NIH_SPENDING_CATS: Cancer;Cancer Genomics;Chronic Liver Disease and Cirrhosis;Clinical Research;Digestive Diseases;Digestive Diseases - (Gallbladder);Genetics;Human Genome;Liver Cancer;Liver Disease;Prevention;Rare Diseases

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

PHR: PROJECT NARRATIVE Bile duct cancers (also termed cholangiocarcinomas; CCA) are usually diagnosed at advanced stages and have poor survival. There is evidence that a portion of the risk for CCA is inherited. Primary sclerosing cholangitis (PSC) is a strong risk factor for development of CCA, but most patients with CCA do not have PSC. We aim to identify genetic variations that explain individual susceptibility to CCA in the presence and absence of PSC.

PI_NAMEs: AMOS, CHRISTOPHER I.;HASSAN, MANAL METWALLY;ROBERTS, LEWIS R (contact)

PROGRAM_OFFICER_NAME: KALIA, SARAH SUJATA

PROJECT_TERMS: Africa;African;American;Asia;Asian;Asian ancestry;Asian population;bile duct;Bile Duct Carcinoma;Biliary Tract Cancer;Biological;cancer prevention;cancer risk;cancer therapy;cancer type;Cholangiocarcinoma;Cholelithiasis;Chromosome 6;Chronic viral hepatitis;Clinical;cohort;Collaborations;Collection;Complex;Consent;Cyst;Data;density;Development;Diagnosis;Disease;DNA;DNA Sequence;East Asian;Environmental Risk Factor;Epidemiology;epidemiology study;Etiology;European;exome sequencing;expectation;Exposure to;Fasciola hepatica;follow-up;Frequencies;Future;Gene Targeting;General Population;Genes;Genetic;Genetic Predisposition to Disease;genetic variant;Genetic Variation;genome wide association study;genome-wide;Genomic DNA;genomic locus;Genotype;Goals;Haplotypes;Heritability;Hispanic ancestry;Immune;improved;Individual;Inflammatory;Inherited;Institution;International;Malignant Neoplasms;Mediating;Methods;Methylene Chloride;Modeling;Molecular;multi-ethnic;novel;Occupational Exposure;Open Reading Frames;Organic solvent product;Outcome;Pathologic;Pathway interactions;Patients;Phase;Polymorphism Analysis;Population;Predisposition;Prevention strategy;Primary Prevention;primary sclerosing cholangitis;Prognosis;prospective;Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial;Publishing;Race;Radiology Specialty;rare variant;recruit;repository;Research;Risk;Risk Factors;Sampling;screening;sex;Single Nucleotide Polymorphism;Specimen;Susceptibility Gene;targeted sequencing;targeted treatment;Toxin;Variant

PROJECT_TITLE: International Consortium for the Genetics of Biliary Tract Cancers Cholangiocarcinoma Genome Wide Association Study

STUDY_SECTION: CHSA

STUDY_SECTION_NAME: Cancer, Heart, and Sleep Epidemiology A Study Section[CHSA]


ADMINISTERING_IC: AI

ARRA_FUNDED: N

FUNDING_MECHANISM: SBIR-STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Digestive Diseases;Emerging Infectious Diseases;Foodborne Illness;Hepatitis;Hepatitis - A;Infectious Diseases;Liver Disease;Neurosciences;Orphan Drug;Prevention;Rare Diseases

ORG_CITY: DOYLESTOWN

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: HARLINGENE LIFE SCIENCES LLC

ORG_STATE: PA

PHR: Project Narrative There is no effective antiviral drug to treat acute hepatitis A. Despite an effective vaccine, hepatitis A virus (HAV) still causes thousands of hospitalizations and many deaths each year in the United States alone. It is a much more serious problem in the developing countries, and it is also an agent of bioterror concern. However, there is currently no effective antivirals to treat severe HAV infections. A drug called DHQ was under development for hepatitis B and also has activity against HAV but had neurotoxicity in culture and long-term animal studies. Harlingene Life Sciences has modified this drug to be hepatoselective (HS) and is developing it for HAV. HS-DHQ would be the first and only HAV antiviral drug to mitigate liver injury in acute hepatitis A.

PI_NAMEs: DU, YANMING  (contact)

PROGRAM_OFFICER_NAME: DAVIS, MINDY I

PROJECT_TERMS: Ablation;Acids;Acute Hepatitis;acute liver injury;adaptive immune response;Afferent Neurons;Animals;anti-hepatitis B;Anti-viral Agents;Anti-viral Therapy;Binding Proteins;Biochemical;biodefense;Biological Assay;Biological Sciences;Bioterrorism;Blood;Brain;Caco-2 Cells;Categories;Cell Culture Techniques;Cell Line;Cellular Assay;Central Nervous System;Cessation of life;Chemoprevention;clinical development;Clinical Research;Complex;cytotoxicity;Data;Developing Countries;Development;Disease;Disease Outbreaks;Dose;Drug or chemical Tissue Distribution;effective therapy;effectiveness evaluation;efficacy evaluation;Emerging infection;Enteral;Exposure to;Family;Hepatitis A;Hepatitis A Virus;hepatitis A virus antibodies;Hepatitis B;Hepatitis B Antiviral;Hepatitis B Therapy;Hepatitis B Virus;Hepatocyte;Hospitalization;Human;human model;improved;In Vitro;in vitro Assay;in vivo;Infection;Innate Immune Response;Integration Host Factors;Lead;lead candidate;lead optimization;Life;Liver;liver inflammation;liver injury;liver transplantation;Messenger RNA;Metabolic;Metabolism;meter;Microsomes;monolayer;mouse model;Mus;nanomolar;National Institute of Allergy and Infectious Disease;neurite growth;Neurons;neurotoxicity;novel;nucleotidyltransferase;Oral;Organ;pathogen;Patients;Performance;Peripheral Nervous System;Permeability;Pharmaceutical Preparations;Pharmacologic Substance;Phase;Plasma;preclinical study;prevent;Prevention;Public Health;Quality Control;Rattus;receptor;relapse prevention;Resistance;Risk;RNA chemical synthesis;RNA Stability;RNA Viruses;Safety;Sanitation;scale up;sciatic nerve;Scientist;Serum;Small Business Technology Transfer Research;Spinal Ganglia;Stream;Structure;Therapeutic;tissue culture;Tissues;Toxic effect;Transcript;transmission process;treatment duration;United States;Untranslated RNA;uptake;Vaccines;Viral;Viral hepatitis;Viral Physiology;viral RNA;Virus;Virus Diseases;Virus Replication;Work

PROJECT_TITLE: Hepatoselective Dihydroquinolizinone (HS-DHQ) Molecules for Treatment and Prevention of Hepatitis A Virus (HAV) Infection

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DCAI-F(12)]


ADMINISTERING_IC: HD

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

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

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

ORG_CITY: BAR HARBOR

ORG_NAME: JACKSON LABORATORY

ORG_STATE: ME

PHR: PROJECT NARRATIVE/RELEVANCE TO PUBLIC HEALTH Spermatogonial stem cells support male gamete production for the reproductive lifetime of the individual and are required for the continuation of our species. Disruption of stem cell self-renewal can cause cancer and infertility. A better understanding of the regulation of the fate of these cells will enhance our knowledge of male infertility and may lead to the development of a male contraceptive. Fertility preservation in young cancer patients is also dependent on spermatogonial stem cells and future regenerative medicine strategies may use the unique developmental potential of these cells for therapy.

PI_NAMEs: BRAUN, ROBERT E (contact)

PROGRAM_OFFICER_NAME: KENT, TRAVIS JOHN

PROJECT_TERMS: Ablation;Adult;adult stem cell;age related;Alleles;Automobile Driving;Biological Assay;Busulfan;Cancer Etiology;Cancer Patient;cdc Genes;Cell Cycle;Cell Cycle Regulation;Cell Fate Control;Cell Maintenance;Cell Nucleus;Cell Therapy;Cells;Chromatin;Chromatin Structure;Complement;Data;Detection;Development;Equilibrium;exhaustion;fertility preservation;Frequencies;Future;Gene Expression;Gene Expression Profile;Gene Expression Profiling;Genes;Genetic Enhancement;Genetic Markers;Genetic Suppression;Germ Cells;Heterogeneity;Individual;Infertility;Knowledge;male;Male Contraceptive Agents;Male Infertility;Mus;mutant;Mutant Strains Mice;Mutation;Natural regeneration;Normal Cell;Phenotype;Phosphorylation;Population;Production;progenitor;Public Health;Publishing;Regenerative Medicine;reproductive;Reserve Cell;Role;S phase;self-renewal;single nucleus RNA-sequencing;single-cell RNA sequencing;Sorting;Spermatogenesis;Spermatogonia;stem cell biomarkers;stem cell self renewal;stem cells;Supporting Cell;Testis;tissue repair;Tissues;transcription factor;Transposase;Work;ZNF145 gene

PROJECT_TITLE: Spermatogonial Stem Cell Maintenance

STUDY_SECTION: CMIR

STUDY_SECTION_NAME: Cellular, Molecular and Integrative Reproduction Study Section[CMIR]


ADMINISTERING_IC: MH

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Mental Health;Pediatric;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: UNIVERSITY PARK

ORG_DEPT: MISCELLANEOUS

ORG_NAME: PENNSYLVANIA STATE UNIVERSITY, THE

PHR: Project Narrative Young-adult men who have sex with men (YMSM) are likely to turn to the Internet to seek information about pre-exposure prophylaxis (PrEP), a highly effective treatment for preventing HIV infection. This investigation will use qualitative and quantitative methods to test promising health communication messaging strategies most likely to enhance Black, Hispanic, and non-Hispanic White YMSM's engagement with online content about injectable and oral PrEP. Findings from this research will inform the design of health communication campaigns to better engage YMSM's attention—a necessary first step toward promoting PrEP uptake and ultimately reducing HIV infection rates among YMSM.

PI_NAMEs: SKURKA, CHRISTOFER J (contact)

PROGRAM_OFFICER_NAME: GREENWOOD, GREGORY LOUIS

PROJECT_TERMS: Address;Age;age group;AIDS prevention;Area;Attention;Awareness;Behavior;behavior influence;Behavioral;Black race;Collection;Communication;Communication Research;Communities;comparative;Continuity of Patient Care;Data;demographics;design;digital communication;effective therapy;Effectiveness;Eligibility Determination;Ethnic Origin;Ethnic Population;experimental study;Exposure to;Eye;Focus Groups;Future;gaze;Goals;Government;Health;Health behavior;Health Benefit;health communication;Hearing;Hispanic;HIV;HIV Infections;HIV risk;infection rate;Information and Communication Theory;Injectable;innovation;insight;interest;Internet;Investigation;Knowledge;Learning;Link;Measures;men who have sex with men;men's group;Methods;multidisciplinary;Not Hispanic or Latino;novel;Oral;Outcome;Patient Self-Report;Pattern;Persons;Persuasive Communication;pill;Population;pre-exposure prophylaxis;preference;prevent;Psychology;Public Health;Race;racial difference;racial population;Randomized;recruit;Research;response;Risk;search engine;Services;social media;social norm;social stigma;Source;tailored messaging;Testing;theories;Time;United States Food and Drug Administration;uptake;Visual;web page;web site;Work;young adult

PROJECT_TITLE: Enhancing Engagement with Online Health Messaging about Oral and Injectable PrEP Among Young-Adult MSM

STUDY_SECTION: HIBI

STUDY_SECTION_NAME: HIV/AIDS Intra- and Inter-personal Determinants and Behavioral Interventions Study Section[HIBI]


ADMINISTERING_IC: HL

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Biomedical Imaging;Cardiovascular;Clinical Research;Genetic Testing;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Heart Disease;Neurodegenerative;Neurosciences;Peripheral Neuropathy;Prevention;Racial and Ethnic Minority Health Research;Rare Diseases

ORG_CITY: NEW YORK

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

ORG_STATE: NY

PHR: PROJECT NARRATIVE Hereditary TTR amyloidosis (hATTR) is a debilitating disease that predominantly affects African American and Hispanic/Latino patients in the U.S., and often escapes diagnosis until symptoms of late-stage heart failure appear. Because new treatments have emerged to delay progression, it is increasingly important to recognize early clinical features of hATTR, in order to hasten diagnoses and improve outcomes. We will take a genetics- first approach to comprehensively study multi-systemic features and cardiac imaging findings in African American and Hispanic/Latino patients at high genetic risk for hATTR, to improve knowledge of disease presentation and penetrance, and to inform strategies for cardiac surveillance and earlier clinical diagnosis.

PI_NAMEs: KONTOROVICH, AMY R. (contact)

PROGRAM_OFFICER_NAME: HONG, YULING

PROJECT_TERMS: Address;Adult;Affect;African American;African American population;Age;age related;Amyloid;Amyloid deposition;Amyloidosis;Apical;associated symptom;biobank;Bypass;Cardiac;cardiac amyloidosis;Caring;Carpal Tunnel Syndrome;Characteristics;Clinical;clinical diagnosis;clinical infrastructure;cohort;Collaborations;Counseling;Diagnosis;Diagnostic;Diphosphates;Disease;disease natural history;Early Diagnosis;Early identification;early screening;Echocardiography;Electronic Health Record;empowerment;Enrollment;Exposure to;Familial Amyloid Neuropathies;Future;Gadolinium;Genetic;genetic approach;Genetic Risk;genomic data;Genotype;Guidelines;Health;health care disparity;Health system;Heart Abnormalities;Heart Diseases;Heart failure;heart imaging;hereditary risk;high risk;Hispanic;Hybrids;imaging approach;imaging modality;imaging study;improved;improved outcome;Individual;Ionizing radiation;Knowledge;Latino;Latino Population;Learning;Link;Magnetic Resonance Imaging;Methods;Minority Groups;minority patient;Modality;multimodality;Natural History;Nerve;New York City;Nomenclature;Non-Invasive Detection;noninvasive diagnosis;novel;novel therapeutics;Nuclear;Pathogenicity;Patients;Penetrance;Phase;phenome;Phenotype;Polyneuropathy;Population;Positron-Emission Tomography;pre-clinical;Prealbumin;Prevalence;prospective;Prospective Studies;Radionuclide Imaging;recruit;Research Infrastructure;Retrospective Studies;Risk;screening;Signal Transduction;Signs and Symptoms;Spinal Stenosis;surveillance imaging;surveillance strategy;Symptoms;Therapeutic;timeline;Tracer;trait;translational genomics;uptake;Variant

PROJECT_TITLE: Uncovering early signals of hereditary TTR amyloidosis in minority populations at high genetic risk

STUDY_SECTION: CICS

STUDY_SECTION_NAME: Clinical and Integrative Cardiovascular Sciences Study Section[CICS]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Immunotherapy;Lung;Lung Cancer;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: WINSTON-SALEM

ORG_DEPT: BIOLOGY

ORG_NAME: WAKE FOREST UNIVERSITY HEALTH SCIENCES

ORG_STATE: NC

PHR: NARRATIVE We identified differences in tumor genomics and the status the tumor microenvironment in non-small cell lung cancer (NSCLC) between Black and White patients. We propose to evaluate drug combinations that reprogram tumor cell metabolism and induce change in the tumor microenvironment, which when coupled with immune checkpoint blockade will help to overcome the survival disparities for Black patients. Results from the proposed research will inform future studies and provide a potential direction for investigator-initiated clinical trials.

PI_NAMEs: FURDUI, CRISTINA MARIA;LIU, LIANG ;ZHANG, WEI  (contact)

PROGRAM_OFFICER_NAME: MERCER, NATALIA

PROJECT_TERMS: Affect;Agreement;Baptist Church;biomarker identification;Biopsy;black lung;black patient;Black race;Cancer cell line;Cancer Center;cancer diagnosis;cancer health disparity;Cancer health equity;Cancer Patient;Catchment Area;CD8-Positive T-Lymphocytes;Cell Line;Cell Physiology;Cell Reprogramming;cell type;Cells;cellular targeting;Chest;Clinical Trials;Combined Modality Therapy;Comprehensive Cancer Center;Coupled;CTLA4 gene;Data;Death Rate;Development;Disparity;Drug Combinations;Drug Targeting;Ecosystem;Engineering;epidemiologic data;Evaluation;Event;exhaust;experience;Future;Gene Amplification;Gene Expression;Gene Expression Profile;Gene Mutation;Genetic Transcription;Genomics;Goals;health disparity;humanized mouse;Immune;immune checkpoint blockade;immunoregulation;Impairment;improved;Incidence;Infiltration;inhibitor;innovation;insight;Knowledge;Link;lipid metabolism;Lipids;Malignant neoplasm of lung;Mass Spectrum Analysis;MCL1 gene;Mediating;Metabolic;Metabolism;Mitochondria;mitochondrial metabolism;Molecular;mouse model;mutant;Myelogenous;Natural Killer Cells;new therapeutic target;Non-Small-Cell Lung Carcinoma;novel;Oncogenes;Oncologist;Organoids;Oxidation-Reduction;Pathway Analysis;Pathway interactions;Patients;Pharmaceutical Preparations;Positioning Attribute;pre-clinical;predicting response;programs;Publishing;racial health disparity;Reactive Oxygen Species;Regulation;Reporting;Research;Research Personnel;Resistance;Resolution;response;Role;Sampling;Shapes;single-cell RNA sequencing;survival disparity;T-Lymphocyte;targeted treatment;Technology;Therapeutic;therapeutically effective;Time;TP53 gene;transcriptomic profiling;transcriptomics;treatment disparity;treatment response;tumor;tumor metabolism;tumor microenvironment;tumor-immune system interactions

PROJECT_TITLE: Overcoming racial health disparities in lung cancer through innovative mechanism-based therapeutic strategies

STUDY_SECTION: BMCD

STUDY_SECTION_NAME: Basic Mechanisms of Cancer Health Disparities Study Section[BMCD]


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Neurosciences;Opioids

ORG_CITY: PITTSBURGH

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: Project Narrative Chronic itch severely diminishes quality of life. However, the neurons that mediate itch in the dorsal root ganglia and dorsal horn have never been observed at a population level. Our proposal will address this issue by providing a network view of how itch input is initially integrated and where KOR agonists act to inhibit this circuitry. These efforts will provide key insight into the neural coding of itch, and may elucidate new avenues for treatment.

PI_NAMEs: KOERBER, H RICHARD;ROSS, SARAH ELIZABETH (contact)

PROGRAM_OFFICER_NAME: KOCH, PETER

PROJECT_TERMS: Affect;Afferent Neurons;Agonist;Brain;Cell Degranulation;cell type;Cells;cellular targeting;Chloroquine;chronic itch;Classification;Clinical;Code;Contact Dermatitis;Coupled;Detection;Disease;dorsal horn;Dryness;excitatory neuron;experimental study;Genetic Recombination;Image;insight;Interneurons;kappa opioid receptors;Knowledge;Mediating;Modeling;Monitor;Nerve;neural;neural circuit;neuroimaging;Neurons;novel;Opioid agonist;Output;Pattern;Pharmaceutical Preparations;Pharmacology;Population;Positioning Attribute;Preparation;Pruritus;Quality of life;response;Role;Skin;somatosensory;Spinal;Spinal Cord;Spinal Ganglia;Stimulus;Testing;tool;two-photon;Urticaria;Visualization

PROJECT_TITLE: Investigating the Neural Circuits of Itch

STUDY_SECTION: NPI

STUDY_SECTION_NAME: Neurobiology of Pain and Itch Study Section [NPI]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Epilepsy;Mental Health;Neurodegenerative;Neurosciences

ORG_DEPT: NEUROLOGY

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: PROJECT NARRATIVE The human brain learns in real-world circumstances by parsing experiences into events, but the neural interactions supporting this function are poorly understood. We will use short films to test memory function while recording from key memory regions in surgical epilepsy patients, then test our findings by using electrical stimulation. The gained knowledge will provide an important translational advance and accelerate new approaches to the diagnosis and management of memory disorders.

PI_NAMEs: LIU, ANLI A (contact)

PROGRAM_OFFICER_NAME: BABCOCK, DEBRA J

PROJECT_TERMS: Acceleration;Address;Affect;Alzheimer's Disease;Brain;Clinical;cognitive neuroscience;Complex;Coupled;Data Set;Diagnosis;Electric Stimulation;Electroencephalography;Epilepsy;epileptiform;Episodic memory;episodic memory impairment;Event;experience;Exposure to;Film;forgetting;Functional Magnetic Resonance Imaging;Future;Goals;High Frequency Oscillation;Hippocampus;Human;innovation;Investigation;Knowledge;Learning;Life;Measures;Medial;Memory;memory consolidation;Memory Disorders;Memory impairment;memory retrieval;Methods;millisecond;Modeling;Monitor;Neocortex;neocortical;Nervous System Disorder;neural;neuroimaging;neuromechanism;neurophysiology;neuropsychiatric disorder;novel strategies;Operative Surgical Procedures;Pathologic;Patients;Performance;Periodicity;Persons;Play;Population;Process;Random Allocation;remediation;Resolution;Rest;Rodent;Role;Series;Signal Transduction;Sleep;spatiotemporal;Speed;Structure;Testing;Time;Translations;Traumatic Brain Injury;way finding;Work

PROJECT_TITLE: Hippocampal-Neocortical Interactions During Naturalistic Learning

STUDY_SECTION: HCMF

STUDY_SECTION_NAME: Human Complex Mental Function Study Section[HCMF]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

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

ORG_CITY: LEXINGTON

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF KENTUCKY

ORG_STATE: KY

PHR: Project Narrative This project will reveal a novel mechanism regulating a female-biased, neuroinflammation-trigged ApoE dysregulation pathway in the context of sex, aging, and brain injury. Furthermore, this study will provide a proof of efficacy for a new drug target, particularly in females, who are vulnerable for diseases associated with neuroinflammation and ApoE dysregulation, including Alzheimer’s disease and brain injury.

PI_NAMEs: WANG, WANG-XIA  (contact)

PROGRAM_OFFICER_NAME: YAO, ALISON Q

PROJECT_TERMS: Acute;Affect;Age;aged;Aging;Alleles;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease risk;Apolipoprotein E;Behavioral Assay;biobank;Biochemical;Biological;Bone Marrow;Brain;brain cell;Brain Injuries;brain tissue;CCAAT-Enhancer-Binding Protein-beta;Cell Separation;Cells;Data;Dementia;Disease;Disproportionately impacts women;efficacy testing;Event;Female;Funding;Genotype;Goals;Health;Histologic;Human;Human X Chromosome;improved;In Vitro;in vivo;Inflammation;Inflammatory;Inflammatory Response;Injury;innovation;Intravenous;Kentucky;Knockout Mice;Knowledge;Late Onset Alzheimer Disease;Link;lipid nanoparticle;liposomal delivery;Liposomes;Macrophage;male;Mediating;Methods;Microglia;microRNA delivery;MicroRNAs;Modeling;Molecular;mouse model;Mus;Myeloid Cells;Nerve Degeneration;Nervous System Physiology;neuroinflammation;neuropathology;new therapeutic target;novel;novel therapeutics;old mice;Pathology;Pathway interactions;protein biomarkers;Proteins;Public Health;Regulation;response;RNA;Role;Sampling;Senile Plaques;sex;sexual dimorphism;Signal Transduction;System;systemic inflammatory response;targeted treatment;Testing;Therapeutic;therapeutic miRNA;Therapeutically Targetable;transcription factor;Universities;Untranslated RNA;X Chromosome

PROJECT_TITLE: MicroRNA lipid-nanoparticle based therapy targets neuroinflammation and ApoE dysregulation in Alzheimer’s disease


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Digestive Diseases;Eczema / Atopic Dermatitis;Food Allergies;Microbiome;Nutrition;Pediatric;Prevention

ORG_CITY: BOSTON

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

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

ORG_STATE: MA

PHR: Project Narrative for the SEAL (Stopping Eczema and ALlergy) Study Food allergy (FA) is an epidemic among children in the U.S., U.K., and other countries. By reducing dry skin, the duration and severity of eczema and preventing eczema exacerbations with skin barrier protection and anti-inflammatory creams, we aim to significantly reduce the incidence of food allergy.

PI_NAMEs: LACK, GIDEON ;LEUNG, DONALD YM;NADEAU, KARI C. (contact)

PROGRAM_OFFICER_NAME: DONG, GANG

PROJECT_TERMS: 1 year old;3 year old;Allergens;Allergic inflammation;allergic response;Allergy to peanuts;Anti-Inflammatory Agents;arm;Atopic Dermatitis;atopy;B-Lymphocytes;Basophils;Biological Markers;Blood;Caring;CD8B1 gene;Cells;Child;Clinical;Clinical Research;cohort;commensal bacteria;comparison control;Complex;Country;Cream;Cytometry;Development;Disease;Dryness;dysbiosis;Eczema;Emollients;Epidemic;Epithelium;filaggrin;food allergen;food challenge;food consumption;Food Hypersensitivity;Functional disorder;Genes;genetic testing;high risk infant;Hypersensitivity;IgE;immune function;Immune response;Immunoglobulin Class Switching;improved;Incidence;infancy;Infant;Inflammation;Inhalant dose form;Interleukin-10;Interleukin-13;Intervention;Intervention Trial;Learning;Life;Lipids;Lymphoid Cell;mast cell;Mediating;Metagenomics;microbial;Monitor;monocyte;novel;Oatmeal Powder;Oral;oral tolerance;Participant;patient retention;Prevalence;prevent;Prevention;primary endpoint;prospective;Proteins;Proteomics;Randomized;Recommendation;recruit;Regulatory T-Lymphocyte;repaired;Research;respiratory;Risk;Role;secondary outcome;Secondary Prevention;Severities;Skin;skin barrier;Skin Care;skin microbiota;Somatic Mutation;standard of care;Staphylococcus aureus;Steroids;Stratum corneum;T cell receptor repertoire sequencing;Techniques;Testing;Th2 Cells;Time;Topical application;transcriptomics;treatment arm;treatment group;trial design;TSLP gene;Variant;γδ T cells

PROJECT_TITLE: SEAL (Stopping Atopic dermatitis and ALlergy) Study: Prevent allergy by enhancing the skin barrier


ORG_CITY: SAN FRANCISCO

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: PROJECT NARRATIVE Just like human cells, bacteria are susceptible to fatal viral infections. Recently there has been increasing excitement about the possibility of using bacterial viruses (called bacteriophages) for therapies to treat bacterial infections as bacteriophages are harmless to human cells. In this proposal, three researchers with complementary expertise join to uncover novel mechanisms by which bacteria fight off bacteriophage infections, with the goal of “helping” the bacteriophages to kill the bacteria more effectively.

PI_NAMEs: BONDY-DENOMY, JOSEPH  (contact)

PROGRAM_OFFICER_NAME: ERNST, NANCY L

PROJECT_TERMS: Address;Affinity;Affinity Chromatography;Anti-Bacterial Agents;Antibiotic Resistance;Antibiotics;Automobile Driving;Bacteria;bacterial fitness;bacterial genetics;Bacterial Infections;Bacterial Physiology;bacterial resistance;Bacteriophages;Binding;Biochemical;Bioinformatics;Biological Assay;Biology;biophysical properties;Cataloging;Cell Death;Cell Fractionation;Cells;Clustered Regularly Interspaced Short Palindromic Repeats;combat;Complement;Complex;Coupled;Cytolysis;Data;Data Analyses;design;Detection;effective therapy;Engineering;Ensure;Essential Genes;Family;fighting;Fortification;Future;gene discovery;gene interaction;Genes;Genetic;Genetic Transcription;Goals;Growth;Human;human pathogen;Immune system;in vivo;Infection;inhibitor;Integration Host Factors;knock-down;Libraries;Lytic;Maps;Mass Spectrum Analysis;Methods;Modeling;multidrug-resistant Pseudomonas aeruginosa;next generation sequencing;novel;Outcome;pathogen;Pathogenesis;Pathway interactions;Predatory Behavior;Predisposition;Process;protein complex;protein protein interaction;Proteins;Proteome;Proteomics;Pseudomonas aeruginosa;Reagent;Repression;Research;Research Personnel;Resistance;resistance gene;resistance mechanism;response;Role;screening;Series;skills;small molecule;success;Surveys;System;Therapeutic;Time;tool;Validation;Virus Diseases

PROJECT_TITLE: Genetic and Proteomic Approaches to Reveal Bacterial Vulnerabilities to Phage Predation

STUDY_SECTION: PCMB

STUDY_SECTION_NAME: Prokaryotic Cell and Molecular Biology Study Section[PCMB]


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Health Services;Machine Learning and Artificial Intelligence;Maternal Health;Maternal Morbidity and Mortality;Mental Health;Networking and Information Technology R&D (NITRD);Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Preterm, Low Birth Weight and Health of the Newborn;Women's Health Research

ORG_CITY: ANN ARBOR

ORG_NAME: POISERA, INC.

ORG_STATE: MI

PHR: PUBLIC HEALTH RELEVANCE STATEMENT Perinatal mood disorders (PMDs) are the most common health complication from pregnancy, and though treatable, most mothers with PMD symptoms never receive diagnosis or treatment. In this SBIR, BetterHope LLC (dba Poisera) will develop a mobile health app to longitudinally monitor perinatal mental health to improve detection and delivery of treatment for PMDs. The Poisera app will identify and treat PMD at earliest onset for 750,000-800,000 women each year to avoid long-term adverse health outcomes for both mother and child.

PI_NAMEs: KERPPOLA, MARIANNA  (contact);MUZIK, MARIA

PROGRAM_OFFICER_NAME: HAIM, ADAM J

PROJECT_TERMS: Address;Adherence;adverse childhood events;application programming interface;arm;attentional control;Behavior;behavioral health;chatbot;Child;Clinical;clinical practice;commercial application;Continuity of Patient Care;cost;cost effectiveness;dashboard;Data;design;Detection;Development;Developmental Delay Disorders;Diagnosis;diagnostic screening;digital;Discipline of obstetrics;Disclosure;Dropout;early pregnancy;effective therapy;Empathy;Enrollment;Ensure;Evidence based treatment;Exercise;experience;Fright;Funding;Goals;Health;Health system;Health Technology;improved;innovation;Insurance Carriers;Intellectual Property;Intervention;Interview;Intuition;Judgment;Knowledge;Licensing;Low Birth Weight Infant;Marketing;maternal morbidity;Maternal Mortality;maternal risk;Measures;Mental disorders;Mental Health;mobile application;Mobile Health Application;Modeling;Monitor;Mood Disorders;motherhood;Mothers;Onset of illness;Outcome;Patients;Perinatal;perinatal mental health;Phase;postnatal;Postpartum Period;Pregnancy;Pregnancy Complications;Pregnant Women;Premature Birth;prenatal;programs;prototype;public health relevance;Randomized, Controlled Trials;Research;Rights;Risk;Risk Assessment;screening;Secure;Small Business Innovation Research Grant;social stigma;Suicide;Surveys;Symptoms;technological innovation;Technology;technology platform;Therapeutic Intervention;Time;treatment planning;United States Preventative Services Task Force;Update;usability;Validation;Woman;women's outcomes

PROJECT_TITLE: Development of an empathetic chatbot to monitor perinatal mental health longitudinally


NIH_SPENDING_CATS: Clinical Research;Eczema / Atopic Dermatitis

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE Atopic dermatitis (AD) is a chronic skin disease marked by allergic inflammation and itch, and is increasingly common among children and adults in the United States. We and others have found that the cytokine IL-18 is dysregulated in human AD, along with IL-18-responsive basophils and group 2 innate lymphoid cells (ILC2s). In this proposal, we investigate the role of IL-18 in mediating ILC2 and basophil responses in AD and AD-like skin disease, in order to advance our mechanistic understanding of AD pathogenesis.

PI_NAMEs: KIM, BRIAN ;VAN DYKEN, STEVEN  (contact)

PROJECT_TERMS: Acute;Adipose tissue;Adult;Allergic;Allergic inflammation;Atopic Dermatitis;Automobile Driving;Basophils;Behavior;Behavioral;Blood;Cell Separation;Cells;Child;Childhood;Chronic;Chronic Disease;Clinical;conditional knockout;cytokine;Data;design;Disease;Disease remission;Effector Cell;Etiology;Exhibits;Exposure to;Flare;Goals;Human;human disease;IL18 gene;Image;Immunofluorescence Immunologic;In Vitro;in vivo;Inflammation;innovation;Interleukin-13;interleukin-18 binding protein;interleukin-18 receptor;Interleukin-4;Interleukins;Knock-out;Knockout Mice;Lung;Lymphoid Cell;Maps;Measures;Mediating;Mediation;Mediator;Modeling;mouse model;Mouse Strains;Mus;Neuroimmune;new therapeutic target;novel;novel therapeutic intervention;Outcome;Pathogenesis;Pathology;Patients;Phenotype;Plasma;Production;Pruritus;Relapse;response;Role;Severity of illness;Signal Transduction;single-cell RNA sequencing;Skin;skin disorder;Skin Tissue;Source;System;targeted treatment;Technology;Testing;therapeutic target;Time;Tissues;transcriptomics;Translating;Treatment Efficacy;United States;Visualization

PROJECT_TITLE: Defining the role of IL-18 in atopic dermatitis


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: DETROIT

ORG_NAME: WAYNE STATE UNIVERSITY

PHR: Project Narrative Incarcerated individuals have higher rates of chronic disease than the general population, including more hypertension, diabetes, high cholesterol, and obesity. The Chronic Disease Self-Management Program (CDSMP) is an evidence-based disease management program that has been utilized in state corrections systems on a limited basis; however, there has been little deliberate research investigation into efficient and effective strategies for scaling up the intervention among older adults within state corrections systems. The research objective of this K01 is to use mixed methods research approaches to engage community-agency CDSMP leaders, correctional staff, and incarcerated individuals in developing strategies to maximize the scalability of the Chronic Disease Self-Management Program among older adults within a state correctional system.

PI_NAMEs: SNEED, RODLESCIA  (contact)

PROGRAM_OFFICER_NAME: GERALD, MELISSA S

PROJECT_TERMS: Age;Area;Assessment tool;biopsychosocial;burden of chronic illness;burden of illness;career;Cholesterol;Chronic;Chronic Disease;Communicable Diseases;Communities;community engagement;Complex;correctional system;cost;Data;depressive symptoms;Development;Diabetes Mellitus;Disease;Disease Management;disease model;Educational workshop;Emergency department visit;Ensure;evidence base;Evidence based program;Exercise;experience;Funding;General Population;Gerontology;Goals;Health;health care service;health disparity;Health Expenditures;Healthcare;Hospitalization;Hypertension;implementation research;implementation science;implementation trial;Imprisonment;improved;Individual;Infrastructure;innovation;Intervention;Interview;Investigation;Justice;knowledge base;Link;Manuals;member;Mental disorders;Mentors;Morbidity - disease rate;mortality;neglect;Obesity;older adult;organizational structure;Outcome;pain symptom;Participant;peer;Persons;Persuasive Communication;physical conditioning;Population;primary health service;prison population;Prisons;Privatization;Process;programs;Randomized;randomized trial;Recommendation;recruit;Research;Research Methodology;Research Personnel;Resource-limited setting;Resources;scale up;Security;Self Care;Self Efficacy;Self Management;self-management program;social;Standardization;Substance abuse problem;Surveys;Testing;Time;Training;women versus men

PROJECT_TITLE: Maximizing the Scalability of the Chronic Disease Self-Management Program (CDSMP) Among Older Adults in State Correctional Settings

STUDY_SECTION: AGCD

STUDY_SECTION_NAME: Career Development For Early Career Investigators Study Section [AGCD-2]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Behavioral and Social Science;Biotechnology;Brain Disorders;Drug Abuse (NIDA only);Electronic Nicotine Delivery Systems;Genetics;Human Genome;Mental Health;Neurosciences;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Prevention;Substance Misuse;Tobacco

ORG_CITY: Loma Linda

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: LOMA LINDA UNIVERSITY

PHR: NARRATIVE Using a unique rat intrauterine e-cigarette exposure model coupled with cutting-edge genomic and epigenomic approaches including the spatial genomics and single-cell sequencing technologies, this project will determine the genomic and epigenomic mechanisms underlying prenatal e-cigarette caused abnormal brain development in the offspring. A large amount of genomic and epigenomic data will be produced, including whole genome sequencing, DNA methylomes, ATAC-seq chromatin accessibility, RNA-seq transcriptomes, and single-nucleus RNA-seq/ATAC-seq, which will provide valuable new insights into the effects of e-cigarette on early central nervous system development, and help explore promising molecular and cellular therapeutic targets for treating e-cigarette vaping-induced brain damage.

PI_NAMEs: WANG, CHARLES  (contact);XIAO, DALIAO

PROGRAM_OFFICER_NAME: LOSSIE, AMY C

PROJECT_TERMS: Adolescent;Adverse effects;Affect;Anxiety;ATAC-seq;Attention deficit hyperactivity disorder;autism spectrum disorder;bioinformatics tool;Biological Assay;bisulfite sequencing;Brain;brain abnormalities;Brain Injuries;Brain region;Cell Nucleus;Cell Therapy;cell type;Cells;Central Nervous System;Chromatin;Chronic;cognitive performance;Computer Analysis;Copy Number Polymorphism;Coupled;Data;Databases;Development;DNA;DNA Sequence Alteration;Electronic cigarette;electronic cigarette use;Embryo;epigenomics;Equilibrium;excitatory neuron;Exposure to;Fetus;Gender;Genes;genome sequencing;genome wide association study;Genomics;Goals;Health;Hyperactivity;inhibitory neuron;insight;Investigation;Knowledge;maternal cigarette smoking;Measures;Mental Depression;Mental disorders;Methods;methylome;Modeling;Molecular;Morphology;multiple omics;Mutation;National Human Genome Research Institute;neonatal brain;neonatal brain development;nerve stem cell;nervous system development;neurobehavior;Neurodevelopmental Disorder;Neurons;Nicotine;offspring;Pathogenesis;postnatal;Predisposition;Pregnant Women;prenatal;prenatal exposure;prenatal nicotine exposure;Public Health;Rattus;Regulation;Risk;single cell sequencing;Single Nucleotide Polymorphism;single nucleus RNA-sequencing;Specific qualifier value;Synapses;System;Techniques;Technology;therapeutic target;Time;transcriptome;transcriptome sequencing;transcriptomics;vaping;whole genome;Whole-Cell Recordings

PROJECT_TITLE: Genomic and Epigenomic Mechanisms of Maternal E-Cigarette induced Abnormal Brain Development


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

ORG_CITY: WALTHAM

ORG_NAME: BRANDEIS UNIVERSITY

PHR: PROJECT NARRATIVE The main aim of this project is to uncover roles of circular RNAs (circRNAs) in Alzheimer’s disease (AD). To do so, we will utilize established Drosophila models of the disease in combination with our collection of 110 strains that will allow us to determine comprehensively whether circRNAs can alter the development or progression of pathology in the AD models. Identifying roles of circRNAs in AD has obvious implications for human health, especially given the incidence of AD and other neurodegenerative disorders in the aging population.

PI_NAMEs: KADENER, SEBASTIAN  (contact)

PROJECT_TERMS: Age;age related;age related changes;Aging;aging mechanism;aging population;Alzheimer's Disease;Alzheimer's disease model;Animal Model;Animals;Apoptosis;Area;Autophagocytosis;Awareness;Behavior;Behavioral;Brain;circular RNA;Collection;Data;Defect;Development;Disease;disease model;Disease Outcome;Disease Progression;disorder control;Drosophila genus;Exons;experimental study;Eye;fly;Gene Expression;Genetic;Genetic Screening;Genomics;Health;healthspan;Homeostasis;Human;Impairment;improved;in vivo;Incidence;Individual;Inflammation;knock-down;Lead;Libraries;life span;Link;Mediating;Methodology;MicroRNAs;Mitochondria;Modeling;Molecular;Motor;Nerve Degeneration;Nervous System Disorder;neural;Neurodegenerative Disorders;Neurons;neuroprotection;neurotoxic;Neurotoxicity Syndromes;overexpression;Oxidative Stress;Parkinson Disease;Pathogenesis;Pathology;Pathway interactions;Phenotype;Post-Translational Protein Processing;protein metabolism;Proteins;Regulation;Research;Resources;RNA;RNA metabolism;RNA-Binding Proteins;Role;screening;success;Surface;System;tau expression;tau interaction;tau Proteins;Testing;Time;Tissues;tool;Whole Organism;Work

PROJECT_TITLE: Systematic and mechanistic assessment of the roles of circRNAs in Alzheimer's Disease


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;Estrogen;Genetics;Neurodegenerative;Neurosciences;Women's Health Research

ORG_CITY: MAYWOOD

ORG_DEPT: PHYSIOLOGY

ORG_NAME: LOYOLA UNIVERSITY CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE The female sex bias in Alzheimer’s Disease incidence is well documented, yet the biological basis for this sex difference is unknown. We have identified estrogen-mediated changes in microRNA expression, a non-coding RNA, that are dependent on age and length of time post-menopause, and these E2-regulated microRNAs are critical regulators of cognition and memory. This proposal will investigate how estrogens regulate microRNAs in the female brain across the lifespan and determine if this process is dysregulated in Alzheimer’s Disease.

PI_NAMEs: PAK, TONI R. (contact)

PROJECT_TERMS: Address;Affect;Age;age effect;age related;Aging;aging brain;Alzheimer's Disease;Alzheimer's disease risk;Binding;Binding Sites;Biogenesis;Biological;Biological Assay;Body System;Brain;Brain region;BRCA1 gene;Cells;Cognition;Complex;Data;deprivation;Estradiol;Estrogen Receptor 2;Estrogens;experimental study;Female;hnRNP-H;Incidence;Kinetics;Length;life span;Link;Maps;Mediating;Memory;men;Microprocessor;MicroRNAs;Molecular;normal aging;novel;Organ;Pathway interactions;Pattern;Postmenopause;posttranscriptional;Process;Proteins;Proteomics;Regulation;Research;RNASE3L gene;sex;Sex Bias;Sex Differences;Signal Pathway;Signal Transduction;Specificity;Testing;Therapeutic;Time;Tissues;trafficking;Trans-Activators;Transcript;treatment strategy;Untranslated RNA;Woman;Women's prevalence

PROJECT_TITLE: Sex-specific regulation of microRNAs in Alzheimer Disease


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Hearing Loss;Neurosciences

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Narrative A common cause of inherited hearing loss – which directly impacts >30 million people and has no cure – is the disruption of cochlear hair cell stereocilia, which are essential for transducing sound vibrations to the brain. This proposal combines advanced genetic tools, high-resolution imaging, and hearing assays to elucidate the basic cell biological mechanisms of stereocilia length regulation and determine the critical window for restoring hair cell function in vivo. Finally, this study will investigate the potential for partial reprogramming technology to expand or reopen this critical window for restoring hearing and cochlear function.

PI_NAMEs: MANOR, URI  (contact)

PROGRAM_OFFICER_NAME: FREEMAN, NANCY

PROJECT_TERMS: Actins;adenovirus mediated delivery;Adult;Apical;Architecture;Attenuated;Binding;Biological;Biological Assay;Brain;Bundling;C-terminal;Cell Maturation;Cell Physiology;Cells;cellular microvillus;Chemicals;Cochlea;Complex;Cytoskeleton;Data;deaf;deafness;Dependovirus;Development;Dimerization;Doxycycline;Elements;Embryo;Epidermal Growth Factor Receptor Pathway Substrate 8;Epithelial Cells;experimental study;Fibroblasts;Filopodia;Future;Genetic;genetic regulatory protein;Growth;Hair Cells;Hearing;hearing impairment;hearing loss treatment;hearing restoration;hereditary hearing loss;high resolution imaging;Human;Image;Immunofluorescence Immunologic;in utero;in vivo;innovation;insight;intestinal epithelium;Kinetics;Knock-out;Knockout Mice;Length;Light;Link;malformation;Mediating;Microfilaments;model organism;Modeling;Motility;Motor;Mus;mutant;myosin XVA;neonate;Neurons;normal hearing;novel;Pathology;Persons;Phenotype;postnatal;Proteins;Regulation;Role;Semicircular canal structure;Sensorineural Hearing Loss;sound;spiral ganglion;Structure;Surface;Synapses;Synaptic Transmission;Technology;tectorial membrane;Testing;Therapeutic;therapy development;tool;Transgenic Organisms;vibration;WHRN gene;Work

PROJECT_TITLE: Investigating the mechanisms of stereocilia length regulation and innovative strategies for restoring hearing


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;HIV/AIDS;Immunotherapy;Infectious Diseases;Neurodegenerative;Neurosciences

ORG_CITY: OMAHA

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF NEBRASKA MEDICAL CENTER

ORG_STATE: NE

PHR: Relevance We propose to study the novel humanized mouse model of Alzheimer’s disease we created which allows, for the first time, studies of disease progression in the face of HIV- 1 infection and antiretroviral therapy. The model now enables studies of immune cell subsets and novel therapies that enables the simultaneous suppression of viral growth while clearing plaques and tangles that affect AD progression. This research builds on groundbreaking work that served to define the mechanism(s) of viral persistence in the central nervous system, deliver medicines to sites of viral growth, and most importantly determine how specific CD4+ T cell subsets can affect the tempo of disease and secondly provide immune based disease to combat progressive viral infections.

PI_NAMEs: GENDELMAN, HOWARD E (contact);MOSLEY, R LEE

PROGRAM_OFFICER_NAME: DALEY, WILLIAM PATRICK

PROJECT_TERMS: abeta accumulation;abeta oligomer;Acceleration;adaptive immunity;Adoptive Transfer;Affect;Aging;AIDS dementia;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's neuropathogenesis;Amyloid;Amyloid beta-Protein;Amyloid beta-Protein Precursor;Amyotrophic Lateral Sclerosis;Animal Model;antiretroviral therapy;APP-PS1;Architecture;Attenuated;Award;beta Chain Antigen T Cell Receptor;Binding;Biochemical;Biomedical Research;Brain;CD4 Positive T Lymphocytes;Cell Physiology;cell type;Cells;Central Nervous System;chemokine;chimeric antigen receptor;Chronic;Clinical;Clinical Trials;Clone Cells;cognitive function;combat;comorbidity;CRISPR/Cas technology;cytokine;Data;Disease;Disease Progression;effector T cell;Emergency Situation;engineered T cells;Engineering;Epitopes;Event;familial Alzheimer disease;Foundations;fundamental research;Future;Genetic;Genetic Transcription;Grant;Growth;Hand;Helper-Inducer T-Lymphocyte;Hippocampus;HIV;HIV Infections;HIV/AIDS;Homeostasis;Human;humanized mouse;Immune;Immune response;Immune system;Immunity;Impaired cognition;in vivo;Infection;Inflammatory;insight;Intervention;Knock-in;Knock-in Mouse;Link;Macrophage;Mediating;Medicine;Microglia;Modeling;Molecular;Molecular Conformation;Monoclonal Antibodies;mouse model;Mouse Strains;Mus;mutant;Mutation;Natural Immunity;Nerve Degeneration;neuroAIDS;Neurodegenerative Disorders;Neurofibrillary Tangles;neuroinflammation;Neurologic;Neuronal Dysfunction;Neurons;neuropathology;neuroprotection;neurotoxic;novel;novel therapeutics;Outcome;Parkinson Disease;Pathogenicity;Pathology;Pathway interactions;Peripheral;Persons;Phenotype;Positioning Attribute;preclinical study;preclinical trial;Prevalence;Process;programs;Regulatory T-Lymphocyte;Research;response;Rest;Role;single-cell RNA sequencing;Site;sound;Strategic Planning;Structure;T-Cell Depletion;T-Cell Receptor;T-Lymphocyte;T-Lymphocyte Subsets;tau Proteins;Testing;theories;Therapeutic;Therapeutic Agents;Time;Tissues;Transcription Alteration;transcriptomics;Transgenic Mice;Translating;United States National Institutes of Health;Viral;Virus;Virus Diseases;Work

PROJECT_TITLE: Neuroprotective Immunity and HIV Dementia

STUDY_SECTION: HCCS

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


NIH_SPENDING_CATS: Neurosciences

ORG_CITY: PORTLAND

ORG_DEPT: OTOLARYNGOLOGY

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: Project Narrative This project will reveal novel ways in which neurons modify the strength of their signaling along their axons and synapses. Electrophysiological and a variety of optical imaging methods will be employed in mouse brain tissue. The results will be of relevance to the development of neural circuits and to the sensitivity of the brain to neuromodulators and pharmaceutical agents.

PI_NAMEs: TRUSSELL, LAURENCE O (contact)

PROGRAM_OFFICER_NAME: LEENDERS, MIRIAM

PROJECT_TERMS: Action Potentials;Axon;Behavior;Biological Models;Brain;brain tissue;Calcium;Cells;Communication;Dendrites;Dimensions;Electrophysiology (science);fluorophore;imaging modality;in vitro Model;Interneurons;Label;Memory;Mus;neonatal brain;Nerve;neural;neural circuit;neurodevelopment;Neuromodulator;neuronal cell body;Neurons;Neurotransmitter Receptor;novel;optical imaging;Pharmacologic Substance;Regulation;Research;response;Role;Sensory;Signal Transduction;Slice;Stretching;Synapses;Translating;transmission process;Work

PROJECT_TITLE: Regulation of axonal and synaptic signaling in interneurons


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Drug Abuse (NIDA only);Mental Health;Neurosciences;Opioids;Pediatric;Social Determinants of Health;Substance Misuse

ORG_CITY: ALBANY

ORG_NAME: ALBANY MEDICAL COLLEGE

PHR: PROJECT NARRATIVE  Social factors contribute to substance use disorders (SUDs), but the molecular mechanisms which support this relationship are unclear. Adolescent drug use is a risk factor for SUDs later in life, but also causes social dysfunction. In this proposal, we will examine how adolescent drug exposure impacts social development in sex- specific ways, and in turn social influence over drug-associated reward learning.

PI_NAMEs: STEPHENS, SHANNON BROOKE ZOE (contact)

PROGRAM_OFFICER_NAME: MOORE, HOLLY MARIE

PROJECT_TERMS: Adolescence;Adolescent;adolescent drug use;Adult;Affect;Area;Association Learning;Behavior;brain cell;conditioned place preference;COVID-19 pandemic;Data;Development;disorder risk;Drug Exposure;Drug Modulation;drug reward;Drug usage;early adolescence;Epidemic;Exposure to;Familiarity;Female;Food;Goals;Immune;Impairment;Investments;Learning;Learning Disorders;Life;life span;male;Measures;Mediating;Memory Disorders;Mental disorders;Microglia;Modeling;Molecular;Morphine;Neuroimmune;Nucleus Accumbens;Opioid;opioid misuse;opioid mortality;opioid use;Outcome;Phagocytes;Phagocytosis;Pharmaceutical Preparations;postnatal;preadolescence;preference;prescription opioid;Proteins;Rattus;receptor;Relapse;Resources;Rewards;Risk;Risk Factors;sex;Signal Transduction;social;Social Behavior;social deficits;Social Development;social factors;social influence;Social Interaction;Social outcome;Stimulus;Substance Use Disorder;Synapses;synaptic pruning;Testing

PROJECT_TITLE: The effect of adolescent drug-induced neuroimmune signaling in sex-specific social development and reward learning.


ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: High blood pressure or hypertension is a common and potent cardiovascular risk factor. Hypertensive heart disease refers to unfavorable enlargement, stiffening and weakening of the hearts of hypertensive patients that increase the risk of developing heart failure. This research examines how changes in microtubular structures within heart muscle cells contribute to these structural and functional abnormalities in order to develop new treatments to prevent and treat hypertensive heart disease and heart failure.

PI_NAMEs: MARGULIES, KENNETH BER (contact);PROSSER, BENJAMIN LEARS

PROGRAM_OFFICER_NAME: DESVIGNE-NICKENS, PATRICE

PROJECT_TERMS: Ablation;Animal Model;Aorta;Architecture;Automobile Driving;Biological Models;C-terminal;Cardiac;Cardiac Myocytes;cardiac tissue engineering;cardiovascular risk factor;Cells;Chronic;clinical translation;Compensation;Complement;Complex;Crosslinker;Cytoskeleton;Data;Defect;density;Dependence;Desmin;elastomeric;Elastomers;Electric Stimulation;Enzymes;Excision;experience;experimental study;Extracellular Matrix;Fibrosis;Functional disorder;Genes;Genetic;genetic approach;genetic manipulation;Goals;Heart;Heart failure;heart function;Heart Hypertrophy;hemodynamics;Human;Hypertension;hypertensive;hypertensive heart disease;Hypertrophy;Impairment;improved;In Situ;In Vitro;in vivo;induced pluripotent stem cell;insight;Intermediate Filaments;Left Ventricular Remodeling;MAP2K6 gene;MAP4;Measurement;Measures;mechanical force;mechanical properties;Mechanical Stress;Mechanics;Microtubule Stabilization;Microtubules;Modeling;mouse model;Muscle Cells;Myocardium;Myofibrils;Myofibroblast;Network-based;new therapeutic target;novel;Organ;Pathologic;Patients;pharmacologic;pressure;prevent;Process;Proteins;Relaxation;Research;Research Design;Resistance;Risk;Role;Sarcomeres;Stress;stressor;Stretching;Structure;superresolution imaging;Tail;targeted treatment;Testing;Therapeutic;therapeutic target;Time;Tissue constructs;Tissue Engineering;Tissue Model;tissue stress;Tissues;Tubular formation;Tubulin;Tyrosine;Update;Ventricular Function;viscoelasticity;Viscosity;Work

PROJECT_TITLE: Mechanical Stress-Dependent Remodeling of the Cardiac Microtubule Network

STUDY_SECTION: CCHF

STUDY_SECTION_NAME: Cardiac Contractility, Hypertrophy, and Failure Study Section[CCHF]


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

ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: Project Narrative Alzheimer's disease (AD) is the leading cause of dementia in the elderly. This project will perform innovative research to study AD risk factor SORL1 and discover new molecular mechanisms involved in AD pathogenesis. The knowledge gained from the proposed research will provide fundamental information needed for development of new therapeutics for treating AD.

PI_NAMEs: LI, LIAN  (contact)

PROGRAM_OFFICER_NAME: LI, TONG

PROJECT_TERMS: Address;Age;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease risk;Alzheimer’s disease biomarker;Amino Acids;Amyloid beta-Protein Precursor;Area;Asparagine;Autopsy;autosome;biomarker development;Brain;brain tissue;case control;Cell membrane;Cell surface;Clinical Trials;Code;cohort;Consensus Sequence;Cytoplasmic Tail;Dementia;Development;Disease;early onset;EGF-Like Domain;Elderly;Endosomes;experimental study;extracellular;familial Alzheimer disease;Fibronectins;follow-up;Frontotemporal Dementia;Functional disorder;Genes;Genetic;genetic risk factor;Glycopeptides;Glycoproteins;glycoproteomics;glycosylation;Human;Impairment;in vivo;innovation;insight;Intervention;Knowledge;Late Onset Alzheimer Disease;Link;loss of function;loss of function mutation;Low Density Lipoprotein Receptor;Lysosomes;Mass Spectrum Analysis;Membrane Proteins;mild cognitive impairment;Modification;Molecular;Molecular Analysis;Mutation;N-Glycosylation Site;Nerve Degeneration;neuropathology;neuroprotection;novel;novel therapeutic intervention;novel therapeutics;Parkinson Disease;Pathogenesis;Pathogenicity;Pathologic;Play;Polysaccharides;Positioning Attribute;Post-Translational Protein Processing;presenilin-1;presenilin-2;protein folding;protein transport;Proteins;rare variant;receptor;Regulation;Research;Risk Factors;Role;Sampling;Site;sortilin;Sorting;System;Tertiary Protein Structure;Testing;therapeutic development;trafficking;trans-Golgi Network;Transmembrane Domain;Treatment Efficacy;Vacuolar Protein Sorting;Validation;Variant

PROJECT_TITLE: Molecular analysis of SORL1 function and dysfunction in Alzheimer's disease

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


NIH_SPENDING_CATS: Brain Disorders;Huntington's Disease;Neurodegenerative;Neurosciences;Rare Diseases

ORG_CITY: ORLANDO

ORG_NAME: UNIVERSITY OF CENTRAL FLORIDA

ORG_STATE: FL

PHR: PROJECT NARRATIVE Quantitation of cerebrospinal fluid (CSF) mutant huntingtin (HTT) is being used in HTT lowering clinical trials as a target engagement biomarker, but we lack the understanding of CSF mutant HTT required to interpret this data in a meaningful way. This study will determine the source and mechanism(s) of mutant HTT entry to CSF in order to better understand what treatment-induced changes mean and assess longitudinal changes in CSF HTT in individuals to correlate to clinical signs and aid in trial participant selection. The results of this study will enable substantive use of CSF HTT quantitation as a biomarker of HTT lowering and Huntington disease onset and/or progression.

PI_NAMEs: SOUTHWELL, AMBER L (contact)

PROGRAM_OFFICER_NAME: MILLER, DANIEL L

PROJECT_TERMS: Active Biological Transport;Acute Brain Injuries;Address;Alleles;Antisense Oligonucleotides;Basal Ganglia;biobank;Biological Markers;Blood;Brain;brain cell;Brain region;British Columbia;Cell Physiology;cell type;Cells;Cerebrospinal Fluid;Clinic;Clinical;Clinical Treatment;clinical trial participant;Clinical Trials;Collection;Complex;Data;Data Analyses;detection assay;Development;Discrimination;Disease;Disease Progression;Dose;Eligibility Determination;extracellular;Flow Cytometry;glymphatic clearance;glymphatic system;Goals;Health;Huntington Disease;Huntington gene;Immunoprecipitation;Individual;injured;Intervention;Kinetics;Knowledge;Longitudinal cohort;Longitudinal Studies;man;Measurement;Measures;MicroRNAs;Monitor;Mus;mutant;Nerve Degeneration;Neurons;neuroprotection;novel;Onset of illness;Participant;Pathway interactions;Patients;Phase;phenotypic data;Placebos;Plasma;pre-clinical;Predictive Value;Proteins;Sampling;Source;Structure;System;Therapeutic;Time;Tissues;tool;Universities;Viral Vector;Work

PROJECT_TITLE: Decoding cerebrospinal fluid huntingtin biomarkers

STUDY_SECTION: CDIN

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


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: EUGENE

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF OREGON

PHR: PROJECT NARRATIVE Disrupted organ size control mechanisms underlie a multitude of birth defects, deficient tissue repair, and cancer. The proposed research studies cellular and molecular processes that perfectly restore size and scale during an astonishing example of innate vertebrate organ regeneration. As such, the project will uncover conceptual and specific mechanisms that may be disrupted in human disease while also guiding novel regenerative medicine approaches.

PI_NAMEs: STANKUNAS, KRYN  (contact);STEWART, SCOTT J

PROGRAM_OFFICER_NAME: SALAZAR, DESIREE LYNN

PROJECT_TERMS: Adult;Anatomy;Apoptosis;bioelectricity;Biological Process;biophysical properties;blastema;Bone Diseases;Calcineurin;candidate identification;cell behavior;Cell Cycle;Cell Lineage;Cell membrane;Cells;Congenital Abnormality;Development;Developmental Biology;Distal;Ectopic Expression;Exhibits;experimental study;Fibroblasts;gain of function;Genes;Genetic;Genetic Epistasis;Genetic Transcription;Growth;Growth Factor;Homeostasis;Human;human disease;Image;In Situ;Individual;Injury;Ions;Kinetics;Lead;Link;loss of function;Malignant Neoplasms;Measurement;Mesenchyme;migration;Modeling;Molecular;mutant;Mutate;Mutation;Natural regeneration;Nature;novel;Organ;organ regeneration;organ repair;Organ Size;Output;Pattern;pharmacologic;Phase;Phenotype;Positioning Attribute;Potassium Channel;PPP3CA gene;Process;progenitor;regenerative;Regenerative Medicine;Reporter;Reporter Genes;Research;research study;restoration;restraint;Second Messenger Systems;Shapes;Signal Transduction;single-cell RNA sequencing;skeletal regeneration;small molecule inhibitor;spatiotemporal;System;Testing;tissue repair;Transcript;transcriptome sequencing;transcriptomics;Transgenic Organisms;Transplantation;tumor;voltage;Voltage-Gated Potassium Channel;Zebrafish

PROJECT_TITLE: Ion signaling, cell transitions, and organ scaling during fin regeneration

STUDY_SECTION_NAME: Development - 1 Study Section[DEV1]


NIH_SPENDING_CATS: Antimicrobial Resistance;Human Fetal Tissue;Infectious Diseases;Organ Transplantation;Transplantation

ORG_CITY: DOYLESTOWN

ORG_NAME: EVRYS BIO, LLC

PHR: PROJECT NARRATIVE An overwhelming number of Americans require immune suppression of variable duration at some point in their lives due to various diseases from asthma to HIV to rheumatologic diseases to organ transplant - during the time at which their immune system is being suppressed these individuals are at great risk for developing an opportunistic viral infection that can be caused by many different types of viruses. Standard of care therapeutic interventions for these patients are restricted by highly focused targeting of only select viruses and the emergence of drug resistant strains. Successful completion of this application will result in a clinically ready, orally taken, antiviral drug that 1) provides protection against highly diverse viruses and 2) limits the acquisition of drug resistance.

PI_NAMEs: REMISZEWSKI, STACY  (contact)

PROGRAM_OFFICER_NAME: DAVIS, MINDY I

PROJECT_TERMS: absorption;acquired drug resistance;Address;Adenoviruses;Adult;Alabama;Allogenic;American;Anti-viral Agents;Asthma;Biological Availability;BK Virus;Canis familiaris;Cell Culture Techniques;Cell Transplantation;Cells;Chemicals;clinic ready;Clinical;clinical development;Clinical effectiveness;Clinical Investigator;clinical practice;Clinical Research;Clinical Trials;Clinical Trials Design;Collaborations;college;commercialization;Communities;Controlled Study;cost;Cytomegalovirus;Cytomegalovirus Infections;Data;design;Disease;DNA Viruses;Dose;drug candidate;drug development;Drug Kinetics;Drug resistance;drug resistant influenza;Economic Burden;Effectiveness;efficacy study;Evaluation;Evolution;Excretory function;Family;Funding;General Hospitals;good laboratory practice;Graft Rejection;Health;Hematopoietic Stem Cell Transplantation;Hepatic;Hepatitis B;Hepatitis Viruses;Herpesviridae;high risk;HIV;Human;Human Herpesvirus 4;Immune system;immunosuppressed;Immunosuppression;In Vitro;in vivo;in vivo Model;Individual;Industry;Infection;infection risk;Influenza A virus;inhibitor;Investigational Drugs;Laboratories;Lead;Letters;Liver;London;Lung;manufacture;Marketing;meetings;member;Metabolism;Modeling;Morbidity - disease rate;mortality;Mus;Opportunistic Infections;Oral;Oral Administration;Organ;organ transplant recipient;Organ Transplantation;Organoids;pathogen;Patient Selection;Patients;Pharmaceutical Preparations;Phase;Plasma;Polyomavirus;post-market;Predisposition;prevent;Primary Infection;product development;Prophylactic treatment;Proteins;prototype;Publishing;Rattus;Recommendation;Regimen;Reporting;Resistance;Resistance development;resistant strain;respiratory virus;Rheumatism;Risk;risk minimization;RNA Viruses;safety practice;safety study;Serial Passage;seropositive;Serum;Sirtuins;Small Business Innovation Research Grant;standard of care;targeted treatment;Testing;Therapeutic;Therapeutic immunosuppression;Therapeutic Intervention;Time;Tissue Donors;Toxic effect;Toxicology;traditional therapy;translational study;Transplant Recipients;Transplantation;Transplantation and Immune System;Travel;Universities;Variant;Viral;Viral Drug Resistance;Viral Physiology;virology;Virus;Virus Diseases;Virus Latency

PROJECT_TITLE: A single antiviral to treat multiple opportunistic infections


NIH_SPENDING_CATS: Brain Disorders;Clinical Research;Congenital Structural Anomalies;Epilepsy;Genetics;Human Fetal Tissue;Human Genome;Neurodegenerative;Neurosciences;Pediatric

ORG_CITY: BOSTON

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: PROJECT NARRATIVE Somatic mutations, those that exists in a subset of cells in the body, impact numerous neurologic disorders. However, because of the difficulty in identifying rare mutations accurately, we do not know the extent to which somatic mutations affect the brain. This proposal applies innovative technology to find somatic mutations that cause epilepsy and brain malformations and makes estimates of the degree to which normal brain development is impacted by somatic mutations.

PI_NAMEs: SHAO, DIANE D (contact)

PROGRAM_OFFICER_NAME: REZAIZADEH, KAVON PAUL

PROJECT_TERMS: Address;Advisory Committees;Affect;Algorithms;analytical method;Area;autism spectrum disorder;Automobile Driving;Autopsy;Awareness;Bioinformatics;Biological Sciences;Boston;Brain;brain malformation;Candidate Disease Gene;career;Cell Cycle;Cell division;Cells;Cellular biology;Child;childhood epilepsy;Childhood Neurological Disorder;Clinical;clinical application;clinical practice;cohort;Communities;Cortical Dysplasia;Data;Detection;Development;Developmental Process;Diagnosis;Disease;DNA;Early identification;Epilepsy;epileptic encephalopathies;Evaluation;exome;exome sequencing;experience;fetal;Future;gene discovery;Genes;Genetic;Genome;genome sequencing;Genomic medicine;Genotype;Goals;hemimegalencephaly;Heritability;Hospital Departments;Human;Human Development;human fetal brain;Human Genetics;Individual;infancy;innovative technologies;insight;Investigation;Laboratories;Life;life span;Malignant Neoplasms;Medical;Medical Genetics;medical schools;Mental disorders;Mentors;Methods;Molecular Biology;Mosaicism;Mutation;Mutation Analysis;Neoplasms;Nerve Degeneration;nerve stem cell;Nervous System Disorder;neurodevelopment;neurogenetics;Neurology;Neurons;Neurosciences;Normal tissue morphology;novel;Pattern;Pediatric Hospitals;Phenotype;Physicians;Population Attributable Risks;postmitotic;postnatal;Pregnancy;Prevalence;Publishing;rare variant;rate of change;Recurrence;Research;Research Personnel;Resources;Risk;Scientist;Single Nucleotide Polymorphism;skill acquisition;skills;Somatic Mutation;Statistical Data Interpretation;Technology;Time;Tissues;tool;Training;Variant;whole genome

PROJECT_TITLE: Somatic Mutations in Neurodevelopment and Disease

STUDY_SECTION: NST

STUDY_SECTION_NAME: NST-1 Study Section[NST-1]


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Behavioral and Social Science;Brain Disorders;Clinical Research;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Emerging Infectious Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Infectious Diseases;Networking and Information Technology R&D (NITRD);Prevention;Primary Health Care;Rural Health;Social Determinants of Health;Substance Misuse;Telehealth

ORG_CITY: BELTSVILLE

ORG_NAME: PACIFIC INSTITUTE FOR RES AND EVALUATION

ORG_STATE: MD

PHR: PROJECT NARRATIVE COVID-19 and necessitated state Medicaid telehealth policies impacting alcohol and substance use disorder treatment delivery provide an opportunity to use varying policy interventions across all states as a natural experiment to investigate the impact of telehealth service expansion on AUD and SUD service utilization. The proposed study aims to evaluate state Medicaid telehealth policies on AUD and SUD treatment use of medically underserved Federally Qualified Health Centers patient populations. Thus, the proposed research is relevant to the NIAAA and NIDA's goals to improve existing behavioral treatments for alcohol and substance use.

PI_NAMEs: WHARTON, MARY KRISTINA (contact)

PROGRAM_OFFICER_NAME: WHITAKER, DAMIYA EVE

PROJECT_TERMS: Address;Adoption;Agricultural Workers;Alcohol consumption;alcohol use disorder;American;analytical method;Annual Reports;barrier to care;Behavior Therapy;Caring;Categories;Characteristics;connected health;Coronavirus;COVID-19;COVID-19 pandemic;Data;Data Analyses;Data Collection;Economics;Enrollment;Essential worker;Evaluation;Family;Federally Qualified Health Center;Funding;Goals;health care delivery;health inequalities;Health Policy;Health Services;Health Services Accessibility;Health system;Healthcare;Homelessness;Improve Access;improved;Individual;Information Systems;innovation;Insurance Coverage;Intervention;Knowledge;Legal;Low income;Measures;Medicaid;medically underserved;medically underserved population;medication-assisted treatment;Mental Health Services;Methods;Migrant;Mission;Modeling;Morbidity - disease rate;mortality;National Institute of Drug Abuse;National Institute on Alcohol Abuse and Alcoholism;Natural experiment;new pandemic;Outcome;pandemic disease;patient oriented;patient population;Patients;people of color;Persons;Policies;Policy Analysis;Population;Population Characteristics;post-pandemic;pre-pandemic;prevent;Primary Care;programs;Provider;Public Housing;Reporting;Research;Resources;response;rural area;Safety;Seasons;Security;Series;Service provision;service utilization;Services;societal costs;Special Population;Statutes and Laws;Stress;substance use;Substance Use Disorder;substance use treatment;Technology;telehealth;underserved community;Underserved Population;Unemployment;United States;United States Health Resources and Services Administration;Variant;Virus;Visit;Woman

PROJECT_TITLE: COVID-19 Telehealth Policies' Impact on Provision of Alcohol and Substance Use Disorder Services at Federally Qualified Health Centers

STUDY_SECTION: AA

STUDY_SECTION_NAME: Epidemiology, Prevention and Behavior Research Study Section[AA-2]


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Attention Deficit Hyperactivity Disorder (ADHD);Brain Disorders;Drug Abuse (NIDA only);Mental Health;Substance Misuse

ORG_CITY: HIGH POINT

ORG_NAME: HIGH POINT UNIVERSITY

PHR: PROJECT NARRATIVE The ultimate goal of this work is to discover candidate medications and develop new molecular tools to study the dopamine D4 receptor (D4R) and its variants, the more common D4.4R variant, and the ADHD- and substance use disorder-associated D4.7R minor variant. Developing new molecular tools to elucidate the role of D4R variant signaling through the discovery of D4.4R- and D4.7R-selective compounds can untangle the important signaling effects of this receptor and identify potential targets for medications development for ADHD and substance use disorders.

PI_NAMEs: BOATENG, COMFORT AHENKAN (contact)

PROGRAM_OFFICER_NAME: HILLERY, PAUL

PROJECT_TERMS: Address;Adrenergic Receptor;Affinity;Agonist;analog;antagonist;Attention;Attention deficit hyperactivity disorder;Cognition;Computer Models;Decision Making;design;Development;Disease;Dopamine D2 Receptor;DRD4 gene;FDA approved;Genetic Polymorphism;Goals;Human;in vivo;Libraries;Ligands;Minisatellite Repeats;Minor;Molecular;neuropsychiatric disorder;novel;Pharmaceutical Preparations;pharmacologic;Physiological;Play;Prevalence;protein structure;rational design;receptor;receptor function;Receptor Signaling;Research;response;Role;Signal Transduction;stimulant use disorder;Substance Use Disorder;Therapeutic;tool;Variant;Work

PROJECT_TITLE: Development of High-Affinity and Selective Ligands as a Pharmacological Tool for the Dopamine D4 Receptor (D4R) Subtype Variants


ORG_CITY: OKLAHOMA CITY

ORG_NAME: OKLAHOMA MEDICAL RESEARCH FOUNDATION

ORG_STATE: OK

PHR: Narrative Errors in the process of distributing chromosomes to the gametes, are the major cause of spontaneous abortions and birth defects and are an important contributor to infertility. This project uses a novel technology based on lacO/lacR (Operator/Repressor) and combines genetic and cellular approaches to unravel the mechanisms of double-strand break repair and by which the homologous chromosomes find each other and establish permanent connections, all of which is of paramount importance in preventing the chromosome segregation errors that lead to birth defects.

PI_NAMEs: PEZZA, ROBERTO JOSE (contact)

PROGRAM_OFFICER_NAME: TAYMANS, SUSAN

PROJECT_TERMS: 3-Dimensional;Affect;Aneuploidy;autosome;Biological Assay;Biological Process;cell behavior;chromosome missegregation;Chromosome Pairing;Chromosome Segregation;Chromosomes;Co-Immunoprecipitations;Communities;Complex;Congenital Abnormality;Cytoskeleton;Data;Development;Disease;DNA Repair;Double Strand Break Repair;Down's Syndrome;Dynein ATPase;Ensure;Event;Failure;Fertilization;Fluorescence;Gametogenesis;Genetic;Genetic Recombination;Genome engineering;genome-wide;genomic locus;Genomic Segment;Germ Cells;Goals;Homologous Gene;Human;in silico;in vivo;Infertility;inhibitor;Karyotype;Kinesin;Knockout Mice;Knowledge;Lac Repressors;Location;Mammals;Measurement;Measures;Mediating;Meiosis;Meiotic Prophase I;Meiotic Recombination;Microscopy;Microtubules;Modeling;Molecular Motors;Motion;Motor;Movement;movie;MSH4 gene;Mus;mutant;new technology;novel;Nuclear Envelope;Physiological;Play;pregnancy disorder;Pregnancy loss;prevent;Process;Productivity;Prophase;Proteins;Proteomics;recruit;Regulation;repaired;Reporter;Research;Resolution;Resources;Role;scaffold;segregation;Seminiferous tubule structure;Sex Chromosomes;simulation;Site;Spermatocytes;SPO11 gene;Spontaneous abortion;Synaptonemal Complex;System;telomere;Testing;Time;Tissues;tool;Translating;Visualization

PROJECT_TITLE: Development of a lacO/lacI based fluorescence reporter-operator system to study chromosome dynamics and double-strand break repair in mouse meiosis.

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


NIH_SPENDING_CATS: Behavioral and Social Science;Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Heart Disease;Networking and Information Technology R&D (NITRD);Physical Activity;Prevention;Social Determinants of Health;Telehealth

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: Project Narrative/Relevance to Public Health Statement Heart failure is projected to affect more than 8-million American adults by 2030 and is a leading cause of morbidity and mortality. Physical activity improves outcomes for patients with heart failure, although most heart failure patients rarely participate in enough physical activity. This research will use mobile technology to characterize real-time factors such as symptoms, mood, and motivation that impact physical activity for heart failure patients, and then use that information to adapt and pilot a mobile health intervention to support heart failure patients in being more physically active.

PI_NAMEs: GOLBUS, JESSICA RACHEL (contact)

PROGRAM_OFFICER_NAME: DONZE, LAURIE FRIEDMAN

PROJECT_TERMS: adaptive intervention;Address;Adult;Affect;American;Behavioral;behavioral health;beneficiary;Biological;Biological Factors;Cardiac rehabilitation;Cardiovascular Diseases;Cardiovascular system;career development;Cellular Phone;Chronic;Chronic Disease;Clinical;clinical encounter;Clinical Trials;cohort;community based participatory research;comorbidity;Data;design;Deterioration;Development;Development Plans;Disease;Disease Management;Doctor of Philosophy;Ecological momentary assessment;Educational workshop;EFRAC;Eligibility Determination;Enrollment;Ensure;Environment;exercise capacity;Feedback;Frequencies;General Population;Geography;Goals;Health Technology;Heart failure;heart failure with reduced ejection fraction;Heart Transplantation;Home;Hospitalization;improved;improved outcome;innovation;Interdisciplinary Study;Intervention;K-Series Research Career Programs;Learning;lifestyle intervention;Longitudinal cohort study;Medicare;Mentors;Mentorship;Methods;mHealth;mhealth interventions;Michigan;mobile computing;Moods;Morbidity - disease rate;mortality;Motivation;Notification;Participant;Patient Participation;Patient-Focused Outcomes;Patients;personalized care;Phenotype;Physical activity;Physical Function;physical inactivity;Population;Predictive Factor;preservation;primary outcome;Process;programs;psychosocial;Psychosocial Factor;Public Health;Quality of life;Questionnaires;racial disparity;Randomized;randomized trial;recruit;Research;Research Activity;research clinical testing;Research Design;Resources;Self Determination;Self Management;sex;skills;smart watch;sociodemographic factors;Statistical Methods;Structure;Surveys;Symptoms;Technology;theories;Time;Time Factors;Training;Training Activity;treatment as usual;Universities;user centered design;Variant;Vision;wearable data;Weather;Work

PROJECT_TITLE: MObile health interVention to INcrease activity in Heart Failure (MOVIN-HF)

STUDY_SECTION: MPOR

STUDY_SECTION_NAME: NHLBI Mentored Patient-Oriented Research Study Section[MPOR(JA)]


ED_INST_TYPE: UNIVERSITY-WIDE

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Cardiovascular;Congenital Heart Disease;Congenital Structural Anomalies;Dental, Oral, and Craniofacial Disease;Genetics;Heart Disease;Human Genome;Pediatric;Primary Immunodeficiencies;Rare Diseases

ORG_CITY: BRONX

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

PHR: PROJECT NARRATIVE: In 22q11.2 deletion syndrome, around 60% of patients present with cardiac defects, largely due to a deletion that includes TBX1; this provides a unique population in which to investigate possible genetic modifiers of heart development. Our lab performed whole genome sequence analysis on human subjects and discovered a subset of chromatin regulatory genes associated with heart defects in 22q11.2 deletion syndrome. This study aims to determine the mechanism by which Tbx1 interacts with these chromatin regulatory genes, particularly Kmt2c and Kmt2d, in mouse heart development.

PI_NAMEs: MILLER, DANIELLA  (contact)

PROGRAM_OFFICER_NAME: MEADOWS, TAWANNA

PROJECT_TERMS: 22q11;Actins;Affect;aortic arch;Apoptosis;Arteries;ATAC-seq;Binding;Biological Assay;Birth;Branchial arch structure;Cardiac;cardiogenesis;Cell Proliferation;cell type;ChIP-seq;Chromatin;Chromatin Remodeling Factor;Code;Complex;conditional knockout;Congenital Abnormality;congenital anomaly;congenital heart abnormality;conotruncal heart defect;Data;Data Set;Defect;Development;Developmental Process;Diagnosis;differential expression;DiGeorge Syndrome;DNA Damage;Embryo;Embryonic Development;Endothelium;Enhancers;Etiology;Event;experimental study;Family;functional genomics;Future;Gene Expression;Gene Expression Profile;gene function;General Population;Genes;Genetic;genetic architecture;Genetic Recombination;Genetic Transcription;genetic variant;Genetic Variation;Genome;genome-wide;Health;Heart;heart defect;Histologic;Histone H3;histone methyltransferase;histone modification;Human;human subject;Immunofluorescence Immunologic;improved;In Situ Hybridization;India ink stain;individualized medicine;Infant;Inherited;Injections;interest;Interruption;Investigation;Knowledge;Live Birth;LoxP-flanked allele;Lysine;Methylation;Methyltransferase;Molecular;mortality;mouse model;Mus;mutant;Mutant Strains Mice;Neural Crest Cell;Pathway interactions;Patient Care;Patients;PECAM1 gene;Pharyngeal Apparatus;Phenotype;Population;Predisposition;Process;Quantitative Reverse Transcriptase PCR;Regulation;Regulator Genes;Role;Sequence Analysis;single-cell RNA sequencing;Smooth Muscle;Stains;Structure;TdT-Mediated dUTP Nick End Labeling Assay;Testing;theories;Therapeutic;transcription factor;Validation;Variant;whole genome

PROJECT_TITLE: Investigation of Chromatin Modifiers to Elucidate the Phenotypic Variability of Congenital Heart Disease in Patients with 22q11.2 Deletion Syndrome

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F10A-K (20)]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Autoimmune Disease;Diabetes;Eye Disease and Disorders of Vision;Neurosciences;Prevention

ORG_CITY: BALTIMORE

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: PROJECT NARRATIVE: Most patients with diabetic eye disease – one of the most common causes of severe vision loss in working-age Americans – respond inadequately to current therapies. Moreover, aside from tight control of serum glucose, little else can be offered to patients to help prevent the development of early stages – or progression to late stages – of diabetic rertinopahy, highlighting the need to examine new molecular targets for its treatment. To expose novel therapeutic targets for the early treatment and/or prevention of this vision-threatening disease, we propose to interrogate the molecular basis whereby hypoxia inducible factor (HIF) accumulation in response to glucose dysregulation promotes progression of early diabetic eye disease.

PI_NAMEs: SODHI, AKRIT SINGH (contact)

PROGRAM_OFFICER_NAME: SHEN, GRACE L

PROJECT_TERMS: Adult;Age;American;angiogenesis;Automobile Driving;Background Diabetic Retinopathy;Blindness;Blood Vessels;Cells;Clinical;Clinical Trials;Complications of Diabetes Mellitus;cost;Development;diabetes control;Diabetes Mellitus;diabetic;Diabetic Retinopathy;Disease;Dose;droplet sequencing;Early treatment;Equilibrium;Event;Exposure to;Eye diseases;Gene Expression;Genes;Genetic;Glucose;Glucose Transporter;glycemic control;Glycolysis;Glycosylated Hemoglobin;Glycosylated hemoglobin A;Growth;Healthcare;high risk;Hyperglycemia;Hypoglycemia;Hypoxia;Hypoxia Inducible Factor;hypoxia inducible factor 1;in vivo Model;inhibitor;Injections;Injury;insight;Insulin;macrovascular disease;Mediating;Mediator;Modeling;Molecular;Molecular Target;Muller's cell;Mus;Neuroglia;new therapeutic target;novel;novel therapeutics;Nuclear;Oxygen;p38 Mitogen Activated Protein Kinase;Pathologic;Pathway interactions;Patients;pharmacologic;Phase;Physiological;prevent;Prevention;Prevention therapy;proliferative diabetic retinopathy;Regulation;Reporting;response;Retina;retinal ischemia;retinal neuron;RNA;Role;Safety;Serum;Signal Pathway;SLC2A1 gene;targeted treatment;Therapeutic;transcription factor;Treatment Efficacy;United States;vascular injury;Vision

PROJECT_TITLE: Hypoxia Inducible Factors and Hypoglycemia in Early Diabetic Eye Disease

STUDY_SECTION_NAME: Pathophysiology of Eye Disease - 1 Study Section[PED1]


NIH_SPENDING_CATS: Breast Cancer;Cancer;Cardiovascular;Heart Disease;Hematology;Prevention;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Women's Health Research

ORG_CITY: Columbus

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: Project Narrative Anthracycline-based chemotherapeutics such as doxorubicin are among the most effective and widely prescribed anticancer agents, but their clinical use is associated with dose-limiting damage to the heart muscle (cardiotoxicity). Using unique genetic mouse models, we found that acute and chronic forms of cardiotoxicity caused by doxorubicin are dependent on an uptake process in the heart that is mediated by the transporter OCT3. The proposed studies are a logical continuation of our prior NCI-funded studies and will directly test the hypothesis that targeted interference of OCT3 with pharmacological inhibitors can mitigate the incidence and severity of this debilitating side effect without affecting the agent’s anticancer properties.

PI_NAMEs: ADDISON, DANIEL ;BAKER, SHARYN D;SPARREBOOM, ALEXANDER  (contact)

PROGRAM_OFFICER_NAME: ADHIKARI, BISHOW B

PROJECT_TERMS: access restrictions;Acute;Acute leukemia;Adriamycin PFS;Affect;aggressive breast cancer;Anthracycline;Antineoplastic Agents;Biological Markers;biomarker driven;Breast Cancer Cell;Breast Cancer cell line;Breast Cancer Model;Calcium-Binding Proteins;Calgranulin A;Cancer cell line;Cancer Patient;Cardiac;cardiac magnetic resonance imaging;Cardiac Myocytes;cardioprotection;Cardiotoxicity;Cardiovascular Physiology;Cell Line;Cells;Chronic;Clinical;combinatorial;Combined Modality Therapy;companion diagnostics;conditional knockout;cytotoxic;Data;Dose;Dose Limiting;Doxorubicin;Drug Kinetics;efficacy evaluation;Etiology;Event;experience;Experimental Models;Famotidine;FDA approved;Funding;future implementation;Genetic;Goals;Heart;heart damage;Heart Injuries;Hematologic Neoplasms;Human;human induced pluripotent stem cells;improved;In Vitro;in vivo;Incidence;Incubated;induced pluripotent stem cell derived cardiomyocytes;inhibitor;insight;Intervention;Knock-in;Knock-out;Knockout Mice;Lead;leukemia;Leukemic Cell;Libraries;Malignant Breast Neoplasm;Measures;Mediating;metabolomics;metaiodobenzylguanidine;Methods;Modeling;mouse model;Mus;Myocardium;novel;Oncology;Organic Cation Transporter;overexpression;Pathway interactions;Patients;Pharmaceutical Preparations;pharmacologic;Plasma;potential biomarker;preservation;prevent;Preventive treatment;Process;Property;Publishing;Regimen;S100A8 gene;S100A9 gene;Safety;Sampling;Serotonin;Severities;side effect;Signal Transduction;single photon emission computed tomography;Solid;Solid Neoplasm;specific biomarkers;Techniques;Testing;Therapeutic;Toxic effect;Toxicokinetics;Treatment Protocols;tumor;uptake;Validation;validation studies;women's diagnosis;Work;X-Ray Computed Tomography

PROJECT_TITLE: Therapeutic Strategies to Mitigate Toxicities of Anthracycline-Based Therapeutics

STUDY_SECTION: MPPA

STUDY_SECTION_NAME: Integrative Myocardial Physiology/Pathophysiology A Study Section [MPPA]


ED_INST_TYPE: GRADUATE SCHOOLS

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Mental Health;Pediatric;Prevention

ORG_CITY: NOTRE DAME

ORG_DEPT: SOCIAL SCIENCES

ORG_NAME: UNIVERSITY OF NOTRE DAME

ORG_STATE: IN

PHR: PROJECT NARRATIVE Marital conflict is linked to a wide range of severe adjustment problems in both children and adults, so a critical need exists to identify mechanisms of constructive prevention and intervention through multi-method, process- oriented analyses. The goal of this research is to test the hypothesis that empathic communication and perceived understanding are key mechanisms that help explain how an RCT intervention improved short-term conflict resolution and long-term emotional security and relational satisfaction within families. This project has the potential to advance understanding of how constructive family conflict behavior is causally linked to relational family outcomes, and it may therefore inform the design of more effective family interventions.

PI_NAMEs: DEVONSHIRE, JOEL  (contact)

PROGRAM_OFFICER_NAME: ESPOSITO, LAYLA E

PROJECT_TITLE: Assessing Mechanisms of Action in Family Intervention: The Roles of Empathic Communication and Perceived Understanding

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F16-H (20)]


ORG_CITY: East Greenwich

ORG_NAME: GORDON RESEARCH CONFERENCES

ORG_STATE: RI

PHR: Project Narrative Implants based on neuroelectronic interfaces, which are central to the treatment of many neurological diseases or injuries and can be used to record and/or stimulate neural activity, are quickly becoming the fastest growing sector of biomedical devices. Despite significant initial successes, various challenges exist with the development and translation of neuroelectronic interfaces for some clinical indications. The proposed conference will support the ability of the international community to come together in partnership to develop multidisciplinary solutions that benefit society.

PI_NAMEs: JUDY, JACK W (contact)

PROGRAM_OFFICER_NAME: GROSS, BROOKS ANDREW

PROJECT_TERMS: Address;Area;Atmosphere;Autonomic nervous system;Brain;career;Chemistry;Child Care;childcare allowance;Chronic;Clinical;clinical practice;clinical translation;Collaborations;Communication;Communities;community building;community engagement;cost;Critical Thinking;design;Development;Devices;Disabled Persons;Disease;effective therapy;Electrodes;Engineering;Environment;Ethics;Event;expectation;experience;Face;Fostering;Fund Raising;Funding;graduate student;Health;Implant;innovation;innovative neurotechnologies;insight;International;Knowledge;materials science;Mathematics;Medicine;meetings;member;Methods;minimally invasive;Minority;Minority Groups;minority investigator;multidisciplinary;Nature;Nervous System;Nervous System Disorder;Nervous System Trauma;neural;neural stimulation;Neurological disability;neuropathology;Neurosciences;Neurosciences Research;neurotechnology;next generation;novel;Participant;Patients;Peripheral Nervous System;Persons;physical model;Play;Positioning Attribute;Postdoctoral Fellow;programs;psychiatric disability;Qualifying;Regulation;Research;Research Personnel;Role;Science;Scientific Advances and Accomplishments;Scientist;skills;Societies;Spinal Cord;Students;success;symposium;System;technological innovation;Technology;Translating;Translations;Travel;Underrepresented Populations;United States National Institutes of Health;unpublished works;Validation;wearable device;Woman;Work

PROJECT_TITLE: 2024 Neuroelectronic Interfaces Gordon Research Conferences and Gordon Research Seminar

STUDY_SECTION_NAME: Special Emphasis Panel[ZNS1 SRB-P (11)]


NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Mental Health;Social Determinants of Health;Substance Misuse

ORG_DEPT: PSYCHOLOGY

ORG_NAME: TEMPLE UNIV OF THE COMMONWEALTH

ORG_STATE: PA

PHR: PROJECT NARRATIVE The relationship between alcohol use and aggression is widely recognized, however treatments for alcohol use disorders rarely focus on treating aggression. As people with both alcohol use and aggression problems may have unique treatment needs including more focus on aggression problems and their relationship to alcohol use, we propose to develop and test a treatment that integrates existing effective treatment for these two problems. Our goal is to learn (1) how acceptable and realistic this integrated treatment would be to administer to patients, and (2) how impactful the treatment would potentially be in reducing drinking and aggression.

PI_NAMEs: COCCARO, EMIL FRANK;MCCLOSKEY, MICHAEL S (contact)

PROJECT_TERMS: acceptability and feasibility;Aggressive behavior;Alcohol abuse;alcohol abuse therapy;Alcohol consumption;alcohol intervention;alcohol use disorder;Alcohols;Anger;Attention;biological sex;Caring;Clinical Trials;clinically significant;Cognitive;Cognitive Therapy;Communities;comorbidity;Coping Skills;Data;Development;digital;drinking;drinking behavior;effective therapy;Elements;epidemiologic data;experimental study;Frequencies;Gender;Goals;Individual;individualized medicine;Integrative Therapy;Intervention;intervention refinement;Learning;Literature;Maintenance;Manuals;meetings;Neurobiology;novel;Outcome;Participant;Patients;personalized medicine;Persons;Phase;Pilot Projects;Preparation;programs;psychosocial;Public Health;Randomized;Randomized, Controlled Trials;Regulation;Relapse;Relaxation;Reporting;Research;Risk Factors;Sample Size;Sampling;secondary analysis;Secondary to;skills training;social;standard of care;Subgroup;symposium;Testing;Therapeutic Intervention;therapy development;Time;treatment effect;Treatment Efficacy;Treatment outcome;treatment research;trial comparing;Work

PROJECT_TITLE: Development of an Integrated Psychosocial Intervention for Alcohol Use Disorder with Comorbid Aggression

STUDY_SECTION_NAME: Clinical, Treatment and Health Services Research Study Section[AA-3]


NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Genetics;Neurodegenerative;Neurosciences;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

PHR: PROJECT NARRATIVE Disruptions in branched-chain amino acid metabolism have been recently implicated in the pathogenesis of multiple neurodegenerative disorders. This project aims to reveal if loss of branched-chain amino acid transaminase-1 (BCAT1) is sufficient to induce neurodegeneration and elucidate how alterations in metabolic homeostasis drive disease progression. Insights from this work will aid the discovery of novel neurodegenerative pathways and further the development of more targeted therapeutics.

PI_NAMEs: DISANZA, BRIANNA  (contact)

PROGRAM_OFFICER_NAME: RANGANATHAN, SRIKANTH

PROJECT_TERMS: Adult;Alleles;amino acid metabolism;Amino Acids;Antimycin A;Antioxidants;Biogenesis;Biological Assay;Branched-Chain Amino Acids;branched-chain-amino-acid transaminase;Caenorhabditis elegans;career;career development;Catabolism;Cell Death;Cells;Central Nervous System;Cerebrum;Childhood;Chronic;Citric Acid Cycle;Computer software;Confocal Microscopy;CRISPR/Cas technology;Critical Thinking;cytotoxicity;Degradation Pathway;Detection;Development;Disease;disease phenotype;Disease Progression;Dopaminergic Cell;Down-Regulation;effective therapy;Enzymes;Etiology;Event;Exhibits;Fluorescent Dyes;Functional disorder;Future;genetic variant;Genus Hippocampus;Glutamate Metabolism Pathway;Glutamates;High Pressure Liquid Chromatography;Homeostasis;Human;Image;Immunofluorescence Microscopy;In Vitro;in vitro Model;Incubated;Induced pluripotent stem cell derived human neuron;Induced pluripotent stem cell derived neurons;insight;Investigation;Isoleucine;knock-down;Knock-in;Knowledge;Label;Lactate Dehydrogenase;Leucine;Link;live cell imaging;Maps;Mass Fragmentography;Measures;Mediating;Metabolic;Metabolic dysfunction;metabolomics;Mitochondria;mitochondrial dysfunction;Modeling;motor impairment;Nerve Degeneration;nerve stem cell;neural;Neurodegenerative Disorders;neuron loss;Neuronal Differentiation;Neurons;neuropathology;neurotoxicity;Nitrogen;novel;novel therapeutic intervention;Onset of illness;oxidative damage;Oxidative Stress;Oxygen Consumption;Pathogenesis;Pathogenicity;Pathology;Pathway interactions;Patients;Phenotype;Production;Proteins;Reactive Oxygen Species;resazurin;Research;Research Technics;Respiration;RNA Interference;Role;Rotenone;Running;skills;Source;stable isotope;Stains;Structure;Superoxides;Supplementation;targeted treatment;Testing;Therapeutic;Therapeutic Intervention;therapeutic target;Toxic effect;Transgenic Mice;Transgenic Model;Valine;Variant;Viral;Western Blotting;Work

PROJECT_TITLE: Investigating branched-chain amino acid transaminase-1 (BCAT1) as a novel metabolic etiology and therapeutic target in neurodegenerative disease

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


NIH_SPENDING_CATS: Microbiome;Neurosciences

ORG_CITY: NEW HAVEN

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Project Narrative: The microbiome and the gut-brain axis has been demonstrated to mediate the symptoms and progression of a wide variety of neurological disease1-6. While the role of the gut-microbiota-T-cell-brain axis in the context of specific neurological diseases has been studied, its role at steady-state and scope of neuroimmune interactions between microbiota-educated-T cells and microglia is not known. It is essential to understand the steady-state gut-brain T cell axis in order to fully understand the molecular mechanisms behind neurological disease to develop better targeted therapeutics.

PI_NAMEs: YOSHIDA, TOMOMI MARIE (contact)

PROGRAM_OFFICER_NAME: MOHAPATRA, DURGA PRASANNA

PROJECT_TERMS: Adoptive Transfer;Affect;Age;Axon;Bacteria;Behavior;Behavioral;Behavioral Assay;Brain;brain cell;career;CD4 Positive T Lymphocytes;Cell Communication;Cell Compartmentation;Cell Physiology;Cell secretion;Cell Separation;Cells;commensal microbes;Consumption;Cues;CXCL10 gene;CXCR3 gene;cytokine;Data Set;density;Dependence;Development;Disease;emotional behavior;Environment;experience;Flow Cytometry;Food;Gene Expression Profile;Genetic Transcription;Gnotobiotic;gray matter;gut microbiome;gut microbiota;gut-brain axis;Human;IL17 gene;Immune;Immune response;immunopathology;Impairment;Injury;Interferon Type II;Interferons;Knowledge;learned behavior;Learning;Leukocytes;Ligands;Location;Lymphocyte;Mediating;memory consolidation;Mentors;Microbe;microbiome;microbiota;microbiota composition;Microglia;Molecular;mouse model;multidisciplinary;Mus;myelination;Nature;Nerve;Nervous System Disorder;neural network;neurodevelopment;Neuroimmune;neuroimmunology;neuroinflammation;Neurologic Symptoms;Neurons;Neurotransmitters;novel therapeutic intervention;Organ;Peripheral;Phenotype;Population;Positioning Attribute;Prefrontal Cortex;prevent;Principal Investigator;Process;programmed cell death protein 1;Property;Publishing;Reaction;receptor;recruit;Research;residence;Rodent;Role;Signal Transduction;single-cell RNA sequencing;Social Behavior;Solid;Surface;Symptoms;synaptic pruning;T cell clonality;T-Lymphocyte;targeted treatment;Testing;Time;Tissues;trafficking;Weaning;Work

PROJECT_TITLE: Investigating the mechanism and role of the steady-state CXCR3-CXCL10 gut-microbiota-brain T cell axis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F01A-V (20)]


ORG_CITY: NEW YORK

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: PROJECT NARRATIVE The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), a subtype of the ionotropic glutamate receptor (iGluR), is a ligand-gated ion channel that mediates fast neurotransmission in the central nervous system. It plays a critical role in learning and memory, and its dysregulation is implicated in neurological conditions like epilepsy and Alzheimer’s disease. The proposed research will elucidate high-resolution three-dimensional structures of AMPARs, reveal molecular basis of their functional assembly and regulation as well as guide in the rational design of therapeutics targeting iGluRs in disease conditions.

PI_NAMEs: YEN, LAURA YAUNHEE (contact)

PROGRAM_OFFICER_NAME: UMANAH, GEORGE KWABENA ESSIEN

PROJECT_TERMS: Acids;Affinity;Agonist;Alzheimer's Disease;antagonist;Binding;Biochemical;biophysical techniques;Biophysics;Brain;Cells;Central Nervous System;Cerebellum;Classification;Complex;Cryoelectron Microscopy;cytotoxic;desensitization;Detection;Disease;Drug Design;Electrophysiology (science);Epilepsy;excitotoxicity;Family;Fluorescence;Foundations;genetic regulatory protein;Glutamate Receptor;Glutamates;Goals;insight;Ion Channel;Ion Channel Gating;Ions;Kinetics;Learning;Ligands;Mediating;Membrane;Memory;Methods;Molecular;Molecular Sieve Chromatography;Motor;Nervous System Disorder;Neurologic;neuron loss;neurotransmission;novel;patch clamp;Pathogenesis;Permeability;Pharmaceutical Preparations;pharmacologic;Pharmacology;Physiological;Play;Polyamines;Positioning Attribute;positive allosteric modulator;protein purification;rational design;receptor;receptor function;Regulation;Research;Resolution;Role;small molecule;Structure;Surface;Synapses;Synaptic Receptors;Techniques;therapeutic target;therapy development;three dimensional structure;Tissues;trafficking

PROJECT_TITLE: Modulation of Heteromeric AMPA-Subtype iGluRs by Auxiliary Subunits

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