NIH_SPENDING_CATS: Aging;Clinical Research;Clinical Trials and Supportive Activities;Neurosciences;Physical Activity

ORG_CITY: DETROIT

ORG_NAME: WAYNE STATE UNIVERSITY

PHR: Project Narrative Endurance exercise is a highly effective intervention for ensuring healthy metabolism and maintaining healthy function during aging, but is unavailable to patients with illnesses or injuries that restrict their movement. Here, we follow up on previous discoveries from the fruit fly model system showing that stimulation of specific regions of the brain can coordinate benefits of exercise in sedentary animals. Here, we propose to follow up by identifying required factors to respond to these stimuli in the exercising brain and muscle, and by extending these results into humans for the first time using virtual reality stimulation to produce some benefits of exercise in sedentary humans.

PI_NAMEs: WESSELLS, ROBERT JOHN (contact)

PROGRAM_OFFICER_NAME: SARE, RACHEL

PROJECT_TERMS: Acute;Address;Adrenergic Agents;Age;age-related disease;Aging;Animals;Automobile Driving;Award;Biological Models;Brain;Brain region;Cardiovascular system;Chronic;Circulation;design;Development;disabled;Drosophila genus;effective intervention;efficacy evaluation;endurance exercise;Ensure;Exercise;exercise capacity;exercise training;experience;Exposure to;Fatty acid glycerol esters;fly;follow-up;Genes;Genetic;genetic analysis;Grant;Health;healthspan;Homeostasis;Homologous Gene;Human;Incidence;Individual;injured;Injury;Intervention;Knowledge;lifestyle factors;Mediating;Mediator;Metabolic;Metabolism;Methods;Modeling;Moderate Exercise;Movement;Muscle;Nervous System;Neurons;Norepinephrine;novel;novel therapeutics;Octopamine;octopamine receptor;Pathway interactions;Patients;Periodicals;Persons;Physiological;Positioning Attribute;Proteomics;receptor;response;Role;sedentary;Signal Transduction;simulation;single molecule;Skeletal Muscle;Stimulus;Therapeutic;Time;time use;Tissues;tool;Up-Regulation;virtual reality;virtual reality simulation;Work

PROJECT_TITLE: Octpamine controls adaptation to endurance exercise in Drosophila

STUDY_SECTION: SMEP

STUDY_SECTION_NAME: Skeletal Muscle and Exercise Physiology Study Section[SMEP]


ADMINISTERING_IC: CA

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Genetics;Rare Diseases

ORG_CITY: NEW YORK

ORG_COUNTRY: UNITED STATES

ORG_DEPT: PATHOLOGY

ORG_FIPS: US

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

ORG_STATE: NY

PHR: PROJECT NARRATIVE 5%-10% of human cancers rely on the alternative lengthening of telomere (ALT)-based mechanism for telomere elongation. We aim to elucidate the molecular cascades underlying the ALT-directed telomere maintenance. We will identify the critical dependencies and novel mechanistic-driven therapeutic targets against ALT-dependent human cancers including ATRX mutant malignant gliomas.

PI_NAMEs: ZHENG, HONGWU  (contact)

PROGRAM_OFFICER_NAME: WITKIN, KEREN L

PROJECT_TERMS: Acceleration;Adopted;Adult;Adverse effects;Affect;Astrocytes;ATRX gene;Biological Models;Catalogs;Cell Death;cell immortalization;Cells;Childhood;chromatin modification;chromosome missegregation;Chromosome Segregation;Chromosomes;Complex;CRISPR screen;DAXX gene;Defect;demethylation;Dependence;Development;DNA biosynthesis;DNA Damage;DNA Double Strand Break;DNA Methylation;DNA Repair;DNA Structure;Event;Functional disorder;Future;Gene Expression;Genetic;Genetic Recombination;Genome Stability;Genomic Instability;Glioma;Goals;Growth;Histone H3.3;Histones;Homeostasis;Human;Impairment;in vivo;Infiltration;isopeptidase;Length;Lysine;Maintenance;Malignant Glioma;Malignant Neoplasms;mature animal;Mediating;Methylation;Mitotic;Modeling;Molecular;Molecular Chaperones;mouse model;mutant;Mutation;novel;Pathogenesis;Pathway interactions;Physiological;Prognosis;programs;Proteins;Publishing;Reader;Regulation;response;Role;Signal Transduction;Specific qualifier value;structural determinants;synthetic lethal interaction;targeted treatment;Telomerase;telomere;Telomere Maintenance;Testing;Therapeutic;therapeutic target;Tissues;Toxic effect;TP53 gene;tumor;tumorigenesis;Validation

PROJECT_TITLE: Identifying molecular vulnerabilities of ALT-dependent cancers

STUDY_SECTION: CG

STUDY_SECTION_NAME: Cancer Genetics Study Section[CG]


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Cancer;HIV/AIDS;Infectious Diseases

ORG_CITY: Columbus

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: Project Narrative Retroviruses have long been recognized as important pathogens of humans and animals, and research on these agents has uncovered important discoveries in cell biology and mechanisms in human disease. The 33rd International Workshop on Retroviral Pathogenesis will continue a long tradition of intimate, engaged scientific interaction on all aspects of retroviral pathogenesis with strong emphasis on animal retroviruses as models of human disease. The conference will convene national and international scientific leaders in the field, together with junior investigators, postdoctoral and student trainees, for scientific presentation and engaged discussion.

PI_NAMEs: GREEN, PATRICK LEE (contact)

PROGRAM_OFFICER_NAME: SAYYED, ZULEKHA I

PROJECT_TERMS: Address;Advisory Committees;Animal Disease Models;Animal Model;Animals;Area;California;Cellular biology;Chicago;Colorado;Development;Disease;editorial;Educational workshop;emerging pathogen;Endogenous Retroviruses;Ethics;Fostering;Goals;graduate student;human disease;human model;human pathogen;Illinois;Immune response;Immunodeficiency and Cancer;Immunologics;innovation;International;Italy;Location;Manuscripts;Mechanics;Medical;Modeling;Molecular;Nobel Prize;Ohio;Participant;Pathogenesis;Postdoctoral Fellow;Principal Investigator;Process;Publications;Research;Research Personnel;Retroviridae;Students;symposium;tumorigenesis;Underrepresented Minority;Universities;virology;virus host interaction;Woman;Work;Writing

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 PCRB-9 (O1)]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Infectious Diseases;Lung;Pneumonia;Pneumonia and Influenza

ORG_CITY: JACKSON

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF MISSISSIPPI MED CTR

ORG_STATE: MS

PHR: Narrative Streptococcus pneumoniae (Spn) kills millions yearly mainly due to pneumococcal pneumonia. We demonstrated that hydrogen peroxide produced by Spn strains oxidizes heme-carrying proteins, releasing and degrading heme, a molecule having a central role in the biological processes of all living organisms including humans. We will investigate the molecular and cellular mechanisms leading to the oxidation of hemoglobin by Spn and the consequences of such oxidative reactions in the pathophysiology of pneumococcal disease.

PI_NAMEs: VIDAL, JORGE EUGENIO (contact)

PROGRAM_OFFICER_NAME: UPADHYAY, MEENU MISHRA

PROJECT_TERMS: Acetyl Coenzyme A;acute infection;Aerobic;Affect;Alveolar;Alveolus;Antioxidants;Arteries;Automobile Driving;Bacteremia;Bacteria;Binding;Binding Proteins;Biochemical;Biological Process;Blood capillaries;Blood Circulation;Bronchi;Bronchioles;capsule;Carbohydrates;Cause of Death;Cells;Cessation of life;Child;cohesion;confocal imaging;cost;cytochrome c;cytotoxic;cytotoxicity;density;Disease;efficacy evaluation;Elderly;Encapsulated;Endothelial Cells;Endothelium;Epithelial Cells;Epithelium;Fermentation;fitness;Functional disorder;Gene Expression;Genes;Genetic;Goals;Growth;Heme;Heme Iron;Hemeproteins;Hemoglobin;Hemoglobin C;Human;Hydrogen Peroxide;Hydroxyl Radical;Image;imaging approach;Imaging technology;In Vitro;in vivo;in vivo Model;Incubated;innovation;Intervention;Invaded;Iron;Iron-Binding Proteins;Knowledge;Link;Lung;Lung infections;Membrane;Meningitis;Microbial Biofilms;Modeling;Molecular;Molecular Target;mouse model;Mus;mutant;novel;Nutrient;Organism;Outcome Study;oxidation;Pathogenesis;Pneumococcal Infections;Pneumococcal Pneumonia;Pneumonia;Population;prevent;Process;Production;programs;Proteins;Pulmonary Pathology;Reaction;receptor;Research;Resistance;response;Role;scaffold;Series;Source;Streptococcus pneumoniae;Structure of parenchyma of lung;Techniques;Toxic effect;transposon sequencing;Veins;Virulence;Virulent;Western Blotting

PROJECT_TITLE: The oxidation of heme-carrying proteins in the pathophysiology of pneumococcal disease

STUDY_SECTION: BV

STUDY_SECTION_NAME: Bacterial Virulence Study Section [BV]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Dementia;Neurodegenerative;Neurosciences;Prevention;Rehabilitation

ORG_CITY: BOSTON

ORG_NAME: HEBREW REHABILITATION CENTER FOR AGED

ORG_STATE: MA

PHR: Narrative: Motoric cognitive risk syndrome (MCR), defined as having both slow walking speed and complaints of declining cognitive function, is common in older adults, and is associated with a very high risk of the future development of dementia. Research by us and others indicates that a form of non-invasive brain stimulation called transcranial direct current stimulation (tDCS) may be used to improve aspects of brain function that support the control of both walking and mental function. In this project, we will use home-based delivery of individually-tailored tDCS and a combination of in-lab and home-based assessments to conduct a multi-site, randomized controlled clinical trial of tDCS in older men and women with MCR, in the hope of demonstrating that six months of stimulation enhances cognition and lowers the risk of the future development of dementia.

PI_NAMEs: HAUSDORFF, JEFFREY M;MANOR, BRADLEY D. (contact)

PROGRAM_OFFICER_NAME: ST  HILLAIRE-CLARKE, CORYSE

PROJECT_TERMS: Address;Alzheimer's disease related dementia;Alzheimer's disease risk;Anatomy;Anxiety;arm;Atrophic;Behavioral;Brain;Brain region;Cephalic;cerebral atrophy;clinically relevant;Cognition;Cognitive;cognitive function;cognitive task;Communities;cost;Dementia;dementia risk;design;Development;Dose;Double-Blind Method;Electric Stimulation;Enrollment;Evaluation;executive function;Exhibits;Exposure to;Frequencies;functional improvement;functional near infrared spectroscopy;Future;Gait;Gait speed;Genetic Crossing Over;gray matter;high risk;Home;home test;Impaired cognition;improved;Individual;insight;Intervention;Intervention Studies;late life;Left;Magnetic Resonance Imaging;Measurable;Measures;mental function;Mobility disability;Moods;Motor;Multi-Institutional Clinical Trial;neural network;neuroimaging;Neuronal Plasticity;noninvasive brain stimulation;normal aging;older adult;older men;older women;open label;Outcome;Participant;Performance;Phase;Pilot Projects;Prefrontal Cortex;primary endpoint;Randomized;Randomized Controlled Clinical Trials;Randomized, Controlled Trials;Research;Resolution;response;Rest;Risk;secondary outcome;Series;Site;smartphone application;Structure;Syndrome;Testing;Therapeutic;Time;transcranial direct current stimulation;trial design;Vascular Dementia;Walking;walking speed;Work

PROJECT_TITLE: Long-term home-based transcranial electrical stimulation for cognitive and motor function in older adults with an increased risk of dementia: a randomized controlled trial

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


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Biotechnology;Chronic Liver Disease and Cirrhosis;Diabetes;Digestive Diseases;Genetics;Hepatitis;Human Genome;Liver Disease;Nutrition;Prevention;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: CINCINNATI

ORG_NAME: CINCINNATI CHILDRENS HOSP MED CTR

PHR: PROJECT NARRATIVE Due to the global epidemic of nonalcoholic steatohepatitis (NASH), the potential market impact for the NASH drug is estimated to be about $20 billion to $35 billion, as populations with fatty diets increasingly fall victim to a condition with no approved treatments. This project aims to demonstrate how our human stem cell-based in vitro steatohepatitis organoid model system mirrors patient's liver phenotype, which can be molecularly and mechanistically used for precise evaluation of heritable and non-heritable factors. Results from these studies will lead to novel drug discovery and diagnostic platforms against NASH, guided by organoid-based genotype- phenotype association, and, in the long term, transform the hepatology medicine through precision hepatology for the broad spectrum of inflammatory and fibrotic disorders in the liver.

PI_NAMEs: TAKEBE, TAKANORI  (contact)

PROGRAM_OFFICER_NAME: LOH, KATRINA SHUEH WEN

PROJECT_TERMS: Adult;Affect;Biological Models;cell injury;Childhood;Clustered Regularly Interspaced Short Palindromic Repeats;Code;cohort;comorbidity;Complex;Complications of Diabetes Mellitus;Data;Data Engineering;Data Set;Development;diabetic;Diagnostic;diagnostic platform;Diet;Disease;Dissection;drug discovery;Environmental Risk Factor;Epidemic;Evaluation;evidence base;falls;Fatty acid glycerol esters;Fibrosis;Foundations;Future;Generations;Genes;Genetic Predisposition to Disease;genetic regulatory protein;genetic risk factor;genetic variant;genome editing;genome wide association study;Genomics;Genotype;Glucokinase;glucokinase regulatory protein;Glucose;glucose metabolism;Goals;Hepatic;Hepatocyte;Hepatology;Heritability;Histologic;Human;Human Engineering;human induced pluripotent stem cells;human stem cells;human tissue;Impairment;In Vitro;Incidence;Inflammation;Inflammatory;innovation;Insulin;Insulin Resistance;Investigation;lens;Life Style Modification;lipid biosynthesis;lipid metabolism;Liver;liver metabolism;loss of function;Malignant - descriptor;Marketing;Mediating;Medicine;Metabolic;Metabolism;Metformin;Mitochondria;mitochondrial dysfunction;mitochondrial metabolism;Molecular;new technology;non-alcoholic fatty liver disease;Non-Insulin-Dependent Diabetes Mellitus;nonalcoholic steatohepatitis;novel therapeutics;Oleic Acids;Organoids;Oxidative Stress;Pathogenicity;Pathway interactions;Patients;Persons;Pharmaceutical Preparations;Phenotype;Pluripotent Stem Cells;Population;population based;pre-clinical research;Prediabetes syndrome;Predisposition;programs;protein function;Research;response;Risk;risk stratification;risk variant;Role;Severities;Single Nucleotide Polymorphism;Steatohepatitis;stem cell organoids;sugar;System;Testing;Therapeutic;therapy development;transcriptomics;Variant

PROJECT_TITLE: Organoid-guided Precision Hepatology for Steatohepatitis

STUDY_SECTION: HBPP

STUDY_SECTION_NAME: Hepatobiliary Pathophysiology Study Section[HBPP]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Depression;Disability Research;Eye Disease and Disorders of Vision;Genetics;Mental Health;Mental Illness;Neurodegenerative;Neurosciences;Rehabilitation

ORG_CITY: ANN ARBOR

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Narrative The different conditions making up inherited retinal degenerations may lead to distress, depression, and all forms of vison related disabilities, and therefore, represent a group of diseases that can be used to understand how best to intervene with care comprised of low vision rehabilitation and distress alleviating psychotherapy. By studying the patient experience of functional vision deficits and vision-related anxieties, we can provide low vision rehabilitation which will be enhanced with psychotherapy addressing the psychosocial needs of the patient. This project is relevant to the National Eye Institute’s goal to support applied clinical research concerning individual quality of life—with a particular focus on the patient perspective and encompassing blindness rehabilitation and brain plasticity, assistive devices and independent living, while also addressing depression in patients coping with vision loss.

PI_NAMEs: JAYASUNDERA, KANISHKA THIRAN (contact)

PROGRAM_OFFICER_NAME: WIGGS, CHERI

PROJECT_TERMS: Address;Affect;Age;Alcohols;Anxiety;Applications Grants;Behavior;Biological;Biological Response Modifier Therapy;Blindness;Brain;Caring;Categories;Chronic;Clinical;Clinical Research;Cognitive Therapy;comparative;comparative efficacy;Cone;Consumption;coping;Coupled;Cross-Sectional Studies;delivery complications;diet and exercise;disability;Disease;disease model;Disease Progression;Distress;Effectiveness;efficacious treatment;emotion regulation;Emotional;emotional distress;experience;Functional disorder;functional gain;functional improvement;Future;gene therapy;Genetic Predisposition to Disease;Goals;Health;Impairment;improved;Independent Living;Individual;individual patient;individualized medicine;Inherited;inherited retinal degeneration;intervention cost;Legal Blindness;legally blind;Life;Link;Measurable;Measures;Medical Care Costs;meetings;Mental Depression;Methodology;Michigan;Multicenter Trials;National Eye Institute;novel therapeutics;open label;Outcome Measure;Patient Outcomes Assessments;Patients;Peripheral;personalized approach;Persons;Pharmaceutical Preparations;Phenotype;Physiological;Principal Investigator;programs;Provider;psychologic;Psychometrics;psychosocial;Psychotherapy;Quality of life;Questionnaires;Randomized;Recording of previous events;Rehabilitation therapy;Research;Retina;Retinal Degeneration;Retinal Diseases;Retinitis Pigmentosa;Rod;Self-Help Devices;sex;shared decision making;Signal Transduction;stem;Subgroup;success;Testing;Therapeutic;three-arm trial;treatment as usual;Unhealthy Diet;Vision;vision rehabilitation;Visual Acuity;Visual disability;visual dysfunction;Visual Fields;Visual impairment;Well in self;Work

PROJECT_TITLE: Determining optimal vision care for emotionally distressed patients with inherited retinal diseases

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 NV-P (81)]


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Genetics

ORG_DEPT: CHEMISTRY

PHR: PROJECT NARRATIVE Ribonucleic acids (RNAs) are essential molecules responsible for transmitting genetic information, catalyzing reactions, and regulating gene expression, and, consequently, have been linked to bacterial pathogenesis, cardiovascular conditions, neurological disorders, mitochondrial diseases, and cancers. This work will take on questions about the structure, function, and dynamics of mitochondrial transfer RNA (tRNA), the proteins that act on these tRNAs, and associated disease-causing mutations using a combination of biochemistry (e.g., kinetic and binding assays, mass spectrometry) and structural biology (e.g., Cryo- EM, x-ray crystallography). Our studies will reveal how mitochondrial transfer RNAs are recognized and processed and help rationalize how patient-derived mitochondrial tRNA mutations alter tRNA stability and processing, which will allow us to seed the discovery of possible new therapeutic targets to treat mitochondrial diseases.

PI_NAMEs: KOUTMOS, MARKOS  (contact)

PROGRAM_OFFICER_NAME: CZAPLINSKI, KEVIN

PROJECT_TERMS: Affect;Binding;Biochemical;Biochemistry;Biogenesis;Biological;Biological Assay;Biology;biophysical properties;biophysical tools;Biophysics;Cancerous;Cardiovascular system;Cell Nucleus;Cells;Cellular biology;Characteristics;Chemicals;Complex;Cryoelectron Microscopy;Cytoplasm;Darkness;Data;Defect;Development;Disease;disease-causing mutation;DNA Sequence;Enzymes;Essential Hypertension;Etiology;Eukaryota;Excision;Exhibits;Gene Expression;Genes;genetic information;Genetic Transcription;Genome;Genomic approach;Genomic DNA;Health;high throughput screening;Human;improved;Inherited;innovation;Introns;Investigation;Kinetics;Knowledge;Link;Malignant Neoplasms;Mass Spectrum Analysis;Messenger RNA;Methods;MicroRNAs;Mitochondria;Mitochondrial Diseases;Mitochondrial DNA;Mitochondrial Myopathies;Mitochondrial RNA;Modification;Molecular;Molecular Biology;Molecular Chaperones;Molecular Conformation;mutant;Mutation;Nature;Nervous System Disorder;new therapeutic target;novel;Pathogenesis;Pathogenicity;Pathology;Pathway interactions;Patients;posttranscriptional;Process;programs;Property;protein complex;protein protein interaction;Proteins;Rationalization;Reaction;Research;Resolution;Respiration;Ribonucleases;Ribosomal RNA;Ribosomes;RNA;RNase P;Roentgen Rays;Role;single-molecule FRET;structural biology;Structure;Telomerase;Testing;tool;Transfer RNA;transmission process;Variant;Viral Genome;Work;X-Ray Crystallography

PROJECT_TITLE: Structural and functional basis for protein-based eukaryotic RNA processing

STUDY_SECTION: MSFB

STUDY_SECTION_NAME: Macromolecular Structure and Function B Study Section[MSFB]


ADMINISTERING_IC: DC

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

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);Aphasia;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Dementia;Frontotemporal Dementia (FTD);Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Neurodegenerative;Neurosciences;Prevention;Racial and Ethnic Minority Health Research;Rare Diseases;Social Determinants of Health

ORG_CITY: PHILADELPHIA

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: TEMPLE UNIV OF THE COMMONWEALTH

ORG_STATE: PA

PHR: Project Narrative This project will advance our theoretical understanding of human semantic memory while providing a set of diagnostic and clinical tools for detecting age-related cognitive impairment in a longitudinal cohort of older African American adults at high risk for dementia. One of our major goals is to disseminate tools for detecting subtle changes in naturalistic language samples that portend the onset of Alzheimer's Disease or an associated disorder. In addition to characterizing language and language change, we will disseminate a database of pupillary functioning spanning tasks, light reflexes, and rest.

PI_NAMEs: REILLY, JAMES JOSEPH (contact)

PROGRAM_OFFICER_NAME: STORKEL, HOLLY LYNN

PROJECT_TERMS: Acoustics;Address;Adult;African American;Age;age related;Age-associated memory impairment;Aging;Alzheimer's Disease;Area;Arousal;Attention;Black race;causal model;cholinergic;Clinical;Cognition;Cognitive;Cognitive aging;cognitive control;cohort;Communication;Comprehension;Darkness;Data;Databases;Dementia;dementia care;dementia risk;density;Detection;Developed Countries;Development;Diagnostic;Diameter;Disease;Early Diagnosis;Early Intervention;Early treatment;executive function;frontal lobe;Functional disorder;functional loss;Goals;Hearing;Heart Rate;heart rate monitor;high risk;Human;Impairment;indexing;Knowledge;Language;language perception;lexical;Light;Linguistics;Link;Longitudinal cohort;Longitudinal Studies;low socioeconomic status;Measures;Methods;mild cognitive impairment;Minority;Minority Groups;Modeling;Morphology;Mydriasis;Neuropsychology;neurotoxic;Noise;novel therapeutics;older adult;open source;Participant;Pathologic;Performance;Phenotype;Philadelphia;Physiological;Physiology;pollutant;Positioning Attribute;Primary Progressive Aphasia;Process;processing speed;Production;public database;Public Health;Pupil;Race;Reflex action;response;Rest;Sampling;Screening procedure;Semantic memory;semantic processing;Semantics;Series;Short-Term Memory;Signal Transduction;socioeconomics;sound;Speed;Standardization;stimulus processing;Surface;theories;Time;tool;Transcript;Traumatic Brain Injury;Underrepresented Minority;Underrepresented Populations;Underserved Population;United States;vector;vigilance;World Health Organization

PROJECT_TITLE: Early Detection and Treatment of Emerging Cognitive-Linguistic Impairment in Minority Cognitive Aging and Primary Progressive Aphasia

STUDY_SECTION: LCOM

STUDY_SECTION_NAME: Language and Communication Study Section[LCOM]


NIH_SPENDING_CATS: Congenital Structural Anomalies;Kidney Disease;Neurosciences;Pediatric;Polycystic Kidney Disease;Rare Diseases

ORG_CITY: TUCSON

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF ARIZONA

ORG_STATE: AZ

PHR: PROJECT NARRATIVE Polycystic kidney disease (PKD) remains the leading cause of inheritable kidney disease, and the fourth leading cause of end stage renal disease. Outside of chronic dialysis or kidney transplant, prophylactic and intervention treatment targets and options remain limited. These studies will directly address the novel role of renal nerves in PKD progression, and potentially offer a new therapeutic mechanism to target for future PKD treatment.

PI_NAMEs: BANEK, CHRISTOPHER T (contact)

PROGRAM_OFFICER_NAME: MARIC-BILKAN, CHRISTINE

PROJECT_TERMS: Ablation;Address;Adult;afferent nerve;Age;antagonist;Argipressin;argipressin receptor;Autosomal Dominant Polycystic Kidney;Autosomal Recessive Polycystic Kidney;autosome;AVPR2 gene;Bilateral;Blood Plasma Volume;Cardiovascular Diseases;Catheters;Cell Proliferation;Child;Chronic;Clinical;Contralateral;Cyst;Cystic kidney;cytokine;Data;Denervation;Dialysis procedure;Disease;Disease Progression;End stage renal failure;FDA approved;Future;Genes;Hypertension;Hypothalamic structure;Inflammation;Inflammatory;Inherited;innovation;Intervention;Investigation;Kidney;kidney cell;Kidney Diseases;kidney dysfunction;Kidney Transplantation;loss of function mutation;Mediating;Mediator;Modality;Modeling;Molecular;mouse model;Nerve;nerve supply;neural;neurotransmission;novel;novel therapeutics;Osmolalities;Pathogenesis;Pathogenicity;Pathway interactions;patient population;Patients;pharmacologic;Phase;PKD2 protein;polycystic kidney disease 1 protein;Polycystic Kidney Diseases;Polydipsia;Polyuria;Pre-Clinical Model;preservation;pressure;Principal Investigator;Proliferating;prophylactic;Publishing;Quality of life;Rattus;Regulation;Renal function;Reporting;Research;Research Personnel;Research Proposals;response;Role;Sensory;Signal Transduction;Stimulus;success;Symptoms;Techniques;Testing;Therapeutic;Time;Tissues;tolvaptan;Vasopressins

PROJECT_TITLE: Renal Denervation to Treat Polycystic Kidney Disease: Mechanisms and Mediators

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 KUDS-Y (05)]


NIH_SPENDING_CATS: Biomedical Imaging;Biotechnology;Cancer;Digestive Diseases;Immunotherapy;Orphan Drug;Pancreatic Cancer;Rare Diseases

ORG_CITY: LOUISVILLE

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF LOUISVILLE

ORG_STATE: KY

PHR: Project Narrative The overall goal of this proposal is to develop an integrated in vivo imaging with immunophenotyping approach to understand the immune evasion mechanisms of pancreatic cancer and develop more effective therapies for this disease. The successful completion of this study may provide an innovative approach to treating pancreatic cancer, and the knowledge gained from this study may also help us develop a rationally designed intervention for pancreatic cancer patients.

PI_NAMEs: GUO, HAIXUN ;YAN, JUN  (contact)

PROGRAM_OFFICER_NAME: WANG, YISONG

PROJECT_TERMS: Anti-CD47;anti-CTLA4;anti-PD-1;anti-PD-L1;anti-PD-L1 therapy;anti-tumor immune response;antitumor effect;Biological Assay;Cancer Control;cancer immunotherapy;Cancer Model;cancer type;CD44 Antigens;CD8-Positive T-Lymphocytes;CD8B1 gene;Cells;Cessation of life;Classification;Clinical;Clinical Trials;Cytometry;Desmoplastic;Diagnosis;Disease;effective therapy;efficacious treatment;Eligibility Determination;Endothelium;Epidermal Growth Factor Receptor;Epigenetic Process;Excision;Exposure to;Glucans;Goals;Granzyme;imaging approach;Immune;immune checkpoint blockade;Immune Evasion;immune imaging;Immune response;Immunity;Immunologic Memory;Immunologics;Immunophenotyping;Immunotherapeutic agent;Immunotherapy;improved;in vivo imaging;ineffective therapies;Infection;Infiltration;innate immune mechanisms;Innate Immune Response;innovation;insight;intraperitoneal;Investigation;ITGAM gene;Knowledge;KPC model;Label;Liver;lymphatic vessel;Macrophage;Malignant neoplasm of pancreas;Malignant Neoplasms;Measures;Mediating;Memory;Metabolic;Modeling;molecular imaging;Monitor;Monoclonal Antibodies;Monoclonal Antibody Therapy;mouse model;Mus;Myeloid Cells;Myeloid-derived suppressor cells;nanobiologic;Neoplasm Metastasis;novel;novel strategies;novel therapeutics;Organ;Pancreas;pancreatic cancer patients;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma model;Paper;particle;Particulate;Patients;Phagocytes;Phagocytosis;Phase;Phenotype;predictive marker;programmed cell death ligand 1;programs;Publishing;Radiolabeled;rational design;recruit;Reporting;Research;response;Shapes;Signal Transduction;Solid;Solid Neoplasm;Stimulus;subcutaneous;success;Surface;Survival Rate;Symptoms;T cell infiltration;T-Lymphocyte;Testing;therapy design;therapy resistant;Time;Tissues;tool;trafficking;Training;transcriptomics;Treatment Efficacy;treatment response;tumor;Tumor Immunity;tumor progression;Tumor-associated macrophages;tumor-immune system interactions;Tumor-infiltrating immune cells;tumorigenic;Vaccination;Visualization;Yeasts

PROJECT_TITLE: Understanding Pancreatic Cancer Immune Microenvironment and Treatment Response through Integrating in vivo Imaging with Immunophenotyping

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 TIR-W (01)]


NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: NARRATIVE Protein synthesis is a key process in cellular function. A common cause of many genetic diseases is type of harmful mutation which interrupts the formation of many cellular proteins, depriving cells of activities necessary for normal function. In this proposal we seek to broaden our understanding of the mechanisms of protein synthesis and use that understanding to develop therapeutic approaches to overcome these harmful mutations.

PI_NAMEs: COOPERMAN, BARRY S. (contact)

PROGRAM_OFFICER_NAME: VATAKIS, DIMITRIOS NIKOLAOS

PROJECT_TERMS: Affect;Aminoglycosides;Anticodon;Binding;Binding Sites;Biochemical;Biological Assay;biophysical techniques;Catalysis;Cell Extracts;Cell Physiology;Cells;Cellular Assay;Clinical Research;Clinical Trials;Codon Nucleotides;Combined Modality Therapy;Complex;Databases;Development;Disease;Enzymes;Eukaryota;experimental study;Future;Genetic Diseases;Grant;Guanosine Triphosphate;high throughput screening;human disease;improved;In Vitro;inhibitor;Inosine;Interruption;Link;Mammalian Cell;Measurement;Measures;Messenger RNA;Modification;Mutation;Nonsense Codon;novel;novel therapeutic intervention;Nucleotides;Patient Selection;Patients;Pharmaceutical Chemistry;Pharmaceutical Preparations;Phase;Positioning Attribute;posttranscriptional;Predisposition;premature;Process;Prokaryotic Cells;Protein Biosynthesis;Proteins;reaction rate;Reader;reconstitution;release factor;Ribosomes;Sedimentation process;Sense Codon;single molecule;Site;Specificity;stoichiometry;Suggestion;System;Terminator Codon;Testing;Therapeutic;Transfer RNA;Translations;virtual screening;Work

PROJECT_TITLE: Mechanisms of Eukaryotic Translation with a Focus on Induced Nonsense Suppression

STUDY_SECTION: MG

STUDY_SECTION_NAME: Molecular Genetics Study Section[MG]


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

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: PROJECT NARRATIVE Understanding cognitive trajectories associated with cancer and cancer treatment is particularly important among older adults who may be more susceptible to cancer-related cognitive impairment as cancer and cancer treatment potentially accelerate already ongoing aging processes. The overall objective of this proposal is to determine risk and biological mechanisms linking cancer, cancer treatment and cognitive functioning. This work may identify susceptibility factors for cognitive trajectories in older adults diagnosed with cancer which may be leveraged to risk-stratify individuals for cognitive decline and develop modifiable targets for intervention.

PI_NAMEs: ORCHARD, SUZANNE GAYE;WARNER, ERICA T (contact)

PROGRAM_OFFICER_NAME: GREEN, PAIGE A

PROJECT_TERMS: Acceleration;Address;Affect;Aftercare;Age;aged;aging process;Alzheimer's Disease;Alzheimer's disease related dementia;Amyloid beta-Protein;Aspirin;Australia;Biological;Biological Assay;Biological Markers;Blood;Blood specimen;Breast;cancer diagnosis;Cancer Patient;cancer risk;cancer therapy;cancer type;cancer-related cognitive impairment;Cardiovascular Diseases;Clinical;Cognition;Cognitive;cognitive change;cognitive function;Data;Data Set;Dementia;dementia risk;Detection;Development;Diagnosis;Diagnostic;Diagnostic Factor;Dose;Early Diagnosis;Education;Elderly;Enrollment;Event;executive function;Female;follow-up;Follow-Up Studies;Genotype;Glial Fibrillary Acidic Protein;Hematopoiesis;Hematopoietic stem cells;high risk population;High-Risk Cancer;human old age (65+);Impaired cognition;improved;Independent Living;Individual;Inflammation;Integration Host Factors;Intervention;Investigation;Light;Link;longitudinal, prospective study;Longterm Follow-up;Malignant Breast Neoplasm;Malignant Neoplasms;Measures;Mediating;Memory;Methodology;Minority;Mutate;neural;neurofilament;neuropathology;novel;novel marker;older adult;Older Population;Outcome;Participant;Persons;Phase;physically handicapped;Placebos;polygenic risk score;Predisposition;premalignant;Prevention;Probability;prospective;Quality of life;Random Allocation;Recording of previous events;Research Design;Resources;response;Risk;Risk Factors;risk stratification;risk variant;sex;Speed;study population;Survivors;tau-1;United States;Work

PROJECT_TITLE: Impact of Cancer on Cognitive Trajectories in Older Adults

STUDY_SECTION: NMBH

STUDY_SECTION_NAME: Neurological, Mental and Behavioral Health Study Section[NMBH]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Drug Abuse (NIDA only);Opioid Misuse and Addiction;Opioids;Pain Research;Substance Misuse

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: Narrative Opioids are commonly prescribed for a variety of pain states but are prone to tampering and diversion. Here we propose to develop subcutaneously injectable opioid depots that would provide on-demand adjustable analgesia suitable for the treatment of acute pain, and that would be highly tamper- and diversion-proof. The device would be controlled by a wearable or handheld light source.

PI_NAMEs: KOHANE, DANIEL S (contact)

PROGRAM_OFFICER_NAME: SOUSA, JASON CARLOS

PROJECT_TERMS: Absence of pain sensation;Acute;Acute Pain;Animal Model;Binding;Black race;chronic pain;covalent bond;Deposition;Development;Devices;Dose;Drug Delivery Systems;Drug Kinetics;Drug or chemical Tissue Distribution;Epidemic;experience;Formulation;Health Personnel;Healthcare Systems;High Prevalence;In Vitro;in vivo;Injectable;Injections;Injury;interest;irradiation;Left;Light;light emission;Liposomes;Local Anesthetics;Morphine;nanoparticle;Nerve;Opioid;opioid abuse;opioid use disorder;Oral;Organic solvent product;Overdose;overdose death;Pain;particle;Patient-Controlled Analgesia;Patients;patients who use opioids;Pattern;Performance;Pharmaceutical Preparations;pill;Polymers;Postoperative Pain;Postoperative Period;Predisposition;prescription opioid;prevent;Procedures;Reaction;Reproducibility;Resistance;response;Site;Solvents;Source;Structure;subcutaneous;success;System;Theft;Time;Tissues;virtual;wearable device

PROJECT_TITLE: Depot formulations for on-demand tamper- and diversion-proof delivery of opioids

STUDY_SECTION: DBTD

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


ADMINISTERING_IC: ES

ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Autism;Brain Disorders;Breastfeeding, Lactation and Breast Milk;Endocrine Disruptors;Genetics;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Urologic Diseases

ORG_CITY: MADISON

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: Narrative Lower urinary tract symptoms (LUTS) impose a significant healthcare burden and reduce quality of life yet risk factors are poorly defined. We propose to lead new efforts in understanding whether BK channels, negative regulators of bladder contraction, are a target of PCB induced voiding dysfunction and whether these channels represent a convergent target for gene x environment interactions. We propose to test to test the hypothesis that developmental exposure to PCBs increases bladder contractility leading to overactive voiding symptoms in part by altering BK channel regulatory subunits.

PI_NAMEs: STIETZ, KIMBERLY PRESTON KEIL (contact)

PROGRAM_OFFICER_NAME: SHREFFLER, CAROL A

PROJECT_TERMS: Adult;Affect;Agonist;Alleles;antagonist;autism spectrum disorder;Automobile Driving;Bathing;Biological Assay;Bladder;Bladder Dysfunction;Bladder Tissue;Brain;Calcium;Calcium Signaling;Carbachol;Cholinergic Agonists;clinical heterogeneity;comorbidity;Data;design;Development;Disease Progression;DNA Sequence Alteration;effective therapy;efficacy evaluation;electric field;Environment;Environmental Risk Factor;Etiology;experience;Exposure to;Functional disorder;Future;gene environment interaction;Genes;Genetic;Genetic Predisposition to Disease;Goals;healthcare burden;improved;in utero;in vivo;Incontinence;Individual;individuals with autism spectrum disorder;Intervention;Lactation;large-conductance calcium-activated potassium channels;Lead;Link;lower urinary tract symptoms;Mediating;Mediator;member;mouse development;mouse model;Mus;Muscarinic Acetylcholine Receptor;Muscarinic Antagonists;Muscarinics;Mutation;Nerve;neurotransmission;Nocturia;offspring;Organ;Overactive Bladder;Pathway interactions;patient population;pharmacologic;Phenotype;Physiology;Polychlorinated Biphenyls;Potassium Channel;Predisposition;Purinoceptor;Quality of life;Quantitative Reverse Transcriptase PCR;receptor;Risk;Risk Factors;sensor;Signal Pathway;Smooth Muscle;Stimulus;symptom treatment;Symptoms;Testing;Tissues;Toxic Environmental Substances;voltage;Western Blotting;young adult

PROJECT_TITLE: Impact of developmental polychlorinated biphenyls on bladder contractility

STUDY_SECTION: KUFD

STUDY_SECTION_NAME: Kidney and Urological Systems Function and Dysfunction Study Section[KUFD]


NIH_SPENDING_CATS: Genetics;Human Genome

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: Project narrative Each time a cell divides it must produce an accurate copy of its genome. This process, termed DNA replication, is essential and defects in DNA replication can lead to mutations, chromosomal rearrangements and cancer. This project will use new technology to understand the molecular mechanisms that control how the genome is replicated.

PI_NAMEs: WHITEHOUSE, IESTYN  (contact)

PROGRAM_OFFICER_NAME: REDDY, MICHAEL K

PROJECT_TERMS: Address;Area;Behavior;Biological Assay;Bypass;Cells;Chromatin;Chromatin Structure;Chromosomal Rearrangement;chromosome replication;Complex;Defect;Derivation procedure;Development;Dissection;DNA;DNA analysis;DNA biosynthesis;DNA Damage;DNA mapping;DNA replication fork;DNA Structure;Environment;Event;Foundations;Funding;G-Quartets;Genetic Transcription;Genome;genome-wide;genomic tools;Goals;Grant;helicase;Hybrids;in vivo;Malignant Neoplasms;Maps;Methods;Molecular;Mutation;Nature;new technology;novel;Nuclear;nuclease;Nucleotides;Pathway interactions;Play;Population;Positioning Attribute;prevent;Process;Proteins;Replicon;Reporting;Research;Resolution;RNA;Role;Saccharomycetales;single molecule;Structure;System;Testing;Time;tool;Work

PROJECT_TITLE: Replication Of Chromosomes In Budding Yeast


NIH_SPENDING_CATS: Chronic Pain;Clinical Research;Clinical Trials and Supportive Activities;Digestive Diseases;Microbiome;Nutrition;Pain Research;Pediatric

ORG_CITY: DURHAM

ORG_DEPT: PEDIATRICS

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: PROJECT NARRATIVE Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction that affects up to 20% of school children worldwide. Children and adults with IBS may improve their symptoms when restricting fermentable carbohydrates from their diet – but this restriction is challenging, does not work in all individuals, and may have unintended health consequences. This proposal will begin to investigate a non-dietary restriction therapy by evaluating psyllium (a soluble fiber) given with meals for fermentable carbohydrate (fructan) induced childhood IBS symptoms.

PI_NAMEs: CHUMPITAZI, BRUNO PEDRO (contact)

PROGRAM_OFFICER_NAME: UNALP-ARIDA, AYNUR

PROJECT_TERMS: Abdominal Pain;Address;Adult;Adverse effects;Affect;Age Years;American;Bifidobacterium;Body Weight decreased;Breath Tests;Carbohydrates;Characteristics;Child;Childhood;Clinical;clinical practice;Clinical Trials;Colon;Comparative Study;Consumption;Cross-Over Studies;Data;Defecation;demographics;Diet;dietary;Dietary Intervention;dietary restriction;Disaccharides;Disease;disorders of gut-brain interaction;Dose;Double-Blind Method;experience;Feces;Fermentation;Fiber;Food;Foundations;Frequencies;Fructans;Functional disorder;Future;Gases;gastrointestinal;gastrointestinal symptom;Glucose;Goals;gut microbiome;gut microbiota;Health;improved;Individual;Ingestion;insight;Intervention;Intracolonic;Irritable Bowel Syndrome;Knowledge;Magnetic Resonance Imaging;Measures;microbial;microbial composition;microbiome composition;Mission;Monosaccharides;National Institute of Diabetes and Digestive and Kidney Diseases;novel;novel therapeutics;Oligosaccharides;Outcome;Outcome Measure;Pain;pain reduction;Participant;Patients;Pattern;Physiological;Placebos;polyol;primary outcome;Production;Propionates;Protocols documentation;Psyllium;Publishing;Randomized;Recommendation;Reporting;response;Schools;secondary outcome;sex;soluble fiber;Symptoms;Testing;Viscosity;Volatile Fatty Acids;Water

PROJECT_TITLE: ASSESSING PSYLLIUM GIVEN WITH MEALS FOR FRUCTAN SENSITIVITY IN CHILDREN WITH IRRITABLE BOWEL SYNDROME

STUDY_SECTION: DNPD

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


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Neurosciences;Physical Injury - Accidents and Adverse Effects;Regenerative Medicine;Rehabilitation;Spinal Cord Injury;Traumatic Head and Spine Injury

ORG_CITY: INDIANAPOLIS

ORG_DEPT: NEUROSURGERY

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: Project Narrative: Our recent discovery suggests the SOX2-mediated in vivo reprogramming strategy generated a great number of neurons for neural repair after injury, with reduced astroglial scar. The preliminary experiment clearly showed that reprogramming modulates the inhibitory glia scar to a permissive environment for a robust CST axonal regeneration following spinal cord injury. We will therefore investigate the alteration of the glial scar and pyramidal neurons underwent the reprogramming process, in order to manipulate this process through an optimize the reprogramming strategy to treat SCI.

PI_NAMEs: WU, WEI  (contact)

PROGRAM_OFFICER_NAME: BAMBRICK, LINDA LOUISE

PROJECT_TERMS: Adult;anterograde transport;Area;Astrocytes;Axon;axon growth;axon regeneration;Brain;Cells;Central Nervous System;Cervical;Cervical spinal cord injury;Chemicals;Chronic;Cicatrix;combat;Communication;Corticospinal Tracts;CSPG4 gene;designer receptors exclusively activated by designer drugs;Development;Distal;Distant;Dorsal;Embryo;Endowment;Environment;Epigenetic Process;experimental study;Failure;Forelimb;Generations;Genes;Genetic;hippocampal pyramidal neuron;Immunohistochemistry;in vivo;Injury;injury and repair;Lead;Lesion;mad itch virus;Maps;Mediating;Modeling;Molecular;Motor;Motor Cortex;motor function improvement;Motor Pathways;motor recovery;Mus;Muscle;Natural regeneration;Nerve Regeneration;nerve stem cell;Nervous System;neural circuit;neural repair;neurogenesis;Neuroglia;neuron loss;neuronal cell body;neuronal circuitry;Neurons;optogenetics;Pain;permissiveness;Pilot Projects;Process;programs;Proteins;reconstruction;Recovery of Function;regenerative;Regenerative capacity;Regenerative Medicine;Regulation;repair strategy;Reporting;response;restoration;Reverse Transcriptase Polymerase Chain Reaction;Role;Sensory;Signal Transduction;single-cell RNA sequencing;Site;Spinal;Spinal Cord;Spinal cord injury;Spinal Cord Lesions;Stem Cell Factor;Structure of rubrospinal tract;Synapses;Synaptic Transmission;System;Techniques;Testing;Therapeutic;Three-Dimensional Imaging;Tissues;Tracer;Transplantation;Viral;Virus;Western Blotting;Work

PROJECT_TITLE: Converting the glial scar to neurons repairs the injured neural circuits for functional recovery following spinal cord injury

STUDY_SECTION: CNNT

STUDY_SECTION_NAME: Clinical Neuroplasticity and Neurotransmitters Study Section[CNNT]


ADMINISTERING_IC: AT

IC_NAME: NATIONAL CENTER FOR COMPLEMENTARY & INTEGRATIVE HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Depression;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Major Depressive Disorder;Mental Health;Mental Illness;Pediatric;Physical Activity;Racial and Ethnic Minority Health Research;Rehabilitation;Serious Mental Illness

ORG_CITY: PROVIDENCE

ORG_NAME: BUTLER HOSPITAL (PROVIDENCE, RI)

ORG_STATE: RI

PHR: PROJECT NARRATIVE Even before the onset of the COVID pandemic, adolescent depression has been increasing, and health disparities and disparities in access to treatment have continued to widen. Yoga-based interventions, shown to be effective in treating depression in adults, may be promising in adolescents as well, thus providing an alternative to the already burdened mental health care system. We propose a multisite pilot trial in preparation for an adequately-powered multisite non-inferiority trial of yoga-based intervention vs. group cognitive- behavioral therapy for adolescents with mild to moderate depression.

PI_NAMEs: UEBELACKER, LISA A (contact);YEN, SHIRLEY

PROGRAM_OFFICER_NAME: MUDD, LANAY MARIE

PROJECT_TERMS: acceptability and feasibility;access disparities;Adherence;Adolescent;adolescent health;Adult;African American;Amber;arm;Asian Americans;Black race;Boston;boys;Breathing;child depression;Child Health;clinically significant;Cognitive Therapy;Country;COVID-19;COVID-19 pandemic;depressive symptoms;Diagnosis;Effectiveness;efficacy trial;eligible participant;Ethics;ethnic diversity;Ethnic Origin;Evidence based treatment;Expectancy;experience;feasibility trial;Feedback;Funding;Future;Gender;Geography;girls;Health;health disparity;Health Personnel;Health Services Accessibility;Healthcare Systems;Home;indexing;India;Individual;innovation;instructor;Intervention;Interview;Knowledge;Life;Major Depressive Disorder;Male Adolescents;Manuals;Mental Depression;Mental Health Services;Meta-Analysis;migration;mindfulness;Mood Disorders;Movement;National Center for Complementary and Integrative Health;opioid use disorder;outreach;Participant;Persons;Phase;pilot trial;Preparation;Prevalence;primary outcome;Procedures;programs;Protocols documentation;Psyche structure;Race;racial diversity;Randomized, Controlled Trials;recruit;Research;Sampling;satisfaction;Schools;self-compassion;Severities;Site;Spiritual well-being;Stress and Coping;Students;systematic review;Teenagers;Time;Training;Trauma;treatment group;trend;Underrepresented Populations;virtual;Vulnerable Populations;Work;Yoga;Youth

PROJECT_TITLE: Pilot multisite randomized controlled trial of yoga to reduce depression inadolescents

STUDY_SECTION_NAME: Special Emphasis Panel[ZAT1 MH (05)]


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cancer;Digestive Diseases;Liver Disease;Nanotechnology

ORG_CITY: CHICAGO

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: NARRATIVE Selective bacterial destruction of tumor tissues may offer improved outcomes compared to current chemotherapies for patients with colorectal liver metastasis (CRLM). Image-guided delivery of cyborg C. Novyi- NT functionalized with nanoparticles directly into the tumor blood supply via selectively placed catheters should permit bacteriolytic treatment of CRLM and the treatment efficacy will be further enhanced by blocking blood flow to the metastases after administration of the cyborg bacterial spores. Image guided delivery and follow-up imaging will provide confirmation of cyborg bacteria spore delivery to the metastases and tracking of tumor colonization for early predictions and optimization of patient care.

PI_NAMEs: KIM, DONG-HYUN  (contact)

PROGRAM_OFFICER_NAME: LIN, CHARLES

PROJECT_TERMS: Address;Anaerobic Bacteria;Animal Model;Antibiotics;Area;Bacteria;Bacterial Spores;Blood flow;Catheters;chemotherapy;Clinical;Clinical Trials;Clostridium;Colorectal;Detection;Development;Disease;Dose;Etiology;Excision;Failure;follow-up;Germination;Goals;Hypoxia;Image;image guided;improved;improved outcome;in vivo;Infusion procedures;interest;Intervention;Intra-Arterial Infusions;Intravenous;iron oxide;Lipase;Liver;Location;Magnetic Resonance Imaging;Magnetism;Measurement;Metastatic Neoplasm to the Liver;Methods;Monitor;Multimodal Imaging;nano;nanocomposite;nanoGold;nanomedicine;nanoparticle;Necrosis;Neoplasm Metastasis;neoplastic cell;novel strategies;Oncology;Oncolytic;Operative Surgical Procedures;Outcome;Patient Care;patient prognosis;Patients;Peptide Hydrolases;pre-clinical;Proliferating;Radio-Opaque;Radiology Specialty;Regimen;Rejuvenation;Reproduction spores;Residual Neoplasm;response;Route;Solid Neoplasm;Study models;Survival Rate;systemic toxicity;Therapeutic Embolization;therapy outcome;Toxic effect;Treatment Efficacy;Treatment-related toxicity;tumor;Tumor Debulking;Tumor Tissue;tumor vascular supply;uptake;Vascular blood supply;Visualization

PROJECT_TITLE: Development of Nanofunctionalized Cyborg C-Novyi NT for Image Guided Trans-arterial Bacteriolytic Embolization of Colorectal Liver Metastasis

STUDY_SECTION: INN

STUDY_SECTION_NAME: Innovations in Nanosystems and Nanotechnology Study Section [INN]


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Immunization;Immunotherapy;Nanotechnology;Orphan Drug;Rare Diseases;Skin Cancer;Vaccine Related

ORG_NAME: DANA-FARBER CANCER INST

PHR: Narrative Merkel cell polyomavirus (MCPyV) positive Merkel cell carcinoma (MCC) is an ideal setting for identifying foreign viral epitopes in diverse HLA alleles that can be leveraged to develop targeted immunotherapies, including cancer vaccines. In this context, we propose to predict and physically identify, processed, presented, and conserved promiscuous HLA epitopes originating from MCPyV. We will validate the T cell immunogenicity of these viral epitopes and develop a nanodisc based off-the-shelf MCC cancer vaccine candidate.

PI_NAMEs: KESKIN, DERIN B (contact)

PROGRAM_OFFICER_NAME: BOURCIER, KATARZYNA

PROJECT_TERMS: Adjuvant;Algorithms;Alleles;Antigen Targeting;Antigen-Presenting Cells;Antigens;Automobile Driving;Avidity;Binding;Biotechnology;cancer cell;cancer genome;cancer immunotherapy;Cancer Vaccines;CD8-Positive T-Lymphocytes;Cell Line;Cells;Characteristics;Collaborations;Credentialing;cytotoxic;Development;Disparate;Down-Regulation;Epitopes;Etiology;Gene Mutation;Generations;Genetically Engineered Mouse;Goals;HLA-A gene;Human;Immune Evasion;Immune system;Immune Targeting;Immunity;Immunization;immunogenic;immunogenicity;Immunologic Memory;Immunotherapy;in vivo Model;Incidence;inhibitor;Knowledge;Letters;Lipids;Malignant Neoplasms;Measures;Medical;Memory;Merkel cell carcinoma;Merkel Cells;Methods;MHC Class I Genes;Michigan;mortality;Mucous Membrane;Mus;Mutation;nanodisk;Neuroendocrine Carcinoma;novel;Pathway interactions;Patients;Pediatric Neoplasm;Peptides;Peripheral Blood Mononuclear Cell;Polyomavirus;Population;prediction algorithm;Principal Investigator;Process;prophylactic;Protocols documentation;Reagent;Reporting;Resources;Skin Cancer;Small T Antigen;Standardization;T cell response;T cell therapy;T memory cell;T-Lymphocyte;T-Lymphocyte Epitopes;Testing;Therapeutic;tool;Training;transcriptome;Transfection;tumor;Tumor Cell Line;tumor microenvironment;tumor-immune system interactions;vaccine candidate;vaccine platform;Vaccines;Validation;Viral;Viral Antigens;Viral Tumor Antigens;Virus;Writing

PROJECT_TITLE: Merkel cell polyomavirus HLA class I epitopes for generating therapeutic T cell-based cancer immunotherapy

STUDY_SECTION: CIC

STUDY_SECTION_NAME: Cellular Immunotherapy of Cancer Study Section[CIC]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Digestive Diseases;Emerging Infectious Diseases;Genetics;Infectious Diseases;Rare Diseases

ORG_CITY: SAINT LOUIS

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE Cryptosporidiosis causes diarrheal disease in immunocompromised patients and infants and it is difficult to treat due to poor performance of the only available drug. The proposed studies will develop methods to identify genes that control the severity of infection by the parasite Cryptosporidium. The advances made here could lead to better treatments for cryptosporidiosis.

PI_NAMEs: SIBLEY, L. DAVID (contact)

PROGRAM_OFFICER_NAME: PESCE, JOHN T

PROJECT_TERMS: Agriculture;Air;Alleles;Animals;Antibiotic Therapy;Antibiotics;Arizona;Attenuated;Candidate Disease Gene;Chromosomes;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;CRISPR/Cas technology;Cryptosporidiosis;Cryptosporidium;Cryptosporidium parvum;Development;diarrheal disease;Drug usage;enteric pathogen;Enterocytes;fitness;forward genetics;Genes;Genetic;genetic analysis;genetic approach;Genetic Crosses;Genetic Polymorphism;Genetic Recombination;genome sequencing;Genomic Segment;Human;Immunocompromised Host;immunodeficiency;In Vitro;in vivo;Infant;Infection;Interferon Type II;Intestines;Iowa;Knockout Mice;Laboratories;Life Cycle Stages;Liquid substance;Maps;Mediating;Meiosis;Methods;Molecular;mouse model;Mus;Oocysts;Outcome;Parasites;Parasitic infection;Pathogenicity;Pattern;Performance;permissiveness;Pharmaceutical Preparations;Phenotype;Polymorphism Analysis;Population;Production;Quantitative Trait Loci;Recombinants;Reporter;reverse genetics;Role;segregation;Severities;Single Nucleotide Polymorphism;Sorting;stem cells;Support System;System;Testing;trait;Universities;Variant;Virulence;Virulent;whole genome;Zoonoses

PROJECT_TITLE: Genetic Basis of Host Infectivity by Cryptosporidium

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


NIH_SPENDING_CATS: Biotechnology;Clinical Research;Digestive Diseases;Genetics;Liver Disease;Obesity;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

PHR: Project Narrative Obesity has strong inflammatory underpinnings, which are associated with the development of type 2 diabetes (T2D), non-alcoholic steatohepatitis (NASH), and hepatocellular carcinoma (HCC), however, the mechanisms by which obesity provokes aberrant inflammation have yet to be clearly defined. In this study, we aim to demonstrate that in obesity and hyperinsulinemia, RNA silencing machinery plays a critical role in generating and responding to pro-inflammatory small extracellular vesicles (sEVs) and therefore controls systemic inflammation and glucose metabolism. Our systematic approaches will reveal novel mechanisms of RNA silencing machinery in EV-mediated immunometabolic regulation in obesity and hyperinsulinemia.

PI_NAMEs: NAKAMURA, TAKAHISA  (contact)

PROGRAM_OFFICER_NAME: BASU, RAJATAVA

PROJECT_TERMS: Address;Adipose tissue;Adolescent obesity;Attention;Body Fluids;Cell Line;Cell secretion;cell type;Cells;chronic inflammatory disease;Coupled;CRISPR/Cas technology;crosslink;Data;Development;Distant;Event;Exhibits;exosome;Exposure to;extracellular;Extracellular Space;extracellular vesicles;FRAP1 gene;Functional disorder;Genes;glucose metabolism;Goals;Hepatic;Hepatocyte;Human;human induced pluripotent stem cells;human model;Hyperinsulinism;In Vitro;in vivo;induced pluripotent stem cell;Inflammation;Inflammatory;Inflammatory Response;intercellular communication;Link;Liver;Macrophage;Macrophage Activation;Malignant Neoplasms;Mediating;Mediator;Metabolic Diseases;MicroRNAs;Modeling;Molecular;Monitor;mouse model;mutant;Non-Insulin-Dependent Diabetes Mellitus;nonalcoholic steatohepatitis;novel;obese patients;Obesity;Pancreas;pandemic disease;Pathogenicity;Pathway interactions;Phase;Physiological;Play;Prevalence;Primary carcinoma of the liver cells;Procedures;Production;Proteins;Protocols documentation;Regulation;Research;response;Risk Factors;RNA;RNA Interference;RNA methylation;RNA-Binding Proteins;Role;Sampling;sensor;Solid;stem cell model;System;systemic inflammatory response;Testing;therapeutic target;Thinness;trait;Transducers;Travel

PROJECT_TITLE: RNA silencing machinery in extracellular vesicle-mediated immunometabolic regulation

STUDY_SECTION: BMDM

STUDY_SECTION_NAME: Basic Mechanisms of Diabetes and Metabolism Study Section[BMDM]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

ORG_CITY: HOUSTON

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

ORG_STATE: TX

PHR: Project Narrative The cardiac conduction system is specialized in the generation and propagation of electrical impulses from the atria to the ventricles to produce a highly coordinated muscle contraction. Cardiac conduction disorders (CCDs) are common arrhythmic disorders that impact the contraction of atria or ventricles. Understanding the molecular and cellular mechanisms leading to CCD may provide a foundation for new therapeutic strategies and the proposed work will elucidate the molecular mechanisms by which the mutation in lamin A/C promotes CCD.

PI_NAMEs: CHELU, MIHAIL GABRIEL (contact)

PROGRAM_OFFICER_NAME: TINSLEY, EMILY

PROJECT_TERMS: Action Potentials;Affect;Age;Age Months;alternative treatment;Arrhythmia;ATAC-seq;Atrioventricular Block;atrioventricular node;Attenuated;Bradyarrhythmias;Bundle-Branch Block;calcium-activated potassium channel small-conductance;Cardiac;Cardiac conduction system;cardiac pacing;Cardiomyopathies;Cell Differentiation process;Cells;Cessation of life;Chromatin Structure;citrate carrier;Crossbreeding;Development;Dilated Cardiomyopathy;Dimensions;Disease;Echocardiography;Electrocardiogram;Electrophysiology (science);epigenetic regulation;Family;Fibrosis;Foundations;Functional disorder;Gene Expression;General Population;Generations;Goals;Heart;Heart Atrium;Heart Block;Heart failure;Heart Rate;Heterozygote;histological studies;Histology;imaging study;Impairment;implantation;inducible Cre;Injections;insight;Ion Channel;kindred;Knock-in Mouse;Knockout Mice;Lamin Type A;Lamins;Left;Light;Link;LoxP-flanked allele;Maps;Mediating;Microscopy;Molecular;mouse model;Mus;Muscle Contraction;Mutate;Mutation;Myopathy;Nodal;nodal myocyte;Nonsense Mutation;novel;novel therapeutic intervention;Optics;Pacemakers;patch clamp;Pathogenesis;Pathologic;Pathway interactions;Patients;Phenotype;postnatal;Predisposition;Refractory;Regulation;Reporter;Role;Sick Sinus Syndrome;Skeletal Muscle;standard care;Surface;System;Tamoxifen;Testing;Therapeutic;three dimensional structure;Time;Tissues;transcriptome sequencing;Ventricular;Ventricular Arrhythmia;Work

PROJECT_TITLE: Mechanisms of Lamin A/C-mediated Cardiac Conduction Disorders

STUDY_SECTION: MPPB

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


ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

ORG_STATE: CA

PHR: PROJECT NARRATIVE The mitotic spindle, the football-shaped cellular machine that segregates the replicated chromosomes into the two daughter cells, is formed by microscopic cellular structures called centrosomes, which are comprised of a highly interconnected network of ~150 proteins. Centrosome duplication occurs precisely once every cell cycle to ensure that dividing cells have exactly two centrosomes, and thus two poles of the football-shaped spindle. The goal of this project is to understand how centrosome assembly reactions and the capacity for spindle pole organization are confined to the centrosome, thereby preventing the formation of aberrant multipolar spindles that have the potential to generate cells with inaccurate chromosome numbers and promote tumorigenesis.

PI_NAMEs: OEGEMA, KAREN F (contact)

PROGRAM_OFFICER_NAME: MILLER, RITA K

PROJECT_TERMS: Address;Aneuploidy;Animals;Biochemical;Caenorhabditis elegans;cancer cell;cancer therapy;Cell Cycle;Cell division;Cells;Cellular Structures;Centrioles;Centrosome;Chromosomal Instability;chromosome replication;Chromosome Segregation;Chromosomes;Collection;Complex;Coupled;D Cells;Data;daughter cell;Docking;Drosophila genus;Embryo;Ensure;Event;Family;gamma Tubulin;Generations;Goals;Human;in vivo;interest;Interphase;Knock-out;Malignant Neoplasms;Manufactured football;Mediating;member;Microscopic;Microtubule-Organizing Center;Microtubules;Mitotic;Mitotic spindle;Modeling;mutant;Nature;Pathway interactions;Phosphorylation;Phosphotransferases;PLK1 gene;prevent;Protein Family;Proteins;Proxy;Reaction;recruit;Regulation;Role;scaffold;segregation;Shapes;Site;targeted agent;Tertiary Protein Structure;TRAF Domain;TRIM Family;TRIM Gene;Tubulin;tumorigenesis;ubiquitin ligase;Work

PROJECT_TITLE: Analysis of Centrosome Dynamics

STUDY_SECTION_NAME: Cell Structure and Function 1 Study Section[CSF1]


NIH_SPENDING_CATS: Biotechnology;Hematology;Rare Diseases

PHR: Project Narrative Myeloproliferative neoplasms (MPNs) are clonal hematologic malignancies that cause significant morbidity and have the propensity to transform to acute leukemia. Current treatment options for MPNs are limited. The studies proposed here will provide deeper insights in the pathogenesis of MPNs, and potentially lead to the development of more effective therapies for patients with MPNs.

PI_NAMEs: OH, STEPHEN TRACY (contact)

PROGRAM_OFFICER_NAME: HAILU, BENYAM

PROJECT_TERMS: Ablation;Acute leukemia;Address;Architecture;Biological Assay;Blocking Antibodies;Bone Marrow;CD34 gene;Cell Death;Cell Proliferation;Cells;Cessation of life;Characteristics;Chronic;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;cytokine;Cytometry;Data;Development;Disease;Disease Progression;effective therapy;Engraftment;Enzyme Inhibitor Drugs;Evaluation;experimental study;Functional dependence;Genes;Genetic;genetic manipulation;Grant;Hematologic Neoplasms;Hematological Disease;Hematopoietic stem cells;Human;Image;in vivo;Inflammatory;insight;Interleukin-1;IRAK1 gene;IRAK4 gene;JAK2 gene;Knock-in Mouse;Knockout Mice;Leukocytosis;Malignant - descriptor;Mediating;Modeling;Monitor;Morbidity - disease rate;mouse model;Mus;Mutation;Myelofibrosis;Myeloproliferative disease;NF-kappa B;NFKB Signaling Pathway;novel;Pathogenesis;Pathway interactions;patient derived xenograft model;Patients;pharmacologic;Play;prevent;Production;Proliferating;PTPRC gene;Receptors, Tumor Necrosis Factor, Type II;reduce symptoms;RELA gene;Research Personnel;Role;Signal Pathway;Signal Transduction;small molecule inhibitor;Splenomegaly;Symptoms;Therapeutic;therapeutic target;TNF gene;TNFRSF1A gene;TNFRSF1B gene;transcriptome sequencing;transplant model;Transplantation;Tumor Necrosis Factor Receptor

PROJECT_TITLE: Dysregulated NFkB Pathway Signaling In Myeloproliferative Neoplasms

STUDY_SECTION: HTBT

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


ED_INST_TYPE: GRADUATE SCHOOLS

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);Biotechnology;Brain Disorders;Dementia;Neurodegenerative;Neurosciences

ORG_CITY: NEW YORK

ORG_NAME: ROCKEFELLER UNIVERSITY

PHR: PROJECT NARRATIVE We have shown that the plasma contact system, which regulates both blood clotting and inflammation, is dysfunctional in human patients and mouse models of Alzheimer's disease (AD), a fatal neurodegenerative disorder. We will use various pharmacological and biochemical techniques to define the contribution of this system in AD pathogenesis. We will also examine the potential of inhibiting the contact system as a therapeutic target for AD and explore the mechanism-of-action of lecanemab, a new and promising FDA-approved therapy for AD.

PI_NAMEs: NORRIS, ERIN H;STRICKLAND, SIDNEY  (contact)

PROGRAM_OFFICER_NAME: MCGAVERN, LINDA

PROJECT_TERMS: Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease patient;Alzheimer's disease therapy;Amino Acids;Amyloid;Amyloid beta-Protein;Amyloid beta-Protein Precursor;Animal Model;Antibodies;Antibody Therapy;Binding;Biochemical;Biological Assay;Blood coagulation;Bradykinin;Brain;Brain Pathology;Cessation of life;Cognition;Cognitive;combinatorial;Complex;Contact Inhibition;Cryoelectron Microscopy;defined contribution;Disease;Drug Targeting;Factor XI;Factor XII;FDA approved;Functional disorder;Generations;Goals;Hemorrhage;High-Molecular-Weight Kininogen;Human;Immunoelectron Microscopy;Impaired cognition;improved;in vivo;Inflammation;Inflammatory;inhibitor;Laboratories;Lead;Link;Mediating;mouse model;Mus;Nerve Degeneration;Neurodegenerative Disorders;neuroprotection;neurotoxicity;novel;novel strategies;novel therapeutic intervention;novel therapeutics;Pathogenesis;Pathologic;Pathology;Pathway interactions;Patients;Peptides;pharmacologic;Plasma;Process;protective effect;Role;Surface Plasmon Resonance;System;Techniques;Therapeutic;therapeutic target;Toxic effect;vascular abnormality;vascular inflammation

PROJECT_TITLE: Contact System and Alzheimer's Disease: Mechanism and Therapeutic Potential

STUDY_SECTION: CDIN

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


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Aging;Arthritis;Bioengineering;Clinical Research;Nutrition;Obesity;Osteoarthritis;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: PITTSBURGH

ORG_DEPT: ORTHOPEDICS

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: Currently, no FDA-approved disease-modifying osteoarthritis (OA) drugs are currently available to stop, slow, or reverse the progression of obesity-associated OA. In this study, two hallmarks of obesity, increased mechanical loading and alterations in adipose tissue metabolism, will be modeled in the microphysiological joint chip (miniJoint) as the physiologic stressors of OA. Through the complementary studies in the miniJoint and animal models, the mechanistic basis of obese adipose tissue-mediated pathological changes of joint elements in humans will be elucidated and help develop novel treatments.

PI_NAMEs: BUNNELL, BRUCE A.;GOODMAN, STUART B;LIN, HANG  (contact)

PROGRAM_OFFICER_NAME: ZHENG, XINCHENG

PROJECT_TERMS: Acceleration;Adipose tissue;Aging;analog;Animal Model;Animals;Arthritis;Biological Assay;bone;Cartilage;cartilage degradation;Cell Separation;Cells;Clinical Data;Clinical Trials;cost;Data;Degenerative polyarthritis;design;Development;Disease;disease model;Dose;Drug Screening;Elements;Engineering;epidemiologic data;Exposure to;Fatty acid glycerol esters;FDA approved;Feeds;Genes;Goals;Histology;Human;human induced pluripotent stem cells;human model;human tissue;Immune;In Vitro;in vitro Model;in vivo;induced pluripotent stem cell;Inflammation;Injury;innovation;insight;Interleukin-1 beta;Joints;Knee;Knee Osteoarthritis;Macrophage;mechanical load;Mechanics;Medial meniscus structure;Mediating;Metabolism;Methods;Mobility decline;Modeling;Molecular;Multipotent Stem Cells;Mus;Non obese;novel;novel therapeutics;obese person;Obesity;Operative Surgical Procedures;osteochondral tissue;Overweight;pain reduction;Palmitates;Pathogenesis;Pathologic;Pathway interactions;Performance;Pharmaceutical Preparations;Phenotype;physiologic stressor;Physiological;Physiology;Play;Property;Reporting;response;Risk;Risk Factors;Rodent;Role;Sampling;Saturated Fatty Acids;scaffold;Sodium;stressor;success;Synovial Membrane;Synovitis;System;Testing;therapeutic target;Time;Tissue Sample;Tissues;tool;transcriptome;transcriptome sequencing;transcriptomics;Translations;Undifferentiated;Weight Gain

PROJECT_TITLE: Defining the unique capacity of the miniature joint model for investigating the role of adipose tissue and its impacts on osteoarthritis

STUDY_SECTION: MTE

STUDY_SECTION_NAME: Musculoskeletal Tissue Engineering Study Section[MTE]


NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Networking and Information Technology R&D (NITRD);Social Determinants of Health

ORG_CITY: MINNEAPOLIS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Project Narrative This project will expand and improve the IPUMS Multigenerational Longitudinal Panel (MLP), the world’s largest longitudinal population data system. This massive data collection incorporates hundreds of millions of linked observations drawn from American censuses, surveys, vital records, and administrative data, creating a transformative shared resource for longitudinal analysis of aging and health. The the new data will advance fundamental knowledge about the causes and consequences of changes in health and well-being of the older population and will support research on the effects of public policies, social institutions, and environmental conditions on the health, well-being, and functioning of people, both over the life course and in their later years.

PI_NAMEs: DREW, JULIA AR;RUGGLES, STEVE  (contact);WARREN, JOHN ROBERT

PROGRAM_OFFICER_NAME: BRAUDT, DAVID BRUCE

PROJECT_TERMS: Adult;Aging;aging population;Agreement;Alzheimer's disease related dementia;Alzheimer's disease risk;American;Biological Markers;Birth;Censuses;Cessation of life;Characteristics;Clinics and Hospitals;Cognition;Cognitive;Cohort Studies;Collaborations;Communities;Computer software;cost;cost effective;Data;Data Analyses;data centers;Data Collection;data dissemination;data quality;Data Security;Data Sources;Databases;Death Certificates;Development;early life exposure;economic outcome;Economics;Education;Electronics;Environmental Exposure;Family;Funding;Goals;Health;Health and Retirement Study;Health system;Hospital Records;improved;Individual;Information Systems;Infrastructure;Institution;Institutional Racism;intergenerational;interoperability;Knowledge;late life;Life;Life Cycle Stages;Link;Location;longitudinal analysis;Longitudinal Studies;machine learning method;Maintenance;Manuscripts;Marriage;Methods;Mission;mortality;Older Population;Outcome;Personal Satisfaction;Persons;Policies;Policy Making;Population;Population Process;program dissemination;prospective;Public Policy;Records;Research;Research Infrastructure;Research Personnel;Research Support;Resource Sharing;Resources;Running;Series;social;Social Processes;Social Security;Source;Surveys;System;Toxic Environmental Substances;Training;United States;United States National Center for Health Statistics;Update;virtual;Wisconsin;Work

PROJECT_TITLE: Multigenerational Longitudinal Panel for Research on Aging

STUDY_SECTION: SSPA

STUDY_SECTION_NAME: Social Sciences and Population Studies A Study Section[SSPA]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Coronaviruses;Emerging Infectious Diseases;Genetics;Infectious Diseases;Neurosciences;Post-Acute Sequelae of SARS-CoV-2 infection (PASC) including Long COVID

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

ORG_STATE: NY

PHR: Project Narrative Loss of smell and other neurological symptoms are prevalent in COVID-19 disease and can be long-lasting, significantly impairing quality of life; however, the underlying cellular mechanisms are poorly defined. We will use a new, genetically manipulatable mouse model that is susceptible to SARS-CoV-2 infection to delineate the mechanisms that underly acute and long-term loss of smell and identify the routes by which the virus can invade the brain.

PI_NAMEs: MILLAR, SARAH E. (contact)

PROGRAM_OFFICER_NAME: SULLIVAN, SUSAN L

PROJECT_TERMS: 2019-nCoV;Ablation;ACE2;ACTL6B gene;Acute;Address;Affect;Anosmia;ATAC-seq;Autopsy;Binding;Biological Assay;Brain;brain pathway;cell type;Cells;Central Nervous System Infections;Cerebrospinal Fluid;Chromatin;Complement;COVID-19;COVID-19 patient;COVID-19 susceptibility;Cranial Nerves;cribriform plate;Data;Defect;Dexamethasone;Diffuse;Disease;Dose;Functional disorder;Gene Expression Profile;Genetic;Hamsters;Human;human data;hyposmia;Impairment;Infection;Infiltration;Inflammation;Inflammatory;interest;Invaded;K-18 conjugate;Knock-in Mouse;Knowledge;lymphatic vessel;Maintenance;Methimazole;Modeling;mouse model;Mus;Natural regeneration;neural;Neurologic;Neurologic Symptoms;Neurons;Nose;Odors;olfactory bulb;Olfactory Epithelium;Pathogenicity;Pathology;Patients;Pattern;Penetration;Phenotype;Population;prevent;Publishing;Quality of life;receptor;Respiratory Signs and Symptoms;Route;SARS-CoV-2 B.1.1.529;SARS-CoV-2 infection;secondary infection;single-cell RNA sequencing;stem cells;sustentacular cell;Symptoms;Testing;therapeutic target;Time;Travel;Viral;Virus;Visualization

PROJECT_TITLE: Mechanisms of anosmia and brain infection in a genetic mouse model of COVID-19

STUDY_SECTION: NIC

STUDY_SECTION_NAME: Neuroscience of Interoception and Chemosensation Study Section[NIC]


NIH_SPENDING_CATS: Cardiovascular;Heart Disease

ORG_CITY: Newark

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: Lay summary Heart cells cannot contract strongly in heart failure patients. We will investigate how a molecule important for maintaining a strong heartbeat is damaged by harmful mechanisms and destroyed in the heart during stress Understanding the step-by-step mechanisms by which this key protein in the heart is destroyed during heart failure should provide valuable information for developing a novel intervention to treat heart failure.

PI_NAMEs: SADOSHIMA, JUNICHI  (contact)

PROGRAM_OFFICER_NAME: SCHWARTZ, LISA

PROJECT_TERMS: Acetylation;Affect;Animals;Antioxidants;Attenuated;Binding;Ca(2+)-Transporting ATPase;Cardiac;Cardiac Myocytes;Cessation of life;Complex;Contracts;Cysteine;Dependovirus;Development;Disulfides;Down-Regulation;Endoplasmic Reticulum;FRAP1 gene;HDAC4 gene;Heart;heart cell;Heart failure;heart function;Human;Impairment;In Vitro;Intervention;Knock-in;Knock-in Mouse;Knock-out;Maintenance;Mediating;mouse model;multicatalytic endopeptidase complex;Mus;Myocardial;Myocardial Ischemia;NADPH Oxidase;novel;oxidation;Oxidative Stress;Oxidoreductase;Pathway interactions;Patients;phospholamban;Play;Post-Translational Protein Processing;Predisposition;pressure;prevent;Production;Proteins;Proteolysis;Proteomics;Reactive Oxygen Species;Records;Regulation;response;restoration;reuptake;Role;Ryanodine Receptor Calcium Release Channel;Sarcoplasm;Sarcoplasmic Reticulum;Signaling Molecule;Stress;Sulfhydryl Compounds;Sumoylation Pathway;System;Testing;TXN gene;Ubiquitin;Wild Type Mouse

PROJECT_TITLE: Cysteine oxidation in the heart


NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Coronaviruses;Coronaviruses Therapeutics and Interventions;Emerging Infectious Diseases;Infectious Diseases;Lung;Orphan Drug;Rare Diseases;Rehabilitation

ORG_CITY: CHARLOTTESVILLE

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: Narrative Acute respiratory distress syndrome (ARDS) is a rapidly progressive state of pulmonary failure associated with high morbidity and mortality, and severe cases require prolonged mechanical and ventilator support with limited therapeutic options. In the current proposal, we aim to advance a novel in vivo lung perfusion (IVLP) method as a surgical therapy to treat severe ARDS, including ARDS caused by SARS-CoV-2 infection. This strategy involves the controlled isolated perfusion of injured lungs with Steen solution for the delivery of targeted therapeutics to the injured lung inside the body.

PI_NAMEs: KRON, IRVING L. (contact);LAUBACH, VICTOR E;ROESER, MARK

PROGRAM_OFFICER_NAME: ZHOU, GUOFEI

PROJECT_TERMS: 2019-nCoV;Acute Lung Injury;Acute Respiratory Distress Syndrome;Affect;Alveolar;alveolar epithelium;antagonist;Anti-Inflammatory Agents;Antiinflammatory Effect;aspirate;Attenuated;attenuation;Blood capillaries;Calcium Channel;Cessation of life;Clinical;clinical translation;COVID-19;COVID-19 patient;Edema;Endothelium;Epithelial Cells;Epithelium;experience;Extracorporeal Membrane Oxygenation;Family suidae;Functional disorder;Future;Histology;Hour;improved;in vitro Model;in vivo;in vivo Model;Infection;Inflammation;inflammatory milieu;inhibitor;Injury;Laboratories;Left;Leukocytes;Lipopolysaccharides;Lung;lung basal segment;lung failure;lung injury;lung ischemia;lung microvascular endothelial cells;Lung Transplantation;Measures;Mechanics;Mediating;Methods;Modeling;monolayer;Morbidity - disease rate;mortality;mouse model;Mus;Natural Immunity;Nature;novel;Operative Surgical Procedures;Outcome;Oxidative Stress;Perfusion;Permeability;pharmacologic;Play;porcine model;preservation;Prevention;protective effect;pulmonary function;pulmonary rehabilitation;receptor;Recovery;Regional Perfusion;Rehabilitation therapy;Reperfusion Injury;Reperfusion Therapy;Reproducibility;Risk;Rodent;Role;SARS-CoV-2 infection;Sepsis;sepsis induced ARDS;Signal Pathway;Signal Transduction;Stomach;targeted delivery;targeted treatment;Testing;Therapeutic;Tight Junctions;TLR4 gene;transplant model;Transplantation;treatment strategy;Vanilloid;Vascular Endothelial Cell;Vascular Endothelium;vascular inflammation;Ventilator

PROJECT_TITLE: Targeted treatment of acute lung injury using isolated lung perfusion

STUDY_SECTION: BTSS

STUDY_SECTION_NAME: Bioengineering, Technology and Surgical Sciences Study Section[BTSS]


NIH_SPENDING_CATS: Genetics

ORG_CITY: SALT LAKE CITY

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: PROJECT NARRATIVE The nuclear envelope surrounds the cell’s DNA and is vital to cell function. This research aims to elucidate important steps in correct assembly and maintenance of the nuclear envelope. This work will generate new insight into human diseases associated with mutations in nuclear envelope proteins, as well as shed light on disease states, such as cancer, where rupture of the nuclear envelope can lead to DNA damage.

PI_NAMEs: ULLMAN, KATHARINE S (contact)

PROJECT_TERMS: Address;aging related disease;Alleles;Anaphase;Appearance;Architecture;Cell division;Cell Nucleus;Cell Physiology;Cells;Cellular biology;Chromatin;chromosome missegregation;cofactor;Communication;Complex;Core Protein;Cytoskeleton;Disease;DNA;DNA Damage;Endosomes;Ensure;env Gene Products;Environment;Equilibrium;Eukaryotic Cell;Event;experimental study;Face;Genomic DNA;Genomic Instability;Grant;human disease;improved;insight;Interphase;Knowledge;Label;Laboratories;Learning;Link;Literature;Maintenance;malformation;Malignant Neoplasms;Mammalian Cell;Maps;Mediating;Membrane;Membrane Proteins;micronucleus;Microscopy;Microtubules;Mitosis;Modeling;Molecular;Morphology;Mutation;Nature;Nuclear;Nuclear Envelope;Nuclear Inner Membrane;Nuclear Lamina;Nuclear Pore;Nuclear Pore Complex;Pathologic;Pathway interactions;Play;Pore Proteins;Positioning Attribute;Proteins;recruit;Reporting;Research;resilience;response;Role;Rupture;scaffold;seal;Secure;Site;Sorting;stem;Structure;System;telophase;Testing;Variant;Work

PROJECT_TITLE: Dynamic Events at the Nuclear Envelope during Mitosis and Interphase


NIH_SPENDING_CATS: Autoimmune Disease;Diabetes;Digestive Diseases;Genetics;Pediatric;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

PHR: Type 1 diabetes is an autoimmune disease in which the immune system attacks and destroys the insulin- producing beta cells in the pancreas. Genetic and environmental factors that influence endocrine and exocrine function are likely to play a role in triggering the immune attack. In this study, we propose to analyze the interplay of these factors in human pancreatic tissues.

PI_NAMEs: MILLMAN, JEFFREY ROBERT (contact);TSE, HUBERT M

PROGRAM_OFFICER_NAME: ZAGHLOUL, NORANN

PROJECT_TERMS: Affect;Amylases;Autoimmune Diseases;Autoimmunity;Beta Cell;Biological Assay;cell type;Cells;Chromatin;chronic autoimmune disease;Coculture Techniques;Communities;Coxsackie B Viruses;Cystic Fibrosis Transmembrane Conductance Regulator;cytokine;Data;Data Set;Development;Diabetes Mellitus;Disease;Endocrine;Enhancers;Environmental Risk Factor;Event;Exocrine pancreas;Forskolin;Functional disorder;Gene Expression;Generations;Genes;Genetic;Genetic Transcription;genome wide association study;Genotype;Hormone secretion;Human;human pluripotent stem cell;human tissue;Immune;Immune response;Immune system;improved;induced pluripotent stem cell;Infection;Inflammation;Inflammatory;Inflammatory Response;insight;Insulin;Insulin-Dependent Diabetes Mellitus;Interferon Type II;Interleukin-1 beta;islet;Islets of Langerhans;Lipase;Macrophage;Methods;multidisciplinary;NF-kappa B;novel;Organoids;Pancreas;patient derived induced pluripotent stem cells;Patients;Peptide Hydrolases;Play;Printing;programs;Proteins;Protocols documentation;Reproducibility;Research;Research Design;risk variant;Role;single cell sequencing;stem;Stress;Structure of beta Cell of islet;success;Swelling;System;T-Cell Activation;T-Lymphocyte;Tissues;TNF gene;tool;Transcript;transcriptomics;Variant

PROJECT_TITLE: Uncovering the Interplay Among Pancreatic Tissue Types, Inflammation, and Genotypes in Type 1 Diabetes

STUDY_SECTION_NAME: Special Emphasis Panel[ZDK1 GRB-W (O2)]


PHR: Narrative Open vascular reconstructions, such as bypass grafting and endarterectomy, remain the gold standard of surgical treatments for occlusive cardiovascular diseases. Mitigation of post-surgery neointimal hyperplasia represents an unmet medical need. This project aims to understand the biology behind the epigenetics of neointimal hyperplasia, and to develop a potential effective means to treat neointimal hyperplasia.

PI_NAMEs: GONG, SHAOQIN -;GUO, LIANWANG  (contact);KENT, K CRAIG

PROGRAM_OFFICER_NAME: THAKAR, RAHUL GAUTAM

PROJECT_TERMS: Abate;Address;Adhesives;Animal Model;Arterial Injury;Arteries;aurora B kinase;Benefits and Risks;Biochemical;Biodistribution;Biological Assay;Biology;Blood Vessels;Bypass;Cardiovascular Diseases;Cell Physiology;Clinical;clinical translation;cofactor;Data;design;Development;Disease;Drug Delivery Systems;Drug Modelings;drug release kinetics;Endarterectomy;Engineering;Enhancers;Epigenetic Process;epigenomics;Failure;Financial cost;Formulation;gain of function;Gene Activation;Gene Expression;Genes;Goals;Histone Code;Human;Hydrophobicity;Hyperplasia;improved;In Vitro;in vivo;inhibitor;innovation;Investigation;Knock-out;Knockout Mice;local drug delivery;Measures;Medical;Methods;Micelles;Modeling;Molecular;mouse model;multidisciplinary;Mus;nanoparticle;nanotechnology platform;novel;Obesity;Operative Surgical Procedures;Pathogenesis;Pathogenicity;Pathway interactions;Patients;Pharmaceutical Preparations;pharmacologic;Phenotype;Physiology;preclinical evaluation;preclinical study;prevent;Prevention;Proteins;prototype;Rattus;Reagent;reconstruction;Role;Safety;Smooth Muscle Myocytes;Sprague-Dawley Rats;Stenosis;Surface;Surgeon;systemic toxicity;telomere;Testing;Therapeutic;Tissues;Toxic effect;transcriptomics;Translations;Vascular Smooth Muscle;Vein graft;Virus Activation;Zucker Rats

PROJECT_TITLE: Epigenetic targeting and nanoplatform-enabled local drug delivery - a two-pronged approach to stenosis prevention after vascular surgery

STUDY_SECTION: SAT

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


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Bioengineering;Brain Disorders;Intellectual and Developmental Disabilities (IDD);Mental Health;Nanotechnology;Neurosciences;Pediatric;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: Nashville

ORG_NAME: VANDERBILT UNIVERSITY

ORG_STATE: TN

PHR: NARRATIVE Abnormalities with synaptic proteins have been identified in multiple neurological and developmental disorders including intellectual disability, autism spectrum disorder, and schizophrenia. Our proposed studies aim to understand molecular and cellular mechanisms of abnormal molecular assemblies at synapses in neurodevelopmental disorders. This research will have the potential to develop new therapeutic strategies to modulate neuronal activity against relevant neurological disorders.

PI_NAMEs: ZHOU, QIANGJUN  (contact)

PROGRAM_OFFICER_NAME: DRISCOLL, JAMIE DANIELLE

PROJECT_TERMS: 3-Dimensional;Address;Adhesions;Affect;Architecture;autism spectrum disorder;Biochemical;Biological Assay;Brain;Cell Adhesion Molecules;cell fixing;cellular imaging;Child;cryogenics;Defect;density;Development;developmental disease;Disease;disease-causing mutation;DLG4 gene;Docking;electron tomography;Electrophysiology (science);Excitatory Synapse;Functional disorder;Genes;genetic variant;Genetic Variation;Glutamate Receptor;Goals;Health;Human;Image;In Situ;Individual;Inherited;innovation;Intellectual functioning disability;interdisciplinary approach;Investigation;Knowledge;Laboratories;Learning;link protein;macromolecular assembly;mass spectrometer;Mass Spectrum Analysis;Membrane;Methods;Molecular;Molecular Abnormality;molecular assembly/self assembly;nano;nanocluster;nanocolumn;nanometer resolution;nanoscale;Nanostructures;Nerve;Nervous System Disorder;neural network;Neurodevelopmental Disorder;Neurons;neuropsychiatric disorder;Neurosciences;neurotransmitter release;new therapeutic target;novel therapeutic intervention;Pathogenesis;pharmacologic;Physiological;Physiology;Positioning Attribute;postsynaptic;postsynaptic density protein;Postsynaptic Membrane;presynaptic;Proteins;Rattus;receptor;reconstitution;Regulation;Research;Research Personnel;Resolution;Sampling;Schizophrenia;Scientific Advances and Accomplishments;Series;Site;structural biology;Structure;success;superresolution imaging;Symptoms;Synapses;Synaptic Cleft;synaptic function;Synaptic plasticity;Synaptic Transmission;Synaptic Vesicles;Synaptosomes;therapeutic development;Training;transmission process;Variant;vesicular release;Visualization

PROJECT_TITLE: Synaptic nanostructure and dysfunction in neurodevelopmental disorders

STUDY_SECTION: NC

STUDY_SECTION_NAME: Neuronal Communications Study Section[NC]


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

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

PHR: Narrative The current standard of care for evaluation and surveillance of regional and metastatic disease in head and neck squamous cell carcinoma is 18F-FDG PET/CT scan, which is highly sensitive but not specific. Due to its nonspecific targeting of any tissue with high metabolism, FDG PET/CT produces a significant number of indeterminate findings and is of limited use for detecting tumors located in areas of high metabolic activity. To address this, we propose that imaging using a tumor-specific PET radiopharmaceutical can improve diagnostic specificity in head and neck cancer patients.

PI_NAMEs: ROSENTHAL, EBEN L. (contact)

PROGRAM_OFFICER_NAME: TANDON, PUSHPA

PROJECT_TERMS: Address;Antibodies;Anxiety;Area;Biopsy;Cancer Detection;Cancer Patient;Caring;Cervical Squamous Cell Carcinoma;Classification;Clinical;Clinical Trials;cost;Detection;Diagnosis;Diagnostic;diagnostic accuracy;Diagnostic Specificity;Disease;Disseminated Malignant Neoplasm;effectiveness evaluation;Enrollment;Epidermal Growth Factor Receptor;Evaluation;Excision;fluorodeoxyglucose;fluorodeoxyglucose positron emission tomography;follow-up;General Anesthesia;Head and Neck Cancer;head and neck cancer patient;Head and Neck Squamous Cell Carcinoma;Head and neck structure;Image;imaging detection;imaging modality;improved;Intraoperative Care;Investigation;Lesion;Malignant Neoplasms;malignant oropharynx neoplasm;Metabolic;Metabolism;Metastatic Neoplasm to Lymph Nodes;molecular imaging;Nature;Neck;Neoplasm Metastasis;non-invasive imaging;novel;Oropharyngeal Neoplasms;Outcome Measure;panitumumab;Patients;PET/CT scan;Phase;Positron-Emission Tomography;Predictive Value;prevent;Primary Neoplasm;Procedures;Radiolabeled;Radiopharmaceuticals;Research Personnel;Screening procedure;Sensitivity and Specificity;Specificity;standard of care;Tissues;tongue root;Tonsil;tumor;unknown primary Carcinoma;Unnecessary Procedures;X-Ray Computed Tomography;Zirconium

PROJECT_TITLE: Secondary Molecular Imaging (SMI) for head and neck cancer

STUDY_SECTION: IGIS

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


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

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: PROJECT NARRATIVE Glaucoma, a leading cause of blindness, is caused by the loss of retinal ganglion cells (RGC), which can continue despite clinical treatment to reduce intraocular pressure (IOP). We identified novel neuroprotective drugs that prevent RGC loss even when IOP is elevated, and developed a long-lasting, gel-forming eye drop technology for efficacious drug delivery to the posterior segment. We expect our system to be synergistic with current IOP- lowering glaucoma therapies, resulting in an improved treatment for glaucoma.

PI_NAMEs: ENSIGN, LAURA  (contact);HANES, JUSTIN S.

PROGRAM_OFFICER_NAME: SONG, HONGMAN

PROJECT_TERMS: absorption;Affect;Agreement;albino mouse;albino rat;Alzheimer's Disease;analog;Animals;axon injury;Back;Binding;blind;Blindness;candidate identification;Cell Death;Cell Survival;Cells;Cessation of life;Choroid;Clinical Treatment;Complement;Cytoprotection;Data;design;Deterioration;Dose;drug action;Drug Delivery Systems;Drug Kinetics;Drug Targeting;Evaluation;Eye;Eyedrops;Family suidae;FDA approved;Formulation;Frequencies;functional genomics;Fundus;Gel;Glaucoma;Goals;Head;Human;improved;In Situ;in vitro Model;in vivo;Injections;kinase inhibitor;Lead;Leucine Zippers;Maintenance;Measures;Mediator;Melanins;Methods;Modeling;Morphology;mouse model;Mus;Nerve Crush;Nerve Degeneration;Neurodegenerative Disorders;Neurons;neuroprotection;Neuroprotective Agents;novel;novel therapeutics;ocular surface;Optic Nerve;optic nerve disorder;Oryctolagus cuniculus;Pathway interactions;Patient Compliance;Patient risk;Patient-Focused Outcomes;Patients;Penetration;Persons;Pharmaceutical Preparations;Phosphotransferases;Physiologic Intraocular Pressure;predictive modeling;preservation;pressure;prevent;Property;Protective Agents;protective effect;protein kinase inhibitor;Rattus;Regimen;response;Retina;Retinal Ganglion Cells;Rodent;Rodent Model;Safety;safety assessment;Saline;Scientist;screening;Signal Transduction;Specificity;Structure;System;Technology;Testing;Therapeutic;Thinness;Tissues;Topical application;Toxic effect;treatment strategy;uptake;Vision;Visual;Visual Fields

PROJECT_TITLE: Topical drug delivery formulations for neuroprotection in glaucoma

STUDY_SECTION_NAME: Pathophysiology of Eye Disease - 2 Study Section[PED2]


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Biotechnology;Cancer;Digestive Diseases;Immunotherapy;Liver Cancer;Liver Disease;Nanotechnology;Orphan Drug;Rare Diseases

PHR: NARRATIVE  We propose image guided transcatheter intra-arterial (IA) delivery of Z-domain mediated aPD-L1 conjugated ferumoxytol (aPD-L1-Z-Fer) permitting combinational local immune checkpoint blockade (ICB) immunotherapy and irreversible electroporation (IRE) of hepatocellular carcinoma. Selective transcatheter IA delivery of our aPD-L1-Z-Fer in a combination with immunogenic IRE treatment will permit efficient local delivery of immunostimulatory ICB molecules, allow an increase in the dosage and improve their safety profile. This salient combination of local ICB immunotherapy and immunogenic IRE offers the potential to significantly improve longitudinal treatment outcomes in liver cancer.

PI_NAMEs: KIM, DONG-HYUN  (contact)

PROGRAM_OFFICER_NAME: HU, ZHANG-ZHI

PROJECT_TERMS: Ablation;Aftercare;Animal Model;anti-cancer;anti-cancer therapeutic;anti-PD-1;anti-PD-L1;anti-PD-L1 therapy;Antibodies;BAY 54-9085;Binding;Binding Proteins;Cancer Etiology;Catheters;Cessation of life;Clinical;Clinical Trials;Combination immunotherapy;Combined Modality Therapy;curative treatments;cytokine;dosage;Dose;Electroporation;Electroporation Therapy;Engineering;Excision;Fc domain;FDA approved;ferumoxytol;Human;image guided;imaging properties;Immobilization;Immune;immune activation;immune checkpoint;immune checkpoint blockade;Immune checkpoint inhibitor;Immune response;Immune system;immune-related adverse events;immunogenic;immunogenic cell death;Immunoglobulin G;Immunohistochemistry;Immunologics;Immunotherapy;improved;in vivo;Intervention;Intra-Arterial Infusions;iron oxide nanoparticle;Ligands;liver cancer model;Local Therapy;Magnetic Resonance Imaging;Malignant neoplasm of liver;Malignant Neoplasms;Measurement;Mediating;Monitor;Monoclonal Antibodies;nanocarrier;Nanoimmunotherapy;Nivolumab;Normal tissue morphology;novel strategies;Oncology;Patients;Primary carcinoma of the liver cells;Procedures;programmed cell death ligand 1;programmed cell death protein 1;Protocols documentation;Radiology Specialty;Resistance;response;Rodent Model;Safety;Site;targeted delivery;Testing;Therapeutic Effect;therapy outcome;Transplantation;Treatment Efficacy;Treatment outcome;tumor;tumor hypoxia;Tumor Immunity;tumor microenvironment;Tumor Tissue;tumor-immune system interactions;Tumor-infiltrating immune cells;Up-Regulation

PROJECT_TITLE: Transcatheter Intra-Arterial Delivery of Oriented Anti-PD-L1 Immune checkpoint inhibitors Immobilized Nanocarriers for Local Combination Immunotherapy of Hepatocellular Carcinoma

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 TIO-D (01)]


NIH_SPENDING_CATS: Autoimmune Disease;Diabetes

ORG_NAME: UNIVERSITY OF CHICAGO

PHR: PROJECT NARRATIVE Type 1 diabetes results from the autoimmune destruction of the islet beta cell mediated in part by beta-cell dysfunction prior to autoimmune attack. Polyamine and hypusine production are important for the translation of a subset of RNAs involved in the unfolded protein response, ER stress, and cytokine response in the beta cell. Using novel mouse models and human samples, we will interrogate the polyamine/hypusine pathway specifically in the beta cell during the pathogenesis of type 1 diabetes.

PI_NAMEs: TERSEY, SARAH A. (contact)

PROGRAM_OFFICER_NAME: WANG, XUJING

PROJECT_TERMS: acute stress;Address;Adult;Amines;Amino Acids;Anabolism;Apoptotic;Applications Grants;Arginine;Autoimmune;autoimmune pathogenesis;Autoimmunity;B-Lymphocytes;Beta Cell;biological adaptation to stress;Cell Death;Cell Physiology;Cells;Cessation of life;Chronic stress;cytokine;Cytokine Activation;Data;Defect;deoxyhypusine synthase;Development;Diabetes Mellitus;diabetes pathogenesis;Diet;Disease;DL-alpha-Difluoromethylornithine;DNA biosynthesis;efficacy evaluation;eIF-5A;Endoplasmic Reticulum;endoplasmic reticulum stress;Enzymes;Functional disorder;Genetic;Genetic Transcription;Health;Human;human model;hypusine;immune activation;immunogenicity;Immunophenotyping;Inbred NOD Mice;Incidence;Inflammation;Inflammatory;inhibitor;Insulin;Insulin deficiency;insulin dependent diabetes mellitus onset;Insulin Resistance;Insulin-Dependent Diabetes Mellitus;Intervention;islet;Islets of Langerhans;lymph nodes;Mediating;Messenger RNA;misfolded protein;Molecular;Monitor;mouse model;mRNA Translation;Mus;neoantigens;Non-Insulin-Dependent Diabetes Mellitus;novel;Ornithine Decarboxylase;Pathogenesis;Pathway interactions;Phase;Polyamines;Prediabetes syndrome;preservation;Prevalence;Production;Proinsulin;Proteins;Putrescine;Reagent;Resolution;response;Ribosomes;RNA;Role;Sampling;Signal Pathway;Signal Transduction;small molecule;small molecule inhibitor;Spermidine;Spermine;Spleen;Stress;T cell response;Techniques;Technology;Testing;tool;translation factor;Translations;Treatment Efficacy

PROJECT_TITLE: The Role of Polyamines and Hypusine in Beta-Cell Dysfunction