NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Dementia;Genetics;Human Genome;Neurodegenerative;Neurosciences;Precision Medicine;Prevention

ORG_CITY: SAN FRANCISCO

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE The proposed work investigates the accuracy of DNA methylation clocks in assessing the risk of Alzheimer's Disease (AD) in genetically admixed populations. This addresses a critical knowledge gap, as existing genome-based prediction methods often do not generalize across diverse ancestries. By leveraging data from a large cohort of admixed individuals with AD and matched controls, this project will enhance methylation clocks by making them "ancestry aware", integrating them with polygenic risk scores, and providing valuable insights into biological aging and its potential as predictive biomarker for AD that generalizes across global populations.

PI_NAMEs: CRUZ GONZALEZ, SEBASTIAN  (contact)

PROGRAM_OFFICER_NAME: MARTIN, DAMALI

PROJECT_TERMS: Address;Admixture;Age;age acceleration;age related;age-related disease;Aging;aging clocks;Alzheimer's Disease;Alzheimer's disease patient;Alzheimer's disease risk;Alzheimer’s disease biomarker;Awareness;biological age;Biological Aging;Biological Markers;Biomedical Research;Blood;Cardiovascular Diseases;Cell Aging;Chronology;Clinical;cohort;Data;Dementia;Diet;Disease;DNA Methylation;epigenetic clock;European ancestry;Genetic;genetic approach;Genetic Risk;Genome;genome wide methylation;Genomic Instability;Genotype;Health;Human;Human Genetics;improved;Individual;insight;Knowledge;Malignant Neoplasms;Measures;Methods;Methylation;methylation pattern;Modernization;Molecular;Neurodegenerative Disorders;Outcome;Performance;personalized medicine;polygenic risk score;Population;Population Heterogeneity;population survey;portability;predictive marker;predictive tools;Process;proteostasis loss;rate of aging;Risk;Risk Assessment;Risk Factors;Risk Marker;risk prediction;Science;Site;Smoking Status;Telomere Shortening;Therapeutic Intervention;Time;tool;Training;transcriptome sequencing;Whole Blood;Widespread Disease;Work

PROJECT_TITLE: The Influence of Admixture on Biological Aging in the Context of Alzheimer’s Disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F03B-L (20)]


ADMINISTERING_IC: VA

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: Veterans Affairs

ORG_CITY: CLEVELAND

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: LOUIS STOKES CLEVELAND VA MEDICAL CENTER

ORG_STATE: OH

PHR: The overall goal of this project is to restore mobility and independence for Veterans with partial paralysis due to stroke, multiple sclerosis, or incomplete spinal cord injury by improving their daily walking capabilities to become functional ambulators in the home or community environments. Our team has developed the Networked Neuroprosthesis System (NNPS), a fully implanted, modular system that can activate paralyzed or partially paralyzed muscles in coordination with volitionally controlled movements. This Stage 1 project will focus on engaging with the FDA to identify remaining pre-clinical data required to secure an Early Feasibility Study Investigational Device Exemption (IDE) and also confirm the clinical trial study design. These activities will prepare the team for a Stage 2 submission that includes the remaining pre-clinical tests, IDE submission, and feasibility study to demonstrate initial feasibility of the NNPS in Veterans with partial paralysis to enable greater independence through enhanced walking ability.

PI_NAMEs: PINAULT, GILLES  (contact)

PROJECT_TERMS: Acceleration;Address;Algorithms;Award;Bladder Control;body sense;cardiovascular health;Case Series;Charge;Clinical;clinical implementation;Clinical Research;Clinical Trials;Clinical Trials Design;Collaborations;Communities;Community Participation;community setting;Contractor;Cumulative Trauma Disorders;daily functioning;Data;decubitus ulcer;Devices;disabled;Drainage procedure;Effectiveness;Electric Stimulation;Electrodes;Elements;Enrollment;Environment;Evaluation;Exclusion Criteria;exoskeleton;Family Caregiver;Family member;FDA approved;Feasibility Studies;feasibility trial;Feedback;Future;Gait;Goals;Hand functions;Health;Home;Human;Implant;implantation;implanted sensor;improved;improved mobility;Individual;Intervention;Intestines;Intramuscular;Life;limb movement;Magnetic Resonance Imaging;Measurement;Measures;meetings;Mental Health;Methods;Modeling;Monitor;Motion;motor impairment;Movement;Multiple Sclerosis;Muscle;Nerve;neuroprosthesis;Outcome;Outcome Assessment;Outcome Measure;Paralysed;Paresis;Participant;participant safety;Peripheral Nerve Stimulation;Peripheral Nerves;Persons;Physiologic pulse;Population;pre-clinical;Preclinical Testing;primary outcome;Quality of life;rehabilitation research;research clinical testing;Research Design;Risk;Running;safety testing;Secure;Series;Site;Societies;spatiotemporal;Spinal cord injury;standard of care;Stimulus;Stroke;Surface;System;Technology;Testing;Time;Training;Translating;Upper Extremity;usability;Veterans;Walking;walking speed;walking stability;Wheelchairs

PROJECT_TITLE: Preparing for a clinical trial to implement a fully implanted neuroprosthesis to restore walking after partial paralysis

STUDY_SECTION_NAME: Rehabilitation Engineering & Prosthetics/Orthotics [RRD5]


ADMINISTERING_IC: HL

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Cardiovascular;Genetics;Heart Disease;Human Genome;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Stem Cell Research - Induced Pluripotent Stem Cell - Non-Human

ORG_CITY: GALVESTON

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF TEXAS MED BR GALVESTON

ORG_STATE: TX

PHR: Project Narrative Understanding how phenotypes vary between and within species despite high degrees of DNA similarity continues to limit our ability to predict disease susceptibility and severity. Transposable elements can regulate gene expression between different tissues within a species and the same tissue between species. By understanding the role TEs play in generating different phenotypes in human and chimpanzee heart-relevant cell types, we can bridge the gap between knowing the DNA sequence and predicting an individual’s disease risk and presentation.

PI_NAMEs: HURLEY, JOHN DENNIS (contact)

PROGRAM_OFFICER_NAME: LIDMAN, KARIN FREDRIKSSON

PROJECT_TERMS: Anatomy;Binding Sites;Biological Assay;Cardiac;Cardiac Myocytes;Cardiovascular system;career development;Cell Culture Techniques;Cell Differentiation process;cell type;Cells;Chromatin;chromatin modification;Collection;Congenital Cardiovascular Abnormality;congenital heart abnormality;Data;Development;differential expression;Disease;Disease susceptibility;disorder risk;DNA;DNA Sequence;DNA Transposable Elements;Doctor of Philosophy;Ectoderm;Elements;Endoderm;Environmental Risk Factor;Epigenetic Process;Event;Fellowship;gastrulation;gene conservation;Gene Expression;Gene Expression Regulation;Generations;Genes;genetic corepressor;Genetic Transcription;Genome;Genomics;Germ Layers;Goals;Heart;heart disease risk;Heart Diseases;histone modification;Human;human tissue;Immobilization;Individual;induced pluripotent stem cell;insight;interest;Junk DNA;Knowledge;Mesoderm;mortality;Mutation;novel;novel strategies;Nucleic Acid Regulatory Sequences;Pan Genus;Pathologic;personalized medicine;Persons;Phenotype;Physiological;Play;pluripotency;pluripotent stem cell differentiation;Postdoctoral Fellow;Predisposition;pressure;Primates;Process;Regulation;Repetitive Sequence;Repression;Research;RNA Processing;Role;Scientist;Severity of illness;skill acquisition;skills;Specific qualifier value;Techniques;Thinness;Time;Tissue-Specific Gene Expression;Tissues;transcription factor;transcriptome sequencing;treatment response;Variant

PROJECT_TITLE: The regulatory impact of transposable elements (TEs) on differential gene expression in closely related species during cellular differentiation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F05-D (21)]


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);Biotechnology;Brain Disorders;Dementia;Gene Therapy;Genetics;Immunotherapy;Neurodegenerative;Neurosciences

ORG_CITY: SAINT LOUIS

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE While clinical trials of antibodies targeting amyloid-beta (Aβ) plaques to treat Alzheimer’s disease (AD) have shown promise, they have also shown significant and potentially fatal dose-limiting side effects, highlighting a continued need for the development of safe and novel anti-Aβ therapies. This proposal seeks to further develop and characterize a novel form of therapy for AD that enhances the ability of monocytes/macrophages to phagocytose and degrade Aβ plaques to reduce AD pathology. Our findings will advance the understanding of peripheral monocyte/macrophage basic biology and how to design safer and more effective myeloid cell-based immunotherapies targeting Aβ.

PI_NAMEs: KIM, ALEXANDER  (contact)

PROGRAM_OFFICER_NAME: SARE, RACHEL

PROJECT_TERMS: Abeta clearance;aged;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease therapy;Amyloid;Amyloid beta-Protein;Antibodies;Antibody Therapy;antigen binding;APP-PS1;Association Learning;Automobile Driving;behavior test;Binding;Biology;bioluminescence imaging;Brain;brain parenchyma;brain tissue;cancer therapy;career;Cell Physiology;Cells;Cellular immunotherapy;chimeric antigen receptor;Clinical;clinical translation;Clinical Trials;Competence;Complication;Core Facility;Data;design;Development;Disease;Doctor of Philosophy;Dose Limiting;Edema;Engineering;Event;experience;extracellular;Fc Receptor;Fellowship;Frequencies;Functional disorder;functional outcomes;Gene Expression Profile;Hemorrhage;Hippocampus;Histology;Human;Image;Immune;Immunology;improved;in vivo;Infiltration;Injections;insight;Intravenous;Label;Lipids;Macrophage;Measures;migration;Molecular;Monoclonal Antibodies;Monoclonal Antibody Therapy;monocyte;mouse model;Mus;Myeloid Cells;Neurodegenerative Disorders;neurofibrillary tangle formation;novel;overexpression;Pathogenesis;Penetration;Peripheral;Phenotype;Physicians;Process;programs;protein biomarkers;Receptor Signaling;recruit;Safety;Scientist;Senile Plaques;side effect;Signal Transduction;single-cell RNA sequencing;Site;skills;Slice;spatial memory;Testing;Therapeutic;Training;transcriptome sequencing;Transgenic Mice;treatment comparison;Universities;Washington;Work

PROJECT_TITLE: Chimeric Antigen Receptor Myeloid Cells for Alzheimer's Disease Therapy

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F01A-V (20)]


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Down Syndrome;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Pediatric

ORG_CITY: CINCINNATI

ORG_NAME: CINCINNATI CHILDRENS HOSP MED CTR

PHR: PROJECT NARRATIVE The proposed project will establish the reliability and validity of cognitive outcome measures for school-age children with Down syndrome. Current clinical trials are plagued by the dearth of clinical outcome measures appropriate and sensitive for individuals with Down syndrome. As our field continues to develop new pharmaceutical and clinical interventions, our project will support this work and have an impact on the 400,000 individuals with Down syndrome living in the United States.

PI_NAMEs: ESBENSEN, ANNA J. (contact)

PROGRAM_OFFICER_NAME: BARDHAN, SUJATA

PROJECT_TERMS: Accounting;Address;Adolescence;Adolescent;Affect;Age;Area;Basic Science;Behavior;behavioral phenotyping;Characteristics;Child;Child Care;Childhood;Chronology;Clinical;clinical outcome measures;clinical translation;Clinical Trials;Cognition;Cognitive;cognitive function;cohort;Common Data Element;Computers;Data Coordinating Center;demographics;Development;Down's Syndrome;effectiveness trial;efficacy trial;emotional functioning;Enrollment;Episodic memory;Evaluation;evidence base;executive function;Floor;follow-up;Funding;Future;gastrointestinal;Gender;Genetic;Goals;Hippocampus;Human;improved;Individual;individual variation;Informal Social Control;Intellectual functioning disability;Intervention;Language;Language Development;Learning;Live Birth;Measurement;Measures;Medical;Memory;mental age;Mental Health;Methods;Motor;mouse model;National Institute of Child Health and Human Development;Natural History;Neuroanatomy;Neuropsychology;non-verbal;Obstructive Sleep Apnea;Outcome;Outcome Measure;Parents;Participant;Pathway interactions;Pattern;Performance;Pharmacologic Substance;Phenotype;Population;Prefrontal Cortex;Problem behavior;processing speed;Property;Psychometrics;Recommendation;recruit;Reporting;Research;Research Priority;School-Age Population;Short-Term Memory;Site;skills;social;sound;success;Testing;Time;Translational Research;treatment trial;United States;United States National Institutes of Health;Validity and Reliability;Variant;verbal;Visit;Work;working group

PROJECT_TITLE: Cognitive Outcome Measures in School Age Children with Down Syndrome (ECODS)

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


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Biomedical Imaging;Breast Cancer;Cancer;Clinical Research;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Nutrition;Prevention;Rural Health;Social Determinants of Health;Women's Health Research

ORG_CITY: DAVIS

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

ORG_STATE: CA

PHR: PROJECT NARRATIVE Community-based breast cancer education can have a positive impact on the screening behavior of California women identified as food insecure. Implementation of evidence-based interventions at food banks in partnership with the community can increase the feasibility and acceptability of targeted efforts to increase screening in low- income communities.

PI_NAMEs: KERBER, CHARLOTTE LORRAINE (contact)

PROGRAM_OFFICER_NAME: ADAMS, GREGORY

PROJECT_TERMS: acceptability and feasibility;Address;Adherence;Adult;Adult women;Age;Area;Behavior;Breast Cancer Detection;breast cancer diagnosis;Breast Cancer Early Detection;Breast Cancer Education;California;cancer care;Cancer Etiology;Cancer health equity;cancer prevention;Cancer Prevention Intervention;Caring;Catchment Area;Cities;Client;Communities;community engaged research;community intervention;Comprehensive Cancer Center;Confidence Intervals;Consolidated Framework for Implementation Research;County;Data;Death Rate;Development;Diagnosis;Disparity;Early Diagnosis;Education;Eligibility Determination;Equity;Event;Evidence based intervention;experience;Family;Focus Groups;Food;food insecurity;Food Supplements;Goals;Health;health equity;High-Income Populations;human old age (65+);implementation outcomes;implementation research;implementation strategy;Improve Access;improved;Incentives;Individual;Intervention;intervention mapping;intervention refinement;Intervention Studies;Interview;Logic;Low income;Malignant Breast Neoplasm;Malignant Neoplasms;Mammographic screening;Mammography;marginalized population;Mediator;Medical;Mentorship;metropolitan;Modeling;mortality;NCI-Designated Cancer Center;Not Hispanic or Latino;Odds Ratio;older women;participant observation;patient navigation;Persons;Pilot Projects;Population;Populations at Risk;Positioning Attribute;Poverty;Prevention education;Process;programs;Provider;Public Health;Recommendation;Reporting;Research;Research Methodology;Research Personnel;Risk;Rural Appalachia;rural area;Sampling;Schedule;screening;screening guidelines;Secure;Services;social determinants;social service provider;socioeconomics;Structure;Surveys;Testing;Training;Underserved Population;United States;uptake;Urban Community;White Women;Woman;women's diagnosis;Women's mortality;Work

PROJECT_TITLE: Implementation of a Community-Based Cancer Prevention Intervention with a Marginalized Population Experiencing Food Insecurity

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F16-T (21)]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Aging;Brain Disorders;Human Fetal Tissue;Neurodegenerative;Neurosciences;Parkinson's Disease;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Nonembryonic - Non-Human;Transplantation

ORG_CITY: NORTH CHICAGO

ORG_DEPT: NEUROSCIENCES

ORG_NAME: ROSALIND FRANKLIN UNIV OF MEDICINE & SCI

ORG_STATE: IL

PHR: Project Narrative Replacement of dopaminergic neurons to treat Parkinson’s disease is a long-standing goal that may be achieved by recruiting stem cells to become dopaminergic neurons. As an alternative to generating dopaminergic neurons from iPSCs, we propose to generate human glial progenitor cells and directly reprogram them into dopaminergic neurons. As such glial progenitor cells are already present in the brains of Parkinson’s patients, this project will establish a model for eventual in vivo reprogramming to generate dopaminergic neurons in situ, without the need to graft exogenous cells as a neuronal replacement therapy for Parkinson’s disease.

PI_NAMEs: PETERSON, DANIEL ALAN (contact)

PROGRAM_OFFICER_NAME: SULLIVAN, LUIS FLANAGAN

PROJECT_TERMS: Address;Adult;Allografting;Award;Brain;Brain Diseases;Bypass;Cardiac Myocytes;Cell Differentiation process;Cells;cellular engineering;Clinical Trials;cost;cost estimate;CSPG4 gene;Cyclic GMP;debilitating symptom;design;Development;Disease;Dopamine;Dopaminergic Cell;dopaminergic neuron;Dyskinetic syndrome;Epigenetic Process;Ethics;Exploratory/Developmental Grant;fetal;Fetal Tissues;Fibroblasts;Foundations;Future;Gene Delivery;Gene Expression;Gene Expression Profile;Generations;Goals;Human;human subject;immunogenicity;In Situ;In Vitro;in vivo;Individual;induced pluripotent stem cell;Induced pluripotent stem cell derived neurons;Injury;innovation;Instruction;Knowledge;Midbrain structure;Modeling;motor symptom;myelination;Neurodegenerative Disorders;Neuroglia;neuronal replacement;Neurons;neurosurgery;non-motor symptom;oligodendrocyte progenitor;Oligodendroglia;Parkinson Disease;Pathology;Patients;pluripotency;pluripotent stem cell differentiation;Population;precision medicine;Preparation;programs;Rattus;recruit;repaired;Replacement Therapy;Reporting;Rodent Model;Runaway;Source;Specific qualifier value;stem cell population;stem cells;success;Symptoms;Testing;Therapeutic;Tissue Donors;Tissue Grafts;transcription factor;vector

PROJECT_TITLE: Generation of Parkinson-derived human glial progenitor cells for dopaminergic neuronal conversion

STUDY_SECTION: CNNT

STUDY_SECTION_NAME: Clinical Neuroplasticity and Neurotransmitters Study Section[CNNT]


ADMINISTERING_IC: MH

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Mental Health;Mental Illness;Neurosciences;Prevention;Psychosis;Schizophrenia;Serious Mental Illness

ORG_CITY: IRVINE

ORG_DEPT: PSYCHOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: Project Narrative The proposed research project will clarify the roles of dispositional emotion regulation strategy use, or tendencies to use specific emotion regulation strategies, and neural connectivity in heterogeneous, developmental pathways to psychosis. This multi-method, two-year study will measure resting-state neural connectivity at baseline, as well as self-reported emotion regulation habits (rumination, expressive suppression, cognitive reappraisal) and attenuated psychosis symptom severity every six months in individuals at clinical high risk for psychosis. The findings of this research could be leveraged to improve the specificity of early identification, thereby facilitating earlier intervention in psychosis, and will further scientific knowledge on affective and biological mechanisms of psychotic symptom onset across multiple units of analysis.

PI_NAMEs: SNYDER, MADELINE  (contact)

PROGRAM_OFFICER_NAME: CORNELL, ASHLEY ROSE

PROJECT_TERMS: Address;Affective;Amygdaloid structure;Attention;Attenuated;Behavioral;Biological;career;cingulate cortex;Clinical;clinical high risk for psychosis;Clinical Pathways;Clinical Research;cognitive reappraisal;Communication;Complement;Complex;Delusions;Development;Developmental Process;Disease;Distress;early experience;Early identification;Early Intervention;emotion regulation;experience;Fellowship;functional decline;functional disability;Functional impairment;Functional Magnetic Resonance Imaging;Genetic Predisposition to Disease;Goals;Habits;Hallucinations;Heterogeneity;high risk;Impairment;improved;Individual;interest;Intervention;Knowledge;Learning;life span;Link;Literature;Longitudinal Studies;Measures;Medial;Methods;Mission;National Institute of Mental Health;National Research Service Awards;neural;neuromechanism;Outcome;Pathology;Pathway interactions;Patient Self-Report;Pattern;Persons;pre-doctoral;Predictive Factor;Predisposition;Prefrontal Cortex;Process;Productivity;Psychopathology;Psychoses;psychosis risk;psychotic symptoms;Reporting;Research;Research Personnel;Research Project Grants;Research Proposals;resilience factor;Rest;Risk Factors;Role;rumination;Sampling;Scientist;Severities;showing emotion;Specificity;Symptoms;Time;timeline;Training;United States National Institutes of Health;Writing

PROJECT_TITLE: Developmental Trajectories of Attenuated Psychotic Symptoms: The Roles of Dispositional Emotion Regulation Strategy Use and Neural Connectivity in Pathways to Psychosis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F16-T (20)]


ADMINISTERING_IC: AI

ED_INST_TYPE: SCH OF BUSINESS/PUBLIC ADMIN

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Asthma;Biotechnology;Health Effects of Indoor Air Pollution;Lung;Neurosciences

ORG_CITY: TUCSON

ORG_DEPT: ADMINISTRATION

ORG_NAME: UNIVERSITY OF ARIZONA

ORG_STATE: AZ

PHR: PROJECT NARRATIVE Asthma is the most common lung disease in both children and adults in the United States and with current care and medications more than 50% of asthmatics report repeated symptoms. Protease-activated receptor-2 has emerged as a novel drug target for asthma. We will use novel compounds to elucidate a role for PAR2 in allergic asthma, using findings from this grant to develop novel therapies for asthma that could complement or replace current treatments.

PI_NAMEs: BOITANO, SCOTT  (contact);LEDFORD, JULIE GUNNELLS

PROGRAM_OFFICER_NAME: MINNICOZZI, MICHAEL

PROJECT_TERMS: Acute;Adult;Afferent Neurons;airway epithelium;airway hyperresponsiveness;Allergens;allergic response;Analgesics;Animals;antagonist;ARRB2;Asthma;asthma model;asthmatic;asthmatic patient;beta-arrestin;Biological Products;Caring;cellular targeting;Child;Chronic;Clinical Trials;Complement;cost;cytokine;Development;Dictyoptera;Disease;efficacy testing;environmental allergen;Epithelial Cells;Epithelium;experimental study;Exposure to;Extrinsic asthma;fungus;G-Protein-Coupled Receptors;Grant;Human;Immune response;improved;In Vitro;in vitro Model;in vivo;in vivo Model;Individual;Inflammation;Inflammatory;Knockout Mice;Ligands;Lung Diseases;MAP Kinase Gene;MAPK Signaling Pathway Pathway;Mediating;Modeling;mouse model;Mucous body substance;Mus;Neurons;neurotransmission;new therapeutic target;Nociceptors;Nodose Ganglion;novel;novel strategies;novel therapeutics;Organ Donor;pain model;PAR-2 Receptor;Pathway interactions;Patients;Peptide Hydrolases;Pharmaceutical Preparations;pharmacologic;Pharmacologic Substance;Physiological;Population;pre-clinical;Pre-Clinical Model;Prevalence;Production;pyroglyphid;Reporting;Respiratory Disease;Respiratory Signs and Symptoms;response;Role;sex as a biological variable;side effect;Signal Transduction;small molecule;Specific qualifier value;Spinal Ganglia;Symptoms;Syndrome;Testing;Therapeutic;United States;Validation

PROJECT_TITLE: A role for pharmaceutical control of protease-activated receptor-2 for the treatment of asthma

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 RCCS-H (03)]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Rare Diseases;Tuberculosis

ORG_CITY: COLLEGE STATION

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR

PHR: PROJECT NARRATIVE Mycobacterium tuberculosis (Mtb) is an exquisitely evolved, incredibly successful, and difficult to treat human pathogen that currently infects one-quarter of the world’s population. We discovered that during Mtb infection of macrophages, mitochondrial reactive oxygen species (ROS) licenses a necrotic cell death pathway that promotes hyperinflammation and poor disease outcomes. We predict that blocking this newly described cell death pathway may benefit tuberculosis patients with underlying genetics or conditions that are associated with ROS accumulation.

PI_NAMEs: PATRICK, KRISTIN LEIGH;WATSON, ROBERT OWEN (contact)

PROGRAM_OFFICER_NAME: ROBINSON, RICHARD THOMAS

PROJECT_TERMS: Acute;acute infection;Alleles;Anti-Bacterial Agents;Apoptosis;Cardiolipins;Catalogs;Cell Death;Cell membrane;cell type;Cells;Cellular biology;Cellular Membrane;Cellular Stress;chronic inflammatory disease;co-infection;comorbidity;Cytolysis;Data;Diabetes Mellitus;Disease;Disease Outcome;Equilibrium;experience;experimental study;Generations;Genes;Genetic;glutathione peroxidase;Goals;Heterogeneity;high risk;HIV;Human;human disease;human pathogen;immunogenic;Immunologics;immunopathology;in vivo;Individual;Infection;Inflammasome;Inflammation;Inflammatory;Intervention;Leprosy;Licensing;Link;Lipid Peroxidation;Lipids;LRRK2 gene;Lung;Macrophage;Malnutrition;Measures;Mediating;Mediator;member;Mitochondria;mitochondrial dysfunction;Modality;Modeling;mouse model;Mus;Mutation;Mycobacterium tuberculosis;Nature;Necrosis;Neutrophil Infiltration;novel;Outcome;Outer Mitochondrial Membrane;overexpression;oxidation;Oxidation-Reduction;Oxidative Stress;Parkinson Disease;Pathogenesis;Pathogenicity;Pathway interactions;Patients;pharmacologic;Phospholipids;Phosphorylation;Phosphotransferases;Play;Population;Predisposition;Production;Protein Biochemistry;Protein Family;Proteins;Reactive Oxygen Species;recruit;response;RIPK1 gene;RIPK3 gene;Role;Smoking;Stress;Testing;Therapeutic Intervention;Tuberculosis;tuberculosis immunity;VDAC1 gene;Vitamin K 3;Work

PROJECT_TITLE: Targeting mediators of oxidative stress to limit hyperinflammatory cell death modalities during Mycobacterium tuberculosis infection

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 IIDB-X (02)]


ADMINISTERING_IC: AA

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;Clinical Trials and Supportive Activities;Dissemination and Implementation Research;Drug Abuse (NIDA only);Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Opioid Misuse and Addiction;Opioids;Prevention;Social Determinants of Health;Substance Misuse

ORG_CITY: ANN ARBOR

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Project Narrative Alcohol and opioid use are leading causes of death in the United States. This study will pilot an innovative and highly scalable digital contingency management treatment among Medicaid beneficiaries with co-occurring opioid and alcohol use disorders to address this dual public health crisis and plan for future implementation.

PI_NAMEs: COUGHLIN, LARA NICOLE;FERNANDEZ, ANNE CHRISTIE (contact)

PROGRAM_OFFICER_NAME: KWAKO, LAURA ELIZABETH

PROJECT_TERMS: acceptability and feasibility;Address;Adoption;alcohol abstinence;Alcohol consumption;alcohol involvement;alcohol use disorder;American;Attention;Behavior;behavioral health;beneficiary;Breakthrough device;Buprenorphine;Caring;Cause of Death;Characteristics;Clinic;Clinical;Communities;community clinic;contingency management;Data;Data Analyses;Development;Diagnosis;digital;disorder prevention;effectiveness/implementation study;effectiveness/implementation trial;Ensure;evidence base;feasibility testing;follow-up;Future;future implementation;Geographic Locations;handheld mobile device;health administration;health equity;Health Personnel;health plan;implementation barriers;implementation strategy;implementation study;improved outcome;Incentives;indexing;innovation;Intervention;Interview;Lived experience;Location;Low income;Medicaid;member;Methadone;Methods;Morbidity - disease rate;mortality;Nonpharmacologic Therapy;Opioid;Opioid agonist;opioid agonist therapy;opioid overdose;opioid use;opioid use disorder;Outcome;overdose prevention;Overdose reduction;overdose risk;Participant;Patient Recruitments;patient retention;Patients;Perception;Pharmaceutical Preparations;Pilot Projects;pilot trial;Policy Maker;polysubstance use;Population;Population Heterogeneity;Provider;Public Health;Randomized;randomized trial;Recovery;recruit;remote technology;research to practice;Risk;Sampling;Site;State Government;Symptoms;tool;Translations;Underserved Population;United States;Work

PROJECT_TITLE: Cultivating Recovery: A Pilot Study of Digital Contingency Management for Co-occurring Opioid and Alcohol Use Disorder

STUDY_SECTION_NAME: Special Emphasis Panel[ZAA1 DD (06)]


NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Dissemination and Implementation Research;Mental Health;Pediatric;Prevention

ORG_CITY: NEW YORK

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

ORG_STATE: NY

PHR: PROJECT NARRATIVE The proposed study seeks to respond to the implementation scale-up and sustainability challenges in low-and- middle-income countries (LMICs), specifically to gaps in implementation management infrastructure and delivery workforce in scaling up evidence-based interventions (EBIs). The study tests a multifaceted and multilevel scale-up model utilizing a two-level train-the-trainer model to develop an implementation infrastructure to support the expansion and sustainment of an evidence-based intervention in one LMIC- Uganda. To also consider maximizing practice sustainability in schools, we will test the EBI scale-up model with and without including additional sustainability strategies (including technical assistance and continuing education strategies).

PI_NAMEs: HUANG, KENG-YEN  (contact);NAKIGUDDE, JANET

PROGRAM_OFFICER_NAME: BEKALU, MESFIN AWOKE

PROJECT_TERMS: Address;Adolescent;Adoption;Advocacy;Advocate;burden of illness;Child;Child Mental Health;Child Support;Childhood;cohort;college;Continuing Education;cost effective;design;Development;Disease;Education;Educational Intervention;Educational Status;Effectiveness;effectiveness/implementation study;effectiveness/implementation trial;evidence base;Evidence based intervention;Goals;Health;Health Personnel;Health Professional;Hybrids;implementation evaluation;implementation framework;implementation intervention;implementation outcomes;implementation process;improved;Infrastructure;Institutionalization;interest;Knowledge;Leadership;Learning;learning progression;learning strategy;Literature;low and middle-income countries;Mental Health;mental health policy;Mental Health Services;Methods;Modeling;National Institute of Mental Health;Nepal;Neurologic;Outcome;Parents;Policies;Policy Maker;Policy Research;population based;Prevention;Preventive;preventive intervention;Process;Psyche structure;Public Health;Randomized;Randomized, Controlled Trials;Research;Resources;Risk;scale up;school health;Schools;skills;Strategic Planning;sustainability framework;System;teacher;Teacher Professional Development;Testing;Trainers Training;Training;tutoring;Uganda;United States;universal prevention;Work

PROJECT_TITLE: Testing multi-level scale-up strategies to implement a school-based population approach of mental health preventive intervention

STUDY_SECTION: SIHH

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


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

ORG_CITY: DALLAS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: Project Narrative Flagellar motility is a major virulence and colonization factor for pathogenic bacteria to infect hosts and promote disease. We found that Campylobacter jejuni, a leading cause of diarrheal disease in humans, utilizes a unique protein to contribute to the formation of the flagellar type III secretion system (fT3SS) that is competent to build the flagellum for motility and colonization. The proposed research will use C. jejuni as a model organism to understand the diversity of components required for the formation of the fT3SS and flagellum in Campylobacterota and other polarly flagellated pathogens including Vibrio cholerae, Pseudomonas aeruginosa, and Helicobacter pylori.

PI_NAMEs: DOBBINS, AMANDA  (contact)

PROGRAM_OFFICER_NAME: MOITRA, KAROBI

PROJECT_TERMS: Animals;Bacteria;Bacteriology;Binding;Biochemical;Biogenesis;Biological Assay;Biology;Birds;Campylobacter jejuni;career;Cells;Co-Immunoprecipitations;Collaborations;Complex;Core Protein;Cytoplasmic Protein;Defect;diarrheal disease;Disease;Ensure;Environment;Equipment;Escherichia coli;Faculty;Flagella;flagellum motility;Fluorescence Microscopy;Genes;Genetic;Genomics;Goals;Guanosine Triphosphate Phosphohydrolases;Helicobacter pylori;Homologous Gene;Human;improved;In Vitro;Knowledge;Mastigophora;Medical center;Membrane Proteins;Mentors;Mentorship;Microscopic;model organism;Molecular;Molecular Biology;Motility;Motor;mutant;Mutation;nanomachine;Nucleotides;Organism;pathogen;Pathogenesis;pathogenic bacteria;periplasm;Phenotype;Play;Postdoctoral Fellow;Protein Biochemistry;protein oligomer;Protein Secretion;Proteins;Pseudomonas aeruginosa;Research;Research Personnel;Resources;Role;role model;Salmonella;skills;structural biology;Structure;Suppressor Mutations;Swimming;System;Tertiary Protein Structure;Training;Type III Secretion System Pathway;Vibrio cholerae;Virulence;Virulence Factors

PROJECT_TITLE: Identification of the Role of FlgW in the Biogenesis of the fT3SS in Campylobacter jejuni

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F07A-B (20)]


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Autism;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Genetics;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Pediatric

PHR: A characteristic of many neurodevelopmental disorders, including autism spectrum disorder, is profound sensory processing deficits. Foxp2 is a transcription factor in the developing and mature brain expressed in specific regions and cell types, mutations in human FOXP2 have been implicated in neurodevelopmental disorders such as speech and language disorders and autism spectrum disorder. I propose to uncover the transcriptomic program and electrophysiological consequences orchestrated by Foxp2 during development in key auditory processing brain areas, including the auditory cortex and the inferior colliculi.

PI_NAMEs: JANKOVIC, MIRANDA  (contact)

PROGRAM_OFFICER_NAME: SCHURMAN, JACLYN REBECCA

PROJECT_TERMS: Adult;Affect;Area;ATAC-seq;Auditory;Auditory area;auditory pathway;auditory processing;autism spectrum disorder;Axon;Behavior;Behavioral;behavioral phenotyping;Brain;Brain region;Brain Stem;Cell Nucleus;cell type;Cells;Characteristics;Chromatin;cognitive function;conditional knockout;Cytoskeleton;Data;Development;differential expression;Dopamine;Dopamine D1 Receptor;Electrophysiology (science);Embryo;excitatory neuron;flexibility;FOXP2 gene;Functional disorder;Gene Expression;Gene Expression Regulation;Genes;Genetic Transcription;Human;In Vitro;Inferior;inhibitory neuron;Interneurons;Language Disorders;Link;LoxP-flanked allele;Mediating;Midbrain structure;migration;molecular phenotype;mouse model;multiple omics;Mus;Mutation;Neocortex;Neonatal;neurodevelopment;Neurodevelopmental Disorder;Neurons;Overlapping Genes;Pathway interactions;Pattern;Population;postnatal;programs;Property;Quality of life;Regulatory Pathway;Resolution;risk variant;Role;selective expression;Sensory;sensory gating;Series;Signal Transduction;single nucleus RNA-sequencing;Social Environment;Specific qualifier value;Speech Disorders;Synapses;Thalamic structure;theories;Time;Tissues;transcription factor;transcriptomics;Whole-Cell Recordings

PROJECT_TITLE: The Foxp2 Influence on the Developing Auditory Pathway

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F03A-E (20)]


ADMINISTERING_IC: DE

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Biotechnology;Dental, Oral, and Craniofacial Disease;Genetics

ORG_CITY: BALTIMORE

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: PROJECT NARRATIVE FoxA proteins are vital for organ development and homeostasis, mutations within this family of proteins have been linked to various cancers and metabolic diseases. Understanding the mechanisms of regulation and coordination of FoxA proteins by studying the fly ortholog Fork head (Fkh) will provide new strategies and insight for therapeutic intervention for the various diseases that FoxA proteins play a significant role in.

PI_NAMEs: LAUGHNER, NATHANIEL  (contact)

PROGRAM_OFFICER_NAME: FUQUA, CHANTEL FAYSAN

PROJECT_TERMS: Adult;Affect;Binding;Binding Sites;Biological Assay;Biotinylation;candidate identification;career;ChIP-seq;Collaborations;Collection;Communication;Computer Analysis;Data;Data Set;Defect;design;Development;Disease;DNA Binding;Drosophila genus;Embryo;Endocrine;Endocrine Glands;Endoplasmic Reticulum;Enhancers;Enzymes;Epithelium;experimental study;fly;Fogs;Gene Expression;Gene Expression Regulation;Genes;genetic manipulation;Genomics;Glucose;glucose metabolism;Growth;Head;Homeostasis;Hypoglycemia;Imagery;In Situ Hybridization;in vivo;insight;Link;link protein;liquid chromatography mass spectrometry;loss of function;Maintenance;Malignant Neoplasms;Mass Spectrum Analysis;Mediating;member;Metabolic;Metabolic Diseases;Metabolism;Modeling;Morphogenesis;Morphology;Mutation;mutation screening;novel;null mutation;Organ;organ growth;Orthologous Gene;Outcome;outer surface lipoprotein;Parkinson Disease;Pathway interactions;Pattern;Peptides;Phenotype;Play;Positioning Attribute;postnatal;Process;Protein Family;Protein Secretion;Proteins;Proto-Oncogene Proteins c-akt;recruit;Regulation;Research;Role;Salivary Glands;Secretory Cell;single-cell RNA sequencing;Site;Techniques;Testing;Therapeutic Intervention;Tissues;Training;transcription factor;Tube;vertebrate embryos;Vertebrates;Winged Helix

PROJECT_TITLE: Uncovering the Regulatory Mechanisms of the Fork Head Transcription Factor

STUDY_SECTION: DSR

STUDY_SECTION_NAME: National Institute of Dental and Craniofacial Research Special Grants Review Committee[DSR]


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);Brain Disorders;Cerebrovascular;Dementia;Genetics;Machine Learning and Artificial Intelligence;Neurodegenerative;Neurosciences;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: Chicago

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

PHR: PROJECT NARRATIVE Senescent cells accumulate in the brain vasculature over time which contributes to inflammation, barrier leakiness, and Alzheimer’s Disease. Our experiments will uncover how senescent cells communicate with their environment and examine how aberrant activation of ancient endogenous sequences contributes to their deleterious effect. We hope to find new treatments for Alzheimer’s Disease by restoring the health of the brain's blood vessels.

PI_NAMEs: SANBORN, MARK ALLEN (contact)

PROJECT_TERMS: abeta accumulation;Ablation;Affect;Age;age related chronic disease;Aging;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Alzheimer's disease patient;Animal Model;Attenuated;Blood - brain barrier anatomy;Blood Vessels;blood-brain barrier disruption;Brain;brain dysfunction;brain endothelial cell;brain health;Brain region;CDKN2A gene;Cell Aging;Cell Communication;Cell Cycle Arrest;Cell model;Cell Physiology;Cell secretion;cell type;Cells;Cerebral endothelium;cerebrovascular;Cerebrovascular Disorders;Cerebrovascular system;convolutional neural network;CRISPR/Cas technology;Data;Data Set;Detection;Disease;Disease Progression;DNA Transposable Elements;Educational process of instructing;Elements;Endothelial Cells;endothelial dysfunction;Endothelium;Environment;experimental study;Exposure to;Feedback;Functional disorder;Gene Expression;genetic manipulation;Genetic Models;Genetic Transcription;healthy aging;Hemorrhage;Human;human data;Human Genome;IFNAR1 gene;Impaired cognition;Impairment;In Vitro;Inflammation;Inflammatory;Interferons;Interruption;Intervention;knock-down;Machine Learning;Mediator;Molecular;molecular dynamics;Molecular Profiling;mouse model;mRNA Expression;Mus;Nerve Degeneration;neuroinflammation;Neurons;NF-kappa B;open source tool;Organism;paracrine;Paracrine Communication;Pathologic;Pathway interactions;Pattern;Phenotype;Predisposition;Proteins;receptor;Regulation;Resources;RNA;senescence;senescence associated secretory phenotype;senescent cell;senolytics;Signal Pathway;Signal Transduction;single-cell RNA sequencing;small hairpin RNA;Sterility;targeted treatment;Testing;Therapeutic Intervention;Time;Tissues;Training;transcription factor;transcriptome;transcriptomics;vascular bed;Vascular Diseases;Viral;Virulence Factors;Work

PROJECT_TITLE: Endogenous drivers of endothelial inflammation in Alzheimer's Disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F03C-K (20)]


NIH_SPENDING_CATS: Asthma;Basic Behavioral and Social Science;Behavioral and Social Science;Chronic Obstructive Pulmonary Disease;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Lung;Mental Health;Pediatric;Prevention;Primary Health Care;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

PHR: PROJECT NARRATIVE As a measure of stressful or traumatic experiences in childhood, adverse childhood experiences (ACEs) have been associated with a high prevalence of multiple chronic conditions throughout the lifespan, including asthma and chronic obstructive pulmonary disease (COPD). Understanding the mechanisms by which ACEs impact obstructive lung disease will further inform the development of interventions to address these complex socio- behavioral factors. Additionally, evaluating the short- and long-term impact that screening for and intervening on childhood adversities has on respiratory health outcomes may inform further integration of ACEs screening and allocation of resources throughout health systems.

PI_NAMEs: MARTINEZ, ADALI  (contact)

PROGRAM_OFFICER_NAME: KHAN, SHAHNAZ

PROJECT_TERMS: Address;Adherence;Adopted;Adoption;Adult;adverse childhood events;Affect;Asthma;Award;Behavioral;beneficiary;Black Populations;California;care coordination;care delivery;care systems;Caring;Child;Child Care;child services;Childhood;childhood adversity;Chronic;Chronic Disease;Chronic lung disease;Chronic Obstructive Pulmonary Disease;Clinic;clinical practice;cohort;Communities;community organizations;comorbidity;Complex;County;Data;Development;Disease;disease registry;Disparity;Drug Prescriptions;early life adversity;economic impact;Economically Deprived Population;Electronic Health Record;Emergency medical service;ethnic diversity;Ethnic Origin;Event;experience;Exposure to;Federally Qualified Health Center;follow-up;Formulation;Guidelines;Health;Health Care Rationing;health care service utilization;health disparity;Health Services;Health system;High Prevalence;high risk;hospital readmission;Housing;implementation science;improved;Individual;Language;Life;Life Cycle Stages;life span;Link;Los Angeles;Lung;lung cancer screening;Malignant neoplasm of lung;marginalization;Measures;Medical;Medical Records;Mentored Patient-Oriented Research Career Development Award;Minority Groups;Modeling;Morbidity - disease rate;multiple chronic conditions;Native-Born;Obstructive Lung Diseases;Outcome;Participant;Patient Care;patient screening;Patients;pediatric patients;Pharmaceutical Preparations;Population Heterogeneity;Positioning Attribute;Prevalence;Preventive care;Preventive service;programs;psychosocial;Race;racial disparity;racial diversity;Recommendation;Records;Resource Allocation;Resources;respiratory;Respiratory Disease;respiratory health;Risk Factors;screening;screening guidelines;service utilization;Severities;social;Social Behavior;Social Conditions;Social support;socioeconomics;System;Testing;therapy development;tool;Training;Trauma;treatment guidelines;United States;uptake;Vaccination

PROJECT_TITLE: Evaluating the Impact of ACEs Screening and Behavioral-Social Support on Obstructive Lung Disease Health Outcomes


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

NIH_SPENDING_CATS: Biotechnology;Gene Therapy;Genetics

ORG_CITY: COLLEGE PARK

ORG_NAME: UNIV OF MARYLAND, COLLEGE PARK

PHR: PROJECT NARRATIVE Double-stranded RNA-based therapeutics, once delivered to a cell, can prevent the expression of disease- related genes of similar sequence through the RNA interference pathway. Despite this clinical application, some basic aspects of how double-stranded RNA moves through cellular membranes into cells remain unclear. This project will broadly contribute to better a better understanding of double-stranded RNA import by characterizing understudied members of a transporter family and specifically contribute insights that could guide the development of therapeutics for diseases by revealing mechanisms that connect double-stranded RNA import with cholesterol trafficking.

PI_NAMEs: LOWERS, VICTORIA  (contact)

PROGRAM_OFFICER_NAME: WOO, SEUNG KYOON

PROJECT_TERMS: Acute;Affinity;Animals;Area;Atherosclerosis;Biochemical;Bioinformatics;Biology;Caenorhabditis elegans;Cardiovascular Diseases;career;Cells;Cellular Membrane;Cholesterol;cholesterol analog;Cholesterol Homeostasis;cholesterol trafficking;cholesterol transporters;Circulation;clinical application;clinically significant;crosslink;Cytoplasm;Cytosol;Data;Defect;design;Detection;Development;Development Plans;Disease;Dominant-Negative Mutation;Double-Stranded RNA;Endocytosis;Excision;experimental study;Extracellular Domain;Family;FDA approved;Fluorescence Resonance Energy Transfer;Future;Gene Silencing;Genes;Genetic;genome editing;Germ Lines;Goals;Hepatocyte;Homologous Gene;Human;improved;in vivo;Individual;insight;Integral Membrane Protein;interest;intergenerational;Joints;Knock-out;Knowledge;Label;Link;Lipids;Low Density Lipoprotein Receptor;Low-Density Lipoproteins;Mammals;Mediating;member;Messenger RNA;Modeling;mosaic;mutant;Neimann-Pick's Disease Type C;Nematoda;neuronal cell body;Oocytes;paralogous gene;Pathway interactions;Pattern;Pharmaceutical Preparations;prevent;Process;Protein Family;Proteins;Regulatory Pathway;Reporting;Repression;Research;Research Personnel;Risk Factors;RNA;RNA delivery;RNA Interference;RNA Interference Pathway;RNA Interference Therapy;RNA Transport;Role;Sampling;Specificity;Standardization;System;Testing;Therapeutic;therapeutic development;therapeutic RNA;Therapeutic Uses;trafficking;Training;transcriptome;transcriptome sequencing;uptake;Vesicle;Visualization;Western Blotting;Work;yeast two hybrid system;Yeasts

PROJECT_TITLE: Import of double-stranded RNA and cholesterol into cells in C. elegans

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F05-Q (20)]


FUNDING_MECHANISM: RESEARCH CENTERS

NIH_SPENDING_CATS: Cancer;Clinical Research;Clinical Trials and Supportive Activities;Immunotherapy;Urologic Diseases

ORG_CITY: BOSTON

ORG_NAME: DANA-FARBER CANCER INST

ORG_STATE: MA

PHR: Project Narrative The proposed research is relevant to public health because it focuses on developing new combination strategies to treating bladder cancer which a common and lethal disease. This project will dissect the mechanisms by which tumor-associated macrophages drive resistance to current systemic therapies and will investigate the mechanisms of tumor-macrophage crosstalk that prevent immunogenic cancer cell death with the ultimate goal of developing more effective macrophage- directed strategies. Thus, the proposed research is relevant to the part of the NIH’s mission to lengthening life.

PI_NAMEs: GLIMCHER, LAURIE HOLLIS (contact)

PROGRAM_OFFICER_NAME: PTAK, KRZYSZTOF

PROJECT_TERMS: Acceleration;Advisory Committees;anti-cancer;Antitumor Response;base;Biological Markers;Biology;Bladder;Bladder Neoplasm;cancer cell;cancer genomics;Cancer Patient;cancer type;career;career development;Cell Death;Cells;checkpoint inhibition;checkpoint therapy;Chronic;Cisplatin;Clinical Trials;Cytotoxic T-Lymphocytes;Dana-Farber Cancer Institute;Data;Development;Disease;DNA Damage;Effectiveness;effectiveness testing;Future;Goals;Hospitals;Human;Immune;immune checkpoint;Immune checkpoint inhibitor;Immune Evasion;Immune Targeting;Immuno-Chemotherapy;immunogenic;Immunotherapy;immunotherapy clinical trials;improved;in vivo;Infiltration;interest;Interferon Activation;Interferons;Invaded;Knowledge;Laboratories;Life;Macrophage;Malignant neoplasm of urinary bladder;Malignant Neoplasms;Mediating;Mentors;Mission;mouse model;Muscle;muscle invasive bladder cancer;next generation;novel;Oncologist;Outcome;Patients;permissiveness;Phenotype;Population Sciences;Positioning Attribute;Pre-Clinical Model;prevent;Principal Investigator;Program Development;programs;Proteins;Public Health;randomized, clinical trials;recruit;Refractory;refractory cancer;Research;Research Personnel;Research Proposals;Resistance;response;Role;Scientist;Signal Induction;Signal Transduction;statistics;Surgeon;Systemic Therapy;T-Lymphocyte;Testing;Therapeutic;therapeutic development;therapeutic target;Therapeutically Targetable;Therapy Clinical Trials;Time;tumor;tumor growth;tumor immunology;tumor microenvironment;Tumor-associated macrophages;United States National Institutes of Health;urologic;Urologist;Woman;Writing

PROJECT_TITLE: Tumor-associated macrophage reprogramming through PARP14 inhibition in muscle-invasive bladder cancer


NIH_SPENDING_CATS: Anxiety Disorders;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Mental Health;Mental Illness;Neurosciences;Pediatric;Precision Medicine

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: There is a pressing need to improve treatment response rates for pediatric anxiety disorders: pediatric anxiety disorders are highly prevalent and impairing, but up to 50% of youth who receive the current first-line psychosocial treatment for pediatric anxiety do not sufficiently improve. The proposed study will use data from an ongoing R61/R33 clinical trial to identify and characterize specific neural and behavioral predictors of the efficacy of a parent-based treatment for anxiety disorders. Findings from this study will elucidate the interplay between neural and behavioral family-level factors and examine how individual differences across modalities predict which families would benefit most from a targeted parent-based intervention, thus furthering efforts to improve treatment response rates by personalizing treatment for pediatric anxiety disorders.

PI_NAMEs: KITT, ELIZABETH RACHAEL (contact)

PROGRAM_OFFICER_NAME: BECHTHOLT, ANITA JEAN

PROJECT_TERMS: Address;Age;Amygdaloid structure;Anxiety;Anxiety Disorders;anxiety symptoms;anxious;Behavior;behavior prediction;Behavioral;Brain;Buffers;career;Child;Child Rearing;Child Support;Childhood;childhood anxiety;Chronic;Clinical;Clinical Trials;connectome based predictive modeling;Data;Distress;Emotions;Face;Family;Fright;Functional Magnetic Resonance Imaging;Funding;Goals;Human;Impairment;improved;Individual Differences;Intervention;Learning;life span;Link;Maintenance;Measures;Medial;Mental disorders;Mentorship;Modality;multimodality;National Research Service Awards;neural;neuroimaging;neuromechanism;novel;Onset of illness;parental role;Parents;Pattern;personalized approach;personalized medicine;Play;predicting response;Prediction of Response to Therapy;Predictive Factor;predictive modeling;Prefrontal Cortex;psychosocial;Randomized;Recommendation;Regulation;Reporting;Research;Risk;Role;Sampling;Stimulus;Techniques;Training;Translating;treatment of anxiety disorders;Treatment outcome;treatment pattern;treatment response;Youth

PROJECT_TITLE: Identifying Multimodal Predictors of Response to Parent-Based Treatment for Pediatric Anxiety


PHR: Project Narrative This project centers on a novel mechanism by which basophils can be activated in an IgE-dependent, but allergen independent fashion. This has direct implications for the role of these cells in both allergic and nonallergic diseases.

PI_NAMEs: EHRLICH, LAURENT  (contact)

PROGRAM_OFFICER_NAME: GONDRE-LEWIS, TIMOTHY A

PROJECT_TERMS: A549;Address;Adenocarcinoma Cell;Affect;Affinity;Allergens;Allergic;Allergic Disease;Allergic Reaction;antigen binding;Antigens;Asthma;Basophils;beta-galactoside;Binding;Binding Proteins;Biological Assay;Cardiovascular Diseases;CD34+ precursor;Cells;Clinical;clinically relevant;Coculture Techniques;crosslink;cytokine;Data;Disease;Enterochromaffin Cells;Enzymes;Epithelial Cells;experimental study;Galectin 3;Glucosamine;glycosylation;Histamine Release;Human;IgE;IgE Receptors;IL3 Gene;IL4 gene;In Vitro;Inflammatory;innovation;insight;Interleukin-13;Interleukin-4;Investigation;Knowledge;Lectin;Link;Lung Adenocarcinoma;Malignant Neoplasms;Masks;mast cell;Measures;Mediating;Mediator;Modeling;Modification;Monoclonal Antibodies;Neuraminidase;novel;omalizumab;Outcome;Pathogenicity;Patients;Pattern;Pharmaceutical Preparations;Physiological;Polysaccharides;precursor cell;preference;Production;receptor;receptor binding;Reporting;Research;response;Role;Serum;Sialic Acids;sialylation;Specificity;Structure;Subcategory;sugar;Sugar Acids;Surface;Tissues;Work;wound healing

PROJECT_TITLE: The Role of IgE in Galectin-3-dependent Activation of Basophils

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F07B-G (20)]


NIH_SPENDING_CATS: Cancer;Genetics

ORG_CITY: LA JOLLA

ORG_NAME: SCRIPPS RESEARCH INSTITUTE, THE

PHR: Principal Investigator: Wu, Xiaohua Project Narrative  Replication stress is highly associated with oncogene expression and tumor development, creating vulnerabilities in cancer that can be exploited for therapeutic purposes. We propose to study a newly identified role of DNA polymerase θ (POLQ) in repair of broken replication forks, and to explore the synergistic effect of POLQ inhibitors and ATR inhibitors to treat cancer cells with high replication stress. Our study will not only address the role of POLQ in modulating genome integrity upon replication stress but will also lay the groundwork for a new targeted cancer treatment using POLQ inhibitors.

PI_NAMEs: WU, XIAOHUA  (contact)

PROGRAM_OFFICER_NAME: WITKIN, KEREN L

PROJECT_TERMS: Address;Biological;Biological Assay;BRCA deficient;cancer cell;cancer therapy;Cell Death;Cells;Combined Modality Therapy;Conceptions;coping;Defect;Development;DNA biosynthesis;DNA Double Strand Break;DNA Repair;DNA replication fork;DNA-Directed DNA Polymerase;Double Strand Break Repair;experience;genome integrity;Genomic Instability;Genomics;inhibitor;innovation;insight;Light;Link;Malignant Neoplasms;Mediating;mouse model;Mus;novel therapeutic intervention;Oncogenes;Pathway interactions;Play;Poly(ADP-ribose) Polymerase Inhibitor;Polymerase;Prevalence;Principal Investigator;Radiation Tolerance;RECQL5 gene;recruit;repaired;replication stress;Replication-Associated Process;Resistance;response;Role;Site;Testing;Therapeutic;Treatment Efficacy;tumor;Xenograft procedure

PROJECT_TITLE: Investigating DNA polymerase O in replication stress and cancer therapy

STUDY_SECTION: MCTA

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


NIH_SPENDING_CATS: Cancer;Immunotherapy;Nutrition

ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: PROJECT NARRATIVE A major barrier to the success of immune checkpoint inhibitor therapies is CD8 T cell exhaustion, which is a state characterized by reduced tumor killing and metabolic insufficiency. Our lab and others have identified mitochondrial stress as a key driver of CD8 T cell dysfunction, yet the impact of mitochondrial stress on connected metabolic pathways remains understudied. This proposal aims to examine the role of altered lipid metabolism in exhausted T cells, which will provide mechanistic insight into the metabolic underpinnings of T cell exhaustion.

PI_NAMEs: SPAHR, KELLIE  (contact)

PROGRAM_OFFICER_NAME: PURI, ANU

PROJECT_TERMS: Acetyl Coenzyme A;Adipose tissue;Antigens;Area;cancer immunotherapy;cancer therapy;carbohydrate metabolism;Carbon;Catabolism;CD8-Positive T-Lymphocytes;Cell Physiology;Cells;checkpoint therapy;Chronic;citrate carrier;Citrates;comparison control;cytokine;Cytosol;Data;environmental stressor;Epigenetic Process;exhaust;exhaustion;experience;Fatty Acids;Flow Cytometry;Functional disorder;functional improvement;Gene Deletion;Genetic;Genetic Transcription;Genus Hippocampus;Glucose;Hypoxia;Immune;immune checkpoint blockade;Immune checkpoint inhibitor;Immune response;Immunotherapy;improved;In Vitro;in vitro Model;in vivo Model;Infiltration;insight;Lipase;lipid biosynthesis;lipid metabolism;Lipids;Lipolysis;Measures;Memory;Metabolic;Metabolic Pathway;Metabolism;Mitochondria;mitochondrial dysfunction;mitochondrial metabolism;Mus;neoplastic cell;nutrient deprivation;overexpression;Oxygen;Pathway interactions;Patient-Focused Outcomes;Phenotype;Play;preservation;prevent;Production;programmed cell death protein 1;programs;receptor expression;Repression;Research;Resected;Resistance;Role;small molecule inhibitor;Source;Spleen;Stress;success;T cell differentiation;T-Cell Activation;T-Lymphocyte;Testing;TNF gene;tumor;Tumor Antigens;Tumor Escape;tumor microenvironment;Weight

PROJECT_TITLE: Understanding the role of altered lipid metabolism in CD8 T cell exhaustion within the tumor microenvironment

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F09C-Z (20)]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Brain Disorders;Congenital Structural Anomalies;Genetics;Human Genome;Intellectual and Developmental Disabilities (IDD);Pediatric;Stem Cell Research;Stem Cell Research - Embryonic - Non-Human

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Project Narrative The Polycomb Repressive Complexes 1 and 2 (PRC1&PRC2) are conserved epigenetic regulators that are required for proper development whose dysregulation is linked to abnormal embryogenesis, various cancers, and neurodevelopmental disorders. While we are beginning to understand the mechanisms behind how PRCs maintain silencing at developmentally regulated genes, we do not know how they establish silencing at previously active genes during differentiation. I will employ a novel dual-degron line to acutely degrade each complex to obtain mechanistic insight into the interplay of PRC1 and PRC2 during polycomb establishment as well as upstream interactions that regulate polycomb localization.

PI_NAMEs: GARCIA, SEGOVIA  (contact)

PROGRAM_OFFICER_NAME: MCINTYRE, JEREMY COLIN

PROJECT_TERMS: Ablation;Acute;Affect;Architecture;Bioinformatics;Cell Differentiation process;Cell Lineage;Cell Nucleus;cell type;Cells;Chemicals;Chromatin;Chromatin Remodeling Factor;Communication;Complex;Data;Data Analyses;Deposition;design;Development;developmental disease;Embryo;Embryonic Development;embryonic stem cell;Environment;Epigenetic Process;epigenomics;ES Cell Line;Event;Excision;experimental study;Feedback;Gene Expression;gene repression;Gene Silencing;Genes;Genetic;Genetic Transcription;genome-wide;Goals;Heterochromatin;Histone H3;histone methylation;histone modification;insight;Intellectual functioning disability;interest;Knock-out;knockout gene;Life;Link;Lysine;Maintenance;Malignant Neoplasms;Methods;Microcephaly;Molecular;Mouse Embryonic Stem Cells;Mutation;Nature;Neurodevelopmental Disorder;Neurons;novel;Nuclear;Pattern;Polycomb;PRC1 Protein;Process;programs;protein degradation;protein function;Proteins;reconstitution;Recovery;Repression;Research;restoration;RNA Binding;RNA-Binding Proteins;Role;Signal Repression;Site;skills;small molecule;spatiotemporal;Training;Training Programs;Transcriptional Activation;transcriptome sequencing;Ubiquitin;Weaver Syndrome;Writing

PROJECT_TITLE: Repressive Heterochromatin Establishment by Polycomb Complexes

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


ADMINISTERING_IC: ES

ED_INST_TYPE: SCHOOLS OF NURSING

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Social Determinants of Health;Women's Health Research

ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE Women's empowerment is a critical factor in achieving gender equality and sustainable development. Many factors play a role in women’s empowerment including the communities where women reside. The proposed study will evaluate the effect of group participation in community-based working group interventions to reduce women’s exposures to household air pollution on improving women’s empowerment in rural Guatemala.

PI_NAMEs: RAHEEL, HINA  (contact)

PROGRAM_OFFICER_NAME: JOUBERT, BONNIE

PROJECT_TERMS: Address;Affect;Age;Ancillary Study;arm;clinical implementation;Clinical Trials;Cluster randomized trial;cognitive interview;Communities;community intervention;community setting;community-level factor;Control Groups;Country;Decision Making;Development;Dimensions;Dose;empowerment;experience;Exposure to;Family member;Fellowship;Field Workers;Fire - disasters;Friends;Funding;gender equality;Goals;group intervention;Guatemala;Guatemalan;Health;health goals;Household;Household Air Pollution;implementation research;implementation science;improved;Individual;instrument;Intervention;intervention effect;intervention participants;Learning;Measures;Mentorship;Modeling;multilevel analysis;National Institute of Environmental Health Sciences;Outcome;Parents;Perception;Persons;Phase;pollutant;Process;programs;Protocols documentation;Randomized;recruit;Recycling;Research;Research Personnel;research study;Resource-limited setting;Resources;response;Rural;Self Efficacy;skills;social;social capital;Social Environment;Social Network;sociodemographic factors;Socioeconomic Status;Support System;Sustainable Development;Testing;Time;Training;treatment arm;United Nations;wasting;Woman;working group;World Health Organization

PROJECT_TITLE: Women's empowerment as a result of ECOLECTIVOS (WERE)


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

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

ORG_CITY: BLACKSBURG

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: VIRGINIA POLYTECHNIC INST AND ST UNIV

ORG_STATE: VA

PHR: PROJECT NARRATIVE Rift Valley fever virus causes severe disease in ruminants and humans, and there are no FDA-approved vaccines or therapeutics to challenge the global spread of RVFV. The RVFV nonstructural small (NSs) protein, the main virulence factor of RVFV, was found to contain multiple LC3-interacting region (LIR) motifs, leading us to hypothesize that NSs is interacting with host key autophagy LC3 proteins to inhibit antiviral autophagy, thus facilitating viral replication and pathogenesis. The proposed research aims to characterize the impact of the NSs-LC3 interaction on the host autophagy pathway and its importance for viral pathogenesis.

PI_NAMEs: PETRACCIONE, KAYLEE  (contact)

PROJECT_TERMS: abortion;Academia;Acetylation;Adult;Aerosols;Affect;Africa;Air;Animals;Area;Autophagocytosis;Autophagosome;Binding;Biogenesis;Bioinformatics;Biological Assay;Bite;Body Fluids;Brain;Calorimetry;career;Cell Nucleus;Cells;Clinical;Co-Immunoprecipitations;Commerce;Congenital Abnormality;Crystallography;Culicidae;Cytoplasm;Cytosol;Data;Death Rate;Disease;Disease Outbreaks;Encephalitis;experimental study;Family member;Fatality rate;FDA approved;Fellowship;flu;Fluorescence;Fractionation;Future;Human;In Vitro;Inbred BALB C Mice;Infection;Infectious Agent;inhibition of autophagy;Invaded;Kinetics;Knowledge;Liver;Livestock;Location;Measures;Mediating;Molecular;mouse model;Movement;Mus;Mutation;Neurologic Deficit;Nuclear;Organ;particle;pathogen;Pathogenesis;Pathogenicity;Pathology;Pathway interactions;Play;Positioning Attribute;Probability;Process;Protein Family;Proteins;Recycling;Regulation;Research;Research Personnel;Rift Valley fever virus;Roentgen Rays;Role;Ruminants;Serum;Side;Structure;Symptoms;Therapeutic;therapeutic target;Tissues;Titrations;trafficking;Training Programs;Transfection;transmission process;Travel;vaccine access;Vaccines;vector mosquito;Viral;Viral Hemorrhagic Fevers;Viral Load result;Viral Pathogenesis;Virginia;Virulence Factors;Virus;Virus Diseases;Virus Replication

PROJECT_TITLE: Rift Valley fever virus NSs protein interacts with LC3 family members to inhibit antiviral autophagy

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F07C-Y (20)]


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Autoimmune Disease;Digestive Diseases;Foodborne Illness;Inflammatory Bowel Disease

ORG_CITY: Newark

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: PROJECT NARRATIVE With more than 6 trillion kilograms of plastic waste produced to date, micro and nano scale plastic particles and fibers (micro-nanoplastics or MNPs), which are the byproduct of environmental and industrial processes have become a ubiquitous and growing contaminant of our environment, food, air and water. Using environmentally relevant MNPs and advanced cellular intestinal and experimental animal models, the proposed study will assess the potential health hazards of ingested MNPs, including 1) their toxicity in the intestine, 2) the extent of their uptake by the intestine and cellular mechanisms that drive uptake, 3) the organs and tissues to which MNPs, once they are taken up by the intestine and enter the circulation, are subsequently distributed, 4) the roles that the plastic type/chemistry (e.g., polyethylene, polystyrene, polyethylene terephthalate), size, and MNP properties play in their uptake and toxicity, and 5) the impact of MNPs on intestinal inflammation and the role of inflammation in toxicity and uptake of MNPs. The results of these studies will help risk assessors and policy makers assess the risks of MNP ingestion, provide the basis and rationale for regulatory action, and will open new areas of research in toxicology and epidemiology for this emerging and novel pollutant.

PI_NAMEs: DEMOKRITOU, PHILIP  (contact);VERZI, MICHAEL P.

PROGRAM_OFFICER_NAME: RAVICHANDRAN, LINGAMANAIDU V

PROJECT_TERMS: absorption;Address;Age;Aging;Air;Animals;Area;Biodistribution;Biological;Biological Monitoring;Blood;Brain;Cells;Chemistry;Circulation;Colectomy;contaminated water;Coupled;Dairying;Darkness;Data;Deposition;design;Diffusion;Digestion;Disease;Disease susceptibility;Endocytosis;Endocytosis Pathway;Environment;Environmental Exposure;Epidemiology;epidemiology study;Epithelium;Excretory function;Experimental Animal Model;Exposure to;fetal;Fiber;Food;Food Packaging;Food Processing;Food Webs;Future;Gene Expression;Genes;Gold;Grain;gut inflammation;hazard;Health;Health Hazards;Heart;HNF4A gene;Hour;Human;Human Volunteers;Image;In Vitro;in vitro Model;in vivo;in vivo Model;Inductively Coupled Plasma Mass Spectrometry;Industrialization;Inflammation;Inflammatory;Inflammatory Bowel Diseases;Ingestion;inhibitor;insight;Intercellular Junctions;interest;intestinal epithelium;Intestinal permeability;Intestines;Kidney;Kilogram;Knockout Mice;Knowledge;laser induced breakdown spectroscopy;Liver;Lung;Measurement;Measures;Meat;Modeling;Molecular;mouse model;mRNA Expression;Municipalities;nano;nanoscale;National Institute of Environmental Health Sciences;novel;Organ;Organoids;particle;Pathway interactions;Placenta;Plastics;Play;Policy Maker;pollutant;Polyethylene Terephthalates;Polyethylenes;Polymers;Polystyrenes;pregnant;Process;Production;Property;pup;Rattus;Research;Research Personnel;response;Risk;Risk Assessment;Role;Sampling;Science;Seafood;Small Interfering RNA;Small Intestines;Surface;Tissues;Toxic effect;Toxicology;Tracer;transcriptome sequencing;uptake;Validation;virtual;wasting;Water;Weather

PROJECT_TITLE: Intestinal uptake, translocation, biodistribution, and toxicity of ingested environmentally relevant micro-nanoplastics (MNPs) and the role of inflammation using advanced cellular and in vivo models

STUDY_SECTION: DBDT

STUDY_SECTION_NAME: Drug and Biologic Disposition and Toxicity Study Section[DBDT]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Autoimmune Disease;Clinical Research;Eye Disease and Disorders of Vision;Genetics;Neurosciences

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Project Narrative Thyroid eye disease is a debilitating and disfiguring condition featuring deposition of hyaluronan and massive tissue fibrosis leading to proptosis, eye muscle restriction, eyelid retraction, dry eye, and optic nerve compression. The molecular basis of the disease is not fully understood, and neither is the regulation of the main signaling axis upon which clinical trials and the new gold standard of treatment is based. Studying the cellular and molecular basis of thyroid eye disease and its key cell surface proteins will identify novel treatment paradigms and targets to improve the treatment of acute and chronic thyroid eye disease.

PI_NAMEs: CHENG, SARAH  (contact)

PROGRAM_OFFICER_NAME: AGARWAL, NEERAJ

PROJECT_TERMS: Acute;Affect;Area;ATAC-seq;Attention;Autoimmune;autoimmune thyroid disease;Automobile Driving;Basic Science;Behavior;Cell Communication;Cell Nucleus;Cell Separation;Cell Surface Proteins;Cell Surface Receptors;cell type;Cells;Chronic;Chronic Phase;Clinical;Clinical Sciences;Clinical Trials;Complex;CRISPR screen;Deposition;Development;Diplopia;Disease;Drug usage;Enhancers;Exophthalmos;Eye;eye dryness;Eye Movements;Eyelid structure;Fibroblasts;Fibrosis;Human;Hyaluronan;Hyperthyroidism;IGF1R gene;improved;In Vitro;Individual;inhibiting antibody;inhibitor;insight;Insulin;insulin regulation;Insulin-Like Growth Factor I;Insulin-Like Growth Factor II;Insulin-Like-Growth Factor I Receptor;knock-down;Literature;Malignant Neoplasms;Medicine;Mentorship;Metabolism;Molecular;Molecular Medicine;multiple omics;Muscle;Nerve compression syndrome;new therapeutic target;novel;Nuclear;Nucleic Acid Regulatory Sequences;Ocular orbit;Oncology;Operative Surgical Procedures;Ophthalmology;Optic Nerve;Orbital Diseases;overexpression;Pathogenesis;Patients;Pharmaceutical Preparations;Phase;Phenotype;Process;Production;Proliferating;Publishing;Quality of life;receptor;Receptor Activation;receptor expression;Receptor Inhibition;Receptor Signaling;Regulation;Regulatory Element;Research;Research Training;Resources;Role;side effect;Signal Transduction;Somatomedins;spatial relationship;standard care;Strabismus;success;Symptoms;T-Lymphocyte;Techniques;Testing;thyroid associated ophthalmopathies;Tissues;Touch sensation;Training;transcription factor;transcriptomics;tumorigenesis;Untranslated RNA;Vision;Work

PROJECT_TITLE: Regulation of IGF-1R in acute and chronic thyroid eye disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F05-D (21)]


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

ORG_NAME: NEW YORK UNIVERSITY

PHR: PROJECT NARRATIVE To investigate both quantitative and qualitative accounts underlying performance heterogeneity throughout the visual field, we use psychophysics and computational modeling. Results will reveal how fundamental visual features are distinctly represented and extracted and how internal noise differs across eccentricity and around polar angle. The findings will constrain visual models and could inform our knowledge of visual deficits and human factors design.

PI_NAMEs: XUE, SHUTIAN  (contact)

PROGRAM_OFFICER_NAME: CLAYTON, EDWIN C

PROJECT_TERMS: Anisotropy;Area;area V1;Basic Science;Behavioral;Computer Models;Cone;Contrast Sensitivity;Data;Dedications;density;design;Development;Dimensions;Environment;Equation;fovea centralis;Frequencies;Functional Magnetic Resonance Imaging;Goals;Heterogeneity;Human;human model;Individual;individual variation;Knowledge;Lead;Link;Location;Measures;Mediating;Meridians;Methods;Modeling;neural;neural correlate;Neurons;Noise;orientation selectivity;Performance;Peripheral;Play;predictive modeling;Property;Psychophysics;Reporting;Resources;Retinal Ganglion Cells;Role;sensory input;Signal Transduction;spatial vision;Special Population;stem;Stimulus;stimulus processing;Surface;System;Testing;translational applications;Translational Research;Vision;Visual;Visual Cortex;Visual Fields;visual performance;Visual System;Weight

PROJECT_TITLE: Unveiling the computations underlying behavioral heterogeneity across and around the visual field

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F02B-Y (20)]


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Genetics;Human Genome;Immunotherapy;Lymphatic Research;Skin Cancer

ORG_DEPT: DERMATOLOGY

PHR: PROJECT NARRATIVE Lymph node metastasis is a key negative prognostic factor in many cancers, including cutaneous melanoma; recent work suggests that lymph node metastasis reduces response to immune checkpoint blockade and induces a state of systemic immunosuppression permissive of distant metastasis. However, we do not have a thorough understanding of how metastasis alters the nodal immune repertoire or how these changes may affect systemic anti-tumor immunity, despite an increasing clinical interest in retaining the draining lymph node basin during treatment. Completion of this proposal will define the role of IL-33 production from lymphatic endothelial cells in maintaining protective anti-metastatic immune networks in the tumor-draining lymph node.

PI_NAMEs: VENTRE, KATHERINE  (contact)

PROGRAM_OFFICER_NAME: BIAN, YANSONG

PROJECT_TERMS: Activated Natural Killer Cell;Affect;Antibodies;Antigens;Biochemistry;Biological Assay;Cancer Center;career;Cells;Clinical;Clinical Trials;cohort;Communication;Computer Analysis;Cutaneous Melanoma;cytotoxicity;Data;Data Analyses;Dermatology;Disease;Disease Outcome;Distant Metastasis;draining lymph node;Effector Cell;Evolution;Floor;Flow Cytometry;Functional dependence;Functional disorder;Genetic Transcription;Human;Image;Immune;immune checkpoint blockade;Immune response;Immunofluorescence Immunologic;Immunologic Surveillance;Immunologics;Immunosuppression;improved;Inflammatory;interest;intravenous injection;Knockout Mice;Ligands;Link;Lung;lung metastatic;Lymph Node Dissections;Lymph Node Mapping;Lymph Node Subcapsular Sinus;lymph nodes;Lymphatic Endothelial Cells;Malignant Neoplasms;Maps;mast cell;Melanoma;Melanoma patient;Mentorship;Metastatic Melanoma;Metastatic Neoplasm to Lymph Nodes;Modeling;Molecular;multidimensional data;multimodality;Mus;Natural Killer Cells;Neoadjuvant Therapy;Neoplasm Metastasis;neoplastic cell;NK Cell Activation;Nodal;Nonmetastatic;Oncologist;Organ;Pathology;Patients;permissiveness;Pharmacology;Population;Positioning Attribute;Primary Neoplasm;Process;Production;Prognostic Factor;Proliferating;Receptor Signaling;Regional Disease;Research Personnel;Resolution;response;Role;Signal Transduction;single-cell RNA sequencing;skills;Solid;Solid Neoplasm;spatiotemporal;Spottings;standard of care;survival outcome;Systemic disease;temporal measurement;Testing;Therapeutic;Therapeutic Intervention;TNF gene;Training;transcriptome sequencing;transcriptomics;tumor;Tumor Immunity;tumor immunology;tumor-immune system interactions;Visceral;Work

PROJECT_TITLE: The influence of lymph node metastasis on local and systemic anti-tumor immunity

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F09C-Z (22)]


ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

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

ORG_CITY: RICHARDSON

ORG_NAME: UNIVERSITY OF TEXAS DALLAS

PHR: PROJECT NARRATIVE Better understanding of the mechanisms that underlie normal aging or a more pathological aging trajectory is an important public health goal. This proposal seeks to continue to follow a cohort of individuals aged across the adult lifespan for 14 years to investigate the cellular and molecular driven influences of within-person change in neurometabolic, cognitive, and brain aging. This project also investigates beta amyloid deposition and genetic risks for developing Alzheimer’s Disease.

PI_NAMEs: KENNEDY, KRISTEN M. (contact);RODRIGUE, KAREN M

PROGRAM_OFFICER_NAME: WAGSTER, MOLLY V

PROJECT_TERMS: abeta deposition;Address;Adoption;Adult;Age;age difference;age related changes;aged;Aging;aging brain;aging process;Alzheimer's Disease;Amino Acids;Antinuclear Antibodies;Antioxidants;Area;Aspartate;association cortex;Atrophic;Award;Bilateral;Biological;Biological Assay;Biological Factors;Biological Markers;Blood;Blood Vessels;blood-based biomarker;Brain;brain health;Brain region;C-reactive protein;Cell Aging;Cerebrum;Choline;Classification;Cognition;Cognitive;cognitive neuroscience;cohort;Creatine;cytokine;Data;Data Set;Education;Energy Metabolism;Enrollment;Ethnic Origin;executive function;Exhibits;Fortification;Functional Magnetic Resonance Imaging;Funding;Future;gamma-Aminobutyric Acid;Genetic Risk;Glial Fibrillary Acidic Protein;Glucose;Glutamates;Glutathione;Goals;gray matter;Growth;Health;health goals;healthy aging;Image;Immune;Immune system;Immunologic Markers;Impaired cognition;improved;in vivo;indexing;Individual;Individual Differences;Inflammation;Inflammatory;inflammatory marker;Inflammatory Response;inhibitor;innovation;interest;Interleukin-6;Knowledge;Lateral;Length;life span;Light;longitudinal design;Longitudinal Studies;machine learning method;Magnetic Resonance Spectroscopy;Maintenance;Measurement;Measures;Memory Loss;Metabolic;Metabolic Marker;millimeter;Modeling;Molecular;Multimodal Imaging;multimodality;Myelin;myoinositol;Neocortex;neural;Neural Inhibition;Neurocognitive;neurofilament;Neuroglia;neuroimaging;neuroinflammation;Neuronal Plasticity;Neurons;Neurotransmitters;Noise;normal aging;novel;novel marker;Outcome;Parietal;Parietal Lobe;Participant;pathological aging;Pattern;Perfusion;Persons;Process;Property;protein biomarkers;Protons;Proxy;Public Health;Research;Resolution;Role;Sample Size;scyllo-inositol;sensory cortex;Statistical Methods;Structure;Taurine;Taxonomy;Techniques;technology development;telomere;Testing;Thick;Thinness;Time;white matter

PROJECT_TITLE: Dopaminergic and Neuroplastic Influences on Longitudinal Change in Cognitive and Brain Aging

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


NIH_SPENDING_CATS: Biotechnology;Chronic Obstructive Pulmonary Disease;Digestive Diseases;Emerging Infectious Diseases;Emphysema;Gene Therapy;Genetics;Infectious Diseases;Liver Disease;Lung;Rare Diseases

ORG_CITY: WORCESTER

ORG_DEPT: GENETICS

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

PHR: PROJECT NARRATIVE Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder that can cause lung emphysema and liver fibrosis in patients. This proposal seeks to evaluate the safety of a gene editing approach to correct the most common genetic cause of AATD and determine its potential to reduce liver and lung disease burden in a mouse model of AATD. This work will facilitate the clinical development of gene editing strategies to treat AATD.

PI_NAMEs: GAO, JENNY  (contact)

PROGRAM_OFFICER_NAME: LACHOWICZ-SCROGGINS, MARRAH ELIZABETH

PROJECT_TERMS: Adenine;adenovirus mediated delivery;Alleles;alpha 1-Antitrypsin;alpha 1-Antitrypsin Deficiency;Alveolar;base editing;base editor;Bioinformatics;Biology;burden of illness;Bystander Effect;Cells;clinical development;clinically relevant;Clustered Regularly Interspaced Short Palindromic Repeats;Computing Methodologies;cost;CRISPR/Cas technology;Deaminase;Deamination;deep sequencing;Dependovirus;Development;Disease;DNA;DNA Double Strand Break;DNA Repair;DNA-Directed DNA Polymerase;elastase inhibitor;Endonuclease I;Engineering;Event;Exhibits;experimental study;Future;gene correction;gene therapy;gene-editing approach;Generations;Genes;Genetic;Genetic Diseases;genotoxicity;Guanosine;Guide RNA;Hepatocyte;improved;In Vitro;in vitro activity;in vivo;Infusion procedures;Inosine;insight;Leukocyte Elastase;Life;Liver;Liver diseases;Liver Fibrosis;Lung;Lung Diseases;Measures;Mechanics;Mediating;misfolded protein;Molecular;morphometry;mouse model;Mus;mutant;Mutation;Neisseria meningitidis;novel;off-target site;Patients;Phenotype;Proteins;Pulmonary Emphysema;pulmonary function;Pulmonology;repaired;Reporter;Safety;Serum;Streptococcus pyogenes;Structure of parenchyma of lung;Testing;Therapeutic;therapeutic genome editing;Tissues;tool;Training;transcriptome sequencing;Transgenic Mice;Variant;Viral;Work

PROJECT_TITLE: Developing a novel adenine base editor tool for in vivo alpha-1 antitrypsin deficiency gene correction.


NIH_SPENDING_CATS: Neurosciences

ORG_CITY: WALTHAM

ORG_DEPT: BIOLOGY

ORG_NAME: BRANDEIS UNIVERSITY

PHR: Project Narrative Synapses are the primary sites of cell-cell contact in the nervous system which rely on protein signaling to determine when and where synapses will develop and to specify their identity as excitatory or inhibitory. Perturbations to this process are implicated in a variety of neurological and neurodevelopmental disorders including autism, epilepsy, and schizophrenia. We propose to utilize the demonstrated ability of Sema4D (signaling via the PlexinB1 receptor) to rapidly promote inhibitory synapse formation to study the mechanisms by which new inhibitory synapses are formed in the brain.

PI_NAMEs: PRANSKE, ZACHARY JAMES (contact)

PROGRAM_OFFICER_NAME: MATTHEWS, MARGUERITE

PROJECT_TERMS: Acute;Address;Adult;Affinity;Aftercare;autism spectrum disorder;Biochemical;Biological;Biological Models;Brain;CD100 antigen;Cell Communication;Cell Physiology;Cell surface;Cells;Central Nervous System;Complex;confocal imaging;Data;density;Development;Dissection;Elements;Epilepsy;Equilibrium;Event;Excitatory Synapse;experimental study;Extracellular Domain;Family;Fc domain;Fluorescence Microscopy;Genetic;gephyrin;Glutamates;Goals;hippocampal pyramidal neuron;Hippocampus;Hour;Human;Image;imaging approach;Imaging Techniques;In Vitro;in vivo;Inhibitory Synapse;insight;Integral Membrane Protein;Invertebrates;Knowledge;Label;Mediating;Mediator;Molecular;Monitor;Mus;N-terminal;Nature;Nervous System;Nervous System Disorder;Nervous System Physiology;neural circuit;Neurodevelopmental Disorder;Neurons;Neurophysiology - biologic function;Neuropilins;Pathway interactions;Phylogeny;plexin;postnatal;postsynaptic;presynaptic;Process;Property;Proteins;receptor;Recombinants;recruit;Regulation;Research;Research Personnel;Resistance;response;Scaffolding Protein;Schizophrenia;Seizures;Semaphorins;Signal Pathway;Signal Transduction;Signal Transduction Pathway;Signaling Molecule;Signaling Protein;Site;spatiotemporal;Specific qualifier value;Surface;Synapses;synaptogenesis;Therapeutic;Time;trafficking;Transgenic Mice;Vertebrates;Virus;Work

PROJECT_TITLE: Cellular and Molecular Mechanisms of Inhibitory Synapse Development


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Diabetes;Mental Health;Neurosciences;Obesity;Prevention;Sleep Research;Social Determinants of Health

ORG_CITY: SALT LAKE CITY

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: PROJECT NARRATIVE Although emerging research suggests that circadian disruption serves as a risk for cardiometabolic disease, there is a lack of research investigating behavioral contributors to circadian disruption. Bedtime procrastination, or delays in bedtime in the absence of external obligations, may disrupt circadian rhythms through alterations in sleep timing. This project seeks to evaluate the impact of bedtime procrastination on circadian disruption and cardiometabolic health, while also investigating the roles of anxiety, reward, and self-regulation in the development of daily bedtime procrastination in order to inform novel treatments for bedtime procrastination and circadian-sleep disturbances.

PI_NAMEs: CARLSON, STEVEN  (contact)

PROGRAM_OFFICER_NAME: CAMPO, REBECCA A

PROJECT_TERMS: Adult;Anxiety;Award;Behavior;Behavioral;biopsychosocial;Body fat;Body mass index;Cardiometabolic Disease;cardiometabolic risk;cardiometabolism;Cause of Death;circadian;Circadian desynchrony;Circadian Dysregulation;Circadian Rhythms;cost;Development;Diabetes Mellitus;Dimensions;Disease;disorder risk;Fellowship;Foundations;glycemic control;Glycosylated hemoglobin A;Health;indexing;Individual;Informal Social Control;innovation;Intervention;intravenous glucose tolerance test;Light;Literature;longitudinal design;Mediating;Melatonin;Modeling;modifiable risk;novel;Overweight;Pathway interactions;programs;Public Health;Reporting;Research;research and development;Rest;Rewards;Risk;Risk Factors;Role;Sampling;Scientist;skills;Sleep;sleep behavior;Sleep Deprivation;Sleep disturbances;sleep health;sleep onset;Statistical Methods;Testing;therapy development;Time;Time Study;Training;training opportunity;United States;young adult

PROJECT_TITLE: Advancing a biopsychosocial model of bedtime procrastination

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F01B-M (20)]


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

ORG_CITY: UNIVERSITY PARK

ORG_NAME: PENNSYLVANIA STATE UNIVERSITY, THE

PHR: Project Narrative The ability to update existing memories to incorporate new information is a critical but understudied aspect of cognition that is particularly sensitive to the deleterious effects of Alzheimer’s disease and other forms of age- related cognitive decline. This proposal aims to investigate the epigenetic and cellular mechanisms underlying memory updating to identify how aging negatively affects these processes. Results from this project will advance our understanding of age-related cognitive decline and may inform future therapeutics treating memory disorders such as Alzheimer's disease.

PI_NAMEs: BRUNSWICK, CHAD ARTHUR (contact)

PROJECT_TERMS: Affect;Age;age effect;age related;age related changes;Age-associated memory impairment;age-related disease;Aging;aging brain;aging hippocampus;Alzheimer's Disease;American;Attention;Brain region;Cognition;Data;Development;Dorsal;Epigenetic Process;Evaluation;Exhibits;experimental study;Future;Gene Expression;Genes;genetic inhibitor;Genetic Transcription;HDAC3 gene;Hippocampus;Histone Acetylation;Histone Deacetylase;Histone Deacetylase Inhibitor;Human;Immediate-Early Genes;Impaired cognition;Impairment;improved;Individual;Interruption;Laboratories;Link;Location;long term memory;Mediating;Memory;Memory Disorders;Memory impairment;memory process;Modification;Molecular;Mus;Neurons;normal aging;novel;NR4A2 gene;old mice;Pathway interactions;pharmacologic;Physiological;Play;Population;prevent;Process;Repression;Research;Risk Factors;Rodent;Role;spatial memory;Testing;Therapeutic;therapeutic target;Training;transcriptome sequencing;Update;Viral;young adult

PROJECT_TITLE: Epigenetic and cellular mechanisms of age-related memory updating impairments


ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: Project Narrative There is a critical need to improve organ preservation times for organ transplant, but unfortunately, many of the current protocols lead to damage of the endothelium. In the proposed project a novel microfluidic vasculature model consisting of primary microvascular endothelial cells will be developed and compared to a rat hindlimb machine perfusion model to understand the role of preservation injury in the microvasculature and how it can be prevented. This will lead to an increase in endothelial focused preservation therapies and subsequently increase the preservation potential of vascular composite allografts, along with other organs such as heart, lung, and kidney, expanding the potential donor pool and patient access to organ transplantation.

PI_NAMEs: ELLIS, BRADLEY WAYNE (contact)

PROJECT_TERMS: Acute;Affect;Allografting;Apoptosis;Apoptotic;Applications Grants;Blood capillaries;Blood Vessels;career development;CASP3 gene;CASP7 gene;Caspase;Caspase Inhibitor;Cell Culture Techniques;cell injury;Cell Survival;Cells;Cellular biology;Chimerism;Clinical;Coculture Techniques;cost;Cryopreservation;Culture Media;Data;Development;Devices;Endothelial Cells;Endothelium;Esthetics;experience;Goals;Heart;Hindlimb;Hour;human induced pluripotent stem cells;human model;Immunologics;improved;In Vitro;in vitro Model;in vivo;Inhibition of Apoptosis;Injury;Ischemia;Isolated limb perfusion;Kidney;Lead;Limb structure;Literature;Lung;Measures;Mediating;Methods;Microfluidic Microchips;Microfluidics;Modality;Modeling;novel;novel strategies;novel therapeutic intervention;novel therapeutics;Operative Surgical Procedures;Organ;Organ Donor;Organ Preservation;Organ Transplantation;Patients;Perfusion;pharmacologic;Phenotype;Physiological;pre-clinical;Predisposition;preservation;prevent;Procedures;programs;Protocols documentation;rational design;Rattus;Recovery;Reperfusion Injury;Reperfusion Therapy;Rodent;Role;System;Targeted Research;Technology;Testing;therapy development;Time;Training;Transplant Recipients;Transplantation;Trauma;Vascular Endothelial Cell;vascular injury;Waiting Lists;wasting;Work

PROJECT_TITLE: Development of Capillary-on-Chip for the Study of Preservation Injury on Microvascular Endothelial Cells

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F10C-B (20)]


NIH_SPENDING_CATS: Biotechnology;Breastfeeding, Lactation and Breast Milk;Digestive Diseases;Genetics;Infectious Diseases;Microbiome;Nutrition

ORG_CITY: CHICAGO

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF CHICAGO

PHR: The project uses a combination of CRSPR/Cas9 gene targeting and gnotobiotic technology to address the role of alpha defensins in shaping the microbiome and response to pathogens.

PI_NAMEs: CHERVONSKY, ALEXANDER V (contact)

PROGRAM_OFFICER_NAME: VAZQUEZ-MALDONADO, NANCY

PROJECT_TERMS: Address;alpha-Defensins;Animal Experiments;Animal Housing;Animals;anti-microbial peptide;bactericide;Behavior;Birth;Breast Feeding;Chemicals;Chicago;Chromosome 8;Chromosome Mapping;colonization resistance;commensal microbes;Complex;Consensus;Country;CRISPR/Cas technology;Data;Defensins;Diet;enteric pathogen;Environmental Risk Factor;Evolution;Exclusion;experimental study;Extracellular Matrix;gastrointestinal epithelium;Gene Expression;Gene Targeting;Genes;Genetic;genetic manipulation;Genetic Polymorphism;Genotype;Germ-Free;Gnotobiotic;Homeostasis;Host Defense;Human;Immune system;immunological status;In Vitro;Inbred BALB C Mice;Individual;Infection;innate immune mechanisms;Institution;interest;intestinal epithelium;Intestines;Investments;Knockout Mice;Light;Litter Size;Metalloproteases;Microbe;microbial community;microbial composition;microbiome;microbiota;microbiota composition;Monozygotic twins;Mouse Strains;Mus;nutrition;Outcome;pathogen;Pathogenicity;Peptides;Regulation;Reporting;resident commensals;Resistance;response;reverse genetics;Role;Shapes;Signal Transduction;Small Intestines;Specificity;Statistical Data Interpretation;stem;stem cells;Stress;Suggestion;Technology;Testing;Transgenes;transmission process;Twin Multiple Birth;Twin Studies;Universities;Variant;Vascularization

PROJECT_TITLE: Alpha defensins: innate keepers of host-commensal homeostasis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 IIDA-F (09)]


NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Lung;Organ Transplantation;Rare Diseases;Transplantation

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

PHR: Narrative The goal of this project is to determine the role of Bone Morphogenetic Protein (BMP) signaling in primary graft dysfunction (PGD). BMP signaling is essential for microvascular homeostasis, and as such, could play an important role in modulating IRI post lung transplantation. We will use novel rodent and in vitro modeling systems together with therapeutic inhibitors to dissect the role of BMP signaling in PGD with the overall goal to develop BMP specific therapeutic strategies that improve lung transplant outcomes.

PI_NAMEs: GILL, BLAKE  (contact)

PROGRAM_OFFICER_NAME: KALANTARI, ROYA

PROJECT_TERMS: activin receptor-like kinase 1;Acute Disease;Acute Lung Injury;Allogenic;Allografting;Alveolar;Biological Models;Blood Vessels;BMP10 gene;bone loss;bone morphogenetic protein 9;bone morphogenetic protein receptors;Bone Morphogenetic Proteins;Brain Death;Breathing;Cells;Chronic Disease;Circulation;Clinical;Complex;Cryopreservation;Data;Development;differentiation protein 1 inhibitor;Dimerization;Dose;Endothelial Cells;Endothelium;Epithelial Cells;Extravasation;FDA approved;Goals;graft dysfunction;Growth Factor;Heterozygote;Homeostasis;Hypoxemia;Immune;Impairment;improved;In Vitro;in vitro Model;in vivo;in vivo Model;Inflammation;Inflammatory;inhibitor therapy;Injury;insight;Intervention;Left;Ligands;Lipopolysaccharides;Literature;Liver;Lung;lung development;lung injury;Lung Transplantation;Microcirculatory Bed;Morbidity - disease rate;mortality;Mothers;mouse model;Mus;novel;novel therapeutics;Organ Transplantation;Outcome;Pathway interactions;Perfusion;Phosphorylation;Play;Prevalence;Process;Property;Protective Agents;protective effect;Proteins;pulmonary arterial hypertension;Pulmonary Pathology;Reperfusion Injury;Rodent;Rodent Model;Role;Signal Pathway;Signal Transduction;Signaling Protein;Solid;survival outcome;Survival Rate;Therapeutic;Time;Tissues;Translating;transplant model;Vascular blood supply;Vascular Endothelial Cell;Vascular Endothelium

PROJECT_TITLE: Dissecting the role of vascular endothelial BMP9 signaling in lung transplantation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F10A-R (08)]


NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Congenital Heart Disease;Congenital Structural Anomalies;Heart Disease;Orphan Drug;Pediatric;Rare Diseases

ORG_CITY: WASHINGTON

ORG_NAME: CHILDREN'S RESEARCH INSTITUTE

ORG_STATE: DC

PHR: Project Narrative: Congenital heart disease (CHD) affects 1 in 10 infants born annually. Cardiac medications are commonly used to support heart function after life-saving corrective surgery, however, their effects on pediatric patients are not extensively studied. This project will investigate developmental changes in cardiac maturity and age-dependent responses to inotropic medications, using both an animal model and cardiac tissue from CHD patients.

PI_NAMEs: SALAMEH, SHATHA  (contact)

PROGRAM_OFFICER_NAME: LIDMAN, KARIN FREDRIKSSON

PROJECT_TERMS: Action Potentials;Adolescent;Adult;Affect;Age;age difference;age effect;age related;age related changes;Animal Model;Animals;Anti-Arrhythmia Agents;Automobile Driving;beta-adrenergic receptor;Biomedical Research;Birth;Calcium;Cardiac;Cardiac Electrophysiologic Techniques;Cardiac Myocytes;Cardiac Surgery procedures;cardiogenesis;Cardiology;career;career development;Cellular Structures;Child;Childhood;clinical care;Clinical Trials;clinically relevant;Collaborations;congenital heart abnormality;Coupling;Critical Care;Cyclic AMP;Data;density;Development;Disease;Dopamine;Electrocardiogram;Electrophysiology (science);Elements;FDA approved;fetal;Foundations;Future;Gene Expression;Genes;genetic regulatory protein;Genomics;Goals;Growth;guinea pig model;Heart;Heart Atrium;heart function;heart pharmacology;Heart Research;Hospitalized Child;Hospitals;Human;human tissue;Impairment;improved;Infant;insight;Institution;Intervention;Ion Channel;Knowledge;Laboratory Research;Left;Life;Low Cardiac Output;Maps;Measures;Mechanics;medication administration;Medicine;Mentors;Microfilaments;Milrinone;Modeling;Molecular;Molecular Biology;Myocardial;Myocardium;Neonatal;neonate;off-label drug;Operative Surgical Procedures;Optics;Patient-Focused Outcomes;Patients;pediatric patients;Pediatric Research;perinatal period;Pharmaceutical Preparations;Pharmacodynamics;pharmacologic;Pharmacology;Pharmacotherapy;phosphoric diester hydrolase;Physiologic intraventricular pressure;Physiological;Physiology;Population;postnatal;postnatal development;postoperative recovery;Preparation;pressure;Principal Investigator;Process;protein expression;Proteins;Proteomics;receptor expression;Research;research study;response;Safety;Sample Size;Sampling;Sarcoplasmic Reticulum;Slice;structural heart disease;Structure;Techniques;Testing;therapy design;Tissue Sample;tissue slice preparation;Tissues;Training;Translations;treatment strategy;Ventricular;Work

PROJECT_TITLE: Investigating age-dependent differences in cardiac drug response

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F10A-R (20)]