NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Clinical Research;Digestive Diseases;Emerging Infectious Diseases;Foodborne Illness;Genetics;Health Disparities and Racial or Ethnic Minority Health Research;Hematology;Human Genome;Infectious Diseases;Racial and Ethnic Minority Health Research;Rare Diseases;Sepsis

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

PHR: Project Narrative To explain the enigmatic endemicity of typhoid fever in the small Pacific island nation of Samoa since at least the 1960s, despite steady improvements in water and sanitation, we hypothesize that a unique strain of S. Typhi entered Samoa decades ago and expanded into the dominant circulating strain, and asymptomatic chronic gallbladder carriers of the strain serve as an effective long-term reservoir and source of infection. Through our close collaboration with the Samoa Ministry of Health, the “Samoa Typhoid Fever Surveillance Initiative,” we propose a series of comparative genomic and geospatial analyses integrating whole genome sequence data of Salmonella Typhi isolates from Samoa with clinical and household epidemiologic data to determine the population structure, evolutionary origins, and local patterns of transmission including the relative role of asymptomatic chronic carriers of Salmonella Typhi. Where previous large scale phylogenetic studies of Salmonella Typhi have demonstrated the feasibility and public health utility of our experimental approaches, none have focused on Samoa nor been implemented as part of an accelerated and coordinated national typhoid control program; therefore, our results will not only contribute a Polynesian perspective to the field of Salmonella Typhi genomics, but also present new information on endemic typhoid fever to assist the Samoa Ministry of Health and our international collaborators in public health decisions.

PI_NAMEs: SIKORSKI, MICHAEL JOSEPH (contact)

PROGRAM_OFFICER_NAME: ALEXANDER, WILLIAM A

PROJECT_TERMS: Acceleration;Acute;Age;Age Years;Antibiotic Resistance;Bacteremia;Bacteria;bacterial genome sequencing;Bacterial Infections;Bile fluid;Biliary;Blood;Blood Circulation;Bone Marrow;chlorination;Cholelithiasis;Chronic;Cities;Clinical;Collaborations;Collection;Communicable Diseases;Comparative Genomic Analysis;comparative genomics;Consumption;contaminated water;Country;Data;Disease;disease model;Disease Outbreaks;Duodenum;Environment;Environmental Risk Factor;epidemiologic data;Epidemiology;Etiology;Evolution;Exhibits;extensive drug resistance;Family member;Female;Filtration;Flushing;food consumption;Food Contamination;Fostering;Founder Effect;Funding;Gallbladder;Gene Deletion;Genes;Genome;genome sequencing;genomic epidemiology;Genomic Segment;Genomics;Genotype;Geography;Goals;Health;Hepatobiliary;Household;Human;improved;Incidence;Incubated;Individual;Infection;International;Intestinal Mucosa;Intestines;Investigation;Island;Link;Liquid substance;Liver;lymphatic drainage;Macrophage;Methods;Modeling;Modernization;Molecular;Mononuclear;Obesity;Pacific Islands;Pattern;Persons;Phagocytes;Phylogenetic Analysis;Phylogeny;Policies;Polynesian;Population;Predisposition;Prevalence;programs;Public Health;Recording of previous events;Relapse;resistance factors;Resolution;Risk;Risk Factors;Role;Salmonella typhi;Samoa;Samoan;Sanitation;Seasons;Sepsis;septic;Series;Silicon Dioxide;Single Nucleotide Polymorphism;Source;spatiotemporal;Spleen;Structure;System;Systemic infection;Technology;Testing;Time;tool;Training;transmission process;Trees;Typhoid Fever;Variant;Virulence Factors;Water;water quality;Water Supply;waterborne;whole genome

PROJECT_TITLE: Genomics of Salmonella Typhi in Samoa: Population structure and genomic epidemiology

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F13-Z(20)L]


ADMINISTERING_IC: AA

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Behavioral and Social Science;Brain Disorders;Clinical Research;Conditions Affecting the Embryonic and Fetal Periods;Contraception/Reproduction;Fetal Alcohol Spectrum Disorders (FASD);Intellectual and Developmental Disabilities (IDD);Machine Learning and Artificial Intelligence;Maternal Health;Mental Health;Neurosciences;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Preterm, Low Birth Weight and Health of the Newborn;Prevention;Rehabilitation;Social Determinants of Health;Substance Misuse;Women's Health Research

ORG_CITY: MINNEAPOLIS

ORG_COUNTRY: UNITED STATES

ORG_DEPT: PSYCHIATRY

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: PROJECT NARRATIVE Prenatal alcohol use (PAU) is a major and growing public health problem, with deleterious consequences on both the mother and child. The proposed project will integrate research on Alcohol Use Disorder, neuroimaging, and machine learning to (1) first investigate sex/gender differences in the relationship between stress reactivity and alcohol misuse via brain function in women outside of pregnancy, (2) then determine the role of social support in this relationship, and (3) finally determine how stress and social support interact as risk and protective factors during pregnancy. By identifying the contributions of stress, social support, and brain function to alcohol misuse, this work will form the basis for the development of sex/gender-informed interventions to prevent alcohol misuse during and outside of pregnancy.

PI_NAMEs: MAXWELL, ANDREA  (contact)

PROGRAM_OFFICER_NAME: BALAKATHIRESAN, NAGARAJA SETHURAMAN

PROJECT_TERMS: Accounting;addiction;Affect;alcohol abuse therapy;Alcohol consumption;alcohol consumption during pregnancy;alcohol cue;alcohol misuse;alcohol misuse prevention;alcohol use disorder;Alcohols;Algorithms;Anterior;binge drinking;biobank;Brain;Brain region;Buffers;career;Centers for Disease Control and Prevention (U.S.);Child;Child Care;Child Development;cingulate cortex;Clinical;Clinical assessments;cohort;Collection;cost;Craniofacial Abnormalities;Cues;Data;data-driven model;Decision Trees;Development;developmental disease;Dorsal;early alcohol use;Emotional;Etiology;Family;Fetal Alcohol Spectrum Disorder;Functional disorder;Functional Magnetic Resonance Imaging;Gender;gender difference;Goals;high risk;Hydrocortisone;Inferior;Insula of Reil;Intervention;Interview;Knowledge;large datasets;Link;Lobule;Machine Learning;machine learning method;Measures;Medicine;men;Mothers;multimodality;neural circuit;neurobehavioral;Neurodevelopmental Disorder;neuroimaging;Neurosciences Research;novel;obstetrical complication;Parietal;Participant;Patient Self-Report;Patients;Perinatal;Persons;Physicians;Play;Pregnancy;Pregnant Women;Premature Labor;prenatal risk factor;prepregnancy;prevent;Prevention;protective factors;Public Health;recruit;Relapse;Reporting;Research;resilience factor;Risk Assessment;Risk Factors;Role;Sampling;Scientist;sex;Signal Transduction;social;Social support;Spontaneous abortion;stillbirth;Stimulus;Stress;stress management;stress reactivity;substance use;Techniques;Testing;Training;trend;United States;United States National Institutes of Health;Woman;women versus men;women's treatment;Work;young adult

PROJECT_TITLE: The role of stress, social support, and brain function on alcohol misuse in women


ADMINISTERING_IC: CA

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Biotechnology;Breast Cancer;Cancer;Immunization;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Women's Health Research

ORG_CITY: TROY

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: RENSSELAER POLYTECHNIC INSTITUTE

ORG_STATE: NY

PHR: Narrative A novel analytic preclinical longitudinal molecular imaging platform that can dissect and quantify intratumor heterogeneity at high-resolution in the context of targeted drug delivery will be developed. Fusion of lifetime- sensing and high-density fluorescence intensity imaging in the Short-Wave Infrared window will provide near cellular resolution maps of subcutaneous xenograft tumors and patient derived xenograft models. Vasculature and glucose metabolism datasets will be integrated with distribution of target engagement of well-known therapeutic antibodies to quantify intratumor heterogeneity at high-resolution in live, intact animals.

PI_NAMEs: BARROSO, MARGARIDA ;INTES, XAVIER  (contact)

PROGRAM_OFFICER_NAME: BECKER, STEVEN

PROJECT_TERMS: 3-Dimensional;Animals;Antibody Therapy;Artificial Intelligence enhanced;Binding;Biochemical;Blood Vessels;cancer cell;cancer imaging;Complex;Data Set;deep learning;deep learning model;density;Deoxyglucose;Detection;detector;Development;Drug Delivery Systems;drug development;drug distribution;drug efficacy;Drug Receptors;Drug Targeting;ERBB2 gene;Fluorescence;fluorescence lifetime imaging;fluorescence molecular tomography;Fluorescence Resonance Energy Transfer;Glucose;glucose metabolism;Goals;Heterogeneity;high resolution imaging;Human;Image;imaging approach;imaging capabilities;imaging platform;Imaging technology;improved;in vivo;in vivo imaging;insight;instrument;intravital microscopy;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary Neoplasms;Maps;Measurement;Measures;Mediating;Metabolic;Metabolism;Methodology;millimeter;Molecular;molecular imaging;Monitor;Multi-modal optical imaging;multimodality;neoplastic cell;non-invasive imaging;novel;optical imaging;Organ;patient derived xenograft model;Patient-Focused Outcomes;Patients;Pharmaceutical Preparations;Play;pre-clinical;preclinical imaging;prevent;Proteins;Reporting;Resistance;Resolution;response;serial imaging;Short Waves;side effect;Signal Transduction;Specificity;subcutaneous;targeted imaging;targeted treatment;Techniques;Testing;Therapeutic;Therapeutic antibodies;Three-Dimensional Image;Time;time use;Tissue imaging;Tissues;Trastuzumab;Treatment Failure;tumor;tumor heterogeneity;tumor microenvironment;Tumor Volume;tumor xenograft;Tumor-Associated Process;user-friendly;Xenograft Model

PROJECT_TITLE: AI enhanced lifetime-based mesoscopic in vivo imaging of tissue molecular heterogeneity

STUDY_SECTION: ITD

STUDY_SECTION_NAME: Imaging Technology Development Study Section[ITD]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

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

ORG_CITY: NEW YORK

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: PROJECT NARRATIVE Neuronal DNA damage and cell-cycle protein dysregulation are features of neurodegeneration that have also been associated with psychiatric diseases (e.g., schizophrenia and bipolar disorder). This study will investigate: 1) how the Rb/E2F pathway, a core component of cell-cycle signaling, is regulated in neurons that have sustained DNA damage and 2) whether this pathway contributes to neuronal DNA damage repair. Completion of this study will support the identification of potential treatment targets for preserving genomic integrity in neurons exposed to genotoxic stress.

PI_NAMEs: ROSENTHAL, DAVID LEON (contact)

PROGRAM_OFFICER_NAME: PINARD, COURTNEY ROSE

PROJECT_TERMS: Anxiety Disorders;Apoptosis;Apoptotic;Attention;Basic Science;Biology;Biosensor;Bipolar Disorder;Brain Diseases;career;Career Choice;CDK2 gene;Cell Cycle;Cell Cycle Progression;Cell Cycle Proteins;Cell Cycle Regulation;cell fixing;cell preparation;Cell Proliferation;Cells;Cellular Assay;Cellular Structures;Complex;Data;Data Analyses;Disease;DNA biosynthesis;DNA Damage;DNA Repair;DNA Replication Induction;Doctor of Philosophy;Etiology;experience;experimental study;Exposure to;functional outcomes;Genetic;Genetic Transcription;genome integrity;Genotoxic Stress;Goals;Heterogeneity;high throughput analysis;Hospitals;human disease;Immunofluorescence Immunologic;Individual;Interphase Cell;Knowledge;Leadership;Link;Longevity;Maps;Measures;Mental disorders;Mentorship;Metabolism;Methods;Microscopy;Mood Disorders;Nerve Degeneration;Neurodegenerative Disorders;Neuronal Dysfunction;Neurons;neuropsychiatric disorder;novel;Outcome;Oxidative Stress;Pathway interactions;pharmacologic;Phosphorylation;Physicians;Physiological;postmitotic;preservation;programs;Proliferating;protein expression;Proteins;Psychiatrist;Quantitative Microscopy;Recording of previous events;Regulation;repaired;Reporter;Research;Research Personnel;Research Project Grants;Resolution;response;Role;Running;S phase;Sampling;Schizophrenia;Scientist;Severities;Signal Pathway;Signal Transduction;single cell analysis;Stress;Systems Biology;Techniques;Testing;Tissues;Training;upstream kinase;Work

PROJECT_TITLE: Noncanonical E2F Regulation in the Neuronal DNA Damage Response

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


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

ORG_CITY: BIRMINGHAM

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: The proposed research is relevant to public mental health because it will dissect the circuits that mediate different components of motivational drive. Motivational deficits are very prominent in psychiatric disorder and can seriously impact an individual’s quality of life. Consequently, the proposed research is relevant to the mission of NIMH because it will create fundamental insights to develop novel treatment options for individuals suffering from motivational deficits.

PI_NAMEs: BEAS, SOFIA  (contact)

PROGRAM_OFFICER_NAME: FERNANDEZ, FERNANDO R

PROJECT_TERMS: Address;Anatomy;Aversive Stimulus;Behavior;behavior test;Behavioral;Brain region;Brain Stem;Cells;Characteristics;Chronic stress;Collaborations;Corpus striatum structure;Data;data acquisition;Data Analyses;Decision Making;Desire for food;Dopamine D2 Receptor;Drug abuse;Electrophysiology (science);Ensure;experimental study;Food;Generations;Genetic Identity;Glutamates;goal oriented behavior;Goals;Head;Hypothalamic structure;Image;Impairment;Individual;insight;interdisciplinary approach;Locomotion;Major Depressive Disorder;Maps;Measures;Mediating;Mediation;Mental disorders;Mental Health;Microscope;microscopic imaging;miniaturize;Mission;motivated behavior;Motivation;motivational processes;Mus;National Institute of Mental Health;neural;neuronal circuitry;Neurons;novel;novel strategies;Nucleus Accumbens;optogenetics;Pain;patch clamp;Pathway interactions;Play;Positioning Attribute;Process;programs;Quality of life;Research;response;Reversal Learning;Rewards;Role;Shelter facility;Signal Transduction;Speed;Stimulus;Structure of paraventricular nucleus of thalamus;Synapses;Techniques;Testing;Thalamic structure;tool;Training;Work

PROJECT_TITLE: Mapping Thalamo-striatal Neuronal Circuits Underlying Motivational Drive

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


NIH_SPENDING_CATS: Anxiety Disorders;Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Clinical Research;Complementary and Integrative Health;Mental Health;Mental Illness;Neurosciences;Post-Traumatic Stress Disorder (PTSD)

ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE Trauma can contribute to the development of dampened reward processing (anhedonia) and disrupted cognitive control, which are precipitants and perpetuators of symptoms in mental health disorders. This mentored-training project will use electroencephalography to characterize neurophysiological correlates of anhedonia and cognitive control impairment in trauma-exposed people, and it will identify the neurophysiological mechanisms of response to treatment in those completing a novel mindfulness-based intervention called vibroacoustically-augmented breath focused mindfulness. Results from this study will delineate individual differences in brain mechanisms of mental health disorders and inform future intervention strategies for trauma-exposed people with these disorders.

PI_NAMEs: MCDERMOTT, TIMOTHY  (contact)

PROGRAM_OFFICER_NAME: AVENILLA, FRANK R

PROJECT_TERMS: Affective;Aftercare;American;Anhedonia;Attention;attentional control;biological adaptation to stress;Brain;career;Caring;Chronic;Clinical Research;Clinical Trials;cognitive control;cortex mapping;COVID-19 pandemic;Data;Data Analyses;design;Detection;Development;Devices;Diagnostic;Disease;early onset;Electroencephalography;Foundations;Frequencies;Functional Magnetic Resonance Imaging;functional MRI scan;Funding;Future;Goals;Human;Impairment;improved;Individual;Individual Differences;Intervention;Life Experience;Measures;Medial;Mental disorders;Mentors;Mentorship;mindfulness;mindfulness intervention;Mindfulness Training;Motivation;multimodality;neurophysiology;Neurosciences;novel;Outcome;Participant;Patients;pediatric trauma;Performance;Persons;Phenotype;Post-Traumatic Stress Disorders;post-traumatic symptoms;Prefrontal Cortex;Reporting;Research;Respiration;response;response biomarker;Rest;reward processing;Rewards;Risk;Sampling;Scanning;source localization;spatiotemporal;statistics;Stimulus;stimulus sensitivity;Symptoms;Testing;Training;training project;Trauma;trauma exposure;treatment response;vibration;Work

PROJECT_TITLE: Neurophysiological mechanisms of anhedonia and cognitive control deficits in trauma-exposed people completing vibroacoustically augmented breath focused mindfulness


ADMINISTERING_IC: NR

ED_INST_TYPE: SCHOOLS OF NURSING

IC_NAME: NATIONAL INSTITUTE OF NURSING RESEARCH

NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Digestive Diseases;Dissemination and Implementation Research;HIV/AIDS;HPV and/or Cervical Cancer Vaccines;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Immunization;Infectious Diseases;Prevention;Primary Health Care;Rare Diseases;Rural Health;Sexually Transmitted Infections;Social Determinants of Health;Vaccine Related

PHR: PROJECT NARRATIVE As people living with HIV (PLWH) are aging, comorbidities such as HPV-related anal cancer, are emerging as a new public health concern for this population. HPV vaccination is an essential component to a cancer prevention plan among PLWH. In efforts to decrease the personal, clinical, and public health burden of anal cancer and other HPV-related disease, we propose to tailor and implement the effective, evidence-based, multi-level 4 PillarsTM Transformation program to promote the uptake of the HPV vaccine among PLWH.

PI_NAMEs: WELLS, JESSICA  (contact)

PROGRAM_OFFICER_NAME: GODETTE, DIONNE

PROJECT_TERMS: Address;Adult;Advisory Committees;Age;Aging;anal pap smear;antiretroviral therapy;Anus;Awareness;cancer health disparity;cancer prevention;career;Caring;chemoradiation;Clinic;Clinical;comorbidity;design;Diagnosis;Disease;Dose;Effectiveness;effectiveness testing;efficacious intervention;Eligibility Determination;Enrollment;evidence base;Evidence based intervention;Exposure to;FDA approved;follow-up;Future;General Population;Geography;Guidelines;high risk;high risk population;HIV;HIV diagnosis;HIV Seropositivity;HPV vaccine acceptance;HPV-High Risk;Human Papilloma Virus Vaccination;Human Papilloma Virus Vaccine;Human Papilloma Virus-Related Malignant Neoplasm;Human Papillomavirus;Immunization;Immunocompromised Host;immunogenic;improved;Incidence;Individual;Intervention;intervention effect;Investigation;Knowledge;Lesion;Life Expectancy;malignant mouth neoplasm;Malignant neoplasm of anus;Malignant neoplasm of cervix uteri;Malignant neoplasm of penis;Malignant Neoplasms;Malignant Vaginal Neoplasm;Measures;Mediator;men;Modeling;Morbidity - disease rate;mortality;novel strategies;Oncogenic;Outcome;Patients;Persons;Pilot Projects;Population;Positioning Attribute;post intervention;premalignant;prevent;Prevention approach;Primary Cancer Prevention;primary endpoint;programs;Prospective cohort;Provider;Public Health;public health priorities;Reach, Effectiveness, Adoption, Implementation, and Maintenance;Recommendation;Research;Research Personnel;Research Proposals;Risk;Risk Reduction;Rural;rural area;rural health disparities;Rural Population;Safety;screening;Screening for cancer;secondary endpoint;Series;sexual debut;Site;Survival Rate;Target Populations;Testing;tumor;uptake;Vaccinated;Vaccination;vaccine acceptance;Vaccine Research;Vaccinee;Vaccines;Vulnerable Populations;Woman;Work

PROJECT_TITLE: Implementing an evidence-based, multilevel intervention to promote HPV vaccination among HIV positive adults


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: MADISON

ORG_NAME: WM S. MIDDLETON MEMORIAL VETERANS HOSP

ORG_STATE: WI

PHR: Gulf War Illness (GWI) affects an estimated 25-32% of the over 700,000 coalition troops deployed to the Persian Gulf as part of the First Gulf War. GWI causes a range of pain, fatigue, gastrointestinal, skin, neurologic, and respiratory symptoms. New treatments to reduce GWI-associated morbidity are critically needed. Research suggests a role for the gastrointestinal microbiome in mediating health, including through impacting metabolism and immunity. The disruption of this microbiome plays a role in multiple diseases, and preliminary data suggest that Veterans with GWI have altered gut microbiota. Here, we will assess gut microbiome function and inflammation in Veterans with GWI who experience gastrointestinal symptoms. We will also evaluate the effectiveness of a dietary fiber prebiotic supplement intervention on improving the quality of life of Veterans with GWI. Together, these data will provide important insight into the underlying role of the gut microbiome in GWI and the potential for treatments targeting the microbiome to reduce GWI symptoms.

PI_NAMEs: SAFDAR, NASIA  (contact)

PROJECT_TERMS: Address;Affect;Age;aging process;associated symptom;Award;Bile Acids;Biological Markers;Butyrates;Chronic;Chronic stress;Clinical Trials;cohort;Collaborations;combat;comorbidity;comparison control;Consumption;cost;Critical Illness;cytokine;Data;Desire for food;Development;Diarrhea;diarrheal disease;Diet;Dietary Fiber;Disease;effectiveness evaluation;Enrollment;experience;Fatigue;Feces;Fermentation;Fiber;Firmicutes;Functional disorder;Funding;gastrointestinal;Gastrointestinal Diseases;gastrointestinal symptom;Genes;Goals;Gulf War;Gulf War veteran;gut homeostasis;gut inflammation;gut microbiome;gut microbiota;gut-brain axis;Health;Human;humanized mouse;Immunity;improved;in vivo Model;Incidence;indexing;Inflammation;Inflammatory;Inflammatory Bowel Diseases;inflammatory marker;insight;Intervention;Intervention Studies;Intestinal permeability;Irritable Bowel Syndrome;Knowledge;knowledge base;Liver diseases;Longitudinal cohort;Longitudinal Studies;Measures;Mediating;Metabolism;metagenomic sequencing;Metagenomics;microbiome;microbiota;Modality;Modeling;Morbidity - disease rate;mouse model;Mus;Muscle Cramp;Nausea;Neurologic Symptoms;novel;novel therapeutics;Outcome;Pain;Patients;Persian Gulf;Persian Gulf Syndrome;Play;Post-Traumatic Stress Disorders;Potato;prebiotics;Predisposition;Production;Quality of life;Questionnaires;Randomized;reduce symptoms;Reporting;Research;Resistance;Respiratory Signs and Symptoms;Risk;Role;Serum;Skin;Source;Starch;stool sample;Structure;Supplementation;Symptoms;Technology;Therapeutic;Time;transcriptome sequencing;translational impact;Veterans;Volatile Fatty Acids;Vomiting;Work

PROJECT_TITLE: BCCMA: Targeting Gut-Microbiome in Veterans Deployment related Gastrointestinal and Liver diseases; CMA5- Functional metagenomics in GWI-related gut dysfunction


NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Basic Behavioral and Social Science;Behavioral and Social Science;Biotechnology;Brain Disorders;Genetics;Human Genome;Neurosciences;Substance Misuse

ORG_CITY: RICHMOND

ORG_DEPT: PHARMACOLOGY

ORG_NAME: VIRGINIA COMMONWEALTH UNIVERSITY

ORG_STATE: VA

PHR: Project Narrative  Alcohol use disorder (AUD) is a major global healthcare burden, but effective therapies are lacking in part due to the complex genetic architecture of alcohol consumption and dependence. A combination of genetic and transcriptomic factors has been proposed as mechanisms underlying variation in alcohol-related behaviors, but these factors are difficult to study in humans due to confounding environmental factors. We hypothesize that by using a novel complex mouse genetic model, we can identify candidate genes and functional pathways which may be involved in the genetic mechanisms affecting ethanol consumption and validate individual candidate genes as potential therapeutic targets by modulating gene expression in a mouse model.

PI_NAMEs: TATOM, ZACHARY  (contact)

PROGRAM_OFFICER_NAME: LORANG-LEINS, DOMINIQUE

PROJECT_TERMS: Acute;Adult;Affect;alcohol behavior;Alcohol consumption;Alcohol dependence;alcohol exposure;alcohol use disorder;Alcohols;Algorithms;Amygdaloid structure;Animal Model;Animals;Behavior;Behavioral;Behavioral Genetics;Bioinformatics;Brain;Brain region;Candidate Disease Gene;candidate identification;career;causal model;causal variant;Chromosome Mapping;Chronic;Complex;Consumption;Data;design;Dopamine;drinking;effective therapy;Emotions;Environmental Risk Factor;Equation;Ethanol;Functional disorder;Future;Gene Expression;Gene Expression Profile;Gene Expression Regulation;gene network;Genes;Genetic;genetic approach;genetic architecture;genetic association;Genetic Models;Genetic Recombination;Genetic Risk;Genetic study;Genetic Variation;genome wide association study;genomic locus;Genomics;Genotype;global health;healthcare burden;Heavy Drinking;Heritability;Human;human data;Human Genome;human model;Individual;Link;Maps;Mediation;Modeling;Molecular;Morbidity - disease rate;mortality;mouse genetics;mouse model;Mus;Nature;Neural Pathways;Neurobiology;novel;Nucleus Accumbens;Pathway Analysis;Pathway interactions;Pattern;Phenotype;Prefrontal Cortex;Primates;protein structure;Quantitative Genetics;Quantitative Trait Loci;Research;Research Personnel;Resolution;Rewards;Risk;Rodent;Sampling;System;Testing;The Jackson Laboratory;Therapeutic;therapeutic target;therapeutically effective;Tissue Banks;Tissue-Specific Gene Expression;Training;trait;Transcript;transcriptome sequencing;transcriptomics;Variant;Viral Vector

PROJECT_TITLE: Genetic and Transcriptomic Mechanisms of Progressive Ethanol Consumption in the Diversity Outbred Mouse


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

ORG_CITY: Nashville

ORG_NAME: VANDERBILT UNIVERSITY

ORG_STATE: TN

PHR: PROJECT NARRATIVE Despite inhibitory neurons being a prominent neuronal subtype implicated in numerous psychiatric illnesses including schizophrenia, depression, and anxiety, there is a critical gap in our knowledge about the fundamental governing properties of the inhibitory synapse. A disproportionate amount of research has focused on delineating excitatory synapse neurobiology, which has uncovered substrates for disease intervention, but to better understand and treat psychiatric illness we must also appreciate the role of inhibitory synaptic transmission. This study aims to uncover the governing properties of the inhibitory synapse from two angles by elucidating the postsynaptic structure that mediates the segregation of neurotransmission and how this segregation facilitates an autonomous role of GABAergic spontaneous release in plasticity mechanisms, ultimately impacting how we approach inhibition in psychiatric illness.

PI_NAMEs: GUZIKOWSKI, NATALIE  (contact)

PROGRAM_OFFICER_NAME: DRISCOLL, JAMIE DANIELLE

PROJECT_TERMS: Action Potentials;Acute;Address;Anxiety;Artemisinins;Binding;Biological Models;Brain-Derived Neurotrophic Factor;Calcium;Calcium Signaling;Categories;Competitive Binding;Data;Disease;Disease Pathway;Drosophila genus;Electron Microscopy;Electrophysiology (science);Equilibrium;Excitatory Synapse;experience;experimental study;gamma-Aminobutyric Acid;Gene Expression;Genes;Genetic Transcription;gephyrin;Glutamates;Health;Hippocampus;Image;inhibitory neuron;Inhibitory Synapse;insight;Intervention;Investigation;Knowledge;Laboratories;Link;Measures;Mediating;Mental Depression;Mental disorders;Molecular;Nanostructures;Neurobiology;Neuromuscular Junction;Neurons;neuropsychiatric disorder;neurotransmission;neurotrophic factor;novel;Pathway interactions;Pharmaceutical Preparations;pharmacologic;postsynaptic;presynaptic;Property;receptor;Regulation;Research;Role;scaffold;Scaffolding Protein;Schizophrenia;segregation;Signal Pathway;Signal Transduction;small molecule;Structure;Support System;Synapses;Synaptic Transmission;Testing;tool;transcriptome sequencing;transmission process;ultra high resolution;Visualization;Work

PROJECT_TITLE: Elucidation of Nanostructure and Function of Spontaneous GABAergic Transmission at the Inhibitory Synapse


ORG_CITY: SEATTLE

ORG_NAME: VA PUGET SOUND HEALTHCARE SYSTEM

ORG_STATE: WA

PHR: Mild traumatic brain injury (mTBI), or concussion, has emerged as a potential risk factor for the development of neurodegenerative conditions including Alzheimer's disease. Alzheimer's disease is characterized in part by the buildup of aggregates of the protein tau within cells of the brain. Yet how mTBI may contribute to the development of this tau buildup remains unknown. Disruption of normal sleep-wake patterns is a frequent complaint after mTBI, while in aging populations, sleep disruption appears to promote the development of neurodegenerative pathology. In this study will test whether sleep disruption after mTBI exposure contributes to the development of post-traumatic tau pathology. We will also specifically test whether the dysfunction of the brain's waste clearance system, called the glymphatic system, links mTBI with tau pathology. These studies may pave the way for new approaches to preventing dementing conditions like Alzheimer's disease in both Veteran and civilian populations exposed to mTBI earlier in life.

PI_NAMEs: ILIFF, JEFFREY J (contact)

PROJECT_TERMS: Acute;Age;Aging;aging brain;Alzheimer's Disease;Alzheimer's disease diagnosis;Amyloid beta-Protein;Anatomy;Behavior assessment;Blood Vessels;Brain;brain cell;Brain Concussion;brain dysfunction;central nervous system injury;Cerebrospinal Fluid;Chronic;Chronic Phase;chronic traumatic encephalopathy;Clinical;Clinical Research;clinical risk;Cortical vasculature;demented;dementia risk;Deposition;Development;Diagnosis;Dose;Drowsiness;epidemiology study;Exhibits;Exposure to;functional decline;Functional impairment;genetic approach;glymphatic clearance;glymphatic dysfunction;glymphatic function;glymphatic system;Histologic;human subject;Image;Immunofluorescence Immunologic;Immunohistochemistry;Impaired cognition;Impairment;improved;in vivo;Individual;injured;Injury;Intercellular Fluid;interstitial;Life;Link;Liquid substance;Magnetic Resonance Imaging;Microdialysis;mild traumatic brain injury;Military Personnel;military veteran;Modeling;mouse model;Mus;Nerve Degeneration;Neurocognitive Deficit;Neurodegenerative Disorders;Neurons;novel;novel strategies;Pathologic;Pathology;Pathway interactions;Pattern;pharmacologic;Physiological;Play;Population;Post-Concussion Syndrome;prevent;Prevention;Process;protein aggregation;Proteins;Recording of previous events;Reporting;response;Risk Factors;Rodent Model;Role;Sampling;Senile Plaques;service member;Sleep;Sleep Deprivation;Sleep disturbances;Sleep Wake Cycle;Slice;System;tau aggregation;tau Proteins;tau-1;Tauopathies;Techniques;Testing;Time;Transgenic Organisms;Translational Research;Traumatic Brain Injury;Veterans;wasting;Wild Type Mouse

PROJECT_TITLE: The role of post-traumatic sleep-wake disruption in the development of tau pathology following mild traumatic brain injury


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Clinical Research

ORG_CITY: OKLAHOMA CITY

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR

ORG_STATE: OK

PHR: Intra-abdominal surgeries are performed daily in the U.S. and over 90% of these surgeries lead to the formation of peritoneal adhesions which increases the risk of mortality. Our studies will reveal potential therapeutic targets for the treatment of peritoneal adhesions. These treatments would increase post-operative survival.

PI_NAMEs: BERRY, WILLIAM L (contact)

PROGRAM_OFFICER_NAME: CHAO, CHIEN-CHUNG

PROJECT_TERMS: Ablation;Actins;Adhesions;Adhesives;Automobile Driving;Cell Separation;cell type;Cells;cofactor;Disease;Extracellular Matrix;Fibrosis;Genetic Transcription;Goals;in vivo;insight;Intestinal Obstruction;Intra-abdominal;Knowledge;Lead;Learning;mechanotransduction;Molecular;Morbidity - disease rate;mortality risk;Mus;myocardin;Myofibroblast;novel;novel strategies;novel therapeutics;Operative Surgical Procedures;Pathway interactions;Patients;PDGFRB gene;Peritoneal;Platelet-Derived Growth Factor;Platelet-Derived Growth Factor alpha Receptor;Postoperative Period;prevent;Prevention therapy;Procedures;Process;programs;Recurrence;Research;Risk;Signal Transduction;Smooth Muscle Myocytes;Techniques;Technology;therapeutic target;Tissues;transcription factor;Vascular Smooth Muscle;wound healing

PROJECT_TITLE: MECHANISMS DRIVING THE FORMATION OF POST-OPERATIVE PERITONEAL ADHESIONS

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CB-H(55)R]


ADMINISTERING_IC: HD

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

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

NIH_SPENDING_CATS: Pediatric

ORG_CITY: CINCINNATI

ORG_NAME: CINCINNATI CHILDRENS HOSP MED CTR

ORG_STATE: OH

PHR: NARRATIVE: Graduates of this fellowship program will be national leaders who will have a significant scientific impact on research in pediatric treatment adherence and relevant health outcomes for many years to come. This program will result in effective interventions that will enhance adherence to medical treatment for children and adolescents with a wide range of pediatric conditions. These advances will reduce the extraordinary negative impact of pediatric nonadherence and enhance children’s health by reducing symptoms, impairment, health care utilization, and the costs of pediatric chronic illness treatment.

PI_NAMEs: HOMMEL, KEVIN  (contact);MCGRADY, MEGHAN EILEEN

PROGRAM_OFFICER_NAME: MILLER, BRETT

PROJECT_TITLE: Enhancing Pediatric Treatment Adherence and Health Outcomes


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Cerebrovascular;Dementia;Neurodegenerative;Neurosciences;Stroke

ORG_CITY: MORGANTOWN

ORG_DEPT: PHYSIOLOGY

ORG_NAME: WEST VIRGINIA UNIVERSITY

ORG_STATE: WV

PHR: Project Narrative Public Health Relevance: Stroke - like many brain diseases - is clearly associated with aging and a plethora of age-related conditions, but age-related co-morbidities, as a variable in stroke occurrence, severity and long-term recovery is seldom studied experimentally, but is one of the identified factors in the lack of progress in the discovery of new therapies for acute stroke brain damage. The Stroke and Alzheimer’s Disease Related Dementias Predoctoral Training Program will formalize and standardize our already strong training programs in the biomedical sciences and focus on aging and stroke research by creating a new generation of young scholars who can address the need for innovative stroke research for the citizens of West Virginia and the nation.

PI_NAMEs: BROWN, CANDICE  (contact)

PROGRAM_OFFICER_NAME: HAAKENSON, CHELSEA MARIE

PROJECT_TERMS: Alzheimer's disease related dementia;Stroke

PROJECT_TITLE: Stroke and Alzheimers Disease Related Dementias


ADMINISTERING_IC: AI

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

ORG_CITY: DALLAS

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: Project Narrative The autophagy pathway plays a key role in antiviral immunity by facilitating the clearance of viral proteins and particles in host cells, but how viruses are specifically targeted for autophagic destruction is still poorly understood. In preliminary studies, this proposal shows a novel autophagy regulator cyclin-dependent kinase- like 5 (CDKL5) that protects mice against lethal infections with neurotropic viruses. The goal of this K08 proposal is to provide a 5-year rigorous training plan for the PI, Dr. Josephine Thinwa to cultivate the skills and resources necessary to build a robust independent research program aimed at investigating the interphase between autophagy and viral pathogens.

PI_NAMEs: THINWA, JOSEPHINE WANJIRU (contact)

PROGRAM_OFFICER_NAME: DUPUY, LESLEY CONRAD

PROJECT_TERMS: Anti-viral Response;antiviral immunity;Autophagocytosis;Autophagosome;Biological Assay;biomedical scientist;Brain;brain tissue;Capsid;Capsid Proteins;career;career development;CDKL5 disorder;Cell Death Induction;cell type;Cells;Central Nervous System Infections;Co-Immunoprecipitations;Communicable Diseases;Cyclin-Dependent Kinases;cytokine;Data;Defect;Defense Mechanisms;Doctor of Philosophy;Double Stranded DNA Virus;experience;Generations;Genes;genome-wide;Goals;Health;Herpesvirus 1;Host Defense;Human;imaging modality;in vivo;Infection;Inflammatory;Inflammatory Response;Institution;Internal Medicine;Interphase;Knockout Mice;Leadership;Learning;Life Cycle Stages;Lysosomes;Mentors;Mentorship;Molecular;Morphogenesis;Mus;mutant;Mutation;Natural Immunity;Neurodevelopmental Disorder;neuron loss;Neurons;neurotropic virus;Nonstructural Protein;novel;particle;pathogen;pathogenic virus;Pathway interactions;Physicians;Physiological;Play;Positioning Attribute;Postdoctoral Fellow;Predisposition;Process;Production;programs;Proteins;prototype;reconstitution;Research;Research Personnel;Resources;RNA;RNA Viruses;Role;Scientist;Sindbis Virus;skills;Small Interfering RNA;Structural Genes;Structural Protein;Technical Expertise;Terminal Disease;Testing;Tissues;Training;Translations;Viral;Viral Load result;Viral Pathogenesis;Viral Proteins;Viral Structural Proteins;Virion;Virus;Virus Diseases;Virus Replication;Work

PROJECT_TITLE: Characterization of CDKL5 function in host antiviral defense

STUDY_SECTION: MID

STUDY_SECTION_NAME: Microbiology and Infectious Diseases Advisory Committee[MID]


FUNDING_MECHANISM: SBIR-STTR RPGS

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Bioengineering;Biotechnology;Clinical Research;Emerging Infectious Diseases;Infectious Diseases;Lung;Prevention;Rare Diseases

ORG_CITY: RENO

ORG_NAME: DXDISCOVERY, INC.

ORG_STATE: NV

PHR: Pertussis (whooping cough) is a highly contagious, airborne disease that is rapidly re-emerging as a serious public health threat in the United States. The study goal is a rapid, point-of-care, antigen-detection, lateral flow immunoassay to detect Bordetella pertussis in nasopharyngeal specimens. If successful, the product will provide early diagnosis that enables effective early treatment and triggers public health measures that limit transmission.

PI_NAMEs: BURNHAM-MARUSICH, AMANDA  (contact)

PROGRAM_OFFICER_NAME: GU, XIN-XING

PROJECT_TERMS: Affinity;Agreement;Annual Reports;Antibodies;antigen detection;Antigen Targeting;antigen test;Antigens;Bacteria;Blood group antigen S;Bordetella pertussis;Case Study;Categories;Cell surface;Cells;Clinic;Clinical;clinically relevant;Commercial grade;Communities;community transmission;Coughing;Country;COVID-19;COVID-19 pandemic;cross reactivity;Data;design;Detection;detection limit;detection sensitivity;Diagnosis;Diagnostic;Disease;Disease Outbreaks;Early Diagnosis;Early treatment;economic impact;Electricity;Epitope Mapping;Equipment;factor A;fungus;Goals;Healthcare;Hospitals;Hour;illness length;Immunoassay;improved;Infant;Infection;Laboratories;Lateral;Libraries;Linear Sequence Epitopes;Measures;microbial;Modeling;Monoclonal Antibodies;Morbidity - disease rate;nasopharyngeal swab;Nasopharynx;Nucleic Acids;Papio;Patients;pediatrician;Performance;Pertussis;Phase;point of care;point of care testing;pre-clinical;preclinical evaluation;Preparation;prevent;prospective;Proteins;Protocols documentation;prototype;Public Health;Rapid diagnostics;rapid test;Reaction;Reproducibility;Research;research clinical testing;Resources;Respiratory Disease;Sampling;SARS-CoV-2 antigen;Sensitivity and Specificity;Serology;Severity of illness;specific biomarkers;Specificity;Specimen;Speed;Statistical Data Interpretation;Symptoms;Target Populations;Testing;tool;Trachea;transmission process;United States;urgent care;Vaccines;Visual;waiver

PROJECT_TITLE: Point-of-care lateral flow immunoassay for diagnosis of pertussis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DCAI-E(13)]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

ORG_NAME: UNIVERSITY OF WASHINGTON

PHR: Project Narrative The heart is one of the most mechanically dynamic organs; it dilates and contracts to cycle its volume in order to pump between 5 to 30 liters of blood a minute. Heart stretch accelerates heart rate; however, how the pacemaker cells controlling heart rate sense and respond to mechanical stretch is unknown. We aim to identify the molecules behind mechanosensation in the cardiac pacemaker.

PI_NAMEs: MORENO, CLAUDIA MARCELA (contact)

PROGRAM_OFFICER_NAME: TJURMINA, OLGA A

PROJECT_TERMS: Acceleration;Acute;Affect;Animals;Area;Arrhythmia;Blood;Calcium;Calcium Oscillations;Cardiac;Cardiac pacemaker;cell type;Cells;Characteristics;Chemicals;Contracts;Coupling;Dependence;Development;Electrophysiology (science);Environment;experimental study;Feedback;Fiber;Generations;Goals;Heart;Heart Atrium;heart electrical activity;heart function;Heart Rate;high resolution imaging;Image;In Situ Hybridization;In Vitro;in vivo;innovation;insight;knock-down;Knockout Mice;Laboratories;Lung;mechanical force;Mechanics;mechanotransduction;Mediating;Modeling;Molecular;mouse model;Mus;nodal myocyte;novel;Organ;overexpression;Pacemakers;Performance;Physiological;Physiological Processes;Piezo 1 ion channel;Piezo 2 ion channel;Piezo ion channels;Positioning Attribute;Preparation;prevent;Process;Proprioception;Protein Isoforms;Pump;Reflex action;Research;response;Right atrial structure;Role;Signal Pathway;Signal Transduction;Space Perception;Specificity;Stretching;superresolution imaging;Telemetry;Testing;Tissues;tool;Toxin;Translations;ultrasound;Venous;voltage

PROJECT_TITLE: Molecular mechanisms of mechanosensation in the cardiac pacemaker

STUDY_SECTION: MPPB

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


NIH_SPENDING_CATS: Clinical Research;Hematology;Infectious Diseases;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Precision Medicine;Sepsis

ORG_CITY: CHAMPAIGN

ORG_NAME: PRENOSIS, INC.

ORG_STATE: IL

PHR: Principal Investigator/Program Director (Last, first, middle): Reddy, Jr., Bobby Project Narrative: In this proposed project, Prenosis intends to introduce a powerful new dimension to the existing NOSIS dataset by generating and analyzing longitudinal, time-series biomarker data that will be linked to the existing time series clinical data from hospital Electronic Medical Records. Using samples that have already been collected and stored in the biobank, we will leverage our existing measurement pipeline to measure the concentrations of 40 critical protein biomarkers from 9,000 follow-up longitudinal samples for ~3,400 patients. Analytics built upon such a dataset could dramatically improve diagnostic, clinical decision support, and drug development products for sepsis and COVID.

PI_NAMEs: REDDY, BOBBY  (contact)

PROGRAM_OFFICER_NAME: KODURI, SAILAJA

PROJECT_TERMS: Admission activity;Adrenal Cortex Hormones;Anti-Infective Agents;Antibiotics;Award;biobank;Biological;Biological Assay;Biological Markers;Classification;Clinical;Clinical Data;clinical decision support;Clinical Trials;commercialization;Computer software;Computerized Medical Record;COVID-19;Data;Data Set;deep learning;demographics;design;Diagnostic;diagnostic biomarker;diagnostic development;Dimensions;drug candidate;drug development;Evaluation;follow-up;Grant;Grouping;Heterogeneity;Hospitals;Hour;Housing;immune modulating agents;Immune response;improved;Infection;insight;interest;Intervention;Libraries;Link;Liquid substance;longitudinal analysis;Machine Learning;Maps;Measurement;Measures;Methodology;model generalizability;mortality;National Institute of General Medical Sciences;novel diagnostics;Outcome;outcome prediction;patient population;Patients;Plasma;Principal Investigator;Probability;product development;prognostic;prognostic value;programs;protein biomarkers;response;Sampling;Sepsis;Series;Serum;success;support tools;Surrogate Endpoint;Syndrome;Testing;Time;time use;tool;treatment effect;Vasoconstrictor Agents;Ventilator;Work

PROJECT_TITLE: Use of Time Series Biomarker and Clinical Data to Construct a Time Trajectory Host Response Map

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-HSS-J(10)B]


ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Genetics;Human Genome

ORG_CITY: WORCESTER

ORG_DEPT: GENETICS

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

ORG_STATE: MA

PHR: Project narrative – public health statement The human genome encodes the genetic information required for human development and health. For this information to be used correctly, the genome needs to be folded in intricate three-dimensional structures, and defective folding can lead to many human diseases including cancer, developmental, and metabolic disorders. We will employ recently developed innovative genomic technologies to identify genetic elements encoded in the human genome that control folding of chromosomes, mediate correct chromosome segregation when cells divide, and ensure chromosomes do not become knotted and entangled with each other.

PI_NAMEs: DEKKER, JOB  (contact)

PROGRAM_OFFICER_NAME: PAZIN, MICHAEL J

PROJECT_TERMS: Address;Affinity;Anaphase;Automobile Driving;Binding;Biology;Biophysical Process;Cell Cycle;Cell Cycle Stage;Cell division;cell type;Cells;Chromatin;Chromatin Loop;chromosome replication;Chromosome Segregation;Chromosome Structures;Chromosomes;cohesin;condensin;Data;Defect;detection assay;developmental disease;Disease;Distal;Elements;Enhancers;Ensure;experimental study;gene correction;Gene Expression;Gene Expression Regulation;Genes;genetic element;genetic information;Genetic Transcription;Genome;Genome Stability;genome-wide;Genomic DNA;Genomic Instability;genomic locus;Genomics;Health;Hi-C;Human Development;human disease;Human Genome;innovation;insight;Interphase;Interphase Chromosome;Investigation;Lead;Liquid substance;Location;Malignant Neoplasms;Maps;Measures;Mediating;Metabolic Diseases;Methods;Mitosis;Molecular;Molecular Machines;new technology;Phase;Play;Polymers;Positioning Attribute;Process;protein complex;Public Health;Research;Resolution;RNA;RNA Splicing;Role;S phase;segregation;simulation;Sister Chromatid;Technology;three dimensional structure;Time;Variant;Work

PROJECT_TITLE: Structural Annotation of the Human Genome

STUDY_SECTION: GCAT

STUDY_SECTION_NAME: Genomics, Computational Biology and Technology Study Section[GCAT]


NIH_SPENDING_CATS: Autoimmune Disease;Biotechnology;Diabetes;Genetics;Human Genome;Nutrition;Pediatric;Precision Medicine;Prevention;Primary Immunodeficiencies;Rare Diseases

ORG_CITY: BALTIMORE

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

ORG_STATE: MD

PHR: NARRATIVE The ClinGen Monogenic Diabetes Expert Panel is determining which genes and genetic variants are involved in certain forms of diabetes known as monogenic diabetes in order to improve our ability to diagnose those forms of diabetes. Determining the specific genetic type of diabetes can improve management of blood sugar levels and other problems associated with the disease. In this project, we will focus on genes and variants that that cause types of monogenic diabetes that involve the immune system, fat distribution, and how the body uses insulin to lower blood sugar.

PI_NAMEs: POLLIN, TONI I. (contact)

PROGRAM_OFFICER_NAME: OREILLY, JULIA JIAQI

PROJECT_TERMS: Accounting;actionable mutation;Address;Adult;Affect;aged;Autoimmune;Autoimmune Diabetes;Autoimmune Diseases;Autoimmunity;Awareness;Blindness;Blood Glucose;blood glucose regulation;BSCL2 gene;Cardiovascular Diseases;Cessation of life;Charcot-Marie-Tooth Disease;Childhood diabetes;Classification;Clinical;ClinVar;Colorectal Cancer;Complex;cost effective;Country;Deposition;Developmental Disabilities;Diabetes Mellitus;Diagnosis;dietary;Disease;Early Intervention;End stage renal failure;Etiology;evidence base;Familial generalized lipodystrophy;Familial partial lipodystrophy;Family member;Fatty acid glycerol esters;FOXP3 gene;Genes;Genetic;Genetic Heterogeneity;genetic testing;genetic variant;Genomics;Goals;HNF4A gene;Hyperglycemia;Hypoglycemia;Immune system;immunodeficiency;Immunodysregulation polyendocrinopathy enteropathy X-linked syndrome;improved;Individual;individualized medicine;Injections;Institution;Insulin;Insulin Resistance;Intellectual functioning disability;International;Leptin;Leptin deficiency;Lipodystrophy;maternal diabetes;maturity onset diabetes of the young;member;neonatal diabetes mellitus;Neurologic Dysfunctions;next generation sequencing;Non-Insulin-Dependent Diabetes Mellitus;Oral;Organ;Outcome;Pancreatic Diseases;Pathogenicity;Patients;Persistent Hyperinsulinemia Hypoglycemia of Infancy;Polyglandular Autoimmune Syndrome Type I;Population Study;PPARG gene;precision medicine;Predisposition;Pregnancy Outcome;prevent;Process;Protocols documentation;Quality of life;rare variant;Research Personnel;resistance gene;Risk;Risk Management;risk prediction;SHORT syndrome;STAT3 gene;Syndrome;Techniques;Testing;Time;type I and type II diabetes;United States;Variant

PROJECT_TITLE: Genomic Clinical Variant Expert Curation Panel for Monogenic Diabetes: A Gateway to Precision Medicine in Diabetes Mellitus

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-MGG-B(50)R]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Cerebrovascular;Childhood Injury;Dementia;Neurodegenerative;Neurosciences;Pediatric;Physical Injury - Accidents and Adverse Effects;Rare Diseases;Social Determinants of Health;Stroke;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury;Unintentional Childhood Injury;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: Fort Lauderdale-Davie

ORG_NAME: NOVA SOUTHEASTERN UNIVERSITY

ORG_STATE: FL

PHR: There is evidence to suggest that traumatic brain injury (TBI) increases the risk of dementia and stroke; however, pathological mechanisms linking these conditions are yet to be fully elucidated. Cerebral amyloid angiopathy (CAA), the accumulation of amyloid protein (most commonly beta-amyloid, associated with Alzheimer's disease) within cerebral vasculature, may be one such mechanism. Following a repetitive mild TBI protocol starting at 2 months of age, we will determine whether cognitive deficits and neuropathology are altered at several timepoints post-TBI (short term: 7 days, and longer-term: 3 months) in a mouse model of CAA, with the goal of identifying mechanisms linking these conditions, which may in turn reveal novel targets for treatment.

PI_NAMEs: ROBISON, LISA SUZANNE (contact)

PROGRAM_OFFICER_NAME: OPANASHUK, LISA A

PROJECT_TERMS: Acute;Adolescence;Affect;Age;Age Months;Alzheimer's Disease;Amyloid;Amyloid beta-Protein;amyloid pathology;Amyloid Proteins;Animal Model;anxiety-like behavior;Athletic;Behavior;Behavioral;biological sex;Blood Vessels;Boxing;Brain;Brain hemorrhage;Brain Injuries;Cerebral Amyloid Angiopathy;Cerebrovascular Disorders;Cerebrovascular system;chronic traumatic encephalopathy;Clinical;Cognitive;Cognitive deficits;contact sports;Dementia;dementia risk;Diffuse Axonal Injury;Domestic abuse;Experimental Designs;Goals;Head;Hockey;Impaired cognition;Impairment;Individual;Injury;interest;Intervention;intimate partner violence;Ischemic Stroke;late life;Learning;Link;Literature;Manufactured football;Memory;memory recognition;mild traumatic brain injury;military service;Modeling;mouse model;Mus;Nerve Degeneration;neuroinflammation;Neuronal Plasticity;neuropathology;novel;object recognition;Outcome;Pathologic;Pathology;Persons;prevent;Procedures;Proteins;Protocols documentation;Recording of previous events;Risk;Soccer;Stroke;stroke risk;Synapses;tau-1;Tauopathies;Time;time interval;Transgenic Mice;Traumatic Brain Injury;Unconscious State;vascular cognitive impairment and dementia;white matter damage;Work;young adult

PROJECT_TITLE: Effects of mild traumatic brain injury in a mouse model of cerebral amyloid angiopathy

STUDY_SECTION: CDIN

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


NIH_SPENDING_CATS: Biomedical Imaging;Cardiovascular

ORG_CITY: BOSTON

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: The proposed competing application of our T32 training program is designed to train clinician-scientists in cardiovascular imaging to prepare them for successful and productive academic careers. The program offers mutli-disciplinary training in a broad and diverse spectrum of areas in cardiovascular medicine with relevance to imaging science. With this renewal, we continue our primary goals of providing leadership in academic cardiovascular imaging and training future leaders in imaging science to improve outcomes in cardiovascular disease.

PI_NAMEs: DI CARLI, MARCELO F (contact)

PROGRAM_OFFICER_NAME: WOO, SEUNG KYOON

PROJECT_TERMS: cardiovascular imaging;Research Training;Training Programs

PROJECT_TITLE: Noninvasive Cardiovascular Imaging Research Training Program

STUDY_SECTION: NITM

STUDY_SECTION_NAME: NHLBI Institutional Training Mechanism Study Section[NITM(OA)]


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

ORG_CITY: HONOLULU

ORG_NAME: UNIVERSITY OF HAWAII AT MANOA

ORG_STATE: HI

PHR: PROJECT NARRATIVE Myocardial infarction (MI) initiates a dynamic cellular response during the early phases of onset, as extensive inflammation propagates throughout cardiac tissues resulting in massive cardiomyocyte death and adverse ventricular remodeling. The RNA-binding protein, tristetraprolin (TTP), has wide-ranging anti-inflammatory effects and has been shown to prevent oxidative stress and mitochondrial dysfunction by binding, and destabilizing the related mRNA transcripts. This proposal explores the regulatory role of TTP in early-onset MI and its therapeutic potential in attenuating cardiomyopathy to improve long-term prognoses.

PI_NAMEs: YAP, JONATHAN  (contact)

PROGRAM_OFFICER_NAME: WANG, WAYNE C

PROJECT_TERMS: Acute;adeno-associated viral vector;Adoptive Transfer;Affect;Anti-Inflammatory Agents;Antiinflammatory Effect;Attenuated;Binding;Calgranulin B;Cardiac;Cardiac Myocytes;Cardiomyopathies;cardioprotection;career development;Cell Death;Cell Line;Cell Physiology;Cells;Cessation of life;ChIP-seq;Coculture Techniques;Comprehension;Coupled;cytokine;Data;Development Plans;early onset;Echocardiography;efficacy evaluation;Excision;experimental study;Exposure to;extracellular;Extracellular Matrix Degradation;Flow Cytometry;gain of function;Gene Combinations;gene editing technology;Gene Expression;Genes;Genetic Transcription;heart function;heart preservation;Histology;Hypoxia;Immune;Impairment;improved;In Vitro;in vivo;Inflammation;Inflammatory;Inflammatory Response;Injury;Ischemia;Knock-out;Leukocytes;Ligation;Link;LoxP-flanked allele;Macrophage;Measurement;Measures;Mediating;Messenger RNA;Methods;Mitochondria;mitochondrial dysfunction;Modality;Modeling;Molecular;Monitor;mouse model;mRNA Expression;Mus;mutant;Mutate;Mutation;Myelogenous;Myeloid Cells;Myocardial Infarction;Myocarditis;next generation sequencing;novel;osteopontin;overexpression;Oxidative Stress;Pathology;Pathway interactions;Pattern;Phase;Play;polymerization;Polymers;prevent;Prevention;Process;Production;Prognosis;Property;Proteins;Reactive Inhibition;Reactive Oxygen Species;recruit;Regulation;repaired;Reperfusion Injury;Reperfusion Therapy;Reporting;Research;Resolution;response;RNA-Binding Proteins;Role;S100A8 gene;S100A9 gene;Sampling;Signal Transduction;Site;sound;spatiotemporal;System;Techniques;Testing;Therapeutic;Time;TIS11 protein;Tissues;Transcript;transcriptome;transcriptome sequencing;transcriptomics;Treatment Efficacy;vector;Ventricular Remodeling;Viral Vector

PROJECT_TITLE: Anti-inflammatory Signaling of RNA-binding Protein, Tristetraprolin, During Myocardial Infarction


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Autoimmune Disease;Biomedical Imaging;Biotechnology;Brain Disorders;Immunotherapy;Multiple Sclerosis;Neurodegenerative;Neurosciences

ORG_CITY: STANFORD

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: STANFORD UNIVERSITY

ORG_STATE: CA

PHR: Project Narrative Multiple sclerosis (MS) is a severely debilitating neurological disease primarily affecting young adults, in which some of the body's own immune cells, known as B lymphocytes (or B cells), unfortunately play an important role in damaging the central nervous system. Although there are promising treatments that remove these deleterious cells, we have no way to accurately select patients for anti-B cell therapies or to quantify the effect of such treatments on the number of B cells in the brain and peripheral organs in real-time. Herein, we propose a novel, highly sensitive and specific imaging toolbox that can be used to non-invasively detect B cells in the whole body and brain, monitor response to anti-B cell therapies, and optimize dosing for individual MS patients.

PI_NAMEs: JAMES, MICHELLE LOUISE (contact)

PROGRAM_OFFICER_NAME: UTZ, URSULA

PROJECT_TERMS: Address;Affect;Affinity;Aftercare;American;Antibodies;Area;B cell therapy;B-Lymphocyte Subsets;B-Lymphocytes;Biological;biomarker driven;Brain;CD19 gene;CD20 Antigens;Cell Count;Cell surface;Cells;Cellular Assay;Cellular biology;Central Nervous System;central nervous system demyelinating disorder;Central Nervous System Diseases;Clinic;Clinical;clinical translation;Clinical Trials;clinically relevant;comparison control;Complex;cost;Data;Detection;Development;disability;Disease;Dose;Evaluation;Experimental Autoimmune Encephalomyelitis;experimental study;Fc domain;FDA approved;Flow Cytometry;Functional disorder;Future;Goals;Human;Image;imaging agent;Immune;immune cell infiltrate;Immunoglobulin Fragments;ImmunoPET;immunoreactivity;improved;In Vitro;in vivo;Individual;Injections;insight;Knowledge;Label;Light;Mediating;Monitor;Monoclonal Antibodies;Monoclonal Antibody CD20;Morbidity - disease rate;mouse model;MS4A1 gene;Multiple Sclerosis;multiple sclerosis patient;multiple sclerosis treatment;Mus;Mutate;Myelin;Nature;Nerve Degeneration;Nervous System Disorder;Neurologic Dysfunctions;Non-Invasive Detection;novel;Organ;Pathogenicity;Pathology;Patient Selection;patient stratification;Patients;Peripheral;Phenotype;Physiological;Plasma Cells;Plasmablast;Play;Positron-Emission Tomography;Prediction of Response to Therapy;Publishing;Radioimmunoconjugate;Relapse;Reporting;response;rituximab;Role;Sensitivity and Specificity;Signal Transduction;spatiotemporal;success;Surface Antigens;Techniques;Therapeutic;Therapeutic Effect;Therapeutic Monoclonal Antibodies;therapeutic target;Time;Tissues;Tracer;Translating;treatment optimization;treatment response;Variant;Visualization;young adult

PROJECT_TITLE: Imaging B cells in the brain and beyond: developing an immuno-PET toolbox to improve understanding and treatment of multiple sclerosis

STUDY_SECTION: EITN

STUDY_SECTION_NAME: Emerging Imaging Technologies in Neuroscience Study Section[EITN]


ORG_CITY: CAMBRIDGE

ORG_NAME: HARVARD UNIVERSITY

PHR: Project Narrative The behavior of biological systems is complex and often unpredictable, challenging our ability to diagnose and treat disease. This proposal requests support for the Harvard Ph.D. Program in Systems Biology, an interdisciplinary program that trains students to develop and use quantitative measurement technologies and mathematical or computational approaches to gain a deeper understanding of how biological systems behave, and to lead the application of systems biology to medicine.

PI_NAMEs: DESAI, MICHAEL M (contact);KLEIN, ALLON MOSHE

PROGRAM_OFFICER_NAME: STEPANEK, LAURIE ELIZABETH

PROJECT_TERMS: programs;Systems Biology

PROJECT_TITLE: Harvard Systems Biology Graduate Program

STUDY_SECTION: TWD

STUDY_SECTION_NAME: Training and Workforce Development Study Section - A[TWD-A]


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Childhood Obesity;Clinical Research;Clinical Trials and Supportive Activities;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Nutrition;Obesity;Pediatric;Prevention

ORG_CITY: PHILADELPHIA

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: TEMPLE UNIV OF THE COMMONWEALTH

ORG_STATE: PA

PHR: PROJECT NARRATIVE Making healthy food choices and eating in moderation during early childhood are central to obesity prevention and are thought to require effortful and goal-directed self-regulation. Scientific knowledge of the cognitive- developmental processes that serve to support children’s appetite self-regulation are surprisingly limited. This investigation will provide new scientific directions for obesity prevention by elucidating cognitive-developmental influences on young children’s ability to make healthy food choices and eat in moderation.

PI_NAMEs: FISHER, JENNIFER ORLET (contact)

PROGRAM_OFFICER_NAME: ESPOSITO, LAYLA E

PROJECT_TERMS: Achievement;Adolescence;Attention;Authoritarianism;Behavioral;Biological;Body mass index;Child;Child Development;Child Rearing;Child Support;Childhood;Cognitive;cognitive process;design;Desire for food;Development;Developmental Process;Diet;Dimensions;early childhood;Eating;Eating Behavior;eating in absence of hunger;emotional functioning;Environment;Evaluation;executive function;expectation;Factor Analysis;Family;feeding;flexibility;Food;Goals;Health Food;Healthy Eating;Informal Social Control;innovation;Investigation;Knowledge;Laboratories;Learning;Low income;Measures;novel;Nursery Schools;Obesity;obesity in children;obesity prevention;obesity risk;obesogenic;Outcome;Overweight;Participant;Pathway interactions;Predisposition;primary caregiver;Process;psychologic;Questionnaires;Regulation;Research;Role;Sampling;School-Age Population;Schools;Science;Scientific Advances and Accomplishments;Self Direction;Shapes;Short-Term Memory;social;Socialization;socioeconomic disparity;Sorting;Structure;Weight

PROJECT_TITLE: Characterizing top-down dimensions of appetite self-regulation among preschoolers

STUDY_SECTION: LCBH

STUDY_SECTION_NAME: Lifestyle Change and Behavioral Health Study Section[LCBH]


NIH_SPENDING_CATS: Behavioral and Social Science;Bioengineering;Brain Disorders;Genetics;Human Genome;Mental Health;Mental Illness;Prevention

ORG_CITY: AUSTIN

ORG_NAME: UNIVERSITY OF TEXAS AT AUSTIN

PHR: PROJECT NARRATIVE Identifying and understanding the genetic bases for psychiatric disease risk and psychiatric comorbidity is key to developing treatments and preventions for psychiatric disorders, and mitigate their downstream consequences. This project will produce a detailed understanding of the shared and unique genetic bases of psychiatric disease risk, along with a suite of novel open-source tools that can be widely used by the scientific community.

PI_NAMEs: NIVARD, MICHEL GUILLAUME;TUCKER-DROB, ELLIOT MAX (contact)

PROGRAM_OFFICER_NAME: PEVSNER, JONATHAN ABRAM

PROJECT_TERMS: Address;alcohol use disorder;Atlases;base;Behavior;Behavioral;biobank;Bioinformatics;Biological;biological sex;Categories;cell type;Circadian Rhythms;Communities;Complex;Computer software;Data;data resource;Derivation procedure;Diagnostic;Dimensions;Disease;disorder risk;Equation;Ethnic Origin;Exhibits;Female;Fright;functional/structural genomics;gene conservation;Genes;Genetic;genetic architecture;genetic association;Genetic Drift;Genetic Models;Genetic Risk;Genetic Variation;genome wide association study;genome-wide;Genomics;Goals;Heritability;Human Characteristics;Individual;insight;interest;Investments;Joints;Knowledge;Life;Magnetic Resonance Imaging;male;Mathematics;Measurement;Mental disorders;Methods;Modeling;National Institute of Mental Health;Nature;Neurons;novel;Ontology;open source;open source tool;Outcome;Output;Patient Self-Report;Pattern;Phenotype;pleiotropism;Prevention;psychiatric comorbidity;psychogenetics;psychosocial;Publications;Registries;Reproducibility;Research;Research Domain Criteria;research study;Risk;risk sharing;Risk Taking;Sampling;Sampling Studies;Schizophrenia;Secure;sex;simulation;social;Specific qualifier value;System;Testing;Tissues;tool;trait;Update;user-friendly;Variant

PROJECT_TITLE: Dissecting the Multivariate Genetic Architecture of Psychiatric Diseases

STUDY_SECTION: BGES

STUDY_SECTION_NAME: Behavioral Genetics and Epidemiology Study Section[BGES]


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

NIH_SPENDING_CATS: Chronic Pain;Complementary and Integrative Health;Contraception/Reproduction;Endometriosis;Infertility;Natural Products;Neurosciences;Pain Research;Women's Health Research

ORG_CITY: COLLEGE STATION

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: TEXAS A&M UNIVERSITY

PHR: PROJECT NARRATIVE Endometriosis is an inflammatory gynecologic disease of reproductive-age women and is characterized by two primary symptoms chronic pelvic pain and infertility. Withania somnifera (active component Withaferin-A), an ancient medicinal plant, has been used to treat inflammatory disorders, neurological diseases or disorders, neuropathic and inflammatory pain, and cancers; and thus, it provides a therapeutic opportunity to treat endometriosis in women. Successful completion of the proposed research is expected to expand the understanding of the therapeutic effects of Withania somnifera/Withaferin-A and establish a novel preclinical and molecular therapeutic basis to use Withaferin-A as a non-steroidal and non-opioid therapy for the treatment of pelvic pain and infertility in women with endometriosis.

PI_NAMEs: AROSH, JOE A. (contact)

PROGRAM_OFFICER_NAME: ALLEN, CATHERINE LEIGH

PROJECT_TERMS: Affect;Age;Allografting;Animals;Area;Ashwagandha;behavior measurement;behavioral study;bioimaging;Brain;Brain region;cell growth;Cell Survival;Cells;central pain;central sensitization;chemokine;chronic pain;chronic pelvic pain;Clinical;cytokine;Disease;Electrophysiology (science);Endometrial;endometriosis;Endometrium;Epithelial Cells;Female Genital Diseases;Female infertility;Fertility;Flow Cytometry;Fluorescence Microscopy;Gene Expression;Gene Expression Profile;genetic signature;Goals;Greater sac of peritoneum;Growth;Hormonal;Immune;immunocytochemistry;in vivo;Infertility;Inflammatory;inflammatory pain;innovation;Intervention;Knowledge;Lactones;laser capture microdissection;Lesion;Malignant Neoplasms;Measures;Medicinal Plants;midbrain central gray substance;Molecular;mouse model;Nervous System Disorder;neuroinflammation;Neurons;non-opioid analgesic;novel;Nucleotides;osmotic minipump;Pain;pain behavior;Pain management;pain model;pain perception;pain relief;Pain Threshold;painful neuropathy;Pathogenesis;Pathologic;Pathway interactions;Patients;Pelvic Pain;peripheral pain;persistent symptom;Phytotherapy;pre-clinical;pre-clinical research;Prevalence;protein expression;Proteins;Quality of life;reproductive;Reproductive Health;reproductive system disorder;Research;Role;spontaneous pain;Stromal Cells;subcutaneous;Synaptic Transmission;Thalamic structure;Therapeutic;Therapeutic Effect;Time;transcriptome sequencing;Uterine cavity;Visceral;Woman;women's reproductive health

PROJECT_TITLE: Phytotherapy for Endometriosis

STUDY_SECTION: ICER

STUDY_SECTION_NAME: Integrative and Clinical Endocrinology and Reproduction Study Section[ICER]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Cocaine;Drug Abuse (NIDA only);Genetics;HIV/AIDS;Human Genome;Infectious Diseases;Neurosciences;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stimulant Use and Misuse;Substance Misuse

ORG_CITY: LA JOLLA

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: PROJECT NARRATIVE People living with HIV (PLWH) are at the higher risk for impaired cognitive functions due to higher use of cocaine that could affect their immune functions and exacerbate CNS (central nervous system) impairment. However, little is known about the HIV harboring cell types in brain, effect of therapy on specific CNS cell types, and the modification of brain functions by cocaine use. Results of proposed innovative single-cell studies employing simian immunodeficiency virus (SIV) infection and nonhuman primate animal models will generate cellular part list for brain regions and will illuminate novel insights into transcriptomic and epigenetic landscapes of CNS and how they are altered by viral infections and cocaine use.

PI_NAMEs: BUCH, SHILPA J.;RANA, TARIQ M (contact)

PROGRAM_OFFICER_NAME: SATTERLEE, JOHN S

PROJECT_TERMS: Affect;Agreement;Anatomy;Animal Model;Animals;Area;Atlases;Biological Assay;Brain;brain cell;brain dysfunction;BRAIN initiative;Brain region;Cell Culture Techniques;Cell Separation;cell type;Cells;Censuses;Central Nervous System;Cocaine;cocaine exposure;cocaine use;cognitive function;combinatorial;Controlled Study;Corpus striatum structure;Data;Data Analyses;data resource;Disease;DNA;Drug abuse;drug of abuse;Environment;Epigenetic Process;epigenetic regulation;epigenome;Future;Gene Expression;Gene Expression Regulation;Generations;Genes;Genetic Transcription;Glass;high risk;Hippocampus;HIV;HIV Infections;Human;Immune;immune function;Impaired cognition;Impairment;Infection;innovation;insight;Macaca mulatta;Macrophage;Mediating;member;Methods;Microglia;Modeling;Modification;Molecular;Monkeys;Morphine;multidisciplinary;Mus;Myelogenous;National Institute of Drug Abuse;Neuropathogenesis;nonhuman primate;novel;Opioid;Pathogenicity;Persons;Pharmaceutical Preparations;Phenotype;Prefrontal Cortex;Primates;Process;programs;Reporting;Research Personnel;response;RNA;Role;single cell ATAC-seq;single cell sequencing;single-cell RNA sequencing;SIV;Specific qualifier value;Tissues;transcriptome;transcriptomic profiling;transcriptomics;United States National Institutes of Health;Validation;Viral;Viral reservoir;Virus Diseases;Work

PROJECT_TITLE: Single cell determinants of brain in the context of viral persistence in SIV/cART/cocaine non-human primates


FUNDING_MECHANISM: RESEARCH CENTERS

ORG_CITY: LOUISVILLE

ORG_NAME: UNIVERSITY OF LOUISVILLE

ORG_STATE: KY

PHR: The University of Louisville (UofL) Hepatobiology and Toxicology COBRE is a unique thematic research center. We have strengthened UofL’s biomedical research infrastructure through the establishment of a thematic multidisciplinary center in hepatobiology and toxicology to enhance the ability of investigators to compete for independent funding. This Phase II proposal builds on our Phase I success and extends and strengthens the scope of the program.

PI_NAMEs: MCCLAIN, CRAIG J. (contact)

PROGRAM_OFFICER_NAME: NANDA, JAGPREET SINGH

PROJECT_TERMS: Acute Liver Failure;Address;Adult;Affect;Alcoholic Liver Diseases;American;Area;biobank;Biomedical Research;career development;Centers of Research Excellence;Child;Cirrhosis;clinical practice;Collaborations;Communication;Communities;Complex;Core Facility;Data Analyses;Development;Diabetes Mellitus;Discipline;Drug abuse;drug induced liver injury;Drug Interactions;education research;Ensure;Environment;Enzymes;experience;FDA approved;Fostering;Funding;Goals;Grant;Health;Hepatitis A;Hepatitis B;Hepatitis C;Home;Homelessness;Industrialization;Industry;Injury;International;Kentucky;Laboratories;Link;Liver;Liver diseases;Liver Failure;liver injury;liver transplantation;Marketing;member;Mentors;Metabolic syndrome;Metabolism;Molecular Target;Morbidity - disease rate;multidisciplinary;National Institute on Alcohol Abuse and Alcoholism;non-alcoholic fatty liver disease;nonalcoholic steatohepatitis;novel;novel therapeutics;nutrition;Obesity;Organ;Overweight;personalized medicine;Pharmaceutical Preparations;Pharmacotherapy;Phase;Phase I Clinical Trials;prevent;Prevention;Primary carcinoma of the liver cells;Process;Program Sustainability;programs;Publications;recruit;Research;Research Infrastructure;Research Personnel;Research Project Grants;Resources;Scientist;Structure;success;Technology;Therapeutic;Toxic Environmental Substances;toxicant;Toxicant exposure;Toxicology;Translational Research;United States National Institutes of Health;Universities;University resources;viral liver disease

PROJECT_TITLE: Hepatobiology and Toxicology COBRE


NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Building Research Capacity at Institutions with Limited NIH Funding;Chronic Liver Disease and Cirrhosis;Digestive Diseases;Hepatitis;Liver Disease;Orphan Drug;Rare Diseases;Substance Misuse

PROJECT_TERMS: Acute Liver Failure;Adult;Affect;Alcoholic Liver Diseases;Alcohols;American;Area;Bioinformatics;Biometry;Budgets;career development;Center Core Grants;Centers of Research Excellence;Child;Clinical Trials;Communities;Community Outreach;Country;Development;Development Plans;Diabetes Mellitus;Drug abuse;drug induced liver injury;Drug Interactions;Ensure;Environment;Environmental Health;Enzymes;Evaluation;Faculty;faculty mentor;FDA approved;formative assessment;Funding;Goals;Grant;Health;Hepatitis A;Hepatitis C;Homelessness;Human Resources;improved;Individual;Industrialization;Kentucky;Letters;Liver;Liver diseases;liver injury;liver metabolism;liver transplantation;Malignant neoplasm of liver;Marketing;Mentors;microbiome;microbiome research;Morbidity - disease rate;multidisciplinary;National Institute of Environmental Health Sciences;National Institute on Alcohol Abuse and Alcoholism;non-alcoholic;non-alcoholic fatty liver disease;nonalcoholic steatohepatitis;novel therapeutics;Obesity;opioid abuse;Overweight;personalized medicine;Pharmaceutical Preparations;Pharmacology and Toxicology;Pharmacotherapy;Phase;Physicians;Pilot Projects;Population;Primary carcinoma of the liver cells;problem drinker;Process;programs;Public Health;Qualifying;recruit;Research;research and development;Research Infrastructure;Research Personnel;Rural;Scientist;senior faculty;Services;Structure;success;Superfund;Teacher Professional Development;Text;toxicant;Toxicology;tumor immunology;United States National Institutes of Health;Universities;Viral hepatitis;viral liver disease

PROJECT_TITLE: Administrative Core


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Chronic Pain;Clinical Research;Neurosciences;Pain Research;Physical Injury - Accidents and Adverse Effects;Spinal Cord Injury;Traumatic Head and Spine Injury

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

PHR: Project Narrative Simultaneous functional imaging of the brain and spinal cord can provide valuable insight into interactions and processing pathways between these organs in normal and abnormal states of spinal cord injury, chronic pain, and motor disease. Ultrahigh-field (7T and above) MRI offers new opportunities to visualize structures of interest with high spatial resolution, enhanced conspicuity and greater sensitivity, however, B1 and B0 inhomogeneities, and the lack of optimized receive coils limit imaging performance at high fields. In this project, we will develop a pre-shimmed parallel transmit array, an optimized receive array, and an RF/ΔB0 array to correct the severe B1 inhomogeneity, maximize the signal-to-noise ratio (SNR), and correct B0 inhomogeneity in simultaneous human brain and spinal cord MR imaging at ultrahigh fields.

PI_NAMEs: YAN, XINQIANG  (contact)

PROGRAM_OFFICER_NAME: WANG, SHUMIN

PROJECT_TERMS: Algorithms;Anatomy;Area;Behavior;Brain;Brain imaging;Central Nervous System;Cerebellum;Cerebrum;Cervical spinal cord structure;Cervical spine;Choking;chronic pain;Communities;Compensation;Complex;Data Analyses;density;design;design and construction;Development;Disease;Electromagnetics;Elements;Engineering;experimental analysis;Functional Imaging;Functional Magnetic Resonance Imaging;Geometry;Goals;Human;human subject;Image;Imaging technology;Impairment;improved;Injury;innovation;insight;interest;Investigation;Magnetic Resonance Imaging;Measures;Mechanics;models and simulation;Motor;motor disorder;Nature;Nervous System Disorder;neural;next generation;Noise;novel;operation;Organ;Pain;Pathway interactions;Pattern;Performance;Physiologic pulse;power consumption;Process;Protocols documentation;Reproducibility of Results;Resolution;response;Rest;Route;Sensory;Signal Transduction;Site;Spinal Cord;spinal cord imaging;Spinal cord injury;Structure;System;Therapy Evaluation;tool;transmission process;Vendor;Vertebral column;virtual;Visualization;Weight;Work

PROJECT_TITLE: Integrated Next-generation RF Transmit, Receive and B0 shimming coil system for brain and spinal cord MRI at 7 Tesla

STUDY_SECTION_NAME: Imaging Technology Development Study Section[ITD]


NIH_SPENDING_CATS: Biotechnology;Breastfeeding, Lactation and Breast Milk;HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Immunization;Infectious Diseases;Maternal Health;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Prevention;Social Determinants of Health;Vaccine Related;Vaccine Related - AIDS;Women's Health Research

ORG_CITY: GAINESVILLE

ORG_NAME: UNIVERSITY OF FLORIDA

PHR: PROJECT NARRATIVE  Young women in sub-Saharan Africa, who are already twice as likely to acquire HIV than their male counterparts, become even more susceptible to HIV infection during pregnancy and the postpartum periods. Because current prophylactic and treatment measures are unlikely to end the morbidity and mortality of HIV/AIDS in women of reproductive age, this project will explore the safety and antiviral properties of the HIV entry inhibitor eCD4-Ig in pregnant and postpartum rhesus macaques. If successful, this project will establish the pre-clinical foundation for testing the ability of eCD4-Ig to combat obstetric HIV infection.

PI_NAMEs: MARTINS, MAURICIO DE AGUIAR (contact)

PROGRAM_OFFICER_NAME: DEYAMPERT, TARA LYNN

PROJECT_TERMS: Address;Adolescent;Affect;Affinity;Africa South of the Sahara;African;African Women;Age;Amniotic Fluid;Anti-HIV Therapy;Anti-Retroviral Agents;Antibodies;antiretroviral therapy;Behavioral;Binding;Biodistribution;Biological;Biological Factors;Biological Products;Birth;Breast Feeding;CCR5 gene;Clinical Research;combat;cost;CXCR4 gene;Dependovirus;Discipline of obstetrics;Dose;Drug Kinetics;efficacy evaluation;env Gene Products;Exclusion;experimental study;Fc Receptor;Female;female sex worker;Fertility Rates;fetal;Fetus;fitness;Foundations;Gene Transfer;Health Personnel;high risk;high risk population;HIV;HIV Entry Inhibitors;HIV Infections;HIV resistance;HIV therapy;HIV/AIDS;Home;Homeostasis;Immunity;Immunoglobulin G;improved;Incidence;Infection;Infusion procedures;Intervention;Lactation;Late pregnancy;Learning;Macaca mulatta;male;maternal serum;Measures;Mediating;Modification;Monitor;Monoclonal Antibody Therapy;Morbidity - disease rate;mortality;Mother-to-child HIV transmission;Mothers;Mucous Membrane;Mutation;neonatal Fc receptor;neutralizing monoclonal antibodies;Outcome;Passive Immunization;peptidomimetics;perinatal HIV;Persons;Pharmaceutical Preparations;Placenta;placental transfer;Plague;Postpartum Period;pre-clinical;Predisposition;Pregnancy;pregnant;Pregnant Women;prevent;Primate Lentiviruses;Property;prophylactic;Prophylactic treatment;receptor;reproductive;Resource-limited setting;Risk;Safety;Serum;sex;simian human immunodeficiency virus;SIV;sociocultural determinant;Testing;Therapeutic;Third Pregnancy Trimester;Time;Vagina;Variant;Vertical Transmission;Viral;Viremia;virtual;Virus;Virus Replication;Woman;young woman

PROJECT_TITLE: eCD4-Ig for preventing and treating obstetric HIV infection

STUDY_SECTION: HIVD

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


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

ORG_CITY: IRVINE

ORG_DEPT: MISCELLANEOUS

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: Circadian rhythms are fundamental for biology and medicine. Modern high-throughput technologies are revealing how the concentrations of many molecular species, including transcripts, proteins, and metabolites oscillate with the day and night cycle in every species, tissues, and organs. In close collaboration with life scientists, this project will develop the informatics tools that will enable the collection, integration, and analyses of this wealth of information and lead to novel and fundamental insights about the organization and regulation of circadian oscillations, their roles in health and disease, and their future applications to precision medicine.

PI_NAMEs: BALDI, PIERRE  (contact)

PROGRAM_OFFICER_NAME: YU, GUOQIN

PROJECT_TERMS: Alzheimer's Disease;analytical tool;Back;Biogenesis;Bioinformatics;Biological Process;Biology;Biomedical Research;Cardiovascular Diseases;Cells;circadian;Circadian Dysregulation;circadian regulation;Circadian Rhythms;cognitive function;cognitive process;Collaborations;Collection;Communities;comparative;Computer software;Cyanobacterium;Data;Data Analyses;data platform;Data Set;data tools;Databases;deep learning;Diabetes Mellitus;Diet;Diet Modification;direct application;Disease;Drug Targeting;Epigenetic Process;Exercise;Feedback;Future;Genetic;Health;high throughput technology;Homeostasis;informatics tool;insight;Laboratories;laboratory experiment;Learning;Learning Disorders;Life;Link;Malignant Neoplasms;Mammals;Manuals;Measures;Medicine;member;Mental Depression;Metabolism;metabolomics;Modernization;Modification;Molecular;novel;Obesity;Organ;Periodicals;Pharmaceutical Preparations;Phase;Precision Health;precision medicine;Premature aging syndrome;Proteins;Proteomics;Regulation;Research;Role;Scientist;Sleep Wake Cycle;Societies;software development;Testing;Time;Tissues;tool;Transcript;transcriptomics;virtual;web platform;web server

PROJECT_TITLE: Bioinformatics Omic Platform for Circadian Biomedical Research

STUDY_SECTION: BDMA

STUDY_SECTION_NAME: Biodata Management and Analysis Study Section[BDMA]


NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Drug Abuse (NIDA only);Lung;Neurosciences;Opioid Misuse and Addiction;Opioids;Substance Misuse

ORG_CITY: LOS ANGELES

ORG_DEPT: NEUROSURGERY

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PROJECT NARRATIVE Opioid overdose often leads to death due to suppression of respiration; therefore, strategies to prevent respiratory depression in addition to treatment of opioid addiction are necessary to prevent deaths in the opioid-use epidemic. Respiratory suppression occurs because neurons in the brain that drive breathing are inhibited (turned off) by narcotics; thus, understanding the neural pathways for breathing will allow us to devise effective neuromodulatory strategies to treat opioid-induced respiratory depression. We have proposed to characterize a novel breathing circuit that, when activated by stimulation of the cervical spine, has the potential to be an effective treatment of opioid-induced respiratory depression, and it is our hope that findings from these studies may lead to new and more effective treatments for respiratory depression secondary to opioid overdoses.

PI_NAMEs: LU, DANIEL  (contact)

PROGRAM_OFFICER_NAME: MOORE, HOLLY MARIE

PROJECT_TERMS: Anatomy;Animals;Area;Behavioral;Brain;Brain Stem;Breathing;Cause of Death;Cells;Cervical;Cervical spinal cord structure;Cervical spine;Cessation of life;Characteristics;Complex;Coughing;Depressed mood;design;Devices;Dorsal;Dose;Drug Implants;effective therapy;Effectiveness;Electric Stimulation;Electrophysiology (science);Elements;Epidemic;experimental study;exposed human population;Exposure to;Frequencies;Gases;Goals;Human;Hypoxia;Implant;Individual;innovation;Learning;learning strategy;Location;Machine Learning;Mammals;Maps;Measures;Metabolic;Monitor;Motor Neurons;Mus;Muscle;Naloxone;Narcotics;neural;Neural Pathways;Neurons;neuroprosthesis;neuroregulation;Neurostimulation procedures of spinal cord tissue;novel;Operative Surgical Procedures;Opiate Addiction;Opioid;Opioid Antagonist;opioid epidemic;opioid overdose;Opioid Receptor;opioid use;optogenetics;Outcome;participant enrollment;Pathway interactions;Patient Care;Patients;Periodicity;pharmacologic;Predisposition;prescription opioid;prevent;Property;Respiration;Respiration Disorders;respiratory;Respiratory Center;Respiratory Muscles;Respiratory physiology;response;Secondary to;Site;Spinal;Spinal Cord;Strenuous Exercise;System;Techniques;Testing;Therapeutic;therapeutic target;Tidal Volume;Time;transcutaneous stimulation;translational approach;translational impact;Variant;ventilation;Ventilatory Depression;Vital Statistics;Work

PROJECT_TITLE: Characterization of Novel Neural Respiratory Circuit to Counter Opioid-Induced Respiratory Depression

STUDY_SECTION: RIBT

STUDY_SECTION_NAME: Respiratory Integrative Biology and Translational Research Study Section[RIBT]


NIH_SPENDING_CATS: Building Research Capacity at Institutions with Limited NIH Funding;Digestive Diseases;Liver Disease

PI_NAMEs: ZHANG, XIANG  (contact)

PROJECT_TERMS: Address;Applications Grants;Attention;Award;Bioinformatics;Biological;Biological Assay;career;career development;Centers of Research Excellence;Chemicals;Chromatography;clinical infrastructure;Clinical Research;Communities;Complex Mixtures;Continuing Education;Data;Data Analyses;Data Collection;Data Reporting;data sharing;Derivation procedure;design;Development;Dimensions;Disease;Drug Interactions;Education;Ensure;Environment;epitranscriptomics;Equipment;experimental study;fatty liver disease;Fee-for-Service Plans;Funding;Future;Goals;Health Sciences;Hepatology;Human Resources;Individual;Infrastructure;innovation;Institution;instrument;Intervention Studies;Leadership;Liver;liver development;Liver diseases;Liver Dysfunction;liver injury;Malignant neoplasm of liver;Mass Spectrum Analysis;meetings;member;metabolomics;method development;Methods;Modality;Modeling;Modification;Molecular Evolution;molecular marker;non-alcoholic;novel;nutrition;operation;Peptides;Performance;Phase;Preparation;Privatization;problem drinker;Procedures;programs;Protein Analysis;Protein Fragment;Proteins;Proteomics;Protocols documentation;Reagent;Research;Research Activity;Research Personnel;Research Support;Resources;RNA;S10 grant;sample collection;Sampling;Science;Services;small molecule;Standardization;Statistical Data Interpretation;success;Techniques;Technology;theories;tool;toxicant;Toxicology;Training;Training and Education;Translational Research;United States National Institutes of Health;Universities

PROJECT_TITLE: Omics Core


ADMINISTERING_IC: FD

IC_NAME: FOOD AND DRUG ADMINISTRATION

ORG_CITY: MANHATTAN

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: KANSAS STATE UNIVERSITY

ORG_STATE: KS

PHR: Project Narrative: The purpose of this application is to facilitate participation by the Kansas State Veterinary Diagnostic Laboratory in Vet-LRN Program Office (VPO) case investigations.

PI_NAMEs: ENSLEY, STEVEN M (contact)

PROGRAM_OFFICER_NAME: CERIC, OLGICA

PROJECT_TITLE: CVM VetLIRN Veterinary Diagnostic Laboratory Program for Kansas State University


PI_NAMEs: BARVE, SHIRISH S (contact)

PROJECT_TERMS: Area;Attention;Award;Biochemical;Biological;Biological Assay;career development;Cells;Centers of Research Excellence;Clinical Research;Communication;Communities;Computer software;Continuing Education;Core Facility;cost;cytokine;Data Analyses;Development;Drug Interactions;Ensure;Environment;Equipment;Evaluation;experience;experimental study;Extramural Activities;Faculty;Fee-for-Service Plans;Fostering;Funding;Future;Genus Hippocampus;Goals;Grant;HIV;Immunologics;Individual;Infrastructure;innovation;Institution;Instruction;instrument;instrumentation;Investigation;investigator training;Journals;Laboratories;Liver;Liver diseases;liver injury;Maintenance;meetings;member;Methodology;microscopic imaging;Mission;Molecular;Molecular Target;multidisciplinary;novel;Pathogenicity;Performance;Phase;Play;programs;protocol development;Protocols documentation;Reagent;Research;research facility;Research Personnel;Resources;Role;Services;Signal Pathway;Specimen;square foot;success;System;Techniques;Technology;Time;Tissues;toxicant;Toxicology;Training and Education;Translational Research;United States National Institutes of Health;Universities;Whole Organism

PROJECT_TITLE: Bioanalytical Core


PI_NAMEs: CAVE, MATTHEW C (contact)

PROJECT_TERMS: Address;Alcoholic Liver Diseases;Animal Experimentation;Animal Model;Animals;Autopsy;biobank;Biological;biological specimen archives;Biology;career development;Centers of Research Excellence;Characteristics;Data;design;Development;Ensure;Equipment and supply inventories;Evaluation;Experimental Animal Model;Experimental Models;experimental study;Fees;flexibility;Fostering;Future;Germ-Free;Gnotobiotic;Goals;gut microbiome;Hepatocyte;Histology;Human;Human Resources;human subject;IACUC;In Vitro;Individual;Infrastructure;Institution;Institutional Review Boards;interest;investigator training;Liver;Liver diseases;Maintenance;Malignant neoplasm of liver;Measures;meetings;member;metabolic phenotype;Mission;Modeling;Mus;Occupational;Operative Surgical Procedures;Phenotype;Procedures;Protocols documentation;Research;Research Personnel;Resources;sample collection;Sampling;Service delivery model;Services;Specimen;Standardization;Structure;success;System;Techniques;Tissue Banks;Toxicology;Training;Training and Education;Translational Research

PROJECT_TITLE: Biorepository and Animal Core


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Drug Abuse (NIDA only);Opioid Misuse and Addiction;Opioids;Substance Misuse

ORG_CITY: RICHMOND

ORG_NAME: INDIVIOR, INC.

ORG_STATE: VA

PHR: Project Narrative Opioid Use Disorder (OUD) constitutes a crisis public health problem in the United States. We are proposing initial human Phase I studies of C4X3256, a non-opioid, highly-selective orexin-1 receptor antagonist for the treatment of opioid use disorder, in addition to pharmaceutical development and preclinical toxicology enabling work for Phase II Proof of Concept.

PI_NAMEs: HEIDBREDER, CHRISTIAN ARTHUR (contact)

PROGRAM_OFFICER_NAME: RAMEY, TANYA S

PROJECT_TERMS: absorption;Abstinence;abuse liability;addiction;ADME Study;Admission activity;Agonist;Animal Model;antagonist;arm;barrier to care;Behavior;Bile fluid;Blood;Buprenorphine;Canis familiaris;capsule;child bearing;Clinical;Clinical Research;Cues;Development;Development Plans;Diagnosis;Dose;drug development;drug metabolism;drug quality;DSM-V;Embryonic and Fetal Development;Excretory function;Fasting;Feces;good laboratory practice;Good Manufacturing Process;healthy volunteer;Human;Human Volunteers;hypocretin;improved;Individual;International;Intravenous;Investigation;Label;manufacture;metabolic abnormality assessment;Metabolism;Methadone;Modality;mu opioid receptors;multidrug abuse;Naltrexone;Nicotine Dependence;non-opioid analgesic;novel;Opioid;opioid treatment program;opioid use;opioid use disorder;opioid withdrawal;Oral;Oral Administration;orexin 1 receptor;Oryctolagus cuniculus;Outpatients;Overdose;Patients;Performance;Persons;Pharmaceutical Preparations;Pharmacologic Substance;Pharmacological Treatment;Pharmacology;Phase;phase 1 study;phase 1 testing;phase 2 study;pre-clinical;preclinical development;Public Health;public health emergency;Rattus;Recovery;reproductive;reproductive toxicity;research clinical testing;residence;Role;Safety;Self Administration;Series;Signal Transduction;Substance Use Disorder;substance use treatment;System;Therapeutic;therapy development;Time;Toxicology;United States;Urine;waiver;Woman;Work

PROJECT_TITLE: Clinical Evaluation of C4X3256, a Non-Opioid, Highly-Selective Orexin-1 Receptor Antagonist for the Treatment of Opioid Use Disorder


NIH_SPENDING_CATS: Bioengineering;Building Research Capacity at Institutions with Limited NIH Funding;Cancer;Chronic Liver Disease and Cirrhosis;Digestive Diseases;Hepatitis;Immunotherapy;Liver Cancer;Liver Disease;Nanotechnology;Orphan Drug;Rare Diseases

PI_NAMEs: HOOD, JOSHUA L. (contact)

PROJECT_TERMS: 3-Dimensional;Adjuvant;Alcoholic steatohepatitis;Antigen Presentation;arginase;Attenuated;Autologous;BAY 54-9085;Bee Venoms;Bees;Biological Assay;Blood;Cancer Etiology;cancer therapy;Cancer Vaccines;Cell Line;Cells;Centers of Research Excellence;checkpoint therapy;Cirrhosis;Coupled;Development;Doctor of Philosophy;Effector Cell;Enzyme-Linked Immunosorbent Assay;exosome;extracellular vesicles;FDA approved;Growth;Harvest;Hepatitis;hepatocellular carcinoma cell line;HepG2;Homing;Human;Immune;Immune Cell Suppression;Immune checkpoint inhibitor;Immune response;Immunity;Immunocompetent;Immunosuppression;Immunotherapeutic agent;Immunotherapy;Impairment;In Vitro;in vivo;Inflammatory;Injections;Investigation;Kupffer Cells;light scattering;Liver;Liver diseases;Liver Fibrosis;Macrophage;Malignant Epithelial Cell;Malignant neoplasm of lung;Malignant Neoplasms;Mediating;Melanoma;MicroRNAs;Modeling;Modernization;Mononuclear;mortality;Mus;Myeloid-derived suppressor cells;nanocarrier;nanomaterials;nanomedicine;nanovesicle;Natural Source;Neoplasm Metastasis;neoplastic cell;Nivolumab;non-alcoholic;nonalcoholic steatohepatitis;Participant;Pathogenicity;Pathologic;Patients;Peptides;Phagocytes;Phenotype;Plasma;polarized cell;Population;Primary carcinoma of the liver cells;problem drinker;Process;Proteins;Quantitative Reverse Transcriptase PCR;recruit;Reporting;Research;response;Role;Source;spheroids;Sting Injury;System;Testing;Therapeutic;Toxicology;Treatment Efficacy;Treatment-related toxicity;tumor;tumor growth;Tyrosine Kinase Inhibitor;Vaccine Adjuvant;zeta potential

PROJECT_TITLE: Project 2 - Joshua Hood, PhD


ORG_CITY: BURLINGTON

ORG_NAME: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE

ORG_STATE: VT

PHR: Project Narrative: Changes in blood flow to match brain activity are essential for brain health, but the consequences of accompanying mechanical forces remain unknown. We recently discovered that brain blood vessels sense forces through the actions of the Piezo1 channel, and we propose here that Piezo1 is crucial in regulating blood flow to sustain neural activity. The focus of this proposal is to determine the mechanisms underlying blood flow regulation by Piezo1 in the brain in normal and hypertensive mouse models, with the ultimate goal of establishing a foundation for future work that seeks to prevent deficits in blood flow in human cardiovascular disease.

PI_NAMEs: HARRAZ, OSAMA F (contact)

PROGRAM_OFFICER_NAME: CHARETTE, MARC F

PROJECT_TERMS: Acceleration;Address;Affect;African American population;Angiotensin II;Animals;arteriole;behavior test;Blood capillaries;Blood flow;blood pressure regulation;Blood Vessels;Brain;brain endothelial cell;brain health;Brain region;Capillary Endothelial Cell;Cardiovascular Diseases;Cations;Cells;cerebral capillary;Cerebral endothelium;cerebrovascular;Cerebrovascular Circulation;Cerebrovascular system;Characteristics;Chronic;clinically relevant;Coupled;Cues;Data;Deceleration;Disease;druggable target;Electrophysiology (science);Endothelial Cells;Endothelium;Engineering;experience;Feedback;fluorescence imaging;Foundations;Friction;Future;gain of function;gain of function mutation;Genetic;Genetic Engineering;Genetically Engineered Mouse;Goals;Health;hemodynamics;High Prevalence;Human;Hyperemia;Hypertension;hypertensive;Image;improved;in vivo;interest;Interoception;Kinetics;Knock-out;Knockout Mice;Laser-Doppler Flowmetry;Lasers;Learning;Measurement;Measures;mechanical drive;mechanical force;mechanical stimulus;Mechanics;Mediating;Membrane Potentials;Memory;Metabolic;Monitor;mouse model;Mus;Mutation;neural;Neurons;neurotransmission;neurovascular coupling;new therapeutic target;Nitric Oxide;novel;Outcome;Peripheral;pharmacologic;Piezo 1 ion channel;Population;Positioning Attribute;prevent;Probability;Production;Proteins;Regional Blood Flow;Regulation;Relaxation;Reporting;Research;response;Risk Factors;Shapes;shear stress;Signal Transduction;spatiotemporal;Stimulus;System;Testing;time use;Transgenic Mice;Translating;two photon microscopy;two-photon;United States National Institutes of Health;Vasodilator Agents;Vibrissae;Work

PROJECT_TITLE: Endothelial Piezo1 channel and cerebral blood flow control

STUDY_SECTION: IVPP

STUDY_SECTION_NAME: Integrative Vascular Physiology and Pathology Study Section[IVPP]