NIH_SPENDING_CATS: Autoimmune Disease;Biomedical Imaging;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Disability Research;Multiple Sclerosis;Neurodegenerative;Neurosciences

ORG_CITY: BALTIMORE

ORG_DEPT: NEUROLOGY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: Project Narrative In this project we plan to show that a simple new blood test, which measures small amounts of proteins coming from nerves in the brain, can be used to help predict the severity of disease in people with multiple sclerosis. This also may be able to help determine whether MS drugs are working to protect the brain tissues.

PI_NAMEs: CALABRESI, PETER A (contact)

PROGRAM_OFFICER_NAME: TAYLOR-BURDS, CAROL C

PROJECT_TERMS: Age;aggressive therapy;Atrophic;biobank;Biological Assay;Biological Markers;Blood;Blood Tests;blood-based biomarker;Brain;brain tissue;brain volume;Central Nervous System Diseases;cerebral atrophy;Cerebrospinal Fluid;Characteristics;Clinical;clinical practice;cohort;comorbidity;Cytoskeletal Proteins;Data;Decision Making;demographics;Demyelinating Diseases;design;Diabetes Mellitus;disability;disability risk;Disability scale;Disability status;Disease;disorder subtype;Electronics;Enhancing Lesion;Enrollment;Europe;follow-up;gray matter;Health;Healthcare;Hyperlipidemia;Hypertension;illness length;Image;Immune;Immunoassay;Immunotherapy;Inflammatory;Injury;Institution;interest;Intervention;kidney dysfunction;Lesion;Light;Magnetic Resonance Imaging;Measures;Mediating;Medical;Monitor;Multicenter Studies;Multiple Sclerosis;multiple sclerosis patient;multiple sclerosis treatment;Nerve;Nervous System Disorder;neurofilament;Neurological disability;Neurons;novel;Obesity;Outcome;Pathologic;Patient Care;Patients;Pharmaceutical Preparations;prognostic;prospective;Proteins;Qualifying;Race;Radiology Specialty;Randomized, Controlled Trials;recruit;Relapse;Research;research clinical testing;Sampling;Serum;Severity of illness;sex;Site;Smoking;Standardization;Technology;tool;Treatment Efficacy;treatment response;United States;Validation;Visit

PROJECT_TITLE: Validation of Serum Neurofilament Light Chain as a Prognostic and Monitoring Biomarker in Multiple Sclerosis

STUDY_SECTION: NSD

STUDY_SECTION_NAME: Neurological Sciences and Disorders B Study Section[NSD-B]


ADMINISTERING_IC: DK

ARRA_FUNDED: N

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Antimicrobial Resistance;Autoimmune Disease;Biodefense and Related Countermeasures;Clinical Research;Clinical Trials and Supportive Activities;Digestive Diseases;Emerging Infectious Diseases;Infectious Diseases;Inflammatory Bowel Disease;Microbiome;Prevention

ORG_CITY: BOSTON

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

ORG_STATE: MA

PHR: NARRATIVE Over the last decade the incidence of Clostridium difficile infection (CDI) and recurrent CDI have increased, thought in part to be due to a loss of key commensal species that provide key bile transforming activities. Patients with inflammatory bowel disease (IBD) are at particularly high risk for recurrent CDI, though the mechanism remains unclear given that CDI studies notably lack IBD patients, a challenging population due to baseline diarrhea. Given the deleterious effect of CDI on patients with IBD, there is an urgent need to understand mechanisms of recurrent CDI in patients with IBD to better risk stratify them utilizing mechanistic data to promptly identify high risk patients and offer appropriate treatments earlier, thus preventing severe complications, improving symptom burden and quality of life.

PI_NAMEs: ALLEGRETTI, JESSICA R. (contact)

PROGRAM_OFFICER_NAME: OSGANIAN, VOULA

PROJECT_TERMS: Bile Acids;Bile fluid;bile salts;Cholates;Clinical;Clinical Data;Clostridium difficile;Colectomy;commensal microbes;Communicable Diseases;Data;deoxycholate;Development;Diagnostic;Diarrhea;Disease;Early identification;Early treatment;Ecosystem;enzyme activity;Epidemiology;Equilibrium;Evaluation;Excision;Exclusion;experience;fecal transplantation;Feces;Flare;Foundations;Gastroenterology;Germination;Goals;gut bacteria;gut inflammation;high risk;Hydrolase;improved;Incidence;Infection;Inflammatory Bowel Diseases;insight;lifetime risk;Liquid Chromatography;Malabsorption Syndromes;Measures;Mentorship;Metabolic;metabolomics;microbial;Microbiology;microbiome research;Monitoring for Recurrence;Morbidity - disease rate;Nature;Organism;Pathogenesis;patient population;Patients;personalized risk prediction;Pilot Projects;Population;Population Control;predictive marker;prevent;prospective;Quality of life;reconstitution;Recurrence;Recurrent disease;recurrent infection;Refractory;Research;resident commensals;Risk;Risk Factors;risk prediction;risk stratification;safety and feasibility;safety assessment;Sampling;Secondary to;Severities;Signal Transduction;Symptom Burden;symptomatic improvement;Symptoms;System;tandem mass spectrometry;targeted treatment;Training;translational scientist;transplantation therapy;Work

PROJECT_TITLE: Understanding Clostridium difficile Infection in Patients with inflammatory Bowel Disease

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Digestive Diseases and Nutrition C Study Section[DDK-C]


ADMINISTERING_IC: NS

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Brain Disorders;Cerebrovascular;Clinical Research;Congenital Structural Anomalies;Neurosciences;Pediatric;Stroke

ORG_CITY: SAN FRANCISCO

ORG_DEPT: ANESTHESIOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: Project Narrative Rupture of vessels in the lesion of brain arteriovenous malformations (AVMs) can cause life threatening intra- brain hemorrhage and long-term disability. Currently, there is no safe and effective medical therapy available to prevent it. This project will test a new therapeutic strategy to prevent the rupture of vessels in brain AVMs.

PI_NAMEs: SU, HUA  (contact)

PROGRAM_OFFICER_NAME: UTZ, URSULA

PROJECT_TERMS: adeno-associated viral vector;adeno-associated virus 9 delivery;adenovirus mediated delivery;Adhesions;Adverse effects;Affinity;angiogenesis;Angiogenic Factor;Antibodies;Arteriovenous malformation;Attenuated;autocrine;Binding;Blood;Blood - brain barrier anatomy;blood-brain barrier disruption;blood-brain barrier permeabilization;Brain;brain arteriovenous malformations;Brain hemorrhage;brain pericytes;cell type;Cells;Cerebral endothelium;Chronic;cost;cytokine;Cytomegalovirus;Data;Development;Dose;efficacy evaluation;Endothelial Cells;Engineering;experimental study;Exploratory/Developmental Grant for Diagnostic Cancer Imaging;extracellular;Extracellular Domain;Extravasation;feasibility testing;FLT1 gene;Functional disorder;Gene Proteins;gene therapy;Genes;Genetic;Goals;Growth;Growth Factor Inhibition;Hemorrhage;Human;improved;Infiltration;Inflammation;Inflammatory;Interruption;Intestines;Intracranial Hemorrhages;Intravenous;intravenous injection;Ischemic Stroke;KDR gene;Kidney Glomerulus;Laboratories;Lesion;Life;liver inflammation;Long term disability;Macrophage;Medical;Membrane;Methods;Microglia;Minor;mouse model;Mus;Natural History;Neurons;novel therapeutic intervention;Organ;overexpression;Pathogenesis;Pathogenicity;Pathologic Neovascularization;Patients;Pericytes;Phenotype;Play;podocyte;prevent;Process;promoter;Protein Secretion;Protein Tyrosine Kinase;Rattus;Reagent;receptor binding;Role;Rupture;Severities;side effect;Signal Transduction;single-cell RNA sequencing;Skin;Structure;Symptoms;Synapsins;System;Testing;Therapeutic Effect;Tight Junctions;Tissues;Toxic effect;Treatment-related toxicity;Tube;Tyrosine Kinase Inhibitor;Vascular Endothelial Growth Factor Receptor-1;Vascular Endothelial Growth Factors;vector

PROJECT_TITLE: Reduction of Brain AVM Severity through Inhibition of Pathogenic Angiogenesis

STUDY_SECTION: BINP

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


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Breast Cancer;Cancer;Genetics;Orphan Drug;Ovarian Cancer;Rare Diseases;Women's Health Research

ORG_CITY: HOUSTON

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

ORG_STATE: TX

PHR: PROJECT NARRATIVE Cancer arises by escaping multiple checkpoint controls. Our preliminary studies reveal that mutant p53 interacts with TopBP1 physically and functionally to perturb the checkpoint control, and induces ACTL6A to promote cisplatin resistance. This proposal will investigate these new mechanisms and develop novel cancer therapy to target checkpoint dysfunction in cancer.

PI_NAMEs: LIN, FANG-TSYR ;LIN, WEEI-CHIN  (contact)

PROGRAM_OFFICER_NAME: LIU, ZHIHUI

PROJECT_TERMS: ACTL6A gene;Antibodies;anticancer activity;Award;Binding;Biochemical;Biological Assay;Breast;cancer cell;Cancer cell line;cancer therapy;CDK4 gene;Cell Cycle;Cell Line;Cells;Cisplatin;cisplatin-DNA adduct;Clustered Regularly Interspaced Short Palindromic Repeats;combination cancer therapy;Combined Modality Therapy;Data;Dependence;DNA biosynthesis;DNA Damage;DNA fiber assay;DNA Repair;DNA replication fork;Dropout;Drug resistance;ERCC1 gene;Exhibits;Functional disorder;G1/S Checkpoint Pathway;G1/S Transition;G2 Phase;gain of function;Gene Silencing;Genome Stability;Goals;Growth;Immunofluorescence Immunologic;In Situ;in vivo;inhibitor;Laboratories;Lead;Legal patent;Ligation;Malignant Breast Neoplasm;Malignant neoplasm of ovary;Malignant Neoplasms;Mediating;Methods;Molecular;mutant;new therapeutic target;Normal Cell;novel;novel therapeutics;Nucleotide Excision Repair;Ovarian;overexpression;Pathologic;patient derived xenograft model;Phase;Platinum;Predisposition;prevent;Proteins;Qualifying;recruit;Regulation;repaired;Replication Initiation;replication stress;Resistance;response;Role;Single-Stranded DNA;Site;targeted treatment;Testing;Therapeutic;therapeutic target;tool;TP53 gene;Translating;TREX1 gene;triple-negative invasive breast carcinoma;tumor progression;Tumor Promotion;Visualization;Xenograft procedure

PROJECT_TITLE: Novel therapeutics for targeting checkpoint dysfunction in cancer

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics - 1 Study Section[MCT1]


NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Cancer;Childhood Leukemia;Down Syndrome;Genetics;Hematology;Intellectual and Developmental Disabilities (IDD);Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: MEMPHIS

ORG_NAME: ST. JUDE CHILDREN'S RESEARCH HOSPITAL

ORG_STATE: TN

PHR: Project Narrative The only curative therapies for either MDS or AML is allogeneic stem cell transplantation, however few patients are eligible, which underpins the need to resolve the cellular and molecular basis of genetically-defined subtypes of MDS and AML with the goal of developing novel therapies. We identified that TIFAB, a commonly deleted gene in del(5q) MDS/AML and modifier of innate immune signaling, affects the function of hematopoietic stem and progenitor cells in response to selective pressures and stressors converging on p53, by regulating the deubiquitinase function of USP15. The overarching significance of this proposal is two-fold: (1) we will uncover the mechanism of transformation from MDS to AML and provide the basis for development of therapies to prevent disease progression; and (2) we will characterize USP15 as a novel regulator and potential therapeutic target in the pathogenesis of AML.

PI_NAMEs: NIEDERKORN, MADELINE  (contact)

PROGRAM_OFFICER_NAME: DAMICO, MARK W

PROJECT_TERMS: Acute Myelocytic Leukemia;acute myeloid leukemia cell;Affect;Allogenic;AML/MDS;Binding Proteins;Biochemical;Biological Assay;Biology;Cancer Biology;Case Study;Catalytic Domain;Cell Line;Cell Physiology;Cells;Chemicals;chromosome 5q loss;Chromosome abnormality;Chromosomes;Clone Cells;Complex;curative treatments;cytopenia;Data;derepression;Development;Disease;Disease Progression;DNA Damage;Down's Syndrome;drug development;drug discovery;Drug Targeting;Drug Utilization;druggable target;Dysmyelopoietic Syndromes;Dysplasia;Eligibility Determination;Event;Exhibits;Familiarity;Family member;FHA Domain;Foundations;Gene Deletion;Genes;Genetic study;Genotoxic Stress;genotoxicity;Goals;Hematopoiesis;Hematopoietic Neoplasms;Hematopoietic stem cells;high risk;Human;Immune;Immune signaling;Impairment;In Vitro;in vivo;Individual;ineffective therapies;innate immune pathways;Investigation;lead candidate;Learning;leukemia;Leukemic Hematopoietic Stem Cell;leukemic stem cell;leukemic transformation;Malignant - descriptor;Malignant Neoplasms;MDM2 gene;member;MLL-AF9;Modeling;Molecular;mouse genetics;mouse model;Mus;Myelogenous;novel;novel drug class;novel therapeutics;Oncogenes;Oncogenic;Pathogenesis;patient prognosis;Patients;Peptide Hydrolases;Phase;Phenotype;Positioning Attribute;Postdoctoral Fellow;Preleukemia;pressure;prevent;Prognosis;programs;Proteomics;Regulation;Reporting;Research;Research Personnel;response;RUNX3 gene;screening;Signal Transduction;small molecule inhibitor;stem cell expansion;stem cell function;stem cell survival;Stem cell transplant;Stress;stressor;Structure;Testing;Therapeutic;therapeutic target;therapy development;Toll-like receptors;TP53 gene;TRAF-Interacting Protein;TRAF6 gene;Training;transcriptome sequencing;UBB gene;Ubiquitin;ubiquitin isopeptidase;Work;Xenograft procedure

PROJECT_TITLE: Elucidating USP16 function and probing its DUB activity in Down syndrome leukemia


ED_INST_TYPE: HOSPITALS

NIH_SPENDING_CATS: Cancer;Cancer Genomics;Digestive Diseases;Genetics;Human Genome;Immunotherapy;Orphan Drug;Pancreatic Cancer;Rare Diseases

ORG_NAME: UNIVERSITY OF TX MD ANDERSON CAN CTR

PHR: PROJECT NARRATIVE  Novel treatments are urgently needed for pancreatic ductal adenocarcinoma (PDAC) because patients with advanced PDAC have a grave prognosis. The current project offers innovative solutions that overcome resistance to immunotherapy. This strategy, when successfully introduced into the clinic, will fulfill the unmet clinical need for improving the survival and quality of life of PDAC patients.

PI_NAMEs: LI, CHUN  (contact);WANG, Y. ALAN

PROGRAM_OFFICER_NAME: SINGH, ANJU

PROJECT_TERMS: advanced disease;Anabolism;analog;Anti-diabetic Drugs;anti-PD-1;Antibodies;Antigens;Attenuated;attenuation;Bioenergetics;C57BL/6 Mouse;cancer immunotherapy;CD8-Positive T-Lymphocytes;cell injury;Cell Maturation;Cell membrane;Cells;chemoradiation;Clinic;Clinical;Clinical Trials;clinically relevant;Coagulative necrosis;Compensation;Cross Presentation;CTLA4 gene;cytokine;Cytometry;Cytotoxic T-Lymphocytes;Data;Dendritic Cells;Development;Disease;effective therapy;Electroporation;Flow Cytometry;Glutamates;Glutaminase;Glutamine;Glycolysis;Human;IL8RB gene;Immune;immune cell infiltrate;immune checkpoint blockade;Immunocompetent;immunogenic cell death;Immunologics;Immunosuppression;Immunotherapy;improved;Infiltration;Inflammatory Infiltrate;Inflammatory Response;inhibitor;innovation;Ionizing radiation;ITGAM gene;Knowledge;KRASG12D;Lymphocyte Activation;Lymphocytic Infiltrate;Malignant Neoplasms;Metabolic;Metabolism;Metastatic Neoplasm to the Liver;Metformin;Mitochondria;Modeling;mouse model;Mus;Mutation;Myeloid-derived suppressor cells;neoplastic cell;novel;novel therapeutics;Operative Surgical Procedures;Oxidative Phosphorylation;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma cell;pancreatic ductal adenocarcinoma model;Pathway Analysis;Pathway interactions;Patients;Penetration;pharmacologic;Phase;Phenformin;Physiologic pulse;Production;Prognosis;programmed cell death protein 1;programs;Protein Array Analysis;PTPRC gene;Quality of life;recruit;Recurrent tumor;Resistance;Respiration;response;Role;Signal Transduction;single-cell RNA sequencing;small hairpin RNA;success;Survival Rate;T-Lymphocyte;Techniques;Testing;theranostics;Time;transcriptome sequencing;tumor;tumor ablation;Tumor Antigens;tumor eradication;Tumor Immunity;tumor microenvironment;tumor-immune system interactions;Up-Regulation;voltage

PROJECT_TITLE: Development of irreversible electroporation-based rational combinations to potentiate the activity of cancer immunotherapy against pancreatic ductal adenocarcinoma

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-OTC-M(08)F]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Clinical Research;Hematology;Infectious Diseases;Lung;Precision Medicine;Rare Diseases;Sepsis

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: Project Narrative Acute respiratory distress syndrome (ARDS) is a common cause of mortality during critical illness. There are no pharmacological therapies for ARDS that address the underlying mechanism of the disease. The purpose of this research is to investigate the role of the receptor for advanced glycation endproducts (RAGE) axis in conferring risk for ARDS and to operationalize the RAGE axis to enrich clinical trials of RAGE-based therapies.

PI_NAMEs: JONES, TIFFANIE KAE (contact)

PROGRAM_OFFICER_NAME: KALANTARI, ROYA

PROJECT_TERMS: Acute Lung Injury;Acute Respiratory Distress Syndrome;Address;Admission activity;Alveolar;alveolar epithelium;Animal Model;Biological Markers;career;Clinical;Clinical Data;Clinical Trials;cohort;Critical Illness;Development;Disease;drug development;Edema;Endothelial Cells;Enrollment;Environment;Epithelial Cells;Functional disorder;Future;Gelatinase B;Genetic;Goals;Heterogeneity;high risk;high risk population;HMGB1 gene;Human;Hypoxemia;Immune response;Impairment;improved;In Vitro;Inflammatory;Inflammatory Response;Injury;Injury to Kidney;innovation;Intensive Care Units;Intervention;Knowledge;Ligands;Liquid substance;Logistic Regressions;Lung;lung injury;Matrix Metalloproteinases;Mechanical ventilation;Mediation;Membrane;Mendelian randomization;Mentorship;Methods;Molecular;molecular phenotype;Molecular Profiling;mortality;novel;novel strategies;Pathway interactions;Patients;Pattern;Pattern recognition receptor;pharmacologic;Plasma;Population;precision medicine;Precision Medicine Initiative;predictive modeling;Prevention;prospective;receptor binding;receptor for advanced glycation endproducts;Research;Risk;Risk Estimate;Risk Marker;risk prediction;Role;S100A12 gene;Sepsis;sepsis induced ARDS;septic;septic patients;Shapes;Signal Transduction;Stromelysin 1;Structure;Subgroup;Syndrome;Techniques;Testing;Therapeutic;Time;Training;translation to humans;translational scientist;treatment response;United States National Institutes of Health;Validation

PROJECT_TITLE: Operationalizing the RAGE Axis in Acute Respiratory Distress Syndrome


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cardiovascular;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: SEATTLE

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: Modified Public Health Relevance Section Genetically-encoded, fluorescent sensors for reactive oxygen species (ROS) provide tremendous potential for studying oxidative stress in real-time, but their low fidelity does currently not allow for prolonged large scale studies in relevant disease models. We aim to significantly accelerate the engineering of ROS sensor proteins by combining structure-guided design with a novel high-throughput platform enabling the functional testing of large variant libraries at high-speed. The fast engineering of fully applicable ROS sensors will allow biomedical researchers to precisely detect the timing and location of oxidative stress caused by environmental stress and genetic disposition, and hence, could guide future research on disease mechanisms, facilitate drug screening, and help to identify novel therapeutic approaches.

PI_NAMEs: BERNDT, ANDRE  (contact)

PROGRAM_OFFICER_NAME: ANSONG, CHARLES KWAKU

PROJECT_TERMS: Acceleration;Acute;Affect;Alzheimer's Disease;Amyloid beta-Protein;biophysical properties;Biophysics;Cardiac Myocytes;Cardiomyopathies;Cardiovascular Diseases;Cell Physiology;cell type;Cells;Cellular Metabolic Process;cellular targeting;Chronic;Color;Coupling;design;Detection;detection sensitivity;Directed Molecular Evolution;Disease;disease model;disease phenotype;Disease Progression;DNA Damage;Drug Screening;Dyes;Engineering;Environment;Failure;Feedback;Fluorescent Probes;Functional disorder;Future;Gene Expression;Genetic;Genetic Engineering;Goals;Green Fluorescent Proteins;high throughput screening;human induced pluripotent stem cells;Hydrogen Peroxide;Hypoxia;Impairment;improved;in vivo;Individual;Induced pluripotent stem cell derived neurons;innovation;Intervention;Ischemia;Kinetics;Libraries;Link;Lipids;Location;Measurement;Measures;Methods;Microscopy;Mitochondria;Modeling;Monitor;Mutation;Nerve Degeneration;neural;Neurons;novel;novel therapeutic intervention;Organ;Oxidative Stress;Oxygen;Pathologic;patient derived induced pluripotent stem cells;Performance;pharmacologic;Phenotype;Physiologic Monitoring;Physiological;Physiological Processes;polydimethylsiloxane;Preparation;Process;Protein Engineering;protein expression;Proteins;public health relevance;Randomized;Reactive Oxygen Species;receptor;red fluorescent protein;Reperfusion Injury;Reperfusion Therapy;Repression;Research Personnel;Resolution;response;restraint;Rhodamine;Role;screening;sensor;Signal Transduction;Site;Specificity;Speed;stem cell model;stem cells;Stress;stressor;Structure;subcellular targeting;Technology;Tertiary Protein Structure;Testing;Time;tool;Variant

PROJECT_TITLE: Structure-guided and high-throughput engineering of genetically encoded sensors for reactive oxygen species

STUDY_SECTION: CMT

STUDY_SECTION_NAME: Cellular and Molecular Technologies Study Section[CMT]


NIH_SPENDING_CATS: Autoimmune Disease;Brain Disorders;Eye Disease and Disorders of Vision;Multiple Sclerosis;Neurodegenerative;Neurosciences

ORG_CITY: WORCESTER

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

PHR: Schafer, Dorothy P. Project Narrative While multiple sclerosis (MS) is an inflammatory demyelinating disease, it is now becoming increasingly appreciated that there is extensive neurodegeneration, which is currently an unmet clinical need. One common feature of neurodegeneration in MS, as well as many other neurodegenerative diseases (Alzheimer’s disease, frontotemporal dementia, etc.), is early loss of synaptic connections. We will now shed new mechanistic light on how synapses are lost in the MS brain and, in the process, identify new strategies for neuroprotection in MS and other neurodegenerative disorders.

PI_NAMEs: SCHAFER, DOROTHY PATRICIA (contact)

PROJECT_TERMS: Ablation;Address;Alzheimer's Disease;Animal Model;Astrocytes;Automobile Driving;Autopsy;axonal degeneration;Axotomy;Binding;Blood;Bone Marrow;Brain;Cell Death;Cells;central nervous system demyelinating disorder;Chimerism;Clinical;Complement;Complement 1q;complement deficiency;Complement Receptor;Data;Demyelinating Diseases;Demyelinations;Dendritic Spines;Development;Disease;Encephalitis;Event;Experimental Autoimmune Encephalomyelitis;experimental study;FDA approved;Fibrinogen;Frontotemporal Dementia;Functional disorder;Genetic;genetic variant;Gliosis;Goals;high resolution imaging;Immune;immune cell infiltrate;Impaired cognition;Infiltration;Inflammation;Inflammatory;Label;Light;Macrophage-1 Antigen;Mediating;Microglia;Modeling;Molecular;Molecular Genetics;mouse model;Multiple Sclerosis;Mus;mutant;Myelin;Nerve Degeneration;Neurodegenerative Disorders;neuroinflammation;Neurons;neuroprotection;nonhuman primate;novel;Optic Nerve;Optic Neuritis;Pathway interactions;Patients;Peripheral;Phagocytes;preservation;prevent;Process;Production;Proteins;receptor;Regulation;Relapsing-Remitting Multiple Sclerosis;Retinal Ganglion Cells;retinogeniculate;Risk Factors;Role;Signal Transduction;Source;Structure;Synapses;synaptic pruning;System;Testing;Therapeutic;Tissues;Visual;visual dysfunction;Visual System;Work

PROJECT_TITLE: How Do Synaptic Connections Change in Demyelinating Disease?

STUDY_SECTION: CMBG

STUDY_SECTION_NAME: Cellular and Molecular Biology of Glia Study Section[CMBG]


NIH_SPENDING_CATS: Aging;Genetics;Human Genome;Prevention

ORG_CITY: NEW YORK

ORG_DEPT: PATHOLOGY

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

ORG_STATE: NY

PHR: NARRATIVE The maintenance of genomic integrity is critical to limit human genetic disease. However key aspects of genome maintenance are poorly understood. The proposed research will reveal novel mechanisms that prevent homologous recombination occurring in G1 phase cells and the mechanisms that prevent ongoing transcription interfering with DNA repair.

PI_NAMEs: TYLER, JESSICA K (contact)

PROGRAM_OFFICER_NAME: REDDY, MICHAEL K

PROJECT_TERMS: Address;Aging;base;Biochemistry;Biological Assay;Cells;Chromatin;Chromatin Structure;CRISPR/Cas technology;Data;DNA;DNA biosynthesis;DNA Double Strand Break;DNA lesion;DNA Repair;DNA Repair Pathway;Double Strand Break Repair;ds-DNA;Event;Excision;extend lifespan;G1 Phase;Gene Expression;Genetic Diseases;Genetic Screening;Genetic Transcription;Genome;genome integrity;Genome Stability;genome-wide;Genomics;Goals;Guide RNA;Histones;homologous recombination;Human body;Human Genetics;innovation;Libraries;Maintenance;Mammalian Cell;Mediating;Molecular Genetics;non-histone protein;Nonhomologous DNA End Joining;novel;Pathway interactions;Positioning Attribute;prevent;Process;programs;Proteins;repaired;Research;Role;Saccharomycetales;screening;Single-Stranded DNA;structural biology;tissue culture;Vision

PROJECT_TITLE: Novel pathways that regulate DNA double-strand break repair events in mammalian cells

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


NIH_SPENDING_CATS: Clinical Research;Complementary and Integrative Health;Dietary Supplements;Lung;Nutrition;Prevention;Pulmonary Fibrosis;Rare Diseases

ORG_CITY: CHARLOTTESVILLE

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: PROJECT NARRATIVE Idiopathic pulmonary fibrosis (IPF) is a chronic form of interstitial lung disease in adults with few therapies that leads to chronic respiratory failure with a high mortality rate. I propose to determine lower plasma phospholipid levels of omega-3 fatty acids and their metabolites as a modifiable risk factor in adults with IPF. By achieving the aims of my proposal, this may lead to clinical trials of therapies that raise omega-3 fatty acid levels for the treatment of IPF.

PI_NAMEs: KIM, JOHN S (contact)

PROGRAM_OFFICER_NAME: GOMEZ, CHRISTIAN RENE

PROJECT_TERMS: Address;Adult;alveolar epithelium;Anti-Inflammatory Agents;antifibrotic treatment;Attenuated;beta-Chemokines;biobank;Biological;Biological Markers;Biology;biomarker validation;Biometry;Bronchoalveolar Lavage Fluid;Carbon Monoxide;career development;CD59 Antigen;cell injury;Cessation of life;Chronic;Clinical;clinical diagnosis;clinical translation;Clinical Trials;cohort;Communities;Data;Death Rate;design;Development Plans;Diffusion;Disease Progression;Docosahexaenoic Acids;Eicosanoid Production;Epidemiology;exercise capacity;Extracellular Matrix;Fatty Acids;Fibrosis;fibrotic interstitial lung disease;fibrotic lung;Foundations;Future;Gene Expression Profile;Goals;Hospitalization;hospitalization rates;idiopathic pulmonary fibrosis;Individual;Inflammatory;Intake;Interstitial Lung Diseases;K-Series Research Career Programs;Lead;Ligands;Light;lipid mediator;Lung;lung injury;Lung Transplantation;Matrilysin;Measures;Mediating;Medical;Mentors;Mentorship;modifiable risk;mortality;mouse model;Multi-Institutional Clinical Trial;Mus;novel;novel marker;older adult;Omega-3 Fatty Acids;Omega-6 Fatty Acids;Oxidative Stress;Participant;participant enrollment;Pathogenesis;Pathway interactions;patient oriented research;Patients;personalized medicine;Phenotype;Phospholipids;Pilot Projects;Plasma;Polyunsaturated Fatty Acids;population based;Positioning Attribute;PPAR gamma;Pre-Clinical Model;Production;Prognosis;Property;Prospective cohort;Pulmonary Fibrosis;pulmonary function;Pulmonary Inflammation;Pulmonary Surfactant-Associated Protein D;Research;Research Personnel;respiratory;Respiratory Failure;Risk;Risk Factors;Role;Sample Size;Sampling;secondary outcome;Serum;Severity of illness;symptomatic improvement;Therapeutic;Therapy Clinical Trials;Time;Training;transcriptome sequencing;transcriptomics;Translational Research;translational scientist;Vital capacity;Walking

PROJECT_TITLE: Role of polyunsaturated fatty acids in pulmonary fibrosis


NIH_SPENDING_CATS: Cancer;Childhood Leukemia;Genetics;Hematology;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: PORTLAND

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: PROJECT NARRATIVE Mutations in CSF3R are associated with poor prognosis in Acute Myeloid Leukemia (AML), a lethal blood cancer. In AML, CSF3R mutations are accompanied by mutations in transcription factors that block CSF3R-driven differentiation to cause an aggressive malignancy. The goal of this proposal is to uncover how these partner mutations inhibit CSF3R-driven differentiation, with the long-term goal of harnessing this molecular understanding to enable new therapeutic development.

PI_NAMEs: MAXSON, JULIA E (contact)

PROGRAM_OFFICER_NAME: KLAUZINSKA, MALGORZATA

PROJECT_TERMS: Acute Myelocytic Leukemia;Adult Acute Myeloblastic Leukemia;Alleles;Binding;Binding Proteins;Biogenesis;Biological Assay;Biology;blocking factor;Blood;Bone Marrow;Cell Line;Childhood;Collaborations;Complex;Core-Binding Factor;Cytokine Receptors;Data;Development;Disease;Down-Regulation;Enhancers;Epigenetic Process;Equilibrium;Event;Evolution;Functional disorder;Future;Genes;Genetic;Genetic Transcription;Goals;Granulocyte Colony-Stimulating Factor Receptors;Hematologic Neoplasms;Hematopoietic;Hematopoietic Neoplasms;Impairment;inducible Cre;inhibitor;knock-down;leukemia;leukemogenesis;loss of function mutation;Malignant Neoplasms;Mediating;Modeling;Molecular;mouse model;mutant;Mutation;myeloblast;Myelogenous;Myeloid Cells;Myeloid Leukemia;neutrophil;NFIX gene;novel;novel therapeutic intervention;novel therapeutics;Oncogenes;Other Genetics;Outcome;Patients;pharmacologic;Phenotype;Physiological;prevent;Production;Prognosis;programs;Proliferating;Recurrent disease;Relapse;Repression;Role;RUNX1 gene;Signal Transduction;STAT protein;STAT3 gene;Stat5 protein;Subgroup;Survival Rate;synergism;Testing;Therapeutic;therapeutic development;transcription factor;Transcriptional Activation;Transgenic Model;Transgenic Organisms;transplant model;tumorigenesis;validation studies;Work

PROJECT_TITLE: Mechanisms of differentiation blockade in CSF3R-mutant AML

STUDY_SECTION: CAMP

STUDY_SECTION_NAME: Cancer Molecular Pathobiology Study Section[CAMP]


PHR: Diabetes is affecting almost 10% of the adult US population. Diabetes dramatically increases the risk of life- threatening complications such as kidney disease and cardiovascular disease. Here we propose a new way to treat both of these complications.

PI_NAMEs: KANTER, JENNY E. (contact)

PROGRAM_OFFICER_NAME: NIHALANI, DEEPAK

PROJECT_TERMS: Acceleration;Adult;Affect;Albuminuria;Antisense Oligonucleotides;Apolipoproteins;Atherosclerosis;Attenuated;Blood Glucose;Cardiovascular Diseases;cardiovascular disorder risk;Cause of Death;Cells;chemokine receptor;Chylomicrons;Complications of Diabetes Mellitus;Coronary Arteriosclerosis;Data;Dependovirus;Diabetes Mellitus;diabetic;Diabetic mouse;Diabetic Nephropathy;Dyslipidemias;Endothelial Cells;Epidemic;Exposure to;Future;Hepatic;High Density Lipoproteins;Human;Hypertriglyceridemia;Impaired Renal Function;Impairment;In Vitro;Infiltration;Inflammatory;inhibitor;Insulin;Insulin-Dependent Diabetes Mellitus;Kidney;Kidney Diseases;LDL Cholesterol Lipoproteins;Life;Link;Lipids;Lipoproteins;Liver;Macrophage;Mediating;Metabolism;Modeling;monocyte;mouse model;Mus;Myeloid Cells;Nephrectomy;new therapeutic target;non-diabetic;Non-Insulin-Dependent Diabetes Mellitus;Normal Range;novel;novel therapeutics;overexpression;Patients;Persons;Pharmacologic Substance;Phenotype;Plasma;Play;podocyte;Population;prevent;Process;recruit;Renal function;Residual state;Risk;Risk Factors;Role;Serum;Severity of illness;targeted treatment;Techniques;Testing;therapeutic target;transcription factor;Triglycerides;Very low density lipoprotein

PROJECT_TITLE: APOC3 mediated dyslipidemia in diabetic kidney disease and atherosclerosis

STUDY_SECTION: PBKD

STUDY_SECTION_NAME: Pathobiology of Kidney Disease Study Section[PBKD]


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Breast Cancer;Cancer;Immunotherapy;Rare Diseases;Women's Health Research

ORG_CITY: CHAPEL HILL

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: Despite the important role of the tumor stroma in cancer progression, the majority of anticancer therapies target cancer cells and not the tumor microenvironment. Here we propose to develop a targeted, protein-based therapeutic platform designed to convert tumor-promoting macrophages to suppress tumorigenesis. This new delivery platform could improve therapeutic outcomes in cancer patients, particularly where tumor-associated macrophages are linked with poor clinical outcomes.

PI_NAMEs: NGUYEN, JULIANE  (contact)

PROGRAM_OFFICER_NAME: HARRIS, RAYMOND D

PROJECT_TERMS: Acute;antagonist;anti-PD-1;anti-PD1 therapy;Antibodies;Antibody Specificity;Antineoplastic Agents;Binding;Breast Cancer Patient;cancer cell;Cancer Patient;cancer therapy;cancer type;CCL2 gene;Cd68;CD8-Positive T-Lymphocytes;Cell Count;Cells;chemokine;chemokine receptor;chemotherapy;Chronic;Clinical;clinical care;Clinical Trials;Communicable Diseases;cytotoxic;Data;delivery vehicle;design;Disease;Dose;Drug Delivery Systems;effector T cell;Epitopes;extracellular;FDA approved;FOXP3 gene;Immune System Diseases;Immunoglobulin Fragments;Immunosuppression;improved;in vivo;Infiltration;Inflammation;Inflammatory;Invaded;Legal patent;Leucine Zippers;Ligands;Link;Macrophage;Malignant Breast Neoplasm;Malignant neoplasm of ovary;Malignant neoplasm of pancreas;Malignant Neoplasms;Mediating;Metastasis Induction;migration;monocyte;monocyte chemoattractant protein 1 receptor;mouse model;Myelogenous;Myeloid-derived suppressor cells;Myocardial Infarction;N-terminal;neglect;Neoplasm Metastasis;neoplastic cell;novel therapeutic intervention;novel therapeutics;Outcome;pathogen;Pathogenesis;Pathway interactions;Patients;PD-1 blockade;Pharmaceutical Preparations;Phenotype;prevent;Proteins;Publishing;recruit;Regulatory T-Lymphocyte;response;Role;Schedule;Signal Transduction;small molecule;Specificity;Structure;System;targeted cancer therapy;Testing;Therapeutic;Therapeutic Effect;therapy outcome;Toxic effect;Treatment Efficacy;triple-negative invasive breast carcinoma;tumor;tumor growth;tumor microenvironment;tumor progression;Tumor Promotion;Tumor Suppressor Proteins;Tumor-associated macrophages;tumorigenesis;Work;wound healing

PROJECT_TITLE: Polarizing Macrophages to Tumor Suppressors by Blocking Multiple CCR2 Chemokine Receptor Epitopes

STUDY_SECTION: GDD

STUDY_SECTION_NAME: Gene and Drug Delivery Systems Study Section[GDD]


NIH_SPENDING_CATS: Cancer;Genetics;Orphan Drug;Ovarian Cancer;Rare Diseases;Women's Health Research

ORG_CITY: FARMINGTON

ORG_NAME: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT

ORG_STATE: CT

PHR: Project Narrative Ovarian cancer is a common and lethal malignancy that metastasizes early and is diagnosed late. Our preliminary observations suggest that a mitochondrial protein, sideroflexin 4, affects both the extent of DNA damage and the degree of DNA repair in ovarian cancer cells. Since both DNA damage and DNA repair affect the response of ovarian cancer to current anticancer chemotherapy, we will test the hypothesis that targeting sideroflexin 4 will enhance the effectiveness of platinum-based drugs and PARP inhibitors used in ovarian cancer therapy.

PI_NAMEs: TORTI, SUZY V (contact)

PROGRAM_OFFICER_NAME: O'HAYRE, MORGAN

PROJECT_TERMS: Address;Affect;anti-cancer;Biogenesis;BRCA1 gene;BRCA2 gene;cancer cell;Cancer Patient;cancer stem cell;cancer therapy;Carboplatin;Cell Culture Techniques;Cell Death;Cell Physiology;Cell-Free System;Cells;Chemotherapy-Oncologic Procedure;Cisplatin;cisplatin-DNA adduct;Cytosol;cytotoxicity;Data;Defect;Diagnosis;DNA Damage;DNA Repair;DNA Repair Gene;DNA Repair Inhibition;DNA Repair Pathway;drug development;drug efficacy;Drug resistance;drug resistance development;Drug usage;Effectiveness;Environment;Enzymes;Epithelial ovarian cancer;experience;experimental study;Exposure to;FDA approved;Germ Lines;Goals;Half-Life;Homeostasis;homologous recombination;improved;in vivo;Inner mitochondrial membrane;Iron;iron metabolism;knock-down;Link;Malignant neoplasm of ovary;Malignant Neoplasms;Mediating;Membrane Proteins;Mitochondria;Mitochondrial Proteins;molecular site;mouse model;mutant;Mutation;Neoplasm Metastasis;new therapeutic target;Nucleotide Excision Repair;Oxidative Stress;Pathway interactions;patient subsets;Patients;Pharmaceutical Preparations;Platinum;Platinum Compounds;Poly(ADP-ribose) Polymerase Inhibitor;Prognosis;protein function;Proteins;recombinational repair;repair function;repaired;response;Role;Sulfur;Testing;Therapeutic;Time;women's diagnosis

PROJECT_TITLE: Targeting sideroflexin 4, a mitochondrial inner membrane protein involved iniron sulfur cluster biogenesis, to enhance the efficacy of DNA-damaging drugs inovarian cancer


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Lung;Lung Cancer;Pediatric;Prevention;Social Determinants of Health;Substance Misuse;Tobacco;Tobacco Smoke and Health;Women's Health Research

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because young adult sexual minority women are disproportionately impacted by smoking-related health disparities, and research to identify effective and scalable counter-marketing approaches to reduce smoking among this priority population is limited. This research will be the first to determine the effects of inoculation with culturally-tailored counter-marketing messages to increase resistance to tobacco industry marketing, explore the impact of counter-marketing messages in relation to minority stress, resilience and social/environmental factors, and explore the mechanisms via emotions, beliefs and attitudes. This proposal directly addresses key scientific priorities in PAR-18-037 for research that leads to the development of acceptable and appropriate health interventions to ameliorate health disparities in SGM populations.

PI_NAMEs: TAN, ANDY SL (contact)

PROGRAM_OFFICER_NAME: ILES, IRINA ALEXANDRA

PROJECT_TERMS: Address;Adoption;Advisory Committees;Alcohol consumption;Antismoking;Attitude;Belief;Bisexual;Cardiopulmonary;cigarette smoking;cisgender;Communicable Diseases;Communication;Communities;comparison control;Data;Development;Disproportionately impacts women;Dose;Drug usage;Emotions;Environmental Risk Factor;evidence base;experimental study;Feedback;Foundations;Future;gender minority group;gender minority health;Goals;Health;Health Disparities Research;health disparity;Heterosexuals;high risk;Homophobia;Imagery;Immunity;Industry;informant;Intention;Intervention;Interview;Knowledge;Language;Lesbian;Lesbian Gay Bisexual Transgender;Lesbian Gay Bisexual Transgender Queer;Link;Marketing;meetings;member;Methods;minority stress;minority stressor;Modeling;non-smoker;Persons;Pilot Projects;Population;positive emotional state;promote resilience;Public Health;Qualitative Research;Randomized;Research;Research Methodology;Research Personnel;resilience;resilience factor;Resistance;Risk;Risk Behaviors;Science;Sexual and Gender Minorities;sexual minority group;sexual minority women;Smoke;Smoker;Smoking;Smoking Behavior;smoking-related cancer;social;social determinants;Surveys;Testing;therapy design;tobacco advertising;tobacco exposure;Tobacco Industry;Tobacco smoking behavior;Vaccines;Victimization;Woman;Work;young adult

PROJECT_TITLE: Project RESIST: Increasing Resistance to Tobacco Marketing Among Young Adult Sexual Minority Women Using Inoculation Message Approaches

STUDY_SECTION: ARM

STUDY_SECTION_NAME: Addiction Risks and Mechanisms Study Section[ARM]


NIH_SPENDING_CATS: Biotechnology;Genetics;Lung;Neonatal Respiratory Distress;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period

ORG_CITY: SAINT LOUIS

ORG_DEPT: PEDIATRICS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE Mutations in the ABCA3 gene are the most common genetic cause of severe breathing problems among infants and children. As medical treatment options remain limited, affected patients may require lung transplantation for survival. We will use human lung cell lines to determine how specific ABCA3 mutations cause breathing problems and to discover FDA-approved medications to treat breathing problems in infants and children with ABCA3 mutations.

PI_NAMEs: WAMBACH, JENNIFER  (contact)

PROGRAM_OFFICER_NAME: LIN, SARA

PROJECT_TERMS: A549;Affect;Alleles;alveolar lamellar body;alveolar type II cell;ATF6 gene;ATP phosphohydrolase;ATP-Binding Cassette Transporters;Azithromycin;Biological Assay;Breathing;Cell Line;Cell Survival;Cellular Metabolic Process;Cellular Stress;Child;Childhood;Cloning;CRISPR/Cas technology;cystic fibrosis patients;Cystic Fibrosis Transmembrane Conductance Regulator;Degradation Pathway;Development;Diameter;Disease;Endoplasmic Reticulum;Epithelial Cells;Epithelium;FDA approved;Fluorescence;functional genomics;Gene Mutation;Genes;Genetic;Genetic Recombination;genetic variant;genome editing;genomic platform;Green Fluorescent Proteins;Human;Hydroxychloroquine;Impairment;In Vitro;Individual;individual response;individualized medicine;Infant;Interstitial Lung Diseases;Label;Lecithin;Lentivirus;Liposomes;Location;Lung;Lung Transplantation;Lysosomes;Mediating;Medical;member;Membrane;Mendelian disorder;model development;multicatalytic endopeptidase complex;Mutagenesis;mutant;Mutation;Neonatal Respiratory Distress;Parents;Pathogenicity;Pathway interactions;Patients;Pharmaceutical Preparations;Phospholipids;Physiological;Privatization;Protease Inhibitor;Proteins;pulmonary function;Pulmonary Surfactants;Regulator Genes;respiratory distress syndrome;Respiratory Failure;RNA Splicing;screening;Site;small molecule;stable cell line;Steroids;Stress;surfactant;surfactant function;surfactant production;surfactant replacement;System;targeted treatment;Tertiary Protein Structure;Testing;Toxic effect;trafficking;Ubiquitin;uptake;Variant;Vesicle;virulence gene;VX-809

PROJECT_TITLE: Functional Characterization of ABCA3 Genomic Variants

STUDY_SECTION: LIRR

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


ADMINISTERING_IC: AG

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Biotechnology;Brain Disorders;Dementia;Genetics;Human Genome;Neurodegenerative;Neurosciences;Precision Medicine;Prevention

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

PHR: NARRATIVE/PUBLIC HEALTH STATEMENT:  Alzheimer’s disease affects 6 million Americans, and yet nearly all clinical trials for new treatments have failed. This project is designed to identify plasma proteins associated with Alzheimer’s disease and with rate of cognitive decline, which may help identify people at risk for future Alzheimer’s disease and may inform targets for novel therapeutics.

PI_NAMEs: FOHNER, ALISON ELIZABETH (contact)

PROGRAM_OFFICER_NAME: LUO, YUAN

PROJECT_TERMS: adjudication;Affect;African American;Aging;Alzheimer disease prevention;Alzheimer's Disease;Alzheimer's disease diagnosis;Alzheimer's disease pathology;Alzheimer's disease risk;Alzheimer’s disease biomarker;American;Area;Award;Biological Assay;Biological Process;Biology;biomarker discovery;Brain;brain magnetic resonance imaging;cardiovascular health;career;career development;caucasian American;cerebral atrophy;Cerebrospinal Fluid;clinical biomarkers;clinical diagnosis;Clinical Trials;Cognition;Cognitive;Cognitive deficits;cognitive testing;Cohort Studies;Collaborations;Cross-Sectional Studies;Data;Data Analyses;design;Development Plans;Diagnosis;Diagnostic;Disease Outcome;Doctor of Philosophy;Drug Targeting;Early identification;Epidemiology;Etiology;experience;forging;Framingham Heart Study;Funding;Future;Genetic;genome sequencing;genome wide association study;genomic data;Genomics;Goals;Grant;Health;high dimensionality;Immune;Impaired cognition;improved;Individual;innovation;instrument;Jackson Heart Study;Learning;longitudinal analysis;Measures;men;Mendelian randomization;Mentored Research Scientist Development Award;Mentorship;Methods;multidimensional data;multiple omics;National Heart, Lung, and Blood Institute;Nerve Degeneration;neuroinflammation;new technology;new therapeutic target;novel;novel marker;novel therapeutics;older adult;Outcome;Participant;Pathology;Pathway interactions;Persons;Plasma;Plasma Proteins;population based;Populations at Risk;Positioning Attribute;prevent;Prevention;Productivity;professor;prospective;Protein Analysis;protein biomarkers;Proteins;Proteomics;Public Health;rapid test;recruit;Research;Research Design;Research Personnel;Resources;Risk;risk stratification;Role;routine care;Sampling;Signaling Protein;skills;targeted treatment;tau Proteins;Techniques;therapeutic target;Time;Training;Universities;Washington;whole genome;Woman

PROJECT_TITLE: Integrated multi-omics approach to identify early protein biomarkers in Alzheimer's disease and cognitive decline

STUDY_SECTION: AGCD

STUDY_SECTION_NAME: Career Development For Early Career Investigators Study Section [AGCD-2]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biotechnology;Digestive Diseases;Infectious Diseases;Orphan Drug;Rare Diseases;Vector-Borne Diseases

ORG_CITY: MILWAUKEE

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

ORG_STATE: WI

PHR: PROJECT NARRATIVE Schistosomiasis is a tropical parasitic disease afflicting ~200 million people worldwide with therapy reliant on a single drug (praziquantel, PZQ) that displays several non-optimal features, including a lack of knowledge about how this drug works. We have recently identified the flatworm target of PZQ, a breakthrough that now permits a screening campaign for novel ligands and regulators of this target. Identification of novel small molecules that show both efficacy at this target and activity against parasitic flatworms ex vivo and in vivo provides a rigorous pipeline for the discovery of next generation anthelmintics, which are urgently needed in the clinic and field.

PI_NAMEs: MARCHANT, JONATHAN S (contact);SCAMPAVIA, LOUIS DANIEL

PROGRAM_OFFICER_NAME: JOY, DEIRDRE A

PROJECT_TERMS: Adult;Affinity;analog;Anthelmintics;Antiparasitic Agents;Attention;Biological Assay;Biology;Characteristics;chemotherapy;Child;Clinic;Clinical;clinically relevant;cohort;Collaborations;Communicable Diseases;counterscreen;Country;Coupled;cytotoxic;cytotoxicity;Data;Data Set;Disease;Drug Design;Drug Targeting;Electrophysiology (science);Evaluation;Exhibits;Failure;Field Reports;Florida;follow-up;Generations;Goals;Hand;Health;helminth infection;Helminths;high throughput screening;improved;In Vitro;in vivo;Infection;inhibitor;insight;Ion Channel;Knowledge;Laboratories;Lead;lead optimization;lead series;Life Cycle Stages;Ligands;Light;Mediation;medical schools;Miniaturization;Modeling;Molecular;mouse model;nanomolar;neglected tropical diseases;new therapeutic target;next generation;novel;Paralysed;Parasites;Parasitic Diseases;Permeability;Persons;Pharmaceutical Chemistry;Pharmaceutical Preparations;pharmacophore;Pharmacotherapy;Platyhelminths;Population;Populations at Risk;Praziquantel;Praziquantel resistance;Preparation;Property;prophylactic;receptor;Research;response;scaffold;Schistosoma;Schistosoma mansoni;Schistosomiasis;School-Age Population;screening;Series;Site;small molecule;Source;Structure-Activity Relationship;Surface;Testing;therapeutic effectiveness;Time;Triage;TRP channel;Validation;Wisconsin;Work

PROJECT_TITLE: Identification of novel anthelmintics through a target-based screen of a parasite ion channel

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


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

PHR: Project Narrative Large scale proteomic analysis of Alzheimer’s disease (AD) patients has identified a connected network of proteins associated with AD. To determine whether the M4 protein network and its key hub proteins, including Plectin (Plec) modulates AD risk, this project will dissect Plec’s function in the nervous system and validate the protein network structure using cross-species analysis. My results will determine the function of a predicted AD target in the adult brain, its role in the protein network, and validate protein network structure with the goal of elucidating novel AD pathophysiological mechanisms and develop novel therapeutics.

PI_NAMEs: LEE, TOM V (contact)

PROJECT_TERMS: Adult;age related;age related neurodegeneration;Aging;aging brain;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease patient;Alzheimer's disease risk;Alzheimer's disease therapeutic;Attenuated;Autopsy;Behavior;Biological;Biological Assay;Biology;Brain;brain tissue;career;career development;Cerebrospinal Fluid;clinical diagnosis;clinical translation;Co-Immunoprecipitations;college;Crosslinker;Cytoskeleton;Data;data integration;Data Set;Dementia;design;Development Plans;Dissection;Drosophila genus;Electrophysiology (science);Environment;Ethics;experience;experimental study;fly;Functional disorder;Funding;Genes;Genetic;Genetic Screening;Goals;Grant;Histology;Homeostasis;Homologous Protein;Human;Immunoprecipitation;Impaired cognition;Impairment;improved;Induced Neurons;Institution;International;knock-down;laboratory experience;large scale data;Leadership;Link;Maintenance;Mass Spectrum Analysis;Mediating;Medicine;meetings;Mentors;Mentorship;Modeling;Molecular;Morphology;mutant;Nervous System;network architecture;Neurodegenerative Disorders;Neurofibrillary Tangles;Neurology;Neuromuscular Junction;neuron development;neuron loss;Neurons;neuropathology;Neurosciences;neurotoxicity;neurotransmission;novel;novel therapeutics;overexpression;Pathogenesis;Pathology;Pathway Analysis;Phosphorylation;plectin;postsynaptic;pre-clinical;presynaptic;Presynaptic Terminals;prodromal Alzheimer's disease;protein expression;protein function;protein protein interaction;Proteins;Proteomics;Research;Research Personnel;Research Training;Retina;RNA Interference;Role;Scientist;skill acquisition;skills;Structure;symposium;Symptoms;Synapses;synaptic function;System;Systems Biology;tau expression;tau Proteins;Tauopathies;Technology;Testing;Therapeutic;therapeutic target;Tissues;tool;Toxic effect;Training;translational approach;translational scientist;Translations;United States;Validation;Writing

PROJECT_TITLE: FUNCTIONAL VALIDATION OF A PLECTIN-ASSOCIATED ALZHEIMER'S DISEASE PROTEIN NETWORK


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

ORG_CITY: LOS ANGELES

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PROJECT NARRATIVE STING agonists are a promising anticancer treatment currently being explored in pancreatic ductal adenocarcinoma (PDAC), a disease which is notoriously resistant to current therapies. A systematic metabolomic and proteomic proﬁling identiﬁed previously unappreciated consequences of STING activation in PDAC malignant cells, speciﬁcally the depletion of nucleotide pools and activation of the replication stress response pathway. This proposal will examine mechanistic underpinnings of these observations and will test rationally designed therapies with the goal of deﬁning new therapeutic options for PDAC for future clinical translation.

PI_NAMEs: DONAHUE, TIMOTHY R (contact);RADU, CAIUS GABRIEL

PROGRAM_OFFICER_NAME: WILLIS, KRISTINE AMALEE

PROJECT_TERMS: Agonist;Anabolism;anti-cancer treatment;anti-PD-1;antitumor effect;ATR gene;Biochemical Process;biological adaptation to stress;cancer cell;Cancer Etiology;cancer therapy;cell growth;Cell Line;Cell Reprogramming;Cells;Cellular Metabolic Process;Clinical;clinical translation;Clinical Trials;cofactor;Combined Modality Therapy;Consumption;cytokine;Data;Data Analyses;Deoxyribonucleosides;Deoxyribonucleotides;Dependence;design;Disease;DNA biosynthesis;DNA Repair;DNA Replication Induction;Endothelium;Enzymes;Family;Future;Gene Activation;Genetic;Genetic Models;Genetic Transcription;Goals;Immune;immune checkpoint blockade;Immunocompetent;immunoregulation;Impairment;implantation;improved;In Vitro;in vivo;in vivo Model;Inflammatory;inhibitor;Interferon Type I;Interferons;Investigation;Knowledge;Link;Malignant - descriptor;Malignant neoplasm of pancreas;Malignant Neoplasms;Mass Spectrum Analysis;Mediating;member;Metabolic;Metabolism;metabolomics;mortality;mouse model;NADP;neoplastic cell;Niacinamide;Nicotinamide adenine dinucleotide;nicotinamide phosphoribosyltransferase;Non-Malignant;novel;novel therapeutic intervention;novel therapeutics;nucleotide metabolism;Nucleotides;overexpression;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma cell;pancreatic ductal adenocarcinoma model;PARP9 gene;Pathway interactions;patient derived xenograft model;phosphoproteomics;Phosphoric Monoester Hydrolases;Poly(ADP-ribose) Polymerases;prevent;Process;Production;Property;Proteins;Proteomics;rational design;Recycling;replication stress;repository;Resistance;Role;SAM Domain;sensor;Signal Induction;Signal Pathway;Signal Transduction;Solid Neoplasm;Source;Stimulator of Interferon Genes;Stress Response Signaling;synergism;Testing;Therapeutic;Therapeutic Effect;therapy design;tripolyphosphate;tumor;tumor growth;tumor microenvironment;Up-Regulation

PROJECT_TITLE: Leveraging Vulnerabilities Induced by STING Activation in Pancreatic Cancer

STUDY_SECTION: TCB

STUDY_SECTION_NAME: Tumor Cell Biology Study Section[TCB]


NIH_SPENDING_CATS: Breast Cancer;Cancer;Clinical Research;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Precision Medicine;Racial and Ethnic Minority Health Research;Social Determinants of Health;Women's Health Research

PHR: PROJECT NARRATIVE Despite long-standing racial disparities in breast cancer outcomes, the underlying molecular mechanisms are poorly understood. In this study, we will investigate the causal link between race-dependent differences in DNA repair capacity and the outcome disparities of triple-negative breast cancer (TNBC), as well as test the chemo- sensitizing effect of VCP inhibition. Thus, the proposed project will help improve personalized treatment decisions for African American TNBC patients to improve their survival outcomes and reduce breast cancer disparities.

PI_NAMEs: LIU, YING ;SHAO, JIEYA  (contact)

PROGRAM_OFFICER_NAME: SHARMAN, ANU

PROJECT_TERMS: Adjuvant Chemotherapy;African American;African American Women;Aggressive Clinical Course;American;ATP phosphohydrolase;Automobile Driving;Biological;Biological Assay;brca gene;Breast Cancer cell line;Breast Cancer Model;Breast Cancer Patient;Breast Cancer Treatment;cancer cell;Cancer cell line;cancer health disparity;Cell Line;Cell Survival;Cells;Chemoresistance;Chemosensitization;chemotherapy;Chromatin;chromatin protein;Clinical;cohort;Coupled;cytotoxic;Data;Data Set;differential expression;Disease;Disparity;Disproportionately impacts women;DNA;DNA Crosslinking Agent;DNA Damage;DNA Double Strand Break;DNA Repair;DNA Repair Pathway;Double Strand Break Repair;Encyclopedias;European;Excision;FANCD2 protein;Fluorescence;G22P1 gene;Genome Stability;genotoxicity;GMNN gene;high risk;homologous recombination;homologous recombination deficiency;hormone receptor-positive;Immunohistochemistry;improved;improved outcome;In Vitro;in vivo Model;Incidence;inhibitor;Intervention;knock-down;Link;Malignant Breast Neoplasm;Malignant neoplasm of ovary;Measures;Molecular;mortality;mortality risk;Mus;Mutagens;mutant;Neoadjuvant Therapy;neoplastic cell;Nonhomologous DNA End Joining;Not Hispanic or Latino;novel;Nuclear;Outcome;outcome disparities;p53-binding protein 1;Pathway interactions;Patients;Pattern;personalized medicine;Phosphorylation;Pilot Projects;Poly(ADP-ribose) Polymerase Inhibitor;predictive marker;Prognosis;prognostic;Protein Dynamics;protein expression;Protein Inhibition;Proteins;Proteomics;Race;racial difference;racial disparity;relapse risk;repaired;Reporter;Reporting;response;Role;Sample Size;Sampling;Site;sociodemographics;survival disparity;survival outcome;Testing;The Cancer Genome Atlas;therapeutic target;Tissues;Treatment Efficacy;Treatment outcome;treatment response;triple-negative invasive breast carcinoma;tumor;Tumor Tissue;valosin-containing protein;Woman;Xenograft Model

PROJECT_TITLE: Understanding the role of DNA damage repair in racial disparities of triple-negative breast cancer outcomes

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


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Brain Cancer;Brain Disorders;Cancer;Neurosciences;Rare Diseases

ORG_CITY: AUSTIN

ORG_DEPT: NEUROSURGERY

ORG_NAME: UNIVERSITY OF TEXAS AT AUSTIN

PHR: Glioblastoma is a uniformly fatal brain cancer with poor response to treatment and high rates of recurrence. This proposal describes application of a tissue-engineered model of the interface between glioblastoma and its associated blood vessels for systematic characterization of the mechanisms by which blood vessels promote GBM cells to migrate away from primary tumors, eventually leading to tumor recurrence.

PI_NAMEs: SEIDLITS, STEPHANIE KRISTIN (contact)

PROGRAM_OFFICER_NAME: BECKER, STEVEN

PROJECT_TERMS: 3-Dimensional;Address;Affect;Atomic Force Microscopy;Behavior;Biochemical;Biocompatible Materials;Biomechanics;Biomedical Engineering;Blood Vessels;Brain;brain tissue;cancer cell;cell behavior;Cell Communication;Cell Culture Techniques;cell motility;Cell secretion;Cell Survival;Cells;chemical property;Chemicals;Chemotherapy and/or radiation;Clinical;Coculture Techniques;combat;Coupling;Cues;Development;effective therapy;Endothelial Cells;Environment;Event;Excision;Exhibits;Experimental Models;experimental study;Exposure to;Extracellular Matrix;Glioblastoma;Glioma;Heterogeneity;Individual;Infiltration;innovation;insight;Invaded;Knowledge;Malignant neoplasm of brain;Measures;mechanical properties;mechanical signal;Mechanics;migration;Modeling;neoplastic cell;neuro-oncology;new therapeutic target;Operative Surgical Procedures;Patients;Phenotype;Population Heterogeneity;Primary Neoplasm;Proliferating;Property;Recurrence;Recurrent tumor;Reporting;Resistance;response;Role;single-cell RNA sequencing;Site;stem;Stimulus;targeted treatment;therapy resistant;three dimensional cell culture;Tissue Engineering;Tissues;transcriptomics;treatment response;tumor;Tumor Cell Invasion;Tumor Cell Migration;tumor microenvironment;tumor progression;Tumor Promotion;tumor xenograft;Vascularization;virtual;Xenograft procedure

PROJECT_TITLE: Tissue-Engineered Models of Glioblastoma for Evaluating Treatment Response

STUDY_SECTION: TME

STUDY_SECTION_NAME: Tumor Microenvironment Study Section[TME]


NIH_SPENDING_CATS: Biotechnology;Cardiovascular;Congenital Heart Disease;Congenital Structural Anomalies;Heart Disease;Orphan Drug;Pediatric;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Transplantation

ORG_CITY: WINSTON-SALEM

ORG_NAME: WAKE FOREST UNIVERSITY HEALTH SCIENCES

PHR: PUBLIC HEALTH RELEVANCE: Heart failure as a result of congenital heart defects is a leading cause of morbidity and mortality worldwide and effective treatment options are greatly needed. Cell therapy has provided new avenues of treatment but much work still needs to be done, especially in the pediatric population. We propose that delivery of pre-conditioned human cardiac-derived c-kit+ progenitor cells will improve cardiac function in heart failure.

PI_NAMEs: MAXWELL, JOSHUA THOMAS (contact)

PROGRAM_OFFICER_NAME: SCHRAMM, CHARLENE A

PROJECT_TERMS: 5 year old;Address;Adhesions;Adhesives;Adolescent;Adult;adult stem cell;Aftercare;Age;Allogenic;angiogenesis;Autologous;Autopsy;Binding;Biological Assay;Biological Response Modifier Therapy;Calcium Oscillations;Calcium Signaling;candidate identification;Cardiac;Cardiac Myoblasts;Cardiac Myocytes;Cardiovascular Diseases;Cardiovascular system;Cell Adhesion Molecules;Cell Extracts;Cell Separation;Cell Therapy;Cells;cellular transduction;Chemicals;Child;Childhood;Clinical Trials;comparison control;Congenital Heart Defects;Congenital Heart Surgery;cytokine;Data;Echocardiography;Economic Burden;effective therapy;Electric Stimulation;electrical property;Endothelial Cells;Engraftment;exosome;Exposure to;Fibroblasts;Fibrosis;Functional disorder;Gene Expression;Genes;Genetic Engineering;genetic manipulation;Genotype;Heart;Heart failure;heart function;Heart Transplantation;hemodynamics;Histologic;Human;Hypertrophy;improved;In Vitro;in vivo;inhibitor;Injections;insight;Integrins;Label;Measurement;Methods;Monitor;Morbidity - disease rate;mortality;Muscle Cells;Myocardial Infarction;Myocardium;Natural regeneration;novel;Operative Surgical Procedures;paracrine;Paracrine Communication;Patients;pediatric heart failure;pharmacologic;Phenotype;Play;Population;prevent;programs;Proliferating;Proteins;Proto-Oncogene Protein c-kit;public health relevance;Publishing;Pulmonary artery structure;Rattus;regeneration potential;Regenerative capacity;Regenerative Medicine;release factor;reparative capacity;response;Reverse Transcriptase Polymerase Chain Reaction;RNA;Role;small hairpin RNA;stem cell therapy;stem cells;success;Testing;Therapeutic;Therapeutic Intervention;Treatment Efficacy;Up-Regulation;Work

PROJECT_TITLE: Electrical Stimulation of Human CPCs

STUDY_SECTION: MIM

STUDY_SECTION_NAME: Myocardial Ischemia and Metabolism Study Section[MIM]


ADMINISTERING_IC: EY

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Eye Disease and Disorders of Vision;Gene Therapy;Genetics;Neurodegenerative;Neurosciences;Orphan Drug;Rare Diseases

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: PROJECT NARRATIVE Phosphodiesterase (PDE6)- related retinopathies blind nearly 72,000 individuals worldwide, and there is currently no treatment available to stop disease progression. CRISPR-mediated gene editing, is a challenging clinical treatment option due to its gene- and mutation-specific guide RNA (gRNA) targeting requirements and delivery. We propose to address this problem by developing an efficacious strategy to treat cone degenerations, identify and optimize the CRISPR delivery method best suited for these conditions, and finally, enable treatment in a manner that is not mutation specific.

PI_NAMEs: NOLAN, NICHOLAS DAVID (contact)

PROGRAM_OFFICER_NAME: AGARWAL, NEERAJ

PROJECT_TERMS: Ablation;Address;Adult;Aerobic;aerobic glycolysis;Affect;Age;Anemia;antagonist;Atrophic;bench-to-bedside translation;bHLH-PAS factor HLF;blind;Carbon;Cells;Cessation of life;Choroid;Citric Acid Cycle;Clinical Treatment;Clinical Trials;clinically significant;Clustered Regularly Interspaced Short Palindromic Repeats;Cone;cost;Coupling;Disease;Disease Progression;efficacy evaluation;Enzymes;Functional disorder;Funding;Gene Mutation;gene therapy;Genes;Genetic;Genetic Recombination;Glucose;Glycolysis;Goals;Guide RNA;hemangioblastoma;Human;Hypoxia Inducible Factor;Individual;inducible Cre;Inherited;Injections;Investigational New Drug Application;Kidney;Knock-out;Knowledge;Lead;Mediating;Metabolic;Metabolic Pathway;Methods;Modeling;mouse model;Mouse Strains;Mus;Mutation;Neurodegenerative Disorders;normoxia;novel;novel strategies;Oral Administration;Outcome;oxidation;Patients;pharmacologic;Phase;phosphoric diester hydrolase;photoreceptor degeneration;Photoreceptors;preservation;Process;Procollagen-Proline Dioxygenase;Production;promoter;Proteins;repaired;response;Retina;Retinal Cone;Retinal Degeneration;Retinal Diseases;Retinal Dystrophy;retinal rods;Retinitis Pigmentosa;Rod;Role;RPE65 protein;Safety;Source;Starvation;Structure of retinal pigment epithelium;Subgroup;Teenagers;Testing;Therapeutic;therapeutic genome editing;Tissue Sample;tool;Translating;Ubiquitination;vector;Vertebrate Photoreceptors;VHL protein

PROJECT_TITLE: Therapeutic Editing of Rod Glycolysis Rescues Retinal Degeneration


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Autism;Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Clinical Research;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Pediatric;Prevention

ORG_DEPT: PSYCHIATRY

PHR: Project Narrative Developmental language impairments are pervasive in the general population, posing a substantial public health burden that could be mitigated by earlier identification and intervention. The proposed studies will longitudinally examine the development of the neural networks subserving native language processing throughout the first year of life to delineate patterns associated with both typical and delayed language acquisition. These findings will inform the identification of early biomarkers for language impairments – including those associated with Autism Spectrum Disorder – and pave the way for earlier diagnosis and interventions.

PI_NAMEs: WAGNER, LAUREN E (contact)

PROGRAM_OFFICER_NAME: KAU, ALICE S

PROJECT_TERMS: adult with autism spectrum disorder;adverse outcome;Affect;Age Months;Anisotropy;Area;autism spectrum disorder;Behavioral;Birth;Brain;Brain region;career;Cerebellum;Cerebrum;Child;Childhood;collaborative environment;Communication;connectome;Contralateral;Corpus Callosum;Coupling;Data;Development;Diffusion Magnetic Resonance Imaging;Disease;early detection biomarkers;Early Diagnosis;Early identification;Early Intervention;Educational process of instructing;effective intervention;Emotional;Employment;Environment;Etiology;Exhibits;experience;Fellowship;Foundations;Functional Magnetic Resonance Imaging;Funding;Future;General Population;graduate student;High Prevalence;high risk;Image;imaging study;improved;indexing;Individual Differences;infancy;Infant;Information Dissemination;Infrastructure;Japanese;Language;Language Delays;Language Development;Language Development Disorders;language impairment;language outcome;language processing;Left;Life;Literature;longitudinal design;Longitudinal Studies;Magnetic Resonance Imaging;Measures;Methods;National Institute of Child Health and Human Development;National Research Service Awards;neural;neural network;neurodevelopment;Neurodevelopmental Disorder;neuroimaging;Neurosciences;Newborn Infant;non-Native;Outcome;Pattern;Population;postnatal;Prevalence;Public Health;Research;Research Training;Resources;response;Rest;Risk;Role;Sample Size;Sign Language;skills;Sleep;Social outcome;Speech;speech processing;Statistical Models;Stimulus;Stream;Structure;support network;symptomatology;Therapeutic Intervention;Time;Toddler;tractography;Training;United States National Institutes of Health;white matter

PROJECT_TITLE: Early Neurodevelopmental Trajectories of Typical and Atypical Language Acquisition


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Biodefense and Related Countermeasures;Clinical Research;Coronaviruses;Dental, Oral, and Craniofacial Disease;Emerging Infectious Diseases;Infectious Diseases;Neurosciences;Post-Acute Sequelae of SARS-CoV-2 infection (PASC) including Long COVID;Prevention

ORG_CITY: Columbus

ORG_DEPT: OTOLARYNGOLOGY

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: Project Narrative COVID-19 may have significant neurotropic impacts on multiple sensory functions, spanning smell, taste, chemesthesis, hearing, and balance. This research will extensively investigate and capture short-term and long-term COVID-associated multisensory dysfunctions, their recovery, and their relationship with patients’ disease profiles, which will enable more comprehensive understanding to better support future patient care and recovery.

PI_NAMEs: ZHAO, KAI  (contact)

PROGRAM_OFFICER_NAME: SULLIVAN, SUSAN L

PROJECT_TERMS: 2019-nCoV;ACE2;Acute;Affect;Ageusia;Anosmia;Auditory;Basal Cell;Case Study;Cessation of life;Characteristics;China;Cochlea;cohort;Common Cold;common symptom;comparison group;Confusion;Coronavirus;Coughing;COVID-19;COVID-19 impact;COVID-19 long hauler;COVID-19 pandemic;COVID-19 patient;COVID-19 screening;dashboard;Data;Dendrites;Disease;Disease Outbreaks;Dizziness;Epidemiologist;epidemiology study;Equilibrium;expectation;Face;Fever;flu;Functional disorder;Future;General Population;Glucose;Goals;Handwashing;Headache;health care settings;Hearing;Herpes Simplex Infections;Hospitalization;Hypoxia;Individual;Infection;Inflammation;Ion Exchange;Labyrinth;Long COVID;long term consequences of COVID-19;Magnetic Resonance Imaging;Measurement;Measures;Mediating;Methodology;Modality;Mucous body substance;multidisciplinary;multisensory;nasal obstruction;neural;neuroinflammation;Neurologic;Neurologic Symptoms;neurosensory;neurotropic;olfactory bulb;Olfactory Epithelium;olfactory sensory neurons;Outcome Study;pandemic disease;Pathway interactions;Patient Care;Patient Self-Report;patient subsets;Patients;Perception;Peripheral;persistent symptom;Persons;Phase;post SARS-CoV-2 infection;post-COVID-19;Public Health;receptor;Recovery;Reporting;Research;SARS-CoV-2 B.1.1.529;SARS-CoV-2 B.1.617.2;SARS-CoV-2 infection;Schools;Sensory;sensory system;Severities;Severity of illness;Smell Perception;Social Distance;Sudden Hearing Loss;Supporting Cell;sustentacular cell;Symptoms;System;Taste Perception;Testing;Time;timeline;Tinnitus;Trigeminal System;Upper Respiratory Infections;Vaccination;Variant;variants of concern;Vertigo;Vestibular dysfunction;Vestibular function;Viral;Virus;Virus Diseases;West Nile;Workplace;ZIKA

PROJECT_TITLE: Short-term and long-term impact of COVID-19 on multiple sensory systems

STUDY_SECTION: NIC

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


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Anorexia;Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Clinical Research;Eating Disorders;Mental Health;Mental Illness;Neurosciences;Nutrition;Precision Medicine;Serious Mental Illness

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: PROJECT NARRATIVE This study will be the first to apply a multi-dimensional framework of reward processing to determine how `liking', `wanting' or incentive salience, and instrumental learning is altered in anorexia nervosa and bulimia nervosa, is influenced by outcome valence (reward, punishment) and stimulus modality (taste, money), and corresponds to overlapping and divergent clinical symptoms at study entry and after one year. Advancing our understanding of dimensional constructs underlying symptom heterogeneity in eating disorders, and that predict symptom change over time, will improve diagnostic classification, identify novel therapeutic targets, and drive innovative treatment development for these often chronic and sometimes deadly disorders.

PI_NAMEs: WIERENGA, CHRISTINA E (contact)

PROGRAM_OFFICER_NAME: CHAVEZ, MARK RAY

PROJECT_TERMS: Address;Adopted;Adult;aged;Anorexia Nervosa;approach behavior;Association Learning;avoidance behavior;Behavior;Behavioral;Binge Eating;Biological Markers;Body Weight decreased;Brain;Bulimia;Caring;Chronic;Classification;Clinical;clinical predictors;Clinical Treatment;Complex;Computer Models;Consumption;Corpus striatum structure;Coupled;Dangerousness;Data;Death Rate;Decision Making;Diagnosis;Diagnostic;diagnostic criteria;diagnostic strategy;dietary restriction;Dimensions;Disease;disorder subtype;Dopamine;Eating;Eating Disorders;effective therapy;Etiology;Exhibits;experience;Failure;financial incentive;food restriction;Functional Magnetic Resonance Imaging;hedonic;Heterogeneity;Impairment;improved;incentive salience;Incentives;innovation;Learning;Machine Learning;Magnetic Resonance Imaging;Maintenance;Measures;medical complication;Mental disorders;Modality;Modeling;Motivation;neural;neural circuit;neural correlate;neuromelanin;new therapeutic target;novel;Operant Conditioning;Outcome;Participant;Patients;Performance;physical symptom;Positive Valence;precision medicine;predictive marker;Process;Psychological reinforcement;Psychopathology;psychosocial;Punishment;purge;Research Domain Criteria;response;reward dysfunction;reward processing;Rewards;Role;Signal Transduction;Stimulus;Substantia nigra structure;Sucrose;Symptoms;System;targeted treatment;Taste Perception;Tea;Testing;therapy development;Time;Vomiting;Woman

PROJECT_TITLE: Incentive Processing and Learning in Anorexia Nervosa and Bulimia Nervosa

STUDY_SECTION: APDA

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


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;Biomedical Imaging;Brain Disorders;Clinical Research;Dementia;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Neurodegenerative;Neurosciences;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: BOCA RATON

ORG_DEPT: PSYCHOLOGY

ORG_NAME: FLORIDA ATLANTIC UNIVERSITY

ORG_STATE: FL

PHR: Project Narrative There is inconsistent evidence indicating that Bilingualism might increase Cognitive Reserve and or resilience (CR/R). We propose a multidisciplinary longitudinal study to compare Bilinguals and Monolinguals with amnestic Mild Cognitive Impairment from an equivalent cultural background in neuropsychological and neuroimaging data. Our findings will advance understanding of the complex interactions between neural, environmental, and sociocultural factors and the role of Bilingualism in CR/R in MCI, paving the way for new targets for interventions and providing fundamental insight into the role of language(s) in the aging brain.

PI_NAMEs: COOMBES, STEPHEN ;ROSSELLI, MONICA  (contact)

PROGRAM_OFFICER_NAME: SUTTERER, MATTHEW

PROJECT_TERMS: Acculturation;Address;Adult;Age;Age Years;Aging;aging brain;Alzheimer's Disease;Alzheimer's disease related dementia;amnestic mild cognitive impairment;Area;bilingualism;Biological;Brain;brain volume;Cognition;Cognitive;cognitive change;cognitive function;cognitive reserve;cohort;Cohort Studies;community engaged research;Complex;Cultural Backgrounds;Data;Data Collection;data sharing;Dementia;design;Diffusion Magnetic Resonance Imaging;Dissociation;Educational Background;Educational Status;Ensure;entorhinal cortex;Environmental Risk Factor;ethnic difference;Ethnic Origin;Ethnic Population;Exhibits;Failure;Funding;Hippocampus;Hispanic;Hispanic Populations;Impaired cognition;indexing;Individual;Inferior;Inferior frontal gyrus;innovation;insight;interest;Intervention;Language;Learning;longitudinal dataset;longitudinal design;Longitudinal Studies;Magnetic Resonance Imaging;Measures;Mediating;Medical center;mild cognitive impairment;Modification;MRI Scans;multidisciplinary;multimodal neuroimaging;Nerve Degeneration;neural;neuroimaging;neuroprotection;Neuropsychology;older adult;outreach;Parietal Lobe;Population;Positioning Attribute;prospective;Prospective Studies;Prospective, cohort study;Psyche structure;recruit;Research;Research Personnel;resilience;resilience in aging;Resistance;response;Risk;Role;Running;Semantics;Short-Term Memory;social culture;sociocultural determinant;Spanish;Spanish/English;Statistical Models;Stress Tests;Structure;Testing;theories;Time;Translating;United States National Institutes of Health;white matter

PROJECT_TITLE: Prospective study of bilingualism and cognitive reserve in the aging brain of Hispano adults with MCI


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: COLUMBIA

ORG_NAME: HARRY S. TRUMAN MEMORIAL VA HOSPITAL

PHR: Project Narrative: Coronary atherosclerosis, one of five top causes for cardiovascular hospitalization in U.S. Veterans, is a chronic progressive disease characterized by the thickening and hardening of arteries as a result of buildup of atherosclerotic plaques. In this application, a combination of molecular, cellular, and genetic approaches with gain-of- and loss-of- function studies will be utilized to establish novel mechanisms by which Olfactomedin 2 promotes the development and progression of atherosclerosis through mediating vascular smooth muscle foam cell formation and later apoptosis. The outcome of the project may lead to identification of new molecular targets for the prevention and therapy of atherosclerosis.

PI_NAMEs: CHEN, SHIYOU  (contact)

PROJECT_TERMS: Acute myocardial infarction;Acyl Coenzyme A;Antibodies;Aorta;Apolipoprotein E;Apoptosis;Arterial Fatty Streak;Arterial Intimas;Arteries;Aspirin;atherogenesis;Atherosclerosis;Biochemical;Blood flow;cardiovascular health;Cardiovascular system;CCAAT-Enhancer-Binding Proteins;Cell Lineage;Cell Physiology;Cells;Cholesterol;Cholesterol Esters;Chronic;Clinical;Complex;Coronary Arteriosclerosis;Coronary artery;Data;Development;Disease;Down-Regulation;effective therapy;Elements;Event;Fibrates;Foam Cells;General Population;genetic approach;Goals;Heart failure;High Density Lipoprotein Cholesterol;High Fat Diet;high risk;Histologic;Homologous Protein;Hospitalization;Human;improved;In Vitro;in vivo;Inflammatory;Inflammatory Response;inhibitor;Interleukin-1 beta;knock-down;Lesion;Lipids;loss of function;Macrophage;Mediating;military veteran;Molecular;Molecular Target;Morbidity - disease rate;mortality;Mus;Myelogenous;new therapeutic target;novel;Nuclear;olfactomedin;Outcome;overexpression;oxidized low density lipoprotein;Pathway interactions;Pharmaceutical Preparations;pharmacologic;Phenotype;Play;Prevention;Progressive Disease;protein expression;Proteins;Role;Serum;Signal Pathway;Signal Transduction;Signaling Protein;Smooth Muscle Myocytes;Sterol O-Acyltransferase;sterol O-acyltransferase 1;Stroke;Testing;Therapeutic;Therapeutic Agents;therapeutic development;vascular inflammation;Vascular Smooth Muscle;Veterans

PROJECT_TITLE: Novel Mechanisms Underlying the Development of Atherosclerosis


ORG_CITY: CINCINNATI

ORG_NAME: CINCINNATI VA MEDICAL CENTER RESEARCH

PHR: Breast cancer (BC) is a leading cause of cancer related death in American women with higher rates of this disease observed in Veteran populations compared to nonveterans. With the rapid expansion in the number of women Veterans, more women from this group are expected to be diagnosed with BC with heightened needs for women’s health care anticipated. While BC death rates have declined with advances in detection and treatment, a large number of US women are still expected to die of BC. The RON receptor and its ligand, HGFL, are coordinately upregulated in human BCs and recent studies show that RON levels are predictive of metastasis and reduced overall survival. However, the mechanisms by which RON and HGFL contribute to more aggressive BC remain incompletely understood. This study will examine a newly discovered function of these proteins in disrupting innate signaling cascades and will evaluate the efficacy of blocking RON in combination with selective immunomodulatory approaches to combat BC mortality.

PI_NAMEs: WALTZ, SUSAN E (contact)

PROJECT_TERMS: Affect;aggressive breast cancer;American;Apoptosis;attenuation;Biological;Blood Circulation;Breast;Breast Cancer Cell;Breast Cancer Model;breast cancer progression;Breast Epithelial Cells;breast tumorigenesis;Cancer Death Rates;Cancer Etiology;cancer subtypes;CD8-Positive T-Lymphocytes;Cell Count;Cell Physiology;Cell Proliferation;Cells;Cessation of life;Clinical Research;clinically relevant;combat;combinatorial;Combined Modality Therapy;comparison control;cytokine;Cytotoxic T-Lymphocytes;Data;Death Rate;Detection;Development;Diagnosis;Disease;Early Diagnosis;efficacy evaluation;Exhibits;experimental study;Female;Functional disorder;Funding;Gene Expression Profile;Growth;Healthcare;Hepatocyte;Human;Immune;immune cell infiltrate;Immunodeficient Mouse;immunoregulation;Inflammation;Inflammatory;inhibitor;Innate Immune Response;innate immune sensing;insight;Interferon Suppression;Interferon Type I;Interferons;Interleukin Suppression;Invaded;IRAK4 gene;knock-down;Knowledge;Laboratories;Ligands;Link;Macrophage;macrophage stimulating protein;Malignant Breast Neoplasm;mammary;mammary epithelium;Mammary Neoplasms;Mediating;Mediator;Messenger RNA;Metastatic Neoplasm to the Liver;Metastatic Neoplasm to the Lung;migration;military veteran;Modeling;Molecular;molecular subtypes;mortality;Mouse Mammary Tumor Virus;mouse model;Mus;Neoplasm Metastasis;neoplastic cell;novel;novel marker;Oncogenic;Organoids;overexpression;paracrine;Pathway interactions;Patients;Pattern;Pattern recognition receptor;permissiveness;pharmacologic;Phenocopy;Phenotype;Phosphotransferases;Play;Polyomaviruses Middle T Proteins;Production;Prognosis;Progressive Disease;Protein Deficiency;protein function;Proteins;Publishing;receptor;Receptor Protein-Tyrosine Kinases;Receptor Signaling;reconstitution;recruit;Recurrence;Regulation;response;Role;Signal Pathway;Signal Transduction;stem-like cell;T cell response;T-Lymphocyte;Testing;Therapeutic;transcription factor;transcriptome sequencing;Transgenic Mice;Transplantation;treatment response;treatment strategy;tumor;tumor growth;Tumor Immunity;tumor initiation;tumor microenvironment;tumor progression;Tumor Promotion;Up-Regulation;Veterans;Woman;Women's Group;Women's Health;Women's mortality;Work

PROJECT_TITLE: Ron Receptor Tyrosine Kinase Signaling in Breast Cancer


NIH_SPENDING_CATS: Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Kidney Disease;Racial and Ethnic Minority Health Research

ORG_CITY: CLEVELAND

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: CLEVELAND CLINIC LERNER COM-CWRU

PHR: NARRATIVE Chronic kidney diseases (CKD) are common, costly and a significant burden on patients and their families. While structural racism clearly contributes to the 4-fold excess prevalence of CKD in Black compared to white Americans, genetic variants in the APOL1 gene that are unique to some African ancestral populations explain part of the excess CKD risk. This project will define the pathways that translate the genetic association into disease and could identify novel targets for effective CKD treatments in this high-risk population.

PI_NAMEs: BRUGGEMAN, LESLIE A;O'TOOLE, JOHN F.;SEDOR, JOHN R. (contact);WESSELY, OLIVER

PROGRAM_OFFICER_NAME: PARSA, AFSHIN

PROJECT_TERMS: Adhesions;African;African ancestry;Amino Acids;APOL1 gene;Apoptosis;Biochemical;Biological Assay;Biotin;Biotinylation;black patient;Black Populations;Black race;candidate identification;caucasian American;Cell Culture Techniques;Cell Death;Cell membrane;Cell surface;Cell Surface Proteins;Cells;Cessation of life;Chronic Kidney Failure;cost;cytotoxicity;Data;Defect;Disease;disorder risk;Donor person;Drosophila genus;Ectopic Expression;Environment;Esters;European;experimental study;Family;Focal Adhesions;Focal and Segmental Glomerulosclerosis;gain of function;Genetic;genetic association;genetic variant;Genotype;Golgi Apparatus;Haplotypes;Hela Cells;high risk;high risk population;Human;human disease;induced pluripotent stem cell;Inflammatory;Injury;Interferon Type II;Interferons;Kidney;Kidney Diseases;Label;loss of function;Mass Spectrum Analysis;Mediating;Membrane;Methods;Microscopic;Microscopy;Modeling;Morphology;Mus;mutant;Neighborhoods;non-diabetic;novel;Organoids;overexpression;Pathogenicity;Pathway interactions;Patients;Peroxidases;Phenotype;podocyte;Population;Prevalence;promoter;protein complex;Protein Isoforms;Proteins;Proteome;Proteomics;Publishing;Risk;risk variant;Stable Isotope Labeling;Stress;Structural Racism;Surface;System;Techniques;Testing;Toxic effect;trafficking;Translating;Variant;Vesicle;Weight;Work;Zebrafish

PROJECT_TITLE: Mechanisms of Kidney Diseases Associated With APOL1 Variation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DKUS-W(05)]


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Behavioral and Social Science;Brain Disorders;Genetics;Human Genome;Neurosciences;Substance Misuse

ORG_DEPT: NEUROLOGY

PHR: PROJECT NARRATIVE INIA-Neuroimmune is a multi-disciplinary, highly collaborative research consortium that studies immune and inflammatory pathways in the brain, combining novel genomic and systems-level analyses to identify potential treatments for alcohol use disorder. The closely integrated approach using multiple levels of evaluation, from computational to behavioral, will provide key information about genes and biological pathways that contribute to excessive drinking and will identify candidate drug targets for developing new treatments.

PI_NAMEs: MESSING, ROBERT O. (contact)

PROGRAM_OFFICER_NAME: EGLI, MARK

PROJECT_TERMS: Address;alcohol abuse therapy;Alcohol consumption;alcohol research;alcohol use disorder;Alcoholism;alcoholism therapy;Alcohols;Anatomy;Animals;Astrocytes;Behavioral;Biochemical;Biological;Biological Assay;Brain;brain cell;candidate identification;cell type;Cells;Clinical Research;Communication;conflict resolution;Cytokine Signaling;Data;data management;Data Set;Databases;defined contribution;design;Diagnosis;drinking;drug candidate;Drug Compounding;Drug Targeting;Electrophysiology (science);Ensure;Evaluation;Extracellular Matrix Proteins;Functional Imaging;Gene Expression;gene network;Genes;genome wide association study;Genomics;Goals;Heavy Drinking;Human;Human Genome;Immune;Immune signaling;Inflammatory;innate immune mechanisms;Interdisciplinary Study;Investigation;Laboratories;Leadership;Link;Maps;Measures;meetings;Microglia;Modeling;Molecular;multidisciplinary;multimodality;Mutation;National Institute on Alcohol Abuse and Alcoholism;neural circuit;neuroadaptation;Neurobiology;Neuroglia;Neuroimmune;Neuroimmunomodulation;neuroinflammation;Neurons;Neurosciences;new technology;novel;Pathway interactions;Pharmacology;Phase;Post-Translational Protein Processing;preclinical study;Progress Reports;Proteomics;Publications;Reproducibility;Research;Research Personnel;Research Project Grants;Resource Sharing;Resources;response;Risk;Role;Scientific Evaluation;sex;Signal Pathway;single nucleus RNA-sequencing;structural imaging;symposium;System;Testing;transcriptome;transcriptomics;Translating;Translations;treatment strategy;Update;web site

PROJECT_TITLE: 1/11 Integrative Neuroscience Initiative on Alcoholism


NIH_SPENDING_CATS: Biomedical Imaging;Cancer;Clinical Research;Kidney Disease;Precision Medicine;Rare Diseases

ORG_CITY: DALLAS

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: Project Narrative The aim of the proposed research is to investigate the correlation between in vivo magnetic resonance imaging (MRI) measures of cellularity, blood flow and fat accumulation with the recently discovered molecular alterations in the angiogenic and lipogenic pathways that are associated to aggressive behavior in clear cell renal cell carcinoma (RCC). Quantitative measures of cellularity, blood flow and fat fraction will be obtained with diffusion weighted imaging (DWI), arterial spin labeling (ASL) and Dixon-based MRI techniques, respectively.

PI_NAMEs: PEDROSA, IVAN  (contact)

PROGRAM_OFFICER_NAME: WANG, YISONG

PROJECT_TERMS: 3D Print;Age;Aggressive behavior;American;Amino Acids;angiogenesis;arterial spin labeling;Behavior;bHLH-PAS factor HLF;Biological;Biological Markers;Biology;Biopsy;Blood;Blood flow;Blood Vessels;CD34 gene;Cellularity;Cessation of life;Clear cell renal cell carcinoma;Clinical Management;clinical practice;Collaborations;comorbidity;Data;density;Development;Diffusion Magnetic Resonance Imaging;Enzymes;experience;Fatty acid glycerol esters;Fatty Acids;Fatty-acid synthase;Funding;Gene Expression Profiling;Genotype;Glucose;Glycogen;Guidelines;Hepatic;Heterogeneity;Histologic;Human;hypoxia inducible factor 1;Image;imaging biomarker;imaging modality;Immunohistochemistry;in vivo;Incidence;Indolent;inhibitor;Kidney;Kidney Neoplasms;lipid biosynthesis;lipid metabolism;lipidomics;Lipids;Magnetic Resonance Imaging;Malignant Neoplasms;Maps;Measurement;Measures;Metabolic;metabolic phenotype;metabolic profile;metabolomics;Molds;Molecular;Natural History;Neoplasm Metastasis;Nephrectomy;Oils;Oncology;overexpression;overtreatment;Pathologic;Pathway interactions;patient derived xenograft model;Patient Selection;Patients;Perfusion;Physiological;predicting response;predictive marker;Prognosis;prognostic value;Progression-Free Survivals;protein expression;Protocols documentation;Qualifying;Renal Cell Carcinoma;Renal Mass;Reporting;Research;response;Risk;Role;Signal Transduction;Specimen;Stearoyl-CoA Desaturase;success;Surface;Techniques;Testing;Texture;The Cancer Genome Atlas;therapeutic target;Tissue Sample;Tissues;transcription factor;tumor;Tumor Angiogenesis;Tumor Biology;tumor heterogeneity;tumor metabolism;tumor progression;two-dimensional;Unnecessary Surgery;Up-Regulation;urologic;Variant;Vascular Endothelial Growth Factors;VHL Gene Inactivation

PROJECT_TITLE: NON-INVASIVE PHYSIOLOGIC PREDICTORS OF AGGRESSIVENESS IN RENAL CELL CARCINOMA

STUDY_SECTION: MEDI

STUDY_SECTION_NAME: Medical Imaging Study Section[MEDI]


NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Neurosciences

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: Project Narrative The goal of the proposed project is to understand the visual functions of four poorly understood cell types in the primate retina and the mechanisms that underlie their contribution to human vision. We utilize a combination of techniques to accomplish this goal: multi-electrode recordings to study interactions between populations of cells, patch-clamp recordings to study neural circuit mechanisms, and confocal microscopy to study the anatomical structure of the cells; these techniques allow us to study retinal circuits from population coding to cellular and circuit structure. This research will advance our understanding of the functional properties of the primate retina in health and disease, and will contribute to the design of improved techniques for diagnosing and ameliorating visual dysfunction.

PI_NAMEs: CHICHILNISKY, EDUARDO  (contact);MANOOKIN, MICHAEL B;RIEKE, FREDERICK M

PROGRAM_OFFICER_NAME: WRIGHT, CHARLES BAKER

PROJECT_TERMS: Adult;Amacrine Cells;Anatomy;Animal Model;Axon;Blindness;Brain;Cell Shape;cell type;Cells;Cellular Structures;Code;collaborative approach;Complex;Computer Models;Confocal Microscopy;Coupling;Dendrites;density;Dependence;design;Development;Diagnosis;Disease;Electrodes;Exhibits;ganglion cell;Generations;Goals;Health;Hot Spot;Human;improved;Knowledge;Light;Macaca;Membrane;Modeling;Monkeys;Motion;multi-electrode arrays;Mus;neural circuit;neuromechanism;novel;Oryctolagus cuniculus;Output;patch clamp;Pathway interactions;Photophobia;Physiological;Population;postsynaptic;presynaptic;Primates;Property;receptive field;Research;response;Retina;Retinal Ganglion Cells;Rodent;Role;Salamander;Sampling;Shapes;Signal Transduction;spatiotemporal;Stimulus;Stratification;Structure;Synapses;Techniques;Testing;Textbooks;transmission process;Vision;Visit;Visual;visual dysfunction;Visual Motion;visual processing;Work

PROJECT_TITLE: Unique physiological properties of novel ganglion cell types in primate retina

STUDY_SECTION: BDE

STUDY_SECTION_NAME: Biology and Development of the Eye Study Section[BDE]


NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Dissemination and Implementation Research;Health Services;Pediatric;Prevention;Primary Health Care

ORG_CITY: DANVILLE

ORG_NAME: GEISINGER CLINIC

PHR: PROJECT NARRATIVE Diagnosis rates of familial hypercholesterolemia (FH) are low in the United States, despite multiple guidelines and recommendations for screening and treatment of high cholesterol, to prevent heart attacks in those affected. Using a stepped-wedge design, we plan to utilize tools from implementation science to improve uptake, acceptability, and sustainability of FH diagnostic programs in primary care settings. If successful, this study will provide tools generalizable to other health care systems to improve FH diagnosis rates.

PI_NAMEs: GIDDING, SAMUEL S (contact)

PROGRAM_OFFICER_NAME: MINTZER, KEITH A

PROJECT_TERMS: Address;Adherence;Adolescent;Adult;Affect;Age;Algorithms;Atherosclerosis;Awareness;cardiovascular disorder prevention;Cardiovascular system;Caring;cascade genetic testing;Child;Childhood;Cholesterol;Clinic;Clinical;clinical practice;clinical trial implementation;Clinical Trials;Code;collaborative approach;Community Health;Consent;Consultations;cost;Data;Data Science;design;Diagnosis;Diagnostic;diagnostic tool;Early Diagnosis;Early identification;Early treatment;Education;education planning;Educational Intervention;effectiveness/implementation hybrid;effectiveness/implementation trial;Electronic Health Record;Elements;Ethnic Origin;Evaluation;evidence base;evidence based guidelines;exome sequencing;Familial Hypercholesterolemia;Genetic Counseling;genetic counselor;Genetic Diseases;genetic testing;Genomics;Goals;Guidelines;Health;health assessment;health care settings;Healthcare Systems;human centered design;implementation framework;implementation measures;implementation research;implementation science;implementation strategy;implementation tool;improved;Individual;Informatics;insight;Insurance Coverage;Integrated Health Care Systems;interest;Intervention;Life;Link;Lipids;Longterm Follow-up;Low-Density Lipoproteins;Machine Learning;Managed Care;Measures;Medical;medical specialties;Modeling;Morbidity - disease rate;mortality;multidisciplinary;Myocardial Infarction;Outcome;Outcome Assessment;Output;Patient-Focused Outcomes;Patients;pediatric patients;Pediatrics;Pharmaceutical Preparations;premature;Prevalence;prevent;primary care clinician;primary care practice;primary care setting;primary outcome;Program Sustainability;programs;Race;Recommendation;Research;Resources;Rural;satisfaction;Schedule;Science;screening;screening guidelines;Self Efficacy;Services;Specialist;success;Testing;Time;tool;Translations;treatment optimization;United States;uptake;urban area;Work

PROJECT_TITLE: Collaborative Approach to Reach Everyone with Familial Hypercholesterolemia: CARE-FH


NIH_SPENDING_CATS: Aging;Bioengineering;Biomedical Imaging;Brain Disorders;Cerebrovascular;Clinical Research;Data Science;Health Services;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurosciences;Stroke

ORG_CITY: HOUSTON

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

PHR: PROJECT NARRATIVE With endovascular stroke therapy, we now have the ability to dramatically improve patient outcomes after stroke. To date, however, screening for patients that may benefit from this procedure has been relegated to larger academic centers, as the advanced imaging modalities required for this evaluation are not widely available. The goal of our proposal is to develop and validate machine learning-based software tools to identify patients eligible for endovascular stroke therapy using CT angiography, an imaging modality readily available in the vast majority of community hospitals.

PI_NAMEs: GIANCARDO, LUCA ;SHETH, SUNIL  (contact)

PROGRAM_OFFICER_NAME: BOSETTI, FRANCESCA

PROJECT_TERMS: Acute;Age;Algorithms;Angiography;Architecture;biomedical referral center;Blinded;Brain Injuries;brain tissue;Bypass;California;care delivery;Caring;Cause of Death;Cessation of life;Clinical;Clinical Data;Clinical Trials;Communities;community center;Community Hospitals;Computer software;cost;Country;Data;Data Set;Databases;deep learning;deep learning model;deep neural network;Dependence;Detection;Development;disability;Eligibility Determination;Evaluation;Foundations;Future;Goals;Guidelines;Heterogeneity;heterogenous data;Hospital Referrals;Hospitals;Hour;Human;Image;imaging capabilities;imaging modality;improved;Industry Standard;Infarction;Infrastructure;Institution;Intervention;Intravenous;Ionizing radiation;Ischemia;Ischemic Stroke;Location;Long term disability;loss of function;Machine Learning;Magnetic Resonance Imaging;Medical;Methods;Modality;Modeling;multimodality;multiple datasets;neural network architecture;neuroimaging;Neurological outcome;novel;novel strategies;Outcome;Patient imaging;patient screening;Patient-Focused Outcomes;Patients;Performance;Perfusion;perfusion imaging;Population Heterogeneity;post stroke;predictive modeling;Procedures;Protocols documentation;prototype;Qualifying;Race;Radiation exposure;Reader;Reproducibility;Research;Risk;screening;Services;sex;Software Tools;Source;Stretching;Stroke;stroke patient;stroke therapy;success;support tools;System;Testing;Texas;Therapy Evaluation;thrombolysis;Time;Tissues;tool;Training;United States;Validation

PROJECT_TITLE: Deep Learning Enabled Endovascular Stroke Therapy Screening in Community Hospitals

STUDY_SECTION: ANIE

STUDY_SECTION_NAME: Acute Neural Injury and Epilepsy Study Section[ANIE]