ADMINISTERING_IC: AA

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alcoholism, Alcohol Use and Health;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;Clinical Research;Dementia;Neurodegenerative;Neurosciences;Prevention;Substance Misuse

ORG_CITY: CHARLESTON

ORG_NAME: MEDICAL UNIVERSITY OF SOUTH CAROLINA

ORG_STATE: SC

PHR: Project Narrative Completing the aims laid out in this proposal will provide novel insights into both the pathology underlying cognitive impairment in Alcohol Use Disorder (AUD) and the specific mechanisms by which AUD increases the risk of Alzheimer’s Disease. Elucidating such mechanisms would be important not only from a basic science perspective but also from a clinical perspective in that it may reveal novel targets for interventions which can decrease the risk of dementia and cognitive impairment in individuals with AUD. As AUD and Alzheimer’s Disease are both common and debilitating disorders such revelations could result in a significant increase in both life expectancy and quality of life for millions around the world.

PI_NAMEs: WARNER, GRAHAM  (contact)

PROGRAM_OFFICER_NAME: EGLI, MARK

PROJECT_TERMS: Address;alcohol use disorder;Alzheimer's Disease;Alzheimer's disease related dementia;Alzheimer's disease risk;Amyloid;Basic Science;Brain;Clinical;Cognition;Cognitive;cognitive performance;cognitive testing;connectome;cost;Data;Dementia;dementia risk;Disease;Disease Progression;Early Diagnosis;Early Intervention;Ensure;Episodic memory;Functional disorder;Functional impairment;Functional Magnetic Resonance Imaging;Future;graph theory;imaging study;Impaired cognition;Impairment;Individual;insight;Intervention;Knowledge;Lateral;Life Expectancy;Link;Measures;medial temporal lobe;Mediating;memory encoding;mild cognitive impairment;mortality;network dysfunction;neuropathology;novel;novel marker;Outcome;Parietal;Participant;Pathology;Pattern;Preventive measure;Process;Prognosis;Quality of life;Reporting;Research;Rest;Risk;Risk Factors;risk minimization;Role;Short-Term Memory;standard measure;Structure;tau Proteins;therapeutic target;Vulnerable Populations

PROJECT_TITLE: Connectomic Dysfunction Underlying Cognitive Impairment in Alcohol Use Disorder and the Link to Alzheimer’s Disease


ADMINISTERING_IC: DK

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Genetics;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Urologic Diseases

ORG_CITY: Chicago

ORG_COUNTRY: UNITED STATES

ORG_DEPT: PATHOLOGY

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

ORG_STATE: IL

PHR: Project Narrative: Prostatic enlargement continues to be a significant and incurable health problem that will only become more prevalent as life expectancy increases. Thus, there is a dire need for alternative therapies to induce and maintain permanent disease remission. The objective of this proposal is to define the mechanism of how SOX2 maintains multi-potent progenitor cells and promotes prostate enlargement.

PI_NAMEs: VANDER GRIEND, DONALD JAMES (contact)

PROGRAM_OFFICER_NAME: BRUNSKILL, ERIC WAYNE

PROJECT_TERMS: adult stem cell;age related;Aging;Alternative Therapies;Androgen Receptor;BCL2 gene;Binding;Castration;Cell Differentiation process;Cell Survival;Cells;ChIP-seq;Data;Development;Disease remission;Disease Resistance;Embryo;Epithelial Cells;EZH2 gene;Future;Gene Expression;gene repression;Genes;Genetic;Genetic Transcription;Goals;Growth;Health;Histologic;Hormones;Human;Knowledge;Laboratories;Life Expectancy;lower urinary tract symptoms;Mediating;member;men;mouse model;Multipotent Stem Cells;Mus;Natural regeneration;new therapeutic target;novel;novel strategies;Organ;Pathway interactions;Patients;pharmacologic;PIK3CG gene;pluripotency;prevent;Prevention;progenitor;Prostate;prostate enlargement;Prostatic;Publishing;reduce symptoms;Regenerative pathway;Regulation;Resistance;Role;Signal Pathway;single-cell RNA sequencing;Specimen;stem;stem cell expansion;Stem Cell Factor;stem cell function;stem cell genes;stem cell population;stem cells;targeted treatment;Testing;Therapeutic;therapy resistant;Tissues;transcription factor;transcriptome sequencing;Transgenic Mice;Work

PROJECT_TITLE: Function of the Stem Cell Transcription Factor SOX2 in Prostatic Enlargement

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DKUS-B(90)]


ADMINISTERING_IC: LM

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL LIBRARY OF MEDICINE

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

ORG_CITY: PITTSBURGH

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: CARNEGIE-MELLON UNIVERSITY

ORG_STATE: PA

PHR: Project Narrative Recent advances in multiplexed imaging have led to a new generation of technologies for the spatial profiling of the proteome at a single-cell resolution (spatial proteomics), which promise to revolutionize our understanding of cell-cell interactions in the human body. This project aims to develop computational methods to use spatial proteomics data for building a global human tissue atlas. Incorporating spatial information into our understanding of interactions at a single-cell level will reshape how we view development, aging, disease, and more.

PI_NAMEs: DAYAO, MONICA  (contact)

PROGRAM_OFFICER_NAME: DENNIS, ALLISON FRANCES

PROJECT_TERMS: 3-Dimensional;Aging;Atlases;Bayesian Network;Binding;bioimaging;Biological;biological systems;Biology;Cell Communication;cell type;Cells;Complex;computer science;computerized tools;Computing Methodologies;convolutional neural network;Data;Data Set;Dedications;Development;Disease;experimental study;Generations;Genes;Goals;Human;Human BioMolecular Atlas Program;Human body;human tissue;Image;improved;Individual;insight;Insulin-Dependent Diabetes Mellitus;Knowledge;Label;Learning;lymph nodes;Machine Learning;machine learning method;Maps;Membrane;Membrane Proteins;Mentors;Methods;Modeling;Molecular;multidisciplinary;multiplexed imaging;Nature;Neighborhoods;novel;Organ;Pancreas;Pattern;Phenotype;Process;protein biomarkers;protein expression;protein protein interaction;Proteins;Proteome;Proteomics;Research Training;Resolution;Scientist;Shapes;skills;spatial relationship;Standardization;Technology;Tissue atlas;Tissues;tool development;Training;transcriptomic profiling;transcriptomics

PROJECT_TITLE: Machine learning methods for the analysis and modeling of spatial proteomics data

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


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

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

ORG_CITY: NEW HAVEN

ORG_DEPT: GENETICS

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: The  burden  of  Alzheimer’s  disease  (AD)  and  Alzheimer’s  Disease- Related  Dementias  (ADRD)  is  enormous,  yet no effective therapeutics exist for a majority of disease symptoms. The studies outlined in this proposal will  allow  us  to  determine  the  cellular  and  molecular  mechanisms  underlying  microglial  regulation  of  Progranulin  levels  and  associated  neuropathological  phenotypes,  and  therefore  may  lead  to  the  development  of  improved  treatments for neurodegenerative diseases resulting from Progranulin reduction in the future.

PI_NAMEs: LIM, JANGHOO  (contact)

PROGRAM_OFFICER_NAME: OPANASHUK, LISA A

PROJECT_TERMS: Adult;Affect;Alzheimer's Disease;Alzheimer's disease related dementia;Alzheimer's disease risk;Behavioral;Behavioral Assay;behavioral phenotyping;Biochemical;Biology;Brain;Cell Culture System;CRISPR/Cas technology;Data;Dementia;Development;Disease;DNA Sequence Alteration;dosage;efficacy testing;Endocytosis;Frontotemporal Lobar Degenerations;Future;Genetic;Glycoproteins;Goals;Grant;granulin;Heterozygote;Homologous Gene;Human;human disease;human induced pluripotent stem cells;improved;in vivo;insight;Knockout Mice;Knowledge;Link;loss of function;Mediating;Microglia;Molecular;Molecular Target;mouse genetics;Mus;Mutation;nemo-like kinase;Nervous System Disorder;Nervous System Physiology;Neurodegenerative Disorders;Neuronal Ceroid-Lipofuscinosis;neuropathology;novel therapeutic intervention;Onset of illness;overexpression;Pathologic;Pathology;Pathway interactions;patient subsets;Patients;PGRN gene;Phenotype;Phosphotransferases;Plasma;posttranscriptional;prevent;Protein-Serine-Threonine Kinases;Proteins;Proteomics;receptor;Regulation;Research;Role;Serine;Single Nucleotide Polymorphism;Symptoms;targeted treatment;Testing;therapeutic development;Therapeutic Intervention;therapeutically effective;trafficking;Validation

PROJECT_TITLE: Microglial regulation of Progranulin levels

STUDY_SECTION: CMBG

STUDY_SECTION_NAME: Cellular and Molecular Biology of Glia Study Section[CMBG-M]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

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

ORG_CITY: HOUSTON

ORG_DEPT: NEUROSURGERY

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

ORG_STATE: TX

PHR: Retinitis Pigmentosa (RP) is a chronic retinal degenerative disease that affects about 100,000 people in the United States annually and ultimately results with patients becoming blind early on in their adulthood. Regenerative therapies to treat this disease could reduce the incidence of blindness in RP patients as well as dramatically improve their quality of life. This project seeks to identify the gene expression networks that control the photoreceptor regeneration process so that current therapies can directly target and successfully treat patients with RP.

PI_NAMEs: SHIHABEDDIN, EYAD  (contact)

PROGRAM_OFFICER_NAME: AGARWAL, NEERAJ

PROJECT_TERMS: Acute;Adult;Affect;Age;Automobile Driving;autosome;blind;Blindness;Candidate Disease Gene;candidate identification;Cell Cycle;Cell Differentiation process;cell type;Cells;Chronic;Complete Blindness;CRISPR/Cas technology;Data;Data Set;Detection;Disease;E2F transcription factors;experimental study;Fishes;functional restoration;Future;Gene Expression;gene network;Genes;Genetic;Goals;improved;Incidence;Individual;Inherited;Injections;Injury;interest;knock-down;Knowledge;Mammals;model organism;Modeling;Molecular Biology Techniques;Molecular Profiling;Multipotent Stem Cells;mutant;Natural regeneration;Neuroglia;neuron regeneration;Neurons;Nuclear;overexpression;Pathway Analysis;Pathway interactions;Patients;Persons;Photoreceptors;Play;Process;progenitor;Proliferating;promoter;Pythons;Quality of life;Regenerative capacity;Regenerative research;regenerative therapy;Regulator Genes;Research;Retina;Retinal Cone;retinal damage;Retinal Degeneration;retinal neuron;retinal progenitor cell;retinal rods;Retinitis Pigmentosa;Rhodopsin;Rod;Role;sight restoration;Source;stem cell differentiation;stem cell proliferation;stem cells;System;Testing;therapeutic target;transcription factor;transcriptomic profiling;Transgenic Organisms;United States;Vertebrate Photoreceptors;Vision;Work;Zebrafish

PROJECT_TITLE: Rod photoreceptor regeneration in a zebrafish model of Retinitis Pigmentosa.


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Autoimmune Disease;Cancer;Genetics;Hematology;Lupus;Lymphatic Research;Lymphoma;Rare Diseases

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

PHR: NARRATIVE Even though SYK and ZAP70 kinases are almost identical and serve analogous functions, their expression in B- and T-cells is strictly segregated throughout evolution. Whereas the reason for separation of the two kinases is not known, our preliminary results suggest that co-expression of ZAP70 with SYK favors the development of autoimmune disease and B-cell lymphoma. Based on these observations, we will test here the central hypothesis that strict segregation of the two kinases during B- and T-cell development is essential for normal lymphocyte selection and represents a central safeguard against the development of autoimmune disease and B-cell malignancies.

PI_NAMEs: MEFFRE, ERIC ;MÜSCHEN, MARKUS  (contact)

PROGRAM_OFFICER_NAME: RICE, JEFFREY S

PROJECT_TERMS: Ablation;Acceleration;Acute;Alleles;analog;anergy;Antibodies;Autoantibodies;Autoimmune Diseases;autoreactive B cell;autoreactivity;B lymphoid malignancy;B-Cell Acute Lymphoblastic Leukemia;B-Cell Antigen Receptor;B-Cell Development;B-Cell Lymphomas;B-Cell Neoplasm;B-Lymphocytes;Biological Markers;BLNK gene;Calcium Signaling;Cell Death;Cell Proliferation;Cell Survival;cell transformation;Cells;Chronic Lymphocytic Leukemia;Clonal Deletion;Clone Cells;Development;Dominant-Negative Mutation;Engineering;Etiology;Evolution;Flare;Frequencies;Genetic;Genetic study;Human;humanized mouse;Impairment;inducible gene expression;Knock-in;loss of function;Lymphocyte;Malignant - descriptor;Mediating;mouse model;Mus;mutant;novel;Oncogenes;Oncogenic;Onset of illness;optogenetics;Output;Pathologic;patient derived xenograft model;Patients;Peripheral;pharmacologic;phosphoproteomics;Phosphoric Monoester Hydrolases;Phosphotransferases;PIK3CG gene;Preclinical Testing;premalignant;pressure;prevent;Production;promoter;Protein Analysis;Receptor Signaling;remote control;Reporting;Reverse Transcriptase Polymerase Chain Reaction;Rheumatoid Arthritis;segregation;Signal Transduction;single cell proteins;small molecule inhibitor;stoichiometry;Structure of germinal center of lymph node;SYK gene;Systemic Lupus Erythematosus;T-Cell Development;T-Cell Lymphoma;T-Cell Receptor;T-Lymphocyte;Testing;ZAP-70 Gene

PROJECT_TITLE: SYK and ZAP70 kinases in lymphocyte selection


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Clinical Research;Data Science;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Physical Injury - Accidents and Adverse Effects;Precision Medicine;Prevention

ORG_CITY: DAVIS

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

ORG_STATE: CA

PHR: PROJECT NARRATIVE In the US, traumatic injury is the number one cause of death for those under 45 years old and these deaths include many patients dying from the consequences of bleeding. Through leveraging the power of artificial intelligence (a scientific analysis approach similarly used in non-medical fields to help answer questions from large amounts of complex information), an integrated approach to measuring outcome will be developed utilizing biologic, clinical, and electronic medical record (EMR) data. The goal of this project is to lay the ground work for developing early warning detection systems that could identify those at risk of complications early and assist care providers in selecting the best treatment to minimize complications and death from hemorrhage.

PI_NAMEs: CALLCUT, RACHAEL A (contact)

PROGRAM_OFFICER_NAME: KINDZELSKI, ANDREI L

PROJECT_TERMS: Abdomen;Abdominal Cavity;Address;advanced analytics;Area;Artificial Intelligence;Bedside Technology;Biological;Biology;Blood;care providers;Caring;Cause of Death;Cessation of life;Characteristics;Clinical;clinical decision-making;clinical predictors;clinically significant;Coagulation Process;Complex;Computational algorithm;Computational Science;Computerized Medical Record;Computers;Coupled;Coupling;Data;Data Sources;deep learning;Detection;detection platform;Devices;Diagnosis;Diagnostic;digital;Digital biomarker;diverse data;Early Diagnosis;Early identification;Early Intervention;Event;experience;Goals;Health Care Costs;Hemorrhage;Image;improved;Individual;individual patient;individualized medicine;Inflammatory;Injury;insight;Intervention;Knowledge;knowledge network;Life;Liquid substance;Machine Learning;machine learning prediction algorithm;Mentored Research Scientist Development Award;Modeling;mortality;multimodal data;neural;novel;Outcome;Outcome Measure;Pathway interactions;Patients;Pattern;Phenotype;phenotypic biomarker;Physiologic Monitoring;Physiology;Play;point of care;predictive modeling;pressure;preventable death;profiles in patients;Provider;Resuscitation;Risk;sensor;severe injury;Stream;System;Techniques;Technology;Therapeutic;Time;Transfusion;Trauma;Trauma patient;Traumatic injury;treatment effect;Triage;Ultrasonography;ultrasound;United States National Institutes of Health;Work

PROJECT_TITLE: Leveraging Artificial Intelligence Solutions to Develop Digital Biomarkers for Precision Trauma Resuscitation

STUDY_SECTION: BTSS

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


ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Genetics;Human Genome

ORG_CITY: ALBANY

ORG_DEPT: BIOLOGY

ORG_NAME: STATE UNIVERSITY OF NEW YORK AT ALBANY

ORG_STATE: NY

PHR: Public Health Significance  In the proposed research, we will develop a new chemical method for synthesis and purification of long RNA oligonucleotides that will be 10-times faster and two-orders of magnitude cheaper than the conventional methods. Chemical synthesis of long oligonucleotides will allow site-specific incorporation of RNA modifications and will allow to investigate their roles in various genetic diseases.

PI_NAMEs: ROYZEN, MAKSIM  (contact)

PROGRAM_OFFICER_NAME: MORRIS, STEPHANIE A

PROJECT_TERMS: Address;Adenosine;analog;Anions;Biochemical;Biological;Biological Assay;Biomedical Research;Biotinylation;Cells;Cellular biology;chemical synthesis;Chemicals;Chemistry;Communities;Complex;Coumarins;Coupling;cross reactivity;Cyclooctenes;design;Diels Alder reaction;DNA;Electrons;Elements;endonuclease;Exposure to;Failure;flexibility;functional group;Gene Expression Regulation;Genetic Diseases;genomic tools;Genomics;Goals;High Pressure Liquid Chromatography;improved;In Vitro;Initiator Codon;instrument;instrumentation;Isotope Labeling;Label;Length;Light;Messenger RNA;Methodology;Methods;Modification;Molecular;mRNA Translation;National Human Genome Research Institute;Nucleotides;Oligonucleotides;Oryctolagus cuniculus;Perception;Phase;phosphodiester;posttranscriptional;Predisposition;Procedures;Process;process optimization;Production;programs;Proteins;Public Health;Reporting;Research;Research Personnel;Reticulocytes;RNA;RNA chemical synthesis;RNA purification;RNA-Protein Interaction;Role;S phase;Site;Solid;Speed;System;Technology;technology development;therapeutic gene;Time;tool;Transfer RNA;Translations;U2 small nuclear RNA;Ultraviolet Rays;Vertebral column;Visible Radiation;Work

PROJECT_TITLE: Synthesis and non-chromatographic purification of long RNA oligonucleotides containing naturally occurring modification


ADMINISTERING_IC: GM

ED_INST_TYPE: EARTH SCIENCES/RESOURCES

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: ITHACA

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: CORNELL UNIVERSITY

PHR: PROJECT NARRATIVE Crossing over is an essential aspect of meiosis, generating genetic variation and ensuring proper chromosome alignment and segregation. Unsurprisingly, crossover defects are a major contributor to infertility, a problem that impacts almost 1 in 6 couples, and it has been estimated that ~1/4 of fertilized human eggs have the incorrect chromosome number. Understanding how these crossovers are formed will likely have important implications for our understanding of infertility and miscarriage.

PI_NAMEs: PAYERO, LISETTE  (contact)

PROGRAM_OFFICER_NAME: STAMM, JOYCE CHIN-CHIN NG

PROJECT_TERMS: Alleles;alpha helix;Aneuploidy;Binding;Catalytic Domain;Cell division;Chimeric Proteins;Chromosomes;Competence;Couples;Cruciform DNA;Data;Defect;Dissection;DNA;DNA Binding;DNA Binding Domain;egg;endonuclease;Ensure;Excision;experimental study;Failure;follow-up;Frequencies;Genetic;Genetic Crossing Over;genetic information;Genetic Recombination;Genetic Screening;Genetic Variation;genome-wide;Germ Cells;Homologous Gene;Human;Infertility;insight;Length;Location;Measures;Meiosis;Meiotic Recombination;Mismatch Repair;Modeling;mutant;Mutation;novel;nuclease;Pathway interactions;Pattern;Peptides;Phenotype;Play;Process;Production;Proteins;recruit;repaired;Resolution;Role;Saccharomycetales;scaffold;segregation;Specificity;Spontaneous abortion;Spottings;Structure;Testing;Work;Yeasts

PROJECT_TITLE: Uncovering the Role of Exo1 in Meiotic Recombination

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


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;Clinical Research;Clinical Trials and Supportive Activities;Dementia;Neurodegenerative;Neurosciences;Physical Injury - Accidents and Adverse Effects;Stroke;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: BALTIMORE

ORG_DEPT: NEUROLOGY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: PROJECT NARRATIVE We have developed a promising brain-penetrant, small molecule drug candidate, called MW189, that targets dysregulated inflammation in the brain. The proposed Biomarker and Edema Attenuation in IntraCerebral Hemorrhage (BEACH) trial is a phase 2a proof-of-concept study of MW189 in patients with ICH. Success with MW189 will further de-risk the compound for subsequent larger trials of acute CNS injury and/or to develop the drug for Alzheimer’s disease and other age-related dementias.

PI_NAMEs: HANLEY, DANIEL F (contact);VAN ELDIK, LINDA J

PROGRAM_OFFICER_NAME: CLARKE, AKANNI YAO

PROJECT_TERMS: Acute;Acute Brain Injuries;acute care;Address;Adult;Affect;Age;age related;aging related disease;Alzheimer's Disease;Alzheimer's disease related dementia;Alzheimer's disease therapeutic;American;Animal Model;Anti-Inflammatory Agents;Attenuated;attenuation;Biochemical;Biological;Biological Markers;Brain;Brain Injuries;Central Nervous System;Central Nervous System Diseases;central nervous system injury;Cerebral Amyloid Angiopathy;Cerebral Edema;Cerebral hemisphere hemorrhage;Cerebral small vessel disease;cerebrovascular;Chronic;Clinical;clinical candidate;Clinical Research;Clinical Trials;Cognitive deficits;cognitive performance;cytokine;Dementia;Development;Disease;Dose;Double-Blind Method;drug candidate;Drug Kinetics;Edema;Enrollment;Event;Exhibits;Exposure to;Formulation;Functional disorder;Gender;Hour;Human;Impaired cognition;improved;Individual;Inflammation;Inflammatory;Inflammatory Response;Injury;Inpatients;Intervention;Intravenous;Investigation;Kinetics;Laboratories;Link;Measurement;Medical;Molecular;Monitor;Morbidity - disease rate;mortality;Nervous System Trauma;Neuroglia;neuroinflammation;Neurologic;Neurological outcome;neurological recovery;Neuronal Dysfunction;Neuronal Injury;Neurons;neurotoxic;new therapeutic target;novel;novel therapeutics;Outcome;Participant;Pathologic Processes;Patients;Pharmaceutical Preparations;pharmacologic;Phase;Placebos;Plasma;pre-clinical;Preclinical Drug Development;preclinical efficacy;Process;Production;Property;prospective;radiological imaging;Randomized;recruit;response;response to injury;Risk;Safety;safety assessment;Serious Adverse Event;small molecule;success;Symptoms;Synapses;Testing;Therapeutic;therapeutic candidate;therapeutic target;therapeutically effective;Time;Toxicology;Trauma;Traumatic Brain Injury;Traumatic CNS injury;trial readiness;Vascular Diseases;volunteer

PROJECT_TITLE: BEACH: Biomarker and Edema Attenuation in IntraCerebral Hemorrhage Phase 2a Trial


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

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

ORG_CITY: BOSTON

ORG_NAME: TUFTS UNIVERSITY BOSTON

ORG_STATE: MA

PHR: PROJECT NARRATIVE A diminishment in the sense of smell (olfaction) with age is common and compromises quality of life, nutritional status, and personal safety. The olfactory stem cells and the sensory neurons in the nose disappear, and the population of dormant stem cells that are held in reserve fail to activate, despite the pathological changes in the tissue. We seek to activate the reserve stem cells in a controlled fashion in order to treat age-related smell loss; our goal is closely aligned with one of the mission areas of the National Institute on Deafness and Other Communication Disorders.

PI_NAMEs: SCHWOB, JAMES E. (contact)

PROGRAM_OFFICER_NAME: SULLIVAN, SUSAN L

PROJECT_TERMS: Ablation;Acceleration;Address;Adult;Affect;Afferent Neurons;Age;age related;aged;Aging;Anosmia;Area;Back;Basal Cell;Biopsy;Cause of Death;Cell Physiology;Cell Proliferation;cell type;Cells;Cessation of life;conditional knockout;Data;Deterioration;Disease;Elderly;Engraftment;epithelial injury;epithelial repair;Epithelium;epithelium regeneration;Excision;exhaust;exhaustion;extracellular;falls;Fostering;Functional disorder;Gene Expression;gene repression;Genes;genetic manipulation;Goals;Health;Human;In Situ;In Vitro;in vivo;inhibitor;Injury;Intranasal Administration;Knock-out;knockout gene;Lesion;Life;Ligands;Messenger RNA;Mission;Molecular;multicatalytic endopeptidase complex;Multipotent Stem Cells;Mus;National Institute on Deafness and Other Communication Disorders;Natural regeneration;neurogenesis;Nose;notch protein;Notch Signaling Pathway;NOTCH1 gene;Nutritional status;Olfactory dysfunction;Olfactory Epithelium;olfactory sensory neurons;Pathologic;Pathway interactions;Population;Positioning Attribute;Process;Proteins;Proteolysis;Quality of life;receptor;Recovery;Regulation;Reserve Stem Cell;Resort;response;restraint;Rodent;Safety;Sensory;Signal Pathway;Signal Transduction;single-cell RNA sequencing;Smell Perception;stem;stem cell function;stem cells;Supporting Cell;sustentacular cell;System;Testing;Therapeutic;therapeutic target;tissue culture;tissue stem cells;Tissues;Transactivation;transcription factor;Transplantation;Treatment Efficacy;Ubiquitin

PROJECT_TITLE: The Molecular Regulation of Horizontal Basal Cell Activation in the Olfactory Epithelium

STUDY_SECTION: CSS

STUDY_SECTION_NAME: Chemosensory Systems Study Section[CSS]


ED_INST_TYPE: UNIVERSITY-WIDE

NIH_SPENDING_CATS: Biotechnology;Genetics;Infectious Diseases;Malaria;Rare Diseases;Vector-Borne Diseases

ORG_NAME: HARVARD MEDICAL SCHOOL

PHR: Project Narrative The parasite which causes malaria uses a unique, specialized structure known as the basal complex to separate daughter cells during division. We identified a serine-threonine phosphatase involved in the basal complex which is essential for parasite growth and replication. Our goal is to identify and characterize this protein and its substrates and other interactants to determine the role it plays during the division process, as it could be an effective target for developing new anti-malarial drugs.

PI_NAMEs: MORANO, ALEXANDER AENEAS (contact)

PROGRAM_OFFICER_NAME: MCGUGAN, GLEN C

PROJECT_TERMS: Anti-malarials;asexual;Binding;Biological;Biological Assay;Biology;Cell division;Cell Division Process;Cells;Cellular biology;Cessation of life;Characteristics;Complement;Complex;Contractile Proteins;Cre lox recombination system;CRISPR/Cas technology;Dangerousness;Data;daughter cell;Defect;Development;Epitopes;Erythrocytes;Failure;Fever;fitness;Flow Cytometry;Gene Modified;Genes;Genetic;genetic analysis;Goals;Growth;Harvest;Human;Immunofluorescence Immunologic;Immunoprecipitation;In Vitro;in vivo;inducible Cre;knock-down;Knock-out;Malaria;member;Modification;Molecular;Mutation;novel;Parasites;Pathogenicity;Pharmaceutical Preparations;Phenocopy;Phenotype;phosphoproteomics;Phosphoric Monoester Hydrolases;Phosphorylation;Plasmodium;Plasmodium falciparum;Play;Point Mutation;Process;protein complex;Protein phosphatase;protein protein interaction;Protein Serine/Threonine Phosphatase;Proteins;Recombinant Proteins;Recombinants;Resistance;Role;Selection Criteria;Set protein;Structure;Subgroup;System;Testing;Transgenic Organisms;Visualization

PROJECT_TITLE: Characterizing a Serine-Threonine Phosphatase Essential for Asexual Replication in Plasmodium falciparum


NIH_SPENDING_CATS: Autoimmune Disease

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: PROJECT NARRATIVE In addition to T cells, the Tim 3:Bat-3 pathway is highly expressed in dendritic cells (DCs), where its role has not been well characterized. In T cells Tim 3 acts as an inhibitory molecule, is over-expressed on T cells in chronic viral infections and cancer to mediate T cell exhaustion in cancer and chronic viral infections. In contrast, Tim 3 is sub-optimally expressed in a number of human autoimmune diseases including multiple sclerosis, Psoriasis, Rheumatoid arthritis and Type 1 diabetes. This proposal will provide a greater understanding of how Tim 3:Bat-3 pathway regulates DC function so that the pathway can be therapeutically exploited in chronic viral infections, cancers, and autoimmune diseases.

PI_NAMEs: KUCHROO, VIJAY K. (contact)

PROGRAM_OFFICER_NAME: VAZQUEZ-MALDONADO, NANCY

PROJECT_TERMS: Adaptor Signaling Protein;Address;Affect;Antibodies;Antigens;Autoimmune Diseases;Autoimmunity;Binding;Biochemical;cancer clinical trial;CD8B1 gene;Cell Physiology;Cell surface;Cells;Cellular biology;Chiroptera;Chronic;Clinical;Clinical Trials;Communicable Diseases;conditional knockout;cytokine;Data;Dendritic Cells;density;Development;differential expression;effector T cell;exhaust;exhaustion;Experimental Autoimmune Encephalomyelitis;experimental study;Functional disorder;Gatekeeping;Gene Family;Generations;Genes;Genetic Transcription;Glutamates;Human;human disease;Immune response;Immunoglobulins;immunoregulation;in vivo;Inflammation;Inflammatory;Insulin-Dependent Diabetes Mellitus;Interferon Type II;ITGAX gene;Knockout Mice;Laboratories;Macrophage;Macrophage Activation;Malignant Neoplasms;Mediating;member;Molecular;Mucins;Multiple Sclerosis;Mus;Myelogenous;Myeloid Cells;novel;overexpression;Pathogenicity;Pathologic;Pathway interactions;peripheral tolerance;Phenotype;Play;Population;Predisposition;Proteins;Proteomics;Psoriasis;Reporting;Repression;Resistance;Rheumatoid Arthritis;Role;Series;Severities;Signal Transduction;Signaling Molecule;T cell response;T-Cell Development;T-Lymphocyte;Tail;TC1 Cell;Therapeutic;Tissues;Transducers;Transforming Growth Factor beta;Tyrosine;Viral;Viral Cancer;Virus Diseases

PROJECT_TITLE: Role of Tim-3:Bat-3 pathway in inducing tolerogenic DCs and peripheral tolerance

STUDY_SECTION: HAI

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


ADMINISTERING_IC: CA

ED_INST_TYPE: HOSPITALS

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Cancer Genomics;Genetics;Human Genome;Immunotherapy;Prostate Cancer;Urologic Diseases

ORG_NAME: UNIVERSITY OF TX MD ANDERSON CAN CTR

PHR: PROJECT NARRATIVE Most patients with advanced prostate cancer respond poorly to immune checkpoint therapy (ICT). Although recent preclinical and clinical studies have shed some light into the mechanisms underlying the immunoresistance in prostate cancer, the cellular and molecular basics underlying immunoresistance in prostate cancer remain poorly characterized. The proposed work will determine whether cis-aconitate decarboxylase (ACOD1) regulates the functions of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) to promotes prostate cancer progression and resistance to ICT.

PI_NAMEs: WANG, GUOCAN  (contact)

PROGRAM_OFFICER_NAME: LIU, YIN

PROJECT_TERMS: Aconitic Acid;advanced prostate cancer;Affect;Allografting;androgen independent prostate cancer;Anti-androgen Therapy;Anti-Inflammatory Agents;Antimicrobial Effect;Attenuated;Automobile Driving;Cancer Biology;Cancer Patient;cancer type;Carboxy-Lyases;Caring;CD8-Positive T-Lymphocytes;Cell Physiology;Cells;checkpoint therapy;Citric Acid Cycle;Classification;Clinical Research;clinically relevant;Cytometry;Data;Genes;Genetic;Genetic Engineering;Gleason Grade for Prostate Cancer;granulocyte;Human;IL6 gene;Image;Immune;immune resistance;Immunomodulators;Immunosuppression;Impairment;improved;Knock-out;Macrophage;Malignant neoplasm of prostate;Malignant Neoplasms;Mammalian Cell;Mediating;Melanoma;Metabolic;metabolomics;Modeling;Molecular;monocyte;mouse model;multiple datasets;Mus;Myeloid-derived suppressor cells;Neoplasm Metastasis;neutrophil;novel;Pathologic;Patients;pharmacologic;Play;Population;Pre-Clinical Model;preclinical study;Primary Neoplasm;Production;prostate cancer model;prostate cancer progression;Prostatic Neoplasms;recruit;Regulatory Pathway;Resistance;response;Role;single-cell RNA sequencing;STAT3 gene;success;Succinates;T cell infiltration;Testing;therapeutic target;therapy resistant;TNF gene;transcriptome;transcriptome sequencing;treatment response;tumor;tumor microenvironment;tumor progression;Tumor Promotion;Work

PROJECT_TITLE: Cis-aconitate decarboxylase (ACOD1) in PMN-MDSC and prostate cancer progression

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


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Cancer;Cancer Genomics;Clinical Research;Genetics;Hematology;Human Genome;Infectious Diseases;Microbiome;Patient Safety;Precision Medicine;Prevention;Sepsis

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: PROJECT NARRATIVE Neutropenic (NTP) fever and bloodstream infections (BSIs) are common complications in the treatment of hematologic malignancy and are associated with increased morbidity and mortality. The proposed research will determine how the early gut microbiome predicts NTP fever and BSIs, as well as evaluate the impact of specific antibiotic exposures on the gut microbiome in patients receiving chemotherapy and stem cell transplant for the treatment of hematologic malignancy. The ability to predict NTP fever and BSI, utilizing the early gut microbiome, will have a significant public health impact by guiding preventive measures such as antibiotic prophylaxis in those at high risk of these events.

PI_NAMEs: ZIEGLER, MATTHEW  (contact)

PROGRAM_OFFICER_NAME: RANALLO, RYAN

PROJECT_TERMS: Address;Admission activity;Adult;advanced analytics;Advanced Development;Adverse event;Advisory Committees;Affect;Antibiotic Prophylaxis;Antibiotic Therapy;Antibiotics;bacterial community;bacteriome;Benchmarking;beta-Lactams;Bioinformatics;Biological Markers;Biometry;care costs;career;career development;Characteristics;chemotherapy;Child;Clinical;cohort;Collection;colonization resistance;commensal bacteria;Data;Development;Development Plans;Event;experience;Exposure to;Fever;Foundations;Future;gastrointestinal;Goals;gut bacteria;gut dysbiosis;gut microbiome;Gut Mucosa;Health;Hematologic Neoplasms;Hematology;high risk;high risk population;Impairment;individual patient;Infection prevention;infection risk;Inflammation;International;Investigation;Knowledge;Length of Stay;Levaquin;Life;Link;Longitudinal cohort study;Measurement;Measures;Mentored Patient-Oriented Research Career Development Award;Mentors;Methods;Microbe;microbiome;microbiome research;Molecular Epidemiology;Morbidity - disease rate;mortality;Mucositis;Mucous Membrane;Neutropenia;Neutropenic Fever;Oncology;Outcome;outcome prediction;Pathogenesis;Pathway interactions;Patient Admission;patient oriented research;patient population;patient subsets;Patients;Population;Populations at Risk;preference;prevent;Prevention;Preventive measure;programs;prophylactic;Prophylactic treatment;Prospective, cohort study;Proteobacteria;Provider;Public Health;Research;Research Personnel;Resistance;Resources;Risk;Risk Marker;Risk Reduction;Role;Sampling;Sepsis;Series;Serum;skills;statistics;Stem cell transplant;symposium;Taxon;therapy design;Time;Toll-like receptors;Training;Training and Education;transplantation therapy;treatment duration;treatment strategy;Work

PROJECT_TITLE: Impact of early gut microbiome features on risk of neutropenic fever and bloodstream infection in hematologic malignancy

STUDY_SECTION: MID

STUDY_SECTION_NAME: Microbiology and Infectious Diseases B Research Study Section[MID-B]


ORG_CITY: COLD SPRING HARBOR

ORG_NAME: COLD SPRING HARBOR LABORATORY

PHR: The Postbaccalaureate Research Education Program (PREP) at Cold Spring Harbor Laboratory (CSHL) will provide participants with (1) rigorous research experience in genetics and genomics, cancer and molecular biology, neuroscience, quantitative biology, and plant biology, (2) professional skills development, and (3) development of a scientific identity and community through the efforts of a Research Mentor, Direct Mentor and a Near-Peer Mentor, and the immersive and supportive environment of CSHL. CSHL PREP will ensure the successful matriculation of underrepresented minority (URM), students into rigorous and competitive graduate programs, increasing the diversity of the biosciences workforce.

PI_NAMEs: MYAT, MONN MONN  (contact)

PROGRAM_OFFICER_NAME: AKACEM, LAMEESE DANA

PROJECT_TERMS: Administrator;Advisory Committees;Annual Reports;Biological Sciences;Biology;Cancer Biology;career;college;Communication;Communities;course development;Data Analyses;design;Development;Development Plans;Doctor of Philosophy;education research;Educational workshop;Effectiveness;Ensure;Evaluation;Event;experience;Experimental Designs;Faculty;Feedback;Formulation;Funding;Future;Genetic;Genomics;Goals;graduate school preparation;graduate student;improved;Individual;interest;Interest Group;Interview;Journals;knowledge base;Laboratories;Laboratory Research;Learning;Life;matriculation;Measurable;meetings;member;Mentors;Mentorship;Molecular Biology;Neurosciences;Oral;Participant;peer coaching;Plants;Play;Postbaccalaureate;Postdoctoral Fellow;Program Effectiveness;Program Evaluation;programs;Recommendation;Reporting;Research;Research Methodology;resilience;responsible research conduct;Role;Running;Scholars Program;Schools;Science;Scientist;Series;Services;skill acquisition;skills;social organization;Students;success;supportive environment;Surveys;symposium;Tea;Time;timeline;Training;undergraduate research experience;Underrepresented Minority;underrepresented minority student;virtual reality environment;Visit;Writing

PROJECT_TITLE: CSHL PREP

STUDY_SECTION: TWD

STUDY_SECTION_NAME: Training and Workforce Development Study Section - D[TWD-D]


NIH_SPENDING_CATS: HIV/AIDS;Infectious Diseases

ORG_CITY: NEW ORLEANS

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: TULANE UNIVERSITY OF LOUISIANA

ORG_STATE: LA

PHR: Project Narrative Despite the profound benefit of antiretroviral therapy (ART) to patient quality of life, HIV-1 remains an incurable infection. Our proposed studies aim to examine the role of Cytomegalovirus (CMV) in promoting the proliferation of latent HIV-1 infected memory CD4 T cells. In the long-term, the proposed studies will hope to provide a rationale for current well- tolerated CMV antivirals recently approved by the FDA to accelerate clearance of the latent HIV-1 reservoir.

PI_NAMEs: MUDD, JOSEPH CHRISTOPHER (contact)

PROGRAM_OFFICER_NAME: PTAK, ROGER

PROJECT_TERMS: Acceleration;Address;Adoption;Adult;Aftercare;aged;Animal Model;Animals;Anti-viral Agents;Antigens;antiretroviral therapy;Biological Assay;CD4 Positive T Lymphocytes;Cell Compartmentation;Chronic;Cidofovir;Clonal Expansion;co-infection;cohort;comorbidity;comparative;Controlled Study;Cytomegalovirus;daughter cell;Deuterium;DNA;Ensure;examination questions;Exposure to;FDA approved;Future;Genome;Herpesviridae;HIV;HIV-1;Immunocompetent;in vivo;Individual;Infection;Inflammatory;insight;integration site;interest;Interruption;Intervention;Kinetics;Label;latent HIV reservoir;Link;Macaca mulatta;Maintenance;Measurement;Measures;Memory;memory CD4 T lymphocyte;Modeling;multidisciplinary;nonhuman primate;Opportunistic Infections;pathogen;Patients;Persons;pharmacologic;Phenotype;Physiological;Population;Proliferating;Proviruses;Quality of life;Recrudescences;Reporting;Research Personnel;Rest;Rhesus;Role;Sampling;Shapes;Site;SIV;Stimulus;T memory cell;T-Lymphocyte;Time;Tissues;uptake;Viral;viral rebound;Virus

PROJECT_TITLE: Role of RhCMV in shaping the SIV proviral landscape

STUDY_SECTION: HIVD

STUDY_SECTION_NAME: HIV Immunopathogenesis and Vaccine Development Study Section[HIVD]


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Digestive Diseases;Emerging Infectious Diseases;Foodborne Illness;Genetics;Infectious Diseases;Pediatric;Prevention;Rare Diseases

ORG_CITY: CHAMPAIGN

ORG_NAME: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN

PHR: Project Narrative Cryptosporidium is a leading cause of diarrheal disease and deaths in young children and immunocompromised individuals. This project will unravel signaling mechanisms controlling parasite proliferation and sexual stage development. This new knowledge will advance our understanding of parasite biology for the development of future therapies against this deadly diarrheal pathogen.

PI_NAMEs: ALAM, SUMITI VINAYAK (contact)

PROJECT_TERMS: asexual;Biochemical Genetics;Biological;Biological Assay;Biological Models;Biological Process;Biology;Calcium;calcium-dependent protein kinase;Candidate Disease Gene;candidate identification;Cessation of life;chemical genetics;Child;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;Cryptosporidiosis;Cryptosporidium;Cryptosporidium parvum;Dependence;Development;Diarrhea;diarrheal disease;Disease;Disease Outbreaks;drug development;Drug Targeting;effective therapy;enteric infection;Epithelial Cells;Epitopes;FDA approved;Fertilization;Future;Gametogenesis;Gene Modified;Genetic;genetic approach;genetic manipulation;Genome;genome editing;Germ Cells;Goals;Homologous Gene;Human;Immunocompromised Host;immunological status;In Vitro;in vivo;Individual;Infant Mortality;Infection;insight;intestinal epithelium;Intestines;kinase inhibitor;Knowledge;Laboratories;Life Cycle Stages;Link;male;Mediating;Meiosis;Methods;Modeling;Molecular;Molecular Genetics;mouse model;Mus;mutant;Nature;nitazoxanide;novel;novel therapeutics;novel vaccines;Oocysts;Parasite Control;parasite genome;Parasites;pathogen;Pharmaceutical Preparations;Phenotype;Phosphorylation;Phosphotransferases;Plants;Plasmodium;Play;prevent;programs;Proliferating;protein degradation;Protein-Serine-Threonine Kinases;Recreation;Resource-limited setting;reverse genetics;Role;Rotavirus;Sexual Development;Signal Pathway;Signal Transduction;Signaling Protein;stem;superresolution microscopy;System;Technology;Testing;Toddler;Toxoplasma;Transgenic Organisms;transmission process;vaccine development;Vaccines;Water;waterborne outbreak

PROJECT_TITLE: Molecular signaling mechanisms controlling Cryptosporidium proliferation and development

STUDY_SECTION: PTHE

STUDY_SECTION_NAME: Pathogenic Eukaryotes Study Section[PTHE]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Mental Health

ORG_CITY: Aurora

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: Project Narrative The Pathway-RRT seeks to recruit promising physician scientists into a longitudinal research program within the University of Colorado School of Medicine Psychiatry residency. The proposed program will create pathways for strong research productivity while still in residency and seeks to prepare our physician scientists to compete for post-doctoral research positions and future grant funding. We anticipate preparing program graduates to launch into academic careers thus increasing the workforce of physician scientists conducting translational research relevant to the priorities of NIMH.

PI_NAMEs: EPPERSON, C. NEILL  (contact);MIKULICH-GILBERTSON, SUSAN KAY;SAKAI, JOSEPH T

PROGRAM_OFFICER_NAME: CHAVEZ, MARK RAY

PROJECT_TERMS: ABCB1 gene;academic preparation;Address;Annual Reports;Applications Grants;Appointment;Area;Attention;Award;Basic Science;Biometry;Board Certification;burden of illness;career;Career Choice;career preparation;Child;Clinical;Clinical Research;Colorado;cost;COVID-19 pandemic;Data;Data Collection;Dedications;Diagnosis;Economic Burden;Educational workshop;effective therapy;Epidemiology;Ethics;experience;Extramural Activities;Faculty;faculty mentor;Feedback;Fellowship;Fostering;Funding;Future;Genetic;Goals;graduate school;Grant;Growth;improved;innovation;Institution;instructor;interest;Internships;Knowledge;life-long learning;Manuscripts;medical schools;Mental disorders;Mentors;Mentorship;Mission;Monitor;National Institute of Mental Health;National Research Service Awards;neuroimaging;Neurosciences;next generation;novel therapeutic intervention;Operations Research;Oral;Participant;Pathway interactions;Patient Care;Patient-Focused Outcomes;Patients;peer;Pharmacotherapy;Physician's Role;Physicians;Positioning Attribute;Post Graduate Year;post-doctoral training;Postdoctoral Fellow;posters;Prevention;Productivity;professor;programs;Progress Reports;Psychiatrist;Psychiatry;Psychotherapy;Public Health;Qualifying;recruit;Reproducibility;Research;Research Design;research faculty;Research Methodology;Research Personnel;Research Support;Research Training;Residencies;response;responsible research conduct;Role;Scientific Inquiry;Scientist;Services;skill acquisition;Structure;Substance Use Disorder;Surveys;Time;Training;Translating;Translational Research;Translations;United States National Institutes of Health;Universities;Wages;Writing

PROJECT_TITLE: Pathways for Physician Scientist Training in Psychiatric Research


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Coronaviruses;Emerging Infectious Diseases;HIV/AIDS;Infectious Diseases;Post-Acute Sequelae of SARS-CoV-2 infection (PASC) including Long COVID

ORG_CITY: SAN ANTONIO

ORG_NAME: TEXAS BIOMEDICAL RESEARCH INSTITUTE

PHR: Narrative While COVID-19 continues to be a health challenge, very little is known about how COVID-19 affects people living with HIV. Recent reports indicate that people with HIV may have increased susceptibility to developing severe COVID-19 disease when infected with SARS-CoV-2. Combining our nonhuman primate models of COVID-19 and SIV infection, we will characterize the effect of underlying SIV infection on the development of acute and post-acute COVID-19 sequelae.

PI_NAMEs: SINGH, DHIRAJ KUMAR (contact)

PROGRAM_OFFICER_NAME: PLIMACK, MARY KATHERINE BRADFORD

PROJECT_TERMS: 2019-nCoV;Ablation;Acceleration;Acquired Immunodeficiency Syndrome;Acute;acute COVID-19;Affect;Animals;Automobile Driving;CD4 Positive T Lymphocytes;Cell Compartmentation;cell type;Cells;Cessation of life;Chronic;Clinical;Clinical Management;co-infection;comorbidity;comparative;COVID-19;COVID-19 impact;COVID-19 severity;COVID-19 susceptibility;COVID-19 therapeutics;Development;Disease;Exhibits;experience;Foundations;Generations;Goals;Health;HIV;HIV Infections;HIV/AIDS;Immune;immune activation;Immune response;immunodeficiency;Immunologic Factors;Immunologic Techniques;Immunologics;Immunotherapeutic agent;Individual;Infection;insight;Intervention;Knowledge;Long COVID;Macaca;Macaca mulatta;Modeling;Monitor;Mutation;nonhuman primate;pandemic disease;pathogen;Pathogenesis;Pathogenicity;Pathology;Patient Care;Persons;PET/CT scan;Phase;Post-Acute Sequelae of SARS-CoV-2 Infection;Predisposition;prevent;Probability;Radiology Specialty;reconstitution;Reporting;Risk;Role;SARS-CoV-2 infection;SARS-CoV-2 variant;severe COVID-19;SIV;Therapeutic Intervention;Tissues;vaccine development;vaccine hesitancy;Validation;Variant;Viral;Virus;Virus Replication

PROJECT_TITLE: Understanding Co-morbidities: COVID-19 in individuals living with HIV/AIDS

STUDY_SECTION: HCCS

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


NIH_SPENDING_CATS: Congenital Structural Anomalies;Genetics;Kidney Disease;Pediatric;Polycystic Kidney Disease

ORG_CITY: OKLAHOMA CITY

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR

ORG_STATE: OK

PHR: Our work aims at better understanding the role of primary cilia in autosomal dominant polycystic kidney disease. Once we know more about the processes that control ciliary assembly and disassembly, pharmacologic approaches could be designed to slow down cyst progression.

PI_NAMEs: TSIOKAS, LEONIDAS  (contact)

PROGRAM_OFFICER_NAME: MARIC-BILKAN, CHRISTINE

PROJECT_TERMS: Ablation;Acceleration;Affect;Autosomal Dominant Polycystic Kidney;Biochemical;Biological;Cell Cycle;Cell Cycle Progression;Cell Proliferation;cell type;Cells;Centrosome;Cilia;Complex;CRISPR screen;Cyst;Cystic kidney;Cystic Kidney Diseases;Data;Deceleration;design;Development;Disease;Disease Progression;Epithelium;Exposure to;FBXW7 gene;Functional disorder;G1/S Transition;Genes;Genetic;Genetic Diseases;Genetic study;genome-wide;Growth;HDAC6 gene;Housing;improved;Kidney Diseases;Knockout Mice;Mediating;Methods;Mitosis;Mitotic;Modeling;Modification;mouse model;Mus;mutant;Mutation;Names;novel therapeutic intervention;Null Lymphocytes;Organelles;p53-binding protein 1;Pathway interactions;Persons;pharmacologic;Pharmacology Study;PKD1 gene;PKD2 gene;Process;Proliferating;receptor;Renal function;Role;Serum;Signal Pathway;Signal Transduction;Stimulus;theories;Therapeutic;Time;TP53 gene;ubiquitin-protein ligase;Work

PROJECT_TITLE: Ciliary Disassembly, a modifier of Autosomal Dominant Polycystic Kidney Disease

STUDY_SECTION: KMBD

STUDY_SECTION_NAME: Kidney Molecular Biology and Genitourinary Organ Development[KMBD]


NIH_SPENDING_CATS: Genetics

ORG_NAME: NORTHWESTERN UNIVERSITY

PHR: Project Narrative Human non-homologous end joining (NHEJ) pathway represents the predominant repair mechanism for dealing with double strand breaks (DSBs) throughout the entire cell cycle. Its understanding is of great importance for cancer etiology and cancer therapy, due to its significant role in maintaining genome stability and protecting cells from becoming cancerous. Through structural and functional studies, we seek to define the complex molecular mechanisms of NHEJ so that they may be targeted to develop improved approaches to antitumor therapy.

PI_NAMEs: HE, YUAN  (contact)

PROGRAM_OFFICER_NAME: MACARTHUR, LINDA

PROJECT_TERMS: Adaptive Immune System;Address;Apoptosis;Architecture;Biochemical;Cancer Etiology;cancer therapy;Cancerous;Cell Cycle;Cells;Chemicals;Chromatin;Chromosomes;Complex;Coupling;crosslink;Cryoelectron Microscopy;Cytoprotection;Development;dimer;DNA;DNA Damage;DNA-dependent protein kinase;DNA-PKcs;Double Strand Break Repair;ds-DNA;Exons;Filament;G22P1 gene;Genes;Genetic Recombination;Genome;Genome Stability;Genomic Instability;Goals;Holoenzymes;Human;Immune;Immunoglobulin Genes;improved;In Vitro;interdisciplinary approach;Ionizing radiation;LIG4 gene;Ligase;Ligation;Malignant Neoplasms;Mass Spectrum Analysis;mechanotransduction;Modeling;Molecular;Molecular Machines;Nonhomologous DNA End Joining;novel;Nucleosomes;operation;particle;Pathway interactions;Phosphotransferases;Physiological;PIK3CG gene;presynaptic;Process;Reactive Oxygen Species;reconstitution;recruit;Regulation;repaired;Resolution;response;Role;senescence;Signal Transduction;Site;Structure;Structure-Activity Relationship;Synapses;System;Techniques;Testing;Time;Transcription Initiation;tumor;V(D)J Recombination;Visualization;XRCC4 gene

PROJECT_TITLE: Structure and Mechanism of Non-Homologous End Joining

STUDY_SECTION: MSFC

STUDY_SECTION_NAME: Macromolecular Structure and Function C Study Section[MSFC]


NIH_SPENDING_CATS: Behavioral and Social Science;Bioengineering;Cardiovascular;Clinical Research;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Obesity;Physical Activity;Prevention;Sleep Research

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: PROJECT NARRATIVE This project aims to fill important gaps in current methods by developing a comprehensive set of tools to analyze accelerometer data to better understand the links between physical activity, sedentary behavior, and sleep and outcomes such as cardiovascular health, and to make open-source user-friendly software available to apply them. We propose methods to identify and account for non-wear periods through machine learning and multiple imputation approaches under a generalized linear mixed effects model framework in order to correlate behaviors with outcomes. The methods we develop and validate will be useful for studying questions of great importance to public health such as identifying signature patterns of physical activity, sedentary behavior and sleep that may be favorable for cardiovascular health and will provide insights into analytic approaches for studies that involve other types of monitoring data with public health relevance.

PI_NAMEs: DESAI, MANISHA  (contact)

PROGRAM_OFFICER_NAME: WANG, YANLI

PROJECT_TERMS: Accelerometer;Address;Adopted;Algorithms;Attention;Behavior;Behavioral;Blood Pressure;Body mass index;cardiovascular health;cardiovascular risk factor;Categories;Clinical Trials;Communities;Computer software;Data;data imputation;data resource;Devices;diabetes risk;digital;digital monitoring;Dimensions;Environment;Exclusion;Fasting;Health;health data;Hour;Human;Hyperlipidemia;Hypertension;improved;Inflammation;insight;instrument;Insulin Resistance;interest;Knowledge;learning algorithm;Link;Lipids;Machine Learning;machine learning method;markov model;Measurement;Measures;Methods;Modeling;Monitor;monitoring device;Movement;Nature;Non-Insulin-Dependent Diabetes Mellitus;novel;Obesity;obesity in children;open source;Outcome;Participant;Pattern;Personal Satisfaction;Persons;Physical activity;prevent;Public Health;public health relevance;Recommendation;Research;Risk Factors;Sampling;Security;sedentary;sedentary lifestyle;Series;Signal Transduction;simulation;Sleep;sleep behavior;sleep pattern;standard measure;statistical and machine learning;Time;tool;user friendly software;Validation;Visualization;waist circumference;wearable device

PROJECT_TITLE: Novel machine learning and missing data methods for improving estimates of physical activity, sedentary behavior and sleep using accelerometer data

STUDY_SECTION: BLR

STUDY_SECTION_NAME: Biomedical Informatics, Library and Data Sciences Review Committee[BLR]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

ORG_CITY: BEIRUT

ORG_COUNTRY: LEBANON

ORG_FIPS: LE

ORG_NAME: AMERICAN UNIVERSITY OF BEIRUT

PHR: Project narrative. Nicotine flux, the rate of nicotine emitted from ENDS, encapsulates several use-factors that impact nicotine emissions including power and liquid composition. Importantly, nicotine flux may serve as a measure of the rate of nicotine delivery, a key determinant of nicotine dependence. Nicotine flux therefore presents a potentially powerful regulatory lever, if it can be shown empirically to predict nicotine delivery and subjective effects relevant to dependence.

PI_NAMEs: EL HELLANI, AHMAD ;TALIH, SOHA  (contact)

PROGRAM_OFFICER_NAME: FEDOTA, JOHN RAPHAEL

PROJECT_TERMS: Abstinence;abuse liability;Acute;addiction;Aerosols;American;authority;base;Base Ratios;Behavior;Blood;Blood Circulation;Brain;Clinical;Computer Simulation;craving;Dependence;design;Device Designs;Devices;discrete time;Dose;Drug Kinetics;Electronic cigarette;Electronic Nicotine Delivery Systems;Encapsulated;experience;Exposure to;High School Student;In Situ;Inhalation;instrument;Intuition;Knowledge;Left;Link;liquid nicotine;Liquid substance;Lung;mathematical model;Measures;medical schools;Metabolic;Methods;Monitor;National Institute of Drug Abuse;Nicotine;nicotine craving;Nicotine Dependence;nicotine use;Outcome;Participant;Performance;Physiological;Population;Psychological reinforcement;Public Health;public health priorities;Regulation;Reporting;Resolution;Resort;Risk;Robot;Sampling;Sensory;Smoke;Speed;Statutes and Laws;Study Subject;Testing;Time;tobacco products;tool;toxicant;Toxicant exposure;United States Food and Drug Administration;Universities;Venous;Youth

PROJECT_TITLE: Nicotine flux, a potentially powerful tool for regulating nicotine delivery from electronic cigarettes: significance of nicotine flux to the rate of nicotine delivery and subjective effects


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Dementia;Genetics;Neurodegenerative;Neurosciences;Physical Injury - Accidents and Adverse Effects;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury

ORG_CITY: LEXINGTON

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF KENTUCKY

ORG_STATE: KY

PHR: Project Narrative Traumatic brain injury (TBI) is a complex and progressive neurodegenerative disorder affecting millions of people each year in the US, as well as being a known environmental risk factor for the development of Alzheimer’s disease-related dementia. However the mechanisms underlying the increased risk to develop Alzheimer’s disease-related dementia following TBI remain unclear. The salient findings from this project will significantly contribute to fundamental knowledge-base of the role of inflammatory response of astrocytes in the aging brain as determinants of outcome following TBI.

PI_NAMEs: MORGANTI, JOSH  (contact)

PROGRAM_OFFICER_NAME: OPANASHUK, LISA A

PROJECT_TERMS: Acute;Affect;age related;aged;Aging;aging brain;aging population;aging related;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease related dementia;Alzheimer's disease risk;Animal Model;Astrocytes;astrogliosis;Automobile Driving;Behavioral;Brain;Calcium;Cells;cerebrovascular;Characteristics;Chronic;Complement;Complex;conditional knockout;Data;Development;Disease;Environmental Risk Factor;Excision;Feedback;Functional disorder;Genetic Models;Gliosis;Heterogeneity;Human;Impaired cognition;Impairment;Incidence;Inflammation;Inflammatory;Inflammatory Response;Ischemia;knockout animal;Knockout Mice;knowledgebase;Lead;Link;loss of function;male;Mediator;Memory impairment;Methods;Microglia;Modality;Modeling;Molecular;mouse model;Multiple Sclerosis;Nerve Degeneration;network dysfunction;neural;neural circuit;neural network;Neurodegenerative Disorders;Neuroglia;neuroinflammation;Neurons;Neurophysiology - biologic function;new therapeutic target;NF-kappa B;novel;old mice;Outcome;Pathway interactions;Persons;Phenotype;Physiology;Populations at Risk;Predisposition;Prevention;progressive neurodegeneration;protein profiling;Publishing;response;response to injury;restoration;Risk;Rodent;Role;Signal Pathway;Signal Transduction;single-cell RNA sequencing;Slice;Spinal cord injury;Synapses;Synaptic plasticity;tau-1;Testing;Time;Tissues;transcription factor;Transcriptional Activation;transcriptome sequencing;transcriptomics;Trauma;Traumatic Brain Injury;young adult

PROJECT_TITLE: Contributions of astrocyte RelA signaling in aging-related neurodegenerative sequelae following TBI

STUDY_SECTION_NAME: Cellular and Molecular Biology of Glia Study Section[CMBG-R]


NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Chronic Liver Disease and Cirrhosis;Digestive Diseases;Hepatitis;Liver Disease;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Substance Misuse

PHR: Narrative: Liver fibrosis is a highly conserved response to hepatic tissue injury. Cirrhosis arises as the common final outcome of uncontrolled fibrotic response, ultimately leading to disrupted hepatic architecture, portal hypertension and end-stage liver disease. Alcoholic liver disease (ALD) is a significant cause of morbidity and mortality worldwide. The studies proposed within this application are designed to explore the CTGF/ADAMTS7 or CTGF/ECM1 axes as systems that regulate repair of the liver and its involvement in alcoholic fibrosis and hepatic progenitor cell activation. The overall goal of this proposal is to understand mechanisms underlying liver repair and to develop novel therapies that would prevent or reverse alcoholic fibrosis.

PI_NAMEs: PI, LIYA  (contact)

PROGRAM_OFFICER_NAME: WANG, JOE

PROJECT_TERMS: Acetaldehyde;ADAMTS;Affect;Alcoholic Hepatitis;Alcoholic Liver Diseases;Alcohols;American;antagonist;Architecture;Biliary;Binding;Binding Proteins;Biological;Cause of Death;Cell Surface Proteins;Cells;Chronic;chronic liver disease;Cicatrix;Cirrhosis;cleavage factor;Collagen;connective tissue growth factor;Data;design;Development;Diagnosis;Disease;Disintegrins;end stage liver disease;Enhancers;Enzymes;Exhibits;experimental study;Extracellular Matrix Proteins;Failure;Family;Family member;FDA approved;Fibronectins;Fibrosis;follow-up;Foundations;Genes;Genetic Transcription;Glycoproteins;Goals;Growth Factor;Growth Factor Gene;Health;Hepatic;Hepatic Fibrogenesis;Hepatic Stellate Cell;Hepatic Tissue;Hepatitis;Hepatocyte;hepatocyte nuclear factor;Human;Imaging Techniques;In Vitro;in vivo;Inflammatory Response;Injury;insight;Integrin alphaV;Integrin Binding;Integrins;Knowledge;Liver;liver cell proliferation;Liver Cirrhosis;Liver Fibrosis;liver inflammation;liver injury;Liver Regeneration;liver repair;liver transplantation;Masks;Mediating;Mediator;Metalloproteases;Molecular Target;Morbidity - disease rate;mortality;Mus;Myofibroblast;Natural regeneration;new therapeutic target;non-invasive imaging;novel;novel therapeutics;Outcome;overexpression;Patients;Peptide Hydrolases;Pharmaceutical Preparations;Portal Hypertension;prevent;Primary carcinoma of the liver cells;problem drinker;Production;programs;Proteins;receptor;regenerative;Regulation;repaired;Reporting;response;Severities;Signal Transduction;simple steatosis;Source;Steatohepatitis;stem cell niche;stem cells;System;targeted treatment;Testing;Therapeutic Intervention;therapy development;Thrombospondins;tissue injury;Tissues;Toxic effect;Transcription Coactivator Gene;transcription factor;transcriptome sequencing;Transforming Growth Factor beta;Transforming Growth Factors;translational potential;United States National Institutes of Health;Up-Regulation;virtual;Zinc

PROJECT_TITLE: Regulation of the pro-fibrotic connective tissue growth factor in alcoholic liver disease: mechanisms and targeting approaches

STUDY_SECTION: HBPP

STUDY_SECTION_NAME: Hepatobiliary Pathophysiology Study Section[HBPP]


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_NAME: VA BOSTON HEALTH CARE SYSTEM

PHR: Multiple myeloma (MM) is a plasma-cell malignancy with increasing incidence with age, median age of diagnosis at 70 years, and with African Americans affected at twice the rate of Caucasians. VA patients have increased risk of MM as there is a reported association with agent orange exposure. In a review of patient records in 2012, over 4,000 patients with MM diagnosis were seen in VA. One of the established therapies for MM is chemotherapy with stem cell transplantation, for which most veterans are not eligible due to age, disease state, and/or co-morbidities. Despite significant therapeutic improvements in MM, patients eventually progress and die from the disease, highlighting the need to identify novel targets and therapies. Leveraging our genomic and transcriptomic data, the proposed studies will identify the impact of dysregulated long-non coding RNAs (lncRNAs) on the pathobiology of MM, with potential to serve as therapeutic targets. These studies will define the functional landscape of lncRNA in MM and allow for development of translational therapies for veterans.

PI_NAMEs: MUNSHI, NIKHIL C. (contact)

PROJECT_TERMS: Affect;African American population;Age;agent orange;Anabolism;Area;Automobile Driving;Biological;c-myc Genes;Caucasians;cell growth;Cell Line;Cell Survival;Cells;chemotherapy;Chromosomes;Classification;Clinical;comorbidity;CRISPR interference;Data;Data Set;Dependence;Development;Diagnosis;differential expression;Disease;DNA;Enzymes;Evaluation;experimental study;Fatty Acids;Genes;genetic manipulation;Genomic Instability;Genomics;Glucose;Glutamine;Growth;high risk;Human Genome;Impairment;improved;In Vitro;in vivo;Incidence;inhibitor;Investigation;Lead;Left;lipid biosynthesis;Malignant Neoplasms;Membrane;Metabolic Pathway;Modeling;Molecular;molecular marker;mouse model;Multiple Myeloma;Mutation;Names;neoplastic cell;Newly Diagnosed;novel;Nutrient;Oligonucleotides;Outcome;outcome prediction;Pathway interactions;patient stratification;patient subsets;Patient-Focused Outcomes;Patients;Plasma Cells;Play;predict clinical outcome;Probability;progression marker;protein protein interaction;Proteins;Records;Regulatory Element;Relapse;Reporting;Research;response;Risk;Risk Marker;RNA;Role;Sampling;Signaling Molecule;Silicon Dioxide;small molecule;small molecule inhibitor;Span 80;Stem cell transplant;Subgroup;survival outcome;Techniques;Therapeutic;therapeutic target;Transcription Coactivator;Transcriptional Regulation;transcriptome sequencing;transcriptomics;Transgenic Organisms;translational applications;translational therapeutics;Untranslated RNA;Up-Regulation;Validation;Veterans

PROJECT_TITLE: Molecular Manipulation to Enhance Anti-Myeloma Response


ORG_CITY: DURHAM

ORG_NAME: DURHAM VA MEDICAL CENTER

ORG_STATE: NC

PHR: On average, 18 U.S. Veterans die by suicide each day. From 2009 to 2018, more than 64,000 Veterans died by suicide, which is roughly the same number of U.S. military fatalities that resulted from the wars in Vietnam, Iraq, and Afghanistan combined. Unfortunately, the genetic basis of suicide remains largely unknown. The overall objective of this application is address this critical gap in our understanding and discover novel, replicable gene x environment (GxE) interactions that increase Veterans’ risk for suicidal thoughts and behaviors. The findings obtained from the proposed work could fundamentally shift understanding of the biology of suicide, lead to new and improved treatments, and improve VA’s efforts to identify and intervene with Veterans at risk for suicide. As such, the present application has tremendous potential to advanced VA’s mission and improve Veterans’ health, safety, and well-being.

PI_NAMEs: BECKHAM, JEAN C.;KIMBREL, NATHAN A. (contact)

PROJECT_TERMS: Address;Afghanistan;Algorithms;Biological;Biology;Borderline Personality Disorder;chronic pain;Circadian Rhythms;Clinical;clinically significant;cohort;Complex;Data;Enrollment;Environment;Environmental Risk Factor;Ethnic Origin;Feeling suicidal;gene environment interaction;Genes;Genetic;Genetic Markers;Genetic Risk;genetic risk factor;Genetic study;genetic variant;genome wide association study;genome-wide;Glutamates;Goals;Health;Heritability;high risk;Human Genetics;Hydrocortisone;improved;International;Intervention;Iraq;Lead;member;Mental Depression;Mental disorders;Military Personnel;Mission;novel;Oxytocin;Pathway Analysis;Pathway interactions;Personal Satisfaction;Phase;Phenotype;Post-Traumatic Stress Disorders;Prevention approach;programs;Qualifying;Recovery;Research;Research Personnel;Risk;Risk Factors;risk variant;rurality;Safety;Sampling;screening;sexual trauma;Signal Transduction;Sleep disturbances;Socioeconomic Status;Statistical Models;Substance Use Disorder;suicidal behavior;suicidal morbidity;suicidal risk;Suicide;Suicide attempt;Suicide prevention;Synapses;Traumatic Brain Injury;Veterans;Vietnam;War;Work

PROJECT_TITLE: A Gene-by-Environment Genome-Wide Interaction Study (GEWIS) of Suicidal Thoughts and Behaviors in Veterans


PHR: Chronic kidney disease (CKD) is an independent risk factor for cardiovascular disease that afflicts large numbers of veterans and leads to severe cardiovascular complications including end-stage kidney disease. Most forms of chronic kidney disease (CKD) that feature persistent tubular damage progress to organ failure. Treatments that curtail chronic tubular injury are therefore desperately needed. The realization that pro- inflammatory cytokines contribute to tubular damage in sterile forms of kidney disease presents an opportunity to develop novel therapies for the prevention of end-stage kidney disease. The proposed studies will examine regulatory factors specifically in the kidney tubular cell (KTC) that constrain inflammatory mediator induction both within the KTC and in infiltrating immune cells. Identifying these factors will benefit the veteran’s population by leading to the rational design of potent, immune-directed therapies to prevent and/or slow the progression of CKD.

PI_NAMEs: CROWLEY, STEVEN D (contact)

PROJECT_TERMS: Ablation;Architecture;Aristolochic Acids;Attenuated;Autoimmunity;Cardiovascular Diseases;cardiovascular risk factor;Cardiovascular system;Cell Cycle Arrest;cell injury;Cells;Chronic;Chronic Kidney Failure;Cisplatin;cytokine;cytotoxicity;Disease;disease model;Disease Progression;End stage renal failure;Generations;GKLF protein;immune cell infiltrate;Immunotherapy;Inflammation;Inflammation Mediators;Inflammatory;injured;Injury;Injury to Kidney;Interleukins;Interruption;Ischemia;Kidney;Kidney Diseases;kidney fibrosis;Kidney Neoplasms;Kruppel-like transcription factors;Ligands;Macrophage;military veteran;Modeling;Molecular Analysis;mouse model;Mus;Myeloid Cells;Nephritis;Nephrons;nephrotoxicity;novel therapeutics;Obstruction;Organ failure;outcome disparities;Pathway interactions;Pattern;Porcupines;Predisposition;preservation;prevent;Prevention therapy;Protein Isoforms;Proteins;rational design;renal damage;repaired;Reperfusion Therapy;Reporting;Role;Serum;Severities;Severity of illness;Signal Transduction;Site;Sterility;Testing;TNF gene;Toxin;Transferase;Tubular formation;Ubiquitin;Veterans;WNT Signaling Pathway

PROJECT_TITLE: Role of M1 Cytokines in the Progression of Chronic Kidney Disease


ORG_NAME: PHILADELPHIA VA MEDICAL CENTER

PHR: Regulatory CD4+ T cells (Tregs) express the transcription factor, Foxp3, and are necessary to maintain intestinal homeostasis; as such, they are an intriguing pharmacologic target for the immunotherapy of inflammatory bowel disease. The Tregs in the intestine are specialized to their environment with the local milieu defining the phenotype and function of the cells. We will utilize murine models and studies of human tissue to define the cellular and molecular pathways that drive maintenance and expansion of small intestine Tregs to identify targets to enhance local Treg numbers and function.

PI_NAMEs: LAUFER, TERRI M. (contact)

PROJECT_TERMS: 3-Dimensional;Affect;Anatomy;Antibiotics;Autoimmune;autoinflammatory;B-Lymphocytes;Birth;Blocking Antibodies;CD4 Positive T Lymphocytes;Cell Communication;Cell Count;Cell Physiology;Cells;Chemicals;Clinical;Colonoscopy;Crohn's disease;Cytoprotection;Data;Defect;Development;Disease;Disease Outcome;Enteritis;Environment;experimental study;Expression Profiling;Flare;Flow Cytometry;FOXP3 gene;Funding;genetic manipulation;Genomic Segment;gut inflammation;gut microbiota;Health;Homeostasis;Human;human tissue;Image;Imaging Techniques;Immune;Immune system;Immunodysregulation polyendocrinopathy enteropathy X-linked syndrome;Immunofluorescence Immunologic;Immunologics;Immunotherapy;improved;Individual;Infant;Infection;Inflammation;Inflammatory Bowel Diseases;innovation;intestinal epithelium;intestinal homeostasis;Intestines;Lamina Propria;Lead;Location;Lymphoid Follicle;lymphoid structures;lymphotoxin beta;Maintenance;Mature B-Lymphocyte;Mediating;men;Methodology;Methods;microorganism;Modeling;Molecular;mouse model;Mucosal Immune Responses;mucosal site;Mucous Membrane;Mus;Organ Donor;Organism;organizational structure;Pathway interactions;Patients;Peripheral;pharmacologic;Phenotype;Physiological;Population;Positioning Attribute;Predisposition;Prevalence;prevent;Process;Recovery;Regulatory Pathway;Regulatory T-Lymphocyte;Research Design;response;segregation;Signal Transduction;Small Intestines;Specimen;Subcellular Anatomy;Therapeutic;Thymus Gland;Tissues;transcription factor;Ulcerative Colitis;Veterans;Villus;Wild Type Mouse

PROJECT_TITLE: Dissecting the intestinal niche for regulatory T cells


ORG_CITY: LOS ANGELES

ORG_NAME: VA GREATER LOS ANGELES HEALTHCARE SYSTEM

PHR: Uncontrolled hypertension is present in 37% of veterans, posing several risks to health, including cerebrovascular disease (CBVD) which increases the risk for Alzheimer’s dementia (AD). In fact, 80% of AD patients have some degree of CBVD, which can worsen response to drugs designed to target pure AD, which may be one reason why billions of dollars of investiment in drug development for dementia has had little impact on therapies. In addition to the 750,000 veterans who currently have dementia, there are predicted to be nearly 900,000 new cases by 2030, so we validate a new animal models and test two drugs to understand how to treat the complexity of this devastating disease which has a catastrophic toll on Veteran patients and their caregivers, global health, Medicare and the US economy and Federal budgets that fund the VA.

PI_NAMEs: FRAUTSCHY, SALLY ANN (contact)

PROJECT_TERMS: Acceleration;Address;Affect;Age;aged;Alzheimer's Disease;Alzheimer's disease related dementia;Alzheimer's disease risk;Amyloid;Amyloid beta-Protein;Animal Model;Animal Testing;antagonist;Area;Astrocytes;Atrophic;Attenuated;Automobile Driving;Behavior;behavior test;Biochemical;Biological Availability;Biological Markers;biomarker validation;Blocking Antibodies;Blood;Blood - brain barrier anatomy;Blood Vessels;Brain;Brain-Derived Neurotrophic Factor;Breeding;Budgets;Caregivers;Cerebral small vessel disease;Cerebrovascular Disorders;Characteristics;Chronic;Clinical;Clinical Data;Combined Modality Therapy;Complement;Complement 3 Convertase;Complement 3b;Complement 5a;Complement Activation;complement C5b;complement pathway;Complement Receptor;Complex;Data;Dementia;Demyelinations;design;Development;Diagnosis;differential expression;Disease;Dissection;Drug Design;drug development;early onset;Encephalitis;Euthanasia;Executive Dysfunction;Exhibits;Extravasation;familial Alzheimer disease;Feedback;Female;Funding;Genes;Genetic Transcription;Glial Fibrillary Acidic Protein;Gliosis;global health;Health;Hemorrhage;Hippocampus;Histologic;Histology;Human;Hypertension;hypertensive;Hypoxia;Image;Impaired cognition;improved;Inflammation;Inflammatory;inflammatory marker;inhibitor;insight;interest;K-18 conjugate;Knowledge;Label;Lasers;Lesion;Letters;Liquid substance;Longitudinal Studies;Magnetic Resonance Imaging;male;Measures;Mediating;Medicare;Methods;Microglia;Microscopy;Microvascular Dysfunction;Minor;mitochondrial dysfunction;mixed dementia;Modeling;monomer;mouse model;multidisciplinary;Mus;myelination;Nerve Degeneration;neuroimaging;neuroinflammation;neuron loss;Neurons;neuropathology;neuroprotection;neurotoxic;neurovascular unit;normotensive;novel;novel therapeutics;Oral;Oral Administration;Outcome;Pathogenesis;Pathogenicity;Pathology;Pathway interactions;Patients;Peptides;Pharmaceutical Preparations;pharmacokinetics and pharmacodynamics;Plasma;Play;Prefrontal Cortex;Process;Protein Isoforms;Proteins;putamen;Randomized;Rat Transgene;Rattus;Receptor Activation;Resistance;response;Risk;Risk Factors;Role;Scanning;Serial Magnetic Resonance Imaging;Serum;sex;Signal Transduction;small molecule inhibitor;Solid;Stroke;Structure;Study models;Subarachnoid Hemorrhage;synergism;tau aggregation;tau Proteins;Tauopathies;Testing;Thalamic structure;Therapeutic;Time;transcriptome sequencing;Transgenic Organisms;Treatment Efficacy;Validation;Vascular Cognitive Impairment;Vascular Dementia;Veterans;white matter;white matter damage

PROJECT_TITLE: Role of Complement Receptor Activation in a Mixed Dementia Model


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Clinical Research;Emerging Infectious Diseases;Infectious Diseases;Lung;Prevention;Rare Diseases;Tuberculosis

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: RELEVANCE TO PUBLIC HEALTH Granulomas are collections of macrophages and lymphocytes that characterize a range of chronic inflammatory conditions. Here, we will investigate the cellular and molecular architecture of human tuberculosis granulomas to learn about how these structures mediate antimicrobial activity against the intracellular bacterium that causes tuberculosis as well as contribute to disease pathogenesis. The insights gained from this study are critical for understanding protective immunity against tuberculosis towards developing new strategies for prevention and treatment.

PI_NAMEs: MODLIN, ROBERT L (contact)

PROGRAM_OFFICER_NAME: EICHELBERG, KATRIN

PROJECT_TERMS: Acute;Address;Affect;Animals;Anti-Inflammatory Agents;anti-microbial peptide;antimicrobial;Architecture;Area;Atherosclerosis;Bacillus;Bacteria;Biological Markers;cell type;Cells;chemotherapy;Chronic;Clinical;Collection;Communicable Diseases;Complex;Confusion;Data;Development;Disease;Evolution;Foamy Macrophage;Genes;Granuloma;Granulomatous;healing;Host Defense;Human;Immune response;Immunity;immunological status;Immunologics;Immunology;Individual;Infection;Infection Control;Infectious granuloma;Inflammation;Inflammatory;Inflammatory Response;insight;interest;Invaded;Learning;Leprosy;Lesion;lipid metabolism;Lung;Lymphocyte;Macrophage;Macrophage Activation;Maps;Mediating;Mediator;microbicide;Mining;Modeling;Modernization;Molecular;Molecular Biology;Molecular Profiling;monocyte;Mycobacterium tuberculosis;Mycoses;Nature;nonhuman primate;Obstruction;Outcome;Parasitic infection;pathogen;Pathogenesis;pathogenic microbe;Pathway interactions;Patients;Population;Prevention strategy;Primary Infection;Primary Lesion;programs;Public Health;Pulmonary Tuberculosis;Reaction;Resistance;response;Role;single-cell RNA sequencing;Sterility;Structure;success;T cell response;T-Lymphocyte;Testing;treatment response;TREM2 gene;Tuberculosis;tuberculosis granuloma;tuberculosis immunity

PROJECT_TITLE: Dynamics of the cellular and molecular architecture of human pulmonary TB granulomas


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Brain Disorders;Cerebrovascular;Clinical Research;Neurosciences;Physical Injury - Accidents and Adverse Effects;Stroke;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury

ORG_CITY: Los Angeles

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: Project Narrative Stroke and traumatic brain injury (TBI) are leading causes of major disability and death, and delays in diagnosis and treatment are associated with higher morbidity and mortality. Current diagnostic standards in stroke and TBI require that patients undergo computed tomography or magnetic resonance imaging in a hospital setting to differentiate ischemic and hemorrhagic subtypes before initiating treatment. Our study proposes to develop a portable, noninvasive stroke/TBI detection and imaging system based on tri-coil eddy current damping technology, thereby rapidly identifying stroke subtypes, accelerating time-to-treatment, and providing early responders with information necessary to more efficiently administer triaged and appropriate intervention in the field or acute care setting.

PI_NAMEs: ZADA, GABRIEL  (contact)

PROGRAM_OFFICER_NAME: HEWETT, SANDRA JEANNE

PROJECT_TERMS: Acceleration;acute care;Affect;Alteplase;American;American Heart Association;Anatomic Models;Brain;Brain hemorrhage;brain parenchyma;brain tissue;Cadaver;Cause of Death;Cephalic;Cerebral hemisphere hemorrhage;Cerebrum;Cessation of life;Characteristics;Classification;Clinical;clinical investigation;Coma;Confusion;Consumption;cost;cranium;Data;Detection;detection platform;Deterioration;Devices;Diagnosis;Diagnostic;diagnostic accuracy;Diagnostic Imaging;diagnostic value;disability;disorder subtype;Dose;Effectiveness;experience;Experimental Models;Frequencies;Gelatin;Goals;Grouping;Guidelines;Health system;Hemorrhage;Hospitals;Hour;Human;Image;Imaging Device;imaging system;improved;Injury;innovation;Institution;Institutional Review Boards;instrument;International;Intervention;Intracranial Hemorrhages;Ischemia;ischemic lesion;Ischemic Stroke;Joints;Journals;Knowledge;laboratory experiment;Lesion;Life;Lifelong disability;Location;machine learning algorithm;magnetic field;Magnetic Resonance Imaging;Measures;Medical;Medical Care Costs;Medical Device;meetings;method development;Methods;Modeling;models and simulation;Morbidity - disease rate;mortality;multidisciplinary;Nervous System Trauma;neuroimaging;Neurologic;Neurological emergencies;Neurosurgeon;Non-Invasive Detection;non-invasive imaging;novel;Outcome;Output;Participant;Patients;Pharmaceutical Preparations;Physicians;portability;Pre-Clinical Model;predictive modeling;Productivity;Property;Protocols documentation;Provider;Publishing;Quality of life;rapid technique;Reporting;research clinical testing;response;Scanning;Scientist;sensor;Shapes;Societies;Stroke;stroke model;stroke patient;stroke therapy;symposium;TBI Patients;Technology;temporal measurement;Testing;Time;Tissues;Translating;Translational Research;Traumatic Brain Injury;Triage;United States National Institutes of Health;Validation;Variant;X-Ray Computed Tomography

PROJECT_TITLE: Noninvasive transcranial detection of intracranial hemorrhage using a tri-coil handheld portable eddy current damping imaging device

STUDY_SECTION: ANIE

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


NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Cystic Fibrosis;Lung;Pediatric;Rare Diseases

ORG_CITY: PITTSBURGH

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: PROJECT NARRATIVE As more people with cystic fibrosis (CF) live longer and healthier lives due to the advent and use of effective CF modulator therapies, a growing number are considering parenthood. However, minimal information exists about how parenthood affects those with CF, limiting the ability to make informed reproductive decisions and to support those who decide to become parents. This long-term, multicenter, observational study will determine the health impact of parenthood on men and women with CF in the era of CF modulators and is the first, large- scale epidemiologic data collection of how becoming a parent interplays with having a chronic disease.

PI_NAMEs: KAZMERSKI, TRACI  (contact)

PROGRAM_OFFICER_NAME: LACHOWICZ-SCROGGINS, MARRAH ELIZABETH

PROJECT_TERMS: 5 year old;Address;Adherence;Adoption;Affect;Behavior Therapy;Blood;Body mass index;Child;Child Rearing;Childhood;Chronic Disease;Clinic Visits;Communication;comparison group;Complex;Comprehensive Health Care;Cross-Sectional Studies;Cystic Fibrosis;Cystic Fibrosis Transmembrane Conductance Regulator;Data;Data Collection;Data Reporting;Decision Making;Defect;Disease;effective intervention;epidemiologic data;evidence base;experience;Fathers;Fostering;Foundations;Funding;Future;Health;health data;Health Personnel;Health Services;Health Surveys;Healthcare;Heart;high risk;Hormonal;improved;Intervention;Interview;Life;Life Expectancy;Link;Longitudinal cohort study;loss of function;Lung;lung health;Membrane;men;Mental Depression;Mental Health;Mission;Modeling;modifiable risk;Modification;Mothers;Multicenter Studies;non-genetic;Observational Study;Outcome;Parents;patient registry;Patients;Persons;Pharmaceutical Preparations;physical conditioning;Population;Pregnancy;prepregnancy;prevent;primary outcome;Principal Investigator;prospective;Prospective Studies;Psychosocial Assessment and Care;pulmonary function;Pulmonary Function Test/Forced Expiratory Volume 1;Quality of life;Registries;Reporting;reproductive;Research;Research Personnel;respiratory;Retrospective Studies;Risk Factors;Role;Self Management;sexual and reproductive health;Stress;Structure;Surveys;Testing;Time;trend;United Kingdom;United States;United States National Institutes of Health;Woman;Work;young woman

PROJECT_TITLE: Health Outcomes of Parents with Cystic Fibrosis (HOPe:CF)

STUDY_SECTION: IRAP

STUDY_SECTION_NAME: Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section[IRAP]


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);Behavioral and Social Science;Brain Disorders;Caregiving Research;Clinical Research;Clinical Trials and Supportive Activities;Dementia;Lewy Body Dementia;Mental Health;Neurodegenerative;Neurosciences

ORG_CITY: Boston

ORG_NAME: EIP PHARMA, INC.

PHR: Dementia with Lewy bodies (DLB), the second most common cause of neurodegenerative dementia after Alzheimer’s disease (AD), is rapidly progressive with a median time from diagnosis to death or nursing home half that seen with AD and extensive burden on both patients and family caregivers. There are no approved treatments, though some drugs approved for other diseases may partially or temporarily relieve some of its cognitive and motor symptoms. The proposed research would advance clinical testing of neflamapimod as a treatment to not only relieve symptoms but also treat the underlying disease process, potentially providing hope for DLB sufferers and their families.

PI_NAMEs: ALAM, JOHN  (contact);GALVIN, JAMES E

PROGRAM_OFFICER_NAME: RYAN, LAURIE M

PROJECT_TERMS: Admission activity;Adverse event;Affect;Aggressive behavior;Agitation;Alzheimer's Disease;American;Attention;basal forebrain;basal forebrain cholinergic neurons;Behavioral Symptoms;Biological Availability;Brain;Cessation of life;cholinergic;Cholinesterase Inhibitors;Clinical;Clinical dementia rating scale;clinical development;clinical efficacy;Clinical Research;Clinical Trials;clinically relevant;Cognition;Cognitive;cognitive testing;Collection;cooperative study;Data;Dementia;Dementia with Lewy Bodies;Dependence;design;Diagnosis;Disease;Dose;Double-Blind Method;Down's Syndrome;Drug usage;Effectiveness;efficacy evaluation;Electroencephalography;Enzymes;Equilibrium;Equipment and supply inventories;executive function;Eye;fall risk;Family;family burden;Family Caregiver;Functional disorder;Future;Grief reaction;Hallucinations;impression;improved;inhibitor;inhibitor therapy;investigator-initiated trial;kinase inhibitor;Laboratories;Measures;Medical;Mental Depression;Mental disorders;Modeling;Monitor;Motor;motor symptom;Movement Disorder Society Unified Parkinson's Disease Rating Scale;Nerve Degeneration;Neurobehavioral Manifestations;neurodegenerative dementia;neuropsychiatry;Neuropsychological Tests;Nursing Homes;off-label use;Oral;Outcome;Outcome Measure;p38 Mitogen Activated Protein Kinase;Parkinson Disease;Pathogenicity;patient population;Patients;Pharmaceutical Preparations;Pharmacodynamics;Phase;phase 2 study;phase III trial;Placebo Control;Placebos;Population;pre-clinical;preclinical study;primary endpoint;primary outcome;Process;Progressive Disease;prospective;Quality of life;Randomized;reduce symptoms;Research;research clinical testing;Rest;Risk;Safety;secondary endpoint;Sleep;Sum;System;Testing;therapeutic target;Thinness;Time;Transgenic Mice;treatment effect;Visual;visual learning

PROJECT_TITLE: A Phase 2b Clinical Study of the P38 Alpha Kinase Inhibitor Neflamapimod in Patients with Mild-to-Moderate Dementia with Lewy Bodies (DLB)

STUDY_SECTION: APDA

STUDY_SECTION_NAME: Adult Psychopathology and Disorders of Aging Study Section[APDA]


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

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

ORG_CITY: LAWRENCE

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: UNIVERSITY OF KANSAS LAWRENCE

ORG_STATE: KS

PHR: PROJECT NARRATIVE The continual trend of “lost in translation” in the search for a successful treatment for Alzheimer's disease (AD) calls for innovative approaches before a viable drug target is established. The outcomes of this research will yield valuable insights into whether a therapeutic shield such as a human ApoE2- based protein therapy that promotes brain metabolic resilience can potentially be developed into an effective and safe disease-modifying strategy for AD, which is vital to the present fight against this devastating and currently untreatable disease.

PI_NAMEs: SIAHAAN, TERUNA J.;ZHAO, LIQIN  (contact)

PROGRAM_OFFICER_NAME: GROTHAUS, PAUL G

PROJECT_TERMS: Address;Adverse reactions;Affect;Age;aging brain;Alleles;Alzheimer's Disease;Alzheimer's disease brain;American;Amyloid;Apolipoprotein E;apolipoprotein E-2;apolipoprotein E-3;apolipoprotein E-4;Biological;Blood - brain barrier anatomy;Brain;Cadherins;Code;cognitive function;Data;Deposition;design;Development;Disease;Drug Targeting;E-Cadherin;Early Onset Familial Alzheimer's Disease;familial Alzheimer disease;fighting;Genes;Genotype;Glucose;glucose metabolism;Glycoproteins;Goals;Health;high risk;Hippocampus;Homeostasis;Human;humanized mouse;improved;innovation;insight;Intervention;Knock-in Mouse;lipidomics;Mediating;Metabolic;Metabolism;Methods;Modeling;Molecular;mouse model;Mus;mutant;Nature;Neurons;neuroprotection;novel;Outcome;Outcomes Research;Pathogenesis;Pathology;Peptides;Persons;Physiological;Play;Predisposition;Preparation;prevent;Prevention;Production;Protein Isoforms;Proteins;proteostasis;Recombinants;Regimen;Research;Research Project Summaries;resilience;Risk;Role;sex;Shapes;Signal Transduction;success;Synapses;tau Proteins;Therapeutic;Translating;Translations;trend;Up-Regulation

PROJECT_TITLE: Reshaping ApoE4 and Alzheimer's Brains with ApoE2

STUDY_SECTION: NOMD

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


ORG_CITY: IOWA CITY

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: Project Narrative The majority of patients survive early phases of sepsis (cytokine storm) and go on to develop long-lasting immunoparalysis state that is characterized by the diminished ability to respond to secondary infections. This proposal will identify cellular and molecular mechanisms that define and support chronic state of immunoparalysis and inability of innate and adaptive cells of the immune system to exert their effector functions.

PI_NAMEs: BADOVINAC, VLADIMIR P (contact)

PROGRAM_OFFICER_NAME: ZHAO, XIAOLI

PROJECT_TERMS: Address;American;Area;Autoimmune Responses;CD8-Positive T-Lymphocytes;Cell Survival;Cells;Chronic;Clinical;cytokine release syndrome;Development;Experimental Models;Functional disorder;Goals;Human;Immune;Immune response;Immune system;Immunosuppression;Individual;Infection;Inflammatory;Life;Lymphocyte;Lymphocyte Count;Lymphopenia;Maintenance;Memory;Molecular;mortality;Mus;Organ;pathogenic bacteria;pathogenic virus;Pathway interactions;Patients;Phase;Population;Predisposition;Public Health;Research;secondary infection;Secondary to;Sepsis;septic;Survivors;T cell response;tumor;Vaccines;Viral

PROJECT_TITLE: Cellular and molecular mechanisms controlling sepsis-induced immunoparalyses state

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


ADMINISTERING_IC: HS

IC_NAME: AGENCY FOR HEALTHCARE RESEARCH AND QUALITY

ORG_CITY: Washington

ORG_NAME: AMERICAN SOCIETY OF HEALTH ECONOMISTS

ORG_STATE: DC

PHR: Project Narrative The purpose of the Twelfth, Thirteenth, and Fourteenth Annual American Society of Health Economists (ASHEcon) Conferences is to enable the community of health economists, health services researchers, and health policy researchers to gather and present research, exchange ideas, gain new skills, and learn about current policy issues. The research presented at each conference encompasses several aspects of health economics and policy research, including both health care and health behaviors. We aim to provide a forum for emerging ideas and empirical results of health economics research to be showcased and discussed.

PI_NAMEs: SLUSKY, DAVID  (contact)

PROGRAM_OFFICER_NAME: KARACA, ZEYNAL

PROJECT_TITLE: Twelfth Annual Conference of the American Society of Health Economists

STUDY_SECTION: HSVR

STUDY_SECTION_NAME: Healthcare Systems and Values Research[HSVR]


ORG_CITY: NASHVILLE

ORG_NAME: VETERANS HEALTH ADMINISTRATION

ORG_STATE: TN

PHR: Advanced chronic kidney disease represents a major cause of morbidity and mortality for our Veterans and is frequently associated with anemia, the inability of the body to produce adequate numbers of red blood cells. This grant investigates the role of mitochondria in the regulation of erythropoietin, the hormone that is made by the kidney and is essential for red blood cell production. Work proposed under this grant will further our understanding of the metabolic causes of anemia associated with kidney failure. This project has potential for the development of novel therapeutic approaches for the management of anemia in patients with chronic kidney disease.

PI_NAMEs: HAASE, VOLKER HANS (contact)

PROJECT_TERMS: Adenine;Adult;alpha ketoglutarate;Anemia;bHLH-PAS factor HLF;Blood;Blood Vessels;Cardiovascular system;Cell Differentiation process;Cell Physiology;Cell Survival;Cells;Cellular Metabolic Process;Characteristics;Chronic Kidney Failure;Clinical Research;Collagen;Complication;Data;Decarboxylation;Development;Dioxygenases;Electron Transport;Electron Transport Complex III;Enzymes;Erythrocytes;Erythroid Progenitor Cells;Erythropoiesis;Erythropoietin;Fibroblasts;fibrogenesis;Fibrosis;Functional disorder;General Population;Genes;Genetic;Genetic Models;Glycoproteins;Grant;Heterodimerization;HIF1A gene;Homeostasis;Hormones;Hydroxylation;Hypoxia;Hypoxia Inducible Factor;In Vitro;Incentives;Injury;Injury to Kidney;innovation;insight;interstitial;interstitial cell;Intravenous;Iron;Kidney;Kidney Diseases;Kidney Failure;kidney fibrosis;Knowledge;Laboratories;Link;Metabolic;Mitochondria;mitochondrial dysfunction;Modeling;Molecular;Morbidity - disease rate;mortality;mouse model;Myofibroblast;novel;novel therapeutic intervention;Nuclear Translocation;Oxygen;Pathogenesis;Patients;PDGFRB gene;Pericytes;Physiological;Play;Prevalence;Procollagen-Proline Dioxygenase;Production;Proliferating;Proline;Protein Isoforms;Public Health;Recombinant Erythropoietin;Recombinants;Regulation;Renal function;Renal Interstitial Cell;Replacement Therapy;Resolution;response;Role;Safety;sensor;Source;therapeutic target;Three-Dimensional Imaging;transcription factor;Transcriptional Regulation;transcriptomic profiling;transcriptomics;transdifferentiation;Translations;United States;Ureteral obstruction;Veterans;Work

PROJECT_TITLE: Cellular and Molecular Mechanisms of Renal Anemia


ORG_NAME: IOWA CITY VA MEDICAL CENTER

PHR: The high prevalence of obesity among veterans is a major health concern because obesity is associated with life threating illnesses including high blood pressure, a medical condition that promote cardiovascular disease. However, the processes by which obesity promote high blood pressure and other cardiovascular risks is not well understood. The research proposed in this application will fill this gap in knowledge by defining the mechanisms of by which the brain drives obesity-associated high blood pressure. This information can lead to improved treatment for cardiovascular disease, bettering the lives of the veterans.

PI_NAMEs: RAHMOUNI, KAMAL  (contact)

PROJECT_TERMS: Ablation;Affect;Blood Pressure;Brain;Cardiovascular Diseases;Cardiovascular Physiology;cardiovascular risk factor;Cardiovascular system;Complex;Congestive Heart Failure;Conscious;Data;Development;diet-induced obesity;Etiology;FRAP1 gene;Functional disorder;Gene Deletion;Genes;Genetic Transcription;Genetically Engineered Mouse;global health;Goals;Health;Healthcare Systems;High Prevalence;Hypertension;Hypothalamic structure;improved;innovation;Kidney;Knowledge;Leptin;leptin receptor;Life;Ligands;Measures;Mediating;Medical;Melanocortin 4 Receptor;Methods;Molecular;mTOR protein;Mus;Myocardial Infarction;Nerve;Neurons;novel;Obesity;Organ;Overweight;Pathway interactions;pharmacologic;Physiological;Population;pressure;Prevalence;prevent;Process;promoter;Protease Inhibitor;protective effect;protein complex;Regulation;Research;Risk Factors;Role;Serine;side effect;Signal Transduction;standard of care;Stroke;System;Technology;Testing;Veterans;Weight Gain;Work;α-Melanocyte stimulating hormone

PROJECT_TITLE: Neuronal Mechanisms of Obesity-Induced Hypertension


FUNDING_MECHANISM: OTHERS

PHR: PROJECT NARRATIVE Heart failure with preserved ejection fraction (HFpEF) constitutes nearly half of all heart failure hospitalizations, and HFpEF is responsible for the death of nearly 1 in 14 Veterans. However, currently there are no treatments that improve mortality in this disease. This proposal aims to test a promising new target that may alter energy utilization and metabolism in the failing right heart in HFpEF. This proposal also supports the training and career development of Dr. Vineet Agrawal to study the disease of HFpEF and identify new therapies for a disease that currently has none.

PI_NAMEs: AGRAWAL, VINEET  (contact)

PROJECT_TERMS: Adipose tissue;Advisory Committees;Affect;Animal Model;Biogenesis;Biopsy Specimen;Cardiac;Cardiac Myocytes;Cardiac Output;career;career development;Cause of Death;Cells;Cessation of life;Clustered Regularly Interspaced Short Palindromic Repeats;Communication;Cyclic AMP;Cyclic AMP-Dependent Protein Kinases;Cyclic GMP;Data;Development;Disease;EFRAC;exercise capacity;Failure;fatty acid oxidation;Foundations;Funding;Generations;Genes;Genus Hippocampus;Goals;Heart;Heart Diseases;Heart failure;heart metabolism;Hospitalization;Human;human induced pluripotent stem cells;Hypertrophy;Impairment;improved;improved outcome;In Vitro;in vivo;induced pluripotent stem cell;knock-down;Knock-out;Knockout Mice;Ligands;Measurement;Measures;Mediating;Mentors;Mentorship;Metabolic;Metabolic dysfunction;Metabolism;metabolomics;Methods;Mitochondria;mitochondrial dysfunction;Modeling;Morbidity - disease rate;mortality;Myocardial;myocardial biopsy;Natriuresis;Natriuretic Peptides;new therapeutic target;novel;novel therapeutics;Obesity;obesity treatment;Outcome;overexpression;Pathogenesis;Pathogenicity;Pathway interactions;patient population;PGC1a Regulation Pathway;pharmacologic;Physicians;preservation;prevent;Principal Investigator;protein expression;receptor;Regulation;Relaxation;Research;Resources;Respiration;Reverse Transcriptase Polymerase Chain Reaction;Right Ventricular Dysfunction;right ventricular failure;Right Ventricular Function;Role;Scientist;Signal Transduction;skills;Structure;Surface;Techniques;Testing;therapeutic evaluation;therapeutic target;Tissues;Training;Training Support;Transgenic Mice;Transgenic Organisms;Ventricular;Veterans;Work

PROJECT_TITLE: A Pathogenic Role for the Natriuretic Peptide Clearance Receptor in Heart Failure with Preserved Ejection Fraction.