NIH_SPENDING_CATS: Cancer;Hematology;Orphan Drug;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Transplantation

ORG_DEPT: PHYSICAL MEDICINE & REHAB

PHR: Project Narrative The experiments in this proposal are aimed at elucidating the interaction between LSCs and their bone marrow niche in PMF. The information gained through this project will advance our understanding of the niche mechanisms that regulate LSCs. This may help identify novel therapeutic targets for PMF.

PI_NAMEs: DING, LEI  (contact)

PROJECT_TERMS: Acute Myelocytic Leukemia;Adult;Allogenic;Apoptotic;bone;Bone Marrow;Bone Marrow Cells;Cell Communication;Cell Cycle;Cell Death;Cells;Clinic;Collagen Fiber;Constitutional Symptom;cost;curative treatments;cytokine;Data;Deposition;design;Development;Disease;Disease remission;effective therapy;efficacy testing;experimental study;Fatty acid glycerol esters;Fibrosis;Fostering;Frequencies;Genetic;Hematopoiesis;Hematopoietic;Hematopoietic Stem Cell Transplantation;Hematopoietic stem cells;in vivo;inhibitor;JAK2 gene;Knowledge;leptin receptor;leukemia;Leukemic Cell;leukemic stem cell;Liver;Lung;Mediating;Mediator;Modeling;Molecular;Monoclonal Antibodies;mouse genetics;Mus;mutant;Mutation;Myelofibrosis;Myeloproliferative disease;Myofibroblast;Neoplasms;new therapeutic target;novel;novel therapeutics;Pathogenesis;Pathway interactions;Patients;Platelet-Derived Growth Factor alpha Receptor;prevent;Primary Myelofibrosis;Recurrence;Regulation;Reporting;Research;Reticulin;Retroviridae;Role;self-renewal;side effect;Skin;Source;SPI1 gene;Stem cell transplant;Stromal Cells;synergism;targeted treatment;Testing;Therapeutic;transcription factor;Transplantation;tumor microenvironment;Tyrosine Kinase Inhibitor

PROJECT_TITLE: Understanding and targeting bone marrow microenvironment in myelofibrosis

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


ADMINISTERING_IC: AI

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Genetics

ORG_CITY: MEMPHIS

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: ST. JUDE CHILDREN'S RESEARCH HOSPITAL

ORG_STATE: TN

PHR: Robust immune tolerance conferred by Foxp3 transcriptional regulation  Regulatory T cells actively suppress self-destructive T cells that cause a variety of autoimmune diseases. We propose to uncover the mechanisms governing the suppressive capacity of regulatory T cells conferred by their induction and lineage stability through their master regulator Foxp3.

PI_NAMEs: FENG, YONGQIANG  (contact)

PROGRAM_OFFICER_NAME: JIANG, CHAO

PROJECT_TERMS: Address;Adult;Affect;Algorithms;anti-tumor immune response;Antigen Targeting;Autoimmune Diseases;Autoimmunity;Biology;Buffers;Bypass;Cell Count;Cell Physiology;Cues;Defect;deprivation;Development;DNA Sequence;early onset;Enhancers;Epigenetic Process;epigenetic regulation;experimental study;FOXP3 gene;Gene Expression;Genes;Genetic;genetic element;Genetic Transcription;Genetic Variation;Goals;Immune;immune activation;Immune Tolerance;immunological status;Immunologics;Immunosuppression;Impairment;improved;Incidence;Individual;insight;Interleukin-2;Investigation;Life;life span;Literature;Maintenance;Measures;Mediating;Methods;mouse genetics;Mouse Strains;Mus;Mutant Strains Mice;Mutation;Nature;Neonatal;neonate;novel;Nuclear Protein;Operative Surgical Procedures;Outcome;Output;pharmacologic;Play;postnatal;Process;promoter;Regulation;Regulatory Element;Regulatory T-Lymphocyte;Reporting;Role;Severities;single-cell RNA sequencing;Specificity;T cell differentiation;T-Cell Receptor;T-cell receptor repertoire;T-Lymphocyte;Techniques;Testing;Thymectomy;Thymus Gland;tool;Transcription Process;Transcriptional Regulation;Uncertainty;Variant

STUDY_SECTION: CMIB

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


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging

ORG_CITY: TALLAHASSEE

ORG_DEPT: BIOLOGY

ORG_NAME: FLORIDA STATE UNIVERSITY

ORG_STATE: FL

PHR: Project Narrative The least understood parts of the striated muscle sarcomere are the thick filament, connecting filament and the Z-disk. Almost 40% of myopathy mutations occur in the thick filament backbone in which the coiled-coil myosin tails pack in order to bear the force produced by the myosin heads while another group of disease-causing mutations occur among proteins of the Z-disk, which anchors thin filaments into a bipolar array. This project seeks to understand through 3-D imaging of these three muscle components how mutations alter their structures resulting in defects of muscle function.

PI_NAMEs: TAYLOR, KENNETH ALLEN (contact)

PROGRAM_OFFICER_NAME: FLICKER, PAULA F

PROJECT_TERMS: Actins;Affect;Cardiac Myocytes;Chemicals;crosslink;Cryo-electron tomography;Cryoelectron Microscopy;Defect;Development;disease-causing mutation;Drosophila genus;Drosophila melanogaster;Electron Microscope;Elements;Excision;Filament;Freezing;Funding;Future;Genetic;Goals;Human;Hydration status;Image;image reconstruction;In Situ;Invertebrates;Investigation;Learning;Link;Methodology;Methods;Microscope;Molecular;Muscle;Muscle Cells;Muscle function;Mutation;Myofibrils;Myopathy;Myosin ATPase;nanometer resolution;Nucleotides;plasma protein Z;Plastic Embedding;Property;Proteins;Research Project Grants;Resolution;Sarcomeres;Signaling Protein;Smooth Muscle Myocytes;Striated Muscles;Structure;System;Tail;Thick Filament;Thin Filament;Thinness;Three-Dimensional Image;Three-Dimensional Imaging;Vertebral column;Visualization;Work

PROJECT_TITLE: cryoEM Studies of Muscle

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


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Neurosciences

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Neurons are highly polarized cells with a cell body, neuronal processes, and specialized sub-cellular structures. This polarity is essential for neuronal function, and requires the precise localization of RNA, proteins, and lipids to discrete neuronal compartments to ensure compartment-specific functions. This application will investigate mechanisms by which proteins are localized and enriched in axonal compartments to allow dynamic and compartmentalized responses to external growth-promoting signals. An improved knowledge of spatial modes of signaling in neurons is critical for a fundamental understanding of axon development and maintenance, and will guide new therapeutic measures for nerve repair after injury.

PI_NAMEs: KURUVILLA, REJJI  (contact)

PROGRAM_OFFICER_NAME: TYLER, WILLIAM A

PROJECT_TERMS: Acute;Address;Adult;Affect;Attenuated;Axon;axon growth;Biochemical;Biochemistry;Carbon;Cell Physiology;Cells;Coupled;Couples;Coupling;Cues;Cytoplasm;Development;Diameter;Distal;Endosomes;Ensure;Environment;Enzymes;experimental study;geranylgeranylation;Goals;Growth;Growth Cones;Homeostasis;Image;improved;in vivo;in vivo evaluation;Injury;Knowledge;Length;Life;Link;Lipids;Maintenance;Measures;Mediating;Messenger RNA;Modification;Monitor;Monomeric GTP-Binding Proteins;Morphology;mouse genetics;Mus;mutant;Natural regeneration;Nerve Growth Factors;nerve repair;nerve supply;Neurons;neurotrophic factor;NGFR Protein;novel therapeutics;permissiveness;pharmacologic;Phosphorylation;polarized cell;prenyl;prenylation;Presynaptic Terminals;Process;Protein Biosynthesis;protein expression;protein function;Protein Geranylgeranylation;protein geranylgeranyltransferase;Protein Isoprenylation;Protein Synthesis Inhibition;Proteins;recruit;Regulation;repaired;response;RNA;Role;Signal Transduction;spatiotemporal;Subcellular structure;Sympathetic Ganglia;Testing;Tissues;trafficking;Translations

PROJECT_TITLE: Coupled axonal protein synthesis and lipidation in axon growth and homeostasis

STUDY_SECTION: NDPR

STUDY_SECTION_NAME: Neurodifferentiation, Plasticity, Regeneration and Rhythmicity Study Section[NDPR]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

PHR: Narrative Overall Program The central theme of our PPG is that high-density lipoprotein (HDL) function is a critical determinant of atherosclerosis (plaque buildup in arteries) in chronic human diseases associated with increased risk of heart attack and stroke. Specifically, this Program will study diverse detrimental changes to HDL cargo and function, including 1) reactive dicarbonyl modifications to HDL lipids and proteins, 2) pro-inflammatory microbial small RNAs on HDL, and 3) molecular networks within a novel kidney-intestine-artery axis. In addition, we explore new therapeutic strategies to improve HDL function and reduce atherosclerosis using dicarbonyl scavengers and non-targeting locked-nucleic acids (ntLNA).

PI_NAMEs: LINTON, MACRAE F (contact)

PROGRAM_OFFICER_NAME: LIU, LIJUAN

PROJECT_TERMS: Acceleration;adduct;analog;Apoproteins;Arterial Fatty Streak;Arteries;atherogenesis;atheroprotective;Atherosclerosis;atherosclerosis risk;Bioinformatics;Biometry;cardiovascular risk factor;Cardiovascular system;Cell Death;chemical synthesis;Cholesterol;Chronic;Chronic Kidney Failure;Data Analyses;Development;Disease;Endocytosis;Ensure;Environment;Event;Experimental Designs;Familial Hypercholesterolemia;Functional disorder;functional loss;Gene Expression;Goals;Heterozygote;high density lipoprotein-3;High Density Lipoproteins;Human;human disease;Impairment;improved;in vivo;Inflammation;Inflammatory;Intestines;Kidney;Lesion;Lipid Peroxidation;Lipids;Lipoproteins;locked nucleic acid;Low Density Lipoprotein oxidation;Lymphatic;lymphatic dysfunction;Lysine;Macrophage;Measurement;mesenteric lymphatics;microbial;microbiome;MicroRNAs;Modeling;Modification;Molecular;Multiomic Data;Mus;Myocardial Infarction;NAPE-PLD;Necrosis;novel;novel therapeutic intervention;Output;particle;Pathogenicity;Phospholipids;Plasma;programs;Proteins;receptor;Research;Residual state;Resolution;Rheumatoid Arthritis;Risk;Role;small molecule;Small RNA;Stroke;Structure;Testing;TLR7 gene;transcriptome sequencing;Untranslated RNA

PROJECT_TITLE: HDL Function in Human Disease

STUDY_SECTION: HLBP

STUDY_SECTION_NAME: Heart, Lung, and Blood Program Project Study Section[HLBP(OA)]


PROJECT_TERMS: Animals;Award;Bioinformatics;Biometry;Biostatistics Core;Budgets;Code;Communication;Data Analyses;Documentation;Ensure;Equipment;Expenditure;Experimental Designs;Grant;High Density Lipoproteins;human disease;human subject;Institutional Policy;meetings;Methods;model development;Policies;Procedures;Reagent;Reporting;Reproducibility;Research Personnel;Services;simulation;Travel;Untranslated RNA;Validation;Work

PROJECT_TITLE: Administration and Biostatistics Core

STUDY_SECTION_NAME: Heart, Lung, and Blood Program Project Study Section[HLBP]


ADMINISTERING_IC: CA

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Cancer Genomics;Genetics;Human Genome;Lung;Lung Cancer;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Precision Medicine;Prevention

ORG_CITY: ANN ARBOR

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE Leveraging the rich Boston Lung Cancer Survival Cohort (BLCSC) database with 11,164 lung cancer cases, we aim to develop new statistical methods to identify novel biomarkers linked to lung cancer. The BLCSC was the first study that discovered the relevance of EGFR mutations to treatment response in 2004, starting the era of targeted therapy. The findings from the proposal will potentially further impact the medical practice, with our strong collaborative team, rich databases and sound statistical methodologies.

PI_NAMEs: LI, YI  (contact)

PROGRAM_OFFICER_NAME: CHEN, HUANN-SHENG

PROJECT_TERMS: Biological Markers;Boston;Cancer Model;Cancer Prognosis;cancer risk;cancer survival;Cations;Chronic Obstructive Pulmonary Disease;Clinical;clinical risk;cohort;Cohort Studies;Computer software;Cox Proportional Hazards Models;Dana-Farber Cancer Institute;Data;Data Reporting;Databases;Dependence;design;dietary;Disease Outcome;disorder prevention;DNA;DNA Methylation;DNA Sequence Alteration;Enrollment;Ensure;Epidermal Growth Factor Receptor;Epigenetic Process;feature detection;feature selection;Gene Chips;Gene Expression;gene network;General Hospitals;Genes;Genetic;Genetic Variation;Goals;Heterogeneity;high dimensionality;Image;Individual;interest;kernel methods;Learning;learning strategy;Leukocytes;Linear Models;Link;Literature;Long-Term Survivors;Malignant neoplasm of lung;Malignant Neoplasms;Massachusetts;Medical;Methodology;Methods;Methylation;Modeling;Modification;Molecular;molecular marker;mortality;Mutate;Mutation;mutational status;novel;novel marker;Oncogenic;open source;Outcome;Pathology;Pathway interactions;Performance;Play;precision medicine;Procedures;Prognostic Marker;prognostic value;Proportional Hazards Models;quantitative imaging;radiomics;Research Personnel;Risk Factors;Role;Sample Size;Serum;sex;Site;Smoking;Solid;sound;Statistical Methods;Statistical Models;Structure;survival outcome;targeted treatment;Texture;transcriptome;transcriptome sequencing;Treatment outcome;treatment response;treatment strategy;tumor;Tumor Tissue;Uncertainty;Work

PROJECT_TITLE: New Statistical Methods for Modelling Cancer Outcomes

STUDY_SECTION: BMRD

STUDY_SECTION_NAME: Biostatistical Methods and Research Design Study Section[BMRD]


ED_INST_TYPE: SCHOOLS OF MEDICINE

NIH_SPENDING_CATS: Autism;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Genetics;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Pediatric;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: LA JOLLA

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

ORG_STATE: CA

PHR: Narrative The proposed research is relevant to public health because autism spectrum disorder (ASD) and intellectual disability are pervasive and debilitating disorders of childhood, with no targeted treatments. MEF2C Haploinsufficiency Syndrome (MHS) or 5q14.3 microdeletion syndrome are severe neurodevelopmental disorders with autism like features and destructive outcomes in affected children that result from loss of expression of the transcription factor MEF2C. This project is relevant to the NIH’s mission to enhance life and reduce disability, with a goal of understanding the role and regulation of intellectual disability and autism-linked genes like MEF2C in microglia and their resulting contribution to ASD pathology to identify novel potential therapeutic targets.

PI_NAMEs: COUFAL, NICOLE GABRIELE (contact)

PROGRAM_OFFICER_NAME: DOSS, ARGENIA LANISHA NECOLE

PROJECT_TERMS: Affect;Aging;Alleles;Anti-Inflammatory Agents;autism spectrum disorder;autistic children;Behavioral;Behavioral Assay;behavioral phenotyping;Biological Models;Brain;cell type;Cells;Cerebrum;Child;Childhood;chromatin immunoprecipitation;Clustered Regularly Interspaced Short Palindromic Repeats;Coculture Techniques;Communication;Data;Data Set;density;Dependence;Development;Developmental Disabilities;Diagnosis;disability;Disease;Drug Screening;Drug Utilization;effective therapy;Engraftment;Enhancers;Environment;Epigenetic Process;Functional disorder;Gene Expression;gene network;Genes;Genetic Transcription;Genomics;glial cell development;Goals;Heterozygote;Human;human data;Immunity;Impairment;improved outcome;In Vitro;in vivo;in vivo Model;induced pluripotent stem cell;Inflammation Mediators;Inflammatory;insight;Intellectual functioning disability;Interleukin-10;Interleukin-6;Knowledge;Life;Link;Macrophage;Maps;Measurement;Measures;Mediating;Methods;microdeletion;Microglia;migration;Mission;Modeling;motor behavior;Mus;Mutation;myocyte-specific enhancer-binding factor 2;myocyte-specific enhancer-binding-factor 2C;nerve stem cell;neurodevelopment;Neurodevelopmental Deficit;Neurodevelopmental Disorder;Neurons;new therapeutic target;novel;Organoids;Outcome;Pathogenesis;Pathology;Pathway interactions;Phagocytosis;Pharmacological Treatment;Phenotype;pre-clinical;Prosencephalon;Public Health;Regulation;Reporting;Research;response;Role;Science;social;Social Behavior;social deficits;Social Interaction;stem cell model;Stimulus;Synapses;synaptic pruning;Syndrome;System;Techniques;Testing;Therapeutic;therapeutic target;Thick;transcription factor;transcriptomics;United States;United States National Institutes of Health

PROJECT_TITLE: The Contribution of Microglial MEF2C to Brain Development

STUDY_SECTION: CMBG

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


NIH_SPENDING_CATS: Cancer

ORG_CITY: TAMPA

ORG_NAME: H. LEE MOFFITT CANCER CTR & RES INST

PHR: MDMX is a key regulator of p53 DNA binding and transcriptional activity. Elucidating the structure and regulation of MDMX is essential for development of novel cancer therapeutics. Our recent work revealed that phosphorylation sites in intrinsically disordered regions of MDMX play important roles in regulating MDMX interaction with p53 and other cellular proteins, and are important for efficient activation of p53 during DNA damage response. This proposal will further investigate how MDMX phosphorylation sites in disordered regions regulate its structure and function using molecular biology and NMR spectrometry. These experiments will advance the understanding of how stress signals activate p53 by regulating MDMX-p53 interaction, and may reveal novel strategy for targeting MDMX.

PI_NAMEs: CHEN, JIANDONG  (contact);DAUGHDRILL, GARY W

PROGRAM_OFFICER_NAME: AMIN, ANOWARUL

PROJECT_TERMS: Affinity;Allosteric Regulation;Avidity;Binding;Binding Sites;Biological;biophysical techniques;cancer therapy;Complex;Development;Disease;DNA Binding;DNA Binding Domain;DNA Damage;Drug Targeting;experimental study;flexibility;Generations;Genetic Transcription;Gymnastics;Homologous Gene;Human;In Vitro;in vivo;inhibitor;insight;intermolecular interaction;Knowledge;Length;Malignant Neoplasms;Maps;MDM2 gene;Measurement;Mediating;Modeling;Molecular;Molecular Biology;Molecular Conformation;NMR Spectroscopy;novel;novel strategies;Nuclear Translocation;overexpression;Pathway interactions;Phosphorylation;Phosphorylation Inhibition;Phosphorylation Site;Play;Proteins;Regulation;Relaxation;resistance mechanism;response;Role;Signal Transduction;small molecule;Spectrometry;Stress;Structure;Surface;Testing;Therapeutic;TP53 gene;tumor;Work

PROJECT_TITLE: Allosteric Regulation of MDMX by Protein Disorder

STUDY_SECTION: TCB

STUDY_SECTION_NAME: Tumor Cell Biology Study Section[TCB]


PROJECT_TERMS: Anti-Inflammatory Agents;Antiatherogenic;Antiinflammatory Effect;Apolipoprotein A-II;Apoproteins;atheroprotective;Atherosclerosis;atherosclerosis risk;Biological Assay;Cholesterol;Chronic Kidney Failure;cost;Cost Analysis;Development;Disease;experimental study;Familial Hypercholesterolemia;Functional disorder;Goals;Health Services Accessibility;High Density Lipoproteins;human disease;Impairment;in vitro Assay;Individual;Inflammation;Inflammatory;instrumentation;Laboratories;Lipoproteins;Macrophage;Mediation;method development;Methodology;Methods;oxidation;Post-Translational Protein Processing;Preparation;Procedures;Process;Protein Analysis;Research;Research Personnel;Research Project Grants;reverse cholesterol transport;Rheumatoid Arthritis;Science;Services;Standardization;Training and Education

PROJECT_TITLE: Lipoprotein and HDL Function Core


NIH_SPENDING_CATS: Genetics;Human Genome

ORG_CITY: DAVIS

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: Project Narrative In all life forms on earth, DNA carries the hereditary genetic information. Transcription copies DNA into RNA, a key process that permits gene expression. On occasion, the nascent RNA can become entangled with the DNA, resulting in an alternative three-stranded nucleic acid structure called an R-loop. R-loops form universally under normal conditions and are thought to play physiological roles in cells, including human cells. Studies have suggested, however, that under conditions where transcription is perturbed, harmful R-loops are created, leading to DNA breaks and chromosome anomalies. What distinguishes “good” from “harmful” R-loops remains unknown. Similarly, how harmful R-loops arise as a result of perturbed transcription is unclear. Using innovative technologies developed by my group, we will characterize the formation of so-called harmful R- loops under conditions of perturbed transcription in human cells. We will also determine whether harmful R- loops, or perturbed transcription itself, are the cause of the DNA breaks. Finally, we will determine if an enzyme known to relieve the DNA break problem is acting by resolving harmful R-loops or remediating the altered transcription. This work will benefit our understanding of fundamental cellular processes acting in our genome and will provide insights into a range of human disorders linked to perturbed transcription.

PI_NAMEs: CHEDIN, FREDERIC LOUIS (contact)

PROGRAM_OFFICER_NAME: KRASNEWICH, DONNA M

PROJECT_TERMS: Address;Attention;Biochemical;Biogenesis;Cell model;Cell Physiology;Cells;Chromosome abnormality;Data;Defect;Disease;DNA;DNA Damage;DNA Structure;DNA-Directed RNA Polymerase;Enzymes;Functional disorder;Gene Expression;genetic information;Genetic Transcription;Genome;Genomic Instability;Genomics;Human;Inherited;innovative technologies;insight;Knowledge;Life;Light;Link;Maintenance;Mammalian Cell;Mammals;Measures;Metabolism;Monitor;Nuclear;nucleic acid structure;overexpression;Pathway interactions;Pattern;Phenotype;Physiological;Planet Earth;Play;Process;remediation;Resolution;ribonuclease H1;RNA;RNA Processing;RNA Splicing;Role;Structure;Time;Work;Yeasts

PROJECT_TITLE: Understanding the mechanisms underlying R-loop biogenesis and resolution in mammals

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


NIH_SPENDING_CATS: Atherosclerosis;Cardiovascular

PI_NAMEs: DAVIES, SEAN STEPHEN (contact)

PROJECT_TERMS: adduct;analog;Animal Model;Animals;Atherosclerosis;atherosclerosis risk;Biological;Blood;Cell model;Chemicals;Chronic Kidney Failure;Cultured Cells;Disease;Ensure;experimental study;F2-Isoprostanes;Familial Hypercholesterolemia;Functional disorder;Goals;Half-Life;High Density Lipoproteins;Human;human disease;in vivo;Individual;Instruction;instrumentation;Investigation;Lipid Peroxidation;Lipids;Liquid substance;Lysine;Malondialdehyde;Measurement;Measures;Medicine;Metabolism;methyl group;Modification;Participant;Phosphatidylethanolamine;Post-Translational Protein Processing;programs;Proteins;Pyridoxamine;Reaction;Reagent;Research Personnel;Rheumatoid Arthritis;Role;Sampling;small molecule;Testing;Tissue Sample;Tissues;Vitamin B6

PROJECT_TITLE: Lipid Peroxidation Analytical Core


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Contraception/Reproduction;Mental Health;Neurosciences;Pediatric

ORG_CITY: CAMBRIDGE

ORG_DEPT: PSYCHOLOGY

ORG_NAME: HARVARD UNIVERSITY

ORG_STATE: MA

PHR: PROJECT NARRATIVE The proposed research will use two of the largest datasets on child and adolescent neurodevelopment in existence to inform how puberty influences the development of the brain and emerging risk for mental illness. Using measures of puberty and hormones, paired with multiple metrics of brain development, we will disentangle the relationship between age, puberty, and hormone concentrations and brain development, and establish how different measures of brain development interrelate across puberty. In addition, we will examine the neurodevelopmental mechanisms that help explain why early puberty increases an individual’s risk for mental health problems including depression and anxiety.

PI_NAMEs: BARCH, DEANNA ;SOMERVILLE, LEAH HELENE (contact)

PROGRAM_OFFICER_NAME: ZEHR, JULIA L

PROJECT_TERMS: Acceleration;Address;Adolescence;Adolescent;Age;Anxiety;Attention;Behavioral;Biological Assay;boys;Brain;Brain imaging;brain pathway;Child;Childhood;Clinical;cognitive development;cohort;connectome;Coupling;Data;data analysis pipeline;data modalities;Data Set;Development;emerging adult;Ensure;Ethnic Origin;Evaluation;Foundations;Funding;girls;Goals;Hormonal;Hormones;Human;human data;Individual;informant;Investigation;Link;Literature;Longitudinal cohort;Longitudinal Studies;Measures;Mediating;Mental Depression;Mental disorders;Mental Health;Methods;Modality;Modeling;multimodal modeling;multimodality;neurodevelopment;novel;Pathway interactions;Patient Self-Report;Process;Psychopathology;pubertal timing;Puberty;puberty transition;Race;Research;Risk;Sampling;Socioeconomic Status;Structure;Symptoms;System;Testing;Time;United States National Institutes of Health;Variant;Work;Youth

PROJECT_TITLE: Characterizing pubertal and age mechanisms of neurodevelopment and association with rising internalizing symptoms

STUDY_SECTION: CPDD

STUDY_SECTION_NAME: Child Psychopathology and Developmental Disabilities Study Section[CPDD]


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

ORG_DEPT: PHARMACOLOGY

PHR: PROJECT NARRATIVE One type of phospholipase A2 controls the biosynthesis of eicosanoids central to inflammation, another type controls incorporation of polyunsaturated fats (PUFAs) into phospholipids, one acts to remove oxidized lipids, and another is critical to the functioning of macrophage cells, while a triacylglycerol lipase plays a critical role in fatty liver disease. Understanding how the activity of these critically important enzymes are controlled, regulated and inhibited will lead to the development of clinical interventions to control disease.

PI_NAMEs: DENNIS, EDWARD A (contact)

PROGRAM_OFFICER_NAME: BARSKI, OLEG

PROJECT_TERMS: Address;Adopted;Allosteric Site;Anabolism;Biological Assay;Calmodulin;Catalytic Domain;Cells;clinical development;disorder control;Drug Targeting;Eicosanoids;Enzymes;Fatty Acids;fatty liver disease;genome wide association study;Goals;Grant;group V secretory phospholipase A2;Hispanic Populations;Human;Hydrolase;In Vitro;Inflammation;interest;Intervention;Learning;Lipase;lipidomics;Lipids;lipoprotein-associated phospholipase A(2);macromolecule;Macrophage;Measures;member;Membrane;Methods;Micelles;Molecular;Molecular Conformation;mutant;Mutation;Nature;non-alcoholic fatty liver disease;nonalcoholic steatohepatitis;novel;oxidized lipid;Phosphatidylinositol 4,5-Diphosphate;Phospholipase;Phospholipase A2;Phospholipids;Physiological;Platelet Activating Factor;Play;polyunsaturated fat;Proteins;Recombinants;Regulation;Role;Specificity;Triglycerides;Water;Work

PROJECT_TITLE: Action of Lipolytic Enzymes


ORG_CITY: MADISON

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: PROJECT NARRATIVE The development of new life-saving medicines requires access to new chemical structures with unprecedented structures. We are interested in designing new reactions that harness the energy of light to generate highly reactive intermediates that engage in reactions that cannot be accomplished using standard non-photochemical strategies. The focus of our research is the design of catalysts that can control the outcomes of these high-energy reactions in predictable ways.

PI_NAMEs: YOON, TEHSHIK P (contact)

PROGRAM_OFFICER_NAME: YANG, JIONG

PROJECT_TITLE: SYNTHETIC PHOTOCHEMISTRY

STUDY_SECTION: MRAB

STUDY_SECTION_NAME: Maximizing Investigators’ Research Award B Study Section[MRAB]


PI_NAMEs: VICKERS, KASEY C (contact)

PROJECT_TERMS: Academic Medical Centers;analysis pipeline;Area;Atherosclerosis;Award;Bioinformatics;Biometry;Biotechnology;ChIP-seq;Chromium;Chronic Kidney Failure;Collaborations;Communication;Complex;Data Analyses;data integration;data management;Data Set;Dedications;design;Equipment;experience;experimental study;extracellular;Familial Hypercholesterolemia;Functional disorder;Funding;Genes;Genetic Transcription;Genomics;Goals;Grant;High Density Lipoproteins;High-Throughput Nucleotide Sequencing;High-Throughput RNA Sequencing;human disease;Human Resources;Individual;Informatics;Joints;laboratory experience;Lead;Leadership;Libraries;Lipoproteins;member;Messenger RNA;Methods;Modification;Multiomic Data;multiple omics;next generation;Preparation;programs;Proteins;Protocols documentation;Publications;Quality Control;Recommendation;Recording of previous events;Research;Research Design;Research Personnel;Resources;Ribosomal RNA;RNA;RNA analysis;RNA immunoprecipitation sequencing;Science;service programs;Services;single-cell RNA sequencing;skills;Small RNA;success;System;Technology;Testing;tool;Training;transcriptome sequencing;transcriptomics;Transfer RNA;Universities;Untranslated RNA;Work

PROJECT_TITLE: Non-Coding RNA Analytical Core


NIH_SPENDING_CATS: Amyotrophic Lateral Sclerosis (ALS);Brain Disorders;Neurodegenerative;Neurosciences;Rare Diseases

ORG_CITY: GAINESVILLE

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF FLORIDA

PHR: Amyotrophic lateral sclerosis (ALS) stands out as an example where clinicians can observe weakness begin in a hand or foot, before progressively spreading to adjacent limbs and beyond to produce generalized paralysis. In the initial funding period of this award, our laboratory has uncovered evidence that this defining progressive phenotypic feature of SOD1-ALS may be explained by prion-like characteristics of mutant SOD1 as it spreads along neuroanatomically connected pathways. In the renewal application, we will focus on determining the contribution of intrinsic strain-like attributes of SOD1 mutants and extrinsic non-cell autonomous processes that may govern the prion-like spread of disease-causing SOD1 conformations.

PI_NAMEs: BORCHELT, DAVID R (contact);CHAKRABARTY, PARAMITA

PROGRAM_OFFICER_NAME: GUBITZ, AMELIE

PROJECT_TERMS: Acceleration;Age;Amyotrophic Lateral Sclerosis;Anatomy;Animals;Anti-Inflammatory Agents;Astrocytes;Attention;Award;Biological;Biological Models;Biology;Central Nervous System;Characteristics;cytokine;Data;design;Disease;Disease Progression;disease-causing mutation;early onset;encryption;Exhibits;familial amyotrophic lateral sclerosis;foot;Funding;Goals;Hand;Human;illness length;improved;In Vitro;Individual;Inflammatory;Inherited;Injections;insight;Laboratories;Life;Limb structure;Link;Literature;Microglia;misfolded protein;Modeling;Molecular Conformation;Motor Neuron Disease;Mus;mutant;Mutation;Nerve Degeneration;Neuroanatomy;Neurodegenerative Disorders;neuroinflammation;Neurons;Newborn Infant;novel;Paralysed;Pathogenesis;Pathologic;Pathology;Pathway interactions;Patients;permissiveness;Phenotype;Population;Preparation;prion-like;Prions;Process;Property;Protein Conformation;Proteins;Reaction;Recombinant adeno-associated virus (rAAV);Recombinants;Research;Resistance;Role;Route;sciatic nerve;selective expression;Signal Transduction;Site;Source;Spinal;Spinal Cord;success;superoxide dismutase 1;Tissues;Transgenic Mice;transmission process;Variant;vector;Visualization;Work;young adult

PROJECT_TITLE: Modeling the progression of SOD1-linked motor neuron disease

STUDY_SECTION: CMND

STUDY_SECTION_NAME: Cellular and Molecular Biology of Neurodegeneration Study Section[CMND]


NIH_SPENDING_CATS: Neurodegenerative;Neurosciences

PHR: Project Narrative Defects in mitochondria structure and function have been linked to human health problems including metabolic syndrome, cardiovascular diseases, and neurodegeneration. This proposal aims to determine fundamental mechanisms that control structure, turnover, and safeguarding of mitochondria. The successful completion of this work will provide major insights into the pathogenesis and treatment of human disease.

PI_NAMEs: SESAKI, HIROMI  (contact)

PROGRAM_OFFICER_NAME: ANSONG, CHARLES KWAKU

PROJECT_TERMS: age related neurodegeneration;biological adaptation to stress;Biology;Cardiac Myocytes;Cardiovascular Diseases;Cell Death;Cells;Charcot-Marie-Tooth Disease;Complex;Contracts;Defect;Disease;Dynamin;Endoplasmic Reticulum;Equilibrium;Event;Evolution;experimental study;Feedback;Goals;Grant;Guanosine Triphosphate Phosphohydrolases;Health;Human;human disease;Immune;in vivo;insight;Intervention;Label;Laboratories;Life;Link;Logic;Mediating;Membrane;Membrane Fusion;Metabolic syndrome;Mitochondria;Mitochondrial Proteins;Molecular;Monitor;Mus;Mutate;Nerve Degeneration;Neurodevelopmental Disorder;Neuronal Differentiation;Neuropathy;OPA1 gene;Optic Atrophy;Organelles;Parkin;Pathogenesis;Pathway interactions;Phase;Physiological;PINK1 gene;Proteins;Reaction;Regulation;response;Role;Shapes;Site;stem cells;Structure;Translating;ubiquitin ligase;Ubiquitination;Work

PROJECT_TITLE: Structure, Turnover and Safeguard of Mitochondria

STUDY_SECTION: MRAC

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


NIH_SPENDING_CATS: Aging;Atherosclerosis;Cardiovascular;Clinical Research;Heart Disease;Heart Disease - Coronary Heart Disease;Prevention

PROJECT_TERMS: adduct;Anti-Inflammatory Agents;Antiatherogenic;Antibodies;Antiinflammatory Effect;Antioxidants;Arterial Fatty Streak;atheroprotective;Atherosclerosis;autosome;cardiovascular disorder risk;cardiovascular risk factor;CD36 gene;CETP gene;Cholesterol;clinical translation;Coronary Arteriosclerosis;Development;Disease;disorder risk;Drug Kinetics;epidemiology study;Event;Failure;Familial Hypercholesterolemia;Fourier Analysis;Generations;Goals;Heterozygote;High Density Lipoproteins;Human;human disease;Impairment;improved;Inflammation;Inflammatory;inhibitor;Interleukin-1 beta;LDLR gene;Lesion;Lipids;Low Density Lipoprotein oxidation;Low-Density Lipoproteins;Macrophage;macrophage scavenger receptors;Mediating;Mediation;Mendelian randomization;Metabolism;Modeling;Modification;Mus;Mutation;Necrosis;Nicotinic Acids;Patients;phase 1 study;Phospholipids;Plasma;Play;Post-Translational Protein Processing;premature;preservation;prevent;Recurrence;Regulatory T-Lymphocyte;Residual state;Resolution;reverse cholesterol transport;Risk;Role;Safety;secondary analysis;Serum;small molecule;Small RNA;targeted treatment;Testing;Therapeutic;Therapeutic Agents;translational study;Uncertainty

PROJECT_TITLE: Dicarbonyl Scavengers to Improve HDL Function and Reduce Atherosclerosis in FH


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Drug Abuse (NIDA only);Neurosciences;Substance Misuse

ORG_CITY: MINNEAPOLIS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Project Narrative Drug addiction is among the most devastating and costly public health care conditions. A major factor in addiction is compulsive reward-seeking driven by the incentive motivational value of reward-associated cues. The proposed studies will examinine how the brain represents the incentive value of cues, and the neural circuit mechanisms by which these cues drive motivated behavior.

PI_NAMEs: RICHARD, JOCELYN M (contact)

PROGRAM_OFFICER_NAME: MOORE, HOLLY MARIE

PROJECT_TERMS: Abstinence;addiction;adverse outcome;Affect;alcohol seeking behavior;basal forebrain;Behavior;Behavior Control;Behavioral Mechanisms;behavioral response;Brain;brain based;calcium indicator;Calcium Signaling;cocaine seeking;Complex;Conditioned Stimulus;cost;Cues;Decision Making;Drug Addiction;Drug usage;Electrophysiology (science);Emotional;Fiber;Fluorescence;Future;gamma-Aminobutyric Acid;Globus Pallidus;Goals;Healthcare;in vivo;Incentives;Individual;Knowledge;Measures;mental representation;Modeling;motivated behavior;Motivation;Motor output;neural;neural circuit;neural model;neuromechanism;Neurons;neuropsychiatric disorder;neuroregulation;neurotransmission;Nucleus Accumbens;optogenetics;Outcome;outcome prediction;Output;Pathway interactions;Pattern;Pharmaceutical Preparations;Photometry;Population;Positive Reinforcements;Predictive Value;Property;Public Health;Punishment;Rattus;Relapse;Research;Rewards;Role;Signal Transduction;Stimulus;Structure;targeted treatment;Testing;Thalamic structure;Time;Ventral Tegmental Area;Virus;Work

PROJECT_TITLE: Neural basis of incentive and expected value representations

STUDY_SECTION: NMB

STUDY_SECTION_NAME: Neurobiology of Motivated Behavior Study Section[NMB]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Aging;Clinical Research;Eye Disease and Disorders of Vision;Genetics;Human Genome;Neurodegenerative;Neurosciences

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS EYE AND EAR INFIRMARY

PHR: Project Narrative Elevated eye pressure is a common, potentially blinding complication of steroid treatments used for many eye diseases. We do not completely understand why only some people develop high eye pressures when treated with steroids. Our study aims to uncover the genetic risk factors for developing high eye pressures from steroids, and the insights gained could help avoid this treatment complication.

PI_NAMEs: SOBRIN, LUCIA  (contact)

PROGRAM_OFFICER_NAME: SONG, HONGMAN

PROJECT_TERMS: Alternative Therapies;Antiinflammatory Effect;biobank;Blindness;cell type;Cells;Clinical;Clinical Management;Code;cohort;Complication;cost efficient;Data;Development;Dexamethasone;Disease;Disease Outcome;DNA;Ear;Endothelial Cells;Enrollment;Exhibits;exome;exome sequencing;exposed human population;Exposure to;Eye;Eye diseases;Family history of;follow-up;Formulation;Functional disorder;Genes;Genetic;Genetic Predisposition to Disease;genetic risk factor;Genetic study;Genetic Transcription;genetic variant;Genetic Variation;Genome;genome wide association study;genome-wide;genomic data;Genotype;Glaucoma;Glucocorticoids;Healthcare;high risk;Human;in silico;Injections;insight;Massachusetts;Measurement;Medicine;Methods;Morbidity - disease rate;novel;Ocular Hypertension;Open-Angle Glaucoma;Ophthalmology;Optic Nerve;Participant;Patients;Persons;pharmacologic;Phenotype;Physiologic Intraocular Pressure;Predisposition;pressure;Primary Open Angle Glaucoma;Probability;rare variant;Recording of previous events;recruit;Response Elements;Risk;Risk Factors;Sample Size;Sampling;screening;Source;steroid hormone;Steroids;Structure of sinus venosus of sclera;surveillance strategy;Susceptibility Gene;targeted sequencing;Testing;Trabecular meshwork structure;trait;Transcript;transcriptome;transcriptome sequencing;Untranslated RNA;Validation;Variant;variant detection

PROJECT_TITLE: Elucidating novel mechanisms for glucocorticoid-induced ocular hypertension


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Diabetes

ORG_CITY: MILWAUKEE

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

PHR: PROJECT NARRATIVE Dysfunction of insulin secretion causes diabetes. This work investigates the molecular mechanism by which the cortical actin web of β cells regulates glucose-stimulated insulin granule secretion. The results from this work will inform new knowledge of the nanoscale remodeling of the actin cortex in insulin release, a question that is largely unknown yet critical to preserve and restore β cell function in diabetes.

PI_NAMEs: LOU, XUELIN  (contact)

PROGRAM_OFFICER_NAME: SECHI, SALVATORE

PROJECT_TERMS: Ablation;Actins;Acute;Address;Adult;Animals;Automobile Driving;beta Actin;Beta Cell;Biological Assay;blood glucose regulation;cell cortex;Cell Physiology;Cellular biology;cellular imaging;clinically relevant;Complex;confocal imaging;Cytoplasmic Granules;Data;Diabetes Mellitus;diabetes pathogenesis;Docking;Dynamin;Exocytosis;F-Actin;Functional disorder;Genes;Genetic;Genetic Models;Genetic study;Glucose;Human;Image;Imaging Techniques;Impairment;In Vitro;in vivo;insight;Insulin;insulin granule;insulin regulation;insulin secretion;Integrins;Internet;Investments;islet;Knowledge;live cell imaging;Mediating;Membrane;Metabolic;Microfilaments;Microscopy;Molecular;mouse model;Mus;nano;nanoscale;Nanostructures;Non-Insulin-Dependent Diabetes Mellitus;novel;novel therapeutics;Patients;Plasma;Play;polymerization;Polymers;preservation;prevent;Process;recruit;Regulation;Reporting;Research;Research Personnel;Resolution;Role;Signal Pathway;Signal Transduction;Structure;superresolution imaging;superresolution microscopy;Testing;tool;trafficking;Vesicle;Work

PROJECT_TITLE: ArpC3-mediated actin remodeling in insulin granule exocytosis and diabetes

STUDY_SECTION: CSME

STUDY_SECTION_NAME: Cell Signaling and Molecular Endocrinology Study Section[CSME]


NIH_SPENDING_CATS: Biotechnology;Eye Disease and Disorders of Vision;Genetics;Infectious Diseases;Sexually Transmitted Infections

ORG_CITY: FARMINGTON

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT

ORG_STATE: CT

PHR: Herpes Simplex Virus Types 1 and 2 (HSV-1 and HSV-2), are ubiquitous human pathogens responsible for oral, genital and sight-threatening ocular infections that can be life threatening even in immunocompetent adults. In individuals with compromised immune systems, HSV infections are often fatal. Our goal is to contribute to the understanding of mechanisms underlying replication of this virus and to provide information that will lead to novel and effective antiviral therapies.

PI_NAMEs: WELLER, SANDRA K (contact);WRIGHT, DENNIS L.

PROGRAM_OFFICER_NAME: DUPUY, LESLEY CONRAD

PROJECT_TERMS: Adult;Affect;Age;Anti-viral Therapy;Bacteria;Bacteriophage lambda;Binding;Biochemical;biophysical techniques;Blindness;C-terminal;Cell Physiology;Cells;Communicable Diseases;Complex;Complication;Cornea;Data;Disease;DNA;DNA biosynthesis;DNA Damage;DNA Repair Gene;DNA Viruses;Double Stranded DNA Virus;Encephalitis;Eye Infections;Filament;Genetic;Genetic Engineering;Genetic Recombination;Genitalia;Genome;Goals;Growth;Head;Herpes Labialis;Herpes Simplex Infections;Herpesviridae;Herpesvirus 1;Human;Human Herpesvirus 2;human pathogen;Hydrophobicity;Immune system;Immunocompetent;in vivo;Individual;Infection;Insecta;insight;Keratitis;latent infection;Lesion;Life;Mammals;Mediating;Modeling;neonatal infection;Nonhomologous DNA End Joining;novel;nuclease;Nucleoproteins;Oral;Organism;Pathway interactions;Periodicals;Persons;Plants;Play;Population;Process;Production;Productivity;protein protein interaction;Proteins;Proteomics;Protozoa;recombinase;recruit;Recurrence;Replication Initiation;Replication Origin;Replication-Associated Process;Reporting;response;Role;Shoulder;Simplexvirus;Single-Stranded DNA;spleen exonuclease;SS DNA BP;System;Testing;Time;Viral;viral DNA;Viral Genome;Viral Proteins;viral transmission;Virion;Virus;Virus Replication;Virus Shedding;Vision;Widespread Disease

PROJECT_TITLE: Genetics of HSV DNA Replication

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IDM-W(02)M]


ADMINISTERING_IC: DE

ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cancer;Dental, Oral, and Craniofacial Disease;Digestive Diseases;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Prevention;Rare Diseases

ORG_CITY: KANSAS CITY

ORG_DEPT: DENTISTRY

ORG_NAME: UNIVERSITY OF MISSOURI KANSAS CITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE Oral epithelial dysplasia (OED) is a precancerous oral lesion associated with an increased risk of malignant transformation. The objective of this proposal is to evaluate the feasibility of an innovative approach for quantitative risk stratification of OEDs using Fourier transform infrared spectroscopic imaging and machine learning techniques. This approach can potentially allow clinicians to make objective, accurate, and evidence- based risk assessment for individual OED patients and facilitate early oral cancer diagnosis.

PI_NAMEs: WANG, RONG  (contact);WANG, YONG

PROGRAM_OFFICER_NAME: OKI, NOFFISAT

PROJECT_TERMS: absorption;Address;Algorithms;Anatomy;Artificial Intelligence;Benign;Biochemical;Biological;Biological Markers;Biopsy;cancer diagnosis;Carbohydrates;Characteristics;Classification;Clinical;Coupled;Data;Development;Diagnosis;Diagnostic;digital pathology;Discrimination;Disease;efficacy evaluation;Epithelium;Evaluation;evidence base;feature extraction;Fingerprint;Fourier Transform;Functional Imaging;Future;Goals;Hematoxylin and Eosin Staining Method;high risk;Histologic;Histopathologic Grade;Image;Image Analysis;imaging approach;imaging modality;imaging system;Immunohistochemistry;Individual;innovation;Intervention;Intraepithelial Neoplasia;Label;Lesion;Lipids;Machine Learning;machine learning classifier;Malignant - descriptor;malignant mouth neoplasm;Medical;Methods;Microscope;Microscopic;model development;Molecular;Molecular Profiling;Monitor;Morphology;mouth squamous cell carcinoma;multimodality;Nature;novel;novel strategies;Nucleic Acids;oral carcinogenesis;Oral cavity;oral cavity epithelium;Oral Diagnosis;oral lesion;Oral mucous membrane structure;oral tissue;Outcome;Patients;Performance;premalignant;Premalignant Cell;prevent;Prevention;Prognosis;Proteins;Research;Research Design;Risk;Risk Assessment;risk stratification;Sampling;spectroscopic imaging;Spectrum Analysis;Stains;Stratification;Subgroup;System;Techniques;Testing;Tissue Extracts;Tissues;tool;Training;training data;unsupervised clustering;Validation;Work;World Health Organization

PROJECT_TITLE: Infrared Spectroscopic Imaging and Machine Learning for Risk Stratification of Oral Epithelial Dysplasia


ORG_CITY: New York

ORG_NAME: HOSPITAL FOR SPECIAL SURGERY

ORG_STATE: NY

PHR: The signaling pathways that are activated by the pro-inflammatory cytokine TNFa and by the EGFR, a tyrosine kinase receptor with important roles in development and diseases such as cancer, are controlled through a pair of signaling scissors called ADAM17 (a disintegrin and metalloprotease 17) and its regulators, iRhom1 and iRhom2. In this proposal, we will use cell-based assays to perform structure/function analyses and will study genetically modified mice to discover how exactly the maturation and function of ADAM17, including its remarkable on/off switch and its substrate selectivity, are controlled by the iRhoms. We hope that our results will provide a better understanding of these vital signaling pathways and will uncover new targets for treatment of TNFa- and EGFR-dependent pathologies, such as autoimmune disease and cancer.

PI_NAMEs: BLOBEL, CARL PETER (contact)

PROGRAM_OFFICER_NAME: NIE, ZHONGZHEN

PROJECT_TERMS: Anabolism;Autoimmune Diseases;Binding;Biochemical;Biological;Biological Assay;cancer therapy;Cell surface;Cells;Complex;cytokine;Cytoplasmic Tail;Cytoprotection;Development;Disease;Disintegrins;Endoplasmic Reticulum;Epidermal Growth Factor Receptor;Gene Modified;Genetic;Goals;Immune;in vivo;Inflammatory;intestinal barrier;Ligands;Malignant Neoplasms;Membrane;Metalloproteases;Molecular;Mus;mutant;Myeloid Cells;novel;Pathology;Pathway interactions;Property;Proteins;Receptor Protein-Tyrosine Kinases;Regulation;Role;Septic Shock;Signal Pathway;Signal Transduction;Signaling Molecule;Site;skin barrier;Structure;TNF gene;Transmembrane Domain

PROJECT_TITLE: Role of iRhoms and ADAM17 in EGFR and TNFalpha signaling

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


NIH_SPENDING_CATS: Atherosclerosis;Cardiovascular;Clinical Research;Digestive Diseases;Kidney Disease;Lymphatic Research

PI_NAMEs: KON, VALENTINA  (contact)

PROJECT_TERMS: Acceleration;adduct;Adverse effects;Affect;Apolipoprotein A-I;Arterial Fatty Streak;Atherosclerosis;Blood Vessels;carbohydrate metabolism;Cardiovascular Diseases;Cardiovascular system;Chronic Kidney Failure;Circulation;Clinical;Communication;Complement;Control Animal;Data;Development;dysbiosis;Environment;Functional disorder;Generations;High Density Lipoproteins;Human;human disease;ileum;in vivo;Indican;Inflammatory;Injury to Kidney;intestinal epithelium;Intestines;Kidney;Kidney Diseases;Knock-out;Link;Lipids;Lipoproteins;Liver;Lymph;lymph flow;Lymphangiogenesis;Lymphatic;lymphatic dysfunction;Lymphatic Endothelial Cells;lymphatic pump;Lymphatic System;lymphatic vessel;Lysine;Mediator;mesenteric lymphatics;Mesentery;microbial;MicroRNAs;Modification;Mus;Nerve;Organ;Organoids;oxidant stress;particle;Pathogenesis;Pathogenicity;Pathway interactions;Patients;perpetrators;Phenotype;Plasma;Production;protein metabolism;protein structure function;Proteins;Research;Role;Small Intestines;Small RNA;Source;stem;Structure;Testing;Toxin;Uremia;Vascular Diseases

PROJECT_TITLE: Modified Intestinal apoAI-particles and Lymphatics Accelerate CKD-driven CVD


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Breastfeeding, Lactation and Breast Milk;Genetics;Nutrition;Pediatric;Prevention;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Women's Health Research

ORG_CITY: SANTA CRUZ

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF CALIFORNIA SANTA CRUZ

PHR: Program Director/Principal Investigator (Hinck, Lindsay, E.): This research addresses the public health concern of lactation insufficiency: a substantial problem impacting women's and children's health worldwide. Even though mother's milk is optimal nutrition for infants, there is a gap in understanding how the milk supply is generated during pregnancy and there are few medical inventions to support women who experience lactation insufficiency. Thus, the proposed research is relevant to the part of the NIH's mission that pertains to the cell and developmental biology of somatic stem/progenitor cells, organ development, pregnancy and pediatric growth and nutrition. PHS 398 (Rev. 01/18 Approved Through 03/31/2020) Page Continuation Format Page

PI_NAMEs: HINCK, LINDSAY E (contact)

PROGRAM_OFFICER_NAME: RUSSO, DENISE

PROJECT_TERMS: 3-Dimensional;Address;adult stem cell;Alveolar;Alveolar Cell;animal tissue;Biochemical;Biological Assay;Birth;Breast;Cell division;Cell Fraction;cell type;Cells;Cellular biology;Child;Child Health;Childhood;Data;Development;Developmental Biology;dietary;Differentiation and Growth;DNA biosynthesis;DNA Damage;Epithelial Cells;Epithelium;Event;experience;Generations;Genetic;genetic manipulation;Goals;Gold;Growth;Health;Human;Human Milk;Image;improved;Infant;infant nutrition;innovation;Intervention;invention;Knowledge;Lactation;Ligands;Liquid substance;Mammals;mammary;Mammary gland;Medical;Methods;Milk;milk production;Milk Substitutes;milk supply;Mission;Mitosis;Mitotic;Morbidity - disease rate;mortality;Mothers;Mus;notch protein;novel;nutrition;Organ;organ growth;Organoids;Outcome;Pathway interactions;Pharmaceutical Preparations;pharmacologic;Phase;Plants;Polyploid Cells;Polyploidy;Pregnancy;prevent;Principal Investigator;Process;programs;Prolactin;Public Health;receptor;Regulation;replication stress;Research;response;Risk;Role;side effect;Signal Pathway;Signal Transduction;Source;stem cell differentiation;stem cell expansion;stem cells;Testing;Tissues;United States National Institutes of Health;Woman

PROJECT_TITLE: Notch/Robo Regulated Mechanisms Governing Cell Fate Acquisition

STUDY_SECTION: ICI

STUDY_SECTION_NAME: Intercellular Interactions Study Section[ICI]


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Back Pain;Chronic Pain;Neurosciences;Pain Research

ORG_CITY: NEW YORK

ORG_DEPT: ORTHOPEDICS

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: Narrative Discogenic pain is a major contributor to back pain and a leading cause of global disability with few effective treatments. This project determines inflammatory factors, specifically the role of tumor necrosis factor alpha (TNFα) in the onset and progression of discogenic pain including identifying neuroinflammatory interactions and cross-talk between intervertebral discs and dorsal root ganglia in rat and human model systems. We also apply cell and animal models and use next generation sequencing analyses to identify mechanisms and screen novel targets for efficacy in treating chronic discogenic pain.

PI_NAMEs: IATRIDIS, JAMES C. (contact)

PROGRAM_OFFICER_NAME: PINTUCCI, GIUSEPPE

PROJECT_TERMS: Address;Adult;Affect;allodynia;Anabolism;Animal Model;Anterior;anti-depressive agents;Back Pain;Behavior;Behavioral;Bioinformatics;Biological Models;Biomechanics;Catabolism;Cell Culture Techniques;Cell model;Cell Separation;Cells;Chronic;Combined Modality Therapy;Critical Pathways;Data;Defect;Degenerative Disorder;Diagnosis;disability;disability impact;discogenic pain;Disease;duloxetine;effective therapy;Female;Functional disorder;ganglion cell;Genes;Growth;healing;Height;Human;human model;In Vitro;in vitro Model;in vivo;in vivo Model;Inflammation;Inflammatory;inhibitor;Injections;Injury;interdisciplinary collaboration;Intervention;Intervertebral disc structure;intervertebral disk degeneration;intervertebral disk surgery;Investigation;male;Measurement;Measures;Mechanics;Mediating;Molecular;Molecular Analysis;molecular marker;Molecular Target;monoamine;Nervous System;neural;neuroinflammation;neuropathology;neurovascular;next generation sequencing;novel;novel therapeutics;Operative Surgical Procedures;Outcome;Pain;Pain Free;pain model;painful neuropathy;Pathogenesis;Pathology;Pathway interactions;Patients;Peripheral Nervous System;PGRN gene;Pharmaceutical Preparations;Play;prevent;Proteins;Puncture procedure;radiological imaging;Rattus;receptor;Receptors, Tumor Necrosis Factor, Type II;Refractory;response;Role;Sampling;Science;Sex Differences;single-cell RNA sequencing;spinal disk injury;Spinal Ganglia;Spinal Stenosis;Spine surgery;surgical pain;Techniques;Thinking;Time;Tissues;TNF gene;TNFRSF1A gene;TNFRSF1B gene;transmission process;treatment strategy;Tumor Necrosis Factor Receptor

PROJECT_TITLE: Role of TNFalpha in discogenic pain progression and as a treatment target

STUDY_SECTION: SBSR

STUDY_SECTION_NAME: Skeletal Biology Structure and Regeneration Study Section[SBSR]


NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Heart Disease;Prevention;Women's Health Research

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: PROJECT NARRATIVE Inflammation is crucial for the host defense response, but unregulated inflammation is a key promoter of cardiovascular events including heart attacks and stroke. Specialized pro-resolving mediators (SPMs) are derived from naturally occurring essential polyunsaturated fatty acids and support the body’s innate immune response to actively downregulate inflammation without suppressing immune system function. The proposed research project aims to identify which specific SPMs may be beneficial for preventing cardiovascular events and reducing inflammation in humans, and what clinical and genetic factors determine their circulating levels in blood, with the goal of accelerating the development of new SPM-targeted therapeutics for disease prevention.

PI_NAMEs: MORA, SAMIA  (contact)

PROGRAM_OFFICER_NAME: HONG, YULING

PROJECT_TERMS: Acceleration;Acute;Age;Anabolism;Anti-Inflammatory Agents;Applied Research;Aspirin;atherothrombosis;Biologic Characteristic;Biological;Biological Assay;Biological Markers;Blood;Blood Platelets;cardioprotection;cardiovascular disorder prevention;cardiovascular risk factor;Cardiovascular system;case control;CD59 Antigen;Chemicals;Cholesterol;Chronic;Clinical;clinical practice;Clinical Trials;clinically significant;cost efficient;cytokine;defense response;Development;Diabetes Mellitus;Diet;disorder prevention;Dose;Elements;Event;fundamental research;Future;Gene Expression;Genes;Genetic;Genetic Determinism;genome wide association study;Genotype;Goals;Growth;Host Defense;Human;Immune response;immune system function;Individual;Infection;Inflammasome;Inflammation;Inflammation Mediators;Inflammatory;Inflammatory Response;Innate Immune Response;insight;interest;Interleukin-6;Intervention;Knowledge;Leukocytes;Link;Lipids;Lipoxins;Macrophage;Mass Spectrum Analysis;Measures;Mediator;Methotrexate;Modification;Myocardial Infarction;National Heart, Lung, and Blood Institute;Obesity;Pathway interactions;Patients;Phenotype;Placebos;Plasma;Play;Polyunsaturated Fatty Acids;Population;prevent;Prevention;Primary Prevention;Process;programs;promoter;Prospective Studies;Public Health;Randomized;Regulation;Research;Research Project Grants;Residual state;Resolution;Resources;response;Risk;Role;Rupture;secondary analysis;Secondary Prevention;sex;side effect;Signaling Molecule;Smoking;Stroke;stroke event;systemic inflammatory response;targeted treatment;temporal measurement;Testing;Therapeutic;Time;trait;Woman;Women's Health

PROJECT_TITLE: Targeting the Active Resolution of Inflammation for Cardiovascular Disease Prevention

STUDY_SECTION: CHSA

STUDY_SECTION_NAME: Cancer, Heart, and Sleep Epidemiology A Study Section[CHSA]


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Genetics;Human Genome;Immunotherapy;Lung;Lung Cancer;Precision Medicine;Radiation Oncology

ORG_CITY: BALTIMORE

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

PHR: PROJECT NARRATIVE The work we have proposed has a direct impact on the treatment of non-small cell lung cancer with chemoradiation and immunotherapy. As resistance mechanisms of chemoradiation with immunotherapy are not being intensely studied using relevant preclinical cancer models, our findings can have an immediate and large impact on the field. Lastly, the study of resistance mechanisms against chemoradiation with immunotherapy in lung cancer may allow a broader understanding of resistance mechanisms in other cancers and expose new pathways to target treatment resistance.

PI_NAMEs: MCFARLAND, CHRISTOPHER DENNIS;TRAN, PHUOC T. (contact)

PROGRAM_OFFICER_NAME: LIN, CHARLES

PROJECT_TERMS: Abscopal effect;Animals;anti-PD-L1;anti-PD-L1 therapy;anti-tumor immune response;Attention;Bar Codes;Biological Assay;Biological Availability;Biological Models;cancer immunotherapy;Cancer Model;cancer subtypes;Cell Line;Cells;chemoradiation;chemotherapy;Clinic;Clinical Research;Clustered Regularly Interspaced Short Palindromic Repeats;co-clinical trial;Collaborations;Combination immunotherapy;Combined Modality Therapy;Coupled;curative treatments;Dedications;deep sequencing;disease model;Dose;Genetic;Genetically Engineered Mouse;Genomics;Genotype;Goals;High-Throughput Nucleotide Sequencing;Human;Immune;Immune system;Immunocompetent;immunogenic;Immunologics;Immunotherapeutic agent;Immunotherapy;improved;In Vitro;in vivo;in vivo Model;inhibitor;innovation;Left;Link;Local Therapy;Lung;Malignant neoplasm of lung;Malignant Neoplasms;Maps;Mediating;Modality;Modeling;Molecular;Molecular Target;neoplastic cell;Non-Small-Cell Lung Carcinoma;novel;Oncogenes;Oncology;Oral;Pathway interactions;patient derived xenograft model;Patient-Focused Outcomes;Patients;Pharmaceutical Preparations;Pharmacogenetics;Pharmacogenomics;Phase I/II Clinical Trial;pre-clinical;preclinical study;Preclinical Testing;Probability;Process;programs;Radiation;Radiation Oncologist;radiation response;Radiation therapy;Radio;Radiogenomics;research and development;Research Project Grants;Resistance;resistance mechanism;response;Route;Sampling;Scheme;standard of care;Standardization;success;System;targeted agent;Techniques;Testing;therapy resistant;tool;treatment effect;Treatment Protocols;treatment response;tumor;tumor growth;tumor microenvironment;tumorigenesis;Validation;Veterinarians;Work

PROJECT_TITLE: Tumor-barcoding coupled with high-throughput sequencing for quantitative radiogenomics of the abscopal response in NSCLC


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

ORG_CITY: CORAL GABLES

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

PHR: PROJECT NARRATIVE Brain injury is the leading cause of death and disability worldwide. Motor Vehicle Crashes account for 50% of all TBIs. The leading causes of TBI vary by age: falls are the leading cause of TBI among persons aged 65 years and older; transportation is the leading cause of TBI among persons under the age of 65 years. Estimates suggest that sports-related brain injury accounts for close to 300,000 injuries each year. Currently, there are no established successful therapies treating acute TBI and there is a critical need to develop new strategies for assessing injury severity as well as guiding therapeutic interventions. The proposed research seeks to reduce cell death by inflammation that occurs in the brain and peripheral organs within days of TBI, and to devise therapies to treat TBI-related comorbidities and help in long-term recovery of function. The development of new treatments that can be given in the first hours after TBI may prevent or reverse much of the brain and peripheral organ damage resulting from TBI with a goal of restoring normal function and behavior.

PI_NAMEs: DE RIVERO VACCARI, JUAN PABLO;KEANE, ROBERT W (contact)

PROGRAM_OFFICER_NAME: AWWAD, HIBAH OMAR

PROJECT_TERMS: Acute;Affect;Age;Animals;Apoptosis;Appearance;Behavior;Biological Assay;Body Fluids;Brain;Brain Injuries;Cardiovascular system;CASP1 gene;Caspase;Cause of Death;Cell Death;Cell Physiology;Cells;Central Nervous System;Circulation;Clinic;comorbidity;comparison control;Control Animal;controlled cortical impact;Data;Deposition;Development;disability;Endocrinology;Exhibits;experimental study;extracellular;Extracellular Space;extracellular vesicles;falls;Flow Cytometry;Functional disorder;Goals;Hematology;Histologic;Hour;Human;human old age (65+);Immune;Immune signaling;Immunohistochemistry;Immunologics;improved;in vivo;Inflammasome;Inflammation;Inflammatory;inflammatory milieu;Inflammatory Response;injured;Injury;Innate Immune Response;innovation;insight;Interleukin-1 beta;Leucocytic infiltrate;long term recovery;Lung;Lymphocyte;Macrophage;Mediating;Modeling;Molecular;Monoclonal Antibodies;Mus;Natural Immunity;Neurodegenerative Disorders;neutralizing antibody;neutrophil;Neutrophil Infiltration;Organ;Outcome;Pathogenesis;Patients;Pattern;Peripheral;Persons;Play;Predisposition;prevent;Protein Secretion;Proteins;Reaction;Reactive Oxygen Species;Recovery of Function;recruit;Research;Role;Serum;Severities;Signal Transduction;Sports;systemic inflammatory response;TBI Patients;Testing;Therapeutic;Therapeutic Effect;Therapeutic Intervention;therapeutic target;tissue injury;Tissues;Transportation;Traumatic Brain Injury;uptake;Vehicle crash;Vesicle;Western Blotting;Work

PROJECT_TITLE: Role of ASC in TBI-Mediated Systemic Inflammation.

STUDY_SECTION: BINP

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


ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

PROGRAM_OFFICER_NAME: LIU, LIJUAN

PROJECT_TERMS: Agonist;Apolipoprotein E;Area;Arterial Fatty Streak;Atherosclerosis;Attenuated;Binding;Biological Process;Cardiometabolic Disease;Cardiovascular Diseases;Cells;Chronic;Circulation;Complex;cytokine;Deposition;Disease;Endocytosis;Environment;extracellular;field study;Functional disorder;Gene Expression;High Density Lipoproteins;Human;human disease;Immune;Impairment;In Vitro;in vivo;Inflammation;Inflammatory;inhibitor;Ischemia;Knowledge;Lesion;lipid metabolism;Lipids;Lipoproteins;Literature;locked nucleic acid;Low-Density Lipoproteins;Macrophage;Macrophage Activation;Mediating;microbial;microbiome;MicroRNAs;Modeling;Modification;mouse model;Mus;novel;nucleic acid inhibitor;nucleic acid-based therapeutics;particle;Pathology;Pathway interactions;Phagocytosis;Phenotype;Process;Property;receptor;Receptor Activation;Reporting;Repression;response;RNA Transport;Route;Signal Transduction;single-cell RNA sequencing;Small RNA;Stimulus;Testing;Therapeutic;therapy design;TLR7 gene;TLR8 gene;Toll-like receptors;Untranslated RNA;uptake;western diet;Work

PROJECT_TITLE: Macrophage small RNA export to HDL protects against inflammation and atherosclerosis

STUDY_SECTION_NAME: Heart, Lung, and Blood Program Project Study Section[HLBP]


ADMINISTERING_IC: DC

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Biomedical Imaging;Clinical Research

ORG_CITY: LOS ANGELES

ORG_DEPT: OTOLARYNGOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PROJECT NARRATIVE In the present proposal, we will continue to procure and process temporal bones, promote and share human ear tissue with basic inner ear researchers and create an uploaded digital library of temporal bone images. We will test new inner ear tissue processing protocols designed to preserve DNA, RNA as well as the morphology. We will develop a deep learning-based stain transformation framework to visualize specific anatomical structures and will continue to develop novel imaging modalities, and molecular biological applications to the human temporal bone.

PI_NAMEs: ISHIYAMA, AKIRA  (contact)

PROGRAM_OFFICER_NAME: CYR, JANET

PROJECT_TERMS: 3-Dimensional;Anatomy;Animal Model;Animals;Archives;Autopsy;Biological;bone imaging;Bone Tissue;Celloidin;Clinical;Collaborations;Collection;contrast imaging;deep learning;design;digital;Digital Libraries;DNA;DNA Fragmentation;DNA Sequence;DNA sequencing;Ear;experience;Genes;hands on instruction;Harvest;Hematoxylin and Eosin Staining Method;High Resolution Computed Tomography;high resolution imaging;Histopathology;Human;human imaging;Image;image archival system;imaging modality;Imaging Techniques;Immunofluorescence Immunologic;improved;In Situ Hybridization;interest;Laboratories;Labyrinth;Libraries;Magnetic Resonance Imaging;meetings;Messenger RNA;Methods;Modality;Modernization;Molecular;Molecular Biology Techniques;Morphology;Mus;National Institute on Deafness and Other Communication Disorders;Neurons;novel;Nucleic Acids;Organ;Phase;preservation;Process;prospective;Proteins;Protocols documentation;reconstruction;Registries;Research;Research Personnel;Resolution;Resources;RNA;sample fixation;Scientist;Services;Specimen;spiral ganglion;Stains;Structure;symposium;synchrotron radiation;Techniques;Temporal bone structure;Testing;three-dimensional visualization;Time;Tissue Banks;Tissue Fixation;tissue processing;Tissues;tool;ultra high resolution;Update;virtual;Visualization;web site;X-Ray Computed Tomography

PROJECT_TITLE: Modern Cellular and Molecular Techniques to Study the Human Temporal Bone


NIH_SPENDING_CATS: Cancer;Clinical Research;Immunization;Immunotherapy;Infectious Diseases;Vaccine Related

ORG_CITY: HANOVER

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: DARTMOUTH COLLEGE

ORG_STATE: NH

PHR: PROJECT NARRATIVE T cells specific for previously encountered viruses are abundant in tissues throughout the body, including tumors, and can be leveraged for cancer immunotherapy. This proposal will further our understanding of how these cells function and develop novel strategies to enhance their efficacy. In doing so we will drive the translation of virus-specific T cell based immunotherapy toward clinical use.

PI_NAMEs: ROSATO, PAMELA  (contact)

PROGRAM_OFFICER_NAME: HARRIS, RAYMOND D

PROJECT_TERMS: 2019-nCoV;adaptive immune response;adaptive immunity;Address;anti-PD-L1;Automobile Driving;Blood Tests;cancer immunotherapy;CD8-Positive T-Lymphocytes;cell killing;Cell Physiology;Cells;Cellular immunotherapy;Clinic;Clinical;clinical translation;clinically significant;combinatorial;Complement;cytokine;Cytomegalovirus;Cytomegalovirus Infections;cytotoxic;Data;Detection;Development;Environment;Epstein-Barr Virus Infections;exhaustion;Functional disorder;Human;Human Herpesvirus 4;human model;Immune;immune checkpoint blockade;Immunologic Surveillance;Immunologics;Immunotherapy;in vivo;Infection;Inflammatory;Influenza A virus;influenza infection;innovation;Knowledge;Malignant Neoplasms;Melanoma;Melanoma patient;Melanoma Tumor;Memory;Messenger RNA;Methods;Modality;Modeling;mouse model;Mus;Natural Immunity;neoplasm immunotherapy;neoplastic cell;novel;novel strategies;pathogen;Patients;Peptides;Population;Predisposition;Production;programmed cell death ligand 1;recruit;Resistance;Slice;Solid Neoplasm;Specificity;Stains;System;T-Lymphocyte;targeted treatment;Testing;Therapeutic;tissue resident memory T cell;Tissues;translational therapeutics;Translations;Treatment Efficacy;tumor;Tumor Antigens;tumor growth;Tumor Immunity;Vaccines;Viral;Viral Antigens;Virus;Virus Diseases;Work

PROJECT_TITLE: Therapeutically harnessing anti-viral resident memory T cells in solid tumors

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


ED_INST_TYPE: GRADUATE SCHOOLS

NIH_SPENDING_CATS: Cancer;Genetics

ORG_NAME: COLUMBIA UNIV NEW YORK MORNINGSIDE

PHR: PUBLIC HEALTH RELEVANCE STATEMENT (PROJECT NARRATIVE) The efficiency with which messenger RNAs (mRNAs) are recruited to the ribosome for translation intro proteins is a carefully controlled aspect of gene expression in eukaryotes whose dysregulation has been causally linked to tumorigenesis, tumor growth, drug resistance, and metastasis in many human cancers. Using a powerful combination of reagents and experimental approaches that are unique to the principal investigator’s and collaborator’s laboratories, this project will elucidate the molecular mechanisms that drive and control mRNA recruitment during eukaryotic translation initiation. The results of these studies will deepen our understanding of the mechanisms that control gene expression and the molecular pathogenesis of various cancers as well as identify targets for the development of anticancer therapeutics.

PI_NAMEs: GONZALEZ, RUBEN L (contact)

PROGRAM_OFFICER_NAME: MAAS, STEFAN

PROJECT_TERMS: Affinity;anti-cancer therapeutic;Antineoplastic Agents;Binding;Binding Proteins;Biochemical;Biological Assay;Biophysics;cancer therapy;Cell Extracts;Complex;Cryoelectron Microscopy;Data;data exchange;Defect;Development;Discrimination;Drug resistance;Drug Targeting;Eukaryota;Eukaryotic Initiation Factor-1;eukaryotic initiation factor-5B;Eukaryotic Initiation Factors;Event;Exhibits;FDA approved;Fluorescence Microscopy;fluorophore;Future;Gene Expression;Hand;Human;In Vitro;Individual;Initiator Codon;Initiator tRNA;Label;Laboratories;Length;Letters;Link;Maintenance;Malignant Neoplasms;Measures;Mediating;Messenger RNA;Modeling;Molecular;mutant;Neoplasm Metastasis;Oncogenic;overexpression;Pathogenesis;Physiological;polyadenosine;Positioning Attribute;Preparation;Principal Investigator;Process;Proteins;public health relevance;Reagent;Recombinants;reconstitution;recruit;Regulation;Resolution;Ribosomal Proteins;Ribosomes;Role;Saccharomyces cerevisiae;Series;Signal Transduction;single molecule;single-molecule FRET;Site;Specificity;Structure;System;Text;Therapeutic;Time;time use;Translating;Translation Initiation;Translations;tumor growth;Tumor-Derived;tumorigenesis;Yeasts

PROJECT_TITLE: The mechanism and regulation of mRNA recruitment during eukaryotic translation initiation

STUDY_SECTION: MG

STUDY_SECTION_NAME: Molecular Genetics Study Section[MG]


NIH_SPENDING_CATS: Brain Disorders;Cancer;Cancer Genomics;Genetics;Human Genome;Neurosciences;Skin Cancer

ORG_NAME: CEDARS-SINAI MEDICAL CENTER

PHR: Narrative  Melanoma is an aggressively metastasizing disease and is only second in the number of life-years lost per cancer-related death in the US, and the estimated cost of melanoma to the US economy is ~$3.5 billion per year. Our proposed studies will not only provide new insights into the critical roles of AMPK in melanoma with emphasis on melanoma brain metastasis, but also will have strong translational implications in developing novel therapeutic approaches to target metabolic vulnerabilities of brain metastatic melanoma cells for the treatment of this deadly metastatic cancer.

PI_NAMEs: YENNU NANDA, VASHISHT G;ZHENG, BIN  (contact)

PROGRAM_OFFICER_NAME: SNYDERWINE, ELIZABETH G

PROJECT_TERMS: 5'-AMP-activated protein kinase;Address;Anchorage-Independent Growth;ATP Citrate (pro-S)-Lyase;Biguanides;Biology;BRAF gene;Brain;cancer cell;cancer genomics;cancer survival;Catalytic Domain;Cell model;cellular targeting;Cephalic;Cessation of life;Clinical;Complex;Computational Biology;cost estimate;Cutaneous Melanoma;Diabetes Mellitus;Disease;Disseminated Malignant Neoplasm;Drug Targeting;Enzymes;Genes;Genetically Engineered Mouse;genomic data;Growth;Homeostasis;Human;immune checkpoint blockade;immunodeficiency;Immunotherapy;inhibitor;insight;Knock-out;Knowledge;lipid biosynthesis;Malignant Neoplasms;MEKs;Melanoma;Melanoma Cell;Melanoma patient;Memorial Sloan-Kettering Cancer Center;Metabolic;Metabolism;metabolomics;Metastatic malignant neoplasm to brain;Metastatic Melanoma;Metformin;Mitochondria;Modeling;Monitor;mouse model;Mus;mutant;Mutate;Mutation;Neoplasm Metastasis;new therapeutic target;NF1 gene;NF1 mutation;novel;novel therapeutic intervention;Nude Mice;Oncologist;Oxidative Phosphorylation;Pathway interactions;Patients;Pharmaceutical Preparations;phase 1 study;Phase I Clinical Trials;Phenformin;Phosphorylation Inhibition;pre-clinical;Proliferating;Regulation;Reporting;Research Personnel;response;Role;Sampling;sensor;Signal Pathway;Signal Transduction;single-cell RNA sequencing;Soft Agar Assay;Solid Neoplasm;subcutaneous;Surgeon;targeted treatment;The Cancer Genome Atlas;Therapeutic;Therapeutic Effect;therapeutically effective;tumor;tumor metabolism;tumor progression;Tumor Promotion;tumor xenograft;University of Texas M D Anderson Cancer Center;Xenograft Model;Xenograft procedure;years of life lost

PROJECT_TITLE: Role of AMPK in melanoma brain metastasis

STUDY_SECTION_NAME: Tumor Cell Biology Study Section[TCB]


NIH_SPENDING_CATS: Aging;Atherosclerosis;Cardiovascular

PI_NAMEs: DAVIES, SEAN STEPHEN (contact)

PROJECT_TERMS: adduct;Aorta;Apolipoprotein E;Apoptotic;Arachidonic Acids;Arterial Fatty Streak;Atherogenic Diet;Atherosclerosis;Automobile Driving;Cells;Cholesterol;Cholesterol Esters;Chronic Kidney Failure;Coronary artery;cytokine;Development;Disease;Enzymes;Equilibrium;Family;Gene Expression;Goals;GPR55 receptor;High Density Lipoproteins;human disease;Hydrolysis;hypercholesterolemia;Inflammation;Inflammatory;inhibitor;Intestines;ketoaldehyde;Kidney Diseases;Lesion;Ligands;Lipids;Lymph;Lysine;Macrophage;mesenteric lymph node;microbial;Modeling;Modification;mortality;Mus;NAPE-PLD;Necrosis;novel;Patients;Pattern Recognition;Pattern recognition receptor;Peripheral;peroxidation;Phagocytosis;Phenotype;Play;Probability;protein expression;Proteins;Reducing diet;Rest;Role;Rupture;Small RNA;Testing;Tissues

PROJECT_TITLE: Modification of HDL and Macrophage Function in Atherosclerosis


NIH_SPENDING_CATS: Chronic Obstructive Pulmonary Disease;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Health Services;Lung;Machine Learning and Artificial Intelligence

PHR: The proposed research will investigate the comparative effectiveness and safety of therapies for chronic obstructive pulmonary disease (COPD) and will develop a clinical prediction rule for inhaler adherence. I will complete this research using large, longitudinal healthcare databases of patients with COPD treated in routine clinical practice. The overarching goal is to supplement existing data from randomized controlled trials to refine treatment strategies for COPD and thereby improve clinical outcomes.

PI_NAMEs: FELDMAN, WILLIAM BRAND (contact)

PROGRAM_OFFICER_NAME: YE, JANE

PROJECT_TERMS: Activities of Daily Living;Address;Adherence;Adrenal Cortex Hormones;Age;Agonist;Algorithms;Area;authority;Award;Azithromycin;Biometry;Budesonide;Caring;Cause of Death;Characteristics;Chronic;Chronic Obstructive Pulmonary Disease;Clinical;clinical practice;clinical predictors;Clinical Trials;Code;comorbidity;comparative effectiveness;comparative effectiveness study;comparative safety;compare effectiveness;Complex;Computerized Medical Record;cost;Costs and Benefits;Coughing;Data;data management;Databases;design;Disease;Disease Outcome;Dose;Dryness;Dyspnea;education planning;Elderly;Epidemiology;ethnic minority;experience;Face;fluticasone;formoterol;Frequencies;Future;Glean;Glycopyrrolate;Goals;Grant;Guidelines;Health system;Healthcare;Healthcare Systems;Hospitalization;improved;inclusion criteria;Inhalation;Inhalators;insight;Insurance;Insurance Benefits;insurance claims;Intervention;Link;Literature;longitudinal dataset;Lung;Machine Learning;machine learning method;Mentors;Mentorship;meter;Morbidity - disease rate;mortality;Muscarinic Antagonists;novel;older adult;Ontology;optimal treatments;Outcome;Outcome Measure;Patient Care;Patients;Performance;Pharmaceutic Policy;Pharmaceutical Preparations;Pharmacoepidemiology;Pneumonia;Powder dose form;Predictive Value;Public Health;racial minority;Randomized, Controlled Trials;Research;Research Personnel;Risk;Safety;Sample Size;Schedule;Scientific Advances and Accomplishments;Severity of illness;Shapes;skills;Smoking Status;Spirometry;Symptoms;Techniques;Testing;tool;Training;Treatment Effectiveness;treatment guidelines;treatment strategy;trial comparing;trial design;Uncertainty;Uninsured Medical Expense;validation studies;Woman;Work

PROJECT_TITLE: Improving COPD Outcomes: Using Real-World Data to Analyze Treatment Effectiveness, Safety, and Adherence

STUDY_SECTION: MCBS

STUDY_SECTION_NAME: NHLBI Mentored Clinical and Basic Science Study Section[MCBS(OA)]


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Cancer;Genetics;Lung;Lung Cancer;Precision Medicine;Prevention;Tobacco;Tobacco Smoke and Health

ORG_CITY: PULLMAN

ORG_NAME: WASHINGTON STATE UNIVERSITY

ORG_STATE: WA

PHR: Project Narrative The major mode of metabolism of NNK, a major contributor to the induction of lung cancer in smokers, is via the formation of its pro-carcinogenic metabolite, NNAL. Two enantiomers of NNAL are formed -- (R)-NNAL and (S)-NNAL, with (R)-NNAL the major isoform formed in the lung and both enantiomers detoxified by glucuronidation. We provide novel preliminary data demonstrating a strong and statistically significant inverse association between the ratio of urinary (R)-NNAL-glucuronide (Gluc)/(S)-NNAL-Gluc and lung cancer risk in smokers from two independent large cohort studies, and this novel, stable biomarker of lung cancer risk reflects the potential importance of (R)-NNAL in the carcinogenicity of NNK and strongly supports the goals of this proposal which is to evaluate the importance of different NNAL enantiomers and glucuronides in lung cancer carcinogenesis and to elucidate novel urinary biomarkers of lung cancer risk focusing on the NNAL formation and elimination pathways.

PI_NAMEs: LAZARUS, PHILIP  (contact);YUAN, JIAN-MIN

PROGRAM_OFFICER_NAME: SIMONDS, NAOKO ISHIBE

PROJECT_TERMS: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol;4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone;Alleles;Asian;Biological Markers;Black race;Blood specimen;Cancer Burden;Cancer Etiology;cancer risk;carcinogenesis;carcinogenicity;Carcinogens;Cells;Cessation of life;Chemopreventive Agent;Chinese;cigarette smoking;cohort;Cohort Studies;Communities;Complex;Copy Number Polymorphism;cost effective;Cytochrome P450;Cytosol;Data;Development;Drug Metabolic Detoxication;enantiomer;Enzymes;Exhibits;Genes;Genetic Markers;Genetic Polymorphism;genetic variant;Genetic Variation;genome wide association study;genome-wide;Genotype;Glucuronides;Glucuronosyltransferase;Goals;Health;high risk;Human;improved;insight;Isomerism;Liver;Lung;lung cancer prevention;lung cancer screening;lung carcinogenesis;lung development;Malignant neoplasm of lung;Mediating;Metabolic;Metabolism;Microsomes;mortality;Nicotine;Nitrosamines;novel;novel strategies;Oxidoreductase;Pathway interactions;Pattern;Phenotype;phenotypic biomarker;Play;Population;precision cancer prevention;Predisposition;Prevention strategy;prospective;Prospective cohort;Prospective, cohort study;protective pathway;Protein Isoforms;recruit;Risk;Role;sample collection;screening;Singapore;Smoker;Smoking;smoking cessation;SNP genotyping;targeted sequencing;Tissues;Tobacco;Tobacco smoke;Tobacco-Associated Carcinogen;urinary;Urine;Validation;Variant;Women's Health

PROJECT_TITLE: Gene-tobacco carcinogen interactions and lung cancer risk - a novel approach for precision cancer prevention

STUDY_SECTION: CBSS

STUDY_SECTION_NAME: Cancer Biomarkers Study Section[CBSS]


ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: PROJECT NARRATIVE While immunotherapy for cancer can have remarkable effects at prolonging patients' lives, it only is successful in a minority of patients. This is because patients need functional immune cells within their tumors to respond to these immune boosting therapies. We and others have shown that the capacity of tumor cells to consume metabolites can starve infiltrating immune cells, although the mechanisms are unclear. We will use preclinical models to understand how cancer immunity is regulated by metabolism, as well as analyze immune cells from patients treated with immunotherapy in combination with metabolism altering drugs.

PI_NAMEs: DELGOFFE, GREG M. (contact);NAJJAR, YANA ;POHOLEK, AMANDA CATHERINE

PROGRAM_OFFICER_NAME: LIU, YIN

PROJECT_TERMS: Acetylation;Address;angiogenesis;Angiogenesis Inhibitors;anti-PD-1;Antigens;Automobile Driving;cancer cell;cancer immunotherapy;cancer infiltrating T cells;cancer therapy;Cell Physiology;cell type;Cells;Chromatin;Chronic;Clinical Trials;cofactor;Complex;Consumption;Cytotoxic T-Lymphocytes;Data;demethylation;Environment;Epigenetic Process;epigenome;exhaust;exhaustion;experience;Functional disorder;functional outcomes;Gene Expression;Genes;Genetic Transcription;Goals;histone methylation;histone modification;Histones;Hypoxia;Immune;immune cell infiltrate;immune checkpoint blockade;Immunologic Memory;Immunology;Immunosuppression;Immunotherapeutic agent;Immunotherapy;In Vitro;in vivo;Infiltration;inhibitor;Knowledge;Ligands;Link;Machine Learning;Malignant Neoplasms;Mediating;Melanoma;Melanoma patient;Metabolic;Metabolic stress;Metabolism;Metformin;Methylation;Minority;Mitochondria;Modeling;Modification;Monoclonal Antibodies;mouse model;Mus;neoplastic cell;Non-Insulin-Dependent Diabetes Mellitus;novel;Oxidative Stress;Oxygen;patient subsets;Patients;PD-1 blockade;Pharmaceutical Preparations;Pre-Clinical Model;programmed cell death protein 1;Proliferating;Reactive Oxygen Species;receptor;Regimen;Research Personnel;Resistance;resistance mechanism;response;Role;Signal Transduction;Site;Solid Neoplasm;Starvation;stem;stressor;success;synergism;System;T cell differentiation;T cell infiltration;T-Lymphocyte;transcription factor;transcriptional reprogramming;tumor;tumor hypoxia;Tumor Immunity;tumor metabolism;tumor microenvironment

PROJECT_TITLE: Dissecting the role of hypoxia in T cell differentiation in cancer

STUDY_SECTION: TTT

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


NIH_SPENDING_CATS: Bioengineering;Biotechnology

PHR: Directed evolution has proven to be a valuable technique for adapting enzymes to do elaborate chemistries that would otherwise be synthetically challenging. A major bottleneck to evaluating the hundreds to thousands of individually mutated library members involves the screening of products using colorimetric reporter or bioactivity assays, or time-consuming chromatography-based analyses on the experiments themselves. We propose to combine our respective strengths in biochemistry and mass spectrometry to develop a sensitive, accurate high throughput mass spectrometry based workflow to expedite the screening of a directed evolution library without the reliance on chromatography techniques in order to identify significant biocatalytic transformations.

PI_NAMEs: SANCHEZ, LAURA MARGARET (contact)

PROGRAM_OFFICER_NAME: BOND, MICHELLE RUEFFER

PROJECT_TERMS: Acids;Acoustics;Agonist;alpha ketoglutarate;Amino Acid Substitution;analog;Analytical Chemistry;antagonist;assay development;Automation;Biochemical;Biochemical Reaction;Biochemistry;Biological Assay;Biology;Biotechnology;Cells;Chemicals;Chemistry;Chromatography;Confounding Factors (Epidemiology);Constitution;Consumption;Coupled;Cyclization;Deposition;Detection;Development;Dioxygenases;directed differentiation;Directed Molecular Evolution;Enzymes;Escherichia coli;Evolution;experimental study;Family;Foundations;Future;Gas Chromatography;Generations;Genes;genomic locus;Glutamate Receptor;high dimensionality;High Pressure Liquid Chromatography;Homologous Gene;Image;imaging software;Individual;Industrialization;Industry;Infrastructure;innovation;ion mobility;Isomerism;Kainic Acid;Laboratories;Lactones;Lead;Libraries;Mass Fragmentography;mass spectrometric imaging;Mass Spectrum Analysis;Measurement;member;Metabolic Biotransformation;Methodology;microbial;microbial colonization;Molecular Weight;mutant;Mutate;Mutation;Natural product discovery;Nature;Neurotoxins;non-Native;novel;Nuclear Magnetic Resonance;Outcome;Polymerase Chain Reaction;Process;Production;Proteins;Pyrrolidines;Rapid screening;Reporter;Research;Research Personnel;Sampling;screening;Screening Result;Site;small molecule;Specificity;Spectrometry;Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization;Spottings;Statistical Data Interpretation;Synthesis Chemistry;System;tandem mass spectrometry;Techniques;Technology;Therapeutic;Time;tool;Variant;vector;Work

PROJECT_TITLE: Development of a high throughput platform for screening directed evolution libraries

STUDY_SECTION: EBIT

STUDY_SECTION_NAME: Enabling Bioanalytical and Imaging Technologies Study Section[EBIT]


ED_INST_TYPE: UNIVERSITY-WIDE

NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Cardiovascular;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Heart Disease;Physical Activity;Prevention;Social Determinants of Health

ORG_CITY: BRONX

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

PHR: Narrative Cardiovascular disease (CVD)—a leading cause of death as well as a leading driver of health care costs— disproportionately effects certain demographic and socioeconomic groups; under-resourced neighborhoods may be partially to blame. Resources may improve with “neighborhood redevelopment”, but whether redevelopment improvements translate to better health for all is not clear. To examine the relationship between neighborhood redevelopment and CVD-related health/health disparities, the proposed study will use three complementary approaches: (1) a natural experiment, (2) qualitative analysis, and (3) micro-simulation and system dynamics modeling.

PI_NAMEs: CHAMBERS, EARLE C (contact)

PROGRAM_OFFICER_NAME: REDMOND, NICOLE

PROJECT_TERMS: Accounting;Address;Affect;Alcohol consumption;allostatic load;Area;Black race;Budgets;Calibration;Capital;Cardiovascular Diagnostic Techniques;Cardiovascular Diseases;cardiovascular effects;cardiovascular health;Cause of Death;Cessation of life;Clinical;clinical diagnosis;cohort;Communities;comparison group;Coronary Arteriosclerosis;cost;Data;Data Sources;design;Development;Diabetes Mellitus;Diet;Disparity;dynamic system;Electronic Health Record;Ethnic Origin;Event;experience;Food;future implementation;Goals;Health;Health behavior;health care availability;Health Care Costs;health disparity;health equity;Health Priorities;Health Surveys;healthy aging;Heart failure;Hispanic;Housing;human old age (65+);Hypertension;improved;Incidence;Income;Individual;insight;interest;Interview;Investments;Long-Term Effects;Low income;Measures;Mediating;member;Methods;middle age;Modeling;models and simulation;Modification;mortality;Myocardial Infarction;Natural experiment;Neighborhoods;older adult;older patient;Outcome;Patients;Perception;Persons;Physical activity;Physiological;Policies;Poverty;Price;Primary Care;Process;Quality-Adjusted Life Years;Race;Racial Segregation;Research;Research Personnel;Resources;Risk Factors;Sampling;simulation;Smoking;social determinants;social health determinants;Social Network;Social Work;sociodemographic disparity;sociodemographic factors;sociodemographic group;sociodemographics;socioeconomics;Source;System;Time;Translating;Visit;Walking

PROJECT_TITLE: Bronx Neighborhood Redevelopment and CVD in mid-life and older adults

STUDY_SECTION: CIHB

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


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Drug Abuse (NIDA only);Mental Health;Neurosciences;Prevention;Stimulant Use and Misuse;Substance Misuse

ORG_CITY: AUSTIN

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF TEXAS AT AUSTIN

ORG_STATE: TX

PHR: Project Narrative Daily experience, such as stress and exercise, shapes various brain functions, including the capacity to learn environmental stimuli associated with rewards, such as addictive drugs or palatable foods. Maladaptive assignment of incentive-motivational value to environmental stimuli is thought to drive craving and relapse when exposed to those stimuli. The goal of this project is to determine the influence of stress and exercise on reward learning mechanisms in the brain dopaminergic system, thereby providing mechanistic insights into the effects of daily experience on vulnerability to addictive disorders.

PI_NAMEs: MORIKAWA, HITOSHI  (contact)

PROGRAM_OFFICER_NAME: MOORE, HOLLY MARIE

PROJECT_TERMS: Acute;acute stress;addiction;Adrenergic Receptor;Affect;Agonist;Amphetamines;antagonist;Automobile Driving;biological adaptation to stress;Brain;Buffers;Cocaine;conditioned place preference;conditioning;Corticotropin-Releasing Hormone;craving;Cues;Dependence;Development;disorder risk;dopaminergic neuron;Exercise;experience;Exposure to;Female;Food;Genetic;genetic manipulation;Glutamates;Goals;high risk population;in vivo;incentive salience;Incentives;Inositol;insight;Lead;Learning;Life Style;Location;locus ceruleus structure;Long-Term Potentiation;male;Measurement;Measures;Mediating;Mediator;Memory;Mental disorders;Metabotropic Glutamate Receptors;Microdialysis;Motivation;N-Methyl-D-Aspartate Receptors;N-Methylaspartate;Neurons;non-drug;noradrenergic;Norepinephrine;Pharmaceutical Preparations;Phase;Play;Predictive Value;Predisposition;Prevention strategy;Process;psychostimulant;Rattus;receptor;Regulation;Relapse;response;restraint stress;Rewards;Risk;Risk Factors;Risk Reduction;Role;Running;Sensory;Shapes;Signal Transduction;Slice;social defeat;Stimulus;Stress;Stressful Event;Symptoms;Synaptic plasticity;synergism;System;Testing;transmission process;tripolyphosphate;Ventral Tegmental Area

PROJECT_TITLE: Experience-Dependent Regulation of Reward Learning and Addiction Vulnerability

STUDY_SECTION: PMDA

STUDY_SECTION_NAME: Pathophysiological Basis of Mental Disorders and Addictions Study Section[PMDA]


NIH_SPENDING_CATS: Bioengineering

ORG_CITY: Columbus

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: Project Narrative The goal of this research is to create a quantitative mass spectrometry platform for effective analysis of isomeric species of lipids and saccharides, which are important in metabolism, protein structure, and cell-to-cell signaling. The novelty of the proposed approach lies in the use of accelerated droplet chemistry to enhance analyte signal and confer unique fragmentation patterns to differentiate isomers when analyzed in tandem MS. The significance is that we achieve femtomole level sensitivity by coupling the droplet reaction platform to separation techniques allowing analysis of <1 µL samples of complex mixtures in a high throughput fashion, a process that is of great importance in many other fields including combinatorial chemistry.

PI_NAMEs: BADU-TAWIAH, ABRAHAM  (contact)

PROGRAM_OFFICER_NAME: BARNES, CHARLES ASHLEY

PROJECT_TERMS: Acceleration;Acids;Address;adduct;analytical method;anomer;Biological Process;Biomedical Research;Blood capillaries;Cell Physiology;Cells;Charge;Chemicals;Chemistry;Clinical Research;combinatorial;combinatorial chemistry;Complex Mixtures;Coupling;Dedications;Derivation procedure;design;Development;Devices;Dimensions;disease diagnosis;Electrospray Ionization;Environment;experimental study;Exposure to;Gases;Generations;Goals;High Pressure Liquid Chromatography;high throughput analysis;Human;improved;In Situ;Injections;instrument;instrumentation;interest;ion mobility;ion source;ionization;Ions;Isomerism;Lipids;Liquid Chromatography;liquid chromatography mass spectrometry;mass spectrometer;Mass Spectrum Analysis;Metabolism;method development;Methods;milligram;millisecond;Modification;Mole the mammal;Molecular Conformation;monomer;Monosaccharides;Nature;Noise;novel;Nucleic Acids;Pattern;Performance;Phase;Plasma;Play;Positioning Attribute;Process;programs;protein structure;Proteins;Reaction;Reactive Oxygen Species;Reagent;Research;Role;Sampling;Signal Transduction;Silicon Dioxide;Solvents;Source;Spectrometry;Spectrometry, Mass, Electrospray Ionization;Stereoisomer;Structure;sugar;tandem mass spectrometry;Techniques;Technology;Time;Triglycerides;voltage

PROJECT_TITLE: Integrating Accelerated Droplet Chemistry with LC-MS for High Throughput Quantitative Analysis


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cancer;Clinical Research;Lung;Lung Cancer;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD)

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: PROJECT NARRATIVE Major research efforts have been devoted to the development of nonlinear reconstruction algorithms – from model-based reconstruction to deep learning, these algorithms have demonstrated many advantages such as improved image quality, reduced radiation dose, and additional diagnostic information that are not achievable with traditional linear reconstructions. However, only a disproportionately small number has reach the clinic due to the lack of a predictive image quality analysis framework to quantify diagnostic performance, control algorithm behavior, and ensure consistent performance for robust clinical deployment. The propose effort use a combination of analytic and machine learning approaches to drive much-needed quantitative assessment standards that directly relate image quality to diagnostic performance and establish optimal strategies for robust, reliable clinical deployment of nonlinear algorithms.

PI_NAMEs: GANG, JIANAN GRACE (contact)

PROGRAM_OFFICER_NAME: TANDON, PUSHPA

PROJECT_TERMS: 3D Print;Address;Adoption;Algorithms;Anatomy;Appearance;Beauty;Behavior;Biological Models;Clinic;Clinical;clinical application;clinical translation;clinically relevant;Complex;Data;data-driven model;Databases;deep learning;deep learning algorithm;deep neural network;Dependence;Derivation procedure;design;Development;Diagnostic;Dictionary;Digital Libraries;Dimensions;Dose;Ensure;Evaluation;flexibility;Image;Image Analysis;imaging system;Imaging Techniques;improved;insight;interest;Lead;Lesion;Libraries;low dose computed tomography;Lung;lung cancer screening;Lung CAT Scan;lung lesion;Lung nodule;Machine Learning;machine learning method;Measures;Medical Imaging;Methods;Modeling;neural network;Nodule;Noise;Non-linear Models;novel;Outcome;Output;Patients;Performance;Play;predicting response;Predictive Analytics;Property;Protocols documentation;public database;quantitative imaging;Radiation Dose Unit;radiomics;reconstruction;Research;response;Role;Sampling;Scanning;Scheme;screening;shape analysis;Shapes;Signal Transduction;simulation;Source;Statistical Models;success;System;targeted imaging;Techniques;Technology;Texture;training data;Transcend;Work;X-Ray Computed Tomography

PROJECT_TITLE: Nonlinear performance analysis and prediction for robust low dose lung CT

STUDY_SECTION: ITD

STUDY_SECTION_NAME: Imaging Technology Development Study Section[ITD]


NIH_SPENDING_CATS: Bioengineering;Clinical Research;Emergency Care;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Hematology;Infectious Diseases;Machine Learning and Artificial Intelligence;Palliative Care;Precision Medicine;Sepsis

ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE Sepsis the leading cause of death among critically ill patients in the United States. Despite decades of research on sepsis, there still remains much to be learned regarding the underlying mechanisms of disease. Biorepositories of human biospecimens provide us with the opportunity to better understand sepsis. This application is aimed at developing a screening algorithm and novel consent approach in order to support existing and novel methods of biospecimen collection in sepsis patients.

PI_NAMEs: ESPER, ANNETTE M. (contact);KAMALESWARAN, RISHIKESAN

PROGRAM_OFFICER_NAME: ZHAO, XIAOLI

PROJECT_TERMS: Accident and Emergency department;Acute;acute care;Algorithms;Ambulances;Animal Model;Antibiotics;Artificial Intelligence;biobank;Biological;Cause of Death;cell type;Cells;Cessation of life;Characteristics;Clinical;Clinical Research;clinical translation;cohort;Collection;Conceptions;Consent;Critical Care;Critical Illness;Cryopreserved Cell;Death Rate;Decision Making;design;Development;Diagnosis;Disease;Disparity;Early treatment;Electronics;Enrollment;Environment;Ethics;experience;Family;Functional disorder;gender disparity;Health;hospital care;Hospital Mortality;Hospitals;Hour;Human;Immune response;improved;improved outcome;Individual;Infection;Informed Consent;Integration Host Factors;Intensive Care Units;interoperability;Intervention;Learning;Length of Stay;Maintenance;Managed Care;Measures;Methods;Modeling;mortality;mortality risk;multimodality;multiple omics;novel;novel strategies;operation;Organ;Outcome;Patient Admission;patient population;Patient-Focused Outcomes;Patients;personalized management;Phenotype;Physiological;Population;Population Heterogeneity;precision medicine;preservation;Procedures;Process;racial disparity;recruit;repository;Research;Research Personnel;Research Support;Resources;Risk;screening;Sepsis;septic patients;Severities;Site;Source;Specimen;Standardization;surrogate decision maker;Suspensions;targeted treatment;Testing;Time;treatment and outcome;Trust;United States;Variant;Volatilization;ward;wearable sensor technology

PROJECT_TITLE: Scalable and Interoperable framework for a clinically diverse and generalizable sepsis Biorepository using Electronic alerts for Recruitment driven by Artificial Intelligence (short title:  SIBER-AI)

STUDY_SECTION: CIDH

STUDY_SECTION_NAME: Clinical Informatics and Digital Health Study Section[CIDH]