ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Brain Disorders;Depression;HIV/AIDS;Infectious Diseases;Mental Health;Neurosciences;Prescription Drug Misuse;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Substance Misuse

ORG_CITY: AMHERST

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: STATE UNIVERSITY OF NEW YORK AT BUFFALO

PHR: PROJECT NARRATIVE Polypharmacy is an increasingly common problem among aging persons with HIV (PWH), particularly since it could worsen toxicity from antiretroviral therapy and the adverse effects of comorbid diseases. This application proposes to systematically evaluate the influence of aging and concomitant drugs on ART neurotoxicity and its effects on cognition and depression and to explore the molecular and cellular mechanisms. The identification and validation of pharmacological factors affecting ART neurotoxicity, cognition, and depression would have substantial public health relevance and could support early intervention and treatment optimization.

PI_NAMEs: LETENDRE, SCOTT L;MA, QING  (contact)

PROGRAM_OFFICER_NAME: MARIC, MAJA

PROJECT_TERMS: Address;Adult;advanced analytics;Adverse effects;Affect;Age;Aging;aging related;Amyloid;analytical method;Anti-Cholinergics;antiretroviral therapy;Area;Astrocytes;Benzodiazepines;Biological;Blood;Categories;Cell Culture Techniques;Central Nervous System;Clinical;clinical translation;Clonazepam;Coculture Techniques;Cognition;Cognition Disorders;Cognitive;cohort;comorbidity;Data;Data Analyses;Data Sources;Databases;Disease;Dose;Drug Combinations;drug distribution;Drug Kinetics;drug metabolism;Drug Prescriptions;Drug usage;Early Intervention;Early treatment;Elderly;experimental study;extracellular vesicles;follow-up;Frequencies;Future;General Population;HIV;HIV anti-retroviral;Human;human pluripotent stem cell;improved;Incidence;induced pluripotent stem cell;insight;Intervention;Knowledge;longitudinal analysis;longitudinal database;Major Depressive Disorder;Masks;Measures;Medical;Mental Depression;Mental Health;Methods;Mitochondria;Modeling;Molecular;Mood Disorders;Moods;multidisciplinary;multiple drug use;National NeuroAids Tissue Consortium;nerve stem cell;Neurites;neuroAIDS;neurobehavioral;Neurocognitive;Neurocognitive Deficit;Neuronal Injury;neuroprotection;neurotoxic;neurotoxicity;novel;Older Population;Opioid;Participant;Pathogenesis;Pathology;Performance;Persons;Pharmaceutical Preparations;pharmacokinetic model;pharmacologic;Physiological;Physiology;Polypharmacy;prevent;public health relevance;Renal function;Research;Risk;Sample Size;Severities;sex;Source;Specimen;System;Therapeutic;Toxic effect;treatment optimization;Validation

PROJECT_TITLE: Aging, Polypharmacy and Neurotoxicity in Adults Living with HIV

STUDY_SECTION: HCCS

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


ADMINISTERING_IC: CA

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Cancer;Immunotherapy;Lung;Lung Cancer;Pulmonary Fibrosis;Radiation Oncology

ORG_CITY: PHILADELPHIA

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: Project 3 Narrative: This project aims to provide evidence for Carbon-, Proton and Electron FLASH sparing effects of normal organs at risk for development of early/late toxicities following thoracic irradiation. In parallel, non-inferiority of FLASH vs. standard irradiation in achieving local tumor control of non-small cell lung cancer will be evaluated. 1

PI_NAMEs: ABDOLLAHI, AMIR  (contact)

PROJECT_TERMS: 3-Dimensional;Affect;Biophysics;Blood Vessels;Cancer Etiology;Cancer Model;Cancer Patient;Carbon;Carbon ion;Cardiovascular system;Cells;Cessation of life;Chest;Chronic Obstructive Pulmonary Disease;clinical translation;clinically significant;comorbidity;connective tissue growth factor;curative treatments;Data;Dependence;Development;Distant Metastasis;Dose;Dose Rate;Electrons;Endostatins;Esophagus;Evolution;Exposure to;Fiber Optics;fibrotic lung;Foundations;Functional disorder;Gender;Genes;genetic regulatory protein;Goals;Heart;Heavy Ions;Heterogeneity;Homeostasis;Human;Hypoxia;image guided;immune checkpoint blockade;Immune response;In Vitro;in vivo;in vivo monitoring;Inferior;Inflammatory Response;innovation;insight;Inter-tumoral heterogeneity;Interferon Activation;Interferons;irradiation;Lung;lung injury;Malignant neoplasm of lung;Malignant neoplasm of thorax;Malignant Neoplasms;Memory;Modality;Modeling;Molecular;Monitor;multiscale data;new technology;Non-Small-Cell Lung Carcinoma;Normal tissue morphology;novel;optical sensor;Organ;Organoids;Outcome;Oxygen;particle;Pathway interactions;Perfusion;Phenotype;Physiological;Population;Pre-Clinical Model;pressure;primary endpoint;Probability;protective effect;Protons;Pulmonary Fibrosis;Quality of life;Radiation;Radiation Dose Unit;Radiation therapy;Radiation Tolerance;Radiation Toxicity;rapid detection;regeneration potential;Regimen;Resistance;Resolution;Risk;Role;senescent cell;sensor;Signal Transduction;Site;Solid;Stimulator of Interferon Genes;Structure of parenchyma of lung;Testing;Therapeutic;tissue injury;Tissues;tool;Toxic effect;transcriptomics;Transforming Growth Factor beta;translational study;tumor;tumor growth;tumor hypoxia;Tumor Oxygenation

PROJECT_TITLE: Project 3: Carbon and Electron FLASH radiotherapy for mitigation of normal lung injury in NSCLC


ADMINISTERING_IC: OD

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH

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

ORG_CITY: BOSTON

ORG_NAME: TUFTS UNIVERSITY BOSTON

ORG_STATE: MA

PHR: PROJECT NARRATIVE: Metastatic osteosarcoma (OS) in humans and dogs remains a therapeutic challenge, compounded by a low mutational landscape and absence of clear molecular drivers that limit the utility of immune checkpoint blockade and classic kinase pathway inhibition. Data suggest that OS may be particularly vulnerable to targeting of metabolic pathways; indeed, I have shown that loss of monocarboxylate transporter (MCT) 1 and 4 function in OS cells leads to intracellular lactate accumulation, altering tumor cell phenotype and impairing aerobic glycolysis. Building upon these data, I will employ a comparative cross-species approach to define the regulation and function of MCT1/4 in OS, assess the therapeutic potential of MCT inhibition using zebrafish and mouse models of OS, and explore strategies for synthetic lethality, ultimately creating a blueprint for future clinical translation.

PI_NAMEs: GARDNER, HEATHER LYNN (contact)

PROGRAM_OFFICER_NAME: TANDON, RITESH

PROJECT_TERMS: Adolescent;aerobic glycolysis;Affect;Amputation;Animal Disease Models;Animal Model;arginase;Binding;Bioinformatics;bisulfite sequencing;cancer cell;cancer genome;Canis familiaris;cell growth;Cell membrane;Cell Proliferation;Cells;Chemicals;chemotherapy;ChIP-seq;Chromatin Conformation Capture and Sequencing;Chromatin Interaction Analysis by Paired-End Tag Sequencing;Clinical;clinical development;clinical translation;Clinical Trials;comparative;Comparative Genomic Analysis;Complement;Credentialing;Data;Dependence;design;Development;Disease;Disease Outcome;Down-Regulation;Doxorubicin;Drug Combinations;Ensure;Environment;Exhibits;flexibility;FOXM1 gene;Future;Gene Expression Profile;genetic manipulation;Genetic Transcription;Genome;Genomics;Glutaminase;Glycolysis;Growth;Human;immune checkpoint blockade;Immune checkpoint inhibitor;Immune response;Immunosuppression;Immunotherapeutic agent;Immunotherapy;Impairment;improved;In Vitro;in vivo;inhibitor;innovation;Invaded;kinase inhibitor;knockout gene;Lactic acid;Link;Long Term Survivorship;loss of function;Malignant Bone Neoplasm;Mediating;Mediator;Medical Genetics;Mentors;Metabolic;Metabolic Pathway;metabolic profile;Metabolism;Metastatic Osteosarcoma;Microscopic;Modeling;Molecular;mouse model;Mus;Mutation;Neoplasm Metastasis;neoplastic cell;Nutrient;Oncology;Operative Surgical Procedures;Osteosarcoma;Pathway interactions;Persons;Phenotype;Phosphotransferases;Positioning Attribute;Primary Neoplasm;programs;Proliferating;Recording of previous events;Refractory;Regulation;Research;Resistance;Resources;Scientist;skills;small molecule inhibitor;Somatic Mutation;STAT3 gene;targeted agent;Therapeutic;therapeutic target;Training;Transcriptional Regulation;translational oncology;tumor;tumor growth;Tumor Immunity;tumor metabolism;tumor microenvironment;Universities;Variant;Work;Xenograft procedure;Zebrafish

PROJECT_TITLE: Elucidating the therapeutic utility of targeting metabolic dependencies in osteosarcoma


ADMINISTERING_IC: DK

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Digestive Diseases

ORG_CITY: CHAPEL HILL

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: Project Narrative Relevance: There is a need for physician scientists. Providing a meaningful research experience in the early years of training is often instrumental to motivating these researchers. The proposed program is designed to answer this need.

PI_NAMEs: DELLON, EVAN SAMUEL (contact)

PROGRAM_OFFICER_NAME: CASTLE, ARTHUR

PROJECT_TERMS: Area;career;Dedications;Diabetes Mellitus;Digestive System Disorders;early experience;Endocrine System Diseases;Enrollment;Environment;experience;faculty mentor;Funding;Goals;Health;Hematological Disease;Institution;interest;Kidney Diseases;Liver diseases;medical schools;Medical Students;Metabolic Diseases;National Institute of Diabetes and Digestive and Kidney Diseases;North Carolina;Nutrition Disorders;Obesity;Outcome;Participant;Physicians;programs;Research;Research Personnel;Research Project Grants;Research Training;role model;Schools;Students;success;Training Programs;Universities;Urologic Diseases;Work

PROJECT_TITLE: Short Term Research Training


NIH_SPENDING_CATS: Aging;Biotechnology;Cancer;Precision Medicine;Prostate Cancer;Urologic Diseases

ORG_CITY: STANFORD

ORG_DEPT: UROLOGY

ORG_NAME: STANFORD UNIVERSITY

ORG_STATE: CA

PHR: PROJECT NARRATIVE Compared to biopsies, serum biomarker measurements eliminate invasive procedures to patients, are less expensive and most importantly, may help identify neuroendocrine prostate cancer (PCa), a lethal variant of PCa, earlier so that new therapies can be started in a timely manner. N-glycoproteomic analyses of sera from patient-derived xenografts (PDXs) represent a new paradigm of protein biomarker discovery that overcomes the most challenging limitation of proteomic profiling based approaches. In this proposal, we will identify human-specific N-glycosylated proteins in a mouse background with high sensitivity using PCa PDX models and validate potential biomarkers associated with tumor volume in PCa patient sera.

PI_NAMEs: BROOKS, JAMES D. (contact);PITTERI, SHARON

PROGRAM_OFFICER_NAME: MCKEE, TAWNYA C

PROJECT_TERMS: Adenocarcinoma;androgen deprivation therapy;Benign Prostatic Hypertrophy;Bioinformatics;Biological Assay;Biological Markers;biomarker discovery;Biopsy;cancer biomarkers;Cancer Histology;Cancer Patient;candidate marker;candidate selection;candidate validation;Castration;Cell surface;chemotherapy;Clinic;Clinical;Clinical Trials;cohort;Cryopreservation;Cryopreserved Tissue;Databases;Development;Disease;Extracellular Matrix;Foundations;Fractionation;Future;Glycopeptides;Glycoproteins;glycoproteomics;glycosylation;Goals;Histologic;Human;Image;Immunodeficient Mouse;implantation;improved;individualized medicine;International;Malignant neoplasm of ovary;Malignant neoplasm of prostate;mass spectrometer;Mass Spectrum Analysis;Measurement;Measures;Methods;Monitor;Monitoring for Recurrence;Mus;Neuroendocrine Prostate Cancer;Non-Invasive Detection;novel;novel strategies;novel therapeutics;Pathologic;patient derived xenograft model;Patient Monitoring;patient response;Patient Selection;Patient Triage;Patients;Peptides;Pharmaceutical Preparations;potential biomarker;Procedures;profiles in patients;programs;Prostate Adenocarcinoma;protein biomarkers;protein complex;Protein Glycosylation;Protein Isoforms;Proteins;Proteomics;Quality of life;Reaction;Resistance;resistance mechanism;Resolution;Resources;response;Sampling;Sensitivity and Specificity;Series;Serum;Serum Proteins;specific biomarkers;standard of care;Systemic Therapy;targeted treatment;Testing;therapy development;Time;treatment response;tumor;Tumor Subtype;Tumor Tissue;Tumor Volume;tumor xenograft;Validation;Variant

PROJECT_TITLE: Identification of serum protein biomarkers by profiling N-glycoproteomes of patient-derived xenografts of neuroendocrine prostate cancer


PHR: NARRATIVE This project will investigate the use of proton pencil beam scanning (PBS) to deliver FLASH enhanced radiotherapy. The approach will examine the complex interplay between spatio-temporal beam parameters and FLASH, optimization algorithms for modeling biological effects and treatment planning, and development of FLASH specific methods for ultra-fast dose monitoring, robotic positioning, image guidance, and quality assurance. The goal is to further optimize the FLASH effect by PBS machine tuning and FLASH delivery with existing clinical proton accelerator technology.

PI_NAMEs: WIERSMA, RODNEY  (contact)

PROJECT_TERMS: Algorithms;Animal Experiments;Animals;beamline;Biological;Biological Models;Biology;Blood capillaries;Canis familiaris;Clinical;clinical implementation;Complex;Computer software;design;Development;Diffusion;Dose;Dose Rate;Ensure;experience;experimental study;Future;Gamma Rays;Goals;image guided;instrumentation;Investigation;Ions;irradiation;Linear Energy Transfer;Location;Measurement;Measures;Methodology;Methods;Modeling;Modernization;Monitor;Mus;Nature;Normal tissue morphology;Outcome;Outcome Measure;Outcome Study;Overdose;Oxygen;particle;particle beam;Patients;Phase I Clinical Trials;Physiologic pulse;Plug-in;Positioning Attribute;preclinical study;prevent;Procedures;proton therapy;Protons;quality assurance;Radiation;Radiation therapy;Radiobiology;Reactive Oxygen Species;Research;Resolution;Robotics;Safety;Scanning;spatial temporal variation;spatiotemporal;Speed;Structure;success;System;Tail;Techniques;Technology;Testing;Time;Tissues;tool;translational study;Translations;transmission process;treatment planning;tumor;Validation;Variant;Vascular blood supply;Vendor

PROJECT_TITLE: Project 4: Development and validation of Pencil Beam Scanning methodology for particle FLASH radiotherapy


NIH_SPENDING_CATS: Cancer;Radiation Oncology

PHR: NARRATIVE (Core A) The overall goal of this Core is to provide organizational support and oversight of the scientific and budgetary component to the overall Program Project. This will ensure the timely performance of the proposed work and evaluation of its results. The Administrative Core will also play an essential as an interface with the NIH/NCI.

PI_NAMEs: KOUMENIS, CONSTANTINOS  (contact)

PROJECT_TERMS: Administrator;Communication;Ensure;Equity;Evaluation;Goals;Grant;Laboratories;Manuscripts;meetings;member;Mission;National Cancer Institute;Operations Research;particle;Pennsylvania;Performance;Play;Principal Investigator;programs;Radiation Oncology;Radiation therapy;Regulation;Research Personnel;Resources;Running;symposium;translational study;Travel;United States National Institutes of Health;Universities;Visit;Work

PROJECT_TITLE: Core A: Administrative Core


NIH_SPENDING_CATS: Biotechnology;Brain Cancer;Brain Disorders;Cancer;Cancer Genomics;Clinical Research;Genetics;Human Genome;Neurosciences;Orphan Drug;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: Narrative We propose to leverage a systems biology approach to dissect and target the cellular states that are driving malignant brain tumors in adults and children. We will characterize clinical samples and models by single-cell expression profiling, perform advanced computational analyses and test regulators of cell state as novel therapeutics for these incurable malignancies.

PI_NAMEs: SUVA, MARIO LUCA (contact)

PROGRAM_OFFICER_NAME: LI, JERRY

PROJECT_TERMS: Adult;Animals;Apoptosis;Automobile Driving;Biological Assay;cancer cell differentiation;Cancer Etiology;Cell model;Cells;cellular targeting;Cessation of life;Characteristics;Chemoresistance;Child;Clinical;clinically relevant;Computer Analysis;Disease;disease model;Disease Progression;Evolution;Failure;functional genomics;Genetic;Glioma;Human;In Vitro;in vivo;Invaded;Knowledge;Malignant Glioma;Malignant neoplasm of brain;Malignant Neoplasms;Methodology;Modeling;Natural regeneration;neurodevelopment;novel;novel therapeutics;Patients;Phenotype;Proliferating;Research;Resolution;Sampling;self-renewal;single-cell RNA sequencing;stem cells;stemness;Systems Biology;Testing;Therapeutic;therapy resistant;tumor;tumor growth;tumor heterogeneity;tumor initiation;tumorigenesis;virtual

PROJECT_TITLE: Dissecting the cellular hierarchies of malignant gliomas by single-cell functional genomics

STUDY_SECTION: CG

STUDY_SECTION_NAME: Cancer Genetics Study Section[CG]


ADMINISTERING_IC: GM

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Building Research Capacity at Institutions with Limited NIH Funding;Neurosciences

ORG_CITY: OMAHA

ORG_NAME: CREIGHTON UNIVERSITY

ORG_STATE: NE

PI_NAMEs: HE, ZHI-ZHOU  (contact)

PROJECT_TERMS: Animal Model;Auditory;Auditory area;Auditory Brainstem Responses;Auditory Evoked Potentials;Biochemistry;Biological Models;Biomedical Research;brain stem auditory evoked potentials;Centers of Research Excellence;Clinical Investigator;Communication;Communities;Complex;Consultations;Core Facility;Dedications;design;Development;Doctor of Medicine;Doctor of Philosophy;educational atmosphere;Electrophysiology (science);Elements;Emerging Technologies;Environment;Equipment;Experimental Models;Faculty;Family;Fee-for-Service Plans;Foundations;Funding;Gene Mutation;Goals;Hearing;hearing impairment;Human;Image;Individual;Infrastructure;instrument;instrumentation;Interdisciplinary Study;Laboratory Research;Larva;Mass Spectrum Analysis;Measures;medical schools;Mentors;Methodology;mid-career faculty;Midwestern United States;model organism;Molecular Biology;mouse model;multidisciplinary;Neurosciences;otoacoustic emission;outreach program;Phenotype;Physics;Physiology;Play;Principal Investigator;Productivity;professor;Protocols documentation;Research;Research Personnel;Research Project Grants;Research Support;Resources;response;Role;Science;scientific atmosphere;Scientist;Services;single molecule;software development;Structure;Techniques;Technology;technology development;Universities;vestibular system;Whole Organism;Zebrafish

PROJECT_TITLE: Physiology and Technology Core


PHR: NARRATIVE This Core will provide infrastructure to ensure that each participating institution and radiation modality (proton, carbon, and electron) will have consistent and repeatable FLASH dose. The proposal includes a multi- disciplinary group with radiation oncologists and biologists who will work very closely with physicists to ensure procedural consistency for FLASH radiation. Reliable, safe, and consistent irradiations, determination of dose and dose rate are the primary functions of this Core.

PI_NAMEs: DIFFENDERFER, ERIC S (contact)

PROJECT_TERMS: 3D Print;Abdomen;absorption;Aftercare;animal imaging;Animal Model;Animals;Area;biodosimetry;Biological Models;Calibration;canine model;Canis familiaris;Carbon;Cell Survival;Collimator;Consult;Custom;Dose;Dose Rate;dosimetry;electron radiation;Electrons;Ensure;Equipment;Experimental Neoplasms;experimental study;file format;Goals;image guided;Infrastructure;innovation;Institution;International;ionization;irradiation;Leg;Linear Energy Transfer;manufacture;Measurement;Measures;Methods;millisecond;Modality;Modeling;Monte Carlo Method;mouse model;multidisciplinary;Mus;Normal tissue morphology;novel;operation;Outcome;particle;Pelvis;Physics;Procedures;Protocols documentation;Proton Radiation;Protons;quality assurance;Quality Control;Radiation;Radiation Dose Unit;Radiation Oncologist;Radiation therapy;Records;Relative Biological Effectiveness;Reporting;Reproducibility;Research Personnel;restraint;Role;Safety;Sampling;Site;Standardization;Structure;success;Support System;System;Techniques;Technology;Time;tool;translational study;tumor;Tumor Tissue;Validation;Visualization;Work;X-Ray Computed Tomography

PROJECT_TITLE: Core B: Physics-Dosimetry Core


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cancer;Clinical Research;Data Science;Lung;Lung Cancer;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Precision Medicine;Prevention

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: NARRATIVE Most lung cancers present as pulmonary nodules; so, to improve survival from lung cancer, we need to identify with noninvasive strategies the disease early among a majority of benign nodules. This project focuses on establishing an integrative approach to early detection leveraging repeated measures of chest CT imaging features of lung nodules over time, of the rate of change of a high sensitivity blood biomarker hsCYFRA 21-1, and of longitudinal clinical patterns from the electronic health record. This research will inform the management of lung nodules identified on lung cancer screening CT scans, and should reduce the time to diagnosis and the mortality of lung cancer.

PI_NAMEs: LANDMAN, BENNETT A.;MALDONADO, FABIEN  (contact)

PROGRAM_OFFICER_NAME: MAZURCHUK, RICHARD V

PROJECT_TERMS: Academic Medical Centers;Address;Algorithms;Anxiety;Artificial Intelligence;Benign;Biological Assay;Biological Markers;biological specimen archives;biomedical informatics;Blood;Blood Proteins;blood-based biomarker;Cancer Detection;Cessation of life;chest computed tomography;Classification;Clinical;Clinical Data;Clinical Management;Clinical Markers;clinical predictive model;clinical predictors;cohort;Community Hospitals;computed tomography screening;convolutional neural network;cost;Data;data mining;Data Science;Data Sources;deep learning;deep learning model;demographics;Diagnosis;Diagnostic;diagnostic accuracy;Discrimination;Disease;Dose;early detection biomarkers;Early Diagnosis;Electronic Health Record;Enrollment;Funding;Goals;Health Care Costs;Healthcare;high risk population;Image;imaging biomarker;improved;Individual;innovation;Intervention;Joints;large scale data;Lead;longitudinal analysis;low dose computed tomography;Lung;lung cancer screening;lung lesion;Lung nodule;Machine Learning;machine learning method;Malignant - descriptor;Malignant neoplasm of lung;Malignant Neoplasms;Measurement;Measures;Modeling;Modernization;molecular marker;Monitor;Morbidity - disease rate;mortality;neural network algorithm;Nodule;noninvasive diagnosis;novel;Oncology;Operative Surgical Procedures;Outcome;patient oriented;Patients;Pattern;Performance;Phenotype;Population;predictive modeling;predictive signature;Predictive Value;premalignant;Procedures;programs;Prospective cohort;quantitative imaging;Radiation;Radiology Specialty;rate of change;Research;research clinical testing;Resources;Risk Assessment;Risk Estimate;Scanning;screening program;serial imaging;Series;Serum;Source;structural imaging;Structure;Testing;Thoracotomy;Time;Training;Validation;X-Ray Computed Tomography

PROJECT_TITLE: Novel Integrative Approach for the Early Detection of Lung Cancer using Repeated Measures


PHR: Narrative A critical component of the experimental work proposed across all Projects is the study of preclinical animal models to assess efficacy and toxicity of proton/carbon particle FLASH radiotherapy as compared to standard particle radiotherapy. To this end, Core C will study the pathological changes occurring in the animal model to understand how neoplastic and normal tissues respond to the application of different experimental radiotherapies. This type of assessment will contribute to test the overall hypothesis that proton/carbon particle FLASH radiotherapy is superior to standard particle radiotherapy in protecting normal tissues while the two modalities are equipotent in controlling malignant growth.

PI_NAMEs: RADAELLI, ENRICO  (contact)

PROJECT_TERMS: Address;Algorithms;Animal Experiments;Animal Model;animal tissue;Animals;Archives;Autopsy;Biological;Biological Markers;Biological Process;Board Certification;Canis familiaris;Carbon;Cells;Classification;Clinical;Collaborations;Collection;Comparative Pathology;Computer software;Consultations;cytokine;Data;Dedications;Development;digital imaging;digital pathology;efficacy evaluation;Ensure;Epithelium;Evaluation;experience;Fibrosis;functional status;Goals;Growth;Hematoxylin and Eosin Staining Method;Histological Techniques;Histology;Histopathology;Image Analysis;Immune;immune cell infiltrate;Immunofluorescence Immunologic;Immunohistochemistry;immunological status;In Situ Hybridization;Inflammation;Inflammatory;Infrastructure;interest;Label;Laboratories;Lesion;Macrophage;Malignant - descriptor;Measurable;Modality;Modernization;Molecular;Morphology;Mus;neoplastic;neoplastic cell;neutrophil;Normal tissue morphology;Outcome;Paraffin Embedding;particle;Pathologic;Pathologist;Pathology;pathology imaging;Patients;personalized approach;Phenotype;Play;Population;pre-clinical;Pre-Clinical Model;preclinical study;Preparation;preservation;Procedures;programs;Protocols documentation;Protons;Radiation therapy;Reproducibility;Research Design;Research Personnel;response;Rodent;Role;Route;Sampling;Services;Severities;Signal Pathway;Sirius Red F3B;Slide;Solid;Specimen;Stains;Standardization;Structure;System;T-Lymphocyte;Techniques;Technology;Testing;Therapeutic Index;Time;tissue preparation;Tissue Sample;Tissues;tool;Toxic effect;Training;translational study;Translations;Trichrome stain method;tumor;tumor microenvironment;Variant;whole slide imaging;Work

PROJECT_TITLE: Core C: Comparative Pathology Core


NIH_SPENDING_CATS: Building Research Capacity at Institutions with Limited NIH Funding;Genetics;Hearing Loss;Neurosciences;Regenerative Medicine

PI_NAMEs: TAO, LITAO  (contact)

PROJECT_TERMS: Adult;Affect;Agonist;Alleles;Animal Model;Aromatase;ATAC-seq;autosome;Binding;Birth;Cell Death;Cell Differentiation process;cell type;Cells;Chimeric Proteins;Clustered Regularly Interspaced Short Palindromic Repeats;Cochlea;Compensation;Consumption;CRISPR-mediated transcriptional activation;curative treatments;Data;design;Development;Distal;DNA Sequence Alteration;efficacy evaluation;Enhancers;Epigenetic Process;flexibility;Gene Expression;Generations;Genes;Genetic Transcription;GFI1 gene;Guide RNA;hair cell regeneration;Hair Cells;Hearing;hearing impairment;hearing loss treatment;Histones;Homeostasis;Human;improved;in vivo;in vivo Model;Methods;Mus;mutant;Mutation;Natural regeneration;Organ Culture Techniques;overexpression;Patients;Persons;prevent;Process;progressive hearing loss;promoter;recruit;Regulatory Element;Resources;Sensorineural Hearing Loss;Sensory Hair;single cell ATAC-seq;Specificity;Stimulus;Supporting Cell;System;Techniques;Testing;Therapeutic;Time;transcription factor;transdifferentiation;Transgenic Animals;Work

PROJECT_TITLE: Pou4f3 enhancers in hearing loss treatment


NIH_SPENDING_CATS: Cancer;Networking and Information Technology R&D (NITRD);Radiation Oncology

PHR: PROJECT NARRATIVE The Biostatistics Core (Core D) provides comprehensive and expert analytic tools to support the mission of the P01 program project to rigorously test the hypothesis that Proton/Carbon/Electron Particle FLASH RT is superior to Standard Particle RT in protecting normal tissues while the two modalities are equipotent in controlling malignant growth. The core supports the public health mission of the NIH by supporting rigorous statistical design and analysis for all experiments conducted within the auspices of the Program Project, thus ensuring high levels of reproducibility.

PI_NAMEs: PUTT, MARY E. (contact)

PROJECT_TERMS: Address;analytical tool;Animals;anti-cancer research;Biometry;Biostatistics Core;Canis familiaris;Carbon;Clinical;Clinical Trials;cloud based;Code;Collaborations;Consult;COVID-19 pandemic;Data Analyses;data sharing;Data Storage and Retrieval;design;Dose;Dose Rate;Electrons;Ensure;experience;experimental study;Grant;Graph;Growth;innovation;Institution;interest;Knowledge;Malignant - descriptor;Manuscripts;Mission;Modality;Normal tissue morphology;particle;Phase;Population;pre-clinical;pre-clinical research;Preparation;Program Research Project Grants;programs;Protocols documentation;Protons;Public Health;Qualifying;Radiation Dose Unit;Radiation Oncology;Radiation therapy;Reproducibility;Reproducibility of Results;Research;Research Design;Research Personnel;Research Project Grants;Sample Size;Secure;skills;Statistical Data Interpretation;System;Testing;Time;tool;translational study;tumor growth;United States National Institutes of Health;Work

PROJECT_TITLE: Core D: Biostatistics Core


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biotechnology;Clinical Research;Immunization;Infectious Diseases;Malaria;Malaria Vaccine;Orphan Drug;Prevention;Rare Diseases;Vaccine Related;Vector-Borne Diseases

ORG_CITY: CLEVELAND

ORG_DEPT: PATHOLOGY

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

ORG_STATE: OH

PHR: Our proposal's goal is to develop new approaches for the prevention and treatment of human malaria caused by Plasmodium vivax (P. vivax). This type of malaria, known as vivax malaria, is the most widely distributed type of malaria with 3.3 billion people at risk and at least 15 million clinical cases worldwide each year. The proposal aims to isolate and produce monoclonal antibodies that recognize molecules essential for the parasite to infected liver and red blood cells from individuals who have become immune to vivax malaria. The production and characterization of these human monoclonal antibodies will help in the design and development of vaccines against vivax malaria and provide novel therapeutics to both prevent and treat individuals at risk or infected with this parasite.

PI_NAMEs: KING, CHRISTOPHER L (contact)

PROGRAM_OFFICER_NAME: PESCE, JOHN T

PROJECT_TERMS: Address;Adjuvant;Adult;Affinity;Africa South of the Sahara;Antibodies;Antigens;apical membrane;Area;B-Lymphocytes;Beds;Binding Proteins;Biological Assay;Biomass;Blood;Brazil;Cambodia;Cells;Cessation of life;Child;Chimeric Proteins;Chronic Disease;circumsporozoite protein;Clinical;Clone Cells;Complement;Copy Number Polymorphism;Data;design;Development;disorder risk;Drug resistance;Epitopes;Erythrocytes;Ethiopia;Event;experimental study;Exposure to;Fever;Gene Dosage;Gene Modified;Genetic Polymorphism;Geography;Goals;Health Policy;Hepatic;Hepatocyte;Human;human monoclonal antibodies;Immune;Immune Sera;Immunity;Immunize;Immunoglobulin G;Immunologist;In Vitro;in vitro Assay;in vivo;Individual;Infection;Infection prevention;Injections;innovation;Invaded;Knowledge;Liver;Longitudinal cohort;Lymphocyte;Malaria;Malaria Vaccines;Measures;Mediating;migration;Monoclonal Antibodies;Morbidity - disease rate;mortality;mouse model;neutralizing monoclonal antibodies;next generation;novel strategies;novel therapeutics;novel vaccines;Papua New Guinea;parasite invasion;Parasites;Patients;Plasmodium falciparum;Plasmodium vivax;Plasmodium vivax vaccine;Population;Population Heterogeneity;Populations at Risk;prevent;Prevention;Prevention approach;Primary Infection;Production;Proteins;Public Health;rational design;receptor;receptor binding;Recommendation;Relapse;Residual state;Reticulocytes;Risk;Risk Reduction;Role;sample fixation;Solomon Islands;Sporozoites;structural determinants;Syndrome;Technology;Time;Transcend;Transgenic Organisms;transmission process;vaccine development;vaccine strategy;Vaccines;Vivax Malaria;Work

PROJECT_TITLE: Defining targets of protective immunity to vivax malaria using human monoclonal antibodies

STUDY_SECTION: CRFS

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


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Cancer;Clinical Research;Neurofibromatosis;Neurosciences;Pediatric;Pediatric Cancer;Prevention;Rare Diseases

ORG_CITY: IOWA CITY

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: Project Narrative There are no effective chemotherapies for MPNST patients and our understanding of MPNST development from benign precursor lesions is limited. We hypothesize that the three tumor suppressor products of the INK4a/ARF/INK4b locus, the only genes besides NF1 known to be significantly altered in the precursor lesions, serve cooperative functions with other players to suppress the transformation of benign neurofibromas to MPNSTs. These studies, which comprehensively examine the mechanisms and biological significance of INK4a, ARF, and INK4b inactivation in MPNST pathogenesis using mouse and human models, may facilitate earlier diagnosis and future pre-emptive chemotherapeutic interventions targeting the precursor lesions in NF1 patients.

PI_NAMEs: DARBRO, BENJAMIN WILL;DODD, REBECCA D (contact);QUELLE, DAWN E

PROGRAM_OFFICER_NAME: LEE, CRYSTAL ANNE

PROJECT_TERMS: Age;Agreement;Animal Model;Antineoplastic Agents;Automobile Driving;Benign;Biological;Biological Assay;Biology;Cause of Death;CDK4 gene;CDKN2A gene;Cell model;cell transformation;Cells;chemotherapy;Classification;Clinical;clinically significant;Clustered Regularly Interspaced Short Palindromic Repeats;Development;Diagnostic;Disease;Drug resistance;Drug Targeting;drug-sensitive;Early Diagnosis;Event;Frequencies;Future;Genes;Genetic;genetic analysis;genomic locus;Histologic;Human;human model;Hyperactivity;improved;In Vitro;in vivo;in vivo Model;individualized medicine;inhibitor;inhibitor therapy;innovation;insight;Learning;Lesion;Link;liquid biopsy;Literature;Malignant - descriptor;Malignant Neoplasms;Mediator;MEKs;Modeling;Molecular;mouse model;Mus;Neoplasms;neurofibroma;Neurofibromatosis 1;Neurofibrosarcoma;new combination therapies;NF1 gene;Oncogenic;overexpression;Pathogenesis;Pathway interactions;Patients;Peptides;Pharmaceutical Preparations;pharmacologic;Physiological;Plasma;Plexiform Neurofibroma;pre-clinical;preclinical study;preemptive intervention;premalignant;prevent;Prevention;prognostic assays;prognostic value;Proteomics;RAS driven tumor;reconstitution;Reporting;Resistance;Role;Sampling;Specimen;targeted treatment;Testing;Therapeutic Intervention;therapy resistant;transcriptome sequencing;tumor;Tumor Biology;tumor DNA;Tumor Markers;tumor progression;Tumor Suppressor Proteins;Up-Regulation;Work

PROJECT_TITLE: Ink4a/ARF/Ink4b locus in Neurofibromatosis Type 1

STUDY_SECTION: CMBG

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


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Diabetes;Nutrition

ORG_CITY: MINNEAPOLIS

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: PUBLIC HEALTH RELEVANCE Type 2 diabetes (T2D) is a critical public health concern with high mortality rates due to increased risks for many major life-threatening pathologies that is largely driven by chronic hyperglycemia. In response to chronic nutrient excess such as hyperglycemia, inappropriate levels of autophagy (organelle breakdown/recycling) are observed and associated with pancreatic β-cell failure through unknown mechanisms. In this proposal, we will study the unexplored interactions between two major nutrient-sensor proteins (O-GlcNAc Transferase; OGT and mechanistic Target of Rapamycin; mTOR), and their downstream contribution to β-cell mass and insulin secretion that are maintained through the process of autophagy, with the long-term goal of generating new therapeutic targets to prevent T2D.

PI_NAMEs: JO, SEOKWON  (contact)

PROJECT_TERMS: Address;Affect;Apoptosis;Autophagocytosis;Autophagosome;Beta Cell;Biological Assay;Biology;Blood Glucose;blood glucose regulation;career;Cause of Death;Cell Physiology;Cell Survival;Cells;Chronic;Communication;Complex;Cues;Data;Death Rate;Dedications;Development;Diabetes Mellitus;diabetic;diabetic patient;Disease;Economic Burden;Environment;Enzymes;extracellular;Failure;FRAP1 gene;Functional disorder;Gene Expression;Genus Hippocampus;Glucose;glycosylation;Goals;Health;Homeostasis;Human;Hyperglycemia;Imaging Techniques;improved;In Vitro;in vivo;inhibitor;innovation;Insulin;insulin secretion;islet;Islets of Langerhans;Knockout Mice;Knowledge;Leadership;Life;Link;Lipids;Mentors;Metabolic;Metabolic dysfunction;Metabolism;Minnesota;Mitochondria;mitochondrial dysfunction;Modeling;mouse model;Mus;new therapeutic target;Non-Insulin-Dependent Diabetes Mellitus;novel;Nutrient;O-GlcNAc transferase;Oral;Organelles;Pathology;Pathway interactions;Patients;peptide O-linked N-acetylglucosamine-beta-N-acetylglucosaminidase;Phase;Phenotype;Phosphotransferases;Physiological;Physiology;Post-Translational Protein Processing;Prediabetes syndrome;Prevalence;prevent;Process;Proliferating;Property;protein expression;Proteins;Public Health;public health relevance;Recycling;Regulation;Research;Resources;Respiration;response;Risk;sensor;Shapes;Signal Pathway;Signal Transduction;Stress;Structure of beta Cell of islet;success;targeted treatment;Technical Expertise;Testing;Therapeutic;Training;TSC2 gene;Universities;Up-Regulation;Writing

PROJECT_TITLE: Regulation of Autophagy-driven Pancreatic Beta Cell Function by Nutrient Sensor Proteins


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Natural Products

ORG_CITY: CAMBRIDGE

ORG_DEPT: CHEMISTRY

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

PHR: Project Narrative Rare and unnatural carbohydrates play an essential role in the potency and selectivity of over 100 FDA-approved drugs and countless bioactive natural products. However, in spite of their importance to human health, synthetic challenges limit access to these important pharmacophores. The research described in this proposal seeks to develop new catalytic methods for the selective synthesis of diverse carbohydrate structures to enable the study and treatment of human disease.

PI_NAMEs: WENDLANDT, ALISON  (contact)

PROGRAM_OFFICER_NAME: BOND, MICHELLE RUEFFER

PROJECT_TITLE: Selective Catalytic Strategies for Carbohydrate Synthesis

STUDY_SECTION: SBCA

STUDY_SECTION_NAME: Synthetic and Biological Chemistry A Study Section[SBCA]


NIH_SPENDING_CATS: Genetics;Immunization;Immunotherapy;Infectious Diseases;Malaria;Rare Diseases;Vaccine Related;Vector-Borne Diseases

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

PHR: PROJECT NARRATIVE Plasmodium infections cause more than 200 million cases of malaria each year and more than 3.4 billion people are at risk for contracting this devastating infectious disease. The goal of this research is to understand the differentiation, function and maintenance of parasite-specific memory CD4 T cells that are critical for resistance to blood stage Plasmodium infection. These studies will provide new insight that will be used to develop and enhance immune-based interventions against malaria.

PI_NAMEs: BUTLER, NOAH SULLIVAN (contact)

PROJECT_TERMS: adaptive immunity;Address;Affect;Agonist;Anti-malarials;Antibody Response;Antigen-Presenting Cells;Applied Genetics;B-Lymphocytes;Biology;Blood;burden of illness;CD4 Positive T Lymphocytes;Cell Physiology;Cells;Cessation of life;Characteristics;cofactor;Communicable Diseases;Contracts;cytokine;Data;Defect;Deposition;deprivation;Development;Disease;DNA;drinking water;Enzymes;Epigenetic Process;Erythrocytes;Exhibits;Family;Family member;Genetic;genetic approach;global health emergency;Glutamine;Goals;Helper-Inducer T-Lymphocyte;Hemoglobin;hemozoin;Immune;Immune response;Immunity;Immunologic Memory;Immunology;Immunotherapy;Impairment;improved;Individual;Infection;Inflammasome;Inflammation;innovation;insight;Intervention;Journals;Knowledge;Link;Maintenance;Malaria;Mediating;Medicine;Memory;memory CD4 T lymphocyte;Metabolic;Metabolism;Molecular;Molecular Genetics;Mus;Natural Immunity;Nature;novel;novel strategies;Parasite Control;Parasites;Parasitology;pathogen;Pathogenesis;Phenotype;Plasmablast;Plasmodium;Population;Populations at Risk;Predisposition;programs;Publications;Reagent;Regulation;Reporting;Research;Resistance;Resolution;response;Severity of illness;Shapes;Signal Transduction;Symptoms;System;T cell differentiation;T cell response;T-Cell Development;T-Lymphocyte Subsets;Testing;tool;Vaccines

PROJECT_TITLE: Development and function of CD4+ memory T cells during malaria

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IDIA-R(02)]


NIH_SPENDING_CATS: Bioengineering;Networking and Information Technology R&D (NITRD)

ORG_CITY: TEMPE

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS

ORG_STATE: AZ

PHR: Allosteric drug mechanisms promise superior target selectivity, reduced drug toxicity and increased drug safety, but the rational development of allosteric drugs still faces fundamental challenges. In this project, we address these challenges with the development of novel and widely applicable computational methods to predict protein conformational fluctuations that form the basis for allosteric drug mechanisms. We first apply our methods to identify allosteric mechanisms and drug binding sites in matrix metallo-proteinases implicated in inflammatory disease and tumor metastasis, but the proposed methodology is general and applicable to other drug target proteins.

PI_NAMEs: HEYDEN, MATTHIAS  (contact)

PROGRAM_OFFICER_NAME: GERSHENSON, ANNE

PROJECT_TERMS: Address;Algorithms;Allosteric Site;Binding;Binding Sites;chronic inflammatory disease;clinical application;cluster computing;computer framework;Computer Hardware;Computer software;computerized tools;Computers;Computing Methodologies;conformational conversion;cost;Data;Detection;detection method;Development;Diffusion;Disease;Drug Binding Site;drug candidate;Drug Design;drug development;drug discovery;drug mechanism;Drug Targeting;Drug toxicity;Event;Exhibits;expectation;Extracellular Matrix Degradation;Face;Family;FDA approved;Freedom;Frequencies;Frustration;Future;Generations;Goals;high dimensionality;Homologous Protein;Individual;Inflammatory;inhibitor;interest;interoperability;Knowledge;Laboratory Research;Lead;Link;Matrix Metalloproteinase Inhibitor;Matrix Metalloproteinases;medication safety;member;Methodology;Methods;millisecond;Molecular Conformation;molecular dynamics;Motion;Neoplasm Metastasis;novel;open source;Pathologic;Pharmaceutical Preparations;pharmacologic;Potential Energy;Property;Protein Conformation;Protein Dynamics;protein function;Proteins;Protocols documentation;rational design;Sampling;Side;side effect;simulation;small molecule inhibitor;software development;Structure;supercomputer;Surface;System;Techniques;Therapeutic Uses;tumor;Universities;Validation;vibration

PROJECT_TITLE: Understanding Essential Protein Dynamics through the Anharmonic Properties of Thermally Excited Vibrations

STUDY_SECTION: MSFB

STUDY_SECTION_NAME: Macromolecular Structure and Function B Study Section[MSFB]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Cocaine;Drug Abuse (NIDA only);Genetics;Human Genome;Neurosciences;Stimulant Use and Misuse;Substance Misuse

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: Understanding neuronal subtype-specific function of NAc in cocaine addiction Project Narrative Drug addiction is an urgent social and health problem contributing to the death of more than 90,000 people and incurs a yearly cost of over $700 billion in the United States (see NIDA website). Although the nucleus accumbens (NAc) of the middle brain is known to play an important role in drug addiction, the molecular mechanism and neuronal circuit involved is largely unknown. In this proposal, we propose to use the clinically relevant intravenous cocaine self-administration (IVSA) mouse model and single cell RNA-seq to identify the neuron subtypes and circuits mediating the addictive process.

PI_NAMEs: ZHANG, YI  (contact)

PROGRAM_OFFICER_NAME: SATTERLEE, JOHN S

PROJECT_TERMS: Abstinence;addiction;Animal Behavior;Behavioral;Brain;Brain Diseases;Brain region;Cell Nucleus;cell type;Cells;Cessation of life;Chronic;clinically relevant;Cocaine;Cocaine Dependence;cocaine self-administration;cost;Coupled;Data;Development;Disease;Dissociation;Drug Addiction;drug of abuse;Enzymes;Epigenetic Process;epigenetic profiling;experimental study;Gene Expression Profile;Gene Expression Profiling;Genetic;genetic approach;Genetic Transcription;Goals;Health;Heterogeneity;Human;Intravenous;knock-down;Label;Mediating;Mental disorders;Modeling;Molecular;Motivation;mouse model;Mus;National Institute of Drug Abuse;neural circuit;neuronal circuitry;Neurons;new therapeutic target;Nucleus Accumbens;overexpression;Persons;Pharmaceutical Preparations;Phase;Play;Process;Psychological reinforcement;Regulation;Relapse;relapse risk;Rewards;Role;Saline;Self Administration;single-cell RNA sequencing;social;System;targeted treatment;Therapeutic Intervention;Tissue-Specific Gene Expression;transcriptome;transcriptomic profiling;United States;Viral;web site

STUDY_SECTION: PMDA

STUDY_SECTION_NAME: Pathophysiological Basis of Mental Disorders and Addictions Study Section[PMDA]


ADMINISTERING_IC: MD

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

NIH_SPENDING_CATS: American Indian or Alaska Native;Behavioral and Social Science;Biodefense and Related Countermeasures;Clinical Research;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Data Science;Emerging Infectious Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Infectious Diseases;Prevention;Racial and Ethnic Minority Health Research;Rural Health;Social Determinants of Health

ORG_NAME: NATIONAL BUREAU OF ECONOMIC RESEARCH

PHR: OTHER PROJECT INFORMATION – Project Narrative The COVID-19 pandemic and associated mitigation strategies have been shown to disparately impact socially vulnerable and under-served minority groups in the US. This proposed study develops an innovative approach to analyzing the effects of COVID-19 mitigation policies on American Indian populations living on tribal lands and in rural areas, by integrating big data and deep learning techniques with primary data collection. Our research efforts seek to improve American Indian health by understanding and evaluating these NPI measures on an NIH- designated disparity community.

PI_NAMEs: AKEE, RANDALL K. Q. (contact)

PROGRAM_OFFICER_NAME: FERNANDEZ, ANGELA R

PROJECT_TERMS: Address;Advocate;Affect;American Indian community;American Indian Population;American Indian Tribe;American Indians;analytical tool;Area;authority;Behavior;Behavioral;Big Data;Businesses;California;Cellular Phone;Cessation of life;Chronic;Clinic;Communities;Commuting;computer science;consumer behavior;cost;County;COVID-19;COVID-19 impact;COVID-19 incidence;COVID-19 pandemic;COVID-19 prevention;Data;Data Analyses;Data Collection;data hub;data resource;Data Set;Data Sources;data warehouse;Death Rate;deep learning;design;Destinations;Diabetes Mellitus;Dimensions;Disparity;Disparity population;economic behavior;Economic Conditions;economic impact;Economic Policy;Economics;effectiveness evaluation;effectiveness measure;Elderly;Employment;End stage renal failure;Epidemic;Evaluation;Future;Geography;Goals;Health;Health behavior and outcomes;Health care facility;health care service;health care service utilization;Health Policy;Healthcare;Home;implementation intervention;improved;Indian reservation;Indigenous;infection rate;innovation;Intervention;intervention effect;Interview;Link;Measures;Medical;member;Methods;minority communities;Minority Groups;Movement;Natural experiment;Nature;non-Native;novel;operation;Outcome;outcome disparities;pandemic disease;Pattern;Personal Satisfaction;Persons;Play;Policies;Population;prevent;Public Health;public health emergency;public health research;Public Policy;Recommendation;Relaxation;Research;Research Design;Reservations;response;Role;Rural;rural Americans;rural area;Sampling;SARS-CoV-2 infection;SARS-CoV-2 transmission;secondary analysis;Services;Social Behavior;Social Conditions;Social Distance;Social Impacts;social vulnerability;Source;Surveys;Techniques;Time;Transportation;Travel;tribal community;tribal lands;tribal Nation;Tribes;underserved community;underserved minority;United States National Institutes of Health;Vaccines;Virus;Visit;Vital Statistics;Vulnerable Populations;Work

PROJECT_TITLE: The Impacts of Mitigation Strategies to Prevent COVID-19 Transmission in American Indian Communities

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-PSE-W(56)R]


NIH_SPENDING_CATS: Bioengineering;Neurosciences

PHR: Project narrative:  It has been a long-standing goal of neuroscience to directly “see” electric activities in a complex neuronal network. Existing optical imaging techniques require the incorporation of fluorescent molecular probes into neuron in order to detect electric activities, which is limited by photobleaching and can perturb cellular physiology. This study aims to develop a novel optical technique that detects neuroelectric activities without any fluorescence probes.

PI_NAMEs: CUI, BIANXIAO  (contact);MUELLER, HOLGER

PROGRAM_OFFICER_NAME: KUMSA, DOE WONDWOSSEN

PROJECT_TERMS: absorption;Action Potentials;Area;Axon;Back;Biomedical Engineering;Brain;brain tissue;Calcium;Cardiac Myocytes;Cell Physiology;Cell-Free System;Cells;Complex;Computer software;Data;Dendrites;design;Detection;detection method;Dissociation;Dopamine;dopaminergic neuron;Dyes;electrical potential;Electrophysiology (science);extracellular;Film;flexibility;Fluorescence;fluorescence imaging;Frequencies;Funding Opportunities;Goals;Hippocampus;Image;Imaging Techniques;improved;interest;Label;Lasers;Location;Measurement;Measures;Methods;Microscope;Midbrain structure;Molecular Probes;multi-electrode arrays;neural circuit;Neurons;Neurosciences;novel;optical imaging;Optics;Pacemakers;patch clamp;Photobleaching;Phototoxicity;Process;Property;Proteins;Reaction Time;Research;Research Personnel;Research Project Grants;Resolution;response;Sampling;Scanning;sensor;Shapes;Signal Transduction;Site;Slice;Spottings;stem cells;System;Techniques;Technology;Thinness;Time;tool;voltage;voltage sensitive dye;Work

PROJECT_TITLE: Label-free Optical Recording of Neuroelectric Activities


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Immunotherapy;Radiation Oncology;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Embryonic - Human;Transplantation

PHR: Project Narrative: Our project will develop the next generation of optically-clear immune compromised zebrafish for dynamic single cell imaging of human cancers, embryonic and induced-pluripotent stem cells, T cells, and blood. These models are amenable to large-scale transplantation studies and can be used to dynamically visualize engrafted cell behaviors in the context of preclinical therapy evaluation including drug combination therapies, radiation, and immunotherapies.

PI_NAMEs: LANGENAU, DAVID MICHAEL (contact)

PROGRAM_OFFICER_NAME: MIROCHNITCHENKO, OLEG

PROJECT_TERMS: Ablation;Address;Adult;Animal Model;Animals;Apoptosis;B-Lymphocytes;Biological;Biological Immunotherapy;Blood;Blood Cells;cancer cell;CD34 gene;cell behavior;Cell Cycle;Cell Death;Cell division;cell growth;Cell Physiology;Cell Transplantation;cell type;Cells;cellular imaging;chimeric antigen receptor T cells;Clinical;Combination Drug Therapy;Communities;cost;cytokine;Development;DNA Damage;drug sensitivity;Embryo;Engraftment;fluorescence imaging;Genotype;Goals;Growth;Human;human disease;human imaging;human tissue;Image;imaging approach;Imaging Device;imaging platform;Immune;immunodeficiency;Immunotherapy;in vivo;in vivo Model;induced pluripotent stem cell;Knock-in;Label;Laboratories;Macrophage;malignant muscle neoplasm;Malignant Neoplasms;Methods;Mission;Modeling;Mus;mutant;National Heart, Lung, and Blood Institute;National Institute of Arthritis, and Musculoskeletal, and Skin Diseases;National Institute of Child Health and Human Development;National Institute of Diabetes and Digestive and Kidney Diseases;National Institute of Neurological Disorders and Stroke;Natural Killer Cells;Natural regeneration;Neoplasm Metastasis;neoplastic cell;next generation;novel;novel therapeutics;Optics;patient derived xenograft model;Pharmaceutical Preparations;Pharmacodynamics;Poly(ADP-ribose) Polymerase Inhibitor;Positioning Attribute;pre-clinical;pre-clinical assessment;Pre-Clinical Model;pre-clinical therapy;Proliferating;Protocols documentation;Radiation;radiation response;real-time images;Recording of previous events;Recovery;regenerative biology;regenerative cell;regenerative tissue;Research;Resolution;response;Rhabdomyosarcoma;Self Assessment;self-renewal;stem;stem cell self renewal;stem cells;Study models;success;T-Lymphocyte;temozolomide;Testing;Therapeutic;Therapy Evaluation;tool;Transgenic Organisms;translational impact;transplant model;Transplantation;treatment response;tumor;tumor growth;Umbilical Cord Blood;United States National Institutes of Health;Visualization;Work;Xenograft Model;Xenograft procedure;Zebrafish

PROJECT_TITLE: Developing preclinical xenograft models in zebrafish.

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-GGG-A(55)R]


NIH_SPENDING_CATS: Digestive Diseases;Genetics

ORG_DEPT: SURGERY

ORG_NAME: BOSTON UNIVERSITY MEDICAL CAMPUS

PHR: PROJECT NARRATIVE This grant proposal investigates how the digestive enzyme trypsin becomes activated inside the pancreas and initiates the inflammatory disease pancreatitis. The scientific approach uses novel genetically modified mice in which trypsin activation has been altered. The results from the proposed experiments will advance our understanding of the disease and aid in the development of therapeutic interventions.

PI_NAMEs: GEISZ-FREMY, ANDREA  (contact)

PROGRAM_OFFICER_NAME: SERRANO, JOSE

PROJECT_TERMS: Acceleration;acute pancreatitis;Address;Affect;Age of Onset;Animal Experiments;Applications Grants;Arginine;Cathepsins B;chronic pancreatitis;design;Development;Disease;DNA Sequence Alteration;Enzymes;Event;Exhibits;Experimental Genetics;experimental study;Gene Modified;Generations;Genetic;Genetic study;Genotype;Heterozygote;Human Genetics;Inflammatory;insight;Knock-in Mouse;Knockout Mice;Knowledge;Laboratories;Mediating;Modeling;mouse model;Mouse Strains;Mus;mutant;Mutant Strains Mice;Mutation;novel;novel therapeutics;Pancreas;Pancreatitis;Pathogenesis;Pathogenicity;Pathologic;Pathway interactions;Peptide Hydrolases;premature;Preventive;Process;Protein Isoforms;Severities;Severity of illness;Testing;therapeutic development;Therapeutic Intervention;Trypsin;Trypsinogen

PROJECT_TITLE: Mechanisms of Trypsin Activation in Pancreatitis

STUDY_SECTION: DNPD

STUDY_SECTION_NAME: Digestive and Nutrient Physiology and Diseases Study Section [DNPD]


ADMINISTERING_IC: AR

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Aging;Bioengineering;Biomedical Imaging;Cardiovascular;Clinical Research;Osteoporosis;Physical Injury - Accidents and Adverse Effects

ORG_CITY: BIRMINGHAM

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: NARRATIVE — HEALTH RELEVANCE Cardiometabolic conditions, such as type 2 diabetes mellitus and hypertension, increase the risk for fractures, which is a substantial public health problem in older adults in the United States. The proposed study will utilize 25 years of previously collected data regarding biomarkers and incident cardiometabolic disease from the Coronary Artery Risk Development in Young Adults (CARDIA) study, and add validated vertebral strength data, to further our understanding on how cardiometabolic disorders and hallmarks of cardiometabolic disease over the life span impact vertebral strength, a surrogate for vertebral fracture risk.

PI_NAMEs: WRIGHT, NICOLE C (contact)

PROGRAM_OFFICER_NAME: NICKS, KRISTY

PROJECT_TERMS: abdominal CT;Adult women;aged;Attenuated;Biological;Biological Markers;biomarker identification;Biomechanics;Black race;blood glucose regulation;Bone Density;bone health;bone mass;Bone Resorption;bone strength;burden of illness;Cardiometabolic Disease;cardiometabolism;cardiovascular health;Central obesity;Classification;Clinical;Clinical Data;cohort;Coronary Artery Risk Development in Young Adults Study;Data;Dependence;Dual-Energy X-Ray Absorptiometry;Eligibility Determination;epidemiology study;Equation;Evaluation;Female;Fracture;fracture risk;fragility fracture;glucose metabolism;Goals;Health;health assessment;health data;high risk population;Hyperlipidemia;Hypertension;Image;Individual;Inflammation;Intervention;Investigation;Life Cycle Stages;life span;Lipids;male;Measurement;Measures;Mediating;Medicaid;men;Modeling;Molecular;mortality risk;Non-Insulin-Dependent Diabetes Mellitus;novel;nursing home length of stay;older adult;Osteoclasts;Osteogenesis;Participant;Pattern;Predictive Factor;Public Health;Questionnaires;Race;Renal function;Research Design;Research Personnel;Role;Scanning;sex;Spinal Fractures;spine bone structure;Technology;Time;United States;Vertebral Bone;women of color;X-Ray Computed Tomography

PROJECT_TITLE: Evaluating the Association between Cardiometabolic Health Over the Lifespan and Vertebral Strength

STUDY_SECTION: NAME

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


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Behavioral and Social Science;Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Heart Disease;Physical Activity;Prevention;Social Determinants of Health

ORG_DEPT: MISCELLANEOUS

PHR: NARRATIVE There is strong evidence for the association between sedentary behaviors and cardiovascular diseases such as coronary heart disease and stroke. We will identify and test the physiological effects and feasibility of a multi-level strategy for reducing sedentary behavior. Long-term, our findings will inform a large clinical trial that can test whether sedentary behavior reduction can decrease cardiovascular disease risk.

PI_NAMEs: HANSON, ERIK D (contact)

PROGRAM_OFFICER_NAME: SHIROMA, ERIC JITSUO

PROJECT_TERMS: Acute;Adherence;Adoption;Adult;Advisory Committees;Aorta;arm;arterial stiffness;Behavior;behavior change;Behavior Therapy;Behavioral;Behavioral Model;Benchmarking;Biological;Blood;Brain;Cardiovascular Diseases;cardiovascular disorder prevention;cardiovascular disorder risk;cardiovascular health;Cardiovascular system;Chronic;Clinical Trials;Communities;Coronary heart disease;Cross-Over Trials;Data;design;Development;Dose;efficacy testing;endothelial dysfunction;Environment;Exposure to;feasibility testing;feasibility trial;Femur;Focus Groups;Frequencies;Future;Goals;Guidelines;Heart;hemodynamics;Hormonal;Hour;Individual;International Agencies;Interruption;Intervention;Intervention Studies;Laboratory Study;Level of Evidence;Link;Literature;Lower Extremity;Measures;Metabolic;middle age;Modeling;mortality;National Heart, Lung, and Blood Institute;novel strategies;Organ;Outcome;Participant;Persons;Physical activity;Physical environment;Physiologic pulse;Physiological;Policies;Policy Developments;Posture;predictive marker;prevent;Questionnaires;Randomized;randomized, clinical trials;Recommendation;Research;response;Risk Behaviors;Risk Factors;sedentary lifestyle;shear stress;social culture;Social Environment;Stroke;Stroke Volume;Supination;Testing;therapy design;Translations;Walking;Work

PROJECT_TITLE: Sitting Interruption and Whole-body Cardiovascular Health: Linking Physiological Responses to Risk Behaviors

STUDY_SECTION: CCHS

STUDY_SECTION_NAME: Clinical Integrative Cardiovascular and Hematological Sciences Study Section[CCHS]


NIH_SPENDING_CATS: Autoimmune Disease;Clinical Research;Genetics;Kidney Disease;Rare Diseases

PHR: Project Narrative IgA nephropathy, the most common primary glomerulonephritis in the world, often resulting in end-stage kidney disease with no disease specific treatment. Although it is known to be an autoimmune disease, the mechanisms that underlie the production of the critical autoantigen that mediates disease progression are unknown. The proposed studies will integrate single-cell RNA analysis with a novel cell-surface glycophenotyping to analyze the specific immune cell populations responsible for autoantigen production.

PI_NAMEs: REILY, COLIN ROBERT (contact)

PROGRAM_OFFICER_NAME: CHAN, KEVIN E

PROJECT_TERMS: Acute;Address;Affect;Alleles;Antigen-Antibody Complex;ATAC-seq;Autoantibodies;Autoantigens;Autoimmune;Autoimmune Diseases;B-Lymphocytes;Binding;Biochemical;Biopsy;Blood;Cell secretion;Cell surface;cell type;Cells;Characteristics;chromatin immunoprecipitation;chromatin remodeling;Circulation;Clinical;cofactor;cytokine;Cytokine Signaling;Data;Deposition;Development;Diagnosis;Disease;disease phenotype;Disease Progression;End stage renal failure;Enzymes;Exhibits;Flow Cytometry;follow-up;Galactose;Gene Expression;Genes;Genetic Transcription;Genotype;Glomerulonephritis;glycosylation;glycosyltransferase;Glycosyltransferase Gene;Hematuria;IGA Glomerulonephritis;IgA1;IgG autoantibodies;Immune;Immunofluorescence Immunologic;Immunoglobulin A;Immunoglobulin G;In Vitro;Inflammation Mediators;inflammatory milieu;inhibitor;Injury;Injury to Kidney;Interleukin-10;Interleukin-4;Interleukin-6;Kidney;knock-down;Lectin;Mediating;Methods;Nature;novel;Nucleotides;Pathogenesis;Pathogenicity;Pathway interactions;patient stratification;Patients;Peripheral Blood Mononuclear Cell;pharmacologic;Phenotype;Population;Process;Production;Prognosis;Protein Kinase;Recombinants;Recurrence;Regulation;response;RNA analysis;Role;Sampling;Serum;Sialyltransferases;Signal Induction;Signal Pathway;Signal Transduction;Single Nucleotide Polymorphism;Stains;STAT1 gene;STAT3 gene;Technology;Testing;Time;TNFSF5 gene;transcription factor;Transcriptional Activation;transcriptome;transcriptomics;virtual

PROJECT_TITLE: Distinct Glycophenotypes with Abnormal Signaling Define a Subpopulation of B cells Responsible for Production of Galactose-Deficient IgA1, the Main Autoantigen in IgA Nephropathy

STUDY_SECTION: PBKD

STUDY_SECTION_NAME: Pathobiology of Kidney Disease Study Section[PBKD]


ADMINISTERING_IC: HD

ED_INST_TYPE: SCHOOLS OF SOCIAL WELFARE/WORK

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

NIH_SPENDING_CATS: Clinical Research;Contraception/Reproduction;Disability Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Pediatric;Prevention

ORG_CITY: WALTHAM

ORG_NAME: BRANDEIS UNIVERSITY

PHR: PROJECT NARRATIVE Studies to date suggest that the sexual and reproductive health (SRH) care needs of adolescents and young adults with disabilities are not well met. The proposed study will generate national, population-based estimates of sexual and reproductive health risks and outcomes among transition-age adolescents and young adults with disabilities, and also examine their unmet needs and barriers to SRH care. The study will produce an evidence-based, accessible sexual and reproductive health education toolkit for adolescents and young adults with disabilities to improve their SRH and healthcare experiences and promote active engagement in their own care.

PI_NAMEs: HORNER-JOHNSON, WILLI ;MITRA, MONIKA  (contact)

PROGRAM_OFFICER_NAME: POPKIN, RONNA

PROJECT_TERMS: Address;Adolescent and Young Adult;Adult;Age;aged;Appointment;care outcomes;Caregivers;Caring;Clinical;Clinical Trials;Collaborations;Communication;Consent;Data;Development;Developmental Disabilities;Dimensions;disability;Disabled Persons;Disparity;Education;Educational Curriculum;Educational Materials;efficacy testing;evidence base;experience;Family;Female;Foundations;Future;Gender;Growth;Health;health care disparity;health care service;health care service utilization;Health education;health knowledge;Health Priorities;Health Resources;health service use;Health Services;Healthcare;improved;innovation;Intellectual functioning disability;Intervention;Interview;Knowledge;Literature;male;member;Methods;Multimedia;Outcome;Parents;patient-clinician communication;Patients;peer;Persons;pilot test;Population;population based;Population Heterogeneity;preference;Provider;provider communication;Reproductive Health;Reproductive Health Services;Research;Resources;response;Risk;Sampling;service utilization;Services;sexual and reproductive health;Sexual Health;sexually active;Surveys;Target Populations;Teenagers;Testing;tool;transition to adulthood;United States;United States National Institutes of Health;Woman;women with disabilities;Writing;young adult;young man;young woman;Youth

PROJECT_TITLE: Addressing Sexual and Reproductive Health Care Disparities and Barriers among Adolescents and Young Adults with Disabilities


NIH_SPENDING_CATS: Genetics

ORG_DEPT: BIOLOGY

ORG_NAME: STATE UNIVERSITY OF NEW YORK AT BUFFALO

ORG_STATE: NY

PHR: Narrative: The protein synthesis machinery has long been recognized as a therapeutic target of vast potential. The eukaryotic translation initiation factor 4B promotes a protein synthesis program that opposes both metastatic behavior in cancers and activity of other initiation factors in cells; hence, our work determining mechanisms by which eIF4B operates and is regulated could open new avenues for early detection and treatment of cancer and other diseases.

PI_NAMEs: WALKER, SARAH ELIZABETH (contact)

PROGRAM_OFFICER_NAME: REDDY, MICHAEL K

PROJECT_TERMS: 5' Untranslated Regions;Acceleration;Address;Affect;Affinity;Behavior;Binding;Biological Assay;C-terminal;cancer therapy;cell behavior;cell growth;Cell Physiology;Cells;cofactor;Complex;Cryoelectron Microscopy;Cytoplasmic Granules;Data;Dependence;Disease;Disseminated Malignant Neoplasm;Early Diagnosis;Early treatment;eIF-4B;Eukaryotic Initiation Factors;Event;experience;Future;Gel;Genetic;genome-wide;Growth;human disease;improved;In Vitro;in vitro activity;in vitro Assay;Investments;Knowledge;Link;Malignant Breast Neoplasm;Malignant Neoplasms;Mammals;Mechanics;Mediating;Messenger RNA;Mitotic;Modeling;Modification;Molecular;mRNA capping;mRNA Translation;Mus;Mutation;mutation screening;Neoplasm Metastasis;Outcome;Pathogenesis;Pathway interactions;patient prognosis;Patient-Focused Outcomes;Patients;Peptide Initiation Factors;Phenotype;Phosphorylation;Play;Post-Translational Protein Processing;preference;programs;Protein Biosynthesis;Proteins;Proteome;recruit;Reporter;Repression;response;Ribosomal Proteins;ribosome profiling;Ribosomes;RNA;RNA Binding;RNA Helicase;RNA Recognition Motif;RNA Sequences;RNA vaccine;Role;Scanning;Signal Transduction;Site;Specificity;Structure;synergism;Testing;therapeutic target;tool;Transcript;transcriptome;Translating;Translation Initiation;Translational Repression;Translations;tumor progression;tumorigenic;Work;Yeasts

PROJECT_TITLE: Molecular mechanisms of eukaryotic translational control

STUDY_SECTION: MGA

STUDY_SECTION_NAME: Molecular Genetics A Study Section[MGA]


NIH_SPENDING_CATS: Brain Disorders;Drug Abuse (NIDA only);Neurosciences;Opioid Misuse and Addiction;Opioids;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Prescription Drug Misuse;Substance Misuse

ORG_CITY: LA JOLLA

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: NARRATIVE  Opioids have been abused enormously in our society in the past decade to the degree that it is at present an epidemic affecting our youth. In the current application, we focus on the effect of opioids, namely methadone, on the formation and development of the human brain in the fetus during pregnancy when pregnant women are using or abusing methadone. The idea behind this proposal is to be able to understand the mechanisms by which deleterious effects happen as a result of methadone use/abuse in order to counter them and mitigate the impairment induced by opioids on fetal brain integrity.

PI_NAMEs: HADDAD, GABRIEL G (contact)

PROGRAM_OFFICER_NAME: POLLOCK, JONATHAN D

PROJECT_TERMS: 3-Dimensional;Address;Affect;Astrocytes;Blood;Brain;Buprenorphine;Cessation of life;Cognitive;Data;Dendritic Spines;Dependence;Development;Disease;Drug abuse;Electrophysiology (science);Emergency department visit;Epidemic;Ethics;excitatory neuron;Fentanyl;fentanyl abuse;fetal;Fetal Development;Fetus;Genetic;Glucose;Glycoproteins;Heroin;heroin use;Hormones;Human;human fetal brain;imaging study;Imaging Techniques;Impairment;in utero;inhibitory neuron;Investigation;Life;Maternal Exposure;maternal opioid use;Membrane;Methadone;Methods;Molecular;Morbidity - disease rate;mortality;Mothers;multi-electrode arrays;multiple drug use;Neonatal Abstinence Syndrome;neural network;Neurites;Neurons;new technology;new therapeutic target;novel;offspring;Opiate Addiction;Opioid;opioid abuse;opioid epidemic;opioid exposure;opioid overdose;opioid use in pregnancy;Organoids;overdose death;patch clamp;Patch-Clamp Techniques;Pattern;postsynaptic;Pregnancy;Pregnant Women;prescription opioid;presynaptic;productivity loss;Property;receptor;Regulation;Societies;statistics;Structure;Synapses;synaptic function;Synaptic plasticity;Synaptic Transmission;synaptogenesis;Techniques;Thrombospondin 1;Youth

PROJECT_TITLE: Effect of methadone on the developmental properties of human brain organoids

STUDY_SECTION: DBD

STUDY_SECTION_NAME: Developmental Brain Disorders Study Section[DBD]


NIH_SPENDING_CATS: Bioengineering;Breast Cancer;Cancer;Nanotechnology;Neurosciences;Women's Health Research

ORG_CITY: LOS ANGELES

ORG_NAME: CEDARS-SINAI MEDICAL CENTER

PHR: PROJECT NARRATIVE The growth factor receptor, HER3, facilitates tumor resistance and metastasis, hence the HER3-targeted particle we have developed may mediate therapeutic efficacy to tumors escaping current clinical interventions. This project will test whether current targeted inhibitors used in the clinic shift both HER2+ and triple-negative tumor cells to a HER3-targeted phenotype for entrapment by our HER3-targeted particles. These particles, or nano- capsids, will also be evaluated for targeting resistant tumors that have metastasized to the brain, thus offering improved alternatives for tumor types with few to no current treatment options.

PI_NAMEs: MEDINA-KAUWE, LALI K (contact)

PROGRAM_OFFICER_NAME: HARRIS, RAYMOND D

PROJECT_TERMS: Acute;Address;Adjuvant Therapy;Antibodies;Automobile Driving;Benchmarking;Binding;Biological Markers;Blood - brain barrier anatomy;blood-brain barrier crossing;Brain;Breast Cancer Cell;Breast Cancer Patient;Breast Cancer Treatment;Bypass;Capsid;Carboplatin;Cell Communication;Cell surface;Cell Surface Receptors;Cell Survival;Cells;Cephalic;chemotherapy;Clinic;Clinical;Clinical Treatment;Clinical Trials;Clonal Expansion;Combined Modality Therapy;density;Diagnosis;Dimerization;docetaxel;Down-Regulation;effective intervention;EGF gene;EGFR inhibition;Endosomes;Epidermal Growth Factor Receptor;Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor;ERBB2 gene;Estrogens;Experimental Models;Exposure to;Growth;Growth Factor Receptors;Heart;HER2 inhibition;Homing;Human;human model;human tissue;Immune Evasion;Immunocompetent;immunodeficiency;Implant;improved;In Vitro;individual response;inhibitor;Intervention;Intracranial Neoplasms;lapatinib;Ligands;Liver;Malignant Breast Neoplasm;Mammary Neoplasms;Mediating;Membrane;Metastatic malignant neoplasm to brain;Modeling;Molecular;mouse model;Mus;nano;nanobiologic;Nanostructures;Neoadjuvant Therapy;Neoplasm Metastasis;neoplastic cell;particle;Patients;Penetration;Pertuzumab;Phenotype;Phosphotransferases;Pre-Clinical Model;pressure;Prevalence;Primary Neoplasm;Progesterone Receptors;Prognosis;Proteins;receptor;receptor mediated endocytosis;Recurrence;Refractory;Reporting;Resistance;response;Route;self assembly;Serum;Signal Transduction;Site;targeted treatment;Testing;Therapeutic;therapeutic target;Tissues;Toxic effect;trafficking;Trastuzumab;Treatment Efficacy;Treatment Protocols;triple-negative invasive breast carcinoma;tumor;Tumor Cell Invasion;Tumor Escape;tumor growth;tumor heterogeneity;tumor progression;Tumor Tissue;tumor xenograft;Tyrosine Kinase Inhibitor;Up-Regulation;Viral

PROJECT_TITLE: Targeting inhibitor-resistant breast tumors with HER3-homing nano-capsids

STUDY_SECTION: DT

STUDY_SECTION_NAME: Developmental Therapeutics Study Section[DT]


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cancer;Electronic Nicotine Delivery Systems;Lung;Lung Cancer;Prevention;Tobacco

ORG_CITY: Columbus

ORG_NAME: OHIO STATE UNIVERSITY

PHR: Public Health Relevance Statement While tobacco cigarette smoking is well known to cause lung cancer, it is not established if electronic cigarette (e-cig) use also causes lung cancer. Studies will be performed in a chronic mouse model of e-cig exposure to determine the duration and intensity of e-cig inhalation required for initiation of lung cancer as well as the role of vape free radicals and nicotine levels. Longitudinal studies with imaging of lung cancer development will be performed with histopathology confirmation, the underlying mechanisms of cancer onset, and potential approaches to ameliorate/prevent e-cig-induced lung damage will be identified, providing important insights toward defining the cancer risk of e-cigs.

PI_NAMEs: ZWEIER, JAY LOUIS (contact)

PROGRAM_OFFICER_NAME: JOHNSON, RONALD L

PROJECT_TERMS: 3-nitrotyrosine;Acetaldehyde;Address;Adenocarcinoma;adenoma;Adverse effects;Aerosols;Aldehyde oxidase;Aldehydes;Alveolus;animal imaging;antioxidant enzyme;Biochemical;Biological Assay;Blood;Bronchioles;cancer initiation;cancer risk;carcinogenesis;catalase;Cell Physiology;Cell Proliferation;Chronic;cigarette smoking;comparative;cytokine;Detection;Development;Devices;DNA Damage;e-cigarette aerosols;Electron Spin Resonance Spectroscopy;Electron Transport;Electronic cigarette;electronic cigarette use;electronic cigarette user;electronic liquid;Electronic Nicotine Delivery Systems;Enzyme-Linked Immunosorbent Assay;Enzymes;Epithelium;Evaluation;Exposure to;Female;Fluorescence;Formaldehyde;Free Radicals;Gender;Generations;glutathione peroxidase;histopathological examination;Histopathology;Image;Imaging Techniques;Immunohistochemistry;Incidence;Inflammation;Inflammatory;inflammatory lung disease;Inhalation;inhibitor;Injury;innovation;insight;Knowledge;Longitudinal Studies;Lung;lung carcinogenesis;Lung Diseases;lung imaging;lung injury;Lung Neoplasms;Magnetic Resonance Imaging;male;Malignant neoplasm of lung;Malignant Neoplasms;Malondialdehyde;Measurement;Measures;Mediating;Mesenchymal;Metabolism;microCT;Mitochondria;Modeling;mouse model;Mus;NADPH Oxidase;neoplastic;Nicotine;Nicotine Dependence;Nitric Oxide Synthase;non-invasive imaging;Oxidants;Oxidation-Reduction;oxidative DNA damage;Oxidative Stress;Oxidative Stress Induction;Pathology;Pathway interactions;Peroxonitrite;Phase;Poison;Premalignant Cell;prevent;Process;Production;Proteins;Public Health;public health relevance;Pulmonary Inflammation;Pulmonary Pathology;Reactive Oxygen Species;Reporting;Research;Risk;Role;SOD2 gene;Solid;Spin Trapping;stemness;Stress;Structure of parenchyma of lung;superoxide dismutase 1;Superoxides;Therapeutic;Therapeutic Intervention;Time;Tissues;Tobacco;Toxic effect;toxicant;tumor;Tumor Markers;vaping;Western Blotting;Work;X-Ray Computed Tomography

PROJECT_TITLE: Electronic cigarette derived free radicals, oxidative stress and inflammation in lung cancer development

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CVRS-N(50)]


NIH_SPENDING_CATS: Clinical Research;Digestive Diseases;Liver Disease

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE Ischemia/reperfusion (I/R) injury is a causative factor of morbidity and mortality during liver resection, and transplantation. Steatotic livers has significantly more vulnerable to I/R injury associated with these operations. There are no therapeutic strategies to reduce this I/R injury in steatotic livers. Therefore, our goal of this proposal is to develop novel therapeutic strategies to attenuate I/R injury in steatotic livers.

PI_NAMEs: KIM, JAE-SUNG  (contact)

PROGRAM_OFFICER_NAME: SHERKER, AVERELL H

PROJECT_TERMS: Affect;Attenuated;Autophagocytosis;Bioenergetics;Cell Death;Cessation of life;clinically relevant;Complement;Cysteine;Diet;dimer;efficacy evaluation;efficacy testing;Environment;Event;Excision;experimental study;Genetic;Goals;Hepatectomy;Hepatic;Hepatocyte;High Fat Diet;Histidine;Homeostasis;Homo;Human;Impairment;improved;In Vitro;in vivo;in vivo Model;innovation;insight;Intervention;Iron;Iron Overload;Ischemia;Knockout Mice;Liver;Liver Failure;liver injury;liver ischemia;liver transplantation;Mediating;Membrane Proteins;Mitochondria;mitochondrial dysfunction;Mitochondrial Proteins;Modeling;Molecular;monomer;Morbidity - disease rate;mortality;mouse model;Mus;Necrosis;novel;novel therapeutic intervention;operation;Outer Mitochondrial Membrane;Oxidation-Reduction;Pathologic;Patients;Permeability;pharmacologic;preclinical study;Predisposition;Reperfusion Injury;Reperfusion Therapy;Role;Safety;Slice;Stabilizing Agents;Structure;Testing;Therapeutic;therapeutically effective;Thinness;Tissues;Translating;translational study;Transplantation;Wild Type Mouse

PROJECT_TITLE: Autophagy in liver injury

STUDY_SECTION: HBPP

STUDY_SECTION_NAME: Hepatobiliary Pathophysiology Study Section[HBPP]


NIH_SPENDING_CATS: Autoimmune Disease;Digestive Diseases;Genetics;Human Genome;Inflammatory Bowel Disease;Microbiome;Nutrition

PHR: PROJECT NARRATIVE The human microbiome has been implicated in numerous aspects of health and disease. The goal of this proposal is to determine the functional consequences of bacterial adaptation in the inflammatory intestinal environment. New insights into the contribution commensal bacterial adaptations to early stages of gut inflammation will be a powerful strategy for detecting and treating early stages of IBD and preventing progression into the debilitating chronic phase of IBD.

PI_NAMEs: CHU, HIUTUNG  (contact)

PROGRAM_OFFICER_NAME: HUDSPETH, KELLY

PROJECT_TERMS: Adopted;Aerobic;Anaerobic Bacteria;Anti-Inflammatory Agents;bacterial metabolism;Bacteroides fragilis;Cells;Chemicals;Chronic;Chronic Phase;Coculture Techniques;cohort;Colitis;Collection;Colon;commensal bacteria;commensal microbes;Data;Dendritic Cells;Development;Diet;Disease;Environment;Exposure to;field study;fitness;gastrointestinal;Genes;Genetic;genetic variant;Genetic Variation;Genome;genome sequencing;genome-wide;Genomics;Gnotobiotic;Goals;Grant;gut bacteria;gut colonization;gut inflammation;gut microbiota;Health;Homeostasis;host-microbe interactions;Human;Human Microbiome;Immune;immune function;Immune response;Immune Tolerance;Immunity;Immunologics;immunoregulation;In Vitro;Inflammation;Inflammation Mediators;Inflammatory;Inflammatory Bowel Diseases;Inflammatory Response;insight;Interleukin-10;intestinal homeostasis;Intestines;Knock-out;Laboratories;Life Style;Link;lonely individuals;member;Metabolic;Metabolic Pathway;metabolomics;microbial;microorganism;Modeling;Mucosal Immune Responses;Mucous Membrane;murine colitis;Mus;Mutation;novel;Output;Oxidative Stress;Oxygen;Oxygen Consumption;Pathogenicity;Phenotype;prevent;Property;Reactive Oxygen Species;Research;Research Project Grants;Resistance;Respiration;response;Sampling;Shapes;T-Lymphocyte;Testing;Time;Tissues;transcriptome sequencing;Variant;whole genome;Work

PROJECT_TITLE: Bacterial adaptions in host-microbe interactions.

STUDY_SECTION: DHMI

STUDY_SECTION_NAME: Digestive System Host Defense, Microbial Interactions and Immune and Inflammatory Disease Study Section[DHMI]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Brain Disorders;Clinical Research;Dementia;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Machine Learning and Artificial Intelligence;Mental Health;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences;Prevention;Social Determinants of Health

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: Narrative  With a growing aging population worldwide, Alzheimer’s Disease and Related Dementias (ADRD) is expected to affect nearly 14 million Americans alone by 2060, contributing to long-term disability, reduced quality of life, and substantial healthcare costs. We will utilize large longitudinal electronic health record (EHR) data from three prominent academic centers and advanced informatics technology to thoroughly investigate the role of bilingualism on age-related cognitive health outcomes. We will develop informatics methods to assist with extensive screening, recruitment, and in-depth analysis of phenotypic information collected from both patient surveys and EHR data, while exploring novel pathways by which bilingualism influences cognitive reserve, or the ability to cope with neurological stress, in elderly bilingual and monolingual adults.

PI_NAMEs: DOSSETT, MICHELLE L;XU, HUA ;ZHOU, LI  (contact)

PROGRAM_OFFICER_NAME: HARRELL, ERIN

PROJECT_TERMS: Address;Adult;Affect;Age;Age of Onset;age related;age related cognitive change;age related neurodegeneration;Age-associated memory impairment;Aging;aging population;Algorithms;Alzheimer's disease related dementia;American;Behavioral;bilingualism;Boston;brain health;California;case finding;Characteristics;Clinical;Cognition;Cognitive;cognitive change;cognitive enhancement;cognitive function;cognitive process;cognitive reserve;cohort;comorbidity;Complex;Computing Methodologies;Confounding Factors (Epidemiology);coping;cost;Data;Dementia;design;Discipline;disorder prevention;Education;Elderly;Electronic Health Record;electronic health record system;electronic structure;Electronics;Environment;ethnic diversity;experience;Face;Future;Generations;Geography;Health;Health Care Costs;health care delivery;Health Sciences;Health Services Research;Health system;Healthcare Systems;Immigrant;Impaired cognition;improved;Individual;Informatics;innovation;insight;Institution;instrument;interdisciplinary approach;Intervention;Investigation;Knowledge;Language;Life;Life Style;Long term disability;Longitudinal Surveys;Machine Learning;machine learning algorithm;Maps;Measures;Methods;Morbidity - disease rate;Natural Language Processing;Nature;Needs Assessment;neural;Neurologic;Neurology;Neuropsychology;novel;novel therapeutic intervention;observational cohort study;older adult;Outcome;Pathway interactions;Patient Recruitments;Patients;Phenotype;Physical activity;Population;Population Heterogeneity;Prevention;primary outcome;Process;Prospective Studies;Prospective, cohort study;protective factors;Psychiatry;psychologic;Psychology;Quality of life;racial diversity;recruit;Registries;Reproducibility;Research;Research Support;resilience;Role;Sample Size;screening;Site;social;social health determinants;Social support;Standardization;statistics;Stress;Surveys;Technology;Testing;Texas;Text;theories;Time;time use;tool;Translating;Universities;US State;Work

PROJECT_TITLE: Leveraging Longitudinal Data and Informatics Technology to Understand the Role of Bilingualism in Cognitive Resilience, Aging and Dementia


NIH_SPENDING_CATS: Biotechnology

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Project Narrative: Public Health Relevance Protein-protein interactions (PPIs) are involved in nearly all biological processes, including cell proliferation, growth, differentiation, and apoptosis. Identification of collagen-protein interaction modulators will aid in the development of novel therapeutics for maladies including cancer, fibrosis, diabetes, and neurodegenerative disease in addition to serving as important chemical tools for elucidating fundamental aspects of human biology and biochemistry. Hyperstable collagen peptides and peptide mimics containing aza-amino acid residues offer the possibility to study previously elusive interactions between collagen triple helices and the myriad proteins that comprise the human collagen interactome.

PI_NAMEs: CHENOWETH, DAVID MICHAEL (contact)

PROGRAM_OFFICER_NAME: KOCH, PETER

PROJECT_TERMS: Address;alpha helix;Amino Acid Substitution;Amino Acids;Apoptosis;Area;Behavior;Binding Proteins;Binding Sites;Biochemistry;Biological;Biological Assay;Biological Availability;Biological Process;Biology;Biophysics;Carbon;Cell Physiology;Cell Proliferation;Cells;Chemicals;Chemistry;Collagen;Complex;Coupled;Crystallography;Cyclic Peptides;Data;DDR2 gene;Development;Diabetes Mellitus;Enzymes;Evaluation;Extracellular Matrix;Fibrosis;Future;Glycine;Goals;Growth;Health;Human;Human Biology;Hydrocarbons;Hydrogen Bonding;improved;Individual;insight;interfacial;Interstitial Collagenase;Knowledge;Laboratories;Location;Malignant Neoplasms;Methods;Modification;Multiprotein Complexes;Nature;Neurodegenerative Disorders;Nitrogen;novel;novel therapeutics;Pathology;Patient-Focused Outcomes;Peptide Synthesis;Peptides;peptidomimetics;Peptoids;Periodicity;Phase;Property;protein aminoacid sequence;protein protein interaction;Proteins;public health relevance;rational design;regenerative healing;Regulation;Resistance;response;scaffold;Science;self assembly;Solid;Structure;Surface;synthetic peptide;System;Therapeutic;Thermodynamics;thermostability;Time;tool;triple helix;Vertebral column;wound healing;X ray diffraction analysis

PROJECT_TITLE: Peptide Mimics of the Collagen Triple Helix

STUDY_SECTION: SBCB

STUDY_SECTION_NAME: Synthetic and Biological Chemistry B Study Section[SBCB]


NIH_SPENDING_CATS: Diabetes;Neurosciences;Pregnancy

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Project narrative Dysfunction or loss of endocrine beta-cells leads to diabetes. Pancreatic islets receive neuronal input from sympathetic and parasympathetic nerves and these interactions are essential for hormone secretion. During pregnancy, beta-cells respond to high metabolic demand by increasing their mass and secretory function. The goal of this project is to address the role of sympathetic nerves in regulating the structural and functional plasticity of beta-cells during pregnancy using whole organ clearing, 3D imaging, and nerve ablation studies in mice.

PI_NAMEs: YAMAMOTO, JOSELYN STIBALIS (contact)

PROGRAM_OFFICER_NAME: BODDIE, THOMAS ARTIS

PROJECT_TERMS: 3-Dimensional;Ablation;acetylcholine transporter;Address;Adult;Affect;American;Anatomy;Animal Model;Architecture;Area;autonomic nerve;Beta Cell;Biological Assay;Blood Glucose;blood glucose regulation;Blood Vessels;Cardiovascular Diseases;Cell Proliferation;Cells;Choline O-Acetyltransferase;cholinergic;Chronic Disease;Communication;Compensation;defined contribution;density;Development;Diabetes Mellitus;Diabetes prevention;Disease;Endocrine;endocrine pancreas development;experimental study;Fellowship;Functional disorder;functional plasticity;Genetic;glucose tolerance;Goals;Health;Health Care Costs;Hormone secretion;Hormones;human tissue;Image;Impairment;improved;Injury;insight;Insulin;Insulin Resistance;insulin secretion;insulin sensitivity;Insulin-Dependent Diabetes Mellitus;islet;Islet Cell;Islets of Langerhans;Laboratories;Leadership;Life;LoxP-flanked allele;Maintenance;Mentors;Metabolic;Molecular;Morphology;Mus;Nerve;Nerve Growth Factors;nerve supply;Neuronal Plasticity;Neurons;neurotrophic factor;Non-Insulin-Dependent Diabetes Mellitus;Obesity;Optics;Organ;Pancreas;Pathologic;Pathway interactions;PDGFRB gene;Pericytes;Peripheral;Peripheral Nerves;Physiological;Pregnancy;pregnant;preservation;prevent;Proliferating;Quality of life;Regulatory Pathway;Reporting;Research;Research Personnel;Resources;response;Retinal Diseases;Role;Secretory Cell;Signal Transduction;skills;spatial relationship;Structure;Sympathectomy;Testing;Three-Dimensional Imaging;Training;Tyrosine 3-Monooxygenase;Universities

PROJECT_TITLE: Role of Sympathetic Innervation in Islet Plasticity during Pregnancy.


NIH_SPENDING_CATS: Brain Disorders;Dental, Oral, and Craniofacial Disease;Mental Health;Neurosciences

ORG_CITY: SAN FRANCISCO

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: Project Narrative Mental illnesses such as bipolar disorder and schizophrenia are most often treated with a class of medications called neuroleptics, which block dopamine signaling in the brain. Long-term treatment is often complicated by the development of abnormal movements, such as lip smacking and tongue protrusion, termed tardive dyskinesia. This project will use brain recordings in a mouse model of tardive dyskinesia, to better understand how dopamine and the brain cells it regulates cause involuntary movements.

PI_NAMEs: NELSON, ALEXANDRA  (contact)

PROGRAM_OFFICER_NAME: CHEN, DAOFEN

PROJECT_TERMS: Acute;Address;Affinity;Aftercare;Animal Model;Animals;antagonist;Antipsychotic Agents;Area;Attenuated;Basal Ganglia;Behavior;Binding;Biochemistry;Bipolar Disorder;Brain;brain cell;cell type;Chronic;Corpus striatum structure;designer receptors exclusively activated by designer drugs;Detection;Development;Disabling;Dopamine;Dopamine Antagonists;Dopamine D2 Receptor;dopamine D3 receptor;Dopamine Receptor;Dyskinetic syndrome;Electrophysiology (science);experience;experimental study;Face;Fiber;Formulation;Ganglia;Gastrointestinal Diseases;Genetic;genetic manipulation;Goals;Haloperidol;Head;in vivo;Individual;inhibitor;innovation;integration site;Intervention;Involuntary Movements;Knock-out;Label;Link;Lip structure;Measures;Mental disorders;Migraine;Modeling;Monitor;mouse model;Movement;Mus;neural;neural correlate;Neurons;Optics;optogenetics;Oral cavity;orofacial;Output;Pathway interactions;Patients;Pattern;Pharmaceutical Preparations;pharmacologic;Pharmacology;Photometry;Physiological;Play;Population;Prevention;Psychiatric therapeutic procedure;receptor;response;Role;Schizophrenia;sensor;Severities;Signal Transduction;Specificity;Tardive Dyskinesia;temporal measurement;Testing;Tetrabenazine;theories;therapeutic development;Tongue;tool;Up-Regulation;Upper Extremity

PROJECT_TITLE: Striatal Microcircuit Mechanisms of Tardive Dyskinesia

STUDY_SECTION: CNNT

STUDY_SECTION_NAME: Clinical Neuroplasticity and Neurotransmitters Study Section[CNNT]


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

ORG_NAME: WHITEHEAD INSTITUTE FOR BIOMEDICAL RES

PHR: 8. PROJECT NARRATIVE Toxoplasma gondii is a parasite and NIAID category B Biodefense agent that chronically infects about a quarter of the world's population, causing recurrent ocular lesions in about 2% of cases and life-threatening infections in immunocompromised individuals. The proposed study will characterize the mechanisms that allow parasites to enter a chronic state that is resistant to all current therapies and acts as a reservoir for reactivation. Our work will lay the molecular foundation for future therapies that can prevent and eliminate chronic Toxoplasma infections.

PI_NAMEs: LOURIDO, SEBASTIAN  (contact)

PROGRAM_OFFICER_NAME: MCGUGAN, GLEN C

PROJECT_TERMS: 5' Untranslated Regions;acute infection;Address;Binding;biodefense;Brain;Categories;Cell Culture Techniques;Chromatin;Chronic;CRISPR screen;curative treatments;Cyst;Data;Development;differentiation in vitro;Disease;Disease Reservoirs;Down-Regulation;Elements;Environmental Risk Factor;Event;Exposure to;Failure;Foundations;Future;Genes;Genetic;Genetic Transcription;Goals;Homeostasis;Immunocompetent;Immunocompromised Host;Individual;Infection;insight;Lesion;Licensing;Life;Link;Maintenance;Mediating;Messenger RNA;Molecular;Monitor;mouse model;Mus;Mutation Analysis;National Institute of Allergy and Infectious Disease;Nucleic Acid Binding;Parasites;Pathway interactions;Population;posttranscriptional;Prevalence;prevent;Process;programs;promoter;Proteins;Proteomics;Recurrence;Regulation;Regulatory Pathway;Reporter;Resistance;Resolution;response;ribosome profiling;Ribosomes;RNA;Role;screening;Stress;Structure;Tissues;Toxoplasma;Toxoplasma gondii;Toxoplasmosis;Transcript;transcription factor;Transcriptional Regulation;transcriptome sequencing;Translational Regulation;Translations;Video Microscopy;Virulence;Work

PROJECT_TITLE: Development and maintenance of chronic toxoplasmosis

STUDY_SECTION: PTHE

STUDY_SECTION_NAME: Pathogenic Eukaryotes Study Section[PTHE]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Clinical Research;Dementia;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: GAINESVILLE

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: PROJECT NARRATIVE Our main goal is to provide concrete real-world evidence from large collections of real-world data (RWD) to fill the knowledge gaps in our knowledge of Alzheimer’s disease (AD) risk and heterogeneous progression pathways in the sexual and gender minority (SGM) populations as well as their disparities in AD outcomes. We will leverage our access to large collections of RWD from the OneFlorida+ and INSIGHT networks – two clinical research networks contributing to the national Patient-Centered Clinical Research Network (PCORnet). More importantly, this project will establish a framework for creating RWD-based virtual cohort, which can inform national pragmatic trials across PCORnet for future SGM aging clinical studies.

PI_NAMEs: BIAN, JIANG  (contact);GUO, YI ;WANG, FEI

PROGRAM_OFFICER_NAME: KARRAKER, AMELIA WILKES

PROJECT_TERMS: Affect;age related;Aging;Alabama;Algorithms;Alzheimer disease prevention;Alzheimer's Disease;Alzheimer's Disease Pathway;Alzheimer's disease patient;Alzheimer's disease related dementia;Alzheimer's disease risk;American;billing data;Caring;Cause of Death;Characteristics;Clinical;clinical care;Clinical Medicine;Clinical Research;clinical risk;Cognitive;cohort;Collection;computable phenotypes;Consumption;cost;Data;Data Science;Degenerative Disorder;Dementia;Disadvantaged minority;disease disparity;Disease Outcome;Disease Progression;Disparity;Electronic Health Record;ethnic minority;Face;federated learning;Florida;Future;gender difference;gender minority group;gender minority health;gender minority status;Goals;Grain;Health;Heterogeneity;Individual;Knowledge;Machine Learning;machine learning method;Mediation;Methodology;Methods;mild cognitive impairment;minority disparity;Modeling;Natural Language Processing;neighborhood safety;New York;novel;Onset of illness;Outcome;Pathway interactions;patient oriented;Patients;Pattern;Phenotype;phenotyping algorithm;Population;pragmatic trial;Prevention;Proliferating;racial minority;Research;Research Priority;Risk Factors;risk stratification;Rural Minority;Severities;Severity of illness;Sex Differences;Sexual and Gender Minorities;sexual minority group;social cohesion;social health determinants;socioeconomic disadvantage;Standardization;Structure;Subgroup;success;Syndrome;Testing;Time;tool;translational impact;underserved minority;virtual

PROJECT_TITLE: Disparities of Alzheimer's disease progression in sexual and gender minorities

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-HSS-J(02)M]


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

ORG_CITY: WASHINGTON

ORG_DEPT: NEUROSCIENCES

ORG_NAME: GEORGETOWN UNIVERSITY

ORG_STATE: DC

PHR: Narrative APOE4 is associated with cognitive dysfunction in aged individuals and increased Alzheimer’s risk. A better understanding of the mechanisms by which APOE4 could alter cognition, and whether specific therapeutics could target these pathways, is critically needed.

PI_NAMEs: CONANT, KATHERINE E (contact)

PROGRAM_OFFICER_NAME: DIBATTISTA, AMANDA

PROJECT_TERMS: Abeta clearance;Acceleration;Address;Adult;Affect;age related changes;aggrecan;aging population;Alleles;Alzheimer's Disease;Alzheimer's disease risk;Amyloid beta-Protein;antagonist;anti-depressive agents;Antibodies;Apolipoprotein E;apolipoprotein E-4;Area;Astrocytes;Attenuated;Behavioral;Binding;Brain;brevican;CCR5 gene;Central Nervous System;chemokine;Cognition;Cognitive;cognitive reserve;cohort;collagenase 3;critical period;CSPG3 gene;Data;Dendrites;Deposition;Disintegrins;Dose;Elderly;Enzyme Tests;Equilibrium;Event;experience;experimental study;Extracellular Matrix;Family member;FDA approved;flexibility;Fluorescence;Future;gamma-Aminobutyric Acid;Gelatinase B;Glutamates;Hippocampus;Human;Impaired cognition;Impairment;Individual;Interneurons;Learning;Lectin;Link;Long-Term Effects;Long-Term Potentiation;Matrix Metalloproteinase Inhibitor;Matrix Metalloproteinases;Measures;memory consolidation;Memory impairment;Metalloproteases;Mus;Nerve Degeneration;neuronal cell body;Neuronal Plasticity;Neurons;neurotransmission;Parvalbumins;Pathway interactions;Peptide Hydrolases;Pharmaceutical Preparations;Physiological;Play;Population Dynamics;post stroke;preclinical study;Proteolysis;Publishing;Pyramidal Cells;RANTES;receptor;Regulation;Reversal Learning;Risk;risk variant;Rodent;Short-Term Memory;Slow-Wave Sleep;Stains;Testing;Therapeutic;Time;Tissue Inhibitor of Metalloproteinase-1;transmission process;venlafaxine;Western Blotting

PROJECT_TITLE: ECM regulation and neuronal plasticity in mice harboring a common risk allele for Alzheimer's

STUDY_SECTION: CDIN

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