infection;Initiator Codon;insight;Knowledge;Life Cycle Stages;Liver;Liver diseases;Macaca;Mediating;Membrane;Modeling;Molecular;Morbidity - disease rate;Morphology;mortality;Multivesicular Body;Mus;mutant;Mutation;novel;Outcome;palmitoylation;particle;Play;Prevention;Process;Proteins;Publishing;rational design;Rattus;recruit;Recycling;Research;Risk;RNA Viruses;Role;Side;Sorting;Surface;Testing;trafficking;transmission process;Vaccines;vesicle transport;Viral;Viral Pathogenesis;Viremia;Virion;Virus;Virus Diseases;Work

PROJECT_TITLE: Mechanism for hepatitis E virus exit from polarized hepatocytes

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IDIA-S(02)]


ADMINISTERING_IC: TW

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: FOGARTY INTERNATIONAL CENTER

NIH_SPENDING_CATS: Genetics;HIV/AIDS;Human Genome

ORG_CITY: BALTIMORE

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

ORG_STATE: MD

PHR: Eastern Nigeria Research Ethics Training (ENRICH) Program Project Narrative  The Eastern Nigeria Research Ethics Training (ENRICH) Program is a collaborative research ethics training program to be implemented jointly by the University of Nigeria, Nsukka (UNN), NIH/FIC-funded Center for Bioethics and Research (CBR) and University of Maryland School of Medicine (UMSOM). The program will provide 40 master's degrees, two hundred short- and twenty-five medium-term trainings in research ethics training to faculty members, members of ethics committees and individuals who are identified as potential leaders in bioethics by their institutions in eastern Nigeria.

PI_NAMEs: ADEBAMOWO, CLEMENT ADEBAYO (contact);EZEOME, EMMANUEL ;OGUNDIRAN, TEMIDAYO OLUSADE

PROGRAM_OFFICER_NAME: SINA, BARBARA J

PROJECT_TERMS: Africa;Africa South of the Sahara;Artificial Intelligence;Awareness;Behavioral Sciences;Bioethics;Collaborations;Community Medicine;Congo;Country;COVID-19 pandemic;Data Science;Degree program;Development;Disease;Education;Emerging Communicable Diseases;Ensure;Epidemiology;Ethics;Ethics Committees;experience;Faculty;Funding;Future;Genomics;Ghana;Grant;Health;Health Technology;Individual;innovation;Institution;institutional capacity;International;Intramural Research Program;Kenya;Leadership;Malawi;Maryland;Master of Science;medical schools;member;Mozambique;Needs Assessment;Nigeria;Nigerian;nutrition;Occupations;pedagogy;Persons;Population;Privatization;programs;Public Health;Research;Research Ethics;Research Ethics Committees;Research Institute;Research Personnel;Research Project Grants;Resources;responsible research conduct;Rwanda;scale up;Science;Social Sciences;South Africa;student participation;Students;Teaching Hospitals;Training;Training Programs;Uganda;United States National Institutes of Health;Universities;wearable health device;Work


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Brain Disorders;Cocaine;Drug Abuse (NIDA only);Genetics;HIV/AIDS;Human Genome;Infectious Diseases;Neurodegenerative;Neurosciences;Opioid Misuse and Addiction;Opioids;Stimulant Use and Misuse;Substance Misuse

ORG_CITY: NEW YORK

ORG_DEPT: PSYCHIATRY

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: Little is known how HIV affects the brain in the era of combination antiretroviral therapy, and how drug abuse, including cocaine and opiates, could be detrimental to the HIV infected brain. Our project, using human tissues from the Manhattan HIV Brain Bank, will explore gene expression programs in single brain cells and neural circuits of the HIV infected brain in the context of opiate or cocaine abuse.

PI_NAMEs: AKBARIAN, SCHAHRAM  (contact);MORGELLO, SUSAN

PROGRAM_OFFICER_NAME: SATTERLEE, JOHN S

PROJECT_TERMS: 3-Dimensional;addiction;Affect;antiretroviral therapy;Autopsy;Brain;brain cell;brain tissue;case control;CD4 Positive T Lymphocytes;Cell Count;Cell Nucleus;cell type;Cells;Central Nervous System Diseases;Cessation of life;Chromatin;Chromosomes, Human, 6-12 and X;Chronic;Clinical;Clinical Data;Cocaine;Cocaine Abuse;cocaine exposure;cohort;comorbidity;Complex;Corpus striatum structure;Data;Diagnosis;Diagnostic;Disease;DNA;Documentation;Drug abuse;drug of abuse;DSM-V;Elements;Epidemic;epigenome;experimental study;Exposure to;Freezing;Funding;Gene Expression;Genetic Transcription;Genome;genome-wide;genomic data;genomic locus;Genomics;Goals;Hi-C;high dimensionality;High Prevalence;high risk;HIV;HIV Genome;HIV Infections;HIV-associated neurocognitive disorder;HIV/AIDS;Human;human tissue;Individual;innovation;insight;Interview;Link;Maps;Microglia;Midbrain structure;Molecular Conformation;Monitor;motor disorder;National Institute of Drug Abuse;Neostriatum;neural;neural circuit;neuroAIDS;Neuroanatomy;Neurobehavioral Manifestations;Neurobiology;Neurocognitive;neurogenomics;Neurologic;Neurologic Symptoms;Neurological status;Neurons;novel;Nuclear;Nuclear RNA;Opioid;opioid abuse;opioid exposure;Pathogenesis;Pathology;Pattern;Peripheral;Persons;Plasma;Population;Prefrontal Cortex;Process;programs;prospective;Recording of previous events;Resources;RNA;RNA Probes;single nucleus RNA-sequencing;Site;Sorting;Statistical Data Interpretation;Structure;Substance abuse problem;Substance Use Disorder;Substantia nigra structure;Syndrome;therapy adherence;Toxicology;Transcript;transcriptome;transcriptome sequencing;transcriptomic profiling;transcriptomics;Urine;Viral;Virus Latency

PROJECT_TITLE: Single nuclei transcriptome profiling in addiction circuitry of the HIV+ brain


ADMINISTERING_IC: GM

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Bioengineering;Genetics

ORG_CITY: CAMBRIDGE

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

ORG_STATE: MA

PHR: Project narrative Enhancer-promoter interactions are fundamental regulatory elements warranting time and space-specific transcription regulation. This research proposal will (1) establish an experimental platform to study the dynamics of enhancer-promoter interactions and to perform mechanistic and functional studies in a prototype gene during neuronal differentiation. Then, (2) generalize genome-wide the mechanistic results.

PI_NAMEs: GABRIELE, MICHELE  (contact)

PROGRAM_OFFICER_NAME: JONES, LATAISIA CHERIE

PROJECT_TERMS: 3-Dimensional;Acute;Address;Advisory Committees;Bioinformatics;Biological;Biological Models;Biomedical Engineering;Cancer Etiology;Cell Differentiation process;cell fixing;Cells;Chromatin;Chromatin Loop;chromosome conformation capture;Computer Models;Consensus;Dedications;Defect;Development;developmental disease;Disease;Distal;Educational process of instructing;Enhancers;equity, diversity, and inclusion;Experimental Designs;FOXG1B gene;Gene Activation;Gene Expression;gene induction;Genes;Genetic Transcription;genome editing;genome-wide;Genomic approach;Goals;histone modification;Histones;image processing;imaging system;improved;insight;Knowledge;Label;Lead;live cell imaging;Maintenance;Malignant Neoplasms;Measures;Mentors;Methodology;Methods;Modeling;Molecular Conformation;Mouse Embryonic Stem Cells;Neuronal Differentiation;Neurons;Outcome;outreach;Pathologic;Pathology;Phase;Physical condensation;Physiological;Physiology;Play;pluripotency;Polymers;Population;Principal Investigator;promoter;Proteins;prototype;Regulation;Regulatory Element;Reporting;Research;Research Personnel;Research Proposals;Resolution;Role;simulation;single cell analysis;single cell genomics;skills;spatiotemporal;Structure;success;Techniques;temporal measurement;Testing;Time;Tissues;Training;Transcription Initiation Site;Transcriptional Activation;Transcriptional Regulation;ultra high resolution;Visualization;Work;Writing

PROJECT_TITLE: Dissecting enhancer-promoter looping and gene induction dynamics in differentiation


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

ORG_CITY: MILWAUKEE

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

ORG_STATE: WI

PHR: Abnormal lipid metabolisms are often associated with inappropriate activation of immune cells such as macrophages, leading to a disease called atherosclerosis. Atherosclerosis is the most common cause of death and this project seeks to identify and characterize the mechanisms that link aberrant lipid metabolisms to atherosclerosis. Identification of the novel molecular mechanisms offers new sites of therapeutic interventions.

PI_NAMEs: CUI, WEIGUO ;SILVERSTEIN, ROY L (contact)

PROGRAM_OFFICER_NAME: CHEN, JUE

PROJECT_TERMS: Ablation;Adopted;Atherosclerosis;Attenuated;Binding;Biochemical;Bone Marrow;Cause of Death;CD36 gene;Cells;Collaborations;Coupled;Data;Development;Diet;Disease;Dynamin;Dyslipidemias;fatty acid metabolism;fatty acid oxidation;Fatty Acids;Feedback;Foam Cells;Gene Modified;Genetic;Genetic Transcription;Goals;Immune;immune activation;Immunologics;in vivo;Infusion procedures;inhibitor;Interleukin-6;Intracellular Accumulation of Lipids;Knowledge;Ligands;Link;lipid metabolism;Lipids;Macrophage;Macrophage Activation;Mediating;metabolic abnormality assessment;Metabolic Pathway;metabolic profile;Mitochondria;mitochondrial dysfunction;Modeling;Molecular;monocyte;Morphology;Mus;new therapeutic target;novel;novel therapeutic intervention;Nuclear Hormone Receptors;Oxidative Phosphorylation;Oxidative Stress;oxidized low density lipoprotein;Pathway interactions;pharmacologic;Phenotype;Phosphotransferases;PIM1 gene;Play;PPAR gamma;Process;Production;programs;Protein-Serine-Threonine Kinases;Proteins;Publishing;Resistance;response;Role;scavenger receptor;Serine;Signal Transduction;Site;Stat3 protein;Surface;Testing;Therapeutic Intervention;transcription factor;Up-Regulation;uptake

PROJECT_TITLE: Pim1 kinase coordinates PPAR gamma pathway and mitochondrial function to mediate pro-atherogenic responses in macrophages

STUDY_SECTION: AICS

STUDY_SECTION_NAME: Atherosclerosis and Inflammation of the Cardiovascular System Study Section[AICS]


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging

ORG_CITY: SAN FRANCISCO

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: Project narrative: The goal of this project is to develop a chemical strategy to measure the labile iron pool in vivo with PET. Building on our preliminary data with 18F-TRX, a first in class, Fe(II) activated radiotracer, we will synthesize and evaluate in vitro and in vivo a series of Fe(II) activated transcyclooctene and 18F-tetrazine click partners that we expect to improve measurements of LIP by reducing the background signal from unreacted TRX and/or more completely reacting with high LIP levels in diseased tissues.

PI_NAMEs: EVANS, MICHAEL JOHN (contact);RENSLO, ADAM R

PROGRAM_OFFICER_NAME: ATANASIJEVIC, TATJANA

PROJECT_TERMS: Abdomen;Acute;analog;Animal Model;Animals;Anti-malarials;antimicrobial;Artemisinins;Benchmarking;Biodistribution;Biological;cancer type;Cardiovascular Diseases;catalyst;Cell Line;Cells;Chemicals;Child;Chloroquine;Clinical;Clinical Trials;clinically relevant;cohort;Coupling;Data;design;Desmoplastic;Development;Discipline of Nuclear Medicine;Disease;Dose;Dose Limiting;Drug Kinetics;Exhibits;Generations;Genetic;Glioma;Goals;Half-Life;Hepatobiliary;Human;Image;image translation;imaging modality;imaging study;ImmunoPET;improved;In Vitro;in vivo;Inductively Coupled Plasma Mass Spectrometry;inhibitor;Injections;innovation;insight;Iron;iron metabolism;Knowledge;KRASG12D;Libraries;Liver;liver cancer model;Lysosomes;Malignant Neoplasms;Measurement;Measures;Modeling;mouse model;Multifocal Lesion;Mus;Neurodegenerative Disorders;Normal Cell;Normal tissue morphology;Nutrient;optical imaging;Pancreas;pancreatic cancer model;Pancreatic Ductal Adenocarcinoma;Pathology;PET/CT scan;Pharmaceutical Preparations;pharmacologic;Pharmacology;Physiology;Positron-Emission Tomography;Prodrugs;protein crosslink;prototype;Radioisotopes;radioligand;radiotracer;Reaction;Reagent;Refractory;Regulation;response;Role;sensor;Series;Serum;Signal Transduction;small molecule;Starvation;subcutaneous;success;targeted treatment;Techniques;Testing;Therapeutic;Tissues;Toxic effect;Tracer;tumor;U251;uptake;virtual

PROJECT_TITLE: Developing a pretargeting strategy to detect Fe(II) for nuclear medicine applications

STUDY_SECTION: IPCA

STUDY_SECTION_NAME: Imaging Probes and Contrast Agents Study Section[IPCA]


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Cervical Cancer;Clinical Research;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Immunotherapy;Infectious Diseases;Microbiome;Prevention;Racial and Ethnic Minority Health Research;Sexually Transmitted Infections;Social Determinants of Health;Women's Health Research

ORG_CITY: CLEVELAND

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

PHR: Project Narrative African American women living in the United States experience an undue higher burden of cervical cancer and a >2 times higher mortality rate than European American women. The resident microbiome has been implicated as important in the progression of many cancers but its role in cervical cancer is unclear. In this project we will study how the microbiome in African American women affects host immunity and the progression of the disease.

PI_NAMEs: AVRIL, STEFANIE ;BURGENER, ADAM  (contact)

PROGRAM_OFFICER_NAME: HOWCROFT, THOMAS K

PROJECT_TERMS: Acceleration;Accounting;Affect;African American;African American Women;African Women;American;Anaerobic Bacteria;Arginine;Bacteria;Biological Markers;Biology;Butyrates;Cancer Burden;Cancer Etiology;cancer health disparity;cancer risk;carcinogenesis;carcinogenicity;Cells;Cervical;Cervical Intraepithelial Neoplasia;Cervix Neoplasms;Cessation of life;Classification;Clinic;Cohort Studies;Colposcopy;Communities;cost effective;Coupled;Data;Databases;Death Rate;Developing Countries;Disease;Disease Progression;Disease remission;Disparity;Disseminated Malignant Neoplasm;dysbiosis;Environment;Epithelium;European;experience;Female;female reproductive tract;Flow Cytometry;FRAP1 gene;Functional disorder;Gardnerella vaginalis;Gene Expression;Generations;Genes;Genitalia;health disparity;High Prevalence;high risk;HPV-High Risk;Human Papillomavirus;Immune;Immune checkpoint inhibitor;Immune response;Immunity;Immunology;Immunosuppression;improved;In Vitro;in vivo;Inflammation;Inflammatory;Infrastructure;Institution;Interleukin-6;Intervention;Lactobacillus;Limited Stage;Link;Malignant neoplasm of cervix uteri;Malignant Neoplasms;Measurement;Mediator;metabolomics;Metagenomics;metaproteomics;microbial;microbiome;microbiome research;microbiome therapeutics;microorganism;Mobiluncus;Molecular;Molecular Profiling;mouse model;Mucosal Immunity;Mucous Membrane;Mus;novel therapeutic intervention;Outcome;Pathogenesis;Pathology;Pathway interactions;Persons;Phenotype;Population;predictive marker;Preventive vaccine;Prevotella;Process;Propionates;prospective;Prospective Studies;Proteins;recruit;Regulatory T-Lymphocyte;Role;Sampling;single-cell RNA sequencing;Socioeconomic Status;survival disparity;Systems Biology;T-Lymphocyte;Techniques;The Cancer Genome Atlas;Tissues;TNF gene;Treatment outcome;Tryptophan;Tryptophan 2,3 Dioxygenase;tumor progression;tumor-immune system interactions;Uganda;United States;vaccine access;Vaccines;Vagina;vaginal microbiome;vaginal mucosa;Woman;women's outcomes

PROJECT_TITLE: The Microbiome and Mucosal Immunity in Cervical Cancer Disparities

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-OBT-Y(55)R]


NIH_SPENDING_CATS: Cancer;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Dissemination and Implementation Research;HPV and/or Cervical Cancer Vaccines;Health Services;Immunization;Infectious Diseases;Prevention;Primary Health Care;Sexually Transmitted Infections;Vaccine Related

ORG_CITY: LOS ANGELES

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: Narrative Human papillomavirus (HPV) causes enormous morbidity, yet despite a safe and effective HPV vaccine, adolescent HPV vaccination rates are low due to parental vaccine hesitancy, suboptimal clinician communication, and ineffective procedures within primary care practices. We have developed two potentially scalable implementation strategies to raise vaccination rates: one trains clinicians on optimal HPV vaccine communication while the other adds practice-based changes in HPV vaccine workflow processes; both have been found to be effective on a limited scale. We are partnering with 8 health systems and 72 practices to compare the effectiveness and cost-effectiveness of the two implementation strategies and to assess provider, practice, and health system factors relevant to their implementation; the ultimate goal is to develop two nationally scalable implementation strategies to raise HPV vaccination rates.

PI_NAMEs: SZILAGYI, PETER G (contact)

PROGRAM_OFFICER_NAME: CHOLLETTE, VERONICA

PROJECT_TERMS: 17 year old;Address;Adolescent;Adoption;American;arm;Cessation of life;Childhood;Clinical Nurse Specialists;collaborative care;Communication;compare effectiveness;cost;cost effective;cost effectiveness;design;Effectiveness;effectiveness evaluation;Eligibility Determination;Evaluation;Evidence based practice;Feedback;Goals;Health;health assessment;health organization;Health system;health training;Human Papilloma Virus Vaccination;Human Papilloma Virus Vaccine;Human Papilloma Virus-Related Malignant Neoplasm;Human Papillomavirus;implementation process;implementation science;implementation strategy;improved;interest;Learning;Logic;Maintenance;Malignant Neoplasms;Medical;Medical Care Costs;Methods;Modeling;Morbidity - disease rate;organizational readiness;Outcome;Parents;point of care;Population;Practical Robust Implementation and Sustainability Model;practice factors;prevent;primary care practice;primary outcome;Procedures;Process;Provider;provider communication;provider factors;Qualitative Methods;Randomized;Reach, Effectiveness, Adoption, Implementation, and Maintenance;Readiness;recruit;Research;scale up;secondary outcome;Series;Survey Methodology;System;Techniques;Telephone;Testing;Training;treatment as usual;uptake;Vaccination;vaccination outcome;vaccine acceptance;vaccine delivery;vaccine hesitancy;vaccine strategy;Vaccines

PROJECT_TITLE: The STOP-HPV Scale-Up Study

STUDY_SECTION: SIHH

STUDY_SECTION_NAME: Science of Implementation in Health and Healthcare Study Section[SIHH]


NIH_SPENDING_CATS: Biotechnology;Cardiovascular;Complementary and Integrative Health;Dietary Supplements;Heart Disease;Microbiome;Nutrition;Prevention

ORG_CITY: CHICAGO

ORG_DEPT: SURGERY

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE Cardiovascular disease is a leading cause of morbidity and mortality globally, and up to 50% of vascular procedures such as balloon angioplasty, stenting, and surgical bypass to treat cardiovascular disease fail due to restenosis from neointimal hyperplasia in the treated artery. There is a critical unmet need to develop novel therapies which reduce restenosis susceptibility and to understand their underlying mechanisms. This proposal seeks to establish a novel pathway linking prebiotic fiber, butyrate from microbial fermentation of fiber, activation of free fatty acid receptor 3 in peripheral arteries, and the arterial remodeling response that could be used to develop new diagnostic and therapeutic approaches for patients undergoing vascular surgery.

PI_NAMEs: HO, KAREN J. (contact)

PROJECT_TERMS: absorption;Agonist;Angioplasty;Antibiotic Therapy;Antibiotics;Arterial Injury;arterial remodeling;Arteries;Attenuated;attenuation;Bacteria;Balloon Angioplasty;Biological;Biological Assay;Biology;Blood Vessels;Butyrates;Bypass;Cardiovascular Diseases;Cause of Death;Cell Physiology;Cells;Complex;Cyclodextrins;Data;Development;Devices;Diet;Dietary Fiber;dietary manipulation;Encapsulated;Endothelial Cells;Endothelium;Environment;Family suidae;fecal transplantation;Fermentation;Fiber;Food;food science;Formulation;Genetic;Germ-Free;gut microbes;gut microbiota;host-microbe interactions;Hyperplasia;iliac artery;improved outcome;in vivo;in vivo evaluation;Inflammation;Inflammatory Response;Injury;innovation;Institution;Intestines;Knockout Mice;Knowledge;Ligands;Link;Mediating;Microbe;microbial;Microbiology;microbiota;Modeling;Molecular;Morbidity - disease rate;mortality;mortality risk;mouse model;Mus;Nonesterified Fatty Acids;novel;novel diagnostics;novel strategies;novel therapeutic intervention;novel therapeutics;Nutritional Science;Operative Surgical Procedures;Pathway interactions;Patients;Peripheral;Pharmaceutical Preparations;pharmacologic;phenomenological models;porcine model;prebiotics;Predisposition;prevent;Prevention therapy;Procedures;Process;Prodrugs;Production;Publications;receptor;Receptor Activation;Research;response;response to injury;restenosis;Rodent Model;Series;Small Interfering RNA;Smooth Muscle Myocytes;Stents;Supplementation;Surgical Injuries;Surgical Models;Testing;therapeutic development;Transgenic Mice;Translating;translational applications;Translations;tributyrin;vascular injury;Vascular Smooth Muscle;Volatile Fatty Acids;Work

PROJECT_TITLE: Targeting the Meta-organismal Butyrate Pathway to Prevent Arterial Restenosis after Vascular Surgery

STUDY_SECTION: SAT

STUDY_SECTION_NAME: Surgery, Anesthesiology and Trauma Study Section[SAT]


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Neurosciences;Pediatric;Substance Misuse;Underage Drinking

ORG_CITY: Huntington

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: MARSHALL UNIVERSITY

ORG_STATE: WV

PHR: PROJECT NARRATIVE Binge drinking accounts for the majority of alcohol consumed by adolescents in the US and occurs during a critical period of brain development. It is also associated with lasting cognitive impairment and increased likelihood of developing an alcohol use disorder later in life. This research is relevant to the NIH/NIAAA mission because it represents an innovative strategy centered on astrocyte-neuron interactions that will expand our understanding of the long-term effects of adolescent binge drinking and the contribution of non-neuronal cells.

PI_NAMEs: RISHER, MARY-LOUISE  (contact)

PROGRAM_OFFICER_NAME: CUI, CHANGHAI

PROJECT_TERMS: Acute;Adenosine;Adolescence;Adolescent;adolescent alcohol exposure;adolescent binge drinking;Adult;Affect;Agonist;alcohol exposure;alcohol use disorder;Alcohols;Astrocytes;Attenuated;Behavior;Behavioral;binge drinking;Brain;Central Nervous System;Chronic;Cognitive deficits;Communication;Coupling;critical developmental period;critical period;Data;Dendritic Spines;designer receptors exclusively activated by designer drugs;Development;Drug Exposure;Electrophysiology (science);Ethanol;Fright;Functional disorder;Future;Glutamates;Goals;High School Student;Hippocampus;Homeostasis;Impaired cognition;Impairment;Incidence;innovation;insight;Ions;Knowledge;Learning;Life;Link;Long-Term Effects;Mediating;Mediator;Memory;Memory impairment;Mission;Modeling;Molecular;National Institute on Alcohol Abuse and Alcoholism;Neuroglia;neuron loss;neuronal circuitry;Neurons;neurotransmission;novel;Output;Peripheral;Positioning Attribute;prevent;Prevention;Process;Rattus;Recording of previous events;Recovery;Regulation;Reporting;Research;Research Personnel;resilience;Short-Term Memory;Signal Transduction;Site;Slice;spatiotemporal;Structure;Synapses;Synaptic Cleft;synaptic function;Synaptic Transmission;Testing;underage drinking;United States National Institutes of Health

PROJECT_TITLE: Effects of adolescent ethanol exposure on astrocyte-neuronal crosstalk

STUDY_SECTION: AA

STUDY_SECTION_NAME: Neuroscience and Behavior Study Section[AA-4]


NIH_SPENDING_CATS: Bioengineering;Cancer;Clinical Research;Lung;Lung Cancer;Radiation Oncology;Rare Diseases

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: Public Health Relevance Statement: Photodynamic therapy (PDT), in combination with surgery, offers a potential locally curative treatment and has been demonstrated in clinical trials, including in malignant mesothelioma, to substantially prolong patient survival. In this translational project we will optimize singlet oxygen dosimetry instruments for direct quantitative measurements of the major cytotoxic agent (excited-state singlet oxygen) generated in PDT, which could significantly improve the accuracy and hence efficacy of this modality, both for this particular clinical application and more generally in other tumor sites. Being fiberoptic based, the technology will be suitable for implementation in any tumor site that is accessible to PDT (interstitial, endoscopic, intraoperative).

PI_NAMEs: HADFIELD, ROBERT HUGH;ZHU, TIMOTHY C. (contact)

PROGRAM_OFFICER_NAME: ANDERSON, AFROUZ AZARI

PROJECT_TERMS: Aminolevulinic Acid;attenuation;biophysical model;Calibration;Clinical;clinical application;Clinical Research;clinical translation;Clinical Trials;clinically relevant;Consumption;Coupled;curative treatments;cytotoxic;Cytotoxic agent;design;design and construction;Detection;detector;Development;diffuse reflectance spectroscopy;Dose;dosimetry;Feedback;Fiber Optics;fibrosarcoma;first-in-human;gallium arsenide;Generations;Goals;Growth;head-to-head comparison;Hematoxylin and Eosin Staining Method;improved;In Situ;in vivo;indexing;Indium;individual patient;instrument;interstitial;Lasers;Light;Location;luminescence;Malignant mesothelioma;Malignant Pleural Mesothelioma;Measurement;Measures;Mediating;Mesothelioma;minimally invasive;Modality;Modeling;Monitor;Mus;nanowire;Noise;novel;Operative Surgical Procedures;optical fiber;Optics;Outcome;Oxygen;Patients;Performance;performance tests;Pharmaceutical Preparations;phosphorescence;Photobleaching;photon-counting detector;Photons;Photosensitizing Agents;Phototherapy;Physiologic pulse;Pleural photodynamic therapy;Porfimer Sodium;pre-clinical;Pre-Clinical Model;preclinical evaluation;preclinical study;Property;prototype;public health relevance;PUVA Photochemotherapy;quantum;Radiation;Reaction;response;Signal Transduction;Singlet Oxygen;singlet state;Site;Stains;System;Techniques;Technology;Temperature;temporal measurement;Testing;Time;Tissues;Treatment Efficacy;tumor;Uncertainty

PROJECT_TITLE: Optimizing singlet oxygen dosimetry for photodynamic therapy (PDT)

STUDY_SECTION: IGIS

STUDY_SECTION_NAME: Imaging Guided Interventions and Surgery Study Section[IGIS]


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);Behavioral and Social Science;Bioengineering;Brain Disorders;Cardiovascular;Data Science;Dementia;Depression;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Machine Learning and Artificial Intelligence;Mental Health;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences;Physical Activity;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: BOSTON

ORG_NAME: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)

PHR: Project Narrative Green space or trees and natural vegetation can provide mental health benefits and possibly lower risk of neurodegenerative diseases such as Alzheimer’s disease and related dementias (ADRD); however, green space is often measured poorly in epidemiologic research. I propose to integrate high-resolution images from Google Street Views to derive ground-level objective measurements of green space into a diverse prospective cohort study using deep learning algorithms, mediation analysis and geographic mixtures. This research will enable unprecedented perspectives on exposures that drive ADRD and related cognitive decline risk, and will provide translational insights into potential interventions to optimize opportunities for ADRD prevention and reduce racial disparities in ADRD.

PI_NAMEs: PESCADOR JIMENEZ, MARCIA IXCHEL (contact)

PROGRAM_OFFICER_NAME: KWOK, RICHARD K

PROJECT_TERMS: Acceleration;Accounting;Adult;Affect;African American;African American population;Age;aged;Air Pollutants;Alzheimer's disease related dementia;Alzheimer's disease risk;Baltimore;Biological;Biometry;Black race;built environment;Cardiovascular Diseases;career;Chicago;Chinese;Cities;Clinical;cognitive function;cohort;comorbidity;Complex;County;Cross-Sectional Studies;Data;Data Sources;deep learning;deep learning algorithm;dementia risk;design;Diagnosis;dimension reduction;Disparity;economic impact;Environment;Environmental Hazards;Epidemiology;epidemiology study;ethnic minority;Ethnic Origin;Ethnic Population;Exposure to;Family;Funding;Geographic Factor;Geography;Goals;Green space;Health;Health Benefit;Healthcare Systems;healthy aging;high resolution imaging;Hispanic;Hispanic Populations;Hypertension;Image;Imagery;Impaired cognition;Incidence;indexing;Individual;innovation;insight;Intervention;Life Cycle Stages;Link;Literature;longitudinal analysis;Longitudinal Studies;Los Angeles;Measurement;Measures;Mediating;Mediation;Mediator;men;Mental Depression;Mental Health;Methodology;Methods;Minority;Multi-Ethnic Study of Atherosclerosis;multidimensional data;neurocognitive disorder;Neurodegenerative Disorders;new technology;New York;Noise;Not Hispanic or Latino;novel;older adult;Pathway interactions;Patients;Physical activity;physical inactivity;Plants;Poaceae;Population;Population Heterogeneity;Prevalence;Prevention;Prevention strategy;Prospective cohort;Prospective, cohort study;public health intervention;Questionnaires;Race;racial disparity;racial health disparity;racial minority;racial minority population;racial population;Research;Resolution;Risk;Risk Factors;Risk Reduction;Role;segmentation algorithm;skills;Social Environment;Social Impacts;Techniques;Time;Training;Trees;United States National Institutes of Health;urban public health;Woman

PROJECT_TITLE: Neurodegenerative diseases and the role of green space: A deep learning assessment

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


NIH_SPENDING_CATS: Biotechnology;Gene Therapy;Genetics;HIV/AIDS;Immunization;Infectious Diseases;Prevention;Sexually Transmitted Infections;Vaccine Related;Vaccine Related - AIDS

PHR: Project Narrative Broadly neutralizing antibodies delivered in ‘IgG form’ with recombinant adeno-associated virus (AAV) can mediate protection against HIV/SHIV acquisition in animal models. However, little is known about alternative immunoglobulin types such as IgA and IgM, and/or the amounts of AAV-delivered antibodies that are able to reach the main viral entry points: the rectal and vaginal mucosa. In this project we will tackle these key matters and assess 1) mucosal levels, and 2) protection that can be afforded by different immunoglobulin types, when delivered with AAV.

PI_NAMEs: MARTINEZ-NAVIO, JOSE MARIA (contact)

PROGRAM_OFFICER_NAME: PALIN, AMY COLLEEN

PROJECT_TERMS: adeno-associated viral vector;adenovirus mediated delivery;Animal Model;Antibodies;Antibody Binding Sites;antigen binding;Avidity;Binding Sites;Biological Availability;Bypass;Characteristics;Circulation;Clinical Trials;contagion;Cost efficiency;delivery vehicle;Dependovirus;Development;dimer;Dose;Environment;experimental study;fighting;Future;Gene Delivery;Goals;Half-Life;HIV;HIV Antibodies;HIV envelope protein;HIV Infections;Human;IgG1;Immune system;immunogenicity;Immunoglobulin A;Immunoglobulin G;Immunoglobulin M;Immunoglobulins;in vivo;Injections;Location;Long-Term Effects;Macaca;Mammals;Mediating;Modeling;Monkeys;Monoclonal Antibodies;monomer;Mucous Membrane;Mus;Mutation;neutralizing antibody;Pathogenicity;Periodicals;Peripheral;Persons;Polymeric Immunoglobulin Receptors;Polymers;Property;prophylactic;Prophylactic treatment;Proteins;Recombinant adeno-associated virus (rAAV);rectal mucosa;Rectum;Route;Safety;safety and feasibility;Secretory Component;Serum;Sexual Transmission;simian human immunodeficiency virus;SIV;Sterility;Surface;transgene expression;transmission process;vaginal mucosa;Vertebral column;Viral

PROJECT_TITLE: Vectored delivery of anti-HIV antibodies for mucosal protection

STUDY_SECTION: HIVD

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


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Digestive Diseases;Emerging Infectious Diseases;Infectious Diseases

ORG_CITY: DALLAS

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: Project Narrative The oxysterol 25-Hydroxycholesterol (25HC) controls a major branch of immune cell function and drives essential biological processes including B-cell migration, inflammasome activation, viral suppression, and inhibition of bacterial pathogens. This proposal examines the anti-bacterial mechanism of 25HC, with a specific focus on determining how oxysterols prevent bacterial interactions with host membranes through alterations in the levels of a specific pool of cell surface cholesterol, termed “accessible cholesterol”. A deeper understanding of the biochemical and cellular mechanisms of 25HC revealed by this work will lead to a greater understanding of the innate and adaptive immune responses that controls human infectious disease and will reveal new therapeutic opportunities promoting resolution of acute bacterial infection.

PI_NAMEs: ALTO, NEAL MATHEW (contact);RADHAKRISHNAN, ARUN

PROGRAM_OFFICER_NAME: HUDSPETH, KELLY

PROJECT_TERMS: 25-hydroxycholesterol;Acute;adaptive immune response;Animals;Anti-Bacterial Agents;B-Lymphocytes;Bacteria;Bacterial Infections;Biochemical;biochemical tools;Biochemistry;Biological Process;Biophysics;Biosensor;cell growth;Cell membrane;cell motility;Cell Physiology;Cell surface;cell type;Cells;Chemicals;Cholesterol;Cholesterol Homeostasis;Circulation;combat;Communicable Diseases;Cultured Cells;cytokine;Development;Distant;Drug or chemical Tissue Distribution;emerging pathogen;Endoplasmic Reticulum;Epithelial Cells;Epithelium;Fatty Liver;Functional disorder;Gene Modified;Genetic;Glean;Goals;gut bacteria;gut colonization;Gut Mucosa;Heart Diseases;Homeostasis;Human;Human Biology;human pathogen;Immune;Immune system;Immunity;Immunologics;in vivo;Infection;Inflammasome;Inflammatory;Inflammatory Response;Innate Immune Response;innovation;insight;Intracellular Membranes;lipid metabolism;Lipids;Listeria;Listeria monocytogenes;Listeriosis;live cell imaging;Macrophage;Mammalian Cell;Mammals;Mediating;Membrane;Membrane Proteins;Membrane Structure and Function;Metabolic Pathway;microbial;model organism;Molecular;Molecular Probes;Monitor;Motility;mouse model;Movement;Mucosal Immune System;Mucous Membrane;Mus;Natural Immunity;new technology;novel therapeutics;Organism;Outcome;Parasites;pathogen;Pathogenesis;pathogenic bacteria;pathogenic microbe;Pathogenicity;Pathway interactions;Penetration;pharmacologic;Physiological;Play;prevent;Process;Production;Property;Protocols documentation;Regulation;Regulatory Pathway;Resolution;response;Role;Shigella;Shigella flexneri;Signal Pathway;Site;small molecule;Surface;Surface Tension;System;Technology;Testing;Therapeutic Intervention;Time;Tissues;Toxin;transmission process;Viral;Virus;Visualization;Work

PROJECT_TITLE: Oxysterol Regulation of Microbial Pathogenesis

STUDY_SECTION: HIBP

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


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Aging;Clinical Research;Complementary and Integrative Health;Neurosciences;Prevention

ORG_CITY: STORRS-MANSFIELD

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: UNIVERSITY OF CONNECTICUT STORRS

ORG_STATE: CT

PHR: NARRATIVE Despite the well-known risk of noise exposure and the rich literature concerning the benefits of musical training, the risk-benefit interplay has gone largely uninvestigated. The objective of the current work is to investigate how musical training and noise exposure interact to influence age-related declines to auditory brain function. The outcomes of this work may suggest new approaches to promote healthy aging and clinical recommendations about harnessing the therapeutic properties of music training to maximize benefits and minimize hazards.

PI_NAMEs: SKOE, ERIKA E (contact)

PROGRAM_OFFICER_NAME: ST  HILLAIRE-CLARKE, CORYSE

PROJECT_TERMS: Accounting;Acoustics;Address;Adult;Age;age effect;age related;age related decline;Aging;aging brain;Attention;Auditory;Auditory Evoked Potentials;Auditory Threshold;Benefits and Risks;Biometry;Brain;Childhood;Clinical;clinically significant;Cochlea;college;Communities;comparison control;Confounding Factors (Epidemiology);Data;design;dosimetry;Ear;Elderly;Environment;Exposure to;Fortification;functional decline;hazard;Health Benefit;Health Hazards;healthy aging;Hearing;hearing loss risk;Human;improved;Injury;innovation;instrument;Interview;Investigation;Knowledge;late life;Lead;Life;Link;Literature;Loudness;Measures;Medial;Mediating;Methodology;Methods;middle age;multidisciplinary;Music;musician;neural;neural circuit;Neurosciences;Noise;noise exposure;Noise-Induced Hearing Loss;normal hearing;novel;novel strategies;older adult;Outcome;Pilot Projects;Play;preservation;Prevention;Property;protective effect;Publishing;Recommendation;Recurrence;Reflex action;Research;Resources;Risk;Risk Factors;risk mitigation;Selection Bias;Socioeconomic Status;sound;Speech Perception;Structure;System;Testing;Therapeutic;Training;Work;young adult

PROJECT_TITLE: The Noisy Life of the Musician: Implications for Healthy Brain Aging


NIH_SPENDING_CATS: Aging;Cardiovascular;Heart Disease

ORG_CITY: COLUMBIA

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF MISSOURI-COLUMBIA

PHR: Project Narrative The TRPV4 ion channel is expressed in heart cells with aging. Activation of TRPV4 leads to excessive heart contraction and arrhythmia. This proposal investigates the role of TRPV4 in cardiac arrhythmia following excess of the Angiotensin II hormone.

PI_NAMEs: DOMEIER, TIMOTHY LEE (contact)

PROGRAM_OFFICER_NAME: SCHWARTZ, LISA

PROJECT_TERMS: Acute;age related;aged;Aging;Angiotensin II;Arrhythmia;Autopsy;Biological Aging;Blood Pressure;Blood Volume;Calcium;Calcium Signaling;Cardiac;Cardiac Myocytes;Cardiovascular Diseases;Cardiovascular Pathology;Cardiovascular Physiology;Cations;Cause of Death;cell type;Chronic;Clinical Trials;comorbidity;coronary fibrosis;Coupling;Data;Echocardiography;Electrocardiogram;Electrophysiology (science);Experimental Designs;Family;Genetic;genetic approach;genetic manipulation;Goals;Heart;heart cell;heart damage;heart function;Heart Hypertrophy;Histologic;Homeostasis;Hormones;in vivo;in vivo monitoring;Incidence;inhibitor;Injections;Ion Channel;Ischemia;Knock-out;Knowledge;Link;Mechanics;Mediator;member;Microelectrodes;Modeling;Monitor;Mus;Muscle Cells;Myocardial Contraction;Myocardial Infarction;normal aging;novel;old mice;Osmosis;osmotic minipump;overexpression;peptide hormone;Perfusion;pharmacologic;Physiological;Predisposition;prevent;programs;Publishing;receptor;Receptor Activation;Receptor, Angiotensin, Type 1;Regional Perfusion;Reperfusion Injury;Reperfusion Therapy;Research;response;Role;Signal Transduction;Stimulus;Stress;Stretching;Tail;Testing;therapeutic target;trafficking;TRP channel;Vanilloid;Veins;Ventricular;Ventricular Arrhythmia;Ventricular Remodeling

PROJECT_TITLE: Cardiomyocyte TRPV4 and Angiotensin-II induced ventricular arrhythmia with aging

STUDY_SECTION: MPPB

STUDY_SECTION_NAME: Integrative Myocardial Physiology/Pathophysiology B Study Section[MPPB]


ADMINISTERING_IC: DE

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Cancer;Clinical Research;Clinical Trials and Supportive Activities;Dental, Oral, and Craniofacial Disease;Digestive Diseases;Precision Medicine;Prevention;Rare Diseases

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Narrative There is an urgent need to develop prevention options to halt the progression of oral premalignant lesions (OPL) into head and neck squamous cell carcinoma (HNSCC). We recently conducted a Phase IIa trial in individuals with OPL to explore the potential of metformin to prevent oral cancer (M4OC-Prevent trial; NCT02581137), which represented the first study evaluating the chemopreventive potential of metformin in OPL, and achieved a histologic response rate of 60%. By leveraging the wealth of clinical and genetic information and tissue and body fluid resources from this trial with our expertise in decoding cancer promoting pathways, the long-term goal of our project is to define mechanism-based biomarkers predicting a response to metformin and suitable therapeutic options to overcome drug resistance.

PI_NAMEs: GUTKIND, JORGE SILVIO  (contact);LIPPMAN, SCOTT M

PROGRAM_OFFICER_NAME: BACCAGLINI, LORENA

PROJECT_TERMS: Antineoplastic Agents;Automobile Driving;Biological Markers;biomarker identification;Body Fluids;cancer initiation;cancer prevention;Cells;Cessation of life;Chemoprevention;Chemopreventive Agent;Clinical;Clinical Data;Clinical Trials;Colon Carcinoma;cost;CRISPR screen;Cyclic AMP-Dependent Protein Kinases;Data;Development;Dinoprostone;Disease;DNA Sequence Alteration;double-blind placebo controlled trial;Drug resistance;epidemiologic data;Evaluation;former smoker;Foundations;FRAP1 gene;Funding;Future;Genetic;Genetic Determinism;genetic information;genome-wide;Goals;Head and Neck Squamous Cell Carcinoma;Histologic;Histopathologic Grade;Immune;Immune Evasion;Immunologic Surveillance;improved;In complete remission;Incidence;Individual;individualized prevention;Inflammation;Inhibition of Cell Proliferation;insight;Institution;Investigation;Lesion;Malignant Conversion;malignant mouth neoplasm;Malignant Neoplasms;Mediating;Metformin;Modeling;Molecular;Monitor;mTOR inhibition;multimodality;never smoker;Non-Insulin-Dependent Diabetes Mellitus;Non-Steroidal Anti-Inflammatory Agents;novel;Oral;oral cancer prevention;oral premalignancy;partial response;Pathway interactions;Patient Selection;Patients;Pharmaceutical Preparations;Phase;Phase II Clinical Trials;PIK3CG gene;Play;Precancerous Conditions;predictive marker;premalignant;prevent;Prevention;prevention clinical trial;Prevention strategy;Prevention trial;Preventive;programs;Prostaglandins;PTGS2 gene;Randomized;receptor;Resistance;resistance mechanism;Resources;response;Role;Safety;self-renewal;Signal Transduction;Specimen;STK11 gene;Stratification;System;Testing;Therapeutic;Tissues;Toxic effect;treatment response;tumor;tumor progression

PROJECT_TITLE: Targeting Signaling Vulnerabilities for Oral Cancer Prevention

STUDY_SECTION: CPSS

STUDY_SECTION_NAME: Cancer Prevention Study Section[CPSS]


NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Alcoholism, Alcohol Use and Health;Genetics;Lung;Rare Diseases;Regenerative Medicine;Substance Misuse

ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: Circadian pathway controls several of the body functions including how organs response and recover from injury. Chronic alcohol ingestion is associated with circadian pathway dysfunction while also dramatically increases the risk of severe lung injury and disrepair, leading to scar formation following an injury. Understanding the mechanisms by which alcohol disrupts circadian pathway and provokes disrepair could identify preventative or therapeutic interventions that promote healthy lung repair following injury.

PI_NAMEs: SUEBLINVONG, VIRANUJ  (contact)

PROGRAM_OFFICER_NAME: LIN, LI

PROJECT_TERMS: Acute;Acute Lung Injury;Acute Respiratory Distress Syndrome;Alcohol abuse;Alcohols;Animal Model;Antisense Oligonucleotides;ARNT gene;Attenuated;attenuation;Bleomycin;Brain;Cells;Chest imaging;chromatin immunoprecipitation;Chronic;chronic alcohol ingestion;Cicatrix;circadian;Circadian Dysregulation;Collagen;Custom;Data;Deposition;design;Diagnosis;experience;experimental study;Fibroblasts;Fibrosis;Foundations;Functional disorder;Gel;Genes;Goals;health related quality of life;Immunoprecipitation;improved outcome;In Vitro;in vivo;Incidence;Inflammatory;inhibitor;Injury;Intestines;Knockout Mice;Lentivirus Vector;Liver;Lung;Lung Diseases;lung injury;lung repair;Measures;Mediating;Molecular;mortality;Mus;Muscle;Myofibroblast;novel;Nuclear;Organ;Orphan;overexpression;Pathogenesis;Pathway interactions;Physiological;Plasmids;posttranscriptional;pre-clinical;Preclinical Testing;Predisposition;preventive intervention;problem drinker;Public Health;receptor;Recovery;repaired;Research;response;Retinoids;Risk;RNA;Role;Signal Pathway;Stress;Structure of parenchyma of lung;Supportive care;Survivors;Testing;TGFB1 gene;Therapeutic;Therapeutic Effect;Therapeutic Intervention;therapeutically effective;tissue injury;tissue repair;Tissues;transcription factor;transcriptomics;United States;Untranslated RNA;wound healing

PROJECT_TITLE: Alcohol-mediated Clock genes interfere with lung injury and repair

STUDY_SECTION: LIRR

STUDY_SECTION_NAME: Lung Injury, Repair, and Remodeling Study Section[LIRR]


NIH_SPENDING_CATS: Aging;Biotechnology;Genetics;Hematology;Human Genome;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: Los Angeles

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: Project Narrative: In this proposal, we will investigate how the old bone marrow environment influences the heterogeneous expansion of stem and progenitor cells. This research can help improve the diagnosis and treatment of many age-associated diseases including bone marrow failure, leukemia and lymphoma. In addition, our findings can help improve the bone marrow transplantation and develop new treatment strategies in regenerative medicine.

PI_NAMEs: ELOWITZ, MICHAEL B;LOIS, CARLOS ;LU, RONG  (contact)

PROGRAM_OFFICER_NAME: WILLIAMS, JOHN

PROJECT_TERMS: Age;age effect;age related;age related changes;age-related disease;Aging;aging related;Bar Codes;Blood;Blood Cells;bone aging;bone invasion;Bone Marrow;Bone Marrow Cells;Bone marrow failure;Bone Marrow Transplantation;Cell Count;cell type;Cells;cellular imaging;Clonal Expansion;Clone Cells;Complex;Data;Databases;Diagnosis;Engineering;Environment;experimental study;Exposure to;Gene Expression;Genes;Genomics;Hematological Disease;Hematopoiesis;Hematopoietic;Hematopoietic stem cells;Hemorrhage;imaging modality;Imaging Techniques;improved;In Situ;Individual;Infection;Injury;intercellular communication;Knock-out;leukemia;leukemia/lymphoma;Maps;Memory;Mesenchymal;Methods;migration;Molecular;MPP3 gene;Mus;Mutagenesis;Mutation;novel therapeutic intervention;old mice;Optics;Positioning Attribute;progenitor;Recording of previous events;Regenerative Medicine;Research;Resolution;Role;Signal Pathway;Signal Transduction;single cell genomics;stem cell expansion;System;Testing;therapeutic target;Variant;Work

PROJECT_TITLE: Using spatial, single-cell genomic recording to investigate age-associated clonal hematopoiesis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-VH-C(02)M]


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Dental, Oral, and Craniofacial Disease;Genetics;Human Genome;Orphan Drug;Precision Medicine;Rare Diseases

ORG_CITY: SAINT LOUIS

ORG_DEPT: OTOLARYNGOLOGY

ORG_NAME: WASHINGTON UNIVERSITY

PHR: PROJECT NARRATIVE Although progress has been made in head and neck squamous cell carcinoma (HNSCC), the mainstays of treatment continue to be surgery, radiation, and chemotherapy -- unfortunately, most patients have poor prognoses, with spread to lymph nodes and poor responses to treatment representing two of the most common reasons patients die from this disease. We recently found that some tumors cells are in an unusual transcriptional state called the “hybrid epithelial-mesenchymal” (hybrid-EM) state, and these hybrid-EM cells are primarily responsible for invasion and metastasis in HNSCC. Our initial forays investigating how this state is regulated revealed that the genes involved in producing cholesterol also play a role in HNSCC invasion, and we therefore propose to 1) test drugs targeting cholesterol pathways in sophisticated models, 2) find other cholesterol genes that could be targeted to treat HNSCC, and 3) apply the same strategy that we used to identify the cholesterol pathway to find other pathways important in invasion.

PI_NAMEs: MITRA, ROBI D;PURAM, SIDHARTH VENKATA (contact)

PROGRAM_OFFICER_NAME: CHEN, ZHONG

PROJECT_TERMS: adverse outcome;Anabolism;attributable mortality;Binding;Bromodomains and extra-terminal domain inhibitor;Cancer Etiology;candidate selection;Cell Line;Cells;chemotherapy;Cholesterol;cholesterol biosynthesis;Cholesterol Homeostasis;Cisplatin;Clinical Trials;CRISPR interference;Data;Disease;drug development;Drug Kinetics;Drug Targeting;drug testing;Enhancers;Epigenetic Process;Epithelium;experimental study;extend lifespan;Fatty Acids;FDA approved;Gene Expression;gene network;gene synthesis;Gene Targeting;Genes;Genetic Transcription;genome-wide analysis;Goals;Head and Neck Cancer;Head and Neck Squamous Cell Carcinoma;Human;Hybrids;improved;In Vitro;in vivo;in vivo Model;inhibitor;insight;Invaded;knock-down;Lead;Learning;Length;lymph nodes;Malignant Neoplasms;Mass Spectrum Analysis;Mesenchymal;Metabolic Pathway;Metabolism;metabolomics;mevalonate;Modeling;Molecular;Morbidity - disease rate;mortality;Neoplasm Metastasis;neoplastic cell;Oncology;Operative Surgical Procedures;Organoids;Outcome;oxidation;Pathway interactions;Patients;Pharmaceutical Preparations;Phenotype;Pre-Clinical Model;prevent;Process;Prognosis;protein biomarkers;Proteins;Radiation;Radiation therapy;Recurrence;response;Role;single cell analysis;single cell sequencing;small molecule;small molecule inhibitor;Smoking History;targeted treatment;Technology;Testing;therapeutic target;transcriptome sequencing;Treatment Failure;treatment response;tumor;tumor heterogeneity;tumor xenograft

PROJECT_TITLE: Deciphering epigenetically-regulated pathways to improve targeted therapy for invasion and metastasis in head and neck cancer

STUDY_SECTION: MCTA

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics A Study Section[MCTA]


ORG_CITY: ANN ARBOR

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Dietary restriction (DR) represents one of the most effective means to extend lifespan in all tested organisms, including mammals. DR also improves health-span and reduces the risk of various age-dependent diseases including neurodegenerative diseases such as Alzheimer’s disease (AD). Our work will lead to a better understanding of how DR promotes longevity and its regulation by the chemosensory system, and how it reduces the risk of age-dependent neurodegenerative diseases such as AD.

PI_NAMEs: XU, SHAWN  (contact)

PROJECT_TERMS: Address;Affect;age related neurodegeneration;age-related disease;Aging;Alzheimer's Disease;Animal Behavior;Behavior;Caenorhabditis elegans;CD2 Antigens;Chemicals;Communication;Cues;Data;detection platform;dietary restriction;Dopamine;Environmental Risk Factor;Esthesia;extend lifespan;fly;Food;Genetic;Genetic Models;GTP-Binding Proteins;healthspan;Homologous Gene;improved;insight;Intestines;Invertebrates;life span;Longevity;Longevity Pathway;Mammals;Mediating;Modeling;monoamine;neural;Neurodegenerative Disorders;Neurons;Neurosciences;neurotransmission;Norepinephrine;novel;Nutrient;Octopamine;octopamine receptor;Odors;Organism;Pathway interactions;Perception;Physiological Processes;Play;Process;Protocols documentation;Regulation;Research;Risk Reduction;Role;sensor;Sensory;sensory system;Serotonin;Signal Transduction;Signaling Protein;System;Testing;tool;transmission process;Work;Yeasts

PROJECT_TITLE: Chemosensation and longevity in C. elegans

STUDY_SECTION: CSS

STUDY_SECTION_NAME: Chemosensory Systems Study Section[CSS]


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

NIH_SPENDING_CATS: Cancer;Immunotherapy;Lung;Lung Cancer

ORG_CITY: CAMBRIDGE

ORG_DEPT: MISCELLANEOUS

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

PHR: Project Narrative Immune responses are drastically impacted by the environmental context in which they occur. Here we aim to elucidate the impact of lung tumor-specific dysfunction of tumor-reactive CD8+ T cell populations and elucidate which immunological mechanisms contribute to their induction. Determining factors of differential T cell activation will enable the generation of rational and novel immune-modulatory agents for cancer immunotherapy.

PI_NAMEs: SPRANGER, STEFANI  (contact)

PROGRAM_OFFICER_NAME: LIU, YIN

PROJECT_TERMS: Address;Affect;anti-PD-1;anti-tumor immune response;cancer immunotherapy;Cancer Patient;cancer therapy;cancer type;CD8-Positive T-Lymphocytes;CD80 gene;CD86 gene;Cell Physiology;Cells;Chronic;Clinical;Clinical Data;clinical practice;clinical predictors;Communicable Diseases;Cross Presentation;CXCR3 gene;Data;Dendritic cell activation;Dendritic Cells;Development;Disease;draining lymph node;effector T cell;Environmental Impact;Epigenetic Process;exhaust;exhaustion;experience;Exposure to;Functional disorder;Generations;Grant;Immune;immune checkpoint blockade;Immune Evasion;immune modulating agents;Immune response;Immunity;Immunologics;immunoregulation;Immunosuppression;Immunotherapy;Impairment;imprint;Infiltration;insight;Interleukin-12;K-ras mouse model;Knowledge;KRAS oncogenesis;KRAS2 gene;Lung;Lung Adenocarcinoma;Lung Neoplasms;Malignant neoplasm of lung;Malignant Neoplasms;Mediastinal;Mediastinal lymph node group;Mediating;Melanoma;Minority;Modeling;Molecular;mouse model;Mutation;neoplastic cell;Non-Small-Cell Lung Carcinoma;novel;Organ;Patients;Phenotype;Population;pre-clinical;prevent;Production;programmed cell death protein 1;programs;receptor;Refractory;Regulatory T-Lymphocyte;Reporting;Resistance;resistance mechanism;response;restraint;Role;Site;STK11 gene;Structure of parenchyma of lung;T cell differentiation;T cell infiltration;T cell regulation;T cell response;T-Cell Activation;T-cell inflamed;T-Lymphocyte;T-Lymphocyte Subsets;Testing;Therapeutic Agents;Therapeutic Intervention;Time;Tissues;TP53 gene;Translating;tumor;Tumor Antigens;tumor eradication;Tumor Immunity;tumor-immune system interactions;Up-Regulation;Virus Diseases;Work

PROJECT_TITLE: Understanding the induction of T cell dysfunction in the context of lung cancer

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


NIH_SPENDING_CATS: Bioengineering;Machine Learning and Artificial Intelligence

ORG_CITY: DUARTE

ORG_NAME: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE

PHR: Public Health Relevance / Project Narrative G protein-coupled receptors (GPCRs) are some of the most important and scrutinized drug targets, largely because of their direct and broad involvement in human physiological processes, and their pharmacological malleability. The primary goal of this project is to analyze GPCRs and their complexes with several G-proteins in order to uncover the spatiotemporal determinants of G protein coupling by developing an innovative toolkit combining Molecular Dynamics simulations with system biology approaches such as Bayesian Network modeling. Using this system agonistic toolkit we will identify (i) the time correlated concerted motions in residue clusters that are critical to GPCR activation, (ii) residue pairs involved in allosteric communication from the ligand binding site to the G protein coupling site, and (iii) residue pairs in the GPCR:G protein interfaces that contribute to the G protein coupling strength and selectivity.

PI_NAMEs: RODIN, ANDREI ;VAIDEHI, NAGARAJAN  (contact)

PROGRAM_OFFICER_NAME: FARRELL, CATHERINE MARY

PROJECT_TERMS: Adopted;Agonist;Algorithmic Software;Algorithms;Bar Codes;Base Sequence;Bayesian Modeling;Bayesian Network;Binding Sites;Biological Assay;Cell membrane;Cells;Communication;Communities;Complex;Computer software;conformational conversion;Coupling;Data;Data Analyses;Data Reporting;design;drug discovery;Drug Targeting;Elements;Environment;Event;experimental study;explainable machine learning;Explosion;Family;Fluorescence Resonance Energy Transfer;Frequencies;G-Protein-Coupled Receptors;Glean;Goals;Grant;GTP-Binding Proteins;high dimensionality;Human;innovation;insight;Knowledge;Label;Ligand Binding;Ligands;machine learning method;Maps;Mediating;Methods;Mining;Molecular Conformation;molecular dynamics;molecular scale;Motion;Nature;Neighborhoods;novel strategies;pharmacologic;Physiological Processes;predictive test;Principal Component Analysis;Property;protein complex;Protein Dynamics;Protein Sequence Analysis;Proteins;public health relevance;receptor;Receptor Activation;Resolution;sensor;Series;Site;spatiotemporal;stem;structural determinants;Structure;System;Systems Biology;Techniques;Testing;three dimensional structure;Time;tool;Transducers;Validation

PROJECT_TITLE: An integrated toolkit combining computational systems biology techniques with molecular dynamics simulations to delineate functionality of GPCRs

STUDY_SECTION: BLR

STUDY_SECTION_NAME: Biomedical Informatics, Library and Data Sciences Review Committee[BLR]


NIH_SPENDING_CATS: Breast Cancer;Cancer;Estrogen;Genetics;Women's Health Research

ORG_DEPT: CHEMISTRY

ORG_NAME: GEORGIA INSTITUTE OF TECHNOLOGY

PHR: Project Narrative/Relevance: Breast cancer (BCa) ranks second only to lung cancer as the leading cause of US cancer deaths in women. This application describes a preclinical study aimed at repurposing deferiprone (Def), an FDA-approved drug, as a template for the discovery of novel histone lysine demethylase (KDM) inhibitors optimized for BCa therapy.

PI_NAMEs: OYELERE, ADEGBOYEGA  (contact)

PROGRAM_OFFICER_NAME: AGYIN, JOSEPH KOFI

PROJECT_TERMS: 4T1;antagonist;Apoptosis;Bioinformatics;Breast Cancer Cell;Breast Cancer cell line;Breast Cancer therapy;Breast Carcinoma;Cancer Cell Growth;Cancer Etiology;cancer subtypes;Cell Survival;Cells;Cessation of life;Chemoprevention;Clinical;clinical development;Compensation;cytotoxic;cytotoxicity;Data;design;Drug Kinetics;Drug resistance;Endocrine;Epidermal Growth Factor Receptor;Epigenetic Process;ESR1 gene;Estrogen Receptor Modulators;Estrogen Receptors;Exhibits;Family;FDA approved;Fulvestrant;Functional disorder;gene repression;Heterochromatin;Histone Deacetylase;histone methyltransferase;Histones;Hormones;Human;In Vitro;in vivo;Incidence;inhibitor;insight;Investigation;Iron Chelation;KDM5B gene;Lead;lead candidate;Lysine;Malignant Breast Neoplasm;Malignant neoplasm of lung;Malignant Neoplasms;MDA MB 231;Measures;Mediating;Medical;member;Modality;Modeling;mouse model;Neoplasm Metastasis;neoplastic cell;novel;novel therapeutics;Oxidases;paralogous gene;Patients;Pharmaceutical Preparations;Pharmacodynamics;pharmacologic;Positioning Attribute;preclinical study;Progesterone Receptors;Property;Proteins;Reader;receptor expression;Receptor Signaling;Relapse;Resistance;Role;Signal Transduction;success;T47D;Tail;Tamoxifen;targeted treatment;Testing;Therapeutic Agents;Therapeutic Intervention;Toxicology;triple-negative invasive breast carcinoma;tumor;tumor growth;Veins;Woman;Women's mortality;Xenograft procedure

PROJECT_TITLE: Reposition and Optimization of Deferiprone for Breast Cancer Therapy

STUDY_SECTION: DMP

STUDY_SECTION_NAME: Drug Discovery and Molecular Pharmacology Study Section[DMP]


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

NIH_SPENDING_CATS: Aging;Atherosclerosis;Cardiovascular;Genetics;Heart Disease;Heart Disease - Coronary Heart Disease

ORG_DEPT: VETERINARY SCIENCES

PHR: Heart attacks occur when either a coronary blockage grows to large or when a small blockage “breaks” causing a blot clot to form, and since these potentially deadly plaques are small, often the heart attack or stroke occurs without any warning or prior symptoms. Currently, we have very few tools try to make a weak plaque stronger, so we want to identify the role of a particular set of proteins that play a major role in determining both the size and strength of a coronary plaque. Our evidence suggests that a currently available, FDA approved drug may meet this goal; therefore the goal of this study will be to clearly identify how this target changes disease progression and test the drug in a large animal model of coronary disease to pave the way for use in humans.

PI_NAMEs: BOWLES, DOUGLAS K (contact)

PROGRAM_OFFICER_NAME: PLAYFORD, MARTIN P

PROJECT_TERMS: acute coronary syndrome;Angiography;Animal Model;Apolipoprotein E;Area;Arterial Fatty Streak;Atherosclerosis;Benign;Calcium-Activated Potassium Channel;Cause of Death;cell type;Cells;Cessation of life;Characteristics;Clinical;Clinical Trials;Coagulation Process;Collagen;combat;Complex;Coronary;Coronary Angiography;Coronary Arteriosclerosis;Coronary heart disease;coronary lesion;coronary plaque;cost;Development;disease model;Disease Progression;Drug Targeting;drug testing;Familial Hypercholesterolemia;Family suidae;FDA approved;Foam Cells;Foundations;Gene Expression;Gene Modified;Genes;Genetic;Goals;Heart Diseases;Histology;Hospitals;Human;Immunohistochemistry;In Vitro;in vivo;Infiltration;Inflammation;Inflammatory;Inflammatory Response;inhibitor;Knockout Mice;Lesion;Link;Macrophage;Mammals;Medial;Mediating;Mediator;migration;Modeling;Mus;Myocardial Infarction;myocardin;Necrosis;next generation;novel;Outcome;Pathogenesis;Pharmaceutical Preparations;pharmacologic;Phenotype;Play;porcine model;pre-clinical;Proliferating;recruit;Regulator Genes;Reporter;Role;Rupture;Set protein;Signal Transduction;Smooth Muscle;Solid;Stroke;Symptoms;Testing;Therapeutic;therapeutically effective;Tomatoes;tool;transcription factor REST;transcriptome sequencing;transdifferentiation;Translating;translational potential;ultrasound;United States

PROJECT_TITLE: Cell-specific role and therapeutic potential of KCa3.1 in atherosclerosis

STUDY_SECTION: AVI

STUDY_SECTION_NAME: Atherosclerosis and Vascular Inflammation Study Section[AVI]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Brain Disorders;Mental Health;Mental Illness;Neurosciences

PHR: NARRATIVE Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive method for clinical brain stimulation that can treat psychiatric disorders. However, the mechanism by which rTMS modulates activity in cortical circuits is poorly understood. This project will determine how rTMS modulates the activity of excitatory and inhibitory cell types in the brain, paving the way for more effective treatments.

PI_NAMEs: WILKE, SCOTT ALLEN (contact)

PROGRAM_OFFICER_NAME: TILGHMAN, JESSICA IRENE

PROJECT_TERMS: Action Potentials;Acute;Address;Affect;Animal Model;awake;Brain;Brain region;Calcium Signaling;cell cortex;cell type;Cells;Chemosensitization;Chronic;Clinical;clinical effect;clinical efficacy;Collaborations;design;Disinhibition;effective intervention;effective therapy;Electromagnetics;Equilibrium;excitatory neuron;Excitatory Synapse;experimental study;Face;FDA approved;Fiber;Frequencies;Functional disorder;Future;Head;Hour;Human;in vivo;inhibitory neuron;Interneurons;Investigation;Long-Term Potentiation;Major Depressive Disorder;Measures;Mediating;Mental disorders;Methods;Modeling;Motor;Mus;National Institute of Mental Health;Nervous System Disorder;neural;Neurons;Neurosciences;neurotransmission;noninvasive brain stimulation;novel;Obsessive-Compulsive Disorder;off-label use;optogenetics;Pathologic;permissiveness;Photometry;Physiologic pulse;Prefrontal Cortex;Protocols documentation;rational design;redshift;repetitive transcranial magnetic stimulation;Research;response;Rodent;Stress;Synapses;Synaptic plasticity;System;targeted delivery;Techniques;Testing;Thalamic structure;Therapeutic;Therapeutic Effect;therapeutic target;Time;tool;Treatment Protocols;United States National Institutes of Health

PROJECT_TITLE: Prefrontal circuit mechanisms of repetitive transcranial magnetic stimulation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-NV-Q(91)S]


NIH_SPENDING_CATS: Biotechnology;HIV/AIDS;Immunization;Immunotherapy;Infectious Diseases;Prevention;Vaccine Related;Vaccine Related - AIDS

ORG_CITY: CINCINNATI

ORG_NAME: CINCINNATI CHILDRENS HOSP MED CTR

PHR: PROJECT NARRATIVE HIV remains a global pandemic with no efficacious vaccine to prevent the millions of new infections that occur each year. This proposal explores an innovative mechanism for circumventing natural killer cell immunosuppressive activity, a roadblock to HIV vaccine success. The outcomes of this study will include advancement of an efficacious strategy for enabling vaccine-mediated induction of immune responses capable of preventing HIV infection.

PI_NAMEs: VELU, VIJAYAKUMAR ;WAGGONER, STEPHEN N. (contact)

PROGRAM_OFFICER_NAME: SHAPIRO, STUART Z

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;adaptive immune response;adaptive immunity;Affinity;Animal Model;Animals;Antibodies;Antibody Response;Antigens;autoreactivity;B-Lymphocytes;Biological Assay;CD4 Positive T Lymphocytes;Cell Death;cell killing;Cells;Cessation of life;Chronic;Clustered Regularly Interspaced Short Palindromic Repeats;comorbidity;Development;Dissection;Dose;Enzyme-Linked Immunosorbent Assay;Evaluation;experimental study;Flow Cytometry;Fostering;Generations;Genes;global health;Goals;Granzyme;Helper-Inducer T-Lymphocyte;high risk;HIV;HIV envelope protein;HIV Infections;HIV vaccine;Human;human model;Immune;Immune response;Immunity;Immunization;Immunologics;immunoregulation;Immunosuppression;Impairment;improved;In Vitro;in vivo;Individual;Infection;Infusion procedures;inhibitor;innovation;Invaded;Investigation;Killer Cells;life span;Macaca;Macaca mulatta;Measurable;Measures;Mediating;Mediator;Modeling;Molecular;Mus;Natural Killer Cells;neutralizing antibody;next generation;nonhuman primate;novel vaccines;Outcome Study;pandemic disease;pathogen;perforin;Persons;Phase;Population;prevent;Prevention;public health intervention;receptor;Recording of previous events;Rectum;Research;response;restraint;Role;Scheme;simian human immunodeficiency virus;SIV;small molecule;small molecule inhibitor;Structure of germinal center of lymph node;success;T cell response;T memory cell;T-Cell Activation;T-Lymphocyte;Testing;Time;tool;Toxicity Tests;tumor;Vaccination;vaccine efficacy;vaccine response;vaccine strategy;Vaccines;Viral;Virus;Work

PROJECT_TITLE: Blocking granzyme-mediated immune suppression to enhance HIV vaccine efficacy


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Dementia;Neurodegenerative;Neurosciences;Physical Injury - Accidents and Adverse Effects;Prevention;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury

ORG_CITY: BALTIMORE

ORG_DEPT: ANESTHESIOLOGY

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

PHR: Project Narrative Although clinical and experimental studies demonstrate olfactory dysfunction (OD) after traumatic brain injury (TBI), the underlying mechanisms and treatment remain elusive. The aim of our research is to investigate the inflammatory mechanisms underlying OD in a well-established controlled cortical impact mouse TBI model in order to allow future development of early and accurate diagnosis of TBI predisposing to dementia. Elucidating the underlying mechanisms of OD after TBI might be necessary not only to understanding the nature of neurodegeneration but also to developing disease management strategies for treatment and prevention.

PI_NAMEs: LIU, SHAOLIN ;WU, JUNFANG  (contact)

PROJECT_TERMS: Ablation;accurate diagnosis;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease related dementia;Anosmia;Atrophic;Behavior;behavioral impairment;Biochemical;Cells;Chronic;Clinical;Clinical Research;Cognitive;Cognitive deficits;controlled cortical impact;cytokine;Data;Dementia;designer receptors exclusively activated by designer drugs;Development;Diagnosis;Disease Management;Disease Progression;early detection biomarkers;Early Diagnosis;Early identification;effective therapy;Electrophysiology (science);epidemiology study;Exhibits;experimental study;Functional disorder;functional improvement;functional outcomes;Future;Generations;Genetic;glial activation;Hippocampus;hyperphosphorylated tau;Impairment;In Vitro;in vivo;Incidence;Infiltration;Inflammation;Inflammatory;Inflammatory Response;inhibitor;Injury;interdisciplinary approach;Ion Channel;Knockout Mice;Link;Literature;Mediating;Medical;Microglia;Microscopy;Modeling;Molecular;Mus;NADPH Oxidase;Nature;Nerve Degeneration;network dysfunction;neurobehavioral test;Neurodegenerative Disorders;Neurofibrillary Tangles;neuroinflammation;Neurologic;neuronal excitability;Neurons;neuropathology;neuropsychiatry;neurotoxic;olfactory bulb;Olfactory dysfunction;Olfactory Pathways;operation;Pathogenesis;Pathologic;Pathology;Pathway interactions;Peripheral;pharmacologic;piriform cortex;Population;Positioning Attribute;Prevention;prodromal Alzheimer's disease;Prognosis;Quality of life;Reactive Oxygen Species;Recording of previous events;Research;Risk;Risk Factors;Role;Sensory Disorders;Severity of illness;Signal Transduction;Structure;Survivors;Symptoms;Synapses;synaptic function;tau-1;TBI Patients;Therapeutic;Therapeutic Effect;Trauma;Traumatic Brain Injury;treatment strategy

PROJECT_TITLE: The inflammatory mechanisms underlying olfactory dysfunction in prognosis of TBI progression to dementia

STUDY_SECTION: BNRS

STUDY_SECTION_NAME: Behavioral Neuroendocrinology, Neuroimmunology, Rhythms, and Sleep Study Section [BNRS]


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Biotechnology

ORG_CITY: PASADENA

ORG_NAME: CALIFORNIA INSTITUTE OF TECHNOLOGY

PHR: PROJECT NARRATIVE  Directed evolution exploits the seemingly boundless sequence space available to Nature’s catalytic machinery to repurpose enzymes for new-to-nature chemical transformations. The proposed research will harness the evolvability of cytochrome P450 enzymes to expand the activity domain of biocatalysis to include chemo- and enantioselective functionalizations of N-heterocycles. This research will contribute to our fundamental understanding of enzyme catalysis and evolution and will expedite drug discovery by providing an enzyme-controlled chemodivergent platform for the sustainable synthesis of pharmaceutically privileged motifs.

PI_NAMEs: KENNEMUR, JENNIFER L. (contact)

PROGRAM_OFFICER_NAME: MCINTYRE, JEREMY COLIN

PROJECT_TITLE: Development of Biocatalysts for Chemodivergent Functionalizations of Heterocycles


NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Mental Health;Neurosciences;Substance Misuse

ORG_CITY: LOS ANGELES

ORG_DEPT: PSYCHOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PROJECT NARRATIVE The objective of this translational project is to test the effects of acute stress induction on cognitive flexibility and habit learning among individuals with alcohol use disorder (AUD) compared to matched controls. The proposed study will elucidate the acute stress-response neurocircuitry in humans with AUD, compared to matched controls, that predisposes them towards habitual learning.

PI_NAMEs: RAY, LARA A. (contact)

PROGRAM_OFFICER_NAME: FALK, DANIEL EVAN

PROJECT_TERMS: acute stress;Alcohol consumption;alcohol use disorder;Alcoholic beverage heavy drinker;Alcohols;Amygdaloid structure;base;Behavioral Model;biological adaptation to stress;brain circuitry;chronic alcohol ingestion;Chronic stress;Clinical;Clinical assessments;clinical diagnosis;Cognitive;cognitive task;comparison control;Complex;Decision Making;drinking;eligible participant;Female;flexibility;Functional Magnetic Resonance Imaging;Goals;habit learning;Human;Image;Individual;Insula of Reil;Investigation;Learning;Literature;male;Measures;Mediating;Methods;neural;neural circuit;Neurobiology;neuroimaging;Outcome;Participant;pre-clinical;Predisposition;Prefrontal Cortex;recruit;response;Risk;Role;Sampling;Science;sex;Sorting;Stress;Testing;theories;translational approach;translational impact;Wisconsin

PROJECT_TITLE: The effects of stress on decision-making in alcohol use disorder: A translational approach

STUDY_SECTION_NAME: Clinical, Treatment and Health Services Research Study Section[AA-3]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Cerebrovascular;Dementia;Genetics;Neurodegenerative;Neurosciences;Physical Activity;Prevention;Sleep Research

ORG_CITY: HERSHEY

ORG_DEPT: NEUROSURGERY

ORG_NAME: PENNSYLVANIA STATE UNIV HERSHEY MED CTR

PHR: PROJECT NARRATIVE The ε4 variant of apolipoprotein E (APOE4) is the strongest and most common genetic risk factor for Alzheimer’s disease, but the underlying reason for this risk remains unclear. APOE4 is also a risk factor for heart disease, and is known to cause fatty plaque build-up in blood vessels, as well as impair blood flow. We propose that impaired blood flow and blood vessel movement caused by APOE4 can affect sleep and interfere with the clearance of waste products from the brain, promoting the brain cell death that causes Alzheimer’s disease. To test this idea, we will measure changes in brain blood vessel size, monitor sleep stages and quality, and assess levels of brain inflammation and cellular waste in a mouse carrying the human APOE4 gene. This study will also test the effects of exercise on these processes, and determine whether exercise can correct the overall changes caused by APOE4.

PI_NAMEs: DREW, PATRICK JAMES;GLUCKMAN, BRUCE J;PROCTOR, ELIZABETH A (contact)

PROGRAM_OFFICER_NAME: NEWMAN, ELIZABETH

PROJECT_TERMS: abeta accumulation;Acceleration;actigraphy;Affect;Age;Aging;Alleles;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease risk;Amyloid beta-Protein;Animals;Apolipoprotein E;apolipoprotein E-3;Appearance;Area;Arteries;Atherosclerosis;awake;Behavioral;Binding;Biological Assay;Blood - brain barrier anatomy;Blood brain barrier dysfunction;Blood flow;Blood Vessels;Brain;brain cell;brain tissue;Cause of Death;cerebral artery;cerebrospinal fluid flow;Cerebrovascular Circulation;cerebrovascular health;Cerebrovascular system;cholesterol transporters;Chronic;Cortical vasculature;Custom;cytokine;Darkness;Development;Diameter;Disease;driving force;Electroencephalography;Encephalitis;Event;Exercise;experience;Feedback;Functional disorder;Gene Frequency;Genes;genetic risk factor;Genotype;glymphatic clearance;Heart Diseases;Human;Image;Immune;immune clearance;immunoreactivity;Impairment;improvement on sleep;Individual;Inflammation;Inflammatory;Knock-in Mouse;Late Onset Alzheimer Disease;Light;lipid metabolism;Lipids;Machine Learning;mathematical model;Measures;Mediating;Metabolic;Metabolic dysfunction;Metabolic Pathway;metabolomics;Molecular;Molecular Profiling;Monitor;Movement;Mus;neural;Neurobiology;neuroinflammation;neurotoxic;neurovascular;neurovascular coupling;Nitric Oxide;Pathologic;Pathology;Pathway interactions;Pattern;pharmacologic;Phase;Physiological;Physiology;Polysomnography;Population;Preventive therapy;Process;Production;protein aggregation;receptor;Research;response;Risk;Risk Factors;Running;sedentary;Signal Transduction;Sleep;Sleep disturbances;sleep pattern;sleep quality;Sleep Stages;Societies;Staging;Stimulus;Stroke;tau aggregation;tau Proteins;Technical Expertise;Testing;Time;timeline;two-photon;Variant;Vascular Diseases;Vasodilation;Vasodilator Agents;vigilance;Waste Products;wasting;Work

PROJECT_TITLE: Impaired Vasoreactivity, Sleep Degradation, and Impaired Clearance in the APOE4 Brain

STUDY_SECTION: CDIN

STUDY_SECTION_NAME: Chronic Dysfunction and Integrative Neurodegeneration Study Section[CDIN]


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Behavioral and Social Science;Chronic Pain;Clinical Research;Clinical Trials and Supportive Activities;Disability Research;Fibromyalgia;Genetics;Neurosciences;Pain Research

ORG_CITY: SALT LAKE CITY

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: 8. PROJECT NARRATIVE  Fibromyalgia affects millions of Americans every day, reducing their quality of life, capacity to work and ability to care for themselves, making it a significant public health problem. The goal of this project is to determine the effectiveness and safety of metformin in treating pain, mood and cognitive symptoms of fibromyalgia, and identify the underlying mechanism for its actions. Understanding these pathways is a critical step in developing non-addictive pain treatments and has enormous potential to reduce the harm from chronic opioid use.

PI_NAMEs: OKIFUJI, AKIKO ;TAYLOR, NORMAN  (contact)

PROGRAM_OFFICER_NAME: WANG, YAN Z

PROJECT_TERMS: 5'-AMP-activated protein kinase;Affect;affective disturbance;American;antinociception;Anxiety;anxiety symptoms;arm;Biochemical Markers;Blood;Caring;Cells;central sensitization;Chronic;chronic painful condition;chronic widespread pain;Clinical;Clinical Research;comorbidity;Complex;Consent;cost;cytokine;Data;Databases;Development;Diabetes Mellitus;disability;disabling symptom;Dose;Double-Blind Method;double-blind placebo controlled trial;effective therapy;effectiveness evaluation;Enzymes;experience;Fatigue;Fibromyalgia;fibromyalgia patients;FRAP1 gene;Future;Gene Expression;Genes;Genetic Transcription;Goals;Harm Reduction;Healthcare;Hyperalgesia;IL18 gene;Immune;Impaired cognition;improved;Inflammasome;Inflammation;Inflammatory;Insulin Resistance;interest;Interleukin-1 beta;Leukocytes;Mechanics;Medical;Mental Depression;Messenger RNA;Metabolic;Metabolism;Metformin;Methods;Modeling;mood symptom;Neurobehavioral Manifestations;neuroinflammation;Neuropathy;Nociception;Non-Insulin-Dependent Diabetes Mellitus;novel;opioid use;Pain;Pain intensity;Pain management;Pain Measurement;pain relief;pain symptom;Pathway interactions;Patient Self-Report;Patients;Peripheral;Pharmaceutical Preparations;Phase II Clinical Trials;Phenotype;Phosphorylation;Phosphotransferases;Physical Function;Pilot Projects;Placebo Effect;Placebos;Play;Polymerase Chain Reaction;Population;pre-clinical;Pre-Clinical Model;preclinical study;primary endpoint;Process;Productivity;prospective;Public Health;Quality of life;Questionnaires;Randomized;Randomized, Controlled Trials;Rattus;receptor;recruit;reduce symptoms;Research;Resources;Role;Safety;secondary endpoint;Severities;Sleep disturbances;Spinal cord injury;symptom treatment;Symptoms;Testing;Time;transcription factor;Treatment Efficacy;Work

PROJECT_TITLE: Metformin as a novel, mechanistic treatment of fibromyalgia; a proof of concept RCT

STUDY_SECTION: AMSC

STUDY_SECTION_NAME: Arthritis and Musculoskeletal and Skin Diseases Clinical Trials Study Section [AMSC]


ADMINISTERING_IC: HD

ED_INST_TYPE: SCHOOLS OF NURSING

IC_NAME: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Conditions Affecting the Embryonic and Fetal Periods;Depression;Disability Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Maternal Health;Maternal Morbidity and Mortality;Mental Health;Mental Illness;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Preterm, Low Birth Weight and Health of the Newborn;Prevention;Social Determinants of Health;Violence Against Women;Violence Research;Women's Health Research

ORG_CITY: CHARLOTTESVILLE

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: Project narrative Women with disabilities are at heightened risk for intimate partner violence (IPV), and mood disorders, yet the extent to which these risks affect pregnancy outcomes has not been studied. The proposed study will leverage existing population-based data, and will integrate qualitative data designed to improve the understanding of the role of context, risk, and protective factors for IPV and depression among women with disabilities.

PI_NAMEs: ALHUSEN, JEANNE L (contact)

PROGRAM_OFFICER_NAME: WEINBERG, DAVID H

PROJECT_TERMS: Access to Information;Address;Admission activity;adverse birth outcomes;adverse pregnancy outcome;Affect;Attitude;barrier to care;Birth;Caring;clinical practice;contextual factors;Critical Care;Data;Death Rate;depressive symptoms;design;Development;Disabilities experience;disability;disabled;Disparity;disparity reduction;Domestic Violence;ethnic diversity;Evaluation;Evidence based intervention;experience;Female of child bearing age;Focus Groups;Foundations;Future;Goals;Health;Health Personnel;Health Promotion;Healthcare;Healthcare Systems;illicit drug use;improved;Incidence;Individual;Infant;infant outcome;Intervention;Interview;intimate partner violence;Knowledge;Low Birth Weight Infant;maternal outcome;Mediating;Mental Depression;Mental disorders;Methods;Mood Disorders;Morbidity - disease rate;Mothers;Neonatal Intensive Care Units;Nurse Midwives;Nurses;Outcome;Perinatal;Perinatal Care;perinatal health;perinatal outcomes;perinatal period;Phase;Physicians;Policies;population based;Predictive Factor;Pregnancy;Pregnancy Outcome;pregnant;Pregnant Women;Premature Birth;Prenatal care;preventive intervention;protective factors;Provider;Psychosocial Stress;racial diversity;Recommendation;Reporting;Research;Research Personnel;Resources;Risk;Risk Assessment;Risk Factors;risk mitigation;Role;Sampling;sociodemographics;substance use;symptomatology;System;Testing;Tobacco;Underserved Population;unintended pregnancy;Violence;violence prevention;Woman;women with disabilities;Women's Group;women's outcomes

PROJECT_TITLE: Psychosocial stress and its relation to maternal and infant outcomes among women with disabilities

STUDY_SECTION: CMPC

STUDY_SECTION_NAME: Clinical Management of Patients in Community-based Settings Study Section[CMPC]


NIH_SPENDING_CATS: Aging;Arthritis;Bioengineering;Chronic Pain;Clinical Research;Nanotechnology;Osteoarthritis;Pain Research

ORG_DEPT: ORTHOPEDICS

PHR: Project Narrative  Osteoarthritis is a disabling musculoskeletal disease affecting millions of people worldwide. Despite the clinical significance of joint osteoarthritis, there is no disease-modifying treatment. In this project, we will develop a novel intra-articular injection nanomedicine to address the underlying pathology of osteoarthritis.

PI_NAMEs: JIN, LI  (contact);LI, XUDONG J.;MILLER, MARK

PROGRAM_OFFICER_NAME: ZHENG, XINCHENG

PROJECT_TERMS: Address;Adult;Affect;Animals;Anti-Inflammatory Agents;Antiinflammatory Effect;Arthritis;Binding;Cartilage;cartilage degradation;Cartilage Matrix;Cell membrane;Charge;Chondrocytes;chondroprotection;clinical translation;clinically relevant;clinically significant;confocal imaging;Confocal Microscopy;Degenerative polyarthritis;Disabling;Disease;Dose;Drug or chemical Tissue Distribution;Drug usage;efficacy evaluation;Electrostatics;Evaluation;experimental study;FPR1 gene;Free Radical Scavenging;fullerene C60;Fullerenes;Goals;Growth Factor;Harvest;Health Care Costs;Histology;Human;Hyaluronic Acid;in vivo;in vivo imaging system;Infiltration;Inflammation;Inflammation Mediators;Inflammatory;Injections;injured;Injury;Interleukin-1 beta;Intra-Articular Injections;joint destruction;joint inflammation;joint injury;Joints;Knee;Knee joint;Knee Osteoarthritis;knee pain;Macrophage;Measures;Mechanics;Medial meniscus structure;Mediator;microCT;Modality;Modeling;Monitor;mouse model;multiplex assay;Mus;Musculoskeletal Diseases;nanomedicine;nanoparticle;nanotechnology platform;Neuropeptides;Nociception;novel;Outcomes Research;Pain;Pathogenesis;Pathology;Penetration;Peptides;Permeability;Persons;Pharmaceutical Preparations;Phenotype;prevent;Property;receptor;regenerative;Research;Spinal Ganglia;Steroids;Surface;Symptoms;Synovial Membrane;synthetic peptide;Therapeutic Effect;therapeutic target;Time;Tissue Harvesting;Tissues;Translations;Treatment Efficacy;uptake

PROJECT_TITLE: Macrophage Anchoring Nanomedicine to Replace Steroids for Intra-articular Injection

STUDY_SECTION: MTE

STUDY_SECTION_NAME: Musculoskeletal Tissue Engineering Study Section[MTE]


NIH_SPENDING_CATS: Biotechnology;Digestive Diseases;Hepatitis;Hepatitis - C;Immunization;Infectious Diseases;Liver Disease;Prevention;Vaccine Related

ORG_CITY: COLUMBUS

ORG_NAME: RESEARCH INST NATIONWIDE CHILDREN'S HOSP

PHR: Narrative Although direct acting antivirals can cure Hepatitis C virus (HCV) infection, a vaccine is necessary to stop new infections, and re-infections in cured individuals. However, the progress on HCV vaccine development has been stymied by a lack of animal models. The proposed studies will identify the immune correlates of protection against hepacivirus persistence and will characterize the rat model for future testing of traditional as well as more recent (mRNA vaccines) vaccination approaches for hepaciviruses.

PI_NAMEs: KAPOOR, AMIT  (contact)

PROGRAM_OFFICER_NAME: GAUTAM, RAJEEV

PROJECT_TERMS: Acceleration;Address;Adenovirus Vector;Adenoviruses;Adjuvant;Animal Model;Animals;Anti-viral Agents;Antigens;B-Lymphocytes;Biological Assay;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;cell killing;Cell surface;Cellular Immunity;Chronic;chronic infection;Communication;cytokine;Data;Dissection;env Gene Products;Epitope Mapping;Escape Mutant;experimental study;Failure;Future;Genetic Variation;Goals;Hepatitis C;Hepatitis C Vaccine;Hepatitis C virus;Hepatitis C-Like Viruses;Human;Human papillomavirus 16 E1 protein;Humoral Immunities;Immune;Immunity;Immunocompetent;in vivo;Individual;Infection;innovation;insight;Knowledge;Mediating;Modeling;Mus;Nature;neutralizing antibody;Nonstructural Protein;novel;Outcome;Pan Genus;Paper;Phenotype;Play;prevent;Proteins;Rattus;Reporting;RNA vaccine;RNA Virus Infections;Rodent;Role;single-cell RNA sequencing;Stains;Structural Protein;T-Cell Depletion;T-Lymphocyte;T-Lymphocyte Epitopes;Testing;transcriptome;Vaccinated;Vaccination;vaccination strategy;vaccine development;vaccine failure;vaccine trial;vaccine-induced immunity;Vaccines;Variant;Viral;Virus;Virus Diseases

PROJECT_TITLE: Immune correlates of protection against hepacivirus persistence.

STUDY_SECTION: IHD

STUDY_SECTION_NAME: Immunity and Host Defense Study Section[IHD]