NIH_SPENDING_CATS: Cardiovascular;Congenital Structural Anomalies;Genetics;Orphan Drug;Pediatric;Precision Medicine;Rare Diseases

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: PROJECT NARRATIVE RASopathies are a group of neurodevelopmental genetic syndromes that are characterized by overlapping clinical manifestations, including cardiac abnormalities, developmental delay, and tumor predisposition. The management of RASopathies is clinically challenging due to the heterogenous presentation of the symptom and no specific treatments are available; hence, novel therapies are urgently needed for these disorders. The present application addresses this clinical need by exploring potential new mechanisms and therapies in models of RASopathies.

PI_NAMEs: CASTEL, PAU  (contact);PHILIPS, MARK REID

PROGRAM_OFFICER_NAME: PARISI, MELISSA

PROJECT_TERMS: Address;Affect;Anatomy;Animal Model;Appearance;Biochemical;Bioenergetics;Biological Assay;Biology;Biomass;Cardiac Myocytes;Cardiovascular Abnormalities;Cell model;Cells;Childhood;Clinical;Clinical Trials;Complex;Congenital Disorders;Costello syndrome;Cutaneous;Data;Defect;Development;Developmental Delay Disorders;Disease;effective therapy;Embryonic Development;evidence base;experimental study;Face;family genetics;Functional disorder;gain of function;Genes;Genetic;Genetic Diseases;Germ Lines;Germ-Line Mutation;Growth;Heart Abnormalities;heart defect;High Prevalence;improved outcome;Individual;inhibitor;insight;Investigation;Learning;Link;Malignant Neoplasms;MAP Kinase Gene;MAP2K1 gene;Measures;Metabolic;Metabolic Pathway;metabolic phenotype;Metabolism;metabolomics;Mitochondria;mitochondrial dysfunction;Mitogen-Activated Protein Kinase Inhibitor;Modeling;Molecular;Morphology;mouse model;Myocardium;Neurocognitive;new therapeutic target;Newborn Infant;novel;novel therapeutics;Oxidation-Reduction;Oxygen Consumption;Pathogenesis;Pathogenicity;Pathologic;Pathway interactions;patient population;Phenocopy;Phenotype;pre-clinical;Pre-Clinical Model;preclinical study;Predisposition;Primary Cell Cultures;Ras Inhibitor;Regulation;Research;Research Support;Respiration;Role;Sampling;Signal Pathway;Signal Transduction;Skeletal Muscle;Source;Symptoms;Syndrome;System;targeted treatment;Techniques;Therapeutic;Therapeutic Intervention;therapeutic target;Time;Tissues;treatment strategy;tumor;Variant

PROJECT_TITLE: Energetic metabolism in RASopathies as a novel therapeutic target

STUDY_SECTION: CSRS

STUDY_SECTION_NAME: Cellular Signaling and Regulatory Systems Study Section[CSRS]


ADMINISTERING_IC: GM

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Clinical Research;Genetics;Hematology;Infectious Diseases;Precision Medicine;Sepsis

ORG_CITY: PROVIDENCE

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: RHODE ISLAND HOSPITAL

ORG_STATE: RI

PHR: Project Narrative Sepsis is responsible for 20% of deaths worldwide. We propose to use advanced computational biology approaches with deep RNA sequencing data to improve the diagnosis and treatment of sepsis. This new equipment will translate the data collected to a test that can be used on patients to improve care.

PI_NAMEs: MONAGHAN, SEAN FARRELL (contact)

PROGRAM_OFFICER_NAME: ZHAO, XIAOLI

PROJECT_TERMS: Alternative Splicing;anti-PD1 antibodies;Bacteria;Biology;Caring;Cells;Cessation of life;comparison control;Computational Biology;Computer Analysis;Computing Methodologies;Critical Illness;Data;Diagnosis;diagnostic value;Disease;Entropy;Equipment;Event;Excision;Exons;Functional disorder;Genes;Genetic Transcription;Human;Immune response;improved;Intensive Care Units;Intervention;Introns;Joining Exons;microbial;Molecular;new therapeutic target;novel;Outcome;outcome prediction;pathogen;Patients;Population;potential biomarker;precision medicine;Proteins;Resources;RNA;RNA metabolism;RNA Splicing;Sampling;Sepsis;septic patients;Testing;transcriptome sequencing;Translating;Translations;Triage;Virus;Whole Blood

PROJECT_TITLE: Improving Sepsis Care with Deep RNA Sequencing Data


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Chronic Pain;Headaches;Mental Health;Migraine;Neurodegenerative;Neurosciences;Pain Research;Peripheral Neuropathy;Sleep Research

ORG_CITY: TALLAHASSEE

ORG_DEPT: CHEMISTRY

ORG_NAME: FLORIDA AGRICULTURAL AND MECHANICAL UNIV

ORG_STATE: FL

PHR: Contact PD/PI: Ablordeppey, Seth Project Narrative According to the American Sleep Association, 50-70 million US adults have a sleep disorder, insomnia being the most common specific sleep disorder with 30% of adults reporting short term issues and 10% reporting chronic insomnia. Meanwhile, 37.9% US adults reported unintentionally falling asleep during the day at least once in the preceding month, while 4.7% reported nodding off or falling asleep while driving at least once in the preceding month. Given that drowsy driving is responsible for 1,550 fatalities and 40,000 nonfatal injuries annually in the US, this remains a serious public health crisis requiring serious attention. Meanwhile, neuropathic pain estimated in the general population to range between 3% and 17%, lacks an effective treatment as most of the available treatments have only moderate efficacy and present significant side effects that limit their use. Therefore, other therapeutic approaches, such as the development of biased 5-HT7R agonists which have been demonstrated to have therapeutic advantages for treating certain sleep disorders and neuropathic pain and are proposed in this application, are urgently needed. The current supplement is requested in support of the aims of this parent application. Contact PD/PI: Ablordeppey, Seth Project Narrative Page 8

PI_NAMEs: ABLORDEPPEY, SETH Y (contact)

PROGRAM_OFFICER_NAME: GARTRELL, KYUNGSOOK

PROJECT_TERMS: 5 year old;Address;Adult;Affinity;Agonist;Agreement;American;Amino Acids;analog;Animals;antagonist;Attention;autism spectrum disorder;Automobile Driving;beta-arrestin;Binding;Biological Availability;Brain;Budgets;Cardiotoxicity;Central Nervous System Diseases;Characteristics;Chemicals;Chronic Insomnia;Cognitive;Collection;cost;design;Desire for food;Development;Docking;Doctor of Philosophy;Drowsy Driving;drug discovery;Drug Kinetics;effective therapy;Electrons;enantiomer;Epilepsy;Equipment;Evaluation;Expenditure;falls;Fragile X Syndrome;Funding;Future;General Population;Goals;graduate student;Grant;GTP-Binding Proteins;High Pressure Liquid Chromatography;Homology Modeling;hydrophilicity;Hydrophobicity;improved;in vivo;Injury;instrument;Intellectual Property;Lead;Left;Life;Ligands;Maintenance;Manuals;Manuscripts;Metabolic;Methods;Migraine;Molecular Conformation;Moods;Motor;mouse model;New Agents;non rapid eye movement;novel;Pain Threshold;painful neuropathy;parent project;Parents;Penetration;Performance;Pharmaceutical Preparations;pharmacologic;Physiologic Thermoregulation;Plasma;Play;Postdoctoral Fellow;pre-clinical;Predisposition;Price;Progress Reports;Property;Psychophysiology;Public Health;Pump;receptor;recruit;REM Sleep;Reporting;Research;Research Personnel;Rodent;Role;screening;Serotonin;serotonin 7 receptor;side effect;Signal Pathway;Signal Transduction;Sleep;Sleep Architecture;Sleep Disorders;sleep pattern;Sleeplessness;Solvents;Students;success;Summary Reports;System;Testing;Tetrahydroisoquinolines;Therapeutic;Training;Visit;Water;Work;X-Ray Crystallography

PROJECT_TITLE: Instrument Supplemental Grant


ED_INST_TYPE: SCHOOLS OF MEDICINE

NIH_SPENDING_CATS: Genetics

ORG_CITY: NEW YORK

ORG_DEPT: GENETICS

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: PROJECT NARRATIVE Perturbations of the intercellular signaling systems that control organ growth are a major source of human disease, associated with a wide range of developmental, physiological disorders as well as most forms of cancer. The proposed research is relevant to public health because solving how such systems normally function to direct as well as terminate growth as organs develop is essential for the development of more effective diagnostic and therapeutic treatments for this enormously broad range of afflictions. Thus, the proposed research is relevant to NIH's mission to reduce the burden to society arising from genetic and environmental disorders of fundamental aspects of human development and physiology.

PI_NAMEs: STRUHL, GARY  (contact)

PROGRAM_OFFICER_NAME: WELLS, MELISSA LYNN

PROJECT_TERMS: Animals;Body part;Bone Morphogenetic Proteins;Cells;Complement;Complex;Development;Diagnostic;Dimerization;Disease;Drosophila frizzled protein;Drosophila genus;Family;Fatty acid glycerol esters;fly;G-Protein-Coupled Receptors;Gene Expression;Gene Structure;Genes;Genetic;Genetic Enhancer Element;Goals;Growth;Health;Human;Human Development;human disease;insight;Leg;Logic;Malignant Neoplasms;man;member;Mission;Modeling;Molecular;morphogens;Organ;organ growth;Pattern;Physiological;Physiology;Porifera;programs;Protein Secretion;Proteins;Public Health;receptor;recruit;Research;response;Role;Signal Transduction;Signal Transduction Pathway;Signaling Molecule;Societies;Source;System;Testing;Therapeutic;Tissues;tool;transcription factor;Transgenic Organisms;United States National Institutes of Health;Wing;Work

PROJECT_TITLE: Morphogen control of organ growth in Drosophila

STUDY_SECTION: MRAC

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


NIH_SPENDING_CATS: Genetics;Human Genome

ORG_CITY: MADISON

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: PROJECT NARRATIVE Cell division is an essential process by which replicated chromosomes are equally segregated to daughter cells, however this process is prone to errors, which can result in chromosomal instability and lead to cancer and developmental diseases. There are potential molecular mechanisms contributing towards faithful chromosome segregation that have not yet been adequately explored, one of which is the evolution and maintenance of chromosome organization throughout mitosis. Our proposed work of defining the spatial organization of mitotic chromosomes and kinetochores required for accurate chromosome segregation using innovative imaging methods is of fundamental importance to public health because a clear understanding of the mechanisms underlying faithful chromosome segregation will contribute towards developing better therapeutic and detection strategies for cancer and developmental diseases for improved patient outcomes.

PI_NAMEs: SUZUKI, AUSSIE  (contact)

PROGRAM_OFFICER_NAME: MILLER, RITA K

PROJECT_TERMS: 3-Dimensional;Aneuploidy;aurora B kinase;Binding;Calibration;Cell division;Cell Nucleus;Cells;Centromere;Chromatin;Chromosomal Instability;chromosome loss;Chromosome Positioning;chromosome replication;Chromosome Segregation;Chromosome Structures;Chromosome Territory;Chromosomes;Computer software;Coupled;daughter cell;Defect;Detection;developmental disease;Ensure;Evolution;Frequencies;Gene Expression Regulation;Genomics;Goals;imaging modality;improved;Individual;innovation;insight;Interphase;Kinetochores;Maintenance;Malignant Neoplasms;Mammalian Cell;Mediating;Methods;Microtubules;Mitosis;Mitotic;Mitotic Chromosome;Molecular;Needles;Pathway interactions;Patient-Focused Outcomes;Phosphorylation;Phosphotransferases;Positioning Attribute;Process;protein structure;Proteins;Public Health;Quantitative Microscopy;Regulation;segregation;spatiotemporal;superresolution microscopy;Testing;Therapeutic;Tumor Promotion;Work

PROJECT_TITLE: Chromosome dynamics and organizations necessary for faithful chromosome segregation


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Bioengineering;Nanotechnology;Physical Injury - Accidents and Adverse Effects;Regenerative Medicine

ORG_CITY: SAINT LOUIS

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: SAINT LOUIS UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE The goal of this proposal is to acquire new equipment, the NanoSight Pro instrument for nanoparticle tracking analysis (NTA) to enhance the capability and productivity of my research lab. The NTA system will be used to characterize the nanoparticles and bioparticles that will deliver immunomodulatory factors to reduce inflammation, enhance regeneration, and restore function in traumatized musculature.

PI_NAMEs: GARG, KOYAL  (contact)

PROGRAM_OFFICER_NAME: CHAO, CHIEN-CHUNG

PROJECT_TERMS: Biomimetics;Cell Physiology;Chronic;Cost Savings;data quality;design;Equipment;experimental study;Extracellular Matrix Proteins;FDA approved;Fibrosis;FK506;functional restoration;Goals;Helper-Inducer T-Lymphocyte;Immune response;immunomodulatory strategy;immunoregulation;Immunosuppressive Agents;Impairment;implantation;improved;Inflammation;Inflammatory Response;Injury;Investments;Measurement;Mediating;Muscle;muscle form;Muscle function;muscle regeneration;Muscular Atrophy;muscular structure;nano;nanoinstrument;nanoparticle;Natural regeneration;Outcome;Outcomes Research;Pharmaceutical Preparations;Porifera;Productivity;Recovery;regeneration function;regenerative;regenerative approach;regenerative therapy;repaired;Research;Resolution;Rodent Model;scaffold;Schedule;severe injury;Site;Skeletal Muscle;Sprain;Systems Analysis;T-Lymphocyte Subsets;Trauma;volumetric muscle loss;Work

PROJECT_TITLE: Acquiring Nanoparticle Tracking Analysis System to Enhance Lab Productivity and Capability


ADMINISTERING_IC: NS

ED_INST_TYPE: UNIVERSITY-WIDE

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Brain Disorders;Genetics;Neurosciences

ORG_CITY: BRONX

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

PHR: Narrative Episodic Ataxia type 2 (EA2) and Familial hemiplegic migraine (FHM1) are neurological disorders resulting from mutations in the CACNA1A gene, which encodes the pore-forming subunit of the P/Q type calcium channel (Cav2.1). Recently, CACNA1A patients presenting primarily with cognitive defects have been described, suggesting a novel cellular mechanism may lead to their symptoms. Here we propose to delineate the effects of CACNA1A mutations on the calcium channel auxiliary subunit a2d.

PI_NAMEs: KURSHAN, PERI T (contact);SNELL, HEATHER DANIELLE

PROGRAM_OFFICER_NAME: RIDDLE, ROBERT D

PROJECT_TERMS: Address;Affect;Ataxia;Awareness;Behavioral;Biological Models;biophysical properties;Biophysics;Brain;Caenorhabditis elegans;Calcium Channel;career development;cell fixing;Cell surface;Cells;Cerebellum;Characteristics;Classification;Clustered Regularly Interspaced Short Palindromic Repeats;Cognitive;Cognitive deficits;Complementary DNA;confocal imaging;Data;Defect;Developmental Delay Disorders;Disease;disease phenotype;Doctor of Philosophy;Dominant-Negative Mutation;Electrophysiology (science);Embryo;Environment;Episodic ataxia;expectation;Familial Hemiplegic Migraine;Foundations;Genes;Genetic;Goals;Homologous Gene;Human;Image;imaging approach;immunocytochemistry;Impaired cognition;in vivo;in vivo Model;Intellectual functioning disability;Kidney;Lead;Mediating;Mediator;Methods;Modeling;Molecular;Molecular Biology;molecular imaging;Motor;motor deficit;motor disorder;mouse model;Movement Disorders;mutant mouse model;Mutate;Mutation;Nematoda;Nervous System;Nervous System Disorder;Neurobehavioral Manifestations;Neuromuscular Junction;neuronal excitability;Neurons;Neurosciences;novel;P-Q type voltage-dependent calcium channel;parent grant;Patient-Focused Outcomes;Patients;pharmacologic;Phenotype;Play;Postbaccalaureate;presynaptic;Presynaptic Terminals;programs;Property;Publishing;Purkinje Cells;Q-Type Calcium Channels;Research;Role;Structure;Surface;Symptoms;Synapses;synaptic function;Synaptic Vesicles;System;Techniques;Testing;Therapeutic Intervention;Training;Transfection;vesicular release;voltage;Work

PROJECT_TITLE: Assessing synaptic and intrinsic effects of patient-derived ID-associated CACNA1A mutations using multiple models

STUDY_SECTION: NC

STUDY_SECTION_NAME: Neuronal Communications Study Section[NC]


ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

FUNDING_MECHANISM: RESEARCH CENTERS

NIH_SPENDING_CATS: Autoimmune Disease;Digestive Diseases;Inflammatory Bowel Disease;Microbiome

ORG_CITY: LOUISVILLE

ORG_DEPT: DENTISTRY

ORG_NAME: UNIVERSITY OF LOUISVILLE

ORG_STATE: KY

PHR: Narrative Host and microbial metabolites play a crucial role in the regulation of inflammation and are linked to the onset of diverse human diseases, such as periodontal disease, inflammatory bowel disease, cancer, and Alzheimer’s disease. This proposal aims to establish a CoBRE-Metabolomics facility under Functional Microbiomics Core by purchasing TSQ Quantis Triple-Stage Quadrupole Mass Spectrometer. This facility will enable identification and quantification of both targeted- and untargeted metabolites across various pathophysiological conditions.

PI_NAMEs: LAMONT, RICHARD J (contact)

PROGRAM_OFFICER_NAME: CUPIT, PAULINE

PROJECT_TERMS: Achievement;Alzheimer's Disease;animal facility;Area;Award;Bioinformatics;Biological Assay;Core Facility;Dedications;experience;Faculty;forging;Funding;Germ-Free;Gnotobiotic;human disease;imaging facilities;Inflammation;Inflammatory;Inflammatory Bowel Diseases;inflammatory marker;innovation;Interdisciplinary Study;Link;Malignant Neoplasms;mass spectrometer;Mentors;metabolomics;microbial;microbiome;microbiome research;microbiome sequencing;microbiota;Pathogenesis;Pathogenicity;Periodontal Diseases;Phase;Play;Process;programs;Qualifying;Regulation;Research Personnel;Research Support;Resources;Role;small molecule;Source;United States National Institutes of Health;Universities

PROJECT_TITLE: Functional Microbiomics, Inflammation and Pathogenicity


ADMINISTERING_IC: AI

ED_INST_TYPE: GRADUATE SCHOOLS

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Genetics;HIV/AIDS;Infectious Diseases

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

PHR: Project Narrative We propose to develop, validate, and apply a suite of powerful new tools to interrogate the functions, interactions, and cellular localizations of individual splice variants of HIV-1, which is the virus that causes AIDS and infects over 1 million people each year. In 2020, over 37 million people, including 1.7 million children, were living with the virus, and over 500,000 died from AIDS. For a robust eradication of the virus, additional research such as the work proposed here is desperately needed to eliminate knowledge gaps in our understanding of viral infection and replication.

PI_NAMEs: SHERER, NATHAN M (contact);SMITH, LLOYD M

PROGRAM_OFFICER_NAME: REFSLAND, ERIC WILLIAM

PROJECT_TERMS: 3' Splice Site;Acquired Immunodeficiency Syndrome;Alternative Splicing;Cells;Child;Classification;Code;Complex;Detection;Development;DNA;Exons;Fluorescence Microscopy;Fluorescent in Situ Hybridization;Gene Expression;gene product;Genes;Genetic Transcription;Glycoproteins;HIV;HIV Genome;HIV-1;Immune Evasion;immunoregulation;improved;in vivo;Individual;Integration Host Factors;interest;Introns;Investigation;knock-down;Knowledge;Life Cycle Stages;Maps;Mass Spectrum Analysis;Messenger RNA;Microscopy;Morphologic artifacts;mRNA Precursor;multiplex assay;new technology;novel virus;Open Reading Frames;Organism;overexpression;Pathway Analysis;Persons;Polyproteins;Post-Translational Protein Processing;Process;Production;protein expression;Proteins;Proteomics;Research;Resolution;RNA;RNA Sequences;RNA Splicing;RNA Stability;RNA-Protein Interaction;Site;Small Interfering RNA;Spliced Genes;System;Techniques;Technology;Therapeutic;tool;Transcript;transcriptome;transcriptome sequencing;Translations;vaccine development;Variant;Viral;Viral Proteins;Virion;Virus;Virus Diseases;virus host interaction;Virus Replication;Western Blotting;Work

PROJECT_TITLE: Deciphering HIV-1 alternatively spliced transcript function with HyPR-MS

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IIDB-X(02)]


NIH_SPENDING_CATS: Antimicrobial Resistance;Behavioral and Social Science;Biodefense and Related Countermeasures;Clinical Research;Emerging Infectious Diseases;HIV/AIDS;Infectious Diseases;Prevention;Sexually Transmitted Infections

PHR: Narrative: This study aims to examine the engagement, effective use, the potential for antimicrobial resistance, and potential transmission of bacteria among Doxy-PEP users. A prospective cohort of Doxy-PEP users will be enrolled to investigate factors, mapped to the information-motivation-behavioral skills theoretical model, to evaluate their impact on Doxy-PEP engagement and effective use. Biological samples from Doxy- PEP users, eligible non-users (a control cohort), and their sexual partners will be collected to assess trends in antimicrobial resistance of specific pathogens, the impact on the presence or absence of resistance genes, and the potential for transmission of pathogenic bacteria between sexual partners.

PI_NAMEs: ZUCKER, JASON  (contact)

PROGRAM_OFFICER_NAME: HUEBNER, ROBIN E

PROJECT_TERMS: Address;Adoption;Affect;AIDS prevention;Antibiotics;Antimicrobial Resistance;Bacteria;Behavior;Behavioral;beta-Lactams;Biological;Bisexual;Caring;Clinical;cohort;Communities;comparative genomics;cost;design;Doxycycline;Effectiveness;Eligibility Determination;Enrollment;Epidemic;ethnic minority;Event;experience;falls;Frequencies;Future;Gays;Guidelines;Health;HIV;Hospitals;Incidence;Individual;infection rate;Informed and educated patient;insight;Intervention;Knowledge;Laboratories;Maps;Medical center;men who have sex with men;metagenomic sequencing;Metagenomics;Methods;Monitor;Motivation;Mycoplasma genitalium;Neisseria gonorrhoeae;New York;Nose;Organism;Participant;pathogen;pathogenic bacteria;Patients;Persons;Pharmaceutical Preparations;Pharyngeal structure;Policies;Population;pre-exposure prophylaxis;Predictive Factor;Presbyterian Church;Prevalence;Prevention strategy;programs;prophylactic;Prophylactic treatment;prospective;Prospective cohort;Provider;Public Health;racial minority;Randomized, Controlled Trials;recruit;Rectum;Resistance;resistance gene;resistome;Resources;Risk;Sampling;scale up;sex;Sexual Partners;Sexually Transmitted Diseases;skills;STI prevention;Testing;Tetracycline Resistance;Tetracyclines;Theoretical model;transmission process;trend;Universities;uptake;Urine;Visit

PROJECT_TITLE: Doxy4STICare - Doxycycline for Sexually Transmitted Infections; A Comprehensive Assessment of Antimicrobial Resistance and Engagement

STUDY_SECTION: HCCS

STUDY_SECTION_NAME: HIV Comorbidities and Clinical Studies Study Section[HCCS]


NIH_SPENDING_CATS: HIV/AIDS;Infectious Diseases

ORG_CITY: Columbus

ORG_DEPT: PATHOLOGY

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: PROJECTIVE NARRATIVE Despite of potent antiretroviral therapies, HIV infection still persists attributing to the chronic inflammation and the accelerated aging-related diseases, thus requiring its elimination for a cure. We identified that HIV Nef protein induces polo-like kinase 1 (PLK1) through increase of its protein SUMOylation and nuclear accumulation, and propose to study PLK1 as a Nef’s novel host effector to promote survival and immune escape of HIV/SIV viral reservoirs. Chemical compounds targeting PLK1 will be investigated in terms of their therapeutic potential to reduce or eliminate persistent HIV/SIV viral reservoirs ex vivo.

PI_NAMEs: LING, BINHUA "JULIE" ;ZHU, JIAN  (contact)

PROGRAM_OFFICER_NAME: SANDERS, BRIGITTE E

PROJECT_TERMS: Acceleration;Acquired Immunodeficiency Syndrome;Acute;age acceleration;aging process;aging related disease;Animal Model;Animals;Anti-Retroviral Agents;antiretroviral therapy;Binding;CD4 Positive T Lymphocytes;Cell Death;Cell Line;Cell Survival;Cells;cellular targeting;Cessation of life;Chemicals;Chronic;chronic infection;Clinic;cofactor;Cytotoxic T-Lymphocytes;Disease;efficacy study;Epidemic;Event;Goals;HIV;HIV Infections;HIV/AIDS;Human;Immune;immune activation;Immune signaling;improved;Individual;Inflammation;inhibitor;insight;Integration Host Factors;Investigation;Life Cycle Stages;Macaca;Mediating;Modeling;Modification;Molecular;nef Protein;novel;Nuclear;Pathogenesis;Patients;Plasma;Play;PLK1 gene;Post-Translational Protein Processing;preclinical efficacy;programmed cell death ligand 1;protein function;Proteins;Reagent;Reporting;Risk;RNA;Role;Safety;Sampling;Signal Transduction;SIV;small molecule inhibitor;Structure-Activity Relationship;Study models;Sumoylation Pathway;Testing;Therapeutic;therapeutic development;Tissues;Toxic effect;Vial device;Viral;Viral Proteins;Viral reservoir;Virus Diseases;virus host interaction

PROJECT_TITLE: Antagonize Host Survival and Immune Escape Mechanisms for Elimination of HIV Viral Reservoirs

STUDY_SECTION: HVCD

STUDY_SECTION_NAME: HIV Molecular Virology, Cell Biology, and Drug Development Study Section[HVCD]


NIH_SPENDING_CATS: Biotechnology;Complementary and Integrative Health;Natural Products

ORG_CITY: GAINESVILLE

ORG_NAME: UNIVERSITY OF FLORIDA

PHR: PROJECT NARRATIVE  Natural products are the best source of drugs and drug leads and terpenoids, the largest family of natural products, have a wide range of clinically important activities including antibiotic, anticancer, antimalarial, and immunosuppressant properties. The proposed studies will lead to the discovery of new natural products with important biological activities, facilitate future discovery efforts by the development of systems dedicated to facile identification of terpenoids in bacteria, and result in the characterization of natural product biosynthetic enzymes. A greater understanding of terpenoid biosynthesis will also provide insights into how nature constructs medicinally relevant compounds and how these enzymes may be used as tools for future discoveries in biochemistry, bioengineering, and drug development.

PI_NAMEs: RUDOLF, JEFFREY DANIEL (contact)

PROGRAM_OFFICER_NAME: BOND, MICHELLE RUEFFER

PROJECT_TERMS: Actinobacteria class;Address;Administrative Supplement;Anabolism;anti-cancer;Anti-malarials;Antibiotics;Award;Bacteria;Bacterial natural products;Biochemistry;Bioinformatics;Biological;Biomedical Engineering;Biotechnology;Chemicals;Clinical;Collaborations;combinatorial;Complex;Cyclization;Cytochrome P450;Dedications;Development;drug development;drug discovery;Engineering;Enzymatic Biochemistry;Enzymes;equipment acquisition;experience;Family;Funding;Future;Gene Cluster;Genome;Genomics;Immunosuppressive Agents;In Vitro;in vivo;innovation;insight;interdisciplinary approach;Libraries;Mass Fragmentography;Medicine;metabolomics;Methodology;Mining;National Institute of General Medical Sciences;Natural Product Drug;Natural Products;Nature;novel;novel therapeutics;Outcomes Research;Pathway interactions;Pharmaceutical Preparations;programs;Property;Proteins;Research;small molecule;Source;Structure-Activity Relationship;success;synthetic biology;Systems Development;terpene synthase;Terpenes;Terpenoid Biosynthesis Pathway;tool;Up-Regulation;X-Ray Crystallography

PROJECT_TITLE: Administrative Supplement for Equipment Purchases for NIGMS-Funded Awards: GCMS


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

ORG_CITY: DALLAS

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: Project Narrative This project aims at defining mechanisms responsible for the formation and maintenance of the neuromuscular junction (NMJ), and the survival of motor neurons. This is important because abnormal formation or function of the NMJ, as well as the loss of motor neuron, is implicated in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Therefore, identifying regulatory mechanisms responsible for structural and functional changes in the NMJ will enable us to improve current treatment strategies for neurodegenerative diseases such as ALS.

PI_NAMEs: LIN, WEICHUN  (contact);ROTHERMEL, BEVERLY A

PROGRAM_OFFICER_NAME: RANGANATHAN, SRIKANTH

PROJECT_TERMS: Acetylcholine;Acetylcholinesterase;Address;Amyotrophic Lateral Sclerosis;Anabolism;Central Nervous System;Choline O-Acetyltransferase;Cholinergic Receptors;cholinergic synapse;Coupling;Cysteine-Rich Domain;Development;Dihydropyridine Receptors;Elements;Enzymes;Feedback;Future;Gene Deletion;Genes;Goals;improved;insight;Investigation;Maintenance;Mediating;Modeling;Motor Neurons;Mus;Muscle;Nerve;Neurodegenerative Disorders;neuromuscular function;Neuromuscular Junction;neuron loss;neuronal survival;Neurotransmitters;Pattern;Peripheral;Play;postsynaptic;prevent;Proteins;Research Project Grants;Signal Transduction;Skeletal Muscle;Structure;Synapses;synaptogenesis;therapeutic development;treatment strategy

PROJECT_TITLE: Patterning and Formation of the Neuromuscular Junction


ORG_CITY: SYRACUSE

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UPSTATE MEDICAL UNIVERSITY

PHR: Project Narrative Many human diseases including genetic disorders and cancers are caused by mutations in transcription factors or their dysregulation. The overall goal of this project is to determine the mechanism of transcription by eukaryotic RNA polymerase I (Pol I) and how it is dysregulated in disease. This work will provide fundamental knowledge about the basic molecular mechanism of Pol I transcription and discover key steps that may be targeted in cancer and developmental disorders to enhance health and reduce illness.

PI_NAMEs: KNUTSON, BRUCE ALAN (contact)

PROGRAM_OFFICER_NAME: WAIRKAR, YOGESH PRABHAKAR

PROJECT_TERMS: Architecture;Binding Proteins;Biochemical;Bioinformatics;Biological Assay;Cancer Etiology;Cells;Complement;Complex;Defect;developmental disease;Diagnosis;Disease;DNA Polymerase I;DNA Polymerase II;DNA-Protein Interaction;Down-Regulation;Fibrinogen;Genetic;Genetic Diseases;Genetic Transcription;Genomics;Goals;Health;Human;human disease;innovation;interdisciplinary approach;Intervention;Knowledge;Lead;Link;Malignant Neoplasms;Maps;Methods;Molecular;Mutation;new therapeutic target;novel;Peptide Initiation Factors;Process;Proteins;Proteomics;Regulation;Research;Ribosomal DNA;Ribosomal RNA;Ribosomes;RNA;RNA Polymerase I;Role;Structural Models;Structure;Testing;Therapeutic;therapy development;transcription factor;Transcriptional Activation;Translating;Up-Regulation;Work;Yeasts

PROJECT_TITLE: New Paradigms for the molecular basis of RNA polymerase I transcription

STUDY_SECTION: MGB

STUDY_SECTION_NAME: Molecular Genetics B Study Section[MGB]


NIH_SPENDING_CATS: Bioengineering

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: The goal of this administrative supplement of the parent award, R35GM118090, is to purchase a Prometheus Panta from NANOTEMPER for the simultaneous detection of nano-Differential Scanning Fluorimetry (nanoDSF), Backreflection, Dynamic Light Scattering (DLS) and Static Light Scattering (SLS). The Prometheus Panta, will allow us to carry out protein and protein complex analysis rapidly, accurately, label- free, and with low sample requirement of ~10 L at a wide range of protein and protein complex concentrations of between 5 µg/mL – 250 mg/ml. This analysis will include protein and protein complex quality assessment and buffer condition optimization for biochemical and structural (X-ray crystallography and single particle cryo- EM) analysis, assessing thermal stability of protein, protein-ligand, protein complexes and protein mutants as a readout for protein ligand binding and protein integrity, respectively.

PI_NAMEs: MARMORSTEIN, RONEN  (contact)

PROGRAM_OFFICER_NAME: BARSKI, OLEG

PROJECT_TERMS: Acetyltransferase;Administrative Supplement;analytical ultracentrifugation;Area;Arylalkylamine N-Acetyltransferase;Back;Binding Proteins;Biochemical;Biochemistry;biophysical tools;Biophysics;Blood capillaries;Buffers;Complex;Complex Analysis;Cryoelectron Microscopy;Dedications;Detection;Detergents;Development;Enzymes;FASN gene;flexibility;Goals;Home;indexing;Individual;inhibitor;instrument;instrumentation;Label;Laboratories;Ligands;light scattering;Maintenance;melting;Membrane Proteins;Molecular;molecular mass;Molecular Sieve Chromatography;Molecular Weight;mutant;N-terminal;nano;Organic solvent product;parent grant;parent project;particle;Pathway interactions;Pennsylvania;Philadelphia;Photometry;protein aggregation;protein complex;Proteins;Radial;Reaction;Regulation;Ribosomes;RNA;Sampling;Scanning;small molecule;Technology;Temperature;United States National Institutes of Health;Universities;X-Ray Crystallography

PROJECT_TITLE: Molecular Mechanisms, Pathways and Inhibition of Acetyl-Transfer Reactions

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


ORG_CITY: CHICAGO

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE from Parent Award Eukaryotic cells encode thousands of different membrane proteins that are critical for growth and survival. We have discovered a new pathway that directs the biogenesis of multi-pass membrane proteins at the endoplasmic reticulum membrane. Deﬁning how the cellular machinery coordinates this fundamental process is essential for understanding how healthy cells function, with important implications for the treatment of human diseases.

PI_NAMEs: KEENAN, ROBERT J (contact)

PROJECT_TERMS: Anabolism;Biochemical;Biogenesis;Bioinformatics;Biological;Cell membrane;Cell Physiology;Cells;Cellular biology;Code;Endoplasmic Reticulum;Enzymes;Eukaryota;Eukaryotic Cell;Genes;Genetic;Growth;Human;human disease;Human Genome;insight;Link;Membrane;Membrane Proteins;Molecular;novel;parent project;Pathway interactions;Process;Prokaryotic Cells;Proteins;receptor;Transmembrane Domain;Work

PROJECT_TITLE: Membrane protein biogenesis at the ER


ORG_CITY: BALTIMORE

ORG_DEPT: PHYSIOLOGY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Narrative: We propose to develop optogenetic and chemigenetic tools to visualize and control the metabolism of single mRNAs with high spatiotemporal resolution in live cells. We will use the tools to investigate the molecular mechanism of RNA decay and localized translation. The experimental tools will be valuable for studying post-transcriptional gene expression which is important to decipher the molecular mechanism of neural development, learning and memory formation, and to develop therapeutic treatment for neurological diseases.

PI_NAMEs: WU, BIN  (contact)

PROGRAM_OFFICER_NAME: YEH, ALVIN TIEN-WEI

PROJECT_TERMS: Address;Anterior;Biological;Biological Process;Cells;Chemicals;Clustered Regularly Interspaced Short Palindromic Repeats;Code;Communities;Dendrites;Dendritic Spines;Development;Fibroblasts;Gene Expression;Gene Expression Regulation;Genes;genetic approach;Goals;Growth Cones;Guide RNA;knock-down;Lasers;Learning;Light;Lighting;Memory;Messenger RNA;Metabolism;Methods;Microscopy;Molecular;mRNA Translation;Nervous System Disorder;neurodevelopment;neuromechanism;neuronal growth;Neurons;Oocytes;optogenetics;Play;Post-Transcriptional Regulation;posttranscriptional;Protein Biosynthesis;Proteins;Reagent;Research;Resolution;RNA;RNA Decay;RNA Degradation;RNA Editing;RNA Interference;RNA metabolism;RNA-Binding Proteins;Role;small molecule;spatiotemporal;Technology;temporal measurement;Therapeutic;Time;tool;translation assay;Translations;Visualization;Work

PROJECT_TITLE: Developing optogenetic and chemogenetic approaches to control RNA metabolism in live cells


NIH_SPENDING_CATS: Building Research Capacity at Institutions with Limited NIH Funding

ORG_CITY: OKLAHOMA CITY

ORG_NAME: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR

ORG_STATE: OK

PI_NAMEs: AKINS, DARRIN R. (contact)

PROGRAM_OFFICER_NAME: ARORA, KRISHAN


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: BURLINGTON

ORG_NAME: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE

ORG_STATE: VT

PHR: Overall Component Gary S. Stein and Janet L. Stein, Program Directors Building on a record of significant contributions, this highly collaborative program, pursued by a team of scientists and physician-investigators, will explore epigenetic mechanisms that regulate and respond to parameters of genome organization. The Program Project facilitates the conceptual and experimental integration required to advance understanding of functional parameters of epigenetic control that will provide novel insights into breast cancer onset and progression, and provide potential diagnostic and/or therapeutic value.

PI_NAMEs: STEIN, GARY S. (contact);STEIN, JANET L

PROGRAM_OFFICER_NAME: WEINREICH, MICHAEL DALE

PROJECT_TERMS: Address;advanced breast cancer;aggressive breast cancer;Animal Model;Bioinformatics;Biometry;bone;Breast Cancer Cell;breast cancer metastasis;Bromodomain;Cancer Cell Growth;cell growth;Cell model;Cells;Chromatin;clinically relevant;Diagnostic;Dimensions;Endocrine;Ensure;Epigenetic Process;epitranscriptomics;Experimental Designs;Gene Expression;Gene Expression Regulation;Genes;Genome;Genome Components;genome editing;Genomics;Hormone Responsive;hormone therapy;in vivo Model;insight;Link;Malignant Breast Neoplasm;mammary epithelium;Mediating;Mitotic;Modification;Molecular;multidisciplinary;new technology;Normal Cell;novel;Nuclear;Organoids;Patients;Phenotype;Physicians;Physiological;programs;Proliferating;Proteins;public database;Reader;Regulation;Reproducibility;Research;Research Personnel;Resistance;Resource Sharing;Resources;response;Role;Scientist;Selective Estrogen Receptor Modulators;Specimen;Standardization;synergism;Therapeutic;therapy resistant;Time;Tissues;transcription factor;tumor;ultra high resolution;Untranslated RNA;Visualization

PROJECT_TITLE: Diversity supplement to P01CA240685 to characterize bromodomain proteins associated with endocrine therapy resistance in breast cancer


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

ORG_CITY: MILWAUKEE

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

PHR: Atherosclerosis is initiated and promoted by the arterial accumulation of apolipoprotein B (apoB)-containing lipoproteins which activate a chronic inflammatory response. Our group recently made the novel discovery that a key blood clot lysis protein, tissue-type plasminogen activator (tPA), in hepatocytes limits the production of apoB-lipoproteins in mice and cultured human primary hepatocytes. The overarching objective of this proposal is to explore the underlying mechanisms by which hepatocyte tPA lowers plasma apoB-containing lipoprotein- cholesterol levels, and thereby alleviates atherosclerosis.

PI_NAMEs: ZHENG, ZE  (contact)

PROGRAM_OFFICER_NAME: LIU, LIJUAN

PROJECT_TERMS: Alteplase;Apolipoproteins B;Atherosclerosis;atherosclerosis risk;Binding;Blood;Blood coagulation;cardiovascular disorder risk;Cells;Cholesterol;Chronic;comparison control;Cytolysis;Data;Diameter;Diet;Dyslipidemias;Fatty acid glycerol esters;fatty liver disease;Hepatic;Hepatocyte;Homeostasis;Human;Hypertriglyceridemia;IDL lipoproteins;Inflammatory Response;inhibitor;insight;intrahepatic;LDL Cholesterol Lipoproteins;Lipids;lipoprotein cholesterol;Lipoproteins;Liver;Low Density Lipoprotein Receptor;Low-Density Lipoproteins;Mediating;Molecular;Mus;new therapeutic target;novel;particle;Plasma;Plasminogen;Plasminogen Activator;Population;Production;Proteins;Residual state;Risk;Role;Serum;Source;Testing;Therapeutic;therapeutic target;Triglycerides;Very low density lipoprotein;Very low density lipoprotein cholesterol;Wild Type Mouse

PROJECT_TITLE: The role of hepatocyte tPA in hepatic VLDL production.

STUDY_SECTION: AVI

STUDY_SECTION_NAME: Atherosclerosis and Vascular Inflammation Study Section[AVI]


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

PHR: PROJECT NARRATIVE Biofilm formation, a crucial bacterial lifestyle for persistence in particular niches, tolerance to antimicrobials and virulence in many pathogens, is governed by environmental and self- generated stimuli. How the information encoded in multiple sensory inputs is extracted and integrated to control biofilm development is poorly understood. Using the multi-drug resistant human pathogen Pseudomonas aeruginosa as model system, the proposed research will investigate how light, nutrients and population-density signals, individually and in combination, control biofilm development.

PI_NAMEs: MUKHERJEE, SAMPRITI  (contact)

PROGRAM_OFFICER_NAME: KEANE-MYERS, ANDREA

PROJECT_TERMS: 3-Dimensional;anti-microbial tolerance;Architecture;Bacteria;bacterial genetics;Basic Science;Behavior;Biochemistry;Biological;Biological Models;Chemicals;clinically relevant;Communities;Cues;Decision Making;design;detection of nutrient;Development;Environment;Fluorescence Microscopy;genome-wide;Goals;human pathogen;Individual;interdisciplinary approach;Knowledge;Learning;Life Style;Light;mathematical model;Mediating;Microbial Biofilms;Molecular;Molecular Biology;Multi-Drug Resistance;multidrug-resistant Pseudomonas aeruginosa;multiple drug use;novel therapeutic intervention;Nutrient;Nutrient availability;Organism;pathogen;Pathway interactions;Photoreceptors;Population Density;Process;programs;Pseudomonas aeruginosa;quorum sensing;Regulation;Repression;Research;response;Role;Sensory;sensory input;sensory integration;Signal Pathway;Signal Transduction;Stimulus;structural biology;Structure;System;Virulence;Work

PROJECT_TITLE: Probing the role of sensory cues in the regulation of bacterial biofilm development

STUDY_SECTION: MRAA

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


NIH_SPENDING_CATS: Cannabinoid Research;Endocannabinoid System Research;Obesity

ORG_NAME: CITY COLLEGE OF NEW YORK

PHR: Administrative Supplement to NIH R16 GM145403 (Stark): Introduction Sartorius Octet R2 System for Label-free Kinetic and Binding Affinity Analysis This administrative supplement application requests funds to purchase 2-channel Sartorius OCTET equipment for label-free, real-time quantitative measurement of protein-protein and protein-ligand binding affinities and rates, in support of a parent award entitled “Molecular Drivers of FABP-mediated Endocannabinoid Signaling for Appetite Regulation.” This Dip-and-Read Bio- layer interferometry platform will overcome the challenges of currently limited access to a colleague’s aging surface plasmon resonance instrument which is located at a distance from the parent project laboratory. The new equipment described in this supplement request will offer several advantages: (1) technological advances will improve ease-of-use, reliability, and throughput; and (2) it will improve the technical skills and productivity of a research team that includes trainees who span a broad range of career stages and demographic backgrounds.

PI_NAMEs: STARK, RUTH E. (contact)

PROGRAM_OFFICER_NAME: PEI, WUHONG

PROJECT_TERMS: Abbreviations;Address;Administrative Supplement;Affinity;Aging;Amides;Animal Model;Appetite Regulation;Applications Grants;Autoimmune Diseases;Binding;Binding Proteins;Binding Sites;Biological Assay;Biophysics;career;Cell Nucleus;Chemicals;Chimera organism;Complex;Desire for food;Diffusion;Dissociation;Drug Design;Drug Modulation;endocannabinoid signaling;Endocannabinoids;Enterocytes;Enzymes;Equipment;Esters;Exhibits;experimental study;fatty acid amide hydrolase;fatty acid-binding proteins;Fatty Acids;Fluorescence;Funding;Genetic Transcription;Glycerol;Health;heart disease risk;Human;Hydrophobicity;improved;In Vitro;in vitro testing;Inflammation;instrument;Interferometry;Intestines;Kinetics;Knock-out;Knockout Mice;Label;Laboratories;Ligand Binding;Ligand Binding Domain;Ligands;Lipase;Liver;Measurement;Measures;Mediating;member;Metabolic;Modeling;Molecular;Molecular Chaperones;Molecular Conformation;Monitor;Mus;neuroprotection;NMR Spectroscopy;Non-Insulin-Dependent Diabetes Mellitus;Obesity;Outcome;Pain;parent project;Pattern;Peroxisome Proliferator-Activated Receptors;Phenotype;Physiological;preference;pressure;Productivity;programs;Protein Binding Domain;protein complex;protein protein interaction;Proteins;receptor binding;recruit;Regulation;Relaxation;Request for Applications;Research;Risk;Role;Signal Transduction;Signaling Molecule;Site;Surface Plasmon Resonance;System;Technical Expertise;Technology;Testing;Thermodynamics;Thinness;thyroid hormone receptor associated protein 220;Time;Titrations;Underrepresented Populations;United States National Institutes of Health;Vertebral column


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Digestive Diseases;Immunotherapy;Nanotechnology;Orphan Drug;Pancreatic Cancer;Rare Diseases

ORG_CITY: QUEENS

ORG_DEPT: PHARMACOLOGY

ORG_NAME: ST. JOHN'S UNIVERSITY

PHR: Narrative Scarcity of curative therapy and poor patient survival are critical issues in the treatment of pancreatic cancer. In the parent NIH R16 award, we proposed to develop a pancreatic tumor directed nanoformulations for the simultaneous delivery of novel class of anticancer molecules to target dense tumor fibrosis, angiogenesis and cancer cells. In work supported by this grant supplement, we will investigate the uptake of our nanoformulation in cancer cells and growth in 3D tumor spheroids.

PI_NAMEs: PATEL, KETANKUMAR D. (contact)

PROJECT_TERMS: 3-Dimensional;Address;Albumins;angiogenesis;anti-cancer;anticancer activity;Antineoplastic Agents;Apoptosis;Award;Biological Assay;Body Weight;c-myc Genes;cancer cell;Cancer Etiology;cancer type;Cell Culture Techniques;Cell Line;Cell Proliferation;Cell Survival;Cells;Cessation of life;chimeric antigen receptor T cells;Circulation;clinically relevant;Coculture Techniques;Collagen Type I;combinatorial;curative treatments;Cysteine;cytotoxicity;density;Deposition;design;Desmoplastic;Development;Drug Delivery Systems;Drug Kinetics;Drug resistance;effective therapy;efficacy evaluation;Emerging Technologies;Endothelial Cells;Environment;Equipment;Evaluation;Extracellular Matrix;Fibroblasts;Fibrosis;fluorescence microscope;Focal Adhesion Kinase 1;Formulation;Fostering;gemcitabine;graduate student;Grant;Growth;Hematology;Hepatotoxicity;Human;Hyaluronic Acid;Hybrids;Immune checkpoint inhibitor;Immunohistochemistry;improved;In Vitro;in vivo;indexing;innovative technologies;Intravenous;Investigation;kinase inhibitor;Kinetics;KRAS2 gene;Laboratories;liposomal formulation;liposome vector;Liposomes;Malignant neoplasm of pancreas;Malignant Neoplasms;Mediating;Mediator;Mentors;Metabolism;Methods;Microscope;Microsomes;Monoclonal Antibodies;mortality;mutant;Mutation;nanoformulation;nanoliposome;nanomolar;nanoparticle;Nanotechnology;nanotherapeutic;Nature;Neoplasm Metastasis;neoplastic cell;novel;Oncogenic;Oncoproteins;overexpression;Pancreas;pancreatic cancer cells;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma cell;pancreatic neoplasm;Parents;Pathogenesis;Pathway interactions;Patients;Penetration;Pharmaceutical Preparations;pharmacologic;Plasma;Play;Prognosis;Proliferating;Protac;Protein Secretion;Proteins;racial diversity;recruit;Research;Research Methodology;Research Proposals;Resistance;Resistance development;Resolution;Role;Scanning;Science;Side;Solid Neoplasm;Solubility;spheroids;Stomas;Students;Survival Rate;targeted treatment;Testing;therapeutically effective;three dimensional cell culture;three-dimensional modeling;Toxic effect;Training;translational approach;tumor;Tumor Angiogenesis;tumor growth;Tumor Markers;tumor microenvironment;Tumor Volume;tumor xenograft;ubiquitin-protein ligase;undergraduate student;underrepresented minority student;United States National Institutes of Health;Universities;uptake;Vascular blood supply;Western Blotting;Work;Xenograft Model

PROJECT_TITLE: Combination of tumor targeted therapy with stroma modulating agent for PDAC


NIH_SPENDING_CATS: Nutrition;Obesity

ORG_CITY: SEATTLE

ORG_NAME: FRED HUTCHINSON CANCER CENTER

ORG_STATE: WA

PHR: Project Narrative Fat reserves release hormones called adipokines that act on neural circuits to regulate decisions on several physiological processes including hunger, immunity, and reproduction. If not tightly coupled to energy status, adipokine release is detrimental to the organism and leads to obesity and metabolic disorders. By studying how fat stores communicate nutrient state to an organism we will elucidate the molecular and cellular mechanisms that underpin healthy energy balance.

PI_NAMEs: RAJAN, AKHILA  (contact)

PROGRAM_OFFICER_NAME: MASKERI, BAISHALI

PROJECT_TERMS: Address;Adipocytes;adipokines;Adopted;age acceleration;Bacteria;Behavior;Cell Physiology;Cells;Chronic;Communication;Complex;coping;Coupled;detection of nutrient;diet-induced obesity;Disease;Drosophila genus;Eating;energy balance;Energy Metabolism;Event;Evolution;Fatty acid glycerol esters;Food;Food Energy;Food Supply;Future;Gene Expression;Goals;healthy lifestyle;Homeostasis;Hormones;Human;Hunger;Immunity;impaired capacity;Investigation;Maps;Membrane Fusion;Metabolic;Metabolic Diseases;Modeling;Molecular;neural circuit;novel strategies;Nutrient;nutrient deprivation;Nutritional;Obesity;Organism;Outcome;Pathway interactions;Physiological;Physiological Processes;Physiology;Prevalence;Process;protein function;Proteins;Regulation;Reproduction;response;Signal Transduction;System;Testing;tumor progression

PROJECT_TITLE: Cellular mechanisms governing nutrient sensing and organismal energy homeostasis


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

ORG_CITY: BINGHAMTON

ORG_DEPT: PSYCHOLOGY

ORG_NAME: STATE UNIVERSITY OF NY,BINGHAMTON

PHR: Cognitive impairment and dementia are leading contributors to disability and are increasing at an alarming rate as the population ages. This project will provide important information on the function of the arterioles that perfuse the hippocampus, a deep brain region critically involved in learning and memory. We will investigate the role of hippocampal arterioles in cognitive decline associated with healthy aging, and how this may be accelerated during chronic hypertension and contribute to vascular cognitive impairment and dementia.

PI_NAMEs: CHAPMAN, ABBIE C (contact)

PROGRAM_OFFICER_NAME: YIN, XILING

PROJECT_TERMS: Acceleration;Adult;Affect;Age;Age Months;Aging;Angiotensin II;arteriole;Atrophic;Blood capillaries;Blood flow;Blood Vessels;Brain;Brain Hypoxia-Ischemia;Brain region;Buffers;cerebral microvasculature;cerebrovascular;Cerebrovascular Disorders;cerebrovascular pathology;Cerebrum;Chronic;Clinical Research;Cognition;Cognitive;Cognitive aging;Data;Dementia;density;disability;endothelial dysfunction;Endothelin-1;Endothelium;Female;Functional disorder;Goals;Health;healthy aging;hemodynamics;hippocampal atrophy;Hippocampus;Hypertension;hypertensive;hypoperfusion;Impaired cognition;Impairment;improved;In Vitro;in vivo;Inbred SHR Rats;Individual;Infarction;Injury;ischemic injury;Knowledge;Learning;Lesion;male;Measures;Mediator;Memory;Memory impairment;Memory Loss;Metabolic;Microcirculation;middle age;Modeling;Muscle function;Nature;Neurocognitive;Neuronal Injury;Neuronal Plasticity;Neurons;neurovascular;neurovascular coupling;new therapeutic target;normal aging;normotensive;novel;Outcome Study;oxidative damage;Oxidative Stress;Oxidative Stress Pathway;Pathogenesis;Pathologic;Pathway interactions;Patients;Perfusion;Persons;pharmacologic;Population;Postmenopause;Predisposition;pressure;prevent;Property;protective pathway;Publishing;Rattus;response;Rest;Risk;Risk Factors;Role;Serum;sex;Sex Differences;Signal Transduction;Structure;Therapeutic;TNF gene;Vascular Cognitive Impairment;vascular cognitive impairment and dementia;Vascular Dementia;Vascular Smooth Muscle;Vasoconstrictor Agents;Vasodilation;white matter

PROJECT_TITLE: The Role of the Hippocampal Vasculature in Vascular Cognitive Impairment and Dementia

STUDY_SECTION: BINP

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


NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Neurosciences

ORG_CITY: MORGANTOWN

ORG_NAME: WEST VIRGINIA UNIVERSITY

ORG_STATE: WV

PHR: PROJECT NARRATIVE Visual impairment is a terrifying prospect. Our long-term goal is to eliminate or reduce this health burden by understanding the biological mechanisms that underlie vision in health and disease. With this goal in mind, we propose to create a Center of Excellence in visual sciences at West Virginia University to strengthen the scientific community focused on understanding processes essential to optimal visual health.

PI_NAMEs: RAMAMURTHY, VISVANATHAN  (contact)

PROGRAM_OFFICER_NAME: KOVBASNJUK, OLGA NIKOLAEVNA

PROJECT_TERMS: Affect;Appalachian Region;Award;Biochemistry;Biological;Biology;Biomedical Engineering;Centers of Research Excellence;Clinical;Collaborations;Communities;comorbidity;Core Facility;Coupled;Disease;effectiveness evaluation;Environment;Extramural Activities;Funding;Goals;Grant;Health;Incidence;Infrastructure;interdisciplinary approach;Investigation;Mentors;multidisciplinary;National Institute of General Medical Sciences;Network Infrastructure;Neurosciences;novel strategies;Ophthalmology;Patients;Population;Positioning Attribute;Prevention approach;Process;programs;recruit;Research;Research Infrastructure;Research Personnel;Scientist;Translating;Universities;Vision;vision science;Visual;Visual disability;Visual impairment;Visual System;West Virginia;Work

PROJECT_TITLE: Visual Sciences Center of Biomedical Research Excellence


NIH_SPENDING_CATS: Neurosciences;Sleep Research

ORG_CITY: DAVIS

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

ORG_STATE: CA

PHR: PROJECT NARRATIVE The circadian clock controls most aspects of human life and health. Based on our studies during the past 13 years, we believe that temperature preference rhythm in Drosophila is an innovative model for understanding fundamental regulatory mechanisms of body temperature rhythms in mammals. Our studies will expand the current understanding of mammalian body temperature rhythm, sleep disorders, and general sleep-associated issues, such as jet lag or the sleep disturbances common to night-shift workers.

PI_NAMEs: HAMADA, FUMIKA  (contact)

PROGRAM_OFFICER_NAME: AKACEM, LAMEESE DANA

PROJECT_TERMS: Body Temperature;Calcitonin Receptor;circadian pacemaker;Circadian Rhythms;Disease;Drosophila genus;Environment;Exhibits;fly;Foundations;Genes;Goals;Health;Homeostasis;Homologous Gene;Human;Human body;innovation;insight;Jet Lag Syndrome;Knowledge;Life;Link;Mammals;Metabolism;Modeling;Molecular;Motor Activity;neural circuit;neuromechanism;Neuropeptide Receptor;Outcome;Output;Pacemakers;Pathway interactions;Pattern;Physiology;preference;Process;Receptor Signaling;Research;shift work;Sleep;Sleep Disorders;Sleep disturbances;sleep regulation;Temperature;Time;Wakefulness

PROJECT_TITLE: Molecular and Neural Mechanisms of Temperature Preference Rhythm in Drosophila


PHR: Project Narrative Human reproductive health can be compromised both genetically or by exposure to myriad compounds found in prescription drugs, food containers and toxic waste products found in the environment. This work is significant because it will identify genetic and biochemical pathways that may be direct targets of these insults during gametogenesis. A detailed understanding of these pathways will aid in identifying the underlying causes of human infertility, birth defects and pregnancy loss by exposure to environmental contaminants.

PI_NAMEs: BURGESS, SEAN M (contact)

PROGRAM_OFFICER_NAME: VATAKIS, DIMITRIOS NIKOLAOS

PROJECT_TERMS: 3-Dimensional;Address;Affect;Aneuploidy;Architecture;Behavior;Binding;Biochemical Pathway;Biology;biophysical properties;BRCA1 gene;Cell Nucleus;Cells;Chromatin;Chromatin Loop;Chromosome abnormality;Chromosome Pairing;Chromosome Structures;Chromosomes;Code;Complex;Congenital Abnormality;Country;Crowding;Cytoskeleton;Data Set;Diffusion;Drug Prescriptions;Ensure;Environment;Environmental Pollutants;epigenetic marker;Epigenetic Process;Equilibrium;Eukaryota;Event;Exposure to;Female;Food Container;Gametogenesis;Genetic;Genetic Recombination;Germ Cells;Goals;Grant;Homologous Gene;homologous recombination;Human;human female;Image;Infertility;insight;Knowledge;Lead;lens;Life;male;Male Infertility;Mammals;Mediating;Meiosis;Meiotic Prophase I;men;model organism;Modeling;Molecular;Monitor;Motion;Motor;Movement;mutant;nanoscale;Nuclear;Nuclear Envelope;Nuclear Pore Complex;Oogenesis;Organism;Outcome;Pathway interactions;Patients;Polymers;Positioning Attribute;Pregnancy loss;prevent;Process;Prophase;Proteins;reproductive;Reproductive Health;response;Role;Saccharomycetales;sex;Sex Differences;Sexual Reproduction;Sperm Count Procedure;Spermatogenesis;Spontaneous abortion;Synapses;System;telomere;Testing;Time;time use;Waste Products;Work;Yeasts;Zebrafish

PROJECT_TITLE: Homolog Pairing in Meiosis


NIH_SPENDING_CATS: Neurosciences

ORG_CITY: WALTHAM

ORG_DEPT: BIOLOGY

ORG_NAME: BRANDEIS UNIVERSITY

ORG_STATE: MA

PHR: PROJECT NARRATIVE Neurons can communicate with each other via electrical and chemical signals, as well as membrane-bound packets called extracellular vesicles. These vesicles carry cargo that can contribute to normal brain function, but in neurological disorders including Parkinson’s and Alzheimer’s Diseases, they can also spread toxic proteins throughout the brain. Our research will help us understand how extracellular vesicles are packaged, released and spread in the nervous system, and may identify new strategies to treat a wide variety of neurological diseases.

PI_NAMEs: RODAL, AVITAL ADAH (contact)

PROGRAM_OFFICER_NAME: MILLER, DANIEL L

PROJECT_TERMS: Acute;Affect;Alzheimer's Disease;Animals;Autophagocytosis;Binding;Biogenesis;Biological Assay;Biological Process;Brain;Cell Line;Cell membrane;Cell Physiology;cell type;Cells;Chemicals;Chronic;Communication;Complex;Cytokinesis;Development;Disease;disease model;Drosophila genus;Endosomes;Engineering;Event;experimental study;extracellular vesicles;field study;fly;Future;Gene Proteins;Genes;Goals;Human;in vivo;inducible gene expression;insight;intercellular communication;Interruption;Kinetics;Light;Link;Lipid Bilayers;Lipids;Maps;Measures;Membrane;Membrane Protein Traffic;Microscopy;Modeling;Morphology;Multiprotein Complexes;mutant;Mutation;Nervous System;Nervous System Disorder;Nervous System Physiology;Neurologic;Neuromuscular Junction;Neurons;optogenetics;Organism;Parkinson Disease;Pathologic;Pathology;Phenotype;Physiological;Physiology;Play;Process;protein complex;protein degradation;Proteins;proteostasis;Quality Control;recruit;Regulation;repaired;Research;Resolution;response;Rest;Role;Signal Transduction;Sorting;Synapses;synaptic function;Synaptic Vesicles;System;Testing;therapeutic target;Time;tool;trafficking;Vesicle;vesicular release;Visualization

PROJECT_TITLE: Visualizing and Manipulating Neuronal ESCRT Dynamics in vivo


NIH_SPENDING_CATS: Bioengineering;Clinical Research

ORG_DEPT: ANATOMY/CELL BIOLOGY

PHR: PROJECT NARRATIVE Excessive or inappropriate recruitment of immune cells is a major driver of tissue damage in inflammation-associated diseases including atherosclerosis, arthritis, and autoimmune diseases. The migration of cancer cells causes dissemination and metastasis which greatly reduces survival rates. Understanding the basic mechanisms that allow cells to maintain migratory behavior will suggest new therapeutic strategies to improve outcomes in disease.

PI_NAMEs: COLLINS, SEAN RYAN (contact)

PROGRAM_OFFICER_NAME: AINSZTEIN, ALEXANDRA M

PROJECT_TERMS: Actins;Actomyosin;Address;Affect;Arthritis;Atherosclerosis;Autoimmune Diseases;Behavior;Behavior Control;Biochemical;Biological Process;Biosensor;cancer cell;cell motility;Cell Polarity;cell type;Cells;Chemicals;Cues;Cytoskeleton;Defect;depolymerization;Development;Disease;Disseminated Malignant Neoplasm;Drug Targeting;Elements;Environment;Experimental Genetics;experimental study;F-Actin;Family;Feedback;Fluorescence Resonance Energy Transfer;Glioblastoma;Goals;Guanosine Triphosphate Phosphohydrolases;HL60;Image;Immune;Immune response;improved outcome;Individual;Inflammation;Inflammatory;Leukocytes;Light;Maintenance;Maps;Measurement;Measures;Mediating;Mediator;Microscopy;migration;Modeling;Molecular;Molecular Target;Mutation Analysis;Nature;Neoplasm Metastasis;neutrophil;new therapeutic target;novel therapeutic intervention;Optics;optogenetics;Output;Pattern;Play;Process;Proteins;Proteomics;receptor;recruit;redshift;Regulation;Research;Resolution;response;rho;rho GTP-Binding Proteins;Role;scaffold;segregation;Signal Pathway;Signal Transduction;Structure;Survival Rate;System;Testing;Tissues;tool;Travel

PROJECT_TITLE: Actin gating of crosstalk between Rho GTPases in cell migration


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

ORG_CITY: CINCINNATI

ORG_DEPT: NEUROSURGERY

ORG_NAME: UNIVERSITY OF CINCINNATI

PHR: PROJECT NARRATIVE Cortical spreading depolarizations (CSDs), or “brain tsunamis” are waves of electrical activity that occur in 60% of patients with traumatic brain injury (TBI) and are associated with poor outcomes. In this proposal we test the hypothesis that CSDs disrupt communications between the cortex and the hippocampus. Successful completion of this project will help determine how CSDs cause poor outcomes, and hence can identify treatment targets.

PI_NAMEs: NGWENYA, LAURA BENJAMIN (contact)

PROGRAM_OFFICER_NAME: AWWAD, HIBAH OMAR

PROJECT_TERMS: Address;Amyloid beta-Protein Precursor;Animals;Antibodies;Area;Axon;axon injury;behavior test;Behavioral;Blood Vessels;Brain;Brain-Derived Neurotrophic Factor;Bulla;C-terminal;career;career development;Cerebral cortex;Cessation of life;Chemicals;Clinical Research;Cognitive;Cognitive deficits;cognitive function;cognitive task;Communication;Critical Thinking;entorhinal cortex;Episodic memory;excitatory neuron;Experimental Designs;Experimental Models;extracellular;fluid percussion injury;FOS gene;frontal lobe;Functional disorder;Glutamate Receptor;Glutamates;Goals;Hippocampus;Histology;Hospitalization;Hour;Immediate-Early Genes;Immunofluorescence Immunologic;Immunohistochemistry;Impaired cognition;Injury;insight;interest;Knowledge;Label;Laboratories;Lateral;Mentorship;Methods;Morphology;Neuronal Injury;Neurons;neuropathology;novel;object recognition;Outcome;parent grant;Pathology;Performance;Perfusion;Physicians;Prefrontal Cortex;Protocols documentation;Randomized;Research;Research Proposals;Scientific Advances and Accomplishments;Scientist;Silver Staining;skills;Sprague-Dawley Rats;Stains;success;Synapses;TBI Patients;Techniques;Testing;Tissues;Traumatic Brain Injury;United States;white matter

PROJECT_TITLE: Defining the remote effects of cortical spreading depolarizations on hippocampus after traumatic brain injury


ADMINISTERING_IC: DE

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Dental, Oral, and Craniofacial Disease;Genetics;Infectious Diseases;Microbiome

ORG_CITY: HOUSTON

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

PHR: PUBLIC HEALTH RELEVANCE STATEMENT This study will provide an understanding of the nature of FomA essentiality in Fusobacterium nucleatum and identify other essential genes, paving the way for developing narrow-spectrum, targeted antibiotics to treat periodontal and related systemic diseases effectively.

PI_NAMEs: WU, CHENGGANG  (contact)

PROGRAM_OFFICER_NAME: MCNEALY, TAMARA L

PROJECT_TERMS: Acids;Adhesions;Adhesives;adverse pregnancy outcome;Affect;Alleles;Antibiotic Therapy;Antibiotics;antimicrobial;Bacteria;beta barrel;Biological Assay;Butyrates;Cell Death;Cell Physiology;Cell Survival;Cells;Clustered Regularly Interspaced Short Palindromic Repeats;Colorectal Cancer;combat;Communities;Complex;Core Protein;Coupled;CRISPR interference;Cytoplasm;Data;Degradation Pathway;density;dental biofilm;Dental Plaque;Development;Diffusion;dysbiosis;Equilibrium;Escherichia coli;Essential Genes;experimental study;Extravasation;fatty acid transport;Fusobacterium;Fusobacterium nucleatum;Gene Order;Generations;Genes;Genetic;Genome;Goals;Gram-Negative Bacteria;Growth;Health;High-Throughput Nucleotide Sequencing;Human;hydrophilicity;In Vitro;Infection;Inflammatory Bowel Diseases;innovation;Insertional Mutagenesis;Ions;Knowledge;Libraries;Link;Lipids;Liposomes;Lysine;Lysine Degradation Pathway;major outer membrane protein;Membrane;Methodology;Methods;Metronidazole;microbial;microbial community;Molecular;Mutagenesis;mutant;Nature;Nutrient;Operon;Oral;oral biofilm;oral carcinogenesis;Oral cavity;Orphan;pathobiont;Pathogenesis;Periodontal Diseases;periplasm;Physiological;Plasmids;Population;Positioning Attribute;Production;programs;Proteins;public health relevance;Reporting;Research;Research Personnel;Rheumatoid Arthritis;Role;Structure;Swelling;System;Systemic disease;Techniques;Testing;tool;VDAC1 gene;wasting;Water

PROJECT_TITLE: Study of essential genes in Fusobacterium nucleatum

STUDY_SECTION: ODCS

STUDY_SECTION_NAME: Oral, Dental and Craniofacial Sciences Study Section[ODCS]


PHR: Project Narrative (From the original application) Defective and damaged proteins are rapidly degraded by a molecular machine called the proteasome. If the proteasome does not function efficiently, this can lead to toxic accumulation of abnormal proteins. This project aims to better understand how cells regulate the proteasome to prevent this from happening. Mis-regulation of the proteasome plays important roles in cancer, neurodegenerative diseases and some rare genetic disorders. In the long-term, our fundamental insights into proteasome regulation will lead to new treatments for these diseases.

PI_NAMEs: LEHRBACH, NICOLAS JOHN (contact)

PROGRAM_OFFICER_NAME: PHILLIPS, ANDRE W

PROJECT_TERMS: Animals;Biological Assay;Caenorhabditis elegans;Cancerous;Cell Physiology;Cells;Development;Disease;Ensure;Eukaryotic Cell;Failure;genetic approach;Genetic Screening;Health;Human;Hyperactivity;improved;Individual;insight;Intervention;Malignant Neoplasms;Molecular;Molecular Machines;multicatalytic endopeptidase complex;Nerve Degeneration;Neurodegenerative Disorders;novel;pharmacologic;Physiology;Play;Post-Translational Protein Processing;prevent;Proteasome Inhibitor;Protein Biosynthesis;protein degradation;Proteins;Quality Control;rare genetic disorder;Regulation;Reporter;Resistance;Role;Signal Transduction;stressor;trafficking;Work

PROJECT_TITLE: Regulation of Proteasome Capacity


NIH_SPENDING_CATS: Biotechnology;Gene Therapy;Genetics

PHR: RNA editing catalyzed by the ADAR enzymes is perturbed in a variety of human diseases. In addition, siRNA and miRNA-triggered RNA interference (RNAi) pathways hold promise for the development of new therapeutic RNAs. The proposed studies will extend our basic understanding of the process of RNA editing, lead to new methods for the control of RNA editing and advance approaches for the modification and optimization of therapeutic RNAs.

PI_NAMEs: BEAL, PETER A. (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TERMS: ADAR1;Address;Adenosine;Administrative Supplement;Antisense Oligonucleotides;Area;Autoimmune Diseases;Award;Binding;Chemicals;Chemistry;Code;Codon Nucleotides;Complex;Coupled;Dedications;design;Development;Disease;DRADA2b protein;Enzymes;gene function;Gene Silencing Pathway;Genes;Goals;Guanosine;Human;human disease;improved;inhibitor;Inosine;interest;Laboratories;Lead;Length;Malignant Neoplasms;Methods;MicroRNAs;Modification;Molecular Biology;mutant;Mutation;novel;novel therapeutics;parent grant;Pathway interactions;Process;Property;Proteins;pseudotoxoplasmosis syndrome;Reagent;Regulation;Research;Research Personnel;Research Support;RNA;RNA Editing;RNA Interference Pathway;RNA Sequences;RNA-Binding Proteins;RNA-Protein Interaction;screening;skin disorder;Small Interfering RNA;Structure;targeted cancer therapy;Therapeutic;therapeutic RNA;tool;Up-Regulation;Work

PROJECT_TITLE: Supplement: Defining and Controlling Protein-RNA interactions in editing and interference pathways


PHR: Cilia are tiny hair-like projections on the surface of the cell that can serve as antennae to sense the cell’s environment or beat to move fluid. Defects in cilia cause disorders known as ciliopathies that affect numerous organs, including the brain, kidneys, eyes, and lungs, which require cilia for their formation or function. The aim of this project is to understand how a newly discovered family of widely conserved, yet poorly understood, ciliary proteins contributes to cilia assembly and function.

PI_NAMEs: WINEY, MARK  (contact)

PROJECT_TERMS: Adolescent;Affect;Axonal Transport;Behavior;beta Tubulin;biophysical analysis;Biophysics;Bos taurus;Brain;Cattle;cell motility;Cell Physiology;Cell surface;Cells;Centrioles;Centrosome;cerebrospinal fluid flow;Chlamydomonas;Chlamydomonas reinhardtii;Cilia;ciliopathy;cilium motility;comparative;Cryoelectron Microscopy;Defect;dimer;Disease;Distant;egg;Electron Microscopy;Environment;Epilepsy;Eukaryotic Cell;experimental study;Extracellular Fluid;Eye;Family;Functional disorder;Genetic;Goals;Hair;Human;Human Pathology;Hydrocephalus;improved;Individual;Infertility;Inherited;Juvenile Myoclonic Epilepsy;Kidney;kinetosome;Lead;Liquid substance;Lung;Mammalian Oviducts;Maps;Mediating;Microscopy;Microtubule Triplet;Microtubules;Mitosis;Motility;Movement;Mucous body substance;Mus;mutant;Myoclonus;Neurons;Normal Cell;novel therapeutic intervention;Null Lymphocytes;Organ;Organism;Orthologous Gene;Pathogenesis;Pathology;Pathway interactions;Phenotype;Play;Point Mutation;Polymers;Post-Translational Protein Processing;Predisposition;Primary Ciliary Dyskinesias;Process;protein function;protein structure;protein transport;Proteins;Proteomics;recruit;Resolution;rib bone structure;Role;Seizures;sex;Site;Sperm Motility;Stress;Structure;Tetrahymena;Tetrahymena thermophila;tool;trafficking;Tubulin;Vertebrates;Work

PROJECT_TITLE: MIPs (Microtubule Inner Proteins) function in cilia and basal bodies

STUDY_SECTION_NAME: Cell Structure and Function 1 Study Section[CSF1]


ORG_CITY: Los Angeles

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: PROJECT NARRATIVE Synapses are the primary substrates driving information transfer throughout our nervous system. Defects in synaptic communication are associated with a vast number of neurological, neurodegenerative, and neuropsychiatric diseases including epilepsy, autism, schizophrenia, ALS, and Alzheimer’s Disease. While their importance is undeniable, the mechanisms that establish and modulate the diversity of synaptic strength remain enigmatic. This proposal seeks to reveal fundamental insights into what determines and adaptively modifies the diversity of presynaptic function at glutamatergic synapses in development and plasticity. Ultimately, this knowledge is necessary to understand the etiology of neural diseases resulting from synaptic dysfunction and develop effective therapeutic strategies.

PI_NAMEs: DICKMAN, DION KAI (contact)

PROJECT_TERMS: Address;Administrative Supplement;Alzheimer's Disease;autism spectrum disorder;Automobile Driving;botulinum toxin type C;Botulinum Toxins;Calcium;Calibration;Chemosensitization;Clustered Regularly Interspaced Short Palindromic Repeats;Communication;Coupling;Data;Defect;Development;Disease;Drosophila genus;Electrophysiology (science);Epilepsy;Etiology;experimental study;Functional disorder;Genes;Genetic;Glutamates;Health;Heterogeneity;Homologous Gene;imaging approach;Individual;innovation;insight;Knowledge;Mental disorders;Microscopy;Modeling;Molecular;Motor;Motor Neurons;Muscle;Muscle Contraction;Mutagenesis;nanoscale;Nanostructures;Nervous System;Nervous System Disorder;neural;Neurodegenerative Disorders;Neurodevelopmental Disorder;Neuromuscular Junction;Neurons;Neurophysiology - biologic function;neuropsychiatric disorder;postsynaptic;presynaptic;Property;Protein Isoforms;ratiometric;Reporter;RNA Splicing;Role;scaffold;Schizophrenia;Site;Structure;superresolution imaging;Synapses;synaptic function;Synaptic plasticity;System;therapeutically effective;transmission process;ultra high resolution;Vesicle

PROJECT_TITLE: Administrative Supplement (Diversity) to Generating functional diversity from molecular homogeneity at glutamatergic synapses


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Eye Disease and Disorders of Vision;Neurosciences;Sleep Research

ORG_NAME: METHODIST HOSPITAL RESEARCH INSTITUTE

PHR: PROJECT NARRATIVE Although sleep is generally believed to be essential for survival, the neuronal mechanisms by which it affects brain function are largely unknown. We propose to use non-human primates and perform multiple-electrode recording simultaneously in three cortical areas, including visual and prefrontal cortex, to examine, for the first time, the dynamics, coding, and mechanisms of the post-sleep improvement in neural function and perception. Our research has the potential to advance our understanding of the neural mechanisms underlying sleep and thus provide future solutions to ameliorate sleep disorder and its detrimental effects on cognitive performance.

PI_NAMEs: DRAGOI, VALENTIN  (contact)

PROGRAM_OFFICER_NAME: FLANDERS, MARTHA C

PROJECT_TERMS: Affect;Animals;Area;area V1;area V4;Behavior;behavior influence;Behavioral;Brain;Code;cognitive performance;Communication;Complex;discrimination task;Electric Stimulation;Electrodes;Electrophysiology (science);Exhibits;experimental study;Eye;Frequencies;Future;Goals;Human;improved;improvement on sleep;Individual;Jaw;Learning;Macaca;member;Napping;neural;neural circuit;neural network;neuromechanism;Neurons;Neurophysiology - biologic function;nonhuman primate;optogenetics;Perception;Performance;Persons;Play;Population;practical application;Prefrontal Cortex;Prevalence;Procedures;Property;Prosthesis;receptive field;Research;response;Rest;Role;Sensory;sensory cortex;Sleep;Sleep Disorders;Slow-Wave Sleep;Stimulus;Stream;Synapses;Testing;Time;Visual;visual coding;Visual Cortex;visual information;Wakefulness

PROJECT_TITLE: The Impact of Sleep on Network Coding and Perceptual Performance


NIH_SPENDING_CATS: Biotechnology;Wound Healing and Care

ORG_CITY: Nashville

ORG_NAME: VANDERBILT UNIVERSITY

ORG_STATE: TN

PHR: Project Narrative We are investigating wound-induced syncytia that form around epithelial wounds via cell-cell fusion. Our current results indicate that the initiating trigger for these fusions is plasma membrane damage to cells around the wound, as generated by our current ablation laser. We propose to use this equipment supplement to purchase a fiber laser that would not generate such collateral plasma membrane damage, enabling us to understand how this type of damage contributes to wound-induced responses, including the formation of wound-induced syncytia.

PI_NAMEs: HUTSON, M. SHANE;PAGE-MCCAW, ANDREA  (contact)

PROGRAM_OFFICER_NAME: CHAO, CHIEN-CHUNG

PROJECT_TERMS: Ablation;Area;Cell fusion;cell injury;Cell membrane;Cells;Cytolysis;Cytoplasm;epithelial wound;Epithelium;Equipment;Fiber;Giant Cells;Image;in vivo;Lasers;Membrane;Microscope;millisecond;parent grant;Parents;Peripheral;Physiologic pulse;response;Role;temporal measurement;wound;wound bed

PROJECT_TITLE: Cell fusion and the role of syncytia in the response to epithelial damage

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1(80)-S]


ADMINISTERING_IC: AT

IC_NAME: NATIONAL CENTER FOR COMPLEMENTARY & INTEGRATIVE HEALTH

ORG_CITY: MINNEAPOLIS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PI_NAMEs: OSBORN, JOHN W (contact)

PROGRAM_OFFICER_NAME: HORGUSLUOGLU, EMRIN U

PROJECT_TERMS: Advocate;Anatomy;Autonomic nervous system;Budgets;Calendar;Cardiovascular system;Clinical;Clinical Research;Clinical Trials Design;Collaborations;Communication;Complex;Contracts;Data;data exchange;Ensure;Event;experience;Feedback;Future;Goals;Head;Health Insurance Portability and Accountability Act;Human Resources;Immune system;Institution;interest;journal article;Link;Medical;meetings;member;Metabolic;metabolomics;Minnesota;multidisciplinary;Nerve;neuroregulation;Newsletter;Operative Surgical Procedures;participant enrollment;Patients;payment;Productivity;Reporting;Research;Research Personnel;Scientist;Secure;Surgeon;System;therapy design;Transfer Agreement;United States National Institutes of Health;Universities;Update;web site

PROJECT_TITLE: Administrative Core


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Depression;Drug Abuse (NIDA only);HIV/AIDS;Infectious Diseases;Mental Health;Mental Illness;Neurosciences;Prevention;Social Determinants of Health;Stimulant Use and Misuse;Substance Misuse

ORG_CITY: WINSTON-SALEM

ORG_NAME: WAKE FOREST UNIVERSITY HEALTH SCIENCES

ORG_STATE: NC

PHR: Public Health Relevance  Stimulant use disorder and depression are both more common in people with HIV (PWH) than in the general population and often co-occur, particularly in the context of chronic psychosocial stress. Psychosocial stress interacts with stimulant use and depression to compromise neuroimmune function and exacerbate central nervous system pathology associated with HIV disease, but the mechanisms that mediate these relationships are not well understood. Using a randomized controlled trial design, this study applies an evidence-based intervention that boosts positive affect in PWH to advance our understanding of the causal associations amongst these prevalent comorbidities in a population that is critical to ending the HIV epidemic.

PI_NAMEs: CARRICO, ADAM WAYNE;MEADE, CHRISTINA S (contact)

PROGRAM_OFFICER_NAME: LIN, YU

PROJECT_TERMS: Adherence;Affect;Anhedonia;antiretroviral therapy;Autonomic nervous system;behavioral outcome;biological adaptation to stress;biological sex;Brain;Cellular Immunity;Cellular Phone;Central Nervous System;Chronic;Chronic stress;Clinical;Clinical Trials;Cocaine;comorbidity;Complex;contingency management;Cues;Depressed mood;Desire for food;Diagnostic;Discrimination;Disease;Enrollment;Epidemic;evidence base;Evidence based intervention;experience;Experimental Designs;Feedback;Functional disorder;Functional Magnetic Resonance Imaging;General Population;Genes;Genetic Transcription;Goals;HIV;hypothalamic-pituitary-adrenal axis;immune activation;Immunologics;Impairment;improved;incentive salience;Individual;Inflammation;Inflammatory;inflammatory marker;Inflammatory Response;innovation;Intervention;Leukocytes;Life Stress;Link;Mediating;Mediator;Mental Depression;Methamphetamine;Modeling;Mood Disorders;Motivation;multiple chronic conditions;Nervous System Physiology;neural;neurobehavioral;Neuroimmune;Neuroimmunomodulation;neuropathology;Neurophysiology - biologic function;neuropsychiatric symptom;Neurosecretory Systems;new therapeutic target;Participant;Pathology;Pathway interactions;Peripheral;Persons;pleasure;Population;pre-clinical;psychologic;Psychological adjustment;Psychosocial Stress;psychosocial stressors;public health relevance;Randomized;Randomized, Controlled Trials;Relapse;resilience;response;Rest;reward circuitry;reward processing;Rewards;secondary analysis;Signal Pathway;Signal Transduction;social stigma;social stress;stimulant use;stimulant use disorder;Stress;Stress and Coping;substance use;systemic inflammatory response;Testing;theories;therapy adherence;Transcriptional Regulation;translational approach;trial design;Viral;Viral Load result;Viremia;Waiting Lists

PROJECT_TITLE: Neuroimmune pathways linking chronic psychosocial stress to co-occurring stimulant use and depression in HIV disease: a mechanistic clinical trial

STUDY_SECTION_NAME: Special Emphasis Panel[ZDA1 MXS-N (A1)]


NIH_SPENDING_CATS: Biotechnology;Cancer;Genetics

ORG_CITY: ARLINGTON

ORG_NAME: UNIVERSITY OF TEXAS ARLINGTON

PHR: PROJECT NARRATIVE Maintaining the repertoire of small nuclear ribonucleoproteins (snRNP) is crucial for regulate messenger RNA metabolism, which determines the isoforms of nascent transcripts and produces a variety of protein isoforms necessary for the cellular function. Therefore, investigating the quality control mechanisms of snRNP at the molecular level is fundamental for understanding gene expression profiles in both normal and disease development. The proposed study aims to investigate the molecular function of snRNP-specific proteins as gatekeepers of snRNP biogenesis and as key switch controlling the protection of full-length nascent transcripts.

PI_NAMEs: SO, BYUNG RAN RANNY (contact)

PROGRAM_OFFICER_NAME: CZAPLINSKI, KEVIN

PROJECT_TERMS: 3' Untranslated Regions;5' Splice Site;Address;Affinity Chromatography;Alternative Splicing;Base Pairing;Binding Proteins;Binding Sites;Biochemical;Biogenesis;Biological Assay;Cancer Patient;Cell Physiology;Cells;Characteristics;Code;Complex;Core Assembly;Coupled;crosslink;Data;Development;Disease;Ensure;Formaldehyde;Gatekeeping;Gene Expression Profile;Gene Expression Regulation;Goals;Immunoprecipitation;In Vitro;Introns;Length;Malignant Neoplasms;Messenger RNA;Metabolism;Methods;Molecular;Motor Neurons;Mutation;novel;Oncogenes;Outcome;particle;Play;Polyadenylation;premature;prevent;Productivity;Protein Isoforms;Proteins;Quality Control;Regulation;RNA;RNA metabolism;RNA Splicing;Role;Small Nuclear Ribonucleoproteins;Small Nuclear RNA;Spliceosomes;Transcript;Tumor Suppressor Proteins;U1 Small Nuclear Ribonucleoprotein;U1 small nuclear RNA;U1A protein

PROJECT_TITLE: The role of U1 snRNP proteins in snRNP biogenesis and gene expression regulation


NIH_SPENDING_CATS: Biotechnology;Contraception/Reproduction;Estrogen;Genetics;Human Genome;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Women's Health Research

PHR: NARRATIVE The proposed research is relevant to public health because defects in germline mechanisms are responsible for various genetic and epigenetic diseases. This study has high potential to identify novel epigenetic mechanisms that govern distinct sexually dimorphic processes in spermatogenesis and oogenesis. The outcome of this study will contribute to significant, transformative advances in germline biology, and to our understanding of human reproduction and reproductive health.

PI_NAMEs: NAMEKAWA, SATOSHI  (contact)

PROGRAM_OFFICER_NAME: SALAZAR, DESIREE LYNN

PROJECT_TERMS: Address;Administrative Supplement;ATAC-seq;Biology;Cell Separation;Cells;Cleavage Under Targets and Release Using Nuclease;Complement;Complex;Defect;Deposition;Development;Developmental Process;Disease;DNA Damage;egg;Embryo;Ensure;Epigenetic Process;epigenetic regulation;epigenome;epigenomics;experimental study;Female;Foundations;Gene Expression;Gene Expression Regulation;Generations;Genetic;Genome;Germ Cells;Germ Lines;Global Change;Grant;Hi-C;Human;innovation;Laboratories;Life;Maintenance;male;Meiosis;Mitosis;Molecular;next generation;novel;oocyte maturation;Oogenesis;Outcome Study;Ovary;parent project;Pathway interactions;Positioning Attribute;postnatal;Process;Production;programs;Public Health;Reproduction;Reproductive Health;Research;Research Support;response;Sex Chromosomes;sexual dimorphism;single cell analysis;single cell sequencing;Sorting;sperm cell;Spermatocytes;Spermatogenesis;stem cells;System;Techniques;Testis;therapy development;Work

PROJECT_TITLE: Epigenetic gene regulations in the germline


NIH_SPENDING_CATS: Biotechnology;Brain Cancer;Brain Disorders;Cancer;Genetics;Hematology;Human Genome;Lymphatic Research;Lymphoma;Neurosciences;Rare Diseases;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: KINGSVILLE

ORG_NAME: TEXAS A&M UNIVERSITY-KINGSVILLE

PHR: Project Narrative The fate and function of cells, tissues, organs, and organisms are determined by the expression of specific set of genes in the genome. This project aims to pinpoint the mechanism controlling DNA demethylation which is the principal means of gene expression regulation and genome stability. The outcome of this project will shed light on DNA methylation-specific regulation of gene expression and DNA damage repair in human cells and may have broader impacts on a variety of human diseases including cancer and neurodegenerative diseases.

PI_NAMEs: KIM, HAEYOUNG  (contact)

PROGRAM_OFFICER_NAME: FAUPEL-BADGER, JESSICA

PROJECT_TERMS: anti-cancer therapeutic;Attention;Biological Assay;Biomedical Research;Cell Physiology;cell type;Cells;CRISPR/Cas technology;demethylation;Development;digital;DNA;DNA Methylation;DNA Repair;drug discovery;Enzymes;epigenetic marker;Epigenetic Process;Family;Gene Expression Regulation;Genes;Genome;Genome Stability;Glioblastoma;high throughput screening;Human;human disease;Induced Neurons;Induced pluripotent stem cell derived human neuron;Light;Link;Lymphoma;Malignant Neoplasms;Neurodegenerative Disorders;Neurons;novel;Organ;Organism;Outcome;Pathway interactions;Process;Production;Proteins;Resistance;Role;Survival Rate;System;Techniques;Tissues;translocase

PROJECT_TITLE: Requisition of Bio-RAD QX200 Digital Droplet PCR System


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Back Pain;Neurosciences;Pain Research

ORG_CITY: SAINT LOUIS

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: WASHINGTON UNIVERSITY

PHR: PROJECT NARRATIVE Intervertebral disc degeneration is one of the greatest contributors to low back pain, yet little is known of how the disc generates pain in the sensory nerve roots, or dorsal root ganglia. This supplemental project will promote retention of emerging scholars in research-focused careers, enhance the quality of faculty research mentorship, and provide critical support to trainees working in intervertebral disc pathophysiology.

PI_NAMEs: SETTON, LORI A. (contact);TANG, SIMON YUE-CHEONG

PROGRAM_OFFICER_NAME: PINTUCCI, GIUSEPPE

PROJECT_TERMS: Academia;Advocacy;afferent nerve;Affinity;Biomedical Engineering;Biomedical Research;career;cohort;Collaborations;Communication;Communities;Custom;design;Development;Doctor of Philosophy;doctoral student;Educational process of instructing;Educational Status;Educational workshop;Engineering;Evaluation;experience;faculty mentor;faculty research;Fellowship;Focus Groups;Functional disorder;Funding;Goals;Group Interviews;In Vitro;induced pluripotent stem cell;Institution;inter-institutional;interest;Intervertebral disc structure;intervertebral disk degeneration;Learning;Low Back Pain;Mentors;Mentorship;Methods;Midwestern United States;minority scientist;Modeling;Molds;mouse model;Nervous System;Neurons;Occupations;Outcome;Pain;parent grant;Positioning Attribute;Postbaccalaureate;pre-doctoral;Process;programs;Publishing;Readiness;Research;Schools;skills;Spinal Ganglia;student participation;success;Surveys;symposium;Travel;undergraduate student;Universities;Washington;Work;Writing

PROJECT_TITLE: Intervertebral Disc Degeneration and Cross-Talk with the Nervous System - NOSI Diversity Supplement

STUDY_SECTION: SBSR

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


NIH_SPENDING_CATS: Autoimmune Disease;Digestive Diseases;Infectious Diseases;Inflammatory Bowel Disease;Neurosciences

ORG_CITY: PULLMAN

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: WASHINGTON STATE UNIVERSITY

PHR: Project Narrative We propose to investigate how the nervous system and immune system interact to achieve the resolution of infection and the specificity of innate immunity, two important but poorly understood issues in immunology. Failure to properly resolve infection or to ensure appropriate innate immune responses to specific pathogens can lead to uncontrolled inflammation, which has now been recognized as a unifying mechanism for many inflammatory diseases, such as arthritis, sepsis, and inflammatory bowel disease. Understanding the molecular and neuronal mechanisms responsible for neural regulation of both infection resolution and innate immune specificity could benefit the development of new treatments for infectious diseases and innate immune disorders.

PI_NAMEs: SUN, JINGRU  (contact)

PROGRAM_OFFICER_NAME: ZHAO, XIAOLI

PROJECT_TERMS: Arthritis;Back;Biological Models;Caenorhabditis elegans;Development;Disease;Ensure;environmental change;Failure;G-Protein-Coupled Receptors;Heart Rate;Homeostasis;Human;Immune;Immune response;Immune system;Immune System Diseases;Immunity;Immunologics;Immunology;improved;Infection;infectious disease treatment;Inflammation;Inflammatory;Inflammatory Bowel Diseases;Innate Immune Response;Mediating;Molecular;Natural Immunity;Nervous System;Nervous System control;neural network;Neurobiology;Neuroimmune;Neurons;neuroregulation;neurotransmission;pathogen;Research;Resolution;Sepsis;Specificity;theories

PROJECT_TITLE: Neuronal and molecular mechanisms underlying neural regulation of innate immunity


NIH_SPENDING_CATS: Bioengineering

ORG_CITY: DENVER

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF DENVER (COLORADO SEMINARY)

ORG_STATE: CO

PHR: 8. Project Narrative  The proposed project is relevant to public health because it will develop and validate technology to detect ethylene as a unique biomarker of oxidative stress. Ethylene is a product of lipid peroxidation and in-turn a measure of oxidative stress, which is related to numerous diseases. The development of sensitive fluorescent probes could broaden the study of the biological production and role of ethylene, which is in line with the mission of the National Institute of General Medical Sciences (NIGMS).

PI_NAMEs: MICHEL, BRIAN  (contact)

PROGRAM_OFFICER_NAME: ASLAN, KADIR

PROJECT_TERMS: Alkenes;Biological;Biological Markers;biological systems;BODIPY;Carbon Monoxide;Cardiovascular Diseases;catalyst;Detection;detection limit;Development;Disease;Environment;Ethylenes;Exhalation;Fluorescent Probes;Growth;improved;insight;interdisciplinary approach;interest;Ligands;Lipid Peroxidation;Lipid Peroxides;Location;Malignant Neoplasms;Mammals;Measures;metalloenzyme;Methods;Mission;Modification;Molecular Probes;National Institute of General Medical Sciences;Neurodegenerative Disorders;novel strategies;Oxidative Stress;Plant Growth Regulators;Play;Production;programs;Public Health;Reaction;Reaction Time;Reactive Oxygen Species;Reporting;Research;Resolution;response;Role;Ruthenium;Sampling;sensor;Signal Transduction;small molecule;Stress;Technology;technology validation;Transition Elements;Work

PROJECT_TITLE: Organometallic Sensors for Cellular Small Molecule Detection


NIH_SPENDING_CATS: Complementary and Integrative Health;Dietary Supplements;Genetics;Nutrition;Prevention

ORG_NAME: UNIVERSITY OF WASHINGTON

PHR: Project Narrative This project aims to elucidate how oxidation of different types of fatty acids, either produced by human body or acquired through diet, influences ferroptosis, an emerging pathway of cell death that is significant in cancer and degenerative diseases. It will fill in important knowledge gaps between lipid peroxidation and eventual cell death, which could lead to new ways to modulate ferroptosis and, thus, new prevention strategies and treatments for ferroptosis-related diseases.

PI_NAMEs: FU, DAN ;XU, LIBIN  (contact)

PROGRAM_OFFICER_NAME: STILL, PATRICK COLBY

PROJECT_TERMS: access restrictions;adduct;Alcohols;Aldehydes;Animal Model;anti-cancer;Apoptosis;Arachidonic Acids;ASCL1 gene;biological systems;cancer cell;Cancer cell line;cancer therapy;Cell Death;Cell model;Cells;Characteristics;chemical bond;Chemicals;Chemistry;Chemopreventive Agent;Chemosensitization;Conjugated Linoleic Acids;Cysteine;Dairy Products;Degenerative Disorder;Development;Diet;Disease;Edible Plants;experimental study;Exposure to;Fatty Acids;Gene Expression;Gene Targeting;Genes;Glutathione;glutathione peroxidase;Goals;Human body;Hydrogen;Image;in situ imaging;inhibitor;innovation;Intervention;Iron;knock-down;Knowledge;Lead;Linoleic Acids;Linolenic Acids;Lipid Peroxidation;Lipid Peroxides;lipidomics;Lipids;Location;Malignant Neoplasms;Measures;Meat Products;Mediating;Membrane Lipids;Microscopy;Momordica charantia;Monounsaturated Fatty Acids;Outcome;oxidation;Pathway interactions;perhydroxyl radical;peroxidation;pi bond;Play;Polyunsaturated Fatty Acids;Pomegranate;prevent;Prevention;Prevention strategy;Proteins;Proteomics;Resistance;Role;Ruminants;Signal Transduction;Spatial Distribution;Testing;Time;Tissue-Specific Gene Expression;transcriptome sequencing;Visualization

PROJECT_TITLE: Elucidate the mechanisms of ferroptosis mediated by nonconjugated and conjugated polyunsaturated fatty acids

STUDY_SECTION: BBM

STUDY_SECTION_NAME: Biochemistry and Biophysics of Membranes Study Section[BBM]


NIH_SPENDING_CATS: Genetics;Human Genome

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

PI_NAMEs: CHEDIN, FREDERIC LOUIS (contact)

PROGRAM_OFFICER_NAME: KRASNEWICH, DONNA M

PROJECT_TERMS: Address;Affect;Attention;Biochemical;Biogenesis;Cell Line;Cell model;Cell Physiology;Cells;Chromatin;Chromosome abnormality;Chromosome Segregation;Complement;CpG Islands;Data;Defect;Deposition;Developmental Gene;Disease;DNA;DNA Damage;DNA Structure;DNA-Directed RNA Polymerase;Enzymes;Functional disorder;Gene Expression;genetic information;Genetic Transcription;Genome;Genome Stability;Genomic Instability;genomic profiling;Genomics;Goals;Health;Histones;Human;human disease;Human Genome;Hybrids;Inherited;innovative technologies;insight;Knowledge;Length;Life;Light;Link;Maintenance;Mammalian Cell;mammalian genome;Mammals;Measures;Mediating;Metabolism;Monitor;Nature;Normal Cell;Nuclear;nuclease;nucleic acid structure;Nucleosomes;Outcome;overexpression;Pathologic;Pathway interactions;Pattern;Phenotype;Physiological;Physiological Processes;Planet Earth;Play;Population;preservation;Prevalence;Process;programs;promoter;recruit;remediation;Resolution;ribonuclease H1;RNA;RNA annealing;RNA Processing;RNA Splicing;Role;single molecule;Single-Stranded DNA;Stress;Structure;Technology;termination factor;Time;Transcription Process;transcription termination;Work;Yeasts

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


NIH_SPENDING_CATS: Digestive Diseases;Infectious Diseases;Machine Learning and Artificial Intelligence

ORG_CITY: DALLAS

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: PROJECT NARRATIVE Necroptosis is a type of genetically encoded necrotic cell death that is associated with many human diseases, including cancer, inflammatory bowel disease, liver injury, pancreatitis, neurodegenerative disorders, and a diverse range of viral, bacterial, and fungal infections. Here, we are requesting the IncuCyte® S3 live-cell imaging system for real-time and reliable quantification of cell death kinetics, perform label-free quantification of cell death using machine-learning algorithms, and monitor activation of necroptosis-mediating molecules. This live-cell imaging system will dramatically boost our capabilities, productivity, and rigor in deciphering the mechanisms that govern the execution of necroptosis.

PI_NAMEs: NAJAFOV, AYAZ  (contact)

PROGRAM_OFFICER_NAME: MASKERI, BAISHALI

PROJECT_TERMS: Apoptosis;Apoptotic;Bacterial Infections;Bypass;Cell Death;Cell membrane;Cells;cost effective;Data Analyses;Disease;Equipment;experimental study;Fluorescent Probes;Health;Human;human disease;imaging system;Inflammatory;Inflammatory Bowel Diseases;Kinetics;Label;Ligands;live cell imaging;liver injury;machine learning algorithm;Malignant Neoplasms;Mediating;Methodology;Methods;Microbe;Molecular;Monitor;Mycoses;Necrosis;Neurodegenerative Disorders;new therapeutic target;Pancreatitis;parent project;Permeability;Phosphorylation;Phosphotransferases;Productivity;Proteins;real time monitoring;Real-Time Systems;Regulation;Reporter;RIPK1 gene;RIPK3 gene;Rupture;Signal Transduction;System;Therapeutic Intervention;Time;TNF gene;ubiquitin-protein ligase;upstream kinase;Virus Diseases;Water

PROJECT_TITLE: Molecular Mechanisms of Programmed Necrosis Execution