ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

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

ORG_CITY: WORCESTER

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

PHR: PROJECT NARRATIVE The studies in this project will explore the therapeutic potential of targeting KDSR, a metabolic enzyme which we hypothesize plays and important role in preventing buildup of a toxic metabolite (3KDS) in multiple subtypes of cancer cells such as triple negative breast cancer cells. This toxic metabolite may be produced in higher levels in cancer cells compared to normal cells and tissues, making this a potentially cancer-selective therapy. We will identify the factors that produce this toxic metabolite in cancer cells and compare/contrast their activities in cancer cells versus normal cells. These efforts will help us develop effective strategies around this new target, such as how to identify the cancer subtypes that would respond well, and what toxicities to normal cells to be aware of.

PI_NAMEs: KIM, DOHOON  (contact)

PROGRAM_OFFICER_NAME: CHEN, WEIWEI

PROJECT_TERMS: Affect;Anabolism;Animal Model;Awareness;Biological Markers;Breast Cancer Cell;cancer cell;cancer cell subtype;cancer subtypes;cancer therapy;cancer type;Cells;Cessation of life;Colorectal Cancer;Complex;Cytoprotection;Dependence;Distal;Drug Metabolic Detoxication;Endoplasmic Reticulum;endoplasmic reticulum stress;Environment;Enzymes;Foundations;Functional disorder;Future;Genetic Engineering;Impairment;inhibitor;insight;ketodihydrosphingosine;Malignant Breast Neoplasm;Malignant Neoplasms;Membrane;Metabolic;misfolded protein;Modeling;multicatalytic endopeptidase complex;Normal Cell;Normal tissue morphology;novel;Oxidoreductase;Palmitates;Palmitoyl Coenzyme A;Pathway interactions;patient derived xenograft model;Patients;Play;Poison;Poisoning;Predisposition;prevent;Production;Property;proteostasis;response;Role;Serine;serine palmitoyltransferase;Shock;Sphingolipids;targeted cancer therapy;Therapeutic;therapeutic target;Tissues;Toxic effect;triple-negative invasive breast carcinoma;tumor;Tumor Markers;Tumor Tissue;Ubiquitin;uptake;Work

PROJECT_TITLE: Targeting the detoxification function of the enzyme KDSR for cancer therapy

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics - 2 Study Section[MCT2]


ADMINISTERING_IC: HL

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Lung;Neonatal Respiratory Distress;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn;Rare Diseases

ORG_CITY: KANSAS CITY

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: CHILDREN'S MERCY HOSP (KANSAS CITY, MO)

ORG_STATE: MO

PHR: Project Narrative Bronchopulmonary dysplasia (BPD) is a severe lung disease in premature infants characterized by abnormalities in blood vessel and air sac development. How endothelial cells regulate formation of blood vessels and air sacs during lung development, and how this is disrupted in infants with BPD is not fully understood. In this proposal, we will study how delta like 4, an endothelial molecule, regulates blood vessel and air sac formation during normal and abnormal (BPD) lung development to identify new therapies for BPD.

PI_NAMEs: SAMPATH, VENKATESH  (contact)

PROGRAM_OFFICER_NAME: SOOD, BEENA G

PROJECT_TERMS: Acute Lung Injury;Address;Adrenal Cortex Hormones;AGTR2 gene;Air Sacs;Alveolar;alveolar epithelium;angiogenesis;Asthma;Behavior;blood vessel development;Blood Vessels;Brain;Bronchopulmonary Dysplasia;Capillary Endothelial Cell;Carbonic Anhydrase IV;Cardiovascular system;cell fate specification;cell injury;Cell Line;Cell Lineage;Cell Ontogeny;Cell Physiology;Cells;Child;Data;Defect;Development;deviant;Distal;efficacy testing;Embryo;Endothelial Cells;Endothelium;Epithelial Cells;Exhibits;Experimental Models;Exposure to;Gases;gene network;Germ Lines;Glucocorticoids;Goals;Growth;Growth Factor;Hepatocyte Growth Factor Receptor Signaling Pathway;Heterogeneity;HGF gene;Human;Hyperoxia;Impairment;Infant;innovation;insight;Knowledge;Ligands;Lung;lung development;Lung Diseases;lung injury;lung microvascular endothelial cells;Mediating;Molecular;molecular phenotype;Morphogenesis;mortality;mouse model;Mus;Necrosis Induction;neonatal exposure;neonatal mice;notch protein;novel therapeutics;paracrine;Pathologic;Pathway interactions;Perinatal;Population;postnatal;Pre-Clinical Model;Premature Infant;Prodrugs;programs;Proteins;receptor;Regulation;Repression;respiratory morbidity;response;restoration;Risk Factors;Role;Sampling;Signal Transduction;single-cell RNA sequencing;Small Interfering RNA;Specific qualifier value;Testing;Therapeutic;Transcription Coactivator;transcriptome;Transgenic Organisms;translational potential;Trees;Type I Epithelial Receptor Cell;Validation;validation studies;Vascular Endothelial Growth Factors;Vascularization

PROJECT_TITLE: DLL4 in the Developing Lung and Bronchopulmonary Dysplasia (BPD)

STUDY_SECTION: LIRR

STUDY_SECTION_NAME: Lung Injury, Repair, and Remodeling Study Section[LIRR]


ADMINISTERING_IC: GM

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: RALEIGH

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: NORTH CAROLINA STATE UNIVERSITY RALEIGH

ORG_STATE: NC

PHR: Project Narrative The regulatory interface between the genome and epigenome is inherently important across biological systems and disease states due to its control of gene expression, among other fundamental cellular processes. Yet because this interface is highly dynamic and varies depending on genomic locus, it is difficult to probe and control in direct ways and could have consequences for the accuracy of genome and epigenome editing. Here we propose multiple parallel approaches to engineer proteins that can bind DNA modifications in a genomic sequence-specific manner.

PI_NAMEs: KEUNG, ALBERT  (contact)

PROGRAM_OFFICER_NAME: ASLAN, KADIR

PROJECT_TERMS: Address;Affinity;Automobile Driving;Awareness;Base Pairing;BCAR1 gene;Binding;Binding Proteins;Biochemical;Biological;Biological Assay;biological research;biological systems;Biotechnology;bisulfite sequencing;Cell Physiology;cell type;Cells;Chemicals;Clustered Regularly Interspaced Short Palindromic Repeats;Detection;Development;Diagnostic;Dimensions;Directed Molecular Evolution;Discipline;Disease;DNA;DNA Binding;DNA Modification Process;DNA Restriction-Modification Enzymes;Engineering;Epigenetic Process;epigenome;epigenome editing;Etiology;Eukaryota;Event;Exhibits;experimental study;Gene Expression;Gene Expression Regulation;Genes;Genetic;Genetic Engineering;Genome;genome editing;Genomic DNA;genomic locus;Genomics;Hour;Immunologics;Immunoprecipitation;imprint;innovation;insight;Life;Location;Major Groove;Maps;Measurement;Measures;Methylation;Modification;Molecular;Mutation;nanopore;Nature;novel;Nucleic Acids;Nucleotides;Pattern;Phenotype;Prokaryotic Cells;Protein Engineering;Proteins;Reagent;Reporting;RNA Splicing;Role;Safety;Sensitivity and Specificity;Site;Specificity;Stimulus;Structure;Surface;System;Technology;Therapeutic;Tissues;tool;whole genome;Work;yeast two hybrid system;Yeasts;Zinc Fingers

PROJECT_TITLE: Engineering locus-specific binders to DNA modifications

STUDY_SECTION: GCAT

STUDY_SECTION_NAME: Genomics, Computational Biology and Technology Study Section[GCAT]


ADMINISTERING_IC: AA

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Mental Health;Neurosciences;Rehabilitation;Social Determinants of Health;Substance Misuse

ORG_CITY: Auburn

ORG_DEPT: PSYCHOLOGY

ORG_NAME: AUBURN UNIVERSITY AT AUBURN

ORG_STATE: AL

PHR: RELEVANCE (See instructions): The proposed research and career development plans are relevant to public health because Alcohol Use Disorder (AUD) affects nearly a quarter of adults in the United States who drink alcohol, leading to 88,000 deaths, crime, and $249 billion in costs per year. Given the evidence of AUD as a neurobiological disorder, developing non-invasive, neuroscience derived treatments that can be effectively used in clinical settings is essential to combatting the negative impacts of this disease. This proposed project is relevant

PI_NAMEs: FEDE, SAMANTHA JEAN (contact)

PROGRAM_OFFICER_NAME: KUMAR, SHAILESH

PROJECT_TERMS: Address;Adult;Affect;Aggressive behavior;Alcohol abuse;alcohol abuse therapy;Alcohol consumption;alcohol craving;alcohol cue;alcohol intervention;alcohol response;alcohol use disorder;Alcohols;anti social;antisocial behavior;Area;Attention;attentional bias;attentional modulation;Attenuated;Award;Behavior;Behavior Therapy;Brain;career;career development;Cessation of life;Chronic;Clinical;Cognition;Cognitive;comparative efficacy;Coping Skills;cost;craving;Crime;cue reactivity;Data;Decision Making;design;Development;Development Plans;Disease;drinking;Drops;efficacy evaluation;Emotional;expectation;FDA approved;Feeling;frontal eye fields;Functional Magnetic Resonance Imaging;Goals;Health;human imaging;imaging study;Impairment;improved;Impulsivity;incentive salience;Individual;Instruction;Intervention;intervention effect;intimate partner violence;Judgment;Learning;learning ability;Lesion;Link;Magnetic Resonance Imaging;Mental Health;Morals;MRI Scans;Nature;neglect;neural;neural circuit;neural patterning;Neurobiology;neurofeedback;Neurons;neuroregulation;Neurosciences;Outcome;Patients;Pharmaceutical Preparations;Phase;Population;Positioning Attribute;Prefrontal Cortex;Principal Investigator;programs;Protocols documentation;Public Health;Publishing;recidivism;reduced alcohol use;Relapse;relapse prediction;repetitive transcranial magnetic stimulation;Research;research and development;response;Role;social;Social Behavior;Stimulus;Structure;substance use;Techniques;Time;Training;Transcranial magnetic stimulation;treatment as usual;United States;Variant;Work

PROJECT_TITLE: A Combined Neurofeedback-TMS Intervention for Alcohol Use Disorder

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


FUNDING_MECHANISM: SBIR-STTR RPGS

ORG_CITY: DURHAM

ORG_NAME: 21MEDTECH LLC

PHR: PROJECT NARRATIVE There is an urgent need for the development of innovative methods to manage infections associated with cardiovascular implantable electronic devices (CIEDs). Within this project, 21MedTech is developing a novel bioresorbable envelope that releases a controlled amount of antibiotics over time to reduce CIED associated infections. Success with these goals and FDA clearance will enable release of an innovative product that will improve morbidity and mortality outcomes in patients with CIEDs.

PI_NAMEs: YU, JIAYI  (contact)

PROGRAM_OFFICER_NAME: DANTHI, NARASIMHAN

PROJECT_TERMS: Address;aging population;Amino Acids;Animal Model;Animals;Antibiotic Therapy;Antibiotics;Bacteria;biodegradable polymer;biomaterial compatibility;cardiac implant;Cardiovascular system;Cefazolin;clinically relevant;Colony-forming units;combat;commercialization;comorbidity;comparative;controlled release;copolymer;Cyclic GMP;Data;Death Rate;design;Development;Device Removal;Devices;dosage;Dose;Drug Kinetics;drug release profile;Electronics;Esters;Exhibits;Film;Financial Hardship;Formulation;Goals;Gram-Negative Bacteria;Hernia;Hospital Costs;Hospitalization;Hour;Implant;implant associated infection;implantable device;implantation;improved;In Vitro;in vivo;Incidence;Infection;infection burden;infection management;Infection prevention;infection rate;Inflammatory Response;innovation;Kinetics;Label;Licensing;Marketing;Methods;microbial;Minocycline;Modeling;Morbidity - disease rate;mortality;non-opioid analgesic;novel;Operative Surgical Procedures;Oryctolagus cuniculus;Outcome;pathogen;Patients;Pharmaceutical Preparations;Pharmacodynamics;Phase;Polyesters;Polymers;Population;Postoperative Period;Preparation;prevent;Procedures;prophylactic;Quality of life;Rattus;Residual state;Rifampin;Risk;risk selection;Safety;safety assessment;Series;Skin;soft tissue;standard of care;Sterilization;stoichiometry;success;surgery outcome;Surgical Replantation;Thick;Time;tissue repair;Titanium;Urea

PROJECT_TITLE: ARRAY: A novel polymeric mesh for prophylactic antibiotic protection of cardiac implantable electronic devices


ADMINISTERING_IC: DC

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

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

ORG_CITY: WINSTON-SALEM

ORG_DEPT: NEUROSCIENCES

ORG_NAME: WAKE FOREST UNIVERSITY HEALTH SCIENCES

PHR: NARRATIVE Our perception and enjoyment of food is often described in terms of “flavor”, which involves the interplay between taste and aroma (smell). However, we have surprisingly little scientific insight into how the brain creates the multisensory experience of flavor. Here we take a unique approach to this issue, tracking brain activity of animals from birth to adulthood to uncover how the foods they eat shape their flavor processing system.

PI_NAMEs: MAIER, JOOST  (contact)

PROGRAM_OFFICER_NAME: SABRI, MERAV

PROJECT_TERMS: Address;Adult;Animal Model;Animals;awake;Biological Models;Birth;Brain;Common Cold;Complex;computational basis;Coupled;Data;Development;Diet;Dissociation;Eating;Electrophysiology (science);experience;experimental study;Exposure to;extracellular;Face;Food;Foundations;Goals;Health;Human;human imaging;human subject;Imaging Techniques;Individual;insight;Intervention;Intuition;Life;Life Experience;life span;Link;Mission;Modality;Modeling;multisensory;Nature;neural;neural circuit;neuromechanism;Neurons;non-invasive imaging;novel;Olfactory Cortex;operation;Outcome;Pattern;Perception;Persons;Physiology;postnatal;postnatal development;Prevention;Process;Rattus;Recording of previous events;Research;Research Personnel;Resolution;response;Rodent;Sensory;sensory input;Sensory Process;sensory system;Series;Shapes;Smell Perception;Stimulus;System;Taste Perception;Techniques;temporal measurement;Work

PROJECT_TITLE: Development of the multisensory computations underlying flavor processing

STUDY_SECTION: NIC

STUDY_SECTION_NAME: Neuroscience of Interoception and Chemosensation Study Section[NIC]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Autoimmune Disease;Kidney Disease;Lupus

ORG_CITY: OMAHA

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF NEBRASKA MEDICAL CENTER

ORG_STATE: NE

PHR: PROJECT NARRATIVE Systemic lupus erythematosus (or lupus) is a chronic, often debilitating autoimmune disease that attacks a number of parts of the body. Damage to the kidneys (lupus nephritis) is a serious and common complication of lupus, affecting approximately 50% of patients, and current treatments are only partially effective and have serious side effects. Our proposal focuses on novel mechanisms of kidney injury in lupus: iron-induced inflammation, fibrosis and cell death (ferroptosis). Our studies will help us better understand a novel mechanism of renal injury in lupus, and whether blocking these processes could serve as a new or complementary treatment strategy for lupus nephritis.

PI_NAMEs: BOESEN, ERIKA INGRID (contact)

PROGRAM_OFFICER_NAME: CHAN, KEVIN E

PROJECT_TERMS: Acute;Adrenal Cortex Hormones;Affect;Age;Albuminuria;American;antioxidant enzyme;Antioxidants;Attenuated;Autoimmune Diseases;Binding;Biological Markers;Black race;Body part;Cell Culture Techniques;Cell Death;Cell Death Induction;cell injury;cell type;Cells;Cessation of life;child bearing;Chronic;Chronic Kidney Failure;Clinical Research;Coenzyme A Ligases;Complementary therapies;Complication;Data;Disease;Disease remission;Drug Targeting;Enzymes;Excretory function;experimental study;Exposure to;Family member;FDA approved;Fibrosis;Filtration;Genetic;genetic approach;glutathione peroxidase;Goals;Homeostasis;Immune system;Immunosuppression;Impairment;In Transferrin;in vivo;Inflammation;inhibitor;Injury;Injury to Kidney;insight;Iron;Iron Chelating Agents;Iron Chelation;iron metabolism;Kidney;kidney cell;kidney dysfunction;Link;Literature;Lupus;Lupus Nephritis;Mediating;Mediator;Modeling;mouse model;Mus;Nephrons;New Zealand;Newly Diagnosed;novel;novel strategies;novel therapeutic intervention;NZW Mouse;Organ;Oxidative Stress;Pathway interactions;patient biomarkers;patient prognosis;Patients;Permeability;Pharmaceutical Preparations;podocyte;premature;Process;protein metabolism;Proteinuria;Publishing;renal damage;Renal tubule structure;Reporting;Risk;Role;Scheme;side effect;Signal Transduction;Source;Stimulus;systemic autoimmune disease;Systemic Lupus Erythematosus;targeted agent;Testing;Transferrin;treatment strategy;Tubular formation;Up-Regulation;uptake;urinary;Urine;Work;young woman

PROJECT_TITLE: Mechanisms of iron-mediated renal injury in lupus nephritis

STUDY_SECTION: PBKD

STUDY_SECTION_NAME: Pathobiology of Kidney Disease Study Section[PBKD]


ADMINISTERING_IC: NS

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Neurosciences

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

PHR: PROJECT NARRATIVE The Neuroscience Postbaccalaureate Research Education Program (NeuroPREP) will contribute to national efforts aiming to address these systemic problems by increasing access for UR students to graduate training in Neuroscience. We will build regional networks of Schools to identify, recruit and foster program participation from students who currently lack access to in-depth research experiences. After 2 years, NeuroPREP students will be fully prepared to pursue graduate training in neuroscience.

PI_NAMEs: HOLY, TIMOTHY ;MORON-CONCEPCION, JOSE A;TAGHERT, PAUL H (contact)

PROGRAM_OFFICER_NAME: MATTHEWS, MARGUERITE

PROJECT_TERMS: Acceleration;Address;Admission activity;Adopted;Advisory Committees;Ally;Arts;Attention;Bees;Brain;Brain Diseases;candidate identification;career;career development;Clinical;cohort;college;Communication;Communities;community building;Critical Thinking;Dedications;design;Doctor of Philosophy;Education;education research;Educational Curriculum;Engineering;Ensure;Environment;Equity;equity, diversity, and inclusion;Evaluation;Exclusion;experience;Faculty;faculty mentor;Feedback;Fostering;Foundations;Funding;General Population;Generations;Goals;graduate school;graduate student;Grant;High School Student;Individual;innovation;Institution;Instruction;Interdisciplinary Education;interest;laboratory experience;Learning;matriculation;Mechanics;Medicine;Mentors;Methods;Mind;Missouri;Modernization;Molecular;Neuronal Dysfunction;Neurophysiology - biologic function;Neurosciences;Neurosciences Research;Oral;outreach;Participant;Pathway interactions;peer;peer coaching;Population;Postbaccalaureate;posters;Process;professional atmosphere;programs;Public Speaking;Readiness;recruit;Research;Resources;Running;Schools;Science;Scientist;skills;social;social media;Societies;student participation;Students;System;Talents;Teacher Professional Development;Technical Expertise;Techniques;Teenagers;Training;Training Programs;undergraduate student;Underrepresented Populations;Universities;Wages;Washington;Work;Writing

PROJECT_TITLE: The WUSTL PREP post-bacc program to enhance doctoral readiness in neuroscience


ADMINISTERING_IC: MH

ED_INST_TYPE: GRADUATE SCHOOLS

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Depression;Genetics;Human Genome;Mental Health;Mental Illness;Neurosciences;Pediatric;Social Determinants of Health

ORG_CITY: Princeton

ORG_NAME: PRINCETON UNIVERSITY

ORG_STATE: NJ

PHR: PROJECT NARRATIVE Children who experience early life adversity are often more sensitive to stress later in life, which can more easily lead to anxiety disorders and depression. This work seeks to identify how early experiences become encoded in the brain through changes in the three-dimensional structure of DNA. We will develop novel molecular tools to test how these structural changes may render the brain more sensitive to future stress experience.

PI_NAMEs: PENA, CATHERINE JENSEN (contact)

PROGRAM_OFFICER_NAME: LEINWAND, SARAH GOLDBERG

PROJECT_TERMS: 3-Dimensional;Adult;Anxiety;Anxiety Disorders;ATAC-seq;Award;Behavior;Behavioral;behavioral response;behavioral sensitization;biobehavior;Biological;Brain;Cell Nucleus;cell type;Cells;Child;childhood adversity;Chromatin;chromatin modification;Chromatin Structure;Clinical Research;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;Computer Analysis;Creativeness;Cues;Data;design;Development;DNA Structure;early experience;Early identification;early life adversity;Enhancers;Epigenetic Process;epigenome;epigenome editing;experience;experimental study;Failure;Functional disorder;Future;Gene Expression;Genes;Genetic Risk;Genetic Transcription;genome-wide;genomic locus;Goals;high reward;high risk;histone modification;In Vitro;in vitro testing;in vivo;Individual;innovation;Intervention;Lead;Life;life span;lifetime risk;Link;Lysine;Memory;Mental Depression;Mental disorders;Mental Health;Mission;Modeling;Molecular;Mood Disorders;mouse model;Mus;National Institute of Mental Health;Neurobiology;novel;Outcome;postnatal;postnatal development;preclinical study;preservation;Process;programs;promoter;Recurrence;Research;Research Project Grants;response;Rewards;Risk Factors;Role;Scientist;Shapes;Site;social stress;social stressor;Specificity;Stimulus;Stress;Stressful Event;stressor;Suicide;Testing;three dimensional structure;Time;tool;transcription factor;transcriptomics;Translating;Ventral Tegmental Area;Work

PROJECT_TITLE: Epigenetic priming of response to future stressors


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Dementia;Depression;Major Depressive Disorder;Mental Health;Mental Illness;Neurodegenerative;Neurosciences;Sleep Research

ORG_DEPT: ANESTHESIOLOGY

PHR: PROJECT NARRATIVE Treatment resistant depression (TRD) in older adults is a leading cause of disability, dementia, and poor quality of life. Deficient slow waves sleep is at the nexus of depression and cognitive dysfunction in older adults, but novel treatments have not targeted this core pathophysiology. These combined Phase 1 and Phase 2 mechanistic clinical trials will investigate whether propofol confers slow wave sleep enhancement, resulting in longer-term improvements to sleep structure, cognitive function, and mood.

PI_NAMEs: LENZE, ERIC J;PALANCA, BEN JULIAN (contact)

PROGRAM_OFFICER_NAME: EVANS, JOVIER D

PROJECT_TERMS: Accounting;Address;Adverse event;Aftercare;Age;aging population;alertness;Alzheimer's disease related dementia;Alzheimer's disease risk;Anesthetics;anti-depressive agents;Autonomic nervous system;Behavior;Biological Markers;Clinical Trials;Cognition;Cognitive;cognitive function;Dementia;Depressed mood;depressive symptoms;design;disability;Disease;Dose;Double-Blind Method;Dryness;Elderly;Electrodes;Electroencephalography;Enrollment;Evaluation;Excess Mortality;executive function;Frequencies;Functional disorder;Future;glymphatic system;Goals;Grant;Home;Homeostasis;Hour;Impaired cognition;improved;Individual;Infusion procedures;innovation;Intervention;Liquid substance;Measures;Mental Depression;Modeling;Moods;new therapeutic target;Nonpharmacologic Therapy;novel;novel strategies;novel therapeutics;older adult;Outcome;Participant;Pathway interactions;Patients;Pattern;pharmacologic;Phase;Physiological;Population;Populations at Risk;precision medicine;primary endpoint;primary outcome;Propofol;Public Health;Quality of life;Randomized;Reaction Time;recruit;Recurrence;Research Domain Criteria;restoration;Risk;secondary outcome;Sedation procedure;Serious Adverse Event;Severities;sex;Sleep;Sleep Deprivation;Sleep disturbances;sleep pattern;Slow-Wave Sleep;statistics;Structure;suicide mortality;Synaptic plasticity;Testing;therapeutic target;Titrations;treatment-resistant depression;Unconscious State;United States National Institutes of Health;vigilance;wearable device;Work

PROJECT_TITLE: Slow Wave Induction by Propofol to Eliminate Depression (SWIPED) Trial


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Cardiovascular;Electronic Nicotine Delivery Systems;Heart Disease;Lung;Prevention;Pulmonary Hypertension;Tobacco;Tobacco Smoke and Health

ORG_CITY: NEW ORLEANS

ORG_NAME: LSU HEALTH SCIENCES CENTER

ORG_STATE: LA

PHR: Narrative This NRSA F30 fellowship will provide an invaluable training opportunity for a future physician scientist as she develops into an emerging leader in cardiovascular and pulmonary disease related research. The proposed studies will investigate the impact of chronic e-cigarette vapor inhalation on cardiopulmonary function and explore the efficacy of an antihypertensive drug, losartan, in preventing any detrimental effects. Findings from this study will further our understanding of the negative consequences of e-cigarettes and may identify novel therapeutic targets for the treatment of e-cigarette related cardiopulmonary dysfunction.

PI_NAMEs: WHITEHEAD, ANNA KATHRYN (contact)

PROGRAM_OFFICER_NAME: POSTOW, LISA

PROJECT_TERMS: Acetylcholine;Angiotensin II;Angiotensin Receptor;Angiotensins;antagonist;Anti-Hypertensive Agents;Blood Vessels;Cardiopulmonary;cardiopulmonary system;Cardiovascular Diseases;career;career development;Cause of Death;Chemicals;Chronic;cigarette smoking;combustible cigarette;Data;Disease;e-cigarette aerosols;Electronic cigarette;electronic cigarette use;Electronic Nicotine Delivery Systems;electronic vape;Ensure;Exhibits;experimental study;Fellowship;Fibrosis;Flavoring;Fostering;Functional disorder;Future;Homeostasis;Impairment;Inflammation;Inhalation;interest;Investigation;Lead;Losartan;Lung;Lung Diseases;lung injury;Mediating;Medical Research;Medicine;Mentors;Modeling;Molecular;mouse model;multidisciplinary;Mus;National Research Service Awards;new therapeutic target;Nicotine;nicotine exposure;nicotine inhalation;nicotine vapor;NOS3 gene;Operative Surgical Procedures;Oral Ingestion;Patients;Peptidyl-Dipeptidase A;Perception;Phosphorylation;Physicians;pre-clinical research;prevent;Propylene Glycols;Pulmonary Heart Disease;Pulmonary Hypertension;receptor;Receptor Signaling;Renin-Angiotensin System;Research;Right Ventricular Hypertrophy;right ventricular remodeling;Risk Factors;Role;Safety;Scientist;Signal Transduction;smoking prevalence;Systolic Pressure;Techniques;Testing;tool;Training;training opportunity;United States Food and Drug Administration;vaping;vaping associated lung injury;Vascular Diseases;Vasodilation;vegetable glycerin;Ventricular;Work

PROJECT_TITLE: E-cigarette Inhalation and Cardiopulmonary Dysfunction


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Clinical Research;Dementia;Neurodegenerative;Neurosciences;Parkinson's Disease;Precision Medicine

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

PHR: PROJECT NARRATIVE Individuals with Parkinson disease (PD) often develop a combination of motor, cognitive, and psychiatric problems that adds substantial morbidity, mortality and economic burden to patients, families and society. In order to develop and evaluate more personalized interventions, individual-level biomarkers are needed. This study will apply new, innovative neuroimaging approaches to identify individual-level brain network biomarkers of PD, examine the relationship of these biomarkers with clinical features and neuropathology, and determine if these biomarkers predict longitudinal cognitive decline and dementia in PD.

PI_NAMEs: CAMPBELL, MEGHAN C (contact);GRATTON, CATERINA

PROGRAM_OFFICER_NAME: BABCOCK, DEBRA J

PROJECT_TERMS: abeta deposition;Address;Affect;Age;alpha synuclein;Amyloid beta-Protein;Attention;Behavioral;behavioral impairment;Biological Markers;Brain;brain dysfunction;Brain Pathology;cholinergic;Clinical;clinical application;clinical development;clinical heterogeneity;Cognition;Cognitive;Cognitive deficits;cohort;Complex;Data;Defect;Dementia;denoising;Deposition;disease heterogeneity;Disease Progression;Dorsal;Economic Burden;Evaluation;Exhibits;Family;Foundations;Functional disorder;Functional Magnetic Resonance Imaging;Future;Gait abnormality;Genetic;Impaired cognition;improved;Individual;individual variation;innovation;Link;Location;Magnetic Resonance Imaging;magnetic resonance imaging biomarker;Maps;Measures;Mental disorders;Methods;Morbidity - disease rate;mortality;Motor;Motor Cortex;motor deficit;network dysfunction;Neurodegenerative Disorders;neuroimaging;neuropathology;neurophysiology;Neurotransmitters;non-demented;non-motor symptom;novel;novel strategies;Parkinson Disease;Parkinson's Dementia;Participant;Pathology;Pathway Analysis;Patient Selection;patient stratification;Patients;personalized intervention;personalized medicine;Persons;Phenotype;Positron-Emission Tomography;predictive marker;Prognostic Marker;Proteins;psychiatric symptom;recruit;research clinical testing;Research Design;Rest;Rewards;Scanning;Societies;Symptoms;System;tau Proteins;Testing;Time;Work

PROJECT_TITLE: Precision-Mapping Functional Connectivity in Parkinson's Disease

STUDY_SECTION: CNN

STUDY_SECTION_NAME: Clinical Neuroscience and Neurodegeneration Study Section[CNN]


NIH_SPENDING_CATS: Cancer;Genetics

ORG_CITY: LA JOLLA

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

ORG_STATE: CA

PHR: PROJECT NARRATIVE The Mediator complex (MED) is one of the key factors in transcription machinery, and we identified Med30 gene is highly amplified in various of cancer patients, and significantly co-amplified with the oncogenic transcription factor Myc. However, little is known about the functional contribution of MED30 to transcription activity of Myc, in synergistic way to promote cancer progression; and how the Mediator big complex stabilizes itself. The proposed studies are aimed at understanding the roles of cancer-related MED30 and MED at the molecular, cellular, and physiological levels, gaining insight into phase separation-involved protein complex stabilizing mechanism, and the potentials of inhibiting MED30 as a therapeutic strategy for disrupting Mediator complex in overactive-transcribed cells including Myc-amplified cancer.

PI_NAMEs: JIN, CHUNYU  (contact)

PROGRAM_OFFICER_NAME: JAKOWLEW, SONIA B

PROJECT_TERMS: Affinity;Automobile Driving;Binding;Biological;Cancer Biology;cancer cell;Cancer Patient;cancer type;carcinogenesis;Cell Survival;Cells;ChIP-seq;Competitive Binding;Complement;Complex;Data;Dissociation;DNA Damage;drug development;Drug Targeting;Enhancers;Event;Exhibits;extracellular;Frequencies;Gene Activation;Gene Amplification;Gene Expression;Generations;Genes;Genetic;Genetic Transcription;Genomic Instability;Glioblastoma;Goals;Growth;Head;histone modification;In Vitro;in vivo;Individual;insight;Interruption;Knock-out;Link;Malignant neoplasm of pancreas;Malignant Neoplasms;MED15;Mediator;Molecular;mouse model;MYC Gene Amplification;Oncogenic;overexpression;Pharmaceutical Preparations;Phase;Phenotype;Phosphotransferases;Physical condensation;Physiological;Play;programs;Proliferating;promoter;Property;protein complex;Protein Complex Subunit;protein degradation;Proteins;Proto-Oncogene Proteins c-myc;rapid growth;Reagent;Regulation;replication stress;response;RNA Polymerase II;Role;screening;Signal Transduction;small molecule;Tail;Testing;Therapeutic;therapeutic target;Transcription Alteration;transcription factor;Transcriptional Activation;Transcriptional Regulation;tumor progression;Work

PROJECT_TITLE: Phase Separation-involved Roles of Mediator Complex in Myc-amplified Cancer


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Genetics;Human Genome

ORG_CITY: CLEVELAND

ORG_DEPT: BIOLOGY

ORG_NAME: CLEVELAND STATE UNIVERSITY

ORG_STATE: OH

PHR: PROJECT NARRATIVE: Advanced age is a leading risk factor for many different health risks, thus interventions that target common underlying age-related molecular alterations would be especially beneficial. SIRT6 is a gene shown to regulate multiple cellular functions that change during the aging process, and increasing SIRT6 function can extend lifespan. This proposal seeks to better understand and optimize the role of SIRT6 as a pro-longevity gene, with the goal of translating these findings to prevent and treat age-related health issues and extend healthy lifespan in humans.

PI_NAMEs: TAYLOR, JACKSON RICHARD (contact)

PROGRAM_OFFICER_NAME: CARTER, CHRISTY

PROJECT_TERMS: Adipose tissue;Age;age related;age related changes;age related decline;age-related disease;Aging;aging process;Applications Grants;ATAC-seq;Attenuated;Bioinformatics;Body System;Candidate Disease Gene;career;Cell Culture Techniques;Cell Physiology;ChIP-seq;Chromatin;chromatin modification;Chromatin Remodeling Factor;Chromatin Structure;comparative;CRISPR/Cas technology;Data;Deacetylase;Dedications;design;design and construction;Development;Disease;DNA Repair;DNA Transposable Elements;Drosophila melanogaster;Educational workshop;effective therapy;Elderly;Enzymes;Epigenetic Process;epigenomics;experimental study;extend lifespan;Family;Fat Body;Female;fly;Future;Gene Expression;gene interaction;Genes;Genetic;genome-wide analysis;Genomics;glucose metabolism;Goals;HDAC4 gene;Health;healthspan;healthy aging;Heterochromatin;Histones;Human;improved;Individual;insight;Intervention;life span;Link;lipid metabolism;Liver;Longevity;longevity gene;Maintenance;male;Mammals;Measures;Mentors;Methyl-CpG-Binding Protein 2;Modeling;Molecular;Mus;Muscle;mutant;Nervous System;next generation sequencing;Orthologous Gene;overexpression;Pathway interactions;prevent;programs;Proteins;Regulation;Research;Resources;Risk;Risk Factors;Role;SIRT1 gene;Sirtuins;skills;Solid;System;Telomere Maintenance;Testing;Therapeutic;Tissues;tool;Training;Training Activity;Transcriptional Regulation;transcriptome;transcriptome sequencing;transcriptomics;Transgenic Organisms;Translating;Tumor Suppression

PROJECT_TITLE: Mechanisms of Lifespan Regulation by Sirt6 in Drosophila melanogaster


ORG_CITY: CHARLOTTE

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF NORTH CAROLINA CHARLOTTE

PHR: Principal Investigator/Program Director (Last, First, Middle): Afonin, Kirill, A PROJECT NARRATIVE  Beyond their traditionally known roles as carriers and regulators of genetic information, nucleic acids have auspiciously emerged as versatile therapies for taking advantage of cellular pathways to drive the sensing, targeting, and silencing of a variety of diseases. With MIRA support, we will explore additional nanotechnology- based therapeutic options that enlist a biocompatible nucleic acid-encoded platform (SMART NANPs) for the controlled immunostimulation and modulation of therapeutic responses. This research program aims to advance the envisioned technology towards personalized medicine and aid in addressing top public health challenges in the U.S. as they relate to cancer (through vaccines and immunotherapies), cardiovascular diseases (through regulated coagulation), and drug overdose and safety (through the biodegradable nature of the platform and its functional regulation).

PI_NAMEs: AFONIN, KIRILL A (contact)

PROGRAM_OFFICER_NAME: KODURI, SAILAJA

PROJECT_TERMS: Address;Architecture;Biodistribution;Biological;biomaterial compatibility;Biopolymers;cancer cell;Cardiovascular Diseases;cell behavior;Cell Physiology;Cell Reprogramming;Cells;Clinical;clinical application;Coagulation Process;Code;Communicable Diseases;Communication;data platform;Dendritic Cells;Diagnosis;disability;Disease;Drug Delivery Systems;Formulation;Funding;genetic information;Goals;Health Personnel;Human;Immune;immune modulating agents;Immune response;Immune system;Immunologic Stimulation;Immunologics;Immunology;Immunotherapy;interdisciplinary approach;Interferons;Knowledge;Learning;Life;Machine Learning;Malignant Neoplasms;Modality;Molecular;monocyte;nanoparticle;Nanotechnology;Nature;next generation;Nucleic Acids;Overdose;Pathway interactions;Patients;personalized medicine;Pharmaceutical Preparations;prevent;Principal Investigator;programs;Property;Public Health;Regulation;Reproducibility;Research;Role;Safety;self assembly;Signal Transduction;Source;Specific qualifier value;Structure-Activity Relationship;Technology;Therapeutic;therapeutic nanoparticles;therapy outcome;Thrombin;Toxic effect;translational oncology;Translations;treatment response;Vaccines;Work

PROJECT_TITLE: SMART NANPs: new molecular platform for communication with human immune system and modulation of therapeutic responses

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


NIH_SPENDING_CATS: Genetics

ORG_CITY: MILWAUKEE

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

ORG_STATE: WI

PHR: PROJECT NARRATIVE While the DNA sequence defines what proteins are possible, when and where a DNA sequence is translated into a protein is determined by ‘epigenetic’ modifications that occur on top of (‘epi’) the DNA sequence (‘genetics’). The location and timing of epigenetic modifications are controlled by groups of proteins that ‘write’, ‘read’, and ‘erase’ these modifications. We focus on a group of 'reader' proteins linked to human inflammatory diseases with the long-term goal of finding new ways to target these proteins with chemical probes and small- molecule drugs.

PI_NAMEs: SMITH, BRIAN CHRISTOPHER (contact)

PROJECT_TERMS: Achievement;Acyl Coenzyme A;Acylation;Animal Model;Attenuated;Binding;Biological Process;Biology;Biophysics;Bromodomain;Cardiovascular Diseases;Cell model;Chemicals;Chromatin;Clinical Trials;Coupled;Development;Disease;DNA Sequence;drug development;Epigenetic Process;Genetic;Genetic Transcription;Goals;Health;Histones;Hot Spot;Human;human disease;Individual;Inflammation;Inflammatory;inhibitor;Knowledge;Language;link protein;Location;Lysine;Malignant Neoplasms;Mediating;medical schools;Metabolic;Metabolism;Mission;Modification;multidisciplinary;National Institute of General Medical Sciences;novel;Nuclear Proteins;Pharmaceutical Preparations;precision medicine;programs;protein structure;Proteins;Reader;Reading;recruit;Research;screening;Signal Pathway;small molecule;structural genomics;Structure;Testing;Therapeutic;therapeutic target;tool;transcription factor;Transcriptional Regulation;transcriptomics;Translating;Variant;Wisconsin;Writing

PROJECT_TITLE: Discovering and Exploiting Selectivity within Tandem Bromodomains

STUDY_SECTION: MRAE

STUDY_SECTION_NAME: Maximizing Investigators' Research Award - E Study Section[MRAE]


ORG_CITY: HOUSTON

ORG_NAME: RICE UNIVERSITY

ORG_STATE: TX

PHR: PROJECT NARRATIVE Peroxisomes are subcellular compartments housing critical metabolic reactions and are essential for normal human and plant development. The experiments of this proposal utilize a genetically tractable multicellular organism to elucidate the molecular regulation of the biogenesis, dynamics, and degradation of this essential organelle. Results from these studies will illuminate mechanisms of peroxisome dysfunction that contribute to common age-related diseases and inherited peroxisome biogenesis disorders, which are often fatal in infancy or childhood.

PI_NAMEs: BARTEL, BONNIE  (contact)

PROGRAM_OFFICER_NAME: MILLER, RITA K

PROJECT_TERMS: Address;age-related disease;Biochemical;Biogenesis;Biological;Biology;Blindness;Cells;Childhood;Defect;Development;Disease;Disparate;Eukaryota;experimental study;Functional disorder;Genetic;Genetic Models;Growth;hearing impairment;Housing;Human Development;infancy;Inherited;insight;Knowledge;Life;live cell imaging;Membrane;Metabolic;Modeling;Molecular;Mouse-ear Cress;Nerve Degeneration;next generation;Non-Insulin-Dependent Diabetes Mellitus;Organ;Organelles;Organism;oxidative damage;Oxidative Stress;peroxisome;plant growth/development;Plants;Process;Protein Import;Quality Control;Reaction;Recycling;Regulation;Scientist;Symptoms;Syndrome;System;Training;Vesicle;Yeasts

PROJECT_TITLE: Peroxisome biogenesis, dynamics, and degradation

STUDY_SECTION: MRAD

STUDY_SECTION_NAME: Maximizing Investigators' Research Award - D Study Section[MRAD]


ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Project Narrative: This research uses a quantitative pharmacology approach to understand the complex distribution and metabolism of antibodies and their small molecule payloads from the whole organism to single-cell level. By combining high-resolution molecular imaging approaches to quantify distribution with computational simulations of drug transport, more effective antibody drug conjugates can be rationally designed for cancer immunotherapy and newer non-oncological disease applications.

PI_NAMEs: THURBER, GREG  (contact)

PROJECT_TERMS: Animal Model;Antibodies;Antibody-drug conjugates;Automobile Driving;Binding;cancer immunotherapy;cell killing;Cells;Clinic;Clinical effectiveness;clinical efficacy;Complex;Computer Models;Computer Simulation;Computing Methodologies;design;Development;Disease;Dose;Drug Kinetics;Drug Transport;Engineering;Goals;graphical user interface;Hybrids;IgG Receptors;IgG1;imaging approach;Immune;Immune response;Immune system;Immunocompetent;immunogenic cell death;Immunologic Stimulation;insight;interest;Investments;Malignant Neoplasms;Measurement;Measures;Mediating;Metabolism;Molecular;molecular imaging;mouse model;New Agents;novel;patient population;Patient Selection;Pattern;Pharmaceutical Preparations;Pharmacology;Population;preclinical development;Property;Proteins;rational design;receptor-mediated signaling;Research;Resolution;Role;Scientist;small molecule;Solid Neoplasm;success;synergism;Tertiary Protein Structure;Therapeutic;treatment response;uptake;Whole Organism;Work

PROJECT_TITLE: Designing Antibody Drug Conjugates for Durable and Complete Therapeutic Responses


ADMINISTERING_IC: HS

IC_NAME: AGENCY FOR HEALTHCARE RESEARCH AND QUALITY

ORG_DEPT: UROLOGY

PHR: PROJECT NARRATIVE The burden of urinary incontinence (UI) on American women is immense in human and financial terms, and continues to rise with the growing population of older adults. The goal of this proposal is to improve the care for UI provided to an ethnically diverse population of women and, in doing so, decrease the utilization of specialty care while improving patient outcomes and reducing disparities in care. Three Southern California medical groups will participate in implementation of PCOR evidence, and the intervention will be evaluated in a cluster randomized controlled trial and results disseminated broadly.

PI_NAMEs: ANGER, JENNIFER TASH (contact)

PROGRAM_OFFICER_NAME: ZHANG, XINZHI

PROJECT_TITLE: A Practice-based Intervention to Improve Care for a Diverse Population of Women with Urinary Incontinence


ADMINISTERING_IC: LM

IC_NAME: NATIONAL LIBRARY OF MEDICINE

NIH_SPENDING_CATS: Data Science;Networking and Information Technology R&D (NITRD)

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: Project Narrative Data that offer precise descriptions of data—metadata—are critical scientific resources that facilitate the discovery, reuse, and reproducibility of the data to which they refer. Our goal is to create methods and tools that improve the quality of scientific metadata hosted in public repositories, and thus enhance the discoverability and re-use of public biomedical datasets. Making data more accessible through scientifically rigorous metadata will accelerate the ability to make transformative data-driven biomedical discoveries using public data archives.

PI_NAMEs: MUSEN, MARK A (contact)

PROGRAM_OFFICER_NAME: FARRELL, CATHERINE MARY

PROJECT_TERMS: Acceleration;Age;Biological Specimen Banks;biomedical scientist;Collection;Common Data Element;Communities;Computers;Data;data archive;Data Collection;data repository;data reuse;Data Science;Data Set;Disease;experimental study;FAIR principles;Funding Agency;Goals;improved;indexing;information organization;Information Technology;interoperability;Knowledge;Libraries;Link;Manuals;Metadata;metadata standards;Methods;Names;Natural Language Processing;Numerical value;Ontology;Pharmaceutical Preparations;place fields;Process;public repository;Records;Reporting;repository;Reproducibility;Research;Research Personnel;Resources;Retrieval;sample collection;Sampling;Science;Scientist;search engine;secondary analysis;Specific qualifier value;Speed;Standardization;Structure;Technology;Testing;Time;tool;Variant;Work

PROJECT_TITLE: The Metadata Powerwash - Integrated tools to make biomedical data FAIR


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

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

ORG_CITY: PITTSBURGH

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: Epstein-Barr virus (EBV) is a ubiquitous gamma-herpesvirus associated with nasopharyngeal carcinoma (NPC), which has an estimated global cancer burden of ~78,000 cases per year. On average, more than 90% of adults worldwide are seropositive but control of the latent and lytic infection cycles is paramount to EBV pathogenesis in the nasopharynx. This proposal seeks to redefine the EBV principal oncoprotein, latent membrane protein 1 (LMP1), as a virulence factor that facilitates the induction of the lytic cascade.

PI_NAMEs: SHAIR, KATHY  (contact)

PROGRAM_OFFICER_NAME: ALARCON, RODOLFO M

PROJECT_TERMS: 3-Dimensional;activating transcription factor 1;Adult;Air;airway epithelium;Antibodies;Attenuated;Binding;Biological Assay;Biology;BZLF1 gene;Cancer Burden;Cell Culture Techniques;Cell Line;cell type;Cells;China;CRISPR/Cas technology;cytokine;D Cells;Data;Elements;Engineering;Epithelial Cells;Epithelium;Epstein-Barr pathogenesis;Epstein-Barr Virus Infections;Epstein-Barr virus LMP-1 protein;Evolution;Excision;Failure;Focal Infection;functional genomics;gammaherpesvirus;Genes;Genetic Complementation Test;Genetic Polymorphism;Genetic Transcription;Genomic Instability;Human Herpesvirus 4;Immediate-Early Genes;Immediate-Early Proteins;Immunoglobulin A;Inflammatory;Integration Host Factors;keratinocyte;latent infection;Life Cycle Stages;Liquid substance;Lytic;Lytic Phase;Lytic Virus;Maps;Membrane Proteins;Methods;Modeling;Molecular;mucosal site;mutant;Mutation;Nasopharynx;Nasopharynx Carcinoma;neoplastic;Nose;Oncogenes;Oncoproteins;Oral mucous membrane structure;Pathogenesis;Patients;permissiveness;Phase;Phenotype;Population;Production;programs;promoter;Protein Array;protein protein interaction;Proteins;Proteome;recombinant virus;Recombinants;Regulation;Reporter;response;Role;Series;seropositive;Signal Transduction;single-cell RNA sequencing;Stratified Epithelium;Testing;Tissues;transcription factor;Transcription Factor AP-1;Transcriptional Regulation;transcriptome;tumor;Variant;Viral Genome;Viral Proteins;Virulence Factors;Virus Replication;Virus Shedding;Western Blotting;Zebra

PROJECT_TITLE: Epstein-Barr virus molecular pathogenesis in the nasopharynx and the role of LMP1 in lytic infection

STUDY_SECTION: VIRA

STUDY_SECTION_NAME: Virology - A Study Section[VIRA]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Dementia;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Mental Health;Neurodegenerative;Neurosciences;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: ATLANTA

ORG_DEPT: FAMILY MEDICINE

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: Project Narrative As the elderly population in United States continues to grow rapidly, Alzheimer's disease poses a major public health challenge, and the disease may disproportionately burden older African Americans. Our proposal is designed to reduce the knowledge gaps regarding the role of modifiable risk factors such as perceived stress and how it may differentially impact cognitive function in high-risk groups. Findings from our proposal would lay the foundation of understanding the association of stress and cognitive impairment, mechanistic pathways, and targeted interventions to reduce Alzheimer's disease disparities.

PI_NAMEs: KULSHRESHTHA, AMBAR  (contact)

PROGRAM_OFFICER_NAME: HOOKER, EMILY DIANE

PROJECT_TERMS: abeta deposition;acceptability and feasibility;Address;Affect;African American;African American population;Aging;Alzheimer disease prevention;Alzheimer's Disease;Amyloid beta-Protein;Area;Attention;Behavior;Behavior Therapy;Behavioral Mechanisms;Biological Markers;Blood Vessels;Board Certification;Brain;Cardiovascular Diseases;cardiovascular disorder epidemiology;cardiovascular disorder risk;cardiovascular risk factor;career;Chronic stress;Clinical;clinical care;Clinical Research;Clinical Trials;Cognition;Cognitive;cognitive function;cognitive performance;cohort;Cohort Studies;Complex;coping;Data Analyses;Dementia;design;Diet;Discrimination;Disease;disease disparity;Disparity;Elderly;Episodic memory;Ethnic Origin;Event;executive function;experience;Family Physicians;Family Practice;Foundations;Glucocorticoids;Goals;Health;health disparity;high risk;high risk population;Hormones;hypothalamic-pituitary-adrenal axis;Impaired cognition;improved;Incidence;Individual;interdisciplinary approach;Intervention;Knowledge;Life;Life Cycle Stages;lifestyle intervention;Literature;Longitudinal Studies;Measurement;Measures;Mediating;Memory;Mentored Patient-Oriented Research Career Development Award;mild cognitive impairment;Minority Groups;minority stress;modifiable risk;Modification;multidisciplinary;Nature;Nerve Degeneration;neurodevelopment;Neuropsychology;novel;Online Systems;Outcome;Pathway interactions;patient oriented;Patients;Pattern;perceived discrimination;perceived stress;Persons;physical inactivity;Population;Prevalence;prevent;Prevention;Prevention strategy;Preventive Medicine;Primary Care;primary outcome;prodromal Alzheimer's disease;Program Description;programs;prospective;Psychological Stress;psychosocial stressors;Public Health;Questionnaires;Race;racial population;Reasons for Geographic And Racial Differences in Stroke;Reduce health disparities;Research;Research Personnel;Risk Factors;Role;Smoking;Socioeconomic Factors;specific biomarkers;Stress;stress reduction;stressor;Subgroup;tau Proteins;Testing;Training;Training Programs;United States;United States National Institutes of Health;Universities;web-based intervention;Work

PROJECT_TITLE: Association of Perceived Stress and Cognition

STUDY_SECTION: NIA

STUDY_SECTION_NAME: Behavior and Social Science of Aging Study Section[NIA-S]


NIH_SPENDING_CATS: Aging;Neurosciences

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

PHR: This study will establish basic cellular and molecular mechanisms underlying neuron-glia communication across lifespan. The project is focused on elucidating the roles of Toll-like receptor signaling in mediating interactions between dying neurons and phagocytic glia. The TLR pathway is an evolutionarily conserved component of the innate immune system and its dysregulation is linked to human disorders. By establishing how this pathway directs neuron, neurite, and synapse clearance in the developing and adult nervous system, this research will build an essential foundation for effective clinical approaches to treating neurodevelopmental and psychiatric disorders.

PI_NAMEs: BROIHIER, HEATHER  (contact)

PROGRAM_OFFICER_NAME: TYLER, WILLIAM A

PROJECT_TERMS: Adult;Affinity;Apoptosis;Apoptotic;Automobile Driving;axon guidance;axon injury;brain health;Cells;Clinical;Communication;Competence;Consumption;density;detection platform;Development;Disease;Drosophila genus;Early Diagnosis;Embryo;Ensure;Excision;fly;Foundations;Human;in vivo Model;Inflammation;Innate Immune System;insight;interest;Investigation;life span;Ligands;Link;Maintenance;MAP Kinase Gene;Mediating;Mental disorders;Modeling;Molecular;Natural Immunity;Necrosis;Nervous System;neural circuit;Neurites;neurodevelopment;Neurodevelopmental Disorder;Neuroglia;neuron loss;Neurons;neurotransmission;novel;Olfactory Pathways;Pathway interactions;Pattern;Phagocytes;Phagocytosis;Phenotype;Play;Population;presynaptic;Presynaptic Terminals;prevent;Process;Publishing;receptor;Receptor Signaling;Research;Role;Rupture;Shapes;Signal Pathway;Signal Transduction;spatiotemporal;Specificity;Speed;Stereotyping;success;Support System;Synapses;synaptic function;synaptogenesis;System;Testing;Toll-Like Receptor Pathway;Toll-like receptors;tool;TXN gene;virtual;Work

PROJECT_TITLE: Retooling innate immunity: An investigation of TLR-mediated glial priming across lifespan


NIH_SPENDING_CATS: Brain Disorders;Neurodegenerative;Neurosciences;Physical Injury - Accidents and Adverse Effects;Traumatic Head and Spine Injury

ORG_CITY: PHILADELPHIA

ORG_DEPT: PHARMACOLOGY

ORG_NAME: DREXEL UNIVERSITY

PHR: Project Narrative The major problem being addressed by this study is the lack of understanding on how to modulate the process of clearance of glutamate, the main chemical for communication in the brain. We have developed compounds that modulate the activity of glutamate transporters, the proteins responsible glutamate clearance in the brain. Our goal is to fully understand the mechanisms of modulation of the activity of these transporters, using these compounds and refined and modern technologies. This information could lead to the development of therapies for many CNS disorders that have dysfunctional levels of glutamate, including traumatic brain injury, stroke, ALS, epilepsy, neuropathic pain among others.

PI_NAMEs: BOUDKER, OLGA ;MORTENSEN, ANDREIA C K (contact);REYES, NICOLAS

PROGRAM_OFFICER_NAME: UMANAH, GEORGE KWABENA ESSIEN

PROJECT_TERMS: Acute;Address;Affect;Allosteric Site;American;Amino Acid Transporter;Antibodies;Binding;Biological Assay;biophysical analysis;Brain;Central Nervous System Diseases;Chemicals;Chronic;clinically relevant;Communication;Complex;Computer Models;conformational conversion;Cryoelectron Microscopy;design;Development;drug discovery;Drug Targeting;Elevator;Enhancers;Epilepsy;Excision;Excitatory Amino Acid Transporter 1;Excitatory Amino Acids;excitotoxicity;extracellular;Fluorescence Resonance Energy Transfer;Future;Glutamate Transporter;Glutamates;Goals;Homologous Gene;Human;improved;in vitro Model;in vivo Model;Injury;Knowledge;Measurement;Mediating;Membrane;Methods;Microscopy;Modernization;Molecular;Molecular Conformation;Movement;multidisciplinary;Mutagenesis;nanobodies;Neurodegenerative Disorders;neuron loss;Neuronal Injury;neuroprotection;neurotoxic;Neurotransmitters;novel strategies;Pain;painful neuropathy;particle;Peripheral;Pharmaceutical Chemistry;pharmacologic;Phylogenetic Analysis;Play;Population;Process;programs;Property;Proteins;Research;Resolution;Role;Sampling;scaffold;single molecule;small molecule;Specificity;Stroke;Structure;Synaptic Cleft;Techniques;Technology;Testing;therapy development;thermostability;three dimensional structure;Transmembrane Transport;Traumatic Brain Injury;Variant;Vesicle;virtual screening;X-Ray Crystallography

PROJECT_TITLE: The mechanism of allosteric modulation of glutamate transporters

STUDY_SECTION: BPNS

STUDY_SECTION_NAME: Biophysics of Neural Systems Study Section[BPNS]


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

ORG_CITY: SEATTLE

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: RELEVANCE Intracellular pathogens remain on of the largest human health burdens in the 21st century. By characterizing the mechanism of host-pathogen interactions using the model intracellular bacterium L. monocytogenes we will define the fundamental mechanisms employed by intracellular pathogens to promote disease and the host response to these infections

PI_NAMEs: WOODWARD, JOSHUA  (contact)

PROGRAM_OFFICER_NAME: BAQAR, SHAHIDA

PROJECT_TERMS: 4 hydroxynonenal;Actins;Affinity;Aldehydes;antimicrobial;Antimicrobial Effect;Antimicrobial Resistance;Bacteria;Bacterial Infections;Binding;Biochemical;Biological Response Modifiers;Bone Marrow;Cells;Cytosol;Detection;Disease;Dissection;Drug Metabolic Detoxication;Enzymes;Eukaryotic Cell;Exhibits;Exposure to;fitness;foodborne;foodborne illness;Funding;Gallbladder;Genes;Genetic;Genetic study;Genetic Transcription;genome-wide;Glean;Grant;Growth;Health;Host Defense;Human;human pathogen;Immune;immune activation;Immune response;In Vitro;in vivo;Individual;Infection;Inflammation;Inflammatory Response;Innate Immune Response;Innate Immune System;insight;Invaded;Listeria monocytogenes;Macrophage;Mediating;Mediator;Membrane Transport Proteins;microbial;Modeling;Molecular;Motility;mouse model;Mus;NF-kappa B;NFKB Signaling Pathway;Nitric Oxide;Nitric Oxide Synthase;novel;Nucleotides;Organism;pathogen;Pathogenesis;pathogenic bacteria;Pattern recognition receptor;Periodicity;Physiology;polymerization;Polymers;Predisposition;Process;Production;Proteins;Public Health;Reactive Nitrogen Species;Resistance;resistance factors;resistance mechanism;response;Role;Second Messenger Systems;Signal Transduction;Testing;tissue culture;tool;Toxic effect;transmission process;transposon sequencing;Virulence;Whole Organism Analysis

PROJECT_TITLE: Listeria monocytogenes physiology and host pathogen interactions

STUDY_SECTION: BACP

STUDY_SECTION_NAME: Bacterial Pathogenesis Study Section[BACP]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Bioengineering;Brain Disorders;Cerebrovascular;Dementia;Neurodegenerative;Neurosciences;Stroke;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: RENO

ORG_NAME: UNIVERSITY OF NEVADA RENO

ORG_STATE: NV

PHR: PROJECT NARRATIVE Blood flow within the brain must be tightly controled to prevent damage to small blood vessel in cases where perfusion pressure is too high or in ischemia, where pressure is too low. Blood must also be redirected to highly active brain regions to maintain activity. We propose a series of studies that will investigate a class of molecules called “transient receptor potential channels” that detect the brain’s needs and redirect blood flow to maintain an optimal state.

PI_NAMEs: EARLEY, SCOTT  (contact)

PROGRAM_OFFICER_NAME: CHARETTE, MARC F

PROJECT_TERMS: Address;age related;Aging;ANK1 gene;Architecture;arteriole;Basic Science;biomedical imaging;Blood;Blood flow;Blood Vessels;Brain;brain health;Brain region;Capillary Endothelial Cell;Cells;cerebral artery;cerebral capillary;Cerebral endothelium;cerebral microvasculature;Cerebral small vessel disease;cerebrovascular;Cerebrovascular Disorders;cerebrovascular pathology;Cerebrovascular system;Cerebrum;Chemicals;Collaborations;Collection;detector;Development;Disease;Endocrine;Ensure;Family;Genetic;Genetic Models;Goals;Health;Homeostasis;imaging approach;Investigation;Ion Channel;Ischemia;Knowledge;Metabolic;Microcirculation;mouse model;nanoscale;neurochemistry;neurovascular coupling;next generation;paracrine;Perfusion;Physiological Processes;pressure;prevent;Process;Reactive Oxygen Species;receptor;Research;Research Design;Research Personnel;Resources;response;Role;sensor;Sensory;Series;Signal Transduction;Smooth Muscle Myocytes;Stimulus;Stroke;superresolution microscopy;Testing;TRP channel;TRPA channel;Vanilloid;vascular cognitive impairment and dementia;vasoconstriction

PROJECT_TITLE: TRP channels as fundamental sensors of the cerebral microcirculation


ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Maternal Health;Nutrition;Obesity;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Physical Activity;Preterm, Low Birth Weight and Health of the Newborn;Prevention;Women's Health Research

ORG_CITY: UNIVERSITY PARK

ORG_DEPT: MISCELLANEOUS

ORG_NAME: PENNSYLVANIA STATE UNIVERSITY, THE

PHR: PROJECT NARRATIVE Managing gestational weight gain offers lifelong health benefits in both mothers and their offspring, and is especially critical in pregnant women with overweight and obesity who have increased risks for adverse health outcomes. The proposed research aims to test efficacy of the enhanced, Healthy Mom Zone 2.0 intervention that adapts dosage intensity to regulate gestational weight gain (primary outcome) and impact secondary outcomes (maternal physical activity, energy intake, sleep, eating behaviors; infant birth weight; implementation markers) using an innovative, automated digital platform with remote delivery and model-based predictive control system to deliver personalized dosage recommendations. Impact of this research is an effective and scalable intervention for dissemination in the real world (e.g., adjunct to prenatal care) to manage prenatal weight gain and ultimately reduce risks for adverse perinatal outcomes.

PI_NAMEs: DOWNS, DANIELLE SYMONS (contact)

PROGRAM_OFFICER_NAME: EVANS, MARY

PROJECT_TERMS: Address;Architecture;attentional control;Behavior;Birth Weight;Body mass index;Categories;Cognitive;Control Groups;COVID-19 pandemic;Data;design;digital platform;dosage;Eating;Eating Behavior;Education;Effectiveness;efficacy evaluation;efficacy testing;efficacy trial;energy balance;Energy Intake;feasibility trial;Future;Gestational Age;gestational weight gain;Goals;Grant;Guidelines;Health;Health Benefit;health care delivery;Healthy Eating;high body mass index;high risk;Individual;Infant;Infant Health;infant outcome;innovation;Intake;Intervention;Low Birth Weight Infant;Maternal Health;Measurement;Measures;Methodology;mHealth;Modeling;Modification;Monitor;Mothers;novel;Obesity;offspring;Outcome;Outcome Measure;Outcome Study;Overweight;perinatal outcomes;Persons;Phase;Physical activity;post intervention;Pregnancy;Pregnant Women;prenatal;Prenatal care;prepregnancy;primary outcome;Qualifying;Randomized;randomized trial;Recommendation;remote delivery;Remote session;Research;restraint;Risk;Risk Reduction;scale up;secondary outcome;simulation;Sleep;social;social cognitive theory;System;theories;Time;tool;Translational Research;web interface;Weight Gain;Woman

PROJECT_TITLE: Efficacy of a Novel Digital Platform to Scale-Up a Personalized Prenatal Weight Gain Intervention Using Control Systems Methodology

STUDY_SECTION: HSDO

STUDY_SECTION_NAME: Human Studies of Diabetes and Obesity Study Section[HSDO]


NIH_SPENDING_CATS: Autoimmune Disease;Immunotherapy;Kidney Disease;Lupus;Rare Diseases

ORG_CITY: BOSTON

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

ORG_STATE: MA

PHR: NARRATIVE Neutrophils initiate organ damage in many autoimmune diseases driven by antibody-antigen immune complexes. We have shown that IgG antibody deposition within blood vessels triggers rapid neutrophil capture and tissue injury via their IgG receptors, called FcγRs, suggesting that these receptors serve as a key link between autoantibody deposition and organ damage. In this project we will interrogate whether FcγR activated neutrophils convert into longer lived antigen presenting cells, which activate T cells to fuel inflammation and associated organ damage in autoimmune disorders.

PI_NAMEs: MAYADAS, TANYA N (contact)

PROGRAM_OFFICER_NAME: RICE, JEFFREY S

PROJECT_TERMS: Abbreviations;Acceleration;acquired immunity;Acute;Antibodies;antigen binding;Antigen Presentation;Antigen-Antibody Complex;Antigen-Presenting Cells;Antigens;Autoantibodies;Autoimmune;Autoimmune Diseases;autoimmune pathogenesis;Automobile Driving;Autophagocytosis;Behavior;Biological Assay;Blood;Blood Vessels;Categories;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Communication;Cell Differentiation process;cell killing;cell motility;Cells;Characteristics;chemokine receptor;chronic autoimmune disease;Chronic Disease;Clinical;Complex;Coupled;Crohn's disease;Cross Presentation;cytokine;Data;Dendritic Cells;Deposition;differential expression;Disease;draining lymph node;End stage renal failure;Evolution;Exposure to;Fluorescein-5-isothiocyanate;Frequencies;Generations;Genes;Glomerulonephritis;Goodpasture Syndrome;Granulocyte-Macrophage Colony-Stimulating Factor;Heart Diseases;Human;human tissue;humanized mouse;IgG Receptors;Immune response;Immunize;immunogenic;Immunoglobulin G;Immunosuppressive Agents;imprint;In Vitro;in vivo;Inflammation;Inflammatory;inhibitor;Injections;Injury;Injury to Kidney;insight;intravital microscopy;Kidney;Link;Lupus;Lupus Nephritis;Malignant Neoplasms;Mediating;Modeling;Molecular;mouse model;multi-photon;Mus;Nephritis;nephrotoxicity;neutrophil;Neutrophil Activation;NF-kappa B;novel;Organ;organ injury;Ovalbumin;Ovum;Patients;Phase;Phenotype;phenotypic biomarker;Polysaccharides;Population;prevent;Process;programs;Property;Proteins;receptor;recruit;renal damage;Reporter;response;Rheumatoid Arthritis;Risk;Role;Serum;single-cell RNA sequencing;Spleen;Systemic Lupus Erythematosus;T-Cell Activation;T-Cell Proliferation;T-Lymphocyte;Testing;Therapeutic Intervention;tissue injury;trafficking;transcription factor;transcriptome;transcriptome sequencing;transcriptomic profiling;transcriptomics;transdifferentiation;Tubulointerstitial Nephritis;Tumor Immunity;uptake

PROJECT_TITLE: Neutrophil plasticity in autoimmune disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DKUS-H(02)]


NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Digestive Diseases;Health Services;Liver Disease;Patient Safety

ORG_CITY: INDIANAPOLIS

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: PROJECT NARRATIVE Patients with the complications of advanced liver disease often have difficulties after hospital discharge that result in early readmission. Poor outcomes for these patients during this transitional time could be improved through the use of innovative transitional care models. This proposal aims to examine the effect of a transitional care model, The Transitional Liver Clinic, in reducing readmissions, improving quality of life, and improving patient experience.

PI_NAMEs: ORMAN, ERIC  (contact)

PROGRAM_OFFICER_NAME: UNALP-ARIDA, AYNUR

PROJECT_TERMS: Acute;Address;Alcoholic Hepatitis;American;Area;Ascites;Caring;Characteristics;Chronic lung disease;Client satisfaction;Clinic;Clinical;Cognition Disorders;cohort;Communication;Communities;comorbidity;Complex;Data;Disease;Education;Elderly;Emergency department visit;experience;follow-up;Gastrointestinal Hemorrhage;Health;health care delivery;health care service utilization;Healthcare;Heart failure;Hepatic Encephalopathy;Hepatology;hospital readmission;Hospitalization;Hospitals;Impaired cognition;implementation science;improved;improved outcome;Indiana;Individual;innovation;Intervention;Lead;Liver;Liver Cirrhosis;Liver diseases;Medical;Medication Errors;Medication Management;Modeling;mortality;multidisciplinary;Outcome;participant enrollment;Patient Care;Patient Discharge;Patient Readmission;Patient-Focused Outcomes;Patients;Peritoneal Fluid;Persons;Population;programs;Provider;provider communication;Quality of life;Questionnaires;Randomized;randomized trial;randomized, clinical trials;Randomized, Controlled Trials;Reporting;Research Personnel;Resources;satisfaction;Schedule;secondary outcome;Severity of illness;Substance Use Disorder;System;telehealth;Telephone;tertiary care;Testing;Time;Transitional Care Planning;treatment as usual;treatment optimization;treatment planning;Treatment Protocols;trial comparing;Universities;Visit;Work

PROJECT_TITLE: The Transitional Liver Clinic (TLC): Reducing Liver Disease Readmission

STUDY_SECTION: ICSC

STUDY_SECTION_NAME: Interdisciplinary Clinical Care in Specialty Care Settings Study Section[ICSC]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Genetics;Infectious Diseases;Lung;Pulmonary Fibrosis

ORG_NAME: RESEARCH INST OF FOX CHASE CAN CTR

PHR: PROJECT NARRATIVE Fibrosis is the excessive accumulation of interstitial extracellular matrix (ECM) generated by activated fibroblasts and is a condition that can affect nearly every organ of the body. However, how activated fibroblasts are epigenetically regulated to maintain its activation and allow for pro-fibrotic gene expression is unclear. By elucidating how the ECM and fibrosis-inducing viruses alter fibroblasts’ chromatin landscape, this innovative study will expand our current understanding of how fibrotic disease develop, with the potential to uncover novel molecular linchpins that could serve as biomarkers or therapeutic targets in the future.

PI_NAMEs: GARDINER, JAYE C (contact)

PROGRAM_OFFICER_NAME: GIBBS, KENNETH D

PROJECT_TERMS: 2019-nCoV;Affect;Applied Skills;ATAC-seq;Bacterial Infections;Binding;Binding Proteins;Biological Markers;brahma;Categories;Cells;Cellular biology;Chemicals;ChIP-seq;Chromatin;chromatin remodeling;Chronic Obstructive Pulmonary Disease;clinically relevant;Communication;Complex;Connective Tissue;Coxsackie B Viruses;Cues;cytokine;Data;Deposition;Development;Disease;DNA-Directed RNA Polymerase;Environment;epigenetic memory;Epigenetic Process;epigenetic regulation;Excision;experimental study;extracellular;Extracellular Matrix;Failure;falls;Fibroblasts;Fibrosis;Future;Gene Expression;Gene Expression Regulation;Genes;Genetic Transcription;Goals;Grant;Growth Factor;Hepatitis B Virus;Histone Acetylation;Human;human pathogen;idiopathic pulmonary fibrosis;In Vitro;in vivo;Infection;Inflammatory Response;Influenza A virus;innovation;insight;interstitial;Knockout Mice;Lead;Link;Liver Fibrosis;Malignant Neoplasms;Mediating;memory acquisition;Mesenchymal;Molecular;mouse model;Myofibroblast;netrin-G1;novel;Nucleosomes;Organ;Organ failure;Pancreas;pancreatic cancer patients;Pancreatitis;Pathologic;Patient Isolation;Phenotype;Play;Predisposition;Process;programs;Pulmonary Fibrosis;recruit;Regulation;repaired;Reporting;Research;Resolution;Respiratory syncytial virus;Respiratory Tract Infections;response;Role;Signal Transduction;Simplexvirus;skill acquisition;small molecule inhibitor;Specificity;Stimulus;Testing;therapeutic target;Time;tissue repair;Tissue Sample;Tissues;Transcription Coactivator;Transcription Initiation;transcriptome sequencing;Transforming Growth Factor beta;Tropism;Viral;virology;Virus;Virus Diseases;Work;wound healing

PROJECT_TITLE: Elucidating the epigenetic regulation of extracellular matrix and virus-induced fibroblast activation


NIH_SPENDING_CATS: Biotechnology;HIV/AIDS;Immunization;Infectious Diseases;Prevention;Vaccine Related;Vaccine Related - AIDS

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: PROJECT NARRATIVE A major obstacle to rational HIV-1 vaccine design is the lack of an animal model where the induction of broadly neutralizing antibodies (bNAbs) can be achieved in a consistent and reproducible manner and the molecular events leading to bNAb elicitation deciphered. This application proposes a novel “reverse vaccinology” approach in SHIV infected and SOSIP Env trimer immunized rhesus macaques to overcome this roadblock.

PI_NAMEs: SHAW, GEORGE M (contact)

PROGRAM_OFFICER_NAME: CHAKRABARTI, BIMAL KUMAR

PROJECT_TERMS: Acceleration;Affinity;Amino Acid Substitution;Animal Model;Antibodies;Antibody Response;Antigens;Apical;Automobile Driving;B-Lymphocytes;Binding;Binding Sites;Biological;Biological Assay;Chemicals;Chronic;design;Development;Epitopes;Event;genome sequencing;Germ Lines;HIV-1;HIV-1 vaccine;Human;Immunization;Immunize;Immunogenetics;Immunologics;innovation;insertion/deletion mutation;Laboratories;Macaca;Macaca mulatta;mimicry;Modeling;Molecular;Monoclonal Antibodies;neutralizing antibody;next generation sequencing;novel;Pathway interactions;Pattern;Peptides;Polysaccharides;pre-clinical;Prevalence;Primates;Reproducibility;response;Reverse engineering;Rhesus;simian human immunodeficiency virus;Structure;Testing;Time;transmission process;Vaccine Design;vaccine trial;vaccinology;Virus

PROJECT_TITLE: Reverse Vaccinology in SHIV Infected Macaques as a Molecular Guide for HIV-1 Vaccine Design

STUDY_SECTION: HIVD

STUDY_SECTION_NAME: HIV Immunopathogenesis and Vaccine Development Study Section[HIVD]


NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Biotechnology;Complementary and Integrative Health;Infectious Diseases;Lung;Microbiome;Nutrition;Orphan Drug;Rare Diseases

ORG_CITY: Rockville

ORG_NAME: RISE THERAPEUTICS, LLC

ORG_STATE: MD

PHR: PROJECT NARRATIVE The dysregulated immune response in ARDS patients is directly related to severity and lethality of endemic and pandemic respiratory viruses. R-3750 is a functionally directed synthetic biology medicine that rebalances the immune system, eliminating self-destructive immune responses without compromising the immunological recognition of pathogens. R-3750 combines the safety and ease of administration of a probiotic with the targeted delivery of an immunologically focused drug that can be used to mitigate viral-induced ARDS.

PI_NAMEs: FANGER, GARY ;FURLAN FREGUIA, CHRISTIAN  (contact)

PROGRAM_OFFICER_NAME: MINNICOZZI, MICHAEL

PROJECT_TERMS: Acute Lung Injury;Acute Respiratory Distress Syndrome;Affect;airway epithelium;Animal Model;Antigens;Biological Markers;Biology;biomarker identification;capsule;Cell Line;Cells;Chemistry;Clinic;Clinical;Clinical Trials;Combined Modality Therapy;Complication;Coronavirus Infections;current pandemic;cytokine;Data;Defense Mechanisms;Dendritic Cells;Development;Diet;Disease;Dose;Down-Regulation;drug development;Drug Kinetics;Drug toxicity;Economics;Educational process of instructing;Effector Cell;Engineering;Enzyme-Linked Immunosorbent Assay;Epithelial Cells;Epithelium;Equilibrium;Evaluation;Flow Cytometry;Food Industry;Funding;Future;General Population;Genes;Grant;gut microbiome;gut microbiota;Health;Hematology;Histopathology;Human;Hyperactivity;Immune;Immune response;Immune system;Immunity;Immunologics;immunoregulation;Inflammation;Inflammatory;Inflammatory Response;Influenza;influenza infection;Infrastructure;Ingestion;Innate Immune Response;innovation;Intestines;Investments;Lactococcus lactis;Leukocytes;Life;Link;Lung;lung injury;lung microbiome;manufacture;Measures;Mediating;Medicine;microbial;microbiome;microbiome therapeutics;Modeling;mouse model;Mucous Membrane;Mus;mutational status;neutrophil;Neutrophil Activation;Neutrophil Infiltration;Neutrophilia;novel;novel marker;novel strategies;novel therapeutics;Oral;pandemic disease;pathogen;pathogenic virus;Pathway interactions;Patients;Pharmaceutical Preparations;Pharmacologic Substance;Phase;Play;Population;Positioning Attribute;Probiotics;Process;programs;Proteins;Regulatory T-Lymphocyte;research clinical testing;respiratory virus;Role;Safety;screening;Severities;Severity of illness;Small Business Innovation Research Grant;Surface;synthetic biology;T-Lymphocyte;targeted delivery;Temperature;Testing;Therapeutic;Tissue-Specific Gene Expression;Tissues;Toxicology;Up-Regulation;Viral;Virus Diseases;White Blood Cell Count procedure;Work

PROJECT_TITLE: A Novel Synthetic Biology-Derived Microbiome Therapeutic to Treat Viral-Induced Acute Respiratory Distress Syndrome (ARDS)

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-BST-F(10)B]


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Cancer;Clinical Research;Dissemination and Implementation Research;Electronic Nicotine Delivery Systems;Lung;Lung Cancer;Prevention;Social Determinants of Health;Tobacco;Tobacco Smoke and Health

ORG_DEPT: SOCIAL SCIENCES

ORG_NAME: HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH

PHR: PROJECT NARRATIVE Policies to limit the use of electronic nicotine delivery systems (ENDS, or e-cigarettes) are of major interest to public health decision makers across the US, who must balance the potential risks of ENDS to adolescents (e.g., nicotine addiction, adverse effects on brain development) and potential benefits to adults (e.g., for smoking cessation). Public health research can inform policymaking, but strategies are needed to effectively disseminate such research to policymakers in the face of potentially complicated tradeoffs. This project will develop and evaluate a dissemination strategy – a decision support tool – that could improve the accessibility, usefulness, and public health impact of research evidence.

PI_NAMEs: SMITH, NATALIE RIVA (contact)

PROGRAM_OFFICER_NAME: RADAEV, SERGEY

PROJECT_TERMS: Administrator;Adolescent;Adult;Adverse effects;Affect;Area;Assessment tool;Award;Benefits and Risks;Brain;Cancer Control;cancer prevention;cancer risk;career;career development;Communication;cost;Data;Decision Analysis;Decision Making;design;Development;Development Plans;Dissemination and Implementation;dissemination science;dissemination strategy;economic evaluation;Education;Effectiveness;Electronic cigarette;Electronic Nicotine Delivery Systems;Equilibrium;Equity;experience;experimental study;flexibility;Foundations;Future;Goals;Health;health economics;Health Policy;implementation research;implementation science;improved;Individual;informant;insight;interest;Interview;Licensing;Literature;Malignant Neoplasms;Mentorship;Methods;models and simulation;Nicotine Dependence;novel strategies;Phase;Pilot Projects;Policies;Policy Maker;Policy Making;Policy Research;Politics;Postdoctoral Fellow;prevent;Public Health;public health research;Public Health Schools;Public Policy;public policy on tobacco;Publishing;Recommendation;Recording of previous events;Reporting;Research;Research Activity;research data dissemination;Research Peer Review;Research Personnel;Resources;Risk;Schools;Science;Scientist;smoking cessation;Statutes and Laws;success;support tools;Taxes;Time;Tobacco Control Research;tool;Training;Training Activity;Uncertainty;Weight;Work

PROJECT_TITLE: Developing and evaluating a decision support tool to disseminate tobacco control research and inform policy implementation


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

PHR: In ischemia, traumatic brain injury, and neurodegenerative diseases, deficiencies in neurovascular coupling contribute to neuronal damage. Our proposal will address this issue through experiments that dissect the circuitry enabling communication between neurons and the vasculature with the goal of developing new therapies.

PI_NAMEs: ROSS, SARAH ELIZABETH (contact);VAZQUEZ, ALBERTO L

PROGRAM_OFFICER_NAME: HEWETT, SANDRA JEANNE

PROJECT_TERMS: Alleles;Alzheimer's Disease;awake;Blood flow;Blood Vessels;Cerebral Amyloid Angiopathy;cerebrovascular;Cerebrovascular Circulation;Cerebrovascular Disorders;Cerebrum;Clinical;Communication;Correlative Study;Data;Diameter;Etiology;experimental study;Genetic;Goals;hemodynamics;Homeostasis;Image;inhibitory neuron;insight;Ischemia;Knowledge;Laser-Doppler Flowmetry;Mediating;Methods;Microscopy;Monitor;Mus;Myoepithelial cell;neural;neural circuit;Neurodegenerative Disorders;neuromechanism;Neurons;neurovascular coupling;Nitric Oxide;Nitric Oxide Synthase;Nitric Oxide Synthase Type I;novel therapeutics;optogenetics;Output;Parvalbumins;Pathogenesis;Perfusion;Pericytes;photoactivation;Population;Positioning Attribute;Process;Regulation;Relaxation;Research;response;Signal Transduction;Stroke;Structure;Testing;Time;Tissues;tool;Traumatic Brain Injury;two-photon;Vasodilation;Vasodilator Agents;Vibrissae;Visualization

PROJECT_TITLE: Neural circuit basis for neurovascular coupling

STUDY_SECTION: BINP

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


NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Digestive Diseases;Hepatitis;Liver Disease

ORG_CITY: ROOTSTOWN

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: NORTHEAST OHIO MEDICAL UNIVERSITY

PHR: Project Narrative Relevance: NAFLD is one of the most common chronic liver diseases worldwide. Completion of the proposed studies will help determine the role of hepatic TMEM141 in regulating the pathogenesis of NAFLD, bile acid metabolism, and mitochondrial functions, and may lead to a new strategy for treatment of NAFLD. Thus, this project is highly relevant to human health.

PI_NAMEs: ZHANG, YANQIAO  (contact)

PROGRAM_OFFICER_NAME: GARCIA, MARTHA

PROJECT_TERMS: absorption;Bile Acid Biosynthesis Pathway;bile acid metabolism;Bile Acids;Binding;Biological Process;C57BL/6 Mouse;Cholestasis;Cholesterol;Cholesterol Homeostasis;chronic liver disease;Clinical Trials;Complex;Data;db/db mouse;Developed Countries;Development;diabetic;Diet;Endocrine;Fatty acid glycerol esters;fatty acid oxidation;FDA approved;Feedback;fibrogenesis;Fructose;G-Protein-Coupled Receptors;Gene Modified;Generations;Genes;Genetic;Goals;Health;Hepatic;Hepatocyte;hepatocyte nuclear factor;Homeostasis;Hormones;Human;Hydrogen Peroxide;Inflammation;inhibitor;Integral Membrane Protein;Investigation;Lipolysis;Liver;Liver Cirrhosis;Liver Mitochondria;male;Malignant neoplasm of liver;Mediating;Metabolic;Mitochondria;Molecular;Mus;new therapeutic target;non-alcoholic fatty liver;non-alcoholic fatty liver disease;nonalcoholic steatohepatitis;novel;novel therapeutic intervention;overexpression;Pathogenesis;Pathogenicity;Pathway interactions;Patients;Pharmaceutical Preparations;Play;prevent;Primary carcinoma of the liver cells;Production;Protein Family;Proteins;Reactive Oxygen Species;receptor;Regulation;Repression;Role;Signal Pathway;Signal Transduction;Steatohepatitis;Superoxides;Synthetic Genes;targeted treatment;Triglycerides;uptake;western diet

PROJECT_TITLE: Mechanisms Underlying the Pathogenesis of Non-alcoholic Fatty Liver Disease

STUDY_SECTION: HBPP

STUDY_SECTION_NAME: Hepatobiliary Pathophysiology Study Section[HBPP]


NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome;Neurosciences;Pediatric;Stem Cell Research;Stem Cell Research - Embryonic - Human

ORG_CITY: CINCINNATI

ORG_NAME: CINCINNATI CHILDRENS HOSP MED CTR

PHR: The basal ganglia play crucial roles in regulating brain function such as cognition and voluntary purposeful movements, and abnormal development and/or function of these brain nuclei have been associated with childhood neurological disorders including attention deficit hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD) and Tourette’s syndrome. Recently human patient studies have revealed that, like in mice, the Gsx2 transcription factor is essential for basal ganglia development. In this proposal, we combine mouse genetics with molecular, biochemical, and genomic studies to elucidate the mechanisms underlying the role of Gsx2 in basal ganglia development with a specific focus on modeling a known pathological human variant using a novel mouse model.

PI_NAMEs: CAMPBELL, KENNETH J (contact);GEBELEIN, BRIAN

PROGRAM_OFFICER_NAME: RIDDLE, ROBERT D

PROJECT_TERMS: Alleles;Amino Acids;Anatomic Models;Anatomy;Anterior;Attention deficit hyperactivity disorder;Basal Ganglia;Behavioral;behavioral phenotyping;Binding;Binding Sites;Biochemical;Biochemistry;Bioinformatics;Biological Assay;Brain;Cell Culture Techniques;Cell Nucleus;cell type;Child;Childhood Neurological Disorder;Cleavage Under Targets and Release Using Nuclease;Cognition;Corpus striatum structure;Coupled;Data;Data Analyses;Data Set;Development;dimer;Disease;DNA;DNA Binding;DNA-Binding Proteins;Dorsal;Dystonia;Electrophoretic Mobility Shift Assay;Elements;Embryo;Enhancers;Exhibits;Functional disorder;functional genomics;Gene Activation;Gene Expression;Gene Expression Profiling;Gene Expression Regulation;gene repression;Genes;Genetic;Genetic Enhancer Element;Genetic Transcription;genetic variant;Genomic approach;Genomics;Gilles de la Tourette syndrome;Goals;Grant;Histologic;homeodomain;Human;human embryonic stem cell;Image;In Vitro;in vivo;insight;Intellectual functioning disability;Intellectual impairment;Interneurons;Lateral;Magnetic Resonance Imaging;Maps;Mediating;Modeling;Molecular;monomer;Morphology;mouse genetics;mouse model;Movement;Mus;mutant;nerve stem cell;neural circuit;neural patterning;neurogenesis;Neurologic Symptoms;Neuronal Differentiation;Neurons;Nonsense Codon;novel;Obsessive-Compulsive Disorder;olfactory bulb;Outcome;Pathologic;Patients;Pattern;Phenotype;Play;postnatal;Process;progenitor;Prosencephalon;Protein Deficiency;Publishing;Regulation;Regulatory Element;Reporter;Repression;Research;Resolution;Role;Site;Specific qualifier value;Specificity;Symptoms;System;Telencephalon;Testing;transcription factor;Transcriptional Regulation;transcriptome sequencing;Variant;Work

PROJECT_TITLE: Roles of Gsx factors in basal ganglia development

STUDY_SECTION: NCF

STUDY_SECTION_NAME: Neurogenesis and Cell Fate Study Section[NCF]


NIH_SPENDING_CATS: Genetics;Neurodegenerative;Neurosciences;Rare Diseases;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_DEPT: ANATOMY/CELL BIOLOGY

PHR: PROJECT NARRATIVE The etiology of SPAST-based hereditary spastic paraplegia (termed HSP-SPG4) remains unknown and controversial. No effective therapy is available for HSP-SPG4 patients. This proposal, supported by strong preliminary data, is aimed at elucidating the contributions of two disease mechanisms, the knowledge of which may lead to effective treatments.

PI_NAMEs: QIANG, LIANG  (contact)

PROGRAM_OFFICER_NAME: RANGANATHAN, SRIKANTH

PROJECT_TERMS: Accounting;Acetylation;Adult;Age;Alleles;Anatomy;Animals;Axon;axonal degeneration;behavior test;Behavioral;Biological;Cell Line;Corticospinal Tracts;Cultured Cells;cytotoxicity;Data;Deacetylase;Defect;design;Development;Disease;Dose;effective therapy;Enzymes;Etiology;Experimental Models;fly;gain of function;Gait;gait examination;Gene Mutation;Genes;Glutamates;HDAC6 gene;Hereditary Spastic Paraplegia;Heritability;Human;human induced pluripotent stem cells;induced pluripotent stem cell;Induced pluripotent stem cell derived human neuron;insight;Knock-out;Knockout Mice;Knowledge;Laboratories;live cell imaging;loss of function;Lower Extremity;Microtubules;Minor;Molecular;Morphology;motor deficit;mouse model;Mus;mutant;Mutate;Mutation;Neurodegenerative Disorders;Neurofibrillary Tangles;Neurons;novel;Parents;Pathogenicity;Patients;Pharmaceutical Preparations;Phenotype;Phosphorylation;Predisposition;Property;Prosencephalon;Protein Isoforms;Proteins;Reporting;Resolution;response;Role;spasticity;spastin;Squid;Stress;Swelling;Symptoms;Synapses;Testing;Toxic effect;Transgenic Mice;Tubulin

PROJECT_TITLE: Elucidating the etiology of SPAST-based Hereditary Spastic Paraplegia

STUDY_SECTION: SYN

STUDY_SECTION_NAME: Synapses, Cytoskeleton and Trafficking Study Section[SYN]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Mental Health;Neurosciences;Women's Health Research

ORG_NAME: GEORGIA STATE UNIVERSITY

PHR: PROJECT NARRATIVE The goal of this proposal is to significantly expand our knowledge of the neurochemical mechanisms that determine the reward value of social interactions as well as to elucidate important sex differences in these mechanisms. An improved understanding of how social interactions are assigned a valence by males and females has potential to suggest novel, sex- specific strategies for treating neuropsychiatric disorders for which alterations in social behavior are a key symptom.

PI_NAMEs: ALBERS, H. ELLIOTT (contact);HUHMAN, KIM L

PROGRAM_OFFICER_NAME: BREEDEN, ANDREW LEE

PROJECT_TERMS: Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;Data;Development;Disease;Dopamine;dopamine system;Dose;drug of abuse;Female;Gender;Goals;Hamsters;Hypothalamic structure;improved;Incidence;Knowledge;Lateral;Maintenance;male;Measures;Medial;Mediating;Mesocricetus auratus;mesolimbic system;neural circuit;neurochemistry;Neurodevelopmental Disorder;neuromechanism;Neurons;neuropsychiatric disorder;novel;Nucleus Accumbens;Oxytocin;Oxytocin Receptor;Periodicity;preference;Prefrontal Cortex;pressure;Prevalence;Property;Publishing;Receptor Activation;Regulation;response;reward circuitry;Rewards;Rodent;Role;Same-sex;Scanning;Series;sex;Sex Differences;Shapes;Site;small hairpin RNA;social;Social Behavior;Social Interaction;social relationships;Social Values;Stimulus;Symptoms;System;Testing;translational potential;Ventral Tegmental Area;women versus men

PROJECT_TITLE: Sex-dependent regulation of social reward by oxytocin in the mesolimbic reward circuitry

STUDY_SECTION: NNRS

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


NIH_SPENDING_CATS: Brain Disorders;Genetics;Neurodegenerative;Neurosciences;Parkinson's Disease;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: CHICAGO

ORG_DEPT: NEUROLOGY

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: Narrative: Certain groups of DA neurons degenerate in Parkinson’s disease. The proposed aims seek to explore the developmental origins of distinct groups of DA neurons, and correlate this with their intrinsic features and vulnerability.

PI_NAMEs: AWATRAMANI, RAJESHWAR B (contact)

PROGRAM_OFFICER_NAME: SULLIVAN, LUIS FLANAGAN

PROJECT_TERMS: Adult;Anatomy;Autopsy;Axon;Bioenergetics;Cells;Characteristics;Classification;cohort;Corpus striatum structure;Data;Dendrites;Development;Disease;disease model;Dopamine;dopaminergic neuron;Dorsal;Electron Transport Pathway;Embryo;Embryonic Development;Endowment;Event;Floor;Foundations;Gene Expression;Genes;genetic approach;Genetic Transcription;Goals;Human;insight;Label;Laboratories;Lateral;Link;Locomotion;Maps;Medial;Midbrain structure;Mitochondria;Modeling;Molecular;Morphology;motor symptom;Nerve Degeneration;Neural tube;Neuroanatomy;neurogenesis;neuron development;neuronal survival;Neurons;novel;oxidant stress;Oxidative Phosphorylation;Parkinson Disease;pars compacta;Physiological;Physiology;Population;Production;progenitor;Property;Recording of previous events;release of sequestered calcium ion into cytoplasm;Resistance;Sampling;Signal Transduction;single-cell RNA sequencing;SOX6 gene;Substantia nigra structure;Techniques;Testing;tool;Toxin;transcription factor;transcriptome;transcriptomics;Translating;Transplantation;Variant;Ventral Tegmental Area;Work

PROJECT_TITLE: Developmental underpinnings of substantia nigra vulnerability


NIH_SPENDING_CATS: Brain Disorders;Genetics;Mental Health;Mental Illness;Neurosciences

ORG_CITY: Aurora

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: Excitation induced entry of calcium ions into neurons through L-type voltage-gated calcium channels (LTCC) influences neuronal plasticity by regulating synapse structure and gene expression. Elucidating LTCC mechanisms regulating neuronal plasticity is relevant for understanding normal learning and memory as well as learning deficits in intellectual disabilities, neuropsychiatric disorders and neurodegenerative diseases. Changes in LTCC channel function and regulation of synapse structure and gene expression have been implicated in cognitive impairments associated with Alzheimer’s disease, Down syndrome, autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia. Linkage of LTCC’s to multiple neuropsychiatric and neurological diseases further supports a key role for these channels in regulating central forms of plasticity that control neuronal function throughout the brain. Previous studies demonstrated that highly localized signaling processes occur near the LTCC that are important for both channel modulation and downstream signaling to transcription factors in the nucleus. However, the molecular mechanisms that coordinate coupling of LTCCs to signaling molecules that regulate synapses in neuronal dendrites and also transcription factors that ultimately act in the nucleus are not well understood. Thus, given LTCC links to multiple nervous system diseases, it is becoming increasingly important to understand these fundamental mechanisms by which LTCCs control synapse structure and neuronal gene expression. Accordingly, here we will characterize fundamental mechanisms by which LTCCs regulate postsynaptic dendritic spine structure and also relay information from synapses to control gene expression in the nucleus, including in pathways relevant to synapse loss Alzheimer’s, autism, and schizophrenia.

PI_NAMEs: DELL'ACQUA, MARK L (contact)

PROGRAM_OFFICER_NAME: DRISCOLL, JAMIE DANIELLE

PROJECT_TERMS: A kinase anchoring protein;Alzheimer's Disease;Attention deficit hyperactivity disorder;autism spectrum disorder;Binding Proteins;Biochemical;Bipolar Disorder;Brain;Calcineurin;calcineurin phosphatase;Calcium Channel;Calcium ion;Cell Nucleus;Complex;Coupling;Cyclic AMP;Cyclic AMP-Dependent Protein Kinases;Dendrites;Dendritic Spines;Distal;Down's Syndrome;Endoplasmic Reticulum;Equilibrium;Excitatory Synapse;Face;Feedback;Gene Expression;Genes;Genetic Transcription;Glutamate Receptor;Glutamates;Hippocampus;Human;Impaired cognition;Intellectual functioning disability;Knowledge;Lead;Learning;Link;Long-Term Potentiation;Maintenance;Major Depressive Disorder;Mediating;Memory;Mental Depression;Molecular;myocyte-specific enhancer-binding factor 2;N-Methyl-D-Aspartate Receptors;N-Methylaspartate;Nervous System Disorder;Neurodegenerative Disorders;neuronal cell body;Neuronal Plasticity;Neurons;neuropsychiatric disorder;novel;nuclear factors of activated T-cells;Pathway interactions;Pattern;Phosphoric Monoester Hydrolases;Phosphotransferases;Play;postsynaptic;Potassium;Process;Protein Dephosphorylation;Protein Kinase;Proteins;receptor;Receptor Activation;Regulation;Research;response;Response Elements;Rodent;Role;Scaffolding Protein;Schizophrenia;sensor;Signal Pathway;Signal Transduction;Signaling Molecule;STIM1 gene;Structure;Synapses;synaptic function;Synaptic plasticity;transcription factor;Transcription Factor AP-1;Transcriptional Regulation;Vertebral column;voltage;Work

PROJECT_TITLE: L-type Ca2+ Channel Spike Regulation of Spine Structural Plasticity and Excitation-Transcription Coupling

STUDY_SECTION: NTRC

STUDY_SECTION_NAME: Neurotransporters, Receptors, and Calcium Signaling Study Section[NTRC]


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

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: Project Narrative Over 5 million older adults annually receive post-acute care services from skilled nursing facilities and home health agencies to facilitate the transition from the hospital back to the community. Stakeholders have raised concerns that upcoming Medicare payment reforms for skilled nursing facilities and home health agencies may have negative effects for some patient populations. The proposed study will provide critical information for policymakers, healthcare providers, and payers on the impact of these payment reforms on access to and quality of care overall and across vulnerable patient populations and diagnostic subgroups.

PI_NAMEs: LELAND, NATALIE ELIZABETH (contact);MROZ, TRACY MITCHELL

PROGRAM_OFFICER_NAME: KIM, THERESA YOUNGJOO

PROJECT_TERMS: access disparities;Acute;acute care;Address;Administrator;Alzheimer's Disease;Alzheimer's disease diagnosis;Back;Behavior;care delivery;care outcomes;care providers;care systems;Caring;Categories;Characteristics;Clinical;Communities;Complex;Data;Dementia;Diagnostic;dual eligible;ethnic minority;Experimental Designs;financial incentive;Focus Groups;Frontline worker;functional status;Funding;geographic difference;Goals;Growth;Health;Health Personnel;Health Services Accessibility;Hip Fractures;Home;Home Health Agency;hospital readmission;Hospitalization;Hospitals;Incentives;Individual;Interview;Link;Location;Measures;Medical;medically necessary care;Medicare;Medicare claim;Methodology;Methods;Modeling;multiple data sources;Natural experiment;Occupational Therapy;older adult;Outcome;Patient Agents;Patient Discharge;patient expectation;patient population;Patient Selection;patient subsets;Patients;Pattern;payment;Physical therapy;Policies;Policy Maker;Process;Provider;Published Comment;Quality Control;Quality of Care;racial minority;rapid growth;Recovery of Function;Rehabilitation therapy;rehabilitative care;response;Rural;rural patients;rural residence;service delivery;Services;Skilled Nursing Facilities;Speech Therapy;stakeholder perspectives;Subgroup;System;Time;United States Centers for Medicare and Medicaid Services;Vulnerable Populations

PROJECT_TITLE: The impact of post acute care payment changes on access and outcomes

STUDY_SECTION: HSOD

STUDY_SECTION_NAME: Health Services Organization and Delivery Study Section[HSOD]