ORG_CITY: CORAL GABLES

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

ORG_STATE: FL

PHR: Leigh’s syndrome is a devastating newborn neurodevelopmental mitochondrial disorder. This is a genetically heterogeneous disorder always associated with cellular lesions that affect mitochondrial bioenergetics. This project will examine the molecular mechanism underlying two forms of LS due to mutations in LRPPRC or TACO1, which are involved in different aspects of mitochondrial RNA metabolism and gene expression. These studies will uncover the role of these proteins on mitochondrial mRNA folding and test whether accumulation of aberrant RNA secondary structures is a common theme leading to pathogenesis.

PI_NAMEs: MORAN, JOHN CONOR (contact)

PROGRAM_OFFICER_NAME: BARDHAN, SUJATA

PROJECT_TERMS: Aerobic;Affect;Age;Appearance;ATP Synthesis Pathway;Attenuated;base;Binding;Binding Sites;Biochemical;Bioenergetics;Biogenesis;Biological Assay;Cell Line;cell type;Chemicals;Child;Childhood;Collaborations;Complex;complex IV;CRISPR/Cas technology;crosslink;Cultured Cells;cytochrome c oxidase;Cytochrome-c Oxidase Deficiency;Cytoplasmic Granules;Data;Defect;Development;Developmental Delay Disorders;dimethyl sulfate;Disease;DNA;Ensure;Enzymes;Etiology;Functional disorder;Gene Expression;Gene Expression Regulation;gene-editing approach;Genes;genetic variant;Goals;High-Throughput Nucleotide Sequencing;Human;Human Cell Line;Immunoprecipitation;Infant;innovation;interest;Knock-out;Knowledge;Lead;Leigh Disease;Lesion;Leucine;Medicine;Messenger RNA;Mission;Mitochondria;Mitochondrial Diseases;Mitochondrial DNA;mitochondrial messenger RNA;Mitochondrial Proteins;Mitochondrial RNA;Modification;Molecular;mouse model;mRNA Expression;mRNA Stability;mRNA Translation;mutant;Mutate;Mutation;National Institute of Child Health and Human Development;Nerve Degeneration;Newborn Infant;Nuclear;oligomycin sensitivity-conferring protein;Oxidative Phosphorylation;Pathogenesis;Pathogenicity;Pathology;Pathway interactions;Patients;Phenotype;Physicians;Physiological;Polyadenylation;Polyadenylation Pathway;polypeptide;posttranscriptional;prevent;Property;Protein Biosynthesis;Proteins;PTGS1 gene;reconstitution;Regulation;Respiratory Chain;Ribonucleosides;Ribosomal RNA;ribosome profiling;RNA;RNA Folding;RNA metabolism;RNA Processing;RNA Stability;Role;Scientist;skills;Structural defect;Structural Models;Structure;success;System;Technology;Testing;Therapeutic;therapeutic target;Training;Trans-Activators;Transcript;Transcription Process;transcriptome;Transfer RNA;Translations;Variant

PROJECT_TITLE: Mitochondrial mRNA structure as a driver of Leigh Syndrome

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F08-M(20)L]


ADMINISTERING_IC: HL

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Biotechnology;Genetics;Lung;Rare Diseases

ORG_CITY: HOUSTON

ORG_COUNTRY: UNITED STATES

ORG_DEPT: ANESTHESIOLOGY

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

ORG_STATE: TX

PHR: NARRATIVE Our studies are designed to lay the groundwork for novel therapeutic approaches for treating patients with acute respiratory distress syndrome (ARDS). If successful, these studies will introduce microRNA-based therapy into the treatment of ARDS.

PI_NAMEs: ELTZSCHIG, HOLGER K. (contact)

PROGRAM_OFFICER_NAME: ZHOU, GUOFEI

PROJECT_TERMS: 3' Untranslated Regions;Acute Lung Injury;Acute Respiratory Distress Syndrome;Acute respiratory failure;Alveolar;alveolar epithelium;Applications Grants;Attenuated;Binding;Binding Sites;Biological Models;Breeding;Clinical Trials;design;DNA Sequence Alteration;Epithelial Cells;experience;Funding;Generations;Genes;Genetic;Genetic study;Goals;HIF1A gene;Homozygote;Human;Hypoxia;In Vitro;in vitro Model;in vivo;Inflammation;Inflammatory;Link;Liquid substance;Lung;lung injury;Macrophage;Mechanical ventilation;Mechanics;Mediating;Messenger RNA;Microarray Analysis;MicroRNAs;Modeling;mosaic;Mucositis;Mucous Membrane;Mus;Mutation;nanoparticle;neutrophil;non cardiogenic pulmonary edema;novel therapeutic intervention;Operative Surgical Procedures;overexpression;Pathway interactions;Patients;Periodicity;preclinical safety;pressure;prevent;promoter;Pulmonary Edema;Pulmonary Inflammation;Repression;Resolution;Role;safety study;Stretching;Supportive care;Testing;Therapeutic;therapeutic miRNA;Tissues;Toll-like receptors;transcription factor;treatment strategy;Untranslated Regions;ventilation;Ventilator-induced lung injury

PROJECT_TITLE: microRNA miR-147 Dampens Alveolar Epithelial Inflammation During ARDS


NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Biotechnology;Lung;Orphan Drug;Rare Diseases

ORG_CITY: PITTSBURGH

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: There is an unmet need for new therapies to reduce the high morbidity and mortality associated with ARDS. We propose a systematic analysis of protein ubiquitination networks in ARDS. Specifically, we will focus on identifying novel ubiquitin pathways that modulate the inflammatory cascade, the function of mitochondria/mitophagy, and the activation of DAMPs/inflammasome in the lung, in the effort to develop novel therapeutics for ARDS. This proposal will lay the groundwork for future studies aimed at the discovery of small molecules targeting protein ubiquitination pathways in ARDS.

PI_NAMEs: CHEN, BEIBEI  (contact)

PROGRAM_OFFICER_NAME: GOMEZ, CHRISTIAN RENE

PROJECT_TERMS: 26S proteasome;Acute Respiratory Distress Syndrome;Adrenal Cortex Hormones;Affect;alveolar epithelium;Alveolus;Angiotensin II Receptor;antagonist;Area;Attenuated;Bacterial Infections;Binding;biochemical tools;Biological Process;Blocking Antibodies;Cells;Clinical Treatment;CRISPR/Cas technology;cytokine;Data;Death Rate;Disease;drug discovery;Edema;epithelial injury;experimental study;Functional disorder;Future;Gases;Gene Transfer;Genes;genetic approach;high throughput screening;Impairment;in vivo;Infection;Inflammasome;Inflammatory;inflammatory modulation;Inflammatory Response;Intervention;Investigation;Length of Stay;Lung;lung injury;Lysosomes;Messenger RNA;Mitochondria;Modeling;Molecular;Morbidity - disease rate;mortality;novel;novel therapeutics;Pathway interactions;Patients;Play;Pneumonia;pre-clinical;Process;Protein Analysis;protein degradation;Proteins;Pulmonary Inflammation;Research Personnel;Role;Sepsis;Site;small molecule;Stimulus;T-Cell Receptor;Ubiquitin;ubiquitin-protein ligase;Ubiquitination

PROJECT_TITLE: Systematic Investigation of Protein Ubiquitination in ARDS


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Breast Cancer;Cancer;Clinical Research;Genetics;Women's Health Research

ORG_CITY: SAN ANTONIO

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER

PHR: Project Narrative Cancer cells use various mechanisms to manage their survival such as repairing DNA damage resulting from unchecked DNA replication. Moreover, the ability of cancer cells to repair radiation or chemotherapy drug- induced DNA damage also serves as one of the mechanisms for therapy resistance. Consistent with this, several DNA repair factors are reported to be overexpressed in cancer patients. Therefore, drugs that are capable of suppressing DNA repair responses of cancer cells will have promising therapeutic outcomes. This study proposes to develop a novel inhibitor that is derived from a FDA approved anti-depressant, which will suppress breast cancer growth and metastasis by inhibiting key proteins such as FOXM1, which are involved in DNA repair pathway. Furthermore, this inhibitor has potential to enhance the efficacy of the current chemotherapy drugs and prolong survival of breast cancer patients.

PI_NAMEs: RAO, MANJEET KUMAR (contact);VADLAMUDI, RATNA K

PROGRAM_OFFICER_NAME: AGYIN, JOSEPH KOFI

PROJECT_TERMS: aggressive breast cancer;analog;anti-depressive agents;Anti-estrogen Therapy;Binding;Biochemical;Biological Assay;Biophysics;BRCA1 gene;Breast Cancer Patient;breast cancer progression;breast cancer survival;cancer addiction;cancer cell;Cancer Center;Cancer Patient;cancer subtypes;Cell model;Cells;chemotherapy;Chemotherapy and/or radiation;Clinic;Clinical;clinical development;Confocal Microscopy;coping;Defect;Distant Metastasis;DNA;DNA biosynthesis;DNA Damage;DNA Repair;DNA Repair Gene;DNA Repair Pathway;drug development;Endocrine;Estrogen receptor positive;Excision Repair;FDA approved;Feedback;FOXM1 gene;Funding;Future;Genes;genotoxicity;Goals;Growth;homologous recombination;hormone therapy;Human;humanized mouse;Imipramine;Immune;Immunofluorescence Immunologic;improved;inhibitor;innovation;knock-down;Legal patent;Lesion;Malignant Breast Neoplasm;Malignant Neoplasms;Modeling;Molecular Biology;Mutation;Neoplasm Metastasis;Nodal;Nonhomologous DNA End Joining;Normal Cell;novel;novel therapeutics;Oncogenic;Outcome;overexpression;Pathway interactions;patient derived xenograft model;Patients;Pharmaceutical Preparations;pharmacokinetics and pharmacodynamics;Phase I Clinical Trials;Play;Positioning Attribute;Predisposing Factor;Privatization;programs;Proliferating;Proteins;Regimen;Relapse;repaired;Reporting;Resistance;response;Role;safety testing;Signal Transduction;Structure;Tamoxifen;targeted treatment;Testing;Therapeutic;therapeutic evaluation;therapeutic target;therapy development;therapy outcome;therapy resistant;Toxic effect;Translating;translational potential;treatment response;triple-negative invasive breast carcinoma;tumor;tumor xenograft;Xenograft Model;Xenograft procedure

PROJECT_TITLE: FoXM1 inhibition: a novel therapeutic avenue to treat breast cancers


ADMINISTERING_IC: AI

ED_INST_TYPE: GRADUATE SCHOOLS

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Digestive Diseases;Infectious Diseases

ORG_CITY: PHILADELPHIA

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: DREXEL UNIVERSITY

PHR: PROJECT NARRATIVE Reovirus (ReoV) is an enteric dsRNA virus which can infect a wide range of mammals and is often used in oncolytic research. I have found that ReoV induces ZBP1-dependent necroptosis and apoptosis, though the mechanism by which this occurs is largely unclear. Identifying how ZBP1 is activated and assessing the importance of ZBP1-induced cell death to ReoV clearance and pathogenesis will have potentially important ramifications for the treatment of ReoV-initiated disease.

PI_NAMEs: DEANTONEO, CARLY ANN (contact)

PROGRAM_OFFICER_NAME: MOITRA, KAROBI

PROJECT_TERMS: Apoptosis;Autoimmune Diseases;cancer therapy;Caspase;Celiac Disease;Cell Death;Cell Death Induction;cell type;Cells;cellular targeting;Cessation of life;Child;cytokine;Cytoplasm;Dangerousness;Disease;Double Stranded RNA Virus;Double-Stranded RNA;Enteral;Epithelial Cells;Gastroenteritis;Germ Lines;Host Defense;Human;Immune;Immune response;immunogenic;Immunologics;in vivo;Infection;Inflammation;Inflammatory;insight;Intestinal Diseases;intestinal epithelium;Intestines;Left;LGR5 gene;Ligands;Link;Lytic;Mammals;Mediating;Modality;Molecular;Molecular Conformation;Mus;Nature;neoplastic cell;Oncolytic;Outcome;pathogen;Pathogenesis;Pathway interactions;Pattern;Phosphotransferases;Polyubiquitin;Reovirus;Reovirus Infections;Research;RIPK3 gene;RNA;RNA immunoprecipitation sequencing;Role;sensor;Signal Transduction;Testing;Tissues;Ubiquitination;villin;Viral;Viral Pathogenesis;Virion;Virus;Virus Diseases;Z-DNA Binding Protein

PROJECT_TITLE: Reovirus Z-RNAs activate ZBP1 dependent necroptosis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F07A-A(20)]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

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

ORG_CITY: Nashville

ORG_NAME: VANDERBILT UNIVERSITY

ORG_STATE: TN

PHR: PROJECT NARRATIVE Alzheimer’s disease (AD) is the most common cause of dementia in the elderly population, with a prevalence that is expected to double by 2050 and limited treatment options currently available. Given the high costs, long timelines, and high clinical failure rates of new AD drugs, drug repurposing has emerged as a strategy to increase success in AD drug development. This project proposes two independent approaches leveraging novel genetics and informatics methods to identify drug repurposing candidates for AD in a high-throughput manner, both combined with clinical validation of candidate drugs using data from electronic health records and healthcare claims.

PI_NAMEs: GRABOWSKA, MONIKA ELIANA (contact)

PROGRAM_OFFICER_NAME: LUO, YUAN

PROJECT_TERMS: Academic Medical Centers;Aducanumab;Adult;Affect;All of Us Research Program;Alzheimer's Disease;Alzheimer's disease diagnosis;Amyloid beta-Protein;Area;Award;biobank;candidate validation;career;Cholinesterase Inhibitors;Clinical;Clinical Data;clinical development;Cognition;Colorectal Cancer;Complex;cost;COVID-19;Data;Data Set;Databases;Dementia;Development;Diagnosis;Disease;drug action;drug candidate;drug development;drug repurposing;Drug Targeting;Drug usage;Elderly;electronic health data;Electronic Health Record;Evaluation;Failure;Functional disorder;Future;Gene Expression;Gene Expression Profile;Genes;Genetic;genetic approach;Genetic study;genetic variant;genome wide association study;Glutamates;Health;Healthcare;HIV/AIDS;Human;Hyperlipidemia;Hypertension;Impaired cognition;Impairment;improved;In Vitro;Individual;Informatics;insight;interest;Investigation;Machine Learning;Maps;Medicare;Medicine;Memory;Memory Loss;Mendelian randomization;Methods;Monoclonal Antibodies;Natural Language Processing;Nerve Degeneration;novel;novel therapeutics;Patients;Pharmaceutical Preparations;Pharmacotherapy;Phenotype;Physicians;Population;pre-clinical;Prevalence;Proteins;randomized, clinical trials;Research;Research Personnel;Resources;Rheumatoid Arthritis;Safety;Scientist;Short-Term Memory;skills;statistics;success;Therapeutic Effect;Time;timeline;tool;transcriptome;transcriptomics;United States;United States Centers for Medicare and Medicaid Services;United States Food and Drug Administration;United States National Institutes of Health;Validation;virtual;Work

PROJECT_TITLE: Computational drug repurposing for Alzheimer's disease


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Eye Disease and Disorders of Vision;Genetics;Neurodegenerative;Neurosciences;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: BALTIMORE

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Project Narrative Retinal ganglion cell (RGC) injury in mammals leads to irreversible vision loss, however, in zebrafish lost RGCs are robustly regenerated due to endogenous stem cells present in all vertebrate retinas, Müller glia. We created a novel zebrafish model designed to reveal cellular, chemical, and genetic factors regulating RGC regeneration in fish and will draw comparisons of these factors to a mouse model where regeneration is absent. These studies are designed to provide insights necessary to stimulate regenerative potential in the mammalian retina, thus supporting the development of transformative therapeutics for restoring visual function.

PI_NAMEs: EMMERICH, KEVIN  (contact)

PROGRAM_OFFICER_NAME: AGARWAL, NEERAJ

PROJECT_TERMS: Ablation;Acute;adaptive optics;Address;Apoptosis;Area;Articulation;axon regeneration;behavior test;Blindness;Brain;Candidate Disease Gene;Cell Death;cell injury;cell regeneration;Cell Survival;cell type;Cells;Chemicals;Chronic;Clinical;Collaborations;Competence;Computer Analysis;confocal imaging;CRISPR/Cas technology;cytokine;Data;design;Development;Disease;DNA Damage;Drug Screening;endogenous stem cells;Enzymes;Fishes;gene function;Genes;Genetic;Genome;Genomics;Glaucoma;Goals;high throughput screening;Histone Deacetylase;Homologous Gene;Human;human disease;Immune;Immune system;in vivo;in vivo imaging;Individual;Inflammatory;Injury;insight;Interneurons;Kinetics;knockout gene;Knowledge;Larva;Leber's Hereditary Optic Neuropathy;Light;light transmission;Link;Mammals;Measurement;Methods;Metronidazole;Microglia;Microscopy;model design;Modeling;Molecular;mouse model;Muller's cell;Mus;mutant;N-Methylaspartate;National Eye Institute;Natural regeneration;Necrosis;Nerve Crush;nerve damage;Neurodegenerative Disorders;neuroprotection;Neuroprotective Agents;Nitroreductases;novel;Optic Nerve;optical lattices;Outcome;Pathway interactions;Pharmaceutical Preparations;Play;Process;Prodrugs;protective effect;Proteins;regeneration model;regeneration potential;regenerative;Regenerative capacity;Regenerative research;Regenerative response;Reporter;Research;Resolution;response;response to injury;Retina;retinal damage;Retinal Degeneration;retinal ganglion cell degeneration;retinal ganglion cell regeneration;Retinal Ganglion Cells;retinal neuron;retinal progenitor cell;retinal regeneration;retinal rods;Role;screening;Signal Transduction;single-cell RNA sequencing;Specificity;stem cells;Stimulus;System;Techniques;teleost fish;Testing;Therapeutic;transcriptomics;Transforming Growth Factor beta;Transgenic Model;Vertebrates;Vision;Visual;Work;Zebrafish

PROJECT_TITLE: Identification of Cellular, Molecular and Genetic Factors Regulating RGC Regeneration


ADMINISTERING_IC: NS

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Neurodegenerative;Neurosciences

ORG_CITY: DURHAM

ORG_DEPT: PSYCHOLOGY

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Project Narrative Microglia-neuron crosstalk is critical for the formation, refinement, and survival of synaptic connections in the brain. The microglial receptor colony-stimulating factor 1 has two ligands, one of which, interleukin-34 (IL34), is produced by neurons, however its role in microglia function is unknown. Disrupted IL34 signaling is implicated in neurodevelopmental and neurodegenerative diseases that are characterized by synapse loss/dysfunction, thus my project aims to elucidate how IL34 expression is regulated in neurons and what IL34 does to impact microglial interactions with neurons in development.

PI_NAMEs: DEVLIN, BENJAMIN  (contact)

PROGRAM_OFFICER_NAME: MOHAPATRA, DURGA PRASANNA

PROJECT_TERMS: Adult;Age;Alzheimer's Disease;Animals;Anterior;Behavior;Blocking Antibodies;Brain;Brain region;cell type;cingulate cortex;cohort;Communication;Corpus striatum structure;critical developmental period;critical period;CSF1R gene;cytokine;Data;Designer Drugs;designer receptors exclusively activated by designer drugs;Development;developmental plasticity;Embryo;Ensure;excitatory neuron;Excitatory Synapse;experimental study;Functional disorder;Gene Expression;Genetic;Genetic Transcription;Goals;Immunohistochemistry;Inflammatory;Interleukins;Interneurons;LacZ Genes;Ligands;Macrophage;Macrophage Colony-Stimulating Factor;Macrophage Colony-Stimulating Factor Receptor;Measures;Messenger RNA;Microglia;Molecular;mRNA Expression;Mus;Neonatal;Nerve Degeneration;neural;neural circuit;Neurodegenerative Disorders;neurodevelopment;Neurodevelopmental Disorder;Neuroglia;neuronal circuitry;Neurons;novel;Organ;Parkinson Disease;Phagocytosis;postnatal;prevent;protein expression;Proteins;Proxy;receptor;reconstruction;Regulation;Reporter;Reporting;Research;Role;Signal Transduction;social cognition;Synapses;Synaptic plasticity;synaptic pruning;synaptogenesis;Testing;timeline;Tissues;Ultrasonics;vocalization;Work

PROJECT_TITLE: Neuron-Microglia Crosstalk in Development: A new role for the neuron-derived cytokine IL34 in microglial function


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

NIH_SPENDING_CATS: Asthma;Basic Behavioral and Social Science;Behavioral and Social Science;Lung;Neurosciences

ORG_CITY: GAINESVILLE

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF FLORIDA

PHR: NARRATIVE Abnormal amygdala function is responsible for anxiety, a common comorbidity in asthma that is associated with poorer asthma control and decreased quality of life. Uncovering how asthma impacts the amygdala and the mechanisms that link amygdala function with asthma control will reveal new targets for intervention.

PI_NAMEs: REZNIKOV, LEAH R (contact)

PROGRAM_OFFICER_NAME: LACHOWICZ-SCROGGINS, MARRAH ELIZABETH

PROJECT_TERMS: Ablation;Acute;Address;Airway Disease;Airway Resistance;Amygdaloid structure;Anatomy;Anti-Anxiety Agents;Anxiety;anxiety treatment;Asthma;asthma exacerbation;asthmatic;Attention;Attenuated;Behavior;Brain;Brain region;Brain-Derived Neurotrophic Factor;Bronchoconstriction;calmodulin-dependent protein kinase II;Central Nervous System;Cessation of life;comorbidity;Cre lox recombination system;Cyclic AMP-Responsive DNA-Binding Protein;Data;Dendritic Spines;density;Development;Excitatory Amino Acid Antagonists;excitatory neuron;experience;Extrinsic asthma;FDA approved;Frequencies;Fright;Functional disorder;Gene Expression;Gene Transfer;Genes;Glutamate Receptor;Golgi Apparatus;Guidelines;holistic approach;Human;Impairment;Intervention;Link;Magnetic Resonance Imaging;Maintenance;Manganese;Measures;Mediating;Mediator;Mental disorders;MK801;Modeling;Molecular;mortality;mouse model;mRNA Expression;Mus;N-Methyl-D-Aspartate Receptors;N-Methylaspartate;Neuronal Plasticity;Neurons;NMDA receptor antagonist;Nose;optogenetics;Outcome;Ovalbumin;overexpression;Pathologic;Patients;Peripheral;Pharmaceutical Preparations;pharmacologic;prevent;Price;Quality of life;Receptor Signaling;Regulation;Risk Factors;Signaling Protein;Stains;Structure;targeted treatment;Testing;Therapeutic Intervention;transcription factor;Transgenic Mice;Vertebral column

PROJECT_TITLE: Central Nervous System Plasticity in Airway Disease

STUDY_SECTION: RIBT

STUDY_SECTION_NAME: Respiratory Integrative Biology and Translational Research Study Section[RIBT]


NIH_SPENDING_CATS: Aging;Biotechnology;Cardiovascular;Heart Disease;Heart Disease - Coronary Heart Disease;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: CINCINNATI

ORG_NAME: CINCINNATI CHILDRENS HOSP MED CTR

ORG_STATE: OH

PHR: Relevance The relevance of this application is rooted in the fundamental translational biology of how the immune system impacts cardiac disease presentation and resolution. It is very important to understand and define the basic science mechanisms underlying how the adult human heart heals after ischemic injury and how the immune system intimately regulates this process. Here we will attempt to define therapeutic applications for directly altering the immune response in the heart during and after injury.

PI_NAMEs: MOLKENTIN, JEFFERY D (contact)

PROGRAM_OFFICER_NAME: ADHIKARI, BISHOW B

PROJECT_TERMS: Acute;Adult;adult stem cell;Affect;Agonist;Area;Atherosclerosis;Bacteria;Basic Science;Biology;Cardiac;Cardiac Myocytes;cardiac repair;cardiovascular health;Cell membrane;Cell Therapy;Cells;Cicatrix;Communication;Compensation;Complement Activation;Data;Dendritic Cells;direct application;Disease;DNA;Effectiveness;Endosomes;Fibroblasts;functional improvement;fungus;Gene Targeting;Genetic;Goals;healing;Heart;heart damage;Heart Diseases;Heart failure;Heart Injuries;Immune response;Immune signaling;Immune system;in vivo;Infarction;Infection;Inflammasome;Inflammation;Inflammatory;Inflammatory Response;Injection of therapeutic agent;Injections;injured;Injury;innate immune mechanisms;Innate Immune Response;Interferons;Ischemia;ischemic injury;life span;Macrophage;Mediating;mouse genetics;Mus;Muscle Cells;Myocardial Infarction;Myocardial Ischemia;Natural regeneration;Nature;Neurosecretory Systems;neutrophil;novel;novel therapeutics;Pathway interactions;Patients;Pattern recognition receptor;Performance;physical property;Process;Production;programs;Proteins;Receptor Signaling;recruit;regenerative;Rejuvenation;Reperfusion Injury;Reperfusion Therapy;Research;Resolution;response;response to injury;RNA;Rodent Model;Signal Pathway;Signal Transduction;stem cells;Stimulator of Interferon Genes;System;Therapeutic;Tissue Expansion;Tissues;TLR2 gene;TLR3 gene;TLR4 gene;TLR5 gene;TLR6 gene;TLR7 gene;TLR8 gene;Toll-like receptors;Virus;Western World;Zymosan

PROJECT_TITLE: Innate immune response signaling in cardiac injury healing

STUDY_SECTION: MPPB

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


NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Genetics;Human Genome;Huntington's Disease;Neurodegenerative;Neurosciences;Orphan Drug;Rare Diseases

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

ORG_STATE: MA

PHR: PROJECT NARRATIVE Our large scale genetic investigation of Huntington's disease (HD) patients revealed that the timing of onset is significantly delayed in subjects carrying duplicated CAA-CAG interruption in HTT gene, due to decreased length of uninterrupted CAG repeat and potentially reduced somatic repeat expansion. In order to advance this promising human-validated therapeutic target, we propose to determine potential of base editing strategies to convert CAG at various locations in the huntingtin CAG repeat to CAA. Our human-based therapeutic base editing strategies for CAG-to-CAA conversion, which do not change huntingtin protein sequence, can be applied to all HD patients and are expected to produce very strong effects, representing a significant and clinically relevant advancement toward development of effective and safe treatments for HD.

PI_NAMEs: LEE, JONG-MIN  (contact)

PROGRAM_OFFICER_NAME: MILLER, DANIEL L

PROJECT_TERMS: Affect;Age;Age of Onset;Alleles;Amino Acid Sequence;Animal Model;base editing;base editor;Biological Models;Brain;CAG repeat;Cell Culture Techniques;Cell model;Cells;Clinical;Clinical Trials;clinically relevant;clinically significant;Clone Cells;Clustered Regularly Interspaced Short Palindromic Repeats;Code;Corpus striatum structure;Data;Development;Disease;disease model;DNA Repair Gene;effective therapy;Engineering;Evaluation;Future;Gene Modified;Gene Targeting;Genes;Genetic;genome editing;genome wide association study;genome-wide;Glutamine;Heritability;Human;Huntington Disease;Huntington gene;induced pluripotent stem cell;innovation;insight;Interruption;Investigation;Knock-in Mouse;Knowledge;Length;Liver;Location;Methods;Modeling;Modification;Molecular;molecular phenotype;mouse model;Mus;Mutation;Neuronal Differentiation;novel;novel therapeutics;Nuclear;Onset of illness;Outcome;Patients;Persons;Phenotype;Positioning Attribute;pre-clinical;prevent;Research;Role;Route;Specificity;Stains;Study models;Symptoms;Testing;Therapeutic;therapeutic target;therapeutically effective;transcriptome sequencing;Treatment Efficacy;treatment strategy;Variant;virtual;Work

PROJECT_TITLE: Therapeutic Potential of Base Editing Strategies to Convert CAG to CAA in Huntington's Disease

STUDY_SECTION: MNG

STUDY_SECTION_NAME: Molecular Neurogenetics Study Section[MNG]


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Clinical Research

ORG_CITY: NEW YORK

ORG_DEPT: DERMATOLOGY

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: NARRATIVE Inflammation is central to many chronic conditions, including rheumatoid arthritis, asthma, atherosclerosis and inflammatory skin disease. Increased levels of secreted phospholipase A2 are observed in these conditions, resulting in cleavage of membrane phospholipids into lysophospholipids and fatty acids. In this proposal, we investigate the recognition of these phospholipid breakdown products by T cells, which will open up avenues of investigation into the functions of lipid-specific T cells in the context of inflammation.

PI_NAMEs: DE JONG, ANNEMIEKE  (contact)

PROGRAM_OFFICER_NAME: UNDALE, ANITA H

PROJECT_TERMS: Acute;Anti-Inflammatory Agents;antigen binding;Antigen Presentation;Antigen-Presenting Cells;Antigens;Arachidonic Acids;Arthritis;Asthma;Atherosclerosis;Autoantigens;Autoimmune;autoreactive T cell;Binding;Biological Assay;Blood;blood fractionation;CD1 Antigens;CD1a antigen;Cell Culture Techniques;Cell membrane;Cell Separation;Cells;Chronic;Clinical;Clonal Expansion;Complex;Cross Reactions;Eicosanoid Production;Eicosanoids;Enzymes;Fatty Acids;Flow Cytometry;Generations;Homeostasis;Homing;Human;Hydrophobicity;Immune;Immune system;immunoregulation;in vivo;Individual;Infection;Inflammation;Inflammatory;insight;Investigation;Lecithin;Link;lipid mediator;Lipids;Lysophosphatidylcholines;Lysophospholipids;Membrane;MHC antigen;MHC Class I Genes;Modeling;novel;Pathogenesis;Pathway interactions;Patients;Peptides;Phenotype;Phospholipase A2;phospholipase A2 inhibitor;Phospholipids;Physiological;Population;prevent;Proteins;Psoriasis;Regulation;Regulatory T-Lymphocyte;response;Rheumatoid Arthritis;Role;sensor;Skin;skin disorder;Specificity;System;T cell receptor repertoire sequencing;T cell response;T-Cell Activation;T-Cell Receptor;T-Lymphocyte;T-Lymphocyte Subsets;Therapeutic;therapy development;Tissues;tool

PROJECT_TITLE: Role of secreted phospholipase A2 in the activation of human CD1-restricted T cells

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IMM-T(57)]


NIH_SPENDING_CATS: Bioengineering;Brain Disorders;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurosciences;Radiation Oncology

ORG_CITY: DALLAS

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: PROJECT NARRATIVE Patients with multiple brain metastases, a cancer which has spread to multiple places in the brain, have poor survival or quality of life after single fraction stereotactic radiosurgery or whole brain radiotherapy. We will develop and study a new treatment strategy for multiple brain metastases using spatial and temporal fractionated stereotactic radiosurgery by frameless GammaKnife. The new procedure uses artificial intelligence to optimize and manage the treatment to improve patients’ survival and quality of life after the treatment.

PI_NAMEs: GU, XUEJUN  (contact);LU, WEIGUO ;WARDAK, ZABIHULLAH

PROGRAM_OFFICER_NAME: OBCEMEA, CEFERINO H

PROJECT_TERMS: Address;Adverse effects;Adverse event;Affect;Aftercare;Artificial Intelligence;automated segmentation;Brain;brain size;Brain Stem;Caring;Clinic;Clinical;clinical practice;Clinical Trials;Cranial Irradiation;Data;Dedications;design;Development;Distant;Dose;effective therapy;Ensure;falls;Feedback;follow-up;Foundations;Functional disorder;Goals;imaging Segmentation;improved;Infrastructure;innovation;Interdisciplinary Study;irradiation;Knowledge;Learning;learning progression;Life;Life Expectancy;Malignant Neoplasms;Maximum Tolerated Dose;Medical;Metastatic malignant neoplasm to brain;Morbidity - disease rate;Neoplasm Metastasis;Nervous System Disorder;Neurocognitive;Neurocognitive Deficit;Neurologic;novel;novel therapeutic intervention;Optic Nerve;Organ;outcome prediction;patient population;Patients;Performance;Phase;Phase I/II Clinical Trial;Prediction of Response to Therapy;preservation;Procedures;prospective;Quality of life;Radiation;Radiation necrosis;Radiation Oncologist;Radiation therapy;Radiation Therapy Oncology Group;Radiation Toxicity;Radiosurgery;Relapse;Research;response;Retrospective Studies;Site;Solid;spatiotemporal;System;targeted treatment;Technology;technology development;Therapeutic Intervention;Tissues;tool;Translating;Treatment outcome;treatment planning;Treatment Protocols;treatment strategy;tumor;United States

PROJECT_TITLE: An artificial intelligence-driven distributed stereotactic radiosurgery strategy for multiple brain metastases management

STUDY_SECTION: BCHI

STUDY_SECTION_NAME: Biomedical Computing and Health Informatics Study Section[BCHI]


ADMINISTERING_IC: DK

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

ORG_CITY: LEXINGTON

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF KENTUCKY

ORG_STATE: KY

PHR: PROJECT NARRATIVE Cardiovascular disease (CVD), the number one killer in men and women, is associated with the prevalence of nonalcoholic fatty liver disease (NAFLD). Consumption of fructose, primarily found in sugar-sweetened beverages and processed foods, is a major risk factor for development of both NAFLD and CVD. The primary goal of this proposal is to determine the mechanisms by which fructose increases cholesterol levels, which will yield insight into novel therapeutic options for NAFLD and associated CVD risk.

PI_NAMEs: HELSLEY, ROBERT NATHANIEL (contact)

PROGRAM_OFFICER_NAME: SASLOWSKY, DAVID E

PROJECT_TERMS: Acetyl Coenzyme A;Acetylation;acylcarnitine;Advisory Committees;Affect;Aging;Animals;Atherosclerosis;Biological Assay;Biopsy;Carbon;Cardiometabolic Disease;cardiometabolic risk;Cardiovascular Diseases;cardiovascular disorder risk;career development;Carnitine Palmitoyltransferase I;Catabolism;Cells;Cholesterol;cholesterol biosynthesis;Cholesterol Homeostasis;Citrates;Clustered Regularly Interspaced Short Palindromic Repeats;cohort;Collaborations;Committee Members;Communication;Consumption;Coupled;Data;Development;Development Plans;dietary;Dietary Sugars;Dyslipidemias;Educational workshop;Ensure;Enzymes;Epigenetic Process;Exhibits;fast protein liquid chromatography;Fat-Restricted Diet;fatty acid oxidation;fatty acid-transport protein;feeding;Female;Food;Fructose;Funding;Genes;Genetic Transcription;genetic variant;Goals;Hepatic;Hepatocyte;Human;hypercholesterolemia;Image;Impairment;In Vitro;in vivo;innovation;insight;Isotope Labeling;Kentucky;Ketohexokinase;knock-down;Knock-out;Knockout Mice;Laboratory Study;Learning;Link;lipid biosynthesis;Lipids;liquid chromatography mass spectrometry;Liver;LoxP-flanked allele;Lysine;male;Mass Spectrum Analysis;Measures;Mediating;men;Mentored Research Scientist Development Award;Mentors;Messenger RNA;Metabolic;Metabolic Diseases;Metabolism;metabolomics;Methodology;Mitochondria;Modification;Molecular;Monosaccharides;mortality;mouse model;Mus;Mutagenesis;non-alcoholic fatty liver disease;Non-Insulin-Dependent Diabetes Mellitus;novel therapeutics;Nuclear;nutrient metabolism;Obesity;Obesity associated liver disease;Observational Study;overexpression;Pathway interactions;Patients;Persons;Phenotype;Phosphorylation;PPAR alpha;Prevalence;Process;Production;protein expression;Proteins;Proteomics;Radiolabeled;Reducing diet;Regulation;Reporter;Research;Research Institute;Research Personnel;response;Risk Factors;Rodent;Role;Serum;Signal Pathway;Signal Transduction;skills;Small Interfering RNA;SRE-2 binding protein;stable isotope;Stable Isotope Labeling;Sterols;sugar;sweetened beverage;symposium;Techniques;Testing;Tracer;Training;Transcriptional Regulation;Triglycerides;Universities;Water;Woman

PROJECT_TITLE: Elucidating Molecular Mechanisms Linking Fructose to Cholesterol Metabolism

STUDY_SECTION: DDK

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


ADMINISTERING_IC: EB

ED_INST_TYPE: ORGANIZED RESEARCH UNITS

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering

ORG_CITY: CAMBRIDGE

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

PHR: The proposed research is focused on innovative instrumentation that will enable fundamental advances in the field of Dynamic Nuclear Polarization (DNP) NMR at high magnetic fields, making this powerful technique far more readily available and useful to the national and international biomedical research communities. DNP NMR has been demonstrated to increase the signal to noise ratio by a factor of more than 400 in NMR spectroscopy and has foremost applications in the study of structural biology of membrane, soluble and amyloid proteins, but the DNP signal falls off at very high magnetic field. Our pioneering research will build and demonstrate the instrumentation needed for improved signal intensities in high magnetic field DNP NMR by developing pulsed gyrotron oscillators and the necessary switches and modulation techniques for controlling the gyrotron output.

PI_NAMEs: TEMKIN, RICHARD J (contact)

PROGRAM_OFFICER_NAME: WANG, SHUMIN

PROJECT_TITLE: Innovative Instrumentation for High Magnetic Field DNP NMR

STUDY_SECTION: EBIT

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


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Biotechnology;Building Research Capacity at Institutions with Limited NIH Funding;Immunization;Immunotherapy;Infectious Diseases;Orphan Drug;Rare Diseases;Vaccine Related;Vector-Borne Diseases

ORG_CITY: EL PASO

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF TEXAS EL PASO

PHR: Narrative Chagas disease (ChD) is a parasitic disease that affects millions of people in Latino America and is an emerging infectious disease in the USA, Canada and Europe. The available drugs used to treat ChD are very toxic and partially effective. The goal of the proposed research is to develop a novel combine immune and drug therapy to treat chronic ChD.

PI_NAMEs: MALDONADO, ROSA A (contact)

PROGRAM_OFFICER_NAME: BERNAL, FEDERICO

PROJECT_TERMS: Acute;Adjuvant;Affect;Agonist;Animals;Antiparasitic Agents;Australia;Benznidazole;bioluminescence imaging;Canada;cancer therapy;Cardiomyopathies;CD8-Positive T-Lymphocytes;Cell membrane;Chagas Disease;chemotherapy;Chronic;Chronic Phase;Combined Modality Therapy;Country;cytokine;Diagnosis;Disease;Dose;drug candidate;drug standard;Drug usage;effective therapy;Effectiveness;Emerging Communicable Diseases;enzyme linked immunospot assay;Enzyme-Linked Immunosorbent Assay;Europe;experimental study;extracellular vesicles;Flow Cytometry;flu;Goals;Histopathology;Human;Immune response;Immuno-Chemotherapy;Immunologic Memory;Immunotherapeutic agent;Immunotherapy;improved;In Vitro;in vivo;Infection;inhibitor;Japan;Keyhole Limpet Hemocyanin;Latin America;Latino;Leishmaniasis;Measures;Membrane Proteins;Modeling;mouse model;Mucins;Mus;N-myristoyltransferase;neglected tropical diseases;Nifurtimox;nonhuman primate;novel;novel therapeutic intervention;novel therapeutics;Parasitemia;Parasites;Parasitic Diseases;Patients;Peptides;Persons;Pharmaceutical Preparations;Pharmacotherapy;Phase;preclinical development;Preventive vaccine;Production;prophylactic;Public Health;Research;Serious Adverse Event;Spain;Sterility;success;Symptoms;T-Cell Activation;Technology;Testing;Therapeutic;therapeutic vaccine;Trypanosoma cruzi;United States;vaccine candidate;vaccine platform;Vaccines;Validation

PROJECT_TITLE: New Treatments for Chronic Chagas Disease


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

ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

ORG_STATE: CA

PHR: PROJECT NARRATIVE This proposal aims to investigate how the allosteric regulation of the Sodium-Calcium Exchanger (NCX) by intracellular sodium affects heart function. NCX influences heart contractility by extruding cytoplasmic Ca2+ and alterations in its activity are associated with pathological conditions such as chronic heart failure and ischemia- reperfusion. Understanding NCX mechanisms of regulation and their potential physiological impact will assist in designing ways to modulate NCX activity, helping advance knowledge of treatment for heart failure and in developing new therapeutic and pharmacological applications.

PI_NAMEs: OLCESE, RICCARDO ;OTTOLIA, MICHELA  (contact)

PROGRAM_OFFICER_NAME: TJURMINA, OLGA A

PROJECT_TERMS: Action Potentials;Address;Adult;Affect;Allosteric Regulation;Animals;Anti-Arrhythmia Agents;Calcium;Cardiac;Cardiac health;Cardiac Myocytes;Cell membrane;Cells;Cessation of life;Clustered Regularly Interspaced Short Palindromic Repeats;Congestive Heart Failure;Coupling;CRISPR/Cas technology;Cytoplasm;Darkness;Data;design;Development;Drug Targeting;Echocardiography;electrical property;Electrophysiology (science);Equilibrium;Event;Excision;extracellular;Genes;Genomics;Goals;Heart;Heart Contractilities;Heart failure;heart function;Homeostasis;Hypertrophy;Imaging Techniques;in vivo;inhibitor;Investigation;Ions;Ischemia;Knowledge;Link;Measures;mechanical properties;Membrane Potentials;Membrane Proteins;Modification;Mus;Muscle Cells;Mutate;Mutation;Myocardial Ischemia;novel;novel therapeutic intervention;novel therapeutics;operation;Organ;Pathologic;Perception;Perfusion;pharmacologic;Phase;Physiological;Physiology;Play;Process;Property;Proteins;Regulation;Reperfusion Injury;Reperfusion Therapy;Research;Research Personnel;response;Role;Route;Shapes;Site;Sodium;Sodium-Calcium Exchanger;Spottings;System;Ventricular;Work

PROJECT_TITLE: Sodium Dependent Inactivation of the Na+-Ca2+ exchange: Relevance to Cardiac Function

STUDY_SECTION: ESTA

STUDY_SECTION_NAME: Electrical Signaling, Ion Transport, and Arrhythmias Study Section[ESTA]


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: SAN FRANCISCO

ORG_NAME: VETERANS AFFAIRS MED CTR SAN FRANCISCO

PHR: Few neurological conditions are as complex and devastating as stroke. It is a major cause of disability in the United States and in the aging population of veterans. While there have been important strides taken toward optimizing functional recovery, a substantial proportion of stroke survivors continue to experience long-term motor disability. The goal of this proposal is to develop a better neurophysiological model of the circuit basis of recovery and to use this to test new therapeutic approaches. We hope to use this knowledge to create novel therapies to promote motor recovery. 1

PI_NAMEs: GANGULY, KARUNESH  (contact)

PROJECT_TERMS: Affect;aging population;Animals;Area;Behavior;Binding;Brain;Chronic;Complex;Corpus striatum structure;Data;design;disability;Electrophysiology (science);experience;Frequencies;Goals;grasp;Impairment;improved;Individual;kinematics;Knowledge;Learning;Lesion;Link;Long term disability;Medicine;Methods;military veteran;Modeling;Motor;Motor Cortex;Motor disability;motor impairment;motor recovery;motor rehabilitation;Movement;Nature;neural network;Neurologic;neurophysiology;neuroregulation;novel therapeutic intervention;novel therapeutics;Outcome;Pattern;Performance;Play;Population Dynamics;post stroke;Publishing;Recovery;Recovery of Function;recruit;Regulation;Rehabilitation therapy;Residual state;Rodent Model;Role;Site;skills;Source;Stroke;stroke model;stroke rehabilitation;stroke survivor;Testing;Therapeutic;Training;United States;Upper Extremity;Veterans;Work

PROJECT_TITLE: Neurophysiological Basis for Enhancing Motor Recovery After Stroke

STUDY_SECTION_NAME: Brain Health and Injury[RRD1]


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Behavioral and Social Science;Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Dietary Supplements;Hypertension;Microbiome;Nutrition;Precision Medicine;Prevention;Social Determinants of Health

ORG_CITY: CHICAGO

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE We use the existing Illinois Precision Medicine Consortium infrastructure to enroll All of Us Research Program participants to implement DASH diet modules targeting blood pressure reduction. Our clinical study in collaboration with the NPH consortium will provide causal and mechanistic insight into the role diet plays in BP regulation and will provide a preventive foundation for personalized diet recommendations for BP control.

PI_NAMEs: ASCHEBROOK-KILFOY, BRISEIS A;BURTON-FREEMAN, BRITT ;CORNELIS, MARILYN C;HO, JOYCE ;VAN HORN, LINDA VERNER (contact)

PROGRAM_OFFICER_NAME: CLARK, DAVID

PROJECT_TERMS: Adherence;Algorithms;All of Us Research Program;Behavioral;Beverages;Bioinformatics;Biological;Biological Markers;Black Populations;Blood Pressure;blood pressure control;blood pressure reduction;blood pressure regulation;Calories;cardiometabolism;Cardiovascular Diseases;cardiovascular risk factor;Cardiovascular system;Cerebrovascular Disorders;Chicago;Cities;Clinic Visits;Clinical;clinical center;Clinical Research;clinical research site;clinical trial participant;Collaborations;Communities;Complex;Consent;Controlled Environment;DASH diet;Data;Data Collection;data resource;Diet;dietary;dietary adherence;dietary constituent;Dietary Intervention;Dietary Practices;Dietary Sodium;Domiciles;Eating;egg;Elements;Enrollment;Environmental Risk Factor;epidemiology study;Ethnic Origin;Fatty acid glycerol esters;feeding;Flavonoids;Food;Food Patterns;Foundations;Fruit;Genetic;Genetic Status;Geography;Goals;Grain;Health;Health Personnel;Health Service Area;Hypertension;hypertensive;Illinois;Individual;individual response;individual variation;Infrastructure;insight;Intake;inter-individual variation;Intervention;Investigation;Kidney Diseases;Knowledge;Link;Measures;Mediating;metabolomics;Methods;microbial;microbiome;microbiome research;Modeling;modifiable risk;Morbidity - disease rate;mortality;novel;novel marker;nutrition;Nutritional;nutritional genomics;Nutritional Science;Nutritional Study;Outcome;Participant;Pathway interactions;Patient Self-Report;personalized nutrition;Physiological;Plant Proteins;Play;Population;population based;Population Characteristics;population health;Precision Health;precision medicine;precision nutrition;premature;prevent;Preventive;primary outcome;Property;Protocols documentation;Public Health;Race;Randomized, Controlled Trials;Recommendation;recruit;Reporting;Research;Research Personnel;response;Risk;Role;Science;Site;socioeconomics;Sodium;Specific qualifier value;Subgroup;systematic review;Techniques;Technology;Testing;Time;Universities;Variant;Vegetables

PROJECT_TITLE: Nutrition Precision Health for All of Us (Chicago Center)


ADMINISTERING_IC: ES

ED_INST_TYPE: SCHOOLS OF NURSING

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Effects of Indoor Air Pollution;Rural Health;Social Determinants of Health

ORG_DEPT: OTHER HEALTH PROFESSIONS

PHR: PROJECT NARRATIVE The public is concerned about the high rates of lung cancer from environmental exposure to tobacco smoke and radon. We will identify geological and atmospheric conditions that increase radon intrusion into homes, translate this knowledge into increased residential awareness of lung cancer risk, facilitate home radon testing and report back, and increase access to affordable and adequate radon mitigation. By bringing residents and traditional (e.g., public libraries) and non-traditional (e.g., low interest loan providers) organizations to the table to reduce radon exposure, the way communities address environmental health issues will be transformed.

PI_NAMEs: HAHN, ELLEN J (contact)

PROGRAM_OFFICER_NAME: O'FALLON, LIAM

PROJECT_TERMS: Address;Advocate;Atmosphere;atmospheric conditions;Awareness;Back;cancer risk;Certification;Charcoal;citizen science;Collaborations;Communities;cost;County;Data;Data Analyses;Data Collection;design;Detection;detector;Diagnostic Reagent Kits;digital;Disease;Environment;Environmental Exposure;Environmental Health;Environmental Risk Factor;environmental tobacco smoke exposure;Equipment;Feedback;Gases;Geological Survey;Geology;Geoscience;Health;health literacy;Home;home test;improved;Information Dissemination;information seeking behavior;interest;Kentucky;Knowledge;knowledge integration;Libraries;Low income;Malignant neoplasm of lung;Maps;Marketing;Measurement;member;Monitor;novel;Outcome;Policy Maker;Precipitation;Procedures;programs;Property;Provider;Radon;Reach, Effectiveness, Adoption, Implementation, and Maintenance;remediation;Reporting;Risk;Rural;Rural Community;Sampling;Seasons;Self Efficacy;Smoking;Soil;Technology;Temperature;Testing;Time;time use;Tobacco smoke;Training;Translating;usability;web site

PROJECT_TITLE: Radon on the RADAR

STUDY_SECTION: CIHB

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


NIH_SPENDING_CATS: Biotechnology;Brain Cancer;Brain Disorders;Cancer;Immunotherapy;Neurosciences;Orphan Drug;Rare Diseases

ORG_CITY: CHARLOTTESVILLE

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: Glioblastoma (GBM) is the most common and lethal brain cancer, and there is a dire need for new therapeutic approaches. We previously showed that Diacylglycerol kinase-α (DGKα) is a potential therapeutic target for GBM, with DGKα inhibition having the exciting potential to directly attack cancer cells but possibly also boost the anti-tumor immune response. More recently we showed that the abandoned drug ritanserin could be repurposed as a DGKα inhibitor, potentially accelerating the clinical development of this strategy. Ritanserin has shown greater promise in combination with other agents. Our newest results show that intermittent dosing of ritanserin—with a low dose every two to three days—is extremely effective in a mouse model of GBM with an intact immune system. We have also found a potential new mechanism of DGKα inhibition in the immune system. This proposal will test the effects of DGKα inhibition on these immune cells, as well as following up on the mechanisms and activity of intermittent low dosing of DGKα inhibitors, alone and combined with other agents, in treating GBM in mouse models. The results should inform the clinical development of DGKα inhibition as a novel treatment for GBM and identify new mechanisms.

PI_NAMEs: PUROW, BENJAMIN W. (contact)

PROGRAM_OFFICER_NAME: KOTLIAROVA, SVETLANA

PROJECT_TERMS: Acceleration;Affect;Aftercare;angiogenesis;anti-PD-1;anti-PD1 antibodies;anti-tumor immune response;Area;Binding;Biological Availability;Biological Response Modifiers;blood-brain barrier penetration;Brain Neoplasms;cancer cell;Cells;Cessation of life;checkpoint inhibition;chemotherapy;clinical development;clinical investigation;clinical translation;Combined Modality Therapy;CSF1R gene;cytokine;Data;Diacylglycerol Kinase;Dichloromethylene Diphosphonate;Diglycerides;Dose;exhaustion;Family;Family member;follow-up;Glioblastoma;Grant;Half-Life;Hour;Human;Immune;immune checkpoint;Immune system;Immunity;Immunocompetent;immunodeficiency;Immunologics;Immunotherapeutic agent;Immunotherapy;improved;In Vitro;in vitro testing;in vivo;Inflammatory;inhibitor;Knockout Mice;Ligands;Lipids;Liposomes;Literature;Macrophage;Malignant neoplasm of brain;Malignant Neoplasms;Mediating;member;Mesenchymal;Microglia;Modeling;mouse model;Mus;Natural Killer Cells;novel;novel therapeutic intervention;Oncology;Operative Surgical Procedures;Oral;Orphan Drugs;Patients;PD-1 inhibitors;Pharmaceutical Preparations;pharmacologic;Phenotype;Phosphatidic Acid;Phosphotransferases;Physiologic pulse;Positioning Attribute;Primary Brain Neoplasms;programmed cell death ligand 1;protein geranylgeranyltransferase;Protein Isoforms;Proteins;Radiation;Receptor Inhibition;Refractory;Regimen;Regulation;Reporting;Resistance;restraint;Ritanserin;Role;serotonin receptor;Stimulus;T cell anergy;T-Lymphocyte;targeted treatment;temozolomide;Testing;Therapeutic;therapeutic target;Toxic effect;translational therapeutics;treatment comparison;Treatment Protocols;Wild Type Mouse

PROJECT_TITLE: Novel immunotherapeutic potential of DGKalpha inhibition for glioblastoma

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


NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Project Narrative The human genome sequence lays the foundation for identifying disease‐associated mutations and genetic variations, insights into gene regulation, genomic tools, and therapeutics. We and others discovered a novel class of long non‐coding (lnc)RNAs called DoGs (for “downstream of genes”) expressed when cells experience stress (e.g. heat, high salt, oxidative stress, viral infection and cancer); DoGs are rapidly produced when transcription of normal genes aberrantly continues. We will apply the most recent advances in RNA sequencing technology and functional genomic approaches to discover the role(s) of DoG RNAs in cell physiology.

PI_NAMEs: NEUGEBAUER, KARLA M (contact);STEITZ, JOAN A.

PROGRAM_OFFICER_NAME: RIGAS, MARC

PROJECT_TERMS: Achievement;Address;Aging;Architecture;Back;Biogenesis;Cell Nucleus;Cell Physiology;Cell Survival;cell type;Cells;Cellular Stress;Chromatin;Chromosomes;Code;Data;Disease;Environment;Exons;experience;exposed human population;Exposure to;Failure;Feedback;Feeds;first responder;Foundations;functional genomics;Gene Expression;Gene Expression Profile;Gene Expression Regulation;Gene Order;gene repression;Genes;Genetic Transcription;Genetic Variation;Genomic approach;genomic tools;Goals;Health;Heat Stress;Heat-Shock Response;Histones;Human;Human Cell Line;Human Genome;Individual;Infection;insight;Interferon-beta;Interferons;Introns;knock-down;Knowledge;Learning;Length;Libraries;Malignant Neoplasms;Mediating;Messenger RNA;Methodology;Methods;Modeling;Modification;Molecular;Mouse Cell Line;mRNA Precursor;Mus;Mutation;novel;Nuclear;Nuclear RNA;Osmosis;Outcome;Oxidative Stress;Parents;Pathway interactions;Pattern;physiologic stressor;Physiological;Play;Poly A;Polymerase;Post-Translational Protein Processing;Preparation;Production;Proteins;Publishing;Recording of previous events;Recovery;Regulation;repository;Research;response;RNA;RNA analysis;RNA chemical synthesis;RNA Polymerase II;RNA Processing;RNA Splicing;Role;Site;Sodium Chloride;Stress;Structure;Technology;Testing;Therapeutic;therapeutic RNA;Transcript;Transcription Elongation;Transcription Initiation Site;transcriptome;transcriptome sequencing;Untranslated RNA;Viral Cancer;Virus Diseases;Withdrawal;Work

PROJECT_TITLE: Biogenesis and function of a novel class of stress-induced long non-coding RNAs

STUDY_SECTION: MGA

STUDY_SECTION_NAME: Molecular Genetics A Study Section[MGA]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Bioengineering;Biotechnology;Emerging Infectious Diseases;Hematology;Infectious Diseases;Sepsis

ORG_CITY: Newark

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: PROJECT NARRATIVE  This project will develop a highly specific, sensitive, rapid, and easy to use a point of care test to rapidly detect blood stream infections due to the fungi Candida and Cryptococcus including Candida auris and Cryptococcus gattii, newly emerging diseases. This research will benefit public health by increasing the speed that these infections can be detected, ensuring that the best treatment for each specific infecting organism is selected.

PI_NAMEs: ALLAND, DAVID  (contact)

PROGRAM_OFFICER_NAME: RITCHIE, ALEC

PROJECT_TERMS: Affect;amplification detection;antigen detection;antigen test;assay development;Bacteria;base;Biological Assay;Blood;Blood Circulation;Blood specimen;Blood Tests;Blood Volume;Buffers;Candida;Candida albicans;Candida auris;Candida glabrata;candidemia;Cerebrospinal Fluid;Cessation of life;Clinical;Clinical Trials;clinically relevant;Code;Collaborations;Communicable Diseases;Cryptococcus;Cryptococcus gattii;Cryptococcus neoformans;design;Detection;detection assay;Development;Diagnosis;Diagnostic;diagnostic assay;Disease;DNA Sequence;Dryness;effective therapy;Ensure;experience;FDA approved;Freeze Drying;Fungemia;fungus;HIV;Immunocompromised Host;improved;Individual;Infection;Infection Control;innovation;Laboratories;Lateral;Life;low and middle-income countries;Magnetic Resonance;Medical Care Costs;melting;Methods;Molds;mortality;Multi-Drug Resistance;Mycoses;Nested PCR;novel strategies;Nucleic Acids;organ transplant recipient;Organism;Pacific Northwest;pandemic disease;Patient Care;Patients;Performance;Phase;Pneumonia;point of care;point of care testing;point-of-care diagnostics;preclinical study;Preparation;Probability;Process;prototype;Public Health;rapid detection;rapid diagnosis;Reaction;Reagent;Reporting;Research;Risk;Sampling;Sensitivity and Specificity;Serum;Signal Transduction;Solid;Specificity;Speed;Staphylococcus aureus;Stream;Technology;Temperature;Testing;testing access;Time;Training;treatment duration;United States;user-friendly;Virulent

PROJECT_TITLE: Simple and rapid POC detection for fungemia

STUDY_SECTION: CRFS

STUDY_SECTION_NAME: Clinical Research and Field Studies of Infectious Diseases Study Section[CRFS]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Anxiety Disorders;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Mental Health;Mental Illness;Post-Traumatic Stress Disorder (PTSD)

ORG_CITY: GREENSBORO

ORG_NAME: UNIVERSITY OF NORTH CAROLINA GREENSBORO

PHR: Project Narrative Posttraumatic stress disorder (PTSD) is a debilitating and chronic psychiatric illness associated with severe personal and public costs that affects approximately 6.4% of the U.S. population (~21 million Americans). Although PTSD is characterized by inflexible emotion regulation across experiential, behavioral, and physiological systems, little is known about how emotion regulation manifests into rigid response patterns that are crucial to the maintenance of this disorder. This proposal seeks to evaluate the interplay between negative emotion differentiation (NED), or the extent to which people discretely experience negative emotions, and self-reported avoidance and resting respiratory sinus arrythmia in PTSD using ambulatory assessment (i.e., ecological momentary assessment, ambulatory psychophysiology), and offers the potential to improve our understanding of how PTSD is developed and maintained over time.

PI_NAMEs: PUGACH, CAMERON  (contact)

PROGRAM_OFFICER_NAME: AVENILLA, FRANK R

PROJECT_TERMS: Active Learning;Adult;Affect;American;Behavioral;Belief;biological adaptation to stress;Biological Markers;Brain region;Cardiac;Chronic;Clinical;Communities;conditioned fear;cost;Cues;Data;Diagnosis;Diagnostic;Disease;Drops;Ecological momentary assessment;Educational workshop;emotion regulation;Emotional;Emotions;Environment;environmental adaptation;Etiology;experience;Exposure to;Extinction;falls;Feeling;flexibility;Fright;Functional impairment;Funding;Goals;Grain;Health Care Costs;Heart Rate;Impairment;improved;indexing;Individual;information processing;insight;Intervention;Investigation;Knowledge;Label;Laboratories;Learning;Life;Link;Maintenance;Measurement;Measures;member;Mental disorders;Mentorship;Modeling;Monitor;multilevel analysis;National Institute of Mental Health;National Research Service Awards;negative affect;negative emotional state;Neurocognitive Deficit;Outcome;Parasympathetic Nervous System;Patient Self-Report;Pattern;Periodicity;Peripheral;Persons;physical conditioning;Physiological;Population;Populations at Risk;post-traumatic stress;Post-Traumatic Stress Disorders;Prevalence;prevent;Process;productivity loss;psychiatric comorbidity;psychologic;Psychophysiology;Public Health;Regulation;Research;Respiration;respiratory;response;Rest;Risk;Role;Self Perception;Services;Severities;Sinus;skills;Stimulus;suicidal;symptomatic improvement;Symptoms;System;Testing;theories;Time;Training;trait;Trauma;trauma exposure;Trauma recovery;traumatic event;United States National Institutes of Health;Variant

PROJECT_TITLE: The Interplay Between Negative Emotion Differentiation and Emotion Regulation Problems in Posttraumatic Stress Disorder


NIH_SPENDING_CATS: Biotechnology;Immunization;Infectious Diseases;Prevention;Sexually Transmitted Infections;Urologic Diseases;Vaccine Related;Women's Health Research

ORG_CITY: ALBUQUERQUE

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR

ORG_STATE: NM

PHR: PROJECT NARRATIVE Chlamydia trachomatis is the most common bacterial sexually transmitted infection, causing infertility, ectopic pregnancy, and pelvic inflammatory disease in women. Despite the availability of effective treatment, the prevalence of chlamydia continues to rise, highlighting the need for a prophylactic vaccine. This proposal seeks to identify Chlamydia trachomatis vaccine candidates by investigating the functions of antibodies to specific epitopes of Chlamydia trachomatis proteins involved in binding and entering host cells, providing a novel approach for Chlamydia trachomatis vaccine development.

PI_NAMEs: FRIETZE, KATHRYN M. (contact)

PROGRAM_OFFICER_NAME: CONNOLLY, KRISTIE LEE

PROJECT_TERMS: Adhesions;Animal Model;Antibiotic Therapy;Antibodies;Antibody Response;Antibody Specificity;antibody test;Antibody titer measurement;Antibody-mediated protection;Antigens;Automobile Driving;Bacteria;Bacteriophages;Binding;CD4 Positive T Lymphocytes;Cell Culture Techniques;Cells;Chlamydia;Chlamydia Infections;Chlamydia trachomatis;chlamydia vaccine;Complement;Data;design;Ectopic Pregnancy;effective therapy;Engineering;Epitopes;experience;Female;female reproductive tract;Genitourinary system;Genitourinary System Infection;Goals;Human;Immune;Immune response;Immune Sera;Immunity;Immunization;Immunize;immunogenic;immunogenicity;In Vitro;in vitro Assay;in vivo;Infection;Infertility;innovation;interest;Interferon Type II;Knowledge;Licensing;long-term sequelae;major outer membrane protein;male;Mediating;mouse model;Mucous Membrane;Mus;Nature;neutrophil;novel;novel strategies;Oryctolagus cuniculus;Passive Transfer of Immunity;Pathology;Pelvic Inflammatory Disease;Peptides;Phagocytes;Prevalence;Preventive vaccine;prophylactic;Proteins;Publishing;Recording of previous events;reproductive tract;Research;response;Role;Safety;screening program;Sexually Transmitted Diseases;T cell response;T-Lymphocyte;Test Result;Testing;treatment program;tubal infertility;United States National Institutes of Health;uptake;urogenital tract;vaccine access;vaccine candidate;Vaccine Design;vaccine development;vaccine platform;vaccine strategy;Vaccines;Virus-like particle;Woman;Work

PROJECT_TITLE: Bacteriophage virus-like particle vaccines for Chlamydia trachomatis urogenital infection

STUDY_SECTION: VMD

STUDY_SECTION_NAME: Vaccines Against Microbial Diseases Study Section[VMD]


ORG_NAME: DANA-FARBER CANCER INST

PHR: PROJECT NARRATIVE Some small cell lung cancers (SCLCs) are highly and selectively sensitive to inhibition of the histone demethylase LSD1, but the biological mechanisms utilized by LSD1 to drive SCLC are not well understood. This proposal seeks to understand the underlying causative mechanisms by which LSD1 drives SCLC tumorigenesis and neuroendocrine differentiation utilizing both cell lines and isogenic CRISPR-based in vivo mouse models. We will also test a rational combination therapeutic approach to overcome LSD1 inhibitor resistance, which if successful, could ultimately have a significant impact on treatment strategies for this recalcitrant cancer.

PI_NAMEs: OSER, MATTHEW GILBERT (contact)

PROGRAM_OFFICER_NAME: FORRY, SUZANNE L

PROJECT_TERMS: 3' Untranslated Regions;ASCL1 gene;Binding;Binding Proteins;Biological;Cancer cell line;Cancer Patient;Cell Line;Chromatin;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;CRISPR/Cas technology;Data;derepression;Engineering;Epigenetic Process;experimental study;Foundations;Gene Expression;gene repression;Genes;Genetic;Genetic study;Genetically Engineered Mouse;genome-wide;genomic locus;Goals;histone demethylase;Immunocompetent;immunodeficiency;immunogenicity;In Vitro;in vivo;Induction of Apoptosis;inhibitor;insight;KDM1A gene;Laboratories;Link;loss of function;Malignant Neoplasms;MAP Kinase Gene;MEK inhibition;Messenger RNA;Minority;Modeling;Molecular;mouse model;Mus;mutant;Neuroendocrine Cell;neuroendocrine differentiation;neuroendocrine phenotype;Neuroendocrine Tumors;Neurosecretory Systems;novel;Pathway interactions;patient derived xenograft model;Patient Selection;pre-clinical;Pre-Clinical Model;predictive marker;Principal Investigator;Proliferating;Repression;Research;Resistance;screening;selective expression;small cell lung carcinoma;targeted treatment;Testing;Therapeutic;treatment strategy;tumor;tumor initiation;tumorigenesis;ubiquitin ligase;Validation;Writing

PROJECT_TITLE: Mechanisms by which LSD1 Promotes Neuroendocrine Differentiation and Small Cell Lung Cancer

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


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Infectious Diseases;Prevention;Tickborne Diseases;Vector-Borne Diseases

ORG_CITY: HADLEY

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF MASSACHUSETTS AMHERST

PHR: Project Narrative Electronic biosensors are important for health diagnostics, disease prevention and treatment, although nonspecific charge interferences have prevented conventional biosensors from real-time detection in physiological environment. The proposed research intends to bring in and validate a new biosensor concept, which can be free of nonspecific interference and provide generic solution to the specific biodetection in physiological environment, potentially leading to advanced biomedical devices for point-of-care diagnostics. The sensor concept will be concreted by implementing it in the early detection of tick-borne diseases, which currently have imposed serious threat to public health but lacked timely diagnostics.

PI_NAMEs: YAO, JUN  (contact)

PROGRAM_OFFICER_NAME: MULVANEY, SHAWN PATRICK

PROJECT_TERMS: antibody detection;Area;Binding;biochip;Biological;Biological Markers;Biosensing Techniques;Biosensor;Charge;Chemical Interference;clinical diagnostics;Data;design;Detection;Devices;Diagnosis;Diagnostic;Disease;disease diagnosis;disorder prevention;Early Diagnosis;electrical measurement;Electronics;Environment;Exposure to;FDA approved;fluid flow;Future;Goals;Health;Human;Human Bites;Immune response;improved;In Vitro;Intervention;Ionic Strengths;Lyme Disease;mechanotransduction;Microfluidics;Monitor;multiplex detection;nano;nanowire;Nucleic Acids;Organelles;pathogen;Pathogen detection;Performance;Physiological;Play;point-of-care diagnostics;Preparation;prevent;Prevention;Public Health;receptor;Research;resilience;Resolution;Risk;Role;Sampling;screening;sensor;Signal Transduction;Silicon;structural imaging;Structure;System;Techniques;Testing;tick bite;Tick-Borne Diseases;tick-borne pathogen;Ticks;Time;Transcend;Transistors;transmission process;Validation

PROJECT_TITLE: Bioinspired mechanogating biosensors for real-time biodetection


NIH_SPENDING_CATS: Hematology

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: PROJECT NARRATIVE Studies proposed here are designed to elucidate mitochondrial-mediated mechanisms that contribute to red blood cell (RBC) production, are specifically involved in last stages of precursor maturation and may be altered in erythroid disorders. Specifically, the findings from this application are aimed at identifying new components of the RBC production path to devise effective organelle- based therapies for erythroid disorders and efficacious approaches for improving RBC generation.

PI_NAMEs: GHAFFARI, SAGHI  (contact)

PROGRAM_OFFICER_NAME: QASBA, PANKAJ

PROJECT_TERMS: Address;Area;Biology;Cell Differentiation process;Cell Maturation;Cells;Chromatin;Collaborations;Communication;Computational Biology;confocal imaging;design;differential expression;Disease;efficacious treatment;Erythroblasts;Erythrocytes;Erythroid;Erythroid Cells;Erythropoiesis;Exhibits;Exposure to;FOXO3A gene;Gene Modified;Generations;Genes;Genomic approach;Genomics;Glycolysis;Goals;Hemoglobin;improved;In Situ;Knowledge;Label;Mediating;Membrane Potentials;Metabolic Pathway;metabolic profile;metabolomics;Mitochondria;mitochondrial membrane;Modeling;Moderate Activity;Morphology;Mus;novel therapeutics;Nuclear;Organelles;Pathway interactions;Phenotype;Phosphotransferases;Physical condensation;Physiological;PINK1 gene;Positioning Attribute;Process;Production;programs;Property;Pyruvate;Pyruvates;Regulation;Research;segregation;Shapes;superresolution imaging;Technology;Testing;Therapeutic;Therapeutic Intervention;transcription factor

PROJECT_TITLE: Mitochondria in the Regulation of Terminal Erythropoiesis

STUDY_SECTION: BBHV

STUDY_SECTION_NAME: Basic Biology of Blood, Heart and Vasculature Study Section [BBHV]


FUNDING_MECHANISM: RESEARCH CENTERS

ORG_CITY: GAINESVILLE

ORG_NAME: VETERANS HEALTH ADMINISTRATION

PHR: Poor emotion recognition has been associated with poor quality of interpersonal relationships, loss of employment, behavioral problems, reduced social reintegration, social isolation and even suicide. Deficits in emotion recognition are common in traumatic brain injury (TBI) and in post-traumatic stress disorder (PTSD) but these deficits have not been well studied in Veterans with both mild TBI (mTBI) and PTSD. Currently there are no interventions for emotion recognition in Veterans with mTBI and PTSD, and interventions for severe TBI have lacked training of both facial and vocal emotion recognition. In a preliminary study of an innovative combination of facial and vocal modalities, a multimodal affect recognition training (MMART) showed promise but lacked attention training that is an essential component in recognizing emotions in our daily lives. Given the need to improve relationships and productivity in Veterans with mTBI and PTSD, a study is needed to determine the effectiveness of a MMART combined with attention training.

PI_NAMEs: WAID-EBBS, JULIA KAY (contact)

PROJECT_TERMS: Address;Affect;Affective;Aftercare;Attention;Brain;Clinical;clinical care;Cognitive;cohort;Communication;community reintegration;Complex;Control Groups;Deterioration;Development;effectiveness evaluation;efficacy study;Emotional;Emotions;Employment;Exhibits;experience;Expressed Emotion;Face;Facial Expression;feasibility testing;Florida;Functional disorder;Future;Hour;Image;Impairment;improved;indexing;innovation;Interpersonal Relations;Intervention;Life;Linear Regressions;Loudness;Measures;Methods;mild traumatic brain injury;Modality;multimodality;Multiple Sclerosis;neurological rehabilitation;Neuropsychology;novel;Outcome;Parkinson Disease;Participant;Performance;Persons;Post-Traumatic Stress Disorders;Problem behavior;Process;Productivity;Protocols documentation;Quality of Care;Quality of life;Randomized;Randomized, Controlled Trials;Rehabilitation therapy;Research Design;Resolution;response;Role;Sampling;selective attention;service member;showing emotion;social;social communication;Social Interaction;Social isolation;Stimulus;Stroke;Suicide;sustained attention;Task Performances;Testing;Time;Training;Translating;Traumatic Brain Injury;treatment effect;treatment group;treatment response;trend;verbal;Veterans;Work

PROJECT_TITLE: Innovative multimodal and attention training to improve emotion communication in Veterans with TBI and PTSD

STUDY_SECTION: RRDS

STUDY_SECTION_NAME: Rehabilitation Research and Development SPiRE Program[RRDS]


NIH_SPENDING_CATS: Autism;Brain Disorders;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Pediatric;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: BERKELEY

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: Narrative Infection during pregnancy is known to increase the probability of offspring developing autism, yet the mechanism is not fully understood. Recently, we have found that fetal macrophages in the brain may secrete a pro-inflammatory molecule that we hypothesize could accelerate inflammation and disturb the proper development of neurons. This project aims to elucidate the mechanism of action of this pro-inflammatory molecule and determine whether its inhibition could be a new therapeutic strategy for treating autism induced by infection during pregnancy.

PI_NAMEs: COSCOY, LAURENT  (contact)

PROGRAM_OFFICER_NAME: KAU, ALICE S

PROJECT_TERMS: Acceleration;adaptive immunity;Affect;Amniotic Fluid;Antibodies;Area;autism spectrum disorder;autocrine;Behavior;behavioral phenotyping;Biological Assay;Blood;Brain;brain cell;CCL2 gene;Cell Line;Cells;Cerebrospinal Fluid;Child;Chronic;chronic inflammatory disease;COVID-19 severity;cytokine;Data;Development;Diagnosis;Disease;effective therapy;Embryo;Environmental Risk Factor;Enzyme-Linked Immunosorbent Assay;Exposure to;Female;fetal;Fetus;Genetic;Human;IL17 gene;Immune;immune activation;immune stimulant;Immunofluorescence Immunologic;Impairment;Infection;Inflammation;Inflammation Mediators;Inflammatory;Innate Immune Response;Innate Immune System;Interleukin-6;Leukocyte L1 Antigen Complex;Ligands;Macrophage;male;maternal immune system;Measures;Mediating;Meninges;Microglia;migration;model of autism spectrum disorder;Modeling;Molecular;Mothers;mouse model;Mus;nerve stem cell;Neurodevelopmental Disorder;neuron development;neutralizing antibody;novel therapeutic intervention;offspring;paracrine;Pathogenesis;Placenta;Poly I-C;Pregnancy;pregnant;Probability;Proliferating;Proteins;Reporting;response;Role;Sepsis;Signal Transduction;Signaling Molecule;single nucleus RNA-sequencing;single-cell RNA sequencing;stem cell function;stem cell homeostasis;Structure of choroid plexus;Testing;Therapeutic;therapeutically effective;Time;TLR3 gene;TLR4 gene;Toll-like receptors;Ventricular;Virus;Virus Diseases;Wild Type Mouse;Work

PROJECT_TITLE: Roles of Calprotectin in a mouse model of maternal immune activation


NIH_SPENDING_CATS: Cancer;Clinical Research;Digestive Diseases;Immunotherapy;Orphan Drug;Pancreatic Cancer;Rare Diseases

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: PROJECT NARRATIVE The dismal outcomes of pancreatic cancer and its unresponsiveness to immunotherapy is, in part, due to the pro-tumorigenic, immunosuppressive tumor microenvironment engendered by infiltrating myeloid and fibroblastic cells. We have identified MerTK, Tyro3 and Axl receptor tyrosine kinases as important but distinct regulators of immunosuppressive myeloid cells and potentially cancer-associated fibroblasts. This research will elucidate mechanisms by which these kinases hinder the immune response and will evaluate novel, clinically applicable therapeutic agents that could magnify the response to current immunotherapies.

PI_NAMEs: EARP, H. SHELTON (contact);PYLAYEVA-GUPTA, YULIYA

PROGRAM_OFFICER_NAME: WATSON, JOANNA M

PROJECT_TERMS: Acceleration;anti-PD-1;anti-PD1 therapy;Antigen Presentation;Apoptotic;attenuation;Autoimmunity;axl receptor tyrosine kinase;Biological Availability;Blood;Cancer Etiology;CD4 Positive T Lymphocytes;Cell Physiology;Cells;Cessation of life;chemotherapy;Chronic;Circulation;clinical application;Clinical Trials;Complex;Cues;Cytotoxic Chemotherapy;Data;Diagnosis;Disease;druggable target;effector T cell;efficacy testing;Elements;Family;Fibroblasts;Frequencies;Frustration;Gene Expression;Gene Expression Profile;Genetic;Germ Lines;Goals;Growth;Heterogeneity;Human;Immune;immune cell infiltrate;Immune response;Immunity;immunogenic cell death;Immunologic Monitoring;Immunologics;Immunotherapy;Incidence;Infiltration;Inflammation;Inflammatory Response;inhibitor;Interferons;kinase inhibitor;knockout animal;Ligands;lymph nodes;Macrophage;Malignant neoplasm of pancreas;Malignant Neoplasms;Mediating;Metastatic Neoplasm to the Liver;Modeling;monocyte;mouse model;Mus;Myelogenous;Myeloid Cells;Myeloid-derived suppressor cells;neoplasm immunotherapy;Neoplasm Metastasis;Neoplasms;neoplastic cell;novel;Operative Surgical Procedures;Oral;Outcome;Paclitaxel;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma model;paracrine;Patients;PD-1 blockade;phase I trial;Phenotype;Phosphotransferases;Play;pre-clinical;Pre-Clinical Model;prevent;programs;Radiation therapy;Receptor Protein-Tyrosine Kinases;Regulation;Research;Resistance;response;restraint;Role;Signal Transduction;single cell sequencing;small molecule inhibitor;success;synergism;T cell infiltration;T-Cell Proliferation;T-Lymphocyte;targeted treatment;Testing;Therapeutic;Therapeutic Agents;Therapeutic Uses;therapy resistant;Time;trafficking;tumor;tumor growth;Tumor Immunity;tumor microenvironment;tumor-immune system interactions;tumorigenic;Wild Type Mouse;Work

PROJECT_TITLE: Divergent Roles of MerTK,Tyro3, and Axl in Pancreatic Cancer and Metastasis

STUDY_SECTION: CII

STUDY_SECTION_NAME: Cancer Immunopathology and Immunotherapy Study Section[CII]


ORG_CITY: Aurora

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: Project Narrative Most melanomas fail to immune checkpoint blockade therapy because of lack of immune cells within the tumors. Our proposed study will look at how a newly- identified chemokine scavenger on tumor lymphatics regulates immune cell infiltration into melanoma, with the aim of targeting this molecule for immunotherapy.

PI_NAMEs: ZHU, YUWEN  (contact)

PROGRAM_OFFICER_NAME: CARDONE, MARCO

PROJECT_TERMS: Ablation;anti-tumor immune response;antitumor effect;Binding;Biological Assay;cancer immunotherapy;CD8-Positive T-Lymphocytes;cell motility;Cell Therapy;Cells;Characteristics;checkpoint therapy;chemokine;chemokine receptor;Clinical;CXCL10 gene;CXCL9 gene;CXCR3 gene;effector T cell;Endocytosis;Endothelial Cells;Endothelium;Exhibits;Extracellular Matrix;G-Protein-Coupled Receptors;Generations;Genetic;Glycosaminoglycans;Homing;Human;Image;Immune;immune cell infiltrate;immune checkpoint blockade;immune function;Immune response;Immunity;Immunologic Sensitization;Immunologics;immunoregulation;Immunotherapy;improved;In Vitro;in vivo;Infiltration;Inflammation;Inflammatory;Investigation;Leukocytes;Ligands;Lymphatic;Lymphatic Endothelial Cells;Malignant Neoplasms;Melanoma;Melanoma Tumor;migration;Modeling;Molecular;Monoclonal Antibodies;Mus;Mutagenesis;neoplasm immunotherapy;novel;novel strategies;Orphan;Outcome;Pathway interactions;Patients;Peptides;Play;Positioning Attribute;Pre-Clinical Model;Publications;receptor;Refractory;Research Proposals;Role;scavenger receptor;Stromal Cells;T cell infiltration;T cell response;T-Lymphocyte;targeted cancer therapy;Techniques;Testing;Therapeutic;Tissues;tumor;tumor growth;Tumor Immunity;tumor microenvironment;tumor progression;two photon microscopy

PROJECT_TITLE: Melanoma Immunotherapy with GPR182 blockade


NIH_SPENDING_CATS: Bioengineering;Cancer;Eye Disease and Disorders of Vision;Radiation Oncology;Rare Diseases

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: Project narrative / public health relevance statement Eye plaque brachytherapy has been an effective and established treatment for intraocular melanoma (the most common eye cancer in adults) and retinoblastoma (the most common eye cancer in children). Unlike the general trend in external beam radiotherapy, the advancement of plaque therapy lags behind in terms of intensity modulated delivery due to the limitation in the current capability of quality assurance. This project aims to develop a novel, easy-to-use, and low-cost device that allows fast and accurate quality assurance of loaded plaques, thereby ensuring the safety of patient treatment and facilitating the utilization of intensity modulation in plaque therapy.

PI_NAMEs: XING, LEI  (contact)

PROGRAM_OFFICER_NAME: OBCEMEA, CEFERINO H

PROJECT_TERMS: 3D Print;Address;Adult;Affect;Air;base;Biological Assay;Biological Models;Brachytherapy;Calibration;Clinical;clinical center;clinically significant;Computer software;cost;cost effective;Data;design;design and construction;detector;Device Designs;Devices;Diameter;digital;Distributional Activity;Dose;Ensure;Evaluation;experimental study;External Beam Radiation Therapy;Eye;Eye Neoplasms;flexibility;Geometry;Glues;Goals;Gold;Health;Human;Human Resources;Image;image guided;implantation;improved;Individual;Intensity-Modulated Radiotherapy;lens;Lesion;Libraries;Location;Malignant Childhood Neoplasm;malignant neoplasm of eye;Malignant Neoplasms;Measurement;Measures;Methodology;Methods;Modality;Modeling;Molds;Monte Carlo Method;Normal tissue morphology;novel;Operative Surgical Procedures;Optics;Organ;Outcome;patient oriented;patient safety;Patients;Pattern;Performance;personalized medicine;Positioning Attribute;Process;programs;prototype;public health relevance;quality assurance;Radiation therapy;Radioactive;Radioactivity;Recommendation;Reporting;Research Design;Retinoblastoma;Safety;Sclera;Secure;Shapes;Side;Signal Transduction;Software Tools;Source;Structure;Surface;Surgical sutures;System;Techniques;Testing;theories;Thinness;Time;Toxic effect;treatment optimization;treatment planning;trend;tumor;Uncertainty;Uveal Melanoma;Vendor;Visual

PROJECT_TITLE: Improving the Safety and Quality of Eye Plaque Brachytherapy by Assembly with Intensity Modulated Loading


NIH_SPENDING_CATS: Bioengineering;Brain Cancer;Brain Disorders;Cancer;Genetics;Nanotechnology;Rare Diseases

ORG_CITY: MINNEAPOLIS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: PROJECT NARRATIVE An explosion of recent studies has indicated that altered mechanical forces in a cell’s environment is a poten- tially targetable and quantifiable factor in disease, much like mutations in DNA or proteins, which makes intui- tive sense given that cancer is often diagnosed by detecting a lump that feels harder and stiffer than the sur- rounding tissue. Understanding how cell-surface proteins sense and respond to force will result in new therapeutic avenues and diagnostic tools for diseases like cancer, heart disease, muscular dystrophy, and polycystic kidney disease. 1

PI_NAMEs: GORDON, WENDY RYAN (contact)

PROGRAM_OFFICER_NAME: BARNES, CHARLES ASHLEY

PROJECT_TERMS: Antigens;Area;Biochemical;Biological;Biophysics;cell motility;Cell Physiology;Cell Surface Proteins;Cell Surface Receptors;cell type;Cells;cellular imaging;Characteristics;Clustered Regularly Interspaced Short Palindromic Repeats;Creativeness;CRISPR screen;Development;Diagnosis;diagnostic tool;Disease;DNA;endonuclease;Engineering;Environment;Explosion;Glioblastoma;Heart Diseases;improved;Individual;innovation;Intuition;Left;Link;link protein;Malignant Neoplasms;Mass Spectrum Analysis;Measures;mechanical force;mechanical signal;mechanical stimulus;Mechanics;mechanotransduction;Medicine;Molecular;Molecular Conformation;Muscular Dystrophies;Mutation;Nanostructures;notch protein;novel therapeutics;Phenotype;Polycystic Kidney Diseases;Process;programs;Proteins;Proteolysis;receptor;Research;response;RNA Binding;Science;sensor;Signal Pathway;Signal Transduction;Specificity;stem cell differentiation;T-Lymphocyte;technological innovation;Technology;technology development;Testing;Therapeutic;Tissues;Vision

PROJECT_TITLE: Decoding mechanotransduction mechanisms of cell-surface receptors

STUDY_SECTION: MRAC

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


ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Biotechnology;Digestive Diseases;Emerging Infectious Diseases;Foodborne Illness;Immunization;Infectious Diseases;Microbiome;Prevention

ORG_CITY: BALTIMORE

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

PHR: Narrative Human norovirus and Clostridium difficile are the leading causes of acute gastroenteritis with significant morbidity and mortality. To date there is still no single vaccine available on the market. The goal of this project is to develop a novel oral passive immunoprophylactic strategy to prevent the infections and diseases associated with the two pathogens.

PI_NAMEs: FENG, HANPING  (contact);YUAN, LIJUAN

PROGRAM_OFFICER_NAME: RANALLO, RYAN

PROJECT_TERMS: Acute;aged;Animal Disease Models;Animal Model;anti-toxin;Antibiotic Resistance;Antibiotic Therapy;antibiotic-associated diarrhea;Antibiotics;Antibodies;Binding;Body Weight decreased;capsule;Carbohydrates;Characteristics;Chromosomal Insertion;Clinic;Clinical;Clostridium difficile;commercialization;Communicable Diseases;Data;Development;Diarrhea;Disease;DNA cassette;Dose;Dried Yeast;Drug or chemical Tissue Distribution;Dryness;Encapsulated;Engineered Probiotics;Engineering;Enteral;enteric pathogen;Erythrocytes;Excipients;Family suidae;Formulation;Future;Gastroenteritis;Genes;Genome;Gnotobiotic;Goals;gut microbiota;Hand;Health care facility;Hemagglutination;high risk population;Hospitalization;Human;human model;In Vitro;in vivo;Individual;Infection;Infection prevention;Intestinal Secretions;Intestines;Lead;Long-Term Care;Marketing;Mediating;Methods;microbiota;microbiota transplantation;Monitor;Morbidity - disease rate;mortality;Mus;nanobodies;Norovirus;novel;Oral;Oral Administration;passive antibodies;pathogen;pathogenic bacteria;Patients;prevent;Prevention strategy;Preventive;Probiotics;Process;Production;Prophylactic treatment;Saccharomyces;scale up;Site;Symptoms;Technology;technology platform;Testing;Therapeutic;tool;Toxin;transmission process;Traveler's diarrhea;vaccine access;vaccine development;Vaccines;Variant;Viral;Viral Load result;Virulence Factors;Virus-like particle;Yeasts

PROJECT_TITLE: Preventing norovirus and Clostridium difficile gastroenteritis by engineered probiotic yeast Saccharomyces boulardii secreting multi-specific single-domain antibodies

STUDY_SECTION: DDR

STUDY_SECTION_NAME: Drug Discovery and Mechanisms of Antimicrobial Resistance Study Section[DDR]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Coronaviruses;Coronaviruses Therapeutics and Interventions;Coronaviruses Vaccines;Emerging Infectious Diseases;Immunization;Infectious Diseases;Prevention;Vaccine Related

ORG_CITY: PISCATAWAY

ORG_NAME: RUTGERS, THE STATE UNIV OF N.J.

PHR: Project Narrative This project will enable the prospective identification of a class of possible SARS-CoV-2 variants that can escape the prevalent immune response, thereby helping identify new candidate immunogens for inclusion in next- generation vaccines. This project will also provide potent inhibitors of diverse highly substituted SARS-CoV-2 variants.

PI_NAMEs: KHARE, SAGAR D (contact)

PROGRAM_OFFICER_NAME: PLIMACK, MARY KATHERINE BRADFORD

PROJECT_TERMS: 2019-nCoV;ACE2;Active Immunization;Aerosols;Algorithm Design;Antibodies;Antigens;Binding;Biological Assay;Biotechnology;candidate identification;clinical development;clinically relevant;Communities;design;Development;Directed Molecular Evolution;Drug Kinetics;Epitopes;Event;FDA Emergency Use Authorization;Future;Human;Immune Evasion;Immune response;Immunity;Incidence;Infection;inhibitor;Intervention;Knowledge;Laboratories;Libraries;Lung;Machine Learning;Medical;molecular modeling;Monoclonal Antibody Therapy;mutation screening;neutralizing antibody;next generation;novel;novel vaccines;outbreak concern;parallel computer;Passive Immunization;Pharmacologic Substance;Property;prospective;Protein Engineering;Proteins;Reagent;receptor;receptor binding;Sampling;SARS-CoV-2 B.1.1.529;SARS-CoV-2 inhibitor;SARS-CoV-2 transmission;SARS-CoV-2 variant;Site;Structure;Surface;Technology;Tertiary Protein Structure;Testing;Therapeutic;Therapeutic Intervention;therapeutically effective;tool;training data;Tropism;Vaccination;vaccination strategy;Vaccines;Variant;variants of concern;Viral;viral fitness;Yeasts

PROJECT_TITLE: Seeing the Unseen: High-Throughput Prospective Profiling and inhibition of SARS-CoV-2 receptor-binding domain variants

STUDY_SECTION: MSFA

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


NIH_SPENDING_CATS: Aging;Biotechnology;Clinical Research;Genetics;Wound Healing and Care

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

PHR: As the population ages, the incident of non-healing ulcerative wounds dramatically increases, which is associated with increased mortality rates. Currently, the biochemical changes associated with both age and the non-healing wound pathologies are unknown. Herein, we will employ a multi-disciplinary team, novel pre-clinical models, and “state of the art” technologies coupled to a pertinent patient population to explore the underlying mechanisms and bioactive lipids associated with aging and non-healing wounds.

PI_NAMEs: CHALFANT, CHARLES E. (contact);KORDULA, TOMASZ K

PROGRAM_OFFICER_NAME: CHAO, CHIEN-CHUNG

PROJECT_TERMS: Ablation;Acceleration;Age;Aging;Agonist;Anabolism;Anti-Inflammatory Agents;Arachidonic Acids;Binding;Biochemical;Biological Markers;Cells;ceramide 1-phosphate;ceramide kinase;chronic wound;Complex;Coupled;CRISPR/Cas technology;Cytosolic Phospholipase A2;Data;Death Rate;decubitus ulcer;Dermal;Development;Dinoprostone;Eicosanoid Production;Eicosanoids;Endothelium;Enzymes;Etiology;Exhibits;Fibroblasts;Foundations;Generations;Genetic;genetic manipulation;Genetically Engineered Mouse;healing;Human;Hydroxyeicosatetraenoic Acids;Immunoglobulin Class Switching;Impaired wound healing;In Vitro;in vivo;Inflammatory;inhibitor;Knock-in Mouse;Knock-out;Knockout Mice;Laboratories;Link;lipid mediator;lipidomics;Lipids;Lipoxygenase;Liquid substance;Mediating;Metabolism;Methods;migration;Modeling;Molecular;Molecular Biology;mouse model;multidisciplinary;Mus;mutant;neutrophil;new technology;non-healing wounds;novel;old mice;Outcome;Pathology;patient population;Patients;Phase;Phenotype;Phosphatidylinositol 4,5-Diphosphate;phosphatidylinositol phosphate, PtdIns(4,5)P2;Phosphatidylinositols;Phospholipase A2;Phospholipases A;Physiological;Physiology;Plasma;Population;pre-clinical;Pre-Clinical Model;Process;Production;Prostaglandin-Endoperoxide Synthase;Prostaglandins;Regulation;response;Role;Signal Pathway;Site;skin ulcer;small molecule;small molecule inhibitor;Sphingolipids;Technology;Testing;Therapeutic;Tissues;Variant;wound;wound healing

PROJECT_TITLE: The role and mechanistic regulation of cPLA2alpha in eicosanoid biosynthesis and wound healing

STUDY_SECTION: MIST

STUDY_SECTION_NAME: Molecular and Integrative Signal Transduction Study Section[MIST]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Depression;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Pediatric;Social Determinants of Health;Suicide

ORG_CITY: SAN DIEGO

ORG_NAME: SAN DIEGO STATE UNIVERSITY

PHR: PROJECT NARRATIVE An expanding body of theory-driven research has consistently shown how factors related to sexual minority stigma, including structural, interpersonal, and intrapersonal factors, may drive sexual orientation-based mental health disparities. However, public health research has so far been unable to produce strong causal, longitudinal evidence on how structural forms of sexual minority stigma may jeopardize mental health outcomes among sexual minorities, including suicidal ideation, suicide attempts, and depressive symptoms. The proposed secondary analysis of a large public health dataset (Add Health) will include advanced three- level multi-membership longitudinal models to examine three key aspects yet missing to facilitate causal inferencing regarding the mental health sequelae of structural sexual minority stigma exposure.

PI_NAMEs: VAN DER STAR, ARJAN  (contact)

PROGRAM_OFFICER_NAME: LEITMAN, DAVID ISAAC

PROJECT_TERMS: Address;Adolescent;Adult;Advocacy;Affect;Attitude;Automobile Driving;Climate;Data;Data Set;depressive symptoms;design;Development;Disparity;Dose;Education;Elements;Etiology;European;Exposure to;Feeling suicidal;Gender;gender diverse;harassment;Health;health disparity;health equity;Heterosexuals;improved;indexing;Individual;Inequity;Institutionalization;internalized stigma;Laws;Legal;Libido;Life Cycle Stages;lifetime risk;Literature;Longitudinal Studies;Maps;Marriage;Mental Depression;Mental Health;middle age;migration;Modeling;National Longitudinal Survey of Adolescent to Adult Health;Outcome;Participant;Pattern;Persons;Policies;Population;programs;Public Health;public health research;Reporting;Research;residence;response;Risk Factors;Role;secondary analysis;Sex Orientation;sexual minority;sexual minority youth;Shapes;social stigma;Specificity;Statutes and Laws;Stretching;Suicide attempt;theories;Time;US State;Violence;young adult

PROJECT_TITLE: The Mental Health Consequences of Life Course-Varying Exposure to Structural Sexual Minority Stigma: Advancing Causal Inference Using Longitudinal Models Moderated by Sexual Orientation

STUDY_SECTION: SPIP

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


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Genetics;Human Genome;Immunotherapy;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE Rhabdomyosarcoma (RMS) is a highly malignant skeletal muscle tumor, with frequent activation of the Ras signaling pathway, and poor outcomes for patients with relapsed or metastatic disease. We have identified that PAK4 as a key signaling node in RMS and will validate it as a new therapeutic target, in combination with chemotherapy or other targeted agents, for high-risk RMS. The proposed research is relevant to public health and the NIH's mission because understanding and validating new therapeutic targets for pediatric sarcomas will improve the treatment of such tumors while minimizing toxic effects of current therapy.

PI_NAMEs: YUSTEIN, JASON  (contact)

PROGRAM_OFFICER_NAME: VENKATACHALAM, SUNDARESAN

PROJECT_TERMS: 3-Dimensional;Address;Adolescent;Advanced Malignant Neoplasm;Alternative Splicing;anti-PD-1;Biochemical;Biology;bioluminescence imaging;Cells;Cellular Indexing of Transcriptomes and Epitopes by Sequencing;checkpoint inhibition;chemotherapy;Child;childhood sarcoma;clinical application;Clinical Treatment;Clinical Trials;clinically relevant;combinatorial;Combined Modality Therapy;Cytotoxic Chemotherapy;Data;Development;differential expression;Disease;Drug Combinations;Drug Screening;efficacy evaluation;Equipment and supply inventories;Evaluation;Ewings sarcoma;Family;functional genomics;Genes;Genetic;Genetically Engineered Mouse;Goals;Guanosine Triphosphate Phosphohydrolases;high risk;Histology;Human;Immune;Immune checkpoint inhibitor;improved;in vivo;in vivo Model;Informatics;inhibitor;innovation;insight;Knock-out;Knowledge;Malignant Skeletal Muscle Neoplasm;MAP Kinase Gene;Mediating;Metastatic Neoplasm to the Lung;Mission;Modeling;Molecular;Molecular Profiling;Monitor;Mus;mutant;Mutation;new therapeutic target;NF1 gene;novel;novel therapeutic intervention;novel therapeutics;Oncogenic;Operative Surgical Procedures;p21 activated kinase;Pathway interactions;Patient-Focused Outcomes;Patients;pharmacologic;Phenotype;Phosphatidylinositols;phosphoproteomics;Phosphotransferases;pre-clinical;Pre-Clinical Model;preclinical evaluation;Protein Isoforms;Protein Kinase;Protein Splicing;Protein-Serine-Threonine Kinases;Proteins;proteogenomics;proteomic signature;Proto-Oncogene Proteins c-akt;Public Health;Radiation;RAS inhibition;Ras Signaling Pathway;Receptor Protein-Tyrosine Kinases;Receptor Signaling;Regimen;Regulation;Relapse;Reporter;Research;Resistance;Resources;Rhabdomyosarcoma;RNA Splicing;Role;Secondary to;selective expression;Serine;Signal Pathway;Signal Transduction;SN-38;Soft tissue sarcoma;Survival Rate;targeted agent;targeted treatment;Therapeutic;Therapeutic Intervention;therapy resistant;Toxic effect;transcriptomics;Treatment Protocols;tumor;tumor growth;tumor microenvironment;United States National Institutes of Health

PROJECT_TITLE: Dissecting and targeting oncogenic functions of PAK4 in high-risk rhabdomyosarcoma

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


NIH_SPENDING_CATS: Genetics;Stem Cell Research;Stem Cell Research - Embryonic - Human

PHR: PROJECT NARRATIVE Proper control of gene expression underlies all biological processes and importantly those involved in cellular differentiation and responses to external stresses. Accordingly, defects in core regulators of gene expression are the basis of many human diseases ranging from cancer to neurological disorders. We study how the mechanisms of gene expression are temporally coordinated such that cellular differentiation programs and responses to stress are executed in a timely and accurate manner.

PI_NAMEs: UNAL, ELCIN  (contact)

PROGRAM_OFFICER_NAME: CHOW, CHI-WING

PROJECT_TERMS: Address;Affect;antagonist;Binding;Biological;Biological Process;Cell Differentiation process;Cells;Cellular Stress;Chromatin;chromatin modification;Chromatin Remodeling Factor;CLN1 gene;CLN2 gene;Code;Coin;Coupled;Cyclins;Defect;Developmental Gene Expression Regulation;Disease;Distal;Down-Regulation;Endoderm;Ensure;Event;experimental study;G1/S Transition;Gene Activation;Gene Cluster;Gene Expression;gene repression;Genes;Genetic Transcription;genome-wide;genome-wide analysis;Goals;Gonadal Dysgenesis;Human;Human Development;human disease;human embryonic stem cell;insight;Link;Liquid substance;Malignant Neoplasms;MDM2 gene;Measurement;Meiosis;Melanoma;Messenger RNA;Metabolic Diseases;Mitosis;Mitotic;Modeling;Molecular;mRNA sequencing;Names;Nervous System Disorder;Nucleosomes;Open Reading Frames;Outcome;Pathologic;Pathway interactions;Phenotype;pluripotency factor;Positioning Attribute;Process;Production;programs;promoter;Protein Biosynthesis;protein expression;Protein Isoforms;Protein Synthesis Inhibition;Proteins;Proteome;Proto-Oncogenes;recruit;Regulation;Regulator Genes;Repression;response;Ribosomes;Role;Saccharomycetales;Series;Signal Transduction;stem cell differentiation;Stress;Testing;TP53 gene;Transcript;transcription factor;Transcription Initiation Site;Transcriptional Activation;Translating;trend;Tumor Suppressor Proteins;Yeasts

PROJECT_TITLE: Developmental Regulation of Gene Expression by Long Undecoded Transcript Isoforms

STUDY_SECTION: CSRS

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