ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Cancer Genomics;Genetics;Human Genome;Lung;Lung Cancer;Nanotechnology

ORG_CITY: OMAHA

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: UNIVERSITY OF NEBRASKA MEDICAL CENTER

ORG_STATE: NE

PHR: Project Narrative: FDA-approved PARP inhibitors have demonstrated great efficacy for BRCA-mutated (or homologous recombination repair (HRR)-deficient) cancers in preclinical and clinical studies, but limited efficacy for HRR- proficient cancers. With the aim to expand the clinical application to majority of cancer patients and address the inefficient delivery and off-target toxicity, this project will provide a safe and effective formulation for efficient and selective codelivery of DNA methylation inhibitor azacytidine and PARP inhibitors into tumor tissues.

PI_NAMEs: SUN, JINGJING  (contact)

PROGRAM_OFFICER_NAME: FU, YALI

PROJECT_TERMS: Address;Affect;Aftercare;Azacitidine;Biodistribution;Biological Availability;biophysical properties;bisulfite sequencing;Cancer Model;Cancer Patient;cancer type;chemical conjugate;Clinical;clinical application;clinical predictors;Clinical Research;Clinical Trials;Combined Modality Therapy;Complex;Computer Models;cyanine dye 5;cytotoxic;cytotoxicity;Data;deep sequencing;Defect;Detection;Development;DNA;DNA Damage;DNA Methylation;DNA Methyltransferase Inhibitor;DNA Modification Methylases;DNA Repair;DNA Repair Inhibition;dosage;Dose;Dose Limiting;Drug Combinations;Drug Kinetics;Effectiveness;Ensure;Epigenetic Process;epigenetic regulation;epigenetic therapy;Experimental Neoplasms;FDA approved;Formulation;Future;Gene Expression;Generations;Genes;High Pressure Liquid Chromatography;Histocompatibility Antigens Class I;homologous recombination;homologous recombination deficiency;Human;hydrophilicity;Hydrophobicity;Immune;Immune response;Immune system;improved;in vivo;inhibitor;Innate Immune System;insight;Label;Lewis Lung Carcinoma;Malignant Breast Neoplasm;Malignant Neoplasms;Maximum Tolerated Dose;Methylation;methylation pattern;Modeling;Mutate;Mutation;nanocarrier;nanoformulation;nanosized;neoantigens;Non-Small-Cell Lung Carcinoma;novel;Pathway interactions;patient derived xenograft model;Patients;Penetration;Pharmaceutical Preparations;Play;Poly(ADP-ribose) Polymerase Inhibitor;Polymers;preclinical study;Process;promoter;Property;recombinational repair;repaired;Reporting;response;Role;Safety;Site;Solid Neoplasm;Stimulator of Interferon Genes;synergism;Therapeutic;Time;Tissues;Tobacco-Associated Carcinogen;Toxic effect;transcriptome sequencing;Treatment Efficacy;Treatment-related toxicity;tumor;tumor growth;tumor microenvironment;Tumor Tissue;tumor-immune system interactions;Up-Regulation;Validation;Western Blotting;whole genome;Xenograft Model

PROJECT_TITLE: Ultra-Small Epigenetic-Regulating Nanocarrier for Enhanced Synthetic Lethal Therapy

STUDY_SECTION: DBTD

STUDY_SECTION_NAME: Drug and Biologic Therapeutic Delivery Study Section[DBTD]


ADMINISTERING_IC: HL

ARRA_FUNDED: N

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Cardiovascular;Genetics;Heart Disease;Women's Health Research

ORG_CITY: Boulder

ORG_COUNTRY: UNITED STATES

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF COLORADO

ORG_STATE: CO

PHR: PROJECT NARRATIVE Heart valve disease affects ~13% of the US population over 75 years old, but interestingly, men have a two- fold higher risk for developing calcified valves whereas women tend to present with severely fibrotic valves. This proposal aims to investigate these sex differences, particularly the dynamic interplay between sex-specific immune cell interactions with resident valve interstitial cells, which subsequently leads to increasing valve fibrosis and calcification. Our approach includes the 3D culture of valve interstitial cells in hydrogel matrices that mimic the valve microenvironment, as well as mouse models that can mimic valve disease, and then use these models to identify small molecule drugs, specific for men and women, that could mediate fibro- calcification of their heart valves.

PI_NAMEs: ANSETH, KRISTI S. (contact);WEISS, ROBERT M

PROGRAM_OFFICER_NAME: EVANS, FRANK

PROJECT_TERMS: 3-Dimensional;Adult;Affect;aged;Animal Model;antagonist;Anti-Inflammatory Agents;Aorta;aortic valve;aortic valve disorder;Aortic Valve Stenosis;ATAC-seq;biological sex;Blood flow;cadherin-11;calcification;Calcium Channel;Cell Communication;Cells;Chromatin;chromatin modification;Chromatin Remodeling Factor;Coculture Techniques;Collagen;CREBBP gene;Cues;cytokine;Data;Deposition;Disease;Disease Progression;DNA;efficacy testing;EFRAC;Encapsulated;Epigenetic Process;Exposure to;Family suidae;Female;Fibroblasts;Fibrosis;Functional disorder;Gene Expression;Genes;Goals;Heart Valve Diseases;Heart Valves;high risk;Histones;Human;Hydrogels;hypertensive;Image;Immune;immune function;Immune response;In Situ;In Vitro;in vitro Model;in vivo;Inflammation;Inflammatory;inhibitor;insight;interstitial cell;Left ventricular structure;Macrophage;male;Mediating;Mediator;men;Methodology;Methylation;Microscopy;mimetics;Modeling;Molecular;Molecular Target;mouse model;Mus;Myofibroblast;Osteoblasts;osteopontin;Patients;Pharmaceutical Preparations;Phenotype;Physiologic calcification;Play;Population;Process;Progressive Disease;promoter;receptor;recruit;Regulation;Role;SERPINE1 gene;Severity of illness;sex;Sex Differences;sexual dimorphism;Signal Transduction;small molecule;small molecule inhibitor;targeted treatment;Testing;therapeutic evaluation;three dimensional cell culture;Tissues;transcription factor;transcriptome sequencing;ultra high resolution;Validation;Woman;women patients

PROJECT_TITLE: Hydrogel matrices to study the role of inflammation and biological sex on aortic valve fibrocalcification

STUDY_SECTION: MPPA

STUDY_SECTION_NAME: Integrative Myocardial Physiology/Pathophysiology A Study Section [MPPA]


ADMINISTERING_IC: DA

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Drug Abuse (NIDA only);Networking and Information Technology R&D (NITRD);Precision Medicine;Prevention;Substance Misuse;Tobacco;Tobacco Smoke and Health

ORG_CITY: LA JOLLA

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

ORG_STATE: CA

PHR: PROJECT NARRATIVE Despite tobacco use being the leading preventable cause of death in the United States, over 51 million U.S. adults continue to use tobacco products. This research proposal could substantially advance treatment development for tobacco use disorders and addictions broadly by evaluating the validity of the VR-AB biomarker for use as a predictive and/or surrogate endpoint in clinical smoking cessation trials. The validation of reliable biomarkers of addiction such as attentional bias would greatly benefit treatment development by providing earlier identification of treatment efficacy, thus shortening trial lengths and costs considerably, and by the identification of subpopulations, or biotypes, that may be more likely to respond to a given treatment.

PI_NAMEs: COURTNEY, KELLY ELIZABETH (contact)

PROGRAM_OFFICER_NAME: HERRMANN, EVAN SULLIVAN

PROJECT_TERMS: addiction;Adult;Aftercare;Age;attentional bias;Attenuated;Behavior;Behavioral;Biological Markers;biotypes;candidate validation;Cause of Death;Cigarette Smoker;cigarette user;Clinical;comparison control;cost;craving;Cues;Data;Development;Dose;Double-Blind Method;Drug Addiction;Early identification;effective therapy;Eye;follow-up;gaze;Goals;improved;interest;Length;National Institute of Drug Abuse;neurophysiology;Nicotine;nicotine craving;nicotine cue;nicotine use;nicotine user;novel;Outcome;Participant;Pharmaceutical Preparations;pharmacologic;placebo group;Placebos;potential biomarker;predictive marker;Protocols documentation;Psychological reinforcement;Randomized;Relapse;relapse risk;Research Proposals;Resources;response biomarker;Risk;sample fixation;Sampling;sex;smartphone based assessment;smoking cessation;Smoking Cessation Intervention;Surrogate Endpoint;Technology;Testing;therapy development;Time;Titrations;Tobacco;Tobacco use;Tobacco Use Disorder;tool;Treatment Efficacy;United States;Validation;varenicline;virtual reality;Visit

PROJECT_TITLE: Advancing VR-based attentional bias as a biomarker for tobacco use disorder

STUDY_SECTION: ARM

STUDY_SECTION_NAME: Addiction Risks and Mechanisms Study Section[ARM]


ADMINISTERING_IC: EY

ED_INST_TYPE: GRADUATE SCHOOLS

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Eye Disease and Disorders of Vision;Neurosciences

ORG_CITY: NEW YORK

ORG_DEPT: PSYCHOLOGY

ORG_NAME: COLUMBIA UNIV NEW YORK MORNINGSIDE

ORG_STATE: NY

PHR: PROJECT NARRATIVE The brain is a predictive organ: its memories of the past are used to adaptively guide behavior in anticipation of events that might occur seconds, minutes, hours, or longer in the future. This project will uncover how the brain can simultaneously represent anticipatory signals at multiple timescales, how these signals are influenced by top-down goals, and how they can guide future-oriented behavior. Understanding how hierarchical anticipation signals support behavior at a range of timescales will yield important insights into how flexible, future-oriented actions are planned and implemented in a constantly changing world.

PI_NAMEs: ALY, MARIAM  (contact);BALDASSANO, CHRISTOPHER

PROGRAM_OFFICER_NAME: WIGGS, CHERI

PROJECT_TITLE: Hierarchies of spatiotemporal anticipation in the human brain


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Cancer Genomics;Clinical Research;Genetics;Human Genome;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Patient Safety;Precision Medicine;Prevention;Prostate Cancer;Radiation Oncology;Urologic Diseases

ORG_CITY: MILWAUKEE

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

ORG_STATE: WI

PHR: NARRATIVE Prostate cancer impacts the lives of ~190,000 men diagnosed each year in the United States and, given the high 5-year relative survival rate of >95%, approaches to minimize treatment toxicities are needed. Bladder and rectal toxicities resulting from prostate cancer radiotherapy are dose-limiting, costly to the healthcare system, and negatively impact quality of life. This study will apply our novel machine learning method to develop and validate integrated dose-volume-genetic risk models for late bladder and rectal toxicity and assess feasibility of incorporating these models into clinical workflow as a critical step towards giving Radiation Oncologists the tools they need to personalize therapy and reduce toxicities.

PI_NAMEs: HALL, WILLIAM ;KERNS, SARAH L. (contact);OH, JUNG HUN

PROGRAM_OFFICER_NAME: DIVI, RAO L

PROJECT_TERMS: 3-Dimensional;Angiotensin-Converting Enzyme Inhibitors;Angiotensinogen;Bioinformatics;Biological;Bladder;Calibration;cancer care;Cancer Patient;cancer radiation therapy;Clinic;Clinical;clinical decision-making;Clinical Oncology;clinical practice;Clinical Research;cohort;Collaborations;Computer software;Computerized Medical Record;Conformal Radiotherapy;cost;Data;Data Set;design;Diagnosis;DNA;Dose;Dose Limiting;efficacy trial;Etiology;experimental arm;explainable machine learning;feasibility testing;Fibrosis;follow-up;Fractionated radiotherapy;Future;gastrointestinal;Genetic;Genetic Predisposition to Disease;Genetic Risk;Genitourinary system;genome wide association study;Goals;Healthcare Systems;Hemorrhage;Heritability;high risk;improved;improved outcome;Incidence;Individual;individual patient;Inflammation;Inherited;Injury;innovation;interest;International;Intervention;Life;Linkage Disequilibrium;Machine Learning;machine learning method;Malignant neoplasm of prostate;Medical;member;men;Methods;Modeling;Molecular;Mutagenicity Tests;Normal tissue morphology;novel;Oncology;Operative Surgical Procedures;Outcome;Pain;participant enrollment;Pathway interactions;Patient Selection;Patients;Penetrance;personalized medicine;Phase;Physicians;polygenic risk score;Predisposition;prevent;Prevention;prospective;prospective test;Prostate Cancer therapy;prostate radiotherapy;Publications;Quality of life;Radiation;Radiation exposure;Radiation Oncologist;Radiation Oncology;Radiation therapy;Radiation Therapy Oncology Group;Radiogenomics;randomized trial;Rectum;Risk;Saliva;Sampling;simulation;Single Nucleotide Polymorphism;Subgroup;Surveys;Survival Analysis;Survival Rate;Survivors;Testing;Therapy trial;Time;tissue injury;tool;Toxic effect;Training;training data;treatment planning;Treatment-related toxicity;trial design;tumor;United States;Validation;Work

PROJECT_TITLE: Multi-cohort validation of machine learning radiogenomic models (ML-RGx) to predict late toxicity in prostate cancer

STUDY_SECTION: CDMA

STUDY_SECTION_NAME: Clinical Data Management and Analysis Study Section[CDMA]


ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Genetics;Human Genome;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD)

ORG_CITY: SEATTLE

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: Project narrative A variety of experimental methods, most notably the Hi-C assay, have been developed to measure the chromatin 3D architecture that is often represented in the form of a “contact matrix.” Despite considerable progress in analyzing these contact matrices, computational tools that can perform joint analyses of Hi-C and other types of data are still lacking, hindering the progress toward deciphering the relationship between genome structure and function. Here, we propose to develop novel machine learning methods that can integrate time-course Hi-C data and RNA-seq data, co-embed genome sequences, and low-coverage contact data for resolution enhancement, and translate between Hi-C and ATAC-seq.

PI_NAMEs: WANG, SHENG  (contact)

PROGRAM_OFFICER_NAME: GILCHRIST, DANIEL A

PROJECT_TERMS: 3-Dimensional;Address;Architecture;ATAC-seq;Biological;Biological Assay;Cell Cycle;Cell Differentiation process;Cell Physiology;cell type;Chromatin;Chromatin Structure;Collection;Computer software;computerized tools;Data;Data Set;Development;Dimensions;Disease;Disease Progression;DNA;Endothelial Cells;Enhancers;experimental study;Future;Gene Expression;Gene Expression Regulation;Genes;Genetic Transcription;Genome;genome-wide;genomic data;genomic locus;Genomics;Graph;Health;Hi-C;high dimensionality;human embryonic development;insight;interest;Joints;Learning;Machine Learning;machine learning method;machine learning model;Maps;Measures;Memory;Messenger RNA;Methods;Modality;Modeling;Molecular;Nature;novel;open source;Play;pre-trained model;Predictive Analytics;Process;promoter;protein protein interaction;Resolution;Resources;RNA Splicing;Role;Series;spatiotemporal;Structure;System;three dimensional structure;Time;tool;Training;transcriptome sequencing;Translating;translational model;Translations;United States National Institutes of Health

PROJECT_TITLE: Deep integrative analysis of Hi-C data

STUDY_SECTION: BDMA

STUDY_SECTION_NAME: Biodata Management and Analysis Study Section[BDMA]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Neurosciences

ORG_CITY: DAVIS

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: Project Narrative. Proprioception is the ability to internally sense limb position and posture and is encoded by sensory neurons called proprioceptors, which transform changes in muscle length and force into electrical signals that are transmitted to locomotor circuits in the spinal cord. Normal proprioceptor function is essential for purposeful movement and is impaired in a variety of conditions, including spinal cord injury, aging, and amyotrophic lateral sclerosis; however, little is known about how electrical signals in proprioceptors are sent. This research will enhance scientific understanding of mammalian proprioception by systematically defining how voltage-gated sodium channels (NaVs) differentially shape proprioceptive signaling in the healthy nervous system, with important implications for understanding and ultimately treating conditions in which proprioception is impaired.

PI_NAMEs: GRIFFITH, THEANNE NICOLE (contact)

PROGRAM_OFFICER_NAME: CHEN, DAOFEN

PROJECT_TERMS: Acceleration;Action Potentials;Acute;Address;Affect;Afferent Neurons;Aging;Amyotrophic Lateral Sclerosis;Animals;Antibodies;Axon;Behavior;behavior test;Behavioral;Biophysical Process;Biophysics;body sense;Brain;Central Nervous System;Code;comparison control;Complement;conditional knockout;Cre driver;Data;Dependence;Development;Disinhibition;efficacy study;Electrophysiology (science);experimental study;Future;Genetic;Goals;human disease;Immunohistochemistry;Impairment;In Vitro;Individual;inducible Cre;insight;Intention Tremor;Knock-out;Knockout Mice;Length;Limb structure;Mammals;mechanotransduction;Modeling;monosynaptic reflex;Motor;motor behavior;motor control;motor deficit;Motor Neurons;mouse model;Movement;Mus;Muscle;Mutation;Nerve;Nervous System;Neurologic;neuronal excitability;Neurons;Neurosciences;neurotransmission;novel therapeutics;optogenetics;Parvalbumins;patch clamp;Pathway interactions;Peripheral;Peripheral Nervous System Diseases;Physiologic pulse;Piezo 2 ion channel;Play;Positioning Attribute;Posture;Preparation;Proprioception;Proprioceptor;Protein Isoforms;Proteins;Publishing;Recovery;Reflex action;Reporting;Research;response;Role;SCN1A protein;SCN8A gene;Sensory;sensory input;Shapes;Signal Transduction;Skeletal Muscle;Sodium;Sodium Channel;Spinal;Spinal Cord;Spinal cord injury;Stretching;superresolution imaging;synaptic depression;Synaptic Transmission;Tendon structure;Testing;Time;Tissues;transmission process;voltage;voltage gated channel;Weaning;Work

PROJECT_TITLE: The electrical basis of proprioceptive signaling

STUDY_SECTION: SMN

STUDY_SECTION_NAME: Sensory-Motor Neuroscience Study Section[SMN]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biotechnology;Clinical Research;Digestive Diseases;Infant Mortality;Infectious Diseases;Liver Disease;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Precision Medicine;Pregnancy;Preterm, Low Birth Weight and Health of the Newborn;Prevention;Rare Diseases;Sexually Transmitted Infections;Women's Health Research

ORG_CITY: SAN FRANCISCO

ORG_DEPT: OBSTETRICS & GYNECOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: NARRATIVE There is an urgent need for improved diagnostic tests in pregnancy, when timely and adequate treatment is of crucial importance to reduce the risk of congenital syphilis, whose rates have been rising exponentially in the U.S. The overarching goal of these studies is to discover new candidate molecules for novel diagnostic markers for syphilis in pregnancy and congenital syphilis.

PI_NAMEs: GAW, STEPHANIE LINA (contact)

PROGRAM_OFFICER_NAME: GLOCK, JONATHAN A

PROJECT_TERMS: Affect;Aftercare;Anemia;Antibodies;Antibody titer measurement;Antigens;Bacterial RNA;biobank;Biological Assay;Biological Markers;Birth;Blindness;Blood specimen;Blood Tests;care coordination;Clinical;clinical practice;Complex;Congenital Syphilis;Counseling;Data;Development;Diagnosis;diagnostic biomarker;Diagnostic tests;Disease;Dose;Drops;Early Diagnosis;Enrollment;Exanthema;Fetus;Future;Gestational Age;Goals;hearing impairment;Hepatosplenomegaly;high risk;Icterus;improved;indium arsenide;Infant;Infant Mortality;Infection;innovation;Intramuscular;Latent Syphilis;Live Birth;Location;longitudinal analysis;Low Birth Weight Infant;Mass Spectrum Analysis;Maternal-fetal medicine;Metabolic;metabolomics;Molecular;multiple omics;Neonatal;novel;novel diagnostics;novel marker;Nucleic Acid Amplification Tests;Oral;Patients;Penicillins;Performance;Perinatal Infection;postnatal;Pregnancy;pregnant;Premature Birth;prenatal;Prevalence;Prognosis;Prospective cohort;protein biomarkers;proteomic signature;Proteomics;Recording of previous events;Research;Resources;response;Risk Assessment;risk minimization;Risk Reduction;Sampling;Sensitivity and Specificity;Serology;Serology test;Severity of illness;skeletal abnormality;Spontaneous abortion;stillbirth;Structural Congenital Anomalies;Syphilis;Testing;Time;transcription mediated amplification;transmission process;Treatment Protocols;treatment response;Treponema pallidum;ultrasound;Umbilical Cord Blood;United States;Vagina;Woman

PROJECT_TITLE: Multi-omic approaches to identify novel biomarkers for the diagnosis of syphilis in pregnancy and assessment of treatment response

STUDY_SECTION_NAME: Special Emphasis Panel[ZAI1 FDS-M (M1)]


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Depression;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Machine Learning and Artificial Intelligence;Major Depressive Disorder;Maternal Health;Maternal Morbidity and Mortality;Mental Health;Mental Illness;Microbiome;Neurosciences;Nutrition;Pediatric;Pregnancy;Prevention;Racial and Ethnic Minority Health Research;Serious Mental Illness;Social Determinants of Health;Women's Health Research

ORG_CITY: Chicago

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE Perinatal depression (PND) affects 10-20% of women during pregnancy and for a year following birth and increases the risk of morbidity for mothers and infants, but because the causes and risk factors for PND are largely unknown, clinicians can predict neither which women are at risk nor the most beneficial preventive interventions and precise treatments. Our initial results in a small sample of low-income women of color showed that multiple bacterial metabolic processes in the mother’s gastrointestinal tract were associated with depressive symptom severity early in pregnancy. We propose to use systems biology approaches, such as machine learning and network modeling, to predict, identify the mechanisms, and determine causal role of maternal gut microorganisms in PND to reduce the negative consequences of this debilitating disorder for the mother, the infant, and their families.

PI_NAMEs: PENALVER BERNABE, BEATRIZ  (contact)

PROGRAM_OFFICER_NAME: GIRARDI, GUILLERMINA

PROJECT_TERMS: adverse outcome;Affect;Aminobutyric Acids;Animal Model;antepartum depression;Bayesian Network;Behavior;bile acid metabolism;Bile Acids;Biochemical Pathway;Birth;Black race;black women;Blood;Blood specimen;Brain;Breast Feeding;Characteristics;clinical translation;Coin;Communication;Coupling;Data;depressive symptoms;Development;Diet;Disease;Elements;Endocrine system;Ethnic Origin;Etiology;Experimental Animal Model;explainable machine learning;Family;fecal microbiota;fecal transplantation;Feces;Female;First Pregnancy Trimester;Future;gamma-Aminobutyric Acid;Gastrointestinal tract structure;Gene Expression Profile;Genetic;Germ-Free;gut microbiota;Health;heart rate variability;High Risk Woman;Hormones;Human;Immune;Immune system;improved;Infant;Inflammatory;Latina;Latina Population;Life Style;Link;Longitudinal Studies;Low income;Machine Learning;machine learning model;Measures;Mediating;Mental disorders;Mental Health;Metabolic;Metabolism;metabolome;metabolomics;Metagenomics;microbial;microbial community;microbial genome;microbial host;microbiota-gut-brain axis;microorganism;Modeling;modifiable risk;Moods;Morbidity - disease rate;Mothers;mouse model;multiple omics;Mus;network models;neurodevelopment;Neurologic;Neurotransmitters;Not Hispanic or Latino;novel;novel marker;Participant;Pathway Analysis;Pattern;Perinatal;perinatal depressive symptom;perinatal period;peripartum depression;Physical activity;Play;Postpartum Period;predictive marker;Pregnancy;pregnant;Premature Birth;Prevention;preventive intervention;Process;Production;Progesterone;prospective;Proxy;psychosocial;Public Health;Questionnaires;Race;recruit;Research Infrastructure;Risk;Risk Factors;Role;Sampling;Second Pregnancy Trimester;Serotonin;Serum;Severities;Sleep;sociodemographics;stool sample;Stress;Symptoms;System;systemic inflammatory response;Systems Biology;Taurine;Testing;theories;transcriptome;transcriptomics;translational study;Trauma;trend;Tryptophan;Tryptophan Metabolism Pathway;United States;Visit;Volatile Fatty Acids;Woman;women of color;Work;wristband

PROJECT_TITLE: Prediction, mechanisms and causality: a systems biology approach to elucidate the role of the dynamic interplay between maternal and microbial systems in the pathobiology of perinatal depression

STUDY_SECTION: MESH

STUDY_SECTION_NAME: Biobehavioral Mechanisms of Emotion, Stress and Health Study Section[MESH]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Bioengineering;Clinical Research;Clinical Trials and Supportive Activities;Dental, Oral, and Craniofacial Disease;Digestive Diseases

ORG_CITY: CHICAGO

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

PHR: PROJECT NARRATIVE Swallowing difficulties are extremely common and symptoms of dysphagia result in a substantial reduction in the quality of life for patients regardless of the cause. Unfortunately, our current understanding of the physiologic causes of these symptoms is limited by a lack of tools to accurately measure the mechanics of esophageal emptying. This proposal will utilize new analysis techniques to better understand the causes of esophageal dysfunction to determine methods to improve esophageal function and quality of life.

PI_NAMEs: CARLSON, DUSTIN ALLAN;PANDOLFINO, JOHN E (contact)

PROGRAM_OFFICER_NAME: SHEA-DONOHUE, TEREZ

PROJECT_TERMS: Achalasia;Address;Aftercare;Algorithms;aspirate;Atropine;Biomechanics;Bolus Infusion;botulinum neurotoxin injection;Chicago;Classification;Classification Scheme;clinically relevant;Data;Defense Mechanisms;Deglutition;Deglutition Disorders;Development;Diagnosis;Diagnostic;Diameter;Dilatation - action;Disease;Disease stratification;effective therapy;Elasticity;electric impedance;Esophageal Diseases;Esophagogastric Junction;Esophagus;Esophagus motility;Evolution;Fluoroscopy;Foundations;Functional disorder;Fundoplication;Gastroesophageal reflux disease;Geometry;Goals;Grant;Health;Hybrids;impaired driving performance;Impairment;improved;Injury;Intervention;Malnutrition;Manometry;Maps;Measures;Mechanics;Methods;Modeling;Morbidity - disease rate;mortality;Motility;motility disorder;motor disorder;Muscle;National Institute of Diabetes and Digestive and Kidney Diseases;neuromuscular;new technology;new therapeutic target;novel;novel strategies;novel therapeutic intervention;Obstruction;Outcome;outcome prediction;Pathogenesis;Pathogenicity;patient population;Patients;Peristalsis;Phenotype;Physics;Physiological;Physiology;predict clinical outcome;predicting response;Prediction of Response to Therapy;predictive modeling;pressure;prevent;Property;Prospective cohort;Protocols documentation;Quality of life;Reflux;Relaxation;Resistance;Resolution;response;Scheme;Secondary to;Severity of illness;success;Symptoms;System;Techniques;Testing;Therapeutic Intervention;Time;tool;virtual;Work

PROJECT_TITLE: Evolution of the Chicago Classification: Bridging Physiology and Mechanics

STUDY_SECTION: DNPD

STUDY_SECTION_NAME: Digestive and Nutrient Physiology and Diseases Study Section [DNPD]


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Biotechnology

ORG_DEPT: CHEMISTRY

PI_NAMEs: TEZCAN, FAIK AKIF (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TERMS: Active Sites;Address;amidase;Amides;Architecture;Automobile Driving;Binding;Binding Sites;Biology;Biomimetics;carbene;Catalysis;Cell Physiology;Cell Respiration;Complex;design;design and construction;Dioxygen;Elements;Engineering;Environment;Enzymes;esterase;Esters;Evolution;Genetic Transcription;Geometry;Goals;Health;Human;Hydrolase;Hydrolysis;improved;interfacial;Ions;Knowledge;Lead;metal complex;Metal Ion Binding;metalloenzyme;Metalloproteins;Metals;Methods;Nature;Nova antigen;novel;oxidation;Oxidation-Reduction;Peptides;Phosphoric Monoester Hydrolases;polypeptide;programs;Property;Protein Engineering;protein oligomer;protein structure;Proteins;Rationalization;Reaction;Research;Research Project Grants;scaffold;Scaffolding Protein;Spectrum Analysis;structural determinants;Structure;Structure-Activity Relationship;Technology

PROJECT_TITLE: Design and Evolution of Metal-Based Functions in Supramolecular Protein Scaffolds

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 MBBC-K (02)]


NIH_SPENDING_CATS: Aging;Eye Disease and Disorders of Vision;Neurodegenerative;Neurosciences

ORG_CITY: BIRMINGHAM

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: Glaucoma is one of the leading causes of blindness worldwide and we know that increased eye pressure is a risk factor for glaucoma. The research described in this application is aimed at investigating how centers within the brain signal the eye to control eye pressure.

PI_NAMEs: SAMUELS, BRIAN CHRISTOPHER (contact)

PROGRAM_OFFICER_NAME: SONG, HONGMAN

PROJECT_TERMS: Address;Affect;Alleles;antagonist;Anterior;anterior chamber;Anterior eyeball segment structure;aqueous;Aqueous Humor;aqueous humor flow;Attenuated;attenuation;Autonomic ganglion;biobank;Blindness;Body mass index;Brain;Brain Stem;Candidate Disease Gene;Cell Nucleus;Central Nervous System;Chemical Stimulation;Ciliary Body;Ciliary Muscle;circadian;Circadian Dysregulation;Circadian Rhythms;curve fitting;Data;Databases;design;Development;Dyes;Eye;Fluorescein;Fluorophotometry;Genes;Genetic Polymorphism;genome wide association study;genomic variation;Genomics;Glaucoma;Histologic;Hour;hypocretin;Hypothalamic structure;Injections;insight;interest;Knock-out;Knockout Mice;Knowledge;Lead;Measures;Mediating;Medical;Mendelian randomization;Methodology;Microinjections;modifiable risk;Monitor;Mouse Strains;Mus;Nervous System control;Neurons;Neurotransmitters;novel;Oral;orexin 1 receptor;Participant;Pathway interactions;Peptides;Physiologic Intraocular Pressure;pressure;Primary Open Angle Glaucoma;Production;Proteins;Protocols documentation;Publishing;raphe nuclei;Rattus;receptor;Regulation;Research;Resistance;response;Risk Factors;Role;Saline;Signal Transduction;Site;subcutaneous;System;Testing;The Jackson Laboratory;Time;Tissues;Topical application;trait;Transgenic Mice;United States National Institutes of Health;Variant

PROJECT_TITLE: The role of orexins in regulating intraocular pressure.

STUDY_SECTION_NAME: Pathophysiology of Eye Disease - 1 Study Section[PED1]


ADMINISTERING_IC: AG

ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

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);Brain Disorders;Congenital Structural Anomalies;Dementia;Dental, Oral, and Craniofacial Disease;Lymphatic Research;Neurodegenerative;Neurosciences;Pediatric;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: Los Angeles

ORG_DEPT: DENTISTRY

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: PROJECT NARRATIVE There is an unmet medical need to develop new therapeutic strategies for Alzheimer’s disease (AD). Lymphatic vasculature system regulates fluid homeostasis, waste disposal, and immune functions. The goal of this project is to establish multiplex brain lymphatic activation strategies as a therapeutic approach for AD.

PI_NAMEs: CHEN, JIANFU  (contact)

PROGRAM_OFFICER_NAME: NEWMAN, ELIZABETH

PROJECT_TERMS: 3-Dimensional;Affect;Alzheimer like pathology;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease risk;Amyloid;Amyloid beta-Protein;Animal Model;Behavior;Binding;bone;Brain;cell growth;Cell secretion;Cells;Cephalic;Cerebrospinal Fluid;Chotzen Syndrome;cisterna magna;citrate carrier;Cognitive deficits;Communication;Coupled;craniofacial;Craniosynostosis;cranium;Data;Deep Cervical Lymph Node;Defect;Disease;Drainage procedure;efficacy evaluation;Fluid Balance;Functional disorder;gene therapy;Genetic;Goals;Growth;Health;Hippocampus;Human;hyperphosphorylated tau;immune function;Impairment;implantation;Individual;Inflammation;Injections;Intercellular Fluid;Investigation;Light;loss of function;Lymph Node Drainage;Lymphatic;lymphatic dysfunction;Lymphatic Endothelial Cells;lymphatic vasculature;lymphatic vessel;Mediating;Medical;Meningeal lymphatic system;Meninges;Mesenchymal Stem Cells;Methods;Microscopy;Morphology;mouse model;Mus;Names;Natural regeneration;Nerve Degeneration;Neurocognitive;Neuroglia;novel therapeutic intervention;Organ;Outcome Study;Pathogenesis;Pathology;Patients;Perfusion;Positioning Attribute;premature;receptor;Recombinant Proteins;reconstruction;Refuse Disposal;Reporter;Signal Transduction;Skull Disorder;Solvents;stem cells;Surgical sutures;System;Testing;Therapeutic;Three-Dimensional Imaging;Tissues;tool;Toxic effect;Vascular Endothelial Growth Factor C;Vascular Endothelial Growth Factor Receptor-3;VEGFC gene;Verteporfin;Virulence Factors;Visualization;wasting

PROJECT_TITLE: Multiplex meningeal lymphatic activation for Alzheimer’s disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 AN-B (55)]


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Autoimmune Disease;Behavioral and Social Science;Cardiovascular;Clinical Research;Diabetes;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Pediatric;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: Aurora

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF COLORADO DENVER

PHR: PROJECT NARRATIVE Cardiovascular disease (CVD) is the leading cause of death in people with type 1 diabetes (T1D), and is largely preventable. CVD disproportionately affects Hispanic and non-Hispanic Black people with T1D, but little is know about the factors contributing to these disparities. Our study is uniquely positioned to advance scientific understanding of disparities in CVD risk early in the T1D disease course by leveraging the comprehensive, longitudinal data available from the racially/ethnically diverse SEARCH sample coupled with novel CVD assessments in young adulthood. With continued increase in T1D incidence, especially in Hispanic and NHB youth, the number of individuals living with this condition is projected to triple by 2050, forecasting a substantial rise in the societal burden of managing T1D and preventing its CVD comorbidities. This work has the potential to inform the design of multi-level interventions to prevent CVD in individuals at highest risk due to T1D.

PI_NAMEs: CONWAY, BAQIYYAH ;DABELEA, DANA  (contact);SNELL-BERGEON, JANET KATHLEEN

PROGRAM_OFFICER_NAME: REIS, JARED P

PROJECT_TERMS: Affect;Age;Albuminuria;Black Populations;Black race;Blood Pressure;Blood Vessels;Cardiac;Cardiovascular Abnormalities;Cardiovascular Diseases;cardiovascular disorder prevention;cardiovascular disorder risk;cardiovascular health;Cardiovascular Models;Caring;Cause of Death;Childhood;Clinical;Cohort Studies;Communication;Communities;comorbidity;contextual factors;Coupled;Data;design;Diabetes Mellitus;Diagnosis;Diet;Disease;Disease Outcome;Disparity;Echocardiography;Economics;Education;emerging adult;Enrollment;Environment;ethnic difference;ethnic disparity;ethnic diversity;Ethnic Origin;Ethnic Population;Evaluation;Event;experience;food insecurity;Functional disorder;Health;Health behavior;health care availability;health care quality;health equity;health goals;health inequalities;Health Insurance;Heart Abnormalities;high risk;Hispanic;Incidence;Income;Individual;insulin dependent diabetes mellitus onset;Insulin-Dependent Diabetes Mellitus;Intervention;Interview;Left Ventricular Hypertrophy;Lipids;Low income;Mediating;Methods;Modernization;mortality;Neighborhoods;Not Hispanic or Latino;novel;Outcome;Participant;peer;Persons;Physical activity;Population;Positioning Attribute;Prevalence;prevent;Prevention strategy;Race;racial difference;racial disparity;racial diversity;racial minority population;Reporting;Risk Factors;Sampling;Scientific Advances and Accomplishments;SEARCH for Diabetes in Youth;sleep pattern;Smoking;social;social health determinants;Socioeconomic Factors;Structure;System;Technology;Time;tonometry;Ultrasonography;Unhealthy Diet;Uninsured Medical Expense;vascular abnormality;Visit;Weight;Work;young adult;Youth

PROJECT_TITLE: Disparities in cardiovascular health in young adults with type 1 diabetes

STUDY_SECTION: CRD

STUDY_SECTION_NAME: Cardiovascular and Respiratory Diseases Study Section[CRD]


NIH_SPENDING_CATS: Asthma;Genetics;Lung

ORG_CITY: FARGO

ORG_DEPT: PHARMACOLOGY

ORG_NAME: NORTH DAKOTA STATE UNIVERSITY

ORG_STATE: ND

PHR: Project Narrative  Asthma is characterized by chronic inflammation and airway thickening in the conducting airways leading to respiratory symptoms, lung function decline, and exacerbation. Aryl hydrocarbon receptor (AhR) is an important modulator of host-environment interactions and inflammation, suggesting it may have a key role in asthma pathogenesis. We propose that activation of the AhR signaling in airway smooth muscle (ASM) will reduce inflammation-induced airway hyperresponsiveness and remodeling in asthma. Our studies using human ASM from both non-asthmatics vs. asthmatics, along with animal studies, where we knockout AhR in smooth muscle, will substantially enhance our understanding of how AhR in ASM influence the asthmatic airway structure and function. This is a clinically important step to gain basic fundamental knowledge in the development of novel therapeutic strategies to mitigate remodeling aspects of asthma.

PI_NAMEs: BRITT, RODNEY ;VENKATACHALEM, SATHISH  (contact)

PROGRAM_OFFICER_NAME: LU, QING

PROJECT_TERMS: Adhesions;Adult;Agonist;airway epithelium;airway hyperresponsiveness;airway inflammation;airway remodeling;Allergens;allergic airway inflammation;Animals;antagonist;ARNT gene;Aryl Hydrocarbon Receptor;Asthma;asthma model;asthmatic;asthmatic airway;bioinformatics tool;Cardiovascular system;Cell Cycle;cell motility;Cell Proliferation;Cells;Chemicals;Chronic;Clinical;clinically relevant;clinically significant;CYP1B1 gene;cytokine;Data;Deposition;Development;Diesel Exhaust;Diet;Disease;Disease Progression;Drug Metabolic Detoxication;Environment;Environmental Exposure;Epithelial Cells;Epithelium;Exposure to;Extracellular Matrix;Extrinsic asthma;Female;Functional disorder;Gene Expression;gene repression;Genetic;Goals;Homeostasis;Human;human tissue;Immune;Immune response;Immunofluorescence Immunologic;improved;In Vitro;in vivo;Infection;Inflammation;Inflammatory;inflammatory modulation;Inflammatory Response;Inhalation;interest;Interleukin-13;Knock-out;Knockout Mice;Knowledge;laser capture microdissection;Ligands;Lung;male;Mediating;Messenger RNA;Metabolic;methacholine;migration;Mitogens;Modeling;mouse allergen;mouse model;Mus;Muscle function;Muscle Proteins;muscular structure;Neurons;novel;novel therapeutic intervention;particle;Pathogenesis;Pathway interactions;Physiological;Play;pollutant;Production;Proliferating;Protein Analysis;pulmonary function;pulmonary function decline;Pulmonary Inflammation;Receptor Activation;receptor expression;receptor function;Receptor Signaling;Regulation;respiratory;Respiratory Signs and Symptoms;respiratory smooth muscle;response;Role;sensor;Severity of illness;Small Interfering RNA;Smooth Muscle;Smooth Muscle Myocytes;Structure;Techniques;Testing;Tetrachlorodibenzodioxin;TNF gene;Toxin;transcription factor;transcriptome sequencing;transcriptomics;Transforming Growth Factor beta

PROJECT_TITLE: Aryl hydrocarbon receptor signaling in Airway Inflammation

STUDY_SECTION: LCMI

STUDY_SECTION_NAME: Lung Cellular, Molecular, and Immunobiology Study Section[LCMI]


PHR: N/A – Public Health Relevance remains unchanged SPECIFIC AIMS Type 1 diabetes (T1D) results from the destruction of insulin producing β-cells upon immune infiltration and inflammation of the islets of Langerhans in the pancreas (insulitis). Lifelong insulin therapy is required, although patients remain at risk for both chronic diabetic complications and potentially fatal hypoglycemia. Prior to clinical onset of T1D there is an asymptomatic phase of many years during which β-cell mass and function progressively declines but glucose homeostasis remains normal. This ‘pre-symptomatic’ phase presents a window for therapeutic intervention. Indeed, immune therapies under investigation have shown some success in blunting β-cell decline, with antiCD3 recently receiving FDA approval. However, there are limited means for detecting and tracking the development of insulitis in this ‘pre-symptomatic’ T1D window to guide therapeutic interventions. Further, there is a complete lack of means to track the response to preventative treatment, prior to T1D onset. Clinical imaging modalities have been investigated to detect signatures of insulitis and β-cell decline but have either shown limited success in human subjects or are not practical for widescale deployment. Ultrasound imaging presents many advantages for clinical deployment, including widespread availability and absence of ionizing radiation. Gas-filled microbubble (MB) contrast agents are clinically approved, and are used in detection, therapy and monitoring of a wide range of diseases. We previously used contrast-enhanced ultrasound to detect signatures of insulitis in pre-clinical models based on factors such as altered pancreas perfusion or microvascular leakiness that occur during T1D. While these studies provide support for using contrast-enhanced ultrasound to guide and track therapeutic interventions in ‘pre-symptomatic’ T1D, there exists high potential for further advancements. A key limitation of pancreas imaging in T1D is that islets of Langerhans represent only a few % of the pancreas volume, diluting any disease signature by background signal and reducing sensitivity. Thus, high-resolution approaches are needed to view the specific disease signatures in T1D. Ultrasound localization microscopy (ULM) is an emerging super-resolution microvascular imaging technique that provides microvessel-level spatial resolution noninvasively in vivo, thus potentially enabling the resolution of specific T1D disease associated changes in the pancreas. Our overall goal is to apply ULM and signal processing in combination with novel ultrasound contrast agents to detect disease signatures associated with T1D, to provide image-based guidance and tracking of therapeutic interventions. We will conduct 3 specific aims:  Aim 1: Ultrasound localization microscopy of vascular impairments in the pancreas. The pancreas microvasculature and blood flow change during T1D progression. We will perform ULM with size isolated MBs (SIMBs; 1, 3 & 5 µm diameter), where SIMBs are highly echogenic and will optimize ULM efficiency. ULM will be used to noninvasively map the pancreas microvasculature and flow dynamics to identify vascular impairments associated with insulitis in T1D progression, using murine models. These measurements will be compared with histological analysis of islet microvasculature and insulitis. Aim 2: Mapping the distribution of nanodrop accumulation and microvascular leakiness across the pancreas. Increased microvascular permeability occurs in the pancreas upon chronic inflammation during T1D. Nanodrops (NDs) accumulate within the islet microenvironment during T1D and provide contrast following acoustic vaporization. We will synthesize long-circulating ‘size-isolated’ NDs (SINDs; 0.2, 0.6 & 1.0 µm diameter), that vaporize at clinical MI (<0.7) and provide improved stability. We will characterize the biodistribution of these SINDs and their specificity to accumulate within the infiltrated islet microenvironment, using both ultrasound contrast imaging with histological analysis, in murine models of T1D. We will also assess conditions where ND vaporization minimizes transient or permanent impact on the islet microenvironment.  Aim 3: Apply molecularly targeted microbubbles and nanodrops to the inflamed and infiltrated islet microenvironment. We will target best performing, optimal sized SIMBs to endothelial cell surface markers of inflammation by incorporating peptide ligands against P-, E- and L-selectin. We will use a buried-ligand surface architecture, where the ligand is protected from complement activation by a PEG overbrush, but which can bind its target marker upon application of ultrasound radiation force. Additionally, we will develop an individual bubble tracking approach to determine binding strength of adherent MBs. We will characterize the sensitivity and specificity of target binding in vitro, and perform similar measurements in vivo in models of T1D.  Impact: Assessing inflammation and immune infiltration in the islet microenvironment using contrast-enhanced ultrasound imaging represents a fundamentally new paradigm for diagnosing and tracking T1D progression during the pre-symptomatic phase of disease. The development and application of size isolated microbubbles, nanodrop agents and functionalized microbubbles, and use of super-resolution ULM techniques, represents further innovations which will have broader impact. Therefore, outcomes of this project will aid in diagnosing both the pace of T1D progression and the efficacy of any preventative treatment prior to clinical onset. There also exists viable routes to the clinic for both the contrast agents and ULM techniques for early disease monitoring.

PI_NAMEs: BENNINGER, RICHARD KP (contact);BORDEN, MARK ANDREW;SONG, PENGFEI

PROGRAM_OFFICER_NAME: ARREAZA-RUBIN, GUILLERMO

PROJECT_TERMS: Acoustics;Architecture;Beta Cell;Binding;Biodistribution;Blood flow;blood glucose regulation;Blood Vessels;Cell surface;Chronic;Clinic;Clinical;clinical imaging;Complement Activation;Complications of Diabetes Mellitus;contrast enhanced;contrast imaging;Contrast Media;Detection;Development;Diagnosis;Diameter;Disease;Drops;Endothelial Cells;Functional Imaging;Gases;Goals;Histologic;human subject;Hypoglycemia;Image;imaging modality;Imaging Techniques;immune cell infiltrate;Immunotherapy;Impairment;improved;In Vitro;in vivo;in vivo Model;Individual;Infiltration;Inflammation;inflammatory marker;innovation;Insulin;insulin dependent diabetes mellitus onset;Insulin-Dependent Diabetes Mellitus;insulitis;Investigation;Ionizing radiation;islet;Islets of Langerhans;L-Selectin;Ligands;Maps;Measurement;meter;Microbubbles;Microscopy;Microvascular Permeability;Molecular Target;Monitor;mouse model;nano;novel;Outcome;Pancreas;pancreas imaging;Patients;Peptides;Perfusion;Phase;Pre-Clinical Model;Preventive treatment;public health relevance;Radiation;Recommendation;Resolution;response;Risk;Route;Sensitivity and Specificity;signal processing;Signal Transduction;Specificity;structural imaging;success;Surface;Techniques;Text;Therapeutic Intervention;ultra high resolution;Ultrasonography;ultrasound;vaporization

PROJECT_TITLE: Developing ultrasound contrast agents and signal processing for structural and functional imaging in type 1 diabetes

STUDY_SECTION: IPCA

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


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities

PHR: PROJECT NARRATIVE Anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) immune mediated necrotizing myopathy (IMNM) is an increasingly recognized, severe subset of autoimmune myopathy that causes significant muscle weakness, morbidity, and often permanent physical disability. High quality data, such as from randomized placebo- controlled trials (RCTs), on effective treatment for anti-HMGCR IMNM and understanding of disease immune- pathogenesis are highly limited; and these uncertainties pose a critical barrier to improving outcomes for patients. We will combine clinical and translational approaches to conduct a pilot, exploratory RCT evaluating IVIG (a promising therapy for this condition) as treatment for HMGCR myopathy and leverage this RCT to advance understanding of the potential role of HMGCR-specific CD4+ T cells in disease pathogenesis.

PI_NAMEs: ANDREWS, JAMES  (contact);TINIAKOU, ELENI

PROGRAM_OFFICER_NAME: CARIFI, EMILY FORAN

PROJECT_TERMS: 3-hydroxy-3-methylglutaryl-coenzyme A;Abbreviations;Address;Adult;Affect;Alleles;Antibodies;Antibody titer measurement;Autoantibodies;Autoimmune;Biological Markers;cardiovascular disorder prevention;CD4 Positive T Lymphocytes;Clinical;clinical efficacy;Clinical Trials;Coenzyme A;cohort;Creatine Kinase;Data;Disease;Disease Marker;Dose;double-blind placebo controlled trial;effective therapy;efficacy outcomes;Enzymes;Epitopes;Evidence based treatment;Flow Cytometry;Frequencies;Future;Goals;HLA-DRB1;Human;Immune;Immune System Diseases;Immunoglobulin G;Immunoglobulins;Immunologic Markers;Immunologics;Immunology;immunomodulatory therapies;Immunophenotyping;improved;improved outcome;Individual;innovation;Intervention Trial;intravenous administration;Knowledge;Letters;Measures;Mediating;Morbidity - disease rate;multidisciplinary;Muscle;muscle strength;Muscle Weakness;Musculoskeletal;Myopathy;Myositis;Nature;Odds Ratio;open label;Outcome;Oxidoreductase;Pathogenesis;Patient-Focused Outcomes;Patients;Pharmaceutical Preparations;Phase;phase III trial;physically handicapped;Placebo Control;placebo controlled trial;placebo group;Placebos;Play;Prevalence;Randomized;randomized placebo controlled trial;Recording of previous events;Refractory;Reporting;Research;Resources;response;Rheumatism;Role;Safety;Serum;Skeletal Muscle;Specificity;spelling;T-Lymphocyte;Testing;Therapeutic immunosuppression;therapeutic target;translational approach;translational study;treatment arm;treatment comparison;treatment effect;treatment response;treatment trial;Uncertainty;Work

PROJECT_TITLE: The MIGHT Trial - An Exploratory Clinical Trial of IVIG in anti-HMGCR ImmuneMediated Necrotizing Myopathy

STUDY_SECTION: AMSC

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


ADMINISTERING_IC: NR

IC_NAME: NATIONAL INSTITUTE OF NURSING RESEARCH

NIH_SPENDING_CATS: Behavioral and Social Science;Bioengineering;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Diabetes;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Patient Safety;Prevention;Social Determinants of Health

ORG_CITY: WORCESTER

ORG_DEPT: FAMILY MEDICINE

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

ORG_STATE: MA

PHR: REDDCAT2 Project Narrative Often unmet social needs are identified in the course of clinical care; however, there is no streamlined process to comprehensively and proactively identify and address the most important health-related social needs at the time of hospitalization. The goal of the comparative effectiveness trial is to assess the impact of REDD-CAT on medical service outcomes, diabetes outcomes, and underlying social determinants at 30-days and 90-days following discharge. In partnership with the patient, the REDDCAT2 patient navigator will prioritize reported social needs at the hospital bedside and provide post-discharge navigation support.

PI_NAMEs: MITCHELL, SUZANNE E (contact)

PROGRAM_OFFICER_NAME: GODETTE, DIONNE

PROJECT_TERMS: Accounting;Address;Adult;Adverse event;Algorithms;American;Appointment;Assessment tool;Bedside Testings;blood glucose regulation;burden of illness;care costs;caregiving;Caring;Clinical;clinical care;comparative effectiveness trial;comparison intervention;Complications of Diabetes Mellitus;coping;cost;Couples;Data;Day Care;depressive symptoms;design;diabetes distress;Diabetes Mellitus;diabetes self-management;Diagnosis;effectiveness testing;Emergency department visit;Engineering;evidence base;follow-up;Follow-Up Studies;food insecurity;Funding;Future;Glycosylated hemoglobin A;Goals;Health;Health Care Costs;Health Services;Healthcare;Home;hospital care;hospital readmission;hospital services;Hospitalization;Hospitals;Housing;Impairment;improved;Individual;individual patient;innovation;insight;Intervention;Intervention Studies;Length of Stay;Link;Measurement;Measures;Mediator;Medical;medical complication;Medicare/Medicaid;Mental Depression;National Institute of Diabetes and Digestive and Kidney Diseases;next generation;Non-Insulin-Dependent Diabetes Mellitus;novel;Outcome;Patient Admission;Patient Discharge;patient engagement;patient navigation;patient navigator;Patient Readmission;Patient risk;Patients;Persons;poor health outcome;Population;Process;programs;Protocols documentation;Psychometrics;Quality of life;readmission risk;referral services;Reporting;Research;Research Personnel;Resolution;Rest;Risk;Risk Reduction;screening;Screening procedure;Self Efficacy;Self Management;Services;Severities;skills;social;social determinants;social health determinants;social stigma;Social Work;System;Time;tool;Transportation;treatment as usual;United States National Institutes of Health;Work

PROJECT_TITLE: The Re-Engineered Discharge for Diabetes Care Transitions (REDDCAT2): Screening and Addressing SDOH Needs at Hospital Discharge

STUDY_SECTION: HSQE

STUDY_SECTION_NAME: Health Services: Quality and Effectiveness Study Section[HSQE]


ORG_CITY: DUARTE

ORG_NAME: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE

PHR: NARRATIVE Chromosomal-breaking agents (i.e. clastogens), including ionizing radiation, remain a cornerstone of cancer therapy; nevertheless, their efficacy could be improved by inhibiting the repair of chromosomal breaks in cancer cells. Indeed, inhibitors of the DNA-dependent protein kinase catalytic subunit (DNAPKcs) are being developed for this approach; but to identify the ideal contexts for using such inhibitors, it is critical to understand the role of DNAPKcs in chromosomal break repair, which is the focus of the parent grant and the project in this supplement application. The proposed studies on this project, and training plan for the candidate Ms. Kaela Makins, will support the mission of the NIH to improve cancer treatments and patient outcomes, and advance the specific goals of in this supplement program to enhance diversity in health-related research.

PI_NAMEs: STARK, JEREMY MICHAEL (contact)

PROGRAM_OFFICER_NAME: WITKIN, KEREN L

PROJECT_TERMS: Affect;Aftercare;Antibodies;Biological Assay;Biological Markers;Cancer Biology;cancer cell;cancer therapy;Cell Line;Cells;Chromosomal Breaks;clastogen;Clinical Trials;Collection;Complement;Data;deep sequencing;Development;Dimethyl Sulfoxide;DNA strand break;DNA-dependent protein kinase;DNA-PKcs;Dose;Experimental Designs;experimental study;Exposure to;expression vector;Flow Cytometry;G22P1 gene;Genes;Genetic;Gentian Violet;Goals;Grant;Health;Hour;Human Cell Line;improved;inhibitor;insertion/deletion mutation;interest;Ionizing radiation;kinase inhibitor;Knock-out;Knowledge;Laboratories;lens;Liquid substance;Malignant Neoplasms;Manuscripts;Measures;Mentors;meter;Methanol;Mission;mutant;Nonhomologous DNA End Joining;nuclease;parent grant;Pathway interactions;Patient-Focused Outcomes;Phenotype;Phosphotransferases;Plasmids;Process;programs;Proteins;Protocols documentation;radiation resistance;Radiation therapy;Radiation Tolerance;Recovery;repair function;repaired;Reporter;Reporting;Research;Research Design;Research Personnel;Resistance;response;Roentgen Rays;Role;Site;skills;Small Interfering RNA;Sorting;Stains;Statistical Data Interpretation;Suspensions;Testing;therapeutic target;Time;Training;Transfection;Treatment outcome;Treatment Protocols;tumor;United States National Institutes of Health;vector;Visualization;Western Blotting;Writing;XRCC4 gene

PROJECT_TITLE: Elucidating the role of DNAPKcs in chromosomal break end joining and clastogen


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Drug Abuse (NIDA only);Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Opioid Misuse and Addiction;Opioids;Precision Medicine;Substance Misuse

ORG_DEPT: EMERGENCY MEDICINE

PHR: Narrative Statement Opioid use disorder (OUD) has staggering public health implications, and the current best treatments (medications for opioid use disorder or MOUD) are only marginally effective. This proposal seeks to validate a tool to identify digital biomarkers of craving during MOUD using a wearable sensor, describe distinct trajectories of craving, and identify OUD disease subtypes based on physiologic and clinical data. The resultant algorithms will support real-time precision treatment strategies, predict MOUD responsiveness, and allow tailored prescribing based on dynamic assessment craving.

PI_NAMEs: CARREIRO, STEPHANIE P (contact)

PROGRAM_OFFICER_NAME: FEDOTA, JOHN RAPHAEL

PROJECT_TERMS: addiction;Address;Aftercare;algorithm development;Algorithms;Behavior Therapy;Buprenorphine;Caring;Characteristics;Clinical;Clinical Data;Clinical Trials;Companions;craving;Data;data infrastructure;Data Set;data streams;Development;Devices;Diagnosis;Diagnostic;digital;Digital biomarker;digital health;digital intervention;digital monitoring;digital phenotyping;disease phenotype;disorder subtype;Dose;Event;experience;Fentanyl;Frequencies;Functional disorder;Heroin;Heterogeneity;Human;improved;In Situ;Individual;Individual Differences;insight;Knowledge;Machine Learning;machine learning model;Measures;Mediation;Mediator;medication for opioid use disorder;Methadone;mobile application;Modeling;Monitor;Morbidity - disease rate;mortality;multimodal data;Naltrexone;neurobehavioral;Neuropsychology;novel;open source;Opioid;opioid epidemic;opioid use;opioid use disorder;Outcome;Participant;Pattern;Persons;Pharmaceutical Preparations;Phenotype;Physiological;Physiology;precision medicine;Precision therapeutics;prescription opioid;prospective;psychosocial;Public Health;Recovery;Research Personnel;return to use;sensor;signal processing;Sleep;sociodemographics;software infrastructure;Stream;Stress;success;sustained recovery;Technology;technology development;Time;tool;Toxicology;Training;trait;treatment effect;Treatment Efficacy;Treatment outcome;treatment strategy;United States;wearable data;wearable sensor technology

PROJECT_TITLE: Craving-based Digital Phenotyping During MOUD Treatment

STUDY_SECTION: CIDH

STUDY_SECTION_NAME: Clinical Informatics and Digital Health Study Section[CIDH]


ADMINISTERING_IC: VA

FUNDING_MECHANISM: OTHERS

IC_NAME: Veterans Affairs

ORG_CITY: PORTLAND

ORG_NAME: PORTLAND VA MEDICAL CENTER

ORG_STATE: OR

PHR: Methamphetamine (MA) use disorder is a widespread problem among veterans and has great public health relevance but there are no FDA-approved medications for treatment. Abnormalities in the dopamine system are hallmark characteristics of MA addiction, and studies show that dopamine function can predict the success of treatment outcomes. Medications, however, aimed at regulating dopamine have been unsuccessful. Both MA use and neuroinflammation dysregulate dopamine signaling but the mechanistic link between MA-induced neuroinflammation and dopamine brain function in humans has not been studied. This project, using multi- modal neuroimaging techniques will identify whether ibudilast, an anti-inflammatory agent reduces MA-induced neuroinflammation resulting in improved brain function, connectivity and behavior. If inflammation is associated with brain deficits and ibudilast is proven effective in restoring the integrity of neural networks, the results have the potential to advance therapeutic strategies by identifying neuroinflammation as a critical biomarker.

PI_NAMEs: KOHNO, MILKY  (contact)

PROJECT_TERMS: Acceleration;Accounting;addiction;Animal Model;Anti-Inflammatory Agents;Appointment;Attenuated;Award;Basal Ganglia;Behavior;Behavioral;Biological Markers;biomarker identification;Brain;Brain region;C-reactive protein;career;Caring;Characteristics;Clinical;clinical development;Clinical Trials;cognitive control;Communication;comparison control;computing resources;Corpus striatum structure;craving;cytokine;Decision Making;Dedications;design;Dopamine;dopamine system;Dorsal;Double-Blind Method;Drug abuse;Education;Educational workshop;effective therapy;Endotoxins;Environment;Equipment;Evaluation;Exhibits;experience;FDA approved;Fellowship;financial incentive;Functional disorder;Functional Magnetic Resonance Imaging;functional restoration;Gliosis;Goals;gray matter;Health;Healthcare Systems;hedonic;Human;Image;Impaired cognition;Impairment;improved;indexing;Inflammation;Inflammatory;Intervention;Joints;Journals;Laboratories;laboratory experience;Leadership;Light;Link;Magnetic Resonance Spectroscopy;Measures;Medial;Mediating;meetings;Mentors;Methamphetamine;Methamphetamine dependence;methamphetamine exposure;methamphetamine use;Methamphetamine use disorder;methamphetamine user;Microglia;Midbrain structure;Modeling;Multimodal Imaging;multimodal neuroimaging;Nerve;neural circuit;neural network;Neurobiology;neuroimaging;neuroinflammation;neuromechanism;neuropsychiatry;novel;Oregon;Participant;Performance;Personnel Management;Pharmaceutical Preparations;pharmacologic;Pharmacotherapy;Phenotype;placebo group;Positron-Emission Tomography;Prefrontal Cortex;public health relevance;Publications;Questionnaires;randomized placebo controlled study;Reducing Agents;Research;Research Personnel;Resource Sharing;response;Rest;reuptake;Rewards;Role;Science;Series;Services;Signal Transduction;skills;stimulant use;success;Supervision;Symptoms;System;Techniques;Testing;Therapeutic;tool;Training;Translational Research;transmission process;Treatment outcome;treatment program;treatment strategy;United States National Institutes of Health;Universities;Ventral Striatum;Veterans;Work

PROJECT_TITLE: Brain Function and Connectivity in Methamphetamine Dependence: The Link to Neuroinflammation and the Effects of Ibudilast

STUDY_SECTION: NURA

STUDY_SECTION_NAME: Neurobiology A[NURA]


ADMINISTERING_IC: DE

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Arthritis;Dental, Oral, and Craniofacial Disease;Physical Injury - Accidents and Adverse Effects;Regenerative Medicine

ORG_DEPT: GENETICS

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: PROJECT NARRATIVE  Joints are used for everyday movements and ligament injury compromises joint health due to the fibrous scar tissue that forms and alters native joint movement. This proposed work will use the highly regenerative zebrafish as a model to study ligament regeneration to gain insight into the molecular factors promoting ligament regeneration vs. fibrosis after injury. By understanding the mechanisms driving scar-free ligament regeneration, we can better develop future therapies for acute ligament injury that will rebuild native tissue while also preventing fibrosis.

PI_NAMEs: MO, JULIA  (contact)

PROGRAM_OFFICER_NAME: FUQUA, CHANTEL FAYSAN

PROJECT_TITLE: ECM remodeling and crosstalk with cell fate in zebrafish ligament regeneration


NIH_SPENDING_CATS: Aging;Autoimmune Disease;Bioengineering;Biomedical Imaging;Brain Disorders;Clinical Research;Disability Research;Eye Disease and Disorders of Vision;Multiple Sclerosis;Neurodegenerative;Neurosciences

ORG_CITY: BALTIMORE

ORG_DEPT: NEUROLOGY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Project Narrative This proposal aims to address the important problem of currently being unable to accurately predict the course of multiple sclerosis (MS) in individual people. In ongoing efforts to improve care, we are developing a multi-faceted approach to readily predict and monitor (through state- of-the-art high-resolution brain and retinal imaging) disease severity and progression, in order to guide individualized therapeutic decision-making among people with MS. The clinical need for the predictive tools in MS being developed in this study are an utmost priority given the expanding number of increasingly more effective and potent treatments that may be associated with serious and potentially life-threatening complications.

PI_NAMEs: CALABRESI, PETER A (contact);SAIDHA, SHIV

PROGRAM_OFFICER_NAME: UTZ, URSULA

PROJECT_TERMS: Acceleration;Acute;Address;Age;Aging;Anatomy;Angiography;Anisotropy;Atrophic;Axon;Benefits and Risks;Blood Vessels;Brain;Brain imaging;brain magnetic resonance imaging;Caring;Cells;Central Nervous System;cerebral atrophy;Cerebrovascular Circulation;Cerebrum;Chronic;Clinical;Clinical Trials;clinically relevant;cohort;Decision Making;Demyelinations;density;Development;Diffusion Magnetic Resonance Imaging;disability;Disease;Disease Progression;Distant;Evaluation;Exhibits;Future;ganglion cell;Goals;Grant;gray matter;illness length;Image;imaging approach;Immune;immune cell infiltrate;improved;Individual;Inflammation;Inner Plexiform Layer;insight;Iron;Lesion;Life;Lymphocyte;macula;Magnetic Resonance Imaging;Magnetism;Maps;Measures;Meningeal;Metabolic;Metabolic dysfunction;metabolic rate;Metabolic stress;Metabolism;Methods;Microglia;Microscopic;Monitor;MRI Scans;Multiple Sclerosis;multiple sclerosis patient;multiple sclerosis treatment;Myelin;Nerve Degeneration;Neuroglia;Neurologic;Neuronal Dysfunction;Neurons;neuroprotection;normal aging;novel;Optic Neuritis;Optical Coherence Tomography;Outcome;Outcome Assessment;Outcome Measure;Oxygen;Paper;Pathology;Peripheral;personalized care;personalized therapeutic;Persons;Phenotype;predictive tools;Predisposition;preservation;Process;Publications;Race;recruit;Relapse;Relaxation;remyelination;Resolution;Retina;retinal imaging;Role;Selection for Treatments;Severity of illness;sex;Signal Transduction;Stress;Structure;Synapses;Thalamic structure;Time;Tissues;tool;tractography;trafficking;Trans-Synaptic Degeneration;Venous;Visual;Visual Pathways

PROJECT_TITLE: Imaging Neurodegeneration in Multiple Sclerosis

STUDY_SECTION: CNBT

STUDY_SECTION_NAME: Clinical Neuroimmunology and Brain Tumors Study Section[CNBT]


ADMINISTERING_IC: TW

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: FOGARTY INTERNATIONAL CENTER

NIH_SPENDING_CATS: Antimicrobial Resistance;Clinical Research;Clinical Trials and Supportive Activities;Infectious Diseases;Malaria;Nutrition;Orphan Drug;Rare Diseases;Vector-Borne Diseases

ORG_CITY: BLANTYRE

ORG_COUNTRY: MALAWI

ORG_FIPS: MI

ORG_NAME: KAMUZU UNIVERSITY OF HEALTH SCIENCES

PHR: PROJECT NARRATIVE Given the emerging resistance of malaria parasites to first-line artemisinin-based combination therapy (ACT), new antimalarial drug combinations are urgently needed. Triple ACTs (TACTs) have been identified as the most feasible and affordable alternative solution to ACTs. The combination of artemether with both lumefantrine and amodiaquine is an example of a TACT that benefits from the longer-acting partner drugs, lumefantrine and amodiaquine, having different and potentially opposing resistance mechanisms. However, children with severe acute malnutrition and adults living with HIV are two key subgroups that have been excluded from early dose optimisation studies and Phase 3 studies of this promising TACT, yet . This project will investigate artemether-lumefantrine plus amodiaquine’s disposition and safety in these two key target subgroups. they are at a high risk of malaria adverse outcomes

PI_NAMEs: BANDA, CLIFFORD GEORGE (contact)

PROGRAM_OFFICER_NAME: BANSAL, GEETHA PARTHASARATHY

PROJECT_TERMS: absorption;Acute;Adult;adverse outcome;Africa;African;Amodiaquine;Anti-malarial drug resistance;Anti-malarials;Anti-Retroviral Agents;antiretroviral therapy;Area;artemether;Artemisinins;Award;benflumetol;Biological Availability;career;career development;Child;Clinical;Clinical Pharmacology;clinical translation;Clinical Trials Design;Combined Modality Therapy;Complex;Data;Derivation procedure;Development;Dose;Drug Combinations;Drug Kinetics;early phase clinical trial;efficacy clinical trial;Exclusion;falls;Fatty acid glycerol esters;Future;high risk;HIV;Hour;Individual;innovation;Leadership;Licensing;Malaria;Malawi;Malnutrition;medical specialist;neglect;novel;Parasite resistance;Parasites;Persons;Pharmaceutical Preparations;pharmacodynamic model;Pharmacology;phase 3 study;Phase III Clinical Trials;Plasma;Population;prevent;Product Labeling;Recurrence;Regimen;Research;Resistance;resistance mechanism;Risk;Safety;skills;Subgroup;Supplementation;Target Populations;Therapeutic;Time;tool;Work;World Health Organization

PROJECT_TITLE: Informing optimal dosing of the future antimalarial, artemether-lumefantrine plus amodiaquine, in key neglected target populations of children with severe acute malnutrition and adults living with HIV

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 ICP-P (55)]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Anxiety Disorders;Asthma;Behavioral and Social Science;Brain Disorders;Health Effects of Indoor Air Pollution;Lung;Mental Health;Mental Illness;Neurosciences;Post-Traumatic Stress Disorder (PTSD)

ORG_CITY: CINCINNATI

ORG_NAME: UNIVERSITY OF CINCINNATI

ORG_STATE: OH

PHR: PROJECT NARRATIVE Abnormal fear regulation is observed in psychiatric disorders, particularly PTSD, a debilitating condition afflicting 8% of civilians and about 22% of combat veterans annually. Growing evidence supports an association of autoimmune conditions and severe asthma with PTSD prevalence and risk, however contributory mechanisms are not clear. Using cell-circuit approaches and transgenic manipulations, this R01 will identify T cell-derived inflammatory mediators, cellular substrates and unique forebrain circuits involved in asthma-driven fear dysregulation relevant to PTSD.

PI_NAMEs: LEWKOWICH, IAN PAUL;SAH, RENU  (contact)

PROGRAM_OFFICER_NAME: TONELLI, LEONARDO HERALDO

PROJECT_TERMS: Ablation;Acute Respiratory Distress Syndrome;airborne allergen;airway inflammation;Allergens;Area;Asthma;asthma model;Astrocytes;Autoimmune Diseases;Bacterial Pneumonia;Behavior;Biological Response Modifiers;Blood - brain barrier anatomy;Brain;cell type;Cells;Chronic;chronic inflammatory lung disease;combat veteran;comorbidity;COVID-19;Crohn's disease;Data;Disease;Electrophysiology (science);Ensure;Extinction;Fright;Functional disorder;Gene Expression Profile;Genetic;genetic approach;genetic manipulation;IL17 gene;Immune response;Impairment;Individual;Inflammation;Inflammation Mediators;Inflammatory;Interneurons;Knockout Mice;Knowledge;Link;Losartan;Mediating;Mediator;Mental disorders;Mental Health;Meta-Analysis;Microglia;Modeling;Mus;Nature;neural;neuronal excitability;Neurons;neurotransmission;neutralizing antibody;new therapeutic target;novel;novel therapeutics;optogenetics;Parvalbumins;patch clamp;Pathology;pharmacologic;Physiology;Pneumonia;Post-Traumatic Stress Disorders;Predisposition;Prefrontal Cortex;Prevalence;promoter;Prosencephalon;Psoriasis;Publishing;Pulmonary Inflammation;Pulmonary Pathology;Pyroglyphidae;receptor;Regulation;Reporting;response;Rheumatoid Arthritis;Risk;Risk Factors;Role;Safety;Signal Pathway;Signal Transduction;Site;Slice;Subfornical Organ;Symptoms;Synapses;systemic inflammatory response;T-Lymphocyte;Testing;therapeutic target;therapy resistant;transcriptomics;Transgenic Organisms;Translating;trauma exposure;Up-Regulation

PROJECT_TITLE: Airway inflammation and fear: elucidating immune mediators and neural substrates

STUDY_SECTION: BNRS

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


NIH_SPENDING_CATS: Contraception/Reproduction;Genetics;Infectious Diseases;Malaria;Maternal Health;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Preterm, Low Birth Weight and Health of the Newborn;Prevention;Rare Diseases;Vector-Borne Diseases;Women's Health Research

ORG_CITY: THIKA

ORG_COUNTRY: KENYA

ORG_FIPS: KE

ORG_NAME: MOUNT KENYA UNIVERSITY

PHR: PROJECT NARRATIVE Malaria infection during pregnancy causes red blood cells containing the malaria parasite to attach to the placenta, the organ vital for development and growth of the baby during pregnancy. Placenta infection with malaria disrupts placental function and is linked to poor pregnancy outcomes like low birth weight, premature birth, and stillbirth. This proposal will seek to determine the biological effects through which placental malaria alters placental function and identify strategies for exploiting this knowledge for the development of placental malaria interventions as well as tools for placental malaria detection during pregnancy.

PI_NAMEs: KOBIA, FRANCIS MUNGATHIA  (contact)

PROGRAM_OFFICER_NAME: SINA, BARBARA J

PROJECT_TERMS: Adverse effects;adverse outcome;Africa South of the Sahara;Alkaline Phosphatase;biobank;Biological;Biological Assay;Biological Markers;Blood;Cell Physiology;Cells;Chemoprophylaxis;Child;Circulation;Data;Data Set;Decidua Basalis;Detection;Development;Diagnostic;diagnostic biomarker;diagnostic tool;diagnostic value;differential expression;effective intervention;Environment;Erythrocytes;experience;extracellular vesicles;fetal;Fetal Development;Fetal Growth;Fetal Growth Retardation;Fetus;Follow-Up Studies;Foundations;Genes;Goals;Growth and Development function;HLA Antigens;improved;In Vitro;Infant;Infection;Infectious Pregnancy Complications;Infrastructure;Injury;insight;Intervention;isothermal amplification;Knowledge;Link;Low Birth Weight Infant;Malaria;Malaria Diagnosis;malaria infection;Maternal and Child Health;Mediating;Molecular;Mothers;neonatal morbidity;Neonatal Mortality;neonate;Organ;Outcome;Parasites;Pathway interactions;Personal Satisfaction;Physiology;Placenta;Placental Biology;placental infection;placental malaria;Placentation;Plasmodium falciparum;point of care;point of care testing;Pregnancy;Pregnancy Outcome;Premature Birth;prevent;Preventive treatment;Process;Pyrimethamine;Recommendation;Research;Resistance;Resource-limited setting;Reverse Transcription;RNA;Sampling;Signal Transduction;skills;stillbirth;Syncytiotrophoblast;Testing;therapeutic target;tool;Transcript;transcriptome;transcriptome sequencing;transcriptomic profiling;transcriptomics;trophoblast;Villous;Western Blotting;Woman;Work

PROJECT_TITLE: Molecular and cellular underpinnings of placental malaria


NIH_SPENDING_CATS: Biomedical Imaging;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Disability Research;Mental Health;Mental Illness;Neurosciences;Pediatric;Precision Medicine;Prevention;Psychosis;Schizophrenia;Serious Mental Illness;Suicide

ORG_CITY: BELMONT

ORG_NAME: MCLEAN HOSPITAL

PHR: PROJECT NARRATIVE A first episode of psychosis is a leading cause of disability in young adults, with high risk of suicide and all cause mortality. A substantial part of the burden and cost relates to poor functional outcomes, and the inability to determine the right antipsychotic treatment during the earliest phases of psychotic illness, particularly for those who might need clozapine, a medication that is already known to work best for those who do not respond to conventional antipsychotics. In patients with a first episode of psychosis, the present study aims to determine whether the use of biomarker guided treatment decisions leads to better outcomes and equivalent side effects in people prescribed clozapine compared to conventional antipsychotics, including changes in brain function.

PI_NAMEs: ONGUR, DOST  (contact)

PROGRAM_OFFICER_NAME: RUDORFER, MATTHEW V

PROJECT_TERMS: Acceleration;acute care;Adherence;Adolescence;Age;aged;Agranulocytosis;Antipsychotic Agents;aripiprazole;Biological Markers;blind;Brain;Brain scan;Caring;Clinical;Clozapine;cohort;Complex;Controlled Study;Corpus striatum structure;cost;Country;critical developmental period;critical period;Data;Decision Making;Dedications;Development;disability;dissemination strategy;Dose;early psychosis;Education;efficacy evaluation;efficacy trial;Elements;emerging adult;Employment;expectation;experience;Failure;Family;Family member;Feeling suicidal;first episode psychosis;Functional Magnetic Resonance Imaging;functional MRI scan;functional outcomes;Future;General Population;genetic testing;genomic locus;Genotype;Goals;high risk;HLA-DQB1;Hospitalization;Hospitals;Image;implementation science;improved;improved outcome;indexing;Individual;inpatient service;Lifelong disability;Lived experience;Magnetic Resonance Imaging;Melanocortin 4 Receptor;mortality;National Institute of Mental Health;Neutropenia;Outcome;Patient-Focused Outcomes;Patients;Pattern;Persons;Pharmaceutical Preparations;Pharmacogenetics;Phase;Population;Precision therapeutics;predicting response;predictive marker;preservation;primary outcome;Psychiatry;Psychoses;psychotic;Psychotic Disorders;Publishing;Randomized;randomized, clinical trials;Randomized, Controlled Trials;Receptor Gene;reducing suicide;Research Design;Resistance;responders and non-responders;response;Rest;Risk;risk variant;Risperidone;Schizophrenia;secondary outcome;Services;side effect;specific biomarkers;Subgroup;suicidal morbidity;suicidal risk;support tools;Symptoms;System;Testing;Therapeutic;tool;treatment response;trial comparing;Weight;Weight Gain;Work;young adult;Youth

PROJECT_TITLE: 3/5- Biomarkers to Enhance Early Schizophrenia Treatment (BEEST)

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 BP-S (60)]


NIH_SPENDING_CATS: Cancer;Kidney Disease

ORG_CITY: COLUMBUS

ORG_NAME: RESEARCH INST NATIONWIDE CHILDREN'S HOSP

PHR: NARRATIVE (PUBLIC HEALTH RELEVANCE) Cisplatin is a very effective cancer therapy drug, but it is associated with development of chronic kidney disease (CKD) in up to 65% of the patients resulting in a significant public health burden of reduced long-term health and quality of life that remains unaddressed. Understanding how manipulating tubular O2•– dismutation in Cisplatin- induced CKD impacts mitochondrial function is expected to provide essential data needed for future clinical trial design to reduce CKD burden. This proposal is relevant to the NIH-NIDDK's mission to conduct and support medical research to improve people's health and quality of life using innovative methods, pre-clinically relevant models, and translational tools to develop approaches for repairing damaged tissues, i.e., Cisplatin-damaged kidney tissues.

PI_NAMEs: ZEPEDA-OROZCO, DIANA  (contact)

PROGRAM_OFFICER_NAME: SCHULMAN, IVONNE HERNANDEZ

PROJECT_TERMS: Acute;Address;Adenine;Antioxidants;biobank;Biological Markers;burden of illness;cancer cell;Cancer Patient;cancer therapy;Carbon;Cell Respiration;Cells;chemotherapy;Child;Chronic Kidney Failure;Cisplatin;Clinical Trials Design;Complex;Data;Detection;detection limit;Development;disease model;Dose Limiting;EGF gene;Electron Transport;Epidermal Growth Factor;Excision;Experimental Designs;experimental study;Fibrinogen;Fibrosis;fighting;Free Radicals;Functional disorder;Future;Glucose;Glutathione;Head and Neck Cancer;Health;Human;Hydrogen Peroxide;Impairment;improved;in vitro Model;in vivo;Inflammation;injured;Injury;Injury to Kidney;innovation;inorganic phosphate;Iron;Kidney;Knockout Mice;Link;Malignant Neoplasms;Measures;Mediating;Medical Research;Metabolism;metabolomics;Methods;mimetics;Mission;Mitochondria;mitochondrial dysfunction;mitochondrial metabolism;Modeling;mouse model;Mus;NADP;National Institute of Diabetes and Digestive and Kidney Diseases;Natural regeneration;neoplastic cell;nephrotoxicity;Niacinamide;Nicotinamide adenine dinucleotide;nicotinamide riboside supplementation;Normal tissue morphology;novel;novel diagnostics;novel therapeutic intervention;nutrient absorption;Oxidants;oxidative damage;Oxidative Stress;Pathway interactions;Patients;Pentosephosphate Pathway;Persons;Pharmaceutical Preparations;pharmacologic;pre-clinical;preclinical study;predicting response;Prediction of Response to Therapy;predictive marker;prevent;Public Health;public health relevance;Quality of life;Radiation therapy;Radiation-Induced Cancer;Recurrence;renal damage;Renal function;repaired;Research;response;Retrospective cohort;Retrospective Studies;risk stratification;Schedule;Serum;side effect;SOD2 gene;Sulfhydryl Compounds;Sulfur;Superoxide Dismutase;Superoxides;Testing;Tissues;tool;Tracer;Translating;Translations;Treatment Protocols;Tricarboxylic Acids;Tubular formation;tumor;United States National Institutes of Health;Urine

PROJECT_TITLE: Targeting Tubular Mitochondrial Superoxide Dismutation in Cisplatin Renal Repair

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 KUDS-W (90)]


NIH_SPENDING_CATS: Bioengineering;Dental, Oral, and Craniofacial Disease

ORG_CITY: CAMBRIDGE

ORG_NAME: ADA FORSYTH INSTITUTE, INC.

PHR: Narratives: We will create new dental adhesives and composite materials by formulating an advanced resin network, incorporating therapeutic components and specialized additives that combat bacteria and minimize protein adherence. After conducting rigorous clinical-relevant assessments of the new materials on extracted human teeth, we aim to produce various advanced therapeutic solutions tailored to address various dental cavity challenges.

PI_NAMEs: SUN, JIRUN  (contact);XU, HUAKUN

PROGRAM_OFFICER_NAME: LOPEZ, ORLANDO

PROJECT_TERMS: Address;Adherence;Adhesives;Aging;analog;antimicrobial;Bacteria;cariogenic bacteria;Categories;Clinical;clinically relevant;combat;Composite Dental Resin;Composite Resins;composite restoration;copolymer;Dental;dental adhesive;dental biofilm;Dental caries;Dental Clinics;Dental Etching;dental resin;Dentin;design;Ensure;Environment;Enzymes;Esters;Ethers;Evaluation;Exposure to;Filler;functional group;functional restoration;Goals;Grouping;Health;Human;Hybrids;Hydrolysis;Hydrophobicity;improved;Incidence;innovation;Knowledge;Life;life span;Measures;Methacrylates;Methods;novel;Numerical value;Oral;Patients;Performance;Periodicity;Plant Resins;Poly U;polymerization;Polymers;prevent;Production;Proteins;remineralization;Resistance;restoration;restorative dentistry;restorative resins;Series;Services;Styrenes;System;Testing;Therapeutic;Tooth structure;triethylene glycol;Urethane;Variant

PROJECT_TITLE: Hydrolysis-resistant resin networks for durable and multifunctional dental restorations

STUDY_SECTION: ODCS

STUDY_SECTION_NAME: Oral, Dental and Craniofacial Sciences Study Section[ODCS]


NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Palliative Care;Pediatric;Pediatric Cancer;Prevention;Rare Diseases;Social Determinants of Health

ORG_CITY: DURHAM

ORG_DEPT: PSYCHIATRY

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: RELEVANCE STATEMENT For adolescent and young adult (AYA) cancer survivors, the impacts of treatment are significant and long-lasting, including difficult physical symptoms (e.g., pain, fatigue), emotional distress, and an increased risk of long-term health problems. Engagement in recommended follow-up care is critical; yet, the proportion of AYA survivors who engage in follow-up care rapidly declines with age and time since treatment, resulting in inadequate surveillance for late effects and missed opportunities for symptom management, psychological support, and health promotion. The proposed study examines the efficacy of an accessible digital health intervention, AYA STEPS (Symptom Management and Transitioning to Engagement with Post-Treatment Care for AYA Survivors), that is designed to enhance the ability of AYA cancer survivors to manage their high symptom burden and engage in recommended follow-up care by improving self-efficacy for symptom management and patient activation.

PI_NAMEs: DORFMAN, CAROLINE  (contact)

PROGRAM_OFFICER_NAME: ADAMS, LYNN S

PROJECT_TERMS: Address;Adolescent and Young Adult;Aftercare;Age;age related;age related decline;aged;Agreement;Anxiety;Area;arm;Attention;Awareness;barrier to care;Behavior Therapy;Behavioral;Behavioral Symptoms;Belief;Biological;cancer care;cancer complication;Cancer Survivor;cancer therapy;Cardiovascular Diseases;career;Caring;Child Care;Clinical;Cognitive;Communication;comparison control;comparison group;Competence;coping;Coping Skills;cost;critical developmental period;deprivation;design;Development;Diagnosis;digital health;early onset;Economics;Education;efficacy evaluation;emotional distress;emotional symptom;experience;Face;falls;Family;Fatigue;Feedback;Financial cost;follow-up;Fright;Health;Health Benefit;health care model;health care service utilization;health care settings;health literacy;Health Personnel;Health Promotion;Healthcare;improved;Incidence;indexing;Intervention;intervention effect;Knowledge;Late Effects;Life;Longterm Follow-up;Love;Malignant Neoplasms;Managed Care;Mediating;Mediator;Medical;Medically Underserved Area;Meditation;Mental Depression;mhealth interventions;Modeling;Movement;National Cancer Institute;Nature;North Carolina;novel;older adult;Oncology;Pain;Participant;Patients;Pattern;peer;Phase;physical symptom;Policies;Population;Provider;psychologic;psychosocial;Public Health;Randomized, Controlled Trials;Recommendation;Recurrence;reduce symptoms;Relaxation Therapy;remote delivery;Reporting;Resources;Risk;Rural;Schools;Second Primary Cancers;Self Efficacy;Severities;skills;social;social health determinants;stem;Survival Rate;Survivors;survivorship;Symptom Burden;symptom management;symptom self management;symptom treatment;symptomatic improvement;Symptoms;theories;therapy development;Time;Training;Underinsured;Uninsured;United States National Institutes of Health;Videoconferencing;web platform;Work

PROJECT_TITLE: Symptom Management and Transitioning to Engagement with Post-treatment Care for Adolescent and Young Adult Cancer Survivors (AYA STEPS)

STUDY_SECTION: ICSC

STUDY_SECTION_NAME: Interdisciplinary Clinical Care in Specialty Care Settings Study Section[ICSC]


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

ORG_CITY: NEW YORK

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: PROJECT NARRATIVE:  There are no small molecules in existence that inhibit CAPON-induced tau aggregation and neurodegeneration in the human brain. This application is the first study that seeks to identify small molecules targeting CAPON-centered interactions that modulate tau pathology and neurotoxicity. The proposed research is relevant to public health as small molecule CAPON inhibitors can lead to therapeutic agents for Alzheimer's disease.

PI_NAMEs: GABR, MOUSTAFA  (contact)

PROGRAM_OFFICER_NAME: GROTHAUS, PAUL G

PROJECT_TERMS: absorption;Adaptor Signaling Protein;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease diagnosis;Alzheimer's disease model;Alzheimer's disease patient;Alzheimer's disease therapeutic;Amyloid;Amyloid beta-Protein;amyloid pathology;Animal Disease Models;Animal Model;APP-PS1;Artificial Membranes;Autopsy;Binding;Binding Proteins;Biological Assay;Biophysics;Brain;Cell Membrane Permeability;Cellular Assay;Central Nervous System;Cognitive deficits;computer studies;Data;Dementia;Deposition;drug development;Drug Kinetics;efficacy evaluation;Energy Transfer;Enzyme-Linked Immunosorbent Assay;Enzymes;Evaluation;excitotoxicity;Excretory function;extracellular;Fluorescence;Future;Goals;Heterogeneity;Human;hyperphosphorylated tau;In Vitro;in vitro Assay;in vivo;inhibitor;interest;Knockout Mice;lead optimization;Lesion;Ligands;Link;Mediating;Metabolism;Modeling;molecular modeling;molecular site;mouse model;Mus;N-Methyl-D-Aspartate Receptors;N-Methylaspartate;Nerve Degeneration;Neurofibrillary Tangles;neuron loss;Neurons;neuropathology;neurotoxicity;Nitric Oxide;Nitric Oxide Synthase Type I;Nitric Oxide Synthetase Inhibitor;novel;novel therapeutics;Outcome;Pathogenesis;Pathologic;Pathology;Pharmaceutical Preparations;Phenotype;Pilot Projects;Positioning Attribute;pre-clinical;Production;Program Development;Protocols documentation;Public Health;Pyramidal Cells;Reporting;Research;Role;screening;screening panel;Senile Plaques;Site;Site-Directed Mutagenesis;small molecule;Small Molecule Chemical Library;small molecule inhibitor;small molecule therapeutics;targeted treatment;tau aggregation;tau interaction;tau Proteins;tau-1;Tauopathies;Temperature;Testing;Therapeutic;Therapeutic Agents;Time;time use;Up-Regulation;Validation;Work

PROJECT_TITLE: Small molecule inhibitors of CAPON-induced tau aggregation

STUDY_SECTION: DMPB

STUDY_SECTION_NAME: Drug Discovery and Molecular Pharmacology B Study Section[DMPB]


NIH_SPENDING_CATS: Genetics;Pediatric;Stem Cell Research;Stem Cell Research - Embryonic - Human

ORG_CITY: MILWAUKEE

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

PHR: Project Narrative Our team with broad expertise in early human embryology, bioinformatics, non-human primates, GATA transcription factor biology and epigenetics will tackle previously unexplored transcriptional and signaling events during human amniogenesis. Mechanistic characterizations in hPSC-based systems will be grounded in early cynomolgus macaque embryos, allowing a unique opportunity to elucidate the cellular and molecular properties associated with primate amnion fate progression.

PI_NAMEs: TANIGUCHI, KENICHIRO  (contact)

PROGRAM_OFFICER_NAME: ILEKIS, JOHN V

PROJECT_TERMS: 3-Dimensional;Acceleration;amnion;Automobile Driving;beta catenin;Binding Sites;Bioinformatics;Biology;blastocyst;Bone Morphogenetic Proteins;Bypass;Candidate Disease Gene;cell type;Cells;Cyst;Data;Development;Dissection;Ectoderm;Embryo;Embryology;Embryonic Development;Environment;Epiblast;Epigenetic Process;epigenomics;Event;Exposure to;Fertility;Fetal Development;Fetal Membranes;Fetus;GATA3 gene;Gel;Gene Expression Profile;Genes;Genetic;Genetic Transcription;Glass;Goals;healthy pregnancy;histone modification;Hour;Human;Human Development;human pluripotent stem cell;Implant;implantation;In Vitro;in vitro Model;in vivo;Individual;Investigation;Lateral;Ligands;Light;Liquid substance;Location;loss of function;Macaca fascicularis;mechanical signal;Membrane;Modeling;Molecular;Molecular Profiling;mouse model;Mus;nonhuman primate;novel;Nuclear;pluripotency;Population Heterogeneity;Pregnancy;prevent;Primates;Process;programs;Property;Proteins;Publishing;Reproducibility;Sampling;Side;Signal Transduction;Signaling Protein;species difference;Specific qualifier value;stem cells;System;Testing;TFAP2A gene;tool;Transcript;transcription factor;transcriptomics;Uterus;Validation;WNT Signaling Pathway;Work

PROJECT_TITLE: Molecular regulators of human amniogenesis

STUDY_SECTION: PN

STUDY_SECTION_NAME: Pregnancy and Neonatology Study Section[PN]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE This project will investigate how the body’s internal circadian clock contributes to a mysterious phenomenon in asthma called asthma remission, in which some children outgrow the disease as they physically mature. Applying the knowledge gained by this project could lead to fewer hospitalizations for patients, improved quality of life, and broad benefits to public health. The information produced by this project could ultimately help doctors increase the likelihood that asthmatic children will grow out of their asthma, shifting the goals of asthma treatment from symptom control to cure.

PI_NAMEs: HASPEL, JEFFREY ADAM (contact)

PROGRAM_OFFICER_NAME: LAPOSKY, AARON D

PROJECT_TERMS: Adolescent;Adoptive Transfer;Adult;Affect;Age;age related;aging clocks;airway epithelium;airway remodeling;Allergens;Allergic;Alternaria;Alveolar Macrophages;Anti-viral Response;ARNTL gene;Asthma;asthma exacerbation;asthmatic;Basal Cell;Basic Science;Biological Process;Cells;Child;Chronic;Chronic Disease;Circadian Dysregulation;Circadian gene expression;circadian pacemaker;circadian regulation;Circadian Rhythms;circadian transcriptome;conditional knockout;Cytoprotection;Disease;Disease Outbreaks;Disease remission;Epithelial Cells;Epithelium;Exhibits;experience;experimental study;Genes;Genetic;Genetic Transcription;Goals;Heart Diseases;Hematological Disease;Hospitalization;Immunophenotyping;improved;Infection;Inflammation;Inflammatory Response;injured airway;interest;Interferons;Jet Lag Syndrome;juvenile animal;Knockout Mice;Knowledge;Ligands;Lung;Lung Diseases;lung repair;Maps;Mediating;Methods;Modeling;Mus;Myelogenous;Myeloid Cells;Nose;Nuclear;Pathway interactions;Patients;PD-1/PD-L1;prevent;programs;Public Health;Pulmonary Pathology;Quality of life;receptor;repaired;Reporter;Research Priority;Resolution;respiratory virus;response;Seasons;Sendai virus;sensor;Sleep Disorders;small molecule;suicide gene;symptom treatment;Symptoms;theories;Time;trait;transcriptome sequencing;Translational Research;United States National Institutes of Health;Variant;Viral;Viral Physiology;Viral Respiratory Tract Infection;Virus;Virus Diseases

PROJECT_TITLE: The circadian clock as an age sensor in asthma resolution


NIH_SPENDING_CATS: Cardiovascular

ORG_CITY: HADLEY

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF MASSACHUSETTS AMHERST

PHR: NARRATIVE Ca2+/calmodulin dependent protein kinase II (CaMKII) plays significant roles in neurons, cardiomyocytes, and oocytes. We are fascinated by the multifunctional roles CaMKII plays in human health and will interrogate this important problem using a combinatorial approach from transcriptomics to cell biology.

PI_NAMEs: STRATTON, MARGARET M (contact)

PROGRAM_OFFICER_NAME: CHO, THOMAS Y

PROJECT_TERMS: Affect;Alternative Splicing;Biochemistry;Biological;calmodulin-dependent protein kinase II;Cardiac;Cardiac Myocytes;Cell Communication;cell type;Cells;Cellular Assay;Cellular biology;Chemicals;combinatorial;Communication;Complex;Coupled;Enzymes;Event;fascinate;Fertilization;Genes;Health;Human;Infertility;intercellular communication;interest;long term memory;Mammals;millisecond;Modification;Molecular;Molecular Conformation;Myocardial dysfunction;Nervous System Disorder;Neurons;Oocytes;Organism;Output;Physiology;Play;Production;Proteins;Regulation;RNA Splicing;Role;structural biology;Therapeutic Intervention;Transcript;transcriptomics;Variant;Work

PROJECT_TITLE: Supplement for Unraveling the molecular events driven by CaMKII in Ca2+-coupled cells


NIH_SPENDING_CATS: Cancer;Genetics;Kidney Disease

ORG_CITY: AUGUSTA

ORG_NAME: AUGUSTA UNIVERSITY

ORG_STATE: GA

PHR: Narrative (Relevance) Cisplatin, a widely used chemotherapy drug, elicits both acute and chronic side-effects in kidneys. This application investigates the reciprocal regulation between NF-kB and DNA methylation in persistent renal inflammation as a cause of the chronic side-effect of cisplatin in kidneys. Completion of the work will not only advance the understanding of the chronic kidney problems after cisplatin chemotherapy, but may also identify NF-kB and DNA methylation as novel therapeutic targets.

PI_NAMEs: DONG, ZHENG  (contact)

PROJECT_TERMS: Acute;Acute Renal Failure with Renal Papillary Necrosis;Animals;Antineoplastic Agents;Attenuated;Basic Science;Binding;cancer therapy;Cells;chemotherapy;Chronic;Chronic Kidney Failure;Cisplatin;Complex;Development;DNA Methylation;DNA methyltransferase inhibition;DNA Methyltransferase Inhibitor;DNA Modification Methylases;Feedback;Fibrosis;Genes;Genetic Transcription;Goals;Human;I-kappa B Proteins;Inflammation;Inflammatory;injury and repair;Injury to Kidney;insight;interstitial;Kidney;knockout gene;Knockout Mice;Methylation;Modeling;Molecular;mouse model;nephrogenesis;nephrotoxicity;new therapeutic target;NF-kappa B;Normal tissue morphology;novel;novel strategies;Organ;p65;Pathogenicity;Pathology;Pharmaceutical Preparations;Positioning Attribute;promoter;protective effect;Regulation;Renal function;Renal tubule structure;Reporting;Repression;Research;Role;side effect;Signal Transduction;synaptotagmin I;Testing;Therapeutic;tool;Tubular formation;tumor;tumor xenograft;ubiquitin-protein ligase;Ubiquitination;Work;Xenograft Model

PROJECT_TITLE: Kidney Injury by Cisplatin and Renoprotective Strategies

STUDY_SECTION: PBKD

STUDY_SECTION_NAME: Pathobiology of Kidney Disease Study Section[PBKD]