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

ORG_CITY: CLEVELAND

ORG_DEPT: PHYSIOLOGY

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

ORG_STATE: OH

PHR: PROJECT NARRATIVE: The excess risk for chronic kidney diseases (CKD) in black Americans is largely explained by social determinants of health and the presence of genetic variants in the APOL1 gene. The pathogenetic mechanisms responsible for the genetic association remain poorly understood, hindering the development of specific therapies. This project will anchor gene expression features present in patient-glomerular transcriptomes to those present in iPSC-derived podocytes, to provide novel insights into the molecular function and genetic pathways that distinguish APOL1-G0 from the kidney disease risk variants, laying a groundwork for prognostic biomarkers and novel therapeutics.

PI_NAMEs: GONZALEZ-VICENTE, AGUSTIN  (contact)

PROGRAM_OFFICER_NAME: RANKIN, TRACY L

PROJECT_TERMS: Address;African American;African American population;African ancestry;Alleles;APOL1 gene;Architecture;Area;Bioinformatics;Biological Assay;Biology;Black American;career development;Cell Line;Cell Physiology;cell type;Chemicals;Chronic Kidney Failure;Classification;Clinical;cohort;Complex;Cox Proportional Hazards Models;CRISPR/Cas technology;Data;design;Development;differential expression;Disease;Early Diagnosis;Experimental Models;Gene Expression;Gene Expression Profile;Genes;Genetic;genetic association;Genetic Transcription;genetic variant;Genetic Variation;Genotype;Goals;Health;high risk;high risk population;Human;human induced pluripotent stem cells;in silico;in vitro testing;Individual;inhibitor;insight;Investigation;Kidney;Kidney Diseases;Laboratories;laboratory experience;large datasets;Maps;Measures;Mentors;Mentorship;Modeling;Molecular;mouse model;Mutation;Names;Nephrology;Nephrotic Syndrome;novel;novel therapeutics;Outcome;Participant;Pathogenicity;Pathway Analysis;Pathway interactions;patient oriented research;Patients;Persons;Phenotype;podocyte;Population;preservation;Primates;Principal Investigator;Production;Prognosis;Prognostic Marker;programs;Research;Research Personnel;Research Proposals;Reverse Transcription;Risk;risk variant;Rodent;Science;screening;skills;social health determinants;Specialized Epithelial Cell;stable cell line;stem cells;Stress;Technology;Testing;Therapeutic;therapeutic target;tool;Training;transcriptome;transcriptome sequencing;transcriptomics;Transgenic Mice;Translating;translational scientist;Variant

PROJECT_TITLE: Using transcriptomics and ex vivo organotypic models to discover mechanisms of APOL1-associated podocytopathies


ADMINISTERING_IC: DK

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Digestive Diseases;Infectious Diseases

ORG_CITY: TUSCALOOSA

ORG_COUNTRY: UNITED STATES

ORG_DEPT: BIOLOGY

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF ALABAMA IN TUSCALOOSA

ORG_STATE: AL

PHR: PROJECT NARRATIVE Coxsackievirus B is a common human pathogen that can cause acute and chronic pancreatitis. If we can understand how to block viral replication and the cell-to-cell spread of the virus, this would provide insight towards developing new antiviral therapies to limit the severity of pancreatic damage. We have identified several novel areas of virus-mitochondrial interactions, and based on our findings, we propose to test potential therapies in a mouse model of viral pancreatitis.

PI_NAMEs: SIN, JON  (contact)

PROGRAM_OFFICER_NAME: ANDERSEN, DANA K

PROJECT_TERMS: Acute;acute pancreatitis;Affect;antagonist;Anti-viral Therapy;Antibody titer measurement;antiviral immunity;Area;Attenuated;cancer cell;Capsaicin;Cardiac Myocytes;Cells;Cessation of life;Child;chronic pancreatitis;Coxsackie B Viruses;Coxsackie Viruses;Cytoplasm;Data;Diagnosis;Disease;Disease Progression;effective intervention;Enterovirus;Enzymes;Exocrine pancreas;extracellular vesicles;Hela Cells;high risk;Human;human pathogen;Impairment;In Vitro;Infection;Inflammation;Inflammatory;insight;Ion Channel;Malignant neoplasm of cervix uteri;Malignant neoplasm of pancreas;Mediating;Meningoencephalitis;Menthol;Mitochondria;Mitochondrial RNA;mortality;mouse model;Mus;Myocarditis;neutralizing antibody;Nonlytic;novel;novel therapeutics;Oral;Organ;Pancreas;Pancreatitis;Pathway interactions;Patients;Peptide Hydrolases;Play;Predisposition;premature;prevent;Process;Production;promoter;receptor;Reporting;Ribosomes;Risk Factors;Role;Severities;Signal Transduction;Symptoms;systemic inflammatory response;Testing;Translating;Translations;Tropism;TRP channel;TRPV1 gene;Viral;Viral Load result;Viral Pathogenesis;Viral Proteins;viral RNA;Virus;Virus Diseases;Virus Replication

PROJECT_TITLE: Targeting transient receptor potential channels to suppress proviral mitochondrial fission and mitophagy in order to mitigate CVB pancreatitis

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


ED_INST_TYPE: SCHOOLS OF MEDICINE

NIH_SPENDING_CATS: Digestive Diseases;Genetics

ORG_CITY: LOS ANGELES

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

ORG_STATE: CA

PHR: Project Narrative The proposed research is relevant to public health because it will advance our understanding of the pathogenesis of pancreatitis, a disease with considerable morbidity and mortality and currently without a treatment. Excessive inflammation is a major determinant of pancreatitis severity but its mechanisms are poorly understood The results will establish the importance of mitochondria as a clinically relevant modulator of the inflammation in pancreatitis and identify potential molecular targets amenable for pharmacologic intervention to normalize mitochondrial functions and reduce pancreatitis severity; thus, this proposal is relevant to the NIH’s goal to develop research strategies as a basis for disease treatment.

PI_NAMEs: GUKOVSKY, ILYA  (contact);LEE, BOMI

PROGRAM_OFFICER_NAME: SERRANO, JOSE

PROJECT_TERMS: Acinar Cell;Automobile Driving;Autophagocytosis;cell injury;chemokine;clinically relevant;cytokine;Disease;DNA;Exocrine pancreas;Experimental Models;Genetic;Genetic Models;Goals;Human;human disease;IL18 gene;immune cell infiltrate;Immune response;Impairment;Inflammasome;Inflammation;Inflammatory;Inflammatory Response;Interferons;Interleukin-1 beta;Intervention;Knock-out;Link;Macrophage;Macrophage Activation;Measures;Mediating;Mediator;Mitochondria;Mitochondrial DNA;mitochondrial dysfunction;Modeling;Molecular Target;Morbidity - disease rate;mortality;Pancreas;Pancreatitis;Pathogenesis;Pathogenicity;Pathway interactions;Patients;pharmacologic;Production;Public Health;Research;Role;Serum;Severities;Signal Transduction;Stimulator of Interferon Genes;TBK1 gene;Testing;United States National Institutes of Health

PROJECT_TITLE: Impaired autophagy, mitochondrial dysfunction, and inflammation in pancreatitis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DNPD-A(01)]


ADMINISTERING_IC: TW

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: FOGARTY INTERNATIONAL CENTER

NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Clinical Research;Genetics;HIV/AIDS;Human Genome;Infectious Diseases;Prevention;Rare Diseases

ORG_CITY: NEW ORLEANS

ORG_NAME: LSU HEALTH SCIENCES CENTER

ORG_STATE: LA

PHR: NARRATIVE While cancers are a major cause of death around the globe in people living with HIV infection, those in low- and middle-income countries (LMICs), particularly in sub-Saharan Africa, are much more likely to die from cancer due to shortages of trained cancer researchers, oncologists, and a lack of healthcare infrastructure and expertise in preventing, diagnosing and treating HIV-infection associated cancers. The Tanzania AIDS Malignancies Training and Research Program (TAMTRP) seeks to address these challenges to enhance the cancer research infrastructure of our partnering organization, the Ocean Road Cancer Institute (ORCI) in Dar es Salaam, Tanzania by training a cadre of Tanzanian fellows, researchers and practitioners with career interest in HIV associated malignancies. The TAMTRP program will enable the trainees to develop skills necessary to further both partners' research agenda in clinical research, public health, cancer biology and genomics/bioinformatics, which will translate to better clinical care for HIV-infected cancer patients globally.

PI_NAMEs: MWAISELAGE, JULIUS DAVID;WOOD, CHARLES  (contact)

PROGRAM_OFFICER_NAME: BANSAL, GEETHA PARTHASARATHY

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;AIDS prevention;AIDS related cancer;anti-cancer research;Big Data Methods;Bioinformatics;Biology;Biometry;Cancer Biology;Cancer Center;Cancer Detection;Cancer Diagnostics;cancer genomics;cancer prevention;Cancer Research Infrastructure;cancer therapy;Clinical;Clinical Research;Clinical Trials;Collaborations;data management;design;Detection;Diagnosis;Diagnostic;Doctor of Philosophy;Educational workshop;Epidemiology;Etiology;experience;Future;Genomics;Goals;Health Personnel;Health Sciences;Human Resources;Immunology;Infrastructure;insight;Institution;Instruction;Laboratories;Louisiana;Malignant Neoplasms;Master of Science;Mentors;Methodology;Molecular;Molecular Biology;molecular pathology;neoplasm registry;next generation sequencing;Oceans;Oncology;Pathology;precision oncology;Preparation;Prevention;programs;Public Health;Research;Tanzania;Training;Training and Infrastructure;training opportunity;Translational Research;Universities;Viral;virology


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: PROJECT NARRATIVE  Recombinant adeno-associated virus (rAAV) gene therapies are increasingly becoming a viable treatment option for incurable genetic disorders. However, they are not without toxicity or significant risk, with several rAAV-related deaths and numerous adverse outcomes reported during the past few years alone. Embarking on a new research direction, we will utilize our complimentary expertise in neuroscience, stem cell biology, and engineering to develop new methods for rAAV production and create the first rAAVs with engineered inverted terminal repeats (ITRs) that are safer for human gene therapy.

PI_NAMEs: SHTRAHMAN, MATTHEW  (contact)

PROGRAM_OFFICER_NAME: MORRIS, JILL A

PROJECT_TERMS: Ablation;Acute Kidney Failure;adult neurogenesis;Adverse effects;adverse outcome;Attenuated;Base Pairing;Brain;c9FTD/ALS;Capsid;Cardiopulmonary;Cell Death;Cells;Central Nervous System Diseases;Cessation of life;Child;Clinical Trials;Dependovirus;digital;Disease;DNA;DNA Damage;DNA Sequence;Electroporation;Embryo;Engineering;experimental study;FDA approved;Functional disorder;Gene Delivery;gene product;gene therapy;Genes;Genetic Diseases;Genome;Hippocampus;Histology;Human;immunogenicity;immunoreaction;in utero;in vivo;Injections;Inverted Terminal Repeat;Learning;Learning Disabilities;loss of function;Magnetic Resonance Imaging;Mediating;Medicine;Memory;Methods;Methyl-CpG-Binding Protein 2;mouse model;Mucopolysaccharidosis III;Mus;mutant;Mutation;Names;nerve stem cell;Neurons;Neurosciences;novel therapeutics;Nucleotides;Pathologic;Patients;Production;Proteins;Publishing;R7 Virus;Recombinant adeno-associated virus (rAAV);Recombinants;Reporting;Research;response;Rett Syndrome;Risk;RNA;Single-Stranded DNA;Site;Source;stem cell biology;stem cell proliferation;Structure;Symptoms;Terminal Repeat Sequences;Testing;Therapeutic;Thrombocytopenia;Toxic effect;transgene expression;Transgenes;Tropism;vector;Viral;Viral Genome;Viral Vector;Virus;Work

PROJECT_TITLE: Developing a Synthetic Adeno-Associated Virus (AAV) for Engineering Safer Gene Therapies

STUDY_SECTION: MNG

STUDY_SECTION_NAME: Molecular Neurogenetics Study Section[MNG]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Aging;Atherosclerosis;Biotechnology;Cardiovascular;Clinical Research;Estrogen;Heart Disease;Hematology;Machine Learning and Artificial Intelligence;Menopause;Precision Medicine;Prevention;Women's Health Research

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

ORG_STATE: MA

PHR: PROJECT NARRATIVE / PUBLIC HEALTH RELEVANCE Cardiovascular disease (CVD) is the leading killer of women in the United States and worldwide, and women with premature age of menopause have elevated risk of developing CVD for unclear reasons. Preliminary data suggest women with premature menopause have increased risk of CHIP, a recently recognized asymptomatic blood condition associated with accelerated development of CVD and adverse CVD outcomes. The proposed study will investigate whether CHIP is responsible for CVD in women with premature menopause and will identify new targets for the prevention and treatment of premature menopause-associated CVD.

PI_NAMEs: HONIGBERG, MICHAEL  (contact)

PROGRAM_OFFICER_NAME: WOO, SEUNG KYOON

PROJECT_TERMS: Acceleration;Adult;Advisory Committees;Affect;Age;age related;Antibodies;aptamer;Atherosclerosis;Atherosclerosis Risk in Communities;Award;biobank;Bioinformatics;Biological;Biological Markers;Biology;biomarker identification;Blood;Blood Vessels;Cardiovascular Diseases;cardiovascular disorder prevention;cardiovascular disorder risk;cardiovascular health;cardiovascular risk factor;Cardiovascular system;career;career development;Characteristics;Circulation;Clinical;Clinical Data;Clonal Expansion;cohort;Cross-Sectional Studies;Dana-Farber Cancer Institute;Data;Data Set;Development;Disease;Disease Outcome;DNA;Educational process of instructing;Endocrinology;Etiology;Event;experience;Funding;General Hospitals;Genes;Genetic;Genomics;Goals;Gonadal Steroid Hormones;Grant;Heart Diseases;Heart failure;Heart Valve Diseases;Hematology;Hematopoiesis;Hematopoietic Neoplasms;hematopoietic stem cell expansion;Hospitals;Human;Human Genetics;improved;Incidence;Individual;individualized prevention;Inflammation;Inflammatory;instructor;Investigation;Israel;K-Series Research Career Programs;leukemia;Link;Machine Learning;machine learning method;Massachusetts;Measures;Mediating;Mediation;Mediator;Medical center;medical schools;Medicine;Mendelian randomization;menopausal hormone therapy;Menopause;Mentors;Mentorship;Molecular;Multiomic Data;multiple omics;Mus;Mutation;Myeloproliferative disease;National Heart, Lung, and Blood Institute;next generation sequencing;novel;novel marker;Operative Surgical Procedures;Pathway Analysis;Pathway interactions;Physicians;Positioning Attribute;Postmenopause;pre-clinical;precision medicine;predictive modeling;premature;Premature Menopause;Prevalence;Prevention;Principal Investigator;programs;protein biomarkers;Proteins;proteomic signature;Proteomics;public health relevance;Publishing;Quantitative Trait Loci;Recording of previous events;reproductive epidemiology;Research;Resources;Risk;Risk Factors;risk prediction;risk prediction model;Risk Reduction;Role;Scientist;screening;sex;skills;Somatic Mutation;Structure;targeted biomarker;Testing;Time;Training;Training Programs;Trans-Omics for Precision Medicine;United States;United States National Institutes of Health;Universities;Woman;Women's Health;Work

PROJECT_TITLE: Clonal hematopoiesis as a mediator of cardiovascular disease in women with premature menopause

STUDY_SECTION: MCBS

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


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: NASHVILLE

ORG_NAME: VETERANS HEALTH ADMINISTRATION

ORG_STATE: TN

PHR: PROJECT NARRATIVE This project is focused on developing gene transfer technology for and understanding the metabolic consequences of cystinuria, an inherited kidney disease in veterans. The proposed gene transfer strategies and knowledge gained with cystinuria could lead to development of new therapies for a variety of other human kidney diseases which plague veterans. Our research approach is therefore extremely significant and relevant to the health of veterans and the overall mission of research within the VA.

PI_NAMEs: WILSON, MATTHEW H (contact)

PROJECT_TERMS: absorption;Acute;adeno-associated viral vector;adenovirus mediated delivery;Adult;Affect;Amino Acids;Animal Model;Animals;Blood;Cells;cellular transduction;Chronic;Chronic Kidney Failure;Clinical;Cystine;Cystinuria;Data;Dependovirus;Development;Disease;disease model;Experimental Designs;Feasibility Studies;Foundations;Gene Delivery;Gene Mutation;Gene Transfer;Genetic;Genetic Recombination;Genome engineering;Glutathione;Grant;Health;Human;Hybrids;Image;in vivo;Inherited;Injury;Injury to Kidney;innovation;Kidney;Kidney Calculi;Kidney Diseases;Knowledge;mass spectrometric imaging;Mediating;Medical;Metabolic;Metabolic Pathway;military veteran;Mission;Modeling;Modification;molecular targeted therapies;Morbidity - disease rate;mortality;mouse model;Mus;Mutation;Neonatal;neutralizing antibody;novel;novel therapeutics;Organ;Organoids;Phenotype;Plague;Plasma;pre-clinical;preclinical study;prevent;Proximal Kidney Tubules;Recombinants;reconstitution;Research;side effect;Site;Sodium Chloride;Technology;Technology Transfer;Testing;Therapeutic;Tissues;Trans-Splicing;transgene delivery;transgene expression;Transgenes;translational therapeutics;urinary;Urine;Validation;vector;Veterans;Water

PROJECT_TITLE: Genome engineering therapeutics for cystinuria and its metabolic consequences.


ORG_CITY: SEATTLE

ORG_NAME: VA PUGET SOUND HEALTHCARE SYSTEM

ORG_STATE: WA

PHR: Evidence of cerebellar dysfunction which correlates with the severity of cognitive and emotional symptoms in Veterans with psychiatric disorders is beginning to be elucidated. Aberrant dopamine signaling arising from the ventral tegmental area (VTA) is also a likely contributor to many psychiatric disorders, and it is known that cerebellar nuclei project to the VTA, the heart of the mesolimbic dopamine system which mediates reward and fear learning. We hypothesize that a novel locus of aberrant function in psychiatric disorders stems from faulty circuitry between the VTA and the understudied cerebellum. We will target specific cerebellar-VTA circuits with cutting edge tools to map, characterize, and manipulate this circuit’s function in different cognitive domains. This will result in novel insights into mechanisms and novel interventions for cognitive and emotional symptoms in Veterans, which are of great interest.

PI_NAMEs: CARLSON, ERIK SEAN (contact)

PROJECT_TERMS: Address;Adult;Affect;Amygdaloid structure;Anatomy;Animals;Area;Association Learning;Attention;Behavior;behavior measurement;Behavioral;Behavioral Assay;Brain region;Catecholamines;Cell Nucleus;cell type;Cerebellar Cortex;Cerebellar Diseases;cerebellar lesion;Cerebellar Nuclei;Cerebellum;Clinical Markers;Cognition;Cognitive;cognitive function;cognitive performance;cognitive task;Compensation;Complex;conditioned fear;Cues;Dentate nucleus;Discrimination;Dopamine;Dopamine D1 Receptor;dopaminergic neuron;Electrophysiology (science);Emotional;emotional functioning;emotional symptom;Esthesia;Etiology;Experimental Animal Model;Fiber;flexibility;Fright;Functional disorder;Glutamates;Goals;Grant;Heart;Hemispherectomy;Human;Impaired cognition;Impairment;improved;in vivo;incentive salience;insight;interest;Intervention;Language;Lateral;Learning;Light;Maps;Measures;Mediating;memory recognition;Mental Depression;Mental disorders;mesolimbic system;Midbrain structure;Modeling;Motor;motor deficit;Mus;Mutation;neural;Neuroanatomy;neurobehavioral;Neurobehavioral Manifestations;Neurobiology;Neurons;neuropsychiatric disorder;neuropsychiatric symptom;neuroregulation;nonhuman primate;novel;Nucleus Accumbens;Operant Conditioning;optogenetics;Output;paired stimuli;Parkinson Disease;Pathway interactions;Pattern;Performance;pharmacologic;Photometry;Population;Post-Traumatic Stress Disorders;Precision therapeutics;Production;Psychological reinforcement;Psychoses;Recovery;recruit;response;Rewards;Rodent;Sensory;Severities;Shock;Short-Term Memory;Signal Transduction;social;Social Interaction;Source;stem;Stimulus;stroke recovery;Structure;Symptoms;Testing;Thalamic structure;time interval;tool;Ventral Tegmental Area;vesicular glutamate transporter 2;Veterans;Viral;virtual;With laterality;Work

PROJECT_TITLE: Recruitment of Cerebellar Circuits to Modulate Cognition, Reward and Avoidance of Threat


FUNDING_MECHANISM: RESEARCH CENTERS

ORG_CITY: BALTIMORE

ORG_NAME: BALTIMORE VA MEDICAL CENTER

ORG_STATE: MD

PHR: Rheumatoid arthritis (RA) is a debilitating disease of the joints that affects over 10 out of 1000 Americans, including the Veterans. Further, the prevalence of RA is much higher in women than in men. This is of special relevance to women serving in the military. The aging Veterans constitute another group to bear the brunt of RA. The suffering and disabilities caused by RA impose a huge financial burden on the healthcare and rehabilitation of Veterans. Many potent drugs are available for the treatment of RA; but their prolonged use is associated with severe adverse reactions because these drugs that are given orally or by injection are distributed to all organs of the body. We propose targeted drug delivery to the joint as a better alternative. We reported that an arthritis drug entrapped in liposomes that displayed a novel joint-homing peptide (ART-2) on their surface was more effective than other modes of treatment in a rat arthritis model. We now plan to validate these findings in a different (mouse) model of arthritis to de-risk the technology for translational studies in RA.

PI_NAMEs: MOUDGIL, KAMAL D (contact)

PROJECT_TERMS: Abbreviations;Address;Adjuvant Arthritis;Adverse effects;Adverse reactions;Affect;Aging;American;Amino Acids;Animal Model;anti-arthritic drug;Antibodies;Arthritis;arthritis therapy;arthropathies;Binding;Biodistribution;Bioinformatics;Biological;Blood Vessels;CCL2 gene;CCL3 gene;Characteristics;chemokine;Chronic;Collagen Arthritis;Collagen Type II;combat zone;comparative;comparative efficacy;cyanine;cyanine dye;cytokine;DBA/1 Mouse;Development;Dexamethasone;disability;Disease;Disease susceptibility;Drug Delivery Systems;drug metabolism;Drug Targeting;Drug usage;Endothelial Cells;Evaluation;Exposure to;Financial Hardship;Genetic;genetic makeup;Health;Health Care Costs;Healthcare;Heat shock proteins;Heterogeneity;HLA Antigens;Home;Homing;Human;human model;humanized mouse;IL17 gene;Immune response;Immunity;immunoregulation;improved;in vivo;Inbreeding;Individual;Inflammation Mediators;Injections;innovation;insight;Interleukin-1;Interleukin-6;Investigational Drugs;joint inflammation;joint injury;Joints;Laboratories;Laboratory Research;Legal patent;Ligands;liposomal formulation;Liposomes;men;Methodology;Methotrexate;migration;Military Personnel;military veteran;Modality;Modeling;molecular marker;Mus;Names;nanoparticle;near infrared dye;neoplastic cell;novel;novel therapeutics;Operations Research;Oral;Oral Administration;Organ;Pain;Parents;Pathogenesis;Pathogenicity;Pathology;Patients;Peptide Phage Display Library;Peptides;Pharmaceutical Preparations;pharmacokinetics and pharmacodynamics;pilot test;Poison;Prevalence;Quality of life;RANTES;Rattus;Rehabilitation therapy;Reporting;Research Personnel;Rheumatoid Arthritis;Risk;risk/benefit ratio;screening;Stress;Surface;Susceptibility Gene;Synovitis;systemic toxicity;T-Lymphocyte;Technology;Testing;Therapeutic;Therapeutic Index;Tissues;TNFRSF10A gene;Toxic effect;Trademark;translation to humans;translational applications;translational study;Treatment Efficacy;United States Department of Veterans Affairs;Validation;Vascular Endothelial Cell;Vascular Endothelium;Veterans;Wild Type Mouse;Woman

PROJECT_TITLE: Validation of the joint-homing and drug delivery attributes of novel peptides in a mouse arthritis model


ORG_CITY: BRONX

ORG_NAME: JAMES J PETERS VA  MEDICAL CENTER

ORG_STATE: NY

PHR: Several prevalent diseases in Veterans result in reduced oxygen content, or hypoxia, in vital organs of the body. These include anemia, heart disease, stroke, kidney disease, cancer, amongst others. Every cell in the body has the capacity to turn on genes and proteins in response to hypoxia in an attempt to counter the damage that otherwise results. In some cases, this hypoxia response is beneficial; in other cases, it exacerbates the disease. This proposal seeks to understand how the hypoxia response is controlled. The Potential Impact on Veterans Health Care based upon information gained from these studies is development of targeted treatments that enhance or repress the hypoxia response.

PI_NAMEs: GARCIA, JOSEPH ANTHONY (contact)

PROJECT_TERMS: Acetate-CoA Ligase;Acetates;Acetyl Coenzyme A;Acetylation;Acetylesterase;Acetyltransferase;Acute;Adenine;Adult;Anemia;Behavior;bHLH-PAS factor HLF;Biotinylation;Bolus Infusion;Case Study;Cell Nucleus;Cells;Chromatin;Chronic;Chronic Kidney Failure;Coenzyme A Ligases;Complex;CREBBP gene;Data;Deacetylation;Development;Diet;Disease;Dissociation;Elements;Endocrine;Enzymes;EP300 gene;Erythrocytes;Erythrocytoses;Erythropoietin;Exhibits;Family;Feedback;Gene Expression;Genes;Genetic;Genetic Transcription;Goals;Growth;Healthcare;Heart Diseases;Heart failure;Hematocrit procedure;Hormones;human disease;Hydroxylation;Hypertension;Hypoxia;Hypoxia Inducible Factor;hypoxia inducible factor 1;Immune response;improved;inhibitor;Iron;Iron Overload;Kidney;Kidney Diseases;Knowledge;Label;Length;Liver;Lung Diseases;Malignant Neoplasms;Mammals;Marketing;Measures;Mediating;Medical;member;Modification;Morbidity - disease rate;mortality;mouse model;Mus;normoxia;novel;Nuclear;Nuclear Localization Signal;Organ;Oxygen;Peripheral arterial disease;Pharmacotherapy;Phase;Post-Translational Protein Processing;Process;Procollagen-Proline Dioxygenase;Production;Protein Acetylation;Proteins;Recombinant Erythropoietin;recruit;Regulation;Reporting;Repression;response;Rest;Resveratrol;Role;Safety;side effect;Signal Transduction;SIRT1 gene;Specificity;Stress;Stroke;System;Testing;Thrombosis;Time;transcription factor;Transducers;uptake;Veterans

PROJECT_TITLE: Dynamic Regulation of Erythropoietin Gene Expression in Mammals.


ORG_CITY: SAN ANTONIO

ORG_NAME: SOUTH TEXAS VETERANS HEALTH CARE SYSTEM

ORG_STATE: TX

PHR: Amyotrophic Lateral Sclerosis (ALS) is a special concern for veterans as military service is associated with increased risk of ALS. Research in this project will provide novel insights into the mechanisms of motor neuron degeneration of ALS and evaluate new therapeutic strategies for ALS.

PI_NAMEs: RAN, QITAO  (contact)

PROJECT_TERMS: Ablation;Acceleration;Affect;Amyotrophic Lateral Sclerosis;Apoptosis;Astrocytes;Cell Death;cell type;Cells;Cessation of life;cohort;Degenerative Disorder;Disease;Effectiveness;efficacious treatment;efficacy evaluation;efficacy testing;extend lifespan;glutathione peroxidase;improved;in vivo;inducible gene expression;insight;Intervention;Investigation;Iron;Life;military service;Modality;motor neuron degeneration;Motor Neuron Disease;Motor Neurons;mouse model;Mus;Neuroglia;neuron loss;Neurons;novel;novel therapeutic intervention;Onset of illness;overexpression;Paralysed;Pathogenesis;Production;protective efficacy;Reporting;Research;Risk;Role;small molecule;Spinal;sporadic amyotrophic lateral sclerosis;Stress;Symptoms;Syndrome;System;Testing;Therapeutic;therapeutic target;Tissues;Uterus;Veterans

PROJECT_TITLE: Investigation of Ferroptosis as a Therapeutic Target for ALS


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: NEW HAVEN

ORG_DEPT: SURGERY

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Project Narrative Approximately 25% of human tumors harbor a gain of the “q” arm of chromosome 1, but the functional consequences of this large-scale dosage change are unknown. We will develop and employ novel computational and genetic strategies to characterize the functional consequences of this alteration. These studies will shed light on the physiological effects of a ubiquitous but poorly-understood feature of tumor genomes.

PI_NAMEs: SHELTZER, JASON  (contact);SUN, RUPING

PROGRAM_OFFICER_NAME: JOHNSON, RONALD L

PROJECT_TERMS: addiction;Affect;Aging;Algorithms;Aneuploidy;arm;arm function;cancer addiction;Cancer Biology;cancer cell;Cancer cell line;cancer genome;cancer type;Cells;Chromosomal Gain;Chromosome 1;Chromosome abnormality;Chromosome Arm;Chromosomes;Clustered Regularly Interspaced Short Palindromic Repeats;Computing Methodologies;Data;Development;Diploidy;Disease;Dissection;DNA Sequence Alteration;dosage;Engineering;Evolution;fitness;Frequencies;Genes;Genetic;genetic approach;genetic manipulation;genetic selection;Genomics;Growth;Hematologic Neoplasms;Human;Human Chromosomes;Individual;insight;Knowledge;KRAS2 gene;Length;Malignant - descriptor;Malignant Breast Neoplasm;Malignant neoplasm of lung;Malignant Neoplasms;malignant phenotype;Modeling;mutant;Mutation;Normal tissue morphology;novel;Nucleotides;Oncogenes;Organoids;Patients;Pattern;Phenotype;Physiological;PIK3CA gene;Play;Prevalence;prevent;Process;RB1 gene;Recording of previous events;Recurrence;Research;Research Personnel;Role;Sampling;Series;side effect;Solid;Techniques;theories;therapy design;Time;Tissues;tool;transcriptomics;treatment strategy;tumor;tumor progression;Tumor Promotion;Tumor Suppressor Proteins;tumorigenesis;Work

PROJECT_TITLE: Genomic and functional approaches to characterize Chr1q gains in cancer

STUDY_SECTION: CG

STUDY_SECTION_NAME: Cancer Genetics Study Section[CG]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: PROJECT NARRATIVE Age is the primary risk factor for cognitive decline, and the number of people with age-related dementia is expected to triple to 14 million by 2050 with no effective treatment solutions on the horizon. This research may demonstrate that senescent cells that accumulate with age throughout the body are a source of pro-aging proteins in blood circulation that disrupt brain function. Systemic elimination of senescent cells may reveal a vital new strategy to deplete the progeronic impact of aged blood, ultimately promoting healthy cognitive aging.

PI_NAMEs: SCHAFER, MARISSA JOY (contact)

PROGRAM_OFFICER_NAME: LI, TONG

PROJECT_TERMS: Acceleration;Adipose tissue;Adverse effects;Age;age acceleration;age effect;age related;age related decline;aged;Aging;aging brain;aging mechanism;Attenuated;Biology of Aging;Blood;Blood Circulation;Blood Vessels;Brain;brain dysfunction;brain health;Cell Aging;Circulation;Cognitive aging;cognitive performance;cognitive testing;Cytometry;Dementia;design;Deterioration;effective therapy;empowerment;Encephalitis;experimental study;Functional disorder;Heart;Homeostasis;Human;Image;Impaired cognition;improved;In Vitro;Inflammation;Inflammatory;innovation;Kidney;Knowledge;Label;Liver;Lung;Mediator;Metabolic;Methionine;Methionine-tRNA Ligase;Methods;Modeling;Molecular Analysis;Monitor;mouse model;Mus;Muscle;mutant;neurogenesis;novel strategies;novel therapeutic intervention;old mice;Operative Surgical Procedures;Parabiosis;Pathogenicity;Persons;pharmacologic;Phenotype;Plasma;Plasma Exchange;Plasma Proteins;pre-clinical;prevent;Prevention;pro-aging;Production;Proteins;Proteome;Proteomics;Publishing;Research;Risk Factors;senescence;senescence associated secretory phenotype;senescent cell;senolytics;Source;Spleen;synergism;Tamoxifen;Testing;Therapeutic;Tissues;Transgenic Mice;Transgenic Model;Transgenic Organisms;Travel;Wild Type Mouse

PROJECT_TITLE: Systemic Cell Senescence as a Mediator of Brain Aging Through Circulation


NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Microbiome;Nutrition;Social Determinants of Health

ORG_CITY: NOTRE DAME

ORG_NAME: UNIVERSITY OF NOTRE DAME

ORG_STATE: IN

PHR: Project Narrative This project uses an unprecedented, prospective, longitudinal data set, in a non-human primate model to identify age-related changes in the gut microbiome’s functional capacities across the lifespan. The results will reveal social and environmental drivers of microbiome aging, as well as microbiome features that predict maturation, physical/behavioral aging, and mortality. The proposed research is relevant to human health because it will provide targets for gut microbiome interventions aimed at sustaining healthy aging and improving health for people with microbiome-related disease. The project is highly relevant to NIA's mission of understanding processes that contribute to health and well being across the life span.

PI_NAMEs: ARCHIE, ELIZABETH  (contact)

PROGRAM_OFFICER_NAME: FLORES, ROBERTO L

PROJECT_TERMS: Activities of Daily Living;Adult;Affect;Age;age acceleration;age related changes;Aging;aging clocks;aging related;aging related disease;Animal Model;Behavioral;Biodiversity;Biological;Biological Aging;Birth;Cessation of life;Clinical;Collection;comparative;Complement;Consensus;Data;Data Set;design;Development;Diabetes Mellitus;Disease;early life adversity;Elderly;Environmental Risk Factor;frailty;Genes;gut microbiome;hallmarks of aging;Health;health determinants;healthy aging;Human;human old age (65+);improved;Individual;Individual Differences;individual variation;Inflammation;Intervention;Kenya;Lead;Learning;Life;Life Cycle Stages;life span;Link;Longevity;longitudinal dataset;Malnutrition;Measures;Metabolic Pathway;metagenome;Microbe;microbial;Microbial Taxonomy;microbiome;microbiome analysis;microbiome therapeutics;Mission;Modeling;Morbidity - disease rate;mortality;Nature;nonhuman primate;Obesity;Osteoporosis;Outcome;Papio;Pathway interactions;Pattern;Personal Satisfaction;Persons;Physiology;Population;Population Research;Primates;Probiotics;Process;prospective;Prospective Studies;Research;Risk;Sampling;senescence;Shapes;social;Social Conditions;social factors;Social status;stool sample;System;Taxonomy;Testing;Time;Variant

PROJECT_TITLE: A life course perspective on gut microbiome aging and health in a non-human primate model

STUDY_SECTION: ASG

STUDY_SECTION_NAME: Aging Systems and Geriatrics Study Section[ASG]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

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

ORG_CITY: DURHAM

ORG_DEPT: GENETICS

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Project Narrative This project will investigate the observation that blood vessels remodel and grow toward the site of infections during tuberculosis. This project seeks to understand specific mechanisms by which infecting mycobacteria induce this process and to examine the effects of limiting vascular dysfunction for the host, suggesting new potential therapies for tuberculosis.

PI_NAMEs: TOBIN, DAVID M. (contact)

PROGRAM_OFFICER_NAME: EICHELBERG, KATRIN

PROJECT_TERMS: Acceleration;angiogenesis;Automobile Driving;Bacteria;Binding;Biology;Blood Vessels;Bone Marrow;Cells;Clinical;Cord Factors;Coupled;cyclopropane;Development;Disease;Dissection;Down-Regulation;Environment;Extracellular Matrix;Fibronectins;Generations;Genetic;Genetic Transcription;Genus Mycobacterium;Granuloma;Growth;Human;Hypoxia;Image;Immune response;improved outcome;in vivo;Infection;Inflammatory;inhibitor;Integration Host Factors;Intervention;intravital imaging;Lead;Lipids;Macrophage;Mediating;Modeling;Modification;Molecular;Mus;mutant;mycobacterial;Mycobacterium Infections;Mycobacterium marinum;Mycobacterium tuberculosis;nonhuman primate;novel;nuclear factors of activated T-cells;Outcome;Pathogenicity;Pathologic;Pathologic Neovascularization;Pathway interactions;Pattern recognition receptor;permissiveness;Persons;pharmacologic;Population;Process;Production;Protein Secretion;Proteins;Regulation;response;Role;Shapes;Signal Pathway;Signal Transduction;single cell sequencing;single-cell RNA sequencing;Site;Sorting;Specimen;Stimulus;Structure;Testing;transcriptome sequencing;Transgenic Organisms;Tuberculosis;tuberculosis treatment;Vascular Diseases;Vascular Endothelial Growth Factors;Vascularization;Virulence;Work;Zebrafish

PROJECT_TITLE: Genetic dissection of angiogenesis during mycobacterial infection

STUDY_SECTION: HIBP

STUDY_SECTION_NAME: Host Interactions with Bacterial Pathogens Study Section[HIBP]


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

ORG_CITY: ATLANTA

ORG_DEPT: NEUROLOGY

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: Narrative Women have about two times higher risk for Alzheimer's disease (AD) compared to men, but mechanisms behind this difference are unclear. Our proposal investigates how sex influences gene expression in the brain as a novel reason for the higher risk of AD in women.

PI_NAMEs: WINGO, ALIZA PHAM;WINGO, THOMAS SPURGEON (contact)

PROGRAM_OFFICER_NAME: YAO, ALISON Q

PROJECT_TERMS: Affect;Alzheimer's Disease;Alzheimer's Disease Pathway;Alzheimer's disease risk;Alzheimer's disease test;American;biobank;Biological;biological sex;Brain;brain tissue;case control;causal variant;Communities;Community Health;cost;Data;Dementia;Diagnosis;Disease;disorder risk;Disproportionately impacts women;DNA Resequencing;effective therapy;Etiology;Gene Expression;Gene Expression Profiling;Gene Expression Regulation;Genes;Genetic;Genetic Diseases;Genetic Risk;genetic variant;Genetic Variation;Genets;genome wide association study;genome-wide analysis;Genomics;Heritability;high risk;Human;improved;Individual;Inherited;insight;interest;International;Maps;Mediating;men;Mendelian randomization;Mental Depression;Meta-Analysis;Molecular;mRNA Expression;Nerve Degeneration;Neurosciences;novel;novel strategies;Participant;Pathogenesis;Persons;protein expression;Proteins;Proteome;Proteomics;Proxy;Public Health;Publishing;Quantitative Trait Loci;Regulation;Resources;Role;Science;sex;Sex Differences;Signal Transduction;Site;Source;statistics;Testing;Therapeutic Studies;Transcript;transcription factor;transcriptome;transcriptomics;Variant;web site;Woman;Work

PROJECT_TITLE: Integrative genomic, transcriptomic, and proteomic analyses to investigate sex-specific differences in Alzheimer's Disease


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Pediatric

ORG_CITY: PITTSBURGH

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: Project Narrative This project will allow us to develop a new internalizing module of the Knowledge of Effective Parenting Test (KEPT) and develop computer adaptive test (CAT) versions of both the internalizing (KEPT-I) and externalizing (KEPT-E) modules. Longitudinal data will be collected to examine stability and change sensitivity. These aims will enhance the utility and efficiency of the KEPT for deployment in clinical trials and basic longitudinal research.

PI_NAMEs: LINDHIEM, OLIVER JAMES (contact)

PROGRAM_OFFICER_NAME: ESPOSITO, LAYLA E

PROJECT_TERMS: Address;Adult;Age;aged;anxiety symptoms;Behavior;Calibration;Child;Child Development;Child Rearing;Childhood;Clinical Trials;Communication;Computers;cost;Data;depressive symptoms;Development;Diagnostic;Discrimination;Disease;Disruptive Behavior Disorder;Ethnic Origin;expectation;instrument;Knowledge;Length;Longitudinal Studies;Maintenance;Measurement;Measures;Mission;Modeling;National Institute of Child Health and Human Development;Observational Study;Parents;Pathway interactions;Performance;Productivity;Property;Psychometrics;Race;Research;response;Rewards;Sampling;School-Age Population;sex;skills;Social Desirability;Symptoms;Testing;Time;tool;Validity and Reliability;Work

PROJECT_TITLE: Refining the Measurement of Parenting

STUDY_SECTION: PDRP

STUDY_SECTION_NAME: Psychosocial Development, Risk and Prevention Study Section[PDRP]


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

ORG_CITY: STONY BROOK

ORG_DEPT: NEUROSCIENCES

ORG_NAME: STATE UNIVERSITY NEW YORK STONY BROOK

PHR: Disease, degeneration or aging of the nervous system are among the greatest public health concerns in the United States and are generally considered irreparable, often causing catastrophic damage to the functional capacity of the individual. Now, however, characterization of neural stem cells residing within specific germinal centers of the brain and in cell culture raises hope that functional regeneration of nervous tissue may be feasible, if we learn to exploit neurogenesis for clinical benefit. The research proposal here aims to study how existing brain cells control the integration of new members derived from endogenous neural stem cells in aging brains. If successful, this proposal will lead to advanced understanding of neural stem cell biology, possibly leading to the development of new drugs for repair and regeneration of the nervous system.

PI_NAMEs: GE, SHAOYU  (contact);XIONG, QIAOJIE

PROGRAM_OFFICER_NAME: DIBATTISTA, AMANDA

PROJECT_TERMS: Activities of Daily Living;Adult;Age;age related cognitive disorder;age related decline;age related neurodegeneration;aged;Aging;aging brain;aging population;aging related;Alzheimer's Disease;Alzheimer's disease patient;Animals;Area;Biological Assay;Brain;brain cell;Cell Culture Techniques;Cell Cycle;Cell Proliferation;Cells;Clinical;Cognitive;dentate gyrus;Development;Disease;Elderly;environmental enrichment for laboratory animals;Exhibits;experience;Functional Regeneration;Generations;genetic manipulation;Hippocampus;Homeostasis;human old age (65+);Hyperemia;In Situ;Individual;inorganic phosphate;insight;Interneurons;Learning;Life;lipidomics;Mediating;member;Metabolic;metabolomics;Methods;Nerve Regeneration;nerve stem cell;Nerve Tissue;Nervous System;neural circuit;neural network;neurogenesis;Neuronal Plasticity;Neurons;neurotrophic factor;neurovascular;neurovascular coupling;newborn neuron;normal aging;novel strategies;novel therapeutics;older adult;optogenetics;pathological aging;Persons;Pilot Projects;Play;Prevalence;Process;Public Health;Rattus;receptor;Receptor Activation;Regulation;repaired;Research Proposals;Rodent;Role;screening;Signal Transduction;Sphingolipids;stem cell biology;stem cell niche;Structure of germinal center of lymph node;Testing;Tissues;United States;young adult

PROJECT_TITLE: Mechanistic study of declining hippocampal neurogenesis in the aging brain

STUDY_SECTION: NCF

STUDY_SECTION_NAME: Neurogenesis and Cell Fate Study Section[NCF]


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Complementary and Integrative Health;Infectious Diseases;Microbiome;Nutrition;Prevention;Sexually Transmitted Infections;Topical Microbicides;Women's Health Research

ORG_CITY: LOUISVILLE

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF LOUISVILLE

ORG_STATE: KY

PHR: NARRATIVE Bacterial vaginosis (BV) is a dysbiotic condition of the vaginal microbiome that affects ~29% of reproductive age women and is linked with higher risks of adverse pregnancy outcomes, postsurgical infections, and sexually transmitted infections. Current topically-applied medicines require frequent repeated administrations which can hinder convenience and adherence to treatment, particularly when undergoing multiple weeks of treatment. In this project we will use 3D-printing and computational modeling, iteratively enabled by functional investigation of prototype scaffolds, to design long-acting products that sustain phased-delivery of antibiotics and probiotics to restore and maintain vaginal health.

PI_NAMEs: FRIEBOES, HERMANN  (contact);LEWIS, AMANDA L.

PROGRAM_OFFICER_NAME: CONNOLLY, KRISTIE LEE

PROJECT_TERMS: 3-Dimensional;3D Print;Adherence;Adverse event;adverse pregnancy outcome;Affect;Aftercare;Age;aged;Alginates;Anaerobic Bacteria;anti-fungal agents;Antibiotic Therapy;Antibiotics;Appearance;Atopobium vaginae;Back;Bacteria;Bacterial Vaginosis;Biological Assay;Biomedical Engineering;bioprinting;Calibration;Cell Line;Cells;Clinical;Clinical Research;Clinical Trials;co-infection;Complex;Computer Models;cytotoxicity;Data;delivery vehicle;design;Development;Devices;dysbiosis;engineering design;Epithelial Cells;Epithelium;Equilibrium;experience;Experimental Models;experimental study;fabrication;Female;female reproductive tract;Formulation;Gardnerella;Gardnerella vaginalis;Gelatin;Goals;Growth;gut health;Health;high risk;Histopathology;HIV;Human;improved;improved outcome;In Vitro;in vitro Model;in vitro testing;in vivo;Infection;Infertility;Inflammation Mediators;Investigation;Kinetics;Lactobacillus;Link;mathematical model;Measurement;Measures;Medicine;Metronidazole;Microbe;microbial;microbicide;Modeling;mouse model;Mucous body substance;multidisciplinary;Mus;novel;Oral;Outcome;pathogen;Pelvic Inflammatory Disease;Phase;pre-clinical;Pre-Clinical Model;predictive modeling;prevent;Prevotella;Printing;probiotic therapy;Probiotics;Process;Proliferating;Property;prototype;Reapplication;Records;Recurrence;reduce symptoms;Regimen;reproductive;Retreatment;scaffold;Serum;Sexually Transmitted Diseases;Silicones;Symptoms;Syndrome;Testing;Therapeutic;Therapeutic Agents;Tissues;Topical Antibiotic;Topical application;Treatment Efficacy;Treatment outcome;Treatment Protocols;Uterus;Vagina;vaginal lactobacilli;vaginal microbiome;virtual;Woman;Work

PROJECT_TITLE: 3D-bioprinting  of sustained- and phased-release antibiotic and probiotic scaffolds to treat bacterial vaginosis

STUDY_SECTION: BMBI

STUDY_SECTION_NAME: Biomaterials and Biointerfaces Study Section[BMBI]


ORG_CITY: LOS ANGELES

ORG_NAME: VA GREATER LOS ANGELES HEALTHCARE SYSTEM

PHR: Pancreatitis is a progressive, sometimes fatal, disorder characterized by inflammation, fibrosis, and loss of pancreas functions. It is associated with severe pain, poor quality of life, and increased risk for the deadliest pancreatic cancer. Excessive alcohol consumption, smoking, and age are major risk factors for pancreatitis. The prevalence of these factors results in high pancreatitis incidence in Veterans. In addition, Veterans with pancreatitis have much greater risk of pancreatic cancer than non-Veteran patients. Currently, there is no specific or efficient treatment for pancreatitis, primarily because we do not understand underlying molecular mechanisms. Our recent findings revealed a previously unrecognized role of cholesterol dysregulation in disease pathogenesis and suggest repurposing the available cholesterol-lowering drugs for pancreatitis treatment. The present proposal will validate these results in preclinical mouse and cellular models in order to de-risk future clinical trials and drug development studies. Thus, the proposal addresses unmet and urgent clinical needs of Veterans.

PI_NAMEs: GUKOVSKAYA, ANNA S. (contact)

PROJECT_TERMS: 3-hydroxy-3-methylglutaryl-coenzyme A;Acids;Acinar Cell;Acute;Address;Adverse effects;Age;Amylases;Apoptosis;ATP Citrate (pro-S)-Lyase;Automobile Driving;Autophagocytosis;Benefits and Risks;Biogenesis;Blood;Categories;Cell Death;Cell model;Cells;Cholelithiasis;Cholesterol;cholesterol biosynthesis;Cholesterol Homeostasis;Chronic;Clinical;Clinical Trials;clinically relevant;clinically significant;comparative;cost;Critical Pathways;Cytoplasmic Organelle;Disease;drug development;effective therapy;Enzymes;Etiology;Exclusion;Exocrine pancreas;FDA approved;Fibrosis;Functional disorder;Future;Healthcare;Healthcare Systems;Heavy Drinking;Hospitalization;Human;immune cell infiltrate;Impairment;Incidence;Inflammation;Inflammatory;injured;Intervention;Islets of Langerhans;Lipase;Lysosomal Storage Diseases;Lysosomes;Malignant neoplasm of pancreas;Measures;Medical;Military Personnel;Modeling;Molecular;mouse model;Mus;Mutation;Necrosis;neutrophil;new therapeutic target;novel strategies;Oxidoreductase;Pain;Pancreas;Pancreatitis;Pathogenesis;Pathologic;Pathway interactions;Patients;Pharmaceutical Preparations;pharmacologic;Pharmacotherapy;pre-clinical;Pre-Clinical Model;Prevalence;Preventive;Quality of life;Recycling;Regimen;response;Risk;Risk Assessment;Risk Factors;Role;Serum;Severities;Severity of illness;Simvastatin;Smoking;Speed;Therapeutic;therapeutic target;Tissues;Toxic effect;Treatment Protocols;Trypsinogen;Validation;Veterans

PROJECT_TITLE: Cholesterol-lowering drugs for treatment of pancreatitis: validation of a clinically significant novel therapeutic target and approach


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_NAME: SEATTLE INST FOR BIOMEDICAL/CLINICAL RES

PHR: Narrative  Alzheimer’s disease (AD) has many causes that result in loss of neurons that the brain uses to store memories. Other cells in the brain with the crucial job of protecting neurons are called astrocytes, which can also be damaged in AD, yet have been studied less in AD than other forms of brain pathology. The goal of this project is to understand how damage to astrocytes, especially their ability to detoxify the brain, is involved in AD.

PI_NAMEs: COOK, DAVID G (contact)

PROGRAM_OFFICER_NAME: OPANASHUK, LISA A

PROJECT_TERMS: Acceleration;Address;Adenovirus Vector;Affect;Age;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease patient;Amyloid;Amyloid beta-42;Anabolism;Anatomy;Astrocytes;astrogliosis;Automobile Driving;Autopsy;Back;Binding;Brain;brain control;Brain Pathology;Brain region;Cells;cognitive function;Complement;Data;Dependovirus;Disease;Drug Metabolic Detoxication;Dysmorphology;Electrophysiology (science);Equilibrium;excitotoxicity;extracellular;Extracellular Space;Failure;Family;Functional disorder;gamma-Aminobutyric Acid;Gene Expression;Genetic;Glial Fibrillary Acidic Protein;Glutamate Transporter;Glutamates;Glutamine;Goals;Hippocampus;Homeostasis;Impaired cognition;in vivo;insight;Interneurons;Intervention;Knowledge;Lentivirus;Lentivirus Vector;Measures;Mediating;Memory;Metabolic;Methods;mild cognitive impairment;Molecular Target;Morphology;mouse model;Mus;neuron loss;Neurons;neuropathology;neurotoxic;neurotransmission;Neurotransmitters;novel;Occupations;patch clamp;Pathogenesis;Pathogenicity;Pathology;Pathway interactions;Play;Positioning Attribute;prevent;Process;Property;Proteins;Publishing;Pyramidal Cells;Recovery;Reporting;Research;response;Role;single-cell RNA sequencing;Slice;Specificity;Synapses;Synaptic Transmission;synergism;System;tau expression;tau Proteins;tau-1;Testing;Toxic effect;transcriptomics;translational potential;transmission process;uptake;Work

PROJECT_TITLE: Role of Astrocyte EAAT2/GLT1 Failure in Alzheimer's Disease Pathogenesis

STUDY_SECTION: CDIN

STUDY_SECTION_NAME: Chronic Dysfunction and Integrative Neurodegeneration Study Section[CDIN]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Drug Abuse (NIDA only);Mental Health;Neurosciences;Social Determinants of Health;Substance Misuse;Tobacco;Tobacco Smoke and Health

ORG_CITY: NEWARK

ORG_DEPT: PSYCHOLOGY

ORG_NAME: RUTGERS THE STATE UNIV OF NJ NEWARK

ORG_STATE: NJ

PHR: Project Narrative Social isolation is a critical factor in the etiology of mental health conditions including substance use disorders. While public health efforts have focused on emphasizing positive social experiences to buffer against maladaptive decisions such as substance use, the neural dynamics of how social rewards can foster the development of healthy social connections remains understudied. This proposal will implement behavioral, neuroimaging and innovative, naturalistic social interaction methods to delineate mechanisms underlying social connection, forming a foundation for exploring how such processes are compromised in nicotine-dependent individuals.

PI_NAMEs: CHANG, LUKE JOSEPH;DELGADO, MAURICIO R. (contact)

PROGRAM_OFFICER_NAME: KAUTZ, MARY A

PROJECT_TERMS: adverse outcome;Affective;Animals;Behavior;Behavioral;Brain;Buffers;Communication;coping mechanism;Coping Skills;Corpus striatum structure;craving;Data;design;Development;effective intervention;emotional reaction;Etiology;Event;experience;experimental study;Feedback;Feeling;Fostering;Foundations;Future;Health;Individual;innovation;interest;Laboratories;Literature;maladaptive behavior;Mental Depression;Mental Health;mentalization;Methods;Modeling;mortality;movie;negative affect;neural;neural circuit;Neurobiology;neuroimaging;neuromechanism;Nicotine Dependence;nicotine use;nicotine user;non-drug;non-smoker;Outcome;Participant;Personal Satisfaction;Persons;Pharmaceutical Preparations;Population;preference;Process;psychologic;Public Health;public health priorities;Reaction;recruit;relapse prevention;Reporting;response;reward circuitry;reward processing;Rewards;Risk Taking;Rodent;Role;Self Administration;Shapes;Signal Transduction;Smoker;Smoking;smoking cessation;Smoking History;smoking relapse;social;social attachment;Social Development;Social Environment;Social Interaction;Social isolation;social media;social relationships;Social support;Social Values;Stimulus;Stress;Substance abuse problem;substance use;Substance Use Disorder;System;Testing;Work

PROJECT_TITLE: Characterizing the neural mechanisms of social connection


NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_CITY: CHICAGO

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: Narrative Glucocorticoids are a widely used frontline treatment option to treat inflammatory conditions including autoimmunity and allergy. Yet, little is known about the mechanisms underlying the therapeutic effects. The current application will test the role of newly identified miRNA-342 during Treg-dependent glucocorticoid- mediated treatment of chronic inflammation.

PI_NAMEs: MIN, BOOKI  (contact)

PROGRAM_OFFICER_NAME: JIANG, CHAO

PROJECT_TERMS: 3' Untranslated Regions;Affect;allergic airway inflammation;Animal Model;Area;attenuation;autoimmune inflammation;Autoimmunity;Binding;Biogenesis;Cell Lineage;Cell Physiology;Chronic;Cytoplasm;Defect;Dexamethasone;Disease;Ensure;exosome;Experimental Autoimmune Encephalomyelitis;experimental study;FOXP3 gene;Gene Expression;Generations;Genes;Glucocorticoids;Homeostasis;Human;Human Genome;Hypersensitivity;Immune;immune activation;Immunity;Immunosuppression;Inflammation;Inflammatory;Inflammatory Response;Lead;Mediating;Metabolic;MicroRNAs;Modeling;Molecular;mortality;mouse model;Mus;novel;novel therapeutic intervention;Nucleotides;overexpression;Patients;Play;Predisposition;programs;Proteins;Refractory;Regulation;Regulatory T-Lymphocyte;Reporting;Resistance;response;Ribonuclease III;Role;Serum;Steroid Resistance;Steroids;Testing;Therapeutic Effect;therapy development;Untranslated RNA

PROJECT_TITLE: miR-342, a novel glucocorticoid-responsive miRNA necessary for Foxp3+ regulatory T cell function

STUDY_SECTION: CMIB

STUDY_SECTION_NAME: Cellular and Molecular Immunology - B Study Section[CMIB]


NIH_SPENDING_CATS: Assistive Technology;Bioengineering;Biotechnology;Clinical Research;Infectious Diseases;Prevention

PHR: PROJECT NARRATIVE Our goal is to improve understanding of the causes of infections of joint replacements and non-infectious causes of arthroplasty failure. We are targeting the microorganisms that cause infections directly as well as host response to them and to other causes of arthroplasty failure using a proteomic strategy applied to materials dislodged from the surfaces of knee replacements. Our prior work has led to new diagnostic techniques that are now part of standard guidelines; our new studies, proposed here, are poised to lead to even better diagnostic tests and to inform future treatment and prevention approaches for arthroplasty failure.

PI_NAMEs: PATEL, ROBIN  (contact)

PROGRAM_OFFICER_NAME: XU, ZUOYU

PROJECT_TERMS: alpha-Defensins;Biological Assay;Biological Markers;Clinical;cytokine;design;Detection;Diagnostic;diagnostic development;Diagnostic Procedure;diagnostic strategy;Diagnostic tests;Enterococcus faecalis;Etiology;Failure;Fracture;Future;Gene Expression;Genus staphylococcus;Goals;Guidelines;Human;Immune response;Implant;improved;in vivo;Individual;Infection;insight;joint infection;Knee;knee replacement arthroplasty;lateral flow assay;Liquid Chromatography;Liquid substance;Mass Spectrum Analysis;Measures;microbial;Microbial Biofilms;microbial host;Microbiology;microorganism;neutrophil;new technology;next generation sequencing;novel diagnostics;Organism;Orthopedics;Osteolysis;Pathogenesis;Patients;Performance;Periprosthetic joint infection;Prevention;Prevention approach;Protein Analysis;protein expression;Proteins;Proteome;Proteomics;Reaction;Replacement Arthroplasty;response;response biomarker;Ringer's solution;Sampling;Site;Sonication;Specimen;Staphylococcus aureus;Staphylococcus epidermidis;Sterility;Streptococcus Group B;Surface;tandem mass spectrometry;Technology;Testing;Tissues;Work

PROJECT_TITLE: Proteomic Analysis of Implant Surfaces in Athroplasty Failure

STUDY_SECTION: MTE

STUDY_SECTION_NAME: Musculoskeletal Tissue Engineering Study Section[MTE]


NIH_SPENDING_CATS: Cancer;Cardiovascular;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Hematology;Machine Learning and Artificial Intelligence;Prevention;Racial and Ethnic Minority Health Research;Rare Diseases

ORG_CITY: MILWAUKEE

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

ORG_STATE: WI

PHR: PROJECT NARRATIVE Light chain amyloidosis is an understudied and underserved blood disorder associated with delayed and under diagnosis, particularly among Black individuals, despite warning signs in the form of a premalignant MGUS state and multiple preexisting precursor diagnoses that frequently occur. This project will study patterns of precursor diagnoses in AL amyloidosis cases, associated racial differences, and identification of potentially undiagnosed AL amyloidosis patients using Bayesian machine learning algorithms. This application, in response to the NOSI: Diagnostics and Disease Management Tools for Use in Underserved Populations (NOT-HL-22-006), will create pathways to early diagnosis of AL amyloidosis when it is more treatable, yielding improved outcomes and prolonged survival.

PI_NAMEs: D'SOUZA, ANITA  (contact)

PROGRAM_OFFICER_NAME: WARREN, RONALD Q

PROJECT_TERMS: Affect;African American population;Age;age group;Aging;Agreement;Algorithms;Amyloid;Amyloid Fibrils;Amyloidosis;Bayesian learning;beneficiary;Black Populations;Body System;Calibration;Cardiac;cardiac amyloidosis;Cardiomyopathies;Cessation of life;chemotherapy;Chronic Kidney Failure;Clinical Research;Cohort Studies;Data;Data Reporting;Data Set;Deposition;Diagnosis;Diagnostic;Disease;Disease Management;Disparity;Early Diagnosis;Electronic Health Record;Epidemiology;Ethnic Origin;experience;follow-up;Functional disorder;health disparity;Heart failure;Hematological Disease;high risk;Hypertrophic Cardiomyopathy;improved;improved outcome;Incidence;Individual;Insurance Coverage;Light;Literature;machine learning algorithm;Medicare;Methodology;Monoclonal Gammapathies;Monoclonal gammopathy of uncertain significance;Morbidity - disease rate;mortality;Multiple Myeloma;Myocardial dysfunction;novel;Organ;Outcome;Pathway interactions;Patient-Focused Outcomes;Patients;Pattern;Performance;Physicians;Plasma Cells;Precancerous Conditions;prediction algorithm;premalignant;Prevalence;primary amyloidosis of light chain type;Prognosis;Race;racial difference;racial population;response;Risk;Sampling;Specialist;statistical and machine learning;Symptoms;System;Techniques;Testing;Time;tool;Underserved Population;Validation

PROJECT_TITLE: Early diagnosis of light chain amyloidosis

STUDY_SECTION: CDMA

STUDY_SECTION_NAME: Clinical Data Management and Analysis Study Section[CDMA]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

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

ORG_CITY: BOSTON

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: Project Narrative This project focuses on understanding the molecular mechanism of a major cell-cell communication pathway, initiated by Secreted WNT proteins, and the mechanism by which this pathway governs early embryogenesis in the frog, an important vertebrate model. Our studies will provide critical insights into developmental biology related to understanding human birth defects, and basic principles of cell proliferation and differentiation related to cancer biology.

PI_NAMEs: HE, XI  (contact)

PROGRAM_OFFICER_NAME: WELLS, MELISSA LYNN

PROJECT_TERMS: Address;Biochemical;Biology;Cancer Biology;Cell Communication;Cell Differentiation process;Cell Polarity;Cell Proliferation;Cells;Complex;Congenital Abnormality;CRISPR screen;Degenerative Disorder;Development;Developmental Biology;Disease;Embryo;Embryonic Development;experimental study;Family;genome-wide;Health;Homeostasis;Human;human disease;insight;Investigation;Malignant Neoplasms;Modeling;Molecular;Pathway interactions;Pattern;Proteomics;Rana;receptor;Research;Role;Signal Transduction;Signaling Protein;Tissues;transcriptomics;Wnt proteins;WNT Signaling Pathway;Xenopus

PROJECT_TITLE: Wnt Signaling and Vertebrate embryogenesis

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


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Brain Disorders;Cerebrovascular;Gene Therapy;Genetics;Mucopolysaccharidoses (MPS);Neurosciences;Orphan Drug;Rare Diseases

ORG_CITY: CINCINNATI

ORG_NAME: CINCINNATI CHILDRENS HOSP MED CTR

ORG_STATE: OH

PHR: Narrative: It has been a major unmet medical need for the development of efficient brain delivery across the blood-brain barrier with wide distribution of the therapeutic macromolecules to many types of brain cells in treating a wide variety of neurological diseases. The goal of this project is to develop a novel platform with advanced brain delivery of therapeutic proteins by coalescing in vivo epigenetic alteration of microRNA with targeted gene transfer and restricted transgene expression for improved CNS treatment of Hurler syndrome, a neurologic lysosomal storage disease (nLSD). Such therapeutic approach would have significant and broad application across many other nLSDs or neurological diseases.

PI_NAMEs: PAN, DAO  (contact)

PROJECT_TERMS: adeno-associated viral vector;Adult;Aftercare;Allogenic;Behavioral;Blood - brain barrier anatomy;Brain;brain cell;brain endothelial cell;Capsid;caspase 14;Cell Therapy;cell type;Cells;cerebral microvasculature;Childhood;Circulation;correctional system;Data;Dependovirus;derepression;design;Development;Disease;DNA cassette;Down-Regulation;Drug Delivery Systems;enzyme replacement therapy;enzyme therapy;Enzymes;Epigenetic Process;Erythroid;Excision;Foundations;Frequencies;Functional disorder;Future;Gene Modified;Gene Transfer;Genes;Genetic;Glycosaminoglycans;Goals;Hematopoietic Stem Cell Transplantation;Hereditary Disease;Histopathology;Human;Hybrids;IGF Type 2 Receptor;IGF2 gene;IGF2R gene;improved;in vivo;Inherited;inhibitor;intravenous injection;Knock-out;L-Iduronidase;Live Birth;Luciferases;Lysosomal Storage Diseases;Lysosomes;macromolecule;Mediating;Medical;Megakaryocytes;MEKs;Messenger RNA;Metabolic;microRNA delivery;MicroRNAs;Modeling;Modification;mouse model;Mucopolysaccharidosis I;Mucopolysaccharidosis I H;Mus;Mutagenesis;Nerve;Nervous System Disorder;Neurodegenerative Disorders;Neurologic;novel;novel strategies;Organ;Pathologic;Pathway interactions;Patients;Penetration;Peripheral;Play;Porifera;postnatal period;preclinical evaluation;Production;promoter;prototype;receptor;Receptor Down-Regulation;receptor downregulation;receptor expression;Reporter;Resolution;Role;Severities;Site;Specificity;System;Testing;Therapeutic;therapeutic enzyme;therapeutic protein;trafficking;Transfection;transgene expression;Translations;Up-Regulation;Variant;Vascular Endothelial Cell;Viral Vector;Visceral

PROJECT_TITLE: Advancing CNS drug delivery via epigenetic modulation

STUDY_SECTION: DBD

STUDY_SECTION_NAME: Developmental Brain Disorders Study Section[DBD]


NIH_SPENDING_CATS: Autoimmune Disease;Eye Disease and Disorders of Vision

PHR: PROJECT NARRATIVE Graves’ Ophthalmopathy (GO), the most serious extra-thyroidal complication that develops in patients with autoimmune Graves’ hyperthyroidism, is characterized by increased orbital fat volume and extra-ocular muscle within the unyielding bony orbit, which can have deleterious consequences on eye function. We hypothesize that a novel enzyme, PAPP-A, is a key regulator of GO, and will test this hypothesis using orbital fibroblasts from patients with GO. We anticipate that the results of our proposed experiments could ultimately lead to a novel targeted therapy for patients with GO.

PI_NAMEs: CONOVER, CHERYL A. (contact)

PROGRAM_OFFICER_NAME: MORRIS FEARS, MARGARET A

PROJECT_TERMS: Adverse event;attenuation;Autoimmune;Binding;Biological Availability;Clinical;Clinical Trials;Complication;cytokine;Development;Enzymes;Exophthalmos;experience;experimental study;Eye;Fatty acid glycerol esters;FDA approved;Fibroblasts;Hand;Hyperthyroidism;Inflammatory;innovation;Insulin-Like Growth Factor Binding Protein 4;Insulin-Like Growth Factor I;Insulin-Like Growth-Factor-Binding Proteins;Insulin-Like-Growth Factor I Receptor;lipid biosynthesis;Mediating;Metalloproteases;Monoclonal Antibodies;Nature;neutralizing monoclonal antibodies;new therapeutic target;novel;Ocular orbit;orbit muscle;Outcome;overexpression;Pathogenesis;Pathologic;Patients;Pregnancy-Associated Plasma Protein-A;prevent;Proliferating;Proteolysis;Receptor Signaling;Regulation;Role;Signal Transduction;Surgical Decompression;Testing;thyroid associated ophthalmopathies;Tissues;Work;Zinc

PROJECT_TITLE: Role of PAPP-A in Graves' Ophthalmopathy

STUDY_SECTION: CSME

STUDY_SECTION_NAME: Cell Signaling and Molecular Endocrinology Study Section[CSME]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Amyotrophic Lateral Sclerosis (ALS);Biotechnology;Brain Disorders;Dementia;Frontotemporal Dementia (FTD);Genetics;Human Genome;Neurodegenerative;Neurosciences;Rare Diseases;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

PHR: The purpose of our proposed study is to elucidate how mutations in the heat shock protein DNAJC7 cause ALS/FTD, an untreatable and devastating neurodegenerative disease. We will use induced pluripotent stem cell- derived neurons in combination with quantitative mass spectrometry-based proteomics to elucidate the role of DNAJC7 in human neurons and determine how its dysfunction leads to their dysfunction.

PI_NAMEs: KISKINIS, EVANGELOS  (contact)

PROGRAM_OFFICER_NAME: GUBITZ, AMELIE

PROJECT_TERMS: Affect;Affinity Chromatography;aged;ALS patients;Amyotrophic Lateral Sclerosis;Biochemical;Biological Process;Case Study;Cell model;cell type;Cells;Central Nervous System;Client;Clinical;Coupled;CRISPR/Cas technology;Critical Pathways;Data Set;Disease;DNA Sequence Alteration;exome sequencing;experimental study;follow-up;Fractionation;Frontotemporal Dementia;frontotemporal lobar dementia amyotrophic lateral sclerosis;Functional disorder;functional loss;Genes;Genetic;genetic variant;Heat shock proteins;heat-shock proteins 40;Heat-Shock Proteins 70;Heterozygote;Human;induced pluripotent stem cell;Induced pluripotent stem cell derived neurons;Lead;Light;loss of function;loss of function mutation;Mass Spectrum Analysis;Measures;misfolded protein;Molecular Chaperones;Motor;motor control;Motor Neurons;mutant;Mutation;Nerve Degeneration;Neurodegenerative Disorders;neuron loss;Neuronal Dysfunction;Neurons;novel;Pathogenesis;Pathogenicity;patient derived induced pluripotent stem cells;Patients;Plasmids;Play;polypeptide;postmitotic;Predisposition;Process;protein expression;protein folding;protein function;protein misfolding;protein protein interaction;protein structure;Protein Truncation;Proteins;Proteolysis;Proteome;Proteomics;proteostasis;Rare Diseases;Regulation;RNA;RNA metabolism;RNA Processing;RNA Splicing;RNA-Binding Protein FUS;Role;screening;Solubility;Spinal;sporadic amyotrophic lateral sclerosis;Testing;trafficking;Transcript;transcriptome sequencing;Work

PROJECT_TITLE: Defining the Mechanisms by Which Mutations in DNAJC7 Increase Susceptibility to ALS/FTD

STUDY_SECTION: CMND

STUDY_SECTION_NAME: Cellular and Molecular Biology of Neurodegeneration Study Section[CMND]


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Emerging Infectious Diseases;Infectious Diseases;Neurosciences;Rare Diseases;Vector-Borne Diseases

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: The yellow fever mosquito Aedes aegypti lays its eggs preferentially in standing pools of water in and around human habitation that are infused with organic matter. Pregnant Aedes aegypti are highly attracted to the scent of fermenting African Bermuda grass hay in water, which has been exploited for trapping strategies that aim to lure this major disease vector to its death during the act of egg laying. An improved understanding of the chemosensory basis of Aedes aegypti attraction to hay infusion will help to identify new molecular targets to modulate mosquito egg laying behavior and inform the development of long-lasting synthetic oviposition attractants for improving traps used for mosquito population surveillance and control.

PI_NAMEs: MCMENIMAN, CONOR JAMES (contact)

PROGRAM_OFFICER_NAME: COSTERO-SAINT DENIS, ADRIANA

PROJECT_TERMS: Adhesives;Aedes;Afferent Neurons;African;Analytical Chemistry;Arboviruses;Behavior;behavior test;Behavioral;Behavioral Assay;Biological Assay;Blood;Botanicals;cell type;Cessation of life;Chemicals;Chemoreceptors;Constitution;Culicidae;Cynodon;Data;Dengue;Desiccation;Development;Disease Vectors;egg;Engineering;feeding;Female;Fermentation;field study;Formulation;Future;Genetic;Goals;Grant;Gravid;Heterozygote;Human;improved;Infusion procedures;insight;Laboratories;Ligands;loss of function;man;Mediating;Methods;Molecular;Molecular Target;mutant;neural;neural circuit;Neurons;neurophysiology;novel;Olfactory Pathways;olfactory sensory neurons;Oviposition;Partner in relationship;Pathway interactions;Physiological;Play;Population;Population Control;Population Dynamics;Population Surveillance;preference;pregnant;Puerto Rico;receptor;Research;Resistance;response;Reverse engineering;Role;Searching Behavior;Sensory;Series;Site;Source;Testing;tool;urban setting;vector;volatile organic compound;Water;Yellow Fever;ZIKA

PROJECT_TITLE: Molecular and cellular basis of mosquito olfactory attraction to hay infusion for enhanced vector surveillance and control

STUDY_SECTION: VB

STUDY_SECTION_NAME: Vector Biology Study Section[VB]


NIH_SPENDING_CATS: Complementary and Integrative Health;Dietary Supplements;Digestive Diseases;Infectious Diseases;Natural Products;Nutrition;Orphan Drug;Rare Diseases

ORG_CITY: WASHINGTON

ORG_NAME: GEORGE WASHINGTON UNIVERSITY

ORG_STATE: DC

PHR: Parasitic nematodes such as hookworms are serious health problems in developing countries. New drugs are required for continued control. We will identify and characterize the anti-nematode activity in the bitter melon plant Momordica charantia, which is widely grown for its food and medicinal value throughout the tropics.

PI_NAMEs: HAWDON, JOHN M (contact)

PROGRAM_OFFICER_NAME: MO, ANNIE X  Y

PROJECT_TERMS: Adult;Albendazole;Ancylostoma (genus);Ancylostoma caninum;Anemia;Anthelmintics;aqueous;Area;Biological Assay;Blood;Caenorhabditis elegans;Canis familiaris;Centers for Disease Control and Prevention (U.S.);Cessation of life;Chemical Structure;Chemicals;Child;cognitive development;Communicable Diseases;Data;Developing Countries;Development;Disease;Dose;drug development;Drug resistance;Elderly;Ensure;Esophagus;Exhibits;Exposure to;feeding;Food;Future;gastrointestinal;global health;Goals;Growth and Development function;Haiti;Hamsters;Health;Health Benefit;Hemorrhage;high reward;high risk;Hookworm Infections;Hookworms;Human;In Vitro;in vivo;Individual;Infection;infection rate;Ingestion;Intestines;Iron deficiency anemia;Jamaica;Larva;Lead;Livestock;Measures;Medicinal Plants;Medicine;Melons;Momordica charantia;Morbidity - disease rate;mortality;Myeloma Proteins;Natural Products Chemistry;Nematoda;Nematode infections;novel;novel therapeutics;Oral Administration;Parasitic infection;Parasitic nematode;Periodicals;Persons;Pharmaceutical Preparations;Plant Extracts;Plant Leaves;Plants;Population;Predisposition;Pregnant Women;programs;Proliferating;Protein Deficiency;Pump;Resistance;Rest;Safety;Source;Spectrometry;Tea;Techniques;Testing;tool;Toxic effect;Traditional Medicine;vaccine access

PROJECT_TITLE: Potential of the bitter melon Momordica charantia as a source of anthelmintics

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DCAI-B(82)]


ORG_CITY: TALLAHASSEE

ORG_NAME: FLORIDA STATE UNIVERSITY

ORG_STATE: FL

PHR: A detailed understanding of HIV-1 capsid ultra-structures of as they promote virus infection inside cells, remain unclear. This project will develop key correlative light and cryo-EM (CLEM) workflows to locate and structurally characterize relevant capsids inside cells. The tools developed in the project will improve throughput in structurally imaging of HIV-1 and advance our understanding of virus cell biology, which is of high public health significance.

PI_NAMEs: FRANCIS, ASHWANTH CHRISTOPHER (contact)

PROGRAM_OFFICER_NAME: MCDONALD, DAVID JOSEPH

PROJECT_TERMS: 3-Dimensional;Architecture;Avidity;Behavior;Calibration;Capsid;Cell Nucleus;cell type;Cells;Cellular biology;Classification;Complementary DNA;Complex;Computer software;Cryo-electron tomography;Cryoelectron Microscopy;Data;Data Collection;Detection;Development;Dimensions;Dose;DsRed;Electrons;Elements;experience;Fluorescence;Freezing;Genes;Genetic Transcription;Genome;Genomics;HIV;HIV-1;Ice;Image;imaging approach;improved;In Situ;In Vitro;Infection;insight;Integrase;Integration Host Factors;interest;Investigation;Ions;Label;Light;live cell imaging;Location;Macrophage;Maps;Mediating;Methods;monocyte;Nature;neural network;Nuclear;Nuclear Import;Nuclear Pore;Nuclear Pore Complex;particle;PF4 Gene;Positioning Attribute;Preparation;preservation;Procedures;Productivity;Public Health;recruit;Reporting;Reproducibility;Resolution;Reverse Transcription;RNA;Sampling;sensor;Site;Specimen;structural imaging;Structure;success;System;T-Lymphocyte;Testing;Thinness;Tomogram;tool;trafficking;Training;Validation;viral DNA;Viral Genome;Viral Reverse Transcription;Virus;Virus Diseases;Virus Integration;Virus Replication;Visualization

PROJECT_TITLE: Characterizing functionally relevant HIV-1 structures by correlative light and cryo-electron microcopy (CLEM)

STUDY_SECTION: HVCD

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


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Digestive Diseases;Emerging Infectious Diseases;Foodborne Illness;Infectious Diseases;Rare Diseases

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

PHR: PROJECT NARRATIVE Salmonellosis continues to be a major Public Health challenge and are among the most common causes of food-borne illnesses in the industrialized world. The proposed research will advance the understanding of the pathogenesis of Salmonella infections and may facilitate the development of novel therapeutic and prevention strategies.

PI_NAMEs: GALAN, JORGE E (contact)

PROGRAM_OFFICER_NAME: ALEXANDER, WILLIAM A

PROJECT_TERMS: Actins;Address;Animal Model;antimicrobial;arms race;Bacteria;base;Binding;Biochemical;Biology;Bypass;Cell Physiology;Cells;Cellular biology;cellular targeting;Cessation of life;Citric Acid Cycle;CRISPR/Cas technology;Cryo-electron tomography;Cryoelectron Microscopy;Cytoskeleton;Defense Mechanisms;Development;Ecology;Economic Burden;Elements;Exhibits;foodborne illness;Funding;Gastroenteritis;Gene Expression;Genes;Grant;gut inflammation;Host Defense;Host Defense Mechanism;Human;Immune response;In Vitro;Industrialization;Infection;Inflammatory;Inflammatory Response;Intestines;Laboratories;Learning;Mediating;Mitochondria;Molecular;novel;novel therapeutics;Nutritional Immunity;pandemic disruption;pathogen;Pathogenesis;Pathogenicity;Pathogenicity Island;Pathway interactions;Prevention strategy;Protein Secretion;Proteins;Public Health;Research;Resolution;Role;Salmonella;Salmonella enterica;Salmonella infections;Salmonella typhi;Salmonella typhimurium;Shapes;Signal Pathway;Signal Transduction;Specificity;Structure;System;Systemic disease;Tissues;trafficking;Type III Secretion System Pathway;Typhoid Fever;Vacuole;Vesicle;Visualization;Work

PROJECT_TITLE: Host Cell Signaling Pathways Induced by Salmonella


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Clinical Research;Coronaviruses;Coronaviruses Diagnostics and Prognostics;Coronaviruses Disparities and At-Risk Populations;Emerging Infectious Diseases;Infectious Diseases;Influenza;Lung;Pediatric;Pneumonia and Influenza

ORG_CITY: MADISON

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

PHR: Project narrative We have shown that air samplers in schools detect respiratory viruses, including SARS-CoV-2 and in- fluenza viruses. This project will deploy air samplers to 16 K-12 schools to explore whether air sampling accurately assesses SARS-CoV-2 and influenza virus risk in schools and forecasts transmission of these viruses in the communities where the schools are located. Viral sequencing of air samples will also be performed to ascertain which viral variants are circulating and spreading within and between schools and the broader community.

PI_NAMEs: O'CONNOR, DAVID H. (contact);OCONNOR, SHELBY L

PROGRAM_OFFICER_NAME: BOZICK, BROOKE ALLISON

PROJECT_TERMS: 2019-nCoV;Absenteeism;Age;Air;Air Movements;air sampler;air sampling;Awareness;Behavior Therapy;Censuses;Child;Collection;commune;Communities;community transmission;Consumption;County;COVID-19;COVID-19 burden;COVID-19 detection;COVID-19 diagnostic;COVID-19 pandemic;COVID-19 surveillance;COVID-19 testing;Data;Detection;Diagnostic tests;Disease;Disease Outbreaks;Fatigue;Foundations;Future;high risk;Household;Illness impact;improved;Individual;Infection;infection risk;Influenza;influenza infection;influenzavirus;innovation;Laboratories;Learning;Location;Masks;Measures;Modeling;Oregon;Pattern;Persons;programs;promote resilience;Proxy;Rapid diagnostics;Research Personnel;respiratory;Respiratory Disease;respiratory pathogen;respiratory virus;Risk;risk mitigation;risk prediction;SARS-CoV-2 infection;school district;Schools;Seasons;Sentinel;Sentinel Surveillance;Site;Students;Surveillance Program;surveillance strategy;teacher;Testing;Time;tool;transmission process;United States;Variant;Viral;viral detection;viral transmission;Virus;wastewater samples;Wisconsin

PROJECT_TITLE: Anticipating and rapidly responding to respiratory virus outbreaks with continuous air sampling in K-12 schools

STUDY_SECTION: PRID

STUDY_SECTION_NAME: Population based Research in Infectious Disease Study Section[PRID]


NIH_SPENDING_CATS: Biotechnology;Clinical Research;Duchenne/ Becker Muscular Dystrophy;Gene Therapy;Genetics;Muscular Dystrophy;Neurosciences;Pediatric;Rare Diseases

ORG_CITY: COLUMBUS

ORG_NAME: RESEARCH INST NATIONWIDE CHILDREN'S HOSP

PHR: Narrative Duchenne muscular dystrophy (DMD) and Becker Muscular Dystrophy (BMD) are both due to mutations in the DMD gene DMD occurs due to an absence of a functional dystrophin protein where as BMD is associated with the presence of partially functional dystrophy. However, a fundamental question remains; how much dystrophin is enough to provide benefit. Using large patient cohorts, we will assess the quantity of dystrophin and the molecular mechanisms that allow such expression, and correlate these with clinical features. In addition, using patient- derived cell lines, we will develop vectors for skipping of pseudoexon mutations, as an approach to therapeutic expression of full length dystrophin.

PI_NAMEs: FLANIGAN, KEVIN M (contact)

PROGRAM_OFFICER_NAME: NUCKOLLS, GLEN H

PROJECT_TERMS: Address;Age;Alleles;Becker Muscular Dystrophy;Biopsy;boys;Cell Line;Characteristics;Clinical;clinical phenotype;cohort;Data;Dependovirus;Development;Disease;Duchenne muscular dystrophy;Dystrophin;dystrophinopathy;exon skipping;Exons;Family;functional outcomes;Gene Delivery;gene replacement therapy;gene therapy;gene-editing approach;Genes;Genetic;genomic predictors;Genotype;Goals;improved outcome;insight;Length;life span;Link;Messenger RNA;Methods;micro-dystrophin;Molecular;Muscle;Muscular Dystrophies;Mutation;Mutation Analysis;Myoblasts;Needles;novel;Open Reading Frames;Outcome;patient population;patient subsets;Patients;Phenotype;postnatal;Principal Investigator;Privatization;Prognosis;protective effect;Protein Isoforms;Proteins;Reading Frames;restoration;Retreatment;RNA Splicing;Rod;sample archive;Severities;Severity of illness;Spectrin;Testing;Therapeutic;therapy development;Time;transcriptome sequencing;Transgenes;Variant;vector;Viral Packaging;Work

PROJECT_TITLE: Molecular Mechanisms of Dystrophin Expression in Ameliorated Phenotypes

STUDY_SECTION: SMEP

STUDY_SECTION_NAME: Skeletal Muscle and Exercise Physiology Study Section[SMEP]


ADMINISTERING_IC: MH

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Mental Health;Mental Illness;Neurosciences

ORG_CITY: NEW YORK

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: PROJECT NARRATIVE  The proposed research is relevant to public health because the ability to store and retrieve long-term memories is an essential cognitive function in human daily life, and dysfunction of proper memory storage is a debilitating symptom of many neuropsychiatric disorders such as dementia, major depression, and post- traumatic stress disorder. By utilizing multiple techniques and levels of analysis, including the manipulation and longitudinal recordings of brain-wide circuits over extended time periods, this research will facilitate new insights into the distributed nature of memory encoding in the brain and lead to new mechanistic understandings of mental illnesses.

PI_NAMEs: TOADER, ANDREW  (contact)

PROGRAM_OFFICER_NAME: VAN'T VEER, ASHLEE VICTORIA

PROJECT_TERMS: Alzheimer's Disease;Animal Model;Animals;Anterior;behavior measurement;Behavioral;Behavioral Paradigm;Brain;Brain region;Calcium;career;Cells;Chronic;cingulate cortex;Clinical;Clinical Treatment;cognitive function;Communication;Complex;debilitating symptom;Dementia;design;Disease;Dissection;Doctor of Philosophy;entorhinal cortex;Fellowship;Fiber;Functional disorder;Goals;Head;Health;Hippocampus;Human;Image;Imaging Device;Impairment;Implant;insight;Investigation;Learning;Life;Localized Lesion;long term memory;Major Depressive Disorder;medical schools;member;Memory;memory acquisition;memory consolidation;memory encoding;memory recall;memory retrieval;Mental disorders;Methods;Modeling;Monitor;Mus;Nature;Neocortex;neocortical;neural;neural correlate;Neurons;neuropsychiatric disorder;Neurosciences Research;novel;optical fiber;optogenetics;Patients;Photometry;Physicians;Play;Post-Traumatic Stress Disorders;Process;programs;Psychological reinforcement;Public Health;recruit;Research;response;Retrieval;Role;Scientist;serial imaging;Series;skills;Stimulus;Symptoms;Synapses;System;Techniques;Technology;Testing;theories;Time;Time Study;Training;two-photon;Universities;virtual environment;virtual reality;Work

PROJECT_TITLE: Functional interactions of the entorhinal cortex during systems consolidation


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

NIH_SPENDING_CATS: Genetics;Infectious Diseases

ORG_CITY: ATHENS

ORG_NAME: UNIVERSITY OF GEORGIA

PHR: Project Narrative Invasive fungal disease, estimated to kill over one million people annually, often begins when dormant spores are inhaled from the environment and break dormancy and start active growth within host lungs. If it was possible to perturb the establishment, maintenance, or breaking of dormancy, much fungal disease could be better-managed or possibly eliminated. The study will furnish important information about genes that are highly expressed in dormant spores, and rapidly disappear in actively growing cells.

PI_NAMEs: MOMANY, MICHELLE  (contact)

PROGRAM_OFFICER_NAME: LOVE, DONA

PROJECT_TERMS: Affinity Chromatography;anti-fungal agents;asexual;Aspergillus fumigatus;Cells;Collection;Data;Development;differential expression;Disease;Environment;Flow Cytometry;Fluorescence Microscopy;Fungal Spores;fungus;Future;Gene Deletion;gene product;Genes;Germination;Growth;Human;human pathogen;Inhalation;insight;Investigation;Knock-out;Life Cycle Stages;Lung;Maintenance;Mass Spectrum Analysis;Metabolism;Microscopy;pathogenic fungus;Pattern;Persons;Pilot Projects;Predisposition;Proteins;Reproduction spores;Resistance;Stress;Time;Transcript;Yeasts

PROJECT_TITLE: Investigation of uncharacterized fungal-specific genes in dormant conidia

STUDY_SECTION: PTHE

STUDY_SECTION_NAME: Pathogenic Eukaryotes Study Section[PTHE]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Cannabinoid Research;Clinical Research;Drug Abuse (NIDA only);HIV/AIDS;Infectious Diseases;Neurodegenerative;Neurosciences;Substance Misuse

ORG_CITY: BOYS TOWN

ORG_NAME: FATHER FLANAGAN'S BOYS' HOME

ORG_STATE: NE

PHR: Project Narrative Persons infected with HIV now have a life expectancy that approaches that of the general population, but they remain at a significantly elevated risk of developing cognitive impairments. Recent neuroimaging studies have identified the cortical brain circuits that are centrally involved in these generally mild cognitive impairments, but the underlying molecular mechanisms remain poorly understood, and the potential therapeutic options are very limited. The current project builds on several important discoveries in 2021 and will use advanced dynamic functional brain mapping, systems biology approaches, and structural equation modeling to determine whether parameters of the mitochondrial redox environment drive neuro-inflammation in persons with HIV and whether chronic cannabis use modulates these parameters, with the long-term goal of identifying viable therapeutics.

PI_NAMEs: WILSON, TONY W (contact)

PROGRAM_OFFICER_NAME: LIN, YU

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Address;Adult;Affect;Agreement;Anti-Inflammatory Agents;Area;Attention;Automobile Driving;Behavior;behavior prediction;Behavioral;Brain;Brain Mapping;Brain region;Cannabinoids;Cannabis;Chronic;Cognitive;cognitive function;cognitive performance;comorbidity;comparison control;Complication;Data Analyses;Disease;Economics;Environment;Epidemic;Equation;Exhibits;Foundations;Functional disorder;General Population;Goals;Heel;HIV;HIV Infections;HIV/AIDS;Human;Immune;immune activation;Impaired cognition;Impairment;improved;Inflammation;innovation;instrumentation;Knowledge;Life Expectancy;Link;marijuana use;Mediating;medication compliance;Methods;mild cognitive impairment;Mitochondria;Modeling;Molecular;molecular marker;Motor;Nervous System Disorder;neural;neuroAIDS;neuroimaging;neuroimaging marker;neuroinflammation;Neurologic;Neurophysiology - biologic function;Neuropsychological Tests;Oxidation-Reduction;Participant;Pathologic;Pathway interactions;Performance;Persons;Property;Publishing;Quality of life;Reporting;Request for Proposals;Research;Risk;Sampling;Scientific Advances and Accomplishments;Seminal;Superoxides;System;Systems Biology;Targeted Research;Task Performances;Therapeutic;Unemployment;Viral;virtual;Western World;Work

PROJECT_TITLE: Suppression of Pathological Spontaneous Cortical Dynamics and Inflammation in NeuroHIV


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Dementia;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Neurodegenerative;Neurosciences;Social Determinants of Health

ORG_NAME: RUSH UNIVERSITY MEDICAL CENTER

PHR: PROJECT NARRATIVE The proposed study will: a) quantify age-related change in decision making among >1,500 well-characterized older adults initially free of dementia, b) identify risk factors for decline and document a wide range of adverse consequences including adverse health (e.g., Alzheimer’s dementia) and financial outcomes (e.g., financial exploitation), c) determine the degree to which decline in decision making is due to aging-related changes in the brain and pathologic indices of Alzheimer’s disease and related dementias (ADRDs). The proposed study offers an unprecedented opportunity efficiently determine the risk factors, consequences, and neurobiologic bases of age-related change in decision making and identify modifiable targets to preserve decision making in old age. Findings will have immediate translational implications for behavioral and policy interventions to improve health and financial wellbeing among older adults and greatly extend our understanding of the impact of aging and ADRD-related changes in the brain on financial and health decision making among cognitively healthy older adults.

PI_NAMEs: BOYLE, PATRICIA A (contact)

PROGRAM_OFFICER_NAME: ANDERSON, DALLAS

PROJECT_TERMS: adverse outcome;Affective;age difference;age related changes;age related decline;Aging;aging brain;aging related;Alzheimer's Disease;Alzheimer's disease related dementia;Anxiety;Autopsy;base;Behavioral;behavioral outcome;Blood Vessels;Brain;Chronic Disease;Clinical;Cognition;Cognitive;Collection;Complement;Complex;contextual factors;Data;Data Collection;Decision Making;Dementia;depressive symptoms;Economics;Enrollment;epidemiology study;Exhibits;Face;financial exploitation;Financial Hardship;Fraud;Genetic;Goals;Health;Hemorrhage;Hippocampus;Hospitalization;human old age (65+);improved;Impulsivity;in vivo;indexing;Infarction;Influentials;innovation;Intervention;Knowledge;Life;Link;Loneliness;magnetic resonance imaging biomarker;Measures;Medical;Memory;Microvascular Dysfunction;mild cognitive impairment;mortality;Nerve Degeneration;neural;neurobehavioral;Neurobiology;neuroimaging;neuropathology;Neurotic Disorders;older adult;Older Population;Outcome;Pathologic;Personal Satisfaction;Personality;Persons;Policies;polygenic risk score;pre-clinical;Predisposition;preservation;Psychological Factors;Public Health;Reporting;Research;Resources;Risk;Risk Factors;risk selection;Sex Differences;social;social engagement;Social support;Socioeconomic Status;Stroke;Structure;Testing;Thick;Time;vascular risk factor;Victimization;white matter;White Matter Hyperintensity;Work

PROJECT_TITLE: Epidemiologic Study of Decision Making in Preclinical Alzheimer's Disease

STUDY_SECTION: NAME

STUDY_SECTION_NAME: Neurological, Aging and Musculoskeletal Epidemiology Study Section[NAME]


NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Genetics;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Orphan Drug;Pediatric;Rare Diseases;Rett Syndrome;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Women's Health Research

ORG_CITY: CAMBRIDGE

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

ORG_STATE: MA

PHR: Rett Syndrome is a devastating neurodevelopmental disorder which primarily affects girls, and is caused by mutations in the MECP2 gene. We propose to examine early deficits in cortical neurogenesis and neuronal migration caused by MECP2 mutations, as a way to understand fundamental changes in brain development in Rett Syndrome. These findings will help develop therapeutics targeting these early developmental stages.

PI_NAMEs: SUR, MRIGANKA  (contact)

PROGRAM_OFFICER_NAME: PANCHISION, DAVID M

PROJECT_TERMS: 3-Dimensional;Adult;Affect;Brain;Cell Adhesion;cell type;Cells;Cerebrum;Child;Chromatin Structure;Clinical Research;comparison control;Complex;Custom;Cytoskeletal Modeling;Defect;deficit syndrome;design;Development;Disease;DNA Binding;Down-Regulation;Fiber;Focal Adhesions;FRAP1 gene;Gene Expression;Generations;Genes;Genetic Transcription;girls;Human;Image;imaging capabilities;imaging platform;in vivo;induced pluripotent stem cell;Label;light scattering;Link;live cell imaging;Mass Spectrum Analysis;Methods;Methyl-CpG-Binding Protein 2;Microfluidics;MicroRNAs;migration;Molecular;Morphology;multiphoton microscopy;Mus;Mutation;nerve stem cell;Neurodevelopmental Disorder;neurogenesis;Neuroglia;Neuronal Differentiation;Neurons;new therapeutic target;novel;Organoids;overexpression;Pathway interactions;Patients;Phenotype;phosphoproteomics;Photons;Population;Proteins;Proteomics;Proto-Oncogene Proteins c-akt;Radial;Regulation;Regulator Genes;Resolution;Rett Syndrome;Role;Sampling;Signal Pathway;Signaling Molecule;single-cell RNA sequencing;Speed;stem cell technology;Technology;therapeutic target;three photon microscopy;tissue fixing;Tissue imaging;Tissues;transcription factor;transcriptomics;Travel

PROJECT_TITLE: Early developmental mechanisms of Rett Syndrome


ED_INST_TYPE: SCHOOLS OF PHARMACY

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

ORG_CITY: ALBUQUERQUE

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR

ORG_STATE: NM

PHR: Environmental disasters such as wildfires pose an increasing threat to a growing and aging global population and little is known about the impact of inhaled wildfire smoke on neurological and cardiovascular aging. We will examine the impact of inhaled wildfire smoke in terms of augmenting aging-related circulatory proteins and peptide fragments that compromise BBB integrity and alter microglial function to promote a reduced metabolic, senescent cellular phenotype that may be reversible with treatment of NAD+ boosting compounds and senolytic agents.

PI_NAMEs: CAMPEN, MATTHEW J (contact);OTTENS, ANDREW K

PROGRAM_OFFICER_NAME: OPANASHUK, LISA A

PROJECT_TERMS: Acceleration;Acute;age acceleration;age related;age related changes;Age related pathologies;age-related disease;Aging;aging mechanism;aging process;aging related;Alzheimer's Disease;Amyloid;Amyloid beta-Protein;Animals;Anti-Inflammatory Agents;Astrocytes;Atherosclerosis;Attenuated;biomass fuel;Blood;Blood - brain barrier anatomy;Blood Vessels;Brain;Cardiovascular system;CD36 gene;Cells;cerebrovascular;Chronic;Chronic Disease;Circulation;Complex;Complex Mixtures;Dementia;Disasters;Disease Marker;Elderly;Endothelial Cells;Endothelium;Environment;Environmental Exposure;Environmental Pollutants;Environmental Risk Factor;environmental stressor;Etiology;Event;experience;Exposure to;extreme weather;Gases;Genetic;glial activation;Health;healthspan;Histopathology;Human;Impairment;improved;in vivo;Inflammation;Inflammatory;Inhalation;Laboratories;Life;life span;Ligands;Lung;lung injury;Matrix Metalloproteinases;Mediator;Metabolic;Metabolism;Metalloproteases;Microglia;Molecular;mouse model;multiple omics;neural;neuroinflammation;Neurologic;Neurological outcome;neurological pathology;neuropathology;Outcome;Ozone;Particulate;Pathogenesis;Pathogenicity;pathological aging;Pathway interactions;Peptide Fragments;Peptide Hydrolases;Peptides;pharmacologic;Phenotype;pollutant;Population;Predisposition;pro-aging;Protein Fragment;Proteins;Proteome;Proteomics;receptor;Receptor Cell;recruit;Research;response;Resveratrol;Role;secretory protein;senescence;senolytics;Serpins;Serum;SIRT1 gene;Smoke;Structure;System;tau Proteins;Testing;therapeutic target;Therapeutic Uses;toxicant;Toxicology;United States;Up-Regulation;Vascular Cell Adhesion Molecule-1;Vascular Diseases;Vascular Endothelial Cell;Wildfire;wood smoke

PROJECT_TITLE: Acceleration of Circulatory and Neurological Aging due to Wildfire Exposures

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DKUS-R(04)]


NIH_SPENDING_CATS: Bioengineering;Clinical Research;Digestive Diseases;HIV/AIDS;Infectious Diseases;Liver Disease;Networking and Information Technology R&D (NITRD)

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: PROJECT NARRATIVE Routinely collected data are increasingly used for HIV/AIDS research, but these data are prone to errors and may need to be supplemented with additional data collection. We will create novel statistical methods, study designs, and tools to guide strategies for collecting additional data on subsamples of patient records and for incorporating these additional data into analyses to improve estimation. The proposed methods will be applied to studies using data from the Latin American and East African regions of the International epidemiology Databases to Evaluate AIDS (IeDEA) network.

PI_NAMEs: SHAW, PAMELA A;SHEPHERD, BRYAN EARL (contact)

PROGRAM_OFFICER_NAME: GEZMU, MISRAK

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Address;Africa;African;Aging;Biometry;Clinic Visits;Clinical Data;cohort;Collaborations;Communities;comorbidity;Complex;Computer software;Confidence Intervals;cost effective;Data;Data Collection;data harmonization;Data Sources;data standards;Databases;design;electronic health data;Electronic Health Record;Epidemiology;Fatty Liver;Fibrosis;flexibility;frailty;Funding;Grant;HIV;HIV/AIDS;improved;Incidence;Informatics;interest;International;Latin America;Latin American;Learning;Liver diseases;Liver Fibrosis;Machine Learning;Measurement;Measures;Methodology;Methods;Modeling;novel;open source tool;Outcome;Paper;Participant;patient subsets;Patients;Persons;Phase;prospective;Prospective cohort;Recording of previous events;Records;Research;Research Design;Research Personnel;Resource-limited setting;Resources;Risk Factors;semiparametric;Sentinel;software development;Statistical Methods;Study Subject;Techniques;Time;tool;Translating;Translations;United States National Institutes of Health;Validation;validation studies;Weight;Work;Writing

PROJECT_TITLE: Statistical methods and designs for correlated outcome and covariate errors in studies of HIV/AIDS

STUDY_SECTION: PPAH

STUDY_SECTION_NAME: Population and Public Health Approaches to HIV/AIDS Study Section[PPAH]