NIH_SPENDING_CATS: Cancer;Genetics

ORG_CITY: CHARLOTTE

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF NORTH CAROLINA CHARLOTTE

PHR: Project Narrative This project study how lesions within nucleic acids are repaired by cells to preserve stability in response to endogenous insults or environmental toxins. Our better understanding on repair mechanisms can help to develop new treatment for cancers.

PI_NAMEs: YAN, SHAN  (contact)

PROGRAM_OFFICER_NAME: SHARMAN, ANU

PROJECT_TERMS: Aging;APEXL2 Gene;base;Biochemical;Bioinformatics;brca gene;cancer cell;Cancer Etiology;cancer therapy;cancer type;Cells;Cellular biology;Chemotherapy-Oncologic Procedure;Complex;Data;Deoxyribose;DNA;DNA Damage;DNA glycosylase;DNA metabolism;DNA Repair;DNA Sequence Alteration;DNA Structure;Double-Stranded RNA;egg;Excision;Exonuclease;Feedback;Frequencies;Genetic Transcription;genome integrity;Genome Stability;Hybrids;Hydroxyl Radical;inorganic phosphate;insight;Lesion;Malignant Breast Neoplasm;Malignant neoplasm of liver;Malignant neoplasm of lung;Mediating;Metabolism;Methyltransferase;Modification;Molecular;Molecular Biology;Mutagenesis;NEIL3 gene;Neurodegenerative Disorders;Non-Malignant;novel;nucleic acid metabolism;Nucleic Acids;Oncogenes;Oxidation-Reduction;oxidative DNA damage;Oxidative Stress;Pathway interactions;Phosphodiesterase I;Plasmids;Play;preservation;Process;protein metabolism;protein purification;Proteins;Publishing;Reactive Oxygen Species;reconstitution;Renal Carcinoma;repaired;Reporting;Research;response;RNA;RNA metabolism;RNA Processing;Role;Saccharomycetales;Series;Single Strand Break Repair;Single-Stranded DNA;Site;Structure;System;Testing;Tissues;Toxic Environmental Substances;Transcriptional Regulation;Translations;Tumor Tissue;tumorigenesis;Uterine Cancer;Xenopus

PROJECT_TITLE: Mechanism of APE2 in genome integrity


ADMINISTERING_IC: CA

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Dental, Oral, and Craniofacial Disease;Mental Health;Orphan Drug;Prevention;Rare Diseases;Rehabilitation;Social Determinants of Health

ORG_CITY: CHARLESTON

ORG_COUNTRY: UNITED STATES

ORG_DEPT: OTOLARYNGOLOGY

ORG_FIPS: US

ORG_NAME: MEDICAL UNIVERSITY OF SOUTH CAROLINA

ORG_STATE: SC

PHR: PROJECT NARRATIVE Head and neck cancer survivors suffer high rates of body image-related distress which results in significant psychosocial morbidity and decreased quality of life. However, effective therapies to manage this disorder among head and neck cancer survivors are lacking. We have developed a novel, scalable, tele-cognitive behavioral therapy intervention for head and neck cancer survivors with body image-related distress that could provide the first effective treatment in this population, thereby minimizing psychosocial morbidity, improving quality of life, and developing new standards of clinical care.

PI_NAMEs: GRABOYES, EVAN MICHAEL (contact)

PROGRAM_OFFICER_NAME: NELSON, WENDY

PROJECT_TERMS: Address;Adoption;Affect;Appearance;arm;Attention;attentional control;Body Image;Cancer Intervention;Cancer Survivor;cancer survivorship care;cancer therapy;Caring;Chronic;clinical care;clinical practice;clinically significant;Cognitive Therapy;Consensus;coping;Coping Skills;Data;Deglutition;Disease Management;Distress;Dose;effective therapy;Effectiveness;efficacy evaluation;efficacy testing;Elements;Empathy;Evaluation;evidence base;expectation;follow-up;Functional impairment;Future;General Population;Head and Neck Cancer;Head and neck structure;Image;Impairment;improved;Intervention;Interview;Life;Manuals;Measures;Mediating;Mediator;Mental Depression;Methods;Modeling;Morbidity - disease rate;novel;Oncology;Population;post intervention;primary endpoint;psychologic;psychosocial;Psychosocial Assessment and Care;Psychotherapy;Quality of life;Randomized;Randomized, Controlled Trials;routine care;self-compassion;Site;Site Visit;Smiling;Social isolation;Social Well-Being;Source;Structure;suicide mortality;Supportive care;Surveys;theories;Therapeutic;Therapeutic Intervention;Time;Transact;Treatment Efficacy;treatment strategy

PROJECT_TITLE: A Randomized Controlled Trial to Evaluate a Novel Treatment Strategy for Body Image-Related Distress Among Head and Neck Cancer Survivors

STUDY_SECTION: LCBH

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


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Genetics;Regenerative Medicine;Wound Healing and Care

ORG_CITY: Chicago

ORG_DEPT: DENTISTRY

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

ORG_STATE: IL

PHR: Narrative Wound healing is a complex process that involves thousands of genes and a large number of cells. The studies proposed in this application will use quantitative models and analysis to study complicated interactions in wounds. The results will help us understand wound healing in both health and disease.

PI_NAMEs: DIPIETRO, LUISA A (contact)

PROGRAM_OFFICER_NAME: CHAO, CHIEN-CHUNG

PROJECT_TERMS: Address;Algorithms;angiogenesis;Animals;biological research;cell type;Cells;chronic wound;Cicatrix;Collaborations;Compensation;Complex;Computer Models;Couples;Disease;Elements;epithelial repair;Event;Exhibits;experimental study;Functional disorder;Gene Deletion;Genes;Genomics;healing;Health;Human;in vivo;Inflammation;Knock-out;Messenger RNA;Modeling;Molecular;Mus;novel;Oral mucous membrane structure;Outcome;Pattern;Process;re-epithelialization;Regulatory Pathway;Research;response;Site;Skin;skin healing;skin wound;System;Testing;therapeutic development;tissue repair;Tissues;tool;Transcript;transcription factor;transcriptome;wound;wound healing

PROJECT_TITLE: Complexity and the Wound Healing Response

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


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Aging;Atherosclerosis;Cardiovascular;Digestive Diseases;Heart Disease;Liver Disease;Nutrition

ORG_CITY: LOS ANGELES

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

ORG_STATE: CA

PHR: Relevance to Public Health Atherosclerosis/Cardiovascular Disease (CVD) is the leading cause of death in the US, and therefore creates a significant burden to the national health system and despite lipid lowering treatments adverse events continue to rise. Our discovery that altering bile acid amount and/or composition regulates the selective absorption of lipids and extent of atherosclerotic disease will advance our fundamental understanding of how absorption regulates atherosclerosis progression and may reveal novel opportunities for therapeutic intervention.

PI_NAMEs: TARLING, ELIZABETH JOANNA;VALLIM, THOMAS A (contact)

PROGRAM_OFFICER_NAME: LIU, LIJUAN

PROJECT_TERMS: absorption;Acceleration;Acids;Adult;Adverse event;Affect;atheroprotective;Atherosclerosis;Bacterial Toxins;Bile Acid Biosynthesis Pathway;bile acid metabolism;Bile Acids;Bile fluid;Biological Assay;burden of illness;Cardiometabolic Disease;Cardiovascular Diseases;cardiovascular disorder risk;Cause of Death;Cells;Chemical Structure;Chenodeoxycholic Acid;Cholesterol;cholesterol absorption;Cholesterol Esters;Cholic Acids;Clustered Regularly Interspaced Short Palindromic Repeats;Communication;CYP2C19 gene;CYP7A1 gene;CYP8B1 gene;design;Detergents;Development;Diet;Dietary Fats;Dietary Fatty Acid;Disease;early onset;Enzymes;ezetimibe;Fatty Acids;Gene Expression;Genes;Genetic study;gut-liver axis;Health system;Hepatic;Human Genetics;hypercholesterolemia;Immune;improved;in vivo;Inflammation;Inflammatory;Intake;Intestinal permeability;Intestines;LDL Cholesterol Lipoproteins;Leaky Gut;lipid metabolism;Lipids;Liver;Low-Density Lipoproteins;Mass Spectrum Analysis;Measures;Mediating;Metabolism;muricholic acid;Mus;novel;Nutrient;Pathogenesis;Pathway interactions;Plasma;Property;protective pathway;Public Health;Role;Signal Transduction;Signaling Molecule;System;Testing;Therapeutic;Therapeutic Intervention;tool;transcriptome sequencing;Triglycerides;United States;uptake

PROJECT_TITLE: Targeting the gut-liver axis in cardiovascular disease

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


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Mental Health;Neurosciences

ORG_CITY: NEW HAVEN

ORG_DEPT: NEUROSCIENCES

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: PROJECT NARRATIVE A non-human primate (macaque) brain resource (MacBrainResource, MBR) has been established from slides, tissue and EM blocks generated in the laboratories of Drs. Pasko Rakic and Patricia Goldman-Rakic. This resource will enable scientists worldwide to conduct de novo analyses of the macaque brain at a minimal cost to them and without the sacrifice of any additional animals. To renew MBR for another 5 years would permit the completion of ongoing scientific studies and the initiation of new ones while honoring the public call and scientific commitment to data and resource sharing and a responsible use of animals in research.

PI_NAMEs: DUQUE, ALVARO  (contact)

PROGRAM_OFFICER_NAME: LIU, CHRISTINA HUANG

PROJECT_TERMS: Adult;Age;age group;Amino Acids;Animals;Architecture;Area;Awareness;Axon;Behavior;Brain;brain cell;Brain Pathology;Brain region;brain research;brain tissue;Breeding;Caring;Cataloging;Catalogs;Collection;Communities;connectome;cost;COVID-19 vaccine;Data;data sharing;Date of birth;Development;Electronic Mail;Embryo;Employment;Ensure;Equipment;Equipment and supply inventories;Ethics;experimental study;fetal;Financial Hardship;Fostering;Freezing;Funding;genome analysis;genome sequencing;Grant;Growth;Histologic;Housing;Human;human disease;Human Pathology;Image;indexing;insight;International;Label;Laboratories;Lesion;Logistics;Macaca;Macaca mulatta;Microscopy;Molecular;Monkeys;neurochemistry;Neurons;Neurosciences;nonhuman primate;operation;Pathway interactions;Photography;Phylogenetic Analysis;Physiological;Population;postnatal;postnatal development;prenatal;Primates;Procedures;Process;Publications;Research;Research Personnel;Research Project Grants;Resource Sharing;Resources;restoration;Scientist;Site;Slide;Societies;Specimen;Structure;Surveys;System;Testing;Thymidine;tissue processing;Tissues;Travel;ultrasound;United States National Institutes of Health;Universities;web site;Widow;Work

PROJECT_TITLE: Yale Macaque Brain Resource

STUDY_SECTION: DBD

STUDY_SECTION_NAME: Developmental Brain Disorders Study Section[DBD]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

ORG_DEPT: NEUROLOGY

PHR: Project Narrative. The project establishes a team of researchers dedicated to work together in a national network to determine the most promising new stroke therapies to then be tested in clinical trials, advancing the care for stroke patients. They commit to rigorous testing of potential treatments selected by NINDS to hold great promise for the treatment of stroke.

PI_NAMEs: SANSING, LAUREN H (contact)

PROGRAM_OFFICER_NAME: HEWETT, SANDRA JEANNE

PROJECT_TERMS: Acute;Adherence;Aging;Animal Testing;Animals;behavioral outcome;biomedical imaging;Brain Ischemia;candidate identification;Caring;Cell Death;Cerebral Edema;cerebroprotection;Clinical;Clinical Research;Clinical Trials;Collaborations;Communication;comorbidity;Data Analyses;Data Collection;Dedications;Diabetes Mellitus;disability;Disease;Doctor of Philosophy;efficacy testing;Ensure;Event;excitotoxicity;Failure;Feedback;Filament;Future;Goals;Health;Hypertension;improved;improved outcome;Injury;innovation;Intervention;Ischemia;Ischemic Stroke;Laboratories;Leukocytes;Magnetic Resonance Imaging;Measures;Metabolic syndrome;Methodology;Methods;Microglia;Middle Cerebral Artery Occlusion;Modeling;mortality;MRI Scans;National Institute of Neurological Disorders and Stroke;Nervous System Trauma;neurobehavioral;next generation;novel;Obesity;Operative Surgical Procedures;Outcome;Outcome Assessment;oxidative damage;Pathway interactions;Patients;Perfusion;Physicians;Pneumonia;post stroke;pre-clinical;pre-clinical assessment;pre-clinical research;Predictive Value;programs;Protocols documentation;Randomized;recruit;Reperfusion Therapy;Research Design;Research Personnel;Rodent;Rodent Model;Schedule;Scientist;Site;skills;Specialist;Stroke;stroke model;stroke patient;stroke therapy;Structure;targeted treatment;Testing;therapeutic candidate;therapeutic evaluation;Therapeutic Intervention;Thrombectomy;thromboinflammation;timeline;Tissues;Training;Translating;translational scientist;translational study;Translations;Work

PROJECT_TITLE: Y-SPAN: Yale Translational Cerebroprotection Program in SPAN


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Childhood Leukemia;Genetics;Hematology;Human Genome;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: GAINESVILLE

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: Relevance Statement: Acute myeloid leukemia (AML) is the second most common childhood leukemia and has a dismal prognosis. For over 40 years AML chemotherapy has changed little with the continued reliance on ara-C, daunorubicin and etoposide as frontline agents. The proposed research seeks to define the impact of proteomic and metabolomics landscape of leukemic cells on patient risk stratification and revealing additional layers of the molecular basis of AML prognosis to guide the development of more effective treatments for AML.

PI_NAMEs: LAMBA, JATINDER K. (contact);POUNDS, STANLEY BARRETT

PROGRAM_OFFICER_NAME: AGRAWAL, LOKESH

PROJECT_TERMS: 21 year old;Acute Myelocytic Leukemia;acute myeloid leukemia cell;Adult;Adult Acute Myeloblastic Leukemia;amino acid metabolism;Ara-C;Azacitidine;Biological;Biology;cancer genomics;Cell Line;Characteristics;chemotherapy;Childhood;Childhood Acute Myeloid Leukemia;Childhood Leukemia;Classification;Clinical;Clinical Data;clinical prognosis;clinical translation;Clinical Trials;clinically relevant;cohort;Collaborations;Collection;Creatinine;CRISPR/Cas technology;Custom;Cytarabine;Data;Daunorubicin;Decitabine;demethylation;Development;Diagnosis;Diagnostic;DNA Sequence Alteration;DNMT3B gene;effective therapy;Elderly;Enrollment;Environment;epigenomics;Etoposide;Evaluation;Exposure to;Florida;Genome;genome wide methylation;Genomics;Glucose;Guidelines;human old age (65+);improved;innovation;Knock-out;Leukemic Cell;Malignant Neoplasms;meetings;metabolome;metabolomics;Methods;Methylation;methylome;methylomics;Molecular;Molecular Disease;Multi-Institutional Clinical Trial;Multiomic Data;Mutation;novel;novel therapeutics;Outcome;Pathway interactions;Patient risk;Patients;Pediatric cohort;Pediatric Oncology Group;Pharmaceutical Preparations;pharmacologic;Pharmacology;Phosphotransferases;Positioning Attribute;Procedures;Prognosis;prognostic;Prognostic Factor;Prognostic Marker;Proteins;Proteome;Proteomics;Qualifying;Randomized;Rare Diseases;Recommendation;Recurrence;Reporting;repository;Research;Research Personnel;Risk;risk stratification;Saint Jude Children's Research Hospital;Sample Size;Sampling;screening;Series;success;System;Systems Biology;Therapeutic Intervention;transcriptome;transcriptomics;Translating;Translational Research;Transplantation;Universities;Work

PROJECT_TITLE: Integrated Systems Biology of Pediatric AML

STUDY_SECTION: CBSS

STUDY_SECTION_NAME: Cancer Biomarkers Study Section[CBSS]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

ORG_CITY: AMHERST

ORG_DEPT: CHEMISTRY

ORG_NAME: STATE UNIVERSITY OF NEW YORK AT BUFFALO

ORG_STATE: NY

PHR: Enzyme catalysts are one of the principal components of all living systems and there are many diseases that may be cured by inhibition of a single enzyme. Advances in the understanding of enzyme catalysis from studies of enzymatic reaction mechanisms may prove critical for drug design, to the understanding of metabolic pathways and diseases, and to the resolution of other health-related issues. This proposal describes fundamental experimental and computational studies of the origins of rate accelerations for enzyme catalysts, and for the development of novel inhibitors of metabolic enzymes from pathogenic organisms.

PI_NAMEs: RICHARD, JOHN P (contact)

PROGRAM_OFFICER_NAME: BARSKI, OLEG

PROJECT_TERMS: Acceleration;Address;Adenosine;adenylate kinase;Alcohol dehydrogenase;Amino Acids;Binding;Biochemical Reaction;Carboxy-Lyases;Catalysis;catalyst;cofactor;Collaborations;computer studies;Computing Methodologies;Creativeness;design;Development;Disease;Docking;Drug Design;Enzyme Activation;enzyme mechanism;Enzymes;experimental study;Glycerol-3-Phosphate Dehydrogenase;Goals;Grant;Health;hydroxyl group;inhibitor;Japan;Metabolic;Metabolic Diseases;Metabolic Pathway;Methods;Modeling;Molecular Conformation;Mutagenesis;Mutation;novel;Organism;orotidylic acid;Pathogenicity;Peptides;Plasmodium falciparum;professor;Proteins;Reaction;Research Personnel;Resolution;Side;Site;Species Specificity;Specificity;Structure;Sweden;Tokyo;Triose-Phosphate Isomerase;Trypanosoma brucei brucei;Universities;Work;X-Ray Crystallography

PROJECT_TITLE: Studies on Enzyme Activation and Novel Modes of Inhibition

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


NIH_SPENDING_CATS: Attention Deficit Hyperactivity Disorder (ADHD);Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Health Services;Mental Health;Pediatric;Prevention;Primary Health Care;Sleep Research

ORG_CITY: PITTSBURGH

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: Narrative Sleep problems may be one mechanism through which young children may be at risk for developing ADHD, although first line ADHD interventions, including parent behavioral interventions (PBIs), do not address sleep. We propose to use parenting strategies from the COPEing with ADHD PBI to target sleep disrupting behaviors for children 3-5 years old at elevated risk for ADHD, which will be delivered by behavioral health therapists embedded in pediatric primary care to increase families’ access to intervention. This pilot effectiveness trial is the first step towards developing an early intervention targeting sleep as a mechanism to reduce the prevalence, symptoms, and impairments associated with childhood ADHD.

PI_NAMEs: JOSEPH, HEATHER MARIE (contact)

PROGRAM_OFFICER_NAME: PUGLIESE, CARA ELISABETH

PROJECT_TERMS: 5 year old;Academic skills;Academy;Acute;Address;Affect;American;Attention deficit hyperactivity disorder;Behavior;Behavior Control;Behavior Therapy;Behavioral;behavioral health;Caregivers;Child;Child Behavior;Child Rearing;Childhood;Clinic;Clinical Trials;comparison intervention;coping;Coping Skills;design;Development;Disease;Early Intervention;Economic Burden;Education;effectiveness trial;evidence base;Executive Dysfunction;executive function;experimental study;Failure;Family;feasibility testing;Feedback;Focus Groups;high risk;Hyperactivity;Impaired health;Impairment;improved;improved outcome;improvement on sleep;Impulsivity;inattention;Individual;innovation;Intervention;intervention delivery;intervention program;intervention refinement;Intervention Trial;Link;medical specialties;Mental Health;Needles;Neurodevelopmental Disorder;NIH Program Announcements;Nursery Schools;Outcome;Parents;pediatrician;Pediatrics;pilot trial;Population;Preschool Child;Prevalence;Primary Care;primary care provider;primary care setting;Protocols documentation;Provider;Randomized;Randomized, Controlled Trials;Recommendation;reduce symptoms;Resistance;response;Risk;Risk Factors;satisfaction;School-Age Population;skills;Sleep;Sleep Deprivation;sleep difficulty;Sleep Disorders;Sleep disturbances;social;Social Development;Symptoms;Techniques;Training;Translating;Visit;Waiting Lists;Work

PROJECT_TITLE: A Parent Behavioral Intervention Targeting Sleep Among Preschool Aged Children at Elevated Risk for ADHD: A Pilot Effectiveness Trial in Pediatric Primary Care


NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Genetics;Intellectual and Developmental Disabilities (IDD);Neurodegenerative;Neurosciences;Pediatric;Rare Diseases

ORG_CITY: CLEVELAND

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: CLEVELAND CLINIC LERNER COM-CWRU

ORG_STATE: OH

PHR: Project Narrative Hypomyelinating leukodystrophy (HLD) is a genetically heterogeneous group of neurodegenerative diseases characterized by reduced cerebral myelin formation, as well as cognitive and motor impairment appearing in childhood. In a pair of siblings with HLD, we have discovered a Pro-to-Thr mutation in the coding sequence of the EPRS1 gene that encodes a bifunctional tRNA synthetase (glutamyl-prolyl tRNA synthetase) and leads to its reduced expression without altering its activity. Here, we will investigate in detail the mechanism of reduced expression of EPRS1 in cells and in a novel mouse model of HLD generated by the CRISPR/Cas9 system.

PI_NAMEs: DUTTA, RANJAN ;FOX, PAUL L (contact)

PROGRAM_OFFICER_NAME: MORRIS, JILL A

PROJECT_TERMS: adverse outcome;Affect;Amino Acids;Amino Acyl-tRNA Synthetases;Anticodon;Ataxia;Automobile Driving;Behavioral;Binding;brain magnetic resonance imaging;Cell Nucleus;cell type;Cells;Central Nervous System;Central Nervous System Diseases;Cerebellar Diseases;Cerebrum;Child;Childhood;Clinical;Code;Cognitive;Complex;CRISPR/Cas technology;curative treatments;Cytoplasm;Defect;Disparate;Distant;early adolescence;Elements;Etiology;Exhibits;exome sequencing;experimental study;Functional disorder;Gait abnormality;Gene Modified;Genes;Genetic Code;global developmental delay;Glutamates;glutamic acid-tRNA;glutamyl-prolyl-tRNA synthetase;Growth;Heterozygote;Human Inbreeding;Impaired cognition;in vivo evaluation;Intellectual functioning disability;knock-down;Knock-in Mouse;Lamin Type A;Letters;leukodystrophy;Life Expectancy;Ligase;Ligation;lymphoblastoid cell line;Mediating;Messenger RNA;Methylation;Microcephaly;Molecular;Motor;motor impairment;mouse model;Mus;mutant;Mutant Strains Mice;Mutate;Mutation;Myelin;myelination;Neural Conduction;Neurodegenerative Disorders;Neurologic;Neurologic Deficit;Nomenclature;novel;Nuclear;Nuclear Export;oligodendrocyte progenitor;Oligodendroglia;Parents;Pathologic;Pathologic Nystagmus;Pathology;Pathway interactions;Peripheral Nerves;Phenotype;Point Mutation;Poly(ADP-ribose) Polymerases;Positioning Attribute;Post-Transcriptional Regulation;preclinical evaluation;precursor cell;prenatal;programs;Proline;proline-tRNA;Protein Biosynthesis;protein expression;Proteins;Recombinants;Repression;Role;Siblings;single nucleus RNA-sequencing;small hairpin RNA;spasticity;Specificity;System;Testing;Therapeutic;Therapeutic Intervention;therapeutic RNA;Trans-Activators;Transcript;transcriptomics;Transfer RNA;Transfer RNA Aminoacylation;Translations;Variant;virtual

PROJECT_TITLE: Childhood-onset hypomyelinating leukodystrophy and the multi-tRNA synthetase complex

STUDY_SECTION: MNG

STUDY_SECTION_NAME: Molecular Neurogenetics Study Section[MNG]


NIH_SPENDING_CATS: Lung;Patient Safety

ORG_CITY: BALTIMORE

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

ORG_STATE: MD

PHR: Despite the increasing number of surgical pulmonary resections performed annually the effects of detrimental post-operative inflammation associated with these procedures are poorly understood. We now make a discovery that a proinflammatory cell population, known as the eosinophil, is detrimental to recovery post-lung resection in a translational animal model. Here we explore the physiology of this cell population in a small animal model with the hope of improving both long and short-term post-operative outcomes.

PI_NAMEs: JACOBSEN, ELIZABETH A;KRUPNICK, ALEXANDER S. (contact)

PROGRAM_OFFICER_NAME: GOMEZ, CHRISTIAN RENE

PROJECT_TERMS: Acceleration;Adrenal Cortex Hormones;Age;Animal Model;Animals;Antibodies;biological adaptation to stress;Blood;Blood capillaries;Bone Marrow;Cell Physiology;Cells;Chest;Clinical;clinically relevant;cytokine;Data;Development;Dysbarism;Environment;eosinophil;Eosinophilia;Epithelium;Evidence based practice;Excision;FDA approved;Fluid Balance;Genetic;Granulocyte-Macrophage Colony-Stimulating Factor;Homing;Human;Hypoxemia;Hypoxia;Immune response;improved;improved outcome;Inflammation;Inflammatory;insight;Interleukin-4;Interleukin-5;Interleukin-9;Intervention;knockout gene;Lead;Length of Stay;Liquid substance;Lung;Lung infections;Lymphoid Cell;Malignant neoplasm of lung;Malignant Neoplasms;Mediating;Metastatic Neoplasm to the Lung;Morbidity - disease rate;mortality;Mouse Strains;Nitric Oxide;NOS2A gene;novel;novel therapeutic intervention;Observational Study;operation;Operative Surgical Procedures;Outcome;partial recovery;Pathway interactions;patient response;patient safety;Patient-Focused Outcomes;Patients;Peptide Initiation Factors;Perioperative;Pharmaceutical Preparations;Physiology;Play;Pneumonectomy;Population;Postoperative Period;postoperative recovery;prevent;Procedures;Process;Production;progenitor;Protocols documentation;Pulmonary Edema;Pulmonary Emphysema;pulmonary function;Pulmonary Pathology;Recovery;recruit;Respiratory distress;Respiratory Failure;response;Role;safe patient;Signal Transduction;Steroids;Stress;Structure of parenchyma of lung;Testing;Therapeutic;Thoracic Surgical Procedures;Tidal Volume;Tissues;Toxic effect;United States Agency for Healthcare Research and Quality;Up-Regulation;Ventilator;Wound Infection

PROJECT_TITLE: Targeting a Defined Surgical Stress-Induced Inflammatory Pathway to Improve Peri-Operative Outcomes

STUDY_SECTION: SAT

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


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

NIH_SPENDING_CATS: Biotechnology;Cancer;Colorectal Cancer;Digestive Diseases;Genetics;Human Genome

ORG_CITY: ITHACA

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: CORNELL UNIVERSITY

PHR: PROJECT NARRATIVE Distinct groups of eukaryotic DNA mismatch repair (MMR) family proteins facilitate crossing over between homologs to ensure proper Meiosis I chromosome segregation, and act to prevent recombination between divergent DNA sequences that can lead to chromosomal rearrangements associated with diseases such as cancer. In humans, failures in meiotic chromosome segregation result in aneuploidy syndromes (at least 10% of human pregnancies), which are thought to occur as the result of Meiosis I and II errors, defective or inappropriate recombination, premature homolog separation, and defects in sister chromatid cohesion. Importantly, mutations in MMR genes have been found in about half of hereditary non-polyposis colorectal cancer (2-7% of all colon cancers) patients, and are thought be linked to infertility, underscoring the importance of obtaining new mechanistic understandings and molecular tools to establish allele pathogenicity.

PI_NAMEs: ALANI, ERIC E. (contact)

PROGRAM_OFFICER_NAME: MACARTHUR, LINDA

PROJECT_TERMS: Affect;Alleles;Aneuploidy;base;Binding;Biochemical;Bypass;Chromosomal Rearrangement;Chromosome Segregation;cohesion;Colon Carcinoma;Complex;Cruciform DNA;Deacetylase;Defect;Diffusion;Dimerization;Disease;DNA;DNA biosynthesis;DNA Sequence;endonuclease;Ensure;Eukaryota;Failure;Filament;gene repair;Genetic;Genetic Crossing Over;Genetic Recombination;Genome Stability;genome wide screen;Grant;helicase;Hereditary Nonpolyposis Colorectal Neoplasms;Histones;Homologous Gene;homologous recombination;Human;Hydrolysis;In Vitro;Infertility;Inherited;insertion/deletion mutation;Invaded;Link;Malignant Neoplasms;Mass Spectrum Analysis;Measures;Mediating;Meiosis;Meiotic Recombination;Methods;Mismatch Repair;Modeling;Molecular;Molecular Chaperones;Molecular Conformation;molecular modeling;mutant;Mutation;nuclease;Pathogenicity;Pathway interactions;Patients;Pregnancy;premature;prevent;Protein Family;Proteins;Reaction;reconstitution;recruit;repaired;Research;Role;Saccharomyces cerevisiae;single molecule;Sister Chromatid;Site;Specificity;Syndrome;System;Testing;tool;Topoisomerase;Work

PROJECT_TITLE: Roles for Mismatch Repair Proteins in Maintaining Genome Stability

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


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cardiovascular;Clinical Research;Diabetes;Heart Disease;Heart Disease - Coronary Heart Disease;Neurodegenerative;Neurosciences;Pain Research;Peripheral Neuropathy

PHR: Diabetes mellitus (DM) is associated with significant co-morbidities, specifically those associated with nervous system dysfunction, including increased risk for peripheral artery disease (PAD), and cardiovascular complications. This project will optimize and apply dual isotope hybrid non-invasive imaging approach for evaluation of lower extremity flow, peripheral nerve activity, and vascular calcification in pre-clinical models of PAD and in patients with DM and a spectrum of PAD severity. The proposed multi-isotope imaging of lower extremity flow and nerve activity developed and applied in this project in conjunction with imaging of calcifications of the arteries will characterize the pathophysiology of nerve dysfunction in PAD and this information may lead to a paradigm change in the evaluation and long-term management of patients with DM and PAD.

PI_NAMEs: LIU, CHI ;SINUSAS, ALBERT J (contact);SMOLDEREN, KIM GERMAINE

PROGRAM_OFFICER_NAME: DANTHI, NARASIMHAN

PROJECT_TERMS: 3-Dimensional;Activities of Daily Living;Acute;Albumins;Amputation;analog;Anatomy;Angiography;Arteries;Atherosclerosis;attenuation;Autonomic Dysfunction;autonomic neuropathy;Blood flow;Blood Vessels;calcification;cardiovascular risk factor;Cardiovascular system;Cessation of life;Chronic;claudication;clinical application;clinical imaging;comorbidity;critical limb Ischemia;Data;Death Rate;Denervation;design;Development;Diabetes Mellitus;Diabetic Autonomic Neuropathy;Diabetic Foot;Diabetic Neuropathies;Diagnosis;diagnostic criteria;Dose;End stage renal failure;endothelial dysfunction;Evaluation;Event;Exercise;extracellular;Fibrosis;foot;Functional disorder;Heart;Heterogeneity;high resolution imaging;high risk;Hindlimb;Homeostasis;Hybrids;Hyperglycemia;hypoperfusion;Image;Image Analysis;imaging approach;improved;Ischemia;Isotopes;Label;Legal patent;limb ischemia;Limb structure;Lower Extremity;Maps;Medial;Methods;Microspheres;Microvascular Dysfunction;Modeling;Muscle;Muscle denervation procedure;Nerve;Nerve Block;nerve supply;Nervous System;Neuropathy;non-invasive imaging;Norepinephrine;novel;Orthostatic Hypotension;Oryctolagus cuniculus;Outcome;Oxidative Stress Induction;Pain;Pain in lower limb;particle;Patients;Perfusion;Peripheral;Peripheral arterial disease;peripheral blood;Peripheral Nerves;Phenotype;Physiologic arteriovenous anastomosis;Physiological;Play;porcine model;Positron-Emission Tomography;Pre-Clinical Model;Prevalence;Probability;prognostic value;Quality of life;Quantitative Evaluations;quantitative imaging;Radiolabeled;radiotracer;Registries;Resolution;response;Rest;revascularization;revascularization surgery;Risk;Role;Sclerosis;serial imaging;Severities;Severity of illness;single photon emission computed tomography;Skeletal Muscle;Smooth Muscle;Stress;Structural defect;Sympathectomy;Sympathetic Nervous System;Technology;Testing;Time;Tissues;Translating;Treatment Cost;Treatment outcome;treatment pattern;Vascular calcification;Vasodilation;Vasomotor;Veins;volunteer;Work;X-Ray Computed Tomography

PROJECT_TITLE: Multi-isotope Hybrid PET/CT Imaging of Peripheral Artery Disease in Diabetes

STUDY_SECTION: CTIS

STUDY_SECTION_NAME: Clinical Translational Imaging Science Study Section[CTIS]


NIH_SPENDING_CATS: Cardiovascular;Heart Disease;Maternal Health;Maternal Morbidity and Mortality;Nutrition;Pregnancy;Women's Health Research

ORG_CITY: LOUISVILLE

ORG_NAME: UNIVERSITY OF LOUISVILLE

ORG_STATE: KY

PHR: Project Narrative Pregnancy promotes remarkable changes in maternal metabolism and physiology. To ensure appropriate delivery of oxygen and nutrients to the fetus and maternal organs, the maternal heart undergoes a physiological form of hypertrophy; however, the mechanisms that contribute to this adaptive remodeling are unknown. This project will examine how the maternal heart adapts to the demands of pregnancy, with the goal of understanding how changes in cardiac metabolism influence pregnancy-induced cardiac growth as well as reversal of cardiac growth following pregnancy.

PI_NAMEs: COLLINS, HELEN E (contact)

PROGRAM_OFFICER_NAME: POIZAT, CORALIE ISABELLE

PROJECT_TERMS: Accounting;Affect;Amino Acids;angiogenesis;beta-Hydroxybutyrate;Biochemical;Birth;Carbon;Cardiac;Cardiac health;Cardiac Myocytes;Cardiovascular system;Catabolism;Cause of Death;Cessation of life;Contrast Echocardiography;Data;Death Rate;Developed Countries;Echocardiography;Energy Supply;Ensure;Enzymes;Exercise;Extracellular Matrix;Fatty Acids;Fetus;Genetic Transcription;Glucose;glucose metabolism;Glycerophospholipids;Goals;Growth;Heart;heart dimension/size;Heart failure;heart function;heart metabolism;hemodynamics;High Cardiac Output;Histologic;Histological Techniques;Human;Hypertrophy;in vivo;indexing;Intervention;ketogenesis;Ketone Bodies;Knowledge;Lactation;Late pregnancy;Link;Literature;Live Birth;Liver;Maternal Health Services;Maternal Mortality;Measures;Mechanics;Metabolic;metabolic phenotype;Metabolism;Molecular;Mus;Myocardial;Myocardial dysfunction;Nucleotides;Nutrient;Organ;osmotic minipump;overexpression;oxidation;Oxidoreductase;Oxygen;Pathology;Pathway interactions;Perfusion;Physiological;Physiology;post pregnancy;Postpartum Period;Postpartum Women;Pregnancy;Pregnancy Trimesters;Pregnant Women;prevent;programs;Radiolabeled;Signal Transduction;Source;stable isotope;Structure;Testing;Tissues;Tracer;transcriptome sequencing;Triglycerides;Ventricular;Ventricular Remodeling;Western Blotting;Wit

PROJECT_TITLE: Mechanisms Contributing to Pregnancy-induced Cardiac Remodeling

STUDY_SECTION: BBHV

STUDY_SECTION_NAME: Basic Biology of Blood, Heart and Vasculature Study Section [BBHV]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Diabetes;Genetics;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: PHILADELPHIA

ORG_NAME: CHILDREN'S HOSP OF PHILADELPHIA

PHR: NARRATIVE Pancreas agenesis is a developmental disorder characterized by either a reduction or complete lack of pancreatic mass and heterozygous loss of GATA6 accounts for >60% of all human pancreas agenesis cases. The primary goals of this renewal application are to use complementary mouse and human genetic model systems to better define the mechanisms by which the intersection of RA signaling and GATA6 regulate pancreas development. Furthermore, we will explore how human mutations in GATA6 disrupt this interaction to influence disease severity.

PI_NAMEs: GADUE, PAUL J (contact);LORBERBAUM, DAVID

PROGRAM_OFFICER_NAME: HWA, ALBERT J

PROJECT_TERMS: Affect;Alleles;B cell differentiation;B-Cell Development;B-Lymphocytes;Beta Cell;Binding;Binding Sites;Biological Models;Cell Differentiation process;cofactor;Collaborations;CRISPR/Cas technology;Data;Development;developmental disease;differentiation protocol;Disease;Endocrine;endocrine pancreas development;Enhancers;Event;experimental study;Family;Functional disorder;Funding;GATA4 gene;Gene Expression Regulation;Genetic;Genetic Models;Genetic Transcription;Genome;Goals;High-Throughput Nucleotide Sequencing;Human;Human Genetics;human induced pluripotent stem cells;human model;human pluripotent stem cell;Impairment;in vivo;Individual;induced pluripotent stem cell;insight;Islet Cell;Islets of Langerhans;Loss of Heterozygosity;Molecular;mouse genetics;mouse model;Mus;Mutation;neonatal diabetes mellitus;Non-Insulin-Dependent Diabetes Mellitus;novel;Pancreas;pancreas development;Pancreatic Diseases;Pathogenesis;Pathway interactions;Patients;Phenotype;Productivity;protein protein interaction;Publishing;Regulation;Regulatory Pathway;Role;Severities;Severity of illness;Signal Pathway;Signal Transduction;Specific qualifier value;stem cell fate specification;stem cell population;synergism;System;Technology;Testing;transcription factor;Tretinoin

PROJECT_TITLE: Intersection of signaling pathways and transcription factors regulating islet development

STUDY_SECTION: BMDM

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


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Bioengineering;Biomedical Imaging;Biotechnology;Cardiovascular;Cerebrovascular;Coronaviruses;Coronaviruses Therapeutics and Interventions;Emerging Infectious Diseases;Hematology;Infectious Diseases;Lung

ORG_CITY: BOSTON

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

ORG_STATE: MA

PHR: Narrative We propose to harness our unique expertise in engineered in vitro human vascular tissue models and high- speed volumetric imaging of thrombosis to create an enabling and first-of-its-kind high(er)-throughput real-time imaging-integrated thrombosis-on-chip model to study thrombosis and potential therapeutic agents, taking SARS-CoV-2 infection as a timely example to instruct future preparedness for pandemics and other vascular disorders.

PI_NAMEs: YAO, JUNJIE ;ZHANG, Y. SHRIKE  (contact)

PROGRAM_OFFICER_NAME: GOLDBERG, ILANA GRACE

PROJECT_TERMS: 2019-nCoV;3-Dimensional;Acute;Adopted;Affect;Alteplase;Animal Model;Anti-viral Agents;Anticoagulation;arm;Arteries;Behavior monitoring;bioprinting;Blood flow;Blood Vessels;Capital;Cardiovascular Diseases;Cardiovascular system;Cell Culture Techniques;Cells;Cessation of life;Clinical;Coagulation Process;Collagen Type I;cost;COVID-19;COVID-19 assay;deep vein;Deep Vein Thrombosis;Development;disability-adjusted life years;Disease;drug candidate;drug development;Drug Screening;drug testing;Edema;Endothelium;Engineering;European Union;Event;experience;Fiber;Fibrin;Fibrinolysis;Fibrinolytic Agents;Fibroblasts;Fibrosis;Functional Imaging;Future;Goals;Hematologist;Hematology;Hemorrhage;Hemostatic function;high throughput screening;Hospitalization;Human;Human Engineering;Hypertension;Image;Impairment;improved;In Situ;In Vitro;in vitro Model;Infection;Infiltration;Injury;Investigation;Investments;Label;Leg;Libraries;Limb structure;Lung;miniaturize;Modeling;Molecular;Morbidity - disease rate;mortality;next generation;Obstruction;optoacoustic tomography;Pain;pandemic preparedness;Pathologic;Pathology;Patients;Penetration;Pericytes;Pharmaceutical Preparations;Pharmacotherapy;photoacoustic imaging;Physician Executives;Physiological;Physiology;Plasmin;Plasminogen;Postphlebitic Syndrome;Process;Proliferating;Publications;Pulmonary artery structure;Pulmonary Embolism;real-time images;Reporting;Resolution;response;SARS-CoV-2 infection;Scheme;screening;Services;Site;small molecule;Smooth Muscle Myocytes;Speed;System;Therapeutic;Therapeutic Agents;Thromboembolism;Thrombolytic Therapy;Thrombosis;thrombotic;Thrombus;Time;Tissue Model;Tissues;Travel;Ulcer;United States;Vascular Diseases;vascular injury;Vasculitis;Veins;Venous;venous thromboembolism;Virus Diseases;years of life lost

PROJECT_TITLE: High-throughput Imaging-integrated Vascular Model for Understanding Thromboembolism and Therapeutics Screening

STUDY_SECTION: BMBI

STUDY_SECTION_NAME: Biomaterials and Biointerfaces Study Section[BMBI]


ADMINISTERING_IC: OD

ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

IC_NAME: OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH

ORG_CITY: DAVIS

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: Project Narrative Osteosarcoma is the most common primary bone cancer in humans and survival improvements have not been attained in over three decades; the majority of patients will succumb to metastatic spread. Identification of novel targets in osteosarcoma will be required to advance treatment of this ultimately fatal disease. This project aims to interrogate and define the non-canonical role of the Core Binding Factor Beta (CBFβ) protein in the initiation of protein translation, a process critical for tumor cell survival, thereby improving our understanding of the biology of osteosarcoma and providing a knowledge base for identification of novel targets and therapeutic strategies.

PI_NAMEs: WITTENBURG, LUKE A. (contact)

PROGRAM_OFFICER_NAME: VONKOLLMAR, DESIREE

PROJECT_TERMS: Address;Adolescent and Young Adult;Affect;Binding;Binding Sites;Biological Assay;Biology;Bone neoplasms;Breast Cancer Cell;cancer cell;Cell Line;Cell Survival;Cells;chemotherapy;Combined Modality Therapy;Complex;Core-Binding Factor;Cytoplasm;Data;Development;Diagnosis;Disease;DNA Binding;driver mutation;Family;Future;gene product;Genetic Transcription;Global Change;Goals;Grant;Human;improved;in vivo;insight;Investigation;Knock-out;Knowledge;knowledge base;Measures;member;Messenger RNA;Molecular Target;molecular targeted therapies;mutant;Mutation;Neoplasm Metastasis;neoplastic cell;new therapeutic target;novel;Nuclear;Oncogenic;Oncoproteins;Operative Surgical Procedures;osteoblast differentiation;Osteoblasts;Osteosarcoma;overexpression;Pathogenesis;Pathway Analysis;Pathway interactions;Patients;Peptides;Persons;Post-Transcriptional Regulation;posttranscriptional;primary bone cancer;Primary Neoplasm;Process;Proteasome Inhibition;Protein Biosynthesis;protein expression;Proteins;Radiation therapy;Regulation;Reporting;Research;ribosome profiling;Ribosomes;RNA Binding;RNA Cap-Binding Proteins;Role;Signal Pathway;Signal Transduction;Skeletal Development;System;targeted agent;Therapeutic;therapeutically effective;Time;transcription factor;transcriptome sequencing;Transfection;Translation Initiation;Translations;treatment strategy;tumor heterogeneity

PROJECT_TITLE: Establishing the role of cytoplasmic Core Binding Factor beta in the regulation of osteosarcoma protein translation


NIH_SPENDING_CATS: Cardiovascular;Congenital Heart Disease;Heart Disease;Pediatric;Prevention;Rare Diseases

ORG_CITY: MADISON

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: NARRATIVE Hyperactivity of the cardiac ryanodine receptor/Ca2+ release channel of the sarcoplasmic reticulum (RyR2) may lead to ventricular fibrillation and other lethal cardiac arrhythmias, such as occurs in the arrhythmogenic syndrome catecholaminergic polymorphyc ventricular tachycardia (CPVT), a congenital disease affecting children and young adults with an apparently normal heart. β-blockers are the standard therapy for CPVT, but it often results in incomplete protection. We discovered that selected scorpion venoms contain calcins, a family of peptide ligands of RyR2 that are able to penetrate cellular membranes and mitigate Ca2+-dependent arrhythmias due to RyR2 hyperactivity. In this study, we will develop a rationalized and novel paradigm for the treatment of CPVT based on calcins. These results may be applied to other cardiomyopathies where controlled unloading of intracellular Ca2+ may be desirable.

PI_NAMEs: ALVARADO, FRANCISCO J;VALDIVIA, HECTOR H (contact)

PROGRAM_OFFICER_NAME: TJURMINA, OLGA A

PROJECT_TERMS: Action Potentials;Adrenergic Agents;Adrenergic beta-Antagonists;Affect;Affinity;Agonist;Animal Model;Animals;Anti-Arrhythmia Agents;Arrhythmia;Arrhythmogenic Right Ventricular Dysplasia;Atrial Fibrillation;autosome;Binding;Biological Assay;Buffers;Calcium;Calsequestrin;Cardiac;Cardiac Myocytes;Cardiomyopathies;Catecholaminergic Polymorphic Ventricular Tachycardia;Cell Membrane Permeability;Cell Physiology;Cells;Cellular Membrane;Characteristics;Child;Cyclic AMP-Dependent Protein Kinases;design;Development;Diastole;Disease;Environment;Event;Family;Functional disorder;Genes;Heart;Heart failure;Hyperactivity;Individual;insight;Knock-in;Ligands;Malignant - descriptor;Mediating;member;Membrane;Metabolic;Microfilaments;Modeling;Molecular;Mus;Muscle Cells;Mutation;novel;Oryctolagus cuniculus;Output;Pathologic;Penetration;Peptides;Performance;Perfusion;phospholamban;Phosphorylation;Play;prevent;Process;programs;Property;Proteins;Rationalization;Receptor Gene;Research;Role;Ryanodine Receptor Calcium Release Channel;Sarcolemma;Sarcoplasmic Reticulum;Scorpion Venoms;Signal Transduction;stem;Strenuous Exercise;Stress;Syndrome;Testing;uptake;Ventricular;Ventricular Fibrillation;Ventricular Tachycardia;young adult

PROJECT_TITLE: Partial and Controlled Depletion of SR Calcium by RyR Agonists Prevents Calcium-dependent Arrhythmias

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-TDPS-R(01)]


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);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Dementia;Neurodegenerative;Neurosciences

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Project Narrative The proposed research is relevant to public health because it will help elucidate a potential connection between seemingly different aspects of Alzheimer’s disease. Our findings may help identify new approaches for early detection and ultimately therapeutic intervention in this devastating disorder.

PI_NAMEs: JOINER, WILLIAM J (contact)

PROGRAM_OFFICER_NAME: WAGSTER, MOLLY V

PROJECT_TERMS: Age;alpha-bungarotoxin receptor;Alzheimer disease detection;Alzheimer's Disease;Alzheimer's disease diagnosis;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease patient;Alzheimer’s disease biomarker;Amyloid beta-Protein;Animal Model;Animals;Behavior;Behavioral;Biological Assay;Blood;Cell Line;Cerebrospinal Fluid;cholinergic;Chronic;Clinical Data;Cognition;Complement;Data;desensitization;detection method;Disease;Disease Progression;Disinhibition;Down-Regulation;Early Diagnosis;Effectiveness;Elements;Enzyme-Linked Immunosorbent Assay;Etiology;Exhibits;exosome;experimental study;FDA approved;Goals;high throughput screening;Hippocampus;Impaired cognition;In Vitro;in vivo;Individual;individual patient;inhibitor;interest;knock-down;Lentivirus;Link;Measurement;Measures;Memory;Memory Loss;Methods;Molecular;Molecular Conformation;molecular targeted therapies;morris water maze;mouse model;Mus;Nerve Degeneration;Neurobehavioral Manifestations;neuron loss;Neurons;neurotoxic;Nicotinic Receptors;novel;novel marker;novel strategies;object recognition;Outcome;Pathogenesis;Pathogenicity;Pathway interactions;Peptides;Performance;Permeability;Pharmaceutical Preparations;pharmacologic;Physiological;Predisposition;premature;Prevalence;prevent;Process;Proteins;Public Health;Publishing;rapid detection;receptor;Research;Role;Sampling;Severity of illness;Signal Transduction;small hairpin RNA;Synapses;synergism;tau-1;Temporal Lobe;Testing;Therapeutic Intervention;Time;tool;Transfection

PROJECT_TITLE: The contribution of Ly6h to Alzheimers Disease

STUDY_SECTION: CDIN

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


ADMINISTERING_IC: HD

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

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: RELEVANCE TO PUBLIC HEALTH A woman's supply of eggs (oocytes), which are present in her ovary from birth, are essential for her fertility, and for her long-term health, as loss of the oocyte pool leads to menopause, with increase risks of osteoporosis, cardiovascular disease and muscle atrophy. Mutations in human Nemp1 are associated with early menopause, and loss of Nemp1 in mouse models leads to infertility. By studying how Nemp1 functions using mouse models, we can better understand how we can support a woman's fertility and her health, and diagnose some causes of infertility.

PI_NAMEs: MCNEILL, HELEN  (contact)

PROGRAM_OFFICER_NAME: TAYMANS, SUSAN

PROJECT_TERMS: 3-Dimensional;Adult women;Affect;Affinity Chromatography;Alleles;Aneuploidy;Animals;Appearance;Architecture;Biological Assay;Birth;Cardiovascular Diseases;cardiovascular disorder risk;Cells;Cessation of life;Chimeric Proteins;ChIP-seq;Chromatin;Chromosome Pairing;Chromosome Segregation;Competence;Congenital Abnormality;Coupled;Cultured Cells;Data;Defect;Development;Diagnosis;DNA Damage;early onset;egg;Electron Microscopy;Embryonic Development;env Gene Products;experimental study;Female;female fertility;Female infertility;Female sterility;Fertility;Fertility Disorders;Fishes;fly;gain of function;Gene Expression;Genes;Genetic;Genetic study;Genetic Transcription;genome wide association study;Germ Cells;Germ Lines;Goals;Grant;granulosa cell;Health;Hi-C;histone modification;Histones;Human;Human Genome;Image;in vivo;Infertility;insight;Integral Membrane Protein;Link;loss of function;Mammals;Mass Spectrum Analysis;Meiosis;Membrane Proteins;Menopause;Mothers;mouse model;Mus;Muscular Atrophy;mutant;Mutation;Neurologic Dysfunctions;novel;Nuclear Envelope;Nuclear Structure;Nucleoplasm;offspring;oocyte quality;Oocytes;Oogenesis;Organism;Osteoporosis;Ovarian Follicle;ovarian reserve;Ovary;Ovulation;Pathway interactions;Phenotype;Premature Menopause;Proteins;Proteomics;Public Health;Publishing;Rest;Risk;Role;Sterility;Structure;superresolution microscopy;Tail;Testing;Time;Transcript;transcriptome sequencing;Transgenic Organisms;Variant;Woman;Women's Health;zygote

PROJECT_TITLE: Dissecting the function of Nemp1, a nuclear envelope protein critical for mammalian fertility

STUDY_SECTION: CMIR

STUDY_SECTION_NAME: Cellular, Molecular and Integrative Reproduction Study Section[CMIR]


ORG_CITY: OKLAHOMA CITY

ORG_NAME: OKLAHOMA MEDICAL RESEARCH FOUNDATION

ORG_STATE: OK

PHR: PROJECT NARRATIVE Cardiac and vascular valves are critical for regulating blood and lymph flow within our circulatory system. We have identified certain molecules that are expressed in both vascular and cardiac valves. We will investigate the roles of these molecules in heart valve development and disease.

PI_NAMEs: SRINIVASAN, RAJANARAYANAN S (contact)

PROGRAM_OFFICER_NAME: EVANS, FRANK

PROJECT_TERMS: ADAMTS;aggrecan;Anabolism;aortic valve;Biochemical;Blood flow;Blood Vessels;Cardiac;Cardiovascular system;cell type;Characteristics;Collagen;Data;Defect;Development;Disease;Doxycycline;Elastin;Endothelial Cells;Endothelium;Etiology;experience;Extracellular Matrix;Extracellular Matrix Proteins;FOXC2 gene;gain of function;Genes;genetic approach;Growth;Heart;Heart Valve Diseases;Heart Valves;Homeobox;human old age (65+);In Vitro;Individual;Inflammation;insight;interstitial cell;Light;loss of function;Lymph;lymph flow;Lymphatic;lymphatic development;lymphatic vessel;Lymphedema;Maintenance;mechanical force;Mitral Valve;Modeling;Molecular;mouse model;Mus;novel;Outcome;overexpression;Pathway interactions;Peptide Hydrolases;Pharmaceutical Preparations;pharmacologic;Phenocopy;Phenotype;Physiological;Platelet-Derived Growth Factor;prevent;Production;Proteoglycan;Public Health;rare genetic disorder;Research;response to injury;Role;Side;Signal Pathway;Signal Transduction;small hairpin RNA;STAT1 gene;Structure;Syndrome;Testing;Therapeutic;Thinness;transcription factor;Veins;Venous;versican;Work

PROJECT_TITLE: Novel lymphatic genes that regulate heart valve development and disease

STUDY_SECTION: CDD

STUDY_SECTION_NAME: Cardiovascular Differentiation and Development Study Section[CDD]


ED_INST_TYPE: OTHER SPECIALIZED SCHOOLS

ORG_CITY: CAMBRIDGE

ORG_NAME: HARVARD UNIVERSITY

PHR: Therapeutic T cells can be used to treat cancer, but it is currently not known how the physical properties of the environment in which T cells are manufactured impacts their function. These studies will address this fundamental question using a combination of cell culture studies, and animal validation studies. The resulting knowledge may alter how T cells are currently manufactured for cancer immunotherapy, and could identify new targets to improve anti- cancer immune responses.

PI_NAMEs: MOONEY, DAVID J (contact)

PROGRAM_OFFICER_NAME: BECKER, STEVEN

PROJECT_TERMS: Address;Adoptive Transfer;Animals;anti-cancer;Antitumor Response;cancer immunotherapy;Cancer Patient;CD19 gene;Cell Culture Techniques;Cell Physiology;Cell Separation;Cellular biology;chimeric antigen receptor T cells;cytokine;Dose;Elasticity;Environment;Extracellular Matrix;Gel;Hydrogels;Immune response;imprint;improved;In Vitro;in vivo;Infusion procedures;Knowledge;knowledge of results;leukemia/lymphoma;Malignant Neoplasms;manufacture;mechanical load;Mechanics;Mediating;mimetics;Outcome;Pathway interactions;Patients;Phenotype;Physical environment;physical property;Process;Production;Property;Research;response;Role;Signal Transduction;single-cell RNA sequencing;Solid Neoplasm;stem cell differentiation;success;synaptogenesis;T cell differentiation;T cell therapy;T-Cell Activation;T-Lymphocyte;Time;Tissues;Transcription Factor AP-1;Treatment Efficacy;tumor;validation studies;viscoelasticity

PROJECT_TITLE: Viscoelasticity and T Cell Production


NIH_SPENDING_CATS: Brain Disorders;Genetics;Neurodegenerative;Neurosciences;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: NARRATIVE  In spinocerellar ataxia type 12 (SCA12), the CAG repeat expansion may alter expression and splicing of  PPP2R2B, leading to a change in PP2A targeting and expression of an aberrant polyserine containing protein  that potentially contribute to SCA12 pathogenesis. Using SCA12 knock-mouse and various sets of human  isogenic control and SCA12 iPSC lines, we will look for evidence of altered Bβ1 and Bβ2 expression, aberrant  expression of polyserine containing protein, changes in phosphoproteome and signs of neurotoxicity.

PI_NAMEs: LI, PAN  (contact)

PROGRAM_OFFICER_NAME: RANGANATHAN, SRIKANTH

PROJECT_TERMS: Affinity;Alleles;Alternative Splicing;Alzheimer's Disease;Ataxia;Atrophic;autosome;Brain;CAG repeat;Cell model;Cells;Cerebellum;Cerebral cortex;China;chromatin modification;Clinical;Data;design;Disease;disease model;Exons;experimental study;Gait abnormality;Generations;Genes;Genetically Engineered Mouse;Holoenzymes;Human;human induced pluripotent stem cells;Huntington Disease;India;induced pluripotent stem cell;interest;Italy;Knock-in Mouse;Late-Onset Disorder;Length;Measures;Molecular;mouse model;Mus;Mutation;N-terminal;Nerve Degeneration;Neurodegenerative Disorders;neuropathology;neuropsychiatry;neurotoxicity;novel;overexpression;Pathogenesis;Pathway interactions;Pattern;Phosphoric Monoester Hydrolases;Phosphorylation;polyserine;promoter;Promoter Regions;Protein Isoforms;Protein phosphatase;Proteins;RNA Splicing;RNA-Binding Proteins;Role;Series;Spinocerebellar Ataxias;Syndrome;targeted treatment;Testing;Therapeutic Intervention;Time;Toxic effect;Transcript;Transfection;Tremor;Triplet Multiple Birth;United States;Variant;Work

PROJECT_TITLE: Molecular Pathogenesis of spinocerebellar ataxia type 12

STUDY_SECTION: CMND

STUDY_SECTION_NAME: Cellular and Molecular Biology of Neurodegeneration Study Section[CMND]


NIH_SPENDING_CATS: Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_DEPT: PEDIATRICS

PHR: Project Narrative Inflammation can impair normal hematopoietic stem cell (HSC) function, and can promote the clonal expansion of mutant HSCs. We have identified the tetraspanin family member CD53 as a critical regulator of HSC function in the context of inflammatory stress, and propose to identify the mechanisms by which CD53 regulates both normal and mutant HSCs.

PI_NAMEs: SCHUETTPELZ, LAURA G. (contact)

PROGRAM_OFFICER_NAME: BAI, C BRIAN

PROJECT_TERMS: Address;age related;Agonist;Binding Proteins;Biological Assay;cdc Genes;Cell Count;Cell Cycle;Cell Physiology;Cell surface;Clonal Expansion;Complex;cytokine;Data;Development;DNMT3a;epigenome;Experimental Models;Family;Family member;Genes;Genetic;Goals;Hematopoiesis;Hematopoietic Neoplasms;hematopoietic stem cell quiescence;Hematopoietic stem cells;Homing;Immune response;Immune system;immune system function;Impairment;improved;in vivo;Infection;Inflammation;Inflammatory;Integral Membrane Protein;Knockout Mice;Label;leukemic transformation;Ligation;Mediating;member;migration;Mus;mutant;Mutation;novel;overexpression;Pathway interactions;Phosphoric Monoester Hydrolases;Pilot Projects;prevent;Process;Proliferating;protein complex;Protein Phosphatase 2A Regulatory Subunit PR53;Proteins;Proteomics;Repression;Repressor Proteins;Research;response;response to injury;Risk;Role;Shapes;Signal Transduction;stem cell function;Stimulus;Stress;stressor;Systems Development;Testing;therapeutic development;therapeutic target;Toll-like receptors;tool;TP53 gene;Transcription Repressor;transcriptome sequencing;transcriptomics;Up-Regulation

PROJECT_TITLE: Protection of stressed hematopoietic stem cells by the tetraspanin family member CD53

STUDY_SECTION: HTBT

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


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Dissemination and Implementation Research;Health Services;Lung;Patient Safety

ORG_CITY: MINNEAPOLIS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: PROJECT NARRATIVE Patient outcomes and evidence-based interventions, proven to reduce morbidity and mortality across patients needing mechanical ventilation, are highly variable. The link between this variation may reside at the provider level. This Career Development Award is designed to train a highly qualified pulmonary and critical care physician to become a leader in improving evidence-based practice adherence to patients with acute respiratory failure.

PI_NAMEs: INGRAHAM, NICHOLAS E (contact)

PROGRAM_OFFICER_NAME: KALANTARI, ROYA

PROJECT_TERMS: Acute respiratory failure;Address;Adherence;Algorithms;American;Area;Award;blood glucose regulation;Breathing;care outcomes;care providers;career;Caring;Clinical Research;Critical Care;Critical Illness;Curling's Ulcer;Data;Databases;Day Care;Decision Making;design;Development;Discipline;Electronic Health Record;Enrollment;evidence base;Evidence based intervention;Evidence based practice;experience;Funding;Future;Goals;Grant;Guidelines;Harm Reduction;Health system;Hospitalization;Hospitals;implementation framework;improved;improved outcome;Individual;innovation;Intensive Care;Intensive Care Units;Intervention;intervention mapping;Intervention Trial;Interview;K-Series Research Career Programs;Knowledge;Learning;Length of Stay;Link;Lung;Mechanical ventilation;Mentored Patient-Oriented Research Career Development Award;Mentors;Mentorship;Metadata;Methods;Morbidity - disease rate;mortality;novel;Nurses;Outcome;Patient-Focused Outcomes;Patients;Pattern;Physicians;Pilot Projects;pilot test;Policies;Population;Process;programs;Prone Position;Prophylactic treatment;prospective;Provider;provider adherence;Qualifying;Qualitative Research;randomized, clinical trials;Randomized, Controlled Trials;recruit;Research;Research Design;Research Personnel;Retrospective cohort study;skills;Structure;Survivors;Techniques;Testing;therapy design;Tidal Volume;Time;Training;Variant;ventilation;ward;Work

PROJECT_TITLE: Identifying Areas to Improve ICU Outcomes through Provider Variation

STUDY_SECTION: MPOR

STUDY_SECTION_NAME: NHLBI Mentored Patient-Oriented Research Study Section[MPOR(OA)]


ED_INST_TYPE: GRADUATE SCHOOLS

NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Electronic Nicotine Delivery Systems;Pediatric;Prevention;Social Determinants of Health;Substance Misuse;Tobacco;Tobacco Smoke and Health

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE Although one in every three U.S. high school seniors used e-cigarettes in the past year, the long-term trajectories and consequences of e-cigarette use, and longitudinal associations with other nicotine/tobacco use, tobacco cessation, tobacco use disorder symptoms, and other health consequences beyond 1-3 years remain largely unknown, especially among vulnerable populations. This study will address these critical gaps in public health knowledge by improving estimates of e-cigarette use trajectories, investigating the long-term health consequences associated with trajectories of e-cigarette use among adolescents and young adults, and identifying important risk and protective factors and subpopulations most vulnerable to e-cigarette use and its consequences. Findings from the proposed longitudinal study will be widely disseminated to help guide clinical practice, inform public health policies, and enhance future longitudinal research to reduce tobacco-related harms.

PI_NAMEs: EVANS-POLCE, REBECCA J. (contact)

PROGRAM_OFFICER_NAME: LEE, YOUN OK

PROJECT_TERMS: Adolescent;Adolescent and Young Adult;Adult;Age;age difference;Biological Markers;Cigarette;cigarette smoking;Clinical;clinical practice;clinically relevant;cohort;Complement;Cotinine;Data;Data Reporting;Dimensions;Education;effective intervention;Electronic cigarette;electronic cigarette use;epidemiology study;Ethnic Origin;experience;Future;Generations;Goals;Health;health data;health knowledge;Health Policy;Heterogeneity;High Prevalence;high risk;High School Student;improved;Individual;Investigation;Knowledge;longitudinal analysis;Longitudinal Studies;Measurement;Measures;Modeling;Monitor;Nicotine;nicotine use;Nitrosamines;Outcome;Patient Self-Report;Pattern;physical conditioning;Policies;Policy Maker;Population Assessment of Tobacco and Health;Prevalence;Prevention;prospective;protective factors;Public Health;Race;Reporting;Research;Research Methodology;Risk;Risk Factors;Role;Sampling;secondary analysis;sex;Sex Differences;Sex Orientation;social;sociodemographics;Statistical Methods;substance use;Surveys;Symptoms;Time;Tobacco;tobacco products;Tobacco use;Tobacco Use Cessation;Tobacco Use Disorder;twelfth grade;Vulnerable Populations;Work;young adult

PROJECT_TITLE: E-Cigarette Use among U.S. Adolescents and Young Adults: Longitudinal Associations with Tobacco Use and Health and Dimensions of Risk and Protection

STUDY_SECTION: ARM

STUDY_SECTION_NAME: Addiction Risks and Mechanisms Study Section[ARM]


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;Biomedical Imaging;Brain Disorders;Cerebrovascular;Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Dementia;Lymphatic Research;Neurodegenerative;Neurosciences;Physical Activity;Prevention;Sleep Research

ORG_CITY: SEATTLE

ORG_NAME: SEATTLE INST FOR BIOMEDICAL/CLINICAL RES

ORG_STATE: WA

PHR: PROJECT NARRATIVE This study will test whether training in Tai Chi, an ancient Chinese martial art characterized by intentional body movement, breathing control, and inward calm, promotes sleep and the clearing of wastes from the brain. These studies may shed light on activities that the middle-aged and elderly may engage in to help prevent or offset the risk of dementing disorders such as Alzheimer’s disease.

PI_NAMEs: ILIFF, JEFFREY J;LI, GAIL  (contact)

PROGRAM_OFFICER_NAME: MACKIEWICZ, MIROSLAW

PROJECT_TERMS: Abeta clearance;Abeta synthesis;Affective;aging brain;Alzheimer disease prevention;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease related dementia;Alzheimer’s disease biomarker;Amyloid beta-Protein;Beds;Behavior;Biological Markers;blood oxygen level dependent;Blood Vessels;Brain;Breathing;Cardiovascular Physiology;Cerebrospinal Fluid;cerebrospinal fluid flow;Cerebrovascular Disorders;Chinese;Chronic;Clinical;Clinical Research;Clinical Trials;Cognition;Cognitive;contrast enhanced;cost;demented;Dementia;Deposition;Development;Disease;Elderly;Enrollment;Equilibrium;experience;Failure;Foundations;Frequencies;Functional Magnetic Resonance Imaging;Future;glymphatic clearance;glymphatic dysfunction;glymphatic function;glymphatic system;Goals;Human;improved;improvement on sleep;Individual;Intercellular Fluid;interest;interstitial;Intervention;Intervention Trial;Longitudinal Studies;Magnetic Resonance Imaging;Measurable;Measurement;Measures;middle age;mindfulness;Modality;Moods;Motion;mouse model;Movement;multimodality;novel strategies;Older Population;Outcome;Participant;Pathologic;Pathway interactions;Patient Self-Report;Physical activity;Physiological;Physiological Processes;Pilot Projects;Polysomnography;Posture;pressure;prevent;Prevention;Primary Prevention;prospective;Proteins;Questionnaires;randomized, clinical trials;recruit;Respiration;Respiratory physiology;response;Risk;secondary analysis;Self Assessment;Senile Plaques;Sleep;Sleep Apnea Syndromes;Sleep disturbances;Sleep Fragmentations;sleep quality;solute;study population;Symptoms;Tai Ji;tau Proteins;Testing;Training;Vasomotor;Ventricular;Veterans;wasting;Water;Well in self

PROJECT_TITLE: Tai Chi Practice and Sleep-Active Glymphatic Function

STUDY_SECTION: MESH

STUDY_SECTION_NAME: Biobehavioral Mechanisms of Emotion, Stress and Health Study Section[MESH]


ORG_CITY: ORANGEBURG

ORG_NAME: NATHAN S. KLINE INSTITUTE FOR PSYCH RES

PHR: PROJECT NARRATIVE  Temporal lobe epilepsy (TLE) is a disorder with persistent, severe seizures as well as changes in behavior. We will selectively excite or silence a specific type of nerve cell that is implicated in TLE, mossy cells (MCs), and ask if the seizures and behavioral comorbidities are improved, using experimental mice that simulate TLE. The hypotheses to be tested are novel, will address the epilepsy as well as comorbidities, and will investigate underlying mechanisms so new treatments can be developed in the future.

PI_NAMEs: SCHARFMAN, HELEN E (contact)

PROGRAM_OFFICER_NAME: LEENDERS, MIRIAM

PROJECT_TERMS: Address;Anticonvulsants;Anxiety;Area;Attention;Behavior;behavior test;Behavioral;behavioral impairment;Brain;Cell Survival;cell type;Cells;Characteristics;Chronic;clinically relevant;Cognition;cognitive task;comorbidity;dentate gyrus;Designer Drugs;Development;Disease;Dorsal;entorhinal cortex;Epilepsy;Epileptogenesis;excitotoxicity;experimental study;Frequencies;Future;Glutamates;granule cell;hippocampal cell loss;Hippocampus;improved;improved outcome;Injections;Injury;Kainic Acid;Knowledge;Lead;Methods;Modeling;Mus;Neurons;novel;novel therapeutic intervention;optogenetics;Outcome;Output;Patients;Pharmaceutical Preparations;Pilocarpine;Play;Positioning Attribute;Pyramidal Cells;Quality of life;Rattus;receptor;Recurrence;Research;Research Personnel;Role;Seizures;Site;Status Epilepticus;Syndrome;Temporal Lobe Epilepsy;Testing;Work

PROJECT_TITLE: Mossy Cells in Temporal Lobe Epilepsy

STUDY_SECTION: CNNT

STUDY_SECTION_NAME: Clinical Neuroplasticity and Neurotransmitters Study Section[CNNT]


NIH_SPENDING_CATS: Atherosclerosis;Cardiovascular;Complementary and Integrative Health;Heart Disease;Lymphatic Research;Mental Health;Mental Illness;Natural Products

ORG_CITY: RIVERSIDE

ORG_NAME: UNIVERSITY OF CALIFORNIA RIVERSIDE

PHR: Project Narrative Atypical antipsychotics are widely used in the treatment of psychiatric conditions. However, the use of these drugs is associated with increased risk of cardiovascular disease, the leading cause of death worldwide. This study will provide important new information about the impact of atypical antipsychotics on cardiovascular disease in patients undergoing long-term treatment with these drugs.

PI_NAMEs: CHEN, HONG ;ZHOU, CHANGCHENG  (contact)

PROGRAM_OFFICER_NAME: LIU, LIJUAN

PROJECT_TERMS: Ablation;absorption;Adverse effects;Affect;Agonist;Animal Model;antagonist;Antipsychotic Agents;atherogenesis;Atherosclerosis;Attenuated;atypical antipsychotic;Bipolar Disorder;Blood Circulation;Cardiovascular Diseases;cardiovascular disorder risk;Cause of Death;Chronic;Clinical;clinically relevant;Development;Dietary Fats;driving force;drug development;Drug Interactions;Drug usage;Dyslipidemias;Enterocytes;Etiology;experimental study;Exposure to;Genes;Genetically Modified Animals;Health;Hepatic;Homeostasis;Human;humanized mouse;Hyperlipidemia;Immunofluorescence Immunologic;In Vitro;in vivo;innovation;insight;Intercellular Junctions;Intestinal Absorption;Intestines;KDR gene;Knockout Mice;Knowledge;lacteal;Life Style;Ligands;lipid metabolism;Lipids;Lymphatic;Lymphatic Endothelial Cells;Lymphatic System;lymphatic vessel;Lymphocyte;Major Depressive Disorder;Mediating;Methods;Molecular;Morbidity - disease rate;mortality;mouse model;Mus;novel;novel strategies;Nuclear Receptors;Patients;Pharmaceutical Preparations;pharmacologic;Phytochemical;Pilot Projects;Population;pregnane X receptor;prevent;Property;Proteomics;Psychiatric therapeutic procedure;quetiapine;receptor;Receptor Activation;receptor function;Receptor Signaling;Regulation;Risk;Role;Schizophrenia;sensor;Signal Transduction;single-cell RNA sequencing;Stains;Sulforaphane;Testing;Therapeutic;Tissues;Transmission Electron Microscopy;uptake;Vascular Endothelial Growth Factor Receptor-3;Work;Xenobiotic Metabolism;Xenobiotics

PROJECT_TITLE: Role of PXR in drug-elicited cardiovascular disease

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


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

ORG_CITY: HOUSTON

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

ORG_STATE: TX

PHR: Project Narrative Large scale proteomic profiling of Alzheimer’s disease (AD) patients has identified an interconnected network of proteins that change in levels as the disease advances. To determine the function of these proteins in the brain and link them to specific causes of AD, this project will dissect the role of SMOC1, a key protein predicted to drive changes in the network as a whole, and link individual network components to specific triggers that cause AD. The completion of this study will identify targets for drug development, uncover biological processes underlying AD, and elucidate the role of a predicted AD protein network with high translational potential.

PI_NAMEs: LI-KROEGER, DAVID EDWARD (contact)

PROGRAM_OFFICER_NAME: HAAKENSON, CHELSEA MARIE

PROJECT_TERMS: Acceleration;Adult;Alzheimer's Disease;Alzheimer's disease diagnosis;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease patient;Amyloid beta-42;Amyloid beta-Protein;Architecture;Autopsy;Behavior;beta catenin;Biological Process;Biology;Brain;brain tissue;Calcium Binding;career;career development;cell type;Cells;Central Nervous System;Clinical;clinically relevant;Co-Immunoprecipitations;Cognition;college;Computer software;Data;data integration;design;Development;Development Plans;differential expression;Disease;Disease Progression;Drosophila genus;Drosophila melanogaster;drug development;Drug Targeting;Environment;Ethics;experience;Experimental Models;experimental study;Extracellular Matrix;Extracellular Matrix Proteins;fighting;fly;Functional disorder;Funding;Genetic;Goals;Grant;Histology;Homeostasis;Homologous Protein;Human;Immunoprecipitation;improved;in vivo;Individual;Institution;International;Investigation;knock-down;laboratory experience;large scale data;Leadership;Link;link protein;Maintenance;Mass Spectrum Analysis;Mediating;Medicine;meetings;member;Mentors;Mentorship;Modeling;mutant;Nerve Degeneration;Neuroglia;Neurology;neuronal cell body;Neurons;neuropathology;neurophysiology;Neurosciences;novel;novel marker;Pathogenesis;Pathologic;Pathology;Pathway Analysis;Pathway interactions;pre-clinical;programs;protein expression;protein function;protein protein interaction;Proteins;Proteomics;Publishing;Reporter;Research;Research Personnel;Research Training;RNA Interference;Role;Scientist;Series;Signal Pathway;Signal Transduction;skill acquisition;skills;Structure;symposium;Systems Biology;tau Proteins;Tauopathies;Technology;Therapeutic;therapeutic target;Training;trait;Transforming Growth Factor beta;translational approach;translational potential;translational scientist;Validation;WNT Signaling Pathway;Work;Writing

PROJECT_TITLE: Functional validation of the SMOC1 matrisomal protein network in Alzheimers disease

STUDY_SECTION: AGCD

STUDY_SECTION_NAME: Career Development For Early Career Investigators Study Section [AGCD-2]


NIH_SPENDING_CATS: Asthma;Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Lung;Pediatric;Prevention;Primary Health Care;Social Determinants of Health

ORG_CITY: WASHINGTON

ORG_NAME: CHILDREN'S RESEARCH INSTITUTE

ORG_STATE: DC

PHR: This proposal will focus on broader implementation of a patient-centered, multicomponent hospital-to-home (H2H) transition intervention to optimize care and reduce disparities in asthma by recruiting from both children’s and community hospitals. The proposed research is relevant to public health because will fill crucial gaps in our understanding to improve care transitions and address disparities in high-risk school-aged children hospitalized with asthma. Thus, the proposed research is aligned with NIH’s mission to address health disparities and will provide crucial insights in intervention implementation at all types of hospital settings that care for children.

PI_NAMEs: PARIKH, KAVITA  (contact)

PROGRAM_OFFICER_NAME: KHAN, SHAHNAZ

PROJECT_TERMS: Academic achievement;acceptability and feasibility;Acute;Address;Admission activity;Adolescent;Adult;Affect;aged;American;Asthma;asthma exacerbation;Caregivers;Caring;Child;Child Care;Child health equity;child services;Childhood;Childhood Asthma;Chronic Disease;Clinical;clinical practice;Cognition;community engagement;Community Hospitals;comparison intervention;COVID-19 pandemic effects;Dedications;Disease;disorder control;Disparity;disparity reduction;effectiveness/implementation trial;Emergency department visit;evidence base;Face;Feedback;follow-up;Goals;group intervention;Guidelines;Hand;Health;health care disparity;health care service utilization;health disparity;health equity promotion;health outcome disparity;high risk;high risk population;Home;hospital readmission;Hospitalization;Hospitalized Child;Hospitals;implementation evaluation;implementation facilitators;implementation intervention;improved;improved outcome;Individual;Infrastructure;innovation;Inpatients;insight;interdisciplinary approach;Intervention;Interview;Methods;Mission;Morbidity - disease rate;mortality;multi-component intervention;National Heart, Lung, and Blood Institute;novel;Outcome;Participant;patient oriented;Pediatric Hospitals;Pediatric Research;Pharmaceutical Preparations;pilot trial;pragmatic trial;premature;Prevention;Preventive Health Services;primary care provider;programs;provider communication;Public Health;Quality of Care;racial disparity;randomized trial;recruit;Reduce health disparities;Research;Resources;School Drop-Outs;School-Age Population;Schools;Site;socioeconomics;standardize guidelines;Student Dropouts;successful intervention;telehealth;Testing;trial design;trial enrollment;United States National Institutes of Health;Update;usual care arm;Variant;Work;Youth

PROJECT_TITLE: The Hospital to Home Study: A Pragmatic Trial to Optimize Transitions and Address Disparities in Asthma Care

STUDY_SECTION: HSQE

STUDY_SECTION_NAME: Health Services: Quality and Effectiveness Study Section[HSQE]


NIH_SPENDING_CATS: Cancer;Digestive Diseases;Pancreatic Cancer;Prevention;Rare Diseases

ORG_CITY: Columbus

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: OHIO STATE UNIVERSITY

PHR: PROJECT NARRATIVE Since Extracellular Vesicles (EVs) are shed by virtually all cells into bodily fluids, they are relatively easy to collect, and might be considered the ultimate source of biomarkers for disease diagnostics. However, the clinical utility of EVs is limited by a lack of reliable and reproducible methods to identify and evaluate EV-associated biomarkers. This proposal will utilize a flexible platform based on detection of an innovative EV-marker, which will be combined with mouse models to rigorously validate the potential of EVs as biomarkers for the detection and staging of cancer.

PI_NAMEs: COCUCCI, EMANUELE  (contact)

PROGRAM_OFFICER_NAME: YOUNG, MATTHEW R

PROJECT_TERMS: analytical tool;Animals;Binding;Biological Markers;Biological Process;Blood Circulation;Blood Vessels;Body Fluids;Calibration;cancer biomarkers;cancer cell;Cancer Detection;cancer diagnosis;Cancerous;cell transformation;cell type;Cells;cellular engineering;Clinical;clinical application;clinical diagnostics;clinically relevant;Collection;comparative;design;Detection;Development;Diagnostic;Diagnostic Neoplasm Staging;diagnostic strategy;Diagnostic tests;diagnostic tool;Disease;disease diagnostic;Disease Progression;efficacy evaluation;Engineering;Exposure to;Extracellular Fluid;Extracellular Space;extracellular vesicles;flexibility;Genetically Engineered Mouse;Health;Image;In Vitro;in vitro Model;in vivo;innovation;intercellular communication;Investigation;Label;Luciferases;Malignant Neoplasms;Membrane;Methods;minimally invasive;Modeling;Molecular Profiling;Monitor;mouse model;Mus;Mutation;neoplastic;neoplastic cell;Normal Cell;Normal tissue morphology;novel;Oncogenes;Organ;Pancreas;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma cell;pancreatic ductal adenocarcinoma model;Physiological;Preparation;prevent;Procedures;prognostic;prognostic tool;Proteins;Proteomics;Reproducibility;Research;Retrieval;Role;Sampling;Sensitivity and Specificity;Signal Transduction;single molecule;Source;specific biomarkers;standard of care;Standardization;Structure;Surface;Survival Rate;System;Techniques;Testing;Tissues;tool;transcriptomics;Transgenic Mice;treatment response;tumor;Tumor Burden;tumor progression;Tumor-Derived;Vascularization;vesicular release;virtual;Visualization;Work

PROJECT_TITLE: A SYNTHETIC BIOMARKER TO UNIVERSALLY ASSESS THE RELATIVE CONTRIBUTION OF HEATHY AND CANCEROUS TISSUE TO CIRCULATING EV POOL

STUDY_SECTION: CBSS

STUDY_SECTION_NAME: Cancer Biomarkers Study Section[CBSS]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Dementia;Neurodegenerative;Neurosciences;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: DALLAS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: Project Narrative: Tau pathology accumulates in a progressive pattern that is consistent with propagation along synaptically connected brain circuits. However, it is unknown how they enter neurons and replicate. I propose to use 3D correlative light and electron microscopy combined with fluorescent biosensor systems and novel conformational tau antibodies in human neurons to test how tau seeds access the cytoplasm, and with which cellular sub-components they amplify.

PI_NAMEs: SHAHMORADIAN, SARAH H (contact)

PROGRAM_OFFICER_NAME: YANG, AUSTIN JYAN-YU

PROJECT_TERMS: 3-Dimensional;Alzheimer's Disease;Antibodies;Axon;Biosensor;Brain;Bypass;Cells;Cytoplasm;Data;Dendrites;Diamond;Electron Microscopy;Electrons;Event;Faculty;Human;human stem cells;Image;imaging approach;Immunofluorescence Immunologic;Impaired cognition;In Situ;induced pluripotent stem cell;Label;Light;light microscopy;live cell imaging;member;Methods;microscopic imaging;Modeling;Molecular;Molecular Conformation;Molecular Machines;Monitor;Morphologic artifacts;nanoscale;Neurodegenerative Disorders;neuronal cell body;Neurons;novel;Organelles;Pathologic;Pathology;Pattern;Presynaptic Terminals;Process;protein aggregation;Proteins;Recombinants;Resolution;Resources;Role;spatiotemporal;Subcellular Anatomy;System;tau conformation;tau Proteins;Techniques;Testing;tool;Transgenic Mice;uptake;Visualization

PROJECT_TITLE: Cellular Anatomy of Tau Seeding


ORG_CITY: CHICAGO

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: PUBLIC HEALTH RELEVANCE/NARRATIVE Alzheimer's disease (AD) pathology is characterized by the build-up of amyloid plaques and neurofibrillary tangles in the brain. While these cardinal pathological hallmarks have been recognized for more than one hundred years, there is much about them and their relationship which we still do not understand. The goal of this research is to obtain a deeper understanding of amyloid plaque diversity and the relationship between plaques and tangles.

PI_NAMEs: HANRIEDER, JORG ;SAVAS, JEFFREY NICHOLAS (contact)

PROGRAM_OFFICER_NAME: LI, TONG

PROJECT_TERMS: 3xTg-AD mouse;abeta accumulation;abeta deposition;Aducanumab;Affect;Age;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease diagnosis;Alzheimer's disease model;Alzheimer's disease pathology;Amyloid;Amyloid beta-42;Amyloid beta-Protein;Amyloid beta-Protein Precursor;amyloid pathology;Antibodies;Autopsy;Brain;Brain Diseases;Chronology;Classification;Clinical;cognitive performance;Complex;conformational conversion;Defect;Dementia;Deposition;Dissection;Endocytosis;Event;Extracellular Space;Functional disorder;Goals;human old age (65+);hyperphosphorylated tau;image guided;Impaired cognition;Impairment;Individual;insight;Kinetics;Knock-in;Label;Lasers;Link;Maps;mass spectrometric imaging;Mass Spectrum Analysis;Measures;Metabolism;Methods;Microglia;Molecular;molecular phenotype;mouse model;Mus;Nerve Degeneration;neurofibrillary tangle formation;Neurofibrillary Tangles;Neurons;novel strategies;Pathogenesis;Pathogenicity;Pathologic;Pathology;Pathway interactions;Peptides;Persons;Play;Positron-Emission Tomography;pre-clinical;Presynaptic Terminals;Process;Property;protein aggregation;Protein Analysis;protein degradation;Proteins;Proteomics;proteostasis;public health relevance;Radial;Research;Resolution;Rodent;Role;Senile Plaques;Stable Isotope Labeling;Structure;Synapses;Synaptic Vesicles;tau Proteins;tau-1;Testing;Thinness;Time;timeline

PROJECT_TITLE: Insights into Amyloid Pathogenicity Dynamics


FUNDING_MECHANISM: SBIR-STTR RPGS

NIH_SPENDING_CATS: Biotechnology;Chronic Obstructive Pulmonary Disease;Lung

ORG_CITY: LANSING

ORG_NAME: VERRA THERAPEUTICS, INC.

PHR: PROJECT NARRATIVE Chronic obstructive pulmonary disease (COPD) is a global, multi-phenotypic disease associated with lung damage from repeated external inflammatory insults such as smoke, vaping, forest fires, pollution, chemical exposure, and occupational hazards faced by 1st responders, the military, agricultural workers etc.. There are currently no treatments available for COPD patients that can halt or reverse the course of this disease. A protein has been identified which is responsible for key clinical outcomes in COPD and Verra Therapeutics aims to leverage this protein as a novel target to dramatically impact lung function in these patients.

PI_NAMEs: PRINCE, CHRISTOPHER LUCAS (contact)

PROGRAM_OFFICER_NAME: LU, QING

PROJECT_TERMS: aerosolized;Aerosols;Agricultural Workers;Agriculture;Air;alveolar epithelium;Amino Acid Sequence;analytical method;Animals;arm;aspirate;associated symptom;Binding;Binding Proteins;Biological Assay;Biological Availability;Biological Markers;Biology;Bronchoalveolar Lavage;Cause of Death;Cell Count;Cell Line;Cell surface;Cells;Chemical Exposure;Chronic Bronchitis;Chronic Obstructive Pulmonary Disease;cigarette smoke-induced COPD;Clinical;clinical development;clinically relevant;comparative efficacy;cooking;cost effective;cytokine;Data;Desmosine;Development;Disease;disease model;disease phenotype;Disintegrins;Dose;drug market;Epithelial Cells;Evaluation;Family;Fermentation;first-in-human;forest fires;Future;Growth Factor;Healthcare;Human;immunogenicity;improved outcome;In Vitro;in vivo;indexing;Industrialization;Infiltration;Inflammatory;Inhalation;inhibitor;innovation;Intake;Ligands;Lung;lung injury;Macrophage;manufacture;Maximum Tolerated Dose;member;Membrane;Metalloproteases;method development;Military Personnel;Modeling;Monoclonal Antibodies;mouse model;Mucous body substance;mucus hypersecretion;Nontypable Haemophilus influenza;novel;occupational hazard;Oropharyngeal;Outcome;Particle Size;Pathologic Processes;Patients;Penetration;Peptide Hydrolases;Performance;Persons;Pharmaceutical Preparations;pharmacologic;Phase;phase 1 study;Pollution;Process;Production;Program Development;programs;Proteins;pulmonary function;Pulmonary Inflammation;Quality of life;Rattus;receptor;Retina;Risk;Route;Safety;Severity of illness;Small Business Innovation Research Grant;small molecule inhibitor;Smoke;Smoking;Specificity;subcutaneous;Survival Rate;symptom treatment;T cell response;Therapeutic;therapeutic protein;Tissues;Toxic effect;Validation;vaping;Work

PROJECT_TITLE: A Disease-Modifying Protein Therapeutic for the Treatment of COPD


NIH_SPENDING_CATS: Behavioral and Social Science;Child Abuse and Neglect Research;Childhood Injury;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Pediatric;Prevention;Social Determinants of Health;Violence Research

ORG_CITY: DURHAM

ORG_DEPT: SOCIAL SCIENCES

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Narrative The project will contribute to public health by (1) evaluating the long-term impact and mechanisms of Community Navigation (CN), a community-affordable universal early childhood system of psychosocial care that aims to improve population rates of parent mental health, positive parenting behaviors, child maltreatment rates, and child cognitive and behavioral development; 2) evaluating the impact of CN on reducing disparities in these outcomes across race and income groups; and (3) testing pathways of how access to community resources and parenting efficacy can reduce child maltreatment and improve healthy child development, as well as reduce disparities in these outcomes across race and income groups.

PI_NAMEs: DODGE, KENNETH A (contact)

PROGRAM_OFFICER_NAME: GILBERT, LEAH KAYE

PROJECT_TERMS: access disparities;Address;Advocacy;Advocate;Age;Behavioral;behavioral outcome;Birth;brief intervention;Child;Child Abuse;Child Abuse and Neglect;Child Behavior;Child Development;Child Rearing;Child Welfare;Cognitive;Color;Communities;Community Networks;comparison control;cost;Cost Sharing;Data Analyses;Development;Directories;Discipline;Disparity;disparity elimination;Disparity population;disparity reduction;early childhood;Electronics;Emergency Care;Emotional;Evaluation;Family;Focus Groups;Funding;Home visitation;improved;Income;income disparities;Infant;Infant Mortality;innovation;Intervention;Interview;Investigation;kindergarten;Knowledge;Life;Life Cycle Stages;lower income families;Maternal Mortality;matriculation;Mediating;Mediation;Medical Care Costs;Mental Health;Modeling;Newborn Infant;novel;Nurses;Outcome;outcome disparities;Parents;Pathway interactions;Philanthropic Fund;Population;Pregnancy;Prevention;Primary Care;Process;programs;psychosocial;Psychosocial Assessment and Care;Public Health;Quasi-experiment;Race;racial disparity;Randomized;Randomized, Controlled Trials;Readiness;Resources;Sampling;Scientist;screening;sobriety;social;Socialization;System;Testing;Time;Training;treatment as usual;Treatment Efficacy;United States;Visit;Woman;Work

PROJECT_TITLE: Community Prevention of Child Maltreatment

STUDY_SECTION: PDRP

STUDY_SECTION_NAME: Psychosocial Development, Risk and Prevention Study Section[PDRP]


ED_INST_TYPE: OVERALL MEDICAL

NIH_SPENDING_CATS: Aging;Atherosclerosis;Cancer;Cardiovascular;Genetics;Heart Disease;Heart Disease - Coronary Heart Disease;Rare Diseases

ORG_DEPT: MISCELLANEOUS

ORG_NAME: UNIVERSITY OF TX MD ANDERSON CAN CTR

PHR: PROJECT NARRATIVE The mechanism by which the incidence of cardiovascular events is increased in premature senescence- triggered vascular diseases (PmSVD) induced by ionizing radiation (IR) and in patients with Hutchinson- Gilford progeria syndrome (HGPS) remains largely unknown; hence, there is an urgent need to correct this gap. PmSVD promotes the pro-inflammatory senescent phenotype in endothelial cells, leading to increased cardiovascular disease, but the molecular mechanisms remain largely unknown. Our proposed studies will provide insights into how PmSVD promotes cardiovascular dysfunction and facilitates the development of new therapeutic approaches for PmSVD-induced atherosclerosis.

PI_NAMEs: ABE, JUN-ICHI  (contact);COOKE, JOHN P;LE, NHAT-TU ;YU, BING

PROGRAM_OFFICER_NAME: FLEG, JEROME L

PROJECT_TERMS: Acceleration;Aging;aging related disease;Apoptosis;Atherosclerosis;attenuation;cancer cell;cancer recurrence;Cancer Survivor;Cardiovascular Diseases;Cardiovascular system;Cell Nucleus;Cell Separation;Chronic;Coronary Arteriosclerosis;Cytometry;Data;Development;DNA;DNA Damage;DNA Ligation;Dose;Endothelial Cells;endothelial dysfunction;Enzymes;Event;Feedback;Finding by Cause;Functional disorder;Genes;Genomic DNA;Glutamates;Glycosaminoglycans;Goals;High Fat Diet;Human;Hydrogen Sulfide;Image;In Vitro;in vivo;Incidence;induced pluripotent stem cell;induced pluripotent stem cell technology;Inflammatory;innovation;insight;Ionizing radiation;Ions;Knockout Mice;Knowledge;Machine Learning;Mass Chromatography;Mass Spectrum Analysis;Mechanics;Mediating;Mitochondria;mitochondrial dysfunction;Modeling;Molecular;multiple omics;Mus;new technology;novel;novel strategies;novel therapeutic intervention;overexpression;Oxidation-Reduction;Pathway Analysis;Pathway interactions;Patients;Phenotype;Phosphotransferases;Play;Poly(ADP-ribose) Polymerases;premature;Premature aging syndrome;prevent;Process;Progeria;Protein Kinase C;Radiation therapy;Reactive Oxygen Species;repaired;Reporting;Research;Resistance;Role;senescence;senescence associated secretory phenotype;sugar nucleotide;Sulfate;Syndrome;System;Telomerase;telomere;Testing;Topoisomerase;Transcriptase;Vascular Diseases;Work

PROJECT_TITLE: Premature aging disorders, metabolites, and atherosclerosis

STUDY_SECTION: AVI

STUDY_SECTION_NAME: Atherosclerosis and Vascular Inflammation Study Section[AVI]


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

ORG_CITY: EL PASO

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF TEXAS EL PASO

PHR: Project Narrative The goal of this project is to develop a model of T-ALL invasion of the CNS in a mouse with an intact immune system. We will use this mouse model to determine the feasibility of using anti- chemokine receptor peptides (antagonists) to block both entry and re-entry of T-ALL into the CNS. In addition we will use the model to study the mechanisms that facilitate T-ALL invasion of the CNS.

PI_NAMEs: VINES, CHARLOTTE M (contact)

PROGRAM_OFFICER_NAME: DUGLAS TABOR, YVONNE

PROJECT_TERMS: Acute Lymphocytic Leukemia;Acute T Cell Leukemia;acute T-cell lymphoblastic leukemia cell;Animals;antagonist;Blood;Blood - brain barrier anatomy;Breeding;CC chemokine receptor 7;CCL19 gene;cell type;Cells;Central Nervous System;Central Nervous System Leukemia;Cephalic;chemokine receptor;chemotherapy;Child;Childhood Acute Lymphocytic Leukemia;Childhood Precursor T Lymphoblastic Leukemia;Circulation;Clinical;Complication;conditional knockout;Cranial Irradiation;Data;Development;Diagnosis;Enterobacteria phage P1 Cre recombinase;falls;Flow Cytometry;Generations;glymphatic system;Goals;Growth;Human;Immune;Immune system;in vivo;Intelligence;Interferons;Invaded;Justice;Knock-out;Knockout Mice;leukemia;leukemia relapse;Leukemic Cell;leukemogenesis;Ligands;LoxP-flanked allele;Luciferases;lymph nodes;Lymphatic;Macrophage;Malignant Childhood Neoplasm;Malignant Neoplasms;Manuscripts;Mediating;Meninges;migration;Modeling;Molecular;mouse model;Mouse Strains;Mus;Nervous System Trauma;NOTCH1 gene;novel;Organ;Organism;Outcome;overexpression;Patients;pediatric patients;Peptide Receptor;Peptides;Peripheral;Physicians;prevent;Publishing;receptor;Regimen;Relapse;relapse prevention;Reporting;Research Design;Research Personnel;response;Role;Second Primary Cancers;side effect;Signal Transduction;Site;sphingosine 1-phosphate;T-Lymphocyte;targeted treatment;Testing;Therapeutic;Therapeutic Uses;tool;trafficking;transcription factor;Tumor Cell Invasion;Tumor-infiltrating immune cells;Visualization;Xenograft procedure

PROJECT_TITLE: Development of a Mouse Model to Study Targeted Therapy to Prevent CNS Invasion by Pediatric T-ALL


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Clinical Research;Dementia;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Neurodegenerative;Neurosciences;Physical Activity;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Women's Health Research

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

ORG_STATE: CA

PHR: PROJECT NARRATIVE Extensive health disparities exist in Alzheimer's disease (AD) and AD research for the Black community in that rates of AD are higher among Black individuals, yet there is a lack of research, and hence understanding, of their experience of this disease. Women show a more aggressive profile of AD than men with higher levels of the Alzheimer's causing pathological tau and a faster rate of clinical decline; inflammation and insulin resistance represent potential mechanisms for these differences given their sex disparities and ties to tau. Through a longitudinal observational study using blood-based markers of inflammation, insulin resistance, pathological tau, and measures of physical activity, we aim to answer the following questions in Black women: 1) How do levels of inflammatory markers and insulin resistance relate to changes in tau deposition and cognitive performance over time? 2) Does physical activity represent a protective factor against tau spread and cognitive decline, possibly through its beneficial effects on inflammation and insulin resistance? 3) How do social determinants of health impact these relationships?

PI_NAMEs: BANKS, SARAH  (contact);SUNDERMANN, ERIN ELIZABETH

PROGRAM_OFFICER_NAME: WAGSTER, MOLLY V

PROJECT_TERMS: Adult;Adverse effects;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease risk;Alzheimer’s disease biomarker;Area;Automobile Driving;Behavioral;Biological;Biological Factors;Biological Markers;biopsychosocial;Black American;Black Populations;Black race;black women;Blood;blood-based biomarker;caucasian American;Characteristics;Clinical;Cognition;Cognitive;cognitive function;cognitive performance;cohort;Communities;community advisory board;community based participatory research;community partnership;Coupled;Data;Decision Making;Dementia;Deposition;deprivation;Diabetes Mellitus;Disease;Disparity;Exclusion;experience;Female;Goals;Health;health disparity;health inequalities;high risk;high risk population;High Risk Woman;Immune response;Impaired cognition;indexing;Inflammation;inflammatory marker;Insulin Resistance;Insulin Resistance Pathway;insulin sensitivity;interest;Interleukin-6;Life Style;lifestyle factors;Link;Longitudinal, observational study;Los Angeles;low socioeconomic status;Measures;Mediating;men;modifiable risk;Modification;neuroinflammation;Not Hispanic or Latino;older adult;older women;Outcome;Participant;Pathologic;Pathology;Pathway interactions;Perimenopause;Physical activity;Pilot Projects;Plasma;Play;Population;Positron-Emission Tomography;Prediabetes syndrome;Predisposition;Prevalence;prevent;Prevention;Prevention strategy;Prospective Studies;protective factors;Race;racial difference;racial disparity;receptor;Receptors, Tumor Necrosis Factor, Type II;recruit;Registries;Reporting;Research;Risk Factors;Risk Reduction;Role;sex;sex disparity;Signal Transduction;Site;social determinants;social health determinants;tau aggregation;tau Proteins;tau-1;Time;TNF gene;TNFRSF1B gene;Vulnerable Populations;White Women;Woman;women versus men;women's outcomes;Women's study;Work

PROJECT_TITLE: Understanding Biological and Lifestyle Contributions to Alzheimer's Disease Pathology and Clinical Profiles in Black Women: Defining Prevention Targets in High Risk Groups

STUDY_SECTION: LCBH

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