NIH_SPENDING_CATS: Cancer;Emerging Infectious Diseases;Immunotherapy;Infectious Diseases;Influenza;Pneumonia and Influenza;Skin Cancer

ORG_NAME: CEDARS-SINAI MEDICAL CENTER

PHR: Project Narrative We will interrogate how the innate immune NLR family member NLRC4 in macrophages and dendritic cells affects T cell responses through the modulation of expression of the apoptosis-inducing ligand FasL. We will further determine mechanisms pathogens and tumors exploit to downregulate NLRC4 expression and evade immune responses. These findings will provide critical insights into the non-canonical NLRC4 signaling pathway and identify novel therapeutic targets that can augment or inhibit specific immune responses.

PI_NAMEs: CASSEL, SUZANNE L.;SUTTERWALA, FAYYAZ S. (contact)

PROJECT_TERMS: adaptive immune response;adverse outcome;Affect;AKT1 gene;Anti-viral Response;Antigen-Presenting Cells;Apoptosis;Area;Autoimmune Diseases;Automobile Driving;Binding;CASP1 gene;CD4 Positive T Lymphocytes;Cell Communication;Cell Death;cell injury;Cells;Clinical;Coculture Techniques;combat;Complex;cytokine;Data;Dendritic Cells;Down-Regulation;effector T cell;Evaluation;Family;Family member;Generations;Gram-Negative Bacteria;Growth;human disease;IL18 gene;Immune;Immune checkpoint inhibitor;Immune Evasion;Immune response;Immune signaling;immunogenic;Impairment;improved;In Vitro;in vivo Model;Induction of Apoptosis;Inflammasome;Inflammatory;Influenza;Influenza A virus;influenza infection;innate immune pathways;Innate Immune Response;Innate Immune System;insight;Leucine-Rich Repeat;Ligands;Macrophage;Maintenance;Mediating;Melanoma;Melanoma Cell;Melanoma Tumor;member;microbial products;Modeling;Morbidity - disease rate;mortality;mouse model;Mus;Myeloid Cells;Neoplasm Metastasis;new therapeutic target;novel;novel strategies;Nucleotides;Organ Transplantation;pathogen;Pathogenicity;Pathology;Pathway interactions;Pattern recognition receptor;Phosphorylation;Physiological;Play;prevent;Proteins;receptor;Regulation;response;Role;side effect;Signal Pathway;Signal Transduction;subcutaneous;T cell regulation;T cell response;T-Lymphocyte;T-Lymphocyte Subsets;technological innovation;transcriptome;Treatment Efficacy;tumor;tumor growth;Tumor Necrosis Factor Ligand Superfamily Member 6;tumor progression;Up-Regulation;Viral;Virus Diseases

PROJECT_TITLE: Innate NLRC4 signaling controls adaptive immune responses

STUDY_SECTION: III

STUDY_SECTION_NAME: Innate Immunity and Inflammation Study Section[III]


ADMINISTERING_IC: NS

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

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

ORG_CITY: WINSTON-SALEM

ORG_COUNTRY: UNITED STATES

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_FIPS: US

ORG_NAME: WAKE FOREST UNIVERSITY HEALTH SCIENCES

ORG_STATE: NC

PHR: Project Narrative: Boys’ and men’s ice hockey is a collision sport, and women’s and girl’s hockey a contact sport with a high rate of injury and exposure to repetitive head impacts. Recent studies have shown that repetitive head impacts sustained in collision and contact sports may be related to brain changes, even in the absence of clinically diagnosed concussion. The proposed F31 award will evaluate youth athlete performance metrics as a potential determinant of head impact exposure, and will use a postural control assessment to measure clinical outcomes of cumulative exposure to head impacts; the didactic, mentor-guided fellowship proposed will prepare the applicant towards a career as an independent investigator utilizing a joint background in neuroscience and injury biomechanics towards improving athlete safety.

PI_NAMEs: SWENSON, ABIGAIL GLAZIER (contact)

PROGRAM_OFFICER_NAME: UMOH, NSINI ALEASE

PROJECT_TERMS: 3-Dimensional;Adverse effects;Affect;Age;Award;Biomechanics;boys;Brain;Brain Concussion;Brain imaging;Brain Injuries;career;Cephalometry;Characteristics;Clinical;clinical diagnosis;clinical outcome measures;cognitive function;cohort;contact sports;Custom;Data;design;Diagnosis;Equilibrium;Evidence based intervention;experience;Exposure to;Fellowship;Female;Frequencies;Functional impairment;Future;Gait;girls;Goals;Head;head impact;Hockey;Ice;Ice Hockey;improved;Incidence;Individual;Injury;instrument;Intervention;Intervention Studies;Joints;kinematics;male;Measures;men;Mentors;Mentorship;Methods;Modeling;Musculoskeletal Equilibrium;Neurocognitive;Neurosciences;Outcome;Performance;Play;Policies;Protocols documentation;Recording of previous events;Research;Research Personnel;risk mitigation;Role;Safety;Seasons;sensor;sex;skill acquisition;skills;Speed;Sports;Structure;subconcussion;Subgroup;Testing;therapy design;therapy development;Time;Woman;Youth;youth sports

PROJECT_TITLE: Individual-level determinants and clinical outcomes of head impact exposure in youth hockey


ADMINISTERING_IC: ES

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Aging;Cardiovascular;Climate-Related Exposures and Conditions;Clinical Research;Foodborne Illness;Prevention;Rural Health;Social Determinants of Health

ORG_CITY: Aurora

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: Project Narrative This community-engaged project in San Luis Valley, Colorado seeks to identify cardiometabolic disease risks posed by drought through arsenic for elderly Hispanic and non-Hispanic white adult men and women, through interdisciplinary team science bringing together hydrogeological and epidemiological modeling.

PI_NAMEs: GRIBBLE, MATTHEW O.;JAMES, KATHERINE A  (contact);SMITH, RYAN G

PROGRAM_OFFICER_NAME: JOUBERT, BONNIE

PROJECT_TERMS: Address;Adult;Advisory Committees;Aging;aging population;Arsenic;Biological Markers;biological sex;California;Cardiometabolic Disease;cardiometabolism;Cardiovascular Diseases;case control;Cause of Death;clay;Climate;climate change;climate-related health;cohort;Cohort Studies;Colorado;Communication;Communities;community engaged research;cost;Data;density;design;Diabetes Mellitus;Discipline;Disease Outcome;disorder risk;drinking water;Droughts;Ecosystem;Education;Elderly;Eligibility Determination;empowerment;Environmental Health;epidemiological model;Epidemiologist;Epidemiology;Ethnic Origin;exposure pathway;extreme weather;Future;geochemistry;ground water;Health;Health Benefit;Hispanic;Human;hydrology;Incidence;Individual;innovation;insight;interdisciplinary approach;Intervention;Knowledge;Learning Module;Life Expectancy;Link;Literature;Machine Learning;Measurement;Measures;Mediating;Mediation;Medicare claim;meetings;member;men;Mentored Clinical Scientist Development Program;Methodology;Methods;Modeling;mortality;Natural Disasters;Nested Case-Control Study;Not Hispanic or Latino;novel strategies;Outcome;outreach;Participant;Persons;Population;population based;preventive intervention;programs;prospective;Public Health;Pump;Quality of life;Recommendation;Recording of previous events;remote sensing;Research;Residual state;resilience;Resources;Retrospective cohort study;Risk;Role;Rural;Sampling;Schools;Science;Scientist;secondary analysis;sex;simulation;Source;spatiotemporal;Statistical Methods;STEM career;Time;tool;Toxicology;Uncertainty;United States;Urine;Visit;Water;water conservation;water quality;weather-related disaster;Woman;Work

PROJECT_TITLE: The Impact of Drought on Arsenic Exposure and Cardiometabolic Outcomes in a Rural Aging Population

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-PSE-N(02)]


ADMINISTERING_IC: NR

IC_NAME: NATIONAL INSTITUTE OF NURSING RESEARCH

NIH_SPENDING_CATS: Adolescent Sexual Activity;Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Pediatric;Pediatric - AIDS;Prevention;Sexually Transmitted Infections;Social Determinants of Health;Women's Health Research

ORG_CITY: SAN CLEMENTE

ORG_NAME: CENTER FOR INNOVATIVE PUBLIC HEALTH RESEARCH

ORG_STATE: CA

PHR: If, over time, data suggest that #TranscendentHealth impacts HIV preventive behavior at the population level, it will be unique in that it can be quickly and cost effectively scaled up to impact thousands of trans girls.

PI_NAMEs: YBARRA, MICHELE L. (contact)

PROGRAM_OFFICER_NAME: WILLIS, LEIGH ANDREW

PROJECT_TERMS: 18 year old;acceptability and feasibility;Address;Adolescence;Adolescent;Adoption;Advisory Committees;Affect;AIDS prevention;Area;Behavior;Behavioral;behavioral outcome;Centers for Disease Control and Prevention (U.S.);cisgender;Clinical;cost;cost effective;Data;deafening;Decision Making;Disparate;Ensure;evidence base;experience;Feedback;fluidity;Focus Groups;follow-up;Fostering;Gender;gender affirmation;gender affirming hormone therapy;Gender Identity;gender minority;gender minority group;Gender Role;girls;Goals;health disparity;Health Status;healthy sexuality;high risk sexual behavior;HIV;HIV risk;HIV Seropositivity;HIV/STD;hormone therapy;improved;Individual;intersectionality;Intervention;Intervention Studies;Lived experience;male;member;Mental Health;Motivation;National Institute of Mental Health;Outcome;Outcome Measure;Population;population based;pre-exposure prophylaxis;Prevention program;Preventive;programs;Property;Protocols documentation;Public Health;recruit;Research;Research Project Grants;Resources;response;Risk;Risk Reduction;Sampling;scale up;sex;sexual minority boys;Sexual Partners;skills;social;Technology;Teenagers;Testing;Text Messaging;Textiles;Time;transgender;transgender women;transphobia;Treatment outcome;United States;uptake;Youth

PROJECT_TITLE: Harnessing the power of technology to develop a population-based HIV prevention program for trans girls


ADMINISTERING_IC: GM

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Complementary and Integrative Health

ORG_CITY: AMES

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: IOWA STATE UNIVERSITY

ORG_STATE: IA

PHR: PROJECT NARRATIVE This proposal seeks to enable the use of bacteria as live drug delivery vehicles by optimizing their growth and therapeutic production in the human gut. The public health relevance of this proposal is that successful implementation will allow for the treatment and diagnosis of disease by controlled delivery of sophisticated drugs without the need for injections.

PI_NAMEs: MANSELL, THOMAS J (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TERMS: Bacteria;Biological Response Modifier Therapy;Carbohydrates;Carbon;Cells;Coculture Techniques;Complex;delivery vehicle;disease diagnosis;Drug Delivery Systems;Engineering;Environment;Enzymes;Escherichia coli;fitness;gene product;genome-wide;Goals;Growth;Human;improved outcome;In Vitro;in vivo;Injections;interest;Lactococcus lactis;Libraries;Methods;Mus;Organoids;Outcome;Peptides;Pharmaceutical Preparations;Phenotype;Population;prebiotics;Production;Proteins;public health relevance;Small Intestines;small molecule;small molecule therapeutics;Source;System;Testing;Therapeutic

PROJECT_TITLE: Creating a niche for engineered live biotherapeutics

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


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Bioengineering;Emerging Infectious Diseases;Infectious Diseases

ORG_CITY: ATLANTA

ORG_DEPT: PHYSICS

ORG_NAME: GEORGIA INSTITUTE OF TECHNOLOGY

ORG_STATE: GA

PHR: The rise of antibiotic resistance threatens to negate many advances of modern medicine which rely on antibiotics, in part because a common form of resistance, heteroresistance, is undetectable. We propose to develop a new approach to susceptibility testing, built on interferometric measurement of topography, which is able to detect heteroresistance, and is rapid, robust, and inexpensive. This new technology will help clinicians avoid treatment failure, suggest new combination therapies, and in the long term may be applied to other biomedical problems that involve unrestrained cellular reproduction, such as cancer.

PI_NAMEs: YUNKER, PETER  (contact)

PROGRAM_OFFICER_NAME: YEH, ALVIN TIEN-WEI

PROJECT_TERMS: Address;Adopted;Agreement;Antibiotic Resistance;antibiotic resistant infections;Antibiotic susceptibility;Antibiotics;Bacteria;bacterial resistance;Biomedical Research;Biophysics;Cells;Cessation of life;Clinical;clinical application;Clinical Microbiology;clinically relevant;Combined Modality Therapy;Confocal Microscopy;Consumption;Detection;Development;Dyes;imaging approach;improved;Infection;Interferometry;Intermediate resistance;Knowledge;Laboratories;Laboratory Research;Malignant Neoplasms;Manuals;Measurement;Measures;Medical;Minor;Modern Medicine;new combination therapies;new technology;next generation;novel strategies;Phenotype;physical science;Population;Predisposition;Property;rapid detection;Rapid diagnostics;Reproduction;Resistance;Resolution;Stains;Testing;Therapeutic;Time;Treatment Failure;ultra high resolution;Work;World Health Organization

PROJECT_TITLE: Development of a Rapid Antibiotic Susceptibility Test Capable of Detecting Heteroresistance

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


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Brain Disorders;Clinical Research;Mental Health;Neurosciences

ORG_CITY: PROVIDENCE

ORG_DEPT: NEUROSCIENCES

ORG_NAME: BROWN UNIVERSITY

ORG_STATE: RI

PHR: NARRATIVE Diseases involving brain overexcitability, such as epilepsy, schizophrenia, post-traumatic stress disorder, and autism spectrum disorder, are often debilitating. My recent work has revealed, for the first time, that certain cells in the brain, during states of strong activation, put "the brakes" on in a way that has never been described before; this mechanism of firing, called 'ectopic spiking,' may serve as a check the brain uses to prevent overexcitation, yet we do not understand how ectopics are generated. I propose here to determine the mechanism underlying ectopics, and to elucidate when they occur in awake, behaving animals in the hope that I can use the results of these experiments to identify novel mechanisms that may be implicated in disorders involving brain overexcitability.

PI_NAMEs: THEYEL, BRIAN  (contact)

PROGRAM_OFFICER_NAME: REZAIZADEH, KAVON PAUL

PROJECT_TERMS: Action Potentials;Advisory Committees;Anesthesia procedures;Animals;Astrocytes;autism spectrum disorder;awake;Award;Axon;Behavioral;Brain;brain cell;Brain Diseases;Calcium;career;Cell Communication;Cell Physiology;Cells;Cerebral cortex;Collaborations;Committee Members;Communication;Data;Dendrites;Disease;Doctor of Medicine;Doctor of Philosophy;Electroencephalography;Electrophysiology (science);Epilepsy;Experimental Designs;experimental study;Fire - disasters;Fostering;Frequencies;Future;GABA transporter;Generations;Goals;Grant;Hippocampus;Image;Imaging Techniques;in vivo;induced pluripotent stem cell;insight;Interneurons;Invaded;Investigation;Ion Channel;Lead;Link;meetings;Membrane;Mentors;Modeling;Molecular;Mus;N-Methyl-D-Aspartate Receptors;neocortical;neural circuit;Neurons;neuropsychiatric disorder;Neurosciences;neurotransmitter release;novel;novel strategies;optogenetics;Parvalbumins;patch clamp;Pattern;Physicians;Physiologic pulse;Population;Post-Traumatic Stress Disorders;postsynaptic;postsynaptic neurons;Presynaptic Terminals;prevent;receptor;Research Personnel;responsible research conduct;Role;Schizophrenia;Scientist;Series;Signal Transduction;Site;Somatosensory Cortex;Source;symporter;Synapses;synaptic inhibition;Technical Expertise;Techniques;Testing;Time;Training;Training Support;transmission process;Travel;Vibrissae;voltage;voltage sensitive dye;Work;Writing

PROJECT_TITLE: Origin, Mechanism, and Behavioral Context of Persistent Firing in Cortical Parvalbumin-Positive Interneurons

STUDY_SECTION: NST

STUDY_SECTION_NAME: NST-1 Study Section[NST-1]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Cerebrovascular;Chronic Pain;Headaches;Lymphatic Research;Migraine;Neurosciences;Pain Research;Physical Injury - Accidents and Adverse Effects;Sleep Research;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury

ORG_CITY: SEATTLE

ORG_NAME: SEATTLE INST FOR BIOMEDICAL/CLINICAL RES

ORG_STATE: WA

PHR: PROJECT NARRATIVE Disruption of normal sleep and headaches frequently occur after mild traumatic brain injury (concussion) and can persist in some sufferers for months to years following injury. In this proposal, we will be testing whether post traumatic sleep disruption actually contributes to the development of posttraumatic headaches, and whether impairment of the brain’s waste clearing system, the glymphatic system, contributes to these changes. These studies may lead to new approaches to prevent or treat post-traumatic headache by targeting sleep or the function of this cleaning system.

PI_NAMEs: ILIFF, JEFFREY J (contact);RUSSO, ANDREW F

PROGRAM_OFFICER_NAME: OSHINSKY, MICHAEL L

PROJECT_TERMS: Acceleration;active duty;Acute;Adrenergic Agents;Adrenergic Antagonists;Adrenergic beta-Antagonists;Agreement;allodynia;antagonist;aquaporin 4;associated symptom;awake;Behavior;behavior measurement;Biological Assay;Blood - brain barrier anatomy;Blood Vessels;Brain;Brain Concussion;brain dysfunction;Calcitonin Gene-Related Peptide;Cerebrospinal Fluid;cerebrospinal fluid flow;Chronic;Clinical;Clinical Trials;common symptom;Data;defined contribution;Development;Electroencephalography;Electromyography;experimental study;Face;Filament;fluorescence imaging;Gene Deletion;glymphatic clearance;glymphatic dysfunction;glymphatic function;glymphatic system;Headache;Human;Impairment;improved;Inflammation Mediators;Injury;insight;Intercellular Fluid;interstitial;Intervention;Light;Link;mechanical allodynia;Mechanics;Mediating;Migraine;mild traumatic brain injury;mouse model;Mus;Neuropeptides;noradrenergic;novel;novel strategies;Pathogenesis;Pathway interactions;Patients;Peripheral;pharmacologic;Photosensitivity;Post-Traumatic Headaches;Prazosin;prevent;Prevention;Process;Reporting;Rodent;Rodent Model;Role;service member;Signal Transduction;Sleep;Sleep Architecture;sleep behavior;Sleep Deprivation;Sleep disturbances;Slow-Wave Sleep;Sodium Oxybate;solute;Support System;Symptoms;System;Testing;Therapeutic;Time;Transgenic Mice;Veterans;wasting;water channel

PROJECT_TITLE: Role of Sleep Disruption after mTBI as a Driver of Chronic Post-traumatic Headache

STUDY_SECTION: NPI

STUDY_SECTION_NAME: Neurobiology of Pain and Itch Study Section [NPI]


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

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

ORG_STATE: MA

PHR: Project Narrative: Autism spectrum disorders (ASD) are highly prevalent neurodevelopmental disorders, and surprisingly, the majority of individuals with ASD also exhibit altered sensitivity to light touch. Our prior findings reveal that dysfunction of peripheral somatosensory neurons, not neurons in the brain, causes tactile over-reactivity in ASD models, and this tactile over-reactivity contributes to aberrant social behaviors in mice, yet it is not known how peripheral sensory neuron dysfunction leads to social impairments. The goal of this proposal is to uncover the mechanisms through which peripheral somatosensory neuron dysfunction leads to changes in S1 interneuron development, S1 microcircuit function and S1 long-range connectivity that is critical for social behaviors.

PI_NAMEs: OREFICE, LAUREN LYNN (contact)

PROGRAM_OFFICER_NAME: NUCKOLLS, GLEN H

PROJECT_TERMS: Adult;Afferent Neurons;Anatomy;Attention;autism spectrum disorder;barrel cortex;Behavior;Behavioral;Brain;brain abnormalities;brain dysfunction;Brain region;Cells;Central Nervous System;conditional mutant;Data;Development;DNA Sequence Alteration;Electrophysiology (science);Etiology;Exhibits;experience;Fiber;frontal lobe;Functional disorder;Functional Imaging;Gene Deletion;Gene Mutation;Germ Lines;Glean;Goals;Histologic;Histology;Human;Hypersensitivity;Impairment;In Vitro;in vivo;individuals with autism spectrum disorder;inhibitory neuron;insight;Interneurons;Investigation;Jaw;Lead;Lifestyle-related condition;Light;Measures;Methods;Methyl-CpG-Binding Protein 2;model of autism spectrum disorder;mouse genetics;mouse model;Mus;Mutation;neocortical;Nervous System Physiology;neural;Neurodevelopmental Disorder;Neuronal Dysfunction;Neurons;optogenetics;Output;Pathway interactions;Pattern;Peripheral;Peripheral Nervous System;Phenotype;Photometry;postnatal;Prefrontal Cortex;Process;Property;repetitive behavior;Reporting;Research;response;Role;Sensory;sensory input;sensory stimulus;Severities;Shapes;Skin;social;Social Behavior;social communication;Social Development;Social Interaction;somatosensory;Somatosensory Cortex;Specific qualifier value;Spinal Cord;Structure of trigeminal ganglion;Synapses;Tactile;Techniques;Therapeutic;Touch sensation;transcriptome sequencing;Translating;Vibrissae;Viral;Wild Type Mouse;Work

PROJECT_TITLE: The Effects of Somatosensory Experience on Brain Development and Function in Autism Spectrum Disorders

STUDY_SECTION: DBD

STUDY_SECTION_NAME: Developmental Brain Disorders Study Section[DBD]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Brain Disorders;Clinical Research;Depression;Mental Health;Mental Illness;Networking and Information Technology R&D (NITRD);Neurosciences

ORG_CITY: BERKELEY

ORG_DEPT: PSYCHOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: Project Narrative In our daily lives, we make decisions as to how best to achieve desired positive outcomes and to avoid feared negative outcomes; this is complicated by various forms of uncertainty that impact the probability that any given action will result in a particular outcome. Our understanding of the computations and brain circuitry involved in probabilistic decision-making, and disruption of these mechanisms in anxiety and depression, has been limited by lack of parallel studies using positive (rewarding) and negative (aversive) outcomes. The work proposed here examines commonalities and differences in the computations and brain mechanisms supporting human probabilistic decision-making when potential outcomes are aversive versus rewarding, investigates alterations to these computations and their neural implementation as a function of anxiety and depressive symptomatology, and provides tasks and models that can be used in future clinical studies.

PI_NAMEs: BISHOP, SONIA JANE (contact)

PROGRAM_OFFICER_NAME: FERRANTE, MICHELE

PROJECT_TERMS: Address;Adult;Amygdaloid structure;Anterior;Anxiety;Bayesian Analysis;Bayesian Modeling;Behavior;Behavioral;Behavioral Model;Brain;brain circuitry;cingulate cortex;Clinical Research;computer framework;Computer Models;Corpus striatum structure;Data;Decision Making;depressive symptoms;design;Development;Dimensions;Dorsal;Elements;Factor Analysis;Fright;Functional Magnetic Resonance Imaging;Future;Goals;Human;improved;indexing;Individual Differences;interest;Learning;Life;Link;Literature;Maps;Measures;Mental Depression;Modeling;National Institute of Mental Health;Negative Valence;neural;neural circuit;Operant Conditioning;Outcome;outcome prediction;Parameter Estimation;Participant;Patient Self-Report;Physiological;Play;Positive Valence;Prefrontal Cortex;Probability;Psychological reinforcement;Psychopathology;Punishment;Research;Research Domain Criteria;response;Rewards;Risk;Role;Shock;Structure;symptomatology;System;Task Performances;Uncertainty;Update;Volatilization;Work

PROJECT_TITLE: Computationally modeling individual differences in probabilistic decision-making across positive and negative valence domains


ADMINISTERING_IC: AI

ED_INST_TYPE: EARTH SCIENCES/RESOURCES

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biotechnology;Genetics;HIV/AIDS

ORG_CITY: COLLEGE PARK

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIV OF MARYLAND, COLLEGE PARK

ORG_STATE: MD

PHR: Mutations lead to genetic diversity that fuels virus evolution which leads to viruses that escape drug therapy and the immune response. This work is relevant to human health because it will help define the sources of those mutations that arise during HIV replication, thus providing targets for future approaches to combating HIV.

PI_NAMEs: DESTEFANO, JEFFREY J (contact)

PROGRAM_OFFICER_NAME: LAWRENCE, DIANE M

PROJECT_TERMS: Address;Affect;APOCEC3G gene;Area;Biological Assay;Capsid;Cell Culture Techniques;Cell Nucleus;Cells;Cellular Assay;Complement;Consensus;Coupled;Data;Defense Mechanisms;Development;Divalent Cations;DNA;DNA biosynthesis;DNA-Directed RNA Polymerase;ds-DNA;Environment;Enzymes;Evolution;experimental study;Future;Genetic Complementation Test;Genetic Variation;Genome;Goals;Health;HIV;HIV-1;Human;Immune response;Immunity;improved;In Vitro;in vitro activity;in vitro Assay;in vivo;Kinetics;Lead;Letters;Modernization;Mutagenesis;Mutation;Mutation Analysis;next generation sequencing;novel;Nucleotides;Pharmaceutical Preparations;Pharmacotherapy;Physiological;Polymerase;Positioning Attribute;Process;Production;Proteins;Publications;Reaction;Reporting;Research Personnel;Retroviridae;Reverse Transcription;Ribavirin;RNA;RNA Polymerase II;RNA-Directed DNA Polymerase;Role;Sodium Chloride;Source;System;Time;tool;Variant;Viral;Virion;Virus;Virus Replication;Work

PROJECT_TITLE: Using new Next Generation Sequencing (NGS) approaches to analyze the fidelity of HIV reverse transcription in Endogenous Reverse Transcription reactions (ERT)

STUDY_SECTION: HVCD

STUDY_SECTION_NAME: HIV Molecular Virology, Cell Biology, and Drug Development Study Section[HVCD]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Amyotrophic Lateral Sclerosis (ALS);Brain Disorders;Clinical Research;Dementia;Frontotemporal Dementia (FTD);Genetics;Neurodegenerative;Neurosciences;Rare Diseases;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: HOUSTON

ORG_DEPT: NEUROLOGY

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

ORG_STATE: TX

PHR: PROJECT NARRATIVE Amyotrophic lateral sclerosis (ALS) is a devastating, fatal neurodegenerative disorder with no known cure. A recently discovered mutation in C9ORF72, now recognized as the most common cause of ALS, is providing new insights into fundamental cellular pathways that are disrupted in ALS. This proposal aims to pinpoint the mechanisms underlying impaired axonal transport of autophagic vesicles and lysosomes in C9ORF72 ALS, and test therapeutic strategies for reversing these defects.

PI_NAMEs: BERTH, SARAH HATCH (contact)

PROJECT_TERMS: Affect;Amyotrophic Lateral Sclerosis;Anabolism;Autophagocytosis;Autophagosome;Axon;Axonal Transport;Back;Binding;Biochemical;Biogenesis;Biology;C9ALS;C9ORF72;career;career development;Cells;Cytoplasm;Data;Defect;Development;Disease;disease model;Distal;Drosophila genus;Event;experimental study;fly;Foundations;Fractionation;Frontotemporal Dementia;Functional disorder;Genes;Genetic;genetic manipulation;Goals;Human;Image;imaging modality;Impairment;improved;In Vitro;in vivo;induced pluripotent stem cell;Induced pluripotent stem cell derived neurons;Inherited;insight;Label;Laboratories;Link;live cell imaging;Lysosomes;Membrane;Methods;Microtubules;Modeling;Motor;motor neuron degeneration;Motor Neurons;Mutation;Nerve Degeneration;Neurodegenerative Disorders;neuronal cell body;Nuclear Pore;Nuclear Pore Complex;nucleocytoplasmic transport;Organelles;overexpression;Pathogenesis;Pathogenicity;Pathway interactions;Patients;pharmacologic;Phenotype;Phosphotransferases;Post-Translational Protein Processing;Process;protein aggregation;Proteins;proteostasis;Regulation;retrograde transport;RNA;stress granule;Testing;therapeutic evaluation;therapeutic target;Time;tool;Training;transcription factor;treatment strategy;Tubulin;Vesicle;Work

PROJECT_TITLE: Mechanisms of disruption of axon transport of autophagic vesicles and lysosomes in C9orf72 ALS


ORG_NAME: MOREHOUSE SCHOOL OF MEDICINE

PHR: PROJECT NARRATIVE The proposed research will disclose a new mechanism and signaling cascade that have critical impact on stroke outcome: CYP46A1 → 24S-HC → NMDAR → ischemic brain injury. This is expected to be a significant contribution because it will expand our knowledge of the mechanism of ischemic brain injury. Additionally, it validates and identifies new targets for stoke intervention, e.g., CYP46A1 and those allosteric modulatory sites on NMDAR that are critical for the binding of 24S-HC.

PI_NAMEs: LENG, TIANDONG  (contact)

PROGRAM_OFFICER_NAME: BOSETTI, FRANCESCA

PROJECT_TERMS: Affect;analog;Atherosclerosis;Binding;biomarker identification;Brain;Brain Ischemia;Calcium;cell type;Chemosensitization;Cholesterol;Cholesterol Homeostasis;Data;deprivation;Development;Electrophysiology (science);Enzymes;evidence base;excitotoxicity;Glucose;Glutamates;Goals;Hydroxycholesterols;Image;In Vitro;in vivo;Induced Neurons;Intervention;Ischemic Brain Injury;Ischemic Neuronal Injury;Ischemic Stroke;Knock-out;Knockout Mice;Knowledge;lipid metabolism;liquid chromatography mass spectrometry;Malignant Neoplasms;Measures;Metabolic;Molecular;Mus;N-Methyl-D-Aspartate Receptors;Nervous System;Nervous System Disorder;Neuronal Hypoxia;Neuronal Injury;Neurons;new therapeutic target;Oxygen;Pathologic;pharmacologic;Plasma;positive allosteric modulator;post stroke;Production;receptor function;Recovery;Research;Resistance;Role;Signal Transduction;Site;small molecule;Sterols;Stroke;stroke intervention;stroke model;stroke outcome;stroke patient;Structure-Activity Relationship;success;Testing;Therapeutic Intervention;Transgenic Mice

PROJECT_TITLE: The role of cholesterol metabolic enzyme CYP46A1 and its metabolite 24S-hydroxycholesterol in ischemic stroke.

STUDY_SECTION: NOMD

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


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Breastfeeding, Lactation and Breast Milk;Chronic Pain;Clinical Research;Clinical Trials and Supportive Activities;Depression;Major Depressive Disorder;Maternal Health;Maternal Morbidity and Mortality;Mental Health;Mental Illness;Neurosciences;Pain Research;Patient Safety;Prevention;Serious Mental Illness;Women's Health Research

ORG_CITY: PITTSBURGH

ORG_DEPT: ANESTHESIOLOGY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: PROJECT NARRATIVE Postpartum depression (PPD) affects 28 million mothers worldwide annually and there are no effective preventative therapies. These investigations will identify a patient-informed acceptable dose and pharmacokinetics of ketamine infusion after cesarean delivery, a common mode of birth, and will provide novel data on trajectories of PPD symptoms after CD. The results of these investigations will inform optimal dosing strategies for postpartum ketamine.

PI_NAMEs: LIM, GRACE  (contact)

PROGRAM_OFFICER_NAME: SABBAGH, JONATHAN JACOB

PROJECT_TERMS: Abdomen;Absence of pain sensation;Address;Advisory Committees;Affect;appropriate dose;Birth;CD6 antigen;Cesarean section;Child;Clinical;concept mapping;Data;Deceleration;Depressed mood;depression model;depressive symptoms;design;diaries;Dimensions;Dose;drug disposition;Drug Kinetics;dysphoria;effective therapy;expectation;experience;Future;Goals;Hemorrhage;Hour;Human Milk;improved;Individual;individual variation;Infant Care;Infusion procedures;innovation;instrument;Investigation;Ketamine;Knowledge;Lactation;Longterm Follow-up;Maternal Mortality;Maximum Tolerated Dose;Measures;Mental Depression;Mental Health;milk secretion;Minority;Modeling;Moods;Mothers;multimodality;National Institute of Child Health and Human Development;Nausea;Neonatal;new therapeutic target;NMDA receptor antagonist;non-opioid analgesic;novel;novel strategies;novel therapeutic intervention;Observational Study;open label;Operative Surgical Procedures;Opioid;opioid use;Outcome;Pain;Pain management;pain outcome;pain reduction;Patients;Pharmaceutical Preparations;Pharmacodynamics;pharmacokinetics and pharmacodynamics;Plasma;Population;postcesarean section;Postoperative Pain;Postpartum Depression;Postpartum Period;Postpartum Women;Predictive Factor;Pregnancy;pregnant;prevent;Prevention;Preventive therapy;prospective;Publishing;randomized trial;Recovery;Reporting;Research;Risk;Safety;secondary analysis;Sedation procedure;Serious Adverse Event;side effect;Site;Special Population;Suicide;Symptoms;Testing;Thinking;trial design;Vasoconstrictor Agents;Woman;Work

PROJECT_TITLE: Ketamine to reduce postpartum depression and pain after cesarean delivery


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

ORG_CITY: WASHINGTON

ORG_NAME: GEORGE WASHINGTON UNIVERSITY

ORG_STATE: DC

PHR: Obesity causes multiple complications including hypertension, diabetes and sleep apnea, which contribute to high cardiovascular morbidity and mortality. We have discovered a novel mechanism of these diseases related to signaling of fat-tissue-produced hormone leptin, which excites an ion channel TRPM7 in the carotid body, a peripheral sensor of insufficient blood oxygen. Moreover, we developed a novel treatment for hypertension, diabetes and sleep apnea in obese individuals by blocking this channel.

PI_NAMEs: POLOTSKY, VSEVOLOD Y (contact);SHAM, JAMES SK;STOCKER, SEAN D

PROGRAM_OFFICER_NAME: LAPOSKY, AARON D

PROJECT_TERMS: Acute;Address;Adipose tissue;Animals;Area;Attenuated;Award;Blood;Blood - brain barrier anatomy;Brain;Breathing;cardiovascular health;Cardiovascular system;Carotid Body;carotid sinus;Cations;Cells;Chronic;CISH gene;comorbidity;Data;Denervation;Diabetes Mellitus;diet-induced obesity;Disease;Epigenetic Process;experimental study;Exposure to;Fatty acid glycerol esters;Formulation;Funding;Gene Expression;genetic manipulation;Glomus Cell;Glucose Clamp;glucose metabolism;Goals;Hormones;Human;Hydrogels;Hypercapnia;Hyperglycemia;Hyperinsulinism;Hypertension;hypertension treatment;Hypoxia;in vivo;Injections;intravenous glucose tolerance test;Ion Channel;JAK2 gene;Kidney;Leptin;Leptin deficiency;leptin receptor;Leptin resistance;Link;Metabolism;Modeling;Molecular;molecular assembly/self assembly;Morbidity - disease rate;mortality;Mus;Nerve;Non-Insulin-Dependent Diabetes Mellitus;novel;novel therapeutics;Obese Mice;obese person;Obesity;Obstructive Sleep Apnea;Oxygen;patch clamp;Pathway interactions;Patients;Peripheral;PIK3CG gene;Protein Isoforms;protein tyrosine phosphatase 1B;receptor;reduced food intake;Reflex action;Regulation;Resistance;respiratory;respiratory health;response;Rodent;Role;sensor;Signal Transduction;Site;Sleep;Sleep Apnea Syndromes;small hairpin RNA;Somatotype;STAT3 gene;Stat3 protein;Structure of phrenic nerve;Sympathetic Nervous System;Techniques;Technology;Telemetry;therapeutic target;Tissues;trait;TRP channel;Type I Epithelial Receptor Cell;Viral Vector

PROJECT_TITLE: Leptin signaling in the carotid body: mechanisms and consequences

STUDY_SECTION: RIBT

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


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: Chicago

ORG_DEPT: CHEMISTRY

ORG_NAME: NORTHWESTERN UNIVERSITY

ORG_STATE: IL

PHR: PROJECT NARRATIVE Telomerase has attracted significant attention as a potential target for understanding cancer, aging and uncontrolled cell growth since telomeres and telomerase were demonstrated to have important roles in cell survival. The objective of this multi-PI program is to create and explore the utility of new chemical probes to elucidate key gaps in the knowledge surrounding hTERT, its non-canonical functions, and its involvement in cell senescence, DNA damage repair and aging.

PI_NAMEs: KRON, STEPHEN J.;SCHEIDT, KARL A (contact)

PROGRAM_OFFICER_NAME: AGYIN, JOSEPH KOFI

PROJECT_TERMS: Active Sites;Acute;Adult;Affect;Aging;aging process;American;analog;Attention;Biological;Biological Assay;Buffers;Cancer Biology;cancer cell;Cancer Cell Growth;cancer stem cell;cancer survival;cancer therapy;Catalytic Domain;Cell Aging;Cell division;cell immortalization;Cell Nucleus;Cell Proliferation;Cell Survival;cell transformation;Cells;Cellular Stress;chemical synthesis;Chemicals;Chromosomes;Clinic;clinical candidate;Collaborations;Colon Carcinoma;Complex;conventional therapy;CT26;Defect;design;Development;Diagnosis;DNA biosynthesis;DNA Damage;DNA Double Strand Break;DNA Repair;Double Strand Break Repair;early onset;Evaluation;Experimental Neoplasms;Frustration;Generations;Genetic;genetic approach;Genetic Transcription;genotoxicity;Goals;Growth;Hand;high reward;high risk;Human;Human Activities;improved;inhibitor;insight;Ionizing radiation;Knowledge;Length;Libraries;Link;Magic;Maintenance;Malignant Neoplasms;Methods;Mitochondria;Modeling;Modification;Molecular;Molecular Probes;Mus;Natural Products;Neoplasm Metastasis;novel;Oxidative Stress;Pathway interactions;Pharmaceutical Preparations;pre-clinical;preservation;Process;programs;Proliferating;Radiation;Radiation Induced DNA Damage;Radiation Tolerance;Radiation-Sensitizing Agents;Recurrence;Repetitive Sequence;Reporting;Repression;Research;response;Reverse Transcriptase Inhibitors;RNA-Directed DNA Polymerase;Role;senescence;small molecule;success;targeted treatment;Telomerase;Telomerase inhibition;Telomerase Inhibitor;telomere;Telomere Length Maintenance;Telomere Maintenance;Therapeutic;Tissues;tool;Translating;Translations;tumor;tumor progression;tumorigenesis;uncontrolled cell growth;Work

PROJECT_TITLE: Bioinspired chemical probe approach targeting telomerase reverse transcriptase


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Cardiovascular;Clinical Research;Dementia;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Neurodegenerative;Neurosciences;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: CORAL GABLES

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

ORG_STATE: FL

PHR: PROJECT NARRATIVE To identify new treatment targets, the genomics of Alzheimerʹs disease (AD) has been examined primarily in non-Hispanic White populations. We propose here a genomics study of AD in multiplex families of African ancestry both from the US and Africa. We will use whole-genome sequencing as well as collect biomarker and cardiovascular disease phenotypic data in these populations together with information about ancestry and to identify genetic variation influencing AD thereby extending AD genetic discoveries to these underrepresented groups.

PI_NAMEs: AKINYEMI, RUFUS  OLUSOLA;BYRD, GOLDIE S.;CABAN-HOLT, ALLISON MERCEDES;HAINES, JONATHAN L;PERICAK-VANCE, MARGARET A. (contact);RAJABLI, FARID ;REITZ, CHRISTIANE ;WILLIAMS, SCOTT MATTHEW

PROGRAM_OFFICER_NAME: BENNANI-BAITI, MICHAEL

PROJECT_TERMS: Admixture;Africa;African;African American;African American population;African ancestry;Alzheimer's Disease;Alzheimer's disease risk;Astrocytes;Attitude;Autopsy;Awareness;Biological Markers;Brain;brain tissue;Cardiovascular Diseases;Cardiovascular system;Caribbean Hispanic;Case/Control Studies;Chromosome 5;Clinical;cohort;CRISPR/Cas technology;Data;data integration;Data Set;Decision Making;Dementia;design;Detection;Diagnosis;Disease;disease phenotype;Disease susceptibility;druggable target;Education;Elderly;Enrollment;epigenomics;Ethnic Population;European ancestry;Family;Family member;Family Study;Frequencies;gene discovery;Genes;Genetic;genetic architecture;Genetic Diseases;Genetic Predisposition to Disease;Genetic Risk;genetic risk factor;Genetic study;Genetic Variation;genome sequencing;genome wide association study;Genomics;Geographic Locations;Goals;health data;Heritability;Heterogeneity;High Prevalence;improved;Individual;induced pluripotent stem cell;Induced pluripotent stem cell derived neurons;interest;Measures;Microglia;Molecular;Neurocognitive;Neuropsychology;Not Hispanic or Latino;novel;Pattern;Phenotype;phenotypic data;Plasma;Population;precision medicine;Prevention;Prevention strategy;programs;protective factors;racial population;rare variant;Research Design;Risk;risk prediction;risk variant;Role;Rural Community;Sample Size;Sampling;social health determinants;Testing;Tissue Donations;tool;transcriptomics;Trust;Underrepresented Populations;Underserved Population;Urban Community;Variant;whole genome

PROJECT_TITLE: The Origins of Alzheimer Disease in African Americans

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-PSE-C(55)]


ORG_CITY: CHARLOTTESVILLE

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: PUBLIC HEALTH RELEVANCE STATEMENT (Narrative) Pediatric stroke has the highest incidence in neonates or infants, and may cause severe neurological sequalae, including motor and cognitive deficits. Infection and immune responses are a major risk factor for pediatric stroke, but no immune-directed therapies are available. The goal of this project is to test the pathological functions of blood-borne neutrophils and monocytes in experimental pediatric stroke to develop immunomodulation therapies of this condition.

PI_NAMEs: KUAN, CHIA-YI  (contact)

PROGRAM_OFFICER_NAME: DOPERALSKI, ADELE ELIZABETH

PROJECT_TERMS: 1 year old;Acute;Adaptive Immune System;Address;Adult;Affect;Birth;Blood - brain barrier anatomy;brain parenchyma;Caring;Cells;Cerebrovascular system;Childhood;Childhood stroke;cisterna magna;Clinical Management;Cognitive deficits;cohort;Crime;cytokine;Data;design;Development;Dichloromethylene Diphosphonate;effective therapy;Family;Flow Cytometry;functional improvement;Gelatinase B;Gene Expression;Goals;Heterogeneity;Immune;Immune response;Immune System Diseases;Immune Targeting;immunomodulatory therapies;Immunotherapy;Incidence;Infant;Infarction;Infection;Infiltration;Inflammation;Inflammatory;Inflammatory Response;inhibitor;Injections;insight;Interleukin-1;Invaded;Ischemic Stroke;Leptomeninges;Lipopolysaccharides;Liposomes;Lytic;Measures;Meninges;Messenger RNA;MMP9 gene;monocyte;motor deficit;mouse model;Mus;neonate;Neuroglia;Neurologic;neutrophil;Neutrophil Infiltration;novel;Oral;Outcome;Pathogenicity;Pathologic;Pediatric Brain Injury;Play;post stroke;postnatal;preservation;prevent;public health relevance;Reverse Transcriptase Polymerase Chain Reaction;Risk Factors;Role;single-cell RNA sequencing;Stroke;Testing;tissue repair;transcriptome;transcriptome sequencing;Virulence;Water

PROJECT_TITLE: Neutrophils and Monocytes in Pediatric Ischemic Stroke

STUDY_SECTION: BINP

STUDY_SECTION_NAME: Brain Injury and Neurovascular Pathologies Study Section[BINP]


ADMINISTERING_IC: DK

ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Digestive Diseases;Hematology;Liver Disease;Regenerative Medicine

ORG_CITY: EAST LANSING

ORG_DEPT: PATHOLOGY

ORG_NAME: MICHIGAN STATE UNIVERSITY

ORG_STATE: MI

PHR: PROJECT NARRATIVE Hepatotoxicity caused by overdose of the analgesic drug acetaminophen is a leading cause of acute liver failure (ALF), a serious condition with poor prognosis and few therapeutic options beyond intensive care. High levels of the platelet adhesive protein von Willebrand Factor (VWF) have been linked to an increased risk of liver transplant and death in ALF patients, and experimental evidence suggests that VWF inhibits repair of the acetaminophen-injured liver. The primary goals of this research program are to uncover the mechanisms whereby VWF inhibits resolution of acetaminophen-induced liver injury and to provide proof-of-concept that VWF is a viable target to accelerate recovery after acute liver injury.

PI_NAMEs: LUYENDYK, JAMES P (contact)

PROGRAM_OFFICER_NAME: GARCIA, MARTHA

PROJECT_TERMS: Acceleration;Acetaminophen;acetaminophen-induced liver injury;Acute Liver Failure;acute liver injury;ADAMTS;Adhesions;Adhesives;Analgesics;Basic Science;Binding;Biological Markers;Blood Platelets;Cessation of life;Chimeric Proteins;Clinical;clinical application;clinical development;Clinical Research;clinical translation;cohort;Complex;Creativeness;Cytolysis;Data;Deposition;design;drug induced liver injury;Engineering;Enzymes;FDA approved;Fibrinolytic Agents;gain of function;Gene Modified;Genetic;Goals;Hemorrhage;Hemostatic Agents;Hemostatic function;Hepatic;Hepatotoxicity;Human;inhibiting antibody;injury and repair;innovation;Intensive Care;intrahepatic;Link;Liver;Liver diseases;Liver Failure;liver injury;liver repair;liver transplantation;loss of function;Measures;Mediating;Molecular;Mus;mutant;nanobodies;novel;novel marker;novel strategies;Outcome;Overdose;Pathologic;Patients;Peptide Hydrolases;pharmacologic;Physicians;Plasma;Plasma Proteins;Plasmin;platelet aggregating factor;Platelet Aggregation Inhibition;prevent;Prognosis;programs;Publishing;receptor;Recombinants;Recovery;repaired;Research;Resolution;Rest;Risk;Role;Sampling;Scientist;Signal Transduction;System;targeted treatment;Testing;Therapeutic;therapeutic target;thrombolysis;Thrombus;Tranexamic Acid;translational potential;Translational Research;United States;von Willebrand Disease;von Willebrand Factor

PROJECT_TITLE: Novel strategies to accelerate repair of drug-induced hepatotoxicity

STUDY_SECTION: DBDT

STUDY_SECTION_NAME: Drug and Biologic Disposition and Toxicity Study Section[DBDT]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Building Research Capacity at Institutions with Limited NIH Funding;Cerebrovascular;Dementia;Lewy Body Dementia;Neurodegenerative;Neurosciences;Parkinson's Disease

ORG_CITY: BAYAMON

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSIDAD CENTRAL DEL CARIBE

ORG_STATE: PR

PHR: PROJECT NARRATIVE: Parkinson’s disease (PD), late PD dementia (PDD), and PD-related amyloid angiopathy are looming disasters for public health. The combined direct and indirect cost of PD, including treatment, social security payments, and lost income, is estimated to be nearly $52 billion per year in the United States alone. Nearly 1 million Americans are living with PD (2020), and the numbers are growing, as there is no definitive cure. This proposed research is highly relevant, as the control of systemic β-amyloid peptide production and transport, involving platelets and blood, could slow the advance of late-stage dementia and open up a new approach to therapy.

PI_NAMEs: INYUSHIN, MIKHAIL  (contact)

PROGRAM_OFFICER_NAME: BERNAL, FEDERICO

PROJECT_TERMS: abeta accumulation;abeta oligomer;Abeta synthesis;Affect;Alzheimer's Disease;American;Amyloid;Amyloid beta-Protein;Amyloidosis;anti-microbial drug;antimicrobial;Antiplatelet Drugs;Apolipoproteins;Area;artery occlusion;Autoimmunity;Biochemistry;Biology;Blood;Blood Platelets;Blood Vessels;Brain;brain cell;Brain Neoplasms;brain tissue;Cells;Cerebral Amyloid Angiopathy;Cerebral Thrombosis;Cerebrovascular system;Cerebrum;Chemicals;Coagulation Process;Collaborations;Corpus striatum structure;Data;debilitating symptom;Dementia;density;Development;Direct Costs;Disasters;Disease;disease model;Dopamine;dopaminergic neuron;Encephalitis;experience;experimental study;Facilities and Administrative Costs;frontal lobe;Goals;Hour;immunocytochemistry;Immunofluorescence Immunologic;Impaired cognition;Income;Infectious Agent;Inflammation;Injury;innovation;Lead;Lesion;Membrane;meter;Midbrain structure;motor impairment;mouse model;Mus;natural antimicrobial;Natural Immunity;Neurofibrillary Tangles;neuropathology;novel strategies;novel therapeutics;Oxidopamine;Parkinson Disease;Parkinson's Dementia;Pathogenesis;Patients;payment;Peptides;Physiology;Plasma;Platelet Activation;Platelet Count measurement;Prealbumin;Process;Production;Public Health;Publishing;Qualifying;Research;Role;Senile Plaques;Site;Skin;Slice;Social Security;Source;Specialist;Substantia nigra structure;synucleinopathy;tau aggregation;Testing;Therapeutic;Thrombosis;thrombotic;Time;Tissues;United States

PROJECT_TITLE: Build-up of beta-amyloid in the brain in Parkinson's disease


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Nanotechnology;Neurodegenerative;Neurosciences;Peripheral Neuropathy;Physical Injury - Accidents and Adverse Effects;Regenerative Medicine

ORG_CITY: DURHAM

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: NARRATIVE Untreated peripheral nerve damage results in a tangled mass of disorganized nerve fibers and blocks functional recovery following nerve injury. While significant advances in understanding the molecular mechanisms governing the repair process have been made in recent years, the clinical results of peripheral nerve repair remain disappointing. This proposal seeks to improve nerve repair by mimicking endogenous cues using topographical guidance and concentration gradients of ECM-peptides and growth factors.

PI_NAMEs: BECKER, MATTHEW L (contact)

PROGRAM_OFFICER_NAME: KUMSA, DOE WONDWOSSEN

PROJECT_TERMS: Acceleration;Axon;axon regeneration;Binding;Biocompatible Materials;biodegradable polymer;cell motility;cell type;Cells;Clinic;Clinical;Cues;Data;Defect;Diameter;Elements;experience;extracellular;Extracellular Matrix;fabrication;Fiber;Goals;Growth;Growth Factor;healing;improved;improved outcome;In Vitro;in vivo;Infiltration;Injury;injury and repair;innovation;Integrin Binding;interest;Knowledge;Laboratories;Laminin;Limb structure;long term recovery;Macrophage;migration;Modeling;Molecular;Molecular Analysis;Motivation;motor function recovery;nanofiber;Nanofiber Scaffold;nanopolymer;Natural regeneration;Nerve Block;Nerve Fibers;nerve injury;Nerve Regeneration;nerve repair;Neurites;Neurofibrillary Tangles;Neurons;novel;Operative Surgical Procedures;Outcome;Pathway Analysis;Pathway interactions;Peptide Fragments;Peptides;peptidomimetics;peripheral nerve damage;Peripheral nerve injury;peripheral nerve regeneration;peripheral nerve repair;Peripheral Nerves;Play;Process;Protein Fragment;Proteins;Rattus;reconstruction;Recovery;Recovery of Function;recruit;regenerative;Regenerative capacity;repaired;Reporting;Research;response;Role;Schwann Cells;sciatic nerve;Sensory;Site;Speed;Touch sensation;Transforming Growth Factor beta;Translation Process;Translations;Trauma;tyrosyl-isoleucyl-glycyl-seryl-arginine;United States;Work

PROJECT_TITLE: Synergistic Enhancement of Peripheral Nerve Defect Repair using Peptide Functionalized Aligned Nanofiber Conduits

STUDY_SECTION: NANO

STUDY_SECTION_NAME: Nanotechnology Study Section[NANO]


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Genetics;Neurosciences

ORG_DEPT: BIOLOGY

ORG_NAME: GEORGETOWN UNIVERSITY

PHR: Project Narrative: The results from this work will reveal new signaling mechanisms important for the development of synaptic contacts between cochlear hair cells and spiral ganglion neurons (SGNs). Synaptic loss in the cochlea that results from noise exposure, age, or other factors could be restored through molecular therapies aimed at these mechanisms. Even if auditory input is eventually restored, either through prosthetic or biological means, maintaining SGNs and/or re-establishing their connectivity with hair cells will be critical for normal auditory function.

PI_NAMEs: COATE, THOMAS M (contact)

PROGRAM_OFFICER_NAME: FREEMAN, NANCY

PROJECT_TERMS: Acoustics;Action Potentials;Acute;Adult;Affect;Age;Aging;Area;Attenuated;Auditory;Auditory Brainstem Responses;auditory pathway;Auditory system;autism spectrum disorder;axon guidance;Binding Proteins;Biological;Brain;Cells;Cleavage Under Targets and Release Using Nuclease;Cochlea;cochlear development;Data;deafness;Development;Electrophysiology (science);Eph Family Receptors;Experimental Designs;experimental study;Family;Frequencies;Genes;Grant;Hair Cells;Hearing;hearing impairment;Histology;Human;Image;inhibitor;Inner Hair Cells;Inner Supporting Cell;Laboratories;Link;Maps;Measures;member;Mesenchyme;Modeling;Molecular;Molecular Profiling;Muscle fasciculation;mutant;nerve supply;Nervous System;neural;neuron development;neuron loss;neuronal cell body;Neuronal Differentiation;neuronal excitability;neuronal guidance;neuronal survival;Neurons;noise exposure;Pathway interactions;Pattern;Periodicals;Peripheral;Physiological;Physiology;Play;postnatal;Potassium Channel;Process;Property;Prosthesis;Proteins;Regulation;Regulatory Element;repaired;Research;Role;Semaphorins;Sequence Alignment;Signal Pathway;Signal Transduction;single cell ATAC-seq;single-cell RNA sequencing;Somatomedins;spiral ganglion;Supporting Cell;Susceptibility Gene;Synapses;synaptogenesis;Testing;Time;Tissue Culture Techniques;transcription factor;Trauma;Work

PROJECT_TITLE: Cellular and Molecular Mechanisms of Cochlear Innervation

STUDY_SECTION: AUD

STUDY_SECTION_NAME: Auditory System Study Section[AUD]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Eye Disease and Disorders of Vision;Mental Health;Neurosciences

ORG_CITY: CHICAGO

ORG_NAME: UNIVERSITY OF CHICAGO

PHR: RELEVANCE (See instructions): Many neuropsychiatric disorders including depression, schizophrenia, autism, and attention disorders  involve networks of heterogeneous neurons. We will test mechanistic hypotheses about how populations  of neurons guide behavior in different cognitive conditions. Characterizing the complex relationship  between cell-intrinsic heterogeneity, network, heterogeneity, and behavior will be critical for diagnosing  and developing drug therapies to treat neuropsychiatric disorders.

PI_NAMEs: COHEN, MARLENE ROCHELLE (contact);DOIRON, BRENT D.

PROGRAM_OFFICER_NAME: FLANDERS, MARTHA C

PROJECT_TERMS: Affect;Alzheimer's Disease;Animal Behavior;Area;area MT;Attention;Attention deficit hyperactivity disorder;attentional modulation;autism spectrum disorder;Behavior;Behavioral;Behavioral Paradigm;Brain;Cells;Cognition;Cognitive;cognitive process;Collaborations;Complex;data modeling;Data Set;Diagnosis;Disease;Electric Stimulation;Electrodes;experimental study;Eye Movements;flexibility;frontal eye fields;Heterogeneity;Individual;insight;Instruction;Judgment;Link;Measures;Mental Depression;Modeling;Monkeys;Motion;Motion Perception;Motor Neurons;network models;Neurons;neuropsychiatric disorder;Pattern;Perception;Pharmacotherapy;Physiology;Population;predictive modeling;preference;Primates;Property;receptive field;response;Role;Running;Schizophrenia;selective attention;Sensory;Sorting;Source;Stimulus;Structure;System;Testing;tool;Vision;Visual;Visual attention;Visual Cortex;Visual Motion;visual stimulus

PROJECT_TITLE: CRCNS: Heterogeneous effects of cognition on perception: unique leverage on circuit mechanisms


ADMINISTERING_IC: TW

IC_NAME: FOGARTY INTERNATIONAL CENTER

NIH_SPENDING_CATS: Clinical Research;HIV/AIDS;Infectious Diseases;Mental Health;Neurosciences;Women's Health Research

ORG_CITY: CHAPEL HILL

ORG_DEPT: OBSTETRICS & GYNECOLOGY

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: NARRATIVE This program builds upon the highly successful UJMT Fogarty Global Health Fellowship, now in its tenth year. Its cornerstone is a 12-month, mentored research training opportunity at one of 30 institutions across Africa, Asia, and the Americas. We further strengthen the program with an innovative curriculum on research leadership, new approaches to enhance diversity in global health, and research platforms aligned with regional and international scientific priorities.

PI_NAMEs: CHECKLEY, WILLIAM ;CHI, BENJAMIN H. (contact);KONDWANI, KOFI A;OBERHELMAN, RICHARD A

PROGRAM_OFFICER_NAME: HAYES, UNJA

PROJECT_TERMS: Academy;Active Learning;Address;Area;Award;base;career;Child Health;Collaborations;Communicable Diseases;Country;Critical Pathways;Development Plans;Disease;Educational Curriculum;Environmental Health;experience;Fellowship;Fostering;Funding;Future;global health;Government Programs;Grant;HIV/AIDS;improved;Individual;Institution;International;Investments;Leadership;Learning;Malignant Neoplasms;Manuscripts;Mental Health;Mentors;Monitor;Morehouse School of Medicine;Nervous System Disorder;next generation;North Carolina;Performance;Positioning Attribute;Postdoctoral Fellow;Process;Productivity;programs;Publishing;recruit;Research;Research Methodology;Research Personnel;Resources;Secure;Site;skills;Talents;Training;training opportunity;Training Programs;Underrepresented Populations;United States National Institutes of Health;Universities;Women's Health;Writing

PROJECT_TITLE: UJMT LAUNCH: Training the next generation of leaders in global health research


NIH_SPENDING_CATS: Neurodegenerative;Neurosciences

ORG_CITY: AUSTIN

ORG_NAME: UNIVERSITY OF TEXAS AT AUSTIN

PHR: We recently identified structural and dynamic features of membrane proteins that we hypothesize contribute to their native functions and aberrant aggregation, which is a feature of neurodegenerative disease. We will combine approaches from biophysics and cell biology to probe the role of these features in exocytosis, membrane-binding dynamics, and membrane-induced aggregation, which will provide a molecular mechanism for the activities of these proteins. This work will also prepare the PI to launch an independent scientific career by providing essential training in biophysical spectroscopy and cellular imaging, as well as disciplinary expertise in membrane protein structure and molecular neuroscience.

PI_NAMEs: NEWBERRY, ROBERT WILLIAM (contact)

PROGRAM_OFFICER_NAME: SARRAF, SHIREEN AKHAVAN

PROJECT_TERMS: Address;Adopted;Affinity;alpha synuclein;amphiphilicity;Binding;biophysical techniques;Biophysics;Burial;C-terminal;career;Cell Culture Techniques;Cell model;Cell Physiology;Cells;Cellular biology;cellular imaging;cellular transduction;Collaborations;Data;Disease;Exocytosis;experience;Face;genetic manipulation;Hydrophobicity;Image;In Vitro;insight;Kinetics;Laboratories;Learning;Mammalian Cell;Mediating;Membrane;Membrane Lipids;Membrane Proteins;Mentors;Mentorship;Molecular;Molecular Biology;Molecular Conformation;Monitor;mutation screening;Neck;Nerve Degeneration;Neurodegenerative Disorders;Neuroendocrine Cell;Neurons;Neurosciences;neurotransmission;NMR Spectroscopy;Nuclear Magnetic Resonance;Pathologic;Pathology;Pattern;PC12 Cells;Phase;Phenotype;Physiological;Positioning Attribute;prevent;Principal Investigator;protein function;protein misfolding;protein structure;Proteins;Reporter;Research Training;Role;Shapes;Spectrum Analysis;Structure;Technical Expertise;Testing;Toxic effect;trafficking;Training;Variant;Vesicle;Work;Yeasts

PROJECT_TITLE: Biophysical Determinants of Physiological and Pathological alpha-Synuclein Membrane Interactions

STUDY_SECTION_NAME: NST-2 Study Section [NST-2]


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Cancer Genomics;Clinical Research;Clinical Trials and Supportive Activities;Genetics;Hematology;Human Genome;Immunotherapy;Lymphatic Research;Lymphoma;Orphan Drug;Precision Medicine;Rare Diseases

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PI_NAMEs: LAROCCA, CECILIA  (contact)

PROGRAM_OFFICER_NAME: SONG, MIN-KYUNG H

PROJECT_TERMS: Address;Animal Model;Antineoplastic Agents;Apoptosis;Automobile Driving;Biological Markers;biomarker panel;Biopsy;Breast Cancer Patient;Cancer Patient;cancer therapy;cancer type;Cancerous;Cell Communication;Cell model;Cells;Cessation of life;Clinical;clinical development;clinical predictors;clinical trial enrollment;Clinical Trials;clinically relevant;combinatorial;Combined Modality Therapy;cost effective;Cutaneous;Cutaneous T-cell lymphoma;Data;Development;Devices;Dose;drug candidate;drug development;Drug Screening;drug sensitivity;drug testing;Drug usage;effective therapy;Evaluation;exome sequencing;Familiarity;first-in-human;Freezing;Future;Genetic;genome sequencing;genomic profiling;Genomics;Goals;Grain;Heterogeneity;Histologic;Hour;Human;Image;Immune;Immunofluorescence Immunologic;Immunophenotyping;Immunotherapy;Implant;implantation;improved;In Situ;In Vitro;in vivo Model;Incidence;individual patient;innovation;Investigation;Investigational Drugs;Lesion;Location;Malignant - descriptor;Malignant Breast Neoplasm;Malignant Neoplasms;Measures;Medical;Methods;microdevice;Microscopic;millimeter;Molecular;Molecular Abnormality;Morbidity - disease rate;mouse model;Mus;Mutation;Needles;neoplastic cell;New Agents;novel;Oncogenes;Oncogenic;optimal treatments;Pathway interactions;patient response;Patients;Periodicity;Peripheral;Pharmaceutical Preparations;Pharmacodynamics;Pharmacotherapy;Phenotype;Pilot Projects;Population;Positioning Attribute;potential biomarker;precision medicine;precision oncology;predicting response;predictive marker;Predictive Value;Proliferating;Property;Proteins;Rapid screening;Resistance;Resolution;response;response biomarker;Rice;Risk;safety and feasibility;Sampling;screening;senescence;side effect;Signal Transduction;Signaling Protein;Skin;skin biopsy;skin lesion;Skin Tissue;Specimen;standard of care;systemic toxicity;T-Cell Lymphoma;T-Lymphocyte;Testing;Therapeutic;Time;tissue fixing;Tissues;tool;treatment response;treatment strategy;tumor;tumor microenvironment;tumor-immune system interactions

PROJECT_TITLE: Evaluation of an implantable microdevice for rapid cancer drug screening directly in T cell lymphoma patients

STUDY_SECTION: CONC

STUDY_SECTION_NAME: Clinical Oncology Study Section[CONC]


ED_INST_TYPE: UNIVERSITY-WIDE

NIH_SPENDING_CATS: Bioengineering;Building Research Capacity at Institutions with Limited NIH Funding

ORG_CITY: ROCHESTER

ORG_NAME: ROCHESTER INSTITUTE OF TECHNOLOGY

ORG_STATE: NY

PHR: Project Narrative To expand our knowledge about the cues that promote directed cell migration, we propose a new experimental platform that combines aligned collagen fiber landscapes with soluble biochemical gradients to study directed migration within a complex 3D environment. If successful, our platform will dissect how different cell populations prioritize and respond to simultaneous guidance cues with relevance to early development, immune cell trafficking, vascularization, and cancer invasion.

PI_NAMEs: ABHYANKAR, VINAY V (contact)

PROGRAM_OFFICER_NAME: RIGAS, MARC

PROJECT_TITLE: Directed Cell Motility Along Gradients in Extracellular Matrix Fiber Alignment


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Genetics;Infectious Diseases

ORG_NAME: CARNEGIE-MELLON UNIVERSITY

PHR: PROJECT NARRATIVE I developed new technologies that enable exploration of the understudied process of bacterial biofilm dispersal. I will characterize the signaling mechanisms that coordinate biofilm dispersal in space and time at single-cell resolution for the global pathogen Vibrio cholerae. This research could guide the development of treatments that reduce the duration of Vibrio cholerae infection and thereby decrease the severity of the disease.

PI_NAMEs: BRIDGES, ANDREW A. (contact)

PROGRAM_OFFICER_NAME: ZEITUNI, AMIR E

PROJECT_TERMS: Alleles;Bacteria;bacterial genetics;Binding;Biochemistry;Biology;Biophysics;career;Cell Fractionation;Cell-Matrix Junction;Cells;Communities;comparative;disease transmission;Educational workshop;Environment;Enzymes;Epitopes;Event;Exhibits;extracellular;Failure;Gene Expression;Genes;genetic analysis;Genetic Screening;Goals;Growth;Heterogeneity;Imaging Techniques;Individual;Infection;Knowledge;Life Cycle Stages;Life Style;Light;Liquid substance;Luciferases;Mass Spectrum Analysis;Measures;Mentors;Microbial Biofilms;Microbiology;Microscopy;mimetics;Modeling;Molecular;Monitor;Motility;mutant;Names;new technology;Operon;pathogen;Peptide Hydrolases;Phase;Phenotype;Phosphoric Monoester Hydrolases;Phosphorylation;Phosphotransferases;Population;Process;Production;professor;promoter;Protein Secretion;Proteins;Proteomics;Regulation;Regulon;Reporter;Research;Research Personnel;Resolution;response;Role;screening;sensor;Severity of illness;Signal Transduction;spatiotemporal;Stimulus;Swimming;symposium;System;theories;therapy development;Time;Titrations;tool;Training;transcriptome sequencing;Universities;Vibrio cholerae;Vibrio cholerae infection;Western Blotting;Work;Writing

PROJECT_TITLE: This way out:  Spatiotemporal regulation of Vibrio cholerae biofilm dispersal

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Cardiovascular;Cerebrovascular;Clinical Research;Dementia;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Neurodegenerative;Neurosciences;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: SAN ANTONIO

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER

PHR: PROJECT NARRATIVE This project will support the re-establishment of a well-characterized cohort of Mexican American and non- Hispanic White older adults. We propose to study cognitive status and dementia biomarkers in the cohort, and leverage data collected four decades ago and during the present study to examine the contribution of midlife and late-life risk factors to dementia. This effort has the potential to inform preventive and therapeutic strategies to reduce dementia disparities in the underserved population of Mexican Americans.

PI_NAMEs: SATIZABAL, CLAUDIA L (contact)

PROGRAM_OFFICER_NAME: PERCY-LAURRY, ANTOINETTE LOIS

PROJECT_TERMS: Acceleration;Adult;Affect;aged;Aging;aging population;Alzheimer's Disease;Alzheimer's disease related dementia;Alzheimer's disease risk;Alzheimer’s disease biomarker;Amyloid;Amyloid beta-42;Amyloid beta-Protein;apolipoprotein E-4;Atrophic;Attention;Biological Markers;Blood;Brain;brain magnetic resonance imaging;Cardiometabolic Disease;cardiometabolic risk;cardiometabolism;Cardiovascular Diseases;Cessation of life;Chronic Disease;Clinical;Clinical Research;Cognition;Cognitive;Cognitive aging;cognitive function;cohort;Consensus;Data;Dementia;Diabetes Mellitus;Diffusion Magnetic Resonance Imaging;disability;Disablement;Disease;Disease Outcome;Disparity;Early identification;Educational Status;endophenotype;Enrollment;Epidemiology;ethnic difference;ethnic disparity;Ethnic Origin;Ethnic Population;Etiology;experience;follow-up;functional status;Genotype;Glial Fibrillary Acidic Protein;glucose metabolism;Goals;Grant;health determinants;Health Policy;Heart;High Prevalence;Hippocampus;Hispanic;Hispanic Populations;human old age (65+);imaging biomarker;Impaired cognition;Income;indexing;Language;late life;Life Cycle Stages;lifetime risk;Link;Liquid substance;longitudinal dataset;Longitudinal Studies;Measurement;Measures;Memory;Mexican Americans;Microvascular Dysfunction;middle age;mild cognitive impairment;Mind;Minority Groups;Modeling;Modification;mortality;multidisciplinary;Neighborhoods;Nerve Degeneration;Neurologic;neuropathology;Neuropsychology;Non-Insulin-Dependent Diabetes Mellitus;Not Hispanic or Latino;novel;Obesity;older adult;Outcome;Participant;Pathologic;Pattern;Phenotype;Population;Population Study;Positron-Emission Tomography;pre-clinical;prevent;Preventive;Process;programs;protein TDP-43;psychosocial;Random Allocation;Records;recruit;Research;Risk Factors;Role;sex;Shapes;social culture;sociocultural determinant;Standardization;Structure;success;Survivors;Talents;tau Proteins;Texas;Therapeutic;tool;trend;Underserved Population;United States;Update;uptake;Visuospatial;white matter;White Matter Hyperintensity;Work

PROJECT_TITLE: The San Antonio Heart and Mind Study

STUDY_SECTION: AIMR

STUDY_SECTION_NAME:
Aging, Injury, Musculoskeletal, and Rheumatologic Disorders Study
Section[AIMR]


NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Health Services;Prevention;Social Determinants of Health

ORG_CITY: CAMBRIDGE

ORG_NAME: NATIONAL BUREAU OF ECONOMIC RESEARCH

PHR: OTHER PROJECT INFORMATION – Project Narrative Health insurance plans may impact beneficiary health outcomes by steering them to higher- or lower-quality providers. We will measure the impact of different providers on health outcomes and then use detailed data on plan networks to aggregate provider-level quality scores into plan-level measures. We will analyze the degree to which these measures explain differences in plan-level mortality rates and effects. We will further measure the possible benefits of wide dissemination of these quality scores for policymaking.

PI_NAMEs: ABALUCK, JASON  (contact)

PROGRAM_OFFICER_NAME: NOVAK, PRISCILLA JOY

PROJECT_TERMS: Accounting;Affect;Age;American;beneficiary;Caring;Clinical;cohort;comorbidity;Data;Death Rate;demographics;dual eligible;Economics;Enrollment;Health;Health Insurance;Health Personnel;health plan;Health Promotion;Heterogeneity;Hospital Mortality;Hospitals;improved;instrument;insurance plan;Link;Literature;Marketing;Measures;Medicare;mortality;Noise;novel;Outcome;Patient-Focused Outcomes;Patients;Persons;Physicians;Policies;Policy Making;population health;Provider;provider networks;Quality of Care;Race;Research;Resort;Rewards;sex;Statistical Models;Testing;Variant;Work

PROJECT_TITLE: Does Health Insurance Promote Health through Providers and Networks?

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-HDM-L(90)]


NIH_SPENDING_CATS: Bioengineering;Brain Disorders;Building Research Capacity at Institutions with Limited NIH Funding;Epilepsy;Neurodegenerative;Neurosciences;Prevention

ORG_CITY: DENTON

ORG_NAME: UNIVERSITY OF NORTH TEXAS

PHR: PROJECT NARRATIVE About 40% of epilepsy patients fail to control seizures after treatment, and there is currently no treatment that can prevent epilepsy. The goal of this study is to perform multi-scale electrophysiological investigations combined with advanced computational algorithm development to understand the characteristics of the pathological brain networks during the latent period of epilepsy. The findings of this project will lead to a better understanding of the network mechanisms of epileptogenesis and suggest novel approaches to prevent the process of epileptogenesis.

PI_NAMEs: LI, LIN  (contact)

PROGRAM_OFFICER_NAME: LEENDERS, MIRIAM

PROJECT_TERMS: Aftercare;algorithm development;Animal Model;Animals;Antiepileptogenic;Area;Biological Markers;biomaterial compatibility;Brain;Brain Diseases;Characteristics;Chronic;Clinical;Clinical Research;Computational algorithm;computerized tools;Coupling;Data;design;Development;Early Diagnosis;Effectiveness;effectiveness evaluation;Electrophysiology (science);Elements;Entropy;Epilepsy;Epileptogenesis;Event;Exhibits;experimental study;Future;Goals;Graph;graph theory;High Frequency Oscillation;Intervention;Intractable Epilepsy;Investigation;Kainic Acid;Knowledge;Lesion;Measures;medial temporal lobe;Methods;Modeling;Neocortex;Nervous System Disorder;network architecture;Network-based;neural;Neurons;novel;novel strategies;Outcome Study;Pathologic;Pathology;Patients;Phenotype;Population;prevent;preventable epilepsy;Prevention;Probability;Process;Property;Rattus;Research;Resolution;Seizures;Signal Transduction;Silicon;software development;Spatial Distribution;Status Epilepticus;support vector machine;surgery outcome;Techniques;Temporal Lobe Epilepsy;Testing;Training;Translating;Update

PROJECT_TITLE: New approach for identification pHFO networks to predict epileptogenesis


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Biomedical Imaging;Biotechnology;Brain Disorders;Cerebrovascular;Dementia;Immunization;Neurodegenerative;Neurosciences;Prevention;Rare Diseases;Vaccine Related;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: NEW YORK

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: NARRATIVE Recent clinical trials for Alzheimer’s disease have faced high failure rates in part due to a poor translation of preclinical findings from studies completed in transgenic mice, and immunotherapeutic trials in particular have been impeded by significant complications linked to the clearance of cerebral amyloid angiopathy (CAA). This proposal will utilize TLR9 agonist CpG ODN 1018 to stimulate innate immunity, and represents the first comprehensive evaluation of CpG ODN 1018 efficacy and safety in squirrel monkeys, a non-human primate model with a predilection for age-associated CAA, by integrating biofluid biomarker data with imaging markers and cognitive measures, in addition to post-mortem neuropathology correlates. The study will also feature advanced multi-shell diffusion MRI models to follow whole brain and white matter microstructural changes in response to treatment, and will conclude with an in-depth characterization of the CAA and choroid plexus proteomes using our group’s innovative localized proteomic strategy, which altogether will provide essential data advancing CpG ODN 1018’s feasibility for clinical application, as well as promote further discoveries of CAA diagnostic biomarkers.

PI_NAMEs: SCHOLTZOVA, HENRIETA  (contact)

PROGRAM_OFFICER_NAME: YIN, XILING

PROJECT_TERMS: Acceleration;Adjuvant;age related;Agonist;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Amyloid;amyloid pathology;animal old age;Autopsy;Behavioral;Biological Assay;Biological Markers;Biological Response Modifiers;biomarker signature;Blood;Blood Vessels;Brain;Brain Pathology;brain tissue;cell type;Cells;Cerebral Amyloid Angiopathy;Chronic;Clinical;clinical application;Clinical Trials;clinically relevant;Cognition;Cognitive;cognitive benefits;cognitive task;cognitive testing;cohort;Complication;COVID-19 vaccine;Data;Defect;design;Development;diagnostic biomarker;diagnostic value;Diffusion;Diffusion Magnetic Resonance Imaging;Disease Progression;Effectiveness;Elderly;Environment;Enzyme-Linked Immunosorbent Assay;Evaluation;Failure;Family;FDA approved;Formalin;Goals;Hemorrhage;Hepatitis B Vaccines;Human;Image;imaging biomarker;Immune;Immunohistochemistry;immunoregulation;Immunotherapeutic agent;Impaired cognition;improved;in vivo;Incidence;Individual;Inflammation;innovation;insight;Intervention;Label;laser capture microdissection;Lesion;Link;Liquid substance;Macrophage Activation;Magnetic Resonance Imaging;magnetic resonance imaging biomarker;Maps;Mass Spectrum Analysis;Measures;Methods;Microglia;Modeling;Monitor;Monkeys;mouse model;Natural Immunity;Nerve Degeneration;neuropathology;neuroprotection;new therapeutic target;nonhuman primate;Paraffin Embedding;Pathogenesis;Pathologic;Pathology;Patients;Peripheral;Phenotype;Play;pre-clinical;premature;Primates;Process;Proteins;Proteome;Proteomics;response;Risk Factors;Role;Safety;Saimiri;Saline;screening;Senile Plaques;Severities;social group;Sporadic Cerebral Amyloid Angiopathy;Stimulus;Structure of choroid plexus;System;tau Proteins;tau-1;Techniques;Testing;Therapeutic;Time;Tissue Embedding;TLR9 gene;Toll-like receptors;trafficking;Transgenic Mice;Translations;treatment effect;treatment response;vaccine trial;Vascular Diseases;white matter;white matter change;White Matter Hyperintensity

PROJECT_TITLE: Innate Immunity Stimulation Effects on Biomarkers, Cognition, and the Vascular Amyloid Proteome in a Squirrel Monkey Model of Sporadic CAA

STUDY_SECTION: CNN

STUDY_SECTION_NAME: Clinical Neuroscience and Neurodegeneration Study Section[CNN]


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Neurosciences;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_DEPT: NEUROSURGERY

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: Glioblastoma (GBM) is a highly lethal malignant brain tumor due to its diffuse invasion. It is therefore of paramount importance to understand how GBM cells gain invasiveness in order to identify new therapeutic targets to curb GBM spread. Here, we investigate the functions of Plexin guidance receptors in governing biomechanical properties of migrating GBM cells during GBM invasion along preferred migratory paths.

PI_NAMEs: FRIEDEL, ROLAND HORST (contact)

PROGRAM_OFFICER_NAME: KOTLIAROVA, SVETLANA

PROJECT_TERMS: 3-Dimensional;Actomyosin;Adhesiveness;AMOT gene;Attenuated;Axon;axon guidance;Behavior;Binding;Biochemical;Biological Assay;Biomechanics;Blood Vessels;Brain;brain parenchyma;brain tissue;Cell Line;cell motility;cell type;Cells;Characteristics;clinically significant;Data;Dependence;design;Development;Diffuse;Dissociation;Elements;empowerment;Environment;experimental study;Exposure to;Face;Future;gain of function;Genes;genetic signature;Glioblastoma;Glioma;Goals;Grant;Human;Hypoxia;in vivo;Infiltration;Infiltrative Growth;interstitial;Invaded;Knock-out;Light;Link;live cell imaging;loss of function;Malignant neoplasm of brain;Malignant Neoplasms;Mechanics;Mediating;Mediation;Mediator;Membrane;Membrane Microdomains;Metabolic;migration;Modeling;Molecular;Monomeric GTP-Binding Proteins;mutant;neoplastic cell;neural;new therapeutic target;novel;novel therapeutics;paralogous gene;Pathway interactions;Patients;Pattern;plexin;preference;pressure;Property;Proteins;receptor;Regulation;Role;Route;Semaphorins;Series;Serum;Signal Transduction;Stem cell transplant;stem cells;Stress;Surface;Testing;three-dimensional modeling;Tissues;Traction;Transducers;translational study;transplant model;Transplantation;tumor;Tumor Cell Invasion;Up-Regulation;validation studies

PROJECT_TITLE: Plexin-B2 Function in Glioma Invasion

STUDY_SECTION: TPM

STUDY_SECTION_NAME: Tumor Progression and Metastasis Study Section[TPM]


ADMINISTERING_IC: DA

ED_INST_TYPE: SCHOOLS OF NURSING

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Cannabinoid Research;Clinical Research;Drug Abuse (NIDA only);Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Prevention;Social Determinants of Health;Substance Misuse;Women's Health Research

ORG_CITY: Columbus

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: Project Narrative  Sexual minority women (e.g., lesbian, bisexual, queer women) and gender diverse (e.g., non-binary) sexual minorities assigned female at birth are at elevated risk for cannabis use disorder (CUD) compared to heterosexual women, with this disparity growing in recent years, but little is known about how cannabis use (CU) risk processes unfold on a daily basis among sexual minority women and gender diverse individuals (SMWGD). Existing studies of event-level risk processes among heterosexual women and SMWGD have provided mixed evidence for two risk processes for CU: positive reinforcement (e.g., using to increase positive emotions) and negative reinforcement (e.g., using to decrease negative emotions); however, our preliminary results and the multistage model of substance use provide a potential explanation for these mixed findings by suggesting that these two sets of risk factors may be relevant at different stages of CUD, with positive reinforcement most relevant when CUD symptoms are absent to mild and negative reinforcement becoming dominant when CUD symptoms become more severe. To address existing mixed evidence for event-level risk processes contributing to CU among SMWGD and heterosexual women and advance our understanding of risk factors for CU and CUD in these two populations, we aim to accomplish three specific aims using a measurement burst design (i.e., 5 semi-annual bursts of 14-days with 2 surveys per day) with a sample of SMWGD and heterosexual women: 1) identify changes in the effects of event-level risk factors on CU as CUD develops, 2) test for differences in effects of shared event-level risk factors on CU for SMWGD and heterosexual women, and 3) determine if differences in CU trajectories for SMWGD and heterosexual women contribute to disparities in the development of CUD.

PI_NAMEs: DYAR, CHRISTINA  (contact)

PROGRAM_OFFICER_NAME: DUNSTON, SHEBA KING

PROJECT_TERMS: Address;Affect;Age;assigned female at birth;Bisexual;coping;Data;design;Development;disorder risk;Disparity;Ecological momentary assessment;Education;Emotions;Event;experience;gender diverse;Growth;Heterosexuals;high risk;Individual;Intervention;Lesbian;marijuana use;marijuana use disorder;Measurement;minority stress;Modeling;National Institute of Drug Abuse;negative affect;Negative Reinforcements;nonbinary;Perception;Population;positive emotional state;Positive Reinforcements;Process;queer;recruit;Research;response;Risk;Risk Factors;risk sharing;Sampling;Severities;Sexual and Gender Minorities;sexual minority;sexual minority women;social;social stigma;Stress;substance use;Surveys;Symptoms;Testing;Theoretical model;theories;Time;Woman;young adult

PROJECT_TITLE: Testing a multistage model of risk factors for cannabis use utilizing a measurement burst design among sexual minority women, sexual minority gender diverse individuals, and heterosexual women

STUDY_SECTION: SPIP

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


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Eye Disease and Disorders of Vision;Neurosciences

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: PROJECT NARRATIVE Speech production is disrupted in a number of neurological diseases that involve the basal ganglia, including Parkinson’s disease (PD) and dystonia. We will use a novel experimental approach and combination of analytic techniques to elucidate the contribution of neural activity in cortical-basal ganglia circuits to the hierarchical control of speech production, in subjects undergoing deep brain stimulation surgery.

PI_NAMEs: RICHARDSON, ROBERT MARK (contact)

PROGRAM_OFFICER_NAME: GEBREHIWET, HERMON RUSSOM

PROJECT_TERMS: Acoustics;Area;Articulators;Auditory;auditory feedback;auditory processing;awake;Basal Ganglia;Behavior;Behavioral;Brain;Bypass;cognitive process;Communication;Computer Models;Corpus striatum structure;cortex mapping;Cues;Data;Deep Brain Stimulation;density;Dystonia;Electrocorticogram;Electrophysiology (science);Etiology;Event;Evoked Potentials;Exhibits;Force of Gravity;Frequencies;frontal lobe;Functional Magnetic Resonance Imaging;Human;Inferior;Inferior frontal gyrus;Knowledge;Learning;Linguistics;Maps;Measures;Methods;Modeling;Modification;Motor;motor learning;Movement;nerve supply;Nervous System Disorder;neural;Neurobiology;Neurons;Neurosciences;Noise;nonhuman primate;novel;Operative Surgical Procedures;Parkinson Disease;Pathway interactions;Patients;Perception;Phase;Population;Process;Production;programs;Protocols documentation;response;Rest;Role;Seminal;sequence learning;Series;Shapes;Signal Transduction;Site;Speech;Speech Acoustics;Speech Perception;STN stimulation;Structure of subthalamic nucleus;Superior temporal gyrus;Techniques;Testing;Theoretical model;Time;vocalization

PROJECT_TITLE: Cortical-Basal Ganglia Speech Networks


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

ORG_CITY: SAN FRANCISCO

ORG_DEPT: SOCIAL SCIENCES

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: NARRATIVE Although almost half of the over 1.5 million Medicare beneficiaries who enroll in hospice each year have Alzheimer’s Disease and Related Dementias (ADRD), hospice is poorly suited to the needs of people with dementia. Hospice care for people with dementia is both more expensive and lower quality than for other populations, such as those with cancer. The proposed study will evaluate how recent changes in the way Medicare pays for hospice impacts the quality and costs of care for hospice enrollees with dementia compared to those with cancer, which will help determine how to provide the highest-value hospice care for the hundreds of thousands of people with dementia enrolled in hospice every year.

PI_NAMEs: HUNT, LAUREN  (contact)

PROGRAM_OFFICER_NAME: FAZIO, ELENA

PROJECT_TERMS: Activities of Daily Living;Alzheimer's disease diagnosis;Alzheimer's disease related dementia;Atlases;beneficiary;care costs;career;Caregivers;Caring;Characteristics;Clinical;cohort;comparison group;Complement;Continuity of Patient Care;cost;Data;Data Set;Dementia;Dementia caregivers;design;Development;Diagnosis;Doctor of Philosophy;Emergency department visit;end of life;end of life care;Enrollment;Expenditure;experience;Geriatrics;Goals;health economics;Hospice Care;hospice environment;hospice utilization;Hospitalization;improved;improved outcome;Incentives;Individual;interest;Interview;Knowledge;Leadership;Length of Stay;Life;Life Cycle Stages;Link;Malignant Neoplasms;Medicare;Methods;Modeling;Nurse Practitioners;older adult;Outcome;Pain management;Patients;Pattern;payment;Persons;Policies;Policy Analysis;Population;Positioning Attribute;Prognosis;Provider;Qualitative Research;Quality of Care;Research;Research Personnel;Role;skills;Structure;symptom management;Time;Training

PROJECT_TITLE: Hospice Use in Older Adults with Alzheimer's Disease and Related Dementias: Patterns, Policies, and Caregiver Experiences


NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Drug Abuse (NIDA only);Harm Reduction for Substance Misuse;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Maternal Health;Maternal Morbidity and Mortality;Pregnancy;Prevention;Racial and Ethnic Minority Health Research;Rural Health;Social Determinants of Health;Substance Misuse;Women's Health Research

ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: Narrative: For women who use drugs (WWUD) in the US, the months they are pregnant and postpartum are among the most hazardous of their lives: the US has the highest maternal mortality rate of all industrialized nations, 13%-26% of maternal deaths are attributed to drug use in states where this topic has been analyzed. Disparities are complex and dynamic. To support the development of interventions to help WWUD survive while pregnant and postpartum, the proposed 4-year longitudinal study will use qualitative methods to “walk alongside” Black, White, urban, and rural pregnant/postpartum WWUD to learn about (a) their evolving drug- related and sexual/ reproductive health concerns and practices; (b) the dynamic risk environments in which these concerns and practices occur; and (c) WWUDs’ perceptions of pathways linking these environments to these concerns and practices.

PI_NAMEs: COOPER, HANNAH LF (contact)

PROJECT_TERMS: addiction;Address;amphetamine use;Area;Black race;black women;Cessation of life;cohort;Collaborations;community advisory board;Complex;constructivism;Data;Death Rate;design;Developed Countries;Dimensions;Disease;Disparity;Drug usage;Drug user;Economics;effective intervention;Environment;epidemiology study;Equity;Etiology;Fostering;Foundations;Frequencies;General Population;Generations;Harm Reduction;hazard;Health;Health Promotion;Healthcare;Individual;Inequity;insight;Intervention;Investigation;Journals;Learning;Legal Intervention;Link;Lived experience;Longitudinal Studies;Maternal Health;Maternal Mortality;Methods;Modeling;Needle-Exchange Programs;neglect;novel;opioid use disorder;overdose death;Pathway interactions;Perception;Pharmaceutical Preparations;Policies;Postpartum Period;Postpartum Women;Pregnancy;pregnant;Pregnant Women;prenatal;prevent;Public Health;Publishing;Qualitative Methods;Race;reproductive;Research;Research Methodology;Resistance;Resources;Review Committee;Risk;Rural;rural area;rurality;Sampling;scale up;Scientist;sexual and reproductive health;Shapes;social;Social status;Socioeconomic Status;Testing;theories;therapy development;Time;Urbanicity;Urbanization;Variant;Walking;White Women;Woman

PROJECT_TITLE: Racialized & Structurally Urbanized Risk Environments for Pregnant/Postpartum Women who Use Drugs: a longitudinal qualitative study

STUDY_SECTION: CIHB

STUDY_SECTION_NAME: Community Influences on Health Behavior Study Section[CIHB]


ORG_CITY: MADISON

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: PROJECT NARRATIVE Ionizing radiation is used to treat a large fraction of cancer patients with variable success rates. Radiation can cause immune cell-mediated cancer cell killing but mechanisms are not fully understood. This study will reveal a new mechanism that will improve radiation therapy efficacy and durability through generation of a special kind of memory T cells that are capable of killing cancer cells. It will also test and optimize the use of a novel drug to improve efficacy and durability of radiation therapy. If successful, this study may lead to clinical trials using the drug that has successfully undergone a Phase 1 clinical trial to demonstrate safety for patient use.

PI_NAMEs: MIYAMOTO, SHIGEKI  (contact)

PROGRAM_OFFICER_NAME: PEREZ, J MANUEL

PROJECT_TERMS: Animals;anti-PD-1;Antitumor Response;Arginine;Attenuated;cancer cell;Cancer Patient;CD8-Positive T-Lymphocytes;cell killing;Cell Surface Receptors;Cells;Cessation of life;checkpoint therapy;Chemicals;Chronic;Clinical;Clinical Trials;Clonal Expansion;Cytoplasm;Data;Defect;DNA Binding;DNA Damage;Dose;Drug usage;Family;Gene Modified;Generations;Genes;Immune;improved;in vivo;Inflammatory Response;inhibitor;innovation;Investigation;Ionizing radiation;irradiation;Knowledge;Lysine;Mediating;Memory;Molecular;mouse model;Mus;Mutagens;mutant;Mutate;neoplastic cell;NF-kappa B;novel;novel therapeutics;Nuclear;Oxidative Stress;Oxidative Stress Induction;Pathway interactions;patient safety;Phase I Clinical Trials;Phase II Clinical Trials;Physiological;Post-Translational Protein Processing;Publications;Radiation;Radiation therapy;Regenerative capacity;Research;response;Role;Schedule;Signal Pathway;Signal Transduction;stemness;success;T cell response;T memory cell;Testing;transcription factor;Translations;Transplantation;Treatment Efficacy;tumor;Tumor Antigens;tumorigenesis;Wild Type Mouse

PROJECT_TITLE: Impact of Host NF-kB Signaling in Radiation Therapy

STUDY_SECTION: RTB

STUDY_SECTION_NAME: Radiation Therapeutics and Biology Study Section[RTB]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Foodborne Illness;Pediatric;Rural Health;Social Determinants of Health

ORG_CITY: SALSBURY COVE

ORG_NAME: MOUNT DESERT ISLAND BIOLOGICAL LAB

ORG_STATE: ME

PHR: Project Narrative The long-range goal of the “Communicating Data” project is to create a replicable model of STEM education that engages teachers and students as citizen scientists in collecting data on drinking water in collaboration with community partners; this will lead to improved public health and increased student competency and interest in science. The proposed project is focused on local issues of heavy metal contamination of drinking water in Maine and New Hampshire, including arsenic, uranium, and lead, and will have broad applicability to other water contamination issues across the nation. Teachers and students will partner with local scientists to analyze and communicate their data to the public in order to translate their findings into local action; students will engage in planned activities with their families at home to increase the likelihood of action at the household level.

PI_NAMEs: DISNEY, JANE ELIZABETH (contact)

PROGRAM_OFFICER_NAME: BLACHMAN, DARA

PROJECT_TERMS: Address;Area;Arsenic;Attention;career;Chemicals;Child;citizen science;Clinical;Communication;Communities;community collaboration;community partners;Competence;contaminated drinking water;contaminated water;Data;Data Collection;data communication;data literacy;Data Science;Data Set;data visualization;design;drinking water;Economically Deprived Population;Educational Curriculum;Educational process of instructing;Educational workshop;Environmental Health;experience;Exposure to;Family;Family member;Feedback;Geographic Locations;Goals;Grant;Hardness;health data;health goals;health literacy;Heavy Metals;Home;Household;Immigrant;improved;innovation;Interdisciplinary Communication;interest;intergenerational;Lead;Learning;lectures;Maine;medical schools;Metals;minority communities;Modeling;Motivation;New Hampshire;novel;Outcome;outreach;Parent-Child Relations;Parents;Pathway interactions;Personal Communication;Persons;Poly-fluoroalkyl substances;Population;Privatization;programs;public drinking;Public Health;Research;Research Personnel;Rural;rural area;Rural Community;rural environment;Sampling;School Teachers;Schools;Science;Science, Technology, Engineering and Mathematics Education;Scientist;Secondary Schools;Self Efficacy;Series;Side;skills;socioeconomic disadvantage;Source;STEM career;student participation;Students;Surveys;System;teacher;Teacher Professional Development;Techniques;test strip;Testing;Time;tool;Toxicant exposure;Toxin;Training;Translating;Uranium;urban area;Urban Community;urban setting;Water;Water Pollutants;water sampling;well water;Work

PROJECT_TITLE: Promoting environmental health literacy through scientific communication and intergenerational learning in a K-12 safe drinking water citizen science project (Communicating Data)

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


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Amyotrophic Lateral Sclerosis (ALS);Brain Disorders;Dementia;Frontotemporal Dementia (FTD);Neurodegenerative;Neurosciences;Rare Diseases

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: PROJECT NARRATIVE Disruptions in the nuclear pore complex and nucleocytoplasmic transport have been identified as a prominent pathomechanism underlying Amyotrophic Lateral Sclerosis (ALS) and related neurodegenerative diseases. While alterations to the expression and/or localization of nuclear pore proteins has been observed in multiple models of neurodegeneration, the molecular mechanisms leading to this phenomenon remain poorly understood. This proposal will test the hypothesis that aberrant activation of CHMP7 and ESCRT-III mediated degradation leads to the reduction of nuclear pore proteins from neuronal nuclei as an early event in the pathogenesis of sporadic ALS.

PI_NAMEs: COYNE, ALYSSA  (contact)

PROGRAM_OFFICER_NAME: GUBITZ, AMELIE

PROJECT_TERMS: Amyotrophic Lateral Sclerosis;Antisense Oligonucleotides;Autopsy;Biochemical;Biology;C9ORF72;Cell Nucleus;cell type;Cellular Stress;Data;Defect;Degradation Pathway;Dementia;Disease;env Gene Products;Event;experimental study;exportin 1 protein;familial amyotrophic lateral sclerosis;Frontotemporal Dementia;frontotemporal lobar dementia amyotrophic lateral sclerosis;Future;Genes;genetic manipulation;genomic locus;high resolution imaging;Homeostasis;Human;Image;improved;Individual;induced pluripotent stem cell;Injury;insight;Investigation;Lighting;Link;Maintenance;Mammalian Cell;Mediating;Membrane Proteins;Messenger RNA;Metabolism;Microscopy;Modeling;Molecular;molecular subtypes;Motor Cortex;Mutation;Nature;Nerve Degeneration;Neurodegenerative Disorders;neuronal survival;Neurons;new therapeutic target;novel;Nuclear Envelope;Nuclear Inner Membrane;Nuclear Pore;Nuclear Pore Complex;Nuclear Pore Complex Proteins;nucleocytoplasmic transport;Pathogenesis;Pathogenicity;Pathologic;Pathology;Pathway interactions;Patients;pharmacologic;Play;Pore Proteins;Prevalence;programs;recruit;Reproducibility;response;Role;Sampling;Series;Spinal;sporadic amyotrophic lateral sclerosis;Structure;System;Techniques;Testing;therapeutic target;Tissues;ultra high resolution;Work;Yeasts

PROJECT_TITLE: Mechanisms of nuclear pore complex homeostasis and injury in ALS/FTD and related neurodegenerative diseases

STUDY_SECTION: NST