NIH_SPENDING_CATS: Anxiety Disorders;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Immunization;Mental Health;Mental Illness;Post-Traumatic Stress Disorder (PTSD);Vaccine Related;Women's Health Research

ORG_NAME: NORTHERN CALIFORNIA INSTITUTE/RES/EDU

PHR: PROJECT NARRATIVE Posttraumatic stress disorder (PTSD) is a major public health problem for which current treatments are inadequate. Accumulating preclinical and clinical evidence indicates that acute inflammatory activity impairs fear extinction, which in turn could prevent recovery from PTSD. The proposed research takes a vital first step towards translating this evidence into novel interventions to improve public health by determining the effects of acute inflammatory activity on fear extinction processes in men and women with and without chronic PTSD.

PI_NAMEs: O'DONOVAN, AOIFE  (contact)

PROGRAM_OFFICER_NAME: TUMA, FARRIS KEITH

PROJECT_TERMS: Acute;Affect;Age;Anti-Inflammatory Agents;Antiinflammatory Effect;Biological;Cells;Chronic;Chronic Disease;Chronic Post Traumatic Stress Disorder;Clinical;conditioned fear;cytokine;Data;Double-Blind Method;Electromyography;Emotional;Extinction;Female;Fright;Galvanic Skin Response;General Population;Glucocorticoids;Goals;Heart Rate;Hour;Human;Immune;Impairment;improved;In Vitro;indexing;Individual;Inflammation;Inflammatory;inflammatory marker;innovation;Interleukin-6;Intervention;Learning;learning extinction;Life;Link;male;Measures;Mediating;Memory;memory acquisition;men;Mental disorders;Modeling;National Institute of Mental Health;Negative Valence;neural circuit;neurobehavioral;Neuronal Plasticity;novel;Outcome;Participant;Patients;Persons;Pharmaceutical Preparations;Phase;Placebo Control;placebo group;Placebos;Play;Polysaccharides;Population;Post-Traumatic Stress Disorders;pre-clinical;Pre-Clinical Model;preclinical study;prevent;Process;proliferative phase Menstrual cycle;Protocols documentation;Psychological Stress;psychological stressor;Public Health;Randomized;Recovery;Relapse;Research;Research Domain Criteria;response;Role;screening;sex as a biological variable;Sex Differences;Shock;Signal Transduction;Standardization;Startle Reaction;Strategic Planning;Study Subject;Sum;Symptoms;targeted treatment;Testing;Time;Translating;Trauma;trauma exposure;Typhoid Vaccine;Vaccines;visual stimulus;Woman;women versus men;Work

PROJECT_TITLE: Inflammatory challenge and fear extinction: A model to enhance understanding of posttraumatic stress disorder

STUDY_SECTION: APDA

STUDY_SECTION_NAME: Adult Psychopathology and Disorders of Aging Study Section[APDA]


ADMINISTERING_IC: NS

ARRA_FUNDED: N

ED_INST_TYPE: OVERALL MEDICAL

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Autism;Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Biotechnology;Brain Disorders;Genetics;Intellectual and Developmental Disabilities (IDD);Mental Health;Mental Illness;Neurosciences

ORG_CITY: PORTLAND

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: Project Narrative Synaptic transmission in continuously modulated by short-term plasticity, a ubiquitous property of nerve terminals that rapidly changes the functions of neural circuits without physically restructuring connections. Altered short-term plasticity is implicated in multiple neurological disorders, but this link has been difficult to establish due to a lack of identified molecular mechanisms for plasticity. Building on our recent discovery of two key mechanisms for short-term plasticity, we will use knockout mice to define the molecular interactions and functional consequences of short-term plasticity.

PI_NAMEs: JACKMAN, SKYLER LOFSTRAND (contact)

PROGRAM_OFFICER_NAME: CHURN, SEVERN BORDEN

PROJECT_TERMS: Acceleration;Affect;Affinity;Alzheimer's Disease;Animal Behavior;Animal Model;autism spectrum disorder;Behavior;Behavioral;Binding;Biological Assay;biophysical model;Biophysics;Bipolar Disorder;Brain;Cerebellum;Chemosensitization;Cognition;Cognitive deficits;cognitive function;Computer Models;Data;Data Analyses;Dependence;Disease;Docking;Electron Microscopy;Epilepsy;Exhibits;experimental study;Family;Fiber;Foundations;Freezing;Frequencies;Functional disorder;genetic manipulation;Genetic Screening;Hippocampus;human disease;human model;in vivo;Individual;individuals with autism spectrum disorder;insight;interest;Kinetics;Knock-out;knockout animal;Knockout Mice;Knowledge;Learning;Link;Long-Term Potentiation;Mediating;Memory;Mental Depression;Methods;millisecond;Modeling;Molecular;Mutation;Nerve;nervous system development;Nervous System Disorder;Nervous System Physiology;neural circuit;Neurons;Neurophysiology - biologic function;neurotransmission;neurotransmitter release;Pattern;Phenotype;Physiological;presynaptic;Process;Property;Protein Family;Protein Isoforms;Proteins;Protocols documentation;Recovery;Reporting;reverse genetics;Role;Schizophrenia;screening;sensor;Short-Term Memory;Signal Transduction;Speech Perception;Stimulus;Synapses;Synaptic plasticity;Synaptic Transmission;Synaptic Vesicles;synaptotagmin;Testing;Time;tool;trafficking;transmission process;Vesicle;Work

PROJECT_TITLE: The mechanisms and functions of short-term synaptic plasticity

STUDY_SECTION: NC

STUDY_SECTION_NAME: Neuronal Communications Study Section[NC]


ADMINISTERING_IC: CA

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: IRVINE

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

ORG_STATE: CA

PHR: PROJECT NARRATIVE Guided by experience and leadership in the NCI-sponsored clinical trial networks (NCI-CTNs) throughout my career, this R50 Research Specialist award offers critical support that would enable me to fully engage in high- yield activities across a spectrum of educational, leadership, and clinical trials-related research activities of the NCI-CTNs. Fundamental to each proposed activity is a consistent focus on reducing health disparities by promoting diverse enrollment in modern clinical trials. Exciting new programs are proposed, including an educational series directed at increasing the diversity of potential future NCI-CTN investigators, protected time to develop minority recruitment interventions that can be deployed across the NCI-CTNs, and establishing my home institution (UC Irvine Chao Family Comprehensive Cancer Center) as an active Affiliate Organization within the NCI-DCP Cancer Prevention Clinical Trials Network.

PI_NAMEs: ZELL, JASON  (contact)

PROGRAM_OFFICER_NAME: LINDWASSER, ONN WOLF

PROJECT_TERMS: Advisory Committees;Anus;Award;Cancer Center;cancer prevention;career;Catchment Area;Clinical;Clinical Trials;Clinical Trials Data Monitoring Committees;Clinical Trials Network;Collaborations;Colonic Adenoma;Committee Membership;Comprehensive Cancer Center;Data;Development;Discipline;Division of Cancer Prevention;Education;Eflornithine;Enrollment;Equity;ethnic diversity;experience;Faculty;Family;Future;gastrointestinal;Grant;Home;Institution;Intervention;Lead;Leadership;Malignant Neoplasms;member;Mentors;Minority Recruitment;Modernization;Network-based;novel;Organizational Affiliation;Patients;Phase;Phase III Clinical Trials;Population Heterogeneity;Positioning Attribute;prevent;prevention clinical trial;Preventive;Principal Investigator;programs;racial diversity;randomized trial;Rectum;Reduce health disparities;Research;Research Activity;Research Personnel;Role;Series;Site;Southwest Oncology Group;Specialist;Sulindac;Therapeutic;Time

PROJECT_TITLE: Advancing novel cancer preventive and therapeutic strategies across the modern NCI clinical trial networks

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 SRB-1 (O1)]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Coronaviruses;Coronaviruses Therapeutics and Interventions;Emerging Infectious Diseases;Hematology;Infectious Diseases;Lung;Post-Acute Sequelae of SARS-CoV-2 infection (PASC) including Long COVID;Women's Health Research

ORG_CITY: LA JOLLA

ORG_NAME: SCRIPPS RESEARCH INSTITUTE, THE

PHR: Project Narrative SARS-CoV-2 is the virus responsible for the severe respiratory disease named as coronavirus disease 19 (COVID-19), which has been declared a pandemic in March, 2020. While susceptibility to COVID-19 infection doesn't show any sex specificity, clinical outcomes show that males experience both a higher severity and mortality upon SARS-CoV-2 infection compared to females. Here we describe a COVID-19 mouse model mirroring pathological alterations in coagulation, endothelial activation, and platelet function associated with the human infection, allowing in vivo studies to explore the molecular mechanisms responsible for the sex-specific difference in severity driving the coagulopathy associated with the infection and new therapeutic options for the treatment of severe viral infections.

PI_NAMEs: AIOLFI, ROBERTO  (contact)

PROGRAM_OFFICER_NAME: HILL-PRYOR, CRYSTAL DARLEANE-ROBIN

PROJECT_TERMS: 2019-nCoV;ACE2;Address;Androgens;Automobile Driving;Basic Science;Biology;Blood Coagulation Disorders;Blood Platelets;Cells;China;Clinical;Coagulation Process;combat;complement pathway;Complex;COVID-19;COVID-19 impact;COVID-19 pandemic;COVID-19 pathogenesis;COVID-19 patient;COVID-19 prevention;COVID-19 severity;COVID-19 susceptibility;COVID-19 treatment;Data;Deep Vein Thrombosis;design;Development;Disease;Disease Progression;efficacy testing;Endothelium;Estrogens;experience;extracellular;feasibility testing;Female;Fibrin;Functional disorder;Goals;Hemostatic Agents;Hemostatic function;Hormonal;Hormones;Host Defense Mechanism;Human;Immune;immune activation;Immune response;Immune Targeting;immunothrombosis;in vivo;Incidence;Infection;Inflammatory Response;insight;Intervention Studies;K-18 conjugate;Knowledge;Link;Long COVID;male;Mediating;Modeling;Molecular;molecular targeted therapies;monocyte;mortality;mouse model;Mus;Names;neutrophil;Neutrophil Activation;new therapeutic target;novel;novel strategies;novel therapeutic intervention;novel therapeutics;Organ;Outcome;pandemic disease;pathogen;pathogenic virus;Pathologic;Pathway interactions;Patients;pharmacologic;platelet function;Play;post SARS-CoV-2 infection;Predisposition;Proteins;Pulmonary Embolism;Recovery;recruit;Reporting;Research;Research Personnel;Respiratory Disease;response;Risk;Role;SARS-CoV-2 infection;severe COVID-19;Severities;Severity of illness;sex;Sex Bias;Sex Differences;Sexual Development;Specificity;success;Supplementation;Syndrome;System;targeted treatment;Therapeutic;Therapeutic Effect;Therapeutic Intervention;thromboinflammation;Thrombophilia;Thrombosis;Thrombus;Time;Translational Research;Vascular Diseases;venous thromboembolism;Virus;Virus Diseases;von Willebrand Factor

PROJECT_TITLE: Molecular pathogenesis of COVID-19-associated coagulopathy and new therapeutic approaches

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


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Assistive Technology;Bioengineering;Biomedical Imaging;Cardiovascular;Clinical Research;Heart Disease;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD)

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: PROJECT NARRATIVE  The proposed project aims to address the limitations of current cardiac imaging techniques by developing a wearable ultrasound imager for continuous, non-invasive monitoring of the heart. This technology has the potential to revolutionize the field of cardiac imaging by providing direct and real-time assessment of cardiac functions, which may lead to early detection and improved management of cardiovascular diseases and acute conditions. The development of this wearable technology has the potential to greatly benefit the field of critical care and expand the possibilities for cardiovascular disease management.

PI_NAMEs: XU, SHENG  (contact)

PROGRAM_OFFICER_NAME: HALLER, JOHN WAYNE

PROJECT_TERMS: Acoustics;Acute;Address;Algorithms;Apical;Area;arm;Benchmarking;Blood flow;Blood Pressure;Blood Pressure Monitors;Cardiac;Cardiac Output;Cardiac Volume;Cardiovascular Diseases;cardiovascular health;Cardiovascular system;care outcomes;Chest;Clinical;Clinical Management;clinical practice;Collaborations;Confidence Intervals;convolutional neural network;Coronary Arteriosclerosis;Coupling;Critical Care;Critical Illness;Data;deep learning;deep learning model;density;design;Detection;Development;Devices;Diagnosis;Disease;Disease Management;Early Diagnosis;Echocardiography;effective intervention;Effectiveness;EFRAC;Electrodes;Elements;Ensure;Evaluation;experience;fabrication;FarGo;Fatigue;Feedback;Frequencies;General Anesthesia;Grant;Guidelines;Heart;Heart failure;heart function;heart imaging;Hemoglobin;high risk;Hospitalization;Human body;human subject;Image;Image Enhancement;imager;Imaging Techniques;improved;indexing;Inpatients;Intervention;invention;Lateral;Left;Left ventricular structure;Liquid substance;Lobe;Location;Manuals;Maps;Measurement;Metals;Modeling;Monitor;Morbidity - disease rate;Morphologic artifacts;mortality;Motion;Myocardial dysfunction;Myocardium;Noise;non-invasive monitor;novel;optical fiber;Organ;Outpatients;Participant;Patients;Performance;Perioperative;Positioning Attribute;Process;Research;Resolution;Safety;Sedation procedure;sensor;Shapes;Signal Transduction;Skin;standard of care;Stroke Volume;success;Surface;System;Techniques;Technology;temporal measurement;Testing;Time;Tissues;tool;Transducers;Transesophageal Echocardiography;transmission process;Ultrasonics;Ultrasonography;ultrasound;United States National Institutes of Health;Ventricular;Visceral;wearable device;Work

PROJECT_TITLE: A wearable orthogonal ultrasound array for continuous imaging of the heart

STUDY_SECTION: ITD

STUDY_SECTION_NAME: Imaging Technology Development Study Section[ITD]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Dental, Oral, and Craniofacial Disease;Neurosciences;Nutrition

ORG_CITY: SAN FRANCISCO

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: Project Narrative We investigate in this proposal key neural circuits that control food intake and body weight in the mouse. We apply approaches from systems neuroscience to understand how these circuits are dynamically regulated during a meal and the motivational mechanisms they use to influence behavior. This will reveal basic mechanisms by which hunger and satiety are controlled in the brain.

PI_NAMEs: KNIGHT, ZACHARY A. (contact)

PROGRAM_OFFICER_NAME: CUMMINGS, DIANA M

PROJECT_TERMS: Afferent Pathways;Anatomy;Animals;Architecture;Axon;Behavior;Behavior Control;behavior influence;Behavioral;Biological Assay;Bite;Blood - brain barrier anatomy;Body Weight;Brain;Brain Stem;Calcium;cell type;Cells;Chemicals;Communication;Consumption;Cranial Nerves;Cues;Desire for food;Detection;Eating;experimental study;Feedback;feeding;Feeding behaviors;Fiber;Food;food consumption;gastrointestinal;Gastrointestinal tract structure;glossopharyngeal;hindbrain;Hormones;Hunger;Image;Ingestion;Interneurons;Learning;Mediating;Methods;Motivation;Mus;Nature;Nerve;neural;neural circuit;neuromechanism;Neurons;Neurosciences;Nucleus solitarius;Nutrient;optogenetics;Oral;Oral cavity;Oral Ingestion;Organ;Pathway interactions;Phase;Photometry;Process;Prolactin-Releasing Hormone;Prosencephalon;response;restraint;Role;Satiation;Sensory;sensory feedback;sensory input;Signal Transduction;Site;Smell Perception;Stomach;Structure;success;System;Taste Perception;Testing;Texture;tool;transmission process;Visceral;Vision

PROJECT_TITLE: Neural mechanisms that control the rate of ingestion

STUDY_SECTION: POMD

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


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Depression;Major Depressive Disorder;Mental Health;Mental Illness;Neurosciences;Serious Mental Illness

ORG_CITY: LOS ANGELES

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: Project Narrative Repetitive Transcranial Magnetic Stimulation (rTMS) administered at a frequency of 10 Hz to the left dorsolateral prefrontal cortex (DLPFC) is an effective treatment for Major Depressive Disorder (MDD), yet many patients do not obtain significant benefit. This study aims to develop an innovative personalized- medicine approach to rTMS using a novel “interrogation” procedure, which examines electroencephalogram (EEG) signals recorded from the scalp following different stimulation frequencies to identify the frequency that is most likely to engage brain circuits associated with rTMS antidepressant response for each individual. Results will lay the foundation for a future clinical trial to investigate the efficacy of this customized stimulation approach to treating MDD.

PI_NAMEs: CARPENTER, LINDA L;LEUCHTER, ANDREW F (contact)

PROGRAM_OFFICER_NAME: TILGHMAN, JESSICA IRENE

PROJECT_TERMS: anti-depressive agents;Brain;Brain region;Clinical;Clinical Trials;Data;Depressed mood;design;effective therapy;Effectiveness;Electroencephalography;Failure;Foundations;Frequencies;Future;improved;Individual;individual patient;innovation;interest;Left;Major Depressive Disorder;Measurement;Measures;Mental Depression;Methods;Moods;Neuroanatomy;neurophysiology;novel;novel strategies;Outcome;Patients;personalized approach;personalized medicine;Physiological;Prefrontal Cortex;Procedures;Property;recruit;repetitive transcranial magnetic stimulation;Reporting;response;Scalp structure;Signal Transduction;source localization;symptomatic improvement;Testing;Treatment outcome;treatment response;Validation;Work

PROJECT_TITLE: Resonant Frequency rTMS: A Novel Approach to Target Circuit Modulation in MDD

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 NV-Q (91)]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

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

ORG_CITY: SEATTLE

ORG_NAME: HDT BIO CORPORATION

ORG_STATE: WA

PHR: PROJECT NARRATIVE In vivo delivery of messenger RNA encoding multivalent immunogenic antigens is an effective measure for counteracting emerging/re-emerging virus threats. The proposed study will further our understanding of how muscle-localizing RNA vaccines elicit adaptive immune responses in a multivalent vaccine application by focusing on innate immune responses. We will use antigens of four important human pathogens, SARS-CoV-2, RSV, Influenza, and EV-D68, that are currently causing tripledemic and re-emerging.

PI_NAMEs: KIMURA, TAISHI  (contact)

PROGRAM_OFFICER_NAME: JOFFE, AARON MICHAEL

PROJECT_TERMS: 2019-nCoV;Ablation;adaptive immune response;Affect;Antibodies;Antibody Response;antigen-specific T cells;Antigens;Apyrase;Cancerous;Caspase;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;Cell Differentiation process;Cells;cytokine;Dendritic Cells;Deoxyribonuclease I;Dose;Economic Burden;emerging virus;Emulsions;Enterovirus 68;Family;Flow Cytometry;Formulation;Genes;Health;Helper-Inducer T-Lymphocyte;Human;human pathogen;IFNAR1 gene;immune activation;immune function;Immune response;Immune system;immunogenic;immunogenicity;Immunologics;Immunophenotyping;In Vitro;in vivo;Infiltration;Inflammatory;Inflammatory Response;Influenza;influenzavirus;Innate Immune Response;Interferons;Interleukin-1;Intramuscular;Intramuscular Injections;ITGAM gene;lymph nodes;Measures;Molecular;monocyte;mouse model;mRNA delivery;Mus;Muscle;Muscle Cells;nano-string;nanocarrier;neutralizing antibody;novel strategies;Oils;pharmacologic;Physiologic pulse;Play;protein expression;Replicon;Respiratory syncytial virus;response;RIPK3 gene;RNA;RNA replication;RNA vaccination;RNA vaccine;Role;Signal Pathway;Signal Transduction;Skeletal Muscle;Squalene;Structure of germinal center of lymph node;System;T cell response;T memory cell;Testing;Time;transgene expression;Transgenic Mice;Vaccination;vaccine efficacy;Vaccines;Virus Diseases;Water

PROJECT_TITLE: Immunological mechanism of muscle-localizing self-replicating RNA vaccines

STUDY_SECTION: VID

STUDY_SECTION_NAME: Vaccines Against Infectious Diseases Study Section[VID]


NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Genetics;Hematology;Human Genome;Orphan Drug;Pain Research;Rare Diseases;Sickle Cell Disease

ORG_CITY: AUGUSTA

ORG_NAME: AUGUSTA UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE Sickle cell disease (SCD) afflicts almost exclusively African-Americans in the US and is associated with significant morbidity, poor quality of life, and a shortened life expectancy. Hydroxyurea is the only disease- modifying agent that is FDA-approved for SCD with a mechanism of action to block sickle cell formation through increasing fetal hemoglobin expression; however, hydroxyurea is not highly utilized by SCD patients. This proposal will study the safety, tolerability, and efficacy of an alternative therapy, panobinostat, which also increases fetal hemoglobin, and will explore biomarkers of drug treatment response as a novel and promising disease-modifying agent for SCD.

PI_NAMEs: KUTLAR, ABDULLAH  (contact);PACE, BETTY SUE

PROGRAM_OFFICER_NAME: FRANK, DANIEL J

PROJECT_TERMS: Acetylation;Acute Pain;Adherence;Adult;Adverse event;Affect;African American;African American population;African ancestry;Alternative Therapies;Anemia;Antiinflammatory Effect;Assessment tool;Bioinformatics;Biological Assay;Biological Markers;Birth;Blood Vessels;Body System;carcinogenicity;Cells;chemokine;Child;ChIP-seq;Chromatin;chromatin immunoprecipitation;Chromatin Structure;Chronic;Clinical;cohort;cytokine;Cytoplasmic Protein;Data;Decision Making;design;differential expression;Disease;Disease Outcome;Disparity;Dose;Dose Limiting;efficacy testing;Enrollment;Epigenetic Process;epigenetic silencing;Erythrocytes;Erythroid;experience;FDA approved;Fertility;fetal;Fetal Hemoglobin;follow-up;Funding;gamma Globin;Gene Expression;Genes;Genetic Transcription;genome-wide;Globin;Glutamine;Goals;Hematology;Hemoglobin;Hemolysis;Hemolytic Anemia;Histone Acetylation;Histone Deacetylase Inhibitor;Histone H3;Histone H4;Hospital Costs;hydroxyurea;implementation study;improved;in vivo;Individual;Inflammatory;inflammatory marker;Intervention;Knowledge;Life Expectancy;life span;Measures;Mediating;Medical Economics;medication compliance;Monitor;Morbidity - disease rate;Motivation;motivational enhancement therapy;mouse model;Multicenter Studies;National Heart, Lung, and Blood Institute;NF-kappa B;non-histone protein;novel;novel strategies;Organ;Organ failure;Organ Preservation;Outcome;overtreatment;Oxygen;Participant;Pathology;Pathway interactions;patient engagement;Patients;Pattern;Perinatal;Persons;Pharmaceutical Preparations;Pharmacotherapy;phase 1 study;phase I trial;Plasma;polymerization;Polymers;potential biomarker;preclinical study;predictive marker;primary endpoint;progenitor;protein biomarkers;Protocols documentation;Publishing;Quality of life;Quality of Life Assessment;Rare Diseases;recruit;Regimen;Reperfusion Injury;Research Personnel;response;Reticulocytes;Safety;safety study;Schedule;secondary endpoint;Series;Sickle Cell;Sickle Cell Anemia;sickle erythroid;sickling;side effect;STAT3 gene;Stat3 protein;success;Testing;TFRC gene;Therapeutic;Toxic effect;TP53 gene;transcription factor;transcriptome;transcriptome sequencing;treatment adherence;treatment duration;treatment response;vaso-occlusive pain

PROJECT_TITLE: Phase I study of panobinostat in adults with sickle cell disease: novel approach to recruitment and retention


ADMINISTERING_IC: HD

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

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

ORG_CITY: CAMBRIDGE

ORG_NAME: NATIONAL BUREAU OF ECONOMIC RESEARCH

ORG_STATE: MA

PHR: OTHER PROJECT INFORMATION – Project Narrative This research will investigate the impacts of a variety of influential early childhood interventions on health, mental health, and health-promoting behaviors of the original participants and their children. We investigate dynamic mediators and moderators that promote health, including cognition, and socioemotional skills through midlife. We assess the contribution of health benefits to the quality of life, health costs, and cost- benefit analyses.

PI_NAMEs: HECKMAN, JAMES J (contact)

PROGRAM_OFFICER_NAME: CAPPS, RANDOLPH CHRISTOPHER

PROJECT_TERMS: Adult Children;Affect;Age;Behavior;Caregivers;Child;Child Development;Child Rearing;China;Cognition;Cost-Benefit Analysis;Costs and Benefits;Data;Dependence;design;Development;Disadvantaged;Discipline;early childhood;Economics;Effectiveness;effectiveness evaluation;Emotional;Endowment;Environment;Epidemiology;Evaluation;Family;Family Characteristics;Fertility;Fostering;Generations;Goals;Grain;Growth;Health;Health Benefit;Health Care Costs;Health Promotion;Home;Home environment;Home visitation;Human Development;Influentials;intergenerational;Intervention;Intervention Studies;Jamaica;Learning;Life;longitudinal analysis;Longterm Follow-up;Measurement;Measures;Mediation;Mediator;Medical Care Costs;member;Mental Health;Meta-Analysis;Methodology;Methods;middle age;Minority;Modeling;Monitor;Nursery Schools;nutrition;Outcome;parental role;Parents;Participant;Process;programs;Protocols documentation;Province;Quality of life;Randomized;Reporting;Research;Role;Running;Sampling;scaffold;Siblings;Site;skill acquisition;skills;Social Mobility;socioeconomics;Source;Techniques;Time;tool;treatment effect;Update

PROJECT_TITLE: Synthesizing, Interpreting, and Extrapolating Interventions to Foster Human Development

STUDY_SECTION: SSPA

STUDY_SECTION_NAME: Social Sciences and Population Studies A Study Section[SSPA]


NIH_SPENDING_CATS: Cancer;Digestive Diseases;Genetics;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: WORCESTER

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

PHR: In this project the investigators seek to understand molecular mechanisms underlying the crosstalk between Hippo and Wnt signaling, two signaling pathways that are critical for tissue homeostasis and tumorigenesis. Our study is focused on the gastrointestinal tract, and the proposed studies are essential to gain mechanistic insights into the functional and signaling interactions of these two pathways in regulation of intestinal stem cells and will have important therapeutic implications for GI disease and cancer.

PI_NAMEs: MAO, JUNHAO  (contact)

PROGRAM_OFFICER_NAME: GREENWEL, PATRICIA

PROJECT_TERMS: Alleles;Animal Model;beta catenin;Binding;Cells;Chemicals;Critical Pathways;design;Disease;Event;Excision;Gastrointestinal tract structure;Genes;Genetic;Genetic study;Genetic Transcription;Grant;Growth;Homeostasis;in vivo;insight;intestinal crypt;intestinal epithelium;intestinal homeostasis;Intestinal Neoplasms;intestinal tumorigenesis;Intestines;knockout animal;Malignant Neoplasms;Mediating;Mediator;Molecular;Mutate;MYC gene;novel;novel therapeutic intervention;Nuclear;Oncogenic;Output;palmitoylation;Pathway interactions;Phosphorylation;Phosphotransferases;Play;programs;Proteins;Proteomics;Proto-Oncogenes;Regulation;Reporting;Research Personnel;Role;Signal Pathway;Signal Transduction;small molecule inhibitor;stem cell division;stem cell expansion;stem cells;Testing;Therapeutic;therapeutic target;Time;Tissues;transcription factor;Transcription Factor AP-1;Transcription Repressor;Transcriptional Activation;tumor growth;tumorigenesis;Ubiquitination;WNT Signaling Pathway;Work

PROJECT_TITLE: Mechanism of YAP/TAZ crosstalk with Wnt signaling

STUDY_SECTION: CSRS

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


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

ORG_DEPT: ANESTHESIOLOGY

PHR: PROJECT NARRATIVE Depressed, exaggerated, or dysregulated motivation is characteristic of many mental illnesses, including addiction. This project will expose the neural circuits responsible for ensuring homeostatic and cognitive control over motivation induced by reward-predictive cues to understand both adaptive motivation and how it can become maladaptive.

PI_NAMEs: OSTLUND, SEAN BJORN (contact);WASSUM, KATE M

PROGRAM_OFFICER_NAME: FERNANDEZ, FERNANDO R

PROJECT_TERMS: Acetylcholine;addiction;Anhedonia;Anterior;Basic Science;Behavior;Behavioral;Binge Eating;Biological Assay;Calcium;cell type;Characteristics;cholinergic;cingulate cortex;cognitive control;cognitive reappraisal;cost;Cues;Data;Depressed mood;Desire for food;Development;Disease;Dopamine;dopaminergic neuron;Drops;drug craving;drug seeking behavior;Ensure;Fiber;food craving;Functional disorder;Genetic;Goals;Health;innovation;Interneurons;Knowledge;maladaptive behavior;Mental Depression;Mental disorders;Methods;Midbrain structure;Monitor;motivated behavior;Motivation;neural;neural circuit;neurochemistry;Neuromodulator;Neurons;neuropsychiatric disorder;Nicotinic Receptors;Nucleus Accumbens;optogenetics;Pharmaceutical Preparations;Photometry;prevent;Probability;Process;Regulation;response;Rewards;Risk;Role;Shapes;Signal Transduction;Source;Structure;Substance Use Disorder;System;Testing;Thalamic structure;Time;Work

PROJECT_TITLE: Nucleus accumbens circuits for regulating cue-motivated behavior

STUDY_SECTION: BRLE

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


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Arthritis;Autoimmune Disease;Clinical Research;Prevention;Rheumatoid Arthritis

ORG_CITY: Aurora

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: PROJECT NARRATIVE Rheumatoid arthritis (RA) affects approximately 1% of the population and can lead to significant morbidity, increased mortality, and substantial health-care and societal costs. This project will explore the formation and clearance of neutrophil extracellular traps (NETs) in the lung, which may be a factor leading to the generation of RA-related autoimmunity during the early stages of RA development. Ultimately, these findings can lead to novel approaches for RA prevention that target NETs and immune dysregulation in the lung.

PI_NAMEs: DEMORUELLE, M. KRISTEN  (contact)

PROGRAM_OFFICER_NAME: MAO, SU-YAU

PROJECT_TERMS: Address;Affect;Anti-citrullinated peptide antibody;Antibody Formation;Antigens;Arthritis;Autoimmunity;Basic Science;Binding;Binding Proteins;Biological Markers;Cells;citrullinated protein;Clinical;cohort;comparison control;cytokine;Data;Deoxyribonucleases;Development;Disability prevention;Disease;Enzyme-Linked Immunosorbent Assay;extracellular;Generations;Goals;Health Care Costs;IL17 gene;IL8 gene;Immune;Immunoglobulin G;improved;Incubated;Individual;Ingestion;inhibitor;Interleukin-6;Intervention;joint injury;Label;Lung;Macrophage;Mass Spectrum Analysis;Measures;Mediating;Methods;Microscopy;Mission;Morbidity - disease rate;mortality;Mucous Membrane;multidisciplinary;neutrophil;novel;novel strategies;Pathogenesis;Pathway interactions;Peptide Initiation Factors;peripheral blood;Phagocytosis;Plasma;Population;prevent;Prevention;Prevention trial;Process;Proteins;Publishing;Reporting;Rheumatoid Arthritis;Risk;Risk Factors;Role;Serology;Serum;Site;societal costs;Sputum;Synovial Fluid;TNF gene;Translational Research;United States National Institutes of Health;Work

PROJECT_TITLE: Neutrophil Extracellular Traps in the Lung and Development of Rheumatoid Arthritis-Related Autoimmunity and Arthritis

STUDY_SECTION: ACTS

STUDY_SECTION_NAME: Arthritis, Connective Tissue and Skin Study Section[ACTS]


ADMINISTERING_IC: AA

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Brain Disorders;Clinical Research;Health Services;Precision Medicine;Substance Misuse

ORG_CITY: ATLANTA

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: EMORY UNIVERSITY

PHR: PROJECT NARRATIVE Alcohol use disorder is a debilitating disease, affecting nearly 16 million people in the United States, for which medication treatment is available but underutilized. To support alcohol use disorder medication treatment, this study will utilize multiple data sources, including clinical trial and real-world data, outcome measures, and methodology to identify patient subgroups that are most likely to benefit from each medication used to treat alcohol use disorder. The goal of this award is to clarify uncertainties among clinicians and patients about whether and for whom treatment may work, which can inform clinical practice and increase the adoption of alcohol use disorder medications.

PI_NAMEs: WALLACH, JOSHUA DAVID (contact)

PROGRAM_OFFICER_NAME: FALK, DANIEL EVAN

PROJECT_TERMS: Abstinence;addiction;Adoption;Affect;Alcohol consumption;alcohol response;alcohol use disorder;Ambulatory Care;Award;care outcomes;career development;Characteristics;Chronic Disease;clinical care;clinical decision-making;clinical practice;Clinical Trials;Competence;Conduct Clinical Trials;Data;Data Sources;Databases;Development Plans;Disease;drinking;Effectiveness;Environment;Epidemiology;Evaluation;evidence base;Exclusion Criteria;Frequencies;Goals;Health;Health Personnel;Health Services;Heavy Drinking;hospital care;improved;Individual;innovation;Intervention;Label;Literature;Measures;Medical;Medicare;Medicine;Mentored Research Scientist Development Award;Mentors;Mentorship;Methodology;Methods;multiple data sources;National Institute on Alcohol Abuse and Alcoholism;novel;Observational Study;Outcome;Outcome Measure;patient subsets;Patients;personalized decision;Persons;Pharmaceutical Preparations;Pharmacoepidemiology;Privatization;professor;programs;psychosocial;Public Health;Public Health Schools;Publishing;Recommendation;Research;Research Methodology;Research Personnel;Risk;Sample Size;Sampling;Statistical Data Interpretation;statistical learning;Strategic Planning;Subgroup;Techniques;Testing;Time;Training;Uncertainty;United States;United States Food and Drug Administration;Work;World Health Organization

PROJECT_TITLE: Identifying patient subgroups that are most likely to benefit from medications used to treat alcohol use disorder

STUDY_SECTION: AA

STUDY_SECTION_NAME: Clinical, Treatment and Health Services Research Study Section[AA-3]


ADMINISTERING_IC: VA

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: Veterans Affairs

ORG_CITY: PROVIDENCE

ORG_NAME: PROVIDENCE VA  MEDICAL CENTER

ORG_STATE: RI

PHR: Disorders of the brain and nervous system, including those resulting directly from injuries incurred during military service, are of immediate relevance to Veterans Health. In part because of the complexity of the nervous system, people who have disorders such as spinal cord injury, stroke, post-traumatic stress disorder, amyotrophic lateral sclerosis, or limb loss lack adequate rehabilitation therapies to regain their independence. Through rigorous translational and clinical research conducted by a multidisciplinary team of scientists, engineers, and clinicians, the VA RR&D Center for Neurorestoration and Neurotechnology develops and tests novel device-based approaches to improving the health and lives of Veterans. An explicit goal of the Center is to translate neurotechnology and its applications into clinical practice in service to our Veterans and civilians throughout the US.

PI_NAMEs: GREENBERG, BENJAMIN D (contact);HOCHBERG, LEIGH R

PROJECT_TERMS: Affect;Amputation;Amyotrophic Lateral Sclerosis;Area;arm;Brain;Brain Diseases;career;Clinical;clinical practice;Clinical Research;Clinical Trials;Communication;Communities;computational neuroscience;Data;Dedications;design;Devices;Disease;Early Diagnosis;Education;Engineering;Epilepsy;Family;Funding;Goals;graduate student;Health;Healthcare Systems;Hospitals;Human;Impairment;improved;Infrastructure;Injury;Interdisciplinary Study;Internships;Intuition;Investments;Knowledge;Learning;Leg;limb loss;Limb structure;Medical Device;Mental Depression;Mental disorders;Mental Health;military service;multidisciplinary;Nervous System;Nervous System Disorder;neuroimaging;Neurologic;Neuropsychology;neurorestoration;Neurosciences;neurotechnology;novel;novel diagnostics;Obsessive-Compulsive Disorder;Outcome Measure;Peer Review;Persons;Pilot Projects;Post-Traumatic Stress Disorders;Postdoctoral Fellow;Privatization;Productivity;recruit;Rehabilitation therapy;Research;Research Personnel;Research Project Grants;Resources;Science;Scientist;Seizures;Sensory;Services;Shapes;Spinal cord injury;Strategic Planning;Stroke;Testing;Therapeutic;Training;Translating;Translational Research;undergraduate student;Universities;Veterans

STUDY_SECTION_NAME: Rehabilitation Engineering & Prosthetics/Orthotics [RRD5]


NIH_SPENDING_CATS: Arthritis;Autoimmune Disease;Behavioral and Social Science;Chronic Pain;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Pain Research;Pediatric;Rheumatoid Arthritis;Social Determinants of Health

ORG_CITY: HARTFORD

ORG_NAME: CONNECTICUT CHILDREN'S MEDICAL CENTER

ORG_STATE: CT

PHR: NARRATIVE Pain-related stigma is a significant and understudied psychosocial factor among adolescents with chronic widespread musculoskeletal pain (CWMP), that has been implicated in impairment in health outcomes and quality of life. This project aims to: 1) develop a novel pain-related stigma framework that is useful in assessing outcomes in adolescent CWMP; and 2) develop and validate the Pain-Related Stigma Scale for Adolescents with CWMP (PReSS-A). This study will lay the foundation for understanding pain-related stigma and developing clinical interventions that will target social factors and improve health outcomes in this population.

PI_NAMEs: WAKEFIELD, EMILY O (contact)

PROGRAM_OFFICER_NAME: WANG, YAN Z

PROJECT_TERMS: Adolescent;adolescent health outcomes;Age;Anxiety;anxiety symptoms;Area;authority;career development;Child;Childhood;childhood epilepsy;Chronic;Chronic Childhood Arthritis;chronic pain;Clinical;Collaborations;comparative;comparison group;Connecticut;Consultations;cost;Dedications;depressive symptoms;design;Development Plans;Diagnosis;Diagnostic;disability;Disease;effectiveness evaluation;Equation;Exhibits;experience;Family;Fibromyalgia;Focus Groups;Foundations;Functional impairment;Funding;Future;Goals;Grant;Health;health care service utilization;health disparity;Health Personnel;Impaired health;Impairment;improved;Individual;innovation;Institution;Intervention;Judgment;K-Series Research Career Programs;Measures;Medical;Medical center;medical schools;Mental Depression;Mentorship;Methods;Modeling;Musculoskeletal Pain;National Institute of Arthritis, and Musculoskeletal, and Skin Diseases;novel;Obesity;Outcome;Outcome Assessment;Pain;Pain intensity;Pain Nature;Palliative Medicine;Parents;Pathology;patient population;Patient Self-Report;Patients;Pediatric Hospitals;Pediatrics;peer;Perception;Performance;Physicians;poor health outcome;Population;professor;Property;Provider;Psychologist;Psychometrics;psychosocial;Psychosocial Factor;public health priorities;Quality of life;randomized, clinical trials;Recovery;Reporting;Research;Research Design;Research Personnel;Resources;Role;Sampling;Schools;Site;social;social factors;social relationships;social stigma;Source;Statistical Data Interpretation;Stigmatization;Symptoms;Testing;Training;Treatment outcome;Uncertainty;Universities;Work;Youth

PROJECT_TITLE: The Impact of Social Rejection: Investigating Pain-related Stigma in Adolescents with Chronic Widespread Musculoskeletal Pain

STUDY_SECTION: AMS

STUDY_SECTION_NAME: Arthritis and Musculoskeletal and Skin Diseases Special Grants Study Section[AMS]


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

NIH_SPENDING_CATS: Genetics;Hematology;Human Genome;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: AMES

ORG_DEPT: GENETICS

ORG_NAME: IOWA STATE UNIVERSITY

ORG_STATE: IA

PHR: Project Narrative This research will contribute to fundamental knowledge of the molecular mechanisms required to specify hematopoietic stem cells. The proposed research is relevant to public health because these findings will inform the development of in vitro protocols for the generation of patient-derived hematopoietic stem cells to treat blood disorders such as leukemia, anemia and hemoglobinopathies, enhancing these patient's treatment options and success rates.

PI_NAMEs: ESPÍN PALAZÓN, RAQUEL  (contact)

PROGRAM_OFFICER_NAME: ROY, CINDY

PROJECT_TERMS: Address;Affect;Anemia;Binding;Bioinformatics;Blood;blood treatment;Cells;Cellular Stress;Chromatin;Cleavage Under Targets and Release Using Nuclease;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;Complement;Data;Development;Dissection;epigenetic profiling;epigenomic profiling;experimental study;Family member;FDA approved;Fibroblast Growth Factor;Generations;Genes;Genetic;Genetic Epistasis;Goals;Health;Hematological Disease;Hematopoiesis;Hematopoietic;Hematopoietic Cell Production;hematopoietic differentiation;hematopoietic stem cell emergence;hematopoietic stem cell expansion;hematopoietic stem cell fate;Hematopoietic Stem Cell Specification;Hematopoietic Stem Cell Transplantation;Hematopoietic stem cells;hemogenic endothelium;Hemoglobinopathies;Human;human pluripotent stem cell;Image;Immune system;improved;in utero;In Vitro;in vivo;Inflammasome;Inflammation;Inflammation Mediators;Inflammatory;insight;Interferons;Investigation;Knowledge;Laboratories;leukemia;Light;Mediating;Methods;Microscopy;Modeling;Molecular;mutant;NF-kappa B;Nitric Oxide;Nitric Oxide Pathway;notch protein;novel;Nucleotides;Organism;p65;Pathway interactions;Patients;Pharmaceutical Preparations;Phosphotransferases;Pluripotent Stem Cells;Property;Proteins;Protocols documentation;Public Health;receptor;reconstitution;recruit;Reporter;Reporting;Research;Research Personnel;RIPK2 gene;Role;Signal Pathway;Signal Transduction;Sorting;Specific qualifier value;Stem Cell Development;stem cell technology;stem cells;success;System;Techniques;tool;transcriptome sequencing;transcriptomic profiling;Transgenic Organisms;Translating;Zebrafish

PROJECT_TITLE: Molecular dissection of Hematopoietic Stem Cell specification triggered by inflammatory mediators

STUDY_SECTION: BBHV

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


NIH_SPENDING_CATS: Biotechnology;Coronaviruses;Data Science;Emerging Infectious Diseases;Genetics;Human Genome;Infectious Diseases;Networking and Information Technology R&D (NITRD)

ORG_DEPT: PEDIATRICS

PHR: PROJECT NARRATIVE The Human Leukocyte Antigen (HLA) and Killer-cell Immunoglobulin-like Receptor (KIR) genes are highly complex and varied when compared to the rest of the human genome, but are central for understanding the genetic basis of disease and for improving human health. The system of tools, standards and services that we are building will maximize the use of current and future forms of data for the HLA and KIR genes, facilitating clinical therapies and giving clinicians easier access to research findings. The expanded HLA|COVID-19 Database will serve as a community resource for studying the relationship of HLA and KIR gene variants with many human diseases.

PI_NAMEs: HOLLENBACH, JILL ALLISON;MACK, STEVEN JOHN (contact)

PROGRAM_OFFICER_NAME: KULKARNI, SHILPA S

PROJECT_TERMS: 6p21;Address;Adopted;Advanced Development;Amino Acid Motifs;analytical method;Autoimmune;Basic Science;bench to bedside;Big Data;Bone Marrow;CD94 Antigen;Chromosome 19;Chromosome 6;Clinical;Clinical Data;clinical phenotype;Clinical Research;Code;Collection;Communication;Communities;Complex;complex data;Computer software;Computerized Medical Record;Copy Number Polymorphism;COVID-19;Data;Data Analyses;data format;data management;Data Set;Databases;design;Development;Disease;disease phenotype;electronic data;electronic medical record system;empowerment;exome;experience;Fast Healthcare Interoperability Resources;Fostering;Future;Future Generations;Genes;Genetic;genetic variant;Genetic Variation;genomic data;Genomic Segment;Genotype;Goals;Health;Health Insurance Portability and Accountability Act;health management;Health Status;Health system;HLA Antigens;Housing;Human;Human Chromosomes;human data;human disease;Human Genome;Immune;Immunogenetics;Immunogenomics;Immunoglobulins;improved;Informatics;Infrastructure;infrastructure development;Integrated Health Care Systems;interoperability;Killer Cells;Ligands;Malignant Neoplasms;Medical;Metadata;Methods;Modernization;next generation;novel;open source;Organ Transplantation;pharmacologic;Play;precision medicine;programs;rare variant;receptor;Receptor Gene;Reporting;Research;Research Personnel;Resources;Rest;Role;SARS-CoV-2 antigen;Science;Services;Single Nucleotide Polymorphism;SNP genotyping;Solid;Standardization;System;tool;tool development;translational applications;translational medicine;transmission process;Transplantation;Variant;whole genome;Work

PROJECT_TITLE: Integrated Exchange and Storage of Current- and Future-Generation Immunogenomic Data

STUDY_SECTION: BDMA

STUDY_SECTION_NAME: Biodata Management and Analysis Study Section[BDMA]


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

ORG_DEPT: PHARMACOLOGY

PHR: Successful completion of the proposed studies will significantly advance our knowledge regarding molecular mechanisms that govern human oligodendroglia-specific circRNA landscapes and may identify human oligodendroglia circRNAs that promote myelin lesion repair, which will have a significant impact on myelin disorders. Given the increasingly documented circRNA abnormalities in neurodegenerative and neuropsychiatric diseases, strategies and experimental tools generated by our studies can be readily applied to explore circRNA function in various neural cell types in healthy and diseased human brains far beyond this proposal, which is a critical prerequisite for developing novel diagnosis/prognosis biomarkers and therapeutics.

PI_NAMEs: FENG, YUE  (contact);YAO, BING

PROGRAM_OFFICER_NAME: TYLER, WILLIAM A

PROJECT_TERMS: 3-Dimensional;Affect;Alternative Splicing;Axon;Biogenesis;Biological;Biological Process;Biology;Brain;Brain Diseases;Cell Line;Cell model;Cell Nucleus;Cell Physiology;cell type;Cells;Central Nervous System;circular RNA;Complex;Cyclin-Dependent Kinase 5;Data;Defect;Demyelinating Diseases;Development;developmental disease;Diagnosis;differential expression;differentiation in vitro;Disease;Etiology;Exons;frontal lobe;Goals;Human;human disease;human induced pluripotent stem cells;Impairment;infancy;insight;Knowledge;Lesion;Literature;Mediating;Mental disorders;Messenger RNA;MicroRNAs;Molecular;mouse model;mRNA Precursor;Multiple Sclerosis;Mus;Myelin;myelination;Nervous System Disorder;neural;Neurodegenerative Disorders;Neuroglia;Neurons;neuropsychiatric disorder;novel;novel therapeutics;Oligodendroglia;Pathogenesis;Pathway interactions;Phosphorylation;Play;Porifera;prognosis biomarker;Rattus;Regulation;repaired;Reporting;RNA;RNA-Binding Proteins;Rodent;Role;Schizophrenia;selective expression;Signal Transduction;spheroids;stem cell differentiation;stem cell model;Structure;technology platform;Testing;Therapeutic;tool;transcriptome;transcriptome sequencing;white matter

PROJECT_TITLE: Regulation and function of human neural circular RNAs

STUDY_SECTION: MNG

STUDY_SECTION_NAME: Molecular Neurogenetics Study Section[MNG]


ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: PROJECT NARRATIVE ETS transcription factor gene fusions occur in approximately 50% of prostate cancer patients. This application is designed to elucidate the molecular mechanisms of prostate cancer pathogenesis induced by the cooperation between overexpression of putative oncogenic ETS-related gene (ERG) and inactivation of the p53 tumor suppressor. Findings from the proposed studies will shed new light on prostate pathobiology and lead to identify new targets for development of novel therapeutics for the effective treatment of this subtype of the disease.

PI_NAMEs: WANG, LIEWEI  (contact)

PROGRAM_OFFICER_NAME: GHOSH-JANJIGIAN, SHARMISTHA

PROJECT_TERMS: Acceleration;advanced prostate cancer;Age;Age Months;American;androgen sensitive;anti-cancer;Binding;Cancer Etiology;Cancer Patient;Cancerous;CDK2 gene;Cell Cycle Progression;Cells;Cessation of life;Chromatin;clinically significant;Code;Complex;Data;demethylation;design;Development;disorder subtype;effective therapy;Elderly;Epigenetic Process;Exons;Gene Deletion;Gene Expression;Gene Fusion;Gene Mutation;Gene Proteins;Gene Targeting;Genes;Genetic Transcription;genomic locus;KDM1A gene;Knock-out;Lesion;Malignant neoplasm of prostate;Mediating;men;Metastatic Prostate Cancer;Molecular;Molecular Mechanisms of Action;molecular subtypes;Mus;Mutation;N-terminal;next generation sequencing;novel;novel therapeutics;Oncogene ETS;Oncogenic;overexpression;Pathogenesis;Pathway interactions;Patients;Phosphorylation;Precision therapeutics;programs;promoter;Prostate;prostate cancer cell;Prostate Cancer therapy;prostate carcinogenesis;Prostatic Intraepithelial Neoplasias;Reader;Regulation;Role;Signal Pathway;Signal Transduction;Specimen;Testing;Threonine;TMPRSS2 gene;TP53 gene;TP53 Gene Inactivation;transcription factor;transcriptome;Transgenes

PROJECT_TITLE: Cooperativity of TMPRSS2-ERG fusion with p53 inactivation in prostate cancer pathogenesis

STUDY_SECTION: CAMP

STUDY_SECTION_NAME: Cancer Molecular Pathobiology Study Section[CAMP]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Cancer;Genetics;Prevention

ORG_CITY: DAYTON

ORG_NAME: WRIGHT STATE UNIVERSITY

ORG_STATE: OH

PHR: PROJECT NARRATIVE . This proposed research is relevant to public health because the goal of understanding the molecular mechanisms of the evolutionarily conserved DNA replication checkpoint is to increase our knowledge about genome instability, oncogenesis, and cancer chemotherapy.

PI_NAMEs: XU, YONGJIE  (contact)

PROGRAM_OFFICER_NAME: REDDY, MICHAEL K

PROJECT_TERMS: Affect;anti-cancer;Antineoplastic Agents;Area;Biochemical;Cell Death;Cells;Chemotherapy-Oncologic Procedure;Collection;Complex;Data;Defect;disorder prevention;DNA biosynthesis;DNA replication fork;DNA-Directed DNA Polymerase;Eukaryota;Fission Yeast;forward genetics;Genetic;Genome Stability;Genomic Instability;Goals;helicase;Human;improved;In Vitro;in vivo;Knowledge;Malignant Neoplasms;Mammalian Cell;Methods;Molecular;Monitor;mutant;Mutation;Pathway interactions;Phosphotransferases;prevent;Process;programs;protein purification;Proteins;Public Health;Publishing;reconstitution;replication stress;Research;response;S phase;sensor;Signal Pathway;Signal Transduction;Stress;Study models;tumorigenesis;Work

PROJECT_TITLE: DNA Replication Checkpoint in Fission Yeast

STUDY_SECTION: MRAA

STUDY_SECTION_NAME: Maximizing Investigators? Research Award A Study Section[MRAA]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Biomedical Imaging;Brain Disorders;Clinical Research;Drug Abuse (NIDA only);Machine Learning and Artificial Intelligence;Mental Health;Networking and Information Technology R&D (NITRD);Neurosciences;Opioid Misuse and Addiction;Opioids;Physical Injury - Accidents and Adverse Effects;Precision Medicine;Substance Misuse

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: Recent reports suggest opioid-related deaths reached record levels in the past 12 months, highlighting the risk of relapse to high-potency opioids and the need to provide ongoing medical treatments for those with opioid- use disorder. More convenient imaging tools and sophisticated statistical approaches are needed to capture important neuro-information underlying drug-taking behaviors and to better identify those at increased risk of relapse. A promising clinical tool, functional near-infrared spectroscopy, together with novel computational approaches (e.g., deep learning) may aid in identifying key drivers of relapse vulnerability, thus revealing appropriate treatment approaches to decrease relapse and increase treatment adherence.

PI_NAMEs: REGIER, PAUL  (contact)

PROGRAM_OFFICER_NAME: MOLLICK, JESSICA ANN

PROJECT_TERMS: Accounting;addiction;Adherence;Anxiety;Area;Attention;Behavior;Behavioral;biomarker selection;Brain;Brain imaging;Brain Injuries;career;career development;Classification;Clinical;Cocaine use disorder;Cognitive;comorbidity;Complex;Computational Technique;computerized;computerized tools;cost effective;cue reactivity;Data;Decision Making;deep learning;deep learning model;deep neural network;depressive symptoms;design;Development;Devices;Diagnostic;Drug usage;effective therapy;Executive Dysfunction;executive function;Exhibits;experience;flexibility;Foundations;functional near infrared spectroscopy;Future;Goals;Gur;Harm Reduction;Imaging Device;Imaging Techniques;Imaging technology;improved;improved outcome;Individual;innovation;Knowledge;Lead;Life;Linear Regressions;Measures;Medical;medication compliance;medication nonadherence;medication-assisted treatment;Mental Depression;Mental Health;Mentors;Modeling;multitask;neglect;neural;neural correlate;Neurocognition;Neurocognitive;neuroimaging;Neurosciences;novel;Opioid;opioid epidemic;opioid exposure;opioid mortality;opioid overdose;opioid use disorder;Outcome;outcome prediction;Outpatients;Overdose;overdose death;Overdose reversal;parent grant;Participant;Patients;Pattern;Performance;Persons;Pharmaceutical Preparations;Population;portability;pre-clinical;predict clinical outcome;Prior Therapy;Public Health;Recovery;Recovery Support;recruit;Regulation;Relapse;relapse prevention;relapse risk;Reporting;Research;Research Project Grants;Risk;Scientist;Sexual abuse;Shapes;Short-Term Memory;Site;Source;spatiotemporal;statistics;Subgroup;Suboxone;Surveys;Testing;tool;Training;treatment adherence;Treatment outcome;wearable device

PROJECT_TITLE: Integrating brain, neurocognitive, and computational tools in Opioid Use Disorder (OUD) to characterize executive function and to predict clinical outcomes

STUDY_SECTION_NAME: Adult Psychopathology and Disorders of Aging Study Section[APDA]


ORG_CITY: Nashville

ORG_NAME: VANDERBILT UNIVERSITY

ORG_STATE: TN

PHR: Determining the mechanisms by which myosin II-based contractile systems assemble has promise to provide a mechanistic understanding of force-dependent pathological processes leading to diseases, such as cancer and cardiovascular disease. Identification of therapeutic targets to modify the forces driving disease could have health benefits for the public at large. The research proposed here aims to develop a molecularly detailed and predictive model of how contractile systems generate force to drive cell division, cell movement, and muscle contraction, with the ultimate goal of distinguishing mechanisms used by normal vs. aberrant cells.

PI_NAMEs: BURNETTE, DYLAN TYLER (contact)

PROGRAM_OFFICER_NAME: FLICKER, PAULA F

PROJECT_TERMS: Address;alpha Actinin;Area;beta-Myosin;biophysical properties;Cardiac Myocytes;Cardiovascular Diseases;cell cortex;Cell division;cell motility;Cell Physiology;Cells;Contractile System;Cytokinesis;Developmental Biology;Disease;driving force;Embryo;experimental study;Filament;Funding;Future;Generations;Goals;Health Benefit;In Vitro;in vivo;Individual;Interphase;Investigation;Life;Light;Malignant Neoplasms;Mechanics;Mitosis;Molecular;molecular assembly/self assembly;Molecular Motors;Muscle;Muscle Contraction;muscle stress;Myosin ATPase;Myosin Type II;Nonmuscle Myosin Type IIA;Nonmuscle Myosin Type IIB;Output;paralogous gene;Pathologic Processes;Phosphorylation;predictive modeling;Process;Production;programs;Proteins;Reporting;Research;Role;Sarcomeres;Stress Fibers;Testing;therapeutic target;Work;Zebrafish

PROJECT_TITLE: The assembly and function of cellular contractile systems

STUDY_SECTION: MRAC

STUDY_SECTION_NAME: Maximizing Investigators' Research Award C Study Section[MRAC]


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Cancer;Hematology;Immunotherapy

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Project Narrative Multidimensional immune correlative analysis revealed a striking negative association between CD8 expression on donor NK cells and treatment response in a clinical trial of relapsed/refractory AML patients treated with memory-like NK cells. This proposal aims to explore molecular mechanisms driving a proliferative defect in the CD8+ NK population, and to interrogate the function of the CD8 molecule itself. These findings will provide insights into fundamental mechanisms of human NK cell biology and will have broad implications across the fields of cancer, infection, and autoimmunity.

PI_NAMEs: CUBITT, CELIA CLAIRE (contact)

PROGRAM_OFFICER_NAME: GONDRE-LEWIS, TIMOTHY A

PROJECT_TERMS: Acute Myelocytic Leukemia;Adoptive Cell Transfers;anti-tumor immune response;Antitumor Response;ATAC-seq;Autoimmune Diseases;Autoimmunity;Automobile Driving;Binding;CD8 Antigens;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Physiology;Cell Proliferation;cell transformation;cell type;Cells;Cellular biology;chemotherapy;Chromatin;Clinical;Clinical Trials;CRISPR/Cas technology;curative treatments;cytokine;Cytokine Receptors;cytotoxic;cytotoxicity;Data;Defect;Dimensions;Disease remission;Epigenetic Process;Equilibrium;Exhibits;first-in-human;Future;gene editing technology;Germ Lines;Goals;Hematologic Neoplasms;Hematopoietic Stem Cell Transplantation;Human;IL18 gene;Immune;Immunologic Surveillance;improved;In Vitro;in vivo;in vivo Model;Infection;Inflammatory;insight;Interleukin-12;Interleukin-15;knock-down;Length;Leukemic Cell;loss of function;Lymphoid Cell;Malignant - descriptor;Malignant Neoplasms;Measures;Mediating;Membrane Glycoproteins;Memory;Metabolic;Metabolic Pathway;MHC Class I Genes;Modeling;Molecular;Mus;Natural Killer Cells;NK Cell Activation;NK cell therapy;Patient-Focused Outcomes;Patients;phase 1 study;Phase I Clinical Trials;Phenotype;Population;Prediction of Response to Therapy;Production;Proliferating;receptor;receptor expression;Receptor Signaling;recruit;Refractory;Regulation;Relapse;response;Role;Safety;Signal Transduction;T-Cell Receptor;T-Lymphocyte;telomere;therapy design;Treatment Failure;Treatment outcome;treatment response;tumor;Viral;Work

PROJECT_TITLE: Mechanism of CD8 regulation of natural killer cell biology

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F07-U(20)L]


NIH_SPENDING_CATS: Autism;Brain Disorders;Genetics;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Pediatric

ORG_DEPT: NEUROLOGY

PHR: Relevance Autism spectrum disorder is an early onset, life-long disorder that affects approximately 1% of the population and is defined by fundamental impairments in social communication and restricted or repetitive behavior or interests. This work focuses on understanding how dysfunctions in the autism-linked gene SCN2A, which encodes a neuronal sodium channel, affects neuronal function. This project will shed light on the cellular and circuit mechanisms that contribute to the disorder, and potentially identify developmental timepoints for therapeutic intervention.

PI_NAMEs: BENDER, KEVIN J (contact)

PROGRAM_OFFICER_NAME: DRISCOLL, JAMIE DANIELLE

PROJECT_TERMS: Action Potentials;Address;Adult;Affect;Apical;autism spectrum disorder;Axon;Back;Biological;Birth;Calcium;Cells;Chromatin Remodeling Factor;Complement;Cre-LoxP;critical period;Dendrites;Development;Disease;Distal;early onset;Electrophysiology (science);Engineering;Epilepsy;Etiology;excitatory neuron;exome sequencing;Family;Functional disorder;Future;gain of function;Gene Cluster;Genes;Genetic Techniques;Glutamates;Goals;Heterozygote;High-Throughput Nucleotide Sequencing;hippocampal pyramidal neuron;Hippocampus;Image;Impairment;infancy;insight;Intellectual functioning disability;interest;Knock-in Mouse;Knock-out;Knowledge;Life;Link;loss of function;loss of function mutation;Loss of Heterozygosity;LoxP-flanked allele;member;Missense Mutation;Modeling;mouse genetics;mouse model;Mus;Mutation;Neocortex;neocortical;Neurodevelopmental Disorder;neuronal excitability;Neurons;novel;Physiological;Population;postnatal development;Prefrontal Cortex;Property;Protein Isoforms;Proteins;Pyramidal Cells;Recovery of Function;repetitive behavior;Reporting;restoration;Role;SCN2A protein;SCN8A gene;Shapes;Site;social communication;Sodium Channel;Synapses;synaptic function;Synaptic plasticity;Techniques;Testing;Therapeutic;Therapeutic Intervention;Time;two-photon;Variant;voltage;Work

PROJECT_TITLE: The function of SCN2A in neocortex


NIH_SPENDING_CATS: Cancer;Genetics;Immunotherapy

ORG_CITY: NEW YORK

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

ORG_STATE: NY

PHR: PROJECT NARRATIVE The objective of this project is to establish the genes and pathways negatively regulating the immunostimulatory state of antigen-charged dendritic cells (DC), and to determine how targeting these pathways alters the functional state of DC and impacts induction of tumor immunity.

PI_NAMEs: BROWN, BRIAN D;MERAD, MIRIAM  (contact)

PROGRAM_OFFICER_NAME: KUO, LILLIAN S

PROJECT_TERMS: Address;ALDH1A2 gene;anti-PD-1;Antigen Presentation;Antigens;Antitumor Response;BIRC2 gene;BIRC3 gene;cancer cell;cancer immunotherapy;cancer infiltrating T cells;CD 200;CD8-Positive T-Lymphocytes;Cell Death;Cell Maturation;cell motility;Cell Physiology;Cell Shape;Cells;Cellular biology;Charge;Clinical;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;Cross Presentation;cytokine;Data;Dendritic cell activation;Dendritic Cells;draining lymph node;effector T cell;Equilibrium;Genes;Genetic Transcription;genomic platform;Goals;Human;IL12B gene;IL4 gene;IL4R gene;Immune;Immunity;Immunophenotyping;immunoregulation;Immunotherapy;improved;in vivo;Individual;Infiltration;Inhibition of Apoptosis;inhibitor;interest;Interleukin-12;Interleukin-4;Knock-out;Lesion;Lung Neoplasms;Lymphocyte Activation;Macrophage;Mediating;Modeling;Molecular;Molecular Profiling;mouse model;Mus;Nature;NF-kappa B;NFKB Activation Pathway;Non-Small-Cell Lung Carcinoma;Outcome;Output;Pathway Analysis;Pathway interactions;PD-1 blockade;pharmacologic;Phenotype;Physiology;Population;pre-clinical;Pre-Clinical Model;prevent;Production;programmed cell death ligand 1;programmed cell death protein 1;programs;Regulator Genes;Resolution;response;Role;Signal Transduction;single-cell RNA sequencing;synergism;T cell response;T-Lymphocyte;Testing;Therapeutic;TNFRSF5 gene;TNFSF4 gene;tumor;Tumor Antigens;Tumor Burden;Tumor Expansion;tumor growth;Tumor Immunity;Tumor Promotion;ubiquitin ligase;uptake

PROJECT_TITLE: Deciphering the molecular control of intratumoral dendritic cells

STUDY_SECTION: CII

STUDY_SECTION_NAME: Cancer Immunopathology and Immunotherapy Study Section[CII]


NIH_SPENDING_CATS: Behavioral and Social Science;Biomedical Imaging;Breast Cancer;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Health Services;Prevention;Primary Health Care;Women's Health Research

PHR: Project Narrative Given past health messages that strongly promoted mammography screening, recent revisions to guidelines that promote informed choice constitute a health message reversal that can be difficult for many women to accept. This research will employ nationally representative and longitudinal surveys of women 40-49 that aim to understand women’s affective reactions to screening evidence and the consequences of those reactions for screening preferences and shared decision making with a primary care provider. This research will directly inform how to more effectively communicate about breast cancer screening to maintain credibility and trust when health messages change.

PI_NAMEs: SCHERER, LAURA D. (contact)

PROGRAM_OFFICER_NAME: FERRER, REBECCA

PROJECT_TERMS: Affective;Age;age group;Agreement;Appointment;Attitude;Behavioral Sciences;Breast Cancer Detection;cancer risk;Cognitive;Communication;comorbidity;coping;Decision Aid;Decision Making;Diagnosis;distrust;empowerment;Environment;Equilibrium;Evaluation;expectation;Family;Feeling;Focus Groups;follow-up;Friends;Fright;Future;Guidelines;Harm Reduction;Health;Health Care Rationing;improved;insight;interest;Interview;Knowledge;Longitudinal Studies;Longitudinal Surveys;Mammographic screening;Mammography;Medical;overtreatment;Patients;personalized approach;Persons;pilot test;Population;predicting response;preference;Prevalence;Primary Care;primary care provider;Probability;Randomized;Reaction;Recommendation;Research;response;Risk;screening;Screening for cancer;screening guidelines;shared decision making;social;Social Environment;Source;Suggestion;Surveys;Telephone;Testing;theories;Time;Trust;United States Preventative Services Task Force;Woman

PROJECT_TITLE: Understanding affective processing of scientific evidence to promote informed choice for breast cancer screening

STUDY_SECTION: SPIP

STUDY_SECTION_NAME: Social Psychology, Personality and Interpersonal Processes Study Section[SPIP]


NIH_SPENDING_CATS: Clinical Research;Congenital Structural Anomalies;Genetics;Kidney Disease;Orphan Drug;Pediatric;Rare Diseases

ORG_CITY: BAR HARBOR

ORG_NAME: JACKSON LABORATORY

ORG_STATE: ME

PHR: RELEVANCE TO PUBLIC HEALTH Despite the enormous clinical, societal and economic challenges for patients with end-stage renal disease (ESRD) and the predicted increase due to a growing aging and diabetic population (the two largest risk factors), there have been no new therapies in the past 15 years. By focusing on the genetics of X-linked Alport syndrome, the most common inherited glomerular disease leading to renal failure, and identifying the modifier genes that affect the age-of-onset and severity of the disease, our studies will lead to a better understanding of the initiation and progression of the disease process in general and will help to reveal novel therapeutic targets to combat ESRD in patients with Alport syndrome as well as patients with other forms of kidney disease.

PI_NAMEs: KORSTANJE, RONNY  (contact)

PROGRAM_OFFICER_NAME: PARSA, AFSHIN

PROJECT_TERMS: Affect;Age of Onset;Aging;Albuminuria;Biological;Candidate Disease Gene;candidate identification;Chromosome Mapping;Clinical;cohort;COL4A3 gene;Collagen Type IV;combat;CRISPR/Cas technology;Data;Detection;detection test;diabetic;Diabetic Nephropathy;Disease Progression;Drug Design;Economics;End stage renal failure;Etiology;Event;exome sequencing;Factor X;Family;Female;Focal and Segmental Glomerulosclerosis;Future;Genes;Genetic;genetic analysis;genetic pedigree;Genetic study;genome-wide;Genomic Segment;glomerular basement membrane;Glomerulonephritis;Hematuria;Hereditary nephritis;Heterozygote;Histology;Histopathology;Human;human disease;improved;Inherited;insight;Kidney;Kidney Diseases;Kidney Failure;kindred;Knock-out;Knockout Mice;Lead;Link;male;Maps;Measures;member;Molecular;mouse model;Mus;mutant;Mutant Strains Mice;Mutation;new therapeutic target;novel;novel therapeutic intervention;novel therapeutics;Pathogenesis;Pathway interactions;Patients;Pharmacotherapy;Phenotype;Population;pre-clinical;Process;protective factors;Proteins;Public Health;Renal function;Renal glomerular disease;Research;Resolution;Resources;Risk Factors;Sample Size;Sampling;Severities;Severity of illness;Source;Symptoms;Syndrome;Testing;translational impact;Universities;Urea;Utah;Validation;Variant;X Chromosome

PROJECT_TITLE: Identification of Kidney Disease Modifier Genes in Mouse and Human Alport Syndrome

STUDY_SECTION: PBKD

STUDY_SECTION_NAME: Pathobiology of Kidney Disease Study Section[PBKD]


NIH_SPENDING_CATS: Behavioral and Social Science;Biotechnology;Breast Cancer;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Nutrition;Obesity;Physical Activity;Prevention;Women's Health Research

ORG_CITY: MILWAUKEE

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

ORG_STATE: WI

PHR: Narrative The community of women living with metastatic breast cancer is growing. Many are looking for programs to help support efforts to adopt healthy lifestyle behaviors that can improve quality of life and potentially enhance survivorship. This study examines the effects of “Every Day Counts,” a lifestyle intervention, on body composition, patient reported outcomes, biomarkers of inflammation and insulin resistance, adipokines; and also explores changes in mitochondrial function and miRNA.

PI_NAMEs: SHEEAN, PATRICIA MAUREEN;STOLLEY, MELINDA R (contact)

PROGRAM_OFFICER_NAME: EMENAKER, NANCY J

PROJECT_TERMS: Address;Adherence;adipokines;Adipose tissue;Adopted;Adverse event;African American Women;American Cancer Society;attentional control;Behavior;Behavioral;Biological;Biological Markers;Body Composition;Cancer Survivor;Caring;Chronic Disease;Clinical;clinically significant;Communities;Consensus;Control Groups;control trial;design;differential expression;Dimensions;Disease;Disease Management;Distress;Eating;efficacy evaluation;Evidence based intervention;Exclusion;Exercise;exercise intervention;Exhibits;experience;Fatigue;Feedback;Goals;Guidelines;Habits;healthy lifestyle;improved;Incidence;Inflammation;Inflammatory;innovation;Insulin Resistance;insulin sensitivity;interest;Intervention;intervention effect;Intervention Trial;Lead;Life Style;lifestyle intervention;Mediating;Menopausal Status;Metastatic breast cancer;Methodology;MicroRNAs;Mitochondria;Molecular;multidisciplinary;novel;nutrition;Obesity;Outcome;Participant;Pathway interactions;Patient Outcomes Assessments;Physical activity;Physical Function;physiologic model;Pilot Projects;pilot trial;post intervention;Prognosis;prognosis biomarker;prognostic;Program Sustainability;programs;Quality of life;Randomized;Recommendation;recruit;reduce symptoms;Research;Safety;Serum;Survivors;survivorship;Symptom Burden;symptom management;targeted treatment;Testing;theories;Thinness;Toxicity due to chemotherapy;treatment response;Treatment-related toxicity;trend;tumor progression;Tumor Promotion;Underserved Population;Update;Waiting Lists;Woman;Women's trial;Work;young woman

PROJECT_TITLE: Every Day Counts: A lifestyle program for women metastatic breast cancer

STUDY_SECTION: BMHO

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


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Drug Abuse (NIDA only);Mental Health;Mental Illness;Neurosciences;Substance Misuse

ORG_CITY: WINSTON-SALEM

ORG_DEPT: NEUROSCIENCES

ORG_NAME: WAKE FOREST UNIVERSITY HEALTH SCIENCES

ORG_STATE: NC

PHR: Project Narrative The dopaminergic system is hypothesized to underlie the NIMH Research Domain Criteria construct ‘Reward Learning’ and its subconstructs ‘Reward Prediction Error’ and ‘Probabilistic and Reinforcement Learning.’ Impulse control disorder, which is induced by dopamine receptor agonist medications, consists of increased risky behavior including increased problem gambling – a DSM-V recognized behavioral addiction. The proposed experiments aim to investigate individuals with and without impulse control disorder symptoms to determine the role sub-second dopamine signals play in ‘Reward Learning,’ ‘Reward Prediction Error,’ and ‘Probabilistic and Reinforcement Learning’ in humans and how these constructs and the dopamine system may be altered in patients predisposed to problem gambling and impulse control disorder.

PI_NAMEs: LIEBENOW, BRITTANY  (contact)

PROGRAM_OFFICER_NAME: LIN, YU

PROJECT_TERMS: addiction;Affect;Alcohol dependence;Area;Behavior;Behavior assessment;behavior influence;behavior measurement;Behavioral;Behavioral Sciences;Brain region;Categories;Characteristics;Choice Behavior;Clinical;Clinical assessments;clinical training;Computers;Conscious;Corpus striatum structure;Data;Data Analyses;Data Collection;Decision Making;Deep Brain Stimulation;design;Detection;Diabetes Mellitus;Disease;Doctor of Philosophy;Dopamine;Dopamine Agonists;dopamine system;dopaminergic neuron;DSM-V;Electrochemistry;Electrodes;Event;Exhibits;experience;experimental study;Feedback;Future;Gambling;high risk;Human;implantation;Impulse Control Disorders;Impulsivity;Individual;Learning;Major Depressive Disorder;Manuscripts;Measurement;Measures;Medical;medical schools;Mental disorders;Mentorship;Methods;multidisciplinary;National Institute of Mental Health;neurochemistry;neuroimaging;Neurosciences;neurosurgery;new therapeutic target;novel;novel strategies;Operative Surgical Procedures;Outcome;Parkinson Disease;Participant;Patient Recruitments;Patients;Pharmaceutical Preparations;Play;Population;Preparation;Process;programs;prospective;Protocols documentation;Psychological reinforcement;Punishment;Questionnaires;Recording of previous events;Research;Research Domain Criteria;response;reward processing;Rewards;Risk;Risk Assessment;Risk Behaviors;Risk Taking;Role;Scientist;Signal Transduction;Specificity;Stimulus;Substance Use Disorder;Symptoms;Syndrome;System;Technology;Testing;Time;Training;trait;World Health Organization

PROJECT_TITLE: Dopamine's Role in Impulse Control and Reward Learning in Humans


NIH_SPENDING_CATS: Biotechnology;Cancer;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: BETHESDA

ORG_NAME: HENRY M. JACKSON FDN FOR THE ADV MIL/MED

ORG_STATE: MD

PHR: PROJECT NARRATIVE In RAS-mutated pediatric non-CNS solid tumors, WT RAS signaling underlies therapeutic resistance to therapies targeting either MEK or mutated RAS. This proposal takes a rational approach to assessing combination therapies to designed to treat RAS-mutated pediatric solid tumors that is based on first-principles of inhibiting both mutated RAS and WT RAS signaling to downstream effectors. Hence, this research will inform novel therapeutic approaches designed to prolong the therapeutic window for current targeted therapies and potentially enhance patient survival.

PI_NAMEs: KORTUM, ROBERT  (contact)

PROGRAM_OFFICER_NAME: KONDAPAKA, SUDHIR B

PROJECT_TERMS: Binding;Biological Assay;cancer cell;Cancer cell line;Cancer Patient;cancer type;Cell Culture Techniques;Cell Line;Cells;Childhood;Childhood Solid Neoplasm;Clinical Trials;Combined Modality Therapy;Cytotoxic agent;Data;design;Development;Drug Combinations;Drug resistance;Drug Synergism;Effectiveness;efficacy evaluation;efficacy testing;experimental study;Family member;Farnesyl Transferase Inhibitor;Goals;in vivo;inhibitor;KRAS2 gene;Malignant Childhood Neoplasm;Malignant Neoplasms;MEK inhibition;MEKs;Morbidity - disease rate;mutant;Mutate;neoplastic cell;neuroblastoma cell;novel therapeutic intervention;Outcome;Pathway interactions;patient derived xenograft model;Patients;pediatric patients;Pharmaceutical Preparations;pharmacologic;Phase I Clinical Trials;PIK3CG gene;pre-clinical;Pre-Clinical Model;preclinical study;prevent;Protein Isoforms;PTPN11 gene;RAS genes;RAS inhibition;Ras Inhibitor;ras Proteins;Research;Resistance;Resistance development;Running;Signal Transduction;Solid Neoplasm;synergism;targeted agent;targeted treatment;Testing;Therapeutic;therapeutic target;therapy resistant;Tipifarnib;Tissues;Translating;Treatment Efficacy;tumor;Up-Regulation

PROJECT_TITLE: Preventing Therapeutic Resistance in RAS-mutated Pediatric Cancers


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

NIH_SPENDING_CATS: Autism;Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Bipolar Disorder;Brain Disorders;Clinical Research;Intellectual and Developmental Disabilities (IDD);Machine Learning and Artificial Intelligence;Mental Health;Mental Illness;Networking and Information Technology R&D (NITRD);Neurosciences;Psychosis;Schizophrenia;Serious Mental Illness

ORG_DEPT: MISCELLANEOUS

ORG_NAME: GEORGIA STATE UNIVERSITY

PHR: Project Narrative  There is considerable interest in approaches that capture time-varying connectivity, however existing ap- proaches suffer from three major limitations: 1) extraction of networks and estimation of dynamic features for the most widely used approaches typically makes many limiting assumptions and rely on user defined parameters whose optimality is not guaranteed (e.g. choice of window size, filter settings), 2) methods typically assume relatively simple linear relationships, and 3) most approaches assume the spatial nodes are fixed in time, effec- tively ignoring the possibility of functionally fluid nodes. We propose to address these limitations by developing a family of flexible spatio-temporal models that leverage and blend the concepts of joint blind source separation and deep learning, which we show can reveal important information missed by existing models. We will apply the proposed models to study spatial and temporal aspects of dynamic connectivity across mental illness includ- ing schizophrenia, bipolar disorder, and autism spectrum. 37

PI_NAMEs: ADALI, TULAY ;CALHOUN, VINCE D (contact)

PROGRAM_OFFICER_NAME: FERRANTE, MICHELE

PROJECT_TERMS: Address;Algorithms;Alzheimer's Disease;Area;Attention deficit hyperactivity disorder;autism spectrum disorder;Back;Behavior;Benchmarking;Bipolar Disorder;blind;Brain;Brain Diseases;Classification;clinical care;clinically relevant;Communities;Complex;Computer software;Coupled;Coupling;Data;Data Set;deep learning;diagnostic criteria;Dimensions;Disease;Documentation;Ensure;Evaluation;Evolution;Family;Fingerprint;flexibility;Fractionation;Frequencies;Functional Magnetic Resonance Imaging;Goals;Growth;Individual;interest;Joints;Liquid substance;Mental disorders;Methods;model building;Modeling;Moods;multimodal data;neuropsychiatric disorder;Nonlinear Dynamics;novel;novel strategies;open source;open source tool;Patients;Property;Psychoses;rapid growth;Relaxation;repository;Reproducibility;Research;Research Personnel;Schizophrenia;simulation;social;social cognition;Source;spatial integration;spatiotemporal;Structure;Study models;Subgroup;Symptoms;Testing;Time;tool;translational impact;user-friendly;Validation;web portal;Work

PROJECT_TITLE: Data-driven solutions for temporal, spatial, and spatiotemporal dynamic functional connectivity


ORG_CITY: CHAPEL HILL

ORG_DEPT: BIOLOGY

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: NARRATIVE Research over the last 15 years has revealed that species hybridize more than initially thought, and that hybridization is a common source of genetic variation. This project proposes to determine the environmental and genomic factors that determine the fate of an allelic variant that gets exchanged between species. To do so, we integrate natural collections, method development, and data synthesis to understand the role of hybridization across evolutionary scales.

PI_NAMEs: MATUTE, DANIEL  (contact)

PROGRAM_OFFICER_NAME: ADKINS, RONALD

PROJECT_TERMS: Alleles;Awareness;Behavior;Categories;Chimera organism;climate change;Collection;comparative;Data;Data Set;Drosophila genus;Environment;Eukaryota;Evolution;falls;Gene Exchanges;Genetic;genetic analysis;genetic variant;Genetic Variation;genome sequencing;genomic data;Genomics;Goals;Health;Human;human pathogen;Hybrids;method development;Methods;migration;Nature;Organism;Outcome;parent grant;pathogen;Phenotype;Population;Prevalence;Process;programs;Research;Role;Source;Time;Variant;vector;virulence gene;Work

PROJECT_TITLE: Drivers and consequences of introgression in evolution


NIH_SPENDING_CATS: Neurosciences

PHR: PROJECT NARRATIVE The proposed research is relevant to human health because damage or disease affecting motor cortical dynamics produces disabling and costly motor disorders, which affect over 40 million Americans. This work will use a new toolbox to study how thalamic inputs carrying information from basal ganglia and cerebellum contribute to cortical dynamics and behavior. This project is relevant to the NIH mission because detailed understanding of motor cortical dynamics is expected to advance neuroprosthetics and other therapies, and thus reduce illness and disability.

PI_NAMEs: HANTMAN, ADAM  (contact)

PROGRAM_OFFICER_NAME: CHEN, DAOFEN

PROJECT_TERMS: Affect;American;Animals;Anterior;arm;Automobile Driving;Basal Ganglia;Behavior;Behavioral;Biological Models;Brain;Brain region;Cell Nucleus;Cerebellum;Classification;Collaborations;Complex;Computer Models;cost;Cues;Data;data-driven model;Dimensions;disability;Disabling;Disease;dynamic system;Electrophysiology (science);Experimental Models;experimental study;Foundations;Future;Generations;Genetic;Goals;Hand;Health;Human;innovation;Laboratories;Lateral;Lighting;Methods;Mission;Modeling;molecular marker;Monitor;Motor Cortex;motor disorder;Movement;Mus;Nature;neural;Neurons;neuroprosthesis;Neurosciences;operation;Opsin;Output;Pathway interactions;Pattern;Physiological;Population;Process;Production;Property;repaired;Research;Research Personnel;Rest;Rewards;Role;selective expression;Shapes;Signal Transduction;Stream;System;Testing;Thalamic Nuclei;Thalamic structure;therapy design/development;tool;Transgenic Organisms;transmission process;United States National Institutes of Health;Ventral Lateral Thalamic Nucleus;Work

PROJECT_TITLE: Deconstructing the roles of basal ganglia and cerebellum-related thalamic inputs to motor cortex during control of dexterous behavior

STUDY_SECTION: SMN

STUDY_SECTION_NAME: Sensory-Motor Neuroscience Study Section[SMN]


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Genetics;Human Genome;Infectious Diseases;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Vector-Borne Diseases

ORG_CITY: EUGENE

ORG_NAME: UNIVERSITY OF OREGON

ORG_STATE: OR

PHR: Project Narrative In this MIRA proposal we seek to continue our work at developing computational methods for population genetic inference from whole genome data. We propose three areas of interest: 1) spatial population genetics, 2) the population genetics of adaptation, and 3) development of community library aimed at improving rigor and reproducibility in the field. We will produce multiple tools and resources that will usher in the next generation of inference for the incredibly rich genomic data currently under collection.

PI_NAMEs: KERN, ANDREW D (contact)

PROJECT_TERMS: Africa South of the Sahara;Alleles;Anopheles gambiae;Anopheles Genus;Area;Benchmarking;Collection;Communities;Community Developments;Computing Methodologies;Data;deep learning;Development;diverse data;Evolution;Floods;Funding;Genealogy;Genetic Models;Genetic Recombination;Genome;genome sequencing;genome wide association study;genomic data;genomic variation;Genomics;Geography;improved;interest;Left;Libraries;Methods;next generation;open source;Pattern;Population;Population Explosions;Population Genetics;Process;programs;Publishing;Reproducibility;Research;Resources;response;simulation;Statistical Methods;Structure;supervised learning;System;Techniques;Technology;tool;Variant;vector control;Visualization;whole genome;Work

PROJECT_TITLE: Computational Population Genetics


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Genetics;Neurosciences

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: Project Narrative Organismal development requires stereotypical and random patterning of cell types, dependent on regulation of signaling, transcription, and chromatin. Disruption of either type of patterning during human development can result in severe congenital disorders. Using the fly eye as a genetic model, we aim to understand how these very different patterning mechanisms are coordinated in a single tissue.

PI_NAMEs: ORDWAY, ALISON J (contact)

PROGRAM_OFFICER_NAME: AGARWAL, NEERAJ

PROJECT_TERMS: Address;Affect;antagonist;Binding;Binding Sites;Cell Differentiation process;cell fate specification;cell type;Cells;Chromatin;Cleavage Under Targets and Release Using Nuclease;Clustered Regularly Interspaced Short Palindromic Repeats;Competitive Binding;Congenital Disorders;Coupled;Defect;Development;DNA;Drosophila eye;EMSA;Enhancers;Erinaceidae;experimental study;Eye;Eye Development;fly;Gene Expression;Generations;Genes;Genetic Models;Genetic Transcription;growth factor receptor-bound protein 2;histone modification;Human Development;imaging system;in vivo;Individual;Light;Mediating;migration;Modeling;Molecular;Morphogenesis;Morphology;mutant;Olfactory Pathways;Organ;Organism;Pathway interactions;Pattern;Photoreceptors;Play;Polycomb;precursor cell;Probability;Proteins;Randomized;Regulation;Repression;Reproducibility;Response Elements;Rhodopsin;Role;Sensory;Signal Transduction;Site;smoothened signaling pathway;Specific qualifier value;Stereotyping;Structure;Testing;Tissues;transcription factor;Transcriptional Activation;Vision;Visual System

PROJECT_TITLE: Hedgehog Signaling Coordinates Stochastic and Stereotyped Patterns in the Drosophila Eye

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


NIH_SPENDING_CATS: Biotechnology;Cancer;Immunotherapy

ORG_CITY: DALLAS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: Project Narrative Our study is significant because it will reveal how an immune inhibitory receptor regulates both cancer invasiveness and immune checkpoint function at the interface of cancer and immunology. Our study will also directly guide the development of novel strategies to treat human cancers.

PI_NAMEs: ZHANG, CHENGCHENG  (contact)

PROJECT_TERMS: AIM2 gene;Antibodies;Biology;Blocking Antibodies;cancer immunotherapy;cancer invasiveness;Cancer Patient;cancer therapy;cancer type;Cells;checkpoint receptors;chimeric antigen receptor T cells;Cholecalciferol;Collaborations;Coupled;Development;DNA;extracellular;Family;gain of function;Genetic Transcription;Goals;Hormones;Human;Immune;immune checkpoint;Immunology;Immunosuppression;Immunotherapy;In Vitro;in vivo;Infiltration;Inflammasome;Inositol;insight;ITIM;leukemia;Leukocytes;Ligand Binding Domain;loss of function;Malignant - descriptor;Malignant Neoplasms;Mediator;member;Membrane Glycoproteins;migration;Modeling;Molecular;monocyte;Monocytic leukemia;mouse model;Mus;Myeloid-derived suppressor cells;Natural Immunity;novel;novel strategies;novel therapeutic intervention;patient derived xenograft model;PD-1/PD-L1;PD-L1 blockade;Phosphoric Monoester Hydrolases;Play;progenitor;Proteins;PTPN11 gene;PTPN6 gene;receptor;recruit;Regulation;Role;sensor;Signal Transduction;Solid;stem cells;Supporting Cell;Surface;T-Lymphocyte;Testing;Texas;Therapeutic;tumor;tumorigenic;Up-Regulation;Vitamin D

PROJECT_TITLE: ITIM-receptors for cancer treatment

STUDY_SECTION: TTT

STUDY_SECTION_NAME: Transplantation, Tolerance, and Tumor Immunology Study Section[TTT]


NIH_SPENDING_CATS: Cancer;Clinical Research;Clinical Trials and Supportive Activities;Data Science;Health Services;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Patient Safety

ORG_CITY: BOSTON

ORG_NAME: DANA-FARBER CANCER INST

ORG_STATE: MA

PHR: PROJECT NARRATIVE Electronic health records (EHRs) are now ubiquitous in routine cancer care delivery, but their utility for research and quality improvement has been limited by a dearth of methods for integrating the unstructured data in which most key cancer outcomes are encoded within EHRs. I propose to apply recent innovations in deep learning to integrate structured and unstructured data to create a dynamic pre-trained model of cancer patients' treatment trajectories, and to apply this model to identify patients who are appropriate candidates for clinical trials at times when they are eligible. I will then evaluate the effect of trajectory modeling on clinical trial accrual as I prepare for an independent research career focused on clinical cancer data science.

PI_NAMEs: KEHL, KENNETH L (contact)

PROGRAM_OFFICER_NAME: OSSANDON, MIGUEL

PROJECT_TERMS: Academia;Adult;anti-cancer research;burden of illness;cancer care;cancer clinical trial;Cancer Patient;care delivery;career;Classification;Clinical;clinical candidate;Clinical Data;Clinical Medicine;clinical practice;clinical training;clinical trial enrollment;clinical trial protocol;Clinical Trials;clinically relevant;cohort;Complex;computer scientist;Dana-Farber Cancer Institute;Data;data registry;Data Science;Data Scientist;deep learning;design;Development;Diagnosis;Disease;electronic health data;Electronic Health Record;Eligibility Determination;Enrollment;genomic data;Goals;Government;Health Services Research;Health system;Healthcare Systems;Histology;improved;Industry;innovation;Institution;Intervention;Label;Link;Machine Learning;machine learning model;Malignant Neoplasms;Manuals;Medical Records;Methods;Modeling;multiple data types;Natural Language Processing;neoplasm registry;neural network architecture;novel;Oncologist;Oncology;Outcome;palliative;Pathology Report;patient population;Patients;Phenotype;pre-trained model;precision medicine clinical trials;prevent;Primary Neoplasm;programs;Radiology Specialty;Randomized;Reporting;Research;Research Personnel;Resources;response;Services;Site;skills;Source;Structure;structured data;survival prediction;Systemic Therapy;Techniques;Technology;Text;Therapeutic Trials;Time;tool;Training;transfer learning;trial readiness;tumor progression;unstructured data;Work

PROJECT_TITLE: Deep clinical trajectory modeling to optimize accrual to cancer clinical trials


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Brain Cancer;Brain Disorders;Cancer;Immunotherapy;Nanotechnology;Neurosciences;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

PHR: PROJECT NARRATIVE This project focuses on improving treatment of a pediatric brain cancer, medulloblastoma, that despite aggressive treatments kills 30% of the children from recurrent disease and often leaves the survivors with severe and lifelong treatment-associated cognitive and motor deficits and at risk of subsequent neoplasms. We will use small-molecule toll-like receptor 7 and 8 agonist, resiquimod, packaged in innovative nanoparticles to deliver resiquimod to the tumor, remodel tumor microenvironment and promote antitumor immune response. This project will determine mechanisms of immunotherapy using our novel therapeutic modality and asses its potential in combination with antineoplastic agents to improve treatment outcomes in medulloblastoma.

PI_NAMEs: SOKOLSKY-PAPKOV, MARINA  (contact)

PROGRAM_OFFICER_NAME: FOUNTAIN, JANE W

PROJECT_TERMS: Adjuvant;Affect;aggressive therapy;Agonist;alternative treatment;anti-tumor immune response;Antibodies;Antineoplastic Agents;Blood - brain barrier anatomy;blood-brain tumor barrier;brain tissue;cancer clinical trial;cancer immunotherapy;cancer therapy;CDK4 gene;Cell Proliferation;Cell Survival;Cells;chemotherapy;Child;Childhood Malignant Brain Tumor;Circulation;Clinical;Cognitive deficits;Combined Modality Therapy;CTLA4 gene;cytokine;Data;Development;Diagnosis;Disease Progression;Environment;Exposure to;Flow Cytometry;Formulation;Genetically Engineered Mouse;Glioma;Immune;immune checkpoint;Immune response;Immune system;immunological status;Immunotherapy;Impairment;Implant;improved;In Vitro;in vivo;Infiltration;inhibitor;innovation;interest;Left;Macrophage;Malignant neoplasm of urinary bladder;Malignant Neoplasms;Medulloblastoma;Melanoma;Micelles;Modality;Modeling;motor deficit;mouse model;mTOR Inhibitor;Mus;nano;nanoparticle;Neoplasms;neoplastic cell;novel;novel therapeutics;Operative Surgical Procedures;Outcome;Pathway interactions;Patients;Penetration;Pharmaceutical Preparations;Physiological;PIK3CG gene;Play;Polymers;Population;programmed cell death protein 1;Proto-Oncogene Proteins c-akt;Radiation therapy;Recurrence;Recurrent disease;Recurrent tumor;Reporting;resiquimod;response;Retinoblastoma Protein;Risk;Role;SHH gene;small molecule;Survivors;synergism;T cell infiltration;T-Lymphocyte;targeted agent;Therapeutic;Therapeutic Effect;therapy outcome;Time;timeline;Tissues;TLR7 gene;Toxic effect;transcriptome;treatment effect;Treatment outcome;treatment strategy;tumor;tumor growth;tumor microenvironment;Tumor Promotion;Tumor Tissue;Vaccines

PROJECT_TITLE: Nanoformulated small molecule immunotherapy for SHH medulloblastoma

STUDY_SECTION: CNBT

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


NIH_SPENDING_CATS: Breast Cancer;Cancer;Estrogen;Immunotherapy;Lung;Lung Cancer;Neurosciences;Women's Health Research

ORG_CITY: DURHAM

ORG_NAME: DUKE UNIVERSITY

PHR: Project Narrative Endocrine therapies, optimized to target the cancer cell intrinsic actions of the estrogen receptor (ER), are currently used to treat breast and gynecological cancers. However, the pharmacology of these agents is also influenced by their cancer cell extrinsic actions in the immune system and in the brain where their actions can either increase or decrease therapeutic efficacy. Understanding ER pharmacology in cancer cells, the immune system and in the brain will inform how best to use existing endocrine therapies, be instructive as to approaches to develop the next generation of modulators, and enable the development of new drug combinations for the treatment of breast cancer and non-reproductive cancers.

PI_NAMEs: MCDONNELL, DONALD P (contact)

PROGRAM_OFFICER_NAME: SOMMERS, CONNIE L

PROJECT_TERMS: Activities of Daily Living;Alcohol consumption;Animal Model;antagonist;attenuation;Brain;Breast Cancer therapy;Breast Cancer Treatment;cancer cell;Cancer Model;Cell Physiology;Cells;Complex;cytokine;cytotoxicity;Data;Development;Diet;Disease;Effectiveness;effector T cell;Environment;ESR1 gene;Estradiol;Estrogen Receptor Modulators;Estrogen receptor positive;Estrogen Receptors;Estrogen Therapy;Estrogens;Exhibits;Exposure to;Feedback;gender difference;Glioblastoma;Gonadal Steroid Hormones;hormone therapy;Hypothalamic structure;Immune;Immune system;Immune Targeting;Immunosuppression;Immunotherapy;Incidence;Interferon Type I;Malignant Breast Neoplasm;Malignant Female Reproductive System Neoplasm;Malignant neoplasm of lung;Malignant neoplasm of thyroid;Malignant Neoplasms;Malignant Reproductive System Neoplasm;Melanoma;migration;Myeloid Cells;Nature;neoplastic cell;Neurons;next generation;novel drug combination;Occupational;Outcome;Pathway interactions;Patient-Focused Outcomes;Peripheral;Pharmaceutical Preparations;Pharmacology;Phenotype;Physiology;Population;Process;Proliferating;receptor expression;Receptor Signaling;reproductive;reproductive hormone;Reproductive system;response;Secondary to;sexual dimorphism;Signal Transduction;Smoking;Sun Exposure;T-Cell Activation;targeted agent;Therapeutic;therapy development;Tissues;Treatment Efficacy;tumor;Tumor Biology;tumor growth;Tumor Immunity;tumor microenvironment;Tumor Pathology;Tumor Promotion;Tumor-associated macrophages

PROJECT_TITLE: Manipulating normal estrogen physiology as a therapeutic approach in cancer


NIH_SPENDING_CATS: Genetics;Hematology

ORG_CITY: MERCED

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF CALIFORNIA, MERCED

ORG_STATE: CA

PHR: PROJECT NARRATIVE We recently found that the human transporter ABCB10 moves the natural antioxidant biliverdin out of the mitochondria. Now our goal is to understand how this protein pumps its substrate using the energy from ATP at the molecular level. This study will reveal the mechanical strategy of this transporter and provide ideas to modulate its activity for therapeutic purposes.

PI_NAMEs: ZOGHBI, MARIA ELENA (contact)

PROGRAM_OFFICER_NAME: ANSONG, CHARLES KWAKU

PROJECT_TERMS: Adopted;Affect;Amino Acids;analog;Anemia;Antioxidants;Arginine;ATP Hydrolysis;ATP phosphohydrolase;ATP-Binding Cassette Transporters;Bacteria;base;Biliverdine;Binding;Biochemical;Biological Assay;Biological Transport;Cell membrane;Cessation of life;chemical group;clinically relevant;Coupling;Cryoelectron Microscopy;Data;Detergents;Development;dimer;Dimerization;Embryo;Environment;Erythropoiesis;functional group;gain of function;Goals;Heart;Heme;heme a;Human;Hydrolysis;in utero;In Vitro;inhibitor;Inner mitochondrial membrane;Knockout Mice;Lead;Lipid Bilayers;Lipids;luminescence resonance energy transfer;Measurement;Measures;Mechanics;Membrane;Methodology;Mitochondria;Modeling;Molecular;Molecular Conformation;Movement;Mus;Mutagenesis;mutant;Mutation;Mutation Analysis;Myocardial Ischemia;nanodisk;Nucleotides;Organelles;oxidation;oxidative damage;Oxidative Stress;Physiological;Population;Power stroke;Production;Property;Protein Conformation;Proteins;Publications;Pump;reconstitution;reconstruction;Reporting;Research;response;Role;Site;Structural Models;Structure;Substrate Domain;Substrate Specificity;System;Techniques;Temperature;Testing;Therapeutic;Time;translational medicine;Translational Research;Transmembrane Domain;Uterus;Variant;Work;zinc mesoporphyrin

PROJECT_TITLE: Molecular Mechanisms of The Human Mitochondrial ABC Transporter ABCB10

STUDY_SECTION: BBM

STUDY_SECTION_NAME: Biochemistry and Biophysics of Membranes Study Section[BBM]