NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Neurosciences;Social Determinants of Health

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: Project Narrative We posit that trainees from under-represented groups (URGs) are less likely to persist in neuroscience-focused professional careers due to a lack of a sense of belonging within their professional community. To increase inclusion and retention of URG trainees in neuroscience, we propose a multi-component strategy called Pathways to Neurosciences centered around peer-mentored NeuroCircles and faculty-mentored Pathway Mentors aimed at increasing belonging, promoting excellence in scientific and leadership skills, and increasing social capital within the professional community over the long term. The program design and evaluation plan were developed in parallel to allow us to utilize regular network and psychosocial surveys to understand how the program is working and continuously improve its effectiveness.

PI_NAMEs: BUCKWALTER, MARION S (contact);GOODMAN, MIRIAM B

PROGRAM_OFFICER_NAME: ULLRICH, LAUREN ELIZABETH

PROJECT_TITLE: Pathways to Neurosciences


ADMINISTERING_IC: NS

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Immunotherapy;Neurosciences;Orphan Drug;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: SAINT LOUIS

ORG_COUNTRY: UNITED STATES

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_FIPS: US

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE The proposed research is relevant to public health as it may lead to a new treatment for glioblastoma, and prevent neurological decline and death. By studying how Zika virus works to trigger an immune response against the tumor, we will contribute to fundamental knowledge that will help treat this lethal disease.

PI_NAMEs: CHHEDA, MILAN GIRISH (contact)

PROGRAM_OFFICER_NAME: FOUNTAIN, JANE W

PROJECT_TERMS: 3' Untranslated Regions;Address;Adult;aggressive therapy;anti-tumor immune response;Antibodies;Antigens;Antitumor Response;Biological Assay;Biology;Brain;brain cell;Brain Neoplasms;CD8-Positive T-Lymphocytes;Cells;Cerebral hemisphere;Cessation of life;chemoradiation;chemotherapy;Clinical;Clinical Skills;clinical translation;Clinical Trials;Combined Modality Therapy;CTLA4 gene;cytotoxicity;Deterioration;Disease;effector T cell;Epidemic;epidemic virus;experimental study;Failure;fetal;Flow Cytometry;Genetic;Glioblastoma;Glioma;Goals;Granzyme;Human;Immune;Immune response;Immune system;Immunity;Immunologic Sensitization;Immunologics;Immunology;Immunotherapy;improved outcome;in vivo;Infrastructure;Innate Immune Response;Interferons;Intracranial Neoplasms;Kinetics;Knowledge;Long-Term Survivors;Lytic;Maps;Mediating;Modeling;Mus;Neoplasm Metastasis;neoplastic cell;nerve stem cell;Neurologic;Neuronal Differentiation;novel strategies;Oncolytic;oncolytic virotherapy;oncolytic Zika virus;Operative Surgical Procedures;Outcome;Patients;perforin;Peripheral;Positioning Attribute;prevent;Primary Neoplasm;programmed cell death protein 1;Property;Public Health;Publishing;Radiation;Recombinants;recruit;Research;Resistance;Safety;single-cell RNA sequencing;standard of care;stem cells;System;T cell response;T-Lymphocyte;temozolomide;Testing;Therapeutic;TNFSF10 gene;tumor;Tumor Antigens;tumor immunology;Tumor Necrosis Factor Ligand Superfamily Member 6;Tumor Promotion;Tumor Stem Cells;Tumor-Infiltrating Lymphocytes;virology;Virus;virus testing;Work;Zika Virus;ZIKV infection

PROJECT_TITLE: Leveraging Zika virus and the immune system to treat glioblastoma

STUDY_SECTION: CNBT

STUDY_SECTION_NAME: Clinical Neuroimmunology and Brain Tumors Study Section[CNBT]


ADMINISTERING_IC: HL

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Biotechnology;Cardiovascular;Clinical Research;Gene Therapy;Genetics;Heart Disease;Heart Disease - Coronary Heart Disease;Nanotechnology;Organ Transplantation;Transplantation

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: NARRATIVE We present here a novel approach for targeted delivery of nanomedicines to the coronary microvasculature during ex vivo normothermic perfusion of marginal human hearts. Our approach is based on powerful new methods for nanoparticle targeting and incorporates advanced diagnostic imaging tools to characterize nanoparticle accumulation as well as myocardial perfusion and function. The goal of this work is to develop targeted therapies to treat ischemia-reperfusion injury and improve the availability hearts for transplantation

PI_NAMEs: STENDAHL, JOHN C (contact)

PROGRAM_OFFICER_NAME: WOO, SEUNG KYOON

PROJECT_TERMS: Address;Affect;Allogenic;Antibodies;Biomedical Engineering;Blood flow;Blood Vessels;Cardiac;Cardiopulmonary Bypass;cardiovascular imaging;Cardiovascular system;career;Clinical;clinically significant;Collaborations;Coronary;Coronary artery;coronary vasculature;Data;design;Development;Diagnostic Imaging;Doctor of Philosophy;Documentation;Drug Carriers;Echocardiography;Engineering;Equipment;Ethics;Evaluation;ex vivo imaging;experience;Exposure to;Family suidae;Fellowship;Fluorescence Microscopy;Formulation;Fostering;Foundations;Funding;Goals;Heart;heart function;heart imaging;heart preservation;Heart Transplantation;high risk;Human;Imaging Device;imaging facilities;imaging modality;Imaging Techniques;Immunologics;Impairment;improved;innovation;Institution;instructor;Intervention;Investigation;Ischemia;K-Series Research Career Programs;Kidney;Knowledge;lectures;Life;Link;Liver;Medical Imaging;medical schools;Medicine;meetings;Mentors;Mentorship;Methods;Microscopy;mouse model;multimodality;Myocardial Infarction;Myocardial perfusion;nanomedicine;nanoparticle;nanoparticle delivery;nanoparticle drug;novel strategies;Obstruction;Organ;Organ Procurements;Organ Transplantation;particle;Patients;Perfusion;Pharmacological Treatment;Predisposition;receptor;Reperfusion Injury;Reperfusion Therapy;Research;Research Personnel;restoration;risk mitigation;Science;Scientist;severe injury;single photon emission computed tomography;Small Interfering RNA;Structure;targeted delivery;targeted treatment;Techniques;Technology;Testing;Therapeutic;Therapeutic Effect;Time;Training;Translational Research;Transplantation;Vascular Endothelium;Work;X-Ray Computed Tomography

PROJECT_TITLE: Targeted delivery of nanomedicines to the coronary microvasculature during ex vivo normothermic perfusion of marginal human hearts

STUDY_SECTION: MCBS

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


ADMINISTERING_IC: AI

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Biotechnology;Emerging Infectious Diseases;Infectious Diseases

ORG_CITY: NEW YORK

ORG_DEPT: CHEMISTRY

ORG_NAME: NEW YORK UNIVERSITY

ORG_STATE: NY

PHR: Project Narrative This research will provide a molecular view for how antibiotic resistance is conferred to pathogenic Staphylococcus aureus. Our research will also propose and validate a novel inhibitor type for blocking an important antibiotic resistance mechanism, with the long-term goal of using these compounds in combination with existing antibiotics.

PI_NAMEs: KOIDE, SHOHEI ;TRAASETH, NATHANIEL J. (contact);WANG, DANENG

PROGRAM_OFFICER_NAME: XU, ZUOYU

PROJECT_TERMS: Active Biological Transport;Animals;antibiotic efflux;Antibiotic Resistance;Antibiotics;Antibodies;Arginine;Aspartate;Binding;Biological Assay;Biological Models;Cells;Charge;chemical synthesis;Collaborations;Complex;computational chemistry;Coupled;Cryoelectron Microscopy;Cytoplasm;Data;design;Development;Directed Molecular Evolution;Drug Efflux;Drug resistance;drug resistant bacteria;Drug Transport;Effectiveness;efflux pump;Electrostatics;experimental study;extracellular;Fab Immunoglobulins;Free Energy;global health;Glutamates;Goals;Growth;Human;Hybrids;Immunoglobulin Fragments;improved;Infection;inhibitor;insight;Ions;Knowledge;methicillin resistant Staphylococcus aureus;Methods;Microbiology;miniaturize;Molecular;Molecular Conformation;molecular recognition;multidrug transport;Mutation;NMR Spectroscopy;novel;Organism;pathogenic bacteria;Pathogenicity;Peptides;peptidomimetics;Pharmaceutical Preparations;Phenotype;Play;Positioning Attribute;Protein Engineering;Proteins;protonation;Research;Resistance;resistance mechanism;Resolution;Role;Side;Specificity;Staphylococcus aureus;structural biology;Structure;Synthesis Chemistry;synthetic antibodies;System;Testing;Therapeutic;tool;Toxic effect;unnatural amino acids;Validation

PROJECT_TITLE: Transport Mechanisms and Inhibition of Efflux Pumps in Pathogenic Organisms

STUDY_SECTION: BBM

STUDY_SECTION_NAME: Biochemistry and Biophysics of Membranes Study Section[BBM]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Clinical Research;Congenital Structural Anomalies;Eye Disease and Disorders of Vision;Gene Therapy;Genetics;Neurodegenerative;Neurosciences;Pediatric;Rare Diseases;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: SAN FRANCISCO

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: PROJECT NARRATIVE With no effective treatments currently available, Leber Congenital Amaurosis accounts for 5% of all retinal dystrophies and 20% of blindness in school age children. This proposal aims to establish a retinal organoid model system that recapitulates disease phenotypes to allow for the investigation into mechanistic causes and therapeutic rescue of dominant forms of this disease. These studies will provide a pipeline for therapeutic gene editing to treat individuals with severe dominant retinal diseases.

PI_NAMEs: ULLIAN, ERIK M (contact)

PROGRAM_OFFICER_NAME: NEUHOLD, LISA

PROJECT_TERMS: Affect;Alleles;autosome;Binding;Binding Sites;Biochemical;Biological Models;Blindness;Cell Line;Cell Maturation;Cell Physiology;Child;Clinic;Clustered Regularly Interspaced Short Palindromic Repeats;Cone;CRISPR therapeutics;CRISPR/Cas technology;CRX protein;Defect;Development;developmental disease;Disease;disease model;disease phenotype;disease-in-a-dish;DNA Binding;Dominant-Negative Mutation;early onset;effective therapy;Endonuclease I;Excision;Foundations;Functional disorder;functional restoration;Future;gene replacement;gene therapy;gene-editing approach;gene-targeted therapy;Genes;Genetic Transcription;genome editing;Goals;Histologic;Human;human induced pluripotent stem cells;human subject;improved;In Vitro;in vitro Model;in vivo;Individual;induced pluripotent stem cell;Inherited;insight;Investigation;Knock-out;Laboratories;Lead;Leber's amaurosis;loss of function mutation;Loss of Heterozygosity;Mediating;Modeling;mouse model;Mus;mutant;Mutation;Newborn Infant;novel strategies;novel therapeutic intervention;Organoids;Pathogenesis;patient derived induced pluripotent stem cells;Patients;Phenotype;Photoreceptors;Play;Protein Analysis;protein expression;protein function;protein protein interaction;Protocols documentation;Reporting;Retina;Retinal Degeneration;Retinal Diseases;Retinal Dystrophy;RNA analysis;School-Age Population;sight restoration;Solid;stem cell derived tissues;stem cells;Testing;Therapeutic;therapeutic genome editing;tool;transcription factor;Variant;Vision;Vision research;Work

PROJECT_TITLE: Mechanistic analysis and allellic genome editing of iPSC-derived dominant LCA model

STUDY_SECTION: DPVS

STUDY_SECTION_NAME: Diseases and Pathophysiology of the Visual System Study Section[DPVS]


ADMINISTERING_IC: CA

ED_INST_TYPE: SCHOOLS OF PHARMACY

IC_NAME: NATIONAL CANCER INSTITUTE

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

ORG_CITY: AMHERST

ORG_DEPT: PHARMACOLOGY

ORG_NAME: STATE UNIVERSITY OF NEW YORK AT BUFFALO

PHR: PROJECT NARRATIVE Ovarian cancer remains one of the most deadly forms of cancer, with limited treatment options for the advanced disease setting. Spheroid formation and metabolic shift capability enable ovarian cancer cells to adapt in intraperitoneal and lipid-rich tumor microenvironment, driving drug resistance and metastatic progression. Here we present a new approach to target ovarian cancer spheroids and metabolic vulnerability and describe the preclinical evaluation of this strategy using experimental and computational approaches.

PI_NAMEs: WOO, SUKYUNG  (contact)

PROGRAM_OFFICER_NAME: O'HAYRE, MORGAN

PROJECT_TERMS: 3-Dimensional;Accounting;Adhesions;Adipocytes;adipokines;advanced disease;Anatomy;Anoikis;antagonist;APLN gene;Area;Ascites;Automobile Driving;barrier to care;Basic Science;Biodistribution;cancer cell;Cancer cell line;cancer pharmacology;Cell model;Cells;Cellular Spheroids;Cessation of life;Characteristics;Chemoresistance;chemotherapy;Cisplatin;Clinical;clinically significant;Coculture Techniques;Computer Models;cytotoxic;Data;density;Diagnosis;Disease;Dose;drug development;drug distribution;drug efficacy;Drug Kinetics;Drug resistance;Drug Transport;efficacious treatment;established cell line;experimental study;Extracellular Matrix;fatty acid oxidation;G-Protein-Coupled Receptors;genetic approach;Goals;Greater sac of peritoneum;Growth;Health;Histology;Human;immune cell infiltrate;immune function;Immunocompetent;Immunotherapy;Implant;improved;improved outcome;In Vitro;in vivo;ineffective therapies;inhibitor;intraperitoneal;Invaded;knock-down;Knowledge;Ligands;Link;Lipids;Maintenance Therapy;Malignant Epithelial Cell;Malignant neoplasm of ovary;Malignant Neoplasms;Mesothelium;Metabolic;Metabolic Pathway;Metabolism;metabolomics;migration;Mitochondria;Modeling;Molecular;mortality;mouse model;multidisciplinary;Neoplasm Metastasis;neoplastic cell;Normal tissue morphology;novel;novel strategies;Omentum;Operative Surgical Procedures;Organ;Outcome;Ovarian;Ovarian Carcinoma;Ovarian Serous Adenocarcinoma;overexpression;Paclitaxel;Pathologic;Pathway interactions;patient derived xenograft model;Patient-Focused Outcomes;Patients;Peritoneal;pharmacodynamic model;pharmacologic;Phenotype;Physiological;pre-clinical;Pre-Clinical Model;preclinical evaluation;prevent;Primary Neoplasm;Production;Property;receptor;Receptor Inhibition;Reporting;Research;Resistance;Role;Serous;Site;spatiotemporal;spheroids;standard of care;Surface;Testing;therapeutic effectiveness;Therapeutic Intervention;therapeutic target;Tissues;Toxic effect;TP53 gene;trait;treatment effect;Treatment Effectiveness;Treatment Efficacy;treatment group;tumor;Tumor Burden;tumor microenvironment;tumor progression;Tumor Weights;uptake;women's outcomes;Xenograft procedure

PROJECT_TITLE: Targeting ovarian cancer spheroid formation and metabolic adaptation by APJ inhibition

STUDY_SECTION: DT

STUDY_SECTION_NAME: Developmental Therapeutics Study Section[DT]


NIH_SPENDING_CATS: Biotechnology;Cancer;Colorectal Cancer;Digestive Diseases;Lung;Lung Cancer

ORG_CITY: WEST LAFAYETTE

ORG_NAME: PURDUE UNIVERSITY

ORG_STATE: IN

PHR: There are no small molecule inhibitors in existence to target NatD. This application is the first study that seeks to discover novel small molecules targeting NatD. The proposed research is relevant to public health because the developed NatD inhibitors will increase our understanding of how NatD contributes to cancer progression and its value as a therapeutic target, which is relevant to the mission of NCI.

PI_NAMEs: HUANG, RONG  (contact)

PROGRAM_OFFICER_NAME: FORRY, SUZANNE L

PROJECT_TERMS: A549;Acetylation;Acetyltransferase;Active Sites;Address;adduct;Affinity;analog;Antibodies;Apoptosis;Binding;Biochemical;Biological;Biological Assay;Biological Process;Calorimetry;cancer cell;Cancer cell line;Cancer Patient;CASP9 gene;cell motility;Cell Physiology;Cell Proliferation;Cell Survival;Cells;Chemicals;chromatin remodeling;Chromatin Structure;Clinical;Coenzyme A;Collection;Colon;Colorectal Cancer;Complex;cyanine dye 5;Development;drug discovery;Epigenetic Process;epithelial to mesenchymal transition;Fibroblasts;Fluorescence;Fluorescence Polarization;Fluorescent Probes;fluorophore;Foundations;gene repression;Genomics;Goals;H1299;HCT116 Cells;high throughput screening;Histone Acetylation;Histone H2A;Histone H4;HT29 Cells;Human;human disease;inhibitor;Invaded;Investigation;knock-down;Knowledge;Lung;lung cancer cell;Malignant neoplasm of lung;Malignant Neoplasms;Measures;Mediating;member;meter;Mission;Mitochondria;Molecular;Monitor;mouse model;N-terminal;novel;novel therapeutic intervention;Outcome;Pathway interactions;Peptides;pharmacologic;pharmacophore;Physiological;Play;prevent;Process;Proteins;Public Health;Radioactive;redshift;Reporting;Reproducibility;Research;Resources;response;Roentgen Rays;Role;Sampling;screening;Series;Slug protein;small hairpin RNA;small molecule;small molecule inhibitor;small molecule libraries;stable cell line;Structure;Structure-Activity Relationship;success;System;Testing;Tetracyclines;Therapeutic;therapeutic target;Tissues;Titrations;TP53 gene;tumor growth;tumor progression;Up-Regulation;Xenograft procedure

PROJECT_TITLE: Discovery of small molecule inhibitors for protein N-terminal acetyltransferase D

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-BST-F(55)R]


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Nutrition;Obesity;Physical Activity;Physical Rehabilitation;Prevention;Rehabilitation

ORG_CITY: BERKELEY

ORG_DEPT: NUTRITION

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: We will measure muscle mass and changes in muscle mass in the funded program project, the Adapting MultiPLe behavior Interventions that eFfectively Improve (AMPLIFI) Cancer Survivor Health (1P01CA22997, using a novel, accurate, and non-invasive method the D3- Creatine dilution method. This project will assess, for the first time, how diet, exercise, and aging affects skeletal muscle mass in this at-risk population of older cancer survivors and test the hypothesis that muscle mass and changes in muscle mass are strongly related to changes in functional capacity and physical activity.

PI_NAMEs: CAWTHON, PEGGY MANNEN;DEMARK-WAHNEFRIED, WENDY ;EVANS, WILLIAM J (contact)

PROGRAM_OFFICER_NAME: AGURS-COLLINS, TANYA

PROJECT_TERMS: Acceleration;Activities of Daily Living;Aerobic;Affect;Age;age related;Aging;Area;arm;Behavior Therapy;Body Composition;Body Weight decreased;cancer diagnosis;cancer survival;Cancer Survivor;capsule;Clinical;Clinical Trials;Cohort Studies;comparative efficacy;Control Groups;Creatine;Creatinine;Data;design;Diet;diet and exercise;Dietary Intervention;disability;disability risk;Dual-Energy X-Ray Absorptiometry;effective intervention;Enrollment;Exercise;exercise intervention;exercise program;falls;Fasting;Fatty acid glycerol esters;Fracture;Funding;Gait speed;Health;health assessment;high risk population;Home;Hour;improved;Individual;Ingestion;Intervention;intervention effect;Intervention Trial;lean body mass;life span;lifestyle intervention;Magnetic Resonance Imaging;Malignant Neoplasms;Measurement;Measures;Medical Research;men;Methods;Minority;MRI Scans;Muscle;muscle form;novel;Obesity;older men;Older Population;older women;Outcome;Overweight;Participant;Patients;Performance;Physical activity;Physical assessment;Physical Function;Physical Performance;Populations at Risk;preservation;Prevalence;Program Research Project Grants;programs;Quality of life;reduced muscle mass;response;Risk;Rural;rural setting;Sampling;sarcopenia;Schedule;Skeletal Muscle;Surveys;Testing;Thinness;Time;tool;Urine;validation studies;Venous blood sampling;Visiting Nurse;wasting;weight loss intervention;Woman;X-Ray Computed Tomography

PROJECT_TITLE: AMPLIFIed muscle mass in older cancer survivors enrolled in a diet-exercise program

STUDY_SECTION: BMIO

STUDY_SECTION_NAME: Behavioral Medicine, Interventions and Outcomes Study Section[BMIO]


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

FUNDING_MECHANISM: RESEARCH CENTERS

ORG_CITY: BALTIMORE

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Project Narrative We propose to create a Center that will focus on developing new 3D imaging tools to visualize breast and pancreatic tumors at high spatial resolution. Our multidisciplinary team of clinicians, computational biologists, and bioengineers will develop computer algorithms combined with advanced molecular tools to recognize key types of cells that can contribute to the spread of cancer cells from the primary tumor site to distant sites in 3D.

PI_NAMEs: WIRTZ, DENIS  (contact);WOOD, LAURA DELONG

PROGRAM_OFFICER_NAME: BECKER, STEVEN

PROJECT_TERMS: 3-Dimensional;Address;Advisory Committees;Advocate;anti-cancer research;Beds;Biomedical Engineering;Blood Vessels;cancer cell;cancer imaging;cell type;Cells;Cellular biology;Circulation;Communities;Complex;Computational algorithm;Computer software;cost;Cytometry;data dissemination;Death Rate;deep learning algorithm;Detection;Distant;Distant Metastasis;Engineering;Evaluation;experience;Histologic;Human;Image;Imaging Device;imaging modality;immunocytochemistry;Immunofluorescence Immunologic;insight;Invaded;Label;large datasets;Liver;lymphatic Invasion;Malignant - descriptor;Malignant Breast Neoplasm;Malignant neoplasm of pancreas;Mammary Gland Parenchyma;Mammary Neoplasms;Maps;medical schools;Methods;Microanatomy;Microscopy;Molecular;Molecular Analysis;Morphology;mortality;mouse model;multidisciplinary;multiple omics;Mus;Neoplasm Metastasis;novel;Occupational activity of managing finances;Operative Surgical Procedures;Optics;Organoids;Outcome;pancreatic neoplasm;Pathologic;Pathology;Patients;Phenotype;Physicians;Portal vein structure;Primary Neoplasm;Process;Prognosis;Proteomics;reconstruction;Resected;Resolution;Sampling;Schools;Scientist;serial imaging;Site;Survival Rate;Test Result;Testing;Three-Dimensional Imaging;Tissue imaging;Tissue Sample;Tissues;tool;transcriptomics;tumor;tumor heterogeneity;tumor microenvironment;Venous;Visualization;Wood material

PROJECT_TITLE: Center for 3D Imaging in Cancer Cell Biology


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cancer;Digestive Diseases;Pancreatic Cancer;Rare Diseases

PI_NAMEs: WIRTZ, DENIS  (contact)

PROJECT_TERMS: 3-Dimensional;Address;Advisory Committees;Advocate;anti-cancer research;Architecture;Basic Science;Beds;Biomedical Research;biophysical properties;Budgets;Cancer Biology;cancer cell;cancer imaging;career;Cells;Cellular biology;Chemicals;clinically relevant;Collaborations;Communication;Communities;Comprehensive Cancer Center;Computing Methodologies;Disease;Doctor of Medicine;Doctor of Philosophy;Documentation;Engineering;Ensure;Event;experience;Faculty;Financial Support;Funding;Gene Expression;Goals;Human;Human Resources;imaging modality;Imaging technology;improved;Individual;Infrastructure;innovation;Institutional Review Boards;Lead;Leadership;Liver;Malignant Neoplasms;materials science;Medicine;meetings;member;Mentors;mid-career faculty;Mission;Monitor;multidisciplinary;nanobiotechnology;next generation;Occupational activity of managing finances;Oncology;outreach;Pancreas;pancreatic cancer cells;Pathology;Patient-Focused Outcomes;Patients;pre-clinical research;Productivity;professor;Progress Reports;Publications;Reporting;Research;Research Personnel;Role;Schedule;Schools;skills;Strategic Planning;success;synergism;technology development;Testing;Three-dimensional analysis;Three-Dimensional Imaging;timeline;Tissues;tumor;United States National Institutes of Health;web site;Wood material


NIH_SPENDING_CATS: Biomedical Imaging;Clinical Research;Clinical Trials and Supportive Activities;Neurodegenerative;Neurosciences;Peripheral Neuropathy;Physical Injury - Accidents and Adverse Effects;Rehabilitation

ORG_DEPT: OTHER HEALTH PROFESSIONS

PHR: After peripheral nerve injury to the dominant hand, many patients never regain adequate function of that hand. This project will identify the brain mechanisms that allow people to compensate with the non-dominant hand. With this knowledge, we will be able to improve rehabilitation for people cannot regain adequate function of their dominant hand.

PI_NAMEs: PHILIP, BENJAMIN ALLEN (contact)

PROGRAM_OFFICER_NAME: DOPERALSKI, ADELE ELIZABETH

PROJECT_TERMS: Adult;Amputation;Bilateral;blood oxygen level dependent;Brain;Central Nervous System;Cerebral Dominance;Chronic;Clinical;Communication;Compensation;Contralateral;Data;Environment;Foundations;Functional Magnetic Resonance Imaging;functional restoration;Future;Goals;grasp;Hand;hand dysfunction;Hand functions;Hand Injuries;Health;Impairment;improved;Individual;individualized medicine;injured;intraparietal sulcus;Ipsilateral;Knowledge;Learning;Learning Skill;Left;Magnetic Resonance Imaging;Measures;Motor Cortex;motor recovery;Movement;Nature;nerve injury;neuroimaging;neuromechanism;neuroregulation;Outcome;Participant;Patient Selection;Patients;Performance;Peripheral nerve injury;Persons;precision medicine;Recovery;recruit;rehabilitation strategy;Rehabilitation therapy;Rest;restoration;Role;Stroke;targeted treatment;therapy development;Upper Extremity;visual motor

PROJECT_TITLE: Interhemispheric Communication and Compensation in Peripheral Nerve Injury

STUDY_SECTION: MFSR

STUDY_SECTION_NAME: Motor Function, Speech and Rehabilitation Study Section[MFSR]


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Breast Cancer;Cancer;Clinical Research;Digestive Diseases;Machine Learning and Artificial Intelligence;Pancreatic Cancer;Rare Diseases;Women's Health Research

PI_NAMEs: WU, PEI-HSUN  (contact)

PROJECT_TERMS: 3-Dimensional;Address;Algorithms;Antibodies;Architecture;Blood Vessels;Breast Cancer Cell;breast cancer metastasis;Bypass;cancer cell;cancer imaging;Cancerous;Cell Density;Cells;Cellular biology;Circulation;Collagen Fiber;Color;Complex;Cytometry;Death Rate;deep learning;deep learning algorithm;Detection;Development;diagnostic tool;Distant Metastasis;Duct (organ) structure;Evaluation;Event;Extravasation;Fibroblasts;Histologic;histological stains;Human;human tissue;Image;Imaging Device;imaging modality;Immune;immunocytochemistry;Immunofluorescence Immunologic;Immunohistochemistry;improved;Individual;Invaded;Label;Lateral;Liver;lymphatic Invasion;Malignant Breast Neoplasm;Malignant neoplasm of pancreas;Malignant Neoplasms;Mammary Gland Parenchyma;Mammary Neoplasms;Maps;Metastatic breast cancer;Methods;Microanatomy;Microscopy;Microtomy;Molecular;Molecular Analysis;molecular imaging;mortality;multiplexed imaging;Neoplasm Metastasis;Operative Surgical Procedures;Optics;Outcome;Pancreas;pancreatic cancer cells;pancreatic neoplasm;Pathologic;Penetration;Phenotype;Portal vein structure;preservation;Process;Prognosis;reconstruction;Resected;Resolution;Route;Sampling;Scheme;segmentation algorithm;Semantics;serial imaging;Site;Slide;Stains;Survival Rate;Testing;Three-Dimensional Imaging;Tissue imaging;tissue reconstruction;Tissues;Training;tumor;tumor heterogeneity;tumor microenvironment;Validation;Veins;Venous

PROJECT_TITLE: Tech Core 1


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Breast Cancer;Cancer;Cancer Genomics;Clinical Research;Digestive Diseases;Genetics;Human Genome;Pancreatic Cancer;Precision Medicine;Rare Diseases;Women's Health Research

PROJECT_TERMS: 3-Dimensional;Algorithms;Anatomy;anti-cancer research;Area;Atlases;Bar Codes;Blood Vessels;cancer cell;cancer imaging;cancer risk;Cells;Cellular biology;Clinical;cost;Data;deep learning;design;Development;Extracellular Matrix;Genes;genome-wide;Goals;Heterogeneity;histological specimens;Histology;Human;Image;image registration;Invaded;lymphatic Invasion;Malignant Breast Neoplasm;Malignant neoplasm of pancreas;Malignant Neoplasms;Mammary Neoplasms;Maps;Measures;Messenger RNA;meter;Methods;Microanatomy;Microfluidics;Molecular;multiple omics;Neoplasm Metastasis;neoplastic cell;new technology;novel;Outcome;pancreatic neoplasm;Play;Process;protein biomarkers;Proteins;Resolution;Role;Semantics;Site;Subcellular Anatomy;targeted treatment;Technology;technology development;technology platform;technology validation;Therapeutic Intervention;Three-Dimensional Imaging;Time;tissue fixing;Tissue imaging;tissue mapping;Tissue Sample;Tissues;Training;transcriptome;tumor;tumor heterogeneity;tumor progression;Tumor Tissue;Tumor Vascular Invasion;Venous

PROJECT_TITLE: Tech Core 2


ORG_CITY: DETROIT

ORG_DEPT: PHYSIOLOGY

ORG_NAME: WAYNE STATE UNIVERSITY

ORG_STATE: MI

PHR: Project Narrative The proposed research is relevant to public health because a sedentary lifestyle is a major risk factor for cardiovascular disease and is now considered the number one cause of death due to preventable causes. This proposal examines an important group of neurons within the brain that we propose contribute to the increased incidence of cardiovascular disease in sedentary and hypertensive individuals. Our contribution is significant because it is expected to provide knowledge that could be used to develop therapeutic strategies, which will counteract the effects of a sedentary lifestyle on cardiovascular diseases that are currently burdening the population and our health care system.

PI_NAMEs: MUELLER, PATRICK J (contact);ROSSI, NOREEN F

PROGRAM_OFFICER_NAME: OH, YOUNGSUK

PROJECT_TERMS: Adverse effects;Anatomy;Animals;Automobile Driving;Blood Pressure;blood pressure regulation;Brain;Brain region;Brain Stem;Brain-Derived Neurotrophic Factor;Cardiovascular Diseases;cardiovascular disorder risk;cardiovascular risk factor;Cause of Death;Cessation of life;Clinical;clinically relevant;Clip;COVID-19 pandemic;Data;Development;DLG4 gene;Dominant-Negative Mutation;Economics;Gene Targeting;Glutamate Receptor;glutamatergic signaling;Glutamates;Goals;Health;Health Care Costs;Healthcare;Healthcare Systems;Hypertension;hypertensive;in vivo;Incidence;Individual;innovation;Kidney;Knowledge;Label;Laboratories;laser capture microdissection;Learning;Link;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy;Manganese;Mediating;Memory;Modeling;mRNA Expression;multidisciplinary;Neuroanatomy;Neuronal Plasticity;Neurons;neurophysiology;neurotransmission;normotensive;novel;overexpression;Persons;Phase;Phenotype;Physical activity;physical inactivity;Play;Population;premature;prevent;protein expression;Proteins;Public Health;Rattus;receptor;Research;response;Risk Factors;Role;sedentary;sedentary lifestyle;Series;Signal Transduction;Smoking;Stimulus;Sympathetic Nervous System;Synaptic plasticity;Techniques;Testing;Therapeutic;trend

PROJECT_TITLE: Contribution of neuroplasticity in the rostral ventrolateral medulla to physical inactivity-related cardiovascular disease

STUDY_SECTION: IVPP

STUDY_SECTION_NAME: Integrative Vascular Physiology and Pathology Study Section[IVPP]


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Biotechnology;Cancer;Cancer Genomics;Clinical Research;Digestive Diseases;Genetics;Human Genome;Networking and Information Technology R&D (NITRD);Pancreatic Cancer;Rare Diseases

PI_NAMEs: WOOD, LAURA DELONG (contact)

PROJECT_TERMS: 3-Dimensional;Antibodies;Area;Automobile Driving;Beds;Biological;cancer cell;cancer imaging;cell type;Cells;Cellular Assay;Cellular biology;Clinical;Collaborations;Complex;Cytometry;deep learning;Development;dimensional analysis;Dimensions;Disease;Distant Metastasis;Epithelium;Event;Fibroblasts;Foundations;Frequencies;Gene Expression Profiling;Goals;high dimensionality;Human;human tissue;Image;imaging platform;Imaging technology;Immune;improved;Inflammatory;insight;Invaded;Label;Liver;Malignant - descriptor;Malignant neoplasm of pancreas;Malignant Neoplasms;Maps;Mesenchymal;Molecular;Molecular Analysis;Morphology;multi-scale modeling;multiple omics;Neoplasm Metastasis;new therapeutic target;novel;novel strategies;Pancreas;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma cell;pancreatic neoplasm;pancreatic tumorigenesis;Performance;Population;prevent;Primary Neoplasm;Process;Prognosis;programs;Proteomics;reconstruction;Research;Resolution;Sampling;Stromal Cells;Structure;synergism;Techniques;technology development;Testing;Three-Dimensional Imaging;Tissue Model;Tissue Sample;Tissues;tool;transcriptome;transcriptomics;tumor microenvironment;Validation;Veins;Venous;Work

PROJECT_TITLE: RTB 1


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Biotechnology;Breast Cancer;Cancer;Cancer Genomics;Clinical Research;Genetics;Human Genome;Machine Learning and Artificial Intelligence;Women's Health Research

PI_NAMEs: EWALD, ANDREW JOSEF (contact)

PROJECT_TERMS: 3-Dimensional;Animal Model;Architecture;Basic Science;Biological;Biological Assay;Blood Vessels;breast cancer metastasis;cancer cell;candidate identification;candidate validation;cell behavior;cell type;Cells;Cellular biology;Cellular Structures;Cessation of life;Classification;classification algorithm;Clinical;Complex;Cytometry;Data;deep learning algorithm;Diameter;Disease;Distant;Ensure;Evaluation;Extracellular Matrix;Extravasation;Fibroblasts;Gene Expression;Genetic Transcription;Human;Image;imaging approach;Immune;Immunofluorescence Immunologic;Immunohistochemistry;In Vitro;in vivo;in vivo evaluation;Individual;innovation;insight;Invaded;Malignant Breast Neoplasm;Malignant neoplasm of pancreas;Malignant Neoplasms;Mammary Neoplasms;Masks;Measurement;Mechanics;metastatic process;Microfluidic Microchips;Microfluidics;Modeling;Molecular;molecular marker;mouse model;multiple omics;Mus;Neoplasm Metastasis;novel;Organ;Organoids;Pancreatic Adenocarcinoma;Patients;Phenotype;Pre-Clinical Model;Process;Proteome;Proteomics;Publishing;real-time images;reconstitution;reconstruction;Research;Resolution;response;Sampling;segmentation algorithm;Series;Signal Transduction;single-cell RNA sequencing;Site;spatial relationship;Stains;Structure;synergism;targeted treatment;Techniques;Technology;Testing;Three-Dimensional Imaging;Tissues;Training;training data;transcriptome;transcriptome sequencing;tumor;tumor microenvironment;Tumor Tissue;Validation;Venous;Visualization;Wood material;Work

PROJECT_TITLE: RTB 2


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Anxiety Disorders;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Eye Disease and Disorders of Vision;Mental Health;Mental Illness;Neurosciences

ORG_CITY: WASHINGTON

ORG_NAME: GEORGETOWN UNIVERSITY

ORG_STATE: DC

PHR: Anxiety disorders impact about 20% of the US population and their treatments are only partially effective and often associated with side effects. The goal of this proposal is to identify the neural substrates and circuitry underlying defensive and emotional reactivity in animal models and to investigate novel sites within the neural circuits that are responsible for emergence of emotional dysregulation resembling symptoms seen in human patients. This understanding is vital for developing effective therapies such as deep brain stimulation, especially in circumstances in which anxiety disorders are long-lasting and refractory to therapeutic interventions.

PI_NAMEs: FORCELLI, PATRICK ALEXANDER;MALKOVA, LUDISE  (contact)

PROGRAM_OFFICER_NAME: BREEDEN, ANDREW LEE

PROJECT_TERMS: Acoustics;Acute;Agonist;Amygdaloid structure;anatomical tracer;Anatomy;Animal Model;Animals;antagonist;Anxiety;Anxiety Disorders;anxiety treatment;Architecture;Arousal;Attention;Attenuated;Behavior;Behavioral;behavioral phenotyping;behavioral response;Bicuculline;Blood Pressure;Brain;Cell Nucleus;Data;debilitating symptom;Deep Brain Stimulation;defense response;designer receptors exclusively activated by designer drugs;Disease;Disinhibition;Dissection;Dissociation;effective therapy;Elements;emotion dysregulation;Emotional;emotional reaction;experimental study;Fright;GABA Antagonists;Goals;Heart Rate;hindbrain;Human;Impairment;Individual;Infusion procedures;interest;Knowledge;Magnetic Resonance Imaging;Mediating;Microinjections;midbrain central gray substance;Midbrain structure;Modeling;Motor;Muscimol;National Institute of Mental Health;neural;neural circuit;neuroimaging;nonhuman primate;novel;Pathology;Pathway interactions;Patients;Pattern;pharmacologic;Population;Primates;Prosencephalon;Psychiatry;Pulvinar structure;Refractory;Regulation;Research;Research Domain Criteria;response;Rodent;Rodent Model;Role;Route;Science;Series;Side;side effect;Site;Snakes;social;Social Behavior;social contact;Social Functioning;Social Interaction;Stimulus;Structure;Substantia nigra structure;superior colliculus Corpora quadrigemina;Symptoms;Techniques;Technology;Testing;Therapeutic Intervention;treatment of anxiety disorders;Validation;Visual;vocalization;Withdrawal

PROJECT_TITLE: Limbic-midbrain interactions in defense and emotional arousal

STUDY_SECTION: PMDA

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


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Kidney Disease;Rare Diseases

ORG_CITY: HOUSTON

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF HOUSTON

ORG_STATE: TX

PHR: PROJECT NARRATIVE Focal and segmental glomerulosclerosis (FSGS) is a leading cause of kidney failure, and primary FSGS is often refractory to treatment. This research will probe two novel potential therapeutic targets for FSGS. These targets are the ion channel, KCa1.1 which may be necessary Ca2+ overload in podocytes, and the receptor for advanced glycation endproducts (RAGE), which is necessary for pathogenic effects mediated by the soluble urokinase receptor (suPAR) in podocytes and other cell types.

PI_NAMEs: DRYER, STUART E (contact)

PROGRAM_OFFICER_NAME: BRUNSKILL, ERIC WAYNE

PROJECT_TERMS: Adipocytes;Affect;Albuminuria;Alzheimer's disease patient;Angiotensin II;Animal Model;antagonist;APOL1 gene;Autoimmune;Automobile Driving;autosome;Biological Availability;biophysical properties;Calcium-Activated Potassium Channel;Cell surface;cell type;Cells;Chronic;Chronic Kidney Failure;Circulation;Clinical;Complex;Coupled;CRISPR/Cas technology;Data;density;disease model;Disease Progression;driving force;drug discovery;Exhibits;Exposure to;Focal and Segmental Glomerulosclerosis;Functional disorder;Funding;gain of function mutation;Glomerulonephritis;glomerulosclerosis;Human;Image;Inflammatory;Integrin alphaVbeta3;Ion Channel;Kidney Diseases;Kidney Failure;kidney fibrosis;Knock-out;Knowledge;Literature;Mediating;Modeling;Molecular;Monovalent Cations;mouse model;Mus;nephrin;Nephrosis;Normal Cell;novel;NPHS2 protein;Oral;overexpression;Oxidative Stress;Pathogenicity;Pathologic;Pathway interactions;patient subsets;Patients;Permeability;Pharmaceutical Preparations;Phase II/III Clinical Trial;Plasma;podocyte;preservation;Prognostic Marker;programs;Property;Proteins;Puromycin Aminonucleoside;Rattus;Reactive Oxygen Species;receptor;receptor for advanced glycation endproducts;Receptor Signaling;Recurrence;Refractory;Renal function;Renal glomerular disease;Research;response;Role;Sampling;Serum;Signal Pathway;Signal Transduction;slit diaphragm;small molecule;SRC gene;System;Testing;therapeutic target;Time;TNF gene;Urokinase Plasminogen Activator Receptor;Variant;virtual;Virulence Factors

PROJECT_TITLE: Pathophysiology of FSGS

STUDY_SECTION: PBKD

STUDY_SECTION_NAME: Pathobiology of Kidney Disease Study Section[PBKD]


NIH_SPENDING_CATS: Brain Disorders;Epilepsy;Neurodegenerative;Neurosciences;Physical Injury - Accidents and Adverse Effects;Sleep Research;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury

ORG_NAME: J. DAVID GLADSTONE INSTITUTES

PHR: NARRATIVE Traumatic brain injury (TBI) is a major cause of disability, and leads to sleep disruption and epilepsy over time. The latent phase between TBI and the manifestation of chronic adverse symptoms is associated with activation of an innate immune response with concomitant recruitment of systemic immunocompetent cells, such as monocytes and lymphocytes, into damaged brain areas. Here we propose to determine the role of these peripheral immune cells in neural circuit plasticity that promotes sleep disruption and epileptogenesis in TBI.

PI_NAMEs: PAZ, JEANNE T (contact)

PROGRAM_OFFICER_NAME: AWWAD, HIBAH OMAR

PROJECT_TERMS: 3-Dimensional;Acute;Affect;American;Area;Astrocytes;blood-brain barrier penetration;Brain;Brain Injuries;brain tissue;Bypass;CD4 Positive T Lymphocytes;Cell Physiology;Cells;Chronic;Clinic;Cognition;controlled cortical impact;Convulsants;Cytoprotection;Data;design;Development;disability;effective therapy;Electrocorticogram;Electroencephalography;Electrophysiology (science);Epilepsy;Epileptogenesis;Equilibrium;Euthanasia;Excitatory Synapse;Flow Cytometry;Functional disorder;Funding;genetic manipulation;glial activation;Health;Human;Immune;immune imaging;Immune system;Immunocompetent;Immunohistochemistry;Immunology;Immunotherapy;Impaired cognition;in vivo;Infiltration;Inflammation;Inhibitory Synapse;Injury;Innate Immune Response;Ipsilateral;Lymphocyte;Macrophage;Maintenance;Mediating;Microglia;Modeling;monocyte;mortality;mouse model;Mus;Myelogenous;Nerve Degeneration;network dysfunction;neural;neural circuit;neuroinflammation;Neurologic Deficit;neuron loss;Neuronal Plasticity;Neurons;Neurosciences;optogenetics;Outcome;Patients;Peripheral;Persons;Pharmaceutical Preparations;Phase;Physiology;Play;Population;Post-Traumatic Epilepsy;prevent;protective effect;recruit;Rodent Model;Role;Secondary to;Seizures;Sensory;Severities;Sleep;Sleep Architecture;Sleep Deprivation;Sleep disturbances;sleep epilepsy;sleep spindle;Sleep Stages;Slice;Symptoms;Synapses;synergism;T-Lymphocyte;TBI Patients;Testing;Thalamic structure;Therapeutic;Therapeutic Intervention;therapeutic target;Three-Dimensional Imaging;Time;Tissue imaging;tool;Traumatic Brain Injury;wireless

PROJECT_TITLE: Role of Myeloid And CD4+ T Immune Cells in Post-Traumatic Plasticity

STUDY_SECTION: BINP

STUDY_SECTION_NAME: Brain Injury and Neurovascular Pathologies Study Section[BINP]


ADMINISTERING_IC: HD

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

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

NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Nutrition;Obesity;Precision Medicine;Prevention;Rural Health

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: Project Narrative – The University of North Carolina at Chapel Hill Clinical Center The need for more precise nutrition advice is widely recognized, yet specific differences in genetic, epigenetic, microbiome, and phenotypic drivers of individual variability to diet are not well known. The National Institutes of Health initiative to fund Nutrition for Precision Health (NPH), powered by the All of Us Research Program, will enable major progress in the field of precision nutrition. The University of North Carolina at Chapel Hill Clinical Center will include a diverse cohort of adults from rural and urban communities to study the variability in physiologic responses to diet, anchored by the theme of inflammation as a driver of many chronic disease processes.

PI_NAMEs: MAYER-DAVIS, ELIZABETH J (contact);TATE, DEBORAH F.

PROGRAM_OFFICER_NAME: CLARK, DAVID

PROJECT_TERMS: Adult;Advisory Committees;Age;All of Us Research Program;American diet;Anti-Inflammatory Agents;Basic Science;Biological;Calories;Carbohydrates;Cardiovascular Diseases;Cardiovascular system;Chronic;Chronic Disease;Clinical;clinical center;cohort;Complex;Creativeness;Crossover Design;Data;Diabetes Mellitus;Diet;dietary;dietary guidelines;Dietary Intervention;Dietary Practices;Disease;Enrollment;Ensure;Epigenetic Process;experience;Fatty acid glycerol esters;feeding;Foundations;Funding;Genetic;Genotype;Goals;Health;health goals;Heterogeneity;human old age (65+);improved;Individual;individual variation;Inflammation;Inflammatory;inflammatory marker;Knowledge;Leadership;Literature;Location;Longevity;Malignant Neoplasms;Mediterranean Diet;Metabolic;microbiome;Molecular;Morbidity - disease rate;mortality;multi-site trial;neoplastic;Neurodegenerative Disorders;Non-Insulin-Dependent Diabetes Mellitus;North Carolina;nutrition;Nutritional Science;Nutritional Study;Obesity;Outcome;Participant;participant enrollment;Pathogenesis;people of color;Phenotype;Physiological;Population;Precision Health;precision nutrition;prediction algorithm;Process;Protocols documentation;Public Health;public health research;Recommendation;recruit;Research Design;Research Infrastructure;Research Institute;response;Risk;Risk Reduction;Rural Community;Sampling;Sampling Studies;Site;Subgroup;systemic inflammatory response;Testing;United States National Institutes of Health;Universities;Urban Community;Variant;Visit;Weight

PROJECT_TITLE: Nutrition for Precision Health: The University of North Carolina at Chapel Hill Clinical Center


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Clinical Research;Mental Health;Mental Illness;Neurosciences;Pediatric

ORG_DEPT: PSYCHIATRY

PHR: PROJECT NARRATIVE Deficits in effortful control (the top-down control of self-regulation) represent a major transdiagnostic risk factor for childhood psychopathology, yet associations between the caregiving and neurobiological mechanisms that disrupt the early development of effortful control are unknown. This prospective longitudinal study investigates the development of effortful control in the first three years of life, examining the extent that maternal mind- mindedness (accurately interpreting infant behavior as resulting from infant mental states), as a specific yet critically understudied component of parenting, alters infant brain structural and functional connectivity in key brain regions underlying effortful control development. Findings will elucidate maternal mind-mindedness as a modifiable component of the caregiving environment that can be targeted in early parent-child interventions to enhance infant brain connectivity and support development of effortful control to reduce risk for developmental psychopathology.

PI_NAMEs: LEAN, RACHEL EMMA (contact)

PROGRAM_OFFICER_NAME: BECHTHOLT, ANITA JEAN

PROJECT_TERMS: 2 year old;3 year old;Address;Affect;Age;Anxiety;Attention;Award;Behavior;Behavioral;behavioral response;Birth;Brain;Brain region;Caregivers;caregiving;caregiving research;Child;Child Development;Child Psychiatry;Child Rearing;Childhood;Code;Cognitive deficits;cohort;design;Development;Diagnostic;Diffusion;Diffusion Magnetic Resonance Imaging;early childhood;Emotional;Environment;Evaluation;follow-up;Foundations;Functional disorder;Functional Magnetic Resonance Imaging;functional MRI scan;Goals;high risk infant;Impairment;improved;infancy;Infant;Infant Behavior;Infant Development;Inferior;Informal Social Control;innovation;Institution;Intervention;Investigation;Life;Life Stress;Link;longitudinal, prospective study;Magnetic Resonance Imaging;maternal depression;Measures;Mediating;Mediator;Mental Depression;Mental disorders;mental state;Methods;Mind;Mothers;MRI Scans;multidisciplinary;neonate;neurobiological mechanism;neuroimaging;Neuropsychology;Neurosciences Research;novel;Parent-Child Relations;Parents;Parietal;Perinatal;peripartum depression;Poverty;preventive intervention;Process;prospective;Protocols documentation;Psychologist;Psychopathology;psychosocial;Published Comment;Regulation;Research;response;Rest;Risk;Risk Factors;Risk Reduction;Scheme;School-Age Population;Self Assessment;Shapes;skills;Source;Standardization;Stress;Structure;Testing;Time;Training;verbal;white matter

PROJECT_TITLE: Investigating Links Between Dysfunctional Parenting and Infant Brain Connectivity on Development of Effortful Control

STUDY_SECTION: PDRP

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


ORG_CITY: BOSTON

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

ORG_STATE: MA

PHR: eCD4-Ig is a potent and exceptionally broad HIV-1 and SIV entry inhibitor that, when delivered by an AAV vector, provides rhesus macaques robust long-term protection from new infections, and by itself suppresses viral replication in the absence of anti-retroviral therapies. Here we seek to optimize and better understand these properties of AAV-delivered eCD4-Ig.

PI_NAMEs: FARZAN, MICHAEL R. (contact)

PROGRAM_OFFICER_NAME: ZHOU, YAN

PROJECT_TERMS: adeno-associated viral vector;adenovirus mediated delivery;Adverse event;Antibodies;Antibody Response;Antigen-Antibody Complex;antiretroviral therapy;Award;Cell Culture Techniques;Chimera organism;Collaborations;collaboratory;Communities;cost;Dependovirus;Ensure;Fc domain;FCGR3B gene;Foundations;Funding;Funding Mechanisms;Future;Goals;HIV-1;Human;IgG1;IgG2;immune activation;immune clearance;Immune response;immunogenicity;improved;Infection;inhibitor;Laboratories;Macaca;Macaca mulatta;Mediating;Modeling;Mus;Mutation;nonhuman primate;Patients;peptidomimetics;Persons;prevent;Property;Proteins;receptor;Residual state;response;Rhesus;Role;Serum;simian human immunodeficiency virus;SIV;System;T cell response;Technology;Therapeutic Uses;timeline;Transgenes;tyrosine O-sulfate;Variant;vector;Viral;Viral reservoir;Virus;Virus Replication;Work

PROJECT_TITLE: Therapeutic use of an enhanced form of CD4-Ig

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Neurosciences

ORG_CITY: EUGENE

ORG_DEPT: PSYCHOLOGY

ORG_NAME: UNIVERSITY OF OREGON

ORG_STATE: OR

PHR: Project Narrative A primary reason we forget is because we store a vast number of memories and interference between these memories becomes inevitable. While forgetting may only represent an occasional annoyance for most people, among older adults and those with dementia—groups that are growing at a disproportionate rate— memory confusion and interference-related forgetting can be debilitating problems. The proposed research seeks to identify neural mechanisms that reduce interference-related forgetting, including in younger and older adults, and will lead to fundamental new insight into how the brain resolves interference between similar memories.

PI_NAMEs: KUHL, BRICE ALAN (contact)

PROGRAM_OFFICER_NAME: BABCOCK, DEBRA J

PROJECT_TERMS: Address;Adult;Age;age-related disease;Aging;aging related;Agreement;Animal Model;Area;behavior prediction;Behavioral;Behavioral Paradigm;Benign;Brain;clinically significant;Code;Complex;Computer Analysis;Computer Models;Confusion;Data;data mining;Dementia;dentate gyrus;Diagnostic;Episodic memory;Event;experience;experimental study;forgetting;Functional Magnetic Resonance Imaging;Funding;Future;Goals;high resolution imaging;Hippocampus;Human;improved;insight;Investigation;Learning;Link;Machine Learning;Maps;Measures;Memory;Memory Disorders;motivated behavior;Names;neural;neural patterning;neuroimaging;neuromechanism;Neurosciences;novel;older adult;Pattern;Persons;Property;Psychology;recruit;Research;Retrieval;Rodent;Rodent Model;Role;Stimulus;System;Techniques;Testing;Theoretical model;Visual Cortex;Work;young adult

PROJECT_TITLE: Neural mechanisms for reducing interference during episodic memory formation

STUDY_SECTION: CP

STUDY_SECTION_NAME: Cognition and Perception Study Section[CP]


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Nutrition;Precision Medicine;Prevention

ORG_NAME: TUFTS UNIVERSITY BOSTON

PHR: PROJECT NARRATIVE The New England–based clinical center will implement the NIH Common Fund’s Nutrition for Precision Health initiative, powered by the NIH All of Us Research Program. The clinical center has the capacity and expertise to fulfill the initiative’s objective of obtaining critical information on dietary, microbiome, physiological, metabolic, behavioral, cognitive, environmental, and contextual factors that are expected to contribute to inter- individual variability in responses to foods. These data will be integrated with All of Us–collected genomic, electronic health, and survey data to develop predictive algorithms to inform precision nutrition strategies, with a goal of supporting optimal health for individuals throughout the lifespan and retooling public health initiatives for reducing the risk of chronic disease.

PI_NAMEs: DAS, SAI KRUPA  (contact);KHALILI, HAMED

PROGRAM_OFFICER_NAME: ROSS, SHARON A

PROJECT_TERMS: Address;Adherence;Adult;Adverse event;Aging;algorithm development;Algorithms;All of Us Research Program;Behavioral;biobank;Chronic Disease;Clinical;clinical center;clinical research site;clinical translation;Cognitive;cohort;Collaborations;Community Outreach;Community Participation;contextual factors;Core Facility;Coupled;Cross-Over Studies;DASH diet;Data;Development;Diet;dietary;dietary adherence;dietary control;Dietary Formulations;Dietary intake;Dietary Intervention;Dietary Practices;Discipline of Nursing;Domiciles;doubly-labeled water;eHealth;Enrollment;Ensure;Environmental Risk Factor;experience;feeding;flexibility;Food;Formulation;Funding;General Hospitals;Genomics;Goals;Health;Human;Individual;Individual Differences;individual response;individual variation;Inpatients;inter-individual variation;ketogenic diet;life span;Massachusetts;Measures;Metabolic;metabolomics;Metagenomics;Methods;microbiome;Modeling;Movement;New England;new technology;non-compliance;Non-Insulin-Dependent Diabetes Mellitus;novel;nutrition;Nutritional Study;Oral;Outcome;Outcome Assessment;Participant;participant retention;Patient Recruitments;personalized approach;Phase;Physiological;Population;population based;Positioning Attribute;Precision Health;precision nutrition;prediction algorithm;Productivity;programs;Protocols documentation;Public Health;Randomized;Recommendation;Records;recruit;Research;Resources;response;Risk Reduction;Science;Site;skills;Standardization;Surveys;System;Testing;Thinking;tool;Translational Research;United States Department of Agriculture;United States National Institutes of Health;Universities;Variant;Visit;volunteer

PROJECT_TITLE: Clinical Center for NIH's Nutrition for Precision Health: The All Of Us New England Research Collaborative


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Mental Health;Mental Illness;Pediatric;Precision Medicine;Violence Research

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: Project Narrative The proposed research is relevant to public health because it focuses on establishing child-level and parent- level risk factors in early childhood that specifically predict increases in callous-unemotional (CU) traits, which confer very high risk for disruptive behavior disorders (DBD) in childhood, including aggression, violence, and theft. Once these specific risk factors are identified, treatments and interventions for DBD can be personalized and made more effective to reduce CU traits and risk for DBD. Thus, the proposed research is relevant to the NIMH’s strategic plan to identify clinically useful biomarkers and behavioral indicators of risk for psychopathology and identify and validate new targets for treatment development.

PI_NAMEs: WAGNER, NICHOLAS J;WALLER, REBECCA  (contact)

PROGRAM_OFFICER_NAME: PACHECO, JENNIFER LYNN

PROJECT_TERMS: Address;Adult;Age;aged;Aggressive behavior;Anxiety Disorders;Attention;autism spectrum disorder;Behavior;Behavioral;Biological;biomarker identification;Boston;callous unemotional trait;career;Child;Child Rearing;Childhood;Clinical;clinical biomarkers;Clinical Sciences;Cognitive;Communities;Computers;Crime;critical developmental period;Cues;Data;developmental psychology;Dimensions;Disruptive Behavior Disorder;early childhood;eHealth;Emotional;Emotions;Empathy;Environment;Future;Genes;Goals;Guilt;Heritability;high risk;improved;Individual Differences;innovation;Intervention;Knowledge;longitudinal design;longitudinal, prospective study;Measurement;Measures;Methods;Motivation;multimodality;National Institute of Mental Health;novel;Outcome;Parent-Child Relations;Parents;Participant;Pathway interactions;Pennsylvania;personalized intervention;personalized medicine;phenotypic biomarker;Physiological;Physiology;Predictive Factor;Process;psychopathic personality;Psychopathology;Psychophysiology;Public Health;Records;recruit;Reporting;Research;Research Personnel;respiratory;Risk;Risk Factors;scaffold;Shapes;Sinus;Sinus Arrhythmia;social;social attachment;standard care;Strategic Planning;Symptoms;Temperament;Testing;Theft;Theoretical model;therapy development;Time;treatment strategy;Universities;Violence;visual tracking;Work

PROJECT_TITLE: Risky Parenting and Temperament Pathways To Callous-Unemotional Traits In Early Childhood


ADMINISTERING_IC: AG

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE ON AGING

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

ORG_CITY: BOYS TOWN

ORG_NAME: FATHER FLANAGAN'S BOYS' HOME

ORG_STATE: NE

PHR: Project Narrative In recent decades, the United States has been undergoing a dramatic demographic shift towards an older population, and with this increase comes a higher prevalence of age-related neurodegenerative diseases. The most common neurodegenerative disorder worldwide is Alzheimer’s disease (AD), although much remains unknown regarding the brain physiology underlying the disease process. This proposal aims to help fill this gap in knowledge by training a future physician-scientist whose first major project will utilize a cutting-edge brain mapping method to characterize the aberrant oscillatory dynamics underlying visual processing and visuospatial attention in patients with AD and its common precursor, mild cognitive impairment.

PI_NAMEs: SPRINGER, SETH D (contact)

PROGRAM_OFFICER_NAME: LUO, YUAN

PROJECT_TERMS: Abeta clearance;abeta deposition;Activities of Daily Living;Affect;age related neurodegeneration;Aging;Agreement;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease patient;Amyloid beta-Protein;animal data;Animal Model;Attention;Attentional deficit;base;Biological Markers;Brain;Brain Mapping;career;Clinical;Clinical Skills;Cognition;Cognitive;cognitive function;cognitive neuroscience;cognitive performance;cognitive task;cognitive testing;Compensation;Complex;Data;Dementia;density;Detection;Disease;Early identification;Education;Electroencephalography;Electrophysiology (science);Evaluation;Event-Related Potentials;Exhibits;experience;Frequencies;Frontotemporal Dementia;Functional disorder;Functional Magnetic Resonance Imaging;Future;Goals;healthy aging;High Prevalence;Hippocampus;Human;human old age (65+);hyperphosphorylated tau;Image;Impaired cognition;improved;indexing;Individual;instrumental activity of daily living;Interneurons;Intervention;Knowledge;Learning;Life;Link;Location;Magnetoencephalography;Maps;Measures;Memory;Methods;mild cognitive impairment;millisecond;mouse model;neural;Neurodegenerative Disorders;neuroimaging;Neurology;neurophysiology;Neuropsychological Tests;Neuropsychology;Older Population;Output;Participant;Pathologic;Pathology;Patients;Performance;Persons;Phase;Photic Stimulation;Physicians;Physiology;Population;Positron-Emission Tomography;Prefrontal Cortex;Prevalence;Process;Radiology Specialty;reconstruction;Research;Research Project Grants;response;Rest;Scientist;Secondary to;Severity of illness;Signal Transduction;single photon emission computed tomography;Source;Statistical Data Interpretation;Stimulus;Task Performances;Techniques;temporal measurement;Time;Training;United States;Visual;Visual attention;Visual Cortex;visual processing;visual stimulus;Visuospatial

PROJECT_TITLE: Aberrant cortical entrainment in biomarker-confirmed Alzheimer's disease and mild cognitive impairment


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Drug Abuse (NIDA only);Neurosciences;Prescription Drug Misuse;Stimulant Use and Misuse;Substance Misuse

ORG_CITY: BIRMINGHAM

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: The dopamine transporters and related family members are targets for medications, and secondary targets for psychostimulants such as amphetamine. In this proposal, we will combine biochemistry, biophysics, and behavioral studies with the intent of understanding the transporter domains, the plasma membrane proteins, and the mechanisms underlying the functional modifications of the dopamine transporter that support dysregulated dopamine neurotransmission.

PI_NAMEs: GALLI, AURELIO  (contact);MATTHIES, HEINRICH J.G.

PROGRAM_OFFICER_NAME: TSAI, SHANG-YI ANNE

PROJECT_TERMS: abuse liability;American;Amino Acids;Amphetamine Abuse;amphetamine use;Amphetamines;Animal Model;Behavior;Behavioral;Behavioral Assay;behavioral phenotyping;behavioral study;BIN1 gene;Biochemistry;Biological Models;biophysical analysis;Brain;Cell membrane;Cessation of life;Cytoplasm;Data;Disease;Distal;Dopamine;dopamine transporter;dopaminergic neuron;Drosophila genus;Electrophysiology (science);Elements;Event;extracellular;Family member;fly;Geography;Grooming;Hospitalization;Human;Impairment;Locomotion;Measures;Mediating;Membrane Proteins;Methamphetamine;Mississippi;Modification;Molecular;Molecular Conformation;molecular targeted therapies;Motivation;Neurons;neuropsychiatric disorder;neurotransmission;opioid epidemic;Outcome;Pharmaceutical Preparations;Pharmacotherapy;Phase;Phosphorylation;Phosphotransferases;Post-Translational Protein Processing;preference;Process;Property;psychostimulant;receptor;Regulation;Reporting;Rewards;Role;SNAP receptor;Stimulant;stimulant abuse;syntaxin 1;System;Testing;Translating;United States;United States Substance Abuse and Mental Health Services Administration

PROJECT_TITLE: The Role of the Dopamine Transporter in Psychostimulant Abuse

STUDY_SECTION: MNPS

STUDY_SECTION_NAME: Molecular Neuropharmacology and Signaling Study Section[MNPS]


NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Genetics;Human Genome;Huntington's Disease;Neurodegenerative;Neurosciences;Rare Diseases

ORG_CITY: ANN ARBOR

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: RELEVANCE TO HUMAN HEALTH Huntington’s disease (HD), an inherited neurological disorder characterized by abnormal involuntary movements, severe mental decline, and emotional changes including irritability and depression, currently has no cure. However, due to inherent genetic variability among the human population, patients with the disease display a wide range of symptoms including resilience to progression and severity of HD. By taking advantage of these underlying genetic differences in resilience to HD, the proposed studies will enable the discovery and validation of novel therapeutic targets for treating HD.

PI_NAMEs: GUSELLA, JAMES F;KACZOROWSKI, CATHERINE COOK (contact);WHEELER, VANESSA C

PROGRAM_OFFICER_NAME: MILLER, DANIEL L

PROJECT_TERMS: abnormal involuntary movement;Age;age related neurodegeneration;aging brain;Alleles;Alzheimer's Disease;Animal Model;Animals;Attention;autosome;Behavior;behavioral phenotyping;Brain;Brain region;brain tissue;CAG repeat;Candidate Disease Gene;candidate validation;Clustered Regularly Interspaced Short Palindromic Repeats;Cognitive;cognitive function;cohort;Corpus striatum structure;Data;Dimensions;Disease;disease model;DNA;Emotional;Exons;Functional Imaging;gene interaction;Genes;Genetic;genetic approach;genetic resource;Genetic Variation;genome-wide;Genomic Segment;Genotype;Health;Heterozygote;high dimensionality;Hippocampus;Human;human data;Human Genetics;Human Genome;humanized mouse;Huntington Disease;Huntington gene;Impaired cognition;Individual;Individual Differences;Inherited;innovation;insight;Knock-in;Knock-out;Knockout Mice;Length;life span;Link;Maps;Mediating;Medical;Mental Depression;Methods;Modification;Molecular;Molecular Analysis;Motor;Motor Cortex;motor disorder;motor symptom;mouse genetics;Mus;mutant;Mutation;Nerve Degeneration;Nervous System Disorder;Neurobehavioral Manifestations;Neurobiology;Neurodegenerative Disorders;Neurologist;neuropathology;new therapeutic target;novel;Pathologic;Pathology;Patients;Population;Predisposition;Prefrontal Cortex;Prevention;Psyche structure;Quantitative Trait Loci;resilience;resilience factor;Resolution;Rest;RNA;segregation;Severities;structural imaging;success;Symptoms;synergism;System;Testing;The Jackson Laboratory;trait;transcriptome sequencing;Transgenic Organisms;Translating;translational model;Validation;Variant

PROJECT_TITLE: Genetic Mechanisms Controlling Resilience to Huntington's Disease


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Genetics

ORG_CITY: CHARLOTTE

ORG_NAME: UNIVERSITY OF NORTH CAROLINA CHARLOTTE

PHR: Project Narrative  This study will allow us to understand how modifications on an essential housekeeping protein (Hsp70) are regulated and how these modifications affect the stability of important proteins that bind to Hsp70, particularly those associated with direct regulation of DNA synthesis and repair. The scope of this work has broad implications for a variety of diseases associated with both the DNA damage response and molecular chaperone function, including many types of cancer.

PI_NAMEs: TRUMAN, ANDREW WILLIAM (contact)

PROGRAM_OFFICER_NAME: PHILLIPS, ANDRE W

PROJECT_TERMS: Affect;Alanine;Alzheimer's Disease;anti-cancer therapeutic;ATR gene;Binding;Binding Proteins;Biological Process;cancer type;Cell Cycle Progression;Cell Death;Cell Survival;Cells;Client;Code;Cultured Cells;Data;Disease;DNA biosynthesis;DNA Damage;DNA Maintenance;DNA Repair;experimental study;Exposure to;Feedback;Future;Genetic;genome integrity;Housekeeping;Huntington Disease;In Vitro;in vivo;inhibitor;kinase inhibitor;Malignant Neoplasms;Mammalian Cell;Mediating;Membrane;Modification;Molecular Biology;Molecular Chaperones;Mutation;Neurodegenerative Disorders;novel;Nucleotides;Nutrient availability;Organism;Pathway interactions;Pattern;Phosphoric Monoester Hydrolases;Phosphorylation;Phosphorylation Site;Phosphotransferases;Physiological;Predisposition;Process;Proliferating;protein aggregation;Protein Dephosphorylation;protein folding;Protein Isoforms;protein oligomer;protein transport;Proteins;Proteomics;Publishing;Regulation;repaired;Research;response;Role;Saccharomyces cerevisiae;Signal Transduction;Site;Specificity;System;Techniques;TEL1 Gene;Transcriptional Regulation;Work;XRCC1 gene;Yeasts

PROJECT_TITLE: Understanding the reciprocal regulation between Hsp70 and the DNA damage response

STUDY_SECTION: CSRS

STUDY_SECTION_NAME: Cellular Signaling and Regulatory Systems Study Section[CSRS]


NIH_SPENDING_CATS: Aging;Diabetes;Genetics;Nutrition

ORG_CITY: ATHENS

ORG_NAME: UNIVERSITY OF GEORGIA

ORG_STATE: GA

PHR: Project Narrative  Decades of work have shown that a cycling sugar modification of proteins in the nucleus and cytoplasm of cells is a major mechanism by which what we eat regulates our cellular physiology. In fact, dysregulation of this sugar cycling contributes to major diseases of aging, such as diabetes, cancer and Alzheimer's disease. This project will investigate how this sugar modification regulates gene expression at the level of protein synthesis from messenger RNA.

PI_NAMEs: HART, GERALD WARREN (contact)

PROGRAM_OFFICER_NAME: SECHI, SALVATORE

PROJECT_TERMS: Address;aging related disease;Alzheimer's Disease;Binding;Binding Sites;Cell Nucleus;Cell Physiology;Cells;Chronic Disease;Communication;Cytoplasm;Cytoplasmic Granules;Cytoplasmic Protein;Data;Diabetes Mellitus;Diabetic mouse;DNA Modification Methylases;Eating;EIF-2alpha;Enzymes;Etiology;Foundations;Gene Expression;Genetic Transcription;Glucose;Goals;Heat Stress;Histones;Hyperglycemia;In Vitro;Investigation;Kinetics;Malignant Neoplasms;Maps;Mediating;messenger ribonucleoprotein;Messenger RNA;Metabolic Diseases;Methods;Mitochondrial Proteins;Modification;Molecular;mRNA Decay;mRNA Translation;multicatalytic endopeptidase complex;Nerve Degeneration;novel;Nuclear Proteins;Nutrient;O-GlcNAc transferase;Oryctolagus cuniculus;peptide O-linked N-acetylglucosamine-beta-N-acetylglucosaminidase;Peptides;Phosphorylation;Play;polypeptide;Polyribosomes;Post-Translational Protein Processing;premature;Preparation;prevent;Process;Proteasome Inhibition;protein aggregation;Protein Biosynthesis;protein expression;Proteins;proteostasis;Regulation;response;Reticulocytes;Retina;Ribonucleoproteins;Ribosomal Proteins;Ribosomes;RNA;RNA Polymerase II;Role;sensor;Signal Induction;Signal Transduction;Site;Stress;stress granule;sugar;System;Time;Tissues;Toxic effect;transcription factor;transcriptome;transcriptome sequencing;translation factor;Translational Regulation;Translations;Ubiquitination;Work

PROJECT_TITLE: Regulation of Translation by O-GlcNAc - Resubmission 03-05-2020

STUDY_SECTION: MBPP

STUDY_SECTION_NAME: Membrane Biology and Protein Processing Study Section[MBPP]


NIH_SPENDING_CATS: Cancer;Chronic Liver Disease and Cirrhosis;Digestive Diseases;Liver Cancer;Liver Disease;Rare Diseases

ORG_CITY: NEW YORK

ORG_DEPT: PATHOLOGY

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: PROJECT NARRATIVE Hepatocellular carcinoma arises in the background of chronic inflammation in which hepatic stellate cells play a central role in controlling a liver microenvironment conducive to tumor progression. Our previous and preliminary data indicate that whereas the inactivation of p62 in HSCs promotes HCC, the inactivation of NBR1 represses tumorigenesis through the upregulation of interferon signaling due to impaired chaperone-mediated autophagy. Here we will unravel the precise mechanisms whereby NBR1 regulates the interferon signaling and its contribution to reprograming the liver tumor microenvironment in vivo to block HCC development.

PI_NAMEs: MOSCAT, JORGE  (contact)

PROGRAM_OFFICER_NAME: MERCER, NATALIA

PROJECT_TERMS: Ablation;Address;Agonist;Autophagocytosis;biomarker identification;CD8-Positive T-Lymphocytes;Cells;Chronic;Complex;Data;Data Set;Defect;design;Development;effective therapy;experimental study;Fibrosis;Genetic;Goals;Hepatic Stellate Cell;Hepatocarcinogenesis;Hepatocyte;Human;human data;Immune;Immune system;Immunologic Surveillance;Immunosuppression;Impairment;In Vitro;in vivo;Inflammation;Inflammatory;Innovative Therapy;Interferon Activation;Interferons;Knowledge;Laboratories;Liver;Liver Fibrosis;liver inflammation;Liver neoplasms;Malignant neoplasm of liver;Mediating;member;Molecular;Molecular Chaperones;Mus;Mutation;neoplastic cell;new therapeutic target;novel;Oncogenes;Pathway interactions;Patients;Play;Population;Prevention;Primary carcinoma of the liver cells;Process;programs;Proteins;Proteomics;Publishing;Regulation;Reporter;Repression;response;restraint;Role;scaffold;Signal Pathway;Signal Transduction;stellate cell;targeted treatment;Therapeutic;treatment response;tumor;tumor heterogeneity;tumor microenvironment;tumor progression;Tumor Promotion;tumorigenesis;tumorigenic;Up-Regulation

PROJECT_TITLE: Interferon regulation by NBR1-driven chaperone-mediated autophagy in stellate cells in liver cancer

STUDY_SECTION: TCB

STUDY_SECTION_NAME: Tumor Cell Biology Study Section[TCB]


ED_INST_TYPE: SCHOOLS OF OPTOMETRY/OPHT TECH

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Clinical Research;Diabetes;Eye Disease and Disorders of Vision;Neurosciences

ORG_CITY: BLOOMINGTON

ORG_NAME: TRUSTEES OF INDIANA UNIVERSITY

PHR: Project Narrative Diabetic retinopathy is the leading cause of blindness in working age adults. This research will use high resolution adaptive optics imaging to study the early stages of damage to the retinal blood vessels and photoreceptors. The work will provide the first detailed analysis of local changes in microvascular wall health, and changes in blood flow and blood vessel structure that occur in diabetes and how they relate to progression of diabetic retinopathy.

PI_NAMEs: BURNS, STEPHEN A (contact)

PROGRAM_OFFICER_NAME: GORDIYENKO, NATALIYA

PROJECT_TERMS: 3-Dimensional;adaptive optics;adaptive optics scanning laser ophthalmoscopy;Address;Adult;Age;Anatomy;Animal Model;Area;arteriole;Biological;Biological Markers;Blindness;Blood;Blood capillaries;Blood flow;Blood Vessels;Cells;cellular imaging;Choroid;Clinical;Clinical Pathology;Clinical Treatment;clinically significant;Cone;Consensus;Darkness;Data;Development;Diabetes Mellitus;diabetic;Diabetic Retinopathy;Diameter;Disease;Dropout;Endothelial Cells;Endothelium;Erythrocytes;Evaluation;Failure;follow-up;Future;Goals;Health;high resolution imaging;Human;human imaging;Image;Imaging Techniques;Impairment;improved;indexing;Individual;individual patient;Link;Location;macular edema;Maps;Measurement;Measures;Monitor;Nature;neural;neurovascular coupling;novel strategies;optical imaging;Optics;Patient imaging;Perfusion;Pericytes;Photic Stimulation;Photoreceptors;Play;Regulation;Reproducibility;Research;Resolution;response;Retina;retina blood vessel structure;Retinal Cone;retinal damage;Retinal Diseases;retinal imaging;retinal ischemia;retinal neuron;Risk;Role;routine imaging;Sampling Biases;Scanning;Speed;Structure;Techniques;temporal measurement;Testing;Thick;Time;vascular abnormality;Vascular Diseases;Vascular remodeling;Visit;Visual;visual stimulus;Work

PROJECT_TITLE: Adaptive Optics Imaging of Human Retinal Vascular Structure and Function


NIH_SPENDING_CATS: Bioengineering;Cancer;Cancer Genomics;Genetics;Hematology;Human Genome;Rare Diseases

ORG_CITY: CAMBRIDGE

ORG_NAME: HARVARD UNIVERSITY

PHR: PROJECT NARRATIVE Multiple myeloma is a lethal cancer preceded by well-defined pre-myeloma conditions that are asymptomatic and non-lethal, though the transition between these precursor states and overt multiple myeloma is poorly understood. The bone marrow microenvironment is thought to be altered in patients that progress from pre- myeloma to overt multiple myeloma and a better understanding of this tissue’s involvement in disease development may highlight opportunities for therapeutic intervention prior to the development of overt multiple myeloma. This project aims to analyze single cells from the bone marrow microenvironment across a spectrum of patient disease development, as well as construct a novel computational architecture, to learn about the drivers of this oncogenic transformation.

PI_NAMEs: VINYARD, MICHAEL EDWARD (contact)

PROGRAM_OFFICER_NAME: SCHMIDT, MICHAEL K

PROJECT_TERMS: Acute Myelocytic Leukemia;acute myeloid leukemia cell;Address;Architecture;Automobile Driving;autosome;Blood;Blood Cells;bone cell;Bone Marrow;Cell Differentiation process;cell growth;Cells;Cellular biology;Chromatin;Clinical Trials;Clonal Expansion;cohort;Collaborations;comparative;computer framework;computerized tools;Computing Methodologies;Data;Development;Diagnosis;Differential Equation;Dimensions;Disease;Disease Progression;disorder prevention;DNA;Doctor of Philosophy;Drug Design;Drug resistance;Drug Targeting;Epigenetic Process;epigenome;epigenomics;Equation;Event;experimental study;Gene Expression;Gene Expression Profiling;Gene Expression Regulation;gene regulatory network;Genes;Genetic;Genetic Heterogeneity;Genomics;Germ Lines;Growth;Hematologic Neoplasms;Hematopoietic Neoplasms;Heritability;high dimensionality;Histones;improved;insight;Investigation;KDM1A gene;Learning;Life;Link;Lysine;Machine Learning;machine learning method;Malignant - descriptor;Malignant Neoplasms;Mathematics;Mediating;Methods;Modeling;Multiple Myeloma;multiple omics;Mutation;Neoplasms;neural;novel;Oncogenes;Oncogenic;patient subsets;Patients;Persons;Pharmaceutical Preparations;Plasma Cells;Plasma Enhancement;Play;Precancerous Conditions;prevent;Process;Proliferating;Proteins;Publishing;rate of change;reconstruction;Regulation;Regulatory Element;Repression;Research;Resolution;Role;Sampling;Shapes;single cell ATAC-seq;single-cell RNA sequencing;Susceptibility Gene;System;Techniques;Testing;Therapeutic Intervention;Tissues;transcription factor;transcriptomics;Tumor Suppressor Proteins;United States;Visualization;Work

PROJECT_TITLE: Determining the role of LSD1 in multiple myeloma through a multi-omics approach at single cell resolution


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Biotechnology;Emerging Infectious Diseases;Immunization;Infectious Diseases;Influenza;Lung;Pediatric;Pneumonia and Influenza;Prevention;Vaccine Related

ORG_CITY: BERKELEY

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: PROJECT NARRATIVE Antibiotics are frequently prescribed in for respiratory infections in children, promoting antibiotic resistance. The proposed study will estimate the impacts of vaccination strategies against common respiratory pathogens (Streptococcus pneumoniae, influenza virus, respiratory syncytial virus) on outpatient antibiotic prescribing for respiratory infections in children. The findings from this work will inform vaccine policy decisions, vaccine research priority-setting, and antibiotic resistance mitigation strategies.

PI_NAMEs: KING, LAURA  (contact)

PROGRAM_OFFICER_NAME: UPADHYAY, MEENU MISHRA

PROJECT_TERMS: Acute respiratory infection;Address;age group;Antibiotic Resistance;Antibiotics;Bacteria;Bacterial Antibiotic Resistance;Big Data Methods;Bronchitis;Caring;Cessation of life;Child;Childhood;Clinical Trials;combat;Communicable Diseases;Data;Data Mart;Data Sources;Databases;Decision Making;Development;Dose;Effectiveness;Emergency department visit;Epidemiologic Methods;Epidemiologist;Epidemiology;experience;Fellowship;Future;Goals;Guidelines;Health;Healthcare Systems;Hospitals;Human;improved;Infection;Infection prevention;Influenza;Influenza vaccination;influenza virus vaccine;influenzavirus;large scale data;Licensing;Life;Medical;Methods;Modern Medicine;Morbidity - disease rate;mortality;National Ambulatory Medical Care Survey;novel;Observational Study;Organism;Otitis Media;Outpatients;pathogen;Patients;Persons;Pharmaceutical Preparations;Pharmacy facility;Physicians' Offices;Pneumococcal conjugate vaccine;Policies;Policy Making;Population Attributable Risks;prevent;Privatization;Public Health Schools;Recommendation;Recurrence;Research;research and development;Research Personnel;Research Priority;Resistance;Resources;respiratory pathogen;Respiratory syncytial virus;Respiratory Tract Infections;Sampling;Serotyping;skills;Statistical Methods;Streptococcus;Streptococcus pneumoniae;Streptococcus pyogenes;Study models;Surveys;Therapeutic;Training;Uncertainty;uptake;Vaccination;vaccination strategy;vaccine candidate;vaccine development;Vaccine Research;vaccine strategy;Vaccines;Viral;Virus;Visit;Work

PROJECT_TITLE: Quantifying the impact of vaccines on antibiotic use for respiratory infections in children

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


ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

PHR: Project Narrative Staphylococcus aureus is a major human pathogen responsible for infections that are notoriously difficult to resolve and associated with significant rates of morbidity and mortality. As the rapid rise of antibiotic resistance for this pathogen is quickly depleting treatment options, there is a critical need to identify factors that improve antibiotic efficacy in order to decrease the rates of treatment failure and slow the development of resistance. Completion of this research project will determine the role of manganese availability in antibiotic effectivity, potentially leading to future progress in the generation of innovative strategies that enhance the success of antibiotic treatment.

PI_NAMEs: VELEZ, AMANDA ZOYLA (contact)

PROGRAM_OFFICER_NAME: XU, ZUOYU

PROJECT_TERMS: Affect;Antibiotic Resistance;Antibiotic susceptibility;Antibiotic Therapy;Antibiotics;Autolysin;Bacteremia;Bacteria;Cell Death;cell killing;Cell Wall;Chemosensitization;Clinical;Collaborations;Communicable Diseases;Consumption;Data;Data Analyses;Development;Diet;dietary;Disease;effective therapy;Effectiveness;Endocarditis;Environment;Enzymes;experimental analysis;Experimental Designs;experimental study;Exposure to;Future;Gene Expression;Generations;Goals;Homeostasis;host-microbe interactions;human pathogen;improved;Infection;Infection Control;innovation;insight;Invaded;Laboratories;Leukocyte L1 Antigen Complex;Life;Manganese;Mediating;Mediator;Mentors;Metals;Methods;Microbiology;Modeling;Morbidity - disease rate;mortality;Mus;mutant;Nosocomial Infections;novel;Nutrient;nutrition;Osteomyelitis;Oxacillin;pathogen;Patient Care;Peptidoglycan;Physicians;Predisposition;Prevalence;Proteins;Regulation;Research;Research Personnel;Research Project Grants;Resistance;Resistance development;Role;Scientist;Sepsis;Severities;skill acquisition;skills;skin wound;Staphylococcus aureus;Staphylococcus aureus infection;stem;success;teacher;Technical Expertise;Tissues;Training;Treatment Efficacy;Treatment Failure;Treatment outcome;Vancomycin;Work;Wound Infection;Wound models;Zinc

PROJECT_TITLE: Identifying the role of manganese limitation in antibiotic killing of Staphylococcus aureus

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


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Biotechnology;Clinical Research;Clinical Trials and Supportive Activities;Emerging Infectious Diseases;Immunization;Infectious Diseases;Influenza;Orphan Drug;Pneumonia and Influenza;Prevention;Rare Diseases;Vaccine Related

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: PROJECT NARRATIVE NYU VTEU provides outstanding leadership, scientific innovation, and operational excellence in conduct of high priority NIAID-supported infectious diseases clinical research. NYU VTEU performs clinical trials and clinical studies of infectious diseases to identify new approaches (e.g., vaccines, treatments, diagnostics, biologics, devices, biomarkers) to protect and restore health. NYU VTEU contributes to national preparedness for emerging public health threats through rapid responsiveness and surge capacity.

PI_NAMEs: MULLIGAN, MARK JOSEPH (contact)

PROGRAM_OFFICER_NAME: BURNHAM, ANDREW JAMES

PROJECT_TERMS: Academic Medical Centers;Acquired Immunodeficiency Syndrome;Address;Admission activity;Adult;anti-microbial drug;Antibiotic Resistance;Antibiotics;Area;Avian Influenza;Award;Beds;Biological Assay;Biological Markers;Biological Products;Biomedical Research;Caring;Censuses;Cessation of life;Child;Childhood;Cities;Clinic;Clinical;Clinical Research;Clinical Trials;Clinical Trials Unit;Clinics and Hospitals;combat;Communicable Diseases;Communities;comparative;Country;Dedications;demographics;Dengue;Development;Devices;Diagnostic;Disease;Ebola;Educational process of instructing;electronic health record system;Elements;Emerging infection;Enrollment;Enteral;Epitopes;Evaluation;experience;Facilities and Administrative Costs;Faculty;flu;Funding;Health;Healthcare Systems;HIV/AIDS;Hospitals;Human;Immunology;improved;Individual;Infection;Infectious Diseases Research;Influenza A virus;Influenza A Virus, H1N1 Subtype;Influenza A Virus, H5N1 Subtype;Influenza A Virus, H7N9 Subtype;influenza virus vaccine;innovation;Inpatients;Institution;Institutional Review Boards;International;Laboratories;Laboratory Research;Leadership;Long Island;Malaria;Marriage;medical countermeasure;Medical Research;medical schools;metropolitan;microbial;Microbial Drug Resistance;microbial genomics;microbiome;Middle East Respiratory Syndrome;Modeling;Molecular Epidemiology;Morbidity - disease rate;mortality;Multi-Drug Resistance;multiple omics;National Institute of Allergy and Infectious Disease;neglected tropical diseases;New York;New York City;news;Nipah;Norovirus;novel;novel strategies;operation;Outpatients;outreach;pandemic influenza;Participant;pathogen;Patient Care;Patient Recruitments;Patients;personalized medicine;pharmacokinetics and pharmacodynamics;Population;Predictive Value;priority pathogen;Procedures;Public Health;Qualifying;Readiness;Recording of previous events;recruit;Reporting;Research;Research Activity;Research Priority;Research Support;Resources;Respiratory Tract Infections;response;seasonal influenza;Seasons;Severe Acute Respiratory Syndrome;Sexually Transmitted Diseases;Site;Speed;Study models;Study Subject;System;systems research;Therapeutic;Time;Tuberculosis;United States National Institutes of Health;universal influenza vaccine;Universities;Vaccination;Vaccines;Viral;Visit;Work;ZIKA

PROJECT_TITLE: Establishment of the New York University Vaccine and Treatment Evaluation Unit (NYU VTEU)


ORG_CITY: SALT LAKE CITY

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: Recently approved therapies have shown unprecedented promise in advanced stages of melanoma but clinical management of brain metastases remains challenging. This project strives to understand the mechanisms by which melanomas metastasize to the brain such that more effective therapies can be developed to improve the outcomes for these patients.

PI_NAMEs: HOLMEN, SHERI L (contact)

PROGRAM_OFFICER_NAME: SNYDERWINE, ELIZABETH G

PROJECT_TERMS: AKT inhibition;AKT1 gene;AKT2 gene;AKT3 gene;Biological Models;BRAF gene;Brain;CDKN2A gene;Cell Line;Cessation of life;Clinical Management;Clinical Trials;clinically relevant;Collaborations;Collection;Data;Development;Diagnosis;Disease;Disease Resistance;Distant;Distant Metastasis;Drug resistance;effective therapy;FDA approved;Focal Adhesion Kinase 1;Focal Adhesions;Gene Combinations;Gene Delivery;Genetically Engineered Mouse;Genomics;Goals;Growth;high risk;Histologic;Human;human data;human disease;improved;improved outcome;in vivo;Incidence;inhibitor;interest;Invaded;Knowledge;Lipids;Lung;Malignant Neoplasms;MAP Kinase Gene;MEK inhibition;MEKs;melanocyte;Melanoma;Melanoma Cell;Melanoma patient;Metastatic malignant neoplasm to brain;Metastatic Melanoma;Metastatic Neoplasm to the Lung;Modeling;Molecular;mouse model;Mus;mutant;Neoplasm Metastasis;next generation sequencing;Nonmetastatic;novel;novel therapeutics;Organ;Pathologist;Pathway interactions;patient derived xenograft model;Patient-Focused Outcomes;Patients;Penetrance;pharmacologic;Phosphoric Monoester Hydrolases;Phosphorylation;PI3K/AKT;postnatal;Pre-Clinical Model;prevent;Process;Productivity;Prognosis;Protein Dephosphorylation;Proteomics;Proto-Oncogene Proteins c-akt;PTEN gene;PTK2 gene;Research;Resistance;Resources;response;Risk;Sampling;Scientist;Signal Transduction;Site;Skin Cancer;standard of care;Talents;targeted treatment;Testing;therapeutic target;therapeutically effective;Time;tool;Toxic effect;Translations;Treatment Failure;tumor;Xenograft Model

PROJECT_TITLE: A High-Throughput Model for Human Melanoma

STUDY_SECTION: TPM

STUDY_SECTION_NAME: Tumor Progression and Metastasis Study Section[TPM]


ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Project Narrative The transcription factor TCF-1 (encoded by Tcf7) is required for the development of acute infection-induced central memory T cells (Tcm) and chronic infection-induced T progenitor exhausted cells (TPEX) that mediate durable CD8 T cell responses. Although it is known that Tcf7 is downregulated by pro-inflammatory cytokines during the terminal differentiation of CD8 T cells, it is unclear how cell-extrinsic signals downregulate Tcf7 expression. The proposed project interrogates (1) the molecular mechanism by which the cytokine IL-2 mediates repression of Tcf7 expression in CD8 T cell differentiation and (2) the roles of intrinsic histone deacetylase and TLE co-repressor recruitment activities of TCF-1 in maintaining the transcriptionally and epigenetically distinct populations of TPEX and Tcm.

PI_NAMEs: MURPHY, MAEGAN  (contact)

PROGRAM_OFFICER_NAME: GONDRE-LEWIS, TIMOTHY A

PROJECT_TERMS: Ablation;Acute;acute infection;Address;Affinity;Alpha Interleukin 2 Receptor;Antigens;Attenuated;Binding;Biological Assay;CD8-Positive T-Lymphocytes;cell type;Cells;Cessation of life;Chromatin;Chronic;chronic infection;Clonal Expansion;Cues;cytokine;Cytokine Receptors;cytotoxic;Decision Making;Dependence;Development;Down-Regulation;Effector Cell;Elements;Engineering;Epigenetic Process;exhaust;exhaustion;extracellular;Family;Gene Expression Profile;Gene Expression Regulation;gene repression;Genes;genetic corepressor;Genetic Transcription;Goals;Histone Deacetylase;IL2RA gene;immune checkpoint blockade;Immune response;Immunity;Immunologic Surveillance;Immunotherapeutic agent;Immunotherapy;Infection;Inflammatory;insight;Interleukin 2 Receptor;Interleukin-12;Interleukin-15;interleukin-15 receptor;Interleukin-2;IRF4 gene;Knowledge;Lymphocytic choriomeningitis virus;Malignant Neoplasms;Mediating;Memory;Modeling;Molecular;mouse model;Mus;mutant;Mutate;pathogen;Phenotype;Population;progenitor;Receptor Signaling;recruit;Recruitment Activity;Regulation;Regulatory Element;Repression;Research Project Grants;response;Role;self-renewal;Signal Induction;Signal Pathway;Signal Transduction;stem;T cell differentiation;T cell response;T memory cell;T-Cell Development;T-Lymphocyte;T-Lymphocyte Subsets;TCF Transcription Factor;Testing;Therapeutic;thymocyte;Transcription Coactivator;transcription factor;Transcription Repressor;Transcriptional Regulation;tumor;Tumor Antigens;United States;Up-Regulation;Vaccination;Viral;Viral Cancer;Virus Diseases

PROJECT_TITLE: Defining the regulation and regulatory mechanisms of TCF-1 in CD8+ T cell differentiation


NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Neurosciences

PHR: The objective of this proposal is to use a novel, high-throughput approach to study the function and distribution of previously uncharacterized ganglion cells that send visual information from the retina to the brain. We expect the study outcomes to ultimately aid understanding of changes that occur during disease, development and aging and to lead to improved methods for retinal disease diagnosis and treatment.

PI_NAMEs: PUTHUSSERY, TERESA  (contact)

PROGRAM_OFFICER_NAME: WRIGHT, CHARLES BAKER

PROJECT_TERMS: Address;Aging;Amacrine Cells;Anatomy;Biological Assay;Brain;Calcium;cell type;Cells;Cellular Morphology;Classification;Complex;Cone;Data;density;Development;Disease;disease diagnosis;Electrophysiology (science);Exhibits;fovea centralis;Frequencies;GABA Receptor;ganglion cell;Goals;Human;Image;Immunohistochemistry;improved;In Situ;inhibitory neuron;innovation;insight;Light;Link;Location;Macaca;Maps;Methods;Molecular;Morphology;mosaic;Neurons;novel;Outcome Study;Peripheral;Population;Primates;Property;receptive field;receptor expression;regional difference;response;Retina;Retinal Diseases;Shapes;Signal Transduction;single cell sequencing;Spatial Distribution;spatiotemporal;Structure;Testing;transcriptomics;two-photon;Validation;Variant;visual information;visual processing

PROJECT_TITLE: Structure and Function of Primate Retinal Circuits

STUDY_SECTION: NTRC

STUDY_SECTION_NAME: Neurotransporters, Receptors, and Calcium Signaling Study Section[NTRC]


ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PROJECT NARRATIVE Infections by skin-penetrating gastrointestinal parasitic nematodes, including the threadworm Strongyloides stercoralis, occur in approximately one billion people worldwide and can be fatal to immunosuppressed individuals. The research in this proposal will glean insight into the understudied process by which S. stercoralis senses and responds to mechanical stimuli, and will examine the role of mechanosensation in host finding and skin penetration. Ultimately, this study could lead to the development of strategies that prevent infection, such as skin creams containing compounds that inhibit penetration.

PI_NAMEs: PATEL, RUHI  (contact)

PROGRAM_OFFICER_NAME: PESCE, JOHN T

PROJECT_TERMS: Alginates;Ancylostoma (genus);Animals;Anthelmintics;Behavior;Behavioral;Behavioral Paradigm;behavioral response;behavioral study;Caenorhabditis elegans;Calcium;Candidate Disease Gene;Chloride Channels;comparative genomics;Cream;CRISPR/Cas technology;Cues;Development;drug development;Enterobius;Esthesia;experimental study;Exposure to;Frequencies;gastrointestinal;Gene Expression Profile;Generations;Genes;Genetic;Genetic Transcription;Glean;Goals;Head Movements;Health;Histamine;Hookworms;Human;Hydrogels;Image;immunosuppressed;Individual;individual response;Infection;Infection prevention;Infectious Skin Diseases;Ingestion;insight;Invaded;Knowledge;Larva;Location;Lotion;mechanical properties;mechanical stimulus;Mechanoreceptors;mechanotransduction;migration;Modeling;Molecular Target;Mus;Mutagenesis;mutant;neglected tropical diseases;Nematoda;Nematospiroides dubius;neural circuit;neuromechanism;neuronal circuitry;Neurons;novel;Organism;Parasites;Parasitic nematode;Pathway interactions;Penetration;Persons;Pharmaceutical Preparations;Preventive;Probability;Process;Rattus;Reporter;Reporter Genes;Research;Research Proposals;Resource-limited setting;response;Role;Skin;Soil;Source;Stimulus;Strongyloides;Strongyloides ratti;Strongyloides stercoralis;Strongyloidiasis;Testing;Texture;Therapeutic;Time;Transgenic Organisms;vibration;Video Recording;Walking;Work

PROJECT_TITLE: Mechanosensory Behaviors of Skin-Penetrating Parasitic Nematodes


NIH_SPENDING_CATS: Bioengineering;Neurosciences

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: PROJECT NARRATIVE Understanding how neuromodulators diffuse through the extracellular space (ECS) from release site to target receptor is a crucial component in understanding neuromodulator signaling. Prior computational work has studied diffusion dynamics over spatiotemporal scales that are too small for neuromodulation and lack the capabilities to incorporate factors that only become relevant at larger distances. Thus, this proposal seeks to combine small-scale mechanisms modeled by MCell with algorithms of large-scale mechanisms such as bulk diffusion to evaluate how factors like granularity and anisotropy shape diffusion of acetylcholine, noradrenaline, and dopamine through structurally different regions of macaque cortex.

PI_NAMEs: KRUEGER, JULIANE  (contact)

PROGRAM_OFFICER_NAME: OSBORNE, LESLIE CAROL

PROJECT_TERMS: Acetylcholine;Address;Affect;Affinity;Algorithms;Anisotropy;Architecture;Area;area striata;Attention;Auditory area;Axon;Behavior;Biophysics;Brain;Brain region;cell type;Cellular Morphology;cerebrospinal fluid flow;Chemicals;Communication;Compensation;Computer Models;Data;Dementia;Dendrites;density;Development;Diagnostic;Diffuse;Diffusion;Dopamine;Extracellular Space;falls;Geometry;Goals;Human;human data;Hybrids;in silico;In Vitro;in vivo;Interneurons;Ischemia;Length;Link;Location;Macaca;mathematical model;Measures;Methods;millimeter;Modeling;Molecular;Monkeys;Morphology;Motor Cortex;multi-scale modeling;nanoscale;National Research Service Awards;Neocortex;nerve supply;Nervous System;neural;Neuroanatomy;Neuroglia;Neuromodulator;neuronal cell body;neuropathology;neuroregulation;nonhuman primate;Norepinephrine;normal aging;Outcome;Porosity;Primates;Process;Property;receptor;receptor binding;reuptake;Rodent;Role;Shapes;Signal Transduction;Signaling Molecule;simulation;Site;spatiotemporal;Stratum Granulosum;Stroke;Synapses;Synaptic Transmission;System;Testing;Therapeutic;Time;Tissues;tool;transmission process;Travel;Update;virtual;Work

PROJECT_TITLE: NRSA application: Characterizing acetylcholine, noradrenaline, and dopamine diffusion through the extracellular space in three subregions of macaque neocortex

STUDY_SECTION: NST

STUDY_SECTION_NAME: NST-2 Study Section [NST-2]


NIH_SPENDING_CATS: Biotechnology;Breast Cancer;Cancer;Genetics;Women's Health Research

ORG_CITY: CHARLESTON

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: MEDICAL UNIVERSITY OF SOUTH CAROLINA

ORG_STATE: SC

PHR: PROJECT NARRATIVE The proposed project is relevant to public health because it represents a novel and clinically-relevant potential therapeutic strategy i.e., targeting the protein lysyl oxidase (LOX), to overcome chemotherapy resistance in triple negative breast cancer (TNBC), representing a highly aggressive patient subgroup with worse survival. Once LOX is established as a potent target to overcome chemoresistance pre-clinically using our novel inhibitors in the state-of-the-art experimental models, there is potential for significant advance in the treatment of highly aggressive breast and potentially other treatment-refractory tumors driven by LOX. Thus, the proposed project is relevant to the part of the NIH’s mission that pertains to reducing illness and disability.

PI_NAMEs: SAHIN, OZGUR  (contact)

PROGRAM_OFFICER_NAME: KONDAPAKA, SUDHIR B

PROJECT_TERMS: 3-Dimensional;aggressive breast cancer;Apoptosis;Binding;Biological Assay;Breast;Breast Cancer Cell;Breast Cancer cell line;Breast Cancer Model;Breast Cancer Patient;cancer subtypes;Cell Survival;Cells;Cessation of life;Chemoresistance;Chemosensitization;chemosensitizing agent;chemotherapy;clinically relevant;Clustered Regularly Interspaced Short Palindromic Repeats;Collagen;Communication;CRISPR/Cas technology;crosslink;Cryoultramicrotomy;Data;Death Rate;disability;DNA;DNA Damage;Dose;Doxorubicin;Drug Kinetics;Experimental Models;experimental study;Extracellular Matrix;Fibronectins;Generations;Genes;Genetic Transcription;Goals;HIF1A gene;Hypoxia;Immunofluorescence Immunologic;Immunohistochemistry;In Vitro;in vivo;in vivo Model;Induction of Apoptosis;inhibitor;Integrins;ITGA5 gene;Knock-out;LOXL2 gene;Malignant Breast Neoplasm;Mammary Neoplasms;Maximum Tolerated Dose;Measures;Mediating;Mediator;Methods;Microscopy;Mission;mRNA Expression;multi-photon;mutant;Nature;novel;Nuclear;Organoids;Output;overexpression;oxidation;Paper;paralogous gene;Pathway interactions;patient derived xenograft model;patient subsets;Patient-derived xenograft models of breast cancer;Penetration;Pharmaceutical Preparations;Pharmacodynamics;pharmacokinetics and pharmacodynamics;Pharmacotherapy;Phenotype;Physiological;pre-clinical;protein expression;Protein-Lysine 6-Oxidase;Proteins;Proteomics;prototype;PTK2 gene;Public Health;reconstitution;Refractory;Relapse;Resistance;Role;screening;second harmonic;Signal Transduction;small molecule;small molecule inhibitor;Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization;standard of care;Structure-Activity Relationship;success;System;Techniques;Testing;Therapeutic;therapy resistant;three dimensional cell culture;Toxic effect;trafficking;Transcriptional Regulation;transcriptome sequencing;transcriptomics;triple-negative invasive breast carcinoma;tumor;tumor xenograft;United States National Institutes of Health;Western Blotting

PROJECT_TITLE: Overcoming chemoresistance in triple negative breast cancer