NIH_SPENDING_CATS: Biotechnology;Gene Therapy;Genetics;Hematology;Orphan Drug;Rare Diseases

ORG_CITY: CLEVELAND

ORG_NAME: CLEVELAND CLINIC LERNER COM-CWRU

PHR: Current hemophilia A (HA) treatments include intravenous infusion of FVIII concentrates or bispecific antibodies. However, these treatments are extremely costly, precluding 80% of the global hemophilia population to regular care. The project will explore several new directions of treating HA by targeting the complex posttranslational regulation of FVIII. We hope to develop novel small molecule therapeutics to treat HA based on each patient's mutation profile and help realize the goal of a cure for HA through gene therapy.

PI_NAMEs: ZHANG, BIN  (contact)

PROGRAM_OFFICER_NAME: WARREN, RONALD Q

PROJECT_TERMS: adeno-associated viral vector;adenovirus mediated delivery;Affect;B-domain-deleted factor VIII;Biomedical Engineering;Birth;Bispecific Antibodies;Bispecific Monoclonal Antibodies;Blood Coagulation Factor;candidate identification;Caring;Clinical Trials;Codon Nucleotides;cofactor;Communities;Complementary DNA;Complex;cost;cost effective treatment;Country;Dependovirus;Developing Countries;Disease;Dose;efficacy evaluation;enhancing factor;F8 gene;F9 gene;Factor IX;Factor VIII;gene therapy;Genes;Genetic Transcription;Goals;Health Services Accessibility;Hemophilia A;Hemophilia B;Hemorrhage;Hemostatic function;Hepatotoxicity;Hereditary Disease;Immune response;improved;In Vitro;in vitro activity;in vivo;in vivo evaluation;Infusion procedures;innovation;Intravenous infusion procedures;Investigation;Knowledge;Libraries;Link;Luciferases;male;Messenger RNA;Missense Mutation;Molecular;mouse model;Mus;mutant;Mutation;next generation;Nonsense Codon;Nonsense Mutation;novel;Office Visits;Outcome;Patient Compliance;Patients;Pattern;Pharmaceutical Preparations;pharmacologic;Plasma;Point Mutation;Population;Post-Translational Regulation;Predisposition;Production;protein expression;Proteins;proteostasis;Quality Control;Recombinants;Ribosomes;Safety;screening;small molecule;small molecule therapeutics;Subcutaneous Injections;success;Symptoms;System;Testing;Therapeutic;therapeutic target;Time;trafficking;Translations;Variant;vector;Viral Vector

PROJECT_TITLE: Developing hemophilia A therapeutics by targeting translational and posttranslational regulation of FVIII

STUDY_SECTION: HTBT

STUDY_SECTION_NAME: Hemostasis, Thrombosis, Blood Cells and Transfusion Study Section[HTBT]


ADMINISTERING_IC: NS

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Clinical Research;Congenital Structural Anomalies;Genetics;Muscular Dystrophy;Myotonic Dystrophy;Neurosciences;Orphan Drug;Pediatric;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: RICHMOND

ORG_COUNTRY: UNITED STATES

ORG_DEPT: NEUROLOGY

ORG_FIPS: US

ORG_NAME: VIRGINIA COMMONWEALTH UNIVERSITY

ORG_STATE: VA

PHR: Narrative This proposal seeks to define the molecular mechanisms that contribute to the disease progression of congenital myotonic dystrophy. This is a vital step to extend targeted, disease modifying therapies developed for adults with myotonic dystrophy, into this affected population. This understanding of disease pathogenesis will also allow for development of new biomarkers and identification of targets for future therapeutic development.

PI_NAMEs: JOHNSON, NICHOLAS ELWOOD (contact)

PROGRAM_OFFICER_NAME: NUCKOLLS, GLEN H

PROJECT_TERMS: 16 year old;8 year old;Adolescence;Adult;Affect;Age;age related;Alternative Splicing;associated symptom;Biological Markers;Biopsy;Biopsy Specimen;Birth;Breathing;Cell Aging;Child;Childhood;Clinical;Clinical Investigator;clinical phenotype;Clinical Research;Clinical Trials Design;cohort;Complex;Congenital Myotonic Dystrophy;Data;Data Analyses;Data Correlations;defined contribution;design;Development;differential expression;Disease;Disease Progression;drug development;early childhood;Enrollment;Event;experience;experimental study;Family;Fatigue;feeding;Follow-Up Studies;Future;gastrointestinal;Gene Expression;Genes;Genetic;Genetic Transcription;Goals;Hereditary Disease;IGF2 gene;improved;Individual;infancy;Infant;Intellectual impairment;intergenerational;Link;Longitudinal cohort;Measures;Mediating;Molecular;Motor;Muscle;Muscle function;Muscle hypotonia;muscle progenitor cell;muscle strength;Muscle Weakness;Muscular Dystrophies;Myotonia;Myotonic Dystrophy;Myotonic dystrophy type 1;new therapeutic target;novel;novel therapeutics;Parents;Pathogenesis;Patients;Pattern;Phase;Physical Function;Population;premature;Progressive Disease;Proliferating;Regenerative capacity;RNA;RNA metabolism;RNA Splicing;RNA-Binding Proteins;Role;Sampling;senescence;Severities;Signal Transduction;Skeletal Muscle;SNRPF gene;specific biomarkers;Spliceosomes;stem cell proliferation;Symptoms;Testing;therapeutic development;therapeutic target;Therapeutic Trials;therapy development;transcriptome sequencing;Work

PROJECT_TITLE: Identifying the RNA Splicing and Gene Expression Changes that Cause Congenital Myotonic Dystrophy (Renewal)

STUDY_SECTION: SMEP

STUDY_SECTION_NAME: Skeletal Muscle and Exercise Physiology Study Section[SMEP]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

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

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS EYE AND EAR INFIRMARY

ORG_STATE: MA

PHR: Project Narrative Secreted phosphoprotein 1 (SPP1) shows neuroprotective activity in mouse models of glaucoma and also slows retinal ganglion cell loss that occurs with normal aging. In astrocytes, SPP1 increases mitochondrial function, delivery of ATP from the mitochondria to the cytoplasm, and reduces the expression of inflammatory mediators. SPP1, or small molecules that increase SPP1 expression in the eye, may be attractive candidates for neuroprotective therapies in glaucoma and aging.

PI_NAMEs: JAKOBS, TATJANA CLAUDIA (contact)

PROGRAM_OFFICER_NAME: SONG, HONGMAN

PROJECT_TERMS: Age;Aging;Alpha Cell;Animal Model;Antiinflammatory Effect;Ascorbic Acid;Astrocytes;Attenuated;Blindness;Calcium ion;Cell Communication;Cell Count;Cell Culture Techniques;Cell Survival;Cells;Cellular biology;Cessation of life;Coculture Techniques;Complement 1q;conditional knockout;Crush Injury;cytokine;Cytoplasm;Data;Dendrites;experimental study;Eye;Fluorescence;Fluorescence-Activated Cell Sorting;ganglion cell;Gene Expression;Genes;Genetic;Genetic Recombination;Genetic Transcription;Glaucoma;Goals;Grant;Growth;Human;In Vitro;in vivo;Inflammation Mediators;Inflammatory;inflammatory marker;knock-down;Knock-out;Knockout Mice;Libraries;loss of function;Mammals;Mediating;Messenger RNA;Microglia;Microscopic;Microspheres;Mining;Mitochondria;Modeling;Morphology;mouse model;Mouse Strains;Mus;Nerve Crush;Neurodegenerative Disorders;Neuroglia;Neurons;neuroprotection;neurotoxic;neurotrophic factor;normal aging;Ocular Hypertension;Optic Disk;Optic Nerve;osteopontin;Outcome;Outer Mitochondrial Membrane;Output;overexpression;Oxidative Phosphorylation;Pathway Analysis;Phagocytosis;Physiologic Intraocular Pressure;preservation;Production;promoter;Proteins;Reporter Genes;Resources;Respiration;response;Retina;retinal damage;retinal ganglion cell degeneration;Retinal Ganglion Cells;Risk Factors;screening;Small Interfering RNA;small molecule;small molecule libraries;Structure;System;Testing;Therapeutic;Therapeutic Uses;Thyroid Hormones;TNF gene;transcriptome;transcriptome sequencing;Transgenic Mice;Transgenic Organisms;Tretinoin;VDAC1 gene;Vision;Visual impairment;Voltage-Dependent Anion Channel;Work

PROJECT_TITLE: Cell Biology of Astrocyte-Ganglion Cell Interactions in the Retina and Optic Nerve

STUDY_SECTION_NAME: Pathophysiology of Eye Disease - 1 Study Section[PED1]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: FARMINGTON

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT

ORG_STATE: CT

PHR: Effector T cells are primarily responsible for protecting the body against infection and cancer but how they differentiate and function continuous to be heavily studied. We have recently found that RNA binding proteins control aspects of effector CD8 T cell function. The goal of this research is to study the detailed steps of this process that might lead to new discoveries of therapeutics to treat human disease.

PI_NAMEs: VELLA, ANTHONY T (contact)

PROGRAM_OFFICER_NAME: SINGH, ANJU

PROJECT_TERMS: Address;Alternative Splicing;Antigens;Antitumor Response;Area;Bioinformatics;cancer immunotherapy;cancer infiltrating T cells;Cancer Model;CAR T cell therapy;CD28 gene;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;CD8B1 gene;cell behavior;Cell Physiology;Cells;checkpoint therapy;clinical translation;Clonal Expansion;Confusion;Custom;cytokine;cytotoxicity;Data;Dependence;design;Drug Combinations;effector T cell;Elements;Event;exhaust;exon skipping;Exons;Genes;genetic signature;Genetic Transcription;Genome;Goals;Human;human disease;Human Genome Project;Immune system;Immunization;Immunotherapy;immunotherapy trials;in silico;Individual;infancy;Infection;influenza infection;innovation;Interleukin-2;Introns;Investigation;Link;Malignant Neoplasms;Mediating;member;Messenger RNA;metabolic fitness;Methods;migration;Modeling;Molecular;Mus;NF-kappa B;Nonsense-Mediated Decay;novel;nuclear factors of activated T-cells;Outcome;Output;OX40;Pathway interactions;Patients;Pattern;Play;Poison;Post-Transcriptional Regulation;pre-clinical;premature;Process;Production;programs;Proliferating;protein function;Protein Isoforms;Proteome;Publishing;Rattus;receptor;Receptor Activation;receptor sensitivity;Regulation;Research;responders and non-responders;response;RNA;RNA Editing;RNA Splicing;RNA-Binding Proteins;Role;Series;Signal Transduction;Specificity;Spliceosomes;Surface;T cell differentiation;T cell response;T-Cell Activation;T-Cell Antigen Receptor Specificity;T-Cell Receptor;T-Lymphocyte;Terminator Codon;Testing;Therapeutic;TNF gene;Transcript;Transcriptional Regulation;transcriptome;transcriptome sequencing;transcriptomics;Translating;tumor;Tumor Immunity;Tumor Necrosis Factor Receptor

PROJECT_TITLE: How RNA binding proteins control effector T cell responses

STUDY_SECTION: CIC

STUDY_SECTION_NAME: Cellular Immunotherapy of Cancer Study Section[CIC]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

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

ORG_CITY: NEW YORK

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

ORG_STATE: NY

PHR: PROJECT NARRATIVE The neuromodulators dopamine and acetylcholine converge on many cells throughout the brain to evoke distinct (and occasionally opposite) effects. However, these neuromodulators are typically studied in isolation, leaving their combined effects on the brain and behavior largely unexplored. By revealing where, when and how dopamine and acetylcholine interact in the striatum of mice, this proposal will uncover how multiple neuromodulators cooperate to motivate actions and promote learning.

PI_NAMEs: TRITSCH, NICOLAS XAVIER (contact)

PROGRAM_OFFICER_NAME: FERNANDEZ, FERNANDO R

PROJECT_TITLE: Structure and Function of Striatal Neuromodulatory Dynamics

STUDY_SECTION: NMB

STUDY_SECTION_NAME: Neurobiology of Motivated Behavior Study Section[NMB]


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

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

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Project Narrative Pathogenic α-synuclein (αS) are prion-like aggregates that can spread from cell-to-cell driving diseases progression in Alzheimer’s disease and related dementia (ADRD). We have developed αS fibril-specific nanobodies that can target intracellular αS seeds. In this application, we will develop several nanobody-based agents that can target both intracellular and extracellular αS seeds, to abolish the cell-to-cell transmission of pathogenic αS seeds and alleviate αS-related ADRD.

PI_NAMEs: MAO, XIAOBO ;WANG, WENJING  (contact)

PROGRAM_OFFICER_NAME: SARRAF, SHIREEN AKHAVAN

PROJECT_TERMS: Accounting;Affinity;Alpha Cell;alpha synuclein;Alzheimer's Disease;Alzheimer's disease related dementia;Animal Model;Antibodies;Antibody Therapy;Automobile Driving;Autopsy;Behavioral;Binding;Binding Proteins;Biological Assay;Brain;Brain region;Cell Cycle;Cell membrane;Cells;Collaborations;cost;Cytoprotection;Cytosol;demented;Dementia;Dementia with Lewy Bodies;Dependovirus;design;Development;Directed Molecular Evolution;Disease;Disease Progression;disulfide bond reduction;efficacy testing;Engineering;Environment;Exhibits;experimental study;extracellular;Extracellular Space;immunoreactivity;Impaired cognition;improved;In Vitro;in vivo evaluation;Lewy Body Dementia;Molecular;monomer;multicatalytic endopeptidase complex;nanobodies;Nerve Degeneration;Neurodegenerative Disorders;Neuroglia;neuroinflammation;Neurons;novel;Parkinson's Dementia;particle;Pathogenesis;Pathogenicity;Pathologic;Pathology;Phosphorylation;Positioning Attribute;pre-formed fibril;prion-like;Prions;Protac;protein degradation;Protein Engineering;Proteins;Publishing;Reagent;Recombinants;screening;Series;Serine;Signal Transduction;Specificity;Stereotyping;synucleinopathy;System;targeted agent;targeted treatment;Technology;Therapeutic;Tissues;tool;transmission process;Ubiquitin;ubiquitin-protein ligase;uptake

PROJECT_TITLE: Novel fibril-selective nanobody-based agents targeting intracellular and extracellular α-synuclein aggregates and prion-like propagation induced dementia

STUDY_SECTION: INN

STUDY_SECTION_NAME: Innovations in Nanosystems and Nanotechnology Study Section [INN]


ADMINISTERING_IC: AR

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Bioengineering;Neurosciences;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: DURHAM

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Healthy skeletal muscle has remarkable capacity to regenerate due to the presence of muscle stem cells termed satellite cells, which are dysregulated in various muscle diseases including muscular dystrophies. Satellite cells within skeletal muscle reside in specialized microenvironments called niches, function of which is regulated by other cell types including muscle fibers, capillaries, and neurons. In this project, we will develop a complex multicellular human muscle cell culture model that recreates structure and function of the native satellite cell niche, which in turn will enable novel studies of human muscle physiology, regeneration, and disease.

PI_NAMEs: BURSAC, NENAD  (contact)

PROGRAM_OFFICER_NAME: LINDHURST, MARJORIE JEAN

PROJECT_TERMS: 3-Dimensional;Adult;Aging;angiogenesis;Autoimmune Diseases;Biochemical;Biomimetics;Biophysics;Blood capillaries;Blood Vessels;Cell Communication;Cell Count;Cell Culture Techniques;Cell Differentiation process;Cell Physiology;Cell secretion;cell type;Cells;Chronic Disease;Coculture Techniques;Complex;Congenital Disorders;congenital muscle disorder;Connective Tissue Cells;Denervation;Development;Disease;Endothelial Cells;Engineering;Exercise;Extracellular Matrix;Fiber;Functional disorder;Growth;Heterogeneity;Homeostasis;Human;human induced pluripotent stem cells;Hypoxia;Immune;Impairment;improved;In Vitro;in vitro Model;in vivo;induced pluripotent stem cell;Inflammation;Injury;injury and repair;Laceration;Lead;Life;Ligands;Location;Locomotion;Maintenance;Malignant Neoplasms;MAP Kinase Gene;Metabolic Diseases;Metabolism;Modeling;Motor Neurons;mouse model;Muscle;Muscle Cells;muscle engineering;Muscle Fibers;muscle physiology;muscle progenitor cell;muscle regeneration;muscle repair;Muscle satellite cell;Muscular Atrophy;Muscular Dystrophies;muscular system;Myoblasts;Myopathy;Natural regeneration;Nature;nerve supply;neuromuscular;Neuromuscular Diseases;Neuromuscular Junction;Neurons;neurovascular;notch protein;novel;Organ;Organoids;Outcome;paracrine;Pattern;Pharmaceutical Preparations;Phenotype;Positioning Attribute;Posture;Proliferating;recruit;Regenerative capacity;Regenerative response;repaired;Respiration;response;response to injury;Role;self-renewal;shear stress;Signal Transduction;Skeletal Muscle;skeletal muscle growth;Specific qualifier value;stem cell niche;stem cells;Structure;System;Therapeutic Studies;Tissues;Toxin;Vascularization;VEGFA gene;volumetric muscle loss;WNT Signaling Pathway

PROJECT_TITLE: Engineering Heterocellular Human Skeletal Muscle Tissues to Recreate and Study Native Stem Cell Niche Function

STUDY_SECTION: MTE

STUDY_SECTION_NAME: Musculoskeletal Tissue Engineering Study Section[MTE]


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Biotechnology;Bipolar Disorder;Brain Disorders;Genetics;Human Genome;Mental Health;Neurosciences

ORG_CITY: MADISON

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: PROJECT NARRATIVE Cognitive abilities in humans have a profound impact on life outcomes, and as such, there is inherent scientific value in identifying genes that regulate cognitive phenotypes. Using an in silico approach, we identified the ARHGEF11 gene, which encodes the PDZ-RhoGEF protein, as being of potentially critical importance in the regulation of learning and memory. As PDZ-RhoGEF has not been previously studied in the brain, our proposed studies will characterize the involvement of PDZ-RhoGEF in regulating murine cognition as well as the structure and function of neurons, and our studies will also investigate the molecular and biochemical mechanisms that control PDZ-RhoGEF expression and activity in neurons.

PI_NAMEs: CAHILL, MICHAEL EDWARD (contact)

PROGRAM_OFFICER_NAME: DRISCOLL, JAMIE DANIELLE

PROJECT_TERMS: 3' Untranslated Regions;Affect;Attention;behavioral phenotyping;Binding;Biochemical;Biological Process;Bipolar Disorder;Brain;brain based;Cerebral cortex;Cognition;Cognitive;cognitive ability;Cognitive deficits;cognitive function;cohort;Complex;Data;Dendritic Spines;DISC1 gene;Disease;Down-Regulation;DTR gene;Electrophysiology (science);enzyme activity;Exhibits;Experimental Designs;Functional disorder;Future;Gene Targeting;Gene Transfer;Genes;genome wide association study;genome-wide;Guanine Nucleotide Exchange Factors;hippocampal pyramidal neuron;Human;Human Genome;Image;Impaired cognition;in silico;Individual;interdisciplinary approach;interest;Investigation;knock-down;Lead;Learning;Life;Mediating;Memory;Mental disorders;Messenger RNA;Methods;MicroRNAs;Molecular;Monomeric GTP-Binding Proteins;Mus;Neocortex;neural;Neuroglia;Neurons;Outcome;Pathway interactions;Phenotype;Physiological;Population;Prefrontal Cortex;Probability;Prosencephalon;Proteins;Publishing;Regulation;RNA purification;RNA-Induced Silencing Complex;Rodent;Role;scaffold;Selection Bias;Selection Criteria;Signal Pathway;Signal Transduction;Structure;superresolution imaging;Synapses;synaptic function;Testing;theories;Therapeutic;therapeutic target;Time;ultra high resolution;Viral;Viral Genes;virtual;Visual;Work;yeast two hybrid system;Yeasts

PROJECT_TITLE: A multidisciplinary approach identifying PDZ-RhoGEF (ARHGEF11) as a critical regulator of synapses and cognition

STUDY_SECTION: LMDN

STUDY_SECTION_NAME: Learning, Memory and Decision Neuroscience Study Section[LMDN]


ADMINISTERING_IC: DA

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Behavioral and Social Science;Cannabinoid Research;Clinical Research;Drug Abuse (NIDA only);Pediatric;Social Determinants of Health;Substance Misuse

ORG_CITY: PROVIDENCE

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: BROWN UNIVERSITY

ORG_STATE: RI

PHR: PROJECT NARRATIVE In the wake of more permissive cannabis laws, availability, and positive normative perceptions, cannabis use prevalence during young adulthood continues to rise, and heavy use confers risk for cannabis-related problems and poorer health later in life. Young adulthood is typified by frequent, small-scale transitions, yet it is unclear how these micro-transitions confer risk (or resilience) for subsequent cannabis use, and underlying mechanisms linking the two remain poorly understood. To address these gaps, this proposal will use a 3-year prospective mixed-methods design to assess young adult micro-transitions, cannabis use patterns, and mechanisms linking these two constructs, which will ultimately inform future development of prevention and intervention efforts for young adults with hazardous cannabis use.

PI_NAMEs: ASTON, ELIZABETH  (contact)

PROGRAM_OFFICER_NAME: KIMMEL, HEATHER L

PROJECT_TERMS: Address;Age;age group;Automobile Driving;Behavior;behavior test;behavioral economics;Cannabis;Cannabis policy;cannabis use behavior;Cessation of life;Cognition;cognitive development;college;community-level factor;coping;cost;craving;critical developmental period;Data;Decision Making;design;Development;discounting;disorder risk;Economics;Education;efficacious intervention;Employment;Environment;Evaluation;Event;experience;Family member;Frequencies;Future;Goals;Health;Income;indexing;Individual;Intervention;Interview;Investigation;Late Effects;Life;Link;Long-Term Effects;Longitudinal Studies;marijuana use;marijuana use disorder;Marriage;Mediating;Mediator;Medical;Methods;Modeling;Outcome;Participant;Perception;permissiveness;Play;preference;Prevalence;Prevention;Price;prospective;Psychology;Public Health;Recreation;recruit;reinforcer;Reporting;Research;Research Design;residence;resilience;Resources;Rewards;Risk;Role;social;Statutes and Laws;substance use;Surveys;Symptoms;Testing;Time;willingness to pay;Work;young adult

PROJECT_TITLE: Using behavioral economic domains to characterize cannabis use trajectories among young adults: A prospective mixed-methods investigation

STUDY_SECTION: ARM

STUDY_SECTION_NAME: Addiction Risks and Mechanisms Study Section[ARM]


NIH_SPENDING_CATS: Bioengineering;Cancer;Colorectal Cancer;Digestive Diseases;Genetics;Immunotherapy;Liver Disease;Nanotechnology

ORG_CITY: AUGUSTA

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: AUGUSTA UNIVERSITY

ORG_STATE: GA

PHR: Project Narrative  This proposal will develop the SUV39H1-selective small molecule inhibitor F5446 nanoparticle eNP- F5446 to restore tumor cell sensitivity to cell death induction and to re-activate tumor-infiltrating CTL effector function in colorectal cancer. eNP-F5446 is expected to overcome human colorectal cancer resistance to PD-(L)1 blockade immunotherapy.

PI_NAMEs: LIU, KEBIN  (contact)

PROGRAM_OFFICER_NAME: FU, YALI

PROJECT_TERMS: anti-PD-1;Biodistribution;cancer cell;CD95 Antigens;Cell Death;Cell Death Induction;Cells;Cessation of life;Charge;Collaborations;Colon;colon cancer treatment;Colon Carcinoma;Colonic Neoplasms;Colorectal Cancer;Colorectal Neoplasms;cytotoxic;Cytotoxic T-Lymphocytes;Data;Deposition;Development;Dose;Drug Kinetics;efficacy evaluation;Encapsulated;Epigenetic Process;Functional impairment;Gene Expression;Genes;Granzyme;histone methyltransferase;Histones;Human;Immunocompetent;Immunosuppression;Immunotherapy;improved;in vivo;Infiltration;inhibitor;Knockout Mice;Large Intestine Carcinoma;literate;Literature;liver xenograft;Lysine;Maximum Tolerated Dose;Mediating;metastatic colorectal;Metastatic Neoplasm to the Liver;Microsatellite Instability;Microsatellite Repeats;Modeling;mouse model;Mus;nanoparticle;neoplastic cell;Particle Size;Pathway interactions;PD-1 blockade;Pharmaceutical Preparations;Pharmacologic Substance;Phenotype;Play;pre-clinical;programmed cell death ligand 1;programmed cell death protein 1;promoter;Proteins;Publishing;Regulator Genes;Repression;Resistance;Role;Safety;single cell ATAC-seq;single-cell RNA sequencing;Site;small molecule;small molecule inhibitor;Surface;T memory cell;Testing;Tissues;Toxic effect;Toxicology;trafficking;tumor;tumor growth;Virus Diseases;Work;Xenograft procedure

PROJECT_TITLE: Development of SUV39H1-selective inhibitor for human colon cancer therapy

STUDY_SECTION: ATA

STUDY_SECTION_NAME:
Advancing Therapeutics A Study Section
[ATA]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Biotechnology;Brain Disorders;Dementia;Genetics;Human Genome;Lewy Body Dementia;Neurodegenerative;Neurosciences;Parkinson's Disease;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: JACKSONVILLE

ORG_NAME: MAYO CLINIC  JACKSONVILLE

ORG_STATE: FL

PHR: PROJECT NARRATIVE  Lewy body dementia is a leading cause of Alzheimer’s disease related dementia affecting a large population of our aging society, yet we still do not fully understand the disease mechanisms and thus have no effective way to treat this devastating disease. Towards this, the goal of this proposal is to understand the molecular etiology of Lewy body dementia by studying the strongest genetic risk factor APOE4 which has been shown to have a direct influence on α-synuclein pathology in the human brain and our in vivo mouse models. Herein, we propose to use a multi-omics approach to profile human postmortem brains and utilize mouse model and human induced pluripotent stem cell-derived model to study disease mechanisms and validate the underlying molecular pathways of APOE4-related α-synuclein pathogenesis to inform targeted therapeutic intervention strategies in Lewy body dementia.

PI_NAMEs: ROSS, OWEN A;ZHAO, NA  (contact)

PROGRAM_OFFICER_NAME: LI, TONG

PROJECT_TERMS: 3-Dimensional;Address;Affect;Age;Age Months;Aging;Alleles;alpha synuclein;Alzheimer's disease pathology;Alzheimer's disease related dementia;Apolipoprotein E;apolipoprotein E-3;apolipoprotein E-4;Astrocytes;Autopsy;behavioral phenotyping;Brain;brain dysfunction;Brain region;Brain Stem;Cell Line;Cells;Central Nervous System;Clinic;Corn Oil;CRISPR/Cas technology;Data;Dementia;dementia risk;Development;Dimensions;Disease;disease mechanisms study;effective therapy;Endosomes;Ethnic Origin;Etiology;Excision;Florida;Functional disorder;Future;Gene Expression Profile;Genes;genetic risk factor;genome sequencing;genome wide association study;Genotype;glucosylceramidase;Goals;Homeostasis;Human;human induced pluripotent stem cells;human model;in vivo;Individual;induced pluripotent stem cell;inhibitor;innovation;Innovative Therapy;insight;Intervention;Knock-in Mouse;Late Onset Alzheimer Disease;Lewy Body Dementia;Lewy body pathology;Link;lipid transport;lipidomics;Lipids;Lipoproteins;LoxP-flanked allele;Mediating;Midbrain structure;Modeling;Molecular;Molecular Profiling;mouse model;multiple omics;Mus;Neocortex;Nerve Degeneration;nerve stem cell;neuroinflammation;neuronal survival;Neurons;Organoids;overexpression;Parkinson Disease;Pathogenesis;Pathology;Pathway Analysis;Pathway interactions;Patients;pharmacologic;Phenotype;Population;population stratification;Protein Isoforms;Proteomics;Publishing;Quality of life;Research;Resources;Risk;RNA;Role;Severities;sex;single nucleus RNA-sequencing;Societies;stem cell model;stem cell organoids;Structure;Synapses;System;Tamoxifen;targeted treatment;Technology;Temporal Lobe;Testing;Therapeutic;transcriptome sequencing;transcriptomics;Transgenic Mice;Transgenic Organisms;whole genome;Work

PROJECT_TITLE: Elucidating the Pathomechanisms of APOE4 in Lewy Body Dementia

STUDY_SECTION: CDIN

STUDY_SECTION_NAME: Chronic Dysfunction and Integrative Neurodegeneration Study Section[CDIN]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Brain Disorders;Cancer;Neurosciences;Orphan Drug;Pediatric;Pediatric Cancer;Prevention;Rare Diseases

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: PROJECT NARRATIVE Chemotherapy is a cornerstone of modern cancer therapy, yet it also damages healthy cells in the brain. Here, we combine cutting edge metabolite profiling, chemical detection methods, and genetic approaches to study the molecular mechanisms by which the chemotherapy methotrexate leads to oxidative distress in the choroid plexus, cerebrospinal fluid, and hippocampus. These experiments represent a critical new direction of investigation into how a current limitation of cancer chemotherapy can be reduced or prevented in the brain by leveraging CSF-based solutions.

PI_NAMEs: KANAREK, NAAMA  (contact)

PROGRAM_OFFICER_NAME: CLIFFORD, JOHN LEO

PROJECT_TERMS: Acceleration;Acetylcysteine;adeno-associated viral vector;Adult;Adverse effects;Affect;antioxidant enzyme;antioxidant therapy;Antioxidants;Anxiety;Arginine;Ascorbic Acid;Astrocytes;Ataxia;Behavioral;Brain;brain cell;brain tissue;cancer cell;Cancer Patient;Cancer Survivor;cancer therapy;Cell Respiration;Cells;Central Nervous System;Central Nervous System Lymphoma;Cerebrospinal Fluid;Cessation of life;Chemicals;chemobrain;chemotherapy;Chemotherapy-Oncologic Procedure;Child;Childhood;Childhood Leukemia;Clinical;Cognitive;Confusion;detection method;Disease;Distress;dosage;Encephalitis;Environment;Equilibrium;experience;experimental study;Face;feasibility testing;Feeds;Folic Acid Antagonists;gain of function;Gene Expression;gene therapy;gene-targeted therapy;Genetic;genetic approach;Goals;Health;Health Promotion;Health Status;Heart;Hippocampus;Human;Impaired cognition;improved;Injections;Intervention;Investigation;Learning;leukemia;Life;Lipid Peroxidation;loss of function;Lymphoma;macromolecule;Malignant neoplasm of brain;Measures;Mediating;Memory;Memory impairment;Metabolic;metabolic abnormality assessment;Methotrexate;Microglia;Modernization;Molecular;Monitor;Mus;Myelin;Names;Neoplasm Metastasis;Nervous System Trauma;Neurocognitive;Neurocognitive Deficit;Neurons;neurotoxic;neurotoxicity;Nitric Oxide;Oligodendroglia;Organ;overexpression;Oxidation-Reduction;oxidative damage;Patients;pediatric patients;Performance;Peripheral;Peroxonitrite;Pharmaceutical Preparations;pharmacologic;Poly(ADP-ribose) Polymerases;postsynaptic;preservation;presynaptic;prevent;Preventive care;Preventive treatment;Role;Sampling;Schools;side effect;standard of care;stem;Structure of choroid plexus;Supplementation;survivorship;Symptoms;System;Testing;Therapeutic;therapeutic target;therapeutically effective;tool;Toxic effect;tumor;uptake;vector control;Viral Vector

PROJECT_TITLE: Mechanistic Study of Methotrexate-Induced Oxidative Distress in Neurons and the CSF

STUDY_SECTION: NOMD

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


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Chronic Obstructive Pulmonary Disease;Genetics;Human Genome;Lung;Precision Medicine;Prevention;Women's Health Research

ORG_CITY: HERSHEY

ORG_NAME: PENNSYLVANIA STATE UNIV HERSHEY MED CTR

ORG_STATE: PA

PHR: NARRATIVE COPD is one of the leading risk factors for death, which has strong genetic basis. Currently no therapy exists that can reduce mortality or slow down the progression of the disease. Females tend to have more severe disease outcomes and the prevalence and mortality rate in female are increasing. Multi-omic studies of COPD can reveal disease etiology and guide the development of novel biomarkers, both of which have strong public health relevance.

PI_NAMEs: LIU, DAJIANG  (contact);MANICHAIKUL, ANI WANG;SHIM, YUN MICHAEL

PROGRAM_OFFICER_NAME: LU, QING

PROJECT_TERMS: Acute;Affect;Age;airway obstruction;Anxiety;Apoptosis;Asthma;Atlases;Biological Markers;biomarker identification;Candidate Disease Gene;Capillary Endothelial Cell;causal variant;Cause of Death;cell type;Cells;Cessation of life;Chronic Obstructive Pulmonary Disease;cohort;comorbidity;Data;Data Set;Death Rate;Detection;Development;Diagnosis;Disease;Disease Outcome;Disease Progression;Disease susceptibility;disorder prevention;disorder subtype;Dyspnea;Etiology;Exhibits;experience;Exposure to;Female;Forced expiratory volume function;Genes;Genetic;genetic analysis;genetic architecture;genetic association;Genetic Markers;Genetic Research;Genetic study;genetic variant;genome wide association study;genomic locus;Genomics;Heritability;Human;improved;Individual;Inflammation;innovation;insight;interest;Lead;Link;Lung;Measures;men;Methods;monocyte;mortality;multiple omics;Myofibroblast;National Heart, Lung, and Blood Institute;Non-Small-Cell Lung Carcinoma;novel;novel marker;novel strategies;Pathology;Pathway interactions;Pattern;Peptide Hydrolases;pharmacologic;phenome;Phenotype;Plasma;Plasma Proteins;pollutant;Prevalence;Protease Inhibitor;protein biomarkers;Protein Secretion;Proteins;Proteomics;public health relevance;Pulmonary Emphysema;pulmonary function;Pulmonary Surfactant-Associated Protein D;Pulmonology;Quantitative Trait Loci;Reporting;Reproducibility;Research;Research Personnel;Resources;Risk;Risk Factors;risk variant;Sample Size;Severities;sex;Sex Differences;Signal Transduction;single-cell RNA sequencing;Sleep Apnea Syndromes;smoking prevalence;soluble RAGE;Statistical Methods;statistics;Structure of parenchyma of lung;success;Symptoms;therapeutic development;Time;Tissue Sample;Tissues;transcriptome;United States;Variant;Vital capacity;Whole Blood;Woman;Women's mortality;women's outcomes

PROJECT_TITLE: Multi-omic Characterization of COPD in Females

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 NV-J (96)]


ORG_CITY: BALTIMORE

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: PROJECT NARRATIVE Cardiac amyloidosis results in a restrictive cardiomyopathy that is often caused by a mutation in the protein transthyretin, resulting in dissociation from its complex and uptake into the myocardium where it forms large protein aggregates and amyloid fibrils. The mechanisms that regulate the degradation of transthyretin in the heart and methods to enhance this were unknown until now. This proposal investigates unexplored underpinnings of cardiac amyloidosis and tests a novel mechanism in which increasing Chip phosphorylation via gene mutation and pharmacological protein kinase G activation enhances the removal of mutant transthyretin and improve cardiac function, potentially providing a new and viable therapeutic target for cardiac amyloidosis.

PI_NAMEs: RANEK, MARK JOHN (contact)

PROGRAM_OFFICER_NAME: SHI, YANG

PROJECT_TERMS: 3-Dimensional;Address;Affect;Amyloid;Amyloid Fibrils;Attenuated;biobank;Biological Models;Biopsy;Calcium;Cardiac;cardiac amyloidosis;Cardiac Myocytes;cardiac tissue engineering;Cardiomyopathies;Cell Death;Complex;Coupled;Cyclic AMP-Dependent Protein Kinases;Cyclic GMP;Cyclic GMP-Dependent Protein Kinases;cytotoxicity;Data;Defect;Dependence;Deposition;Depressed mood;Devices;Disease;Dissociation;EFRAC;Excision;Excretory function;extracellular;Failure;Female;Fibroblasts;Functional disorder;Gene Mutation;Genes;Heart;Heart Diseases;Heart failure;heart function;Heat Shock 70kD Protein Binding Protein;Hepatic;Hereditary Disease;Human;human data;human induced pluripotent stem cells;human tissue;Impairment;improved;In Vitro;in vitro Model;in vivo;Incubated;induced pluripotent stem cell derived cardiomyocytes;inhibitor;insight;Isoleucine;Knock-in Mouse;Lysosomes;male;Measures;Mediator;men;meter;Methods;Microfilaments;mimetics;Modeling;Molecular Chaperones;monomer;multicatalytic endopeptidase complex;Mus;Muscle Cells;mutant;Mutate;Mutation;Myocardial;Myocardial dysfunction;Myocardial Infarction;Myocardium;new therapeutic target;novel;novel therapeutic intervention;Organoids;Ovariectomy;Oxidative Stress;Pathogenesis;Pathway interactions;Patients;pharmacologic;phosphodiesterase V;Phosphorylation;Phosphotransferases;Physiological;Plasma;Positioning Attribute;Post-Translational Protein Processing;Postmenopause;Pre-Clinical Model;Prealbumin;Process;Protac;protein aggregation;protein degradation;protein function;protein protein interaction;Proteins;proteostasis;Relaxation;Reporting;Restrictive Cardiomyopathy;Role;Serine;Signal Transduction;Stress;System;Testing;Therapeutic;therapeutic target;Tissue Model;Tissues;tool;translational model;ubiquitin ligase;ubiquitin-protein ligase;uptake;Valine;Variant;Woman;Work

PROJECT_TITLE: Chip phosphorylation stimulates the degradation of mutant transthyretin to attenuate cardiac amyloidosis

STUDY_SECTION: MPPA

STUDY_SECTION_NAME: Integrative Myocardial Physiology/Pathophysiology A Study Section [MPPA]


NIH_SPENDING_CATS: Cardiovascular;Genetics;Heart Disease;Human Genome;Orphan Drug;Rare Diseases

ORG_CITY: HOUSTON

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

ORG_STATE: TX

PHR: The nuclear genome is susceptible to damage by various stressors, which cause DNA lesions including breaks in both DNA strands. We plan to identify and characterize the breaks in the mouse heart, determine their biological and clinical effects, and assess the benefits of preventing the breaks and enhancing their repairs.

PI_NAMEs: MARIAN, ALI J (contact)

PROGRAM_OFFICER_NAME: TJURMINA, OLGA A

PROJECT_TERMS: Arrhythmia;ATAC-seq;Attenuated;Award;Binding;Binding Sites;Biological;Cardiac;Cardiac Myocytes;Cardiomyopathies;Cardiovascular Diseases;Cell Death;cell type;Cellular Stress;Charge;Chromatin;clinical effect;Consumption;Cytosol;Dangerousness;Data;Defect;Dilated Cardiomyopathy;DNA;DNA Damage;DNA Double Strand Break;DNA lesion;Dominant-Negative Mutation;Dose;effective therapy;Enzymes;Fibroblasts;Fibrosis;Gene Expression;Generations;Genes;Genetic;Genetic Transcription;Genome;genome-wide;Genomic Instability;Genotype;Heart;Heart failure;heart function;Heart Transplantation;Heterozygote;Human;improved;inducible Cre;Inflammation;Inflammatory;inherited cardiomyopathy;insight;IRF3 gene;Knock-in;Knock-in Mouse;Lamin Type A;Lamins;Mammalian Cell;Mediating;Molecular;Molecular Genetics;mouse model;Mus;Mutation;Myocardial dysfunction;Nature;Nicotinamide Mononucleotide;novel;Nuclear;Nucleotides;Pathogenesis;Pathogenicity;Pathologic;Pathway interactions;Patients;Phenotype;Poly(ADP-ribose) Polymerases;Predisposition;prevent;Process;Protein Isoforms;Proteins;prototype;Publishing;Regulator Genes;repaired;replication stress;Research Design;response;Role;Sampling;senescence;Site;STING1 gene;stressor;sudden cardiac death;Supplementation;Tamoxifen;Testing;therapeutic target;Time;Titrations;Topoisomerase

PROJECT_TITLE: Mechanisms and Therapeutic Targeting of DNA Damage in Dilated Cardiomyopathy Caused by LMNA Mutations


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

ORG_DEPT: ANATOMY/CELL BIOLOGY

PHR: Project Narrative The proposed studies address the national healthcare issues of altered cognition after mild traumatic brain injury. The prevalence of traumatic brain injury is in the millions of patients every year, with a portion having chronic symptoms, including cognitive dysfunction that significantly impairs quality of life. These studies will examine a potential cellular and network underlying cause of altered cognition and the effect of specific treatments that can be translated into treatments for human patients.

PI_NAMEs: GREER, JOHN ;JACOBS, KIMBERLE MAE (contact)

PROGRAM_OFFICER_NAME: UMOH, NSINI ALEASE

PROJECT_TERMS: Acetylcysteine;Acute;Address;Affect;Agglutinins;Animal Model;Animal Testing;Animals;autism spectrum disorder;Axon;Axotomy;base;behavior test;biocytin;biological sex;Cells;Chronic;Clinical;Clinical Data;Cognition;cohort;cytokine;Data;density;designer receptors exclusively activated by designer drugs;Diffuse;Digestion;disease model;drinking water;effectiveness testing;Electroencephalography;Epidemic;Female;Fiber;Filament;Fire - disasters;fluid percussion injury;Frequencies;Functional disorder;Genetic;glial activation;Healthcare;hippocampal pyramidal neuron;Human;Hypersensitivity;Impaired cognition;Impairment;induced pluripotent stem cell;Inflammation;Inflammatory;Injury;Interleukin-1 beta;Interneuron function;Interneurons;Knockout Mice;Link;male;Measurement;Measures;Membrane;metabolic rate;Microglia;mild traumatic brain injury;Modeling;mouse model;Mus;Mutant Strains Mice;neocortical;network dysfunction;Neurons;Nociception;offspring;optogenetics;Outcome;Outcome Measure;Output;Oxidative Stress;Pain;pain sensitivity;Pain Threshold;Partner in relationship;Parvalbumins;patch clamp;Patients;Perception;Peripheral;persistent symptom;Population;Prevalence;prevent;Property;Public Health;Quality of life;Reactive Oxygen Species;repaired;Rest;Schizophrenia;Sensory;Somatostatin;Stains;Structure;Synapses;TBI Patients;Testing;Time;Touch sensation;Translating;Traumatic Brain Injury;Treatment Effectiveness;Vibrissae;Virus;Wisteria

PROJECT_TITLE: Mild traumatic brain injury alters interneuron structure and function

STUDY_SECTION: BINP

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


NIH_SPENDING_CATS: Breast Cancer;Cancer;Immunotherapy;Nutrition;Obesity;Women's Health Research

ORG_CITY: WASHINGTON

ORG_NAME: GEORGE WASHINGTON UNIVERSITY

ORG_STATE: DC

PHR: NARRATIVE  Efficacy of current αPD-1/PD-L1 immunotherapies in breast cancer is limited. In addition, obesity- associated chronic inflammation and metabolic dysfunction have become an increasing health burden. By focusing on a previously unappreciated source of PD-L1 in white adipose tissue, our proposed study could inform ways to improve efficacy of anticancer immunotherapy, especially among cancer patients who are obese.

PI_NAMEs: CURIEL, TYLER J.;HU, YANFEN ;LI, RONG  (contact)

PROGRAM_OFFICER_NAME: LIU, YIN

PROJECT_TERMS: Ablation;Adipocytes;Adipose tissue;Affect;anti-PD-1;anti-PD-L1;Antibodies;attenuation;behavior influence;Binding;Biology;Breast;Breast Cancer Patient;Breast Cancer therapy;Cancer Biology;Cancer Burden;cancer immunotherapy;Cancer Patient;cancer type;Cell Communication;cell type;Cells;checkpoint therapy;Chronic;Clinical Trials;clinically relevant;Coculture Techniques;Complex;Data;Development;Exclusion;experimental study;Foundations;Gene Expression Regulation;Genetic Transcription;genomic tools;Health;Immune;immune checkpoint;immune checkpoint blockade;immunoregulation;Immunotherapy;improved;In Vitro;Inflammation;insight;Knockout Mice;Link;lipid biosynthesis;lipid metabolism;Lymphocyte;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary Gland Parenchyma;Mammary Neoplasms;Mediating;Metabolic dysfunction;Modeling;Molecular;mortality;mouse model;neoplastic cell;Non obese;novel;novel strategies;Obesity;Pathway interactions;Patients;Positioning Attribute;Prediction of Response to Therapy;predictive tools;programmed cell death ligand 1;programmed cell death protein 1;programs;Proteins;receptor;response;Role;Shapes;Signal Transduction;Solid;Solid Neoplasm;Source;Stromal Cells;System;Testing;Therapeutic;Thinness;tool;Transcriptional Regulation;treatment response;tumor;tumor growth;Tumor Immunity;tumor immunology;tumor microenvironment;tumor progression;Tumor Promotion;Tumor-infiltrating immune cells;tumorigenesis;Up-Regulation;Work

PROJECT_TITLE: Adipocyte PD-L1 in the Breast Tumor Microenvironment

STUDY_SECTION: THI

STUDY_SECTION_NAME: Tumor Host Interactions Study Section[THI]


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Immunization;Infectious Diseases;Neurosciences;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Vaccine Related;Women's Health Research

ORG_CITY: DAVIS

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

ORG_STATE: CA

PHR: PROJECT NARRATIVE This application will address the impact of cytomegalovirus infection during pregnancy, as well as the role of maternal inflammation, on the developing fetal immune system in a translational primate model. Studies will also track virus and T cells to learn how they exert a lasting influence on prenatal and postnatal immunity.

PI_NAMEs: HARTIGAN-O'CONNOR, DENNIS J.;TARANTAL, ALICE F (contact)

PROGRAM_OFFICER_NAME: MAJJI, SAI PRASANNA

PROJECT_TERMS: Acute;Address;Adult women;Age;Antibody Response;Antigen-Presenting Cells;Biological Models;Birth;Blood specimen;Brain;CD8B1 gene;Cell Physiology;Cells;Central Nervous System;Chronic;congenital infection;cytokine;Cytomegalovirus;Cytomegalovirus Infections;Data;design;Development;Disease;early pregnancy;Environment;Enzyme-Linked Immunosorbent Assay;Female of child bearing age;fetal;Fetal Development;fetal programming;Fetus;fetus cell;Flow Cytometry;Fluzone;Frequencies;Goals;Growth;Health;Hematopoietic stem cells;Human;Human Development;human disease;Immune;immune activation;immune function;Immune response;Immune system;Immunity;Immunize;Infection;Inflammation;Inflammation Mediators;Inflammatory;Innate Immune Response;innovation;insight;Investigation;Learning;Link;Live Birth;Location;Lymphoid;Macaca mulatta;maternal immune system;Maternally-Acquired Immunity;Measures;Mediating;Mediator;Metabolic;Microglia;Modeling;Monitor;multidisciplinary;Natural Immunity;neonate;nerve stem cell;neurodevelopment;Nutrient;offspring;Outcome;Peripheral;Phenotype;Placenta;placental infection;placental transfer;Positron-Emission Tomography;postnatal;Predisposition;Pregnancy;prenatal;prenatal exposure;Prevnar;Primary Infection;Primates;radiotracer;response;Rhesus;Role;seropositive;Shapes;systemic inflammatory response;Systems Development;T cell response;T-Cell Activation;T-Lymphocyte;Techniques;Technology;Testing;tool;trafficking;transmission process;Vaccination;vaccine immunogenicity;Virus;Virus Diseases

PROJECT_TITLE: Impact of Maternal Inflammation and Cell Trafficking on Fetal Immune Ontogeny

STUDY_SECTION: PN

STUDY_SECTION_NAME: Pregnancy and Neonatology Study Section[PN]


NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Genetics;Heart Disease;Heart Disease - Coronary Heart Disease

ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

PHR: PROJECT NARRATIVE There are distinct populations of neutrophils that enter the heart after ischemia-reperfusion, and it is unknow whether they have differing effects on cardiac injury. We have identified a population of neutrophils that has a type I interferon response signature and have made neutrophil-specific knock out animals of 2 key genes in this pathway. In these aims we will utilize human cells and mouse models to test if type I interferon is a driver of detrimental neutrophilic inflammation after cardiac ischemia-reperfusion.

PI_NAMEs: LEVIT, REBECCA DIANE (contact)

PROGRAM_OFFICER_NAME: POIZAT, CORALIE ISABELLE

PROJECT_TERMS: Acute;adaptive immune response;Adenosine Monophosphate;Affect;Aftercare;Binding;Biological Assay;Biology;Blood capillaries;Blood Platelets;Bone Marrow;Cardiac;Cell model;Cell Physiology;Cell Separation;Cells;Centrifugation;Chemicals;chemokine;Chronic;Cicatrix;Circulation;Clinical;clinically relevant;Complement Activation;Cyclic GMP;cytokine;Data;density;DNA;DNA Viruses;Endothelium;Event;Exclusion;experimental study;extracellular;Genes;genetic signature;Genetic Transcription;Heart;heart function;Heart Injuries;Hour;Human;IFNAR1 gene;Immune;Immune response;Immune system;Impairment;improved;in vitro Assay;in vivo;Infiltration;Inflammation;Inflammatory;Inflammatory Response;inhibitor;Interferon alpha;interferon alpha receptor;interferon antagonist;Interferon Receptor;Interferon Type I;Interferons;Intervention;Ischemia;Knock-out;knockout animal;Knockout Mice;Leukocytes;Lupus;Macrophage;Measures;Mediating;Modeling;Modernization;Molecular;mouse model;Mouse Strains;Mus;Myocardial Infarction;Myocardial Ischemia;Myocarditis;Myocardium;Nature;neutrophil;Neutrophil Activation;Neutrophil Infiltration;novel;Nutrient;Oxygen;Pathway interactions;Pattern;Peptide Hydrolases;Phenotype;Physiology;Play;Population;Production;Reactive Oxygen Species;receptor;Recovery;Reperfusion Injury;Reperfusion Therapy;Resolution;response;Role;Sampling;Shapes;Signal Transduction;single-cell RNA sequencing;Source;standard of care;Stimulator of Interferon Genes;targeted treatment;Techniques;Testing;Therapeutic Intervention;therapeutic target;Tissues;transcriptomics;type I interferon receptor;Viral;Virus Diseases;Virus Replication

PROJECT_TITLE: Very early drivers of neutrophilic inflammation in cardiac ischemia-reperfusion

STUDY_SECTION: MPPB

STUDY_SECTION_NAME: Integrative Myocardial Physiology/Pathophysiology B Study Section[MPPB]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Antimicrobial Resistance;Bioengineering;Emerging Infectious Diseases;Infectious Diseases;Nanotechnology;Physical Injury - Accidents and Adverse Effects;Prevention

ORG_CITY: MORGANTOWN

ORG_DEPT: ORTHOPEDICS

ORG_NAME: WEST VIRGINIA UNIVERSITY

ORG_STATE: WV

PHR: PROJECT NARRATIVE Open fracture infections are increasingly difficult to treat due to growing antibiotic resistance. This application outlines strategies to revive old antimicrobial agents by hybriding two materials with different dimensions at the nanometer scale to increase antimicrobial properties and to reduce host toxicity.

PI_NAMEs: LI, BINGYUN  (contact)

PROGRAM_OFFICER_NAME: XU, ZUOYU

PROJECT_TERMS: Animal Model;anti-microbial drug;Antibiotic Resistance;antibiotic resistant infections;Antibiotics;antimicrobial;Bacteria;Bacterial Antibiotic Resistance;Bandage;Biomedical Engineering;bone;Bone Transplantation;Carbon nanoparticle;Carbon Nanotubes;Catheters;Cells;Cessation of life;chronic infection;Clinical;clinically relevant;cost;cytotoxicity;Dental Implants;Dimensions;dosage;Drug Delivery Systems;Drug Formulations;Engineering;Femoral Fractures;Fracture Fixation;Gentamicins;Goals;healing;Health Care Costs;Healthcare;Human;Implant;improved;In Vitro;in vivo;in vivo bioluminescence imaging;Individual;Infection;infection management;Infection prevention;infection rate;Injections;innovation;Knowledge;Limb structure;Medical;Mesenchymal Stem Cells;Methods;Microbial Biofilms;Modeling;Morbidity - disease rate;mortality;nanomaterials;nanoparticle;nanoscale;Nanotechnology;Needles;Nitrates;Open Fractures;operation;Orthopedics;Osteoblasts;Osteoclasts;Osteomyelitis;Outcome;Patient Compliance;Patients;Pharmaceutical Preparations;pre-clinical;Predisposition;prevent;Property;Rattus;Recovery;recurrent infection;Reporting;Research;Resistance development;Rifampin;Safety;Silver;Surface;systemic toxicity;Testing;Therapeutic;Tibial Fractures;Tissues;Toxic effect;translational approach;Treatment outcome;Vancomycin

PROJECT_TITLE: Nanohybrid Composites Minimize Antibiotic Resistant Infections

STUDY_SECTION: BMBI

STUDY_SECTION_NAME: Biomaterials and Biointerfaces Study Section[BMBI]


NIH_SPENDING_CATS: Cardiovascular;Heart Disease;Heart Disease - Coronary Heart Disease;Regenerative Medicine

PHR: Project Narrative We are characterizing the function of hapln1a+ epicardial cells and their subsets on cardiomyocyte proliferation and coronary growth during heart morphogenesis and regeneration, utilizing several novel genetic tools and live imaging techniques. Our work will reveal the impact of epicardial subsets on myocardial regeneration and coronary revascularization, and key underlying regulators of both processes. These findings will inform approaches for comprehending and enhancing the limited regeneration displayed by humans after myocardial infarction (MI).

PI_NAMEs: WANG, JINHU  (contact)

PROJECT_TERMS: Adolescent;Adult;base;Biology;Biomedical Engineering;Blood Vessels;Cardiac;Cardiac Myocytes;cardiac regeneration;cardiac repair;Cardiovascular system;cell motility;Cells;Coronary;CRISPR/Cas technology;defined contribution;Deposition;Development;Epicardium;Event;Extracellular Matrix;Genes;Genetic;Goals;Growth;Heart;Heart Atrium;heart damage;Heart failure;Human;Hyaluronan;hyaluronan synthase 1;Imaging Techniques;In Situ Hybridization;Lead;Mammals;Mesothelium;Molecular;Morbidity - disease rate;Morphogenesis;mortality;Muscle;mutant;Myocardial;Myocardial Infarction;Myocardium;Natural regeneration;novel;novel therapeutic intervention;Pathway interactions;pharmacologic;Play;Population;Process;Proliferating;Regenerative capacity;revascularization;Role;Signal Transduction;single-cell RNA sequencing;Structure;Surface;teleost fish;Testing;Therapeutic;Tissues;tool;Transgenic Organisms;United States;Ventricular;Visualization;Work;Zebrafish

PROJECT_TITLE: Characterization of hapln1a positive cells during zebrafish heart regeneration

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 CDD-Q (81)]


ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

PHR: PROJECT NARRATIVE We propose to fabricate a human skin substitute that can be used to treat patients, and will use this project to address two problems that are common to tissue engineering of all vascularized replacement organs, namely how to incorporate a functional microvascular system for organ perfusion and how to avoid immune-mediated rejection by the graft recipient. We will introduce four innovations: (1) we will use the power of 3D printing to replicate the different layers of natural human skin; (2) we will use only human materials to avoid allergic responses; (3) we will create a well differentiated blood vessel system by combining different vessel wall cell types and novel approaches of drug delivery to promote robust and stable engraftment; and (4) we will use tools of genetic engineering (CRISPR/Cas9) and drug delivery to minimize immune-mediated rejection of the graft by human immune system mouse hosts. These advances will both improve upon current skin substitutes and will generate paradigms with broad applications to tissue engineering.

PI_NAMEs: POBER, JORDAN S (contact);SALTZMAN, W. MARK

PROGRAM_OFFICER_NAME: LUNDBERG, MARTHA

PROJECT_TERMS: 3D Print;Ablation;Address;allergic response;Allogenic;Animals;bioink;Biological Models;Biomedical Engineering;Blood Vessels;Body System;Caliber;cell assembly;Cell Survival;Cell Transplantation;cell type;Cell Wall;Cells;Characteristics;Clinical;clinical translation;Collagen;Complex;CRISPR/Cas technology;Cutaneous;Dermal;Dermis;diabetic;Drug Delivery Systems;Elderly;Elements;Endothelial Cells;Endothelium;Engineering;Engraftment;Epidermis;experimental study;extracellular;Fibroblasts;Gene Modified;Genes;Genetic;Genetic Engineering;genetic manipulation;Goals;Graft Rejection;Grant;Growth Factor;healing;HLA Antigens;Human;Immune;Immune Evasion;Immune system;Immunodeficient Mouse;immunogenic;immunogenicity;Immunologics;Impaired healing;Impaired wound healing;improved;innovation;keratinocyte;Knowledge;Link;Mediating;Modeling;Mus;Myelogenous;Natural Killer Cells;Neonatal;novel strategies;Organ;Organ Donor;Organ failure;Papillary;Patients;Pattern;penis foreskin;Perfusion;Pericytes;pharmacologic;Placenta;Population;prevent;Principal Investigator;Printing;Proteins;prototype;Regenerative Medicine;repaired;response;revascularization;Science;self assembly;Skin;Skin graft;Skin repair;Skin Substitutes;Smooth Muscle Myocytes;Source;Structure of umbilical artery;synergism;System;T memory cell;Technology;Therapeutic;Thrombosis;Tissue Engineering;Tissues;tool;Transplantation;transplantation therapy;Ulcer;Vascular Smooth Muscle;Vascular System;Vascularization;Work

PROJECT_TITLE: Optimizing Therapeutic Revascularization by Endothelial Cell Transplantation

STUDY_SECTION: BTSS

STUDY_SECTION_NAME: Bioengineering, Technology and Surgical Sciences Study Section[BTSS]


NIH_SPENDING_CATS: Breast Cancer;Cancer;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Women's Health Research

ORG_DEPT: PATHOLOGY

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: Project Narrative Breast cancer and other solid tumors produce painful and disabling metastases much more frequently at the spine than other skeletal sites, though the underlying forces driving this effect are unclear. Here, we have discovered a new stem cell responsible for forming the vertebrae and will determine how this stem cell drives vertebral metastases and how blocking factors produced by this stem cell may offer new therapeutic opportunities to prevent or treat breast cancer spine metastases.

PI_NAMEs: GREENBLATT, MATTHEW BLAKE (contact)

PROGRAM_OFFICER_NAME: NADEAU, CHRISTINE FRANCES

PROJECT_TERMS: Alleles;Anatomy;Antibodies;Automobile Driving;Biochemical;Biological;Biological Factors;blocking factor;Blood flow;bone;Bone Tissue;candidate identification;Cartilage;CD 200;Cell Lineage;Cell surface;cell type;Cells;Clinical;clinical translation;clinically relevant;Cytometry;disability;Disabling;Disease Progression;driving force;EGF gene;ENG gene;Environment;Flow Cytometry;Fracture;Genetic Markers;Genetic study;Human;Image;Immune;in vivo;long bone;loss of function;Malignant Breast Neoplasm;Malignant neoplasm of lung;Malignant neoplasm of prostate;Malignant Neoplasms;Mediating;Mediator;Metastatic Neoplasm to the Bone;milk fat globule;mineralization;Modeling;mortality;mouse genetics;Mus;Neoplasm Metastasis;neoplastic cell;novel;novel therapeutics;Organoids;Osteoblasts;Pain;Pathology;PECAM1 gene;Phenotype;Population;prevent;PTPRC gene;recruit;response;Role;Signal Transduction;Site;skeletal;skeletal stem cell;skeletal-related events;Skeleton;Solid Neoplasm;Source;Specificity;spine bone structure;stem cells;System;Therapeutic;Therapeutic Studies;translational therapeutics;Transplantation;Tropism;tumor;Tumor-Derived;Vascular Endothelium;Vertebral Bone;Vertebral column;Work;Xenograft procedure

PROJECT_TITLE: Discovery of a stem cell driving breast cancer spine metastases


NIH_SPENDING_CATS: Aging;Arthritis;Genetics;Osteoarthritis

ORG_CITY: SALT LAKE CITY

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: PROJECT NARRATIVE Osteoarthritis (OA) is a painful and debilitating disease involving abnormal remodeling of joint tissues; it is a major cause of disability among the aging and no cure exists. We use genetic studies of families with inherited forms of early-onset OA to discover common genes and pathways that govern susceptibility to OA, and we then determine if the variant genes have altered functions. We develop and characterize a new mouse models that harbor a human susceptibility gene to understand the pathways that are vulnerable to both injury induced and age-related OA to help develop therapies.

PI_NAMEs: JURYNEC, MICHAEL J (contact)

PROGRAM_OFFICER_NAME: ZHENG, XINCHENG

PROJECT_TERMS: 2 year old;Acceleration;Acute;Address;Adult;advanced disease;Affect;Age;age acceleration;age related;aged;Aging;aging population;Alleles;Animals;Attenuated;attenuation;Behavior;Biological Process;biomarker identification;Bone remodeling;cartilage degradation;Cell Physiology;cell type;Cells;Characteristics;Chondrocytes;Choristoma;Chronic;Clinical;Degenerative polyarthritis;design;Development;disability;Disease;Drug Modulation;early detection biomarkers;early onset;effective therapy;Event;experimental study;Family;Family Study;gene discovery;Gene Expression;Gene Expression Profile;Gene Modified;Genes;Genetic;Genetic Recombination;Genetic study;genetic variant;genome editing;Health;Histologic;Homeostasis;Human;human disease;Hyperactivity;Immune;Inflammation;inflammatory marker;Inherited;Injury;insight;Invaded;Joints;Knee;Knee Injuries;Maintenance;Measures;Mediating;Modeling;Molecular;mouse model;Mus;normal aging;novel;Outcome;Pain;Pathway interactions;Pattern;Peptide Initiation Factors;Peptides;Pharmaceutical Preparations;Physiological;Population;Post-Translational Protein Processing;Predisposition;Proteins;receptor;Regulation;response;response to injury;RIPK2 gene;Role;Severities;Signal Pathway;Signal Transduction;Source;Surface;Susceptibility Gene;Synovial Cell;Synovial joint;systemic inflammatory response;targeted treatment;Testing;Therapeutic;therapy development;Tissues;transcriptome sequencing;Traumatic Arthropathy;Ubiquitination;Variant;Weight-Bearing state;Work

PROJECT_TITLE: Contribution of the NOD/RIPK2 signaling pathway to osteoarthritis susceptibility

STUDY_SECTION: SBDD

STUDY_SECTION_NAME: Skeletal Biology Development and Disease Study Section[SBDD]


ORG_CITY: INDIANAPOLIS

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: Project Narrative The research program described in this application seeks to elucidate the molecular biology of two related cell surface receptors known as LRP5 and LRP6. Human patients with mutations in the genes for these proteins exhibit skeletal phenotypes (very dense bone) that attest to the therapeutic potential of harnessing their activity to improve skeletal health in patients with low bone mass disease. We will study mice that express different forms of LRP5 and LRP6, to determine the mechanisms of action for these receptors, and whether they work as a function of exercise to improve bone properties.

PI_NAMEs: ROBLING, ALEXANDER G (contact);WARMAN, MATTHEW L

PROGRAM_OFFICER_NAME: NICKS, KRISTY

PROJECT_TERMS: Address;Adverse event;Affect;Anabolism;Aneurysm;Antibodies;Area;Atherosclerosis;Automobile Driving;Biochemical;Biological Models;Biology;Black Box;bone;bone cell;bone loss;bone mass;bone metabolism;bone strength;Bone Tissue;Cardiovascular Diseases;cardiovascular effects;cardiovascular health;Cardiovascular Physiology;Cardiovascular system;Cell Surface Proteins;Cell Surface Receptors;Cells;Clinical;Collaborations;Compensation;Disease;Disparate;Engineering;epigenetic silencing;Exercise;Exhibits;Failure;Fracture;gain of function mutation;Gene Expression Profile;Gene Proteins;Genetic Transcription;Goals;Health;Histologic;Homeostasis;Human;improved;In Vitro;in vivo;in vivo Model;Indiana;inhibitor;innovation;interest;Intervention;Investigation;Knock-in;Knock-in Mouse;Knock-out;Label;LDL-Receptor Related Proteins;Ligands;loss of function mutation;mechanical load;mechanical signal;Mechanics;mechanotransduction;Mediating;Metabolism;Microscopic;mimetics;Modeling;Molecular;Molecular Biology;Molecular Target;Morphologic artifacts;mouse model;Mus;mutant;Mutation;next generation;Noise;novel;Osteocytes;Osteogenesis;Osteopenia;Osteoporosis;overexpression;Pathway interactions;Patients;Pharmaceutical Preparations;pharmacologic;Phenotype;Physical activity;Physiological;Play;prevent;Process;Productivity;Program Description;programs;Property;protein function;radiological imaging;receptor;Reporting;Research;Resistance;resistance mutation;Resources;response;Risk;Role;side effect;Signal Transduction;skeletal;Skeleton;Specificity;Stroke;Techniques;Therapeutic;Therapeutic Agents;therapy outcome;tibia;tool;transcriptomics;Transgenic Mice;Universities;Vascular calcification;wasting;WNT Signaling Pathway;WNT1 gene;Work

PROJECT_TITLE: Lrp5 and Lrp6 signaling in bone mechanotransduction and metabolism

STUDY_SECTION: SBSR

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


NIH_SPENDING_CATS: Aging;Bioengineering;Machine Learning and Artificial Intelligence

ORG_DEPT: OPHTHALMOLOGY

PHR: The proposed work will uncover longstanding questions on the identify and function of senescent cells in fibrosis across age and sex in the context of fibrosis induced by biomaterials, the foreign body response.

PI_NAMEs: ELISSEEFF, JENNIFER H (contact)

PROGRAM_OFFICER_NAME: OROSZ, ANDRAS

PROJECT_TERMS: Affect;Age;aged;animal old age;Biocompatible Materials;Biological Markers;Biological Process;capsule;CDKN2A gene;Cell Communication;cell type;Cells;Chemistry;Clinical Trials;clinically relevant;Communication;Data Set;Development;Disease;Dissection;Electronics;Equipment Malfunction;Female;Fibroblasts;Fibrosis;Foreign Bodies;Foundations;Functional disorder;Genes;Goals;Heterogeneity;Human;Immune;Immune response;Immune signaling;Immune system;Immunofluorescence Immunologic;Immunologics;immunosenescence;Implant;implantation;in vivo;Internal Breast Prosthesis;juvenile animal;learning strategy;life span;lipidomics;LOX gene;Macrophage;male;medical implant;middle age;Minor;Modeling;Mus;new therapeutic target;old mice;Pathologic;Pattern;Pericytes;Phenotype;Population;Regenerative Medicine;Reporter;Research;response;Role;scaffold;senescence;senescence associated secretory phenotype;senescent cell;senolytics;sex;Sex Differences;Signal Transduction;single-cell RNA sequencing;Sorting;Structure;Surface Properties;T-Lymphocyte;Testing;Therapeutic;Time;tissue repair;Tissues;tool;transcriptome sequencing;transfer learning;Transgenic Organisms;Validation;Work

PROJECT_TITLE: Senescence in the Foreign Body Response Across Lifespan


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Aging;Cancer;Genetics;Hematology;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: BAR HARBOR

ORG_NAME: JACKSON LABORATORY

ORG_STATE: ME

PHR: PROJECT NARRATIVE Aging is a complex process that contributes to reduced function and elevated risk of various diseases in tissues throughout the body, including the blood system. The impact of aging on human health is of increasing societal concern due to the worldwide increase in the age of our population. Our research is relevant to public health because it will provide new information that can be used to develop therapies to sustain a healthy and robust blood system during aging and reduce risk of diseases such as blood cancer, cardiovascular disease, and type 2 diabetes.

PI_NAMEs: TROWBRIDGE, JENNIFER JEAN (contact)

PROGRAM_OFFICER_NAME: HATTANGADI, SHILPA MANOHAR

PROJECT_TERMS: Age;age related;aged;Aging;aging population;Automobile Driving;Behavior;Blood;Bone Marrow;C57BL/6 Mouse;Cardiovascular Diseases;Cell Aging;Cell Senescence Induction;Cells;Clonal Expansion;cofactor;Complex;Data;Dependence;Disease;disorder risk;DNA Methylation;DNA Modification Methylases;DNMT3a;effective intervention;Electron Transport;Excision;Exposure to;flexibility;Frequencies;functional decline;functional improvement;Funding;Genetic;Goals;Growth;Health;healthspan;healthy aging;Hematologic Neoplasms;Hematology;Hematopoiesis;Hematopoietic;Hematopoietic Neoplasms;hematopoietic stem cell aging;Hematopoietic stem cells;Hematopoietic System;Heterogeneity;Human;Impairment;in vivo;Incidence;Individual;Insulin-Like Growth Factor I;Intervention;Laboratories;Mediating;mesenchymal stromal cell;Methylation;middle age;Mitochondria;Mitochondrial DNA;mitochondrial metabolism;Modeling;Monitor;mortality;mouse model;Mus;mutant;Mutation;Myelogenous;Myeloproliferative disease;Non-Insulin-Dependent Diabetes Mellitus;novel;Nuclear;Pathology;pharmacologic;Phenotype;phenotypic data;Population;premature;prevent;Process;Production;Proteomics;Public Health;release of sequestered calcium ion into cytoplasm;Research;Risk;Risk Reduction;self-renewal;senescence;Severities;small molecule therapeutics;Somatic Mutation;System;targeted treatment;Testing;Therapeutic Intervention;therapeutic target;therapy development;Tissues;tool;Work

PROJECT_TITLE: Developing Effective Approaches to Extend Hematopoietic Healthspan by Targeting Cell-Extrinsic and Cell-Intrinsic Alterations at Middle Age

STUDY_SECTION: CMAD

STUDY_SECTION_NAME: Cellular Mechanisms in Aging and Development Study Section[CMAD]


ADMINISTERING_IC: LM

IC_NAME: NATIONAL LIBRARY OF MEDICINE

NIH_SPENDING_CATS: Bioengineering;Clinical Research;Clinical Trials and Supportive Activities;Data Science;Dissemination and Implementation Research;Emergency Care;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Patient Safety;Social Determinants of Health

ORG_CITY: BOSTON

ORG_STATE: MA

PHR: Project Narrative Artificial intelligence technologies are becoming increasingly important tools for making clinical decisions in many health resource allocation settings. This project studies methods that ensure that these technologies mitigate, rather than exacerbate, the outcome disparities arising from treatment decisions. The goal is to design and implement machine learning methods that can identify and correct prediction model errors among subpopulations of patients in real-time clinical decision support settings.

PI_NAMEs: LA CAVA, WILLIAM  (contact)

PROGRAM_OFFICER_NAME: REDDY, GOUTHAM

PROJECT_TERMS: Accident and Emergency department;Admission activity;Algorithms;Artificial Intelligence;Awareness;Behavior;Boston;Breathing;Calibration;care providers;Caring;Clinical;clinical care;clinical decision support;Clinical Decision Support Systems;clinical decision-making;clinical practice;clinical research site;computer infrastructure;Computer software;Data;data streams;Decision Support Model;Dedications;design;Development;Devices;Electronic Health Record;Emergency Department patient;Emergency Department Physician;Emergency department visit;Ensure;Equity;Ethics;Evaluation;Experimental Designs;Goals;Health;health care disparity;health data;health disparity;health inequalities;Health Resources;hospital bed;Hospitals;Human;improved;Individual;Inpatients;Institute of Medicine (U.S.);interest;Knowledge;Learning;live stream;Machine Learning;machine learning algorithm;machine learning method;machine learning model;machine learning pipeline;marginalization;marginalized population;Mathematics;Measures;Medical center;medical specialties;method development;Methods;Mind;Minority Groups;Modeling;Monitor;open source;Organ Transplantation;Outcome;outcome disparities;Outcome Study;Patient Admission;Patient Care;patient subsets;Patient-Focused Outcomes;Patients;Pediatric Hospitals;Performance;Physicians;Population;Population Heterogeneity;predictive modeling;Process;Production;prospective;Prospective Studies;provider adherence;real time monitoring;Recommendation;Reduce health disparities;Research Design;Resource Allocation;Resources;responsible artificial intelligence;Rewards;Risk;risk prediction;risk prediction model;Site;Stream;Subgroup;Suggestion;support tools;Surveys;System;Technology;Testing;Time;time use;tool;Training;treatment and outcome;treatment program;United States National Library of Medicine;Update;Vision;Work

PROJECT_TITLE: Real-time Monitoring and Correction of Clinical Decision Support Systems to Reduce Health Disparities

STUDY_SECTION: CIDH

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


NIH_SPENDING_CATS: Cardiovascular;Congenital Heart Disease;Heart Disease;Heart Disease - Coronary Heart Disease;Pediatric;Rare Diseases

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: PUBLIC HEALTH STATEMENT Heart diseases are the leading cause of death in the US (over 600 000 cases annually), and more than a half of those happen due to sudden cardiac death (SCD). Triggered arrhythmia considered one of the main mechanisms by which SCD occur. The aim of the proposed research is to study if and how activation of large- conductance non-selective ion channels (LCC) in the plasma membrane of cardiac cells during certain pathological conditions adds to the increased arrhythmogenicity of the heart, potentially leading to life- threatening triggered arrhythmias and SCD.

PI_NAMEs: KRYSHTAL, DMYTRO O. (contact)

PROGRAM_OFFICER_NAME: BALIJEPALLI, RAVI C

PROJECT_TERMS: Accounting;Action Potentials;Adult;Arrhythmia;Calsequestrin;Cardiac;Cardiac Myocytes;Catecholaminergic Polymorphic Ventricular Tachycardia;Cause of Death;Cell membrane;Cells;Cessation of life;Connexin 43;Connexins;contactin;Coronary;Coronary artery;Coupled;Data;Defect;Development;Diastole;Disease;Elements;Event;experimental study;extracellular;Gap Junctions;Generations;Genetic;Genetic Diseases;Heart;Heart Atrium;Heart Diseases;implantation;in vivo;Incidence;Infarction;Inherited;Ion Channel;Knock-out;Knockout Mice;Label;Life;Ligation;Measurement;Mechanics;Modeling;Modification;Molecular;mouse model;Mus;Muscle Cells;Mutation;Myocardial Infarction;Paracrine Communication;patch clamp;Pathologic;Pathology;pharmacologic;Predisposition;Protein Isoforms;Public Health;Publishing;Purinoceptor;Purkinje Cells;receptor;Reporting;Research;Risk;Role;Ryanodine Receptor Calcium Release Channel;Sarcoplasmic Reticulum;Signal Pathway;Sinoatrial Node;Source;Stretching;Structure of purkinje fibers;sudden cardiac death;Telemetry;Testing;Therapeutic;three dimensional structure;Tissues;TRP channel;Ventricular;Ventricular Arrhythmia;Ventricular Fibrillation;Ventricular Tachycardia

PROJECT_TITLE: Non-selective Large Conductance Ion Channels In Triggered Arrhythmia


ED_INST_TYPE: SCHOOL OF MEDICINE & DENTISTRY

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Caregiving Research;Clinical Research;Clinical Trials and Supportive Activities;Dissemination and Implementation Research;Health Services;Kidney Disease;Palliative Care

ORG_CITY: ROCHESTER

ORG_NAME: UNIVERSITY OF ROCHESTER

ORG_STATE: NY

PHR: PROJECT NARRATIVE Older adults ≥75 years represent the fastest-growing population to initiate dialysis in the US; despite the life- altering effects of dialysis on quality of life, dialysis is often presented as a default without considering patient preferences, prognosis, and alternative options such as conservative kidney management. This R01 proposal will enable the PI, a fellowship-trained physician-scientist in nephrology and palliative care, and his multidisciplinary team to test the first palliative care intervention for older patients ≥75 years with advanced chronic kidney disease to improve the kidney therapy decision-making process. This research not only has the potential to help thousands of older patients with advanced chronic kidney disease who often have unanswered questions, unmet information needs, and restricted opportunities to share personal treatment preferences with their nephrologists but also has the possibility of creating new models of collaborative care by integrating palliative care into the routine nephrology care.

PI_NAMEs: SAEED, FAHAD  (contact)

PROGRAM_OFFICER_NAME: RADZISZEWSKA, BARBARA

PROJECT_TERMS: academic standard;acceptability and feasibility;Address;Adopted;Affect;Age;Award;Caregivers;Caring;Chronic Kidney Failure;Clinical;clinical care;collaborative care;comparison control;Conflict (Psychology);Consultations;Control Groups;Decision Aid;Decision Making;Deterioration;Dialysis procedure;Dissemination and Implementation;Educational Materials;effectiveness/implementation hybrid;effectiveness/implementation trial;Elderly;Eligibility Determination;Emergency department visit;Emotional;Emotions;end of life;end of life care;Enrollment;experience;Face;Fellowship;functional decline;Funding;Future;Glomerular Filtration Rate;Goals;group intervention;health care service utilization;health service use;Hospitalization;hospitalization rates;Hospitals;improved;Individual;innovation;Intervention;Intubation;Investigation;Kidney;Kidney Diseases;Kidney Transplantation;Knowledge;Life;Life Cycle Stages;Life Support Care;literacy;Longevity;Measures;Medical center;Modeling;mortality;multidisciplinary;multiple chronic conditions;Nephrology;older adult;older patient;Older Population;Outcome;Palliative Care;Paper;patient engagement;Patient Preferences;Patients;Personal Satisfaction;Persons;Physicians;pilot test;Population;pragmatic implementation;preference;Probability;Procedures;Process;Prognosis;Publishing;Quality of life;Regrets;Reporting;Research;Sampling;Scientist;Testing;Training;treatment as usual;United States National Institutes of Health;Universities;Visit;Voice;Work

PROJECT_TITLE: Outcomes of a Palliative Care Intervention to Improve Kidney Therapy-Decision Making for Older People with Advanced CKD

STUDY_SECTION: ICSC

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


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Chronic Pain;Neurodegenerative;Neurosciences;Pain Research;Peripheral Neuropathy;Physical Injury - Accidents and Adverse Effects;Regenerative Medicine

ORG_DEPT: NEUROSCIENCES

PHR: Project Narrative Peripheral nerve injury results in loss of sensation in the skin, impairs quality of life, and leads to neuropathic pain. Sensory nerve function can be restored in part by collateral sprouting of nearby uninjured neurons, but this process is inefficient and might also cause hypersensitivity. Our study to understand how macrophages facilitate collateral sprouting will guide the development of improved therapies to accelerate the progression of sensory recovery in patients with nerve damage while ideally reducing unwanted events such as chronic pain.

PI_NAMEs: JEON, SANGMIN  (contact)

PROGRAM_OFFICER_NAME: GREENWELL, THOMAS

PROJECT_TERMS: Ablation;Acceleration;afferent nerve;Afferent Neurons;analysis pipeline;Anatomy;Animals;Area;Automobile Driving;Axon;axon injury;axon regeneration;Axotomy;Behavioral;Biological;Biological Assay;candidate identification;Cells;chronic pain;Coculture Techniques;convolutional neural network;Custom;Cutaneous;Defect;Denervation;Dermal;Development;Event;Excision;Exhibits;experimental study;Fiber;Genes;Genetic Transcription;Hypersensitivity;Image Analysis;Immune;Impairment;improved;In Vitro;in vivo;injured;Injury;Macrophage;Maintenance;Mechanics;Mediating;Mediator;migration;Modeling;Morphology;Motor;Mus;Myelin;Natural regeneration;nerve damage;nerve injury;Nerve Regeneration;Neurites;Neuronal Injury;Neurons;Nociception;Nociceptors;novel;Numbness;Operative Surgical Procedures;optogenetics;painful neuropathy;Patients;Peripheral;Peripheral nerve injury;Phagocytes;Phase;Phenotype;Play;Population;preconditioning;prevent;Process;Proliferating;Quality of life;Recovery;recruit;Reflex action;reinnervation;Reporting;restoration;Role;Sensory;Site;Skin;spared nerve;spatial relationship;Stimulus;success;Surgical Injuries;System;Tactile;Testing;Therapeutic;Time;Up-Regulation;Wallerian Degeneration

PROJECT_TITLE: Role of immune cells in skin reinnervation by collateral sprouting after peripheral nerve injury

STUDY_SECTION: NPI

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


NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Burden of Illness;Contraception/Reproduction;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Pediatric;Social Determinants of Health

ORG_CITY: MADISON

ORG_DEPT: SOCIAL SCIENCES

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

PHR: Project Narrative/Public Health Relevance Statement  Changing fertility and mortality patterns influence the extent of generational overlap (i.e., shared lifetimes among family members). This is important because both children and elders benefit from intergenerational kin relationships and resource sharing, which may offset the need for public resources and potentially reduce inequality. In this project, we provide new data on generational overlap between grandparents and grandchildren, comparing the U.S. and Denmark and considering variation by socioeconomic status and across demographic sub-groups.

PI_NAMEs: CARLSON, MARCIA JEANNE (contact);FALLESEN, PETER ;FOMBY, PAULA W

PROGRAM_OFFICER_NAME: JEKIELEK, SUSAN

PROJECT_TERMS: Abbreviations;Address;Affect;Affective;Age;Aging;Back;Caring;Child;child bearing;Child Development;Childbirth;cohort;cost;Country;Data;data harmonization;Data Sources;Demography;Denmark;Developed Countries;Economics;Education;Elderly;Employment Status;Ethnic Origin;Europe;experience;Extended Family;Family;Family Demographies;Family dynamics;Family member;family structure;Fertility;Gender;Generations;Government;grandchild;grandparent;Health;Health Surveys;Human;Individual;Inequality;innovation;intergenerational;Investments;Kinship Networks;Knowledge;Length;Life Cycle Stages;Life Expectancy;Methodology;Mobility decline;mortality;National Longitudinal Survey of Adolescent to Adult Health;Outcome;panel study of income dynamics;Parents;Pattern;Personal Satisfaction;Population;Population Registers;Portraits;Positioning Attribute;Prevalence;Probability;Process;public health relevance;Race;Reproduction;Research Personnel;Resource Sharing;Resources;Retirement;Role;Secondary Schools;Shapes;skills;social;Social Class;social disparities;social organization;Social Policies;Societies;Socioeconomic Status;Source;Subgroup;System;Time;timeline;transmission process;Variant

PROJECT_TITLE: Generational Overlap: Changing Demography, Shared Lifetimes, and Family Resources

STUDY_SECTION: SSPA

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


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Behavioral and Social Science;Clinical Research;Pediatric;Prevention;Social Determinants of Health;Substance Misuse;Underage Drinking

ORG_CITY: PROVIDENCE

ORG_NAME: BROWN UNIVERSITY

PHR: Project Narrative: Public Health Relevance Statement During emerging adulthood, alcohol misuse peaks and many individuals start to develop problems with alcohol. While most research on alcohol misuse during this period examines the college context, there are specific work occupations where alcohol misuse is prominent. Thus, the proposed investigation will examine the trajectories of emerging adults entering these high-risk occupations and how the composition of the social network at work contributes to alcohol misuse, which will inform prevention and intervention efforts to reduce heavy drinking and alcohol-related consequences.

PI_NAMEs: MEISEL, MATTHEW K (contact)

PROGRAM_OFFICER_NAME: KERRIDGE, BRADLEY TOWNSEND

PROJECT_TERMS: Absenteeism;Accidents;Adopted;Adult;Age;age group;aged;Alcohol abuse;alcohol consequences;Alcohol consumption;Alcohol dependence;alcohol misuse;alcohol related consequences;alcohol risk;Alcohols;binge drinking;Characteristics;Chronic Disease;college;diaries;drinking;drinking behavior;emerging adult;emerging adulthood;Employee;expectation;Family;food preparation;Frequencies;Friends;Head;Heavy Drinking;high risk;high risk drinking;high school;Individual;Injury;Intervention;Investigation;Job Satisfaction;Life;Link;Literature;Longitudinal Studies;Maintenance;Mediator;member;Occupations;Outcome;Participant;Pattern;Performance;Personnel Turnover;Persons;pressure;Prevention;Productivity;professional atmosphere;psychologic;public health relevance;recruit;repaired;Reporting;Research;Risk;Sales;Sampling;Schools;Self Efficacy;social;social cognitive theory;Social Environment;social factors;social influence;Social Network;social relationships;Social Work;Socialization;theories;Time;Training;Transportation;Work;Workplace;young adult

PROJECT_TITLE: Utilization of a Social Network Approach To Examine The School-To-Work Transition: Examination of High-Risk Work Environments

STUDY_SECTION: SPIP

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


ED_INST_TYPE: GRADUATE SCHOOLS

NIH_SPENDING_CATS: Bioengineering;Biotechnology

ORG_CITY: Boulder

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF COLORADO

ORG_STATE: CO

PHR: The foreign body response (FBR) to implanted biomaterials is a formidable challenge that culminates in the production of an avascular fibrous capsule. This project will identify the mechanistic basis for the events that trigger and sustain the FBR by understanding the role of the protein-biomaterial interface on innate immune cells and then using this knowledge to modulate surface-induced protein dynamics to weaken the FBR and improve the biocompatibility to implants.

PI_NAMEs: BRYANT, STEPHANIE J (contact);KAAR, JOEL

PROGRAM_OFFICER_NAME: VAZQUEZ-MALDONADO, NANCY

PROJECT_TERMS: Adsorption;Attenuated;Automobile Driving;Biocompatible Materials;biomaterial compatibility;biomaterial development;biomaterial interface;Blood;capsule;Cells;Chemicals;Chemistry;clinical translation;clinically relevant;Complex;copolymer;Environment;Event;Fibronectins;Foreign Bodies;Goals;Human;hydrophilicity;Hydrophobicity;Immune;Immunology;Implant;implant coating;implantation;improved;In Vitro;in vivo;Inflammatory;innovation;interdisciplinary approach;interfacial;Knockout Mice;Knowledge;Link;link protein;Liquid substance;Machine Learning;Macrophage;Macrophage Activation;Measurement;Mediating;Medical Device;Membrane Proteins;Methods;Molecular;molecular dynamics;mouse model;multidisciplinary;mutant;Myeloid Cell Activation;Myeloid Cells;Nature;neutrophil;novel;Outcome;Paint;Pattern;Polymers;prevent;Process;Production;Profibrotic signal;protein complex;Protein Dynamics;Protein Engineering;protein folding;Proteins;Research;response;Role;Serum Proteins;Signal Pathway;simulation;single molecule;Surface;surface coating;Testing;Tissues;TLR2 gene;TLR4 gene;Toll-like receptors;transcriptome sequencing;Work

PROJECT_TITLE: Tunable Surface Coatings to Control Protein Dynamics and Attenuate the FBR


NIH_SPENDING_CATS: Cardiovascular;Heart Disease

ORG_CITY: Aurora

ORG_NAME: UNIVERSITY OF COLORADO DENVER

PHR: PROJECT NARRATIVE Cardiac hypertrophy and failure involve a remodeling of the cardiac extracellular matrix, a three-dimensional network of proteins on which cardiac cells are anchored. Understanding how a healthy extracellular matrix transitions into a diseased state may present new therapeutic opportunities. Accordingly, this project will use proteomics strategies to investigate the synthesis and degradation of extracellular matrix proteins during the progression of and recovery from heart failure.

PI_NAMEs: LAM, MAGGIE ;LAU, EDWARD  (contact)

PROGRAM_OFFICER_NAME: WONG, RENEE P

PROJECT_TERMS: 3-Dimensional;Animal Model;antifibrotic treatment;Cardiac;Cardiac Myocytes;Cells;Coculture Techniques;Collagen;Complex;Data;Deposition;Detection;Development;Dimensions;Disease;disease model;Disease Pathway;Disease Progression;Disputes;Event;experimental study;extracellular;Extracellular Matrix;Extracellular Matrix Degradation;Extracellular Matrix Proteins;Failure;Fibroblasts;Fibrosis;Functional disorder;Future;Heart;Heart Diseases;Heart failure;heart function;Heart Hypertrophy;Hypertrophy;In Vitro;in vivo;Individual;induced pluripotent stem cell;insight;interstitial;Intervention;Investigation;Kinetics;Knowledge;Mass Spectrum Analysis;Measurement;Measures;Messenger RNA;Modeling;Molecular;Molecular Chaperones;Morbidity - disease rate;mortality;mouse model;Mus;Myocardial;Myocardial dysfunction;Nature;novel;novel therapeutics;Pathogenesis;Pathologic;Play;pre-clinical;Pre-Clinical Model;Process;Protein Biosynthesis;protein degradation;Protein Secretion;Proteins;Proteome;Proteomics;Protocols documentation;Recovery;Regulation;response;Role;Signal Transduction;spatiotemporal;Stable Isotope Labeling;Stains;stem;Stimulus;Structure;success;Testing;Therapeutic;therapeutic development;Time;Translations;Work

PROJECT_TITLE: Extracellular matrix turnover in pathological cardiac remodeling


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

ORG_CITY: SAN FRANCISCO

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE The purpose of this research proposal is to uncover the functional link between nuclear architecture and brain architecture governed by clustered Protocadherin (Pcdh) genes using mouse olfactory sensory neurons as model system. As Pcdh proteins play an essential role in brain wiring and as dysregulation of their expression is implicated in several neurological disorders, understanding how these genes are expressed in the mammalian brain has direct relevance to human health and disease.

PI_NAMEs: CANZIO, DANIELE  (contact)

PROGRAM_OFFICER_NAME: SULLIVAN, SUSAN L

PROJECT_TERMS: 3-Dimensional;Ablation;Address;Alleles;Architecture;Base Pairing;Biological Assay;Biological Models;Brain;Cell Culture System;Cell Surface Proteins;cell type;Cells;Chromatin;Chromatin Loop;Chromosomes;cohesin;combinatorial;Complex;Coupled;Coupling;Data;Decision Making;Development;Disease;DNA Methylation;Enhancers;Gene Cluster;Gene Expression;Gene Expression Regulation;Gene Order;Gene Silencing;Generations;Genes;Genetic;Genetic Transcription;Genome;Genomic approach;Genomic DNA;Goals;Health;Heterochromatin;histone methylation;Human;in vivo;Individual;Instruction;Label;Life;Link;Maintenance;Mammals;Maps;Measures;Memory;Modeling;Molecular;mouse model;Mus;Names;Nature;Nervous System Disorder;neural;neural circuit;neural patterning;Neurites;neurodevelopment;Neurons;neuropsychiatric disorder;neuroregulation;Nuclear;olfactory sensory neurons;Optics;Pattern;Physiological;Play;postmitotic;prevent;Process;promoter;Property;protein complex;Protein Isoforms;Proteins;Proteome;Publishing;Reader;reconstruction;Regulation;Research Proposals;Resolution;Rest;RNA;Role;Shapes;single cell genomics;stem cells;Structure;Testing;Transcript

PROJECT_TITLE: Investigating stochastic genome folding as a mechanism to generate cell-surface protein diversity required for neural self-avoidance

STUDY_SECTION: MNG

STUDY_SECTION_NAME: Molecular Neurogenetics Study Section[MNG]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Clinical Research;Hematology;Physical Injury - Accidents and Adverse Effects

ORG_CITY: NEW ORLEANS

ORG_NAME: TULANE UNIVERSITY OF LOUISIANA

ORG_STATE: LA

PHR: Project Narrative Trauma is the most prevalent cause of death for those under 40 years of age in the United States. The blood loss that often occurs in trauma causes damage to the lining of the blood vessels. This damage causes disordered blood clotting, as well as multi-organ failure, which leads to high death rates in trauma patients. The proposed project is relevant to public health through investigation of the mechanism underlying this vascular damage, and may identify new therapeutic strategies to reduce the high rates of death in trauma patients with severe blood loss.

PI_NAMEs: JACKSON-WEAVER, OLAN  (contact)

PROGRAM_OFFICER_NAME: CHAO, CHIEN-CHUNG

PROJECT_TERMS: Acute;Age Years;Animal Model;Automobile Driving;Blood coagulation;Blood Coagulation Disorders;Blood Vessels;Cause of Death;Cell Culture Techniques;Cell membrane;Cessation of life;Citric Acid Cycle;clinically relevant;Complex;Data;Death Rate;Dimethyl Sulfoxide;Disease;effective therapy;Endothelial Cells;Endothelium;Enzymes;Event;Functional disorder;Future;Generations;Glycocalyx;Hematological Disease;Hemorrhage;Hemorrhagic Shock;Hypotension;Hypotensives;Hypoxia;Investigation;Ischemia;Knowledge;Life;Link;Lipids;Lysophospholipids;Matrix Metalloproteinases;Mediating;Membrane;Membrane Lipids;Metabolism;Mitochondria;Modeling;Molecular;mortality;Multiple Organ Failure;novel;novel therapeutic intervention;Organ;Organ failure;Outcome Measure;oxidation;Pathology;Pathway interactions;Patients;Phase;Phospholipase A2;Physiology;Plasma;Population;prevent;Production;Property;Proteins;Proteoglycan;Public Health;Publishing;Rattus;Reactive Oxygen Species;Resuscitation;Role;Signal Transduction;Structure;Succinates;Surface;syndecan;Testing;Therapeutic;Tissues;Toxic effect;Trauma;Trauma patient;Traumatic Hemorrhage;United States;Work

PROJECT_TITLE: Alterations to endothelial membrane composition and structure as a driver of the endotheliopathy of trauma

STUDY_SECTION: IVPP

STUDY_SECTION_NAME: Integrative Vascular Physiology and Pathology Study Section[IVPP]


NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Colorectal Cancer;Digestive Diseases;Immunotherapy;Lung;Lung Cancer

ORG_CITY: Columbus

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: PROJECT NARRATIVE Our group discovered that many cancers modulate GARP, a protein that binds and activates latent TGFβ, which suppresses the immune response to cancer. We generated a highly selective antibody that specifically blocks the action of GARP and shows preclinical efficacy in several mouse models of cancer. This project will determine whether our antibody can restore the immune response to lung cancer (especially by T cells), and complete additional research in mouse cancer models to facilitate the translation of this antibody into clinics for the treatment of patients with lung cancer.

PI_NAMEs: LI, ZIHAI  (contact)

PROGRAM_OFFICER_NAME: OLKHANUD, PUREVDORJ BALJINNYAM

PROJECT_TERMS: Address;Affinity;Agonist;anti-PD-1;Antibodies;Antibody-mediated protection;Antigens;Authorization documentation;Binding Proteins;Biogenesis;Blood Platelets;Bone Morphogenetic Proteins;cancer cell;cancer immunotherapy;Cancer Model;cancer therapy;cancer type;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Physiology;Cell surface;Cells;Clinic;Clinical;clinical efficacy;clinical translation;Colon Carcinoma;Colorectal Cancer;CXCR3 gene;Development;Docking;draining lymph node;Epitopes;Exclusion;exhaust;exhaustion;Exposure to;extracellular;Flow Cytometry;Future;Genetic;Goals;Human;Hybridomas;immune checkpoint blockade;Immune response;Immune System Diseases;Immunocompetent;Immunotherapeutic agent;Immunotherapy;Impairment;improved;in vivo;Inflammation;Investigational Drugs;Investigational New Drug Application;Knock-in;Knock-in Mouse;LRRC32 gene;Malignant neoplasm of lung;Malignant neoplasm of ovary;Malignant neoplasm of pancreas;Malignant Neoplasms;Maps;MC38;Monoclonal Antibodies;mouse model;multiple omics;Mus;Nature;Neoplasm Metastasis;Non-Small-Cell Lung Carcinoma;novel;Outcome;Pathway interactions;Patients;PD-1 blockade;Pharmacodynamics;Phase I Clinical Trials;pre-clinical;Pre-Clinical Model;preclinical efficacy;prevent;programs;receptor;Regulatory T-Lymphocyte;Research;Resistance;Risk;Role;Safety;safety study;side effect;Signal Transduction;single-cell RNA sequencing;small molecule inhibitor;Solid Neoplasm;System;T cell differentiation;T-Lymphocyte;targeted treatment;Techniques;Testing;Therapeutic;therapeutic target;Toxic effect;trafficking;Transforming Growth Factor beta;Translations;Treatment Efficacy;tumor;Tumor Immunity;tumor microenvironment

PROJECT_TITLE: Targeting GARP-TGFbeta for Immunotherapy of Non-Small Cell Lung Cancer

STUDY_SECTION: CONC

STUDY_SECTION_NAME: Clinical Oncology Study Section[CONC]


NIH_SPENDING_CATS: Cardiovascular;Genetics;Heart Disease

ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: Narrative: Despite tremendous progress in treating patients with heart failure, this disease remains a leading cause of death across the US population. The experiments in this proposal are focused on understanding the molecular pathways regulating pathological heart growth and heart failure to identify new therapeutic options to prevent and treat this disease.

PI_NAMEs: BECKER, JASON  (contact)

PROGRAM_OFFICER_NAME: TJURMINA, OLGA A

PROJECT_TERMS: Adult;Blood capillaries;Cardiac Myocytes;Cardiomyopathies;Cause of Death;Cell Cycle;Cell division;Cells;Chemicals;density;Diastolic heart failure;Disease;disease model;DNA biosynthesis;DNA Damage;experimental study;Functional disorder;gain of function;Gene Mutation;Genetic;Genetic Diseases;Genetic Models;Glycolysis;Goals;Growth;Heart;Heart failure;HIF1A gene;Human;Hypertrophic Cardiomyopathy;Hypertrophy;improved;innovation;Left Ventricular Hypertrophy;Left Ventricular Remodeling;loss of function;Metabolic;Metabolism;Modeling;Molecular;mortality;mouse model;Mus;mutant;Myocardial;Myocardial dysfunction;non-genetic;novel;novel therapeutics;Pathologic;Pathologic Processes;Pathway interactions;Patients;Play;Population;postnatal;pressure;prevent;Proteins;replication stress;response;Role;Sarcomeres;Secondary to;Signal Pathway;Signal Transduction;Testing;Tissues;Ventricular Remodeling

PROJECT_TITLE: MDM2-HIF signaling in pathological ventricular remodeling

STUDY_SECTION: MPPA

STUDY_SECTION_NAME: Integrative Myocardial Physiology/Pathophysiology A Study Section [MPPA]


NIH_SPENDING_CATS: Infectious Diseases;Kidney Disease;Urologic Diseases

PHR: NARRATIVE Research findings indicate that specialized cells in the kidney tubule are critical to fighting bacterial infections. By examining the mechanisms these cells use to eliminate bacteria, we can gain insight on how kidney infections happen as well as develop new non-antibiotic treatments.

PI_NAMEs: HAINS, DAVID SULLIVAN;SCHWADERER, ANDREW LAWRENCE (contact)

PROGRAM_OFFICER_NAME: MULLINS, CHRISTOPHER V

PROJECT_TERMS: Acidosis;Acids;Acute;Alkalosis;alternative treatment;Anti-Bacterial Agents;anti-microbial peptide;Antibiotic Resistance;Antibiotics;Bacteria;Bacterial Infections;base;Biological;Blood;Cell Physiology;Cell Separation;Cells;Chronic;collecting tubule structure;Communication;Cytoplasm;Data;Disease;Dose;Epithelium;Exposure to;fighting;Foundations;Future;Gene Expression;gene interaction;Genes;Goals;Grant;Health Care Costs;Healthcare;Homeostasis;Human;Immune;In Vitro;in vivo;Injury to Kidney;innate immune function;innovation;insight;Intercalated Cell;intravital imaging;intravital microscopy;JAK1 gene;Janus kinase;Kidney;kidney infection;kidney preservation;Knock-out;Lead;Magnetism;Manuscripts;Mediating;Microbe;Modeling;Morbidity - disease rate;mortality;mouse model;Mus;Nature;novel;novel strategies;novel therapeutic intervention;Organ;Organism;particle;Pathway Analysis;Pathway interactions;Pattern recognition receptor;Phagocytes;Phagocytosis;Phagosomes;Populations at Risk;precision medicine;Predisposition;Prevalence;prevent;Process;Publishing;Pump;Regulation;Renal function;Renal tubule structure;Research;Role;Serum;Signal Pathway;Signal Transduction;single cell mRNA sequencing;Site;Stat3 protein;stressor;therapeutic target;TLR4 gene;transcriptomics;Transducers;Transgenic Organisms;treatment strategy;Urinary tract infection;Urine;Uropathogenic E. coli;vacuolar H+-ATPase

PROJECT_TITLE: A mechanistic approach to intercalated cell phagocytosis

STUDY_SECTION: KUFD

STUDY_SECTION_NAME: Kidney and Urological Systems Function and Dysfunction Study Section[KUFD]