NIH_SPENDING_CATS: Autism;Brain Disorders;Genetics;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Rare Diseases;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: BALTIMORE

ORG_NAME: LIEBER INSTITUTE, INC.

ORG_STATE: MD

PHR: Project Narrative This proposal aims to assess the effects of mutations in the critical brain developmental transcription factor TCF4 during human oligodendrocyte development and maturation. As oligodendrocytes are one of the few cell types in the brain that maintain a self-renewing, proliferative progenitor pool, this work has the potential to shed light on the genetic regulation of oligodendrogenesis and serve as a platform for screening and testing of pro-myelinating drugs and therapies. The long-term goal is to identify a viable therapeutic approach to treat Pitt-Hopkins syndrome, a disease caused by mutations in TCF4, and improve the patients' and families’ quality of life.

PI_NAMEs: ROMERO MORALES, ALEJANDRA INES (contact)

PROGRAM_OFFICER_NAME: PINARD, COURTNEY ROSE

PROJECT_TERMS: 3-Dimensional;Area;ASD patient;autism spectrum disorder;Axon;Biochemical;Biochemistry;Biological;Biological Assay;Brain;Breathing;Cell Death;cell immortalization;Cell Line;cell type;Cells;Clinical;Co-Immunoprecipitations;Collection;Corpus Callosum;de novo mutation;Defect;density;Development;Developmental Delay Disorders;Diameter;differentiation protocol;Disease;disease-causing mutation;Dominant-Negative Mutation;Drug Screening;efficacy testing;Electrophysiology (science);Face;Facies;Family;FDA approved;Fellowship;Fractionation;Fumarates;Genes;Genetic;genetic signature;Goals;Human;Image;Immunofluorescence Immunologic;improved;In Vitro;induced pluripotent stem cell;innovation;Laboratories;model of autism spectrum disorder;Modeling;Molecular;mouse model;multi-electrode arrays;Mus;mutant;Mutation;myelination;Neurodevelopmental Disorder;neuroimaging;neuropsychiatric disorder;oligodendrocyte lineage;oligodendrocyte progenitor;Oligodendroglia;patient derived induced pluripotent stem cells;Patients;PF4 Gene;Pharmaceutical Preparations;pharmacologic;Pharmacological Treatment;Phenotype;Pitt-Hopkins syndrome;Population;Process;progenitor;programs;Proliferating;Proteins;Protocols documentation;Quality of life;Rapid screening;Recovery of Function;Regulation;Research Personnel;screening;Seizures;self-renewal;Specific qualifier value;Speech;spheroids;stem cell model;stem cells;System;Testing;Therapeutic;Therapeutic Intervention;transcription factor;Translational Research;Transmission Electron Microscopy;two-dimensional;Variant;white matter;Work

PROJECT_TITLE: Investigating the effects of TCF4 mutations during oligodendrocyte development and maturation in a human-derived model of autism spectrum disorder

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


ADMINISTERING_IC: GM

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_CITY: DALLAS

ORG_COUNTRY: UNITED STATES

ORG_DEPT: OBSTETRICS & GYNECOLOGY

ORG_FIPS: US

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: Project Narrative Accurate and precise gene expression is essential for cell specification, development, and response to environmental cues. Emerging evidence suggests the process of gene activation is regulated by the formation of mesoscale assemblies of high local concentrations of gene expression machinery, termed biomolecular condensates. My findings will elucidate mechanisms of transcriptional condensate function during cell fate determination.

PI_NAMEs: EPPERT, MIKAYLA  (contact)

PROGRAM_OFFICER_NAME: MCINTYRE, JEREMY COLIN

PROJECT_TERMS: Address;Binding;Biochemical;Biological Process;C-terminal;Case Study;CDT1 Gene;Cell Differentiation process;Cell Lineage;cell type;Cells;Cellular biology;Chimera organism;Chromosome Mapping;comparative;Cues;Data;Development;Disease;DNA;Environment;epigenomics;Exhibits;experimental study;Gene Activation;Gene Expression;gene regulatory network;Genes;Genetic Transcription;Genome;genomic locus;Genomics;insight;knock-down;Knowledge;Mediating;Microscopy;Modeling;Molecular;Muscle;myocardin;Peptide Initiation Factors;Physical condensation;Play;Process;Processed Genes;programs;Property;Proteins;Proteomics;Regulatory Element;Replication Initiation;response;RNA-Binding Protein FUS;Role;Small Interfering RNA;Smooth Muscle;Smooth Muscle Myocytes;Specific qualifier value;Specificity;Testing;Tissue-Specific Gene Expression;tool;Transactivation;Transcription Coactivator;transcriptome sequencing;transdifferentiation;Work

PROJECT_TITLE: Mechanisms of Transcriptional Condensate Function during Cell State Transitions

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


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

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

ORG_CITY: NEW YORK

ORG_DEPT: PSYCHIATRY

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

ORG_STATE: NY

PHR: PROJECT NARRATIVE Social learning errors strongly influence short-term changes in mood, but it remains unknown how social learning errors relate to long-term mood symptoms, or how social learning errors are encoded by neural activity. The goals of this study are to (1) computationally characterize the relationship between social learning errors and short- and long-term mood, and to (2) determine if social learning errors are encoded in the activity of single neurons in the human substantia nigra, which contains neurons that have previously been observed to encode other nonsocial learning errors. Ultimately, this project will contribute to the field of neuropsychiatry a deepened physiological understanding of the relationship between mood and social learning in both health and psychiatric illness.

PI_NAMEs: DAVIS, ARIANNA NEAL (contact)

PROGRAM_OFFICER_NAME: AVENILLA, FRANK R

PROJECT_TERMS: Acceleration;Address;Affect;Affective;Agreement;Behavior;Behavioral;Behavioral Model;Biological Assay;Brain;Cell Nucleus;Clinical;Cognition;cohort;Complex;Computer Models;Data;Development;Disease;early childhood;Exhibits;expectation;experience;Functional Magnetic Resonance Imaging;Future;Goals;Health;Human;Impairment;Individual;Intervention;Investigation;Knowledge;Learning;Linear Models;Measures;medical schools;Mental disorders;Mental Health;Methods;Midbrain structure;Mission;Modeling;Mood Disorders;mood symptom;Moods;National Institute of Mental Health;negative mood;neural;neuroimaging;neuromechanism;Neurons;neurophysiology;neuropsychiatry;novel strategies;Outcome;pandemic disease;Participant;Patient Self-Report;Patients;Phenotype;Physicians;Physiological;Play;programs;Psychiatrist;Psychiatry;Psychological reinforcement;Research;Resolution;Rewards;Risk;Role;Scientist;Signal Transduction;social;Social Change;Social Environment;social group;social influence;Social Interaction;Social isolation;social learning;social norm;Societies;spatiotemporal;Stimulus;Structure;Substantia nigra structure;Techniques;Testing;Therapeutic;Time;Training;trait;Update;Work

PROJECT_TITLE: Neural computations underlying the relationship between social learning and mood

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F02A-W (20)]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Eating Disorders;Mental Health;Mental Illness;Nutrition;Pediatric;Women's Health Research

ORG_CITY: PHILADELPHIA

ORG_DEPT: PSYCHOLOGY

ORG_NAME: DREXEL UNIVERSITY

ORG_STATE: PA

PHR: Project Narrative Binge eating (BE; i.e., overeating while experiencing a loss of control over eating) is the defining feature of binge-spectrum eating disorders (e.g., bulimia nervosa and binge eating disorder), which typically onset and show peak prevalence during adolescence. Given the importance of interpersonal influences and socioemotional development during adolescence, a promising theory of BE in adolescence posits that experiencing interpersonal stressors predicts BE eating and this relationship is mediated by increases in negative affect. To inform targets for novel, real-time interventions, the proposed study will examine momentary relations between interpersonal stressors, affective states, and BE among adolescent girls with binge-spectrum eating disorders.

PI_NAMEs: D'ADAMO, LAURA  (contact)

PROGRAM_OFFICER_NAME: CORNELL, ASHLEY ROSE

PROJECT_TERMS: Adolescence;Adolescent;adolescent patient;Advanced Development;Affect;Affective;Age;Anger;Anxiety;Assessment tool;Binge Eating;Binge eating disorder;Bulimia;bullying;Characteristics;comorbidity;Conflict (Psychology);critical period;Cross-Sectional Studies;Development;dietary;digital assessment;Disease remission;Eating;Eating Disorders;Ecological momentary assessment;emotion regulation;Emotional;Environment;Evaluation;experience;Female Adolescents;Future;girls;Heterogeneity;Hyperphagia;Individual;Individual Differences;individual variation;Intervention;Link;Literature;Loneliness;loss of control over eating;Maintenance;Measurement;Mediating;Mental disorders;Mental Health;Modeling;Nature;negative affect;novel;Outcome;Participant;peer;personalized intervention;physical conditioning;Prevalence;prospective;prospective test;psychosocial;Recurrence;Research;response;restraint;Role;severe mental illness;social;social emotional learning;social influence;social relationships;Statistical Methods;stressor;Subgroup;Teenagers;Testing;theories;therapy development;Time

PROJECT_TITLE: Dynamic relations between interpersonal stressors, affective states, and binge eating in adolescent girls

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


ADMINISTERING_IC: CA

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: American Indian or Alaska Native;Behavioral and Social Science;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Prevention;Racial and Ethnic Minority Health Research;Rural Health;Social Determinants of Health;Uterine Cancer;Women's Health Research

ORG_CITY: ALBUQUERQUE

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR

ORG_STATE: NM

PHR: OVERALL COMPONENT: THE UNIVERSITY OF NEW MEXICO COMPREHENSIVE CANCER CENTER PROJECT NARRATIVE The NCI-Designated University of New Mexico Comprehensive Cancer Center leads impactful cancer research, cancer care delivery, cancer education and training, and community-based cancer prevention and control efforts across the New Mexico catchment area, in partnership with its Consortium Partner (Lovelace Biomedical/The Lovelace Respiratory Research Institute), Tribal Nations, and community health systems statewide. The Center's overall mission is to reduce the cancer burden and overcome the tremendous cancer health disparities of the New Mexico catchment area and the nation through ground-breaking transdisciplinary research, translation of discoveries to clinical and community interventions, impactful bi-directional community engagement, training of a more diverse cancer workforce, and the delivery of exceptional cancer care.

PI_NAMEs: SANCHEZ, YOLANDA  (contact)

PROGRAM_OFFICER_NAME: BELIN, PRECILLA L

PROJECT_TERMS: Address;Advanced Malignant Neoplasm;Advisory Committees;American Indians;anti-cancer research;Behavioral;Black race;Cancer Biology;Cancer Burden;cancer care;Cancer Center;Cancer Center Support Grant;cancer clinical trial;Cancer Control;Cancer Control Research;cancer education;cancer health disparity;cancer prevention;cancer research center director;care delivery;career;career development;Catchment Area;cellular oncology;Characteristics;Clinic;Clinical;clinical care;Clinical Trials Network;Collaborations;Communities;Community Clinical Oncology Program;community engagement;Community Health;Community Health Systems;community intervention;Community Outreach;community setting;Comprehensive Cancer Center;Data;data modeling;Development Plans;Disparity;Doctor of Philosophy;Education;education access;Educational Activities;Environment;environment related cancer;Environmental Exposure;ethnic diversity;Ethnic Population;Etiology;Evaluation;Event;Extramural Activities;Faculty;Fellowship;Fellowship Program;Fostering;Foundations;Funding;gender diversity;Genetic;Genomic medicine;Goals;Grant;Grant Review;Gynecologic Oncology;hackathon;Health;health equity;Health system;High School Student;Hispanic;hispanic community;HPV screening;improved;Incidence;Individual;Informatics;Infrastructure;Institution;Institutional support resources;Instruction;inter-institutional;Interdisciplinary Study;Intervention;K-Series Research Career Programs;Laboratories;Latino;Leadership;lectures;Logic;Malignant Neoplasms;marginalization;meetings;member;Mentors;Mentorship;Methods;Mexican;Minority;Mission;Modeling;molecular oncology;mortality;multi-ethnic;NCI Center for Cancer Research;New Mexico;Not Hispanic or Latino;novel;Oncology;Outcome Measure;Pattern;Persons;Population;population based;Population Sciences;predictive modeling;programs;Provider;Public Health;Publications;racial diversity;Registries;Research;Research Institute;Research Personnel;Resource Sharing;Resources;respiratory;role model;Rural;Science;Scientist;screening;SEER Program;Series;skill acquisition;skills;social;socioeconomics;Source;Strategic Planning;Structure;Students;Surveys;Technology;Therapeutic;Training;Training and Education;Training Programs;Training Support;Translating;translational cancer research;Translational Research;Translations;Travel;tribal Nation;Trust;tumor registry;Uncertainty;Underrepresented Minority;Universities;Visualization;Woman

PROJECT_TITLE: Precarity in Gynecologic Oncology: A mixed methods study addressing intersections of uncertainty, marginalization, and cancer.

STUDY_SECTION: NCI

STUDY_SECTION_NAME: Cancer Centers Study Section (A)[NCI-A]


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Genetics;Hematology;Human Genome;Orphan Drug;Rare Diseases

PHR: PROJECT NARRATIVE Cancer genomes commonly harbor complex rearrangements that arise through chromothripsis, the catastrophic fragmentation and reassembly of individual chromosomes. Chromothripsis originates from mis-segregated chromosomes in micronuclei, yet our understanding of the causes and consequences of chromothripsis is limited. This proposal seeks to define the mechanisms by which the Fanconi anemia pathway promotes chromosome fragmentation and the generation of highly rearranged chromosomes.

PI_NAMEs: ENGEL, JUSTIN  (contact)

PROGRAM_OFFICER_NAME: ODEH, HANA M

PROJECT_TERMS: Automobile Driving;Base Excision Repairs;Binding;Cancer Biology;cancer cell;cancer genome;cancer predisposition;career development;Cell Cycle;Cell division;Cell model;Cell Nucleus;chemotherapy;Chromosome abnormality;Chromosome Fragile Sites;chromosome missegregation;Chromosomes;chromothripsis;Circular DNA;Clinical;combat;Complex;Congenital Abnormality;congenital bone marrow failure;CRISPR screen;Cytoplasm;Data;Defect;Deoxyribonuclease I;Development Plans;DNA;DNA biosynthesis;DNA Damage;DNA Interstrand Cross-Link Repair;DNA Repair;DNA Sequence Rearrangement;Drug resistance;Elements;Encapsulated;Etiology;Evolution;Exposure to;extrachromosomal DNA;FANCD2 protein;Fanconi Anemia Complementation Group A Protein;Fanconi Anemia pathway;Fanconi's Anemia;Frequencies;fusion gene;Gene Amplification;Gene Rearrangement;Generations;Genes;Genetic;Genetic Transcription;Genome;Genomic Instability;Genomics;Head and Neck Squamous Cell Carcinoma;Human;Hybrids;Individual;Interphase;Knowledge;Laboratories;Ligation;Location;Maintenance;Malignant Neoplasms;Maps;Mediating;micronucleus;Mitosis;Mitotic;Mitotic Chromosome;Monitor;Mutation;neoplastic cell;Nuclear;Nuclear Envelope;Nuclear Structure;nuclease;Oncogenic;Pathologic;Pharmaceutical Preparations;Physiological;pre-clinical;Predisposing Factor;Process;Proteins;recruit;repair enzyme;repaired;Research;Research Personnel;Resolution;response;RNA;Role;Rupture;Source;Structure;System;targeted treatment;Testing;Therapeutic;Training;TREX1 gene;tumor;Tumor Suppressor Genes

PROJECT_TITLE: Dissecting the role of the Fanconi anemia pathway in chromothripsis

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


FUNDING_MECHANISM: NON-SBIR/STTR RPGS

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

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: PROJECT NARRATIVE Pancreatic cancer remains one of the most lethal cancers. This proposal will address the mechanisms by which pancreatic tumor cells grow and metastasize via coordinating the cytoskeletal regulatory machinery with a key amino acid metabolism pathway. Using a comprehensive approach that includes biochemical, cell biological, and mouse models, the information resulting from this research will expand our mechanistic understanding of pancreatic cancer, ideally identifying novel therapeutic targets and strategies to improve the survival of pancreatic cancer patients.

PI_NAMEs: MC NIVEN, MARK A.;RAZIDLO, GINA LYNN (contact)

PROGRAM_OFFICER_NAME: AULT, GRACE S

PROJECT_TERMS: Actins;Amino Acid Metabolism Pathway;Biochemical;biochemical model;Biochemistry;Biological Models;Catabolism;Cell model;Cells;Cellular biology;cytokine;Cytoskeleton;Data;Dependence;detection of nutrient;Disease Progression;Ectopic Expression;Enzymes;Fluorescence Microscopy;Glutamate Receptor;Glutamates;Glutaminase;Glutamine;Goals;Growth;Guanine Nucleotide Exchange Factors;Guanosine Triphosphate;Homeostasis;improved;in vivo Model;Incidence;Inflammatory;insight;Invaded;Link;Malignant neoplasm of pancreas;Malignant Neoplasms;Membrane;Metabolic;Metabolism;Mitochondria;Molecular;Monomeric GTP-Binding Proteins;Motility;mouse model;Neoplasm Metastasis;neoplastic cell;new therapeutic target;novel;novel therapeutic intervention;novel therapeutics;Nutrient;Organoids;Outcome;pancreatic cancer cells;pancreatic cancer patients;Pancreatic Ductal Adenocarcinoma;pancreatic neoplasm;Paracrine Communication;Pathway interactions;Patients;Peripheral;Play;Primary Neoplasm;Process;Production;Prognosis;programs;Proliferating;Proto-Oncogenes;Quantitative Microscopy;Receptor Signaling;Regulation;Research;Role;Signal Pathway;Signal Transduction;Source;Testing;Therapeutic;therapeutic target;therapy resistant;tumor;Tumor Cell Biology;Tumor Cell Invasion;Tumor Cell Migration;tumor growth;tumor metabolism;tumor progression;Tumor Promotion;tumorigenic;uptake

PROJECT_TITLE: Intersection of cytoskeletal regulation with tumor cell metabolism

STUDY_SECTION: TEHM

STUDY_SECTION_NAME: Tumor Evolution, Heterogeneity and Metastasis Study Section[TEHM]


ADMINISTERING_IC: HL

ED_INST_TYPE: UNIVERSITY-WIDE

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Aging;Genetics;Hematology;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: BRONX

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

PHR: PROJECT NARRATIVE Malfunctioning of hematopoietic stem and progenitor cells (HSPCs) is a major driver of myelodysplastic syndromes (MDS). Individuals carrying a DDX41 germline mutation develop MDS later in life, suggesting aging features play a key role in promoting disease. Our study will identify which aspect of aging promotes progressive HSPC dysfunction.

PI_NAMEs: FELIZ NORBERTO, MARIA  (contact)

PROGRAM_OFFICER_NAME: PHILP, DEBORAH

PROJECT_TERMS: 21 year old;Acute Myelocytic Leukemia;Address;Adult;Age;age related;age related changes;Aging;aging process;Anemia;Animals;ATP phosphohydrolase;beta-Galactosidase;Biological Assay;Birth;Blood;Blood Cells;Cell Aging;Cell Count;Cell Lineage;Cells;chemical genetics;Clinical;cytopenia;Data;Defect;Development;Diagnosis;Disease;Dysmyelopoietic Syndromes;Dysplasia;Early Intervention;Embryo;Embryonic Development;Erythroid;Etiology;Evolution;Flow Cytometry;Frequencies;Functional disorder;Functional impairment;Gene Expression;Genes;Genetic;genetic approach;genetic signature;Genotype;Germ-Line Mutation;hallmarks of aging;Health;helicase;Hematopoiesis;Hematopoietic;hematopoietic differentiation;Hematopoietic stem cells;Heterozygote;Human;Immunofluorescence Immunologic;Individual;Ineffective Hematopoiesis;Inflammation;Inherited;insight;Interferon Type I;Intervention;Kidney;Laboratories;Life;Link;loss of function;Lymphoid;Malignant Neoplasms;Marrow;Measurement;Measures;Mediating;metabolomics;middle age;migration;Modeling;Morphology;mutant;Mutate;Mutation;Myelogenous;Myeloid Cells;Myeloproliferative disease;Neutropenia;neutrophil;Neutrophil Activation;NF-kappa B;Pathway Analysis;Pathway interactions;Patients;Persons;Phenotype;Phosphorylation;Play;prevent;pro-aging;Production;Reporter;Role;Second Messenger Systems;self-renewal;senescence;Signal Transduction;single-cell RNA sequencing;Site;stem cell expansion;stem cell function;stem cell homeostasis;Stimulator of Interferon Genes;Symptoms;synergism;TANK-binding kinase 1;Testing;Therapeutic;Thrombocytopenia;Tissue-Specific Gene Expression;trait;Transgenic Organisms;United States;wound;Zebrafish

PROJECT_TITLE: Deciphering genotype-environmental interaction that drives HSPC dysfunction

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


ORG_CITY: MINNEAPOLIS

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF MINNESOTA

PHR: PROJECT NARRATIVE Natural killer (NK) cells are pivotal in the immune response against cancer, acting to directly eliminate cancer cells and recruit other anti-tumor immune populations. This proposal focuses on advancing our understanding of a unique NK cell subtype with enhanced abilities to recruit anti-tumor immune responders, and infiltrate and survive in suppressive tumor environments. Insights gained from this study will contribute to new tools for studying diverse NK cell subtypes and inform the development of NK cell-based therapies for combating cancer.

PI_NAMEs: LOZADA, JOHN ROY (contact)

PROGRAM_OFFICER_NAME: BIAN, YANSONG

PROJECT_TERMS: Address;anti-tumor immune response;Antitumor Response;Atlases;bench to bedside;Bioinformatics;bioinformatics tool;cancer cell;cancer immunotherapy;Cancer Patient;cancer type;CCL3 gene;CD8-Positive T-Lymphocytes;cell killing;Cell Therapy;cell type;Cells;Cellular Immunology;chemokine;Clinical;cytokine;cytotoxic;Data;Dendritic Cells;Development;Disease-Free Survival;engineered NK cell;Engineering;Environment;Exhibits;experience;Fostering;functional genomics;Future;Gene Delivery;Gene Targeting;Genetic Engineering;genetic signature;Genetic Transcription;Genomic approach;Image;Imaging Device;Immune;Immune response;Immunofluorescence Immunologic;immunoregulation;Immunotherapy;improved;in vivo;induced pluripotent stem cell;Infiltration;Inflammatory;Ink;insight;Interferon Type II;IRF4 gene;Link;Malignant Neoplasms;Mediating;Mediator;Memory;Mentors;Methods;Modeling;Natural Killer Cell Immunotherapy;Natural Killer Cells;Neighborhoods;neoplastic cell;next generation;NK cell therapy;novel;NR3C1 gene;overexpression;Patients;peripheral blood;Phenotype;Physicians;Population;Positioning Attribute;Production;programs;Property;recruit;Research;Research Proposals;Residencies;Resources;response;Role;RXRA gene;Scientist;Shapes;single-cell RNA sequencing;skills;Solid Neoplasm;Spatial Distribution;The Cancer Genome Atlas;Tissues;tool;transcription factor;transcriptome sequencing;transcriptomics;tumor;Tumor Immunity;tumor microenvironment;Tumor-infiltrating immune cells;Up-Regulation;Work;XCL1 gene

PROJECT_TITLE: Tissue-Resident Adaptive CD56bright NK Cell Responses in Cancer

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


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Digestive Diseases;Infant Mortality;Infectious Diseases;Microbiome;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Preterm, Low Birth Weight and Health of the Newborn;Women's Health Research

ORG_CITY: Aurora

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: PROJECT NARRATIVE Group B Streptococcus (GBS) is a Gram-positive pathobiont that asymptomatically colonizes mucosal sites including the gastrointestinal tract and the female reproductive tract (FRT), however the interactions with GBS and native microbes in these niches is largely unstudied. We have discovered that Akkermansia muciniphila, a mucosal commensal organism that degrades mucins, promotes GBS vaginal colonization, however, the specific mechanism(s) for this synergy is unknown. This proposal aims to characterize the contribution of A. muciniphila to GBS persistence and how this promotes GBS neonatal disease. (GI)

PI_NAMEs: DORAN, KELLY S (contact)

PROGRAM_OFFICER_NAME: GU, XIN-XING

PROJECT_TERMS: Adherence;adverse pregnancy outcome;Air;Anti-Inflammatory Agents;Bacteria;Bacterial Adhesins;Cell Culture Techniques;Cell Physiology;Cells;Chemotaxis;co-infection;cytokine;Data;Development;Disease;early onset;Environment;Enzyme-Linked Immunosorbent Assay;Epithelial Cells;Epithelium;female reproductive tract;fetal;Fetus;Flow Cytometry;Fluorescence Microscopy;gastrointestinal;Gastrointestinal tract structure;Genes;Genetic Transcription;Group B Streptococcus colonization;gut colonization;Host Defense;Human;Immune;Immune response;in utero;in vivo;Infection;Information Dissemination;interest;Interleukin-10;Intestinal Mucosa;Intestines;intraamniotic infection;Invaded;Knowledge;Late-Onset Disorder;Liquid substance;Meningitis;Microbe;microbial;microbiome research;microbiota;microorganism;Modeling;mouse model;Mucins;Mucosal Immunity;mucosal site;Mucous Membrane;Mus;mutant;Neonatal;neonatal infection;Neurologic;neutrophil;Neutrophil Infiltration;Newborn Infant;Organism;pathobiont;pathogen;pathogenic bacteria;Pathogenicity;Pilum;Play;Pregnancy;Premature Birth;Premature Rupture Fetal Membranes;Production;Role;Serum;Signal Transduction;stillbirth;Streptococcus Group B;Structure;Surface;Survivors;synergism;Systemic infection;transcriptome sequencing;transmission process;Vagina;Vaginal delivery procedure;vaginal microbiota

PROJECT_TITLE: Polymicrobial Interactions that Facilitate Mucosal Colonization by Group B Streptococcus

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


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Heart Disease;Mental Health;Prevention

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

ORG_STATE: MA

PHR: PROJECT NARRATIVE The proposed study will establish the feasibility and acceptability of a novel, text-enhanced integrative behavioral intervention “One Mind-One Heart (OM-OH),” aimed at reducing cardiovascular disease (CVD) risk in older people with HIV (OPWH). By addressing CVD, a significant comorbidity that affects a growing number of OPWH in psychological distress due to shared pathophysiology linked to systemic inflammation, this work will be instrumental in improving the health and well-being of PWH across the lifespan.

PI_NAMEs: FOLEY, JACKLYN DONNA (contact)

PROGRAM_OFFICER_NAME: CAMPO, REBECCA A

PROJECT_TERMS: acceptability and feasibility;Address;Affect;Amaze;Automobile Driving;behavior change;Behavior Therapy;Behavioral;Benchmarking;Biological Markers;Cardiovascular Diseases;cardiovascular disorder risk;Cardiovascular system;Chronic;Clinical Trials;comorbidity;diabetes prevention program;Disease;effective intervention;efficacy trial;Environment;evidence base;experience;Feedback;Foundations;Functional disorder;General Hospitals;Goals;Health;Heart;HIV;HIV/AIDS;Immune;Immune response;improved;Inflammation;Inflammatory;innovation;Institution;Intervention;Interview;life span;Link;Massachusetts;Mediating;medical schools;meetings;Mentors;Mentorship;Methods;Mind;mindfulness;mindfulness-based stress reduction;multidisciplinary;National Heart, Lung, and Blood Institute;novel;Older Population;Patient Self-Report;Personal Satisfaction;pilot test;programs;Protocols documentation;psychologic;psychological distress;Publications;Publishing;Randomized, Controlled Trials;Research;Research Design;Research Personnel;Research Priority;Risk Behaviors;Risk Reduction;Structure;systemic inflammatory response;Text;Text Messaging;therapy development;Training;Training Programs;treatment as usual;trial design;Work

PROJECT_TITLE: Mindfulness and Behavior Change to Reduce Cardiovascular Disease Risk in Older People with HIV

STUDY_SECTION: MPOR

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


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Brain Disorders;Epilepsy;Genetics;Intellectual and Developmental Disabilities (IDD);Neurodegenerative;Neurosciences;Rare Diseases;Tuberous Sclerosis

ORG_CITY: CINCINNATI

ORG_NAME: CINCINNATI CHILDRENS HOSP MED CTR

ORG_STATE: OH

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because it will increase understanding of the mechanisms of seizure development in childhood epilepsies, including tuberous sclerosis complex and focal cortical dysplasia. Abnormal excitatory neurons in these diseases are thought to play a pro-epileptogenic role in disease progression and exhibit impaired inhibitory input, but it is not clear which cells are critical for effectively inhibiting these hyperexcitable neurons, so this proposal will use a model of focal epilepsy to assess the role of somatostatin interneurons in restraining hyperactive excitatory neurons. Thus, the proposed research is relevant to NIH’s mission to build the knowledge base needed to drive discovery and translation of therapy for epilepsy and will address key goals of the 2021 NINDS Benchmarks for Epilepsy Research, including determining how molecular and cellular function interact with alterations in circuit and network function in the pathogenesis of cortical hyperexcitability and the clinical epilepsies (Benchmark 1c).

PI_NAMEs: DRAKE, AUSTIN  (contact)

PROGRAM_OFFICER_NAME: MATTHEWS, MARGUERITE

PROJECT_TERMS: Ablation;Abnormal Cell;Aftercare;Anatomy;Animals;Anticonvulsants;axonal sprouting;Benchmarking;Brain;Cell Physiology;Cell Survival;Cells;childhood epilepsy;Chronic;Clinical;Cortical Dysplasia;cost;Development;Diphtheria Toxin;diphtheria toxin receptor;Disease;Disease Progression;Electroencephalography;Electrophysiology (science);enhanced green fluorescent protein;Epilepsy;Epileptogenesis;excitatory neuron;Exhibits;FRAP1 gene;Frequencies;Goals;granule cell;Hippocampus;Hyperactivity;Impairment;Induced Neurons;inhibitor;inhibitory neuron;Interneurons;Knock-out;Knockout Mice;knowledge base;Label;Lesion;Mediating;Mentors;Mission;Modeling;Molecular;Monitor;Morphology;mosaic;mouse model;mTORopathies;Mus;mutant;Mutation;National Institute of Neurological Disorders and Stroke;nerve stem cell;Neurologist;Neurons;novel therapeutics;optogenetics;Partial Epilepsies;patch clamp;Pathogenesis;Pathologic;Pathway interactions;Patients;Persons;Pharmacotherapy;Phenotype;Physiological;Play;Positioning Attribute;postnatal;Preventive treatment;Proliferating;protein expression;Public Health;receptor expression;Refractory;Regulation;Reporter;Research;Research Personnel;restraint;Role;Seizures;Severities;Severity of illness;Somatic Mutation;Somatostatin;Temporal Lobe Epilepsy;Testing;therapeutically effective;Training;Transgenic Mice;Transgenic Organisms;translational therapeutics;Tuberous Sclerosis;United States;United States National Institutes of Health;Viral

PROJECT_TITLE: Regulation of Epileptogenesis by Hippocampal Somatostatin Interneurons in a Model of mTORopathies


ADMINISTERING_IC: HD

ED_INST_TYPE: EARTH SCIENCES/RESOURCES

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

ORG_CITY: PISCATAWAY

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: RUTGERS, THE STATE UNIV OF N.J.

ORG_STATE: NJ

PHR: PROJECT NARRATIVE Protein translation is required for normal cell function and is reliant upon proper structure and function of the ribosome, a macromolecule composed of protein and RNA. This work will inform on the role of a male germ cell specific RNA binding protein in ribosome biogenesis and whether some male infertility may be due to abnormal ribosome assembly.

PI_NAMEs: POTGIETER, SARAH  (contact)

PROGRAM_OFFICER_NAME: KENT, TRAVIS JOHN

PROJECT_TERMS: adenosine deaminase;Alleles;Antibodies;Binding;Biogenesis;Biology;Cell Nucleolus;Cell Physiology;cell type;Cells;Cellular biology;CRISPR/Cas technology;Data;Defect;design;Double-Stranded RNA Binding Domain;expectation;experimental study;Fertility;frontier;Genetic;Genetic Transcription;Genome;Germ Cells;Heterogeneity;Immunofluorescence Immunologic;Immunoprecipitation;Infertility;insight;Knockout Mice;Knowledge;Laboratories;macromolecule;male;male fertility;Male Infertility;Mass Spectrum Analysis;Mediating;Mediator;Meiosis;member;Modification;Molecular;Morphology;mouse model;Mus;mutant;Mutant Strains Mice;Normal Cell;novel;Nuclear;Polyribosomes;Population;Principal Investigator;Proteins;Proteome;Proteomics;Reproduction;Reproductive Biology;Research;Ribosomal Interaction;Ribosomal Proteins;Ribosomal RNA;Ribosomes;RNA;RNA analysis;RNA Conformation;RNA Editing;RNA-Binding Proteins;Role;Site;skills;Small Nucleolar RNA;Spermatids;Spermatocytes;Structure;symposium;System;Testing;Testis;Time;Training;Transcript;transcriptome sequencing;translational impact;Translational Regulation;Translations;Universities;Untranslated RNA;Work

PROJECT_TITLE: ADAD1 and ribosome biogenesis in the post-meiotic male germ cell

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F06-J (20)]


NIH_SPENDING_CATS: Breast Cancer;Cancer;Women's Health Research

ORG_CITY: WORCESTER

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

PHR: Narrative Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer that is associated with poor patient outcomes. Triple negative tumor cells are characterized by unstable genomes, and they require the increased activity of cellular pathways that prevent additional DNA damage and cell death. This proposal will investigate one mechanism that protects the genome to enhance the survival of TN tumor cells, with the long- term goal of developing new therapies to treat TNBC patients.

PI_NAMEs: SHAW, LESLIE M (contact)

PROGRAM_OFFICER_NAME: CERO, CHERYL

PROJECT_TERMS: Acute;Adaptor Signaling Protein;aggressive breast cancer;Aneuploidy;Breast Cancer Cell;Breast Cancer Patient;Breast Cancer Treatment;cancer initiation;cancer subtypes;cancer therapy;Cell Cycle;Cell Cycle Arrest;Cell Death;Cell Survival;Chromosomal Instability;Chromosome abnormality;Chromosomes;Data;Development;DNA Damage;efficacy evaluation;Ensure;Exhibits;Feedback;Genes;Genome;genome integrity;Genomic Instability;Goals;Growth;improved;in vivo;Insulin;Insulin Receptor;insulin regulation;insulin signaling;Insulin-Like Growth Factor I;Insulin-Like Growth Factor Receptor;Insulin-Like-Growth Factor I Receptor;IRS1 gene;IRS2 gene;Ligands;Maintenance;Malignant Breast Neoplasm;Mediating;Metabolic;Metabolism;Microtubules;Mitosis;Mitotic;Mitotic spindle;Molecular;Morbidity - disease rate;mortality;Nature;Neoplasm Metastasis;neoplastic cell;novel;novel therapeutic intervention;novel therapeutics;Outcome;Pathway interactions;Patient-Focused Outcomes;Pharmaceutical Preparations;Phase;Phosphorylation;Play;PLK1 gene;polo-like kinase kinase 1;prevent;Process;Proliferating;Proteins;receptor;Receptor Up-Regulation;receptor upregulation;recruit;Regulation;response;Role;segregation;Signal Pathway;Signal Transduction;Site;Stress;Therapeutic;therapeutic target;Toxic effect;Treatment Efficacy;triple-negative invasive breast carcinoma;tumor;Tumor Escape;tumor growth;tumor progression;Work

PROJECT_TITLE: IRS2 and mitotic regulation in breast cancer

STUDY_SECTION: CCB

STUDY_SECTION_NAME: Cancer Cell Biology Study Section[CCB]


NIH_SPENDING_CATS: Cancer;Genetics;Skin Cancer

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: Project Narrative. Stress granules are cytoprotective biological condensates that are induced by cell stress and are hijacked by cancer cells to withstand the harsh environment of tumorigenesis. This proposal leverages a humanized zebrafish melanoma model to test the essentiality and epitranscriptomic influence of stress granule formation in melanoma precursor cells on melanoma initiation and progression in vivo. As stress granules are observed in many cancer systems, the findings of this proposal will uncover foundational knowledge that can be used to exploit a conserved molecular pathway of cancer initiating cells, aiding the effort to control cancer in the long-term by stopping it before it can start.

PI_NAMEs: DRAKE, KYLE DAVID (contact)

PROGRAM_OFFICER_NAME: ELJANNE, MARIAM

PROJECT_TERMS: Ablation;Acceleration;Apoptotic;Binding;Biological;Biological Assay;Biology;Cancer Biology;cancer cell;Cancer Control;cancer initiation;cancer type;Cell Culture Techniques;Cells;Cellular Stress;Chemicals;clinical translation;combat;Complex;CRISPR/Cas technology;Cytoplasm;Cytoplasmic Granules;Cytoprotection;cytotoxic;Data;Development;Disease;Embryo;Environment;epitranscriptomics;Fishes;Flow Cytometry;G3BP1 gene;Genetic;Genetic Engineering;Genetic Transcription;Goals;Human;Image;in vivo;insight;Institution;Knowledge;Label;Length;Malignant Neoplasms;Mediating;melanocyte;Melanoma;melanoma biomarkers;Melanoma Cell;melanomagenesis;Messenger RNA;Modeling;Modification;Molecular;Neoplasm Metastasis;Neural Crest;new therapeutic target;non-Native;Oncogenic;Pathway interactions;Phase;Physical condensation;precursor cell;Proliferating;promoter;Proteins;Regulation;Research;Research Proposals;Ribosomes;RNA;RNA Processing;Role;Running;Sampling;skills;Skin Cancer;Stress;stress granule;stressor;subcutaneous;System;Technical Expertise;Testing;TP53 gene;Training;Transcript;Translation Initiation;Translations;translatome;Transplantation;tumor;Tumor Biology;Tumor Burden;tumor initiation;tumor progression;tumorigenesis;tumorigenic;vector;Visualization;Work;Xenograft procedure;Zebrafish

PROJECT_TITLE: Defining the role of stress granules in cancer initiation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F09A-R (20)]


ORG_CITY: CLEVELAND

ORG_DEPT: PHYSIOLOGY

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

PHR: NARRATIVE This project develops a pipeline that can be used to predict the severity of and best treatment for genetic mutations that lead to a specific type of cardiac disease. The long-term goal is to create a system that will help improve care for people who are at risk of hypertrophic cardiomyopathy.

PI_NAMEs: CAMPBELL, KENNETH S;STELZER, JULIAN  (contact)

PROGRAM_OFFICER_NAME: ADHIKARI, BISHOW B

PROJECT_TERMS: Acceleration;Actins;Address;Animals;Behavior;Benign;Binding;Biological;Biological Assay;Biophysics;C10;Calibration;Cardiac;Cardiac Myosins;Cardiomyopathies;Cardiovascular Physiology;Caring;Cells;Classification;Clinical;clinical database;clinically significant;Collaborations;Complex;computer code;Computer Models;Computer software;Custom;Data;Databases;Dependovirus;design;Development;Disease;DNA Sequence Alteration;effective therapy;efficacy testing;Exhibits;experimental study;Gene Delivery;Genes;Genetic;Genotype;Goals;Growth;Heart;Heart Diseases;hemodynamics;Hypertrophic Cardiomyopathy;Hypertrophy;improved;in vivo evaluation;Individual;Inherited;innovation;Interdisciplinary Study;Lead;Link;Location;Measures;Microfilaments;Missense Mutation;Modeling;Molecular;Molecular Biology;Mus;Muscle function;mutant;Mutate;Mutation;Myocardium;Myosin ATPase;myosin-binding protein C;N-terminal;open source;Organ;Pathogenicity;Patients;Penetrance;Persons;Phenotype;Physiology;Prognosis;Proteins;Publishing;Relaxation;Research;Research Personnel;Resource Sharing;Resources;Risk;Sarcomeres;Satellite Viruses;Severities;simulation;skills;Speed;System;Testing;Thick Filament;Thin Filament;ultrasound;Variant;variant of unknown significance

PROJECT_TITLE: Biological Basis of Genetic cMyBP-C Cardiomyopathies

STUDY_SECTION: BBHV

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


NIH_SPENDING_CATS: Cancer;Cardiovascular;Clinical Research;Heart Disease;Immunotherapy;Precision Medicine;Prevention

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

ORG_STATE: CA

PHR: PROJECT NARRATIVE Immune checkpoint inhibitors (ICI) are potentially lifesaving cancer therapies that can also cause off-target immune-related adverse events such as cardiac toxicities. The purpose of this study is to investigate the risk stratification and outcomes across the spectrum of ICI cardiotoxicity. The results of this study will guide clinicians in maximizing the therapeutic uses of novel cancer therapies while minimizing serious adverse effects.

PI_NAMEs: CHENG, EVALINE  (contact)

PROGRAM_OFFICER_NAME: WANG, WAYNE C

PROJECT_TERMS: Acute;Adverse effects;Affect;Arrhythmia;Assessment tool;biobank;Biological Markers;biomarker driven;Blocking Antibodies;Brain natriuretic peptide;Cancer Patient;cancer therapy;Cardiac;Cardiotoxicity;Cardiovascular system;career;Cells;Cessation of life;checkpoint therapy;Clinical;clinical decision-making;clinical phenotype;Clinical Research;clinically significant;cohort;Collaborations;Competence;Cytometry;Data;Databases;Detection;Development;Diagnosis;Disease;early detection biomarkers;Early Diagnosis;Evidence based practice;Fellowship;forging;Goals;Heart failure;Heart Injuries;Immune;Immune checkpoint inhibitor;Immune Targeting;immune-related adverse events;Immunologic Markers;Immunologic Surveillance;Incidence;Inflammatory;inflammatory marker;International;Knowledge;Life;Malignant Neoplasms;Measurement;Mentors;Monitor;Monoclonal Antibodies;Myocarditis;N-terminal;Natural History;novel;Oncology;oncology program;Organ;Outcome;patient stratification;patient subsets;Patient-Focused Outcomes;Patients;Peripheral;permissiveness;Phenotype;Physicians;predict clinical outcome;premature;prospective;Recommendation;Registries;Regulatory Pathway;Reporting;Risk;Risk Assessment;Risk Management;risk stratification;Role;Scientist;Symptoms;T-Cell Activation;Testing;Therapeutic Uses;Time;Toxic effect;Training;Treatment Failure;trend;Troponin;Troponin I

PROJECT_TITLE: Risk Assessment and Outcomes Across the Clinical Spectrum of Cardiotoxicity from Immune Checkpoint Inhibitors

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


NIH_SPENDING_CATS: Asthma;Chronic Obstructive Pulmonary Disease;Clinical Research;Infectious Diseases;Lung

ORG_CITY: TUCSON

ORG_NAME: UNIVERSITY OF ARIZONA

ORG_STATE: AZ

PHR: While it is recognized that a percentage of severe asthmatics develop fixed airway obstruction, little is known pertaining to the basic underlying mechanisms of this progression. During the first cycle of funding, we proposed that early life respiratory infections in the context of club cell secreted protein (CC16) deficits was a possible link in disease progression and found that CC16 plays important roles in both the circulation and in the airway via interactions with integrin receptor complexes. This renewal proposal will delve into the mechanisms by which CC16 promotes epithelial host defense factors to protect against Rhinovirus infection.

PI_NAMEs: LEDFORD, JULIE GUNNELLS (contact)

PROGRAM_OFFICER_NAME: CROXTON, THOMAS

PROJECT_TERMS: Acute;Address;Adult;airway epithelium;airway hyperresponsiveness;airway obstruction;airway remodeling;Anti-Inflammatory Agents;Anti-viral Agents;Antigens;antimicrobial;Antimicrobial Effect;Apical;Asthma;asthma exacerbation;asthmatic;asthmatic patient;Binding;Blood Circulation;cell motility;Cell secretion;Cells;Child;Chronic lung disease;Chronic Obstructive Pulmonary Disease;Circulation;Clinical;Common Cold;Complex;Development;Diagnosis;Disease Progression;Distal;Epigenetic Process;Epithelial Cells;Epithelium;Family member;Funding;General Population;Goals;Host Defense;Human;Immune response;Impairment;Individual;Infection;Inflammatory Infiltrate;Inflammatory Response;insight;Integrin alpha2beta1;Integrin Binding;Integrins;Invaded;Knowledge;Leukocytes;Life;Ligands;Link;Lung;lung development;Mass Spectrum Analysis;Mediating;migration;mRNA Expression;Mus;Mycoplasma pneumoniae;Nasal Epithelium;neutrophil;Nose;novel;pathogen;peptidomimetics;Phase;Play;Production;prospective;Protein Secretion;Proteins;Publishing;pulmonary function;pulmonary function decline;receptor;Regulation;Reporting;respiratory pathogen;Respiratory System;Respiratory Tract Infections;response;Rhinovirus;Rhinovirus infection;Risk Factors;Role;Sampling;School-Age Population;Serum;Testing;Therapeutic;Tracheal Epithelium;Translational Research;translational study;United States;Viral;Viral Proteins;Virus Diseases

PROJECT_TITLE: Defining mechanisms of CC16 on epithelial-driven host responses to pathogens

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


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Digestive Diseases

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

PHR: Project Narrative Maintenance of a healthy epithelial barrier is essential for intestinal homeostasis, and both genetic deficiencies in barrier function and evidence of functional barrier dysregulation are observed in patients with inflammatory bowel disease. Previous work has shown that colon intraepithelial lymphocytes are required to maintain and repair the epithelial barrier, but their function is largely unstudied. This project aims to understand the role of epithelial antigen presentation in informing tolerance and function of colon intraepithelial lymphocytes, which will increase understanding of the etiology of diseases such as inflammatory bowel disease.

PI_NAMEs: DANIELSON, SARAH MANN (contact)

PROGRAM_OFFICER_NAME: DENSMORE, CHRISTINE L

PROJECT_TERMS: Antigen Presentation;Antigen-Presenting Cells;Antigens;Bacteria;career;Cell Physiology;Characteristics;Citrobacter rodentium;Colon;conditional knockout;Data;Dendritic Cells;Development;Differentiation Antigens;Disease;enteric infection;enteric pathogen;Epigenetic Process;Epithelial Cells;epithelial repair;Epithelium;Etiology;experience;experimental study;Exposure to;Foundations;Functional disorder;Gene Expression Regulation;Genetic;Genome;Goals;Grant;gut bacteria;gut microbiome;Homeostasis;Immune response;Immunologist;Immunology;in vivo;Infection;Inflammation;Inflammatory;Inflammatory Bowel Diseases;inhibitor;Injury;interest;Interleukin-6;intestinal epithelium;intestinal homeostasis;Intestines;intraepithelial;ITGAX gene;Joints;Knockout Mice;Learning;Lymphocyte;Lymphocyte Function;Maintenance;Manuscripts;Memory;MHC Class II Genes;Mucous Membrane;Mus;Myelogenous;Myeloid Cells;next generation sequencing;Pathology;Patients;Pattern;Peptides;Phenotype;Predisposition;prevent;Process;Production;Property;reconstitution;recruit;Regulation;Research Personnel;Role;screening panel;Signal Transduction;single cell ATAC-seq;skills;Small Intestines;sphingosine 1-phosphate;Sphingosine-1-Phosphate Receptor;Stains;T cell receptor repertoire sequencing;T-Cell Receptor;T-cell receptor repertoire;T-Lymphocyte;Technology;Testing;Tissues;trafficking;Transgenic Mice;Work;Writing

PROJECT_TITLE: The recruitment and retention of colon intraepithelial lymphocytes

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Fellowships in Digestive Diseases and Nutrition[DDK-F]


NIH_SPENDING_CATS: Neurosciences;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

PHR: PROJECT NARRATIVE Fetal hematopoietic stem and progenitor cells (HSPC) are restricted from activating emergency myelopoiesis pathways by maternal IL-10, which leads to neutropenia and contributes to neonatal morbidities and mortality. This project will test the hypothesis that maternal IL-10 restricts fetal emergency myelopoiesis via regulation of maternal decidual macrophages that trigger placental serotonin synthesis which is released into the fetal circulation and regulates fetal HSPCs. By systematically identifying the mechanisms by which maternal inflammation is translated across the placenta and sensed in the fetal liver to modulate fetal emergency myelopoiesis, we will uncover nodes along the cascade that might be amenable to therapeutic targeting, ultimately boosting neonatal immune function and improving neonatal outcomes.

PI_NAMEs: COLLINS, AMELIE  (contact)

PROGRAM_OFFICER_NAME: MAJJI, SAI PRASANNA

PROJECT_TERMS: Address;Adult;adverse outcome;Axon;Brain;Cell Physiology;cell type;Cells;Circulation;combat;Communication;cytokine;Decidua;Emergency Situation;Endothelium;Ensure;Event;Failure;fetal;Fetal Liver;Fetus;fetus cell;Flow Cytometry;Functional disorder;Generations;Growth;Hematopoiesis;Hematopoietic;Hematopoietic stem cells;Hepatocyte;high dimensionality;Immune;immune function;improved;In Vitro;in vivo;Infection;Inflammation;Inflammatory;Inflammatory Response;Innate Immune System;Interleukin-10;interleukin-10 receptor;Lead;Link;long-term sequelae;Macrophage;Mediator;metabolomics;Mus;Myeloid Cells;Myelopoiesis;Neonatal;neonatal immune system;neonatal morbidity;Neonatal Mortality;neonatal outcome;neonatal sepsis;Neurodevelopmental Impairment;Neutropenia;neutrophil;novel;offspring;Outcome;Pathway interactions;Placenta;Predisposition;Pregnancy;Premature Birth;prevent;Process;Production;Proliferating;Receptor Signaling;Regulation;Research Project Grants;response;Serotonin;serotonin receptor;Serum;Signal Transduction;single-cell RNA sequencing;stem cell function;stem cells;Supporting Cell;Surveys;Testing;Therapeutic Intervention;therapeutic target;Tissues;transcriptomics;Transgenic Mice;Translating;Validation

PROJECT_TITLE: Determining themechanism of maternal IL-10 restriction of fetal emergency myelopoiesis to improve neonataloutcomes

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 EMS-A (57)]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Cardiovascular;Childhood Obesity;Clinical Research;Diabetes;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Hypertension;Nutrition;Obesity;Pediatric;Physical Activity;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: NARRATIVE This research proposal will apply a mixed-methods approach to understand of the prevalence of, and risk factors for, obesity, diabetes, and hypertension among American Samoan adolescents. Analyses will provide insight to drive future individual and community actions to address risk of chronic disease among this at-risk group. This award will also provide training opportunities to position Ms. Faiai as a leader in public health practice and an independent early career scientist.

PI_NAMEs: FAIAI, MATA'UITAFA  (contact)

PROGRAM_OFFICER_NAME: RIVERS, ROBERT C

PROJECT_TERMS: 14 year old;Address;Adolescence;Adolescent;Adolescent Behavior;Adolescent obesity;Adolescent Risk Behavior;Adult;Affect;Age;age group;aged;American;American Samoa;Award;Behavior;behavior influence;Body Image;cardiometabolism;career;Childhood;Chronic Disease;Communities;Community Actions;cooking;Development;Diabetes Mellitus;Diet;Dietary intake;Disease;disorder risk;early adolescence;Environment;Epidemiologic Methods;Epidemiologist;Epidemiology;epidemiology study;Extended Family;Family;Focus Groups;Food;Food Preferences;food preparation;Friends;Friendships;Future;Geography;Goals;Graph;Habits;Health;Health Food;health professional shortage areas;Health Promotion;Hypertension;improved;Individual;Influentials;insight;Intervention;Interview;Life Style;lifestyle intervention;Markov Chains;Maximum Likelihood Estimate;medically underserved;Mental Depression;Methods;Modeling;Native Hawaiian or Other Pacific Islander;Non-Insulin-Dependent Diabetes Mellitus;Not Hispanic or Latino;nutrition;Obesity;obesity development;Outcome;Overweight;Pacific Islander;Pacific Islands;Parents;Participant;Pathway Analysis;Pattern;peer;Perception;Physical activity;Play;Population;Populations at Risk;Positioning Attribute;Prediabetes syndrome;Prevalence;prevent;Public Health Practice;Qualitative Methods;Research;Research Design;Research Proposals;Risk;Risk Behaviors;Risk Factors;risk mitigation;Role;Samoan;Schools;Scientist;Shapes;skills;social;social capital;social influence;Social Network;statistics;structural determinants;Structure;Surveys;Testing;Time;Training;training opportunity;Translating;Vacuum;Weight;Work

PROJECT_TITLE: Understanding diabetes and related-risk factors among adolescents of American Samoa

STUDY_SECTION_NAME: Fellowships in Diabetes Endocrinology and Metabolic Diseases [DDK-E]


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

ORG_CITY: CHICAGO

ORG_DEPT: SURGERY

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: Primary graft dysfunction (PGD) is the predominant risk for early post-transplant mortality and chronic lung allograft rejection. In this proposal, we will determine complementary mechanisms of cellular necroptosis in the diseased native lungs of recipients that persist in the pre-transplant state as well as in the donor allograft during ischemia-reperfusion injury which result in the release of damage associated molecular patterns necessary for immune activation and initiation of PGD. By identifying novel mechanisms of cellular necroptosis that can be targeted using clinically relevant strategies, we intend to ameliorate PGD in all transplant recipients.

PI_NAMEs: BHARAT, ANKIT  (contact);BUDINGER, GR SCOTT

PROGRAM_OFFICER_NAME: MONGODIN, EMMANUEL FRANCK

PROJECT_TERMS: Acute;Acute Lung Injury;Acute Respiratory Distress Syndrome;Address;Affect;allograft rejection;Allografting;Alveolar Macrophages;American;autocrine;Biological Markers;Cell Death;Cells;chemokine;Chest;Chronic;Clinical;clinically relevant;clinically significant;Complication;Credentialing;Data;Detection;Development;Disease;Endothelium;Engraftment;Epithelium;Foundations;Functional disorder;Generations;Goals;graft dysfunction;HMGB1 gene;Hour;Human;immune activation;Impairment;improved;Incidence;injured;insight;Intervention;Investigation;Ischemia;Laboratories;Life;Lung;lung allograft;Lung Diseases;lung injury;Lung Transplantation;Mediating;Mitochondria;Mitochondrial Electron Transport Complex I;Modeling;Molecular;monocyte;mortality;mouse model;Mus;neutrophil;Neutrophil Infiltration;novel;novel therapeutic intervention;Outcome;Pathogenesis;Pathway interactions;Patients;Pattern;pharmacologic;Play;Population;post-transplant;predictive marker;Predisposition;Procedures;Process;Prostaglandin D2;Protein Kinase Interaction;Publishing;Quality of life;Reactive Oxygen Species;Receptor-Interacting Protein;Recommendation;recruit;Reperfusion Injury;Reperfusion Therapy;Reporting;Research;response;Risk;risk mitigation;risk stratification;Role;Sentinel;Severities;Signal Transduction;Societies;Spleen;Structure of parenchyma of lung;success;Succinates;Survival Rate;Testing;Tissue Donors;TLR2 gene;TLR4 gene;TNF gene;Transplant Recipients;Transplantation

PROJECT_TITLE: Complementary pathways of necroptosis in recipient and donor lung tissue that drive primary lung allograft dysfunction

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 ISB-D (02)]


ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Genetics;Human Genome;Precision Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: LOS ANGELES

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PROJECT NARRATIVE Cell villages pool populations of 10-100 genetically distinct, human stem cell lines to study how genetic variation and environment inﬂuence a spectrum of molecular phenotypes in individuals of diverse ancestral backgrounds. This proposal will develop statistical tools for the design and analysis of powerful, reproducible cell village ex- periments with the goal of enhancing precision medicine. We will build a simulation framework for testing how experimental parameters inﬂuence individual donor growth rate estimates from our preliminary model and will develop a class of hierarchical models for analyzing scRNA-seq village data.

PI_NAMEs: HANSON, CHLOE C (contact)

PROGRAM_OFFICER_NAME: FUFA, TEMESGEN D

PROJECT_TERMS: Acceleration;Address;ATAC-seq;Biological;Biological Assay;Cell Count;Cell Culture Techniques;Cell Line;cell type;Cells;Chemicals;ChIP-seq;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;computerized tools;Data;Data Analyses;Data Reporting;Data Set;data structure;design;Disease;Disease susceptibility;disorder risk;dosage;Dropout;Drops;Ensure;Environment;Experimental Designs;experimental study;flexibility;gene environment interaction;Gene Expression;Gene Expression Profile;Genes;Genetic;Genetic study;Genetic Variation;Goals;Growth;human pluripotent stem cell;human stem cells;improved;in silico;In Vitro;Individual;Length;Measures;Messenger RNA;Methods;Modeling;models and simulation;Molecular;molecular phenotype;nerve stem cell;Nuclear Pore Complex;overpopulation;Pharmacologic Substance;Phenotype;Population;power analysis;precision medicine;Reproducibility;Research;Research Personnel;Sampling;Series;Signal Transduction;simulation;single-cell RNA sequencing;Statistical Data Interpretation;Statistical Methods;Statistical Models;Structure;Techniques;Testing;Therapeutic Intervention;Therapeutic Research;Time;tool;Toxicology;user-friendly;Variant;Viral;Work

PROJECT_TITLE: Hierarchical modeling and simulation to optimize cell village experimental design and the analysis of scRNA-seq data


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cancer;Clinical Research;Pediatric;Prevention;Radiation Oncology

ORG_CITY: GAINESVILLE

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: PROJECT NARRATIVE External beam radiotherapy is an effective and widely used approach for the curative treatment of cancer. Increasing epidemiological evidence suggests that radiation-induced second primary cancers are a significant risk following radiotherapy, and therefore should be considered in the treatment planning and dose optimization processes for both near- and out-of-field organs. The proposed study will develop an end-to-end system for patient-specific dosimetry and cancer risk quantification for all normal organs following radiotherapy, with a focus on children and young adults.

PI_NAMEs: DAWSON, ROBERT JOSEPH (contact)

PROGRAM_OFFICER_NAME: BOULANGER-ESPEUT, CORINNE A

PROJECT_TERMS: Accounting;Adult;Aftercare;Age;Algorithms;American;Anatomic Models;Anatomy;automated segmentation;biological sex;Cancer Center;Cancer Patient;cancer risk;cancer therapy;carbon ion therapy;Cell Proliferation;Child;Childhood;Clinical;clinical implementation;clinical practice;Code;cohort;Computerized Medical Record;curative treatments;Data;Data Set;deep learning;demographics;Deposition;design;Development;Distal;Dose;dosimetry;Epidemiology;epidemiology study;Epithelium;Florida;Future;Gastrointestinal tract structure;Generations;Geometry;Head;Health;Height;high risk;Human;Image;imaging study;Individual;Lateral;Lead;Libraries;Medical Records;Methods;Modality;Modeling;Modernization;neglect;Organ;Output;particle beam;Patient Representative;Patients;pediatric patients;Performance;Photons;Process;process optimization;Programming Languages;prospective;proton therapy;Protons;Publishing;Pythons;Radiation;Radiation therapy;Radiation Tolerance;Reporting;Respiratory System;Risk;risk minimization;Second Primary Cancers;Severities;simulation;Source;Supplementation;Surface;System;Systems Development;Thinness;Tissues;Toxic effect;treatment planning;treatment site;tumor;Tumor Volume;United States;Universities;virtual;Weight;Work;X-Ray Computed Tomography;young adult

PROJECT_TITLE: Development and application of whole-body patient-specific computational mesh phantoms for organ dosimetry and second primary cancer risk quantification following external beam radiotherapy


ADMINISTERING_IC: ES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Dementia;Lewy Body Dementia;Neurodegenerative;Neurosciences;Parkinson's Disease;Prevention;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: BIRMINGHAM

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: Project Narrative Though cognitive impairments occur in up to 80% of all Parkinson’s disease cases, no therapies exist targeting this symptomology and no mechanisms have been proposed for the significant heterogeneity in presentation and onset timing. The proposed research will investigate the role for environmental toxicants in influencing cognitive impairments, and specifically assess the role of aberrant CDK5 activation and increased cellular senescence in driving pathogenic protein accumulation and adult neurogenesis impairment following TCE exposure. This work will increase understanding of cognitive impairments in Parkinson’s disease, ascertain TCE’s mechanism of action, and identify potential therapeutic targets for slowing disease progression and alleviating disease burden caused by Parkinson’s disease dementia.

PI_NAMEs: ADAMSON, ASHLEY  (contact)

PROGRAM_OFFICER_NAME: HOLLANDER, JONATHAN

PROJECT_TERMS: Adult;adult neurogenesis;Aging;Air;alpha synuclein;Area;Astrocytes;Automobile Driving;Autopsy;Brain;Brain region;brain tissue;burden of illness;C57BL/6 Mouse;career;career development;CDK5 gene;CDKN2A gene;Cell Aging;Cell Cycle;Cell Cycle Proteins;Cognition;Cognitive;Cognitive deficits;cognitive impairment in Parkinson's;cognitive performance;Communication;Cyclin-Dependent Kinase 5;Data;Dementia;dentate gyrus;Disease;Disease Progression;disorder risk;dopaminergic neuron;Educational process of instructing;Environment;Environmental Exposure;Environmental Pollutants;Epidemiology;Ethics;Excision;experience;Exposure to;Fostering;Foundations;Ganciclovir;genetic risk factor;Goals;Heterogeneity;Hippocampus;hyperphosphorylated tau;Impaired cognition;Impairment;improved;Inhalation;knock-down;Learning;Lewy body pathology;Link;Measures;Mediating;Memory;Mentors;Mentorship;Modeling;motor deficit;Movement Disorders;Mus;Nerve Degeneration;nerve stem cell;Neurobehavioral Manifestations;Neurodegenerative Disorders;neurogenesis;Neuroglia;neuron loss;Neurons;neurotoxicology;novel;Organic solvent product;Parkinson Disease;Parkinson's Dementia;Parkinsonian Disorders;Pathogenicity;Pathology;Pathway interactions;Patients;Peptides;Pesticides;Phenotype;Phosphotransferases;Population;Positioning Attribute;Preparation;prevent;Process;Proliferating;Proteins;Reporter;Reproducibility;Research;research and development;Research Personnel;Research Proposals;Response Elements;Rodent;Role;Science;Scientist;senescence;senescent cell;Severity of illness;skills;Soil;Solvents;stem cell niche;stem cell population;stem cell proliferation;stem cells;targeted treatment;tau dysfunction;tau-1;teacher;Technical Expertise;Testing;Therapeutic;therapeutic target;Toxic Environmental Substances;toxicant;Training;Training Programs;Trichloroethylene;United States;United States National Institutes of Health;Viral;Water;Work

PROJECT_TITLE: The role for cell cycle regulators in trichloroethylene induced Parkinson's dementia

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


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Brain Disorders;Cardiovascular;Genetics;Infectious Diseases;Social Determinants of Health

ORG_CITY: Nashville

ORG_DEPT: BIOLOGY

ORG_NAME: VANDERBILT UNIVERSITY

ORG_STATE: TN

PHR: PROJECT NARRATIVE Many non-communicable, inflammation-based diseases of aging in Western, urbanized countries are observed at low frequencies in subsistence-level societies, suggesting that these outcomes are not an inevitable part of the natural aging process and may be due to differences in immune activity across lifestyles. This project seeks to understand the biological mechanisms underlying these observations by quantifying the effects of urbanization on peripheral immune system gene expression, DNA methylation, and somatic mutations (clonal hematopoiesis of indeterminate potential) (i) within subsistence-level populations in which individuals are moving to urban city centers, and (ii) between three subsistence-level societies and the US, a highly urban country. The results of this work will contribute to our understanding of how urbanization impacts immune gene regulation and risk of inflammation-based diseases of aging across diverse populations.

PI_NAMEs: WATOWICH, MARINA  (contact)

PROGRAM_OFFICER_NAME: TILAHUN, MULUALEM ENYEW

PROJECT_TERMS: active lifestyle;Address;Adult;Affect;Age;age effect;age related;age related changes;age related decline;age-related disease;Aging;aging process;aging related disease;American;Arthritis;Biological;Bolivia;burden of illness;Calories;Cardiovascular Diseases;cerebral atrophy;Characteristics;Chronic;Cities;Coronary Arteriosclerosis;Country;Data;Data Set;Dementia;Disease;DNA Methylation;Environment;European;Exhibits;experience;Exposure to;Face;farmer;Food;Frequencies;Gene Expression;Gene Expression Regulation;Genes;Genetic;genomic data;Genomics;Health;health data;health knowledge;healthy aging;helminth infection;Hematopoiesis;human old age (65+);Hypertension;Immune;immune activation;immune function;Immune system;Immunologic Tests;Immunologics;Individual;Industrialization;Inflammaging;Inflammation;Inflammatory;insight;Interleukin-6;Intervention;Investments;Kenya;Life Cycle Stages;Life Style;malaria infection;Malaysia;marginalized community;marginalized population;Marketing;Measures;Modernization;modifiable lifestyle factors;Molecular;molecular phenotype;multiple omics;Native-Born;Non-Insulin-Dependent Diabetes Mellitus;normal aging;Older Population;Outcome;pathogen;pathogen exposure;Pathway interactions;Pattern;Peripheral;peripheral blood;Persons;Phenotype;Physiology;Population;Population Heterogeneity;Process;Resources;response;Risk;Runaway;Sampling;sedentary;Societies;socioeconomics;Somatic Mutation;Sterility;Testing;TNF gene;tool;trait;urban setting;Urbanicity;Urbanization;Variant;Work

PROJECT_TITLE: Exploring the consequences of differential immune investment on molecular aging phenotypes in subsistence-level populations

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F18-E (20)]


ADMINISTERING_IC: DE

ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Clinical Research;Dental, Oral, and Craniofacial Disease;Infectious Diseases;Microbiome

ORG_DEPT: DENTISTRY

PHR: Narrative Dental caries is one of the most prevalent chronic diseases in the world with the cariogenic bacterium Streptococcus mutans synergizing with Candida albicans for increased cariogenicity. C. albicans has been shown to enhance S. mutans oxidative stress tolerance and we recently showed that C. albicans catalase enzyme contributes to this enhancement. Further investigation of C. albicans catalase and superoxide dismutase enzymes will elucidate the potential of these enzymes as targets to disrupt S. mutans-C. albicans synergism and prevent caries.

PI_NAMEs: KATRAK, CALLAHAN KASHMIRA (contact)

PROGRAM_OFFICER_NAME: MCGUIRL, MICHELE

PROJECT_TERMS: Acids;Acute;Affect;anticaries;Antimicrobial Effect;Architecture;Bacteria;biofilm species;Biological Assay;Biomass;Candida albicans;Carbohydrates;cariogenic bacteria;catalase;Cells;Chlorhexidine;Chronic;Chronic Disease;co-infection;Coculture Techniques;combat;commensal microbes;Communicable Diseases;Confocal Microscopy;Dental;dental biofilm;Dental caries;Dental Enamel;Dental General Practice;Dental Hygiene;Dental Research;Dentists;Development;Disease;Drug Metabolic Detoxication;early childhood;Effectiveness;efficacy testing;Enzymes;Exhibits;extracellular;Fermentation;fitness;Future;Genes;glucosyltransferase B;Goals;Gram-Positive Bacteria;Growth;Health;Human;Hydrogen Peroxide;Immune;improved;In Vitro;in vivo;Incidence;Individual;Infection;insight;Interruption;Investigation;Knowledge;Learning;Microbial Biofilms;Modeling;Mouthwash;mutant;novel;Operative Surgical Procedures;Oral;oral biofilm;Oral cavity;oral commensal;oral microbial community;oral streptococci;Organism;Outcome;Oxidative Stress;Oxidative Stress Pathway;pathogen;Pathway interactions;Patients;Periodontitis;Persons;Predisposition;prevent;Rattus;Reactive Oxygen Species;Recording of previous events;Research;Research Personnel;Role;Saliva;Salivary;Scientist;Severities;Site;skills;Streptococcus mutans;stress tolerance;stressor;student mentoring;Sucrose;sugar;Superoxide Dismutase;Superoxides;symposium;synergism;targeted treatment;Techniques;Tooth Demineralization;Tooth Loss;Tooth structure;Toothpaste;Training;Up-Regulation;Virulence;Water;Writing;Yeasts

PROJECT_TITLE: Exploring the role of C. albicans oxidative stress pathways in S. mutans reactive oxygen species tolerance

STUDY_SECTION: DSR

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


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Brain Disorders;Genetics;Intellectual and Developmental Disabilities (IDD);Neurosciences

ORG_CITY: SEATTLE

ORG_NAME: SEATTLE CHILDREN'S HOSPITAL

ORG_STATE: WA

PHR: PROJECT NARRATIVE Johanson-Blizzard syndrome is a rare but devastating developmental disorder that is associated with pathogenic variants in UBR1 and is characterized by intellectual disability and psychomotor developmental delays. Using proteomics and genetic tools in C. elegans, we will define the function and mechanisms of action of UBR-1, the sole C. elegans homolog of UBR1/2. Through proteomics, we have identified glutamate metabolic enzymes as putative binding partners for UBR-1 and hypothesize that UBR-1 acts as a master regulator of these enzymes to regulate nervous system function.

PI_NAMEs: PAK, JOSEPH  (contact)

PROGRAM_OFFICER_NAME: JONES, LATAISIA CHERIE

PROJECT_TERMS: Address;Alzheimer's Disease;Animal Behavior;Animal Model;Animals;Behavior;Behavioral;Binding;Binding Proteins;Biochemical;Biochemical Pathway;Biochemistry;Biological Assay;biological systems;Caenorhabditis elegans;Cells;Central Nervous System;Clustered Regularly Interspaced Short Palindromic Repeats;Co-Immunoprecipitations;Data;Data Set;Defect;Development;Developmental Delay Disorders;developmental disease;Disease;Embryo;Engineering;Enhancers;Enzyme Interaction;Enzymes;Exocrine pancreatic insufficiency;experimental study;Family;Fluorescence;galactitol 2-dehydrogenase;Genetic;Genetic study;Genetic Suppression;genetic variant;Glutamate Receptor;Glutamates;Goals;Head;Health system;Homologous Gene;Human;human disease;Human Genetics;Impairment;in vivo;innovation;Intellectual functioning disability;Johanson-Blizzard syndrome;Knock-out;Ligase;Link;Locomotion;Mental Retardation;Metabolic;Metabolic Pathway;Metabolism;Methods;Microscopy;model organism;Motor Activity;Multiple Sclerosis;Mus;mutant;Nervous System;nervous system development;Nervous System Disorder;Nervous System Physiology;neurogenesis;Neurons;Neurotransmitters;next generation;novel;novel strategies;Orthologous Gene;Outcome;Parkinson Disease;Pathogenicity;Pathway interactions;Population;Posture;protein expression;Proteins;Proteomics;Quality Control;Reagent;receptor expression;Regulation;Reporter;Role;Shapes;Speed;Structure;Surface;Symptoms;Testing;tool;Ubiquitin family;ubiquitin ligase;ubiquitin-protein ligase;Validation;Variant;Work;Yeasts

PROJECT_TITLE: Regulation of nervous system health and function by the E3 ligase UBR-1

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


ORG_NAME: UNIVERSITY OF WASHINGTON

PHR: PROJECT NARRATIVE  While heart failure cases in the United States are rapidly increasing, current animal and 2D in vitro models fall short in accurately representing the human cardiac environment and modeling cardiac disease. Engineered heart tissues (EHTs) have emerged as a promising avenue for replicating native cardiac physiology; however, they typically lack perfusable, endothelialized vasculature, despite its critical role in cardiac function. To address this need, this project aims to engineer perfusable EHTs by incorporating an endothelialized lumen to understand how the integration of flow and an endothelium influences EHT function and determine the effect of endothelial dysfunction on cardiac performance.

PI_NAMEs: FREY, ARIANA  (contact)

PROGRAM_OFFICER_NAME: WOO, SEUNG KYOON

PROJECT_TERMS: Address;Adult;advanced disease;American;Animal Model;Animals;Autocrine Communication;Blood flow;Blood Vessels;Cardiac;Cardiac Myocytes;cardiac tissue engineering;cardiogenesis;Cardiovascular Diseases;Cell Adhesion Molecules;Cell Line;Cell Physiology;Cell secretion;Cell Survival;Cessation of life;Chemicals;Collagen;Communication;cytokine;Data;Development;Diameter;Disease;disease model;Drug Screening;Electric Stimulation;Elements;Endothelial Cells;endothelial dysfunction;Endothelin-1;Endothelium;Engineering;Environment;experience;Frequencies;Functional disorder;Gene Expression Profile;Genetic Transcription;Geometry;Heart;Heart Diseases;Heart failure;heart function;hemodynamics;Homeostasis;Human;Hyperglycemia;Hypertension;Hypertrophy;Impairment;improved;In Vitro;in vitro Model;in vivo;Inflammation;Inflammatory;Injections;Light;Link;Mechanics;Methods;Modeling;Molds;Muscle;Myocardial dysfunction;Myocardium;Nitric Oxide;Nutrient;Oxygen;Paracrine Communication;Performance;Perfusion;Pharmaceutical Preparations;Phenotype;Physiological;Physiology;Play;Population;pressure;Process;Production;Public Health;Reactive Oxygen Species;Research;response;Role;Sarcomeres;Signal Transduction;Skeletal Muscle;Stimulus;Stress;stressor;Sturnus vulgaris;success;Techniques;Testing;Thrombosis;Tissue Model;tissue regeneration;Tissues;tool;Tube;United States;vascular factor;Vascularization;Vasodilation;Virus;VWF gene;Work

PROJECT_TITLE: Investigating vascular-cardiac interactions in a perfusable engineered heart tissue


NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Colorectal Cancer;Digestive Diseases;Genetics;Immunotherapy

ORG_CITY: NEW YORK

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: PROJECT NARRATIVE There is an urgent need to identify novel targets and biomarkers of response to immunotherapy in microsatellite stable/mismatch repair-proficient colorectal cancer (CRC). This proposed research will delineate the influence of the frequently mutated RNA-binding protein ZFP36L2 on CRC disease progression and immune evasion. Utilizing a novel syngeneic mouse ZFP36L2 knockout organoid model, a novel ZFP36L2 knockout genetically engineered mouse CRC model, and patient derived organoid models, this proposal aims to advance our understanding of tumor-regulated inflammation and contribute to the development of new treatment strategies to improve the prognosis and quality of life for CRC patients.

PI_NAMEs: LUCKETT, KATHLEEN  (contact)

PROGRAM_OFFICER_NAME: BIAN, YANSONG

PROJECT_TERMS: Address;Alleles;Allografting;Biological Assay;C57BL/6 Mouse;cancer initiation;Cancer Model;Cell Physiology;Cells;Cellular Indexing of Transcriptomes and Epitopes by Sequencing;checkpoint therapy;chemokine;clinically actionable;colon cancer patients;Colorectal Cancer;Cycloheximide;cytokine;Dactinomycin;Data;Development;Disease;Disease Progression;effective therapy;Engineering;Environment;Enzyme-Linked Immunosorbent Assay;Flow Cytometry;Gene Expression;Gene Expression Regulation;Gene Family;genetic regulatory protein;Genetic Transcription;Genetically Engineered Mouse;Histology;Human;Immune;immune cell infiltrate;Immune checkpoint inhibitor;Immune Evasion;Immunologics;Immunotherapy;improved;in vivo bioluminescence imaging;Inflammation;Inflammation Mediators;Inflammatory;Invaded;knock-down;Knock-out;Lead;Link;loss of function;Lymphoid;Malignant Neoplasms;Mediating;member;Messenger RNA;metastatic colorectal;Microsatellite Instability;Microsatellite Repeats;Mismatch Repair;Mismatch Repair Deficiency;Modeling;Monitor;Mus;Mutate;Mutation;Myelogenous;Neoplasm Metastasis;neoplastic cell;novel;novel therapeutic intervention;Operative Surgical Procedures;Organoids;patient subsets;Patients;Prognosis;Proteomics;Quality of life;recruit;Research;response;response biomarker;RNA;RNA-Binding Proteins;Role;Shapes;Submucosa;T cell infiltration;T-Lymphocyte;Tamoxifen;therapeutically effective;tool;Transgenic Mice;Translations;treatment strategy;tumor;tumor growth;tumor initiation;tumor microenvironment;tumor progression;Tumor Tissue;tumor-immune system interactions;Work;ZFP36L2 gene

PROJECT_TITLE: Dissecting the Functional Consequences of Mutations in ZFP36L2 on Tumor Progression and Inflammation in the Tumor Immune Microenvironment of Colorectal Cancer

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


NIH_SPENDING_CATS: Aging;Bioengineering;Biotechnology;Genetics;HIV/AIDS;Immunization;Prevention;Vaccine Related;Vaccine Related - AIDS

ORG_CITY: ATLANTA

ORG_DEPT: CHEMISTRY

ORG_NAME: GEORGIA INSTITUTE OF TECHNOLOGY

ORG_STATE: GA

PHR: Research Narrative Elderly people have a reduced ability towards brisk and sustained responses to new antigens, causes of which are poorly understood but can be attributed to a defective T cell and B cell interaction. Consequently, animal models are limited in their ability to generate antibody responses, necessitating the development of a tissue- engineered model of an aged lymph node. The proposed work will generate aged immune organoids that could serve as a rapid testing platform to identify non- or poor-responder aged individuals to infectious disease vaccines.

PI_NAMEs: SINGH, ANKUR  (contact)

PROGRAM_OFFICER_NAME: PRABHUDAS, MERCY R

PROJECT_TERMS: 3-Dimensional;Acceleration;Adjuvant;Affinity;aged;Aging;aging population;Animal Model;Antibodies;Antibody Affinity;Antibody Response;Antigens;Atomic Force Microscopy;B cell differentiation;B-Lymphocytes;Biocompatible Materials;capsule;CDKN1A gene;Cell Aging;Cell Communication;Cell Cycle Checkpoint Genes;Cell division;Cells;checkpoint inhibition;Chemicals;Chromatin;Coculture Techniques;Collagen;Communicable Diseases;Coupled;Defect;Development;differential expression;draining lymph node;Elderly;Engineering;Enhancers;Epigenetic Process;epigenome;epigenomics;Exhibits;extracellular;Extracellular Matrix;Gene Expression;Generations;Genes;Genetic Transcription;Goals;Helper-Inducer T-Lymphocyte;high risk;histone modification;Homologous Gene;Human;Humoral Immunities;Hydrogels;Immune;Immunoglobulin Class Switching;Immunoglobulin Somatic Hypermutation;Immunoglobulin-Secreting Cells;Immunology;immunosenescence;Infection;Influenza;innovation;insight;IRF4 gene;Kinetics;Life;lymph nodes;Lymphoid;Lymphoid Tissue;Lysine;Maleimides;Maps;Mediating;Methylation;Modeling;Modification;Molecular;multiple omics;Mus;Mutate;Nature;old mice;Organoids;Persons;Phenotype;plasma cell differentiation;Plasma Cells;Plasma Enhancement;Play;Polycomb;Polyethylene Glycols;Population;Process;programs;Proliferating;promoter;Proteins;rapid testing;Reaction;Regulation;Reporting;Research;response;Role;Signal Transduction;Structure of germinal center of lymph node;T-Lymphocyte;Technology;Thick;Tissue Engineering;Tissues;transcription factor;transcriptional reprogramming;transcriptome;United States National Institutes of Health;vaccine trial;Vaccines;Work

PROJECT_TITLE: Hydrogel-Based Aged Immune Organoids to Study Epigenetics and Trajectory of B Cells

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 BBBT-X (83)]


NIH_SPENDING_CATS: Cancer;Genetics;Hematology;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: OMAHA

ORG_NAME: UNIVERSITY OF NEBRASKA MEDICAL CENTER

ORG_STATE: NE

PHR: Project Narrative Hematopoietic stem and progenitor cells (HSPCs) give rise to lineage-committed hematopoietic progenitors (e.g., the megakaryocyte-erythrocyte progenitor (MEP)) capable of differentiating to keep up with hematopoietic demand. In this proposal, I will test sterile alpha motif protein-1(SAMD1)-dependent mechanisms facilitating HSPC activity and erythroid progenitor differentiation, which will inform the development of treatments for hematological pathologies.

PI_NAMEs: SCHAEFER, MEG  (contact)

PROGRAM_OFFICER_NAME: BAI, C BRIAN

PROJECT_TERMS: Acute Myelocytic Leukemia;Amino Acid Motifs;Anemia;Binding;Binding Sites;Biological Assay;Biomedical Research;Blood Cells;Bone Marrow Transplantation;career;career development;CD34 gene;Cell Line;cell type;Cells;Chromatin;Chronic;collaborative environment;CRISPR/Cas technology;Data;Dysmyelopoietic Syndromes;Educational workshop;Enhancers;Environment;Epigenetic Process;Erythrocytes;Erythroid;Erythroid Progenitor Cells;Erythropoiesis;Erythropoietin;experimental study;Fellowship;FRAP1 gene;Gene Expression;Genes;genetic corepressor;Genetic Transcription;Goals;Hematological Disease;Hematology;Hematopoiesis;Hematopoietic;hematopoietic differentiation;Hematopoietic Neoplasms;hematopoietic stem cell fate;Hematopoietic Stem Cell Transplantation;Hematopoietic stem cells;Human;Impairment;in vivo;Institution;knock-down;Knock-out;Learning;leukemia;Link;loss of function;Lysine;Medical center;Megakaryocytes;Mus;Mutation;Nebraska;Parents;Pathology;Persons;Phenotype;Play;Probability;Process;progenitor;Prognosis;Proteins;Publishing;Regulation;Reporting;Repression;Research Proposals;Resources;Role;SAM Domain;Signal Pathway;Signal Transduction;skills;small hairpin RNA;stem cell differentiation;stem cell fate;stem cells;sterility testing;success;System;Testing;therapy development;Training;transcription factor;Transcriptional Regulation;Transplantation;Umbilical cord structure;Universities;Work;Writing

PROJECT_TITLE: Defining Mechanisms of SAMD1 in Hematopoiesis

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


NIH_SPENDING_CATS: Autism;Bioengineering;Biomedical Imaging;Brain Disorders;Cerebrovascular;Clinical Research;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Pediatric

ORG_CITY: DAVIS

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: Project Narrative Many studies utilize resting-state functional magnetic resonance imaging (rsfMRI) metrics, such as functional connectivity (FC), to study the neural underpinnings of autism; however, these findings remain inconsistent, potentially due to heterogeneity in cerebrovascular function, which modulates the blood oxygen level dependent (BOLD) signal of rsfMRI, in addition to neuronal activity. In this study, we utilize a novel, non-invasive method, based solely on rsfMRI BOLD signals, to longitudinally compare cerebrovascular reactivity (CVR), or the vasodilatory capacity of cerebral blood vessels, in autistic and non-autistic children across development (2-12 years old); and potentially identify a subgroup of autism with cerebrovascular differences. We then apply to this novel information to investigate the mechanism linking vascular function to FC and ultimately improve neuronal and vascular interpretations of functional connectivity in autism, during a period of rapid cerebrovascular growth.

PI_NAMEs: LEE, QUIMBY  (contact)

PROGRAM_OFFICER_NAME: KAU, ALICE S

PROJECT_TERMS: 12 year old;2 year old;6 year old;Adult;Adult women;Affect;Age;Aging;Air;Area;Arteries;autism spectrum disorder;autistic;autistic behaviour;Automobile Driving;Biological Factors;Blood flow;blood oxygen level dependent;Blood Vessels;Brain;Brain region;Breathing;Carbon Dioxide;career;cerebrovascular;Cerebrovascular Circulation;cerebrovascular reactivity;Cerebrovascular system;Cerebrum;Child;Childhood;Clinical;Data;Data Set;Databases;Development;Diagnosis;Diagnostic;early childhood;Early Intervention;Etiology;executive function;Female;Frequencies;Functional Magnetic Resonance Imaging;functional MRI scan;Growth;Heterogeneity;Human;Impaired cognition;improved;in vivo;Inhalation;innovation;insight;Link;Maps;Measures;Mediating;Methods;middle childhood;model of autism spectrum disorder;Modeling;Monitor;network models;neural;neuroimaging;neuroimaging marker;Neurons;novel;Participant;phenome;Physiology;Play;Population;programs;Reporting;Research Personnel;respiratory challenge;response;Rest;Role;Scanning;sex;Sex Differences;Signal Transduction;Site;Source;Stimulus;Subgroup;synergism;Techniques;Training;Translations;vascular contributions;Vasodilation;young adult

PROJECT_TITLE: Evaluating cerebrovascular reactivity in autistic and non-autistic children using resting-state functional MRI

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


ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Project Narrative The development of Type 1 Diabetes is dependent upon antigen presentation by conventional type 1 dendritic cells (cDC1) to T cells. Our goal is to develop a chimeric antigen receptor for T cells that can deplete cDC1 and prevent the development of Type 1 Diabetes. If successful, this work will establish dendritic cell subset depletion as a novel therapeutic paradigm which could be applied to multiple autoimmune diseases.

PI_NAMEs: ABOUSAWAY, OMAR  (contact)

PROGRAM_OFFICER_NAME: CASTLE, ARTHUR

PROJECT_TERMS: Address;Age;Antigen Presentation;Antigen-Presenting Cells;Antigens;Autoantigens;Autoimmune;Autoimmune Diabetes;Autoimmune Diseases;Autoimmune Responses;Autoimmunity;autoreactive T cell;autoreactivity;B-Lymphocytes;BCL2 gene;Binding;CD3 Antigens;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;Cell Count;Cell Death Induction;cell type;Cells;Cessation of life;chemokine receptor;Childhood;chimeric antigen receptor;chimeric antigen receptor T cells;Clonal Expansion;Coculture Techniques;Cross Presentation;cytokine;Data;Dendritic Cells;Development;Diabetes Mellitus;diabetic;Dimerization;Disease;Disease Progression;disulfide bond;Dominant-Negative Mutation;Dose;effector T cell;Epitopes;exhaustion;experimental study;Extracellular Domain;Flow Cytometry;FOXP3 gene;Generations;Goals;Human;human disease;Hybridomas;IL17 gene;immunoregulation;improved;in vitro Assay;in vivo;Inbred NOD Mice;Incidence;Infiltration;Insulin;insulin secretion;Insulin-Dependent Diabetes Mellitus;Interleukin-12;islet;Islets of Langerhans;JUN gene;Kinetics;Longevity;lymph nodes;Mediating;Modeling;Modification;Molecular Conformation;monomer;Morbidity - disease rate;mortality;mouse model;Mus;novel;novel therapeutics;overexpression;Pancreas;Patients;Phenotype;pre-clinical;prevent;Prevention;Prevention approach;Preventive therapy;Preventive treatment;Proliferating;Public Health;Regulatory T-Lymphocyte;Replacement Therapy;Risk;Role;single-cell RNA sequencing;Source;Specificity;Spleen;Splenocyte;T cell infiltration;T-Cell Activation;T-Cell Receptor;T-Cell Receptor Therapy;T-Lymphocyte;Therapeutic;therapeutic target;Time;Transgenic Organisms;Wild Type Mouse;Work;XCL1 gene;XCR1 gene

PROJECT_TITLE: Targeting cDC1 with CAR T cells to investigate their role and potential as a therapeutic target in Type 1 diabetes


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Cerebrovascular;Childhood Injury;Clinical Research;Neurosciences;Pediatric;Physical Activity;Physical Injury - Accidents and Adverse Effects;Physical Rehabilitation;Rehabilitation;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury;Unintentional Childhood Injury

ORG_CITY: Aurora

ORG_NAME: UNIVERSITY OF COLORADO DENVER

PHR: PROJECT NARRATIVE. Prescribing aerobic exercise as medicine after concussion is best practice for reducing patient symptom severity, but existing methods to determine the appropriate exercise prescription for individual patients are impractical and may not adequately treat the physiological systems also impacted by concussion. Our research laboratory has expertise in conducting exercise-related clinical trials and measuring physiological function in patients with concussion. Thus, our study will explore clinically feasible post-concussion exercise recommendations optimal for recovery of impaired physiological systems.

PI_NAMEs: WINGERSON, MATHEW J (contact)

PROGRAM_OFFICER_NAME: BONNER, JOSEPH FRANCIS

PROJECT_TERMS: Adolescent;Adopted;Aerobic Exercise;Age;Biological Markers;Brain;Brain Concussion;career;cerebrovascular;Cerebrovascular Disorders;Cerebrovascular system;Characteristics;Child;Chronic Orthostatic Intolerance;Clinical;clinical care;clinical implementation;Clinical Management;clinical practice;Clinical Research;Clinical Trials;Colorado;Complex;Confidence Intervals;Data;Data Science;Development;Diagnosis;doctoral student;Education;Enrollment;Ensure;Epidemiologist;Exercise;exercise intensity;exercise prescription;experience;Family;Functional disorder;functional improvement;Funding;Goals;Guidelines;Homeostasis;Impairment;improved;individual patient;Injury;innovation;Knowledge;Laboratory Research;Liquid substance;Long-Term Effects;Machine Learning;Measures;medical schools;Medicine;Mentorship;Methods;moderate-to-vigorous physical activity;multidisciplinary;novel strategies;Parents;Participant;Patient Self-Report;Patients;Pediatric Hospitals;Physicians;Physiological;Post-Concussion Syndrome;Prevention;Prognosis;Property;Recommendation;Recovery;Recovery of Function;rehabilitation science;rehabilitation strategy;Rehabilitation therapy;Research;Research Personnel;Research Project Grants;Resolution;Resources;Risk;Severities;sex;Shapes;Specialist;Sports Medicine;standard of care;Subgroup;symposium;Symptoms;System;Therapeutic;Therapeutic Effect;Time;Training;United States National Institutes of Health;Universities;Vascular blood supply;vigorous intensity

PROJECT_TITLE: A novel approach to exercise as treatment for injury-induced impairments in cerebrovascular function among adolescents with concussion


ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

ORG_STATE: NY

PHR: Extracellular attractant gradients direct migrating cells to their destination. Using a group of migrating cells in zebrafish embryos as a model, I am investigating how the extracellular matrix shapes an attractant gradient in vivo. Since erroneous cell migration underlies many diseases, my studies will provide a basis to conceive strategies for the treatment of developmental defects and disorders.

PI_NAMEs: O'KEEFFE, CATHERINE ANN (contact)

PROGRAM_OFFICER_NAME: TOYAMA, REIKO

PROJECT_TERMS: Address;Animals;Back;Binding;cancer cell;career;cell motility;Cells;chemokine;chemokine receptor;Cues;Data;Defect;Destinations;Development;Diffuse;Diffusion;Digestion;Disease;Embryo;Embryonic Development;Ensure;expectation;extracellular;Extracellular Matrix;Feedback;Genetic;genetic manipulation;genome editing;Glycosaminoglycans;Heparan Sulfate Proteoglycan;heparanase;Image;Immune response;in vivo;Individual;Institution;Investigation;Laboratories;lateral line;Measures;Mentors;Microscopy;migration;Modeling;Neoplasm Metastasis;Organ;pathogen;Peptide Hydrolases;Primordium;Proteins;Proteoglycan;quantitative imaging;receptor;Regulation;Research Personnel;Resources;Role;Route;Shapes;Signal Transduction;single-cell RNA sequencing;Source;source localization;Stromal Cell-Derived Factor 1;System;temporal measurement;Testing;Tissues;tool;Training;treatment strategy;Work;Zebrafish

PROJECT_TITLE: Regulation of a self-generated attractant gradient by the extracellular matrix

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


NIH_SPENDING_CATS: Biomedical Imaging;Biotechnology;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Digestive Diseases;Orphan Drug;Pancreatic Cancer;Rare Diseases

PHR: PROJECT NARRATIVE In this application, we will conduct a phase I clinical trial testing the safety of a novel agent that targets an integrin that is expressed at high levels in pancreatic cancer stroma. This new drug will have a dual effect on the stroma by targeting both cancer associated fibroblasts and blood vessels that aid the cancer in progression. As part of the clinical trial we will collect patient tissue and blood to determine how this novel therapy acts on cells, and evaluate the effects on blood flow to the tumor using MRI.

PI_NAMEs: EL-RAYES, BASSEL  (contact);LIU, ZHI-REN

PROGRAM_OFFICER_NAME: OLKHANUD, PUREVDORJ BALJINNYAM

PROJECT_TERMS: Address;Aftercare;angiogenesis;anti-tumor agent;Binding;Binding Sites;Biology;Biopsy;Blood;Blood flow;blood perfusion;Blood Vessels;Buffers;cancer cell;CASP8 gene;Cell Survival;Cells;chemotherapy;Clinical;Clinical Trials;Collagen;contrast enhanced;Cytoplasmic Tail;Cytotoxin;Data;Data Set;Deposition;Development;Disease;Dose;drug action;Drug Delivery Systems;Drug Kinetics;Endothelial Cells;Enrollment;Environment;extracellular;Extracellular Matrix;FDA approved;Fibroblasts;gemcitabine;Genetically Engineered Mouse;Goals;Histologic;imaging modality;Immune;Immunodeficient Mouse;Immunofluorescence Immunologic;Impairment;improved;Induction of Apoptosis;inhibitor;innovation;Integrin alphaVbeta3;Integrin Inhibition;Integrins;KPC model;Magnetic Resonance Imaging;Malignant neoplasm of pancreas;Malignant Neoplasms;Measurement;Measures;Monkeys;Mus;Neoplasms in Vascular Tissue;New Agents;non-invasive imaging;Normal tissue morphology;novel;novel therapeutics;Paclitaxel;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma model;pancreatic stellate cell;participant enrollment;Patient-Focused Outcomes;Patients;Perfusion;Pharmaceutical Preparations;Pharmacodynamics;Phase;phase 1 study;Phase I Clinical Trials;Phase Ib Trial;Phosphotransferases;pre-clinical;Pre-Clinical Model;prevent;Prior Therapy;Protein Engineering;Proteins;Rattus;Recommendation;recruit;Refractory;Resistance;response;Role;Safety;safety testing;Sampling;selective expression;single-cell RNA sequencing;Site;Stable Disease;Survival Rate;targeted agent;Therapeutic;therapy resistant;Tissues;tool;Toxic effect;Translating;treatment effect;Treatment Failure;Treatment-related toxicity;tumor;Tumor Angiogenesis;Xenograft Model;Xenograft procedure

PROJECT_TITLE: ProAgio in Pancreatic Cancer

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 CDPT-B (80)]


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Behavioral and Social Science;Clinical Research;Dissemination and Implementation Research;Pediatric;Screening and Brief Intervention for Substance Misuse;Substance Misuse;Underage Drinking

PHR: PROJECT NARRATIVE Brief Alcohol Screening and Intervention for College Students (BASICS) has been shown to be efficacious and effective in diverse settings, however additional research is needed to understand factors that may influence implementation of the intervention with adequate fidelity and sustainability in different contexts. The proposed study will fill an important gap in the literature by providing a foundation of knowledge and strategies for future implementation efforts of brief alcohol interventions on college campuses, providing lessons learned from previous and ongoing implementation attempts that have been successful in adherence to BASICS principles over time and under differing circumstances.

PI_NAMEs: METTERT, KAYNE  (contact)

PROGRAM_OFFICER_NAME: KERRIDGE, BRADLEY TOWNSEND

PROJECT_TERMS: Abstinence;addiction;Address;Adherence;Administrator;Adoption;Alcohol abuse;Alcohol consumption;alcohol effect;Alcohols;Area;behavior change;Belief;Blood alcohol level measurement;brief alcohol intervention;Brief Alcohol Screening and Intervention for College Students;brief motivational intervention;career;Characteristics;Classification;Clinical;Clinical Trials;Code;college;contextual factors;Data Collection;drinking;drinking behavior;Education;Effectiveness;effectiveness trial;efficacy trial;Environment;Evaluation;evidence base;experience;Exploration, Preparation, Implementation, and Sustainment;Face;Familiarity;Family;Family history of;Feedback;follow-up;Foundations;Future;future implementation;Gold;Grant;Harm Reduction;Health Professional;high risk;high risk drinking;implementation barriers;implementation determinants;implementation efforts;implementation intervention;implementation outcomes;implementation research;implementation science;improved;Individual;insight;International;Intervention;intervention delivery;Interview;Knowledge;Licensure;Light;Literature;Measures;Mental Health;Methodology;Methods;Modeling;motivational enhancement therapy;National Institute on Alcohol Abuse and Alcoholism;Obstruction;Online Systems;Outcome;Participant;Pattern;Perception;Personal Satisfaction;Persons;Phase;Population;preference;Prevention;Process;Professional counselor;programs;Proliferating;Provider;Public Health;Publications;Qualitative Methods;Recommendation;Recording of previous events;Reporting;Research;Resources;Risk;Sampling;Schools;Self Efficacy;skills;social norm;Structure;student drinking;student training;Students;Supervision;Surveys;telehealth;Testing;theories;Time;Training;United States;Universities;university student;Washington;welfare;Work

PROJECT_TITLE: Implementation of BASICS: Matching Effective Strategies to Address Common Barriers

STUDY_SECTION_NAME: Special Emphasis Panel[ZAA1 GG (32)]