NIH_SPENDING_CATS: Cancer;Orphan Drug;Precision Medicine;Rare Diseases

ORG_CITY: PROVIDENCE

ORG_NAME: RHODE ISLAND HOSPITAL

ORG_STATE: RI

PHR: PROJECT NARRATIVE  This project is relevant to public health because it addresses cancer drug resistance, a National Cancer Institute (NCI) scientific priority. Malignant cartilage bone cancers have a poor prognosis due to lack of effective drug treatments. The goal of this proposal is to systematically evaluate promising new treatments that target aspartate β-hydroxylase (ASPH), a cell surface protein that influences the growth, spread, and resistance of cancer cells, with the ultimate goal of improving patient survival and quality of life.

PI_NAMEs: TEREK, RICHARD M (contact);WANDS, JACK R

PROGRAM_OFFICER_NAME: CHEN, WEIWEI

PROJECT_TERMS: Address;Adult;Antibody-drug conjugates;Antineoplastic Agents;Apoptosis;Apoptosis Regulation Gene;Aspartate;Biology;Birth;Bone Tissue;cancer cell;cancer drug resistance;cancer therapy;Carcinoma;Cartilage;Catalytic Domain;Cell Line;Cell Proliferation;Cell Surface Proteins;Cell Survival;Cells;Chemoresistance;chemotherapeutic agent;chemotherapy;Chondrosarcoma;Clinical Trials;comparative efficacy;CRISPR/Cas technology;cytotoxic;Cytotoxic Chemotherapy;Data;Development;Doxorubicin;drug development;druggable target;effective therapy;Effectiveness;Embryonic Development;Excision;gain of function;gastrointestinal carcinoma;Gene Expression;Genes;Goals;Growth;Human;human monoclonal antibodies;improved;In Vitro;in vivo;in vivo Model;inhibitor;insight;Integral Membrane Protein;Invaded;knock-down;Knock-out;Link;loss of function;Malignant - descriptor;Malignant Bone Neoplasm;Malignant Neoplasms;Matrix Metalloproteinases;Metastatic Chondrosarcoma;Metastatic Neoplasm to the Lung;Methods;migration;Mixed Function Oxygenases;Modeling;Molecular;Molecular Target;mouse model;Mus;National Cancer Institute;Neoplasm Metastasis;neoplastic cell;Normal Cell;notch protein;novel;novel therapeutic intervention;novel therapeutics;oncofetal antigen;Operative Surgical Procedures;Osteosarcoma;Outcome;Pathway interactions;Patients;Pharmaceutical Preparations;Pharmacotherapy;Phenotype;primary bone cancer;Prognosis;programs;Proliferating;Public Health;Quality of life;receptor;Reducing Agents;Research;Resistance;Role;Sarcoma;Signal Transduction;small molecule inhibitor;Soft tissue sarcoma;standard of care;Supporting Cell;Survival Rate;synergism;targeted cancer therapy;targeted treatment;Testing;therapeutic target;treatment strategy;tumor;tumor growth;tumor progression;Vascular Endothelial Growth Factors;Work

PROJECT_TITLE: ASPH Targeted Therapy for Chondrosarcoma

STUDY_SECTION: SBDD

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


ADMINISTERING_IC: HL

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Aging;Cardiovascular;Heart Disease

ORG_CITY: LOS ANGELES

ORG_COUNTRY: UNITED STATES

ORG_DEPT: ANESTHESIOLOGY

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

ORG_STATE: CA

PHR: NARRATIVE Atrial fibrillation (AF) is the most common cardiac arrhythmia. It occurs in 9% of the population older than 65, and is associated with increased morbidity and mortality. We recently found in humans that the NADPH oxidase isoform 4 (NOX4) is markedly increased in patients with AF. Here we will test the hypothesis in novel fish and mouse models that NOX4 activates novel oxidative stress mechanisms and autophagy that produce specific cellular and electrophysiological changes leading to AF.

PI_NAMEs: CAI, HUA LINDA  (contact);GOLDHABER, JOSHUA I

PROGRAM_OFFICER_NAME: BALIJEPALLI, RAVI C

PROJECT_TERMS: 3-methyladenine;Acute;Angiotensins;Animals;Arrhythmia;Atrial Fibrillation;Attenuated;attenuation;Autophagocytosis;Calcium;calmodulin-dependent protein kinase II;Calpain;Cardiac;Chloroquine;Chronic;cohort;confocal imaging;Coupling;Data;Development;Disease;disease model;Electrocardiogram;Electrophysiology (science);embolic stroke;Environment;Exhibits;experimental study;Fishes;genetic strain;Heart Atrium;Heart failure;Heart Injuries;Heart Transplantation;Human;human old age (65+);in vivo;inhibitor;innovation;insight;Ischemia;Knockout Mice;Maps;Mediating;Mitochondria;mitochondrial autophagy;mitochondrial dysfunction;model organism;Modeling;Molecular;Morbidity - disease rate;mortality;mouse model;multicatalytic endopeptidase complex;Mus;NADPH Oxidase;Nitric Oxide;Nitric Oxide Donors;novel;novel therapeutics;old mice;Older Population;Optics;overexpression;Oxidases;Oxidative Stress;patch clamp;Pathogenesis;Pathway interactions;Patients;Peptide Hydrolases;Phenotype;Phosphorylation;Postoperative Period;prevent;Production;protein expression;Protein Isoforms;Proteins;Reactive Oxygen Species;Reperfusion Injury;Reperfusion Therapy;response;RNA;RNA Interference;Role;RyR2;Sarcoplasmic Reticulum;Sudden Death;Systems Biology;Telemetry;Testing;Therapeutic;Time;Tissues;Transgenic Organisms;Transplant Recipients;Uncertainty;Up-Regulation;voltage;Zebrafish

PROJECT_TITLE: Targeting NOX4-dependent mitochondrial dysfunction, autophagy and defective calcium handling in AF

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CVRS-B(02)]


NIH_SPENDING_CATS: Asthma;Lung;Neonatal Respiratory Distress;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: NARRATIVE  Babies born prematurely who are exposed to oxygen in the neonatal intensive care unit are at increased risk of airway diseases such as asthma, which makes it important to understand how oxygen detrimentally impacts the developing airways. The goal of this proposal is to use human cell and mouse models to investigate a novel, targetable mechanism (hydrogen sulfide) that we believe is normally protective in developing airways and can help to reduce the reactivity and fibrosis that occurs with oxygen exposure (thus reducing asthma in babies and children). The importance of our work lies in the potential application of novel drugs that can enhance hydrogen sulfide for improving airway function in preterm infants and reduce the risk of developing asthma later in life.

PI_NAMEs: PABELICK, CHRISTINA MARIA (contact);PRAKASH, Y. S.

PROGRAM_OFFICER_NAME: NATARAJAN, ARUNA R

PROJECT_TERMS: 3 year old;Adult;Affect;Age;Agonist;Airway Disease;Airway Fibrosis;airway hyperresponsiveness;airway remodeling;Alveolar;Asthma;Biochemical;Body System;Bronchodilation;Bronchopulmonary Dysplasia;Cell model;Cell Respiration;cell type;Child;Childhood;clinically relevant;clinically significant;Cyclic AMP;Data;Development;Enzymes;Epithelium;Equilibrium;Exposure to;Extracellular Matrix;fetal;Fetal Lung;Fetal Reduction;Fibrosis;Functional disorder;Future;Generations;Glutathione;Goals;Growth;HIF1A gene;high risk;Histology;Human;Hydrogen Sulfide;Hyperoxia;Hypoxia;Image;Imaging Techniques;Impairment;improved;In Vitro;in vivo;Inflammatory;Investigation;laser capture microdissection;Life;Lung;Methionine;Mitochondria;mitochondrial dysfunction;Modeling;Molecular;mouse model;Mus;Muscle Mitochondria;Neonatal;neonatal airway;Neonatal Intensive Care Units;neonatal mice;Newborn Infant;normoxia;novel;novel therapeutics;Obstruction;Oxidative Stress;Oxygen;Pathway interactions;Perinatal;pharmacologic;Pregnancy;premature;Premature Infant;preterm newborn;Proliferating;pup;Recovery;Regulation;respiratory smooth muscle;response;Risk;Risk Reduction;Role;S-Adenosylhomocysteine;S-Adenosylmethionine;Signal Pathway;Signal Transduction;Slice;Structure;System;Techniques;Therapeutic;therapeutic development;therapeutic target;Traction;Vulnerable Populations;Work

PROJECT_TITLE: Hydrogen Sulfide in Neonatal Airway Disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CVRS-A(03)]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Clinical Research;Digestive Diseases;Genetics;Human Genome;Orphan Drug;Pancreatic Cancer;Rare Diseases

ORG_CITY: BOSTON

ORG_NAME: DANA-FARBER CANCER INST

ORG_STATE: MA

PHR: PROJECT NARRATIVE KRAS is the dominant oncogenic driver of pancreatic cancer, and new small molecule inhibitors of KRAS have the potential to transform the treatment of this disease. This proposal will use an integrative strategy with genomic and functional genetic approaches in new human and mouse models of pancreatic cancer to investigate the molecular mechanisms of response and resistance to KRAS inhibitors. These studies will form a foundation for development of new biomarkers and combination therapy strategies with KRAS inhibition that can be evaluated in future clinical trials for pancreatic cancer patients.

PI_NAMEs: AGUIRRE, ANDREW JAMES (contact)

PROJECT_TERMS: ARID1A gene;Biological Assay;Biological Markers;Biopsy;cancer cell;cancer type;CDKN2A gene;Cell Cycle Progression;Cells;Clinical;Clinical Trials;clinically relevant;Clustered Regularly Interspaced Short Palindromic Repeats;Combined Modality Therapy;Data;Development;Disease;DNA Damage;drug sensitivity;effective therapy;Engineering;Foundations;functional genomics;Future;Genes;Genetic;genetic approach;Genetic Determinism;Genetic Markers;Genetic Transcription;Genomic approach;Genomics;Genotype;Goals;Human;human data;human model;human RNA sequencing;In Vitro;in vivo;inhibitor;innovation;knockout gene;KPC model;KRAS oncogenesis;KRAS2 gene;KRASG12D;MADH4 gene;Malignant neoplasm of pancreas;Malignant Neoplasms;MAP Kinase Gene;Modeling;Molecular;molecular subtypes;mouse model;Mus;mutant;Mutation;neoplastic cell;Neurons;novel;novel therapeutic intervention;novel therapeutics;Oncogenic;Oncoproteins;Organoids;pancreatic cancer model;pancreatic cancer patients;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma cell;pancreatic ductal adenocarcinoma model;paracrine;Paracrine Communication;Pathway interactions;Patients;Pharmaceutical Preparations;Phenotype;predictive marker;Prognosis;programs;RAS inhibition;Ras Inhibitor;replication stress;research clinical testing;Resistance;resistance mechanism;response;Role;Screening Result;Shapes;Signal Transduction;single-cell RNA sequencing;small molecule inhibitor;System;targeted treatment;Therapeutic;Therapeutic Intervention;TP53 gene;transplant model;Treatment Efficacy;treatment response;tumor;tumor microenvironment;Tumor Suppressor Genes;Tumor Suppressor Proteins

PROJECT_TITLE: Mechanisms of response and resistance to KRAS inhibition in pancreatic cancer

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics - 1 Study Section[MCT1]


ADMINISTERING_IC: GM

ED_INST_TYPE: UNIVERSITY-WIDE

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Aging;Neurodegenerative;Rare Diseases

ORG_CITY: BRONX

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

ORG_STATE: NY

PHR: Project narrative Autophagy, a major way to clear cellular debris, is crucial to prevent accumulation of damaged and non-functional proteins and organelles. Clinically, protein clearance by autophagy is required to prevent many diseases including neurodegeneration at old age. As autophagy declines with age, problems with damaged proteins worsen during life and shorten healthspan. We have established an animal model for endosomal microautophagy (eMI) in the fruitfly Drosophila. eMI is a form of autophagy that can be selective for proteins with a targeting motif and does not require protein unfolding and thus is able to deal with protein aggregates frequently occurring in disease. Having identified eMI in a genetically easily tractable model organism enables us to better characterize the physiological relevance of eMI and simplifies the identification and characterization of novel pathway components with the ultimate goal to identify novel treatment options to improve healthspan.

PI_NAMEs: JENNY, ANDREAS  (contact)

PROGRAM_OFFICER_NAME: MASKERI, BAISHALI

PROJECT_TERMS: Actins;Affect;age related decline;age-related disease;Aging;Animal Model;Autophagocytosis;Autophagosome;Award;Binding;Biochemical;Biological;Biological Process;Cardiovascular Diseases;Caring;Cell Physiology;Cells;Cellular Stress;Clinical;Complex;coping;Coupled;Cytoplasm;Data;Dementia;Development;Disease;disease model;DNA Damage;Drosophila genus;Economic Burden;Electron Microscopy;Endosomes;energy balance;Ensure;Equilibrium;Excision;Fat Body;fly;Functional disorder;Genes;Genetic;Genetic Screening;Glycogen;Goals;healthspan;Heart;human model;human old age (65+);Huntington Disease;Immune System Diseases;improved;in vivo;in vivo Model;Kidney;Kidney Diseases;knock-down;late endosome;Life;lipid metabolism;Liver;Liver diseases;Lysosomes;Machado-Joseph Disease;Malignant Neoplasms;Mammals;Mass Spectrum Analysis;Mediating;Membrane;Mitochondrial Proteins;model organism;Modeling;Molecular Chaperones;multicatalytic endopeptidase complex;Multivesicular Body;Nerve Degeneration;Nervous System;Neurodegenerative Disorders;Nobel Prize;Normal Cell;novel;Nutrient;Organelles;Organism;overexpression;Oxidative Stress;Oxidative Stress Induction;Pathway interactions;Persons;Phosphotransferases;Physiological;Physiology;Predisposition;premature;prevent;Process;protein aggregation;Protein Biosynthesis;protein degradation;Proteins;Proteome;proteostasis;proteotoxicity;Publishing;Reactive Oxygen Species;receptor;Regulation;Research;Resistance;response;Reticulum;Risk Factors;Role;sensor;Societies;socioeconomics;Sorting;Starvation;Stress;System;Testing;Tissues;Transgenic Organisms;treatment strategy;Variant;Vesicle;Wiskott-Aldrich syndrome protein

PROJECT_TITLE: Endosomal Microautophagy in Drosophila

STUDY_SECTION: CSRS

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


NIH_SPENDING_CATS: Breast Cancer;Cancer;Genetics;Radiation Oncology;Women's Health Research

ORG_CITY: CHARLOTTESVILLE

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: Narrative Radiation therapy produces DNA double strand breaks (DSBs) which are thought to be the critical lesion producing the death of cancer cells. We have recently discovered that ZEB1, a well-established driver of the epithelial-to-mesenchymal transition (EMT) has a novel function in DNA repair namely recruiting 53BP1 to DSB’s. We will elucidate the role of the ZEB1-53BP1 axis in DSB repair and test whether this axis can be exploited therapeutically as a biomarker for sensitivity and/or to make cancer cells more sensitive to radiation and PARP inhibitors.

PI_NAMEs: LARNER, JAMES M (contact)

PROGRAM_OFFICER_NAME: WITKIN, KEREN L

PROJECT_TERMS: Area;Base Excision Repairs;Binding;Binding Sites;Biological Assay;Biological Markers;BRCA deficient;BRCA1 gene;BRCA2 gene;Breast;Breast Cancer Cell;Breast Cancer cell line;Breast Cancer Model;Breast Cancer Patient;cancer cell;cancer therapy;Cell Cycle;Cell Hypoxia;Cells;Cessation of life;CHEK1 gene;Chemotherapy and/or radiation;Chromatin;chromatin modification;Chromatin Remodeling Factor;Chromatin Structure;Chromosome abnormality;cytotoxic;Development;DNA Damage;DNA Double Strand Break;DNA Repair;DNA-dependent protein kinase;DNA-PKcs;Double Strand Break Repair;Environment;epithelial to mesenchymal transition;Euchromatin;Excision;G2 Phase;gene repression;Gene Silencing;Genetic Recombination;Genetic Transcription;Genome;Genome Stability;Genomic Segment;Goals;homologous recombination;Hypoxia;Ionizing radiation;Lesion;Link;Malignant Breast Neoplasm;Malignant Neoplasms;Mammalian Cell;Mammary Neoplasms;Maps;Mediating;mouse model;mutant;Mutation;Nonhomologous DNA End Joining;normoxia;novel;novel strategies;ovarian neoplasm;p53-binding protein 1;Pathway interactions;patient response;permissiveness;Phase;Phosphorylation;Play;Poly(ADP-ribose) Polymerase Inhibitor;Polymerase;Population;predictive marker;Proteins;public database;Radiation;radiation resistance;Radiation therapy;Radiobiology;Reactive Oxygen Species;recombinational repair;recruit;Regulation;repaired;Resistance;response;restoration;Role;S phase;Site;Solid Neoplasm;Source;Testing;Therapeutic;therapy resistant;Transcription Repressor;Treatment Efficacy;treatment response;tumor;tumor hypoxia;tumor progression;Xenograft procedure

PROJECT_TITLE: The Role of ZEB1 in promoting therapeutic resistance through its interaction with 53BP1

STUDY_SECTION: RTB

STUDY_SECTION_NAME: Radiation Therapeutics and Biology Study Section[RTB]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Complementary and Integrative Health;Dietary Supplements;Digestive Diseases;Microbiome;Nutrition;Physical Injury - Accidents and Adverse Effects;Prevention

ORG_CITY: WORCESTER

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

PHR: PROJECT NARRATIVE Exposure to total body irradiation produced by nuclear accidents causes gastrointestinal acute radiation syndrome a state of severe intestinal mucosal barrier damage and loss of tissue integrity. Specific members of the intestinal microbiota promote tissue repair and function. Here we will generate novel microbiome therapeutic agents and microbiome-promoting dietary interventions that, by specifically targeting intestinal barrier function, minimize GI-ARS and increase survival after total body irradiation.

PI_NAMEs: BUCCI, VANNI  (contact);MCCORMICK, BETH A

PROGRAM_OFFICER_NAME: RIOS, CARMEN I

PROJECT_TERMS: ABCB1 gene;Antibiotics;Bacteria;Bacteroides;beta-Glucans;Bile Acids;Biological Models;Biological Response Modifier Therapy;Butyrates;Cessation of life;Clinical;Data;Data Analyses;Development;Diet;Dietary Component;Dietary Intervention;dynamic system;dysbiosis;Encapsulated;Engineered Probiotics;Engineering;Environment;Epithelium;Escherichia coli;experimental study;Exposure to;Freeze Drying;gastrointestinal;gastrointestinal bacteria;Genetic Engineering;gut colonization;gut microbiome;gut microbiota;Homeostasis;Hour;Human;Immunity;improved;In Vitro;in vivo;in vivo Model;Infection;Inflammatory;interest;intestinal barrier;intestinal epithelium;Intestines;irradiation;Maintenance;mathematical model;Measures;medical countermeasure;Meditation;member;Metagenomics;Microbe;microbiome;microbiome therapeutics;Mucous Membrane;novel;Nuclear Accidents;Nuclear Warfare;Oral;Oral Administration;Pathway interactions;permissiveness;Personal Satisfaction;Phenotype;Physiological;Physiology;Play;prebiotics;Probiotics;Production;Radiation;Radiation exposure;Radiation Toxicity;Radiobiology;receptor;Recovery;Resistance;Role;Sampling;Sepsis;Succinates;Supplementation;Surface;synthetic biology;System;Temperature;Terrorism;Testing;Therapeutic;Therapeutic Agents;Therapeutic Intervention;tissue repair;Tissues;tool;Whole-Body Irradiation;Work

PROJECT_TITLE: Development of targeted microbiome therapeutics and dietary interventions for potent intestinal barrier promotion to minimize GI-ARS


ADMINISTERING_IC: AR

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Prevention

ORG_CITY: MANHATTAN

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: KANSAS STATE UNIVERSITY

ORG_STATE: KS

PHR: PROJECT NARRATIVE  Non-dividing muscle and nerve cells have limited options to clear harmful biological insults. One such insult is the progressive accumulation of protein aggregates that destroys cellular function and may result in death. The overall goal of this application is to understand how cells normally clear aggregated proteins to eventually develop successful therapeutic strategies to maintain healthy cells.

PI_NAMEs: GEISBRECHT, ERIKA RAE (contact)

PROGRAM_OFFICER_NAME: LINDHURST, MARJORIE JEAN

PROJECT_TERMS: Affect;Autophagocytosis;BAG3 gene;Biochemical;Biochemical Pathway;Biochemistry;Biological;Biological Process;Biopsy;Carrier Proteins;Cell Aging;Cell model;Cell Physiology;cell type;Cells;Cellular biology;Cessation of life;Characteristics;Client;Complex;Data;Development;Disease;Drosophila genus;Event;Exclusion;experimental study;F-Actin;filamin;Funding;Genes;genetic analysis;Genetic Structures;Goals;hallmarks of aging;Homeostasis;Human;imaging approach;in vivo;insight;Interphase Cell;Label;Link;Maintenance;Mechanics;Mediating;Microtubules;Modeling;Molecular;Muscle;Muscle Cells;Muscle Development;Muscle Proteins;mutant;Mutation;Myopathy;Neurodegenerative Disorders;Neurons;novel;Organelles;overexpression;Pathway interactions;Patients;Phosphorylation;Phosphotransferases;Predisposition;prevent;Prevention;protein aggregation;protein degradation;Protein Region;Protein-Serine-Threonine Kinases;Proteins;proteostasis;recruit;Regulation;Role;Sagittaria;Sarcomeres;Serine;Signal Pathway;Site;System;Tendon structure;Testing;Therapeutic;tissue degeneration;trend;Ubiquitin;Work

PROJECT_TITLE: Mechanisms Underlying Muscle Development and Maintenance in Drosophila

STUDY_SECTION: SMEP

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


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

ORG_CITY: DURHAM

ORG_DEPT: SURGERY

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: In this grant, we will structurally characterize spike proteins from SARS-CoV-2 and other Coronaviruses. The overall goals of this study are to determine structures of Cov S proteins to define their conformational states, and to pair these structural data with antigenic and biophysical measures to determine the structural basis for Coronavirus (CoV) spike evolution.

PI_NAMEs: ACHARYA, PRIYAMVADA  (contact);HENDERSON, RORY

PROGRAM_OFFICER_NAME: PLIMACK, MARY KATHERINE BRADFORD

PROJECT_TERMS: 2019-nCoV;advanced simulation;Antibodies;Antigens;betacoronavirus;Biochemical;Biochemistry;Biological;biophysical analysis;Biophysics;combat;Communication;computer studies;Computing Methodologies;Coronavirus;Coronavirus spike protein;COVID-19;COVID-19 susceptibility;Cryoelectron Microscopy;current pandemic;Data;Data Set;design;Economics;Electron Microscopy;Emergency Situation;Engineering;Evolution;expectation;experimental study;Funding;future pandemic;global health;Goals;Grant;Immune Evasion;In Vitro;in vivo;innovation;insight;Kinetics;Life Cycle Stages;Link;Measures;Methods;Mink;Molecular;Molecular Conformation;Mutagenesis;Mutation;Negative Staining;neutralizing antibody;novel vaccines;pandemic response;Pathogenesis;Peptide Hydrolases;Peptides;Population;Positioning Attribute;Predisposition;Property;Protein Conformation;protein structure;Proteins;Proteolysis;Protomer;receptor;receptor binding;reconstruction;Recurrence;Reporting;Research;Resistance;Resolution;Role;SARS-CoV-2 B.1.1.7;SARS-CoV-2 B.1.351;SARS-CoV-2 B.1.617.2;SARS-CoV-2 spike protein;Site;structural biology;Structure;Surface;synergism;Techniques;Technology;TMPRSS2 gene;United States National Institutes of Health;Vaccine Design;vaccine development;vaccine hesitancy;Vaccines;Variant;variants of concern;Viral;Virus;Work;X-Ray Crystallography

PROJECT_TITLE: Effect of natural and engineered variations on structure and biophysics of SARS-CoV-2 spike

STUDY_SECTION: MSFC

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


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Data Science;Drug Abuse (NIDA only);Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Opioid Misuse and Addiction;Opioids;Racial and Ethnic Minority Health Research;Social Determinants of Health;Substance Misuse

ORG_CITY: STANFORD

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: STANFORD UNIVERSITY

PHR: PROJECT NARRATIVE  Opioid use disorder is a key driver of the U.S. opioid overdose crisis, yet treatment remains both underused and unequal. The proposed research is relevant to public health because it focuses on identifying modifiable structural predictors of treatment initiation and retention in care for opioid use disorder. The results of this project are expected to inform multilevel interventions equitably deliver treatment for opioid use disorder, ameliorate the overall health burden of substance use disorders, and reduce health disparities.

PI_NAMEs: KIANG, MATHEW VINHHOA (contact)

PROGRAM_OFFICER_NAME: SU, SHELLEY

PROJECT_TERMS: Address;Affect;Affordable Care Act;Age;American;Area;barrier to care;Big Data;Biometry;Black American;black patient;Black Populations;Black race;Buprenorphine;career;career development;Caring;caucasian American;Characteristics;Client satisfaction;Clinical Treatment;Communities;Community Surveys;Computerized Medical Record;Critical Care;Data;data warehouse;Databases;Death Rate;design;Development Plans;Effectiveness;electronic data;Eligibility Determination;Epidemiology;Equity;ethnic disparity;Ethnic Origin;Ethnic Population;experience;Face;forest;Foundations;Health;Health Personnel;Health Resources;Health Services Accessibility;Healthcare Systems;improved;improved outcome;Individual;innovation;Intervention;Machine Learning;machine learning method;Measures;Medical;medication for opioid use disorder;Mental Health;Mentorship;Methods;Minority Groups;Modeling;multidisciplinary;multiple data sources;Natural experiment;novel strategies;Opioid;opioid overdose;opioid use disorder;Patients;Perception;Persons;Pharmaceutical Preparations;Phase;Population;Prediction of Response to Therapy;Provider;Public Health;Race;racial bias;racial disparity;racial population;Reduce health disparities;Research;skills;social;Specialist;standard of care;structural determinants;Substance Use Disorder;success;Therapeutic;Training;treatment disparity;Treatment outcome;Veterans;Veterans Health Administration;Visit;Work

PROJECT_TITLE: Reducing racial disparities in the treatment of opioid use disorder using machine learning-based causal analysis


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Clinical Research;Coronaviruses;Emerging Infectious Diseases;Infectious Diseases;Influenza;Lung;Pneumonia and Influenza;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: PROJECT NARRATIVE The primary cause of sickness and mortality in respiratory viral infections in humans is often not uncontrolled viral replication, but respiratory distress caused by pro-inflammatory cell infiltration and a loss of epithelial cell resilience and function. An understanding of the baseline host factors present in diverse people is critical to better determine the risk of susceptible populations and novel therapeutic strategies to effectively promote tissue resilience. Importantly, as vaccines for both influenza and SARS-CoV-2 are non-sterilizing, and variants continue to emerge for both, underlying causes of severe viral respiratory diseases will still continue to require adjunctive therapies to complement vaccination campaigns.

PI_NAMEs: ORDOVAS-MONTANES, JOSE MANUEL (contact)

PROGRAM_OFFICER_NAME: LU, QING

PROJECT_TERMS: 2019-nCoV;Airway Disease;airway epithelium;Anabolism;Anti-viral resistance;Anti-viral Response;Area;assault;Basal Cell;Biogenesis;Biology;Cachexia;Cardiovascular system;Cell Physiology;Cell Survival;Cells;cellular resilience;Cholesterol;cholesterol biosynthesis;Clinical;cohort;Complement;Coupled;COVID-19;COVID-19 pandemic;COVID-19 patient;Data;Defect;design;Development;Disease;epidemiology study;Epithelial Cells;epithelial stem cell;Epithelium;Equilibrium;flu;Genes;Genetic study;Glycoproteins;Goblet Cells;Health;Histologic;Host Defense;Host resistance;Human;Immunity;Impairment;in vivo;Individual;Infection;Infiltration;Inflammatory;Influenza;influenza infection;influenzavirus;innovation;Integration Host Factors;Interferons;Investigation;Knowledge;Laboratories;Lead;Light;lipid metabolism;lipidomics;Lipids;Metabolic;Modeling;Molecular;mortality;Mus;Mutation;nasopharyngeal swab;novel;novel therapeutic intervention;obese person;Outcome;Overweight;Oxidoreductase;Pathogenesis;Pathogenicity;Persons;Phenotype;Population;Predisposition;prophylactic;prospective;Publishing;recruit;Regenerative capacity;Research;resilience;Resistance;resistance mechanism;respiratory;Respiratory Disease;Respiratory distress;Respiratory System;respiratory virus;response;Risk;RNA Viruses;screening;seasonal influenza;Secretory Cell;Sensory;severe COVID-19;Severity of illness;Signal Transduction;single-cell RNA sequencing;Specialized Epithelial Cell;stability testing;STAT1 gene;stem cells;Structure of mucous membrane of nose;System;Testing;Therapeutic;Tissues;Up-Regulation;Vaccination;Vaccines;Variant;Viral;Viral Respiratory Tract Infection;Virus;Virus Diseases;Virus Replication;Work;Zinc

PROJECT_TITLE: Balancing epithelial cell resistance and resilience to respiratory viral infections

STUDY_SECTION: LCMI

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


ADMINISTERING_IC: NR

ED_INST_TYPE: SCHOOLS OF NURSING

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF NURSING RESEARCH

NIH_SPENDING_CATS: Anxiety Disorders;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Depression;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Mental Illness;Palliative Care;Post-Traumatic Stress Disorder (PTSD);Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Violence Against Women;Violence Research;Women's Health Research

ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE: This research will develop and examine the feasibility and preliminary efficacy of an intervention to improve psychological distress symptom management related to chronic stigma exposure among Black GM women in a community-based setting. The long-term goal of this intervention is to disrupt the complex interacting psychosocial and behavioral factors that exacerbate symptoms of psychological distress with the hope to eventually prevent and/or reduce poor health outcomes in Black GM women experiencing chronic stigma. The proposed study has high public health significance because it plays an essential role in developing and evaluating evidence-based interventions to improve health among a historically disenfranchised group, i.e., Black GM women. 2

PI_NAMEs: SHERMAN, ATHENA D. F. (contact)

PROGRAM_OFFICER_NAME: BOWEN, MARY ELIZABETH

PROJECT_TERMS: adaptive intervention;Address;Adherence;Applications Grants;Applied Research;barrier to care;Behavior Therapy;Behavioral;Birth;Black race;Cardiovascular Diseases;career;career development;Caring;Chronic;cisgender;clinical training;Collaborations;Communities;community advisory board;community engaged research;community intervention;community-level factor;Complex;coping;Coping Skills;culturally appropriate intervention;depressive symptoms;Discrimination;disenfranchised population;Education;Emotional;Ensure;Evaluation;Evidence based intervention;experience;Face;Feedback;Feeling;Feminine;Focus Groups;Fright;future implementation;Gender;gender behavior;gender minority;gender minority community;gender minority group;gender minority women;General Population;Goals;Health;health care availability;health care settings;Health Insurance;Health Personnel;Healthcare;HIV;improved;Individual;Inflammation;informant;Infrastructure;innovation;Institution;Institutional Racism;Instruction;Intervention;intervention refinement;Interview;Investigation;iterative design;Major Depressive Disorder;male;Manuscripts;Medical;member;Mental Health;Mentorship;Metabolic Diseases;Methods;minority stressor;Modeling;Murder;novel;Participant;Pathway interactions;patient oriented research;peer;persistent symptom;Personal Satisfaction;Persons;Phase;Physiological;Play;Policies;poor health outcome;Population;Post-Traumatic Stress Disorders;post-traumatic symptoms;Preparation;Prevalence;prevent;psychological distress;psychological symptom;psychosocial;Public Health;Publishing;Quality of life;Race;racism;recruit;reduce symptoms;Reporting;Research;Research Ethics;Research Training;resilience;resilience factor;response;retention rate;Risk Factors;Role;Safety;satisfaction;Self Determination;Series;Severities;sex assigned;Sexual and Gender Minorities;Social Functioning;social stigma;Strategic Planning;Surveys;symposium;symptom management;symptom science;symptomatic improvement;Symptoms;Testing;Therapeutic;therapy design;therapy development;Training;Training Programs;transgender;Trauma;Treatment Efficacy;United States;United States National Institutes of Health;Universities;uptake;Victimization;virtual delivery;vulnerable community;Vulnerable Populations

PROJECT_TITLE: A Behavioral Intervention to Reduce Psychological Distress Symptoms among Black Gender Minority Women Experiencing Chronic Stigma

STUDY_SECTION: NRRC

STUDY_SECTION_NAME: Nursing Science Review Committee[NRRC(81)]


NIH_SPENDING_CATS: Genetics;Infertility

ORG_CITY: NEW ORLEANS

ORG_NAME: TULANE UNIVERSITY OF LOUISIANA

ORG_STATE: LA

PHR: PROJECT NARRATIVE Transposons are mobile DNA elements that are ubiquitous in genomes of all animals, including humans. Overactive transposons are correlated with DNA damage and infertility, but it is unclear whether the transposons are playing a causative role in infertility. In this proposal, we will examine transposon activity in germ cells and experimentally block or activate transposition to assess the effects on genome integrity.

PI_NAMEs: HAN, JEFFREY S (contact)

PROGRAM_OFFICER_NAME: MACARTHUR, LINDA

PROJECT_TERMS: Affect;Aging;Alleles;Amino Acid Motifs;Animals;Attenuated;Automobile Driving;Biochemical;Biogenesis;Biological;Biology;Breeding;cell immortalization;Cell Line;Complex;Cultured Cells;Defect;Disease;DNA Damage;Elements;Endosomes;Enterobacteria phage P1 Cre recombinase;Event;Family;Frequencies;Future;Genes;Genetic Polymorphism;Genetic Recombination;Genetic Screening;Genome;genome integrity;Genomics;Germ Cells;Germ Lines;Germ-Line Mutation;Human;human male;human tissue;in vivo;Infertility;insight;Integration Host Factors;Knock-in Mouse;Knock-out;Knockout Mice;Knowledge;Leptotene Stage;male;Male Infertility;Male Sterility;Malignant Neoplasms;mammalian genome;Mammals;Meiosis;Meiotic Prophase I;model organism;Modeling;mouse genetics;mouse model;Mus;mutant;Mutate;Mutation;Nervous System Disorder;Nuclear;overexpression;Pachytene Stage;particle;Pathway interactions;Phenotype;piRNA;Play;Productivity;promoter;Prophase;Regulation;Retrotransposition;Ribonucleoproteins;Role;Small RNA;Sorting;Spermatocytes;tissue culture;trafficking;Transgenes;transposon/insertion element;Wild Type Mouse;Work;Yeasts;Zygonema

PROJECT_TITLE: In vivo biology of mammalian L1 retrotransposition

STUDY_SECTION: GVE

STUDY_SECTION_NAME: Genetic Variation and Evolution Study Section[GVE]


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Cancer;Childhood Leukemia;Genetics;Hematology;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: Columbus

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: PROJECT NARRATIVE The goal of this proposal is to study the immunophenotype of PTPN11 and NPM1 mutant acute myeloid leukemia (AML) and the mechanism of resistance to cytotoxic and targeted therapies. Because PTPN11 mutations can activate similar signaling pathways as FLT3-ITD, we hypothesize that the addition of PTPN11 mutations to NPM1+ AML can clinically phenocopy NPM1+/FLT3-ITD AML with adverse outcomes and therapy resistance. Successful completion of these aims will provide an understanding of the biology of PTPN11 and NPM1 mutant AML and how these cells resist treatment so that more effective therapies can be developed for this patient population.

PI_NAMEs: FOBARE, SYDNEY  (contact)

PROGRAM_OFFICER_NAME: PURI, ANU

PROJECT_TERMS: Acute Myelocytic Leukemia;acute myeloid leukemia cell;Address;adverse outcome;Animals;anti-cancer research;Apoptotic;Biology;Cell Line;Cells;Chemoresistance;chemotherapy;Clinical;Clinical Skills;Clonal Expansion;Communication;Comprehensive Cancer Center;Critical Thinking;cytokine;Cytotoxic Chemotherapy;Data;Data Set;Development;Disease;Disease-Free Survival;Doctor of Philosophy;doctoral student;effective therapy;Engraftment;Experimental Designs;FDA approved;FLT3 gene;Foundations;Frequencies;Future;Genes;Genetic;Goals;Hematologic Neoplasms;Hematology;Human;human disease;immunodeficiency;Immunodeficient Mouse;Immunophenotyping;Immunosuppression;Impairment;improved;Inferior;Interleukin-10;Knowledge;Laboratories;leukemogenesis;Malignant - descriptor;MAP Kinase Gene;MCL1 gene;Measures;Modeling;mouse model;Mus;mutant;Mutate;Mutation;Myeloid Cells;Myeloid Progenitor Cells;New Agents;NF-kappa B;novel;novel therapeutics;nucleophosmin;Ohio;Outcome;overexpression;Pathway interactions;patient population;patient subsets;Patient-Focused Outcomes;Patients;Pharmaceutical Preparations;Phenocopy;Phenotype;PIK3CG gene;Play;Pre-Clinical Model;preclinical study;programs;Proliferating;Proteins;Proto-Oncogene Proteins c-akt;PTPN11 gene;PTPN22 gene;Relapse;Reporting;Research;Research Personnel;Research Proposals;Research Training;Resistance;resistance mechanism;response;Rest;Role;Signal Pathway;Signal Transduction;skills;Supervision;T-Lymphocyte;targeted treatment;Technical Expertise;Testing;Therapeutic;therapy development;Time;Training;transcription factor;Transgenic Organisms;translational scientist;treatment response;treatment strategy

PROJECT_TITLE: The role of PTPN11 and NPM1 mutations in acute myeloid leukemia development and therapy resistance


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Childhood Obesity;Clinical Research;Clinical Trials and Supportive Activities;Natural Products;Obesity;Pediatric;Rare Diseases

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: Pseudohypoparathyroidism is a genetic disorder with limited treatment options, characterized by early-onset obesity, short stature and resistance to multiple hormones. This phase 2 clinical trial and open-label extension study will test the efficacy of theophylline, a phosphodiesterase inhibitor, in pseudohypoparathyroidism. We hypothesize that theophylline will cause weight loss, slow the rate of growth plate closure and decrease hormone resistance in children.

PI_NAMEs: SHOEMAKER, ASHLEY HALL (contact)

PROGRAM_OFFICER_NAME: MALOZOWSKI, SAUL N

PROJECT_TERMS: 12 year old;13 year old;Adolescent;Adult;Anterior Pituitary Gland;Body mass index;Body Weight;Body Weight decreased;bone;bone age;bone epiphysis;Calcitriol;Child;Childhood;Clinical Research;Clinical Trials;Coupled;Cyclic AMP;Data;Disease;Dose;Double-Blind Method;Drug Kinetics;drug repurposing;early-onset obesity;effective therapy;efficacy testing;Energy Metabolism;Enrollment;Enzymes;Epiphysial cartilage;Foundations;Funding;G Protein-Coupled Receptor Signaling;G-Protein-Coupled Receptors;gene repression;Genes;Genetic Diseases;Goals;Gonadal structure;GTP-Binding Protein alpha Subunits, Gs;GTP-Binding Proteins;Heterozygote;high risk;Hormonal;hormonal signals;hormone deficiency;hormone regulation;Hormone replacement therapy;hormone resistance;hormone sensitivity;Hormones;Hypothalamic structure;Impairment;improved;Investigational New Drug Application;Measures;Melanocortin 4 Receptor;Monitor;Mutation;Non-Insulin-Dependent Diabetes Mellitus;Obesity;open label;Outcome Measure;parathyroid hormone-related protein;Patient Recruitments;Patients;pediatric patients;Pharmaceutical Preparations;phase 2 study;Phase II Clinical Trials;Phenotype;Phosphodiesterase Inhibitors;phosphoric diester hydrolase;Pituitary Gland;Placebos;premature;primary outcome;Production;Proteins;Proximal Kidney Tubules;Pseudohypoparathyroidism;PTH gene;Published Comment;Randomized;randomized placebo-controlled clinical trial;randomized, clinical trials;Rare Diseases;receptor;receptor function;Receptor Signaling;Recording of previous events;Resistance;response;Rest;Safety;secondary outcome;Serum;severe early onset obesity;Signal Transduction;Somatotropin;Sympathetic Nervous System;Testing;Theophylline;Thyroid Gland;Thyrotropin;Thyroxine;Treatment Efficacy;Youth

PROJECT_TITLE: Phase 2 Study of Theophylline for the Treatment of Psuedohypoparathyroidism

STUDY_SECTION: MCE

STUDY_SECTION_NAME: Molecular and Cellular Endocrinology Study Section[MCE]


ADMINISTERING_IC: MH

ED_INST_TYPE: GRADUATE SCHOOLS

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

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

ORG_CITY: Princeton

ORG_DEPT: NEUROSCIENCES

ORG_NAME: PRINCETON UNIVERSITY

ORG_STATE: NJ

PHR: PROJECT NARRATIVE This project will investigate how the brain controls behavior by guiding the flow of neural activity between brain regions. Disrupting the brain’s ability to control the flow of neural activity leads to the deficits observed in many neuropsychiatric and neurological disorders, including schizophrenia and autism. By providing insight into the mechanisms controlling neural activity, our work will lay the foundation for improved diagnostics and treatments of these diseases.

PI_NAMEs: BUSCHMAN, TIMOTHY J. (contact)

PROGRAM_OFFICER_NAME: RANGEL GOMEZ, MAURICIO

PROJECT_TERMS: Animals;autism spectrum disorder;Basal Ganglia;Behavior;behavior change;Behavior Control;Behavioral;Brain;brain control;Brain region;Calcium;Cognitive;cognitive control;Corpus striatum structure;Crowding;Diagnostic;Disease;Dopamine;Dorsal;Electrophysiology (science);Environment;Evolution;experience;Foundations;Frequencies;Friends;Image;improved;innovation;insight;learned behavior;Learning;locus ceruleus structure;Medial;memory process;memory recall;Midbrain structure;Modeling;Motor;Motor Cortex;Movement;Mus;Nervous System Disorder;neural;neural patterning;neuromechanism;Neuromodulator;Neurons;neuropsychiatric disorder;neuroregulation;noradrenergic;Norepinephrine;novel;optogenetics;Parietal Lobe;Pattern;Population;Positioning Attribute;predictive modeling;Prefrontal Cortex;Process;recruit;response;Rewards;Role;Route;Schizophrenia;Sensory;sensory cortex;sensory input;Sensory Process;Series;Signal Transduction;spatiotemporal;stimulus processing;Techniques;Testing;Thalamic structure;Time;Ventral Tegmental Area;Work

PROJECT_TITLE: Understanding the Neural Mechanisms Controlling Brain-wide Dynamics

STUDY_SECTION: LMDN

STUDY_SECTION_NAME: Learning, Memory and Decision Neuroscience Study Section[LMDN]


ADMINISTERING_IC: ES

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Behavioral and Social Science;Biotechnology;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Pediatric;Prevention;Social Determinants of Health;Women's Health Research

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

PHR: NARRATIVE The Rhode Island Child Health Study (RICHS) cohort provides a unique and innovative birth cohort resource focused on the fundamental role of the placenta in the programming of children’s health and disease risk by the prenatal environment. During the prior funding period, cohort resources and investigators have made seminal contributions to children’s environmental health and to training the next generation of environmental health scholars. Infrastructure support for sustaining the cohort will support new longitudinal assessments within this extensively characterized resource, enrichment of data management and sharing activities, and new efforts to diversify the participants, measures, and workforce for the cohort—all serving the ultimate goal of catalyzing transformative environmental health research by strengthening and diversifying the scientific workforce.

PI_NAMEs: MARSIT, CARMEN JOSEPH (contact);STROUD, LAURA R

PROGRAM_OFFICER_NAME: GRAY, KIMBERLY A

PROJECT_TERMS: Acceleration;Age;Ancillary Study;Award;Behavioral;biobank;Biological;Birth;cardiometabolism;career;Chemicals;Child;Child Health;Clinical;cohort;Cohort Studies;Collaborations;Collection;Communities;community engaged research;critical period;Data;Data Analyses;Data Collection;data management;Data Scientist;Data Set;data sharing;Development;Disease;Disease Outcome;disorder risk;Diverse Workforce;early childhood;Enrollment;Environment;environmental enrichment for laboratory animals;Environmental Epidemiology;Environmental Exposure;Environmental Health;Environmental Impact;Epidemiologist;Epidemiology;epigenetic clock;Epigenetic Process;epigenetic variation;epigenomics;experience;Faculty;Fellowship;Female;follow-up;Funding;Future;genomic data;Genomics;Goals;Grant;Growth;Health;Infant;Infrastructure;innovation;Investments;K-Series Research Career Programs;Link;Maintenance;marginalized population;Massachusetts;Measures;Mediating;method development;Minority Groups;Molecular;Molecular Biology;Mothers;National Institute of Environmental Health Sciences;neurobehavioral;Newborn Infant;next generation;novel;offspring;open data;Outcome;Participant;Peer Review;Placenta;Placental Biology;population based;Positioning Attribute;post-doctoral training;Postdoctoral Fellow;postnatal;Pregnancy;prenatal;Productivity;prospective;Psychologist;Public Policy;Publications;R24;recruit;Regulation;Research;Research Assistant;Research Personnel;Resources;Rhode Island;Risk Assessment;Role;Sampling;Scientist;Seminal;Sleep;social;social determinants;social epidemiology;social health determinants;Source;structural determinants;structural health determinants;Structural Racism;System;tool;Training;U-Series Cooperative Agreements;Underrepresented Populations;United States National Institutes of Health;validation studies;Variant;Work

PROJECT_TITLE: Enriching the Rhode Island Child Health Study


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Neurosciences;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn;Rare Diseases;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Nonembryonic - Non-Human;Vector-Borne Diseases;Zika Virus

ORG_CITY: GALVESTON

ORG_NAME: UNIVERSITY OF TEXAS MED BR GALVESTON

ORG_STATE: TX

PHR: PROJECT NARRATIVE The proposed project is to study the cellular and molecular mechanisms underlying Zika virus vertical transmission from mother to fetal brain and its associated microcephaly. The outcomes of this study will pave the way toward identification of innovative targets for the development of new treatments or preventive strategies against ZIKV- and possibly other viruses-mediated brain teratogenesis.

PI_NAMEs: WANG, TIAN ;WU, PING  (contact)

PROGRAM_OFFICER_NAME: DALEY, WILLIAM PATRICK

PROJECT_TERMS: Abbreviations;Affect;Animal Model;B-Cell Activation;Biochemical;Biological Assay;Brain;brain cell;Cell Death;Cell model;Cells;Central Nervous System;Collaborations;conditional knockout;congenital zika syndrome;cytokine;Data;Development;Disease Outbreaks;Embryo;Embryonic Development;Endoplasmic Reticulum;Enhancers;Equus caballus;fetal;Fetal Growth Retardation;Fetus;Flavivirus;genetic manipulation;glial activation;Goals;Growth;Human;human embryonic stem cell;Immune;Immunology;Impairment;In Vitro;in vivo;Incidence;Infection;infection rate;Inflammatory;inhibitor-of-apoptosis protein;innovation;Interferon-beta;IRF3 gene;knock-down;Knock-out;Knockout Mice;Light;MAP Kinase Gene;Mediating;Microcephaly;Microglia;Mitogen-Activated Protein Kinases;Molecular;Mothers;Mus;Myelogenous;nerve stem cell;neural;Neuroanatomy;neurogenesis;Neurons;Neurosciences;Newborn Infant;novel therapeutic intervention;Nuclear;Outcome;Outcome Study;Play;Polymerase Chain Reaction;Prevention;Prevention strategy;Production;Productivity;progenitor;Protein-Serine-Threonine Kinases;receptor;Reporting;response;RIPK1 gene;Role;Source;stem cell function;Syndrome;teratogenesis;Testing;Time;TLR3 gene;TLR7 gene;TLR8 gene;TNF Receptor-Associated Factors;TRAF6 gene;Transcription Factor AP-1;transmission process;Ubiquitin;ubiquitin-protein ligase;Vertical Transmission;Viral;Virus;Virus Diseases;Yolk Sac;Zika Virus;ZIKV infection

PROJECT_TITLE: Role of microglia in neural infection

STUDY_SECTION: CNBT

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


ORG_CITY: NEW YORK

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: Project Narrative The proposed research is relevant to public health because it focuses on determining the effects of high fat diet on pancreatic nerve structure, gene expression and function that are crucial to regulating blood glucose. This information is a critical foundation to translational studies to exploit neural signals to treat diabetes. Thus the proposed research is relevant to the part of the NIH's mission that pertains to reducing illness and disability.

PI_NAMEs: STANLEY, SARAH AMY (contact)

PROGRAM_OFFICER_NAME: COOKE, BRAD

PROJECT_TERMS: 3-Dimensional;Affect;Alpha Cell;Beta Cell;Biology;Blood Glucose;blood glucose regulation;Celiac ganglion;Cells;Cholinergic Receptors;critical period;D Cells;Data;density;Diabetes Mellitus;disability;Efferent Neurons;Endocrine;experience;Fasting;Foundations;Functional disorder;Future;Gene Abnormality;Gene Expression;Gene Expression Profile;gene function;Genetic;Genetic Identity;Glucose;Goals;High Fat Diet;high resolution imaging;Hormones;Hyperglycemia;Image;Impairment;improved;insight;Insulin;Insulin deficiency;islet;Islet Cell;Islets of Langerhans;Knowledge;Lipids;Literature;Maps;Measures;Mission;Modeling;Molecular;Morphology;Mus;Nerve;nerve supply;neural;neural circuit;Neural Pathways;Neurons;neuroregulation;neurotransmission;Neurotransmitters;Non-Insulin-Dependent Diabetes Mellitus;novel strategies;Obesity;Organ;Oxidative Stress;Pancreas;Pancreatic Hormones;Pathway interactions;Population;prevent;programs;Public Health;Purinoceptor;receptor expression;Research;response;Role;single-cell RNA sequencing;Slice;Specificity;Structure;Suggestion;Synapses;Techniques;Testing;Therapeutic;therapeutic target;three dimensional structure;Three-Dimensional Imaging;Time;tool;transcriptome;transcriptome sequencing;translational study;United States National Institutes of Health;Variant

PROJECT_TITLE: Neural control of pancreatic endocrine function in obesity and diabetes

STUDY_SECTION: IPOD

STUDY_SECTION_NAME: Integrative Physiology of Obesity and Diabetes Study Section[IPOD]


NIH_SPENDING_CATS: Clinical Research;Genetics;Infectious Diseases;Rare Diseases;Sexually Transmitted Infections

ORG_CITY: INDIANAPOLIS

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: PROJECT NARRATIVE Definition of the how the host and an infecting bacterium interact with each other on a molecular level offers a new strategy to broaden our understanding of infectious diseases but has yet to be done in humans. The purpose of this application is to determine such a network for the skin pathogen Haemophilus ducreyi in experimentally infected human volunteers.

PI_NAMEs: SPINOLA, STANLEY M. (contact)

PROGRAM_OFFICER_NAME: VINCENT, LEAH REBECCA

PROJECT_TERMS: Abscess;Adult;Affect;Africa;Anaerobiosis;Annual Reports;Antibiotics;Ascorbic Acid;Asia;Azithromycin;Bacteria;Bacterial Genes;Bacterial Infections;Binding;Biology;Carbon;case finding;Case Study;Cells;Chancroids;Child;Chronic;Communicable Diseases;Country;Cutaneous;Data;Development;disability;Disease;Endemic Diseases;extracellular;fly;Gene Expression;Genes;Genetic Transcription;Genitalia;genome sequencing;Growth;Hemophilus ducreyi;HIV;HIV-1;Host Defense;Human;Human Volunteers;Immune response;In Vitro;in vivo;Individual;Infection;infection risk;Infectious Skin Diseases;insight;Ions;Leprosy;Lesion;Macrophage;Metabolic;metabolome;metabolomics;Metals;Micro Array Data;Modeling;Molecular;Mus;neglected tropical diseases;neutrophil;novel strategies;Nutrient;Nutritional;Organism;Papua New Guinea;pathogen;Pathogenesis;Pathway interactions;Phagocytes;Phagocytosis;Pharmaceutical Preparations;pressure;Publications;response;single-cell RNA sequencing;Site;Skin;Skin colonization;skin disorder;Source;Testing;therapeutic development;Tissues;Transcript;transcriptome sequencing;transmission process;Treponema pallidum;Ulcer;Upper arm;uptake;Vaccines;Virulence;volunteer;whole genome;World Health Organization;Yaws

PROJECT_TITLE: Determination of the Interactome between Haemophilus ducreyi and the Human Host.

STUDY_SECTION: HIBP

STUDY_SECTION_NAME: Host Interactions with Bacterial Pathogens Study Section[HIBP]


NIH_SPENDING_CATS: Clinical Research;Digestive Diseases;Genetics;Infectious Diseases;Liver Disease;Malaria;Rare Diseases;Vector-Borne Diseases

ORG_CITY: BALTIMORE

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

ORG_STATE: MD

PHR: Narrative Plasmodium vivax parasites have the unique ability to remain dormant in the liver before reactivating weeks or months later to cause relapse infections. This feature, that greatly complicates vivax malaria elimination efforts, remains poorly understood due to the difficulties of studying P. vivax liver-stage parasites. We propose to use a combination of novel ‘omic approaches, including the characterization of host cells and parasites spatially and at the single cell level, to study dormancy in vivo in a non-human primate model, and well as in vitro. Our studies will generate novel biological insights on the regulation of liver-stage dormancy and provide immediately-relevant clinical information to better control this important human pathogen.

PI_NAMEs: SERRE, DAVID  (contact)

PROGRAM_OFFICER_NAME: MCGUGAN, GLEN C

PROJECT_TERMS: Acute;Africa;Anatomy;ATAC-seq;Biological;Biological Assay;Biological Markers;Biology;biomarker identification;Cambodia;Cambodian;cell type;Cells;Clinical;clinically relevant;Collection;Culicidae;Custom;Data;Endogenous Factors;Epigenetic Process;epigenomics;Falciparum Malaria;Foundations;gene complementation;Gene Expression Profile;Gene Expression Profiling;Genetic Transcription;Hepatic;Hepatocyte;Human;human pathogen;humanized mouse;Immune response;improved;In Vitro;in vitro Assay;in vitro Model;in vivo;Infection;infection risk;insight;Knowledge;Laboratories;lipidomics;Liver;liver development;Location;Maintenance;Malaria;Malaria Vaccines;mass spectrometric imaging;Messenger RNA;Metabolic;Methods;Modeling;Molecular;Monkeys;multiple omics;nano;nonhuman primate;novel;novel therapeutic intervention;Organ;Organism;Outcome;Parasites;Patients;Plasmodium falciparum;Plasmodium vivax;Population;Populations at Risk;Prevalence;prevent;Process;Regulation;Relapse;Research;resilience;response;Role;Saimiri;Salivary Glands;single-cell RNA sequencing;Solid;specific biomarkers;Sporozoites;Testing;Tissues;transcriptome sequencing;transcriptomics;United States National Institutes of Health;Variant;vector;Vivax Malaria;Work

PROJECT_TITLE: Multi-Omics Characterization of Plasmodium Vivax Hypnozoites


ORG_CITY: CORAL GABLES

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

ORG_STATE: FL

PHR: Project Narrative Many pathologic conditions are associated with genetic or acquired abnormalities in the levels of hormones secreted by the central nervous system. This project studies Gbeta5-R7, a protein complex highly expressed in the brain, and the new finding is it is responsible for maintaining normal body weight in mice. Mutations in the human genes that encode Gbeta5-R7 are genetically linked in with obesity, and this research will develop a new avenue for understanding, diagnosing and treating obesity and other metabolic disorders.

PI_NAMEs: SLEPAK, VLADLEN Z (contact)

PROJECT_TERMS: Ablation;Acquired Abnormality;Acute;Adult;Affect;Agonist;Alleles;Animals;Antibodies;Beta Cell;biological systems;Body Weight;Brain;Cardiovascular Diseases;Cardiovascular system;Cell Line;Cell Nucleus;Cell Physiology;Central Nervous System;cholinergic;comorbidity;Complex;Controlled Environment;CRISPR/Cas technology;Data;Diabetes Mellitus;Diagnosis;dimer;Disease;effective therapy;energy balance;Energy Intake;Equilibrium;Etiology;Event;experimental study;extracellular;Family;G-Protein-Coupled Receptors;Gene Transfer;Genes;GNB5 gene;Goals;Growth;GTP-Binding Protein beta Subunits;GTP-Binding Protein Regulators;GTP-Binding Proteins;Heterozygote;Homeostasis;Hormone secretion;Hormones;Human;Human Genetics;Hypothalamic Hormones;Hypothalamic structure;In Situ;In Vitro;in vivo;Injections;insight;insulin secretion;Inulin;Investigation;Kidney Diseases;kinase inhibitor;knock-down;Knock-out;knockout gene;Link;Malignant Neoplasms;Maps;Measures;Messenger RNA;Metabolic;Metabolic Diseases;Metabolic syndrome;Metabolism;Molecular;Molecular Abnormality;Mus;Muscarinic Acetylcholine Receptor M3;mutant;Mutation;Nervous System Disorder;Neuroendocrinology;Neurologic;Neurons;Neurosecretory Systems;Neurotransmitters;Non-Insulin-Dependent Diabetes Mellitus;novel;novel therapeutic intervention;Obesity;Organ;overexpression;Pancreas;Pathologic;Pathway interactions;Pattern;peptide hormone;Peripheral;pharmacologic;Phenotype;Phosphorylation;Physiological;Play;Population;protein complex;Proteins;real-time images;Regulation;Research;response;RGS Proteins;Risk Factors;Role;Second Messenger Systems;Series;Signal Transduction;Signaling Protein;Slice;Stimulus;Stroke;Structure;Structure of beta Cell of islet;System;Testing;Tissues;Viral Genes;Viral Vector;Weight Gain

PROJECT_TITLE: The role of regulator of G protein signaling Gbeta5-R7 in neuronal control of body weight

STUDY_SECTION: MIST

STUDY_SECTION_NAME: Molecular and Integrative Signal Transduction Study Section[MIST]


NIH_SPENDING_CATS: Aging;Biotechnology;Congenital Structural Anomalies;Genetics;Osteoporosis;Pediatric;Rare Diseases;Women's Health Research

ORG_CITY: REDLANDS

ORG_NAME: LOMA LINDA VETERANS ASSN RESEARCH & EDUC

PHR: PROJECT NARRATIVE Developing strategies to treat osteoporosis, a major public health threat, would require a thorough understanding of the molecular mechanisms involved in the regulation of bone resorption and bone formation processes. Successful completion of the proposed in vitro studies using primary cultures derived from Lrrk1 knockout mice and in vivo experiments in CRISPR/Cas9 gene modified mice should lead to improved understanding of how leucine rich repeat kinase 1 (LRRK1) regulates osteopetrosis specific transmembrane protein 1 (OSTM1) activation, osteoclast function and thereby bone resorption. Our identification of LRRK1 direct biological substrates and confirmation of the role of LRRK1 phosphorylation of OSTM1 in regulation of osteoclast function and bone resorption in animal models will lead to development of novel anti-resorption drugs for treatment of patients with osteoporosis and osteoporotic fractures.

PI_NAMEs: XING, WEIRONG  (contact)

PROGRAM_OFFICER_NAME: NICKS, KRISTY

PROJECT_TERMS: Acids;Actins;Albers-Schonberg disease;Animal Model;Antibodies;Appearance;Binding;Biological;Biological Assay;bisphosphonate;bone;bone fracture repair;Bone Matrix;Bone necrosis;Bone Resorption;bone turnover;Brain;cathepsin K;Chloride Channels;Complex;Consensus Sequence;Coupled;CRISPR/Cas technology;Cytoplasm;Cytoskeleton;Data;Development;Diffusion;Docking;Drug Targeting;Enzymes;Exhibits;Exocytosis;experimental study;extracellular;F-Actin;Femoral Fractures;Forteo;Functional disorder;Future;Gender;Gene Modified;Gene Mutation;Genetic;Goals;Grant;Homeostasis;Ideal 1;Impairment;improved;In Vitro;in vivo;inhibitor;Integral Membrane Protein;Jaw;Kinesin;Knock-out;knockout gene;Knockout Mice;LAMP-2;Lead;Leucine-Rich Repeat;live cell imaging;Lysosomes;Measures;Mediating;mimetics;Molecular;Monitor;Motor;Movement;Mus;mutant;Mutant Strains Mice;Mutation;novel;Osteoclasts;Osteogenesis;Osteoporosis;osteoporosis with pathological fracture;Ovariectomy;overexpression;Patients;Peptides;Peripheral;Pharmaceutical Preparations;Pharmacotherapy;Phenotype;Phosphorylation;Phosphorylation Site;Phosphotransferases;Play;Postmenopause;Process;protein complex;Protein-Serine-Threonine Kinases;Proteins;Proteomics;Protons;Public Health;Regulation;Resistance;response;Risk;Role;Serine;Serine/Threonine Phosphorylation;Signal Transduction;small molecule inhibitor;spine bone structure;Therapeutic;therapeutic development;Threonine;Tissues;TNFSF11 gene;Tubular formation;vacuolar H+-ATPase;Variant;Wild Type Mouse;Woman;Work

PROJECT_TITLE: Molecular Mechanisms of LRRK1 Regulation of Bone Homeostasis

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


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Climate-Related Exposures and Conditions;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Networking and Information Technology R&D (NITRD);Social Determinants of Health

ORG_CITY: MINNEAPOLIS

ORG_NAME: UNIVERSITY OF MINNESOTA

PHR: Narrative Climate change poses an enormous threat to human health on a global scale. Because the health consequences of climate change vary by location, depending on complex relationships among population characteristics, livelihoods, and built and natural environmental conditions, understanding and mitigating the health impacts of climate change requires information on population and agricultural characteristics at the community level. By providing easy access to detailed data on demographic and socioeconomic characteristics and agricultural activity at community scales and making them readily linkable to data on health, IHGIS will serve as critical infrastructure to support a wide range of environmental health research for public health policy worldwide.

PI_NAMEs: GRACE, KATHRYN ;KUGLER, TRACY A (contact)

PROGRAM_OFFICER_NAME: O'FALLON, LIAM

PROJECT_TERMS: Address;Affect;agricultural activity;Agriculture;base;career;Censuses;Cessation of life;Characteristics;climate change;climate impact;climate-related health;Code;Collection;Communities;Complex;Computer software;Country;Data;Data Set;Database Management Systems;Databases;Decision Making;Demographic and Health Surveys;demographics;Dengue Infection;design;Discipline;Education;Educational workshop;Employment;Enhancement Technology;Ensure;Environmental Exposure;Environmental Health;Environmental Risk Factor;falls;Farm;food insecurity;Foundations;Funding;Geographic Information Systems;Geography;global environment;global health;Goals;Health;health data;health disparity;Health Policy;Health Sciences;Health Surveys;heterogenous data;Housing;Human;human old age (65+);improved;Individual;Infrastructure;Ingestion;International;Investments;Link;Location;Measurement;Metadata;Monitor;National Institute of Environmental Health Sciences;Natural Disasters;online tutorial;outreach;Pattern;Performance;Personal Satisfaction;Persons;Policy Developments;Population;Population Characteristics;Process;Productivity;programs;public health research;Publications;Publishing;Reading;Reporting;Research;Research Personnel;Risk;Science;socioeconomics;software development;spatiotemporal;Standardization;Strategic Planning;Surveys;Time;tool;Training;United States National Institutes of Health;usability;user-friendly;Vector-transmitted infectious disease;virtual;Vulnerable Populations;web based interface;webinar;Work

PROJECT_TITLE: International Population and Agricultural Census Data for Environmental Health Research

STUDY_SECTION: SSPB

STUDY_SECTION_NAME: Social Sciences and Population Studies B Study Section[SSPB]


NIH_SPENDING_CATS: Biotechnology;Cardiovascular;Congenital Heart Disease;Genetics;Heart Disease;Orphan Drug;Pediatric;Rare Diseases

ORG_CITY: IOWA CITY

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: Narrative The goal of this project is to apply chemical genetics to examine the basis for cardiovascular disease and deepen the understanding of diverse physiological roles of the cardiac voltage-gated sodium channel.

PI_NAMEs: AHERN, CHRISTOPHER A (contact);LONDON, BARRY

PROGRAM_OFFICER_NAME: BALIJEPALLI, RAVI C

PROJECT_TERMS: Ablation;Action Potentials;Acute;Affinity;Animals;aorta constriction;Arrhythmia;base;Binding Sites;Biochemical;Biology;Brain;Brugada syndrome;Cardiac;Cardiac Electrophysiologic Techniques;Cardiac Myocytes;Cardiovascular Diseases;Cells;chemical genetics;Chemicals;Chronic;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;Congenital Heart Block;Coupling;Cytoskeleton;Development;Dilated Cardiomyopathy;Disease;Electrophysiology (science);Elements;Engineering;Environment;experimental study;Fibrosis;gain of function mutation;Gene Expression;Gene Targeting;gene-editing approach;Generations;Genes;genetic approach;Genetic Models;Genotype;Goals;Heart;heart function;Heterozygote;Human;Human Pathology;imaging approach;In Situ;In Vitro;in vivo;indium arsenide;induced pluripotent stem cell;Inherited;intraperitoneal;Knockout Mice;lentivirally transduced;Long QT Syndrome;loss of function;Mediating;Molecular;Molecular Conformation;mouse model;Mouse Strains;Mus;Muscle Cells;Mutation;nanomolar;novel;Oral;Outcome;Pathogenicity;Patients;Peripheral;Pharmaceutical Preparations;pharmacologic;Pharmacology;Phenotype;Physiological;Physiology;Play;Predisposition;Production;Protein Isoforms;Proteins;Research;response;RNA;Rodent Model;Role;Route;Sodium;Sodium Channel;stem;Sudden Death;Syndrome;System;therapeutic target;Variant;voltage

PROJECT_TITLE: A Versatile Chemical-Genetic Approach to Determine Bases for Arrhythmogenesis and Sodium Channelopathies

STUDY_SECTION: MPPB

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


NIH_SPENDING_CATS: Asthma;Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Dietary Supplements;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Lung;Nutrition;Pediatric;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: CHICAGO

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: Project Narrative The goals of the proposed study are to test whether fatty acid supplementation to the diet during pregnancy reduces the risk for asthma and allergic disease in children at ages 5-6 years. The burden of asthma in the U.S. has fallen disproportionately on Black children living in low-resourced communities, for whom the prevalence, morbidity and mortality rates far exceeds those for White children. To our knowledge, this will be the first test of prenatal fatty acid levels on asthma and allergy in Black children living in low-resourced environments in the U.S.

PI_NAMEs: CIACCIO, CHRISTINA ELIZABETH;KEENAN, KATHRYN ELIZABETH (contact)

PROGRAM_OFFICER_NAME: FREEMER, MICHELLE M

PROJECT_TERMS: 6 year old;acceptability and feasibility;Affect;Age;Allergic;Allergic Disease;Animals;Asthma;atopy;Betula Genus;biobehavior;Birth;Black American;Black race;black women;Blood;Chicago;Child;Child Development;Childhood Asthma;chronic inflammatory lung disease;Cities;Clinical assessments;Communities;comparison control;Control Groups;cytokine;Data;Death Rate;Denmark;Development;Diet;Dietary Fatty Acid;Dietary Intervention;Disease;Docosahexaenoic acid supplementation;Docosahexaenoic Acids;Double-Blind Method;early childhood;Emergency department visit;Emergency Situation;evidence base;Exposure to;falls;Family;fatty acid supplementation;Fatty Acids;Formula supplementation;Goals;heart rate variability;Hospitalization;hospitalization rates;Human;Hydrocortisone;Hypersensitivity;hypothalamic-pituitary-adrenal axis;immune function;improved;Infant;Infant formula;Inflammation;Inflammatory;Infrastructure;Laboratories;Link;Low income;Measures;Mediating;Medical Records;Morbidity - disease rate;mortality;Mothers;Neighborhoods;neurodevelopment;nutrition;Observational Study;offspring;Omega-3 Fatty Acids;Outcome;Pattern;perceived stress;Pilot Projects;Pregnancy;pregnant;prenatal;prenatal influence;prenatal stress;prenatal testing;Prevalence;programs;prospective;protective effect;Questionnaires;racial disparity;randomized, controlled study;Randomized, Controlled Trials;Regulation;Reporting;Research;Resource-limited setting;response;Risk;Risk Reduction;Side;Stress;stress reactivity;stressor;Supplementation;System;Testing;therapy design;urban setting;Visit;Wheezing;Woman;Work

PROJECT_TITLE: Prenatal Fatty Acid Supplementation and Early Childhood Asthma and Atopy in Black American Families

STUDY_SECTION: BMHO

STUDY_SECTION_NAME: Biobehavioral Medicine and Health Outcomes Study Section[BMHO]


NIH_SPENDING_CATS: Aging;Breast Cancer;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Dietary Supplements;Disability Research;Natural Products;Nutrition;Physical Rehabilitation;Prevention;Rehabilitation;Women's Health Research

ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

ORG_STATE: CA

PHR: PROJECT NARRATIVE The rapidly growing population of older breast cancer survivors (estimated to be >6 million by 2040) is at increased risk for cancer treatment-related accelerated aging. We hypothesize that targeting senescent cells with senolytic agents will improve the adverse age-related effects in frail older breast cancer survivors. If our hypothesis is correct, the impact on clinical practice would be substantial and of paramount importance.

PI_NAMEs: SEDRAK, MINA S (contact)

PROGRAM_OFFICER_NAME: SAMIMI, GOLI

PROJECT_TERMS: Address;adherence rate;Adverse effects;Age;age acceleration;age effect;age related;Age Years;aging process;aging related;Biological Markers;Breast Cancer survivor;Cancer Patient;cancer risk;Cancer Survivor;cancer therapy;Cardiovascular system;CD3 Antigens;CDKN2A gene;Cell Aging;Cell secretion;Cessation of life;chemokine;chemotherapy;childhood cancer survivor;Chronic Disease;Clinical;clinical practice;Clinical Trials;Compensation;cytokine;Data;Development;Diabetes Mellitus;dietary supplements;disability;Double-Blind Method;Eating;experience;Exposure to;extend lifespan;Fatty acid glycerol esters;Fibrosis;fisetin;Food;Frail Elderly;frailty;Fruit;functional decline;Functional disorder;Functional impairment;functional improvement;Gait speed;Growth;Growth Factor;Half-Life;Hand Strength;Human;human old age (65+);human tissue;Immune System Diseases;Impairment;improved;indexing;Inflammation;Inflammatory;instrumental activity of daily living;Interleukin-6;Intervention;late life;Link;Malignant Neoplasms;Measures;middle age;mouse model;Multi-Institutional Clinical Trial;Multicenter Trials;Mus;Musculoskeletal System;necrotic tissue;Neurologic;normal aging;older adult;older patient;Older Population;Oncology;Oral;Patients;peripheral blood;Persons;pharmacologic;Phenotype;phenotypic biomarker;Physical Function;Physical Performance;Physiological;Placebos;Population;pre-clinical;prevent;Prevention;primary endpoint;Pulmonary Fibrosis;Quality of life;Randomized;randomized placebo controlled trial;Reducing Agents;Safety;secondary endpoint;senescence;senescence associated secretory phenotype;senescent cell;senolytics;Serum;SF-36;side effect;Strawberries;Survivors;System;T-Lymphocyte;Testing;therapy design;Tissues;Treatment-Related Cancer;Urine;Woman;Work;young adult

PROJECT_TITLE: Using Senolytics to Improve Physical Function in Older Breast Cancer Survivors

STUDY_SECTION: ASG

STUDY_SECTION_NAME: Aging Systems and Geriatrics Study Section[ASG]


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Behavioral and Social Science;Biodefense and Related Countermeasures;Clinical Research;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Coronaviruses Vaccines;Dissemination and Implementation Research;Emerging Infectious Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Immunization;Infectious Diseases;Maternal Health;Maternal Morbidity and Mortality;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Prevention;Primary Health Care;Racial and Ethnic Minority Health Research;Social Determinants of Health;Vaccine Related;Women's Health Research

ORG_CITY: PROVIDENCE

ORG_NAME: BUTLER HOSPITAL (PROVIDENCE, RI)

ORG_STATE: RI

PHR: Narrative COVID-19 infection is associated with serious health outcomes for pregnant women, and adverse infant outcomes are more likely when a mother has COVID-19. Even though COVID-19 vaccines are considered safe during pregnancy, vaccination rates are very low among pregnant women. This study will involve in-depth assessments with pregnant and postpartum women, and with prenatal care providers, in order to help identify reasons for the low rate of COVID-19 vaccination among perinatal women, as well as possible solutions.

PI_NAMEs: BATTLE, CYNTHIA L. (contact);HARDY, ERICA JOY

PROGRAM_OFFICER_NAME: GIRARDI, GUILLERMINA

PROJECT_TERMS: Address;Admission activity;adverse birth outcomes;adverse outcome;Affective;African American;American College of Obstetricians and Gynecologists;Area;Attention;Attitude;Automobile Driving;Behavior;Black race;care providers;Centers for Disease Control and Prevention (U.S.);Cessation of life;Child;Child Health;Cognitive;Communication;Communities;Counseling;COVID-19;COVID-19 pandemic;COVID-19 risk;COVID-19 vaccination;COVID-19 vaccine;Data;Decision Making;design;Development;Disadvantaged;disadvantaged women;Discipline of obstetrics;Education;effective intervention;Enrollment;ethnic minority;Ethnic Population;experience;Family Practice;Federally Qualified Health Center;Health;health care service;health disparities in women;health disparity;health organization;Health Personnel;high risk;High Risk Woman;improved;Infant;infant outcome;Infection;innovation;Interview;Investigation;Knowledge;Lactation;Latina;Light;Linear Models;Location;maternal morbidity;Maternal Mortality;maternal vaccination;Mechanical ventilation;Medical;Methods;Midwife;Modeling;mortality;Mothers;novel strategies;Nurses;offspring;Outcome;participant enrollment;Patients;Perinatal;perinatal period;perinatal women;Phase;Planning Theory;Population;Postpartum Period;Postpartum Women;Pregnancy;pregnant;Pregnant Women;Premature Birth;prenatal;Prenatal care;Primary Care;Procedures;Provider;provider behavior;psychological symptom;Public Health;racial minority;racial minority women;racial population;Recommendation;recruit;Research;Risk;Role;Safety;Sampling;SARS-CoV-2 infection;Secondary Immunization;Services;Shapes;Spanish;Spanish/English;Structure;Suggestion;Surveys;therapy development;United States;unvaccinated;uptake;Vaccinated;Vaccination;vaccination outcome;vaccine acceptance;vaccine hesitancy;vaccine refusal;Vaccines;Vulnerable Populations;White Women;Woman;women of color;Women's Group;Work

PROJECT_TITLE: COVID19 vaccine hesitancy among perinatal women at risk for health disparities

STUDY_SECTION: HHD

STUDY_SECTION_NAME: Healthcare and Health Disparities Study Section[HHD]


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Bioengineering;Clinical Research;Emerging Infectious Diseases;Infectious Diseases;Influenza;Lung;Pneumonia and Influenza

ORG_CITY: COLLEGE PARK

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIV OF MARYLAND, COLLEGE PARK

PHR: PROJECT NARRATIVE Evaluating the distribution of pathogens within airborne particles generated during breathing is essential for modeling disease transmission and optimizing mitigation strategies. In this project we propose an innovative microcyclone array technology to enable more effective aerobiology studies by improving the accessible particle size range, throughput, fraction count, resolution, and bioavailability. The aerosol fractionation technology, fabricated using a high resolution 3d printing technique, will be integrated with an established exhaled breath collection instrument, enabling system validation through a clinical study of influenza virus aerosol distribution during tidal breathing.

PI_NAMEs: DEVOE, DON L (contact)

PROGRAM_OFFICER_NAME: BOZICK, BROOKE ALLISON

PROJECT_TITLE: Microcyclone arrays for high resolution bioaerosol fractionation and viable virus collection

STUDY_SECTION: ISD

STUDY_SECTION_NAME: Instrumentation and Systems Development Study Section[ISD]


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

NIH_SPENDING_CATS: Breastfeeding, Lactation and Breast Milk;Diabetes;Maternal Health;Maternal Morbidity and Mortality;Nutrition;Obesity;Pregnancy;Prevention;Women's Health Research

ORG_CITY: BATON ROUGE

ORG_NAME: LSU PENNINGTON BIOMEDICAL RESEARCH CTR

PHR: Project Narrative Gestational diabetes mellitus (GDM) affects about 8% of pregnant women in the U.S. and China, and perpetuates the intergenerational cycle of obesity and type 2 diabetes. This project will measure unmethylated INS DNA, a biomarker of insulin-producing cells, in stored blood samples among women after GDM delivery to evaluate associations and predictive ability for new onset type 2 diabetes. If successful, our study will provide novel methodology to assess β-cell death and help transfer this assay into clinical practice for early prevention and potential treatment for inhibiting β-cell apoptosis.

PI_NAMEs: GUNDERSON, ERICA PAULINE;HU, GANG  (contact)

PROGRAM_OFFICER_NAME: LAWRENCE, JEAN M

PROJECT_TERMS: Adult;Affect;aggressive therapy;Amino Acids;Anthropometry;Apoptosis;Asian;Autopsy;Behavioral;Beta Cell;biobank;Biological Assay;Biological Markers;Black race;Blood specimen;C-Peptide;Cell Death;Cell Physiology;cell type;Cells;China;Chinese;Clinical;clinical practice;cohort;Collection;cost effective;Data;Defect;Diabetes Mellitus;diabetes risk;Diagnosis;Diet;digital;Disease;DNA;DNA Methylation;Early treatment;electronic health record system;European;Exercise;Fasting;fasting glucose;feeding;follow-up;Foundations;Functional disorder;Funding;Future;Genes;Gestational Diabetes;Glucose;Glycosylated hemoglobin A;Goals;Heterogeneity;Hispanic;Human;Hyperglycemia;Impairment;improved;in vivo evaluation;indexing;Infant;Insulin;Insulin Resistance;insulin secretion;insulin sensitivity;Insulin-Dependent Diabetes Mellitus;intergenerational;Laboratories;Lactation;Link;Lipids;Longitudinal cohort;longitudinal, prospective study;Measures;Mediating;Meta-Analysis;Methodology;Methylation;Minority;Monitor;Newly Diagnosed;Non-Insulin-Dependent Diabetes Mellitus;novel;novel marker;Obesity;observational cohort study;Observational Study;OGTT;Participant;Pathogenesis;Patients;Peptide Initiation Factors;Populations at Risk;Postpartum Period;Pregnancy;Pregnant Women;prevent;Prevention;Proinsulin;prospective;Prospective cohort;Prospective Studies;Reporting;Research;Research Design;Resources;response;Risk Factors;risk stratification;Sampling;Secretory Cell;Serum;Source;Structure of beta Cell of islet;Techniques;Testing;Therapeutic Intervention;Time;United States National Institutes of Health;Visit;Woman;Women's cohort;women's diagnosis;Women's study

PROJECT_TITLE: Biomarker of Pancreatic B-cell Loss Predicting Progression to Type 2 Diabetes After Gestational Diabetes

STUDY_SECTION: HSDO

STUDY_SECTION_NAME: Human Studies of Diabetes and Obesity Study Section[HSDO]


ORG_DEPT: PEDIATRICS

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: Project narrative The current medical paradigm is to treat most patients according to standard clinical guidelines, which in the majority of cases results in all patients with a similar condition receiving substantially similar treatment, this is in opposition to personalized approaches which use prediction models to assign treatment. We aim to quantify the potential benefits of using a personalized approach by simulating the outcomes of predictive allocation in ~130 previously published NHLBI randomized controlled trials. We will then compare the outcomes of predictive allocation to a secondary simulation where all patients are treated similarly and thus determine under what circumstances and to what extent, would predictive allocation result in a net benefit at the population level.

PI_NAMEs: MANLHIOT, CEDRIC  (contact)

PROGRAM_OFFICER_NAME: SHIROMA, ERIC JITSUO

PROJECT_TERMS: adverse outcome;Affect;arm;Cardiovascular Diseases;Caring;Characteristics;Clinical;Clinical Research;Clinical Trials;Computer Simulation;Conduct Clinical Trials;Control Groups;Data;design;effective intervention;effective therapy;Eligibility Determination;Funding;Future;future implementation;Goals;Guidelines;hazard;improved;improved outcome;Medical;Medicine;Meta-Analysis;Methodology;Methods;National Heart, Lung, and Blood Institute;online resource;Outcome;outcome prediction;Outcome Study;Pathology;patient population;Patients;Pediatric cardiology;Performance;personalized approach;personalized care;personalized medicine;personalized predictions;Pilot Projects;Population;prediction algorithm;predictive modeling;Prevalence;primary outcome;Probability;programs;Publishing;Randomized;randomized trial;randomized, clinical trials;Randomized, Controlled Trials;Recommendation;Regression Analysis;Risk;Risk Factors;Risk Reduction;Sampling;Selection for Treatments;simulation;standard of care;Stratification;Therapeutic;Time;treatment arm;treatment choice;treatment group;treatment strategy;Uncertainty

PROJECT_TITLE: Computational simulation of the potential improvement in clinical outcomes of cardiovascular diseases with the use of a personalized predictive medicine approach

STUDY_SECTION: CDMA

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


NIH_SPENDING_CATS: Autoimmune Disease;Clinical Research;Clinical Trials and Supportive Activities;Diabetes;Digestive Diseases;Pediatric;Prevention

ORG_CITY: GAINESVILLE

ORG_NAME: UNIVERSITY OF FLORIDA

PHR: PROJECT NARRATIVE. Many people think of type 1 diabetes as an autoimmune disease of the insulin-producing cells of the pancreas, however, the exocrine pancreas, which is involved in digestion, is also substantially impacted. The primary goal of this project is to determine when in the development of type 1 diabetes the exocrine pancreas becomes affected and whether stool or blood exocrine pancreas markers predict the onset of type 1 diabetes in those who are at risk. The secondary goal of this project is to investigate what is specifically causing the exocrine pancreas changes seen in type 1 diabetes.

PI_NAMEs: BRUGGEMAN, BRITTANY  (contact)

PROGRAM_OFFICER_NAME: SPAIN, LISA M

PROJECT_TERMS: Affect;Amylases;Atrophic;Autoantibodies;Autoimmune;Autoimmune Diseases;Autoimmunity;Autologous;Beta Cell;Biological Markers;biomarker evaluation;Birth;Blood;career;career development;Cells;Childhood;Clinical;Clinical Investigator;Clinical Markers;Clinical Research;cohort;Cohort Studies;Collaborations;Data;density;Deposition;design;Development;Development Plans;Diabetes Mellitus;diabetes pathogenesis;diabetes risk;Diagnosis;Digestion;Disease;early detection biomarkers;Early identification;Elastases;Endocrine;Endocrinologist;Enrollment;Environment;Evaluation;Event;Exocrine pancreas;Exocrine pancreatic insufficiency;experience;Feces;First Degree Relative;Florida;Functional disorder;functional loss;Funding;Gene Expression;Goals;Heterogeneity;high risk;Human Subject Research;Immune;immune cell infiltrate;Immunoglobulin G;Individual;Inflammatory;Insulin;insulin dependent diabetes mellitus onset;insulin secretion;Insulin-Dependent Diabetes Mellitus;Intervention;Intervention Trial;islet;islet autoimmunity;islet cell antibody;Knowledge;Lead;Learning;Lipase;loss of function;Magnetic Resonance Imaging;Measures;Mentors;Mentorship;Mission;Natural History;next generation;novel;Onset of illness;Organ Donor;Organ Size;Pancreas;Pathogenesis;patient oriented;Patients;Persons;Phenotype;Play;Population;pre-clinical;predictive marker;Prevention strategy;Prevention trial;prognostic value;prospective;protein expression;Research;research clinical testing;Research Design;Research Personnel;Research Proposals;Research Technics;Risk;Risk Marker;Role;Sampling;Scientist;Serum;skills;Slice;success;Techniques;Tissues;Training;Translational Research;treatment response;trial design;Trypsinogen;Universities;Work

PROJECT_TITLE: Natural History and Mechanisms of Exocrine Pancreatic Dysfunction in Pre-Type 1 Diabetes

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Diabetes, Endocrinology and Metabolic Diseases B Study Section[DDK-B]


ADMINISTERING_IC: OD

ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

IC_NAME: OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH

NIH_SPENDING_CATS: Genetics;Lung;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Embryonic - Non-Human

ORG_CITY: RALEIGH

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: NORTH CAROLINA STATE UNIVERSITY RALEIGH

PHR: Project Narrative Cells expressing LGR5 play key roles in organ/tissue development, homeostasis, regeneration, and disease, including cancer. Being able to study them in an animal model that closely resembles human physiology will help us develop therapies for human diseases. In this project we propose to develop a new model that will add novel capabilities permitting the study of the regenerative capacity of the cells after transplantation and their function in health and disease.

PI_NAMEs: PIEDRAHITA, JORGE A (contact)

PROGRAM_OFFICER_NAME: MIROCHNITCHENKO, OLEG

PROJECT_TERMS: Ablation;Address;adult stem cell;Alleles;Anatomy;Animal Model;Basic Science;Bleomycin;Body System;Cell Lineage;Cells;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;Cochlea;Complex;Data;design;Development;Disease;dosage;Dose;Family suidae;Fetal Lung;fetal stem cell;Future;gastrointestinal system;Gene Expression;Generations;Genes;Genetic Transcription;Guidelines;Hair follicle structure;Health;Homeostasis;Human;human disease;improved;In Vitro;in vivo;Injury;injury and repair;interest;Kidney;Label;LGR5 gene;Liver;LOX gene;Lung;lung injury;Maintenance;Malignant Neoplasms;Modeling;Molecular;Morphogenesis;Mus;Natural regeneration;novel;Oral;Organ;Organoids;Pathologic;Performance;Phenotype;Physiological;Physiology;Play;Population;Preparation;Process;promoter;Regenerative capacity;Regenerative research;Regulation;Reporter;Research;Resolution;response;Role;Seminal;Skin;somatic cell nuclear transfer;Spatial Distribution;stem cells;Study models;System;Tamoxifen;therapy development;tissue repair;Tissues;tool;Tracer;Transgenes;Transgenic Organisms;Translating;Transplantation;Validation

PROJECT_TITLE: A Novel Large Animal Model for Studying the Developmental Potential and Function of LGR5 Stem Cells in Vivo and in Vitro

STUDY_SECTION: RIBT

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


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

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

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE Home health care services provide a critical mechanism to support older adults with Alzheimer’s disease and related dementias (ADRD) to remain in their own homes for as long as possible, even after a disruption in care, such as caused by a disaster event. We hypothesize that older Americans with ADRD are at particular risk for poor health outcomes that result from the disruption of a disaster, requiring increased healthcare resources particularly at the end of life, where receiving home health services may be a protective factor. The proposed study will fill immediate and critical gaps in knowledge about the relationship between home health care use and conventional healthcare use after care disruptions and provide evidence for the use of home health care as a strategy to support individuals with ADRD and their caregivers to promote aging in place.

PI_NAMEs: BELL, SUSAN ANNE (contact)

PROGRAM_OFFICER_NAME: NOVAK, PRISCILLA JOY

PROJECT_TERMS: Activities of Daily Living;Acute;Affect;Aftercare;aging in place;Alzheimer's disease related dementia;American;Area;Care given by nurses;Caregivers;Caring;Chronic;climate change;cohort;Communities;Data;Data Set;Dementia;Dependence;Disasters;Disorientation;Distress;Emergency department visit;Emergency Situation;Emotional Disturbance;end of life;end of life care;Environment;Event;Evolution;Exhibits;Exposure to;Funding;Future;Goals;Health;health care service;health care service utilization;health service use;Health Services;Healthcare;healthy aging;Home;Home Care Services;hospice utilization;Hospitalization;Hospitals;Individual;innovation;Knowledge;Lead;Life;Long-Term Care;Measures;Medicare;Medicare claim;medication administration;Methods;Nature;nursing skill;Office Visits;older adult;Older Population;Outcome;Pathway interactions;patient home care;Pattern;Personal Satisfaction;Persons;Play;poor health outcome;Population;pro-aging;programs;protective factors;Quality of Care;Rehabilitation therapy;Research;Resources;Risk;Role;Sampling;Services;Visit;Vulnerable Populations

PROJECT_TITLE: Healthcare use among older adults with dementia after large-scale disasters

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


ADMINISTERING_IC: DE

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Congenital Structural Anomalies;Dental, Oral, and Craniofacial Disease;Genetics;Neurosciences;Pediatric;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: PASADENA

ORG_NAME: CALIFORNIA INSTITUTE OF TECHNOLOGY

PHR: Public Health Relevance Statement Neural crest and ectodermal placode cells are both transient embryonic progenitor cells that arise from the neural plate border. While ~10% of human birth defects affect early neural crest or placode development, the molecular mechanisms underlying these defects are largely unknown. The proposed experiments promise to illuminate the transcriptional events underlying early formation of neural crest and ectodermal placode cells from the neural plate border.

PI_NAMEs: BRONNER, MARIANNE  (contact)

PROGRAM_OFFICER_NAME: SAIFUDEEN, ZUBAIDA

PROJECT_TERMS: Affect;Automobile Driving;c-myc Genes;Cell Lineage;cell type;Cells;Cephalic;Characteristics;Congenital Abnormality;Coupled;Coupling;craniofacial;Data;Defect;Development;Dorsal;Down-Regulation;Ear;Ectoderm;Embryo;embryonic stem cell;Enhancers;Equilibrium;Event;experimental study;Feedback;gain of function;Gastrula;Gene Expression;gene regulatory network;Genes;Genetic Transcription;Grant;Hand;Human;Image;in vivo;lens;loss of function;Maintenance;Mediating;melanocyte;Molecular;neural;Neural Crest;Neural Crest Cell;neural plate;Neural tube;Neural Tube Closure;Neurons;Olfactory Pathways;overexpression;Peripheral Nervous System;Play;pluripotency;pluripotency factor;Population;prevent;Process;progenitor;public health relevance;Regulatory Element;Reporter;Role;Sensory Ganglia;single cell ATAC-seq;single-cell RNA sequencing;Skeleton;Skin;Specific qualifier value;stem cell niche;stem cells;Testing;Time;transcription factor

PROJECT_TITLE: Cell lineage and transcriptional analysis of the vertebrate neural plate border

STUDY_SECTION: NCF

STUDY_SECTION_NAME: Neurogenesis and Cell Fate Study Section[NCF]


NIH_SPENDING_CATS: Bioengineering;Cancer;Clinical Research;Data Science;Hematology;Machine Learning and Artificial Intelligence;Orphan Drug;Precision Medicine;Rare Diseases

ORG_CITY: SEATTLE

ORG_NAME: INSTITUTE FOR SYSTEMS BIOLOGY

ORG_STATE: WA

PHR: Project Narrative The Acute Myeloid Leukemia Digital Twin (AML-DT) system is centered on personalized models that virtually represent a patient's disease; where patients and their doctors work together with an interactive dashboard to visualize dynamic changes in disease trajectory and to explore therapeutic possibilities. The proposed AML-DT prototype system visualizes patient history, makes predictions of disease progression and drug response which can be validated in clinical trials, and gives clinicians and patients a way to make better care plans by providing needed foresight. Our innovative solutions integrate detailed domain-specific knowledge graphs with multiscale dynamical models of the malignancy, providing a foundation for the development of the first AML Digital Twin.

PI_NAMEs: THORSSON, VESTEINN  (contact)

PROGRAM_OFFICER_NAME: OSSANDON, MIGUEL

PROJECT_TERMS: Acute Myelocytic Leukemia;Address;Adult;Advocate;Age Years;Allogenic;Azacitidine;Blood specimen;Bone Marrow;Bone Marrow Aspiration;Caring;chemotherapy;Clinical;Clinical Data;clinical decision-making;Clinical Trials;clinically relevant;Communities;Computer Simulation;cytokine;dashboard;Data;data resource;design;Development;digital twin;Disease;Disease Progression;drug response prediction;drug sensitivity;Engineering;Event;experience;feature selection;Feedback;Finland;Foundations;Generations;Goals;Graph;Hematopoiesis;Hematopoietic Stem Cell Transplantation;Heterogeneity;Immune response;improved;innovation;interactive visualization;Knowledge;knowledge graph;Learning;learning progression;leukemia;leukemia treatment;Light;machine learning method;Malignant Neoplasms;manufacture;Medicine;Methods;Modeling;models and simulation;Molecular;Multi-Institutional Clinical Trial;National Center for Advancing Translational Sciences;novel therapeutics;older patient;Outcome;Outcome Measure;outcome prediction;Output;patient oriented;Patient Selection;Patient-Focused Outcomes;Patients;peripheral blood;personalized decision;Pharmaceutical Preparations;Physiological;predicting response;Property;prototype;Recommendation;Recording of previous events;Refractory;Regimen;Relapse;Research;Research Personnel;Residual Neoplasm;Resistance;response;Scientist;Selection for Treatments;simulation;Somatic Mutation;Source;statistical and machine learning;Survival Rate;System;Systems Biology;The Cancer Genome Atlas;Therapeutic;therapy outcome;traditional therapy;Treatment outcome;treatment response;Treatment-related toxicity;Universities;Update;virtual model;Visualization;Work

PROJECT_TITLE: Prototype System for AML Digital Twins

STUDY_SECTION: CIDH

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


NIH_SPENDING_CATS: Autoimmune Disease;Biotechnology;Brain Disorders;Clinical Research;Myasthenia Gravis;Neurosciences;Rare Diseases

ORG_CITY: LA JOLLA

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Narrative  We propose to study how autoimmune antibodies interact with neurotransmitter receptors to cause disease. We are specifically interested in a subset of neurotransmitter receptors that are targeted in autoimmune encephalitis, autoimmune autonomic ganglionopathy, and myasthenia gravis. The proposed studies will illuminate mechanisms of autoantibody interference with this important group of proteins and enable more targeted therapeutics of these devastating diseases.

PI_NAMEs: HIBBS, RYAN E (contact);MONSON, NANCY L

PROGRAM_OFFICER_NAME: UMANAH, GEORGE KWABENA ESSIEN

PROJECT_TERMS: 3-Dimensional;Address;Affect;Anions;Antibodies;antibody detection;Autoantibodies;Autoimmune;Autoimmune Diseases;Autoimmune Diseases of the Nervous System;Autoimmune encephalitis;Autoimmune Process;Autoimmunity;autoreactivity;Binding;Biochemistry;Biological Assay;biophysical techniques;Blood;Cations;Cell Surface Proteins;Cerebrospinal Fluid;Chromatography;Clinical;Complex;crosslink;Cryoelectron Microscopy;Data;design;Detection;Development;Disease;Dysautonomias;Electrophysiology (science);Encephalitis;Epilepsy;Epitopes;experience;experimental study;Family;Fc Receptor;Fluorescence;Foundations;Glycine Receptors;Human;Immunoglobulin Fragments;interest;Ion Channel Gating;Knowledge;Laboratories;Ligands;Link;Maps;Mediating;Molecular;Molecular Sieve Chromatography;Muscle;Muscle Weakness;Myasthenia Gravis;Nervous System;Nervous System Disorder;neuromuscular;Neurons;neurotransmission;Neurotransmitter Receptor;Nicotinic Receptors;novel;Pathogenesis;Pathogenicity;Pathology;Patients;Proteins;receptor;receptor binding;receptor function;Receptor Inhibition;receptor internalization;Reporting;repository;Research;Resolution;Resources;Sampling;Seizures;serotonin receptor;structural biology;Structure;targeted treatment;Testing;Work

PROJECT_TITLE: Structural mechanisms of autoimmune diseases targeting cys-loop receptors


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Clinical Research;Genetics;Human Genome;Neuroblastoma;Neurosciences;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: NEW YORK

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

ORG_STATE: NY

PHR: PROJECT NARRATIVE Neuroblastoma (NB) arises in the sympathoadrenal lineage of the nervous system. An understudied highly lethal form of NB is characterized by an in-frame fusion within the ATRX gene (ATRX IFF), in which multiple chromatin-interacting domains are deleted from this ATP-dependent SWI/SNF-like chromatin remodeler. Our studies will reveal the role of ATRX IFFs in epigenomic reorganization, gene expression programs, protein interactions, and epigenetic inhibitor sensitivities of this aggressive NB subtype.

PI_NAMEs: BERNSTEIN, EMILY  (contact)

PROGRAM_OFFICER_NAME: FOUNTAIN, JANE W

PROJECT_TERMS: Adolescent;Adult;ATPase Domain;ATRX gene;Automobile Driving;Binding;C-terminal;Cell Death;Cell Death Induction;Cell fusion;Cell Line;Cells;Characteristics;Child;Chimeric Proteins;ChIP-seq;Chromatin;Clinical;clinical subtypes;Cloning;Collaborations;Complex;Data;derepression;Development;Diffuse intrinsic pontine glioma;Disease;disease phenotype;DNA Modification Methylases;Dominant-Negative Mutation;effective therapy;Epigenetic Process;epigenome;epigenomics;Event;Experimental Models;EZH2 gene;Frequencies;Gene Expression;Gene Silencing;Gene Targeting;Genes;Genetic Transcription;Genome;Genomics;Glioma;helicase;Histone H3;histone methylation;In Vitro;in vivo;in vivo Model;Indolent;inhibitor;innovation;knock-down;Length;link protein;Lysine;Malignant Childhood Neoplasm;Malignant Neoplasms;Mediating;Memorial Sloan-Kettering Cancer Center;migration;Modeling;Mutation;N-terminal;nerve stem cell;Nervous System;Neuroblastoma;neuroblastoma cell;Neuronal Differentiation;Neurons;nondeletion type alpha-thalassemia/mental retardation syndrome;novel;Oncogenic;Osteosarcoma;overexpression;patient derived xenograft model;patient subsets;Patients;pediatric department;Pediatric Neoplasm;Pharmacotherapy;Phenotype;Point Mutation;programs;Proliferating;Proteins;Proteomics;RE1-silencing transcription factor;Recurrence;Reporting;response;Role;small hairpin RNA;Therapeutic;therapeutic target;transcriptome;transcriptome sequencing;tumor;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Mechanisms and Modeling of Neuroblastoma-Associated ATRX Alterations

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