NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Coronaviruses;Coronaviruses Therapeutics and Interventions;Emerging Infectious Diseases;Genetics;Infectious Diseases

ORG_DEPT: BIOCHEMISTRY

PHR: Project Narrative The prevalence and disease severity of human coronaviruses range greatly, from the highly infectious SARS-CoV-2 to the endemic common cold coronaviruses 229E and NL63. A deeper understanding of the functions and mechanisms of the major pathogenicity factor Nsp1 could help explain these differences in disease severity among coronavirus genera. Additionally, the results will provide insight into the evolution of Nsp1 among coronaviruses, inform targets for specific Nsp1-based therapeutics, and lay groundwork for treating future coronavirus strains that present a real and repeatable threat to human health.

PI_NAMEs: BALAJI, SHRAVANI  (contact)

PROGRAM_OFFICER_NAME: PLIMACK, MARY KATHERINE BRADFORD

PROJECT_TERMS: 5' Untranslated Regions;Affinity;Anti-viral Response;betacoronavirus;Binding;Binding Proteins;Biochemical;Cell Communication;Cells;Co-Immunoprecipitations;Common Cold;Comparative Study;Core Protein;Coronavirus;Cryoelectron Microscopy;density;design;Development;Disease;Docking;drug candidate;Drug Design;Drug Targeting;effective therapy;electron density;Elements;Environment;Evolution;experimental study;Future;Gene Expression;Genes;Goals;Health;Human;human coronavirus;Immune Evasion;Immunologic Surveillance;improved;In Vitro;inhibitor;insight;Integration Host Factors;Interferon-beta;Knowledge;Maps;Mediating;Messenger RNA;Middle East Respiratory Syndrome;Modeling;Molecular;Mutagenesis;N-terminal;nanomolar;Nonstructural Protein;Pathogenesis;Pathway interactions;Peptide Initiation Factors;Play;Prevalence;Process;Proliferating;promoter;protein function;Proteins;Research;Resolution;Ribosomal Proteins;Ribosomes;RNA;Role;SARS coronavirus;Severe Acute Respiratory Syndrome;Severity of illness;Specificity;Structure;targeted treatment;Therapeutic;Therapeutic Intervention;translation assay;Translation Initiation;Translational Repression;Translations;Viral;Viral Genes;Viral Nonstructural Proteins;Viral Pathogenesis;Virulence Factors;Virus;Virus Replication

PROJECT_TITLE: Probing the ribosome-dependent mechanisms of human alphacoronavirus Nsp1


ADMINISTERING_IC: AG

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

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);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Dementia;Neurodegenerative;Neurosciences

ORG_CITY: GAINESVILLE

ORG_COUNTRY: UNITED STATES

ORG_DEPT: NEUROSCIENCES

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: PROJECT NARRATIVE Age-related cognitive decline impacts a majority of the world’s population. The proposed research is relevant to public health because it provides an innovative approach for mechanistically linking systems-level neural activity to age-related cognitive decline. By understanding the basic principles of neurobiological organization that affect cognition across the aging brain, it will be possible to promote the development of interventions that broadly improve cognition in normal aging and Alzheimer’s disease and meet a mission of the NIA to advance our understanding of age-related cognitive decline.

PI_NAMEs: SMITH, SAMANTHA MARIE (contact)

PROGRAM_OFFICER_NAME: THOMAS, CIBU PAUL

PROJECT_TERMS: Address;Affect;Age;age related;age related changes;Age-associated memory impairment;aged;Aging;aging brain;aging population;Alzheimer's Disease;Alzheimer's disease related dementia;Alzheimer's disease risk;animal old age;Animals;Anterior;Area;Association Learning;Behavior;behavior influence;Behavioral;behavioral impairment;Behavioral Model;Brain;Brain imaging;Brain region;career;caudate nucleus;Cell Nucleus;cellular imaging;cingulate cortex;Clinical Treatment;Cognition;Cognitive;cognitive function;cognitive load;Cognitive Science;Colon;Communication;Compensation;Complex;Corpus striatum structure;Coupling;Data;Dementia;density;Development;Diagnosis;Dorsal;Elderly;Electrophysiology (science);Exhibits;Fellowship;flexibility;Gene Expression;Genetic;Goals;Health;Hippocampus;Human;human old age (65+);imaging approach;Immediate-Early Genes;Impaired cognition;Impairment;improved;in vivo;Individual;innovation;juvenile animal;Laboratories;Learning;learning outcome;learning strategy;Life Expectancy;life span;Link;Longevity;Maps;Mediating;Memory;Mission;Modality;neural;neurobiological mechanism;Neurobiology;neuroimaging;Neurons;neurophysiology;normal aging;older adult;optical imaging;Pathologic;Pattern;Performance;Phenotype;Play;Population;pre-doctoral;preference;Public Health;Publishing;Quality of life;Rattus;receptor;Reporting;Research;Research Proposals;resilience;Resolution;response;Response to stimulus physiology;Rest;Risk;Rodent;Role;Structure;System;Testing;Therapeutic;therapy development;Tissues;Tort;Training;Transfection;Treatment Efficacy;Viral;way finding

PROJECT_TITLE: Examining the contributions of cognitive load and anterior cingulate cortex activity on striatal-hippocampal network coupling in age-related cognitive decline

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F02A-W (20)]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

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

ORG_CITY: ATLANTA

ORG_DEPT: GENETICS

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE Cortical hyperexcitability is an early phenotype of the devastating neurodegenerative disease Amyotrophic Lateral Sclerosis (ALS) which presents across patients of heterogenous genetic backgrounds. The proposed research will determine the effects of cortical hyperexcitability on cell types in the spinal cord key to this disease’s pathology: motor neurons, interneurons, and astrocytes. These experiments are expected to reveal the consequences of early cellular dysfunction in ALS in human cells, ultimately leading the way towards identifying therapeutic targets and thereby furthering the missions of the NIH and NINDS to use fundamental knowledge about the nervous system to reduce the burden of neurological disease for all people.

PI_NAMEs: PIO, TAYLOR  (contact)

PROGRAM_OFFICER_NAME: MATTHEWS, MARGUERITE

PROJECT_TERMS: 3-Dimensional;Address;Age;ALS pathology;ALS patients;Amyotrophic Lateral Sclerosis;Animals;Astrocytes;Autopsy;Biological Assay;Biological Markers;Biological Models;career;cell cortex;Cell Line;cell type;Cells;Chronic;Clinic;Clinical Trials;Complex;Detection;Development;Diagnosis;Disease;Disease Marker;Disparate;DNA Sequence Alteration;early detection biomarkers;Equilibrium;Esthesia;Etiology;excitotoxicity;experience;experimental study;familial amyotrophic lateral sclerosis;Family;Functional disorder;Future;Gene Mutation;Genetic;Genetic Markers;Genetic Variation;Glutamate Transporter;Glutamates;Goals;Heterogeneity;Human;human induced pluripotent stem cells;human stem cell-derived;human tissue;Hyperactivity;In Vitro;in vivo;Inhibitory Synapse;innovation;Interneurons;Knowledge;Light;Literature;Measures;Mission;Modeling;Motor;motor neuron degeneration;motor neuron function;Motor Neurons;motor symptom;Muscle;Muscle Contraction;Mutation;National Institute of Neurological Disorders and Stroke;nerve supply;Nervous System;Nervous System Disorder;Neurodegenerative Disorders;Neuroglia;Neuronal Dysfunction;Neurons;neurotoxicity;optogenetics;Organoids;Pathology;patient population;Patients;Pattern;Persons;Phenotype;Play;Population;promoter;Recording of previous events;Research;Rodent;Role;Scientist;Skeletal Muscle;Slice;Speed;spheroids;Spinal;Spinal Cord;sporadic amyotrophic lateral sclerosis;Students;Survival Rate;Synapses;System;therapeutic target;Tissues;Training;Translating;transmission process;United States National Institutes of Health;uptake;Western Blotting;Work

PROJECT_TITLE: Assessing the Contribution of Cortical Hyperactivity to ALS Phenotypes in a Human-Derived Motor System

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F03C-N (20)]


FUNDING_MECHANISM: NON-SBIR/STTR RPGS

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

ORG_CITY: BALTIMORE

ORG_NAME: LIEBER INSTITUTE, INC.

ORG_STATE: MD

PHR: PROJECT NARRATIVE Norepinephrine (NE) neurons in the locus coeruleus (LC) project widely throughout the central nervous system, playing critical roles in arousal and mood as well as various components of cognition including attention, learning and memory. LC-NE neurons are highly susceptible to degeneration in age-related neurodegenerative disorders, including Alzheimer’s disease (AD). Here, we define the molecular impacts of neuromelanin and AD-related pathology on local gene expression in the human LC.

PI_NAMEs: HICKS, STEPHANIE CARINNE;MARTINOWICH, KERI  (contact)

PROGRAM_OFFICER_NAME: GRAY, ERIN EMILY

PROJECT_TERMS: Acceleration;Age;age related neurodegeneration;Aging;Alzheimer's Disease;Alzheimer's disease model;Anatomy;Animal Disease Models;Animal Model;Arousal;Attention;Bilateral;Binding;Biological;Brain;Brain region;Brain Stem;Catecholamines;Cell Death;Cell Nucleus;cell type;Cells;Central Nervous System;chelation;Chemicals;Chromosome Mapping;Classification;Clinical;Cognition;cohort;computerized tools;Consensus;Data;density;Deposition;Detection;Diagnosis;differential expression;Disease;Disease Progression;disorder prevention;Dorsal;Elderly;Functional disorder;Gene Expression;Gene Expression Profile;Gene Expression Regulation;Generations;Genomics;Heavy Metals;Histology;Human;Human Gene Mapping;human model;Image;Immunofluorescence Immunologic;Impaired cognition;In Situ Hybridization;Joints;late life;Learning;Life;Location;locus ceruleus structure;Maps;Measurement;Memory;Methods;middle age;Modeling;Molecular;Molecular Profiling;Moods;Morphology;multiple omics;Nerve Degeneration;neurochemistry;neuromelanin;Neuromodulator;Neurons;neuropathology;neurotoxic;noradrenergic;Norepinephrine;Onset of illness;Pathology;Pattern;Pigments;Play;Pontine structure;Predisposition;prevent;Prevention;Process;Property;Proteins;proteogenomics;Proteomics;resilience;Resolution;Role;Sampling;Signal Transduction;single nucleus RNA-sequencing;Site;Slice;Spottings;tau aggregation;tau interaction;tau-1;Techniques;Time;Tissues;toxicant;Toxin;transcriptome;transcriptome sequencing;transcriptomics;unsupervised clustering

PROJECT_TITLE: Impact of neuromelanin and Tau accumulation during aging and disease on local gene expression in the human locus coeruleus using spatially-resolved transcriptomics with protein detection

STUDY_SECTION: CNN

STUDY_SECTION_NAME: Clinical Neuroscience and Neurodegeneration Study Section[CNN]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

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

ORG_CITY: CHICAGO

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: Project Narrative Our ability to learn to recognize the category, or behavioral significance, of visual stimuli is essential for planning and carrying out successful behaviors in response to our surroundings. This project develops novel behavioral tasks and neuronal population recording approaches for studying the brain basis of rapid reward- based visual category learning during naturalistic foraging paradigm. The work will provide a detailed and mechanistic understanding about how encoding in and interactions between multiple interconnected brain areas mediate rapid learning and decision making, which is critical for understanding and ultimately addressing the profound deficits of learning, memory and decision making that frequently accompany brain diseases and conditions such as stroke, schizophrenia and Alzheimer’s disease.

PI_NAMEs: FREEDMAN, DAVID J (contact)

PROGRAM_OFFICER_NAME: FLANDERS, MARTHA C

PROJECT_TERMS: Address;Affect;Aging;Alzheimer's Disease;Animals;Area;Attention;Attention Deficit Disorder;attentional control;Behavior;Behavioral;Brain;brain based;Brain Diseases;Brain Injuries;Brain region;Categories;Child;Cognition;Cognitive;Color;Communication;Data;Decision Making;Disease;Dyslexia;experience;experimental study;Face;flexibility;frontal eye fields;Fruit;Funding Mechanisms;Future;Goals;Grouping;Human;Image;Impairment;insight;Juice;Knowledge;Laboratories;Lateral;lateral intraparietal area;Learning;Learning Disabilities;Location;Mediating;Memory;Monitor;Monkeys;Motion;Motor;Nervous System Disorder;neural;neuromechanism;Neurons;Neurosciences;next generation;nonhuman primate;novel;Parietal Lobe;Patients;Perception;pharmacologic;Population;Primates;Process;Psychophysics;Research;response;Rewards;Role;Saccades;Schizophrenia;School-Age Population;Sensory;Series;Shapes;Stimulus;Stroke;superior colliculus Corpora quadrigemina;Surveys;System;targeted imaging;Task Performances;Testing;Training;Uncertainty;Variant;Visual;visual learning;visual processing;visual search;visual stimulus;Work;young adult

PROJECT_TITLE: Neural Mechanisms of Categorical Decisions and Learning During Saccade-Based Visual Foraging

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 ICN-Y (02)]


ADMINISTERING_IC: AI

ED_INST_TYPE: UNIVERSITY-WIDE

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

ORG_CITY: BOSTON

ORG_NAME: HARVARD MEDICAL SCHOOL

ORG_STATE: MA

PHR: Project Narrative Pseudomonas aeruginosa is an opportunistic pathogen that poses a serious health threat to individuals that are immunocompromised or those with cystic fibrosis. In addition, a rise in antibiotic resistance among P. aeruginosa infections makes them particularly difficult to treat. This study is focused on understanding how the P. aeruginosa outer membrane, which serves as a barrier for toxic molecules like antibiotics, is both built and maintained.

PI_NAMEs: KEPPLE, JOHNATHAN LEE (contact)

PROGRAM_OFFICER_NAME: MOITRA, KAROBI

PROJECT_TERMS: acyl group;Acylation;Antibiotic Resistance;Antibiotics;assault;Back;Biological Assay;cell envelope;Cell Membrane Permeability;Cell Wall;Cells;Chemicals;Complement;Coupled;Cystic Fibrosis;Defect;Development;Diagnostic;Dose;Drug Hypersensitivity;Drug resistance;drug resistant pathogen;drug sensitivity;Enterobacteriaceae;Escherichia coli;experimental study;Fluorescent Probes;Genes;Genetic;genetic approach;Glycolipids;Gram-Negative Bacteria;Health;Homeostasis;human pathogen;Hypersensitivity;Immunocompromised Host;Individual;Infiltration;inhibitor;Knowledge;Label;Lateral;Libraries;Lipopolysaccharides;Maintenance;Membrane;membrane biogenesis;Metabolic;mutant;Mutation;Nature;novel;novel antibiotic class;opportunistic pathogen;pathogen;Pathway interactions;Penetration;Peptidoglycan;Permeability;Pharmaceutical Preparations;Phenotype;Phospholipase;Phospholipases A;Phospholipids;Play;prevent;Production;Pseudomonas aeruginosa;Pseudomonas aeruginosa infection;retrograde transport;Role;Sampling;Signal Transduction;Structure;Surface;synthetic lethal interaction;System;Testing;transposon sequencing

PROJECT_TITLE: Novel phospholipase involved in outer membrane homeostasis in Pseudomonas aeruginosa

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


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Dementia;Genetics;Neurodegenerative;Neurosciences

ORG_CITY: SAN FRANCISCO

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: Project Narrative The peripheral immune system has recently emerged as a potential driver of age-related cognitive impairments and neurodegenerative disorders, such as Alzheimer’s disease, with a prominent role posited for CD8+ T cells. Correspondingly, the research described in this proposal aims to investigate the role of circulating aged CD8+ T cells and their secreted factors in driving hippocampal-dependent cognitive decline during aging. Completion of this work will further the understanding of how age-associated changes in the peripheral immune system impact the brain and ultimately identify potential therapeutic candidates to alleviate age-associated impairments in cognition and susceptibility to neurodegenerative disorders, including Alzheimer’s disease.

PI_NAMEs: SUCHAROV COSTA, JULIANA  (contact)

PROGRAM_OFFICER_NAME: WAGSTER, MOLLY V

PROJECT_TERMS: Adaptive Immune System;Adoptive Transfer;Affect;Age;age effect;age related;age related changes;age related decline;age related neurodegeneration;Age-associated memory impairment;age-related disease;aged;Aging;aging brain;aging hippocampus;aging related;Alzheimer's Disease;Antibodies;Area;Automobile Driving;Behavioral Paradigm;Bioluminescence;Bite;blood-brain barrier crossing;Body System;Brain;brain dysfunction;brain parenchyma;Cardiovascular system;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Nucleus;Cells;Cognition;Cognition Disorders;Cognitive deficits;cognitive function;cytokine;Data;Dementia;differential expression;Endothelial Cells;Endothelium;Excision;Exposure to;extend lifespan;Face;Flow Cytometry;Gene Expression;Gene set enrichment analysis;Genes;Genetic Complementation Test;Granzyme;Hippocampus;Human;Immune;Immune system;Immunohistochemistry;Impaired cognition;Impairment;in vivo;Infection;Infiltration;Inflammatory;Injections;insight;juvenile animal;Learning;Link;Mediating;Memory;Microglia;Minor;Modeling;Molecular;Morphology;Mus;Neurodegenerative Disorders;neurogenesis;Neurons;old mice;Oligodendroglia;Ontology;Parabiosis;Pathway interactions;Peripheral;Plasma;Population;Predisposition;pro-aging;Process;Publishing;Quantitative Reverse Transcriptase PCR;Rejuvenation;Reporting;Research;Resolution;Risk Factors;Role;Series;single-cell RNA sequencing;Spleen;subventricular zone;Synapses;Synaptic plasticity;System;systemic intervention;T cell infiltration;T-Lymphocyte;Tail;Testing;therapeutic candidate;therapeutic target;Tissues;transcriptome sequencing;Transfection;Veins;Viral;Western Blotting;white matter;Work

PROJECT_TITLE: The Role of Peripheral Aged CD8+ T Cells in Hippocampal-Dependent Cognitive Decline


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Hearing Loss;Neurosciences;Rare Diseases;Usher Syndrome

ORG_DEPT: OTOLARYNGOLOGY

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

PHR: Public Health relevance. Advancement in the understanding of molecular mechanisms of the inner ear is a prerequisite to developing therapeutic strategies for hearing impairment. The studies outlined in this proposal seek to understand the general function of a calcium binding protein known as CIB2 and its associated pathophysiology due to mutations of CIB2 encoding this protein. Thus the proposed research is developing fundamental knowledge that will help to reduce the burden of human hearing loss.

PI_NAMEs: AHMED, ZUBAIR M. (contact);FROLENKOV, GREGORY I

PROGRAM_OFFICER_NAME: WATSON, BRACIE

PROJECT_TERMS: Actins;Adult;Affect;Age;Apical;Auditory;Binding;Binding Proteins;Buffers;Calcium;Calcium and Integrin Binding Protein 2;Calcium Binding;Calcium-Binding Proteins;Cell membrane;Cell Physiology;Cells;Cellular Morphology;cellular transduction;Cochlea;Complex;confocal imaging;Data;deaf;deafness;Dependovirus;Development;Elements;Ethnic Origin;Etiology;experimental study;extracellular;Family;FAST2 protein;Functional disorder;Funding;Gene Delivery;Genes;Genotype;Goals;GPSM2 gene;Growth;Hair;Hair Cells;Hearing;hearing impairment;hearing preservation;Height;Homeostasis;Human;In Vitro;in vivo;Infant;Integrin Binding;Ions;Knock-in;Knock-in Mouse;Knock-out;Knockout Mice;Knowledge;Labyrinth;Link;Lipids;Liquid substance;Maintenance;Measures;Mechanics;mechanotransduction;Medial;Mediating;member;Membrane;Modeling;Molecular;mouse model;Mouse Strains;Mus;mutant;Mutant Strains Mice;Mutate;Mutation;novel;Outcome Study;patch clamp;Pathogenicity;Pattern;Persons;Phosphatidylserines;Physiological;Population Heterogeneity;prevent hearing loss;Probability;protein complex;Proteins;public health relevance;Regulation;Reporting;Research;Resolution;response;Rest;Role;Scaffolding Protein;Scanning Electron Microscopy;segregation;Severities;Shapes;Speed;Structure;Testing;Therapeutic;transmission process;Usher Proteins;Variant;Vestibular Hair Cells;Work

PROJECT_TITLE: Usher Proteins in the Inner ear Structure and Function

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 ICN-A (02)]


ADMINISTERING_IC: DE

ED_INST_TYPE: SCHOOLS OF SOCIAL WELFARE/WORK

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Autoimmune Disease;Clinical Research;Dental, Oral, and Craniofacial Disease;Digestive Diseases;Eye Disease and Disorders of Vision;Women's Health Research

ORG_CITY: COLUMBIA

ORG_DEPT: SOCIAL SCIENCES

ORG_NAME: UNIVERSITY OF MISSOURI-COLUMBIA

ORG_STATE: MO

PHR: PROJECT NARRATIVE Proper salivary gland functioning is critical for oral health. Sjögren’s Disease, an autoimmune condition that mainly occurs in women, causes salivary gland hypofunction and leads to severe dryness of the oral cavity. This project proposes to apply a novel therapeutic approach involving the specialized pro-resolving mediator aspirin- triggered resolvin D1 together with dexamethasone to promote resolution of inflammation and restore secretory function in salivary glands.

PI_NAMEs: BAKER, OLGA JULIANA (contact)

PROGRAM_OFFICER_NAME: CHANDER, PREETHI

PROJECT_TERMS: adaptive immunity;Adrenal Cortex Hormones;Antinuclear Antibodies;Aspirin;associated symptom;Autoimmune;Autoimmune Diseases;Biodistribution;Cells;Chronic;Clinical;clinical translation;Clinical Trials;cost;cost effective;Coupled;cytokine;Cytokine Signaling;Development;Dexamethasone;Diagnostic;Disease;Disease Progression;dosage;Dose;Dryness;effective therapy;Effectiveness;Epithelial Cells;Epithelium;Exhibits;Female;Follow-Up Studies;FPR2 gene;GTP-Binding Proteins;Human;human disease;humanized mouse;immune function;improved;in vivo;Inflammation;Inflammatory;Inflammatory Infiltrate;Investigation;loss of function;Lymphocyte;Lymphocytic Infiltrate;Macrophage;mathematical model;Mediating;Mediator;mouse model;Mus;novel;novel therapeutic intervention;Onset of illness;Oral cavity;Oral health;Pathway interactions;Patients;Pharmaceutical Preparations;Plasma;preservation;prevent;Quality of life;receptor;Resolution;response;Saliva;saliva secretion;Salivary Gland Tissue;Salivary Glands;Sialadenitis;side effect;Signal Pathway;Sjogren's Syndrome;Steroids;Submandibular gland;System;Time;tissue repair;Translating;treatment optimization;Treatment outcome;Woman;Xerostomia

PROJECT_TITLE: Optimization of a Treatment for Sjögren's Disease Using Aspirin-Triggered Resolvin D1 and Dexamethasone

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 MSOS-A (04)]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

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

ORG_CITY: MINNEAPOLIS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: PROJECT NARRATIVE This proposal aims to address significant gaps in our understanding of how neuropeptides derived from a specific gene (vgf) modulate synaptic plasticity in the nucleus accumbens, and how they modulate neurobehavioral plasticity caused by oxycodone exposure and withdrawal. Elucidating specific mechanisms of plasticity will contribute to the development of novel therapeutics that harness neuropeptides and counteract the impact of opioids on the brain.

PI_NAMEs: ADKE, ANISHA P (contact)

PROGRAM_OFFICER_NAME: LIN, YU

PROJECT_TERMS: Acute;Adaptive Behaviors;addiction;Address;Amino Acids;Animal Model;Basic Science;Behavior;behavior influence;Behavioral;Behavioral Assay;Brain;Brain region;career;cell type;Cells;Central Nervous System;Clinical;Complex;conditional knockout;Corpus striatum structure;Data;Dependence;Development;Dimensions;Drug Exposure;drug withdrawal;Electrophysiology (science);Event;experience;Frequencies;Genes;Glutamates;Hippocampus;Hyperalgesia;In Situ Hybridization;Interneurons;Interruption;Knock-out;Knockout Mice;Laboratory Finding;Length;Location;Locomotion;Maps;Measures;Mediator;Memory;Mental Depression;Messenger RNA;Methods;Modeling;Mus;Names;Nervous System;neural circuit;Neuroanatomy;neurobehavioral;Neuronal Plasticity;Neurons;Neuropeptides;neurotransmission;new therapeutic target;novel;novel therapeutics;Nucleus Accumbens;Opiate Addiction;Opioid;opioid exposure;opioid tapering;opioid use;opioid use disorder;opioid withdrawal;Outcome;Oxycodone;Pain;patch clamp;Patients;Pattern;Peptides;Physicians;Physiologic pulse;Physiological;Physiology;Plants;Play;Population;postsynaptic;Predisposition;presynaptic;Proxy;psychologic;response;reward circuitry;reward processing;Rewards;RNA;Role;Scientist;Sensory;Signal Transduction;skills;Slice;social;Social Behavior;Somatostatin;Spinal Cord;Spinal cord posterior horn;Symptoms;Synapses;Synaptic plasticity;Synaptic Transmission;Techniques;Testing;therapeutic target;Transcript;Transgenic Mice;Translations;transmission process;Viral;Viral Vector;Visualization;Withdrawal;Work

PROJECT_TITLE: VGF in the nucleus accumbens: roles in synaptic and opioid-evoked plasticity

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F02B-Y (20)]


ORG_CITY: HERSHEY

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: PENNSYLVANIA STATE UNIV HERSHEY MED CTR

ORG_STATE: PA

PHR: PROJECT NARRATIVE The nucleolar stress response (NSR) functions to maintain cellular homeostasis when the cell is faced with stress or suboptimal growth conditions. This research proposal will investigate how this stress response is regulated by and how it might impact viral replication of Merkel Cell Polyomavirus, a human tumor virus that causes a highly fatal skin cancer called Merkel Cell Carcinoma (MCC). Such work will advance our understanding of the role of the NSR during viral infections, an area which has not been well described, and identify potential therapeutic targets to prevent the onset of MCC.

PI_NAMEs: PHAM, ALEXANDER MICHAEL (contact)

PROGRAM_OFFICER_NAME: ALARCON, RODOLFO M

PROJECT_TERMS: Address;Affect;Aging;Apoptosis;Area;Binding;Biogenesis;biological adaptation to stress;Biological Assay;Cancer Etiology;Cell Aging;Cell Cycle Arrest;Cell Nucleolus;Cells;Data;Death Rate;Development;Disease;DNA biosynthesis;DNA Damage;ds-DNA;effective therapy;Fibroblasts;Genes;Genetic Transcription;Genome;Goals;Growth;Homeostasis;Human;human DNA;Human Papillomavirus;Immunocompromised Host;In Situ;Incidence;Infection;Integration Host Factors;Intervention;Investigation;latent infection;Life;Ligation;Maintenance;Malignant Neoplasms;MDM2 gene;Merkel cell carcinoma;Merkel Cells;Modeling;novel;novel therapeutics;Nucleolar Proteins;nucleophosmin;Nutrient;older patient;Oncogenic Viruses;Oncoproteins;Pathogenesis;Pathway interactions;Patients;Pharmaceutical Preparations;Phenotype;Play;Polyomavirus;Polyomavirus Infections;prevent;Process;Protein Biosynthesis;protein protein interaction;Proteins;proteostasis;Research;Research Proposals;response;Ribosomal DNA;Ribosomal Protein S6;Ribosomal RNA;Ribosomes;RNA;RNA chemical synthesis;RNA Processing;Role;senescence;sensor;Skin Cancer;Starvation;Stress;stressor;Structure;Therapeutic;therapeutic target;therapeutically effective;TP53 gene;Tumor Antigens;ubiquitin-protein ligase;Viral;Viral Genes;Viral Genome;Viral Proteins;Virus;Virus Diseases;virus related cancer;Virus Replication;Work

PROJECT_TITLE: Deciphering the mechanisms of nucleolar stress response during MCPyV infection

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F07C-S (20)]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Digestive Diseases;Gene Therapy;Gene Therapy Clinical Trials;Genetics;Immunotherapy;Pancreatic Cancer;Rare Diseases

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

PHR: Project Narrative In this application we address the overall hypothesis that a novel population of T cells expressing a protein on their surface termed “CD26” are ideal template to modify and use as a cell therapy for pancreatic cancer. Using a series of experimental models, we will study how the unique properties of these cells allow them to work when administered on their own, and together with other more conventional T cells that are engineered to recognize, mesothelin, a marker present on pancreatic cancer cells. Our team will next conduct a first in human clinical trial in patients with pancreatic cancer to ensure these cells are safe and obtain tumor biopsies and blood samples to understand their fate in pancreatic cancer patients.

PI_NAMEs: LESINSKI, GREGORY B. (contact);PAULOS, CHRYSTAL MARY;WALLER, EDMUND K

PROGRAM_OFFICER_NAME: HENDERSON, LORI A

PROJECT_TERMS: Address;advanced pancreatic cancer;Animals;Antigen Receptors;Antigens;Bar Codes;Bioenergetics;Biopsy;Biopsy Specimen;Blood;Blood specimen;CAR T cell therapy;CD3 Antigens;CD4 Positive T Lymphocytes;CD8B1 gene;Cell Therapy;Cells;cellular transduction;chemokine;chimeric antigen receptor;chimeric antigen receptor T cells;Clinic;Clinical;Clinical Trials;cohort;congenic;cytokine;Data;Dipeptidyl-Peptidase IV;DNA;Dose;Effector Cell;efficacy trial;engineered T cells;Engineering;Engraftment;Ensure;enzyme activity;Enzymes;exhaust;experience;Experimental Models;FDA approved;first-in-human;Flow Cytometry;Frequencies;Goals;Hematologic Neoplasms;Human;Immune;Immunity;Immunocompetent;Immunodeficient Mouse;Impairment;improved;in vivo;Individual;inhibitor;innovation;Lentivirus Vector;Malignant neoplasm of pancreas;manufacture;manufacturing process;Measures;Mediating;Memory;mesothelin;Metabolic;metabolic profile;Metabolism;mitochondrial metabolism;molecular imaging;Mus;Myeloid Cells;Myeloid-derived suppressor cells;novel;overexpression;pancreatic cancer cells;pancreatic cancer patients;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma model;Patients;Peptides;Phase 0/1 Clinical Trial;Phosphatidylinositols;Phosphotransferases;Population;preclinical study;prevent;Property;Proteins;Protocols documentation;recruit;Reporting;Reproducibility;response;Role;Safety;safety assessment;self-renewal;Series;Solid Neoplasm;Specificity;stem;stemness;Surface;System;T cell differentiation;T cell infiltration;T cell therapy;T-Lymphocyte;technology platform;Testing;transcriptomics;Translating;tumor;tumor microenvironment;tumor-immune system interactions;Work

PROJECT_TITLE: Leveraging CD26high Meso-CAR T cells in patients with advanced pancreatic cancer

STUDY_SECTION: CONC

STUDY_SECTION_NAME: Clinical Oncology Study Section[CONC]


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

ORG_CITY: CAMBRIDGE

ORG_NAME: WHITEHEAD INSTITUTE FOR BIOMEDICAL RES

PHR: 8. PROJECT NARRATIVE Toxoplasma gondii chronically infects one quarter of the world’s population, and its reactivation can cause debilitating and life-threatening disease. Key to T. gondii’s pathogenesis is its ability to enter a reversible, semi- quiescent chronic stage that is resistant to clearance by the host immune response and all existing pharmacotherapies. This proposal will investigate how the T. gondii chronic-stage developmental program is initiated and, later, overturned during reactivation, providing new molecular insights to inform the design of novel therapies for toxoplasmosis directed at a radical cure.

PI_NAMEs: LICON, MEREDITH HALEY (contact)

PROGRAM_OFFICER_NAME: PESCE, JOHN T

PROJECT_TERMS: Acute;Antiparasitic Agents;Binding;Chronic;chronic infection;Clinical;Co-Immunoprecipitations;combat;design;Development;Disease;Disease Reservoirs;driving force;Equilibrium;Exhibits;Feedback;gain of function;Genetic;genetic architecture;Genetic Transcription;Goals;Growth;Human;human pathogen;immune clearance;immune function;Immune response;Immunocompetent;Immunocompromised Host;In Vitro;Individual;Infection;insight;knock-down;latent infection;Lesion;Licensing;Life;Link;Maintenance;Mass Spectrum Analysis;Messenger RNA;mimetics;Molecular;Molecular Genetics;Monitor;Mus;Mutation;Names;novel;novel therapeutics;overexpression;Parasites;pathogen;Pathogenesis;Pathology;Pharmacotherapy;Phase;phosphoproteomics;Phosphorylation Site;Population;Positioning Attribute;Post-Translational Protein Processing;prevent;Process;programs;Protein Dynamics;protein protein interaction;Proteins;Proteomics;Recurrence;Regulation;Resistance;response;Ribosomes;RNA-Binding Proteins;Role;screening;Signal Transduction;Stress;Surveys;Testing;therapy design;Time;Toxoplasma;Toxoplasma gondii;Toxoplasmosis;Transcript;transcription factor;transcriptional reprogramming;Translation Initiation;Translational Activation;Translations;Work

PROJECT_TITLE: Investigating differentiation, maintenance, and reactivation of the Toxoplasma chronic stage

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F07B-G (20)]


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Childhood Leukemia;Clinical Research;Genetics;Hematology;Human Genome;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: PORTLAND

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: PROJECT NARRATIVE Internal tandem duplications (ITD) of Fms-like tyrosine kinase 3 (FLT3) is a common driver mutation of acute myeloid leukemia (AML) and confers a poor prognosis for patients with AML, yet inhibitors of FLT3-ITD signaling are rarely curative. The proposed research will utilize single cell chromatin accessibility sequencing, high- resolution epigenetic profiling, functional genetic technologies, and drug sensitivity assays to investigate the epigenetic regulators of the MYC proto-oncogene, a key downstream target of FLT3-ITD signaling that enables uncontrolled leukemic proliferation, at the MYC blood-specific super-enhancer complex. Determination and validation of the regulatory factors of the MYC super-enhancer complex in FLT3-ITD AML will contribute to our understanding of leukemogenesis with the potential to uncover therapeutic targets aimed at the molecular mediators of FLT-ITD signaling.

PI_NAMEs: YASHAR, WILLIAM MONTGOMERY (contact)

PROGRAM_OFFICER_NAME: PURI, ANU

PROJECT_TERMS: Ablation;Active Sites;Acute Myelocytic Leukemia;acute myeloid leukemia cell;Advisory Committees;Binding;biobank;Biological Assay;Biology;Blood;Blood Cells;Cancer Biology;Cell Cycle;Cell Death;Cell Differentiation process;Cell Line;Cell model;Cell Proliferation;Cells;chemotherapy;Chromatin;Cleavage Under Targets and Release Using Nuclease;Clinical;Committee Members;Complex;Computational Biology;conventional therapy;CRISPR-mediated transcriptional activation;Data;design;Development;Disease;Disease remission;driver mutation;Drug Combinations;Drug Screening;drug sensitivity;Drug Targeting;Enhancers;Epigenetic Process;epigenetic profiling;epigenetic therapy;FLT3 gene;Gene Expression;Genetic Techniques;genetic technology;Goals;Head;Hematologist;Hematology;Hematopoiesis;Hematopoietic Neoplasms;improved;Individual;inhibitor;Institution;KDM1A gene;kinase inhibitor;Learning;leukemia;leukemia treatment;Leukemic Cell;leukemogenesis;Maintenance;Malignant Neoplasms;Mediator;Medical;Medical Oncology;member;Molecular;Molecular Target;Mutation;MYC gene;novel;novel therapeutic intervention;novel therapeutics;Oncologist;Oncoproteins;Outcome;overexpression;patient prognosis;Patients;personalized therapeutic;Physicians;professor;Prognosis;Proliferating;Proto-Oncogene Proteins c-myc;Proto-Oncogenes;Refractory;Regulation;Regulatory Element;Relapse;Research;Research Institute;Research Proposals;Resolution;responders and non-responders;response;Sampling;Scientist;Signal Transduction;single cell analysis;single cell ATAC-seq;single cell sequencing;small molecule inhibitor;Stat5 protein;stem cells;Survival Rate;Systems Biology;Techniques;Technology;Testing;Therapeutic;therapeutic target;Training;transcription factor;Transcriptional Regulation;treatment response;Validation

PROJECT_TITLE: Control of the MYC Super-Enhancer Complex in FLT3-ITD Acute Myeloid Leukemia

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F09B-Z (20)]


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Congenital Structural Anomalies;Genetics;Human Genome;Pediatric;Rare Diseases

ORG_CITY: AUSTIN

ORG_NAME: UNIVERSITY OF TEXAS AT AUSTIN

ORG_STATE: TX

PHR: Project Narrative: Defects in the Hedgehog signaling pathway underlie a vast spectrum of human birth defects, including ciliopathies, holoprosencephaly, cleft palate, and a variety of limb defects such as polydactyly. This proposal seeks to fill a fundamental gap in our understanding of Hedgehog signaling regulates gene expression through the GLI proteins. It will determine how the activity of GLI proteins is regulated to repress the expression of HH target genes and which other proteins are required for this activity.

PI_NAMEs: VOKES, STEVEN ALEXANDER (contact)

PROGRAM_OFFICER_NAME: TOYAMA, REIKO

PROJECT_TERMS: Acetylation;Alleles;Anterior;ATAC-seq;Binding;Biological;Biotinylation;Cell Communication;Cells;CHD4 gene;Chromatin;chromatin remodeling;Chromatin Remodeling Factor;ciliopathy;Cleft Palate;cofactor;Complex;Congenital Abnormality;crosslink;Cyclic AMP-Dependent Protein Kinases;Data;Defect;density;derepression;Development;Enhancers;Erinaceidae;Funding;Gene Expression;gene repression;Genes;genetic approach;genetic corepressor;Genetic Transcription;Genomic approach;Genomics;GLI gene;GLI2 gene;GLI3 gene;Goals;Histone Acetylation;Histone Deacetylase;Histone Deacetylation;Holoprosencephaly;Human;Infant;Limb Bud;Limb Development;Limb structure;Link;Mass Spectrum Analysis;Mediating;member;Methods;Modeling;novel;Nucleosomes;NuRD complex;Organ;Pathogenicity;Pathway interactions;Pattern;Polydactyly;prevent;Process;Proteins;recruit;Regulation;Repression;Repressor Proteins;Research;response;Slide;smoothened signaling pathway;Specific qualifier value;Structural defect;Syndrome;System;Testing;Time;Transcription Repressor;Transcriptional Regulation;Validation

PROJECT_TITLE: Cis-regulatory circuitry underlying Hedgehog mediated limb development

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 CDB-B (02)]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Biotechnology;Brain Disorders;Dementia;Genetics;Human Genome;Neurodegenerative;Neurosciences

ORG_CITY: IRVINE

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: PROJECT NARRATIVE  Alzheimer's disease (AD) affects millions of people worldwide, currently has no cure, and is projected to drastically grow in numbers in the coming years. The Octodon degus provides a potential paradigm shift in the predominantly transgenic mouse-dominated AD animal model field, as it is a long-lived rodent that naturally manifests many of the AD-like features seen in human AD. The proposed behavioral, neuropathological, cytoarchitectural, and single-cell spatial transcriptomic characterization of the Octodon degu's relevance to AD can lead to invaluable insights into AD pathogenesis and the discovery of novel therapeutic targets.

PI_NAMEs: GARDUNO, BERNARDO MAXIMILIANO (contact)

PROGRAM_OFFICER_NAME: CHAKROBORTY, SHREAYA

PROJECT_TERMS: Adult;Affect;Age;aged;aging population;Alzheimer like pathology;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease patient;Alzheimer's disease therapeutic;American;Anatomy;Animal Disease Models;Animal Model;Behavior;behavior test;Behavioral;Biological Assay;Brain Mapping;cell type;Cells;Characteristics;Chile;Chilean;Cognitive;Cognitive deficits;cohort;Custom;Data;Data Correlations;data integration;Data Set;design;Development;differential expression;Disease;Dorsal;excitatory neuron;Exhibits;experimental study;field study;Fluorescent in Situ Hybridization;Future;Gene Expression;Gene Expression Profile;gene panel;Gene Targeting;Genes;Genetic;Genetic Engineering;Genetic Markers;Goals;Grant;Hippocampus;Human;Immediate-Early Genes;Immunofluorescence Immunologic;Impaired cognition;inhibitory neuron;insight;Knowledge;Label;Leadership;life span;Link;Manuscripts;Maps;member;Mentors;Mentorship;Methods;model organism;Modeling;mouse model;Mus;neglect;Neurodegenerative Disorders;Neurofibrillary Tangles;neuroinflammation;Neuromodulator;neuropathology;Neurosciences;new therapeutic target;novel;novel therapeutics;Octodon;Octodon degus;Pathogenesis;Pathologic;Pathology;Performance;Persons;Population;Prefrontal Cortex;Production;professor;Proteins;Research;Risk;Rodent;Rodent Model;Role;Scientist;Senile Plaques;sex;single nucleus RNA-sequencing;skills;therapeutic target;Training;trait;transcriptome;transcriptomics;Transgenic Mice;Universities;Western Blotting;Writing

PROJECT_TITLE: Neuropathological and spatial transcriptome brain maps in Octodon degus, a natural Alzheimer's disease rodent model


ADMINISTERING_IC: OD

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH

NIH_SPENDING_CATS: Genetics

ORG_CITY: BOCA RATON

ORG_NAME: FLORIDA ATLANTIC UNIVERSITY

PHR: Project Narrative Understanding how phenotypic diversity arises in both adaptive and pathological states is a fundamental goal of biological research. For decades, the blind cavefish, Astyanax mexicanus, and its conspecific surface-dwelling relatives, have been important systems for addressing how naturally occurring genetic variation influences phenotypic differences. This application will support and ensure diversity at the 8th biennial Astyanax International Meeting, which has been the premiere conference where groups utilizing this model and other non-traditional aquatic systems can gather, discuss the latest research and discuss how to advance the model.

PI_NAMEs: DUBOUE, ERIK ROLANDO (contact);KEENE, ALEX C;KOWALKO, JOHANNA E.;ROHNER, NICOLAS

PROGRAM_OFFICER_NAME: CONTRERAS, MIGUEL A

PROJECT_TERMS: Address;Aggressive behavior;Area;Asia;Atlases;Biological Models;Biological Process;biological research;blind;career;Cells;Central America;Cichlids;Clustered Regularly Interspaced Short Palindromic Repeats;Collaborations;Communities;computerized tools;cost;Country;COVID-19;Crowding;Data;design;Development;Diabetes Mellitus;Disease susceptibility;Ecology;Ensure;Environment;equity, diversity, and inclusion;Europe;Evaluation;Evolution;Explosion;Eye;Eye Development;Fees;Financial Support;Fishes;Florida;Fostering;Gene Transfer Techniques;Genes;Genetic;genetic architecture;Genetic Variation;Genome;Goals;Grant;Home;Hour;human disease;Image;improved;innovation;Insulin Resistance;International;laboratory experiment;Latin America;Latin American;Lead;Letters;Lighting;meetings;Metabolism;Mexican;Mexican Americans;Mexico;model organism;Modeling;Neurosciences;North America;Pathologic;Phenotype;Population;posters;preservation;Productivity;Publications;recruit;Research;Research Personnel;Retinal Pigments;RNA;Role;Science;Scientist;single cell sequencing;Sleep;Sleep Deprivation;social;Stream;Stress;Students;success;Surface;symposium;System;technological innovation;Technology;Texas;Time;tool;trait;Underrepresented Populations;Universities;unpublished works;Vendor;Visual System;Work;Zebrafish

PROJECT_TITLE: Enhancing Diversity at the 8th Astyanax International Meeting (AIM)

STUDY_SECTION_NAME: Special Emphasis Panel[ZOD1 IMST-R (90)]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Biotechnology

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

PHR: PROJECT NARRATIVE  Stereochemistry is the crux of modern organic chemistry; therefore, direct synthetic method to access desired stereoisomer is highly sought after from fundamental organic synthesis to medicinal chemistry perspective. This proposed research describes a novel application of enantioselective photoredox catalysis to achieve stereochemical editing of quaternary stereocenters that is not established with current methods. Ultimately, the results of this proposed research will provide valuable tools to efficiently prepare small molecule drugs and their derivatives, and enhance the productivity of pharmaceutical research to advance human health.

PI_NAMEs: HWANG, TAEHWAN  (contact)

PROGRAM_OFFICER_NAME: LEWIS, MECHELLE MAYLEBEN

PROJECT_TERMS: Acids;Binding;Binding Sites;Biological;Carbon;Catalysis;catalyst;Cations;Chlorides;Complex;Coupled;Coupling;Derivation procedure;Development;Development Plans;drug discovery;Drug Kinetics;Electron Transport;Electrons;Ensure;Environment;Enzymes;epimerization;experience;Exposure to;Future;Genetic Recombination;Goals;Grant;Health;High temperature of physical object;Human;Hydrogen Bonding;innovation;interest;Investigation;Ions;Kinetics;Knowledge;Ligands;Literature;literature survey;Mediating;Methodology;Methods;Modernization;Modification;Natural Products;Natural regeneration;Nickel;novel;novel strategies;Organic Chemistry;Organic Synthesis;Outcome;oxidation;Pharmaceutical Chemistry;Pharmaceutical Preparations;Pharmacologic Substance;Preparation;Process;Productivity;Property;Protocols documentation;racemization;Reaction;receptor;Reporting;Research;Resources;screening;side effect;Site;small molecule;Source;stereochemistry;Stereoisomer;System;Techniques;tool;Transition Elements

PROJECT_TITLE: Stereochemical Editing of Quaternary Stereocenters Enabled by Enantioselective Recombination of C–C Bonds

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F04-S (20)]


NIH_SPENDING_CATS: Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Women's Health Research;Wound Healing and Care

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: Project Narrative Transgender male patients (i.e., assigned female at birth and identifying as male) who undergo gender affirming surgery while on masculinizing testosterone replacement therapy have been reported to have worse scarring and wound healing outcomes compared to those not on testosterone at the time of surgery. Using a variety of cutting-edge techniques, this research will investigate the biological mechanisms responsible for this phenomenon, leading to improved understanding of wound biology and the potential to rewrite perioperative guidelines.

PI_NAMEs: SOARES, VANCE  (contact)

PROGRAM_OFFICER_NAME: STAMM, JOYCE CHIN-CHIN NG

PROJECT_TERMS: Affect;Androgen Receptor;Area;assigned female at birth;Attention;authority;B-Lymphocytes;beta catenin;Biological;Biological Assay;Biology;Birth;Blinded;Cells;Chemicals;Chest;Chromosomes;Cicatrix;cisgender;Clinical;Collagen;Communities;Complex;cytotoxic;Data;Deposition;Dichloromethylene Diphosphonate;Disabling;Disparity;Dorsal;Erinaceidae;Estrogens;Excision;experience;experimental study;Female;Fibroblasts;Flow Cytometry;Four Core Genotypes;Gender Confirmation Surgery;Gender Identity;Gene Expression;Genes;Genetic;genotypic sex;Gonadal Steroid Hormones;Granulation Tissue;Guidelines;healing;Health;Health Care Costs;Healthcare;High Prevalence;Histology;Hormone Receptor;Hormone use;Hormones;Immune;Immune system;Immunofluorescence Immunologic;Impaired healing;Impaired wound healing;improved;Individual;Induction of Apoptosis;Inflammation;Ingestion;keratinocyte;Knockout Mice;Knowledge;Liposomes;Literature;Macrophage;male;Mediating;Mediator;Medical;Modeling;mouse model;Mus;novel;Operative Surgical Procedures;Outcome;Ovary;Paper;Pathology;Pathway interactions;patient population;Patients;Perioperative;personalized medicine;Phenotype;phenotypic biomarker;Phenotypic Sex;Plastic Surgeon;Population;Procedures;Professional Organizations;psychological distress;Reconstructive Surgical Procedures;Reporting;Research;sex;sex assigned;Sex Chromosomes;Signal Pathway;single cell sequencing;single-cell RNA sequencing;Skin wound healing;Standardization;Stimulus;Surgeon;Techniques;Testing;Testis;Testosterone;testosterone replacement therapy;Time;transgender;transgender men;Transgenic Mice;Transgenic Organisms;United States;Visualization;Wild Type Mouse;wound;wound healing;Writing;Y Chromosome

PROJECT_TITLE: Understanding how chromosomal makeup and cross-sex hormone administration affect wound healing in mice

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F10B-C (20)]


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Genetics;Immunization;Infectious Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Stem Cell Research - Induced Pluripotent Stem Cell - Non-Human;Vaccine Related

ORG_CITY: NEW YORK

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

ORG_STATE: NY

PHR: Project Narrative / Relevance For many pathogens, effective vaccines do not exist. The goal of this proposal is to generate stem cell-based therapies against such infectious pathogens.

PI_NAMEs: BHATTACHARYA, DEEPTA ;STURGEON, CHRISTOPHER MICHAEL (contact)

PROGRAM_OFFICER_NAME: FEHR, TUBA HALISE

PROJECT_TERMS: Address;Allogenic;Anti-viral Agents;Antibodies;Antibody Formation;Antibody-mediated protection;Autologous;B cell differentiation;B-Lymphocytes;Bioinformatics;CD19 gene;CD34 gene;Cell Line;Cell Lineage;Cell Therapy;Cells;cellular engineering;Chimera organism;chimeric antigen receptor T cells;chronic infection;Communicable Diseases;Complex;cost;Detection;directed differentiation;engineered stem cells;Engineering;Epigenetic Process;Generations;Genetic;Genetic Engineering;Genetic Transcription;genome editing;Goals;Hematopoietic;Hematopoietic stem cells;HIV;HIV Antibodies;Human;human embryonic development;Human Engineering;human pluripotent stem cell;Immune;Immune Evasion;Immune system;Immunity;Immunocompetent;In Vitro;in vivo;Individual;Infection;influenza virus strain;influenzavirus;insight;Intervention;Knock-in;Lead;Lymphoid;Malaria;Methods;Modification;Monoclonal Antibodies;Mus;Nature;neutralizing antibody;Normal tissue morphology;novel;Output;pathogen;Pathway interactions;plasma cell development;Plasma Cells;Plasmodium;pluripotent stem cell differentiation;Pluripotent Stem Cells;Process;Property;protective effect;Regenerative Medicine;Reproducibility;screening;Signal Transduction;small molecule;Stem Cell Development;stem cell therapy;Technology;Therapeutic;transcriptomics;Transplantation;Vaccine Design;Vaccines;vector;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Engineering pluripotent stem cells to evade and promote immunity

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


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cancer;Clinical Research;Prostate Cancer;Urologic Diseases

ORG_CITY: CLEVELAND

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

ORG_STATE: OH

PHR: PROJECT NARRATIVE Targeted focal resection of prostate cancer has the potential to eliminate the many complications associated with whole-gland removal, but usually cannot even be attempted, because cancerous tissue looks the same as healthy tissue in endoscope images. Fortunately, cancerous tissue is accurately identiﬁable in high-ﬁeld MR images, which opens the door to precise and accurate focal resections using a new kind of surgical robot capable of delivering two needle-sized instruments through a standard transurethral endoscope. By combining this new robot with a single-sided low-ﬁeld MRI scanner that can accurately guide the instruments to lesions identiﬁed in registered high-ﬁeld MR images, we will create a system with the potential to enable targeted, personalized, focal resections for patients who today have no alternative to radical prostatectomy.

PI_NAMEs: GRISSOM, WILLIAM A (contact)

PROGRAM_OFFICER_NAME: TATA, DARAYASH B

PROJECT_TERMS: Ablation;Address;Biopsy;cancer surgery;Cancerous;Clinical;clinical translation;Clinical Trials;Collaborations;commercialization;Complication;design;Devices;Diagnosis;Diameter;Disease;Distress;Endoscopes;Ensure;Environment;Excision;experience;Face;FDA approved;Generations;Gland;Goals;Holmium;Image;Image Enhancement;image guided;image reconstruction;image registration;Image-Guided Surgery;imaging capabilities;imaging platform;Impotence;improved;Incontinence;Individual;Industrialization;industry partner;innovation;instrument;Intervention;Lasers;Lesion;Letters;Magnetic Resonance Imaging;Malignant neoplasm of lung;Malignant neoplasm of prostate;Malignant Neoplasms;Marketing;Memory;men;minimally invasive;Modeling;Morphologic artifacts;MRI Scans;Needles;novel;Operative Surgical Procedures;Pathology;Patients;portability;Postoperative Period;Prevalence;Procedures;Process;Prostate;Prostate Cancer therapy;prostate surgery;Radical Prostatectomy;Research;Resolution;Robot;robot assistance;robotic system;Robotics;Sampling;Scanning;Screening for Prostate Cancer;Side;side effect;standard care;Surgeon;System;Systems Integration;Techniques;Time;Tissues;Training;Translational trial;ultrasound;Update;Urethra;Urinary Incontinence;Urologic Surgeon;Urologist;Visual

PROJECT_TITLE: Harnessing low-field MRI and robotics to enable personalized incisionless prostate surgery

STUDY_SECTION: IGIS

STUDY_SECTION_NAME: Imaging Guided Interventions and Surgery Study Section[IGIS]


NIH_SPENDING_CATS: Genetics;Neurosciences

ORG_CITY: WALTHAM

ORG_NAME: BRANDEIS UNIVERSITY

PHR: PROJECT NARRATIVE The goal of the proposed project is to investigate the regulation of the muscleblind gene, a splicing regulator responsible for Myotonic Dystrophy. In particular we will focus on the role of recently discovered new types of molecules: circular RNAs (circRNA), which we showed in the previous period of the grant has multiple functions in the muscle and brain. The present proposal will uncover the mechanism of action of these molecules; therefore, this project will unravel key regulatory mechanisms of a disease-linked gene.

PI_NAMEs: KADENER, SEBASTIAN  (contact)

PROGRAM_OFFICER_NAME: CZAPLINSKI, KEVIN

PROJECT_TERMS: Adult;Behavior;Behavioral;behavioral phenotyping;Binding;Brain;Buffers;Cell division;Cell Nucleus;Cellular biology;circular RNA;Data;Development;Disease;Drosophila genus;Electrophysiology (science);Exons;experimental study;Family;fly;Gene Expression;gene product;Genes;genetic approach;Genomic approach;Goals;Grant;Homologous Gene;Image;in vivo;innovation;knock-down;Laboratories;Lateral;Link;member;Messenger RNA;Modeling;Molecular;Morphology;mRNA Precursor;Muscle;Myopathy;Myotonic Dystrophy;neural;Neurodegenerative Disorders;Neuromuscular Junction;Neurons;Orthologous Gene;Output;Pathway interactions;Phenotype;Physiological;Physiology;Process;Production;Protein Isoforms;Proteins;Regulation;Regulator Genes;RNA;RNA metabolism;RNA Processing;RNA Splicing;RNA Transport;Role;System;Testing;Tissues;Trans-Activators;Translations;Untranslated RNA;Work

PROJECT_TITLE: Unraveling regulatory functions of circRNAs at the muscleblind locus

STUDY_SECTION: MNG

STUDY_SECTION_NAME: Molecular Neurogenetics Study Section[MNG]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Clinical Research;Infectious Diseases;Mental Health;Neurosciences;Physical Injury - Accidents and Adverse Effects;Precision Medicine;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury

ORG_CITY: MILWAUKEE

ORG_DEPT: NEUROSURGERY

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

ORG_STATE: WI

PHR: Project Narrative Response to and recovery from mild traumatic brain injury (mTBI) is complex, reflecting the interaction of multiple biological, psychological, social, and environmental factors. Ultimately, accurate prognosis and the development of new effective treatments will require the identification of these factors and an elucidation of their mechanistic effects. Based on extensive preliminary data, this application proposes to test the hypothesis that a common herpesvirus, cytomegalovirus (CMV), is an overlooked but treatable source of adverse mTBI outcomes.

PI_NAMEs: MEIER, TIMOTHY B. (contact);SAVITZ, JONATHAN

PROGRAM_OFFICER_NAME: UMOH, NSINI ALEASE

PROJECT_TERMS: Acute;adverse outcome;Affect;Aging;Alzheimer's Disease;Autoimmune Diseases;Behavioral;Biological;Biological Factors;biopsychosocial;Blood;Blood Vessels;blood-based biomarker;Brain;Brain Concussion;Brain Injuries;cell type;chemokine;Chronic;Clinical;Clinical assessments;Clinical Data;clinical effect;clinical phenotype;cofactor;cognitive performance;cohort;Collection;Complex;contact sports;CXCL10 gene;cytokine;Cytomegalovirus;Data;depressive symptoms;Development;Diffusion Magnetic Resonance Imaging;Disease;Education;effective therapy;Encephalitis;Endothelial Cells;Enrollment;Ensure;Environmental Risk Factor;Female;follow up assessment;follow-up;Functional Magnetic Resonance Imaging;Glial Fibrillary Acidic Protein;Goals;Health;Herpesviridae;Herpesviridae Infections;Herpesvirus 1;Hour;Human Herpesvirus 4;immune function;Immunocompromised Host;Immunologics;improved;Individual;Inflammation;Inflammatory;Inflammatory Response;information gathering;Injury;Interferon alpha;latent infection;Magnetic Resonance Imaging;male;Manufactured football;Measures;Mental disorders;mild traumatic brain injury;Morbidity - disease rate;MRI Scans;Multiple Sclerosis;Myeloid Cells;nerve injury;Neurocognitive Deficit;Neurodegenerative Disorders;Neurofilament-L;Neuroglia;neuroinflammation;Neurologic;Neuronal Injury;Neurons;neuropathology;neurophysiology;neuropsychiatric disorder;neurotropic;neurotropic virus;novel;Outcome;Participant;Pathologic;Patients;Pericytes;persistent symptom;personalized medicine;Persons;Pharmaceutical Preparations;physiologic stressor;Physiological;Play;Population;precision medicine;predictive modeling;prevent;Prognosis;prognostic model;Psychological Factors;Psychological Stress;psychological symptom;Public Health;reactivation from latency;Recovery;Research;response;Rest;Risk;Role;seropositive;Severities;Shapes;Sleep disturbances;social factors;Source;Sports;Stress;Structure;Subgroup;Symptoms;tau Proteins;TBI Patients;Testing;Thick;Thinness;TNF gene;Traumatic Brain Injury;UCHL1 gene;Virus Diseases;Visit

PROJECT_TITLE: The role of cytomegalovirus in the physiological and clinical effects of concussion

STUDY_SECTION: ANIE

STUDY_SECTION_NAME: Acute Neural Injury and Epilepsy Study Section[ANIE]


ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: PROJECT NARRATIVE Bone morphogenic proteins (BMPs) represent a major developmental signaling pathway, with mutations in different pathway component genes resulting in developmental abnormalities. Understanding how each component of this pathway contributes to signaling is vital as minor changes in signal levels are sufficient to prevent healthy biological outcomes. This proposal will expand our current understanding of how BMP signaling is regulated at the receptor level, identifying key functional differences between the receptors that we can leverage to study disease causing variants.

PI_NAMEs: PATEL, JEET H (contact)

PROGRAM_OFFICER_NAME: MUKHOPADHYAY, MAHUA

PROJECT_TERMS: Address;Attenuated;Biochemical;Biological;Biological Process;BMP2 gene;bone morphogenetic protein receptor type I;bone morphogenetic protein receptors;Bone Morphogenetic Proteins;Brain;Cardiovascular Diseases;Cell membrane;cell type;Cells;cofactor;Complex;Defect;Development;developmental disease;Developmental Process;Diffusion;dimer;Disease;disease-causing mutation;Embryo;Endocytosis;expectation;Family;Gastrula;Gene Expression;Genes;Genetic Transcription;Glioma;Human;Individual;Insecta;Lateral;Ligands;Limb structure;Lung Diseases;Malignant Neoplasms;Membrane;Minor;Modeling;Molecular;morphogens;mutant;Mutation;Nature;Neural tube;Outcome;Pathway interactions;Pattern;Phosphorylation;Phosphotransferases;prevent;Process;progressive myositis ossificans;receptor;receptor function;receptor internalization;Regulation;Role;scaffold;Shapes;Signal Pathway;Signal Transduction;Signaling Protein;skeletal disorder;System;Testing;Tissues;trafficking;Transforming Growth Factor beta;Transforming Growth Factor beta Receptors;Vertebrates;Work;Zebrafish

PROJECT_TITLE: Molecular basis for BMP receptor specialization and trafficking

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F05-D (21)]


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Clinical Research;Foodborne Illness;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Microbiome;Pediatric;Prevention;Social Determinants of Health

ORG_CITY: ATLANTA

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: EMORY UNIVERSITY

PHR: PROJECT NARRATIVE The gut microbiome, which begins to develop in early life, is associated with many important physiological functions. Harmful exposures during the first year of life (e.g., heavy metals and enteropathogen exposures that are prevalent in drinking water in low-income contexts) can cause gut dysbiosis, which is associated with many adverse health outcomes. This project will investigate if and how improvements to drinking water quality and access influence infant gut microbiome composition among children in Beira, Mozambique, which is critical to improve our understanding of the association between drinking water quality and access on both acute and chronic sequelae related to gut dysbiosis.

PI_NAMEs: VICTOR, COURTNEY  (contact)

PROGRAM_OFFICER_NAME: GONDRE-LEWIS, TIMOTHY A

PROJECT_TERMS: Acute;Address;Age Months;Animals;antimicrobial;Biological;Birth;Chemical Exposure;Chemicals;Child;Child Health;Childhood;chlorination;Chronic;cognitive function;cohort;Communities;Consumption;contaminated drinking water;critical period;Data;design;Development;Diarrhea;Diet;Dose;drinking water;dysbiosis;enteric infection;enteric pathogen;Environmental Exposure;exposure route;Exposure to;Growth;gut dysbiosis;gut health;gut microbiome;gut microbiota;Health;health difference;Heavy Metals;Household;immune function;improved;Individual;Infant;infant gut microbiome;insight;Intervention;Intervention Trial;Knowledge;Life;Link;Low income;maternal microbiota;Measurable;Measures;Metabolic;Metabolism;Metal exposure;microbial;microbiome;microbiome composition;microbiome research;Mozambique;Municipalities;National Institute of Allergy and Infectious Disease;Neighborhoods;novel;Outcome;Parents;Personal Satisfaction;Physiological;Play;Predisposition;prospective;Research;Resistance to infection;response;Role;rural setting;Services;Source;System;Testing;Time;Toxicology;UNICEF;Variant;Water;water quality;Water Supply

PROJECT_TITLE: Evaluating the Influence of an Improved Piped Water Network on Water Quality and Gut Microbiome Composition Among Children in Mozambique

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F18-E (20)]


NIH_SPENDING_CATS: Biotechnology;Cancer;Orphan Drug;Ovarian Cancer;Prevention;Rare Diseases;Women's Health Research

ORG_NAME: HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH

PHR: PROJECT NARRATIVE The intrinsic (or mitochondrially mediated) apoptosis pathway is a fundamental cell death pathway that helps maintain tissue homeostasis and prevent neoplastic transformation. High grade serous ovarian carcinoma (HGSOC), the deadliest and most common subtype of ovarian cancer, is found to have dysregulated expression of the BCL-2 family proteins that control the intrinsic apoptosis pathway, which supports HGSOC tumor cell survival. Thus, we propose to investigate the origins of this apoptotic dysregulation and therapeutically target these proteins to increase tumor cell death and improve patient outcomes.

PI_NAMEs: JOHNSON, LISSAH KYALAMBOKA (contact)

PROGRAM_OFFICER_NAME: ADAMS, GREGORY

PROJECT_TERMS: Accounting;Affect;Air;anti-cancer research;Apoptosis;Apoptotic;BCL-2 Protein;bcl-xlong protein;BCL1 Oncogene;BCL2L1 gene;Buffers;Cancer Biology;cancer cell;cancer risk;cancer type;Carboplatin;carcinogenesis;career;Cell Death;Cell Line;Cell Survival;cell transformation;Cells;Cessation of life;Chemoresistance;Communication;crosslink;Data;Death Rate;Dependence;design;Disease;Drug Targeting;Early Diagnosis;Early treatment;efficacy evaluation;Environmental Health;epidemiology study;Epithelial Cells;Epithelium;Estrogens;experience;Family;Follicular Fluid;Goals;Gonadal Steroid Hormones;Growth;Gynecologic;Homeostasis;homologous recombination;Hormonal;Hormone replacement therapy;Hormones;Human;improved;In Vitro;in vivo;Induction of Apoptosis;innovation;insight;Laboratories;Learning;Liquid substance;Malignant - descriptor;Malignant Epithelial Cell;Malignant Female Reproductive System Neoplasm;Malignant neoplasm of ovary;Malignant Neoplasms;Mammalian Oviducts;Manuscripts;Measures;Mediating;Mentors;Mentorship;metaplastic cell transformation;Methods;Microtubules;mimetics;Mitochondria;Modeling;mouse model;Mutagens;mutant;Neoplasm Metastasis;neoplastic cell;Neoplastic Cell Transformation;Neoplastic Processes;novel;Oncogene Activation;Ovarian;Ovarian Serous Adenocarcinoma;Ovulation;Paclitaxel;Pathway interactions;patient derived xenograft model;Patient-Focused Outcomes;Patients;Persons;Physiological;Platinum;Positioning Attribute;Postdoctoral Fellow;Postmenopause;premalignant;Premalignant Cell;prevent;Process;Progesterone;protein expression;Protein Family;Proteins;Publishing;Recurrence;Recurrent tumor;Regulation;Research;Research Proposals;Risk Factors;Sampling;Science;Scientist;Secretory Cell;Signal Transduction;skills;standard of care;Stress;Survival Rate;symposium;targeted treatment;taxane;Techniques;Testing;Therapeutic;therapeutic target;Therapeutically Targetable;Tissues;TP53 gene;Training;Treatment Effectiveness;treatment response;tumor;Tumor Burden;tumorigenesis;tumorigenic;Up-Regulation;verbal;Woman;women's diagnosis;Writing

PROJECT_TITLE: Understanding and exploiting apoptotic dysregulation in ovarian cancer

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F09A-R (20)]


ORG_CITY: SEATTLE

ORG_NAME: BENAROYA RESEARCH INST AT VIRGINIA MASON

ORG_STATE: WA

PHR: PROJECT NARRATIVE Regulatory T cells (Tregs) are a specialized subset of T cells, regulated by the transcription factor FOXP3, that control peripheral tolerance. A failure in their ability to control self-reactive T cells in the periphery leads to autoimmunity, causing immunopathology and tissue dysfunction. We have discovered a novel mechanism for Treg-mediated suppression, and the studies in this proposal will provide mechanistic insights into this process and provide important data for the potential identification of new therapeutic pathways.

PI_NAMEs: BUCKNER, JANE HOYT;SAVAN, RAM ;ZIEGLER, STEVEN F (contact)

PROGRAM_OFFICER_NAME: JIANG, CHAO

PROJECT_TERMS: Acute;Antigen-Presenting Cells;Autoantigens;Autoimmune Diseases;Autoimmunity;Automobile Driving;autoreactive T cell;CD4 Positive T Lymphocytes;Cell Physiology;Cellular biology;CTLA4 gene;cytokine;Data;Development;Drops;effector T cell;Eragrostis;experimental study;Failure;FOXP3 gene;Functional disorder;Genes;Genetic Transcription;Goals;Homeostasis;Human;Immune;Immune response;Immune system;Immunodysregulation polyendocrinopathy enteropathy X-linked syndrome;immunopathology;Inflammation;insight;Insulin-Dependent Diabetes Mellitus;Interleukin-10;Maintenance;Mediating;Messenger RNA;Modeling;Molecular;mRNA Translation;Multiple Sclerosis;Mus;Mutation;Nature;novel;novel therapeutics;pathogen;Pathway interactions;peripheral tolerance;Polyribosomes;Post-Transcriptional Regulation;Process;programmed cell death protein 1;Proliferating;Protein Biosynthesis;Proteins;receptor;Regulation;Regulatory T-Lymphocyte;Ribosomes;RNA;RNA-Binding Proteins;Role;Signal Transduction;Syndrome;T cell regulation;T-Lymphocyte;T-Lymphocyte Subsets;Testing;Therapeutic Intervention;therapeutic target;Tissues;transcription factor;Translating;Translational Repression;Translations;translatome

PROJECT_TITLE: Regulatory T cells maintain immune homeostasis through translation control

STUDY_SECTION: HAI

STUDY_SECTION_NAME: Hypersensitivity, Autoimmune, and Immune-mediated Diseases Study Section[HAI]


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

ORG_DEPT: NEUROLOGY

PHR: NARRATIVE: This study seeks to identify key regulators of retinal injury and regenerative responses and the gene expression programs that they control. If successful, these regulators could be leveraged to stimulate regenerative responses in the human retina which would be transformational for the treatment of retinal degenerative diseases and cell loss due to retinal injury.

PI_NAMEs: GROSS, JEFFREY  (contact)

PROGRAM_OFFICER_NAME: FORTRESS, ASHLEY

PROJECT_TERMS: Adopted;Adult;Alleles;Amphibia;Birds;candidate identification;Cell Cycle;Cells;Chromatin;Cicatrix;Clinic;Data;Development;Ectopic Expression;Enhancers;Epigenetic Process;epigenetic regulation;experimental study;Eye;Fishes;gain of function;Gene Expression;Gene Expression Regulation;gene function;gene regulatory network;Genes;Histones;Human;Injury;Knock-in;Knowledge;loss of function;Mammals;Mediating;Modeling;Molecular;Muller's cell;Mus;Natural regeneration;Neurons;novel;novel therapeutics;Outcome;Play;progenitor;programs;Proliferating;Proteins;Publishing;regeneration model;regenerative;Regenerative capacity;Regenerative response;response;response to injury;Retina;retinal damage;Retinal Degeneration;retinal regeneration;Role;stemness;Testing;tool;Transgenic Organisms;Vertebrates;Zebrafish

PROJECT_TITLE: Epigenetic Regulation of Retinal Regeneration

STUDY_SECTION: NDPR

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


ORG_CITY: Newark

ORG_DEPT: PHARMACOLOGY

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: Project Narrative: PIEZO2 channels are necessary for sensing inflammation induced mechanical pain affecting millions of Americans each year causing substantial economic and emotional burdens. Identifying robust and selective inhibitory mechanisms of PIEZO2 contributes to an emerging field of mechanosensation which has recently been recognized by the Nobel Prize. We propose an intensive inquiry into the robust, selective inhibition of PIEZO2 channels by a possible lipid modifying enzyme (TMEM120A) contributing to a growing body of evidence implicating lipids as key modulators of mechanosensation.

PI_NAMEs: GABRIELLE, MATTHEW  (contact)

PROGRAM_OFFICER_NAME: MOHAPATRA, DURGA PRASANNA

PROJECT_TERMS: Acute;Adipocytes;Adipose tissue;Affect;American;Amyloid beta-Protein;Analgesics;analog;Animal Model;Area;C Fiber;Catalytic Domain;Cells;Cellular Membrane;Coenzyme A;Data;Dietary Fatty Acid;Economics;Electrophysiology (science);Emotional;Enzymes;Event;experimental study;extracellular;Fatty Acids;Glycerol;Head;Hour;Impairment;Inflammation;Inflammatory;Injections;Investigation;Ion Channel;knock-down;Knowledge;Lecithin;Light;Lipids;Liquid Chromatography;long chain fatty acid;lysophosphatidic acid;mechanical allodynia;Mechanical Stimulation;mechanical stimulus;Mechanics;Mediating;Membrane;Membrane Lipids;Metabolic;Modeling;Modification;Movement;Mus;Mutate;Nerve;Neurons;Nobel Prize;novel;Oryctolagus cuniculus;Pain;Periodicity;Phosphatidic Acid;Phospholipase D;Piezo 1 ion channel;Piezo 2 ion channel;Point Mutation;potassium channel protein TREK-1;premature;Preparation;Production;Proprioception;Proteins;Rattus;Regulation;Reporting;Sensory;Skin;small molecule;Spinal Ganglia;Structure;System;tandem mass spectrometry;Techniques;Testing;Therapeutic;Tissues;Touch sensation;Up-Regulation;Vertebral column;Very Long Chain Fatty Acid

PROJECT_TITLE: Negative regulatory mechanism of mechanically activated PIEZO2 channels by TMEM120A/TACAN

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F03B-L (20)]


ORG_CITY: SALT LAKE CITY

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: Project Narrative Metabolism is a highly regulated process that has a strong influence on many diseases including, cancer, diabetes, and age-related neurodegenerative disorders. Our lab recently discovered a mitochondrial remodeling mechanism called the mitochondrial-derived compartment (MDC) pathway that is responsive to metabolic disruptions in both amino and carbon-sources. New insights into this evolutionary conserved pathway gleaned from the proposed studies will provide further understanding of how mitochondria remodel during metabolic transitions.

PI_NAMEs: PRICE, BO JULIAN (contact)

PROGRAM_OFFICER_NAME: MCINTYRE, JEREMY COLIN

PROJECT_TERMS: 5'-AMP-activated protein kinase;acid stress;Acute;Age;age related neurodegeneration;aging related disease;amino acid metabolism;Amino Acids;Autophagocytosis;Biological Assay;Carbon;career;career development;Cell Aging;Cells;Citric Acid Cycle;Cues;Cyclic AMP-Dependent Protein Kinases;Data;Degenerative Disorder;deprivation;detection of nutrient;Diabetes Mellitus;Diameter;Disease;Environment;Equilibrium;Fermentation;Genetic Transcription;Glean;Glucose;Goals;Growth;Health;Homeostasis;Impairment;innovation;insight;Knock-out;Lead;Lipids;Lysosomes;Malignant Neoplasms;Mammals;Metabolic;Metabolic Diseases;Metabolic stress;Metabolism;metabolomics;Mitochondria;Mitochondrial Membrane Protein;Mitochondrial Proteins;multicatalytic endopeptidase complex;NADH;novel;Nutrient;Outer Mitochondrial Membrane;Output;Oxidative Phosphorylation;Parkinson Disease;Pathway interactions;Peptide Hydrolases;posttranscriptional;Process;protein degradation;Proteins;Publishing;Quality Control;Reaction;Research;Respiration;respiratory;response;Saccharomyces cerevisiae;Signal Pathway;Sirolimus;Sorting;Source;Starvation;Stress;Structure;System;Testing;Training;Translational Repression;Translations;Ubiquitin;uptake;Vacuole;Vesicle;Yeasts

PROJECT_TITLE: Characterization of Glucose Starvation-Induced Mitochondrial-Derived Compartments


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

NIH_SPENDING_CATS: Aging;Neurosciences;Nutrition

ORG_CITY: DAVIS

ORG_DEPT: ZOOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: PROJECT NARRATIVE Robust daily rhythms of physiology and behavior are hallmarks of healthspan and contribute to longevity. This project aims to understand the molecular mechanisms by which metabolic signals from daily feeding-fasting cycles interact with environmental time cues to regulate temporal changes in physiology over the 24-hour day-night cycle. Our findings will shed light on the impact of disrupting metabolic regulation of daily biology rhythms, e.g. in situation of mistimed feeding, and pave the way to identification and characterization of new therapeutic targets for circadian and metabolic disorders.

PI_NAMEs: CHIU, JOANNA CHUNGYEN (contact)

PROGRAM_OFFICER_NAME: FU, YI-PING

PROJECT_TERMS: Address;Animals;Atlases;Behavior;Biological Clocks;Biological Rhythm;Biology;biomarker identification;Brain;Bypass;Cell Physiology;Cells;Chronic Disease;circadian;Circadian Dysregulation;circadian pacemaker;Circadian Rhythms;Collaborations;Communities;Complex;Coupled;Cues;Darkness;Data;Data Discovery;Data Set;Databases;Dedications;Deposition;design;Drosophila genus;Eating;Environment;Equilibrium;Exhibits;Fasting;feeding;fly;Gene Expression;Genetic Transcription;Goals;healthspan;Heart;Hour;insight;Knowledge;Light;Link;Liver;Longevity;Malignant Neoplasms;Mediating;Metabolic;Metabolic Diseases;Metabolism;Molecular;Mus;new therapeutic target;Nutrient;Organ;Output;Pathology;Pathway interactions;Periodicity;Peripheral;Phosphorylation;Physiology;Play;Post-Translational Modification Site;Post-Translational Protein Processing;protein function;protein structure;Proteins;Proteome;Proteomics;public repository;Publishing;Regulation;Reporting;response;Role;searchable database;Serine;Shapes;Signal Transduction;Site;Structure;System;Testing;Threonine;Time;Time-restricted feeding;Tissues;user-friendly;web interface;web server;Work

PROJECT_TITLE: Nutrient-sensitive protein modifications regulate daily biological rhythms

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 ICN-U (02)]


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

ORG_CITY: OKLAHOMA CITY

ORG_NAME: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR

ORG_STATE: OK

PHR: Project Narrative The increasing prevalence of multifocal cerebral microhemorrhages (also known as “cerebral microbleeds) is a significant problem in the aging population, which progressively impair neuronal function and contribute to cognitive decline and gait disorders.Our hypothesis is that aging-induced accumulation of senescent endothelial cells in the cerebral microcirculation is responsible for a pro- fragility microvascular phenotype: senescent cells release activated matrix proteinases and other paracrine factors ("senescence-associated secretory phenotype" or SASP), which promote structural maladaptation to high pressure, degradation of collagen and remodeling of extracellular matrix, thus creating loci of least resistance that can easily burst upon induction of hypertension. Using an approach that combines neuroanatomical analysis, innovative imaging techniques, and integrative cerebrovascular physiology, we will be able to test novel, translationally relevant interventional strategies, senolytics, for prevention of CMHs and protecting cerebral function in the elderly as well.

PI_NAMEs: CSISZAR, ANNA ;UNGVARI, ZOLTAN ISTVAN (contact)

PROGRAM_OFFICER_NAME: ST  HILLAIRE-CLARKE, CORYSE

PROJECT_TERMS: Acceleration;Address;Affect;Age;age related;aged;Aging;aging population;Alzheimer's Disease;Alzheimer's disease pathology;blood pressure elevation;Blood Vessels;Brain;Cell Aging;cerebral microbleeds;cerebral microvasculature;cerebrovascular;Cerebrovascular Physiology;Cerebrum;Clinical;Clinical Research;clinically relevant;Collagen;Cranial Irradiation;detector;Development;Diameter;Elderly;Endothelial Cells;equilibration disorder;executive function;Extracellular Matrix;falls;Gait abnormality;Gene Expression;Genes;genetic manipulation;Goals;Human;Hypertension;Imaging Techniques;Impaired cognition;Impairment;improved;in vivo;innovation;insight;Intervention;Intracranial Hemorrhages;irradiation;Laboratory Animals;Link;Matrix Metalloproteinases;Memory;Microcirculation;mouse model;multiphoton microscopy;Mus;Neuroanatomy;Neurologic Deficit;Neurologic Signs;Neurons;neurovascular;neurovascular unit;novel;novel therapeutic intervention;old mice;older adult;older patient;Older Population;Outcome;Oxidative Stress;paracrine;Pathogenesis;Peptide Hydrolases;pharmacologic;Phenotype;Physiological;pre-clinical;Pre-Clinical Model;preservation;pressure;Prevalence;prevent;Prevention;Prevention approach;Prevention strategy;processing speed;Quality of life;Reactive Oxygen Species;Recurrence;Research;Resistance;Risk;Risk Factors;Rupture;senescence;senescence associated secretory phenotype;senescent cell;senolytics;Stroke;stroke risk;Structure;Testing;Therapeutic Intervention;transcriptomics;Transient Ischemic Attack;United States National Institutes of Health;Vascular Cognitive Impairment;Work

PROJECT_TITLE: Cerebral microhemorrhages and gait abnormalities in aging

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 CN-T (02)]


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

ORG_CITY: PASADENA

ORG_NAME: CALIFORNIA INSTITUTE OF TECHNOLOGY

PHR: Project Narrative The first wave of thymocyte differentiation in the fetal thymus proceeds rapidly and gives rise to specific lineages of innate lymphocytes and innate-like T cells that are not generated by any subsequent wave of development. Based on my preliminary data, I hypothesize that these populations arise from a dedicated precursor cell in the fetal thymus that is using a unique differentiation program. In this proposal, I aim to test test this hypothesis through fate mapping and perturbation studies to construct a full lineage hierarchy of fetal thymocyte differentiation and the gene regulatory networks that govern it.

PI_NAMEs: MACNABB, BRENDAN WILLIAM (contact)

PROJECT_TERMS: Adult;antagonist;Atlases;Bar Codes;Cell Differentiation process;Cell Lineage;Cells;Characteristics;Chromatin;cohort;Collaborations;Complex;CRISPR/Cas technology;Curiosities;Data;Data Set;Dedications;Development;DNA;Embryo;Environment;Epigenetic Process;Erythrocytes;fetal;Fetal Development;fetal stem cell;GATA1 gene;GATA3 gene;gene regulatory network;gene repression;Generations;Genes;Genetic;Genetic Transcription;Helper-Inducer T-Lymphocyte;Hematopoiesis;Hematopoietic stem cells;Homeostasis;Immune;in vivo;Inherited;Kinetics;Life;Link;Lymphocyte;Lymphoid;Lymphoid Cell;Lymphoid Tissue;Macrophage;Maintenance;Maps;mast cell;Mature T-Lymphocyte;Megakaryocytes;member;Molecular;Multipotent Stem Cells;Mus;Organ Culture Techniques;Organogenesis;pathogen;Pathway interactions;Population;postnatal;precursor cell;Pregnancy;Process;progenitor;programs;Property;Repression;Research;response;Role;Signal Transduction;single cell ATAC-seq;single-cell RNA sequencing;Speed;stem;stem cell genes;stem cell population;T cell differentiation;T-Cell Development;T-Lymphocyte;T-Lymphocyte Subsets;Testing;thymocyte;Thymocyte Development;Thymus Gland;timeline;Tissues;transcription factor;Transcriptional Regulation;Work;Yolk Sac;ZNF145 gene;γδ T cells

PROJECT_TITLE: Dissecting the transcription factor networks controlling fetal T-lineage differentiation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F07B-G (20)]


NIH_SPENDING_CATS: Anxiety Disorders;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Cocaine;Drug Abuse (NIDA only);Mental Health;Neurosciences;Post-Traumatic Stress Disorder (PTSD);Stimulant Use and Misuse;Substance Misuse

ORG_CITY: PONCE

ORG_NAME: PONCE SCHOOL OF MEDICINE

ORG_STATE: PR

PHR: PROJECT NARRATIVE The proposed study has considerable relevance for public health as it will elucidate the neurophysiological mechanisms that cause individuals with substance use disorder and trauma-related disorder comorbidity to have poor adherence to treatment and high relapse rates and accordingly, it may ultimately aid in the development of effective therapies. This project aims to elucidate the effects of fear conditioning and cocaine exposure on prelimbic cortex modulation of nucleus accumbens core neurons, concerning drug-seeking behavior in a rat model. Understanding how trauma-related disorders and SUD comorbidity alters the communication within this circuitry may provide the basis for developing new pharmacological interventions that could reduce cocaine relapse.

PI_NAMEs: PEREZ, YOBET A (contact)

PROGRAM_OFFICER_NAME: FALCON-MORALES, EDGARDO

PROJECT_TERMS: Acute Post Traumatic Stress Disorder;Adherence;Adult;Age;American;AMPA Receptors;Amygdaloid structure;Animal Model;attenuation;Behavior;Behavioral;Behavioral Paradigm;Cells;Clinical Research;Cocaine;cocaine exposure;cocaine relapse;cocaine seeking;cocaine self-administration;cocaine use;Cocaine use disorder;Communication;comorbidity;comparison control;conditioned fear;Consumption;Cues;Data;designer receptors exclusively activated by designer drugs;Development;Disease;Drug Exposure;drug seeking behavior;Drug usage;effective therapy;Electrophysiology (science);experience;Exposure to;Extinction;fear memory;Female;Health;High Prevalence;Hour;illicit drug use;Individual;insight;Intervention;Knowledge;male;Memory;Mental disorders;Methodology;Modeling;N-Methyl-D-Aspartate Receptors;N-Methylaspartate;Neurons;neurophysiology;Nucleus Accumbens;optogenetics;Outcome;patch clamp;Patients;Pharmaceutical Preparations;pharmacologic;Play;Post-Traumatic Stress Disorders;postsynaptic;Predisposition;Prefrontal Cortex;public health relevance;Rattus;Relapse;Research;Research Project Summaries;Risk;Role;Self Administration;Severities;sex;Stress;stress disorder;stressor;Structure;Substance Use Disorder;Surveys;Synapses;Synaptic plasticity;Testing;Training;Trauma;trauma exposure;traumatic event;Withdrawal

PROJECT_TITLE: Influence of fear conditioning prior to cocaine self-administration on cocaine seeking in adult rats: assessing the role of the frontostriatal circuits in trauma and cocaine use co-occurrence

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F02A-W (20)]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Diabetes;Digestive Diseases;Hepatitis;Liver Disease;Nutrition;Obesity

ORG_CITY: LA JOLLA

ORG_NAME: SCRIPPS RESEARCH INSTITUTE, THE

PHR: NARRATIVE Obesity is an epidemic in the United States that has led to a great increase in obesity-driven metabolic disorders, including Type 2 diabetes, nonalcoholic fatty liver disease (NAFLD), and nonalcoholic steatohepatitis (NASH). Despite the high incidence of these diseases, therapeutic strategies to treat obesity-driven conditions remain limited. This project will define the potential of pharmacological activation of protective unfolded protein response signaling pathways to promote adaptive remodeling of metabolic tissues, including liver, and alleviate tissue- specific metabolic alterations present in these disorders, and thus informing on translational strategies to intervene in these metabolic diseases.

PI_NAMEs: SAEZ, ENRIQUE  (contact);WISEMAN, ROCKLAND LUKE

PROGRAM_OFFICER_NAME: GARCIA, MARTHA

PROJECT_TERMS: Address;arm;ATF6 gene;Biochemical;Biological;blood glucose regulation;Cardiotoxicity;Cell model;Cell Physiology;Clinical;Complex;Cytosol;Defect;Development;diet-induced obesity;Disease;endoplasm;Endoplasmic Reticulum;endoplasmic reticulum stress;Epidemic;Fatty Liver;Fibrosis;Fostering;Functional disorder;Goals;Health;Hepatic;hepatic gluconeogenesis;improved;in vivo;Incidence;Inflammation;insight;interest;Link;Lipids;Liver;Liver Dysfunction;liver function;MAPK8 gene;Mediating;Metabolic;Metabolic Diseases;Metabolic dysfunction;Metabolism;Molecular;mouse model;mRNA Transcript Degradation;Nature;NF-kappa B;non-alcoholic fatty liver disease;Non-Insulin-Dependent Diabetes Mellitus;nonalcoholic steatohepatitis;novel therapeutic intervention;Nutrient;Obese Mice;Obesity;Organ;Outcome;Pancreas;Pathologic;Pathology;Pathway interactions;pharmacologic;Phenotype;Prevalence;Proteins;response;Reticulum;Role;sedentary lifestyle;side effect;Signal Pathway;Signal Transduction;small molecule;Stress;Therapeutic;Time;Tissue Model;Tissues;TRAF2 gene;transcription factor;translational approach;Translations;Unhealthy Diet;United States;XBP1 gene

PROJECT_TITLE: Pharmacologic targeting of the UPR in obesity-linked liver dysfunction

STUDY_SECTION: BMDM

STUDY_SECTION_NAME: Basic Mechanisms of Diabetes and Metabolism Study Section[BMDM]


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Aging;Bioengineering;Biomedical Imaging;Eye Disease and Disorders of Vision

ORG_CITY: COLLEGE PARK

ORG_NAME: UNIV OF MARYLAND, COLLEGE PARK

ORG_STATE: MD

PHR: Project Narrative Presbyopia corrections so far have not addressed the causative nature of loss of accommodation, and major barriers to innovation result from the need to measure biomechanics in vivo. The goal of this project is to characterize the spatially-varying biomechanical signature of the lens by developing an in vivo measurement of mechanics. Results from this study will provide a method to monitor and plan novel presbyopia treatments that target biomechanics.

PI_NAMEs: SCHUMACHER, JUSTIN SCOTT (contact)

PROGRAM_OFFICER_NAME: AGARWAL, NEERAJ

PROJECT_TERMS: 3-Dimensional;Acoustics;Address;Affect;Age;age related changes;Assessment tool;biomarker identification;Biomechanics;biophysical model;burden of illness;Calibration;Ciliary Muscle;Clinic;Clinical;Collaborations;Crystalline Lens;Data;Defect;Diagnosis;Diagnostic;Early Intervention;Elasticity;elastography;Elements;Evaluation;Eye;Eyeglasses;Family suidae;field study;Frequencies;Goals;Grant;Human;Image;In Situ;in vivo;in vivo imaging system;innovation;insight;instrument;Lateral;Length;lens;Maps;Measurement;Measures;mechanical properties;Mechanics;Methods;Microscopy;Modeling;Modulus;Monitor;Morphologic artifacts;Motion;Myopia;Nature;novel;novel marker;novel therapeutics;Optical Coherence Tomography;Optics;Pathology;Patients;Performance;Physiological;potential biomarker;precision medicine;predictive modeling;Presbyopia;Procedures;programs;Property;Protocols documentation;prototype;Quality of life;Quantitative Evaluations;Refractive Errors;Research;Resistance;Resolution;response;Shapes;Specific qualifier value;Speed;success;Surface;System;Techniques;Testing;Therapeutic;Tissues;Translations;Treatment outcome;vapor;Variant;virtual clinical trial;Vision

PROJECT_TITLE: Combining OCE and Brillouin microscopy to evaluate in vivo lens biomechanics in Presbyopia

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F05-Q (20)]


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Clinical Research;Clinical Trials and Supportive Activities;Digestive Diseases;Genetics;Human Genome;Orphan Drug;Pancreatic Cancer;Precision Medicine;Rare Diseases

ORG_CITY: CHAPEL HILL

ORG_DEPT: SURGERY

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: Narrative We and others have shown that basal tumors, which comprise <20% of PDAC tumors, are resistant to the first- line chemotherapy regimen FOLFIRINOX. We leverage a transformative high sensitivity method of defining the kinome in low input samples such as biopsies, to identify targeted approaches specifically for basal subtype tumors.

PI_NAMEs: JOHNSON, GARY L.;YEH, JEN JEN  (contact)

PROGRAM_OFFICER_NAME: OLKHANUD, PUREVDORJ BALJINNYAM

PROJECT_TERMS: Aftercare;Biopsy;Cell Line;chemotherapy;Chemotherapy-Oncologic Procedure;Clinical Trials;Combination Drug Therapy;Data;effectiveness evaluation;EPHA2 gene;Epidermal Growth Factor Receptor;Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor;Erlotinib;Family;gemcitabine;Gene Expression;Genomics;Human;IGF1R gene;improved;inhibitor;inhibitor therapy;Isotopes;kinase inhibitor;Knowledge;knowledgebase;KRAS2 gene;Label;Malignant neoplasm of pancreas;Mass Spectrum Analysis;Measurement;Medical Oncologist;Methods;Modeling;molecular subtypes;Monitor;multidisciplinary;novel;Organoids;Outcome;Paclitaxel;Pancreatic Adenocarcinoma;Pancreatic Ductal Adenocarcinoma;Pathway interactions;patient derived xenograft model;Patients;Peptide Library;Peptides;pharmacologic;Phosphotransferases;Pilot Projects;precision oncology;Prognosis;protein expression;Protein Kinase;Proteomics;Randomized;Reaction;Receptor Protein-Tyrosine Kinases;Resistance;response;Sampling;standard of care;Subgroup;success;targeted treatment;Therapeutic;Time;transcriptome sequencing;translational scientist;treatment response;tumor;Tumor Cell Line;Tumor Subtype

PROJECT_TITLE: Targeted EGFR for basal subtype pancreatic cancer

STUDY_SECTION_NAME: Clinical Oncology Study Section[CONC]


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

ORG_CITY: La Jolla

ORG_NAME: SALK INSTITUTE FOR BIOLOGICAL STUDIES

PHR: PROJECT NARRATIVE Sensory feedback is critical for effective interaction with the world, requiring neural circuit mechanisms for dynamically adjusting how sensory signals are transmitted as conditions and contexts change. This proposal aims to define how connections between the central amygdala, a structure involved in processing internal states of stress and fear, and the cuneate nucleus, which transmits tactile information, are involved in adjusting the strength of sensory signaling on short time scales as well as following stressful experiences such as chronic isolation. Identifying the neural mechanisms by which social isolation modulates the processing of sensory feedback will help to clarify how chronically altered internal states affect the nervous system and lay the foundation for improved diagnosis and treatment.

PI_NAMEs: MOSKO, JACQUELINE ROSE (contact)

PROGRAM_OFFICER_NAME: OSBORNE, LESLIE CAROL

PROJECT_TERMS: Acute;Affect;Affective;Amygdaloid structure;Animals;Attention;Attenuated;Behavior;Behavior assessment;Behavioral;Behavioral Assay;Biological Assay;Brain;Brain Stem;Chronic;Clothing;Complex;Cues;Data;design;Diagnosis;Discrimination;Disinhibition;Environment;Equilibrium;Esthesia;Experimental Designs;Feedback;Fiber;flexibility;Foundations;Fright;Goals;Hand;House mice;Hypersensitivity;improved;insight;Interneurons;Lead;Link;Measures;Mechanical Stimulation;Mediating;Modality;Movement;Mus;Nervous System;neural;neural circuit;neuromechanism;Neurons;Neuropeptide Gene;novel;Opsin;optogenetics;Pathologic;Pathway interactions;Pattern;Photometry;Physiological;Proxy;Research;response;Rodent;selective expression;Sensory;sensory feedback;sensory processing disorder;sensory stimulus;Signal Transduction;Skin;Social isolation;social stress;somatosensory;Somatosensory Cortex;Source;Stress;stress state;Stressful Event;Structure;Structure of nucleus cuneatus;Tachykinin;Tactile;tactile stimulation;Testing;Texture;Thalamic structure;Time;tool;Touch sensation;transmission process;vigilance;Viral;Work

PROJECT_TITLE: The Effect of Social Isolation on Inhibitory Modulation of Tactile Processing

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F02B-Y (20)]


ORG_CITY: STANFORD

ORG_DEPT: PHYSICS

ORG_NAME: STANFORD UNIVERSITY

PHR: PROJECT NARRATIVE Hypertonic exposure causes cell shrinkage and is thought to induce in vivo protein misfolding and aggregation, which are hallmarks for aging, cancer, and neurodegeneration. However, no studies have determined which endogenous proteins are compromised by hypertonicity, and little is known about the mechanisms that maintain proteome integrity during osmotic stress. The experiments proposed here will characterize the protein quality consequences and responses to hypertonic exposure, identifying determining factors for protein aggregation, refolding, and degradation that may inspire therapeutic strategies for protein-misfolding diseases.

PI_NAMEs: LE, KATHY H (contact)

PROGRAM_OFFICER_NAME: STAMM, JOYCE CHIN-CHIN NG

PROJECT_TERMS: Affect;Alzheimer's Disease;Amyotrophic Lateral Sclerosis;Biochemical;Biological;Biological Assay;Caenorhabditis elegans;career;cell growth;Cell Volumes;Cells;combat;CRISPR library;Data;Degradation Pathway;Disease;Environment;Equilibrium;Exhibits;experience;experimental study;Exposure to;Genetic;genome editing;Glycerol;Goals;hallmarks of aging;Health;Heat Stress;Heat-Shock Response;Human;Huntington Disease;In Vitro;in vivo;Individual;Inflammation;Label;Link;Malignant Neoplasms;Mass Spectrum Analysis;Measures;Mediating;Mentors;misfolded protein;model organism;Molecular;Molecular Chaperones;multicatalytic endopeptidase complex;Nerve Degeneration;Neurodegenerative Disorders;Organism;Osmosis;Oxidative Stress;Parkinson Disease;Pathway interactions;Physiologic pulse;Physiological;Play;Polyubiquitination;Predisposition;Production;programs;protein aggregation;Protein Biosynthesis;protein degradation;protein folding;protein misfolding;Proteins;Proteolysis;Proteome;Proteomics;proteostasis;proteotoxicity;Quality Control;Recovery;Research;Resistance;response;Role;Saccharomycetales;Shock;skills;Specificity;Stress;stress tolerance;Swelling;System;Techniques;Technology;Testing;Therapeutic;tool;Training;training opportunity;Translational Repression;Trehalose;Ubiquitin;virtual;Water;yeast genetics;Yeasts

PROJECT_TITLE: Investigating the role of protein quality control in osmotic stress adaptation