NIH_SPENDING_CATS: Amyotrophic Lateral Sclerosis (ALS);Biotechnology;Brain Disorders;Gene Therapy;Genetics;Neurodegenerative;Neurosciences;Orphan Drug;Rare Diseases

ORG_CITY: CHAMPAIGN

ORG_NAME: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN

PHR: PROJECT SUMMARY The goal of this Administrative Supplement is to support the acquisition of cynomolgus macaques for determining the efficacy and tolerability of a gene therapy for amyotrophic lateral sclerosis (ALS). This Supplement will ensure that our project carries sufficient statistical power to most accurately quantify the effects for our therapeutic agent and as such is critical for the completion of the project, “Optimization of an in vivo base editing strategy to treat SOD1-linked ALS” (5U01NS122102).

PI_NAMEs: GAJ, THOMAS  (contact);PEREZ-PINERA, PABLO

PROGRAM_OFFICER_NAME: BOSHOFF, CHRIS

PROJECT_TERMS: adeno-associated viral vector;Administrative Supplement;Adult;Amyotrophic Lateral Sclerosis;amyotrophic lateral sclerosis therapy;Anatomy;base editing;Clustered Regularly Interspaced Short Palindromic Repeats;cost;Disease;DNA;Dose;efficacy evaluation;Ensure;Formulation;gain of function mutation;gene therapy;Genes;Goals;Housing;Human;Immune response;Immunologics;in vivo;Laboratory Animals;Lead;Link;Macaca fascicularis;Modality;Modeling;mutant;Nervous System;nonhuman primate;novel;nuclease;Paralysed;Patients;Peripheral;Physiological;Production;Property;Proteins;Research;Safety;Severities;Single base substitution;Specificity;superoxide dismutase 1;Therapeutic Agents;Tissues


ADMINISTERING_IC: GM

ARRA_FUNDED: N

ED_INST_TYPE: UNIVERSITY-WIDE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: ROCHESTER

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: ROCHESTER INSTITUTE OF TECHNOLOGY

ORG_STATE: NY

PHR: NARRATIVE Stiffening and disorganization of the extracellular matrix (ECM) can serve as important cellular cues that can promote degenerative processes. The proposed study will determine the relevance of substrate stiffness and topography on the activation of the mechanoreceptor TRPV4 in annulus fibrosus cells and will elucidate whether TRPV4 regulates ECM synthesis/remodeling. Investigating cell-substrate interactions in the annulus fibrosus is of high significance as it will help to properly understand mechanotransduction processes underlying spinal health and disease (e.g. intervertebral disc herniation) and advance tissue engineering approaches.

PI_NAMEs: WUERTZ-KOZAK, KARIN  (contact)

PROGRAM_OFFICER_NAME: FRINCU, CRINA

PROJECT_TERMS: Affect;Agonist;Architecture;Area;cell behavior;Cell Physiology;cell type;Cells;Cues;Data;design;Development;Disease;Disease Progression;Enzyme-Linked Immunosorbent Assay;Enzymes;Extracellular Matrix;Failure;Feedback;Goals;Health;innovation;interest;Intervertebral disc structure;Ion Channel;Knowledge;Low Back Pain;mechanical signal;Mechanical Stimulation;Mechanics;Mechanoreceptors;mechanotransduction;new therapeutic target;Periodicity;pharmacologic;Play;Process;regenerative approach;Research;response;Role;Slipped Disk;Spinal;Stretching;Substrate Interaction;Tissue Engineering;Tissues;tool;transcriptome sequencing;TRP channel;Western Blotting

PROJECT_TITLE: Substrate Stiffness, Topography, and TRPV4 in AF Mechanotransduction


ED_INST_TYPE: SCHOOLS OF MEDICINE

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

ORG_CITY: CHARLOTTESVILLE

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: PROJECT NARRATIVE Cells have defenses, called innate immunity, that allow them to defend themselves against viruses. The endoplasmic reticulum and mitochondria are important parts of the cell that work together to activate innate immune defenses. The proposed research addresses how the communication between the endoplasmic reticulum and mitochondria helps to fight viral infection.

PI_NAMEs: NEWMAN, LAURA ELIZABETH (contact)

PROGRAM_OFFICER_NAME: STOKES, KALYNDA K

PROJECT_TERMS: 2019-nCoV;Adaptor Signaling Protein;Address;Advisory Committees;Age related pathologies;aging related;analog;Anti-viral Response;Area;Autoimmune Diseases;Award;Bacterial Infections;Biological Models;Bromodeoxyuridine;career;career development;Cells;Chronic;Co-Immunoprecipitations;combat;Communication;Complex;Cytoplasm;Cytosol;Data;Dengue;Deoxyuridine;Disease;DNA;DNA Virus Infections;DNA Viruses;Double-Stranded RNA;Endoplasmic Reticulum;Epstein-Barr Virus Infections;Event;Excision;fighting;Genes;Health;Herpes Simplex Infections;Herpesvirus 1;Homeostasis;Host Defense;Human;Human Herpesvirus 4;Immune;Immune response;Immune signaling;Immunology;Impairment;Infection;Inflammation;Influenza;Influenza A virus;innate immune pathways;Innate Immune Response;insight;Interferons;Invaded;Measures;Mediating;Membrane;Microscopy;Mitochondria;Mitochondrial DNA;mitochondrial permeability transition pore;Mitochondrial Proteins;Natural Immunity;new therapeutic target;nuclease;Nucleic Acids;Organelles;Outer Mitochondrial Membrane;pathogen;Pathology;Pathway interactions;pharmacologic;Play;Property;Protein Dynamics;Proteins;Publishing;Regulation;Research;response;RNA Virus Infections;RNA Viruses;Role;Scientist;Severe Acute Respiratory Syndrome;Signal Transduction;Simplexvirus;Site;Stimulator of Interferon Genes;Testing;Tissues;Training;Viral;viral DNA;virology;Virus;Virus Diseases;Virus Replication;Work;ZIKA

PROJECT_TITLE: Role of mitochondrial/ER contacts in the regulation of mtDNA release from mitochondria, innate immune signaling, and responses to viral infection

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


ADMINISTERING_IC: NS

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Brain Cancer;Brain Disorders;Cancer;Gene Therapy;Genetics;Nanotechnology;Neurosciences;Orphan Drug;Rare Diseases

ORG_CITY: ANN ARBOR

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Narrative Glioblastoma multiforme (GBM) is a malignant primary brain cancer which carries a dismal prognosis. STAT3 has been shown to be a very attractive therapeutic target for GBM; albeit, small molecule inhibitors of STAT3 signaling are ineffective, as they exhibit very poor blood brain barrier permeability. Our interdisciplinary team will develop and evaluate a novel and scalable bi-compartmental nanoparticle delivery system that allows controlled co-release of STAT3 siRNA and the chemotherapeutic agent, paclitaxel. This work may result in a new treatment modality for GBM, a tumor type, for which no effective treatments exist.

PI_NAMEs: CASTRO, MARIA G;LAHANN, JOERG  (contact)

PROGRAM_OFFICER_NAME: KOTLIAROVA, SVETLANA

PROJECT_TERMS: Accounting;Adjuvant Chemotherapy;Albumins;Antibodies;Architecture;Biological Assay;Blood;Blood - brain barrier anatomy;blood-brain barrier permeabilization;Brain;Brain Neoplasms;Cancer Patient;Cell Death;cell type;Cells;chemotherapeutic agent;clinically relevant;Combined Modality Therapy;curative treatments;Data;design;Development;docetaxel;Dose;Doxorubicin;drug action;Drug Delivery Systems;Drug Kinetics;effective therapy;efficacy evaluation;Encapsulated;Excision;Exhibits;experimental study;Formulation;Glioblastoma;Glioma;Goals;Growth;Heterogeneity;Human;Immune;Immunity;immunogenic cell death;Immunologic Memory;improved;In Vitro;Infiltration;inhibitor;innovation;innovative technologies;Intracranial Neoplasms;Ionizing radiation;Knowledge;Malignant - descriptor;Malignant neoplasm of brain;Medial;Medical;Mission;Modality;Modeling;Molecular;Mus;nanoparticle;nanoparticle delivery;novel;novel strategies;novel therapeutics;Operative Surgical Procedures;Organ;Paclitaxel;Patients;Pattern;Penetration;Peptides;Phagocytes;Pharmaceutical Preparations;Phase I Clinical Trials;Phenotype;Polymers;pre-clinical;Prognosis;Proteins;Radiation therapy;Reporting;response;RNA;Serum Albumin;side effect;Signal Transduction;Signaling Molecule;Small Interfering RNA;small molecule;small molecule inhibitor;standard of care;Survival Rate;synthetic protein;System;T-Lymphocyte;targeted delivery;Techniques;Technology;temozolomide;Testing;Therapeutic;therapeutic target;Toxic effect;Transcription Factor 3;Transducers;Translating;Translations;Treatment Efficacy;tumor;tumor microenvironment;United States National Institutes of Health;uptake;Validation;Work

PROJECT_TITLE: Systemic Delivery of Targeted Bi-Compartmental Nanoparticles for Glioblastoma Therapeutics

STUDY_SECTION: DMP

STUDY_SECTION_NAME: Drug Discovery and Molecular Pharmacology Study Section[DMP]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Complementary and Integrative Health;Natural Products

ORG_CITY: GREENSBORO

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF NORTH CAROLINA GREENSBORO

ORG_STATE: NC

PHR: PROJECT NARRATIVE  Natural products are a critical component of modern medicine and discovery of new molecules and pathways has the opportunity to positively impact human health. Using a multidisciplinary approach, this proposal seeks to combine diverse bioinformatic and biochemical methodologies to target new classes of RiPP natural products from across the tree of life and reveal their bioactivities. Our results will not only lead to the identification of new pathways and bioactive molecules, but will serve as a basis for future discovery and engineering efforts.

PI_NAMEs: CHEKAN, JONATHAN RODI (contact)

PROGRAM_OFFICER_NAME: BOND, MICHELLE RUEFFER

PROJECT_TERMS: Antibiotics;Artemisinins;bioactive natural products;Biochemical;Bioinformatics;Complement;Development;Elements;Engineering;Enzymes;Family;Future;Gene Cluster;Genome;graduate student;guided inquiry;Health;Human;in silico;insight;interdisciplinary approach;Lead;Life;Link;Logic;Methodology;Mining;Modern Medicine;Natural product discovery;Natural Products;Nature;next generation;novel therapeutics;Organism;Pathway interactions;Penicillins;peptide natural products;Peptides;Pharmaceutical Preparations;Postdoctoral Fellow;Process;Ribosomes;Scientist;secondary metabolite;Techniques;Training;Trees

PROJECT_TITLE: Bioinformatic Guided Discovery and Characterization of New RiPP Natural Products

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


NIH_SPENDING_CATS: Cancer;Genetics

ORG_CITY: STONY BROOK

ORG_DEPT: PHARMACOLOGY

ORG_NAME: STATE UNIVERSITY NEW YORK STONY BROOK

PHR: NARRATIVE A versatile live-imaging platform will enable us to monitor and analyze the cellular processes involved in DNA replication and repair with unprecedented resolution. Better understanding on the mechanism of genome maintenance will promote our effort to exploit DNA replication problems of cancer cells for therapeutic intervention.

PI_NAMEs: KIM, HYUNGJIN  (contact)

PROGRAM_OFFICER_NAME: REDDY, MICHAEL K

PROJECT_TERMS: Affect;Award;biological adaptation to stress;cancer cell;cell behavior;Cell Cycle;Cell Physiology;Cell Proliferation;Cell Survival;Cells;cellular imaging;chemotherapy;DNA biosynthesis;DNA Repair;DNA replication fork;Funding;Genome;genome analysis;Image;imaging platform;instrument;Kinetics;Maintenance;Monitor;mutant;National Institute of General Medical Sciences;Parents;Physiological;Research;Resolution;Systems Analysis;Therapeutic Intervention;Time

PROJECT_TITLE: The interplay of TIMELESS and PARP1 in DNA replication fork stability

STUDY_SECTION: MG

STUDY_SECTION_NAME: Molecular Genetics Study Section[MG]


NIH_SPENDING_CATS: Genetics;Human Genome;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Stem Cell Research - Nonembryonic - Human

ORG_DEPT: BIOCHEMISTRY

PHR: Project Narrative Errors in DNA replication can affect tissue development and cause human diseases, including deficiencies of the immune system and cancer. We propose to study the mechanisms underlying these pathologies to help devise novel diagnostics and therapies.

PI_NAMEs: BIELINSKY, ANJA-KATRIN  (contact)

PROJECT_TERMS: Address;Affect;Animal Model;Cardiomyopathies;Cell Cycle;Cell Line;Cell model;cell type;Cells;cellular development;Chromosomes;Coupled;Defect;Development;Disease;disease-causing mutation;DNA;DNA biosynthesis;DNA replication fork;Double Strand Break Repair;Family;Genetic;Genome;genome editing;Genome engineering;genome integrity;Genome Stability;Growth;helicase;Heterozygote;Homeostasis;Human;human disease;Immune system;immunodeficiency;In Vitro;induced pluripotent stem cell;insight;interest;Laboratories;Length;Lesion;Link;Maintenance;Malignant Neoplasms;Mitotic;Modeling;Molecular;Mutation;Network-based;Neurodevelopmental Disorder;novel diagnostics;novel therapeutics;Pathology;Pathway interactions;Patients;Peptide Hydrolases;Phase;Premature aging syndrome;programs;Proteins;Rare Diseases;repaired;replication stress;Ring Finger Domain;Role;Somatic Cell;Sumoylation Pathway;Telomerase;telomere;Telomere Maintenance;Tissues;Ubiquitin;ubiquitin isopeptidase;ubiquitin-protein ligase;Ubiquitination;whole genome;Work

PROJECT_TITLE: Mechanistic insight into genome stability pathways


ORG_CITY: POTSDAM

ORG_DEPT: BIOLOGY

ORG_NAME: CLARKSON UNIVERSITY

PHR: Project Narrative Biological patterning relies on the coordination of cell-cell communication events across large and small distances, and defects in patterning can lead to human disorders and disease. Cytonemes are one example of an active cell process that coordinates cell signaling for many patterning events during vertebrate and invertebrate development. The goal of this work is to understand both how cytonemes are regulated at the cellular scale and how they contribute to the overall progression of patterning.

PI_NAMEs: HUNTER, GINGER LORAINE (contact)

PROGRAM_OFFICER_NAME: SALAZAR, DESIREE LYNN

PROJECT_TERMS: Actins;Address;Behavior;Biological;Biological Models;cell behavior;Cell Communication;Cell Physiology;Cell Shape;Cells;Chest;Cytoskeleton;Defect;Development;Developmental Process;Disease;Dorsal;Drosophila genus;Drosophila melanogaster;Epithelial Cells;Event;Filopodia;gene induction;Genetic;Goals;Heterogeneity;Homeostasis;Human;interest;Invertebrates;Knowledge;Lateral;Length;Limb structure;Maintenance;Mediating;Microscopy;Morphogenesis;neural plate;notch protein;Pattern;programs;Regulation;Research;Signal Transduction;Spottings;stem cell niche;Surface;Tissues;Work

PROJECT_TITLE: Supplement to Mechanisms of cellular morphogenesis that coordinate signaling during tissue patterning


NIH_SPENDING_CATS: Regenerative Medicine

PHR: PROJECT NARRATIVE The proposed research will tackle a challenge central to public health – understanding the cellular and molecular mechanisms controlling tissue degeneration, regeneration and return to homeostasis in vertebrates – using a comparative approach of organisms that demonstrate varying degrees of natural and cyclical tissue degeneration and regeneration. These efforts will provide insight into mechanisms underlying tissue patterning and homeostasis and the pathological states of hypertrophy and degenerative disease. The specialized equipment requested in this supplement will not only enhance the acquisition of data from current experiments addressing these goals, but will also propel the development of innovative new comparative approaches for answering the overarching questions of the parent award.

PI_NAMEs: LARSON, TRACY ALISON (contact)

PROJECT_TERMS: Address;Anatomy;Behavior;Biological Models;Birds;Breeding;Cell Death;Cell Survival;Cells;Clinical;comparative;Competence;Crowns;data acquisition;Degenerative Disorder;Development;Equilibrium;Equipment;Event;experimental analysis;experimental study;functional restoration;Generations;Genetic;genetic variant;Genomic approach;Goals;Growth;Histologic;Homeostasis;Hypertrophy;Individual;innovation;insight;Knowledge;Link;Literature;Modeling;Modification;Molecular;Mutation;Natural History;Natural regeneration;Nerve Regeneration;neural circuit;neural growth;novel;Organism;Outcome;parent project;Pathologic;Pattern;pharmacologic;Population;prevent;programs;Proliferating;Public Health;regenerative;Regenerative Medicine;Regenerative research;Research;Seasonal Variations;Seasons;Serinus;Songbirds;Sparrows;Specific qualifier value;Stereotyping;System;Testing;tissue degeneration;tissue regeneration;Tissues;Translating;Vertebrates;Work

PROJECT_TITLE: Mechanisms of cyclical degeneration and regeneration in an avian model system


ORG_CITY: Aurora

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: Narrative Optogenetics may make it possible to treat human diseases through modulation of the peripheral nervous system. This requires an optical system capable of interfacing with individual axons. This project aims to develop miniature optical imaging systems that can be implanted for minimally invasive imaging.

PI_NAMEs: CALDWELL, JOHN H;GIBSON, EMILY ;WEIR, RICHARD FERGUS FFRENCH (contact)

PROGRAM_OFFICER_NAME: KUMSA, DOE WONDWOSSEN

PROJECT_TITLE: Diversity Supplement for Darwin Quiroz


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Biotechnology;Genetics;Mental Health;Neurosciences;Social Determinants of Health

ORG_CITY: DURHAM

ORG_NAME: DUKE UNIVERSITY

PHR: PROJECT NARRATIVE: Results from the proposed study are expected to provide fundamental knowledge on the role of sensory experience-mediated changes in chromatin and gene expression in flexible behavior. The proposed experiments will identify basic epigenetic, molecular, and circuit principles by which the environment induces changes in gene expression to alter the function of an individual or ensemble of neurons within a circuit and ultimately modify organismal behaviors. Thus, our findings may lead to novel and cheaper sensory experience-based therapeutic strategies that harness similar types of plasticity against psychiatric disorders, such as autism spectrum disorders, and depressive and anxiety disorders, where misprocessing of sensory information accentuates anxiety and social behaviors.

PI_NAMEs: JONES, CORBIN D;VOLKAN, PELIN C (contact)

PROGRAM_OFFICER_NAME: STEPANEK, LAURIE ELIZABETH

PROJECT_TERMS: Address;Animals;Anxiety;Anxiety Disorders;autism spectrum disorder;Automobile Driving;Award;Behavior;Behavioral;Brain;Budgets;Calcium;Candidate Disease Gene;Chromatin;Complement component C1s;Core Facility;cost;court;Courtship;Cues;Depressive disorder;Detection;differential expression;Ensure;Environment;Epigenetic Process;Equipment;Exhibits;experience;Experimental Genetics;experimental study;Female;fitness;flexibility;fly;Funding;Future;Gene Expression;Gene Expression Profile;Gene Expression Regulation;Gene Modified;Genes;Genetic;genetic manipulation;Genetic Transcription;Goals;Graph;Housing;Image;improved;indexing;Individual;Investigation;knock-down;Knowledge;Laboratories;Lasers;Learning;Light;light microscopy;Link;Maintenance;male;Mediating;Memory;men's group;Mental disorders;Microscope;Molecular;multi-photon;mutant;National Institute of General Medical Sciences;neural;neural circuit;Neurons;neuroregulation;novel;Output;overexpression;parent grant;parent project;Parents;Pheromone;Pheromone Receptors;Preparation;Procedures;Regulation;Regulator Genes;Research;Research Personnel;Resolution;response;Role;Scanning;screening;Sensory;Services;Signal Transduction;single-cell RNA sequencing;social;Social Behavior;Social Environment;social group;social influence;Social isolation;success;Synaptic plasticity;System;Therapeutic;Training;transcription factor;transcriptome sequencing;two photon microscopy;two-photon;Universities;Up-Regulation;Visit

PROJECT_TITLE: Social experience dependent modification of gene regulation and circuit function

STUDY_SECTION: MNG

STUDY_SECTION_NAME: Molecular Neurogenetics Study Section[MNG]


NIH_SPENDING_CATS: Brain Disorders;Congenital Structural Anomalies;Epilepsy;Genetics;Human Genome;Neurodegenerative;Neurosciences;Pediatric;Rare Diseases

ORG_CITY: HOUSTON

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

ORG_STATE: TX

PHR: Project Narrative (3 sentences max) Focal Cortical Dysplasias (FCDs) are among the most common epilepsy-associated structural brain lesions and we and others have shown that 60-90% of patients with FCD type I (FCD I) and FCD type II (FCD II) lack any genetic abnormality when using currently available testing methods. We propose the most comprehensive genetic analysis to date of a unique cohort of FCD I and II patients with unprecedented deep clinical phenotyping. A better understanding of the genetic basis of FCD etiology will lead to the introduction of novel gene-based diagnostic strategies and targeted drugs to fully manage a patient's seizures while avoiding the spectrum of side effects typically associated with current therapeutic interventions.

PI_NAMEs: LAL, DENNIS  (contact)

PROGRAM_OFFICER_NAME: WHITTEMORE, VICKY R

PROJECT_TERMS: Affect;Algorithms;Autopsy;Biological;Blood specimen;Brain;brain abnormalities;brain control;brain tissue;Calibration;Candidate Disease Gene;candidate selection;causal variant;Cell Nucleus;cell type;Cells;Chromosome abnormality;clinical phenotype;cohort;Copy Number Polymorphism;Cortical Dysplasia;Cortical Malformation;Data;Development;Diagnostic;diagnostic strategy;Disease;Drug resistance;Drug Targeting;Epilepsy;Etiology;exome;Frequencies;Gene Expression;Genes;Genetic;genetic analysis;Genetic study;Genetic Transcription;genetic variant;Genotype;Germ Lines;Histopathology;in utero;Individual;Intractable Epilepsy;Lead;Lesion;Loss of Heterozygosity;malformation in cortical development;Malignant neoplasm of brain;Medical Genetics;Meta-Analysis;Methods;migration;Molecular Abnormality;molecular pathology;Mutation;Neocortex;Neurons;novel;novel strategies;Observational Study;Operative Surgical Procedures;Partial Epilepsies;Pathogenicity;Patients;Persons;Pharmaceutical Preparations;Population;Publishing;rare variant;Regimen;Reporting;Research Design;Resected;Resources;RNA;Sampling;Seizures;side effect;single nucleus RNA-sequencing;SNP array;Somatic Mutation;Testing;Therapeutic;Therapeutic Intervention;Tissue Sample;Tissues;Transcription Alteration;transcriptome;Variant;Work

PROJECT_TITLE: Clinical genetics of drug-resistant epilepsy with focal cortical dysplasia

STUDY_SECTION: GHD

STUDY_SECTION_NAME: Genetics of Health and Disease Study Section[GHD]


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

ORG_CITY: BALTIMORE

ORG_DEPT: PHYSIOLOGY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: PROJECT NARRATIVE  Repeat expansion in C9ORF72 gene is the most common cause of both amyotrophic lateral sclerosis (ALS) and Frontotemporal dementia (FTD), two adult onset neurodegeneration diseases. Dysfunction of RNA metabolisms has emerged to play crucial roles in disease etiology. Based on recent findings, we propose to decipher how the dysregulation of RNA modification affect the toxic repeat products and disturb the global gene network, and determine whether targeting the dysfunctional epitranscriptomic pathway can rescue the disease- related phenotypes.

PI_NAMEs: SUN, SHUYING  (contact)

PROGRAM_OFFICER_NAME: GUBITZ, AMELIE

PROJECT_TERMS: Address;Adult;Affect;Amyotrophic Lateral Sclerosis;Brain;C9ORF72;Clinical;Degenerative Disorder;Development;Dipeptides;Disease;DNA Sequence Alteration;epitranscriptomics;Etiology;Eukaryotic Cell;Frontotemporal Dementia;frontotemporal lobar dementia amyotrophic lateral sclerosis;Functional disorder;gene network;Genes;Genetic;Homeostasis;Introns;Learning;Memory;Messenger RNA;methylome;Modification;Molecular;Motor Neurons;Nerve Degeneration;Nervous System;Neurodegenerative Disorders;Neuronal Dysfunction;Neurons;novel therapeutic intervention;Pathologic;Pathway interactions;Patients;Phenotype;Play;Post-Transcriptional Regulation;Predisposition;preservation;Proteins;Regulation;RNA;RNA metabolism;RNA methylation;RNA Processing;RNA-Binding Proteins;Role;Synaptic plasticity;Tissues;Toxic effect;Translations;Untranslated RNA

PROJECT_TITLE: The role of m6A RNA methylation in C9ORF72-ALS/FTD


ORG_CITY: CHICAGO

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE  The organelle trans-Golgi network (TGN) serves as the major sorting compartment and the center for modifications of newly synthesized proteins. In this proposal we aim to dissect the conserved molecular and cellular mechanisms governing TGN remodeling by microbial factors and study the effects on eukaryotic cellular processes. Our discoveries will advance our understanding of TGN morphology maintenance and functions, which will lay the foundation for rational design of therapeutics for a wide variety of human diseases.

PI_NAMEs: CHEN, JUEQI  (contact)

PROGRAM_OFFICER_NAME: ZHAO, XIAOLI

PROJECT_TITLE: Trans-Golgi Network Remodeling by Microbial Factors


ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: PROJECT NARRATIVE The primary cilium is an antenna-like cellular protrusion that allows cells to respond to external signals that instruct cell growth, differentiation, and proliferation. Aberrant ciliary signaling causes pediatric syndromes and can promote cancer development, while imbalances in cilium assembly versus disassembly are commonly observed in tumors and may contribute to uncontrolled cell growth. This proposal aims to improve our understanding of the roles of primary cilia in health and disease by elucidating the molecular pathways that underlie cilium formation, function, and disassembly.

PI_NAMEs: BRESLOW, DAVID KING (contact)

PROGRAM_OFFICER_NAME: AINSZTEIN, ALEXANDRA M

PROJECT_TERMS: Biochemical;Biogenesis;Biological Assay;Cell Cycle;Cell Cycle Progression;cell growth;Cells;Childhood;Cilia;ciliopathy;cilium biogenesis;Clustered Regularly Interspaced Short Palindromic Repeats;CRISPR screen;Defect;Development;Disease;Embryonic Development;Erinaceidae;experimental study;gene product;Genes;Genetic Screening;genome wide screen;Health;Homeostasis;Human body;Image;improved;In Vitro;insight;Knowledge;Link;Malignant Neoplasms;Mediator;Molecular;Monitor;novel strategies;Organelles;Pathway interactions;Perception;Permeability;Physiological;Proliferating;protein transport;Proteins;rab GTP-Binding Proteins;reconstitution;Role;screening;Screening procedure;Sensory;Signal Pathway;Signal Transduction;Structure;Structure of ciliary processes;Surface;Syndrome;System;Tissues;tumor;tumorigenesis;uncontrolled cell growth;Work

PROJECT_TITLE: Mechanisms of Primary Cilium Assembly and Disassembly


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Clinical Research;Dementia;Genetics;Human Genome;Infectious Diseases;Neurodegenerative;Neurosciences

ORG_CITY: NEW YORK

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: Project Narrative This study proposes to use comprehensive profiling of the patients' own immune cells to guide how to manage the complex presentation of brain impairments seen between older HIV individuals from those afflicted with early stages of Alzheimer's disease.

PI_NAMEs: NDHLOVU, LISHOMWA C (contact);VALCOUR, VICTOR

PROGRAM_OFFICER_NAME: MARIC, MAJA

PROJECT_TERMS: Acute;Address;Adult;Age;Age Years;aging population;Alzheimer's Disease;American;antiretroviral therapy;base;Biological;Blood;brain dysfunction;Cell Physiology;cell type;Cells;Central Nervous System Degenerative Diseases;Clinical;Cognition;Cognitive;cognitive performance;cohort;Complex;Data;Detection;Diagnostic;DISC1 gene;Disease;disease classification;DNA Methylation;DNA methylation profiling;Early Diagnosis;Environmental Risk Factor;Epigenetic Process;epigenetic profiling;epigenome;Event;experience;gene editing technology;Genes;Genetic;Genome;geriatric neuroHIV;histone modification;HIV;HIV Infections;HIV-associated cognitive impairment;HIV-associated neurocognitive disorder;Immune;immune activation;Immunologic Markers;Immunologics;Impaired cognition;improved;Individual;Inflammation;Inflammatory Response Pathway;innovation;Intervention;Knowledge;Link;Macrophage;Mediator;Methods;Methylation;methylome;Microglia;mild cognitive impairment;Molecular;monocyte;multidisciplinary;multiple omics;Myeloid Cells;Nerve Degeneration;neuroinflammation;Neuropsychological Tests;new technology;novel;NR4A2 gene;older adult;Outcome;Pathogenesis;Pathway interactions;Patients;Persons;Phenotype;Population;Positioning Attribute;Predisposition;Process;Property;Publishing;Rare Diseases;recruit;Resolution;Role;single cell analysis;single cell technology;single-cell RNA sequencing;Site;Sorting;Specimen;structural imaging;Technology;Testing;THBS1 gene;treatment strategy;Viremia;Work

PROJECT_TITLE: Harnessing Single Cell Epigenome-wide profiling of Myeloid cells to Compare and Contrast Alzheimer's from HIV-Associated Cognitive Dysfunction


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Emerging Infectious Diseases;Gene Therapy;Genetics;Infectious Diseases;Nanotechnology;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_DEPT: GENETICS

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: Project Narrative  Our research program is devoted to cell-specific drug delivery platforms for the treatment of diverse diseases. We will integrate our specialty in pharmaceutics, pharmaceutical chemistry, biomedical engineering, materials formulation, and animal studies to design and validate new drug delivery systems. The goal is to translate our scientific results and technological inventions into more effective drug delivery systems.

PI_NAMEs: DONG, YIZHOU  (contact)

PROGRAM_OFFICER_NAME: KODURI, SAILAJA

PROJECT_TERMS: 3' Untranslated Regions;Address;Animal Model;Animals;Area;base editing;Benzene;Biomedical Engineering;cell type;Cells;Data;design;Disease;Dose;Drug Delivery Systems;Drug Kinetics;Factor VIII;Formulation;Foundations;Gene Expression;Germ Cells;Glycolipids;Goals;Hemophilia A;Hepatocyte;Human;in vivo;innovation;invention;Lead;lipid nanoparticle;Lipids;Macrophage;medical specialties;Messenger RNA;mouse model;mRNA delivery;Multiple Bacterial Drug Resistance;Mus;nanoparticle;novel;novel therapeutics;Pharmaceutical Chemistry;Pharmacy (field);Physiological;Production;programs;Proteins;Research;Safety;stem cell delivery;stem cells;System;Technology;Testing;Therapeutic;tool;Translating;Untranslated Regions;Vitamins

PROJECT_TITLE: Construction of in vivo mRNA delivery systems


FUNDING_MECHANISM: RESEARCH CENTERS

NIH_SPENDING_CATS: Bioengineering;Clinical Research;Machine Learning and Artificial Intelligence

ORG_CITY: CLEMSON

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: CLEMSON UNIVERSITY

ORG_STATE: SC

PHR: NARRATIVE Musculoskeletal disease is one of the leading causes of disability and health care expenses where an estimated 126.6 million Americans (one in two adults) are affected by a musculoskeletal condition costing an estimated $213 billion each year in treatment and lost wages. With an aging population, this figure is only set to increase and become worse since research is hampered by a low and slow rate of translation of basic discoveries into clinical practice, e.g. only 25% of highly promising biomedical discoveries resulted in a published randomized clinical trial and less than 10% were established in clinical practice within 20 years. This COBRE center implements a new concept for translational research, i.e. Virtual Human Trials, to expedite the process from concept development to new deliverable therapeutics, interventions, and devices for musculoskeletal health.

PI_NAMEs: YAO, HAI  (contact)

PROGRAM_OFFICER_NAME: NANDA, JAGPREET SINGH

PROJECT_TERMS: 3-Dimensional;Adult;Affect;aging population;American;Animal Testing;Animals;Area;arthropathies;Artificial Intelligence;authority;Award;Big Data;Bioinformatics;biomarker development;Biomedical Engineering;Biomedical Research;bioprinting;Biosensor;Bone Diseases;Cadaver;career development;Cell Nucleus;Centers of Research Excellence;Clinical;clinical practice;Clinical Research;cluster computing;Collaborations;college;commercialization;Computer Models;Computing Methodologies;Conceptions;cost;cost estimate;Development;Devices;digital;disability;Discipline;Evaluation;experience;Exposure to;Extramural Activities;fabrication;Faculty;flexibility;forging;Foundations;Funding;Generations;Goals;Grant;Growth;Health;Health Resources;Health system;Healthcare;Human;imaging modality;improved;in silico;in vivo;Infrastructure;innovation;Institution;interest;International;Intervention;Leadership;Machine Learning;manufacturing technology;member;Mentors;Microfabrication;Modeling;multi-scale modeling;multidisciplinary;Musculoskeletal;Musculoskeletal Diseases;Musculoskeletal System;new technology;novel;novel therapeutics;Outcome;Patient Care;Patients;Performance;Persons;Phase;Positioning Attribute;pre-clinical assessment;Process;Program Development;programs;Publishing;randomized, clinical trials;Recovery;recruit;Research;Research Infrastructure;Research Personnel;Research Project Grants;Resources;Role;Schools;Science;sensor technology;skills;Source;South Carolina;Specimen;Speed;Stretching;success;Systems Biology;Talents;Techniques;Technology;technology platform;Technology Transfer;tenure track;Testing;Therapeutic;Time;Tissue Model;Tissues;training opportunity;Translational Research;Translational trial;Translations;trend;United States National Institutes of Health;Universities;Validation;Veterinary Medicine;veterinary science;virtual human;Wages;Woman;Work

PROJECT_TITLE: SC COBRE for TranslationalResearch Improving MusculoskeletalHealth (SC-TRIMH)


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

ORG_CITY: PHILADELPHIA

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: Project Narrative Mosaic chromosomal alterations (mCA) are a type of somatic mosaicism characterized by large chromosomal gains or losses. This proposal will develop novel approaches to quantify and localize mCA in kidney, blood and other non-neoplastic tissues to better understand how they contribute to aging and chronic disease. These efforts may help to identify cells with a high burden of mCA, which may lead to novel therapeutic approaches.

PI_NAMEs: WILSON, PARKER C. (contact);ZHANG, NANCY R

PROGRAM_OFFICER_NAME: BRUNSKILL, ERIC WAYNE

PROJECT_TERMS: Affect;Age;age-related disease;Aging;Algorithms;ATAC-seq;autosome;Awareness;Bar Codes;Base Pairing;Biological Assay;Bladder Diseases;Blood;cancer cell;Cell Fraction;Cell Line;Cell Nucleus;cell type;Cells;Chromatin;Chromosomal Gain;Chromosomal Loss;Chromosome abnormality;chromosome X loss;chromosome Y loss;Chromosomes;Chronic Disease;Clonal Expansion;Color;Computer software;Computing Methodologies;cost;Data;Data Set;design;Detection;detection method;digital;Disease Progression;DNA;DNA sequencing;Formalin;Gene Expression;Genes;Genomics;Genotype;Haplotypes;Heart Diseases;Hematological Disease;Heterogeneity;high throughput screening;Human;improved;In Situ;Injury to Kidney;insight;interest;Joints;Kidney;kidney cell;kidney cortex;Kidney Diseases;Length;Libraries;Lithium;Loss of Heterozygosity;male;Malignant Neoplasms;Measurement;men;Methods;Modification;mosaic;Mosaicism;multimodality;multiple omics;Mutation;novel;novel strategies;novel therapeutic intervention;novel therapeutics;Nucleosomes;open source;Organ;Paraffin Embedding;Pathology;Protocols documentation;Rattus;Renal Carcinoma;Renal function;Reporting;Research Personnel;Resolution;Role;Sampling;Sex Chromosomes;single cell sequencing;Somatic Mutation;Technology;Time;Tissue Embedding;Tissues;Transcript;transcriptome sequencing;transcriptomics;Validation;Variant;whole genome;Woman;Work;XCL1 gene

PROJECT_TITLE: Novel methods for detection of mosaic chromosomal alterations

STUDY_SECTION: GCAT

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


ADMINISTERING_IC: HL

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

PHR: Project Narrative This career development proposal has two important components that will benefit public health. The first is the development of the principal investigator into a physician-scientist, which is a uniquely trained medical doctor who by treating patients and conducting research identifies important gaps in our medical knowledge and is positioned to subsequently investigate new therapies. The second is the identification of a previously unexplored contribution of the donor immune system to the immediate post-transplant outcomes after heart transplant.

PI_NAMEs: KOPECKY, BENJAMIN J (contact)

PROGRAM_OFFICER_NAME: NEILSON, KAREN MARY

PROJECT_TERMS: Acceleration;Acute;Adult;Advisory Committees;Allogenic;allograft rejection;Allografting;Antigen Presentation;Antigen-Presenting Cells;Award;beta-Chemokines;Bioinformatics;Biological Assay;Biology;Cardiology;Cardiovascular system;career;career development;Cause of Death;cell type;Cells;cellular imaging;chemokine receptor;Clinical;clinical training;cost;curative treatments;Development;Development Plans;Doctor of Philosophy;Embryo;Fellowship;Flow Cytometry;Genetic Transcription;Goals;Graft Rejection;Heart;Heart failure;Heart Transplantation;Hematopoietic stem cells;Human;IFNGR1 gene;imaging study;Immune;Immune system;Immune Targeting;Immunologics;Immunology;Immunosuppression;Immunosuppressive Agents;improved outcome;in vitro Assay;in vivo;Infection;infection risk;Infiltration;Inflammation;Inflammatory Response;Institution;Interferon Type II;Internal Medicine;intravital imaging;Knowledge;laboratory experience;Life;Macrophage;Macrophage Activation;Malignant Neoplasms;Measures;Mediating;Medical;Mentors;monocyte;Morphology;Mus;Myeloid Cells;novel;novel therapeutics;Outcome;Pathogenesis;Pathway interactions;Patients;Phagocytosis;Physicians;Population;Positioning Attribute;post-transplant;Postdoctoral Fellow;prevent;Principal Investigator;protective effect;Public Health;recruit;Research;Risk;Role;Scientist;Senior Scientist;Signal Pathway;Signal Transduction;single-cell RNA sequencing;skill acquisition;success;T-Lymphocyte;Technical Expertise;Testing;Therapeutic;therapeutic target;Three-Dimensional Imaging;tissue repair;Training;transplant model;Transplantation;United States

PROJECT_TITLE: Dissecting the Role of Donor CCR2- Macrophages During Acute Cellular Rejection After Heart Transplantation

STUDY_SECTION: MCBS

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


NIH_SPENDING_CATS: Genetics;Human Genome

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

ORG_STATE: CA

PHR: PROJECT NARRATIVE The goal of this research program is to gain detailed mechanistic insight into retrotransposition and pre-mRNA splicing. Retroelements and spliceosomal introns comprise ~70% of the human genome and defects in their function results in many human diseases. We aim to use the molecular insight into these essential genetic mechanisms as a foundation for the development of RNA therapeutics.

PI_NAMEs: TOOR, NAVTEJ SINGH (contact)

PROGRAM_OFFICER_NAME: MACARTHUR, LINDA

PROJECT_TERMS: Active Sites;Biochemical;Catalysis;Catalytic RNA;Complex;Cryoelectron Microscopy;Defect;Development;DNA;Eukaryota;Excision;Exhibits;Exons;Foundations;Future;Genetic;genetic element;Genome;Goals;human disease;Human Genome;In Vitro;insight;Introns;Investigation;Knowledge;Ligation;Location;Molecular;mRNA Precursor;Nucleotides;particle;Paste substance;Prevalence;programs;Proteins;Reaction;Research;Resolution;Retroelements;Retrotransposition;Ribonucleoproteins;RNA;RNA Splicing;RNA-Directed DNA Polymerase;single molecule;Spliceosomes;structural biology;Structure;System;therapeutic RNA;thermostability;Work;X-Ray Crystallography

PROJECT_TITLE: Structural Biology of Retrotransposition and pre-mRNA Splicing


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Neurosciences;Rare Diseases

ORG_CITY: WASHINGTON

ORG_NAME: CHILDREN'S RESEARCH INSTITUTE

ORG_STATE: DC

PHR: PROJECT NARRATIVE Efficient sensory processing relies on the development of precise connectivity and deficits in sensory processing are common in many neurodevelopmental disorders (NDDs). However, the mechanisms underlying circuit development and the etiology of sensory deficits in NDDs are poorly understood, precluding the development of effective therapies. In this proposal, we will use a combination of in vivo anatomic, electrophysiologic, and environmental modification techniques in transgenic and knockout mouse models to elucidate the mechanisms by which proper connectivity is established in the developing visual system and how these processes are disrupted in NDDs.

PI_NAMEs: TRIPLETT, JASON  (contact)

PROGRAM_OFFICER_NAME: CLAYTON, EDWIN C

PROJECT_TERMS: Address;anatomical tracing;Anatomy;Anxiety;area striata;Automobile Driving;Computer Models;Data;Development;effective therapy;Electrophysiology (science);environmental enrichment for laboratory animals;Etiology;experience;experimental study;Eye;Fragile X Syndrome;Functional disorder;Genetic;in silico;in vivo;insight;knockout gene;Knockout Mice;Knowledge;Maintenance;Maps;Mediating;Modeling;Modification;Molecular;mouse model;Mus;Neurodevelopmental Disorder;Neurons;novel;overexpression;Population;Process;programs;Retina;Retinal Ganglion Cells;Role;Sensory;sensory mechanism;social communication;Specificity;superior colliculus Corpora quadrigemina;Synapses;Techniques;Testing;therapeutic target;Transgenic Organisms;Vision;Visual;visual dysfunction;visual map;Visual System

PROJECT_TITLE: Mechanisms of Synaptic Specificity in Visual Circuits

STUDY_SECTION: NBVP

STUDY_SECTION_NAME: Neuroscience of Basic Visual Processes Study Section[NBVP]


NIH_SPENDING_CATS: Clinical Research;Physical Injury - Accidents and Adverse Effects;Wound Healing and Care

ORG_CITY: MADISON

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: PROJECT NARRATIVE Trauma is the leading cause of mortality in the US in people under the age of 45 and is predicted to be one of the top contributors to the burden of global disease in this decade. This project aims to understand the early immune response and identify immune-based markers of severe burn injury, one of the most common traumatic injuries worldwide. We will focus on neutrophils as the most abundant white blood cell and the first responders in the human immune defense system to injuries.

PI_NAMEs: DINH, HUY QUANG (contact)

PROGRAM_OFFICER_NAME: CHAO, CHIEN-CHUNG

PROJECT_TERMS: Age;analysis pipeline;Anti-Inflammatory Agents;Back;Behavior;Bioinformatics;Biology;Burn injury;burn model;cell type;Cells;Clinical;Communities;Data;Disease;Environment;Equilibrium;first responder;Flow Cytometry;Genetic Transcription;genomic data;Goals;Heterogeneity;high dimensionality;Human;Image;Immune;Immune response;in vivo;Infection;Inflammation;Injury;innovation;interdisciplinary approach;Leukocytes;method development;Methods;migration;model organism;Modeling;Molecular;mortality;mouse model;multimodality;neutrophil;novel;Organ failure;Outcome;Pathologic;Pathway interactions;Patients;Persons;Phenotype;Play;pre-clinical;prevent;Process;programs;Research;response;Role;Sampling;severe burns;Shock;single cell genomics;single cell technology;Site;System;Time;Tissues;transcriptome;Trauma;Traumatic injury;Validation;wound healing;Zebrafish

PROJECT_TITLE: Neutrophil heterogeneity and plasticity in wound healing

STUDY_SECTION: MRAD

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


NIH_SPENDING_CATS: Cardiovascular;Heart Disease;Orphan Drug;Rare Diseases

ORG_CITY: HARRISONBURG

ORG_NAME: JAMES MADISON UNIVERSITY

PHR: Project Narrative  One of the molecular mechanisms through which both arrhythmogenic cardiomyopathies (AC) and fragile skin diseases (SFWHS and DCWHK) form is via mutations to the protein desmoplakin (DSP), a protein in the desmosome that helps connect the cytoskeleton of neighboring cells to each other. When DSP is destabilized, cell no longer connect to each other as strongly, and this leads to disease. The goal of this project is to study ways to stabilize DSP variants, which will eventually help us develop new therapeutic tools to counteract the molecular mechanisms that underlie desmosomal associated diseases.

PI_NAMEs: WRIGHT, NATHAN THOMPSON (contact)

PROGRAM_OFFICER_NAME: MASKERI, BAISHALI

PROJECT_TITLE: Exploration of Novel Strategies to Preserve Desmoplakin Variant Function


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

PHR: PROJECT NARRATIVE The Maternal Immunization and Determinants of Infant Immunity (MADI) program aims to understand the maternal factors governing immune response during pregnancy and in early life. The MADI Data Management and Biostatistics Core has previously developed a data management tool for the program that provides access by program investigators to all program data. With this supplement funding, the Core aims to enhance its data management system with updated data sharing processes that will improve ease and accuracy; to develop existing data sets for compliance with common standards; and to deploy via the cloud free software that other research teams can use to support their own research in immunology and infectious disease.

PI_NAMEs: PASETTI, MARCELA F (contact)

PROGRAM_OFFICER_NAME: PRABHUDAS, MERCY R

PROJECT_TERMS: Administrative Supplement;Architecture;Biostatistics Core;Catalogs;Child;Child Health;Clinical;cloud based;cohort;Collaborations;Communicable Diseases;Communities;complex data;Computer software;Custom;Data;Data Discovery;data ecosystem;data ingestion;data management;Data Management Resources;data platform;data portal;data quality;data reuse;Data Set;data sharing;data standards;Data Storage and Retrieval;data streams;Databases;design;Development;digital;Disease;FAIR principles;flexibility;Funding;Future;Goals;Harvest;Health;human subject;Immune;Immune response;Immunity;immunological status;Immunologics;Immunology;improved;Infant;Infectious Diseases Research;Institution;interdisciplinary approach;Investigation;Life;Link;maternal vaccination;Mediating;Metadata;Mothers;multidisciplinary;National Institute of Allergy and Infectious Disease;open source;parent project;portability;Practice Management;Pregnancy;Procedures;Process;programs;repository;Research;Research Personnel;Resources;Secure;Services;Site;sociodemographics;System;Talents;tool;United States National Institutes of Health;Update;virtual;Vision;Work

PROJECT_TITLE: Maternal Immunization and Determinants of Infant Immunity, A FAIR, portable, cloud-based immunology data management and discovery platform


ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: Project Narrative Most cells in adult animals are in a non-cycling, quiescent state often referred to as G0. Some cells enter reversible states of G0 while others enter more robust and permanent states of G0, but the differences between reversible G0 and permanent G0 are poorly understood. This work investigates the molecular mechanisms that control different states of G0 across tissues, with an ultimate goal of generating tools to manipulate and control G0, which becomes improperly regulated in both cancer and aging.

PI_NAMEs: BUTTITTA, LAURA A (contact)

PROGRAM_OFFICER_NAME: MILLER, RITA K

PROJECT_TERMS: Aging;Biological;Cell Cycle;Cell Cycle Inhibition;Cell Cycle Regulation;Cells;daughter cell;Development;Equipment;Event;flexibility;G0 Phase;Goals;Malignant Neoplasms;mature animal;Metabolic;Molecular;Nutrient availability;Organ;Organism;Pathway interactions;Physiological;Process;Production;response;Series;Signal Transduction;tissue regeneration;Tissues;tool;Work;zygote

PROJECT_TITLE: Equipment supplement: Probing the flexibility of G0

STUDY_SECTION: MRAC

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


NIH_SPENDING_CATS: Neurodegenerative;Neurosciences

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

PI_NAMEs: SESAKI, HIROMI  (contact)

PROGRAM_OFFICER_NAME: ANSONG, CHARLES KWAKU

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

PROJECT_TITLE: Structure, Turnover and Safeguard of Mitochondria


NIH_SPENDING_CATS: Infectious Diseases

ORG_CITY: PORTLAND

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: Project Narrative  The signaling molecule ubiquitin controls many aspects of human biology. Despite its importance in numerous human diseases, the intricacies of how and where ubiquitin serves a signaling role are unknown. We study the means through which disease-causing bacteria hijack the ubiquitin signal as an approach to understanding its function in regulating human health.

PI_NAMEs: PRUNEDA, JONATHAN N (contact)

PROGRAM_OFFICER_NAME: BARSKI, OLEG

PROJECT_TERMS: Bacteria;Bacterial Infections;Bacterial Interference;Biochemical;Biology;Case Study;Cell Cycle Regulation;Cell Physiology;Disease;Enzymes;Feeds;Health;Human;Human Biology;human disease;innovation;Invaded;Life;Motivation;novel;Outcome;pathogenic bacteria;Play;Polymers;pressure;Process;protein degradation;Proteins;Regulation;Research;Role;Signal Transduction;Signaling Molecule;Specificity;stem;System;tool;Ubiquitin;Ubiquitination;Vision;Work

PROJECT_TITLE: Exploiting bacterial effector proteins to study human ubiquitin signaling


NIH_SPENDING_CATS: Climate-Related Exposures and Conditions;Natural Products

ORG_CITY: Chicago

ORG_NAME: NORTHWESTERN UNIVERSITY

PHR: Project Narrative Methane gas is a major contributor to climate change, which represents a significant threat to human health. Methane-consuming bacteria have the potential to mitigate methane emissions and also produce copper-binding natural products with promising therapeutic applications. This equipment will be used to purify methane-oxidizing and natural product biosynthetic enzymes.

PI_NAMEs: ROSENZWEIG, AMY C. (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TITLE: Metalloenzymes and metal homeostasis


ORG_CITY: IOWA CITY

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: PROJECT NARRATIVE  Cells constantly need to destroy membrane proteins, either because they are damaged or no longer needed. Failure to do this properly can lead to a variety of human health ailments such a neurodegenerative diseases and cancer. This proposal seeks to understand the different pathways that membrane proteins use to undergo degradation.

PI_NAMEs: PIPER, ROBERT C (contact)

PROGRAM_OFFICER_NAME: STOKES, KALYNDA K

PROJECT_TERMS: Ablation;ATP phosphohydrolase;Binding;Binding Sites;Biological;Biological Process;Cell surface;cell type;Cells;Chemicals;Chimeric Proteins;Complex;Data;Defect;Degradation Pathway;Dislocations;Endoplasmic Reticulum;Endosomes;examination questions;exosome;extracellular vesicles;Failure;Family;Goals;Health;Human;human disease;Knowledge;Lead;Learning;Link;Lysine;Lysosomes;Malignant Neoplasms;Mediating;member;Membrane;Membrane Proteins;misfolded protein;Molecular;molecular array;multicatalytic endopeptidase complex;Multivesicular Body;mutant;Neurodegenerative Disorders;Organism;Outcome;Pathway interactions;Peptide Hydrolases;Polyubiquitin;posters;Process;protein degradation;Protein Family;protein folding;Protein Sortings;Proteins;proteostasis;proteotoxicity;Publishing;Quality Control;receptor;Scheme;Sorting;Specific qualifier value;Stress;Structure;System;theories;therapeutic development;Therapeutic Intervention;trans-Golgi Network;Ubiquitin;Vesicle;Work;Yeasts

PROJECT_TITLE: Ubiquitin-dependent sorting in endosomes and the TGN


NIH_SPENDING_CATS: Bioengineering

PHR: Narrative LC8 is a universal hub protein that binds to intrinsically disordered proteins (IDPs) leading to a unique class of multi-valent complexes - ladder-like in structure and `reversibly ordered' in that disassembly is intrinsic to their function and regulation. The dynamic structural properties of LC8-IDP assemblies are critical to the organization and regulation of diverse cellular systems, while aberrant LC8 function is associated with many diseases, including cancer, neurodegenerative diseases and rabies viral infection. Yet, LC8/IDP complexes remain poorly understood due to their complex structural properties, so we will deploy an innovative array of computational and experimental techniques to quantitatively characterize their heterogeneity and fluctuations/dynamics on multiple scales.

PI_NAMEs: BARBAR, ELISAR J;ZUCKERMAN, DANIEL M (contact)

PROGRAM_OFFICER_NAME: GERSHENSON, ANNE

PROJECT_TERMS: Address;Affinity;Architecture;Binding;Binding Proteins;Biochemical;Biophysics;Calorimetry;Cells;Collaborations;Complex;Computer Models;Computing Methodologies;Cooperative Behavior;crosslink;Disease;Dynein ATPase;Electron Microscopy;Elements;Exhibits;experience;experimental study;flexibility;frontier;Heterogeneity;innovation;Kinetics;Ligands;Malignant Neoplasms;Mass Spectrum Analysis;Measurement;Molecular;Molecular Conformation;molecular dynamics;Motor;Neurodegenerative Disorders;novel;Nuclear Magnetic Resonance;Pathway interactions;Population;Property;protein complex;Proteins;Rabies;Regulation;Role;scaffold;sensor;simulation;structural biology;Structure;success;Surface Plasmon Resonance;System;Techniques;theories;Thermodynamics;Titrations;Virus Diseases;Work

PROJECT_TITLE: Multiscale Characterization of a Unique Class of Duplex, Multivalent IDP Systems


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

ORG_CITY: Aurora

ORG_NAME: UNIVERSITY OF COLORADO DENVER

PHR: The proposed administrative supplement to recognize excellence in Diversity, Equity, Inclusion, and Accessibility (DEIA) mentorship seeks to enhance the mentorship capacity within the parent award (R25, Enhancing Science, Technology, EnginEering, and Math Educational Diversity) ensuring that faculty and peer mentors are equipped to support our students effectively. The proposed research is relevant to the part of NIH's mission that pertains to developing the human resources that will ensure the Nation's capability to prevent disease.

PI_NAMEs: NEEVES, KEITH B (contact);WALKER, TARIK DOBBS

PROGRAM_OFFICER_NAME: GATLIN, TINA L

PROJECT_TERMS: Address;Administrative Supplement;Area;Articulation;Behavior;Biomedical Engineering;Biomedical Research;career;college;Colorado;Communication;community college;Complement;cultural competence;Data;design;Development;Disease;Education;education research;Educational Curriculum;Educational workshop;effectiveness evaluation;Engineering;Ensure;Equity;equity, diversity, and inclusion;Ethics;expectation;experience;faculty mentor;faculty support;Faculty Workshop;Fostering;Goals;health equity;Human Resources;improved;Individual;innovation;Institution;Intervention Studies;Journals;Life;Medicine;member;Mentors;Mentorship;Methods;Mission;Modeling;next generation;parent grant;parent project;Pathway interactions;peer coaching;Peer Review;Philosophy;Population;Population Scientist Supplement (R25);prevent;programs;Qualitative Methods;recruit;Research;Scholars Program;Science;Science, Technology, Engineering and Mathematics Education;skills;Structure;Students;success;Surveys;symposium;tool;Training;Training Programs;transfer student;undergraduate student;United States National Institutes of Health;Universities;university student;Work

PROJECT_TITLE: Admin supplement to ESTEEMED Scholars Program in Bioengineering at the University of Colorado Denver


NIH_SPENDING_CATS: Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD)

ORG_CITY: Boston

ORG_NAME: TUFTS UNIVERSITY MEDFORD

ORG_STATE: MA

PHR: Cyclic peptides are an exciting class of drug molecules capable of engaging challenging biological targets, and cyclic peptide natural products have been used in the clinic as immune system suppressants, antibiotics, and antifungals. Unfortunately, it is currently extremely challenging for researchers to design new cyclic peptide drugs to treat specific diseases because it is very difficult to predict the three-dimensional structures any cyclic peptide will adopt and to optimize their pharmacologic properties. In this proposal, we develop new computing algorithms that efficiently and accurately predict structures and properties of cyclic peptides, thereby allowing scientists to much more rapidly and robustly develop novel cyclic peptide drugs.

PI_NAMEs: LIN, YU-SHAN  (contact)

PROJECT_TERMS: Address;Adopted;Affinity;Algorithms;Amino Acids;anti-fungal agents;Antibiotics;Area;Binding;Biological;Biological Availability;Biological Process;Cell Membrane Permeability;Cell Physiology;Characteristics;Clinic;Clinical Data;computational chemistry;computational platform;Computing Methodologies;Cyclic Peptides;Data;Descriptor;design;Development;Dimensions;Disease;drug development;Drug Modelings;extracellular;functional group;functional mimics;fundamental research;Goals;Immune system;improved;In Vitro;in vivo;inhibitor;innovation;invention;Location;Machine Learning;machine learning model;Marketing;Measures;Membrane Proteins;Methods;Modification;Molecular Conformation;molecular dynamics;Molecular Machines;Natural Products;novel;peptide drug;peptide natural products;Performance;Periodicity;Pharmaceutical Preparations;pharmacologic;Population;predictive modeling;preservation;Property;protein aminoacid sequence;protein protein interaction;Proteins;Protocols documentation;Reporting;Research;Research Personnel;Running;scaffold;Scientist;simulation;small molecule;Solubility;Solvents;Speed;Structure;Surface;therapeutic development;Therapeutic Intervention;three dimensional structure;Time;TIMP3 gene;tool;Training;training data;translational impact;user-friendly;Water;water solubility;Work

PROJECT_TITLE: Understanding and designing cyclic peptides

STUDY_SECTION: MSFA

STUDY_SECTION_NAME: Macromolecular Structure and Function A Study Section[MSFA]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: PROJECT NARRATIVE This CCSG provides support for administration; basic, translational, clinical and population science research; shared resources; clinical research infrastructure; deep community outreach and engagement; and education, training, and mentoring programs at the Mayo Clinic Comprehensive Cancer Center.

PI_NAMEs: WILLMAN, CHERYL LYNN (contact)

PROGRAM_OFFICER_NAME: PTAK, KRZYSZTOF

PROJECT_TERMS: Address;Advisory Committees;Allied Health Personnel;Arizona;Basic Science;cancer care;Cancer Center Support Grant;cancer clinical trial;Cancer Diagnostics;cancer health disparity;Cancer health equity;care delivery;Caring;Catchment Area;Clinic;Clinical;clinical care;Clinical Research;Clinical Sciences;Clinical Trials;Communities;community engagement;Community Outreach;community setting;Compassion;Comprehensive Cancer Center;Data;Decentralization;Detection;Development;digital tool;Education;Evaluation;Florida;Funding;Future;Grant;healing;Home;Industry;innovation;Intervention;Knowledge;Laboratories;Leadership;Malignant Neoplasms;member;Mentors;Midwestern United States;Minnesota;next generation;novel;Patients;Peer Review;Physicians;Policies;Population Sciences;prevent;Prevention;programs;recruit;Research;Research Infrastructure;Research Personnel;Resource Sharing;Scientist;Site;Strategic Planning;Testing;Therapeutic Agents;Training;Translating;Translational Research;Virtual Tool

PROJECT_TITLE: Mayo Comprehensive Cancer Center Grant (Funded Extension Supplement)


NIH_SPENDING_CATS: Genetics

ORG_CITY: DALLAS

ORG_DEPT: OBSTETRICS & GYNECOLOGY

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: Project Narrative (Parent Grant R01GM147583) Turning on the right gene at the right time is essential for development and requires the dynamic recruitment of dozens of regulatory factors to specific genomic loci; defects in this process cause human disease. Emerging evidence supports a role for weak multivalent interactions in organizing regulatory factors into multi-component clusters that assemble and disassemble dynamically, yet these types of interactions have been difficult to study as they are only stabilized under specific conditions which enable cluster formation. Investigation into the mechanisms and functions of these weak multivalent interactions in the context of cluster formation will provide novel insights into a fundamental biological process with implications for developmental processes and aberrant gene activation in disease.

PI_NAMEs: SABARI, BENJAMIN  (contact)

PROGRAM_OFFICER_NAME: WAIRKAR, YOGESH PRABHAKAR

PROJECT_TERMS: Amino Acids;Architecture;Biochemical Process;Biological Process;C-terminal;Cell Nucleus;Complex;Data;Defect;Development;Developmental Process;Disease;DNA Binding;Exclusion;functional outcomes;Gene Activation;Gene Expression Regulation;Genes;Genetic Transcription;genomic locus;Grant;human disease;insight;Investigation;Learning;Mediating;Mediator;Methods;Modeling;Molecular;novel;Nuclear Proteins;parent grant;Process;protein protein interaction;Protein Region;Publishing;recruit;Role;Specificity;Testing;Time;tool;transcription factor

PROJECT_TITLE: Organization of transcriptional machinery by weak multivalent interactions


NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Genetics;Human Genome;Neurodegenerative;Neurosciences;Regenerative Medicine

ORG_CITY: CLEVELAND

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: CLEVELAND CLINIC LERNER COM-CWRU

ORG_STATE: OH

PHR: Project Narrative Methods to regenerate photoreceptors represents a major therapeutic goal for inherited retinal disease. Zebrafish have the capacity to regenerate lost neurons following acute injury but mutants with retinal degeneration do not regenerate. This proposal will address critical unanswered questions such as why zebrafish with chronic inflammation in diseased retinas fail to regenerate and to determine how inflammation regulates regeneration.

PI_NAMEs: PERKINS, BRIAN D (contact)

PROGRAM_OFFICER_NAME: FORTRESS, ASHLEY

PROJECT_TERMS: 1 year old;Acute;Address;Animals;ATAC-seq;Blindness;Cell Cycle;Cell Death;cell regeneration;Cells;Cessation of life;Chronic;Chronic Disease;ciliopathy;Cone;CRISPR/Cas technology;cytokine;Cytokine Signaling;Data;Disease;disease model;epigenomics;Exhibits;Gene Expression;gene regulatory network;Genetic;Genetic Diseases;Gliosis;Goals;Human;human model;IL6 gene;Immune response;Immunosuppression;Inflammation;Inflammatory;Inflammatory Response;Inherited;inherited retinal degeneration;Injury;insight;Lesion;Ligands;Light;Link;Literature;Macrophage;Mammals;Methods;Microglia;Modeling;Molecular;Muller's cell;multiple omics;mutant;Natural regeneration;nerve stem cell;Neurons;NF-kappa B;notch protein;NOTCH3 gene;novel;Pathway interactions;pharmacologic;Phase;photoreceptor degeneration;Photoreceptors;prevent;Process;programs;Proliferating;receptor;regenerative;Regenerative research;Regenerative response;Repression;Resolution;response;Retina;Retinal Degeneration;Retinal Diseases;Retinal Dystrophy;retinal neuron;retinal progenitor cell;retinal regeneration;Retinitis Pigmentosa;Role;Signal Pathway;Signal Transduction;single nucleus RNA-sequencing;Source;stem cell proliferation;stem-like cell;Technology;Testing;Therapeutic;Time;TNF gene;Translating;Up-Regulation;Vision;Zebrafish

PROJECT_TITLE: Inflammatory Signaling and Regeneration in Zebrafish models of Retinal Degeneration

STUDY_SECTION: NDPR

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


ORG_CITY: Boulder

ORG_NAME: UNIVERSITY OF COLORADO

PHR: Project Narrative This supplement application requests support to purchase an ÄKTA Pure chromatography system for the efficient and reliable purification of vesicles intended for gene therapy applications. This state-of- the-art instrument supports a wide range of chromatography techniques critical for the isolation and characterization of engineered extracellular vesicles, offering flexibility and scalability. The proposed purchase will enable us to develop a reliable chromatography-based separation method for gectosomes, facilitating its translation into a therapeutic modality.

PI_NAMEs: LIU, XUEDONG  (contact)

PROGRAM_OFFICER_NAME: BARNES, CHARLES ASHLEY

PROJECT_TITLE: Programmable Microvesicles for Intracellular Macromolecule Delivery


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: CHARLESTON

ORG_NAME: RALPH H JOHNSON VA MEDICAL CENTER

PHR: Understanding variation in access to healthcare and the physician workforce will provide actionable information on strategies to address disparities by providing targets for policy-level interventions. This application will use advanced GIS and spatial statistical methods to examine spatiotemporal patterns and identify persistent hotspots of poor outcomes, increased utilization and cost, and increased mortality in patients with diabetes across the VA healthcare system. We will leverage our expertise in diabetes care, equity research, GIS analysis, and advanced spatiotemporal statistics to (1) create a comprehensive and unique database, (2) create a workforce deprivation index that allows incorporation of variation in the physician workforce into policy decisions, and (3) incorporate neighborhood/community factors to inform VA policy to improve Veteran health. This innovative methodology will be applicable across disease states, and once developed can be disseminated to better target systems engineering and intervention development efforts.

PI_NAMEs: HUNT, KELLY J;NEELON, BRIAN  (contact)

PROJECT_TERMS: Address;Adult;Algorithms;Ambulatory Care;Amputation;Area;Attention;Blood Pressure;burden of illness;Caring;Cause of Death;Characteristics;cohort;Communication;Communities;Community Health;Community Healthcare;community-level factor;cost;Data Set;Database Management Systems;Databases;Death Rate;deprivation;Diabetes Mellitus;Dimensions;Disease;Disease Outcome;disorder risk;Disparity;Education;Engineering;Equity;Ethnic Origin;flexibility;geographic disparity;Geographic Information Systems;Geographic Locations;Geography;Goals;Health;health care availability;Health Care Costs;health care model;health disparity;Health Expenditures;health literacy;Health Personnel;Health Services Accessibility;Healthcare;Healthcare Systems;Heart Diseases;High Prevalence;high risk;Improve Access;improved;improved outcome;Income;indexing;Individual;information system analysis;Information Technology;innovation;inpatient service;Institution;Intervention;Kidney Failure;Knowledge;Link;Lipids;Measures;Metabolic Control;Methodology;Methods;Modeling;mortality;Neighborhoods;Non-Insulin-Dependent Diabetes Mellitus;Not Hispanic or Latino;novel;Outcome;outcome disparities;Patient Care;Patients;Pattern;Personal Satisfaction;pharmacy benefit;Physicians;Policies;Policy Maker;Population;population health;Prevalence;Productivity;provider factors;Race;racial disparity;racial minority;Research;Resource-limited setting;Resources;Self Efficacy;spatiotemporal;Statistical Methods;statistics;Stroke;System;therapy development;Time trend;trend;Trust;United States;Variant;Veterans;Visualization

PROJECT_TITLE: Impact of neighborhood and workforce deprivation on diabetes outcomes in Veterans: a spatio-temporal analysis

STUDY_SECTION_NAME: HSR-2 Behavioral, Social, and Cultural Determinants of Health and Care[HSR2]


NIH_SPENDING_CATS: Biotechnology;Cancer;Gene Therapy;Genetics;Immunotherapy;Lung;Lung Cancer;Rare Diseases

ORG_CITY: BUFFALO

ORG_NAME: ROSWELL PARK CANCER INSTITUTE CORP

ORG_STATE: NY

PHR: NARRATIVE Most patients with relapsed small cell lung cancer (SCLC) have a very poor prognosis and the disease kills over 25,000 people annually in the US, highlighting the need for novel therapies to improve survival. A patient's own immune cells may be genetically engineered to recognize and kill tumor cells. This project is focused on using this technology to create patient T cells genetically engineered to optimally kill SCLC tumor cells and test this approach in preclinical models.

PI_NAMEs: BRENTJENS, RENIER JOSEPH (contact)

PROGRAM_OFFICER_NAME: FORRY, SUZANNE L

PROJECT_TERMS: Acute Lymphocytic Leukemia;Address;Anti-CD47;anti-PD-1;anti-tumor immune response;Antibodies;Antigen Targeting;Antigens;Biological Models;Biology;Cancer Biology;cancer cell;cancer therapy;CD19 gene;CD47 gene;Cell Physiology;Cell secretion;Cell surface;Cells;checkpoint receptors;chimeric antigen receptor;chimeric antigen receptor T cells;Clinical;clinical translation;Clinical Trials;clinically relevant;cytokine;Data;design;Development;Disease;Down-Regulation;Eating;engineered T cells;Extensive Stage;Failure;FDA approved;Funding;Ganglioside GD3;gene therapy;Generations;Genetic;Genetic Engineering;Goals;Hematologic Neoplasms;Hepatitis delta Antigens;Heterogeneity;Human;IL18 gene;Immune;immune checkpoint;Immune checkpoint inhibitor;Immune system;Immunocompetent;Immunoglobulin Fragments;Immunotherapy;improved;In Vitro;in vivo;in vivo Model;Interleukin-12;Investigational New Drug Application;Ligands;lung cancer cell;Lymphoma;Macrophage;Malignant neoplasm of ovary;Mediating;Methods;Modality;Molecular;molecular targeted therapies;mouse model;Mutation;neoplastic cell;neuroendocrine cancer;notch protein;novel;novel therapeutic intervention;novel therapeutics;patient derived xenograft model;Patients;Persons;Phagocytosis;Phase I Clinical Trials;pre-clinical;Pre-Clinical Model;Preclinical Testing;Preparation;Prognosis;programmed cell death protein 1;Proteins;receptor;Refractory;Relapse;Resistance;response;Signal Transduction;small cell lung carcinoma;Solid Neoplasm;System;T-Cell Receptor Therapy;T-Lymphocyte;Technology;Testing;Therapeutic;tool;Treatment Failure;tumor;Tumor Antigens;tumor microenvironment;Work

PROJECT_TITLE: Optimizing Dual-Targeted and Dual-Armored CAR T Cells for Small Cell LungCancer


ORG_CITY: HOUSTON

ORG_NAME: MICHAEL E DEBAKEY VA MEDICAL CENTER

PHR: The class of biologic medications are highly effective, yet highly expensive medications. Biologics are different from standard medications because they can only be created using living systems, and are therefore cannot be exactly copied as a “generic” medication. Biologics are among the fastest growing class of medications and are used for diseases of the immune system, cancers, and other conditions. Biosimilars are copy versions of biologic medications and have recently been approved for use in immune conditions. Biosimilars for immune conditions have been shown in early studies to have similar efficacy as original biologics and are available at a significantly cheaper cost. However, many patients and providers have concerns regarding the safety and effectiveness of biosimilar switching as they are not identical. This proposal aims to use a learning healthcare systems approach to study the safety, effectiveness, and Veterans’ views of acceptance of biosimilar switching.

PI_NAMEs: HOU, JASON KEN (contact);WALJEE, AKBAR K

PROJECT_TERMS: Address;Adverse event;adverse event risk;antagonist;barrier to care;Biological;Biological Products;Calibration;Caring;Chronic;Clinical;Collaborations;Complex;Confidence Intervals;Consensus;cost;cost effective;Cost Savings;cost shifting;Crohn's disease;Data;Data Set;deliberative democracy;Disease;Education;Effectiveness;Engineering;Ethics;Event;Flare;Future;gastrointestinal system;Guidelines;Health;Health system;Healthcare;Healthcare Systems;Hospitalization;Immune;Immune System Diseases;improved;Incidence;Inflammatory;Inflammatory Bowel Diseases;infliximab;innovation;Knowledge;Learning;Legal patent;machine learning model;machine learning prediction;Malignant Neoplasms;Manuals;Mediating;Methodology;Methods;military service;Modeling;Operative Surgical Procedures;Organism;Patient Preferences;Patients;peer;Pharmaceutical Preparations;pharmacy benefit;Pharmacy facility;Policies;Pragmatic clinical trial;preference;Prevalence;programs;Provider;Randomized, Controlled Trials;Research;Research Priority;Retrospective cohort study;risk stratification;Safety;safety study;service member;Structure;Suggestion;System;Techniques;TNF gene;tool;Ulcerative Colitis;United States Food and Drug Administration;Veterans

PROJECT_TITLE: Effectivenes, Safety, and Patient Preferences of Infliximab Biosimilar Medications for Inflammatory Bowel Disease

STUDY_SECTION_NAME: HSR-1 Health Care and Clinical Management[HSR1]


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Dental, Oral, and Craniofacial Disease;Neurosciences;Orphan Drug;Radiation Oncology;Rare Diseases

ORG_CITY: BIRMINGHAM

ORG_COUNTRY: UNITED KINGDOM

ORG_FIPS: UK

ORG_NAME: UNIVERSITY OF BIRMINGHAM

ORG_ZIPCODE: B15 2TT

PHR: Project Narrative This project will enhance our basic understanding of the biological effects of precision particle radiotherapy, particularly proton beam therapy, on normal and tumour cells, with a focus on cells derived from solid tumours of the head and neck and brain which are particularly resistant to radiotherapy. This will be accomplished through analysing the comparative impact of particle radiotherapy delivered at both low and high (so called “FLASH”) dose rates on survival of normal versus the tumour cells, and how this this is mediated through specific effects on critical targets (DNA), under conditions of normal and reduced oxygen (hypoxia) which is important for solid tumours that are radiotherapy resistant. This will lead to development of optimal strategies using particle radiotherapy (protons) for the effective treatment of head and neck and brain tumours, minimising the commonly observed acute and long-term adverse side effects caused by the impact of the radiation on the associated normal tissues, and ultimately improve patient benefit and overall survival. 1

PI_NAMEs: PARSONS, JASON  (contact)

PROGRAM_OFFICER_NAME: BUCHSBAUM, JEFFREY

PROJECT_TERMS: 3-Dimensional;Acute;Automobile Driving;Biologic Characteristic;Biological;Biological Process;Biology;Brain;Brain Neoplasms;cancer therapy;cell killing;Cell model;Cell Survival;Cells;cellular targeting;Characteristics;Chronic;Clinical Oncology;combinatorial;comparative;Complex;conventional dosing;Data;Deposition;Development;Distal;DNA;DNA Damage;DNA Double Strand Break;DNA Repair;Dose;Dose Rate;Drug Targeting;effective therapy;Electron Transport;Frequencies;Future;Glioblastoma;Head and Neck Cancer;Head and Neck Neoplasms;Helium;High-LET Radiation;Human;Hypoxia;improved;inhibitor;interest;Ions;irradiation;Knowledge;Lead;Linear Energy Transfer;Malignant Neoplasms;Mediating;Modeling;Molecular;neoplastic cell;Normal Cell;Normal tissue morphology;novel;optimal treatments;Organ;Oxygen;particle;patient response;Patients;Pharmaceutical Preparations;Photons;proton beam;Protons;Radiation;Radiation Dose Unit;radiation effect;Radiation Physics;radiation resistance;Radiation therapy;Radiation Tolerance;Radiobiology;radioresistant;Relative Biological Effectiveness;Research;Resistance;Resources;response;Risk;Roentgen Rays;Role;Sampling;screening;side effect;Solid;Solid Neoplasm;Techniques;Therapeutic;Therapeutic Effect;therapy resistant;three-dimensional modeling;Time;Tissues;treatment strategy;tumor;Tumor Promotion;Tumor Tissue;two-dimensional;Uncertainty

PROJECT_TITLE: Realizing the radiobiological impact of protons and high-LET particles in head and neck cancer and glioblastoma models


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Breast Cancer;Cancer;Cerebrovascular;Neurosciences;Women's Health Research

ORG_CITY: MORGANTOWN

ORG_DEPT: NEUROSCIENCES

ORG_NAME: WEST VIRGINIA UNIVERSITY

ORG_STATE: WV

PHR: Project Narrative Breast cancer is the most commonly diagnosed cancer type among women and the incidence of brain metastases of breast cancer is steadily increasing. I have recently discovered a circadian rhythm in blood brain barrier (BBB) permeability to chemotherapeutics; this project exploits this circadian regulation of BBB permeability to optimally time chemotherapy administration to increase anti-tumor efficacy and reduce adverse side effects of brain metastases treatment. Together, this research will provide essential information with a high potential for clinical relevance to better treat patients with breast cancer.

PI_NAMEs: WALKER, WILLIAM HARRY (contact)

PROGRAM_OFFICER_NAME: XI, DAN

PROJECT_TERMS: ABCG2 gene;Adverse effects;Affect;Anxiety;anxiety-like behavior;Autoradiography;Award;Behavior;Behavioral;Biology;Bioluminescence;Blood - brain barrier anatomy;blood-brain barrier crossing;blood-brain barrier permeabilization;blood-brain tumor barrier;Brain Death;breast cancer metastasis;cancer diagnosis;Cancer Patient;cancer type;career development;Cell Death;chemotherapeutic agent;chemotherapy;circadian;circadian biology;circadian regulation;Circadian Rhythms;clinically relevant;Clustered Regularly Interspaced Short Palindromic Repeats;cognitive function;Cyclophosphamide;Darkness;Data;depressive symptoms;Development;Diagnosis;Disease;Doxorubicin;Equilibrium;genetic approach;Goals;Grant;Hour;Image;Immunohistochemistry;Impaired cognition;improved;Incidence;Inferior;inhibitor;Injections;intravenous injection;Label;laboratory experience;Location;Malignant Breast Neoplasm;Malignant Neoplasms;Medicine;Mental Depression;Mentors;Metastatic malignant neoplasm to brain;mouse model;multidisciplinary;Mus;neuroinflammation;Neuropsychology;Neurosciences;Nonmetastatic;novel;optimal treatments;Outcome;Paclitaxel;Patients;Permeability;Pharmaceutical Preparations;pharmacologic;Phase;Physiological Processes;Quantitative Reverse Transcriptase PCR;Research;Research Personnel;Research Support;side effect;Sleep;Survival Rate;Techniques;Therapeutic;Time;Training;Treatment Efficacy;treatment strategy;trend;tumor;Tumor Burden;tumor growth;United States;Woman;women's diagnosis;Writing

PROJECT_TITLE: Circadian Rhythms in Blood Brain Barrier Permeability and Increased Efficacy of Chemotherapy for Brain Metastases

STUDY_SECTION: NCI

STUDY_SECTION_NAME: Transition to Independence Study Section (I)[NCI-I]


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Breast Cancer;Cancer;Dental, Oral, and Craniofacial Disease;Immunization;Immunotherapy;Orphan Drug;Rare Diseases;Vaccine Related;Women's Health Research

ORG_CITY: CAMBRIDGE

ORG_DEPT: MISCELLANEOUS

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

PHR: PROJECT NARRATIVE Carcinomas, solid tumors of epithelial origin, represent up to 90% of all cancer cases in the United States and present a persistent healthcare challenge. Immunotherapy and chemotherapy are promising treatment strategies for carcinomas, but they have limited efficacy and are associated with side effects that impact patient quality of life. This F99/K00 award proposal focuses on developing a peptide-based hydrogel for the local delivery of chemotherapies and immune checkpoint inhibitors to improve treatment efficacy while avoiding systemic toxicity and side effects.

PI_NAMEs: POGOSTIN, BRETT  (contact)

PROGRAM_OFFICER_NAME: ELJANNE, MARIAM

PROJECT_TERMS: Acids;Address;Adjuvant;Adult;Adverse effects;Affinity;Aftercare;Amino Acids;anti-cancer;anti-CTLA4 antibodies;anti-PD-1;Antibodies;antibody inhibitor;Antigens;Antineoplastic Agents;Award;Behavior;Binding;Biocompatible Materials;Biological;Biological Immunotherapy;Biological Products;biomaterial compatibility;Boronic Acids;Bortezomib;Breast Cancer Model;cancer cell;cancer immunotherapy;cancer recurrence;cancer therapy;cancer vaccination;Carcinoma;Catechols;Cause of Death;Cell Death;Cells;chemotherapy;Combination immunotherapy;controlled release;covalent bond;delivery vehicle;design;Development;Diagnosis;Diffusion;Dose;Drug Controls;Drug Delivery Systems;efficacy evaluation;Epithelium;Face;FDA approved;Flow Cytometry;Glycols;Goals;Half-Life;Head and Neck Squamous Cell Carcinoma;healing;Healthcare;Histology;Hydrogels;Immune;immune checkpoint blockade;Immune checkpoint inhibitor;Immune response;Immunity;immunogenic;immunogenic cell death;Immunotherapeutic agent;Immunotherapy;improved;In Vitro;in vivo;Incidence;Injections;innovation;interest;intravenous administration;Investigation;Kinetics;local drug delivery;Malignant Breast Neoplasm;Malignant Neoplasms;Melanoma;minimally invasive;mouse model;Multiple Myeloma;Mus;Natural Killer Cells;Needles;Patients;Peptides;Pharmaceutical Preparations;Pharmacotherapy;Phase;Physiological;Property;prophylactic;Quality of life;Safety;self assembly;side effect;small molecule;Solid Neoplasm;synergism;System;systemic toxicity;T-Lymphocyte;Tertiary Protein Structure;Testing;Therapeutic;Thinness;Tissues;Toxic effect;Treatment Efficacy;treatment strategy;tumor;Tumor Immunity;United States;water solubility

PROJECT_TITLE: Controlled Antigen Delivery for Prophylactic Cancer Vaccination


NIH_SPENDING_CATS: Genetics;Infectious Diseases

ORG_CITY: BLOOMINGTON

ORG_NAME: TRUSTEES OF INDIANA UNIVERSITY

ORG_STATE: IN

PHR: PROJECT NARRATIVE Bacteria communicate using a process called quorum sensing to cooperatively change expression of genes required for pathogenesis. My lab studies the quorum sensing in marine Vibrio bacteria that are human pathogens to deteremine how cell-cell signaling affects gene expression. In this supplement proposal, I am requesting funds to purchase a ThermoFisher Scientific Sorvall Lynx 6000 superspeed centrifuge and rotors to support the proposed experiments and increase our productivity.

PI_NAMEs: VAN KESSEL, JULIA C. (contact)

PROGRAM_OFFICER_NAME: KEANE-MYERS, ANDREA

PROJECT_TERMS: Affect;Bacteria;Behavior Control;Biochemical;Biological Assay;Biological Models;Biophysics;Cell Communication;cell preparation;Cells;Communication;cost;Development;DNA;Ensure;Environment;Equipment;experimental study;Funding;Gene Expression;Gene Expression Regulation;Genes;Genus Lynx;Goals;human pathogen;improved;intercellular communication;marine;Methods;Molecular Biology;pathogen;Pathogenesis;Physiological;Population Control;Population Density;Process;Productivity;programs;protein purification;Proteins;quorum sensing;Refrigeration;Regulation;repaired;Research;Signal Transduction;Speed;Symbiosis;transcription factor;Vibrio;virulence gene

PROJECT_TITLE: Quorum sensing regulation of bacterial development

STUDY_SECTION: MRAA

STUDY_SECTION_NAME: Maximizing Investigators? Research Award A Study Section[MRAA]


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Aphasia;Behavioral and Social Science;Brain Disorders;Cerebrovascular;Clinical Research;Disability Research;Neurosciences;Rehabilitation;Stroke

ORG_CITY: CHICAGO

ORG_NAME: REHABILITATION INSTITUTE OF CHICAGO D/B/A SHIRLEY RYAN ABILITYLAB

PHR: Project Narrative This project uses cutting-edge techniques from complex systems science and leverages an existing Intensive Comprehensive Aphasia Program dataset (n = 161) to bridge two prominent approaches to conceptualization and rehabilitation of aphasia, namely impairment-focused and life participation. We will model the constellation of relationships between language, cognitive, and psychosocial variables in persons with aphasia, detect putative causal relationships between these variables, and determine the prognostic value of our model. In the long-term, results from this project will a) change the conceptualization of aphasia to a more holistic view that recognizes the complex interplay between impairment and participation, and b) provide data-informed models to identify key intervention targets that will have widespread impact across a person’s life, resulting in improved communication and increased quality of life in a parsimonious and efficient manner.

PI_NAMEs: ASHAIE, SAMEER AFZAL (contact);CASTRO, NICHOL

PROGRAM_OFFICER_NAME: STORKEL, HOLLY LYNN

PROJECT_TERMS: Accounting;Address;Aftercare;Alzheimer's Disease;Aphasia;aphasia rehabilitation;Aphasiology;Auditory;Bayesian Method;Behavior;Brain;Clinical;Cognition;Cognitive;cognitive ability;Communication;Complex;Comprehension;Data;Data Set;Disease;Environment;Etiology;Foundations;Future;Genetic;Goals;Grant;Graph;Impaired cognition;Impairment;improved;Individual;innovation;Intervention;Joints;Language;Language Disorders;language impairment;language processing;large datasets;Life;Link;Literature;Malignant Neoplasms;Measurement;Measures;Medical;Mental Health;Methods;Modeling;Names;network models;Outcome;Persons;physical conditioning;precision medicine;predictive modeling;Probability;prognostic;prognostic value;programs;psychosocial;Psychosocial Factor;Quality of life;Randomized, Controlled Trials;Regression Analysis;Rehabilitation therapy;Research;Role;Sample Size;Science;social engagement;Social Impacts;Speech;Stroke;Structure;System;Techniques;Testing;Time;Treatment outcome;verbal;Work;Writing

PROJECT_TITLE: From Impairment to Participation: A Systems Approach to Understanding the Complexity of Aphasia

STUDY_SECTION: LCOM

STUDY_SECTION_NAME: Language and Communication Study Section[LCOM]


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

ORG_CITY: RALEIGH

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: NORTH CAROLINA STATE UNIVERSITY RALEIGH

ORG_STATE: NC

PHR: Project Narrative The glucose-lowering effect of metformin and the underlying mechanisms have been extensively studied, but the effect of metformin on hepatic lipid metabolism and the action site of metformin warrant further research. To fill in the knowledge gap, we will perform liquid chromatography-high resolution mass spectrometry-based lipidomics, metabolomics, and 13C isotope tracing analysis, employ synthetic metformin probe and intestinal AMPK alpha 1 knockout mice, to quantitatively characterize the connections between metformin-induced metabolic alterations in intestine and hepatic lipid metabolism and to identify molecular targets of metformin. The findings of this study will unravel the role of metformin actions in intestine in modulating hepatic lipid metabolism and provide significant insights into strategies to prevent or treat dietary-induced fatty liver diseases.

PI_NAMEs: LIU, XIAOJING  (contact)

PROGRAM_OFFICER_NAME: NIE, ZHONGZHEN

PROJECT_TERMS: 5'-AMP-activated protein kinase;Affect;Alkynes;Attenuated;Communication;Coupled;Data;dietary;Disease;Epithelial Cells;fatty acid oxidation;Fatty Liver;fatty liver disease;Fructose;Gene Modified;Glucose;Goals;Hepatic;High Prevalence;in vivo;insight;intestinal epithelium;Intestines;Isotopes;Knockout Mice;Knowledge;lipid biosynthesis;lipid metabolism;lipidomics;Lipids;Liquid Chromatography;Liver;Liver diseases;mass spectrometer;Mass Spectrum Analysis;Metabolic;Metabolic Diseases;Metabolism;metabolomics;Metformin;Methods;Molecular Target;Mus;Nature;non-alcoholic fatty liver disease;Organ;Patients;Pharmaceutical Preparations;Pilot Projects;pleiotropism;prevent;Reporting;Research;Resolution;Role;Site;Small Intestines;sugar;Testing;Tissues

PROJECT_TITLE: Investigating the involvement of small intestine in metformin's effect on hepatic lipid metabolism


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Chronic Liver Disease and Cirrhosis;Digestive Diseases;Liver Disease;Organ Transplantation;Regenerative Medicine;Transplantation

ORG_CITY: TALLAHASSEE

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: FLORIDA AGRICULTURAL AND MECHANICAL UNIV

ORG_STATE: FL

PHR: Rheological characterization of cells, tissues, and biomaterials using bulk shear rheology is an indispensable tool for understanding physiologically relevant biophysical properties. Recent advances in rheometer design enables sensitive in vitro and ex vivo rheological measurements needed to characterize and tune the viscoelastic properties of 3D printed hepatocyte organoid systems that mimic the mechanics of native liver tissues. Knowledge gained from the use of advanced rheological instrumentation will aid in establishing a platform for in vivo liver tissue restoration and ex vivo drug screening.

PI_NAMEs: ALI, JAMEL  (contact)

PROGRAM_OFFICER_NAME: FRINCU, CRINA

PROJECT_TERMS: 3-Dimensional;3D Print;Adoptive Transfer;aging population;Autologous;Biochemical;Biocompatible Materials;Biological Models;Biomechanics;biophysical properties;bioprinting;bioscaffold;Cells;Cessation of life;Complex;Data;Dedications;design;Development;diagnostic screening;drug discovery;Drug Screening;Drug Targeting;effective therapy;Engineering;Equipment;Evaluation;Future;Graft Rejection;Health;Hepatic;Hepatic Tissue;Hepatocyte;Implant;implantation;In Vitro;in vivo;in vivo Model;in-vitro diagnostics;Individual;innovation;instrumentation;Investigation;Knowledge;Laboratories;Liver;Liver diseases;Liver Failure;liver function;liver injury;liver transplantation;Measurement;Mechanics;Metabolic;Methods;Modeling;mouse model;novel;Organoids;Pathology;Physiological;Property;rapid technique;Resolution;response;restoration;Rheology;scaffold;screening;Structure;success;System;Therapeutic;three dimensional cell culture;Tissues;tool;Transplantation;United States;viscoelasticity;Work

PROJECT_TITLE: Engineering a Novel Bio-Scaffold for Hepatic Tissue Restoration and Drug Screening


ORG_CITY: PITTSBURGH

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: PROJECT NARRATIVE Stress response mechanisms play a dual role in organism health- they are required for tissue homeostasis and also for minimizing damage during toxic conditions. Intimate molecular knowledge of these mechanisms will thus inform clinical approaches to prolong tissue function under pathobiological conditions. Consistent with the mission of the NIGMS, the research described herein aims to gain such mechanistic understanding and will have broadly relevance to many pathologies from neurodegeneration to cancer.

PI_NAMEs: VASUDEVAN, DEEPIKA  (contact)

PROGRAM_OFFICER_NAME: RIGAS, MARC

PROJECT_TERMS: Adipocytes;Biological;biological adaptation to stress;cell type;Cells;Cellular biology;Cellular Stress;Clinical;combat;Data;Dedications;Defect;Diabetes Mellitus;Disease;Drosophila genus;egg;Egg Yolk Proteins;Fatty acid glycerol esters;Genetic;Health;Hepatocyte;Homeostasis;hormonal signals;improved;insight;Islet Cell;Knowledge;loss of function;Malignant Neoplasms;Mediating;Metabolic;Mission;Molecular;Molecular Biology;mRNA Translation;mutant;National Institute of General Medical Sciences;Nerve Degeneration;Neurons;neuroregulation;nutrient deprivation;oocyte maturation;Oogenesis;Organism;Ovary;Pancreas;Pathology;Pathway interactions;Peripheral;Phenotype;Photoreceptors;Play;protein degradation;Regulation;Research;response;Role;Secretory Cell;sensor;steroid hormone;Stress;Stress Response Signaling;stressor;Techniques;Testing;Therapeutic;Tissues;tool;transcription factor;Yeasts

PROJECT_TITLE: Elucidating the role of the Integrated Stress Response pathway in tissue homeostasis - Admin Supplement


ADMINISTERING_IC: NR

ED_INST_TYPE: SCHOOLS OF NURSING

IC_NAME: NATIONAL INSTITUTE OF NURSING RESEARCH

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Cardiovascular;Clinical Research;Depression;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Mental Health;Social Determinants of Health

ORG_CITY: CHESTNUT HILL

ORG_NAME: BOSTON COLLEGE

PHR: Heart failure (HF) is the fastest-growing cardiovascular disorder and a leading cause of urgent healthcare utilization in the U.S. As managing HF at home has increased in intensity/complexity, the mental health and social determinants of health impact on persons with heart failure and their informal care partner dyads is of growing importance. The goals of this prospective, dyadic- and social determinants of health theory-informed study of 100 dyads are to gain insight to gain insight into the role that social determinants of health play as the root causes of some of the inequities about which we know, and additional inequities we are likely to discover in this study.

PI_NAMEs: BUCK, HARLEAH G;LEE, CHRISTOPHER SEAN (contact)

PROGRAM_OFFICER_NAME: HUSS, KAREN

PROJECT_TERMS: Address;Adult;Advocacy;Affective Symptoms;Anxiety;Area;Behavior;Biological;Cardiovascular Diseases;Caring;Clinical;cohort;Data;depressive symptoms;Development;Discrimination;Dyspnea;Economics;Education;Elements;Enrollment;Equity;Ethnic Origin;experience;Family member;Fatigue;Future;Gender;Goals;Grouping;Health;health care service utilization;health determinants;Health Sciences;Heart failure;Home;improved;Inequity;infancy;informal care;insight;Intervention;Interview;Learning;Link;Maintenance;Managed Care;Measurement;Measures;member;men;Mental Depression;Mental Health;Methods;Modification;Monitor;Nausea;negative affect;Occupations;Outcome;Pain;parity;Patients;Persons;physical conditioning;physical symptom;Physiological;Play;Population;population health;Precision Health;Process;prospective;Psyche structure;Quality of life;Race;Reporting;Research;Resources;Role;Science;Self Care;Signs and Symptoms;Sleep disturbances;social;social determinants;social health determinants;stress management;Symptoms;System;theories;therapy development;Time;White Women;Work

PROJECT_TITLE: Differential Impacts of Person and System Level Determinants of Health on Dyadic Heart Failure Management: The IMPACT-D Study

STUDY_SECTION: ICSC

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


ORG_CITY: Nashville

ORG_NAME: VANDERBILT UNIVERSITY

ORG_STATE: TN

PHR: Project Narrative  Ubiquitin is a post-translational modification that regulates diverse cellular processes and its dysregulation is associated with many human diseases ranging from neurodegeneration to cancer. Here, we propose research directions that will result in a deeper understanding of how ubiquitin networks are regulated during conditions of stress to facilitate the cellular adaptive response. Dissecting these mechanisms will provide a platform for long-term exploration of ubiquitin networks as potential therapeutic targets in the treatment of human diseases.

PI_NAMEs: LEE, ETHAN  (contact)

PROGRAM_OFFICER_NAME: LEWIS, MECHELLE MAYLEBEN

PROJECT_TERMS: 15 year old;adult stem cell;Award;Biochemical;Cell Maintenance;Cell Physiology;Clinical Trials;Density Gradient Centrifugation;Development;Disease;experimental study;Floor;Fractionation;Funding;Goals;Human;human disease;human old age (65+);Malignant Neoplasms;Manufacturer;Mathematics;Methods;Modeling;Molecular;Monitor;Nerve Degeneration;parent grant;Pathway interactions;plasmid DNA;Play;Post-Translational Protein Processing;Protein Analysis;protein purification;Receptor Activation;Research;Research Personnel;response;Role;Services;Speed;Stress;Sucrose;System;therapeutic target;Transfection;Ubiquitin;WNT Signaling Pathway

PROJECT_TITLE: Maximizing Investigators' Research Award (R35 - Clinical Trial Optional)


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

ORG_CITY: WEST LAFAYETTE

ORG_DEPT: PHARMACOLOGY

ORG_NAME: PURDUE UNIVERSITY

PHR: Public Health Relevance (Project Narrative) This project is relevant to NIH’s mission by providing fundamental knowledge regarding cellular and circuit mechanisms underlying behavioral abnormalities associated with Scn2a deficiency. Knowledge gained through the completion of this project provides the basis for the developmental of novel therapeutic interventions to treat autism spectrum disorder related to Scn2a deficiency.

PI_NAMEs: YANG, YANG  (contact)

PROGRAM_OFFICER_NAME: DOSS, ARGENIA LANISHA NECOLE

PROJECT_TERMS: Address;Affect;Animal Behavior;anxiety-like behavior;autism spectrum disorder;Behavioral;behavioral outcome;Brain;Child;clinically relevant;Data;density;Development;Disease;efficacy evaluation;Electrophysiology (science);Elements;Equilibrium;Genes;Genetic;hippocampal pyramidal neuron;Impairment;in vivo;innovation;Intervention;Knock-out;Knockout Mice;Knowledge;Mission;mouse model;Neurodevelopmental Disorder;Neurons;neuropathology;novel;novel therapeutic intervention;optogenetics;Outcome;patch clamp;pharmacologic;Pharmacology;Property;public health relevance;Research Personnel;response;SCN2A protein;Slice;social communication impairment;social deficits;Sodium Channel;Synapses;Technology;Testing;therapeutic development;therapy development;TNFSF5 gene;United States;United States National Institutes of Health;voltage;Work

PROJECT_TITLE: Neuronal and Behavioral Deficits Associated with Scn2a Deficiency in Autism Spectrum Disorder

STUDY_SECTION: DBD

STUDY_SECTION_NAME: Developmental Brain Disorders Study Section[DBD]