NIH_SPENDING_CATS: Asthma;Behavioral and Social Science;Clinical Research;Conditions Affecting the Embryonic and Fetal Periods;Dissemination and Implementation Research;Endocrine Disruptors;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Effects of Indoor Air Pollution;Lung;Patient Safety;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Prevention;Social Determinants of Health

PHR: Narrative There is a dearth of research investigating associations between prenatal exposure to pesticides in urban settings and lung function and respiratory outcomes in children in Latin America, including how associations differ by child sex. Environmental health literacy will be crucial to intervention efforts, however little is known regarding household pesticide use and exposure risks. The aims of this proposal will be met through completion of a rigorous professional development and training program and conducting mentored research examining prenatal pesticide exposures and child lung function and asthma outcomes, while developing and administering an environmental health literacy scale with dissemination of associated outreach materials with long-term goals of delineating risk factors and preventing adverse respiratory outcomes.

PI_NAMEs: ALCALA, CECILIA SARA (contact)

PROGRAM_OFFICER_NAME: O'FALLON, LIAM

PROJECT_TERMS: Address;Adolescence;Age;Agriculture;Area;Asthma;Back;Biological Markers;career;Chemicals;Child;Child Development;Childhood;Cities;cohort;collaborative approach;Communication;Communities;Community Actions;community based participatory research;community engaged approach;community engaged research;community engagement;Community Health;community intervention;Community Outreach;cost effective;Data;Development;Disease;dissemination strategy;effectiveness evaluation;empowerment;Environment;Environmental Health;Environmental Risk Factor;Epidemiology;Ethnography;Exposure to;Faculty;Family;Food Contamination;Fostering;Foundations;Future;global health;Goals;Growth;Health;Health Knowledge Attitudes Practice;health literacy;House Dust;Household;Immune system;implementation science;improved;Individual;Inflammation;interest;Intervention;Joints;Knowledge;Knowledge acquisition;late life;Latin America;Lead;Life Cycle Stages;literacy;Literature;Lung;lung development;Lung Diseases;Measures;Mentors;Mentorship;Methods;Mexico;Modernization;Mothers;Obesity;Organophosphates;Outcome;outreach;Participant;patient engagement;Personal Satisfaction;Persons;pesticide exposure;Pesticides;Positioning Attribute;Pregnancy;prenatal;prenatal environmental exposure;prenatal exposure;prevent;Prevention;Procedures;programs;Prospective Studies;Public Health;public health intervention;pulmonary function;pyrethroid;Qualitative Research;Reporting;Research;Research Methodology;Research Personnel;Resources;respiratory;respiratory health;Risk;Risk Factors;Role;Sampling;Scientist;Second Pregnancy Trimester;sex;skills;social;social stressor;Statistical Methods;statistics;Symptoms;tenure track;Testing;therapy development;Third Pregnancy Trimester;Toxic effect;Toxic Environmental Substances;Toxicant exposure;Toxicology;Training;Training Programs;Translational Research;Urban Community;urban setting;Vulnerable Populations;Woman;Work

PROJECT_TITLE: A Community Partnered Approach to Assessing the Impact of Prenatal Pesticide Exposure on Child Respiratory Outcomes in Mexico City

STUDY_SECTION_NAME: Special Emphasis Panel[ZES1 BWD-D (K9)]


ADMINISTERING_IC: MH

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Mental Health;Neurosciences

ORG_CITY: COLUMBIA

ORG_COUNTRY: UNITED STATES

ORG_DEPT: OTHER BASIC SCIENCES

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA

ORG_STATE: SC

PHR: PROJECT NARRATIVE Circadian-driven clock genes cause time-of-day dependent changes in dopamine release and dopamine receptor activity in the Nucleus Accumbens. Changes in Nucleus Accumbens activity are known to alter response to stressful, aversive stimuli. Using ex vivo and in vivo approaches, we aim to assess how circadian- driven changes in the clock gene expression alter Nucleus Accumbens neuronal physiology through the dopamine 1 receptor and determine how these fluctuations vary neurobiological response to aversive stimuli.

PI_NAMEs: FRANCIS, TANNER CHASE (contact);PORCU, ALESSANDRA

PROGRAM_OFFICER_NAME: NADLER, LAURIE SUE

PROJECT_TERMS: Agonist;Anxiety;Aversive Stimulus;Behavioral;Biochemical Process;biological systems;Brain region;Calcium Signaling;cell type;Cells;circadian;circadian pacemaker;circadian regulation;Circadian Rhythms;Code;Coupled;cryptochrome 2;Cues;Cyclic AMP;Darkness;Data;Development;Disease;Dopamine;Dopamine Receptor;dopamine system;Electrophysiology (science);Environment;Exhibits;Feedback;feeding;Fiber;foot;Foundations;Gene Expression;Genes;Genetic Transcription;Human;in vivo;in vivo monitoring;insight;knock-down;Light;Mental Depression;Metabolism;Methods;molecular clock;Monitor;Mood Disorders;Moods;Mus;National Institute of Mental Health;Neurobiology;neuronal excitability;Neurons;neurophysiology;Nucleus Accumbens;optogenetics;Organism;Outcome;patch clamp;Pathway interactions;Periodicals;Periodicity;Phase;Photometry;Physiological Processes;Physiology;Potassium Channel;Predisposition;Process;Protein Inhibition;Proteins;receptor;Receptor Activation;receptor function;Receptor Mediated Signal Transduction;Receptor Signaling;Regulation;response;Rewards;Rodent;Role;sensor;Shock;Signal Pathway;Signal Transduction;Signal Transduction Pathway;Sleep;Stimulus;Testing;Time;Tyrosine 3-Monooxygenase;Ventral Tegmental Area;voltage;Wakefulness;Work

PROJECT_TITLE: Circadian regulation of dopamine 1 receptor signaling in the Nucleus Accumbens

STUDY_SECTION: BNRS

STUDY_SECTION_NAME: Behavioral Neuroendocrinology, Neuroimmunology, Rhythms, and Sleep Study Section [BNRS]


ADMINISTERING_IC: TR

IC_NAME: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES

ORG_CITY: ANN ARBOR

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: NARRATIVE Tens of thousands of children are hospitalized each year with sepsis, many of whom subsequently develop new supplemental oxygen or mechanical ventilator dependence. Currently, little is known about the timing of and risk factors for its development. The overall objective of this study is to determine when (in-hospital or after discharge) new oxygen or ventilator dependence develops and risk factors for its development.

PI_NAMEs: CARLTON, ERIN FITZGERALD (contact)

PROGRAM_OFFICER_NAME: BROWN, PATRICK

PROJECT_TERMS: Address;Age;Award;care delivery;Characteristics;Child;Chronic;Clinical;Code;Cognitive;cohort;comorbidity;cost;Critically ill children;Data;Dependence;Development;Diagnostic;Durable Medical Equipment;Emotional;Epidemiologic Factors;Face;Family;Foundations;Functional disorder;Funding;Hospital Costs;hospital readmission;Hospitalization;Hospitals;indexing;Infection;Insurance;Intervention;Knowledge;Length of Stay;Life;Mechanical ventilation;Mechanical Ventilators;Medicaid;Medical;Methodology;Morbidity - disease rate;National Center for Advancing Translational Sciences;novel;Organ;Organ failure;Outpatients;Oxygen;Patients;Pattern;pediatric sepsis;Pediatrics;prevent;Prevention;prognostication;Publishing;Recovery;recruit;Research;Research Project Grants;Respiratory Failure;Risk;Risk Factors;secondary infection;Secondary to;Sepsis;Site;supplemental oxygen;Techniques;Testing;Time;Time Factors;Ventilator;Work

PROJECT_TITLE: Timing and risk factors for developing chronic respiratory failure after pediatric sepsis

STUDY_SECTION_NAME: Special Emphasis Panel[ZTR1 CI-5 (01)]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Cancer;Orphan Drug;Ovarian Cancer;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Women's Health Research

ORG_CITY: ALBUQUERQUE

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR

ORG_STATE: NM

PHR: Project Narrative Notch signaling pathway is a therapeutic target of great interest for cancer treatment. The values of current Notch inhibitors in cancer therapy remain to be proven. Therefore, our proposal to repurpose auranofin as a novel Notch pathway inhibitor for combinational ovarian cancer therapy is of great relevance to public health.

PI_NAMEs: FAN, HUA-YING  (contact)

PROGRAM_OFFICER_NAME: O'HAYRE, MORGAN

PROJECT_TERMS: 3-Dimensional;acute T-cell lymphoblastic leukemia cell;Auranofin;Biological Markers;cancer cell;Cancer cell line;cancer drug resistance;cancer recurrence;Cancer Relapse;cancer stem cell;cancer therapy;cancer type;Cell Culture System;Cell Differentiation process;Cell Line;Cell Nucleus;Cell Proliferation;cell type;Cells;Chemoresistance;chemotherapeutic agent;chemotherapy;Chromosomal translocation;Cisplatin;Clinic;Clinical Data;Collection;Complex;D Cells;Data;Development;DNA;Dose Limiting;Drug Kinetics;Drug Synergism;drug testing;Dyes;Environment;Exclusion;FBXW7 gene;FDA approved;gamma secretase;Gene Targeting;Genes;Genetic Transcription;Goals;inhibitor;interest;Ligands;Malignant Female Reproductive System Neoplasm;Malignant neoplasm of ovary;Malignant Neoplasms;Methods;mouse model;Mutation;neoplastic cell;notch protein;Notch Signaling Pathway;NOTCH3 gene;novel;Organoids;ovarian neoplasm;overexpression;Pathway interactions;patient derived xenograft model;Patients;Peritoneal;personalized medicine;Pharmaceutical Preparations;pharmacologic;Pharmacotherapy;Platinum;Platinum Compounds;Play;Pre-Clinical Model;precision medicine;Progression-Free Survivals;Proliferating;Property;Public Health;receptor;Receptor Activation;receptor expression;Recurrence;Relapse;response;Retreatment;Role;secretase;Serous;Signal Transduction;stem cell expansion;synergism;targeted treatment;taxane;Testing;The Cancer Genome Atlas;therapeutic target;Time;Toxic effect;transcriptome;tumor;Tumor Burden

PROJECT_TITLE: Repurposing Auranofin As a Novel Notch Pathway Inhibitor for Combinational Ovarian Cancer Therapy

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 RTRB-S (O1)]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Cancer;Genetics;Immunotherapy;Kidney Disease;Orphan Drug;Rare Diseases

ORG_CITY: IRVINE

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

ORG_STATE: CA

PHR: Narrative Clear Cell Renal Cell Carcinoma (ccRCC) is a devastating disease that is projected to affect 81,800 individuals within the USA in 2023, with a complete response rate to current treatments being only 16%. Over 90% of ccRCC patients harbor genetic alterations of the von Hippel-Lindau (VHL) tumor-suppressor gene. In this proposal we aim to assess a compound that inhibits cyclin dependent kinase 9 (CDK9) as a therapeutic to selectively target ccRCC with VHL alterations.

PI_NAMEs: RAZORENOVA, OLGA V (contact)

PROGRAM_OFFICER_NAME: VENKATACHALAM, SUNDARESAN

PROJECT_TERMS: Affect;antitumor effect;Apoptosis;Architecture;bHLH-PAS factor HLF;cancer cell;cancer therapy;CDK9 Protein Kinase;Cell Line;Cells;Cessation of life;Chemicals;Clear cell renal cell carcinoma;Clinical Trials;Combined Modality Therapy;Complement;Cyclin-Dependent Kinase Inhibitor;Cyclin-Dependent Kinases;Data;Disease;Dominant-Negative Mutation;Doxycycline;Ensure;Exhibits;Genes;genetic approach;Genetic Transcription;Goals;Heterogeneity;Hypoxia Inducible Factor;hypoxia inducible factor 1;Immune;Immune checkpoint inhibitor;Immunocompetent;immunodeficiency;immunodeficient mouse model;improved;In complete remission;In Vitro;in vivo;Individual;inhibitor;Literature;Lung;Malignant Neoplasms;MCL1 gene;Mediating;Metastatic Neoplasm to the Liver;Modeling;mouse model;Mutation;Neoplasm Metastasis;neoplastic cell;Normal Cell;Normal tissue morphology;novel therapeutics;Pathway interactions;patient derived xenograft model;patient stratification;Patients;PD-1 inhibitors;Population;Primary Neoplasm;Proteins;Receptor Protein-Tyrosine Kinases;Regimen;Renal Carcinoma;Reporting;responders and non-responders;response;RNA Polymerase II;Role;Signal Pathway;single-cell RNA sequencing;small hairpin RNA;small molecule;Specificity;synergism;T-Cell Activation;Testing;Therapeutic;therapeutic candidate;therapeutic target;therapeutically effective;Tissues;transcriptome sequencing;Treatment Efficacy;tumor;tumor growth;Tumor Immunity;Tumor Markers;Tumor Suppressor Proteins;Tumor Tissue;tumor-immune system interactions;Tyrosine Kinase Inhibitor;VHL gene;Western Blotting

PROJECT_TITLE: Therapeutic targeting of VHL-deficient clear cell renal cell carcinoma

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 SRB-1 (O2)]


ADMINISTERING_IC: NR

IC_NAME: NATIONAL INSTITUTE OF NURSING RESEARCH

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Emergency Care;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Networking and Information Technology R&D (NITRD);Patient Safety;Pediatric;Prevention;Social Determinants of Health;Telehealth

ORG_CITY: SALT LAKE CITY

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: PROJECT NARRATIVE Findings from this project will provide an effective, practical, and generalizable approach to supporting home monitoring of children with medical complexity (CMC). This will also serve as a model for reducing recurring emergency department (ED) visits and hospital admissions associated with CMC, generalizable to all children with other multiple chronic conditions.

PI_NAMEs: NKOY, FLORY L (contact)

PROGRAM_OFFICER_NAME: HUSS, KAREN

PROJECT_TERMS: Accident and Emergency department;Acute;acute symptom;Adherence;Admission activity;Affect;Age;arm;Asthma;Attention;Body System;care coordination;care systems;caregiving;Caring;Child;Child health care;Child Support;Childhood;Chronic;Chronic Disease;Clinic;Complex;cost;Data;demographics;Dependence;design;Deterioration;Diabetes Mellitus;Disabled Children;Disparity population;Early Diagnosis;Early identification;Early Intervention;efficacy evaluation;Emergency department visit;ethnic minority;Ethnic Origin;experience;Family;Feedback;feeding;Fever;financial incentive;Focus Groups;follow-up;Graph;Health;Health Care Costs;health care disparity;health inequalities;health literacy;Health Personnel;Health Status;Healthcare;high risk;Home;Home Care Services;Hospitalization;Hospitalized Child;Hospitals;Impairment;improved;improved outcome;Incentives;Inequity;Length of Stay;Liquid substance;Medical;mental state;Methods;mhealth interventions;Minority;Mobile Health Application;Modeling;Monitor;Multicenter Studies;multiple chronic conditions;Neurologic;novel;Observational Study;Outcome;Pain;Parents;Pediatric Hospitals;Personal Satisfaction;physically handicapped;pilot trial;Poverty;preference;prevent;programs;Quality of life;Race;racial minority;Randomized;Recurrence;remote monitoring;Reporting;Respiratory distress;Risk;satisfaction;Seizures;Self Efficacy;Severities;social;social health determinants;Stress;Subgroup;Symptoms;System;Technology;Testing;treatment as usual;Visit;Work

PROJECT_TITLE: A Novel mHealth Intervention to Improve Outcomes of Children with Medical Complexity

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


ADMINISTERING_IC: ES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Clinical Research;Conditions Affecting the Embryonic and Fetal Periods;Endocrine Disruptors;Estrogen;Genetics;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Women's Health Research

ORG_CITY: NEW YORK

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

ORG_STATE: NY

PHR: Telomere length (TL) tracks across the life course and is a consequential trait for human health. It is critical to understand environmental factors contributing to the wide inter-individual TL variance at birth. The proposed research will leverage a large birth cohort study to investigate how prenatal exposure to phthalates, a class of endocrine-disrupting chemicals (EDCs), relates to TL, telomerase expression and activity, and cellular markers of replicative senescence in the placenta-newborn unit.

PI_NAMEs: AVIV, ABRAHAM ;COWELL, WHITNEY  (contact)

PROGRAM_OFFICER_NAME: HEACOCK, MICHELLE

PROJECT_TERMS: 8 year old;Acceleration;Adult;Age;Aging;Base Pairing;beta-Galactosidase;biobank;Biological Assay;Biological Markers;Biology;Birth;Blood;Catalytic Domain;CDKN2A gene;Cell Aging;Cell Cycle Checkpoint;Cell Physiology;Chemicals;Child;Child Health;Childhood;Chronic Disease;cohort;Cohort Studies;Collaborations;consumer product;Cosmetics;Data;Disease;DNA Damage;Embryo;Endocrine Disruptors;Enrollment;Environment;Environmental Exposure;Environmental Risk Factor;Enzymes;Epidemiologist;epidemiology study;Estrogen Receptors;Estrogens;Exhibits;experience;Experimental Models;exposed human population;Exposure to;Female;follow-up;Food Packaging;Foundations;Functional disorder;Future;Genetic Transcription;Health;Human;in utero;In Vitro;Individual;insight;inter-individual variation;Investigation;Knowledge;late life;Length;Leukocytes;Life;Life Cycle Stages;lifestyle factors;Ligands;Link;Longevity;male;Measurement;Measures;Mediating;middle childhood;Molecular;molecular marker;Mothers;New York;Newborn Infant;novel;Nuclear Hormone Receptors;Onset of illness;Organ;Outcome;Pathway interactions;Perinatal;Phenotype;phthalates;Placenta;Plasticizers;Positioning Attribute;Pregnancy;prenatal;prenatal environmental exposure;prenatal exposure;Production;prospective;Public Health;Regulation;Research;Risk;RNA-Directed DNA Polymerase;Sampling;senescence;sex;sexual dimorphism;Southern Blotting;Telomerase;telomere;Telomere Shortening;Testing;tool;trait;Umbilical Cord Blood;Universities;Variant;women versus men;Work

PROJECT_TITLE: Impact of Phthalate Exposure on Telomere Biology in Utero

STUDY_SECTION_NAME: Special Emphasis Panel[ZES1 LWJ-K (TL)]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biotechnology;Clinical Research;Genetics;Human Genome;Pediatric;Primary Immunodeficiencies;Rare Diseases

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Project Narrative Inborn errors of immunity are broad group of genetic defects of the immune system that lead to human disease. We have identified patients with susceptibility to infection due to abnormal antibody responses and B cell maturation. In this application, we will identify how immune cell function is altered in these patients, and test a specific gene that we have identified as altered in patients but not healthy individuals, thus having the potential to define a new human disease and provide important insight into how the human immune response is regulated.

PI_NAMEs: COOPER, MEGAN ANNE (contact)

PROGRAM_OFFICER_NAME: MORRIS FEARS, MARGARET A

PROJECT_TERMS: 4 year old;Affect;Affinity;Agonist;Antibodies;Antibody Formation;Antibody Response;Autoimmunity;autosome;B cell differentiation;B-Cell Activation;B-Lymphocytes;Bacteremia;Cell Maturation;Cell Physiology;Chromosome 14;clinical diagnosis;congenital immunodeficiency;Data;Defect;Development;Diagnosis;Disease;disease-causing mutation;DNA;exome sequencing;Family;Family member;Fathers;Female;Gene Expression Regulation;Generations;Genes;Genetic;Genetic Diseases;Genetic Enhancer Element;genetic variant;Genome engineering;genome sequencing;Genomics;Goals;Human;human disease;humoral immunity deficiency;IGH@ gene cluster;Immune;Immune response;Immune system;Immune System Diseases;Immunoglobulin Class Switching;Immunoglobulin G;Immunoglobulin Somatic Hypermutation;Immunoglobulins;improved;In Vitro;Individual;Infection;Inheritance Patterns;Inherited;insight;interest;Interleukin-4;Investigation;Laboratories;Ligands;male;Malignant Neoplasms;Memory B-Lymphocyte;Mission;Molecular;molecular targeted therapies;Mutation;notch protein;novel;overexpression;Pathway interactions;Patient Care;Patients;peripheral blood;Phenotype;PIK3CG gene;Plasma Cells;Plasmablast;Pneumococcal vaccine;Predisposition;Proliferating;Proteins;Recurrence;Regulation;Research;response;Rest;RNA analysis;Serum;Siblings;Signal Pathway;Signal Transduction;Specific antibody deficiency;stem;Stimulus;Streptococcus pneumoniae;Syndrome;Testing;Thymus Gland;TNFSF5 gene;Transcriptional Regulation;transcriptome sequencing;Untranslated RNA;Vaccination;Variant;Work

PROJECT_TITLE: Investigation of a Novel Inborn Error of Immunity with B Cell Deficiency

STUDY_SECTION: CMIB

STUDY_SECTION_NAME: Cellular and Molecular Immunology - B Study Section[CMIB]


ADMINISTERING_IC: GM

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Genetics

ORG_CITY: SEATTLE

ORG_NAME: FRED HUTCHINSON CANCER CENTER

ORG_STATE: WA

PHR: PROJECT NARRATIVE Transcription factors (TFs) play a central role in regulating gene expression and cell identity. As DNA replication removes TFs from DNA and occludes TF binding sites, it is unclear when and how TFs reassociated with nascent DNA. This proposal outlines a series of experiments to determine the kinetics, modality, and impact of TF binding to newly synthesized DNA.

PI_NAMEs: WOOTEN, MATTHEW  (contact)

PROGRAM_OFFICER_NAME: MCINTYRE, JEREMY COLIN

PROJECT_TERMS: Address;Antineoplastic Agents;Architecture;Binding;Binding Sites;Biological Models;Bromodeoxyuridine;career;cell fate specification;cell type;Cells;Chromatin;Chromatin Fiber;Chromatin Modeling;Chromatin Structure;Coupled;Data Analyses;Defect;design;Disease;DNA;DNA Binding;DNA biosynthesis;DNA Polymerase II;DNA replication fork;DNA Sequence;Drosophila genus;Epigenetic Process;Eukaryota;experimental study;Failure;Fiber;Foundations;Gene Expression;Gene Expression Profile;Genetic Transcription;human disease;in vivo;inhibitor;innovation;insight;intercalation;Kinetics;Knowledge;Link;Maintenance;Malignant Neoplasms;Maps;Mediating;Methods;Modality;Molecular;novel;Nucleosomes;Nucleotides;Play;Positioning Attribute;preservation;Process;Proteins;Refractory;Replication Origin;Replication-Associated Process;Research;Research Personnel;Resolution;RNA;RNA Binding;RNA Polymerase II;Role;Sampling;Series;single molecule;small molecule;Specific qualifier value;Structure;System;targeted treatment;Techniques;Testing;Therapeutic Intervention;Time;Tissues;Training;transcription factor;Transcriptional Regulation;Visualization

PROJECT_TITLE: Visualizing transcription factor binding and chromatin assembly on newly synthesized DNA

STUDY_SECTION_NAME: Special Emphasis Panel[ZGM1 TWD-8 (KR)]


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

ORG_CITY: Boulder

ORG_DEPT: MISCELLANEOUS

ORG_NAME: UNIVERSITY OF COLORADO

ORG_STATE: CO

PHR: Project Narrative More than 80% of human protein coding genes are alternatively spliced, effectively increasing the proteome in comparison to the total number of genes. While transposable elements have been largely recognized to provide alternative promoters and enhancers, their contribution to the protein coding sequences is still debated. The goal of this proposal is to understand how transposable elements shape the evolution and diversification of vertebrate proteomes, as well as which events and mechanisms promote their origin and affect their expression.

PI_NAMEs: PASQUESI, GIULIA IRENE MARIA  (contact)

PROJECT_TERMS: adaptive immune response;Affect;Alternative Splicing;Alu Elements;arms race;Biological;Case Study;Cells;Code;constitutive expression;CRISPR screen;Data;Data Set;design;DNA Transposable Elements;Elements;Enhancers;Event;Evolution;Exons;experimental study;Gene Proteins;Genes;Genetic;Genetic Transcription;Genome;Genome engineering;genome-wide;Genomics;Goals;Human;human data;Human Genome;human tissue;Immune;immune function;Immune response;Immunology procedure;immunoregulation;Incidence;Inflammatory Response;interest;Interferon Receptor;Interferon Type I;Interferons;Knock-in;Knock-out;Learning;Life;Macrophage;Messenger RNA;MicroRNAs;Modeling;Modernization;Molecular;Mutation;novel;pathogen;Pathway interactions;Pattern;Peptides;Phenotype;Primary Cell Cultures;Primates;Process;promoter;Protein Isoforms;Proteins;Proteome;Proteomics;receptor;Recurrence;Regulation;Repression;Reproducibility;Research;RNA Splicing;RNA-Binding Proteins;Role;Shapes;Signal Transduction;Site-Directed Mutagenesis;Source;Spliced Genes;Techniques;Testing;Tissues;Training;Transcript;transcriptome;transcriptome sequencing;Trees;type I interferon receptor;Variant;Virus Diseases;Work

PROJECT_TITLE: Understanding how transposons generate new immune gene protein-coding splice variants


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Childhood Injury;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Dissemination and Implementation Research;Emergency Care;Health Services;Mental Health;Mental Illness;Pediatric;Prevention;Serious Mental Illness;Suicide;Suicide Prevention;Violence Research;Youth Violence;Youth Violence Prevention

ORG_CITY: CHICAGO

ORG_NAME: LURIE CHILDREN'S HOSPITAL OF CHICAGO

ORG_STATE: IL

PHR: Project Narrative / Public Health Relevance Statement Suicide is the third leading cause of death among youth ages 12 to 17 in the United States, and emergency department visits by youth for suicidal thoughts or behaviors are increasing over time. There is a critical need to implement evidence-based interventions to prevent youth suicide during the high-risk period after an emergency department visit. To fill this gap, this study will determine the feasibility and acceptability of delivering Caring Contacts (brief messages of care and concern) via text message to adolescents with suicidal thoughts or behaviors after an emergency department visit to reduce suicide risk.

PI_NAMEs: HOFFMANN, JENNIFER ANN (contact)

PROGRAM_OFFICER_NAME: SIMS, BELINDA ENITA

PROJECT_TERMS: acceptability and feasibility;Accident and Emergency department;Address;Adolescent;Adult;Age;Award;care delivery;career;Caring;Cause of Death;Child;comparison group;Consolidated Framework for Implementation Research;Data;digital;digital mental health;effective intervention;Effectiveness of Interventions;effectiveness outcome;effectiveness research;effectiveness/implementation hybrid;effectiveness/implementation study;Emergency department visit;Emergency Department-based Intervention;Emergency Medicine;Evaluation;evidence base;Evidence based intervention;experience;Feeling;Feeling suicidal;field study;follow-up;Foundations;Goals;Health Services Research;high risk;Hospitals;implementation context;implementation evaluation;implementation facilitators;implementation outcomes;implementation science;implementation strategy;Individual;inpatient psychiatric treatment;Intervention;intervention refinement;Interview;Logistics;Maps;Mental Health;Mentored Patient-Oriented Research Career Development Award;Mentorship;Military Personnel;National Institute of Mental Health;Outcomes Research;Outpatients;Participant;pediatric emergency;Phase;Physicians;Population;Positioning Attribute;preference;prevent;preventive intervention;Process;psychiatric emergency;psychiatric inpatient;psychosocial;public health relevance;Randomized, Controlled Trials;recruit;reducing suicide;Research;Research Activity;Research Personnel;Resources;Safety;Sampling;Schedule;Structure;suicidal adolescent;suicidal behavior;suicidal morbidity;suicidal risk;Suicide;Suicide attempt;Suicide prevention;suicide rate;Surveys;Target Populations;Testing;Text Messaging;text messaging intervention;Therapeutic Intervention;Time;Training;Training Activity;Translations;United States;Update;user centered design;Visit;Work;Youth

PROJECT_TITLE: Caring Contacts via text message for suicidal adolescents after emergency department discharge

STUDY_SECTION: SERV

STUDY_SECTION_NAME: Mental Health Services Study Section[SERV]


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Genetics;Infectious Diseases;Tickborne Diseases;Vector-Borne Diseases

ORG_CITY: PULLMAN

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: WASHINGTON STATE UNIVERSITY

PHR: PROJECT NARRATIVE Rickettsiales are a diverse order of obligate intracellular bacteria, including many pathogens vectored to humans by arthropods. A lack of genetic tools for rickettsial agents has long hindered molecular dissection of the host- pathogen interactions that allow these bacteria to cause disease. In our project we are introducing systems into the rickettsial pathogen Anaplasma phagocytophilum to enable the identification and characterization of infection determinants.

PI_NAMEs: BRAYTON, KELLY ANN (contact);PARK, JASON MICHAEL

PROGRAM_OFFICER_NAME: PERDUE, SAMUEL S

PROJECT_TERMS: Alleles;Anaplasma phagocytophilum;Arthropod Vectors;arthropod-borne;Arthropods;Bacteria;beta-Lactamase;Biological;Biological Assay;Biological Models;Biological Process;Biology;Cell Physiology;Cells;Complex;conditional knockout;Cytosol;Data;Dependence;design;Disease;Dissection;Engineering;Essential Genes;Gene Combinations;Gene Deletion;Genes;Genetic;genetic manipulation;Genetic Transcription;Genome;homologous recombination;Host Defense;Human;in vivo;inducible gene expression;Infection;interest;Kinetics;Knock-out;knockout gene;Life Cycle Stages;Link;Luciferases;machine learning algorithm;Mammals;Mediating;Molecular;Monitor;mutant;Nature;Nutrient;Organism;Parasites;pathogen;Phase;Phenotype;promoter;Proteins;Public Health;real time monitoring;Reporter;Rickettsia;System;Techniques;Testing;Tetracyclines;Titrations;tool;tool development;Type IV Secretion System Pathway;Vacuole;vector;vector-borne pathogen

PROJECT_TITLE: Tool development for Anaplasma phagocytophilum to understand determinants of infection

STUDY_SECTION_NAME: Special Emphasis Panel[ZAI1 FDS-M (S1)]


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Aging;Bioengineering;Biomedical Imaging;Brain Disorders;Cerebrovascular;Clinical Research;Clinical Trials and Supportive Activities;Disability Research;Neurosciences;Physical Rehabilitation;Rehabilitation;Stroke

ORG_DEPT: PHYSICAL MEDICINE & REHAB

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

PHR: PROJECT NARRATIVE Many stroke survivors experience movement impairment on one side of the body, which we believe is caused by alternative neural pathways being recruited to produce movements when the normal pathways connecting the brain and body are injured. Ideally, we want to develop rehabilitation interventions to preferentially strengthen the normal pathways, but we do not currently have a method to assess what pathways a given intervention is using. To address this, our project uses functional MRI to map neural activity in the brain, brainstem, and spinal cord, to determine how different neural pathways contribute to hand movement following stroke.

PI_NAMEs: BRIGHT, MOLLY G (contact)

PROGRAM_OFFICER_NAME: BONNER, JOSEPH FRANCIS

PROJECT_TERMS: Activities of Daily Living;Address;Affect;arm;Automobile Driving;Axon;Bilateral;Brachial Paresis;Brain;Brain Stem;Cervical spinal cord structure;Chronic;chronic stroke;Contralateral;Corticospinal Tracts;Data;Data Set;Dependence;design;Devices;Diffuse;Diffusion Magnetic Resonance Imaging;Electroencephalography;experience;Fatigue;Feedback;force feedback;Functional Imaging;Functional impairment;Functional Magnetic Resonance Imaging;functional near infrared spectroscopy;Goals;grasp;Hand;hand dysfunction;hand grasp;hand rehabilitation;Handedness;hemiparetic stroke;Human;Image;imaging approach;imaging study;Imaging Techniques;Impairment;improved;Individual;injured;innovation;insight;interest;Intervention;Ipsilateral;Joints;large datasets;Limb structure;Magnetic Resonance Imaging;Maps;Measures;Methods;Motor;motor control;motor deficit;motor impairment;Motor Neurons;Motor Pathways;Movement;Muscle;neural;Neural Pathways;neuroimaging;Neurons;novel;Paresis;Participant;Pathologic;Pathway interactions;Pattern;Persons;pharmacologic;Physiological;Population;Positioning Attribute;post stroke;Reaction;recruit;Rehabilitation therapy;Research;Residual state;response;Reticular Formation;Scanning;Sensitivity and Specificity;Side;Signal Transduction;Spinal Cord;Stroke;stroke hemiparesis;stroke intervention;stroke rehabilitation;stroke survivor;structural imaging;Structure;synergism;System;theories;Time;tool;Upper Extremity;white matter;Work

PROJECT_TITLE: Mapping Corticoreticulospinal Motor Control Using Brainstem and Spinal Cord fMRI in Chronic Hemiparetic Stroke

STUDY_SECTION: CHHD

STUDY_SECTION_NAME: Function, Integration, and Rehabilitation Sciences Study Section[CHHD-K]


FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

ORG_CITY: ATLANTA

ORG_DEPT: PATHOLOGY

ORG_NAME: MOREHOUSE SCHOOL OF MEDICINE

ORG_STATE: GA

PHR: Narrative: This G-RISE training program addresses the critical need for development of a sustainable diverse pool of biomedical scientists as leading investigators for the 21st century. This will be accomplished by developing and implementing innovative strategies that expands on the strengths of existing programs at MSM.

PI_NAMEs: DEBRUYNE, JASON P;HARRIS-HOOKER, SANDRA  (contact);STILES, JONATHAN K.

PROGRAM_OFFICER_NAME: BLATCH, SYDELLA ANNE

PROJECT_TERMS: Training

PROJECT_TITLE: G-RISE: Educating and Training Tomorrow's Biomedical Workforce

STUDY_SECTION: TWD

STUDY_SECTION_NAME: Training and Workforce Development Study Section - C[TWD-C]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Cancer;Cardiovascular;Cerebrovascular;Clinical Research;Dementia;Hematology;Hodgkin's Disease;Lung;Lymphatic Research;Lymphoma;Neurodegenerative;Neurosciences;Physical Activity;Rare Diseases;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: MEMPHIS

ORG_NAME: ST. JUDE CHILDREN'S RESEARCH HOSPITAL

ORG_STATE: TN

PHR: RELEVANCE Survivors of Hodgkin Lymphoma (HL) have an elevated risk for chronic cardiopulmonary health conditions, cerebrovascular problems, and late-onset neurocognitive impairment. This research aims to determine if radiation and chemotherapy, which can cause damage to the cardiopulmonary system, are also associated with reduced cardiopulmonary functional reserve, and dysregulated cerebral blood flow (CBF). The findings from this study could lead to the development of improved screening, risk assessment, and interventions to improve brain blood flow, cardiopulmonary function, neurocognitive outcomes, and quality of life.

PI_NAMEs: PHILLIPS, NICHOLAS S (contact)

PROGRAM_OFFICER_NAME: DIMOND, EILEEN

PROJECT_TERMS: Adult;Age;aortic arch;Attenuated;Bleomycin;Blood;Blood flow;Brain;Brain imaging;Breast;Cancer Survivor;Carbon Dioxide;Cardiac;Cardiac Output;Cardiopulmonary;cardiopulmonary system;Carotid Arteries;cerebrovascular;Cerebrovascular Circulation;Cerebrovascular Disorders;cerebrovascular pathology;Chemoreceptors;chemotherapy;Chemotherapy and/or radiation;Chest;Child;Chronic pulmonary heart disease;Classification;cohort;Cohort Studies;Communities;comparison control;Data;Demographic Factors;Deposition;Development;Diffuse;Diffusion;Disease;disease diagnosis;Echocardiography;Electrocardiogram;Enrollment;Ethnic Origin;Evaluation;Exercise;Exercise Test;experience;Frequencies;Functional disorder;Gases;Health;Heart Rate;Hemosiderin;high risk;Hodgkin Disease;Hodgkin Lymphoma survivors;Imaging Techniques;Impairment;improved;Incidence;indexing;Intervention;Late Effects;Lead;leukemia;Leukocytes;Leukoencephalopathy;Link;Lung;Lymphocyte;Magnetic Resonance Imaging;Malignant Neoplasms;Measures;Medical;Monitor;Morbidity - disease rate;Near-Infrared Spectroscopy;Neck;Neurocognitive;Neurocognitive Deficit;neurocognitive test;neuroimaging;non-invasive imaging;novel;Outcome;Oxygen;Oxygen Consumption;Participant;Patient Recruitments;Population;prospective;Pulmonary function tests;Quality of life;Race;Radiation;Radiation Dose Unit;Radiation therapy;receptor;recruit;Regulation;Research;Rest;Risk;Risk Assessment;Saint Jude Children's Research Hospital;Sampling Studies;screening;sex;Siblings;Structure of parenchyma of lung;Survivors;System;Systems Analysis;Techniques;Testing;therapy development;Translating;Treatment Factor;ventilation;VO2max;wearable device

PROJECT_TITLE: Cardiopulmonary function and cerebral blood flow in Hodgkin Lymphoma survivors

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 SRB-K (O1)]


ADMINISTERING_IC: DC

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities

ORG_CITY: BOSTON

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: NORTHEASTERN UNIVERSITY

ORG_STATE: MA

PHR: PROJECT NARRATIVE Little is known about the vocal communication of minimally-speaking individuals – they lack quantitative measures designed to specifically capture their subtle vocal development over time, limiting our ability to meaningfully measure their skills, monitor their growth during clinical trials, or create vocal-based augmentative technology for this exceptional population. This proposal aims to generate a sensitive, quantitative metric of vocal communication for minimally-speaking individuals using a novel remote and highly personalized data collection methodology. The results of this work will allow us to determine sensitive vocal communication milestones for profoundly affected minimally-speaking individuals and appropriate outcome measures for clinical trials and interventions.

PI_NAMEs: JOHNSON, KRISTINA TERESA (contact)

PROGRAM_OFFICER_NAME: RIVERA-RENTAS, ALBERTO L

PROJECT_TERMS: Acoustics;Affect;Age;age group;Benchmarking;Caregivers;Clinical;clinical outcome measures;Clinical Trials;clinically relevant;Communication;Complex;cost;data collection methodology;Databases;design;Development;Engineering;Enrollment;Environment;Equipment;Exhibits;Family;Family member;General Population;Genetic Transcription;Growth;Home;human old age (65+);Individual;Infant;Intervention;K-Series Research Career Programs;Label;Language;machine learning algorithm;Maps;Measures;Mentorship;minimally verbal;mobile computing;Monitor;novel;Outcome Measure;Participant;phonology;Physics;Population;rate of change;Reporting;Research;Research Personnel;Research Priority;Sampling;Signal Transduction;skills;smartphone application;sound;Speech;Standardization;Technology;Time;Toddler;Training;Translating;Treatment Efficacy;Visit;vocalization;Work

PROJECT_TITLE: Using Mobile Technology and Real-World Vocalization Samples to Generate Quantitative Metrics of Vocal Communication for Minimally-Speaking Individuals

STUDY_SECTION: CDRC

STUDY_SECTION_NAME: Communication Disorders Review Committee[CDRC]


ADMINISTERING_IC: DA

FUNDING_MECHANISM: SBIR-STTR RPGS

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Drug Abuse (NIDA only);Neurosciences;Opioid Misuse and Addiction;Opioids;Pain Research;Substance Misuse

ORG_CITY: andover

ORG_NAME: EVODENOVO, INC.

PHR: Project Narrative  The opioid epidemic has emerged as a major public health crisis, characterized by high relapse rates and adverse side effects that compromise the effectiveness of existing treatments. EvoDenovo proposes to develop novel, non-opioid-based therapies that dissociate the behavioral and analgesic effects of opioids. We will optimize small molecule inhibitors of a new anti-opioid target for their efficacy in modulating opioid effects in mouse models. Successful completion has the potential to reduce healthcare costs and fulfill the unmet need of OUD sufferers. EvoDenovo RFA-DA-23-021 / PI: Sid A. Labed Project Narrative - Page 1 of 1

PI_NAMEs: LABED, SID AHMED  (contact)

PROGRAM_OFFICER_NAME: NGUYEN, TAM L

PROJECT_TERMS: Absence of pain sensation;Address;Affect;Analgesics;analog;antagonist;Behavioral;behavioral study;Biological Availability;Biology;Brain;Buprenorphine;Caenorhabditis elegans;Chemicals;Clinical Trials;clinically relevant;commercialization;Conduct Clinical Trials;Dependence;design;Development;Dissociation;drug development;Drug Kinetics;drug metabolism;Drug Targeting;Effectiveness;efficacy evaluation;Evaluation;FDA approved;G Protein-Coupled Receptor Signaling;G-Protein-Coupled Receptors;Genetic;global health;Goals;GTP-Binding Proteins;Health Care Costs;Human;in vivo;Individual;inhibitor;Knockout Mice;Lead;lead optimization;Ligands;manufacture;manufacturing process development;Marketing;metabolic abnormality assessment;Methadone;Modeling;Modification;Molecular;mouse model;mu opioid receptors;multidisciplinary;Mus;Neurons;non-opioid analgesic;novel;novel therapeutics;Opiate Addiction;Opioid;opioid abuse;opioid epidemic;Opioid replacement therapy;opioid use;opioid use disorder;opioid withdrawal;Orphan;Pain management;pain relief;Patients;Persons;Pharmaceutical Chemistry;Pharmaceutical Preparations;pharmacologic;Pharmacology;Phase;Physiological;Positioning Attribute;preclinical evaluation;prescription opioid;preservation;Property;Public Health;receptor;Regimen;Relapse;Research;response;Risk;risk mitigation;Rodent;scaffold;Secure;segregation;Series;side effect;Signal Pathway;Slice;small molecule;small molecule inhibitor;small molecule therapeutics;standard of care;Structure-Activity Relationship;Substance Withdrawal Syndrome;success;Symptoms;System;Technical Expertise;Testing;Therapeutic;Time;Toxic effect;Toxicology;Withdrawal Symptom

PROJECT_TITLE: Development of small molecule therapeutics for mitigating opioid withdrawal syndrome

STUDY_SECTION_NAME: Special Emphasis Panel[ZDA1 SAI-S (A1)]


ADMINISTERING_IC: DE

ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Congenital Structural Anomalies;Dental, Oral, and Craniofacial Disease;Genetics;Human Genome;Pediatric;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Embryonic - Non-Human;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: HOUSTON

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

ORG_STATE: TX

PHR: PROJECT NARRATIVE Craniofacial deformity often involves cranial sutures, and adequate understanding of the molecular mechanism underlying cranial suture development is urgently demanded for exploring new diagnostic and therapeutic methods for cranial diseases, such as craniosynostosis and sutural agenesis. Neural crest cells, a multipotent stem cell population during embryonic stage, make great contributions to cranial suture development, especially frontal (metopic) suture. I proposed a multipronged approach to understand how the neural crest-derived cranial suture is coordinately regulated by the complicated signaling network, and how this contributes to the cranial suture development and related diseases, in order to explore novel and critical factors for the diagnostic and therapeutic of cranial suture diseases.

PI_NAMEs: ZHAO, XIAOLEI  (contact)

PROGRAM_OFFICER_NAME: THIRUMANGALATHU, SHOBA

PROJECT_TERMS: Affect;Aftercare;Binding;Bioinformatics;Biological Assay;career;Cell Lineage;Cell Nucleus;Cells;Cephalic;Chromatin;Cleavage Under Targets and Release Using Nuclease;Collaborations;Complex;craniofacial;craniofacial development;Craniosynostosis;Data;Defect;Deformity;Development;Diagnosis;Diagnostic Factor;Differentiation Antigens;Disease;Embryo;FGF2 gene;Fibroblast Growth Factor;Frontal bone structure;gain of function mutation;Genes;genome-wide;Goals;Human;human embryonic stem cell;in vivo;induced pluripotent stem cell;Joint structure of suture of skull;knock-down;Knowledge;large datasets;Learning;Ligation;MAPK3 gene;Maps;Mentors;Mesenchymal Stem Cells;Methods;Modeling;Molecular;molecular phenotype;Morphology;multiple omics;multipotent cell;Multipotent Stem Cells;Mus;Mutant Strains Mice;Mutation;Natural regeneration;Neural Crest;Neural Crest Cell;novel;novel diagnostics;novel therapeutics;Occupations;Pathologic;Pathway interactions;Phase;Phenotype;Phosphorylation;Population;Publishing;Regulation;repaired;Reporting;Repression;Research;Research Personnel;response;Role;self-renewal;Signal Transduction;single cell ATAC-seq;single-cell RNA sequencing;Site;skills;Small Interfering RNA;stem cell population;stem cells;stemness;Surgical sutures;suture fusion;Techniques;Testing;Therapeutic;Tissues;Training;transcriptome sequencing;Writing

PROJECT_TITLE: A signaling crosstalk regulation in neural crest-derived cranial suture

STUDY_SECTION: DSR

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


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Brain Disorders;Cancer;Gene Therapy;Genetics;Immunotherapy;Lung;Lymphatic Research;Nanotechnology;Orphan Drug;Rare Diseases;Tuberous Sclerosis;Women's Health Research

ORG_CITY: Boston

ORG_NAME: TUFTS UNIVERSITY MEDFORD

PHR: Narrative We propose to develop mRNA therapy using lung-targeting lipid nanoparticle, for lymphangioleiomyomatosis (LAM), a destructive lung disease caused by inactivating mutations in TSC1 or TSC2. We will reprogram LAM cells with a TSC2 mutation back to a “normal” state without affecting normal tissue, and can re-normalize the LAM immune microenvironment. The success of this study will open a new therapeutic paradigm of mRNA therapy for LAM with the potential of durable effect and complete remission.

PI_NAMEs: TANG, YAN ;XU, QIAOBING  (contact)

PROGRAM_OFFICER_NAME: VUGA, LOUIS J

PROJECT_TERMS: Acrylamides;Adverse effects;Affect;Alleles;Amides;Amines;Back;cancer infiltrating T cells;Categories;Cell Reprogramming;Cells;circular RNA;clinical translation;Combination immunotherapy;Control Groups;COVID-19 vaccine;Cytostatics;Data;design;Development;Disease;disease model;Disease remission;Engineering;enzyme replacement therapy;FDA approved;Formulation;Genes;Genetic Diseases;Hybrids;Hyperactivity;Immune;improved;In complete remission;in vivo;inhibitor;Lesion;lipid nanoparticle;lipidomics;Lung;Lung Diseases;Lung Lymphangioleiomyomatosis;Lung Transplantation;Lymphangioleiomyomatosis;Medicine;Messenger RNA;metabolome;metabolomics;Modality;Modeling;Modification;Molecular;Molecular Mechanisms of Action;mouse model;mRNA delivery;multimodality;multiple omics;Mus;Mutation;nanocomplexes;nanoparticle;nanoparticle delivery;Nature;Nodule;Normal tissue morphology;novel therapeutic intervention;novel therapeutics;Organ;Pathway interactions;Patients;pre-clinical;preclinical study;Production;programs;Proteins;Proteomics;pulmonary function;rare genetic disorder;Reaction;Replacement Therapy;response;restoration;RNA;RNA replacement;Series;side effect;single cell analysis;Sirolimus;Specificity;Structure;success;System;T cell infiltration;T-Lymphocyte;Tail;Testing;Therapeutic;therapeutic RNA;Time;transcriptome;transcriptomics;Treatment Efficacy;TSC2 gene;Tuberous Sclerosis;tumor;Tumor Burden;tumor growth;tumor microenvironment;Tumor Suppressor Genes;tumor-immune system interactions;Withholding Treatment

PROJECT_TITLE: Develop lung-targeted synthetic lipid nanoparticles for mRNA medicine treating pulmonary lymphangioleiomyomatosis

STUDY_SECTION: BMBI

STUDY_SECTION_NAME: Biomaterials and Biointerfaces Study Section[BMBI]


NIH_SPENDING_CATS: Aging;Biodefense and Related Countermeasures;Biotechnology;Clinical Research;Clinical Trials and Supportive Activities;Emerging Infectious Diseases;Genetics;Immunization;Infectious Diseases;Influenza;Pneumonia and Influenza;Prevention;Vaccine Related

ORG_CITY: MELBOURNE

ORG_COUNTRY: AUSTRALIA

ORG_FIPS: AS

ORG_NAME: UNIVERSITY OF MELBOURNE

PHR: Project narrative There is no consensus on preferred format or regime to maximise responsiveness towards influenza vaccines in older adults. We will leverage our existing biobank of a completed randomised control trial of enhanced influenza vaccines to comprehensively define immunity at the cellular, antibody and transcriptional level to derive how enhanced vaccines benefit older adults. This will provide mechanistic insights into innate and adaptive immune changes that occur during the aging process and the functional consequences to vaccine responses.

PI_NAMEs: DOAK, SOPHIE ALESSANDRA VALKENBURG (contact)

PROGRAM_OFFICER_NAME: PRABHUDAS, MERCY R

PROJECT_TERMS: adaptive immunity;Adjuvant;Age;age effect;age group;aged;aging process;Antibodies;Antibody Response;antigen-specific T cells;Antigens;Avidity;B-Cell Antigen Receptor;B-Lymphocytes;biobank;Biological Markers;CD8-Positive T-Lymphocytes;Cell model;Cellular Immunity;chimeric antigen receptor T cells;Clonal Expansion;Communication;Consensus;cross reactivity;cytokine;Data Analyses;data integration;Dose;experience;Flow Cytometry;Formulation;Genetic Transcription;Geriatrics;Helper-Inducer T-Lymphocyte;high dimensionality;Immune;immune function;Immune response;Immunity;immunogenicity;improved;In Vitro;Inactivated Vaccines;Influenza;Influenza vaccination;influenza virus vaccine;influenzavirus;insight;Maps;Measures;Molecular;Molecular Target;Monoclonal Antibody Therapy;Morbidity - disease rate;Mutation;novel vaccines;older adult;older driver;Outcome;Participant;Peptide/MHC Complex;Phenotype;Population;preempt;pressure;randomized trial;Randomized, Controlled Trials;Recommendation;respiratory infection virus;response;Schedule;seroconversion;Serum;Shapes;single-cell RNA sequencing;ST14 gene;T cell response;T-Cell Receptor;T-Lymphocyte;Therapeutic;Therapeutic Intervention;United States National Institutes of Health;universal vaccine;Vaccination;vaccine development;vaccine failure;vaccine response;Vaccines;Variant

PROJECT_TITLE: REINVIGORATE: Repeated Enhanced INfluenza Vaccines In Geriatrics of a Randomised trial for Antibody and T cell Effects

STUDY_SECTION_NAME: Special Emphasis Panel[ZAI1 VSR-I (S1)]


NIH_SPENDING_CATS: Autism;Behavioral and Social Science;Brain Disorders;Caregiving Research;Clinical Research;Clinical Trials and Supportive Activities;Disability Research;Dissemination and Implementation Research;Intellectual and Developmental Disabilities (IDD);Mental Health;Pediatric;Prevention

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

PHR: PROJECT NARRATIVE The proposed Looking and Language Project (LoLa) will test the theoretical model that looking to the mouth of a speaker in infancy influences later language via caregiver-child engagement and prelinguistic vocal complexity via a longitudinal correlational study and an intervention study. In the K99 phase, I will evaluate conduct the longitudinal correlational study, evaluate the feasibility of a novel intervention that encourages looking to the mouth of a speaker, and conduct a qualitative study to learn about caregivers’ attitudes and perceived barriers towards interventions for infants with autistic older siblings (Baby Sibs), who are highly likely be diagnosed with autism or developmental language disorder. In the R00 portion, I will conduct a randomized controlled trial to assess (a) the effect of the novel intervention on caregiver strategy use, looking to the mouth of a speaker, caregiver-child engagement, prelinguistic vocal complexity, and language and (b) the acceptability of the intervention approach to interested parties in the autism community.

PI_NAMEs: FELDMAN, JACOB I (contact)

PROJECT_TERMS: Adolescent;Adult;Advocate;Age;aged;Attention;Attitude;audiovisual speech;Auditory;autism community;Autism Diagnosis;autism spectrum disorder;autistic;autistic children;Award;Behavior;Brain;Businesses;caregiver education;Caregivers;Child;clinical translation;Clinical Trials;Communities;Correlation Studies;Data;Development;Diagnosis;Early Intervention;Education;Educational process of instructing;efficacy testing;follow-up;Goals;implementation barriers;implementation science;individuals with autism spectrum disorder;infancy;Infant;innovation;interest;Intervention;Intervention Studies;Language;Language Development;Language Development Disorders;Language Disorders;language outcome;Learning;Life;Linguistics;Literature;Longitudinal Studies;Mediating;member;Methodology;Methods;novel;novel strategies;Oral cavity;Outcome;Outcome Measure;Outcome Study;Parents;Phase;Population;Postdoctoral Fellow;pre-doctoral;preemptive intervention;Procedures;Productivity;provider intervention;psychosocial;Qualitative Methods;Qualitative Research;Randomized, Controlled Trials;recruit;Research;Research Methodology;Research Personnel;Siblings;skills;Source;Speech;standard of care;Testing;Theoretical model;theories;Training;Translational Research;treatment and outcome;Visual;Vocation

PROJECT_TITLE: Looking and Language


NIH_SPENDING_CATS: Cancer;Digestive Diseases;Immunotherapy;Infectious Diseases;Orphan Drug;Pancreatic Cancer;Rare Diseases

ORG_CITY: LA JOLLA

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Project Narrative  Pancreatic tumors have low mutational burdens rendering them largely resistant to current immunotherapies. We propose a novel approach using a tumor penetrating peptide (iRGD) and cytomegalovirus (CMV)-specific antigens to re-direct pre-existing CMV immunity against these tumors.

PI_NAMEs: BENEDICT, CHRISTOPHER A;HURTADO DE MENDOZA, TATIANA  (contact)

PROGRAM_OFFICER_NAME: SOMMERS, CONNIE L

PROJECT_TERMS: Accounting;Animals;anti-cancer;anti-tumor immune response;Antigens;antiviral immunity;cancer cell;cancer immunotherapy;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;CD8B1 gene;checkpoint therapy;chemotherapy;Clinical;clinical efficacy;Clinical Trials;clinically relevant;Culture Media;cytokine;Cytomegalovirus;Data;Development;Enzyme-Linked Immunosorbent Assay;Epitopes;experimental study;Extravasation;Flow Cytometry;gemcitabine;Grant;Growth;Herpesviridae;Histology;Human;immune checkpoint blockade;Immune response;Immune system;Immunity;Immunofluorescence Immunologic;Immunotherapy;Implant;improved;Incubated;Individual;Injections;Integrin alphaV;Intra-abdominal;Long-Term Survivors;Malignant neoplasm of gastrointestinal tract;Malignant neoplasm of pancreas;Malignant Neoplasms;Measures;Mediating;Medicine;Memory;Methods;microorganism antigen;Modeling;mouse model;Murid herpesvirus 1;Mus;Mutation;Mutation Analysis;Necrosis;neoantigens;neoplastic cell;Neuropilin-1;novel strategies;optimal treatments;Pancreas;pancreatic cancer cells;pancreatic cancer model;pancreatic neoplasm;Patients;Penetration;Peptides;personalized medicine;Persons;Pharmaceutical Preparations;Phase II Clinical Trials;Phenotype;Population;Production;Resected;Resistance;Site;Slice;Solid;Solid Neoplasm;subcutaneous;T cell infiltration;T cell response;T memory cell;T-Cell Activation;T-Cell Proliferation;T-Lymphocyte;T-Lymphocyte Epitopes;Testing;Therapeutic;translational potential;tumor;tumor growth;tumor microenvironment;Tumor Promotion;Tumor Tissue;tumor-immune system interactions;ultrasound;Viral;Viral Antigens

PROJECT_TITLE: Harnessing Cytomegalovirus (CMV)-specific T-cells for pancreatic cancer immunotherapy

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 SRB-F (O1)]


NIH_SPENDING_CATS: Cancer;Digestive Diseases;Genetics;Orphan Drug;Pancreatic Cancer;Rare Diseases;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Stem Cell Research - Nonembryonic - Human

ORG_CITY: WILMINGTON

ORG_NAME: GLAX, LLC

ORG_STATE: DE

PHR: Project Narrative The main goal of this application is to identify and validate SATB2 inhibitors for the treatment of pancreatic cancer using molecular docking, molecular dynamics simulations, and in vitro cell culture approaches. Since SATB2 is highly expressed in pancreatic cancer tissues, it is an attractive target for therapy.

PI_NAMEs: SRIVASTAVA, RAKESH K. (contact)

PROGRAM_OFFICER_NAME: CHEN, WEIWEI

PROJECT_TERMS: Affect;Amino Acids;Antineoplastic Agents;Apoptosis;Binding;Binding Proteins;Biological Assay;c-myc Genes;Cancer Cell Growth;Cancer Etiology;Cancer Relapse;cancer stem cell;CD44 gene;Cell Culture Techniques;Cell Proliferation;Cell Survival;Cessation of life;chemotherapy;Chemotherapy and/or radiation;ChIP-seq;chromatin remodeling;Conduct Clinical Trials;Data;design;Development;Disease;Distant;Docking;Dose;Drug Combinations;drug resistance development;drug testing;Ductal Epithelial Cell;effective therapy;efficacy validation;embryonic stem cell;Epithelium;Exhibits;FDA approved;Future;Gene Expression;Generations;Genes;Genetic Transcription;Goals;Growth;Human;human pluripotent stem cell;improved;In Vitro;in vivo;Inhibition of Cell Proliferation;inhibitor;innovation;International;Laws;Malignant - descriptor;Malignant neoplasm of pancreas;Malignant Neoplasms;Marketing;Measures;Mesenchymal;meter;Molecular;molecular dynamics;Mus;Neoplasm Metastasis;Normal Cell;novel;Nuclear Matrix-Associated Proteins;Oncogenic;Organ;overexpression;Pancreas;pancreatic cancer cells;pancreatic cancer model;pancreatic cancer patients;Pancreatic duct;pancreatic neoplasm;Pathway interactions;patient derived xenograft model;Patient-Focused Outcomes;Patients;Pharmaceutical Preparations;pharmacokinetics and pharmacodynamics;Play;pluripotency;pre-clinical;Primary Neoplasm;Prognosis;Proliferating;Property;Proteins;Quantitative Reverse Transcriptase PCR;Recurrent tumor;Regulator Genes;Resistance;Role;screening;self-renewal;side effect;small hairpin RNA;spheroids;STAT1 gene;stem cell biomarkers;stem cell self renewal;Structure;Survival Rate;targeted treatment;Testing;Time;Tissues;Toxic effect;transcription factor;Treatment Failure;tumor initiation;Tumorigenicity;Western Blotting

PROJECT_TITLE: Discovery of SATB2 Inhibitors for Pancreatic Cancer


ORG_CITY: IRVINE

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: PROJECT NARRATIVE The population of the world is aging. Age impacts the body’s response to vaccines by reducing the quality and quantity of antibodies which are the main way vaccines provide protection from infectious disease. This proposal will study how aging affects B cells, the cells that make antibodies, therefore allowing the development of better vaccines.

PI_NAMEs: NICHOLAS, DEQUINA ANGELINA (contact);SKOWRONSKA-KRAWCZYK, DOROTA ;WAGAR, LISA

PROJECT_TERMS: adaptive immunity;Address;Adult;Affect;Affinity;Age;age effect;age group;age related;age related changes;aged;Aging;aging population;Antibodies;Antibody Affinity;Antibody Response;Antigens;Archives;Area;Autopsy;B-Lymphocyte Subsets;B-Lymphocytes;Blood;cell age;Cell Aging;Cell Physiology;cell type;Cells;Cellular biology;Cessation of life;Clonal Expansion;cohort;Collaborations;Communicable Diseases;Complement;cytokine;design;Development;Epigenetic Process;extracellular;Flow Cytometry;flu;Foundations;Functional disorder;Gene Expression Profile;Genetic Transcription;High Prevalence;Human;human old age (65+);Immune;Immune system;Impairment;improved;In Vitro;influenza virus vaccine;Intrinsic factor;Knowledge;Longitudinal cohort;Lymphoid Tissue;Maps;Mediastinal lymph node group;Mediator;Memory B-Lymphocyte;Metabolism;Modeling;Molecular;Mus;National Institute on Aging;novel;older adult;Organoids;Participant;peripheral blood;Persons;Phenotype;Population;Positioning Attribute;Productivity;programs;receptor;recruit;Research;response;Role;Sampling;Serum;single-cell RNA sequencing;Sorting;Spleen;Structure of germinal center of lymph node;System;T-Lymphocyte;Technical Expertise;Testing;Time;Tissues;Tonsil;transcriptome;transcriptome sequencing;Vaccination;Vaccine Design;vaccine efficacy;vaccine immunogenicity;vaccine response;Vaccines;young adult

PROJECT_TITLE: Impact of aging on human B cell vaccine responses


NIH_SPENDING_CATS: Bioengineering;Genetics;Human Genome;Immunization;Immunotherapy;Infectious Diseases;Prevention;Vaccine Related

ORG_CITY: CINCINNATI

ORG_NAME: CINCINNATI CHILDRENS HOSP MED CTR

ORG_STATE: OH

PHR: Narrative  Immune-cell memory induced by prior exposure to a pathogen or vaccination provides enhanced protection against a subsequent infection with the same pathogen; yet the molecular mechanisms by which immune cells “remember” previous exposures – over the course of a lifetime – are poorly understood. Here, we combine experimental measurement with mathematical modeling to uncover the epigenetic mechanisms by which immune-cell memory is maintained. The resulting models will provide new insights of value to human health, as immunological memory not only underlies pathogen defense but is dysregulated in many diseases, including autoimmune, allergy and cancer.

PI_NAMEs: BARSKI, ARTEM  (contact);MIRALDI, EMILY

PROGRAM_OFFICER_NAME: GONDRE-LEWIS, TIMOTHY A

PROJECT_TERMS: 3-Dimensional;Address;Allergic Disease;anti-cancer;Antigen-Presenting Cells;Antigens;Asthma;Autoimmune;Autoimmune Diseases;Autoimmunity;Automobile Driving;Binding;Binding Sites;candidate identification;Cell Nucleus;Cell Proliferation;Cells;Characteristics;Chromatin;chromatin modification;chromatin remodeling;Clonal Expansion;Collaborations;computer studies;Computing Methodologies;cytokine;Cytokine Gene;Cytokine Signaling;Data;data integration;Disease;DNA;Endowment;Engineering;Enhancers;Epigenetic Process;epigenome;Event;experimental study;Exposure to;Family;fighting;Gene Expression;Gene Expression Regulation;gene regulatory network;Genes;genome resource;genome-wide;Health;Human;Hypersensitivity;Immune;Immune response;Immunity;Immunologic Memory;improved;Individual;Infection;Inflammatory;insight;Knowledge;Lead;life span;Maintenance;Malignant Neoplasms;Maps;mathematical model;Mathematics;Measurement;Mediating;member;Memory;Methods;Minor;Modeling;Molecular;Molecular Conformation;network models;new technology;NF-kappa B;novel;nuclear factors of activated T-cells;Nuclear Translocation;pathogen;pathogen exposure;Pathologic;Population;promoter;rapid technique;Regulatory Element;Research Design;response;Rest;risk variant;Role;Signal Transduction;single cell ATAC-seq;single cell genomics;single-cell RNA sequencing;Site;SP1 gene;System;T memory cell;T-Cell Activation;T-Lymphocyte;transcription factor;Transcription Factor AP-1;Tumor Immunity;Vaccination;Vaccines

PROJECT_TITLE: An experimentally-refined, dynamic gene regulatory network model of T-cell memory

STUDY_SECTION: MABS

STUDY_SECTION_NAME: Modeling and Analysis of Biological Systems Study Section[MABS]


ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

PHR: Project Narrative This project deals with natural killer (NK) cells which are immune cells that can control infections and tumors. NK cells have potent mechanisms to attack and destroy abnormal cells and promote inflammation, processes that must be controlled, termed tolerance. Here the Yokoyama laboratory presents preliminary evidence using novel experimental tools that will be used in the current proposal to study how NK cells are prevented from inadvertent attack.

PI_NAMEs: YOKOYAMA, WAYNE M. (contact)

PROGRAM_OFFICER_NAME: JOFFE, AARON MICHAEL

PROJECT_TERMS: Abnormal Cell;Affect;Affinity;Alleles;autoreactivity;Cells;Clinic;Complementary DNA;Complex;CRISPR/Cas technology;cytokine;Data;Education;Event;Evolution;Family;Genes;genome editing;Human;Immune;Impairment;Infection Control;Inflammation;Investigation;killer immunoglobulin-like receptor;Knock-in;Knock-in Mouse;Knockout Mice;Laboratories;Lectin;Licensing;Ligands;Major Histocompatibility Complex;Mediating;MHC Class I Genes;Modeling;Mus;Mutant Strains Mice;Natural Killer Cells;NK Cell Activation;Normal tissue morphology;novel;Pathologic;Phenotype;prevent;Process;Production;receptor;Receptor Activation;Receptor Cell;receptor function;Research;response;Signal Transduction;Specificity;Surveys;Tissues;tool;tumor

PROJECT_TITLE: Natural Killer Cell Tolerance to Self

STUDY_SECTION: III

STUDY_SECTION_NAME: Innate Immunity and Inflammation Study Section[III]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Diabetes;Nutrition;Obesity;Physical Activity;Prevention

ORG_CITY: Aurora

ORG_NAME: UNIVERSITY OF COLORADO DENVER

PHR: PROJECT NARRATIVE Physical activity is a cornerstone of the prevention and management of type 2 diabetes, but recommendations still need to be optimized. Our preliminary data suggest that performing multiple short bouts of activity (5 minutes) throughout the day to frequently interrupt sedentary time may be even better to control glucose than the standard approach of single daily continuous bouts of physical activity. We propose to examine whether and how breaking up prolonged sitting, a potential practical strategy, improves glucose control (independent of physical activity) in adults with prediabetes, a population that is at high risk of developing type 2 diabetes.

PI_NAMEs: BERGOUIGNAN, AUDREY  (contact)

PROGRAM_OFFICER_NAME: GOROSPE, RAFAEL

PROJECT_TERMS: Acute;Address;Adult;Adult women;Advocate;American;Behavioral;Biopsy;blood glucose regulation;Body mass index;Calorimetry;carbohydrate metabolism;Carbohydrates;Chronic;Clinical;clinically relevant;combat;Continuous Glucose Monitor;Data;Development;diabetes risk;epidemiologic data;Exercise;Exposure to;Fasting;Fatty acid glycerol esters;Gases;Glucose;glucose disposal;glucose transport;glucose uptake;glycemic control;Glycogen;Glycosylated hemoglobin A;Goals;Guidelines;Health;high risk;Hour;improved;Individual;Infusion procedures;Ingestion;Inpatients;insight;Insulin;insulin sensitivity;Interruption;Intervention;intravenous glucose tolerance test;IRS1 gene;Kinetics;Knowledge;Length;male;Measurement;Measures;Mediating;men;Metabolic;Methods;Modeling;Molecular;Muscle;Non-Insulin-Dependent Diabetes Mellitus;novel strategies;Obesity;OGTT;Overweight;oxidation;Participant;Pathway interactions;Persons;Phosphorylation;Physical activity;PIK3CG gene;Pilot Projects;Plasma;Population;Populations at Risk;Prediabetes syndrome;preservation;prevent;Prevention;progression risk;Publishing;Randomized;Recommendation;Regulation;Research;response;Rest;Risk;Risk Factors;Risk Reduction;sedentary;sedentary lifestyle;Signaling Protein;Skeletal Muscle;Testing;therapy design;Time;total energy expenditure;Tracer;uptake;Walking;Woman

PROJECT_TITLE: Breaking up sedentary behaviors to improve glucose control in a population at risk for developing type 2 diabetes

STUDY_SECTION: CIDO

STUDY_SECTION_NAME: Clinical and Integrative Diabetes and Obesity Study Section[CIDO]


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Cocaine;Drug Abuse (NIDA only);Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Neurosciences;Opioids;Stimulant Use and Misuse;Substance Misuse;Women's Health Research

ORG_CITY: WINSTON-SALEM

ORG_DEPT: NEUROSCIENCES

ORG_NAME: WAKE FOREST UNIVERSITY HEALTH SCIENCES

ORG_STATE: NC

PHR: Environment, social factors and sex are variables that influence vulnerability, maintenance, withdrawal and treatment outcome in human drug addiction. The research proposed in this application will examine all three phases of addiction with a focus on the kappa opioid receptor (KOR) system and extend behavioral (cocaine self-administration), pharmacological (long-term cocaine exposure) and brain changes (using positron emission tomography), in socially housed female and male monkeys. Results from these studies should aid in the development of personalized medicine strategies for drug addiction and the implementation of the KOR system across the addition cycle.

PI_NAMEs: JOHNSON, BERNARD N (contact)

PROGRAM_OFFICER_NAME: BABECKI, BETH

PROJECT_TERMS: Abstinence;abuse liability;Acute;acute stress;addiction;Animal Model;Animals;Autopsy;Behavioral;Binding;Biological Markers;Brain;Characteristics;Chronic;clinically relevant;clinically significant;Cocaine;Cocaine Abuse;cocaine exposure;cocaine overdose;cocaine self-administration;cocaine use;Cocaine use disorder;Darkness;Development;Dopamine;Dopamine Receptor;dopamine system;Dose;drug abuse vulnerability;Drug Addiction;drug of abuse;Dynorphins;Environment;Euphoria;Exhibits;experience;FDA approved;Female;Human;imaging study;Individual;Intake;interest;Intravenous;kappa opioid receptors;Laboratories;Ligands;Literature;Maintenance;male;Measures;Mediating;Modeling;Monkeys;Negative Reinforcements;Neurobiology;Neuronal Plasticity;non-drug;nonhuman primate;Opioid agonist;Opioid Receptor Binding;overdose death;Patients;personalized medicine;Pharmaceutical Preparations;pharmacologic;Pharmacotherapy;Phase;Phenotype;Positron-Emission Tomography;Predisposition;prolonged abstinence;Psychological reinforcement;psychostimulant;Public Health;radiotracer;receptor;receptor binding;receptor function;Regulation;Reporting;Research;Research Design;Research Project Grants;response;Role;Scanning;Schedule;Self Administration;sex;Sex Differences;sex variable;Side;social;Social Behavior;social factors;Social status;Study Subject;System;Tracer;Treatment outcome;Withdrawal;Work

PROJECT_TITLE: Kappa Opioid Receptor Availability, Social Rank, and Cocaine Self-Administration in Female and Male Monkeys


NIH_SPENDING_CATS: Brain Disorders;Cancer;Neurosciences

ORG_NAME: METHODIST HOSPITAL RESEARCH INSTITUTE

PHR: This study leverages powerful predictive modeling of cell-cell communications (CCCExplorer) to delineate the complex pro- and anti-metastatic astrocyte molecular mechanisms, the astrocyte-tumor interaction evolution during disease progression, and their manipulations, in order to provide a valuable means of targeting astrocyte-cancer cell interactions in brain metastasis.

PI_NAMEs: WONG, STEPHEN TC (contact);ZHAO, HONG

PROGRAM_OFFICER_NAME: JHAPPAN, CHAMELLI

PROJECT_TERMS: Anatomy;Animals;Antibody Therapy;Apoptosis;Astrocytes;Biological Assay;Biology;Blood - brain barrier anatomy;blood-brain barrier function;blood-brain barrier penetration;blood-brain tumor barrier;Brain;brain cell;Brain Diseases;Brain Pathology;brain tissue;Breast;cancer cell;Cancer Model;Cancer Patient;cancer recurrence;cancer site;cancer type;CCR5 gene;Cell Communication;Cell model;Cells;Central Nervous System Agents;Cessation of life;chemotherapy;Clinical;Coculture Techniques;comparative;Complex;Computer Models;crizotinib;Data;Development;diagnostic biomarker;diagnostic development;Disease;Disease Progression;Drug Combinations;drug repurposing;early detection biomarkers;Early Diagnosis;Endothelium;Epidermal Growth Factor Receptor;Evolution;Extravasation;Future;gain of function;Growth;Human;I Kappa B-Alpha;IL6 gene;improved;In Vitro;in vivo;Incidence;innovation;kinase inhibitor;knowledge integration;loss of function;Lung;Macrophage;Malignant Neoplasms;MAP Kinase Gene;Mediating;Melanoma;Metastatic malignant neoplasm to brain;Methods;Microglia;Molecular;mouse model;multiplexed imaging;Mus;Nature;Neoplasm Metastasis;neoplastic cell;Neuroglia;Neurosciences;neurosurgery;novel;novel therapeutic intervention;Organ;Outcome;p38 Mitogen Activated Protein Kinase;Paracrine Communication;Pathogenesis;Patients;Penetration;pharmacologic;Physiological;predictive modeling;primary outcome;Process;Protein Secretion;Proteins;Radiation therapy;RANTES;repository;response;Seminal;Signal Pathway;Signal Transduction;small molecule inhibitor;Stimulus;Testing;Therapeutic;Therapeutic Agents;Time;tool;transcriptome sequencing;Trastuzumab;Treatment outcome;treatment response;tumor;Tumor stage;Tumor-Secreted Protein;Xenograft procedure

PROJECT_TITLE: Systematic identification of astrocyte-tumor crosstalk regulating brain metastatic tumors

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


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Drug Abuse (NIDA only);Methamphetamine;Neurosciences;Prescription Drug Misuse;Stimulant Use and Misuse;Substance Misuse

ORG_CITY: CHICAGO

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF CHICAGO

PHR: Project Narrative People differ in their initial behavioral responses to psychomotor stimulant drugs in ways that affect risk for future use or abuse. One source of individual differences may be variation in the brain circuits that mediate the drugs' effects, the same circuits that process other types of reward. In this study, we will examine individual differences in responses to a single dose of methamphetamine on the brain reward circuit in healthy adults, and determine the relationship of these effects to the behavioral rewarding effects of the drug.

PI_NAMEs: DE WIT, HARRIET  (contact)

PROGRAM_OFFICER_NAME: FEDOTA, JOHN RAPHAEL

PROJECT_TERMS: Acute;addiction;Adult;Affect;aged;American;Amphetamines;attentional bias;Behavior;Behavior assessment;behavior prediction;Behavioral;behavioral response;Biological;Brain;Brain region;Corpus striatum structure;Cues;Dependence;Dimensions;Dose;Drug abuse;Drug Experimentation;Drug usage;Euphoria;Exhibits;experience;financial incentive;Functional Magnetic Resonance Imaging;functional MRI scan;Future;Goals;Human;Imaging Techniques;indexing;Individual;Individual Differences;individual response;individual variation;Laboratories;Learning;Link;Measures;Mediating;Methamphetamine;methamphetamine effect;Methodology;misuse of prescription only drugs;neural;Neurobiology;nonmedical use;novel;paired stimuli;Persons;Pharmaceutical Preparations;Placebos;preference;prescription stimulants;Procedures;Process;prototype;Public Health;Reporting;response;Rest;reward anticipation;reward circuitry;reward processing;Rewards;Risk;Risk Factors;risk prediction;Sampling;Source;Stimulant;stimulant dependence;stimulant use;stimulant use disorder;Surveys;System;Techniques;Transcranial magnetic stimulation;Variant;women versus men;young adult;young woman

PROJECT_TITLE: Determinants of Drug Preference in Humans

STUDY_SECTION: BRLE

STUDY_SECTION_NAME: Biobehavioral Regulation, Learning and Ethology Study Section[BRLE]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

ORG_CITY: GRAND RAPIDS

ORG_NAME: VAN ANDEL RESEARCH INSTITUTE

PHR: Project Narrative Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are a common cause of autosomal dominant, familial Parkinson's disease (PD) and the LRRK2 gene contributes to the risk of sporadic PD. Our studies aim to explore novel mechanisms by which mutant forms of LRRK2 lead to neuronal damage in cultured neurons and rat models of PD by elucidating the contribution of enzymatic activity. These studies will have important implications for understanding the molecular pathophysiology of LRRK2-associated PD and for therapeutic drug discovery.

PI_NAMEs: MOORE, DARREN JOHN (contact)

PROGRAM_OFFICER_NAME: SULLIVAN, LUIS FLANAGAN

PROJECT_TERMS: Accounting;adenoviral mediated;Adult;Affinity Chromatography;Animal Model;Attenuated;autosome;Binding;Brain;C-terminal;Cells;Code;Complex;Cultured Cells;Data;Development;Disease;dopaminergic neuron;drug discovery;Etiology;Functional disorder;Gene Silencing;Gene Transfer;Genes;Genetic;Genetic Variation;GTP Binding;Guanosine Triphosphate;Guanosine Triphosphate Phosphohydrolases;Hydrolysis;Impairment;in vivo;Induced Neurons;insight;kinase inhibitor;knock-down;Knowledge;Link;LRRK2 gene;Mass Spectrum Analysis;Mediating;Methodology;Modeling;Molecular;Movement Disorders;mutant;Mutation;Nerve Degeneration;neurodegenerative phenotype;Neurons;neuroprotection;neurotoxic;neurotoxicity;nigrostriatal dopaminergic pathway;novel;novel therapeutics;Outcome;overexpression;Parkinson Disease;Pathogenicity;pharmacologic;Phase I Clinical Trials;Phenocopy;Phosphoric Monoester Hydrolases;Phosphorylation;Phosphotransferases;pre-clinical;Protein Kinase;Proteins;rab GTP-Binding Proteins;Rattus;Risk;risk variant;Rodent;Rodent Model;Role;sporadic Parkinson's Disease;Substantia nigra structure;Tertiary Protein Structure;Testing;Therapeutic;therapeutic target;Tissues;Untranslated RNA;Validation;Variant;Viral

PROJECT_TITLE: LRRK2 Enzymatic Mechanisms of Neurodegeneration in Parkinson's Disease

STUDY_SECTION: NOMD

STUDY_SECTION_NAME: Neural Oxidative Metabolism and Death Study Section[NOMD]


NIH_SPENDING_CATS: Clinical Research;Genetics;Hematology;Infectious Diseases;Rare Diseases

ORG_CITY: DENVER

ORG_NAME: NATIONAL JEWISH HEALTH

PHR: PROJECT NARRATIVE Mutations in the spliceosome represent the most common class of mutations found in patients with Myelodysplastic Syndrome. We are investigating the effect of these mutations on patient host defense with the goal of understanding how these mutations influence patient infection risk.

PI_NAMEs: ALPER, SCOTT  (contact)

PROGRAM_OFFICER_NAME: LEITNER, WOLFGANG W

PROJECT_TERMS: Accounting;Bacteria;Bacterial Infections;Blood Cells;Cause of Death;Cell Differentiation process;Cell Physiology;cell type;Cells;Cessation of life;Chemotaxis;Clinical Data;clinical practice;Colorado;Defect;Disease;Dysmyelopoietic Syndromes;Engineering;Exhibits;Gene Mutation;Genes;genomic data;Goals;Hematologic Neoplasms;Hematopoietic stem cells;Host Defense;Human;Immune signaling;Immune System Diseases;in vivo;Infection;infection rate;infection risk;Lead;Link;Macrophage;mouse model;Mus;mutant;Mutate;Mutation;Myeloid Cells;neutrophil;next generation sequencing;patient health information;Patient risk;Patients;Phagocytosis;Play;Predisposition;Production;programs;risk stratification;Role;Sampling;Signal Pathway;Spliced Genes;Spliceosomes;SRSF2 gene;Technology;Testing;Toll-like receptors;Universities

PROJECT_TITLE: MDS-Associated Spliceosome Mutations Regulate Host Defense


ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Prostate cancer (PCa) remains an incurable disease once progression to the metastatic castration-resistant (mCRPC) state occurs, a state in which we have identified fibroblast activation protein (FAP) as a key feature of the PCa-supportive, immunosuppressive tumor microenvironment permissive to disease progression that is upregulated on the surface of tumor-associated macrophages (TAMs), mesenchymal stem cells (MSCs), and carcinoma-associated fibroblasts (CAFs). The objectives of this proposal are to identify PCa disease states most likely to respond to FAP-targeted therapy as well as evaluating the efficacy, specificity, and toxicity of a novel first-in-class FAP-activated mitochondrial protoxin in advanced preclinical model systems that accurately recapitulate key clinical features of human PCa. Short-term benefits include a greater understanding of how FAP+ cells contribute to PCa pathophysiology particularly with respect to their interaction with the immune system, while providing the necessary preclinical proof-of-principal data needed to translate this innovative therapeutic platform into the clinic over the longer-term.

PI_NAMEs: BRENNEN, WILLIAM NATHANIEL (contact)

PROGRAM_OFFICER_NAME: AGYIN, JOSEPH KOFI

PROJECT_TERMS: abiraterone;advanced disease;Androgen Receptor;Androgens;Anthelmintics;anti-tumor immune response;Antitumor Response;assault;Binding;Biological Models;cancer cell;Cancer Patient;Carcinoma;Castration;Cell Cycle;cell type;Cells;Classification;Clinic;Clinical;clinically relevant;Clustered Regularly Interspaced Short Palindromic Repeats;combat;Cytotoxic T-Lymphocytes;Data;Dependence;design;Disease;Disease Progression;Distant Metastasis;Drug Kinetics;effectiveness evaluation;efficacy evaluation;Embryo;enzalutamide;experimental study;extracellular;Extracellular Fluid;FDA approved;fibroblast-activating factor;Fibroblasts;Functional disorder;Future;Genetically Engineered Mouse;Goals;Growth;Hormonal;hormone therapy;Human;Immune;immune checkpoint blockade;Immune system;Immunologic Surveillance;Immunologics;In Vitro;in vivo;indexing;Individual;Infiltration;innovation;insight;Knockout Mice;Laboratories;lipophilicity;lymph nodes;Malignant neoplasm of prostate;Malignant Neoplasms;Membrane;men;Mesenchymal Stem Cells;Metabolic;Metastatic Prostate Cancer;Mitochondria;Modeling;Mus;Myeloid-derived suppressor cells;nanomolar;Neoplasm Metastasis;Neurosecretory Systems;Normal tissue morphology;novel;Nutrient;Oral;Outcome;Oxidative Phosphorylation;Parasites;patient derived xenograft model;patient population;Patients;Pattern;Pelvic lymph node group;Peptide Hydrolases;permissiveness;Pharmaceutical Preparations;Phenotype;Population;pre-clinical;Pre-Clinical Model;Production;Property;Prostate;prostate cancer progression;Prostate Cancer therapy;protein expression;recruit;Reporting;Resistance;resistance mechanism;response;Role;Series;small molecule;Specificity;Specimen;Stromal Cells;Stromal Neoplasm;Surface;T cell infiltration;targeted treatment;Testing;Therapeutic;Therapeutic Index;Time;Tissues;Toxic effect;Transgenic Model;Transgenic Organisms;Translating;Translations;tumor;tumor growth;tumor microenvironment;tumor progression;Tumor-associated macrophages;tumor-immune system interactions;tumorigenic;Xenograft procedure

PROJECT_TITLE: A First-in-Class FAP-activated Protoxin to disrupt the Tumor-Stroma Parasitic Cycle fueling lethal Prostate Cancer Progression

STUDY_SECTION: DMP

STUDY_SECTION_NAME: Drug Discovery and Molecular Pharmacology Study Section[DMP]


NIH_SPENDING_CATS: Cancer;Digestive Diseases;Genetics;Immunotherapy;Orphan Drug;Pancreatic Cancer;Radiation Oncology;Rare Diseases

ORG_CITY: BRONX

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

PHR: NARRATIVE Carbon ion radiotherapy (CIRT) is currently the world’s most advanced radiotherapeutic technique; compared with traditional photon radiotherapy, it has unique physical characteristics and biological advantages. It is better at protecting the normal tissue and organs surrounding the tumor and is more effective at killing tumor tissue and particularly tumor cells that can normally resist photon radiotherapy. While X-ray therapy using photons travel through our body, carbon ion is like a dart. It stops at a depth inside our body and releases all its energy in the form of a peak dose in the tumor. Since the track stops at a depth, the particle beam does not go through the body, thereby causing less harm to surrounding normal tissues. Since the particles cause DNA damage and the irradiated cells behave as if they are infected by a DNA virus and increase the body’s anti-viral defense system. We are looking into possible immune activating role of CIRT that possibly helps us fight cancer. We are going to look into the immunological consequences of CIRT for the treatment of pancreatic cancer, a devastating disease where we are losing our battle. Our goal is to determine the immunological effectiveness of CIRT compared to XRT (X rays) in mouse pancreatic cancer models for the treatment of both primary and metastatic cancer. If successful, this will allow us to bring a very sophisticated therapy for our cancer patients.

PI_NAMEs: GUHA, CHANDAN  (contact)

PROGRAM_OFFICER_NAME: BUCHSBAUM, JEFFREY

PROJECT_TERMS: Ablation;absorption;adaptive immunity;Address;Anti-CD40;anti-PD-1;anti-PD1 antibodies;Antibodies;Antigen Presentation;antigen processing;Biological;C57BL/6 Mouse;Cancer Etiology;Cancer Patient;Carbon;Carbon ion;Cell surface;Cells;Cessation of life;Characteristics;chemoradiation;Clinical;clinical efficacy;clinically relevant;Coculture Techniques;Combination immunotherapy;Combined Modality Therapy;compare effectiveness;Complex;design;Disease;Disseminated Malignant Neoplasm;Distant Metastasis;DNA;DNA Damage;DNA Double Strand Break;DNA Viruses;Dose;dosimetry;Effectiveness;Engineering;Epigenetic Process;epigenetic silencing;Event;exhaust;Experimental Designs;Exposure to;fighting;Fire - disasters;Genetically Engineered Mouse;Goals;Heavy Ions;High-LET Radiation;Histocompatibility Antigens Class I;Histone Deacetylase;Histone Deacetylase Inhibitor;Immune;Immune Evasion;Immune response;Immunity;Immunocompetent;immunodeficient mouse model;immunogenic;Immunologics;immunoregulation;Immunosuppression;Immunotherapeutic agent;Immunotherapy;improved;In Vitro;in vivo;indexing;Infiltration;inhibitor;interest;Interferon Type I;ionization;Irradiated tumor;irradiation;kinetic model;Linear Energy Transfer;Local Therapy;Malignant neoplasm of pancreas;Malignant Neoplasms;Measurement;Measures;member;Methods;MHC Class I Genes;Modality;Modeling;Molecular;mouse model;Mus;Myeloid Cells;Natural Immunity;Nature;Neoplasm Metastasis;neoplastic cell;Normal tissue morphology;Organ;Outcome;pancreas radiation therapy;pancreatic cancer cells;pancreatic cancer model;pancreatic cancer patients;pancreatic neoplasm;particle;particle beam;Patients;Pattern;Photons;Phototherapy;Prediction of Response to Therapy;prognostic of survival;programmed cell death protein 1;programs;Proteins;proton therapy;Protons;Quality of life;Radiation;Radiation therapy;Radio;randomized trial;Relative Biological Effectiveness;repaired;Reporting;response;Roentgen Rays;Role;Signal Transduction;Solid Neoplasm;Splenocyte;standard of care;success;Survival Rate;System;T-Cell Activation;T-Lymphocyte;Techniques;Testing;Therapeutic;TNFRSF5 gene;Travel;Treatment outcome;Treatment Protocols;tumor;Tumor Antigens;Tumor Cell Line;Tumor Immunity;tumor microenvironment;Tumor Tissue;tumor xenograft;tumor-immune system interactions;Unresectable;Vaccinated;Viral;X-Ray Therapy

PROJECT_TITLE: Relative Immunological Effectiveness (RIE) of Carbon Ion Radiation Therapy for Pancreatic Cancer


NIH_SPENDING_CATS: Biotechnology;Dental, Oral, and Craniofacial Disease;Genetics;Human Genome

ORG_DEPT: DENTISTRY

PHR: PROJECT NARRATIVE Human health relevance: Some humans inherit a harmful genetic mutation, yet they somehow buffer the effects of the mutation and do not show signs of genetic disease. We generated a zebrafish model of buffering to understand how some individuals who should have gotten sick are able to live normal healthy lives. Understanding the naturally occurring mechanisms of buffering is the first step toward new therapeutic strategies capitalizing on innate protective mechanisms in some individuals.

PI_NAMEs: NICHOLS, JAMES TUCKER (contact)

PROGRAM_OFFICER_NAME: SAIFUDEEN, ZUBAIDA

PROJECT_TERMS: Address;Adult;Affect;Animals;Breeding;Buffers;Cells;Counseling;craniofacial;Craniofacial Abnormalities;Defect;Dental;Development;Developmental Process;Disabling;Disease;disease diagnosis;Disease Management;disease phenotype;disorder prevention;DNA;DNA Sequence;DNA Sequence Alteration;Dorsal;Epigenetic Process;epigenome;epigenomic profiling;epigenomics;Equilibrium;Experimental Designs;falls;Fingers;Fishes;flexibility;Future;Gene Expression;Gene Expression Regulation;Gene Family;gene interaction;Genes;Genetic;Genetic Diseases;genetic manipulation;genetic predictors;genetic variant;Genetic Variation;genome editing;genome sequencing;Genotype;Head;Health;Heritability;Human;Human Genetics;Human Genome;improved;Individual;Inherited;Label;Measurement;Measures;Medical;member;Methods;Mission;Modeling;mutant;Mutation;myocyte-specific enhancer-binding-factor 2C;National Institute of Dental and Craniofacial Research;notch protein;novel therapeutic intervention;Oral;Organism;Orthologous Gene;Pathway interactions;Penetrance;Phenotype;Reiterated Genes;Reporting;Research;response;screening;Signal Transduction;skeletal;Skeleton;Specific qualifier value;Statistical Data Interpretation;Symptoms;System;Testing;Tissues;transcription factor;transcriptomic profiling;Variant;Work;Zebrafish;zebrafish genome

PROJECT_TITLE: Mechanisms of developmental buffering

STUDY_SECTION: SBDD

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


NIH_SPENDING_CATS: Complementary and Integrative Health;Dietary Supplements;Nutrition

ORG_CITY: PITTSBURGH

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: Project Narrative The acidic gastric compartment promotes efficient nitration of dietary conjugated fatty acid when consumed with nitrite and nitrate-rich foods (e.g., leafy vegetables) forming nitrated fatty acids that exert protective and anti- inflammatory actions. We recently defined nitrated conjugated linolenic acid as a major nitro fatty acid species in humans and propose to study their mechanism of formation and signaling actions. This will provide dietary approaches to metabolic and inflammatory diseases.

PI_NAMEs: SCHOPFER, FRANCISCO JOSE (contact)

PROGRAM_OFFICER_NAME: BARSKI, OLEG

PROJECT_TERMS: absorption;Animal Model;animal tissue;Anti-Inflammatory Agents;Attenuated;Award;Biological;Biology;Carbon;Conjugated Linoleic Acids;Consumption;COVID-19 impact;Dairy Products;Data;design;Development;Diet;dietary;dietary approach;Dietary Component;Dietary Fatty Acid;Dietary Intervention;dietary nitrate;Digestion;Disease;Enterocytes;Evaluation;Event;Excretory function;Family;Fatty Acids;Food;Future;Health;Heat shock proteins;Homeostasis;Human;human tissue;Human Volunteers;improved;In Vitro;in vivo;Inflammation;Inflammatory;Isomerism;Isotope Labeling;Journals;Knowledge;Linolenic Acids;Lipids;Liquid substance;Literature;Malignant Neoplasms;Mammary gland;Mediating;Mediator;Metabolic;Metabolic Diseases;Metabolic Pathway;Metabolism;microbiome;nitrated conjugated linoleic acid;Nitrates;nitration;Nitrites;Nitrogen Dioxide;novel;nutritional approach;Oral;Pathologic;Pharmaceutical Preparations;pharmacokinetics and pharmacodynamics;pharmacologic;Pharmacology;Plants;pre-clinical;Process;Property;protective effect;protein expression;Proteins;Publishing;Reaction;Reporting;response;Role;Signal Pathway;Signal Transduction;Site;Source;Stomach;Testing;Tissues;urinary;Urine;Vegetables;western diet

PROJECT_TITLE: Formation and metabolism of nitrated fatty acids


ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

PHR: PROJECT NARRATIVE The prevalence of obesity and metabolic disease continue to rise, and are thought to develop in part due to excessive consumption of carbohydrate-rich diets and impaired communication between the gut and the brain. We have previously shown that glucose infusion directly into the gut rapidly modulates the activity of feeding circuits in the hypothalamus and inhibits subsequent feeding, but the mechanism remains unclear. Here we propose using cutting-edge neuroscience and genetic techniques to determine the hormonal and neural mediators of these gut-brain dynamics, and to understand how obesity alters these pathways.

PI_NAMEs: BEUTLER, LISA R (contact)

PROGRAM_OFFICER_NAME: COOKE, BRAD

PROJECT_TERMS: Ablation;absorption;Address;Animals;antagonist;Area;Automobile Driving;Behavioral;Brain;Brain Stem;Calories;Carbohydrates;Cell Line;Cell Physiology;Cell secretion;cell type;Cellular biology;Central Nervous System;Communication impairment;comorbidity;conditional knockout;Consumption;Data;data integration;Development;Diet;Dietary Fats;Diphtheria Toxin;Disparate;Eating;Enterocytes;Enteroendocrine Cell;epigenomics;experimental study;Fatty acid glycerol esters;Feedback;feeding;Fiber;Food;gastrointestinal;Gastrointestinal tract structure;Genetic;genetic approach;Genetic Techniques;Genetic Transcription;Glucose;glucose metabolism;glucose uptake;Goals;gut-brain axis;High Fat Diet;Hormonal;hormonal signals;Hormone secretion;Hormones;Hunger;Hypothalamic structure;in vivo;increased appetite;incretin hormone;Infusion procedures;Ingestion;insight;Intake;Knock-out;Knockout Mice;Knowledge;Macronutrients Nutrition;Mediating;Mediator;Metabolic;Metabolic Diseases;Metabolism;Modeling;Molecular;Monitor;Mus;neural;Neurons;Neurosciences;novel;Nucleus solitarius;Nutrient;Nutritional;Obese Mice;Obesity;obesity development;obesity prevention;obesogenic;Overnutrition;Pathway interactions;pharmacologic;Photometry;Population;preference;Prevalence;Process;programs;Public Health;receptor;Receptor Signaling;response;Role;Satiation;Signal Transduction;Stimulus;Stomach;Structure of beta Cell of islet;Structure of nucleus infundibularis hypothalami;Sucrose;sugar;symporter;Testing;Tissues;tool;Vagus nerve structure;Weight;Work

PROJECT_TITLE: Rapid hormonal modulation of feeding circuit dynamics and its disruption in obesity

STUDY_SECTION: IPOD

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


NIH_SPENDING_CATS: Biotechnology;Clinical Research;Genetics;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Microbiome;Racial and Ethnic Minority Health Research

ORG_CITY: PHILADELPHIA

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Narrative To better understand the genetic basis of adaptive traits in ethnically diverse African populations, we propose to integrate genomic, metabolic, microbiome, epigenomic, and transcriptomic data with detailed phenotype data. We will perform field studies to collect novel biological samples as well as detailed phenotypic data from multiple ethnically diverse African populations. We will incorporate high coverage whole genome sequencing and SNP array data to study African evolution and identify targets of natural selection and to look for genetic associations with anthropometric, gene expression, microbiome, cardio-metabolic and immune related traits. We will use functional genomics approaches, such as high-throughput luciferase assays and Crispr-Cas9 technology to identify causal regulatory variants and characterize their impact on gene expression in vitro and in vivo in model organisms. This study will have important implications for understanding human evolution history and the genetic basis of complex traits of biomedical relevance in populations of recent African descent.

PI_NAMEs: TISHKOFF, SARAH ANNE (contact)

PROGRAM_OFFICER_NAME: ADKINS, RONALD

PROJECT_TERMS: Africa;African;African ancestry;Biological;Biological Assay;Biological Models;Biomedical Research;biomedical resource;cardiometabolism;Cell Line;Cells;Communities;Complex;CRISPR/Cas technology;Data;Diet;epigenomics;ethnic diversity;Evolution;field study;functional genomics;Gene Expression;Genetic;genetic association;genome sequencing;genome wide association study;genome-wide;Genomic approach;genomic variation;Genomics;gut microbiome;Human;Immune;In Vitro;in vivo;in vivo Model;Knowledge;Linkage Disequilibrium;Luciferases;Metabolic;metabolome;metabolomics;microbiome;model organism;Modernization;Natural Selections;novel;Pattern;Persons;Phenotype;phenotypic data;Population;Recording of previous events;Reporter;Sampling;Shapes;Site;SNP array;Source;Structure;trait;transcriptomics;Variant;whole genome

PROJECT_TITLE: Integrative Genomic Analyses of Human Evolution and Adaptation in Africa

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


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Clinical Research;Cocaine;Drug Abuse (NIDA only);Machine Learning and Artificial Intelligence;Neurosciences;Opioid Misuse and Addiction;Opioids;Stimulant Use and Misuse;Substance Misuse;Women's Health Research

ORG_CITY: NEW YORK

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: National studies show that there is more rapid increase in the use of all drugs of abuse by women compared with men, comprising a unique public health concern in the US. However, an overrepresentation of males in neuroimaging studies, and a paucity of studies that explicitly target sex comparisons in addicted populations, contributes to an absence of a clear understanding of sex specific neurobiological mechanisms underlying drug addiction. The study of sex differences (and menstrual cycle/hormonal effects) in the neural underpinnings of reward processing, inhibitory control and cue-reactivity could advance basic neuroscience studies of drug addiction and save resources by minimizing cost and adverse effects during future clinical (medication) trials. Ultimately, results could contribute to the development of individually tailored (gender-based) precision medicine interventions (e.g., to reduce craving).

PI_NAMEs: GOLDSTEIN, RITA Z (contact)

PROJECT_TERMS: Abstinence;addiction;Address;Adverse effects;Anatomy;Behavioral;blood oxygen level dependent;Chronic;Classification;Clinical;Clinical Trials;Cocaine Dependence;cocaine use;Cocaine use disorder;Cognitive;Corpus striatum structure;cost;craving;cue reactivity;Cues;Data;Data Set;design;Development;diagnostic criteria;Dopamine;Drug Addiction;drug of abuse;Drug usage;Early treatment;Emotional;Epidemic;Female;frontal lobe;Functional Magnetic Resonance Imaging;Future;Gender;Goals;Gonadal Steroid Hormones;gray matter;Hormonal;imaging modality;imaging study;Impairment;Impulsivity;Individual;Informal Social Control;Intervention;Intoxication;Machine Learning;machine learning algorithm;Magnetic Resonance Imaging;male;Maps;Measures;men;Menstrual cycle;model generalizability;Modeling;Monitor;neural;neural correlate;neural network;neurobiological mechanism;neuroimaging;Neurosciences;neurotransmission;non-drug;Opiate Addiction;opioid use disorder;Participant;Pattern;Performance;Pharmaceutical Preparations;Phase;Population;precision medicine;predictive tools;Predisposition;Prefrontal Cortex;Proxy;Psychological reinforcement;psychostimulant;Public Health;Recovery;recruit;Recurrent disease;Relapse;Research;Resources;response;Rest;reward processing;Rewards;Role;Scanning;Series;Severities;sex;Sex Differences;sexual dimorphism;Signal Transduction;Specificity;Stimulant;Stimulus;stress reactivity;symptomatology;Symptoms;systematic review;Testing;treatment strategy;Withdrawal;Woman;women versus men

PROJECT_TITLE: Sex differences in the neural correlates underlying impairments in response inhibition and salience attribution in cocaine addiction

STUDY_SECTION: ARM

STUDY_SECTION_NAME: Addiction Risks and Mechanisms Study Section[ARM]


NIH_SPENDING_CATS: Machine Learning and Artificial Intelligence

ORG_CITY: Newark

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: PROJECT NARRATIVE Viruses are efficient machines that seize normal cellular functions for their own benefits. The application of new computational approaches has sparked life into challenging projects and now allows difficult questions relating to viral receptor usage and integration to be addressed. Identification and characterization of these host proteins and the development of targeted inhibitors to them has broad implications for public health, both as it relates to viral pathogenesis as well as diseases relating to gene and oncogene expression.

PI_NAMEs: ROTH, MONICA J. (contact)

PROGRAM_OFFICER_NAME: SAKALIAN, MICHAEL

PROJECT_TERMS: Address;Affinity;Area;Artificial Intelligence;Binding;Binding Proteins;Bioinformatics;Cell Physiology;Computer Assisted;design;Development;Disease;Drug Design;drug discovery;env Gene Products;Foundations;Generations;Genes;inhibitor;Integrase;Knowledge;Lead;leukemia;Life;Membrane Proteins;Modeling;Molecular;Mus;novel;novel strategies;Oncogenes;Orphan;Pathogenesis;programs;Protein Family;protein structure prediction;Proteins;Public Health;receptor;Receptor Cell;Regulation;Research;small molecule;small molecule inhibitor;Specificity;Structure;Tissues;tool;Viral;Viral Pathogenesis;virology;Virus;Virus Receptors

PROJECT_TITLE: Interactions of retroviral and host proteins guided by advanced modeling