ED_INST_TYPE: OVERALL MEDICAL

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Cerebrovascular;Dementia;Genetics;Neurodegenerative;Neurosciences;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: HOUSTON

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: UNIVERSITY OF TX MD ANDERSON CAN CTR

PHR: Projective Narrative Alzheimer's disease (AD) and related forms of dementia are a major public health concern. The goal of the proposed studies is to examine the mechanism and consequences of AD pathology in chimpanzees, the only other living species that naturally develops this disease. Identifying similarities and differences between human and chimpanzee AD may provide important information on the factors that contribute to the profound loss in cognitive functions in human AD.

PI_NAMEs: HOPKINS, WILLIAM D (contact)

PROGRAM_OFFICER_NAME: OPANASHUK, LISA A

PROJECT_TERMS: abeta accumulation;abeta deposition;accelerated epigenetic aging;Acceleration;Age;age difference;age related;age related changes;aged;Aging;Alzheimer like pathology;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease patient;Alzheimer’s disease biomarker;Amyloid beta-42;Amyloid beta-Protein;Animal Model;Animals;astrogliosis;Autopsy;Behavior;behavior test;Behavioral;Biocompatible Materials;biological age;Biological Markers;Biology of Aging;Blood Vessels;Brain;Brain Diseases;brain morphology;Cell Death;Cells;Cerebral Amyloid Angiopathy;Cerebrovascular system;Characteristics;Chronology;Cognition;Cognitive;cognitive change;Cognitive deficits;cognitive function;cognitive performance;cognitive testing;cohort;Cohort Effect;Communities;Comparative Biology;Data;Dementia;density;Deposition;Deterioration;Disease;Elderly;Electron Microscopy;Epigenetic age;epigenetic clock;Epigenetic Process;Etiology;Exhibits;experience;Future;Genetic;Genome;glial activation;Goals;gray matter;Health;Human;human disease;Impaired cognition;Individual;individual variation;Inflammatory;insight;Knowledge;LDL-Receptor Related Protein 1;Lesion;life span;Lipoprotein Receptor;Longevity;Mammals;Measures;Mediating;Memory;Memory impairment;Methylation;Mitochondria;mitochondrial dysfunction;Modeling;Motor Skills;Nerve Degeneration;Neurofibrillary Tangles;neuroinflammation;Neurologic;neuron loss;Neurons;neuropathology;Neuropathy;neurovascular;nonhuman primate;Pan Genus;Pathologic;Pathology;Pattern;Performance;Pericytes;Phosphorylation;Play;Pongidae;Population;Prefrontal Cortex;Primates;Process;Proteins;Public Health;Regression Analysis;Research;Resources;Rodent;Sampling;Senile Plaques;Series;Site;Smooth Muscle Myocytes;species difference;Synapses;tau Proteins;Testing;Therapeutic Intervention;tissue biomarkers;translational study;translational therapeutics;Variant;walking speed;web portal;white matter

PROJECT_TITLE: Alzheimer's Disease Pathology in a Primate Model

STUDY_SECTION: ASG

STUDY_SECTION_NAME: Aging Systems and Geriatrics Study Section[ASG]


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: Biotechnology;Cancer;Cancer Genomics;Genetics;Human Genome;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: CORAL GABLES

ORG_COUNTRY: UNITED STATES

ORG_DEPT: PATHOLOGY

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

ORG_STATE: FL

PHR: Narrative The proposed studies are relevant to public health, because discovery of novel means to treat Ewing sarcoma, exerting fewer deleterious sequelae in survivors, represents a significant unmet need in pediatric oncology. This work is thus relevant to NIH’s mission, in the context of supporting research to identify cures for human disease.

PI_NAMEs: LOMBARD, DAVID BENNER (contact);NEAMATI, NOURI

PROGRAM_OFFICER_NAME: AGYIN, JOSEPH KOFI

PROJECT_TERMS: Acceleration;Affect;analog;Apoptosis;Apoptotic;ATAC-seq;Biological;Biology;bone;Bone neoplasms;Bone Tissue;Cardiovascular Diseases;Cell Survival;cell type;Cells;Cessation of life;Charge;Child;Chromatin;Chromatin Structure;Clinical;Clinical Trials;Cytotoxic Chemotherapy;Data;Disease;Drug Kinetics;Drug Targeting;druggable target;Enhancers;epigenomics;Ewings sarcoma;EWSR1 gene;experimental study;Family;Family member;FDA approved;FLI1 gene;fusion gene;Fusion Oncogene Proteins;Future;Gene Expression;Gene Expression Profile;Gene Expression Regulation;Gene Family;Genes;Genetic Transcription;genome-wide;Goals;Growth;Health;histone modification;Histones;human disease;Impairment;improved;In Vitro;in vivo;inhibitor;innovation;insight;Knockout Mice;Libraries;Link;Localized Disease;long-term sequelae;loss of function;Lysine;Malignant Childhood Neoplasm;Malignant Neoplasms;Maps;Mass Spectrum Analysis;Maximum Tolerated Dose;Microsomes;Mission;Modality;Modification;Mus;new therapeutic target;Normal Cell;novel;novel therapeutic intervention;Nuclear;Oncogenic;Operative Surgical Procedures;Pathway interactions;Patients;Pediatric Oncology;Pharmaceutical Chemistry;Pharmaceutical Preparations;Phenotype;Post-Translational Protein Processing;Prognosis;programs;Property;Proteins;Proteomics;Public Health;Publishing;Quality of life;Radiation;Reader;Recurrence;Relapse;Research;Research Support;Role;Second Primary Cancers;side effect;Sirtuins;Site;small molecule;soft tissue;Specificity;Structure;Survival Rate;Survivors;Testing;Therapeutic;therapeutic target;tool;transcription factor;transcriptome;transcriptome sequencing;transcriptomics;tumor;United States National Institutes of Health;Western Blotting;Work;young adult

PROJECT_TITLE: SIRT5 inhibitors and degraders as novel treatments for Ewing sarcoma

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics - 2 Study Section[MCT2]


ADMINISTERING_IC: AI

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Contraception/Reproduction;Genetics;Infectious Diseases;Rare Diseases;Vector-Borne Diseases

ORG_CITY: UNIVERSITY PARK

ORG_DEPT: BIOLOGY

ORG_NAME: PENNSYLVANIA STATE UNIVERSITY, THE

ORG_STATE: PA

PHR: Project Narrative: Mosquitoes infected with the natural bacterium Wolbachia are currently released worldwide to curb the transmission of Zika and dengue viruses. Wolbachia rapidly spread through host populations by manipulating sexual reproduction to enhance their own maternal transmission. This research will evaluate the initial modifications to sexual reproduction that ultimately enable Wolbachia to spread, self-sustain at high frequencies, and protect local communities from mosquito-borne diseases.

PI_NAMEs: BORDENSTEIN, SETH R (contact)

PROGRAM_OFFICER_NAME: COSTERO-SAINT DENIS, ADRIANA

PROJECT_TERMS: Ablation;Antibodies;Arbovirus Infections;Arboviruses;Arthropods;Bacteria;Bacteriophages;base;Biological Assay;Cells;Cessation of life;Chromatin;Communities;cost effective;Culex pipiens;Culicidae;Cytoplasm;Defect;Dengue;Dengue Virus;Deposition;Deubiquitination;Development;DNA;Drosophila melanogaster;egg;Embryo;Embryonic Development;Event;experimental study;Female;Fertilization;Filtration;fitness;forgetting;Frequencies;gene product;Genes;Genetic;Genetic Models;Genotype;Germ Cells;Immunoprecipitation;Impairment;Individual;Inherited;Injections;interest;knock-down;Knock-out;Lead;Link;male;Mass Spectrum Analysis;Mitotic;Modification;Monitor;Mosquito-borne infectious disease;Names;novel;Nuclear Envelope;Ovary;pandemic disease;particle;Partner in relationship;Pathogenicity;Pattern;Phenotype;Pilot Projects;Population;Population Programs;Population Replacements;Population Sizes;Prevalence;Process;programs;Property;Protamines;protein complex;protein protein interaction;Proteins;Reproduction;reproductive;Research;Research Project Grants;Resistance;RNA Viruses;Scholarship;Seminal Vesicles;sex;Sexual Reproduction;sperm cell;Spermatogenesis;System;Testis;tool;Toxin;Transgenes;Transgenic Organisms;transmission process;Travel;vector control;Vectorial capacity;wasting;Wolbachia;ZIKA;Zika Virus

PROJECT_TITLE: The Mechanism of Cytoplasmic Incompatibility

STUDY_SECTION: VB

STUDY_SECTION_NAME: Vector Biology Study Section[VB]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Bioengineering;Genetics;Human Genome;Machine Learning and Artificial Intelligence;Prevention

ORG_CITY: ANN ARBOR

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Project Narrative Dominance plays a vital role in human evolutionary genetics both in terms of its fitness effect on functional genomic variants and how it shapes complex trait phenotypes, while its distribution on the human genome and biological effects on complex traits are poorly characterized. This work will fill a critical knowledge gap by producing a complete picture of dominance distribution in humans, which will shed a light into many unsolved questions in genetics, including the evolution of dominance. This work will further provide comprehensive statistical frameworks to model the relationship between dominance and complex trait phenotypes, which will substantially improve the transferability of biomedical applications in historically understudied populations, including disease risk prediction and the development of precision medicine.

PI_NAMEs: ZHANG, XINJUN  (contact)

PROGRAM_OFFICER_NAME: MASKERI, BAISHALI

PROJECT_TERMS: Accounting;Address;Admixture;Affect;biobank;Biological;Biology;Collaborations;Communities;Complex;Computing Methodologies;Data Analyses;Demography;Development;Disease;disorder risk;Ecology;European;Evolution;experience;fitness;functional genomics;Genetic;genetic variant;Genome;genome wide association study;genome-wide;genomic data;Genomic Segment;Genomics;Human;Human Genome;human population genetics;improved;Individual;insight;Journals;Knowledge;Machine Learning;machine learning method;Mentors;Methods;Minority Groups;Modeling;Modernization;Mutation;novel;Outcome;Pattern;Phase;Phenotype;Play;polygenic risk score;Population;Population Genetics;Population Heterogeneity;precision medicine;predictive modeling;Recording of previous events;Reporting;Research Personnel;Research Training;Resolution;risk prediction;Role;Series;Shapes;simulation;Statistical Methods;Study Subject;Testing;Training;training opportunity;trait;Variant;Work

PROJECT_TITLE: Dominance on the Human Genome and Non-additive Polygenic Models for Predicting Complex Traits

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


ADMINISTERING_IC: HL

ED_INST_TYPE: SCH OF HOME ECON/HUMAN ECOLOGY

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Behavioral and Social Science;Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Heart Disease;Obesity;Physical Activity;Prevention

ORG_CITY: AMES

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: IOWA STATE UNIVERSITY

ORG_STATE: IA

PHR: PROJECT NARRATIVE Physical activity reduces the risk of cardiovascular disease (CVD), the leading cause of death in the US and globally. However, while we know a great deal about how much aerobic exercise (e.g., walking, jogging) to prescribe in order to reduce CVD risk, we know far less about how much resistance exercise (e.g., weight lifting) to prescribe. This proposed project will add important knowledge by (i) testing the effects of different doses of resistance exercise on CVD risk factors in a clinical trial among adults with overweight or obesity, (ii) exploring possible biologic mechanisms linking resistance exercise to CVD risk, and (iii) identifying which dose(s) of resistance exercise is (are) associated with best compliance, after trial intervention, in a free-living environment.

PI_NAMEs: LEE, DUCK-CHUL  (contact);LEE, I-MIN

PROGRAM_OFFICER_NAME: DONZE, LAURIE FRIEDMAN

PROJECT_TERMS: Address;Adherence;Adult;Aerobic Exercise;Aorta;arterial stiffness;Atherosclerosis;Attenuated;Biological;Blood Pressure;Blood Vessels;Body Composition;Body fat;C-reactive protein;Cardiovascular Diseases;cardiovascular disorder prevention;cardiovascular disorder risk;cardiovascular health;Cause of Death;Chronic;Clinical Trials;Country;Data;Diet;Disease;Dose;Environment;Etiology;Exercise;exercise prescription;exercise training;fasting glucose;General Population;glucose metabolism;Guidelines;Health;Health Benefit;Health Club;improved;Incidence;Inflammation;inflammatory marker;Interleukin-6;Intervention;Intervention Trial;Jogging;Knowledge;LDL Cholesterol Lipoproteins;lifestyle factors;Link;Lipids;Maintenance;Measurement;Measures;Meta-Analysis;Obesity;Observational Study;Overweight;Participant;Patient Self-Report;Persons;Phase;Physical activity;primary outcome;Property;Public Health Practice;Randomized;Randomized, Controlled Trials;Recommendation;Reporting;Research;Residual state;resistance exercise;response;Risk;Risk Factors;Risk Reduction;Shapes;Smoking;Specific qualifier value;Structure;Testing;Time;TNF gene;Translations;Walking;Weight Lifting

PROJECT_TITLE: Dose-Response to Resistance Exercise on Cardiovasular Health

STUDY_SECTION: LCBH

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


ADMINISTERING_IC: ES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Attention Deficit Hyperactivity Disorder (ADHD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Genetics;Mental Health;Neurosciences;Pediatric

ORG_CITY: IOWA CITY

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF IOWA

PHR: Project Narrative and Relevance to Public Health Insecticides are ubiquitous in our environment and the general population is exposed through commercial use and the consumption of fruits and vegetables. Adolescent brain development is a sensitive process influenced by pubertal hormones during which exposures impact neurobehavioral functioning, including exposures to insecticides in occupational and other settings. The research proposed here will advance our understanding of the mechanisms and moderators of these effects by studying both adolescents occupationally exposed to insecticides through working in agriculture and a translational mouse model of this exposure to examine brain mechanisms, which are the first steps to accelerate translation of scientific research into meaningful improvements in human health, optimizing insecticide exposure policies, and developing interventions to protect the brain health of youth.

PI_NAMEs: STEVENS, HANNA E (contact)

PROGRAM_OFFICER_NAME: HOLLANDER, JONATHAN

PROJECT_TERMS: Acceleration;Adolescence;Adolescent;adolescent brain development;Affect;Age;Agriculture;Animals;Antioxidants;Attention;Attention deficit hyperactivity disorder;Behavior;Biological Markers;Brain;brain health;Cell Culture Techniques;Chlorpyrifos;Cholinesterases;cohort;Consumption;cypermethrin;Data;dermal exposure;DNA;DNA Methylation;DNA Modification Process;Dopamine;dopamine system;dopaminergic neuron;Dose;Economics;Environment;Epigenetic Process;epigenome;Etiology;Exposure to;fruits and vegetables;Gene Expression;Gene Expression Regulation;General Population;Genes;Goals;Health;high reward;high risk;Hormonal;Hormone use;Hormones;Household;Human;Impairment;improved;Impulsivity;In Vitro;in vivo;individual variation;Insecticides;Intervention;Investigation;Ion Channel;Knowledge;Lead;life span;Link;Long-Term Effects;Male Adolescents;Mediating;Mediator;Metabolism;Methylation;Midbrain structure;Modeling;Motor Activity;mouse model;Mus;neurobehavior;neurobehavioral;Neurobiology;neurodevelopment;Neurons;novel strategies;Occupational;Occupational Exposure;Outcome;Outcome Assessment;Oxidative Stress;Performance;Peripheral;Pesticides;Play;Policies;Population;Process;Puberty;Public Health;Research;Research Personnel;Risk;Role;Saliva;Sampling;Short-Term Memory;Symptoms;Testing;Testosterone;Time;Toxicology;Translations;urinary;Work;Youth

PROJECT_TITLE: Adolescent Insecticide Exposure and ADHD Risk: Mechanisms of Immediate Effects and Long-term Vulnerability

STUDY_SECTION_NAME: Special Emphasis Panel[ZES1 VSM-S (VC)]


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Nutrition

ORG_CITY: BALTIMORE

ORG_DEPT: ORTHOPEDICS

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

ORG_STATE: MD

PHR: PROJECT NARRATIVE Diseases that affect lipid metabolism cause growth inhibition; however, the mechanism remains unknown due to the lack of knowledge about lipid metabolism in the growth plate. In this proposal, we will use unique transgenic mouse models that can inhibit the use of lipids in the growth plate to comprehensively determine whether the growth plate uses lipids for energy production. The outcome of this proposal will advance our understanding of growth plate metabolism, which will lead to the elucidation of mechanisms underlying growth failure in lipid metabolism disorders.

PI_NAMEs: OTSURU, SATORU  (contact)

PROGRAM_OFFICER_NAME: PINTUCCI, GIUSEPPE

PROJECT_TERMS: acylcarnitine;Address;Adipose tissue;Affect;anaerobic glycolysis;ApoE knockout mouse;Apolipoprotein E;Astrocytes;Biological;Biological Assay;Blood;Blood Vessels;bone;Bone Growth;Bone Marrow;Carnitine Palmitoyltransferase I;cell type;Cells;Chondrocytes;Circulation;Compensation;conditional knockout;Confocal Microscopy;Consumption;Diabetes Mellitus;Diglycerides;Disease;Energy Metabolism;Energy Supply;Energy-Generating Resources;Environment;Epiphysial cartilage;etomoxir;experimental study;Extracellular Matrix;Failure;fatty acid metabolism;fatty acid oxidation;Fatty Acids;glucose metabolism;Growth;Hour;Hydrolysis;Hypoxia;In Vitro;in vivo;Intracellular Accumulation of Lipids;Intravenous;Knock-in Mouse;Knock-out;Knockout Mice;Knowledge;Label;Ligase;Limb structure;lipid disorder;lipid metabolism;lipidomics;Lipids;Macrophage;Malnutrition;mass spectrometric imaging;Mediating;Metabolic;Metabolic Diseases;Metabolism;Microglia;Mitochondria;Modeling;Monitor;mouse model;Mus;novel marker;Nutrient;Outcome;oxidation;Oxygen;Oxygen Consumption;Peroxisomal Disorders;Phenotype;Physiologic Ossification;Play;prevent;Production;Proliferating;Puberty;Reporting;Rest;Role;single-cell RNA sequencing;Stains;stem cells;Testing;transcriptome;Transgenic Mice;Triglycerides;Visualization

PROJECT_TITLE: Lipid metabolism in the growth plate

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 MSOS-K (03)]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Digestive Diseases;Microbiome

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: PROJECT NARRATIVE Special gut proteins called proteases can harm intestinal function in patients with post-infection irritable bowel syndrome (PI-IBS). We have discovered that specific healthy microbes in the gut suppress proteases. We will conduct a randomized, controlled trial of fecal microbiota transplantation to determine efficacy in improving PI- IBS symptoms as well as integrity of gut lining and metabolites produced in the gastrointestinal tract.

PI_NAMEs: GROVER, MADHUSUDAN  (contact)

PROGRAM_OFFICER_NAME: SHEA-DONOHUE, TEREZ

PROJECT_TERMS: Acute;Adult;Adverse event;Affect;Autologous;Beta-glucuronidase;Bilirubin;Biological Markers;Characteristics;Clinical;clinical efficacy;Clinical Trials;cohort;Colon;commensal microbes;Communities;Controlled Clinical Trials;Data;design;Development;Disease;Donor person;Donor Selection;Double-Blind Method;dysbiosis;efficacy evaluation;Engraftment;enteric infection;Environment;fecal metabolome;fecal transplantation;Feces;Female;Food and Drug Administration Drug Approval;Foundations;Functional disorder;Funding Opportunities;Future;Gastroenteritis;gastrointestinal;Gastrointestinal tract structure;Glucuronides;gut microbes;gut microbiota;health care service utilization;healthy volunteer;humanized mouse;Hypersensitivity;Impairment;improved;in vivo;Individual;Infection;Injury;insight;Institutional Review Boards;Intervention;intestinal barrier;Intestinal permeability;Intestines;Investigational Drugs;Irritable Bowel Syndrome;male;Mediating;Mediator;metabolomics;Microbe;microbial;microbiome;microbiota;microbiota composition;Minnesota;Mission;Morbidity - disease rate;mouse model;National Institute of Diabetes and Digestive and Kidney Diseases;New Drug Approvals;Outcome;Pathogenesis;patient subsets;Patients;Peptide Hydrolases;Peripheral;Permeability;pilot trial;Placebo Control;Population;preclinical study;Prospective cohort;Proteins;Quality of life;Randomized;Randomized, Controlled Trials;recruit;response;restoration;Risk;Safety;Severities;symptomatic improvement;symptomatology;Symptoms;System;Taxon;Testing;translational study;Transplant Recipients;transplantation therapy;United States Food and Drug Administration;Visceral

PROJECT_TITLE: Efficacy and Safety of Proteolytic Activity-Guided fecal Microbiota Transplantation for Irritable Bowel Syndrome (PRAGMAT trial)

STUDY_SECTION: DNPD

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


ED_INST_TYPE: SCHOOLS OF PHARMACY

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

ORG_CITY: Newark

ORG_DEPT: PHARMACOLOGY

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: Project Narrative Non-polio enteroviruses (NPEVs) including enterovirus A71, D68, and CV-B3 have caused 10 to 15 million infections and tens of thousands of hospitalizations in the U.S. However, there is a lack of antiviral for the prevention and treatment of these viral infections. In this proposal, we aim to develop orally bioavailable broad- spectrum NPEV antivirals by targeting the viral 2C protein.

PI_NAMEs: WANG, JUN  (contact)

PROGRAM_OFFICER_NAME: DAVIS, MINDY I

PROJECT_TERMS: Acute;acute flaccid myelitis;Anti-viral Agents;anti-viral efficacy;Aseptic Meningitis;Asia;Binding;Biological Assay;Biological Availability;Capsid;Cell Culture Techniques;Child;China;Clinical;clinically significant;Combined Modality Therapy;Complex;Conjunctivitis;Coxsackie Viruses;Data;Development;Disease;Disease Outbreaks;Disparate;drug candidate;Drug Design;drug discovery;Drug Kinetics;Drug resistance;Drug Targeting;Echo Viruses;efficacy study;Encephalitis;Ensure;Enterovirus;Enterovirus 68;Enterovirus 71;Enterovirus Infections;Etiology;FDA approved;Fluoxetine;Foot Diseases;Goals;Grant;Hand's disease;Hand, Foot and Mouth Disease;Hospitalization;human disease;human pathogen;improved;In Vitro;in vivo;in vivo evaluation;indexing;Infant;Infection;inhibitor;Knowledge;Lead;lead candidate;lead optimization;Maximum Tolerated Dose;Meningitis;Morbidity - disease rate;mortality;mouse model;Mouth Diseases;Mus;mutant;Myocarditis;nanomolar;National Institute of Allergy and Infectious Disease;Neonatal;neonatal sepsis;Neurologic;Oral;Organelles;pan-enterovirus;Paralysed;pathogen;Pharmaceutical Preparations;Pharmacology;Polymerase;Prevention;priority pathogen;Property;Protease Inhibitor;Proteins;Publications;recombinant virus;Resistance;Resolution;respiratory;Respiratory Tract Infections;reverse genetics;Rhinovirus;RNA chemical synthesis;Roentgen Rays;Role;Safety;Series;Serotyping;small molecule;Structure;Supportive care;Testing;United States;vaccine access;Vaccines;Viral;Viral Physiology;viral RNA;virology;Virus Diseases

PROJECT_TITLE: Development of 2C inhibitors as broad-spectrum enterovirus antivirals

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 DCAI-B (81)]


ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

PHR: NARRATIVE Anticancer drug resistance often results from cancer cells bypassing the targeted pathway by adopting alternative mechanisms to maintain their growth. We have identified hnRNP A18 as a key regulator of several cellular pathways controlling cancer growth and immune protection. Using structural biology, Computer Aided Drug Design, medicinal chemistry and cellular biology we are developing small molecules that can selectively inhibit hnRNP A18 to prevent cancer cells growth and immune evasion.

PI_NAMEs: CARRIER, FRANCE  (contact);FLETCHER, STEVEN ;WEBER, DAVID JOSEPH

PROJECT_TERMS: 3' Untranslated Regions;5' Untranslated Regions;Adopted;Affinity;analog;angiogenesis;Antibodies;Antineoplastic Agents;Apoptosis;Binding;Biological;Biological Assay;Bypass;cancer cell;Cancer Cell Growth;Cancer Control;cancer drug resistance;cancer therapy;cancer type;Cell Physiology;Cell Proliferation;Cells;Cellular biology;Chemicals;chemotherapy;Clinic;Clinical;Computer Assisted;CTLA4 gene;Data;design;Development;DNA Repair;Dose;Down-Regulation;Drug Combinations;Drug Design;drug resistance development;Effectiveness;efficacy testing;Eukaryotic Initiation Factor-4G;Exhibits;Feedback;flexibility;FRAP1 gene;Generations;Goals;Growth;Heterogeneous-Nuclear Ribonucleoproteins;Homeostasis;Human;Immune;immune checkpoint;Immune checkpoint inhibitor;Immune Evasion;Immune response;Immune Targeting;Immunologist;improved;In Vitro;in vivo;inhibitor;innovation;Lead;Malignant Neoplasms;Mantle Cell Lymphoma;Medicine;Messenger RNA;Metabolism;Methods;Modeling;Modification;multidisciplinary;Mus;Neoplasm Metastasis;Normal Cell;Normal tissue morphology;novel;Oncologist;overexpression;Pathway interactions;Patients;Pharmaceutical Chemistry;Pharmaceutical Preparations;PIK3CG gene;Plasma;precision medicine;prevent;Proliferating;Property;Protein Biosynthesis;Protein Inhibition;Proteins;rational design;Regulatory Pathway;Renal Cell Carcinoma;Reporter;Resistance;response;Reverse Transcriptase Inhibitors;Ribonucleoproteins;RNA;RNA Binding;RNA Polymerase Inhibitor;RNA Recognition Motif;RNA-Binding Proteins;RNA-Protein Interaction;Role;scaffold;Schedule;small molecule;small molecule inhibitor;Solid Neoplasm;Solubility;Specificity;Stress;Structural Biologist;structural biology;targeted cancer therapy;Therapeutic;Therapeutic Agents;Therapeutic Index;three dimensional structure;Toxic effect;Transcript;Translation Initiation;Translational Repression;Translations;Tuberous Sclerosis;tumor;tumor growth;tumor progression;Viral;virtual;Xenograft Model;Xenograft procedure

PROJECT_TITLE: First in Class Small molecules to simultaneously inhibit protein translation and an immune checkpoint in cancers

STUDY_SECTION: DMPC

STUDY_SECTION_NAME: Drug Discovery and Molecular Pharmacology C Study Section[DMPC]


NIH_SPENDING_CATS: Genetics;Nutrition;Obesity

ORG_DEPT: PHYSIOLOGY

PHR: Project Narrative Carrying out this project successfully will give us valuable information on how metabolism of bone marrow adipocyte populations plays critical regulatory roles in the causes of bone loss and lead to new treatments for metabolic bone disorders and osteoporosis. Additionally, it will provide insight into how these fat cells interact with cells that produce blood cells and affect blood cell production.

PI_NAMEs: MACDOUGALD, ORMOND A (contact)

PROGRAM_OFFICER_NAME: BLONDEL, OLIVIER

PROJECT_TERMS: 3' Untranslated Regions;Adipocytes;adipokines;adiponectin;Adipose tissue;Affect;Aging;Animal Model;Antigens;Area;ATAC-seq;Blood Cells;bone;bone fracture repair;bone lead;bone loss;Bone Marrow;bone mass;bone metabolism;Bone Regeneration;Bone remodeling;bone turnover;Caloric Restriction;CD36 gene;Cell Communication;Cells;Cellularity;Characteristics;Communication;cytokine;Development;dietary restriction;Diphtheria;Distal;Endocrine;Enterobacteria phage P1 Cre recombinase;Evaluation;experimental study;extracellular vesicles;Fatty Acids;feeding;Femur;Functional disorder;Genetic Recombination;Glucose;glucose uptake;Hematopoiesis;Hematopoietic;Hematopoietic stem cells;Homeostasis;Impairment;improved;insight;irradiation;Label;Lactation;Leptin;lipid biosynthesis;lipid metabolism;Lipids;Lipolysis;Location;LoxP-flanked allele;Marrow;Metabolic;Metabolic Bone Diseases;Metabolism;MicroRNAs;Molecular;Molecular Profiling;mouse model;Mus;Myelopoiesis;novel;Obesity;Organ;Osteoblasts;Osteoclasts;Osteogenesis;Osteoporosis;Ovariectomy;Pathologic;Physiological;Physiology;Play;Population;Pregnancy;Production;Protein Secretion;recombinase;Regulation;response;Rodent;Role;Site;Small Nuclear RNA;spine bone structure;subcutaneous;Testing;tibia;Tissues;transcriptome sequencing;Triglycerides;uptake;Validation;Visceral;Work

PROJECT_TITLE: Metabolism and functions of bone marrow adipose tissue in the marrow niche

STUDY_SECTION: POMD

STUDY_SECTION_NAME: Pathophysiology of Obesity and Metabolic Disease Study Section[POMD]


NIH_SPENDING_CATS: Autoimmune Disease;Digestive Diseases;Inflammatory Bowel Disease;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: Chicago

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE The intestinal epithelium, constantly exposed to environmental toxins, chemicals, or pathogens, is continually being regenerated and replaced through the proliferation and differentiation of intestinal stem cells and impaired regenerative process, particularly in response to injury, may result in chronic inflammation and disease states such as inflammatory bowel disease. Recent studies have identified a matricellular protein CCN1 as a powerful endogenous regulator that coordinately regulates complex cellular processes in various cell types for intestinal injury repair and regeneration, and this proposal seeks to elucidate its molecular mechanism of action. We anticipate that results from these studies will yield new insights into epithelial cell dedifferentiation into stem cells and stromal cell senescence during repair, and prompt new therapeutic strategies for promoting intestinal injury repair.

PI_NAMEs: JUN, JOON-IL  (contact)

PROGRAM_OFFICER_NAME: GREENWEL, PATRICIA

PROJECT_TERMS: Ablation;Acute;Animal Model;Automobile Driving;Binding;Cell Aging;cell dedifferentiation;Cell Differentiation process;Cell Physiology;cell type;Cells;Characteristics;Chemicals;Chronic;chronic inflammatory disease;Coculture Techniques;Complex;conditional knockout;Cues;Data;Defect;diphtheria toxin receptor;Disease;Disparate;Epithelial Cells;epithelial repair;Epithelial-Stromal Communication;Epithelium;epithelium regeneration;Exposure to;Fibroblasts;gastrointestinal system;Genetic;gut homeostasis;healing;Homeostasis;Impairment;Inflammation;Inflammatory;Inflammatory Bowel Diseases;Injury;injury and repair;insight;Integrin alpha6beta1;Integrin alphaV;Integrin Binding;Integrins;intestinal epithelium;intestinal injury;Intestines;Knock-in Mouse;Knockout Mice;Knowledge;LGR5 gene;Maintenance;Mediating;Mediator;Modeling;Molecular Mechanisms of Action;mortality;mouse model;Mus;mutant;Natural regeneration;new therapeutic target;notch protein;novel therapeutic intervention;Organoids;pathogen;Pathway interactions;Pharmaceutical Preparations;Play;Process;programs;Proliferating;Proteins;receptor;regeneration following injury;regenerative;Regulation;repaired;Reporting;response;response to injury;Role;senescence;senescent cell;senolytics;Signal Transduction;Sodium Dextran Sulfate;Source;spatiotemporal;stem;stem cell proliferation;stem cells;Stromal Cells;Tamoxifen;Therapeutic Intervention;tissue repair;Toxic Environmental Substances;transcriptomics;Up-Regulation;wound healing

PROJECT_TITLE: Coordinated matricellular regulation of intestinal injury repair and regeneration


ORG_CITY: CHARLOTTESVILLE

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: NARRATIVE Endoplasmic reticulum (ER)-associated degradation (ERAD) is the principal ER quality control machinery responsible for the clearance of misfolded ER proteins for cytosolic proteasomal degradation. Our recent studies have revealed a key role of the most conserved SEL1L-HRD1 complex of ERAD in coordinating the activity of another quality control machinery known as ER-phagy to control the maturation and fate of nascent lipoprotein lipase (LPL) in adipocytes; however, the underlying molecular mechanism remains vague. This study will test an exciting hypothesis that SEL1L-HRD1 ERAD regulates ER-phagy activity via ER-phagy receptor CCPG1 to maintain ER homeostasis and ensure the maturation of secreted proteins such as LPL in adipocytes.

PI_NAMEs: QI, LING  (contact)

PROJECT_TERMS: Adipocytes;Architecture;Autophagocytosis;autosome;Biogenesis;Biology;Blood;Cardiovascular Diseases;Cell Cycle Progression;Cells;clinically relevant;Complex;Data;Degradation Pathway;Destinations;diabetes risk;Disease;Endoplasmic Reticulum;Ensure;Enzymes;Event;Genes;Health;Homeostasis;Human;Hydrolysis;Hyperlipoproteinemia Type IV;Hypertriglyceridemia;Impairment;In Vitro;in vivo;insight;interest;Laboratories;Light;Link;lipid metabolism;Lipids;lipoprotein lipase;Lipoproteins;Mediating;misfolded protein;Modeling;Molecular;Molecular Chaperones;Monitor;mouse model;mutant;Mutation;novel;Pathogenesis;Pathogenicity;Pathologic;Patients;Physiological;Process;protein aggregation;protein complex;protein degradation;protein folding;Protein Secretion;protein transport;Proteins;Proteomics;Quality Control;rare genetic disorder;receptor;Regulation;Reporting;response;Role;synergism;System;Testing;Transmission Electron Microscopy;Triglycerides;Variant;Yeasts

PROJECT_TITLE: A central role of SEL1L-HRD1 ERAD in LPL maturation in adipocytes

STUDY_SECTION: BMDM

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


NIH_SPENDING_CATS: Climate-Related Exposures and Conditions;Eye Disease and Disorders of Vision;Neurosciences

ORG_CITY: SEATTLE

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: The surface of the mammalian body is directly exposed to environmental solar light. We have found that many circadian clocks within these tissues respond directly to short- wavelength light using opsin photoreceptors. The goal of this proposal is to analyze the mechanisms of this local photoreception in the mammalian circadian system.

PI_NAMEs: BUHR, ETHAN D (contact)

PROGRAM_OFFICER_NAME: AKACEM, LAMEESE DANA

PROJECT_TERMS: Alleles;Animal Behavior;Behavioral;Biological;Body Surface;Brain;Cell Culture Techniques;Cell Death;Cell Proliferation;cell regeneration;cell type;Cells;circadian;circadian pacemaker;Circadian Rhythms;Cornea;Cues;Darkness;Dermal;DNA Repair;Environment;Evolution;Exposure to;gain of function;Goals;GTP-Binding Proteins;Health;Hour;Human;improved;in vivo;innovation;intercellular communication;interest;Light;light intensity;Lighting;Literature;loss of function;Maintenance;Mammals;Measurement;Mediating;melanocyte;Methods;Modeling;Molecular;Molecular Target;Mus;Nature;Neurons;novel;Opsin;Organism;Pathway interactions;Periodicity;Peripheral;Phase;photoactivation;Photophobia;Photoreceptors;Physiological;Play;Population;preoptic nucleus;Publishing;Reporter;resilience;response;Retina;Retinal Degeneration;Risk;Role;Signal Transduction;Skin;Skin Cancer;solar radiation;Structure of trigeminal ganglion;Sunlight;suprachiasmatic nucleus;Surface;System;Testing;Tissues;Transforming Growth Factor beta;ultraviolet;ultraviolet damage;Ultraviolet Rays;Viola;Visual;Visual System;Work

PROJECT_TITLE: The mechanism of extra-visual circadian photoentrainment in mammals

STUDY_SECTION: CSRS

STUDY_SECTION_NAME: Cellular Signaling and Regulatory Systems Study Section[CSRS]


NIH_SPENDING_CATS: Cardiovascular;Duchenne/ Becker Muscular Dystrophy;Heart Disease;Muscular Dystrophy;Orphan Drug;Pediatric;Rare Diseases

ORG_DEPT: ANATOMY/CELL BIOLOGY

PHR: PROJECT NARRATIVE Novel therapeutic interventions are greatly needed to develop a cure for DMD-cardiomyopathy. The research proposal seeks to reveal connexin 43 as a key molecular mediator of cardiac pathology in DMD. Results gained from these studies may lead to the identification of novel therapeutics to treat DMD-cardiomyopathy through direct targeting of connexin 43 and its sphere of regulation.

PI_NAMEs: FRAIDENRAICH, DIEGO  (contact)

PROGRAM_OFFICER_NAME: LI, HUIQING

PROJECT_TERMS: Affect;Applications Grants;Arrhythmia;beta Tubulin;Ca(2+)-Calmodulin Dependent Protein Kinase;calmodulin-dependent protein kinase II;Cardiac;Cardiac Myocytes;Cardiomyopathies;Colchicine;Communities;Connexin 43;Connexins;Cytoskeleton;Data;density;Disease;Duchenne cardiomyopathy;Duchenne muscular dystrophy;dystrophic cardiomyopathy;Dystrophin;Event;Exhibits;Extracellular Space;Fibrosis;FOXP3 gene;Functional disorder;gap junction channel;Gap Junctions;Glutamic Acid;Goals;Heart;Heart failure;heart function;improved;inhibitor;Injections;insight;Intercalated disc;Ions;Link;Mediating;Mediator;Medical;member;Methionine;Microtubule Polymerization;Microtubules;Modeling;Molecular;Mus;mutant;Mutation;novel therapeutic intervention;novel therapeutics;oxidation;Oxidative Stress;Paclitaxel;Pathologic;Pathology;Pathway interactions;Patients;peptidomimetics;Pharmacologic Substance;Phenocopy;Phosphorylation;polymerization;Polymers;prevent;Proteins;Reactive Oxygen Species;Regulation;Research Proposals;Role;scaffold;Serine;Sodium Channel;stem cells;Stress;System;Testing;Tight Junctions;Triplet Multiple Birth;Tubulin

PROJECT_TITLE: Connexin 43: a new player in Duchenne muscular dystrophy associated cardiomyopathy

STUDY_SECTION: MPPA

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


ADMINISTERING_IC: LM

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL LIBRARY OF MEDICINE

NIH_SPENDING_CATS: Chronic Pain;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Pain Research;Patient Safety;Precision Medicine

ORG_CITY: CHAPEL HILL

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: This application aims to create robust computational tools for analyzing messy observational data on postoperative pain (POP). These methods will enhance the precision of POP phenotype predictions to achieve timely POP control and reduce the risk of opioid overuse. The project will also investigate causal mechanisms of POP and establish the optimal personalized POP management plans, leading to a deeper understanding of the mechanisms behind POP and improved POP clinical decision-making at both the individual and population levels.

PI_NAMEs: ZOU, BAIMING  (contact)

PROGRAM_OFFICER_NAME: YOON, SUNG SUG

PROJECT_TERMS: Acute;Age;Analgesics;analytical method;analytical tool;Anesthesia procedures;Anxiety;Basic Science;Chronic;Clinical;clinical care;clinical decision-making;Cohort Studies;Complex;computerized tools;convolutional neural network;coping;Critical Care;Data;Data Analytics;data modeling;Data Sources;data warehouse;Databases;Decision Making;deep learning;deep neural network;Disparity;Education;effective intervention;Electronic Health Record;Etiology;experience;feature selection;flexibility;Florida;Funding;Goals;Health;Heterogeneity;improved;Individual;individual patient;Inpatients;Investigation;Length of Stay;machine learning model;Measures;Mediation;Methods;Modeling;Morbidity - disease rate;mortality;Network-based;Neural Network Simulation;North Carolina;novel;Operative Surgical Procedures;opioid overuse;opioid use;Outcome;outcome prediction;Pain;Pain intensity;Pain management;Pain Measurement;pain outcome;pain reduction;pain score;patient subsets;Patients;Performance;Perioperative;personalized medicine;Pharmaceutical Preparations;Phenotype;Physicians;Population;Postoperative Pain;Postoperative Period;predictive modeling;Procedures;Process;Race;Recommendation;Regimen;Relaxation;Research;Research Personnel;response;Risk;Risk Factors;risk mitigation;Risk Reduction;semiparametric;sex;Socioeconomic Status;Structure;Subgroup;substance use;Techniques;Testing;Text;Time;tool;United States National Institutes of Health;Universities;user friendly software

PROJECT_TITLE: Robust Computational and Data Analytic Tools for In-depth Understanding Postoperative Pain Mechanism with Enhanced Pain Management and Clinical Decision Making

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 HSS-Z (90)]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Neurodegenerative;Neurosciences;Peripheral Neuropathy;Physical Injury - Accidents and Adverse Effects;Regenerative Medicine;Transplantation

ORG_CITY: FARMINGTON

ORG_NAME: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT

ORG_STATE: CT

PHR: Project Narrative Every year, over half a million Americans suffer from large-gap peripheral nerve injuries that require surgical treatments with neural grafts or engineered graft substitutes, but these treatments suffer from limited availability and efficacy. Our objective is to address these issues by developing novel ionically conductive biodegradable scaffolds for reliable electrical and chemical stimulation to enhance the regeneration of large-gap nerve injuries. By bridging the knowledge gap between how chemical and electrical stimulation influence cell-material interactions and poorly studied nerve regeneration pathways, this project has the potential to significantly enhance large-gap nerve regeneration and functional recovery, ultimately benefitting patients suffering from peripheral nerve injuries.

PI_NAMEs: KUMBAR, SANGAMESH GURAPPA (contact)

PROGRAM_OFFICER_NAME: BAMBRICK, LINDA LOUISE

PROJECT_TERMS: 4-Aminopyridine;Action Potentials;Address;Adverse effects;Affect;Alkanesulfonates;Allografting;American;Animals;Autologous Transplantation;axon regeneration;Biocompatible Materials;biodegradable scaffold;Biodegradation;Biological;biomaterial compatibility;Biomedical Engineering;Blood Vessels;Brain-Derived Neurotrophic Factor;capsule;cell motility;Cells;Chemical Stimulation;Chemicals;Chitosan;Clinical;Complex;controlled release;Convulsants;Crush Injury;Cues;Defect;Disease;disease transmission;dosage;Drug Modelings;drug release kinetics;Electric Conductivity;Electric Stimulation;Engineering;Ensure;Fampridine-SR;Fiber;functional restoration;Future;Gastrocnemius Muscle;Genes;Growth;healing;Human;Hybrids;Hydrophobicity;Immune response;Implant;improved;In Vitro;in vitro Model;in vivo;in vivo Model;Injury;injury and repair;Intervention;Knowledge;Mechanics;Mediating;Minor;Modality;Multiple Sclerosis;Musculoskeletal;Myelin;myelination;Natural regeneration;Nerve;nerve autograft;Nerve Crush;nerve gap;nerve injury;Nerve Regeneration;nerve repair;nerve supply;neural;Neural Conduction;neural graft;Neurons;neurotransmitter release;neurotrophic factor;Neurotrophic Tyrosine Kinase Receptor Type 1;Neurotrophic Tyrosine Kinase Receptor Type 2;Neurotrophic Tyrosine Kinase Receptor Type 3;novel;NTF3 gene;Operative Surgical Procedures;Outcome;Oxidation-Reduction;Pathway interactions;Patients;Pattern;PECAM1 gene;Peripheral nerve injury;peripheral nerve repair;Persons;Pharmaceutical Preparations;Physical Stimulation;Physiological;Polymers;Potassium Channel Blockers;Property;Rattus;Recovery of Function;regenerative approach;Regenerative pathway;Regenerative response;remyelination;repaired;response;Safety;scaffold;Schwann Cells;sciatic nerve;Site;small molecule;standard care;Supporting Cell;Testing;Thick;Tissues;translational potential;Variant;Weight;Work

PROJECT_TITLE: Ionically Conductive Polymeric Biomaterials and Grafts for Nerve Regeneration

STUDY_SECTION: BNVT

STUDY_SECTION_NAME: Bioengineering of Neuroscience, Vision and Low Vision Technologies Study Section[BNVT]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Brain Disorders;Clinical Research;Data Science;Depression;Machine Learning and Artificial Intelligence;Mental Health;Networking and Information Technology R&D (NITRD);Precision Medicine

ORG_CITY: Oakland

ORG_NAME: KAISER FOUNDATION RESEARCH INSTITUTE

ORG_STATE: CA

PHR: Despite decades of research, matching individuals with antidepressant medication is still trial-and-error. This project will apply machine learning methods to detailed longitudinal records data for over 200,000 people taking antidepressant medication in order to identify true patterns of treatment response and develop practical decision rules for clinical practice.

PI_NAMEs: SIMON, GREGORY E. (contact)

PROGRAM_OFFICER_NAME: LUSHIN, VICTOR

PROJECT_TERMS: Address;alternative treatment;analytical method;anti-depressive agents;Belief;Biological Markers;Caring;Characteristics;Clinical;clinical application;clinical phenotype;clinical practice;comorbidity;Data;data harmonization;data resource;Databases;depressive symptoms;Diagnosis;Disease remission;Dose;Dropout;Drug Prescriptions;endophenotype;experience;follow-up;Funding;Future;Genetic;Genomics;Health system;Heterogeneity;Image;improved;improved outcome;Individual;individualized medicine;informatics tool;Intervention;Least-Squares Analysis;Machine Learning;machine learning method;Medical;medical specialties;Mental Health;National Institute of Mental Health;next generation;Patients;Pattern;personalized intervention;personalized medicine;Persons;Pharmaceutical Preparations;Pharmacogenomics;Phenotype;Population Heterogeneity;Practice Guidelines;predicting response;Primary Care;Prognosis;Records;Reproducibility;Research;Research Design;response;Sample Size;Sampling;sociodemographics;Strategic Planning;Structure;Substance Use Disorder;success;Testing;therapy design;Time;treatment effect;treatment guidelines;treatment pattern;treatment response;unsupervised learning;Work

PROJECT_TITLE: Machine learning to personalize antidepressant treatment

STUDY_SECTION: SERV

STUDY_SECTION_NAME: Mental Health Services Study Section[SERV]


FUNDING_MECHANISM: SBIR-STTR RPGS

NIH_SPENDING_CATS: Biotechnology;Emerging Infectious Diseases;Infectious Diseases;Malaria;Prevention;Rare Diseases;Vector-Borne Diseases

ORG_CITY: RIVERSIDE

ORG_NAME: ISCA TECHNOLOGIES, INC.

PHR: Project Narrative This NIH Commercial Readiness Pilot (CRP) project seeks to commercialize a novel product for mosquito control, the first and most critical step in controlling outbreaks of malaria and other mosquito-borne diseases such as West Nile virus, dengue and Zika: SPLAT BAC Plus, a safe, long-lasting larvicide that combines three reduced-risk larval killing agents with attractants for both adult female mosquitoes (inducing preferential egg laying at treated sites) and larval mosquitoes (encouraging feeding on the formulation). Larval control is an effective long-term solution to control mosquito populations, a critical component of vectorial capacity, but use of this tactic is currently hampered by shortcomings in available larvicide products, such as a problematically short field-life and the need to apply quickly after flooding, and by a critical shortage in larvicide active ingredients, particularly after the phase-out of the organophosphate temephos left only four biological modes of action available. By adding an attract-and-kill capacity and incorporating multiple larvicidal AIs into a controlled-release matrix to enable preemptive application, extend their field life, and ensure continued buoyancy and prevent sedimentation, SPLAT BAC Plus will address these limitations in previous larvicides and help to diversify mosquito control programs around the world, which currently rely predominantly on very few chemicals and interventions, leaving them vulnerable to the development of resistance.

PI_NAMEs: MAFRA-NETO, AGENOR  (contact)

PROJECT_TERMS: Adoption;Adult;Adult women;Aedes;Air;Anopheles Genus;Area;Bacillus thuringiensis;Bacteria;Bacterial Artificial Chromosomes;Beds;Behavior;Biological;Blood;Blood-Borne Pathogens;Brazil;Breeding;Chemicals;Collection;commercialization;Consumption;Control Groups;controlled release;Culex (Genus);Culicidae;Data;Dengue;design;Diptera;disease transmission;Dryness;efficacy trial;egg;Ensure;Environment;Exposure to;feeding;Female;Floods;Food;Formulation;Fostering;Friends;Grant;Habitats;Home;Human Bites;Infection;Ingestion;Insecticides;International;Intervention;Invaded;Juvenile Hormones;Larva;larval control;Left;Life;Malaria;malaria mosquito;malaria transmission;Marketing;Measures;Methoprene;mortality;Mosquito Control;Mosquito-borne infectious disease;Names;Nature;novel;Organophosphates;outbreak control;Oviposition;Partner in relationship;Penetration;Persons;Pest Control;Phase;Pilot Projects;Population;Predisposition;preference;prevent;Process;programs;pyrethroid;Rain;Readiness;Regulation;Research;research and development;Residual state;Resistance;Resistance development;Risk;Risk Reduction;Running;Safety;Sales;Sedimentation process;Semiochemicals;Site;Source;Stimulant;success;sucking;Surface;Tanzania;Technology;Temephos;Toxin;transmission process;United States National Institutes of Health;Variant;vector;vector management strategies;vector mosquito;Vectorial capacity;Water;West Nile virus;ZIKA

PROJECT_TITLE: Long Lasting Organic Semiochemical Formulation to Effectively Manage Blood Sucking Diptera.


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

ORG_CITY: MALVERN

ORG_NAME: VENATORX PHARMACEUTICALS, INC.

PHR: Project Narrative: We are optimizing to 1st Preclinical Candidate a class of catechol conjugated β -lactamase inhibitors (CC-BLI) that protect and potentiate β-lactams against Multidrug-Resistant (MDR) Pseudomonas aeruginosa. The compounds will be paired ultimately with ceftolozane, which best supports the potent antibacterial activity, and advanced through Non-GLP toxicology and eventually through IND-enabling activities. The intravenously administered combination would represent a powerful new treatment option against the most problematic, MDR pathogens in the hospital setting.

PI_NAMEs: LIU, BIN  (contact)

PROGRAM_OFFICER_NAME: XU, ZUOYU

PROJECT_TERMS: ADME Study;Anti-Bacterial Agents;Antibiotics;Applications Grants;Bacteria;beta-Lactam Resistance;beta-Lactamase;beta-Lactams;Binding Proteins;Biological;candidate selection;carbapenemase;Carbapenems;Catechols;Ceftazidime;Cells;Cephalosporinase;Chemistry;Chemosensitization;Childhood;Clinical;cytotoxicity;Development;Dose;Down-Regulation;Enzymes;Epidemiology;Equus caballus;Evolution;Family;FDA approved;Formulation;Funding;General Hospitals;General Ward;Generations;Grant;Hospitals;Hydrolysis;In Vitro;Infection;inhibitor;Intravenous;intravenous administration;Iron;Lead;lead optimization;lead series;manufacture;Marketing;Medical;Membrane;Multi-Drug Resistance;multi-drug resistant pathogen;multidrug-resistant Pseudomonas aeruginosa;Mus;novel;Organism;pathogen;periplasm;Pharmaceutical Chemistry;pharmacokinetics and pharmacodynamics;Phase;Plasma Proteins;pneumonia model;Population;pre-clinical;preclinical development;Predisposition;Production;Property;Pseudomonas;Pseudomonas aeruginosa;Research;Resistance;resistance mechanism;resistant strain;Rodent;scale up;Series;Serine;Small Business Innovation Research Grant;Solubility;success;System;Tazobactam;Thigh structure;Toxicology;uptake;VDAC1 gene

PROJECT_TITLE: Broad spectrum β-lactamase inhibitors employing a Trojan horse mechanism to rescue β-lactams against multidrug-resistant Pseudomonas aeruginosa


ORG_CITY: RESTON

ORG_NAME: PARABON NANOLABS, INC.

PHR: PROJECT NARRATIVE A new method of editing the human genome called CRISPR has the potential to treat the hundreds of millions of people with a genetic health condition by allowing defective sequences in their DNA to be overwritten with DNA having corrected sequence. New evidence indicates this editing process is more efficient and less toxic if the corrected DNA is first stitched into a compact package using smaller DNA fragments. In this project, we will develop software that automatically determines the set of DNA fragments, which are unique to each editing situation, that are needed to create such compact packages for the purpose of devising improved genome editing therapies.

PI_NAMEs: ARMENTROUT, STEVEN L (contact)

PROGRAM_OFFICER_NAME: FLICKER, PAULA F

PROJECT_TERMS: 3-Dimensional;Acceleration;Affect;arm;Atomic Force Microscopy;Automation;Base Pairing;bioinformatics tool;Biological Sciences;biomaterial compatibility;Biomedical Research;Capital;Cell Line;Cells;Clinical;clinical application;Clustered Regularly Interspaced Short Palindromic Repeats;combinatorial;commercial application;commercialization;Computer software;CRISPR therapeutics;CRISPR/Cas technology;design;design,build,test;Development;DNA;Effectiveness;Engineering;Face;Flow Cytometry;gene therapy;Genetic;Genetic Diseases;Genetic Engineering;genetic payload;Genetic Template;Genome;genome editing;genome editor;Genomics;Geometry;Goals;Health;Hour;Human;Human Genome;improved;in silico;In Vitro;inhibitor;iterative design;Knock-in;Legal patent;Licensing;manufacture;Marketing;Measures;Medical;Medical Research;Methods;Mission;Modification;molecular modeling;nanocarrier;nanomaterials;nanomedicine;nanosensors;Nanostructures;Nanotechnology;National Institute of General Medical Sciences;novel;Nucleic Acids;Oligonucleotides;operation;Performance;personalized medicine;Persons;Phase;Phase III Clinical Trials;Positioning Attribute;Process;Protocols documentation;repaired;Research;Research Personnel;scale up;Science;self assembly;Services;Shapes;Single-Stranded DNA;Small Business Innovation Research Grant;Software Design;software development;Software Tools;Specific qualifier value;Specificity;Structure;System;Techniques;Testing;therapeutic DNA;therapeutic genome editing;Therapeutic Studies;Tubular formation;Variant;Vendor;Writing

PROJECT_TITLE: Parametric design software for nanostructured CRISPR payloads


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Coronaviruses;Coronaviruses Vaccines;Emerging Infectious Diseases;Immunization;Infectious Diseases;Prevention;Vaccine Related

ORG_CITY: NEWPORT BEACH

ORG_NAME: TECHIMMUNE, LLC

PHR: PROJECT NARRATIVE The WHO and US authorities have declared the outbreak of multiple VOC of SARS-CoV-2 a public health emergency. This proposal focuses on producing innovative multi-epitope universal CoV vaccine candidates against 5 VOCs, using the established mRNA/LNP vaccine platform, and preclinically testing their safety, immunogenicity, and protective efficacy in an innovative susceptible “humanized’ mouse model.

PI_NAMEs: VAHED, HAWA  (contact)

PROGRAM_OFFICER_NAME: GORDON, JENNIFER L

PROJECT_TERMS: 2019-nCoV;Affect;Amino Acid Sequence;Antigen Targeting;Antigens;asymptomatic COVID-19;authority;B-Lymphocytes;Brain;CD8B1 gene;cell mediated immune response;Cells;Cessation of life;China;Coronavirus;coronavirus disease;coronavirus vaccine;Country;COVID-19;COVID-19 outbreak;COVID-19 pandemic;COVID-19 patient;COVID-19 vaccine;design;design and construction;Disease;Disease Outbreaks;DNA Sequence Alteration;Epitopes;Future;Generations;Genome;Goals;HLA A*0201 antigen;HLA-DR Antigens;Human;Humanities;humanized mouse;Immune system;Immunity;immunogenic;immunogenicity;Infection;innovation;Lead;Lung;Messenger RNA;mouse model;mRNA delivery;Mutate;Mutation;neutralizing antibody;novel;novel coronavirus;Outcome;pandemic disease;Pathogenicity;Phase I Clinical Trials;pre-clinical;Preclinical Testing;Predisposition;protective efficacy;Proteins;prototype;Province;public health emergency;Reporting;Risk;Safety;SARS-CoV-2 B.1.1.529;SARS-CoV-2 genome;SARS-CoV-2 infection;SARS-CoV-2 variant;Seasons;South Africa;Speed;Subunit Vaccines;T-Lymphocyte;T-Lymphocyte Epitopes;Testing;Transgenic Mice;universal coronavirus vaccine;universal vaccine;vaccine access;vaccine candidate;vaccine platform;Vaccines;variants of concern;Viral Antigens;Virus

PROJECT_TITLE: A Novel Multi-Epitope-Based Universal Vaccine Against Multiple Coronavirus Variants of Concern

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-AIDC-U(11)]


NIH_SPENDING_CATS: Bioengineering;Biotechnology

ORG_CITY: Valencia

ORG_NAME: FERROLOGIX, INC.

PHR: Project Narrative The goal of this project is to develop a functionally closed, quantitative cell purification system that can isolate rare and specific cell types based on multiple markers at throughputs conducive for cell therapy manufacturing. Current technologies cannot perform rare cell isolation or multitarget sorting at large scale. Our platform can provide a platform for cell therapy manufactures to isolate highly specific cell populations to develop more potent therapies.

PI_NAMEs: MURRAY, COLEMAN  (contact)

PROGRAM_OFFICER_NAME: YEH, ALVIN TIEN-WEI

PROJECT_TERMS: Address;Allogenic;Autologous;Benchmarking;Cell Count;Cell Physiology;Cell Separation;Cell Survival;Cell Therapy;cell type;Cells;Cleaved cell;Development;Devices;digital;Environment;Excision;Goals;Hour;imaging system;Interview;large scale production;Learning;magnetic beads;Magnetism;manufacture;Methods;Monitor;Morphologic artifacts;next generation;operation;parallelization;Phase;Population;Process;Production;Reagent;Sampling;scale up;Sorting;Sterility;Surface;System;T cell therapy;Technology;Therapeutic;Time

PROJECT_TITLE: Functionally Closed Purification and Elution of Untouched Cells using Cleavable Magnetic Beads with Digital Magnetic Sorting


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Data Science;Machine Learning and Artificial Intelligence;Mental Health;Networking and Information Technology R&D (NITRD);Neurosciences

ORG_CITY: MORGANTOWN

ORG_NAME: ISTOVISR

ORG_STATE: WV

PHR: The goal of this project is to scale analytics for large image volumes and thereby accelerate discovery of new biological principles, and remove barriers to communicate and receive this information. We propose to leverage virtual reality to change the way users interact with their data, by providing cutting-edge machine learning methods interpolated with rapid error correction. We propose also that virtual reality can underlie a new mode of interaction among scientific colleagues around 3D/4D data sets, and permit them to make the full extent of their discoveries accessible to experts and non- experts.

PI_NAMEs: DORETTO, GIANFRANCO ;MOREHEAD, MICHAEL DAVID (contact);SPIROU, GEORGE A

PROGRAM_OFFICER_NAME: ANDERSON, PAIGE MARIE

PROJECT_TERMS: 3-Dimensional;4D Imaging;Academia;Acceleration;Active Learning;Adoption;auditory processing;base;Biological;Brain;Brain imaging;BRAIN initiative;Businesses;Clinical;clinical imaging;clinical practice;Clinical Research;Cloud Computing;Communication;Computer software;Computers;cost;Data;Data Set;Democracy;Depth Perception;design;Development;Digital Libraries;Educational Materials;Educational process of instructing;Electron Microscope;Ensure;Environment;extended reality;field study;Goals;Grant;Hour;human-in-the-loop;Image;Image Analysis;improved;Industry;innovation;insight;Internet;Intuition;Knowledge;Language;large datasets;large scale data;Learning;learning strategy;lectures;Libraries;Licensing;Machine Learning;machine learning algorithm;machine learning method;machine learning model;Manuscripts;meetings;Methods;Microscope;Modeling;Modernization;Multimedia;Narration;National Institute of Mental Health;Neurosciences Research;new technology;next generation;novel;Pattern Recognition;peer;Performance;Phase;Philosophy;Population;pre-clinical research;Process;Production;programs;prototype;Publications;Reporting;Research;Resolution;Resources;Running;Sales;Scanning;Science;scientific computing;Scientist;Small Business Innovation Research Grant;Sound Localization;stereoscopic;structural biology;Structure;Students;success;System;Techniques;Technology;technology development;Testing;Three-Dimensional Image;tool;Training;Training and Education;virtual reality;virtual reality environment

PROJECT_TITLE: Scaling Volumetric Imaging, Analysis and Science Communication Using Immersive Virtual Reality


NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Digestive Diseases

ORG_CITY: LOUISVILLE

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF LOUISVILLE

ORG_STATE: KY

PHR: Disorders of gastric function impact >10% of the US population, but remain poorly understood, with a pressing need for new diagnostic tests to better define these diseases. We will translate a new clinical tool for non-invasively assessing gastric dysfunction called “Body Surface Gastric Mapping”, which applies flexible skin electrodes to spatially map underlying patterns of gastric electrical activity. We will apply this promising new diagnostic tool in large clinical studies to define how gastric electrical abnormalities impact disease, and to validate this new diagnostic approach.

PI_NAMEs: ABELL, THOMAS LYMAN (contact);O'GRADY, GREG

PROGRAM_OFFICER_NAME: UNALP-ARIDA, AYNUR

PROJECT_TERMS: Address;Adult;Affect;analysis pipeline;Antral;Anxiety;bioelectricity;Biological Markers;Biomedical Engineering;Bluetooth;Body Surface;Chronic;Clinical;clinical care;clinical diagnostics;Clinical Research;clinical trial readiness;clinically significant;cohort;Consensus;Coupled;Custom;Cutaneous;Data;Devices;Diagnosis;Diagnostic;diagnostic platform;diagnostic strategy;Diagnostic tests;diagnostic tool;Disease;disease phenotype;Dyspepsia;Economic Burden;Economics;electric impedance;Electrodes;Electronics;Electrophysiology (science);Evaluation;Event;flexibility;Frequencies;Functional disorder;Future;Gastric Emptying;Gastroesophageal reflux disease;Gastroparesis;Guidelines;gut-brain axis;Health;Impairment;innovation;insight;Intervention;Journals;Link;Maps;Mental Depression;Methods;Motility;Natural History;Nausea and Vomiting;neuromuscular;new therapeutic target;noninvasive diagnosis;novel;novel diagnostics;novel marker;Outcome;Pathology;Patient Selection;patient subsets;Patients;Pattern;Phenotype;Physiology;Population;preclinical development;Prevalence;programs;Publishing;Quality of life;Radionuclide Imaging;Reflux;Research Personnel;response;response biomarker;Role;Rome;Selection for Treatments;Series;Severities;Signal Transduction;Skin;Stomach;Subgroup;Symptoms;Syndrome;Techniques;Technology;Testing;Tissues;tool;Translating;translational study;Translations;Validation

PROJECT_TITLE: Definitive Evaluation of Gastric Dysrhythmia as a Disease Mechanism by a Novel Body Surface Gastric Mapping Technique


ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

ORG_CITY: BOSTON

ORG_DEPT: PHYSICS

ORG_NAME: NORTHEASTERN UNIVERSITY

ORG_STATE: MA

PHR: Project Narrative Reading the sequence and detecting the diversity of chemical modifications in RNA molecules would be a huge step forward for understanding the biology and disease-causing events in human cells. However, methods that can directly read single molecules are lacking, prompting us to develop an ultra-sensitive technology that directly reads RNA molecules, one at a time, at low-cost and with high throughput. Our method will an array of nanometer scale devices in which individual enzymes replicate RNA and report on the RNA sequence and presence of modifications, all from minute amounts that are equivalent to the number of RNA molecules in a single human cell.

PI_NAMEs: WANUNU, MENI  (contact)

PROGRAM_OFFICER_NAME: NOVA, IAN CURTIS

PROJECT_TERMS: Address;base;base editing;Benchmarking;Binding;Biological;Biological Sciences;Biology;Cells;Chemical Dynamics;chemical reaction;Chemicals;circular RNA;Complementary DNA;Complex;Constitution;cost;Custom;dark matter;Detection;Development;Devices;Disease;DNA;DNA sequencing;Dyes;Enzymes;Escherichia coli;Evaluation;Event;experimental study;frontotemporal lobar dementia amyotrophic lateral sclerosis;Funding;Generations;Genome;genome sequencing;genomic locus;Genomic Segment;Genomics;Harvest;Head;Health;Human;Image;In Vitro;Individual;inorganic phosphate;Kinetics;Label;Length;Maps;Messenger RNA;Methods;Microfluidic Microchips;Microfluidics;Modification;Monitor;Myotonic Dystrophy;nanopore;nanoscale;Nucleotides;operation;Optics;Patients;Pattern;Play;Process;Proteins;Pseudouridine;Reader;Reading;reference genome;Regulation;Reporting;Resolution;Reverse Transcription;RNA;RNA analysis;RNA Probes;RNA replication;RNA Sequences;RNA-Directed DNA Polymerase;Role;Running;Sampling;Signal Transduction;single cell analysis;single molecule;single molecule real time sequencing;Site;Small RNA;Streptavidin;System;Technology;technology platform;Testing;Third Generation Sequencing;Time;tool;Transcript;transcriptome sequencing;Transfer RNA;United States National Institutes of Health;Untranslated RNA;Uridine;Variant;waveguide;Work

PROJECT_TITLE: Direct RNA sequencing using electo-optical zero mode waveguides and custom click fluorescent nucleotides

STUDY_SECTION_NAME: Special Emphasis Panel[ZHG1 HGR-M (O2)]


ADMINISTERING_IC: DE

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Congenital Structural Anomalies;Dental, Oral, and Craniofacial Disease;Emerging Infectious Diseases;Genetics;Infectious Diseases;Pediatric;Rare Diseases;Stem Cell Research;Stem Cell Research - Embryonic - Non-Human;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Nonembryonic - Non-Human;Vector-Borne Diseases;Zika Virus

ORG_CITY: CLEVELAND

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: CLEVELAND CLINIC LERNER COM-CWRU

ORG_STATE: OH

PHR: Project Narrative Despite clinical evidence of craniofacial suture defects resulting in craniosynostosis during prenatal ZIKV infection, yet the etiology remains an enigma and is currently unexplored. Herein, the goal of this proposal is to investigate the molecular mechanisms underlying ZIKV-induced cranial suture fusion that results in craniofacial anomalies. The insights gained will serve as a preclinical platform for development of therapeutic interventions.

PI_NAMEs: CHEN, WEIQIANG  (contact)

PROGRAM_OFFICER_NAME: CHOU, ALICIA YESIU

PROJECT_TERMS: Ablation;Address;Affect;African;Americas;aptamer;Asian;Back;Basic Science;Birth;bone;Bone Diseases;Brain;calcification;calcium phosphate;Calvaria;cell type;Cells;Cephalic;Child;Childhood;Clinical;cohort;Congenital Abnormality;craniofacial;Craniofacial Abnormalities;craniofacial bone;Craniosynostosis;cranium;Data;Defect;Deformity;Deposition;Developmental Delay Disorders;Differentiated Gene;Disease Outbreaks;Down-Regulation;early childhood;Early Intervention;Embryo;Engineering;epidemic virus;Etiology;Expression Library;fetal;fetal infection;Fetus;Future;future pandemic;Gene Expression;Genetic;GLI gene;global health;Goals;Health;Human;Immunocompetent;In Vitro;in vivo;Individual;Infant;infant infection;Infection;innovation;insight;Joint structure of suture of skull;Knock-in Mouse;LacZ Genes;Lentivirus Vector;Link;Mass Spectrum Analysis;Mediating;Mesenchymal;Mesenchymal Stem Cells;Mesenchyme;Microcephaly;mineralization;Modeling;Molecular;Mothers;mouse model;Mus;mutant;neurodevelopment;Neurologic;neurosensory;novel;osteogenic;osteoprogenitor cell;Pathway interactions;Pattern;Peptides;Phenotype;Population;pre-clinical;Pregnancy;premature;prenatal;Process;prospective;protein purification;Proteins;pup;Reporting;Resolution;Risk;Role;Side;single-cell RNA sequencing;Site;stem cells;success;Surgical sutures;suture fusion;Technology;Testing;therapeutic development;Therapeutic Intervention;Tissues;transcriptome;transcriptome sequencing;transcriptomics;transmission process;Vertical Transmission;Viral;Viral Genes;viral transmission;Virus;virus testing;Zika Virus;ZIKV exposure;ZIKV infection

PROJECT_TITLE: Molecular mechanism of Zika virus-induced premature craniofacial suture closure

STUDY_SECTION: SBDD

STUDY_SECTION_NAME: Skeletal Biology Development and Disease Study Section[SBDD]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

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

ORG_CITY: IOWA CITY

ORG_NAME: UNIVERSITY OF IOWA

PHR: PUBLIC HEALTH RELEVANCE: Glaucoma is a common group of age-related neurodegenerative diseases characterized by loss of retinal ganglion cells and their axons that carry information from the eye to the brain. Over 127 genetic risk factors for glaucoma have been mapped to specific places in the genome, however, basic features of these loci (i.e., the causative genes/mutations in each locus and how they affect gene activity) have not been defined, which is an obstacle to targeting them for therapies. Our proposed studies will use a complementary set of human, mouse, and molecular approaches to characterize the important features of three glaucoma risk factor loci by 1) determining the glaucoma-causing gene in each locus, 2) determining the specific DNA variants in the glaucoma-causing genes that confer risk for disease, and 3) determining how these variants alter gene expression and biological pathways that contribute to glaucoma pathogenesis to facilitate development of new sight-saving glaucoma therapies.

PI_NAMEs: ANDERSON, MICHAEL G (contact);FINGERT, JOHN H;SCHEETZ, TODD E

PROGRAM_OFFICER_NAME: SONG, HONGMAN

PROJECT_TERMS: 17q21;Affect;Age;age group;age related neurodegeneration;Alleles;Alzheimer's Disease;Amyloid;Amyloid Beta A4 Precursor Protein;Amyloid beta-Protein;Axon;Binding Proteins;Biological;Biological Assay;Biology;Bite;Blindness;Brain;Candidate Disease Gene;Caring;Cell Survival;Cells;Chromosomes;Code;Complex;Data;Development;Disease;disorder risk;DNA;effective therapy;Enhancers;Enzyme-Linked Immunosorbent Assay;Ethnic Origin;Exons;experimental study;Eye;Family;Family history of;Functional disorder;Ganglia;Gene Expression;Gene Expression Regulation;Genes;Genetic;Genetic Risk;genetic risk factor;Genetic Transcription;Genome;genome wide association study;genome-wide analysis;genomic locus;Genotype;Glaucoma;Goals;Health;Heritability;high risk;Human;insight;Knowledge;Link;Maps;member;Molecular;Mus;Mutation;Nerve Degeneration;Neurodegenerative Disorders;Neurofibrillary Tangles;new therapeutic target;Ocular Hypertension;Open-Angle Glaucoma;Optic Nerve;Pathogenesis;Pathway interactions;Patients;Physiologic Intraocular Pressure;prevent;Primary Open Angle Glaucoma;promoter;Protein Precursors;protein structure;Proteins;Public Health;public health relevance;Race;Recording of previous events;Reporter;Research;Retina;Retinal Diseases;Retinal Ganglion Cells;Risk;Risk Factors;risk variant;Role;Selection Criteria;Senile Plaques;Serotyping;Single Nucleotide Polymorphism;single-cell RNA sequencing;Source;Specificity;targeted treatment;tau Proteins;Testing;Therapeutic Intervention;Tissues;Transcript;transcriptomics;Translating;United States;Variant;Virus;Vision

PROJECT_TITLE: Foundational Biology of Glaucoma GWAS Loci

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


NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Diabetes;Digestive Diseases;Hepatitis;Liver Disease;Nutrition;Obesity

PHR: The number of NAFLD patients is projected to increase from 83.1 million (2015) to 100.9 million (2030), of whom ~27% will have NASH, however, there are no approved drugs for treating NASH. IP6K1 belongs to inositol phosphate kinase family and its expression directly correlates with NASH and cirrhosis in humans. Our preliminary data suggest that agents targeting IP6K1 may provide a novel treatment for NAFLD/NASH, therefore, the studies described here aim to develop potent and selective IP6K1 inhibitors suitable for clinical application and as such, may have a direct impact on outcomes and/or quality of life for patients with NAFLD/NASH.

PI_NAMEs: CHAKRABORTY, ANUTOSH ;WANG, XIAODONG  (contact)

PROGRAM_OFFICER_NAME: GARCIA, MARTHA

PROJECT_TERMS: Adipocytes;Biochemical;Biological Assay;Biological Availability;Body fat;Cells;Cellular Assay;Cholesterol;Cholesterol Esters;Chronic;Cirrhosis;clinical application;Collagen;Data;Development;diet-induced obesity;Diphosphates;Drug Design;Drug Kinetics;efficacy evaluation;efficacy study;Energy Metabolism;Esters;Family;Fatty Acids;Fatty Liver;FDA approved;Fibroblasts;fibrogenesis;Fibrosis;Generations;Gluconeogenesis;glucose tolerance;glucose uptake;Health;Hepatic;Hepatic Stellate Cell;hepatocellular injury;Hepatocyte;High Fat Diet;Human;Hyperglycemia;Hyperinsulinism;in vivo;Inflammation;inhibitor;Injury;Inositol;inositol heptakisphosphate;inositol hexakisphosphate kinase;Inositol Phosphates;Insulin Resistance;insulin secretion;insulin sensitivity;insulin signaling;Knockout Mice;Lead;Ligands;lipid biosynthesis;Lipids;Liver;liver injury;Macrophage;Metabolic;Metabolism;Methods;Mitochondria;mouse model;Mus;nanomolar;non-alcoholic fatty liver disease;nonalcoholic steatohepatitis;Nonesterified Fatty Acids;novel;novel strategies;Obese Mice;Obesity;Oral;Outcome;Oxygen Consumption;Pathway interactions;Patients;Pharmaceutical Chemistry;Pharmaceutical Preparations;pharmacologic;Phenotype;Phosphotransferases;Primary carcinoma of the liver cells;Productivity;Property;Publishing;Quality of life;Research Personnel;Series;Signal Transduction;Steatohepatitis;Stress;System;targeted agent;Testing;Triglycerides;Weight Gain;western diet;Work

PROJECT_TITLE: Novel IP6K1 inhibitors for treatment of NAFLD/NASH

STUDY_SECTION: DMPB

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


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cancer;Clinical Research;Colorectal Cancer;Comparative Effectiveness Research;Digestive Diseases;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Orphan Drug;Patient Safety;Precision Medicine;Prevention;Rare Diseases

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: PROJECT NARRATIVE Rectal cancer is a major public health burden with a high incidence and mortality in the US and worldwide. In this project, we propose to develop imaging biomarkers to predict treatment response and prognosis of patients with rectal cancer. Success of our research may help guide surgery and identify the most effective treatment for an individual patient, which will improve quality of life and patient outcomes.

PI_NAMEs: LI, RUIJIANG  (contact)

PROGRAM_OFFICER_NAME: WANG, YISONG

PROJECT_TERMS: Address;Adopted;advanced disease;Aftercare;Age;aggressive therapy;Architecture;Biological;Biological Markers;Biology;Blood;blood-based biomarker;Cancer Etiology;Cancer Patient;Cessation of life;chemoradiation;chemotherapy;Clinical;Clinical Data;clinical risk;clinical translation;Clinical Trials;clinically relevant;cohort;Combined Modality Therapy;Data;Data Set;deep learning;deep learning model;design;Diagnosis;Disease;disorder control;Distant;Distant Metastasis;effective therapy;Evaluation;Evolution;Gender;Goals;Habitats;Heterogeneity;high risk;Histology;Image;imaging biomarker;Immune;improved;improved outcome;In complete remission;Incidence;Individual;individual patient;innovation;Knowledge;learning strategy;Localized Disease;Location;Machine Learning;Magnetic Resonance Imaging;Malignant Neoplasms;Measurement;Micrometastasis;Modality;Modeling;Morbidity - disease rate;Morphology;mortality;multimodal data;multitask;Neoadjuvant Therapy;novel;novel strategies;Operative Surgical Procedures;Organ Preservation;outcome prediction;overtreatment;Pathologic;Patient observation;patient prognosis;Patient-Focused Outcomes;Patients;Performance;personalized approach;personalized medicine;predicting response;Prediction of Response to Therapy;predictive marker;predictive modeling;Process;Prognosis;prognostic;Prognostic Marker;prognostic model;prognostic value;prospective;Public Health;Quality of life;radiological imaging;radiomics;Recommendation;Rectal Cancer;Recurrence;Recurrent disease;Reproducibility;Research;response;Retrospective cohort;Risk;Risk Factors;Safety;serial imaging;Serial Magnetic Resonance Imaging;standard care;standard of care;Statistical Models;success;Systemic disease;Testing;therapy outcome;tool;Total Mesorectal Excision;Toxic effect;Training;Treatment outcome;treatment response;treatment strategy;tumor;tumor DNA;tumor microenvironment;Validation

PROJECT_TITLE: MRI and blood biomarkers of neoadjuvant therapy response and outcomes in rectal cancer

STUDY_SECTION: CTIS

STUDY_SECTION_NAME: Clinical Translational Imaging Science Study Section[CTIS]


NIH_SPENDING_CATS: Genetics

ORG_CITY: SANTA CRUZ

ORG_NAME: UNIVERSITY OF CALIFORNIA SANTA CRUZ

PHR: PROJECT NARRATIVE Telomeres length equilibrium plays a key role in age-related degenerative disease and cancer. We discovered that, contrary to current models, each telomere has a distinct length distribution. We will test the mechanisms that establish these distinct length distributions.

PI_NAMEs: GREIDER, CAROL W (contact)

PROGRAM_OFFICER_NAME: VATAKIS, DIMITRIOS NIKOLAOS

PROJECT_TERMS: Ablation;Affect;age related;Automobile Driving;Binding;Binding Proteins;Binding Sites;Bone marrow failure;Cell division;Cells;Chromosomes;Complex;Degenerative Disorder;design;Disease;DNA;DNA Binding;Elements;Enzymes;Equilibrium;experimental study;Gene Silencing;Genes;Genetic Transcription;Genomics;Health;Histone Deacetylase;Histone Deacetylation;histone modification;Human;human disease;immunodeficiency;Individual;Lead;Length;Malignant Neoplasms;Measures;Mediating;Methods;Modeling;Molecular;Mutation;nanopore;Nucleotides;Play;Polymerase;promoter;Pulmonary Fibrosis;Regulation;RNA;Role;Saccharomyces cerevisiae;Tandem Repeat Sequences;Technology;Telomerase;Telomerase RNA Component;telomere;Telomere Shortening;Telomere-Binding Proteins;Testing;Transcript;transcription factor;transcriptome sequencing;Untranslated RNA;Work;Yeasts

PROJECT_TITLE: Mechanisms underlying chromosome specific telomere lengths in yeast

STUDY_SECTION: MG

STUDY_SECTION_NAME: Molecular Genetics Study Section[MG]


NIH_SPENDING_CATS: Ataxia Telangiectasia;Behavioral and Social Science;Bioengineering;Brain Disorders;Clinical Research;Disability Research;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences;Orphan Drug;Pediatric;Primary Immunodeficiencies;Rare Diseases

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: Project Narrative Promising disease-modifying therapies are being developed for ataxia-telangiectasia and other pediatric neurological diseases, but current assessment tools are very insensitive at determining efficacy, resulting in large and expensive trials. This project aims to develop precise motor outcome measures, using inexpensive and widely accessible digital technologies, that can sensitively determine if a therapy is effective in children of all ages.

PI_NAMEs: GUPTA, ANOOPUM SATYAWAN (contact)

PROGRAM_OFFICER_NAME: CHEN, DAOFEN

PROJECT_TERMS: 18 year old;6 year old;Accelerometer;Adult;Age;age group;aged;Algorithms;Amyotrophic Lateral Sclerosis;Ankle;arm;Assessment tool;Ataxia;Ataxia Telangiectasia;Behavior;Blood;Caregivers;Characteristics;Child;Child Development;Childhood;Clinical;clinical care;clinical practice;clinical trial readiness;Clinical Trials;Collection;Computers;control theory;Data;Data Set;Development;digital technology;Disease;Disease Progression;drug development;efficacy evaluation;Evaluation;Extensor;Flexor;Gender;Goals;Home;Individual;kinematics;Laboratories;Light;Longitudinal cohort;longitudinal dataset;Machine Learning;machine learning method;machine learning model;Measurement;Measures;Modality;Modeling;Molecular;Motion;Motor;motor control;motor disorder;motor impairment;Movement;multimodality;Mus;Muscle;Nervous System Disorder;Neurodegenerative Disorders;neurofilament;Neurologic;novel;Outcome;Outcome Measure;Participant;Patients;Physical activity;Population;Property;Qualifying;Reporting;Research Personnel;Robotics;sensor;Serum;Severities;Severity of illness;Shapes;signal processing;Speed;Surveys;Symptoms;System;Techniques;Technology;Testing;Time;wearable sensor technology;Work;Wrist

PROJECT_TITLE: Development of real-world motor outcome measures in ataxia-telangiectasia

STUDY_SECTION: CIDH

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


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

NIH_SPENDING_CATS: Brain Disorders;Cancer;Rare Diseases;Tuberous Sclerosis

ORG_CITY: BERKELEY

ORG_DEPT: MISCELLANEOUS

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: Project Narrative Despite great efforts to target mTORC1 in cancer, adverse effects related to the multiplicity of mTORC1- regulated substrates limit the use of mTORC1 inhibitors in the clinic. Recent cryo-EM work from our lab revealed the structural basis of substrate-specific regulatory pathways that could be targeted with greater precision than heretofore. We will determine how regulation of canonical and non-canonical mTORC1 substrates differs, and reveal the structural basis of mTORC1 regulation by the still largely mysterious mechanisms of the GATOR and KICSTOR complexes.

PI_NAMEs: HURLEY, JAMES H (contact)

PROGRAM_OFFICER_NAME: AMIN, ANOWARUL

PROJECT_TERMS: Active Sites;Adverse effects;Affect;Amino Acids;Autophagocytosis;Binding;Binding Proteins;Biochemical;Biogenesis;Biological Assay;Birt-Hogg-Dube Syndrome;cell growth;Cell Line;Cellular Metabolic Process;Clinic;cofactor;Complex;Cryoelectron Microscopy;dimer;Dissociation;EIF4EBP1 gene;feeding;follow-up;FRAP1 gene;Genetic Transcription;Glioblastoma;Growth Factor;Guanosine Triphosphate Phosphohydrolases;Hereditary Malignant Neoplasm;In Vitro;inhibitor;Knock-out;Laboratories;Link;Lysosomes;Malignant Neoplasms;Maps;Molecular;Molecular Conformation;Multiprotein Complexes;Mus;Mutate;Mutation;Nucleotides;Nutrient;Pathway interactions;Patients;Phenotype;Phosphorylation;Phosphotransferases;Proteins;Recombinants;recruit;Regulation;Regulatory Pathway;Renal Cell Carcinoma;Repression;response;Ribosomal Protein S6 Kinase;sensor;Signal Transduction;Sirolimus;Starvation;Structure;Substrate Interaction;Surface;Tacrolimus Binding Protein 1A;Testing;therapeutic target;transcription factor;Tuberous Sclerosis;Tumor Suppressor Proteins;tumorigenesis;Work;Xenograft Model

PROJECT_TITLE: Molecular and structural mechanisms of mTORC1 regulation in cancer

STUDY_SECTION: MSFC

STUDY_SECTION_NAME: Macromolecular Structure and Function C Study Section[MSFC]


NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Kidney Disease;Microbiome;Nutrition;Urologic Diseases

ORG_CITY: BIRMINGHAM

ORG_DEPT: UROLOGY

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: NARRATIVE Increased urinary excretion of oxalate is linked with calcium oxalate kidney stones and may originate from the diet or endogenous metabolism. The goal of this project is to determine if, and how, endogenous oxalate synthesis and gut absorption of dietary oxalate are increased in idiopathic calcium oxalate kidney stone formers and if colonization with the gut bacteria Oxalobacter formigenes can reduce urinary oxalate excretion in this population. The results of the study will guide further investigations on the causes of calcium oxalate kidney stones and lead to the development of targeted therapeutic approaches for reducing calcium oxalate kidney stone risk.

PI_NAMEs: FARGUE, SONIA  (contact)

PROGRAM_OFFICER_NAME: KIRKALI, ZIYA

PROJECT_TERMS: absorption;Address;Adult;Affect;Ascorbic Acid;Attenuated;Automobile Driving;Bacteria;Binding;Body mass index;Calcium;Calcium Oxalate;Cations;Chronic Kidney Failure;Clinical Trials;Consumption;Continuous Intravenous Infusion;Coupled;Data;Development;Diet;dietary;dietary control;Disease;Dose;Economic Burden;Environmental Risk Factor;epidemiology study;Excretory function;Fasting;fecal microbiome;Food;Frequencies;gastrointestinal;Gastrointestinal tract structure;General Practitioners;Glycolates;Goals;gut bacteria;gut colonization;gut microbiome;gut microbiota;healthy volunteer;Homeostasis;Hour;Individual;Infusion procedures;Intestinal Absorption;Intestinal permeability;Intestines;Investigation;Isotopes;Kidney Calculi;Knowledge;Label;Lead;lifestyle factors;Link;Measures;Medical;Metabolic;Metabolism;Methods;microbial;microbiome analysis;novel strategies;novel therapeutic intervention;Obesity;Oral;Oral Administration;Organism;Oxalates;Oxalobacter formigenes;Patients;Permeability;Play;Population;Preparation;Prevention;Primary Hyperoxaluria;Process;Production;Publishing;Quality of life;Rare Diseases;Recurrence;Reporting;Research;Risk;Risk Factors;Role;Source;success;sugar;targeted treatment;Techniques;Testing;Therapeutic;therapeutic development;tool;urinary;Urine

PROJECT_TITLE: Comprehensive Analysis of Oxalate Homeostasis in Calcium Oxalate Kidney Stone Formers

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


ADMINISTERING_IC: OD

ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH

ORG_CITY: COLUMBIA

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: UNIVERSITY OF MISSOURI-COLUMBIA

ORG_STATE: MO

PHR: PROJECT NARRATIVE: OVERALL The evaluation of new genome editing technologies and delivery systems in mice and rat animal systems is a critical and necessary step to assessing their efficiency and safety. Once validated in animal models, these new tools can be incorporated into therapeutic strategies for treating human disease.

PI_NAMEs: BRYDA, ELIZABETH C (contact)

PROGRAM_OFFICER_NAME: MIROCHNITCHENKO, OLEG

PROJECT_TERMS: Acceleration;Animal Model;animal resource;Animals;Biodistribution;Biological;Biological Assay;biomedical resource;Breeding;cell type;clinical application;Communities;comparative;Data;delivery vehicle;disease model;Embryo;Ensure;Evaluation;experience;Fee-for-Service Plans;Funding;Future;gene therapy;Genetic;Genetic Engineering;genome editing;Goals;Health;Health Status;Human;human disease;in utero;in vivo;in vivo evaluation;Infrastructure;Interdisciplinary Study;Maintenance;Medicine;Methodology;Methods;Missouri;Modeling;mouse model;Mus;novel therapeutic intervention;operation;Phenotype;Play;pre-clinical;Preclinical Testing;Protocols documentation;Quality Control;Rat Strains;Rattus;Reagent;Reporter;Reproducibility;Research;Research Personnel;Resources;Rodent;Rodent Diseases;Rodent Model;Safety;Services;somatic cell gene editing;System;Technology;Testing;Therapeutic;Tissues;tool;Translations;United States National Institutes of Health;Universities;Validation;Wild Type Mouse;Work

PROJECT_TITLE: MU Rodent Testing Center for Somatic Cell Genome Editing

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


NIH_SPENDING_CATS: Biotechnology;Gene Therapy;Genetics

PI_NAMEs: O'NEILL-BLAIR, ARMEDIA LORRAIN (contact)

PROJECT_TERMS: animal breeding;animal care;animal colony;Animal Model;animal resource;Animals;Archives;Attention;Biological;Breeding;cohort;Communities;Contracts;cost effective;Cryopreservation;Deposition;disease model;disease phenotype;Embryo;Ensure;experience;Familiarity;Fee-for-Service Plans;Funding;Genetic;genome editing;Germ;Group Affiliation;Health;in vivo evaluation;Infrastructure;interest;member;Missouri;Modeling;Monitor;mouse model;Mouse Strains;Mus;operation;pathogen;Phenotype;Procedures;Production;Protocols documentation;Quality Control;Rat Strains;Rattus;repository;Research;Research Personnel;Resources;Rodent;Rodent Diseases;Role;Services;Site;somatic cell gene editing;System;Testing;testing services;Tissues;United States National Institutes of Health;Universities;working group

PROJECT_TITLE: Resource Section


ADMINISTERING_IC: AG

ED_INST_TYPE: UNIVERSITY-WIDE

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Cardiovascular;Cerebrovascular;Clinical Research;Dementia;Depression;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Neurodegenerative;Neurosciences;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: BRONX

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

ORG_STATE: NY

PHR: Narrative Asian Americans comprise 6% of the U.S. population and represent the fastest growing population group in U.S. The incidence of mild cognitive impairment and Alzheimer’s Disease is higher among racial/ethnic minorities, especially in first generation immigrants. Yet, there are few epidemiological and biological studies of Alzheimer’s disease and dementia in immigrant populations such as Indian Americans. In this first of its kind study, we propose to clinically and biologically phenotype 400 older first-generation immigrants from the southern Indian state of Kerala residing in the tri-state area (New York, New Jersey, and Connecticut) to better understand risk and protection against cognitive decline and dementia in this fast-growing U.S. population segment.

PI_NAMEs: VERGHESE, JOE  (contact)

PROGRAM_OFFICER_NAME: BANDIERA, FRANK

PROJECT_TERMS: Acculturation;Address;Adult;Age;Aging;aging in place;aging related;Alzheimer's Disease;Alzheimer's disease related dementia;Alzheimer's disease risk;American;Anxiety;Area;Asian Americans;Biological;Biological Aging;Biological Markers;biological research;Blood Vessels;Cardiovascular Diseases;Cardiovascular system;Cerebrovascular Disorders;cerebrovascular pathology;Child;Chronology;Clinical;Clinical Research;Cognition;Cognitive;cohort;Complex;Connecticut;coping;Dementia;dementia risk;depressive symptoms;Economics;Education;Electrocardiogram;Epidemiology;epigenetic clock;Epigenetic Process;ethnic minority;Ethnic Origin;Ethnic Population;experience;Funding;Future;Generations;Health;health disparity;High Prevalence;human old age (65+);Immigrant;Immigration;Impaired cognition;Incidence;Income;indexing;Individual;insight;Intervention;Investigation;Language;late life;Learning;Life;Magnetic Resonance Imaging;Measures;Memory;Mental Depression;Metabolic;Microvascular Dysfunction;Migrant;migration;mild cognitive impairment;Moods;Native-Born;New Jersey;New York;Occupations;older adult;Organ;Outcome;Phenotype;Population;Population Group;preservation;primary outcome;Protocols documentation;Psychological Stress;Quality of life;racial minority;racial population;Recording of previous events;Research;Research Personnel;Residencies;resilience;Retirement;Risk;Risk Factors;risk prediction;Role;secondary outcome;sex;social;social health determinants;Social Network;social relationships;Social support;sociocultural determinant;Surveys;Testing;Time;Tissues;United States National Institutes of Health;Validity and Reliability;verbal;Visuospatial;white matter

PROJECT_TITLE: Cognitive decline and dementia in older Kerala Americans

STUDY_SECTION: AIMR

STUDY_SECTION_NAME:
Aging, Injury, Musculoskeletal, and Rheumatologic Disorders Study
Section[AIMR]


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alcoholism, Alcohol Use and Health;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Biotechnology;Brain Disorders;Dementia;Gene Therapy;Genetics;Microbiome;Neurodegenerative;Neurosciences;Prevention;Substance Misuse

ORG_CITY: Aurora

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: PROJECT NARRATIVE We live in a rapidly aging society and in the United States, the population of individuals over the age of 65 is expected to reach 90 million people by 2050. Approximately 40% of elderly people consume alcohol which is associated with accelerated cognitive decline. To goal of this project is to identify specific perturbations in host innate immunity, including regulatory microRNAs, caused by alcohol misuse during aging, to provide a foundation for future clinical interventions to prevent neuroinflammation and early onset dementia in patients of all ages.

PI_NAMEs: SMATHERS MCCULLOUGH, REBECCA LEANNE (contact)

PROGRAM_OFFICER_NAME: CUI, CHANGHAI

PROJECT_TERMS: Acceleration;Acetates;Adult;Age;age effect;age related;age related neurodegeneration;aged;Aging;aging brain;Alcohol consumption;alcohol effect;alcohol exposure;alcohol misuse;alcohol response;Alcohol withdrawal syndrome;Alcohols;Alzheimer's disease related dementia;American;Autologous;Automobile Driving;Bacteria;Behavioral Assay;binge drinking;Blood - brain barrier anatomy;Brain;Central Nervous System;Chronic;Chronic Disease;Clinical;Cognition;Cognitive deficits;cognitive function;commensal bacteria;Cues;Dementia;Dependovirus;design;Development;differential expression;Disease;Disease Progression;Distant;dysbiosis;early onset;Early Onset Alzheimer Disease;Elderly;Endotoxins;Environmental Risk Factor;Epithelium;Ethanol;Ethanol toxicity;fecal microbiota;Foundations;frailty;Future;gene replacement therapy;gene therapy;glial activation;Goals;gut-brain axis;Health;Hippocampus;human old age (65+);immunoregulation;Impaired cognition;improved;In Vitro;in vivo;Individual;Inflammaging;Inflammation;Inflammation Mediators;Inflammatory;inflammatory modulation;Inflammatory Response;Innate Immune Response;Intervention;intestinal barrier;Intestinal permeability;Intestines;Knowledge;Lead;Learning;Lentivirus;life span;lifestyle factors;Macrophage;Measures;Mediating;Memory;Messenger RNA;Metabolism;Microbe;microbial;microbiome;microbiota;Microglia;MicroRNAs;miRNA expression profiling;Modeling;Monitor;mouse model;Mus;Natural Immunity;Nerve Degeneration;neuroinflammation;Neuronal Injury;Neurons;neurotoxic;novel;old mice;older adult;Older Population;Organ;Patients;Permeability;Persons;pharmacologic;Population;Prevalence;prevent;Process;Production;Public Health;response;Role;senescence;Silver;Societies;spectrograph;systemic inflammatory response;therapeutic development;Therapeutic Intervention;therapeutic target;Time;Tissues;Toxic effect;trend;Tsunami;United States;Work

PROJECT_TITLE: Neuroinflammatory GeroMiRs and Alcohol: Defining Mechanisms of ADRD

STUDY_SECTION: NAL

STUDY_SECTION_NAME: Neurotoxicology and Alcohol Study Section[NAL]


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

ORG_CITY: WORCESTER

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

PHR: Project Narrative A critical need is to understand the mechanisms by which alcohol regulates sleep behavior. We uncovered a novel pathway by which norepinephrine engages wake-active dopamine neurons in the ventral periaqueductal gray (vPAG) to produce arousal. In this project we will explore the mechanisms through which ethanol regulates this vPAG signaling pathway, and its role in alcohol-dependent alterations in sleep.

PI_NAMEs: WINDER, DANNY G. (contact)

PROJECT_TERMS: Acute;Adrenergic Receptor;Agonist;Alcohol dependence;alcohol exposure;alcohol response;alcohol use disorder;Alcohols;American;Arousal;Astrocytes;Automobile Driving;Behavior;Biology;Brain;cell type;Chronic;comorbidity;Data;Development;Disease;Dopamine;dopaminergic neuron;Dorsal;Dose;Down-Regulation;effective therapy;Ethanol;experimental study;extracellular;genetic approach;Goals;Immunoelectron Microscopy;in vivo;Individual;Intervention Studies;Knowledge;locus ceruleus structure;Mediating;midbrain central gray substance;mRNA Expression;neurotransmission;noradrenergic;Norepinephrine;novel;Output;Pathway interactions;Patients;Phenocopy;Play;prevent;Property;Proteome;Proteomics;Public Health;Quality of life;Receptor Activation;receptor expression;receptor function;Receptor Signaling;Recording of previous events;Recovery;recruit;Reporting;response;Role;Sedation procedure;sedative;Signal Pathway;Signal Transduction;Sleep;sleep behavior;Sleep Disorders;Sleep disturbances;Sleep Fragmentations;sleep regulation;Sleeplessness;Structure of terminal stria nuclei of preoptic region;Symptoms;System;Testing;therapeutic development;therapeutically effective;transmission process;Up-Regulation;Wakefulness

PROJECT_TITLE: Ethanol modulation of a NE-astrocyte-DA arousal pathway


ORG_CITY: DALLAS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: Project Narrative The human brain is comprised of heterogenous cell types, and understanding the gene expression patterns and chromatin states within each of these cell types will provide important insights into many cognitive disorders. The proposed studies will profile cell types in understudied regions of human and non-human primate brain. The resultant data will contribute to human and non-human primate cell type atlases, as well as identify molecular signatures that distinguish humans from closely related species.

PI_NAMEs: HOPKINS, WILLIAM D;KONOPKA, GENEVIEVE  (contact);SHERWOOD, CHESTER ;YI, SOOJIN

PROGRAM_OFFICER_NAME: YAO, YONG

PROJECT_TERMS: Acceleration;Adolescence;Adult;Age;age related;aging brain;Anatomy;Area;Atlases;autism spectrum disorder;Automobile Driving;Behavior;Brain;brain cell;Brain Diseases;Brain imaging;BRAIN initiative;Callithrix;Callithrix jacchus jacchus;Candidate Disease Gene;Cell Nucleus;cell type;Cells;Chromatin;Cognition Disorders;cognitive capacity;Communities;comparative;Corpus Callosum;Data;Data Set;Development;Disease;Epigenetic Process;epigenomics;Evolution;Exhibits;experimental study;Funding;Gene Expression;Gene Expression Profile;Genetic Transcription;genomic data;genomic variation;Genomics;Goals;Gorilla gorilla;Grant;gray matter;Histologic;Human;human tissue;imaging study;Immunochemistry;In Situ;innovation;insight;Macaca mulatta;Maps;Measurement;Messenger RNA;Methylation;Modeling;Molecular;Molecular Evolution;Molecular Profiling;Monkeys;Multiomic Data;multiple omics;Nervous System Disorder;Neurons;neuropsychiatric disorder;nonhuman primate;oligodendrocyte progenitor;Oligodendroglia;Optic Chiasm;Pan Genus;Pan paniscus;Papio;Pattern;Phenotype;Pongidae;Preparation;Primates;Process;programs;Pyramidal Tracts;Research;Resolution;Resources;RNA;Rodent;Saimiri;Sampling;Schizophrenia;Shapes;single cell genomics;single molecule;single nucleus RNA-sequencing;spatiotemporal;synergism;System;Technology;Tissues;transcriptomics;Validation;Variant;white matter;Work

PROJECT_TITLE: Cellular resolution multi-omics of white matter tracts in developing human and non-human primate brain for cell atlases

STUDY_SECTION_NAME: Special Emphasis Panel[ZMH1 ERB-L (06)]