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

ORG_CITY: DALLAS

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: Project Narrative Humans are under increasing threat from viral infection, particularly from epidemic and pandemic viruses that spill over from other animals (e.g. Ebola virus, SARS coronavirus, influenza A virus). This proposal will use evolutionary genetics to determine whether the animals that harbor such viruses also possess species-specific antiviral proteins that could be leveraged for therapeutic development.

PI_NAMEs: SCHOGGINS, JOHN W. (contact)

PROGRAM_OFFICER_NAME: LEITNER, WOLFGANG W

PROJECT_TERMS: Animals;antiviral drug development;Area;arms race;Atlases;Biochemical;Biological;Biology;Biomedical Research;Carnivora;Cells;Chiroptera;combat;Development;Ebola virus;efficacy validation;epidemic virus;Genes;Genetic;genetic approach;Genetic Screening;Goals;Human;human model;Immune response;Immunology;Influenza A virus;Interferons;Mammals;Medical;Molecular;mouse model;Natural Immunity;novel;Outcome;pandemic virus;pathogenic virus;Primary Cell Cultures;Primates;Proteins;response;Rodent;SARS coronavirus;Testing;therapeutic development;Viral;Viral Genes;Viral Genome;Viral Proteins;virology;Virus;Virus Diseases;Zoonoses

PROJECT_TITLE: A functional evolutionary genetic approach to combat viral infection


ADMINISTERING_IC: NS

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

ORG_CITY: SAN FRANCISCO

ORG_COUNTRY: UNITED STATES

ORG_DEPT: NEUROLOGY

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: STATEMENT OF PUBLIC HEALTH RELEVANCE The proposed research is relevant to public health because, as our population ages, the financial and societal burden of neurodegenerative diseases will greatly expand over the coming decades. This proposal seeks to generate knowledge and resources around a broad-based understanding of tau metabolism. The proposed research is relevant to the NIH's mission of extending healthy life and reducing the burdens of illnesses like neurodegeneration, since its findings will enhance related efforts to target tau clearance and develop therapies for neurodegenerative diseases such as FTD.

PI_NAMEs: AGARD, DAVID A.;KAO, AIMEE  (contact);KARCH, CELESTE MARIE;YOKOYAMA, JENNIFER S

PROGRAM_OFFICER_NAME: SHEWMAKER, FRANK PAUL

PROJECT_TERMS: Age;Autophagocytosis;burden of illness;Cells;Cellular Structures;Data;Databases;Decision Making;Deposition;design;Disease;DNA Sequence Alteration;Frontotemporal Dementia;Frontotemporal Lobar Degenerations;Gene Mutation;Genes;Genetic Risk;genetic variant;Genomics;Goals;Half-Life;Homeostasis;improved;In Vitro;Induced Neurons;Investigation;Knowledge;Lead;Leadership;Life;Lysosomes;member;Metabolism;Mission;Modeling;Molecular Chaperones;Molecular Structure;multicatalytic endopeptidase complex;mutant;Mutation;Nerve Degeneration;Neurodegenerative Disorders;Online Systems;Organizational Models;overexpression;Pathologic;Pathway interactions;Peptide Hydrolases;polygenic risk score;Population;Post-Translational Protein Processing;Process;Production;Proteins;Proteolysis;Public Health;public health relevance;Research;Resources;Risk;risk variant;Series;Structure;synergism;tau aggregation;tau mutation;tau Proteins;Tauopathies;Testing;therapy development;Toxic effect;transcriptomics;United States National Institutes of Health;Update;Variant;Work

PROJECT_TITLE: Tau Metabolism in FTD: From Gene Mutations to Molecular Chaperones and Lysosomal Proteases


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

PI_NAMEs: KAO, AIMEE  (contact)

PROJECT_TERMS: Achievement;Administrator;Alzheimer's Disease;Award;Biological;Biological Markers;biomedical imaging;Budgets;California;cloud based;Collaborations;Communication;Consult;Consultations;Data;data dissemination;data exchange;data management;data platform;data sharing;Databases;Endowment;Ensure;Foundations;Gene Mutation;Genomics;Homeostasis;Housing;Human Resources;Infrastructure;insight;Leadership;Maps;Mediating;meetings;member;Metabolism;mid-career faculty;Molecular Chaperones;Neurology;Occupational activity of managing finances;online resource;Output;Pathway interactions;Peptide Hydrolases;Persons;polygenic risk score;Positioning Attribute;Preparation;Productivity;programs;Progress Reports;radiological imaging;recruit;Reporting;Research;Research Personnel;Resources;San Francisco;Scientific Advances and Accomplishments;Scientist;Secure;shared database;success;tau Proteins;tool;Translating;United States National Institutes of Health;Universities;Variant;Washington;web site;Work

PROJECT_TITLE: Core A: Administrative and Data Sharing Core


ADMINISTERING_IC: CA

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Cancer;Cancer Genomics;Clinical Research;Genetics;Human Genome;Immunotherapy;Skin Cancer

ORG_CITY: NEW HAVEN

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because it will systematically study the complex biology underlying effective versus ineffective anti-cancer immune responses in melanoma in response to cancer immunotherapy. These studies will benefit many laboratories studying the host immune response to cancer. The project is relevant to NCI’s mission because it will have a major impact on our understanding of the progression and treatment of cancer.

PI_NAMEs: BOSENBERG, MARCUS W;MILLER-JENSEN, KATHRYN  (contact)

PROGRAM_OFFICER_NAME: ZAMISCH, MONICA

PROJECT_TERMS: adaptive immunity;Address;anti-cancer;anti-tumor immune response;Area;Biology;cancer cell;cancer immunotherapy;Cancer Patient;cancer regression;cancer therapy;Cell Communication;Cell model;Cell secretion;cell type;Cells;checkpoint therapy;chemokine;Classification;Clinical;Collecting Cell;combinatorial;Communication;Complex;Computer Models;Computing Methodologies;CTLA4 blockade;cytokine;Data;design;Fibroblasts;functional plasticity;Goals;Human;Immune;Immune checkpoint inhibitor;Immune response;Immune system;Immunologics;Immunotherapy;improved;in vivo;innovation;intercellular communication;Laboratory Study;Ligands;Lymphocyte;Macrophage;Malignant Neoplasms;Maps;Measurement;Mediating;Melanoma;Melanoma patient;Melanoma Tumor;Metastatic Melanoma;Mission;Modeling;monocyte;mouse model;Mus;Myeloid Cells;neoplastic cell;next generation;novel therapeutic intervention;Pathology;patient subsets;Patients;pharmacologic;Population;predictive modeling;programmed cell death protein 1;Property;Public Health;Publishing;receptor;Receptor Cell;receptor expression;Research;Resistance;response;Sampling;Shapes;Signal Transduction;single cell analysis;single-cell RNA sequencing;support network;Systems Analysis;Systems Biology;T cell infiltration;T cell response;T-Lymphocyte;Testing;Therapeutic;therapeutic target;Time;Translating;translational impact;tumor;tumor heterogeneity;tumor microenvironment;tumor progression;tumor-immune system interactions

PROJECT_TITLE: Systems analysis of cell-cell communication networks and immune activity in the melanoma tumor microenvironment


ADMINISTERING_IC: LM

IC_NAME: NATIONAL LIBRARY OF MEDICINE

NIH_SPENDING_CATS: Data Science;Genetics;Human Genome;Machine Learning and Artificial Intelligence;Microbiome;Networking and Information Technology R&D (NITRD)

ORG_CITY: CHICAGO

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE Although the microbial communities living in (and on) the human body play a key role in disease, understanding how the microbiome affects health has been limited by small sample sizes, which make it impractical to accurately detect complex ecological dynamics. We will compile and organize publicly available data to create the largest human microbiome dataset in the world, and use machine learning to uncover novel insights into human health that have until now been lost in the noise. The compendium and models will enable microbiome researchers to generate robust characterizations of the complex relationship between microbiota and their hosts, which can in turn support novel, more reliable diagnosis of disease and bring the field one step closer to developing microbiome-based therapeutics.

PI_NAMEs: BLEKHMAN, RAN  (contact);GREENE, CASEY S

PROGRAM_OFFICER_NAME: FARRELL, CATHERINE MARY

PROJECT_TERMS: Affect;Automated Annotation;bioinformatics tool;Biological;Biological Markers;Classification;Code;Collection;community living;Complex;Data;Data Set;Databases;Descriptor;Development;dimension reduction;Disease;disease diagnosis;Environment;Etiology;falls;fecal microbiome;Generations;Genomics;Health;Human;Human body;Human Microbiome;improved;Individual;insight;Internet;Interview;Link;Machine Learning;machine learning model;Meta-Analysis;Metadata;metagenomic sequencing;Metagenomics;Methods;microbial;microbial community;microbiome;microbiome analysis;microbiome research;microbiome therapeutics;microbiota;model building;model organism;Modeling;Noise;novel;novel therapeutic intervention;Ontology;Output;Pathway interactions;Pattern;Play;Process;Publishing;Research Personnel;Resources;Ribosomal RNA;Running;sample collection;Sample Size;Sampling;Sequence Read Archive;Shotguns;Signal Transduction;Site;Standardization;Supercomputing;System;Techniques;Time;tool;Training;training data;trait;Variant;Visualization;Visualization software;web app;web services;Width;Writing

PROJECT_TITLE: Human Microbiome Compendium: large-scale curation and processing of human microbiome datasets


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

PI_NAMEs: AGARD, DAVID A. (contact)

PROJECT_TERMS: 2019-nCoV;Affect;Affinity;age related;Air;Binding;Biochemical;Biochemistry;Biological Assay;cell behavior;Cells;Cellular biology;Cellular Structures;Chromatography;Complex;Cryo-electron tomography;Cryoelectron Microscopy;Dissociation;Electron Microscopy;extracellular;Fixatives;Gene Mutation;Genetic;genetic variant;Goals;graphene;Homeostasis;In Vitro;innovation;insight;interest;Light;Lysosomes;magnetic beads;Mammalian Cell;media use;Metabolism;Methodology;Methods;Molecular;Molecular Chaperones;Molecular Conformation;Molecular Structure;Mutation;novel;novel strategies;Organelles;overexpression;Oxides;Peptide Hydrolases;preservation;Process;protein complex;protein expression;protein structure;Proteins;reconstitution;Resolution;Sampling;structural biology;Structure;tau aggregation;tau Proteins;Technology;Therapeutic Intervention;Thinness;Tissues;Water

PROJECT_TITLE: Core B: Macromolecular and Cellular Structure Core


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Neurosciences

ORG_CITY: MADISON

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: The developing nervous system exhibits plasticity during formation of connections (synapses) between neuronal partners; disruption of which can lead to abnormal processing (dysfunction) of the brain. We observe synaptic reorganizations during development of connections in the inner retina and the main goal of this research is to determine the cell-autonomous and non-cell autonomous mechanisms that regulate the timing and occurrence of synaptic reorganizations during retinal circuit assembly. Our research will reveal the mechanisms driving developmental plasticity and circuit organization during establishment of sensory circuits and will determine circuit plasticity motifs that can be accentuated or curtailed as part of repair strategies for retinal degenerative diseases.

PI_NAMEs: HOON, MRINALINI  (contact)

PROGRAM_OFFICER_NAME: WRIGHT, CHARLES BAKER

PROJECT_TERMS: 3-Dimensional;Address;Afferent Neurons;Amacrine Cells;Automobile Driving;Axon;Bipolar Neuron;Birth;Brain;cell type;Cells;Chlorides;Cues;dark rearing;Data;Dendrites;Development;developmental plasticity;Electron Microscopy;Electrophysiology (science);Ensure;Environment;Equilibrium;Event;Exhibits;experience;Eye;Feedback;Functional disorder;gamma-Aminobutyric Acid;Gene Expression;Glutamate Receptor;glutamatergic signaling;Glutamates;Goals;Immunohistochemistry;Impairment;in vivo;Inhibitory Synapse;Knowledge;Light;light microscopy;Maintenance;Mediating;Mus;Nervous System;Neurons;neurotransmission;Neurotransmitters;Organism;Output;patch clamp;photoreceptor degeneration;Photoreceptors;Physiology;Pluripotent Stem Cells;Positioning Attribute;presynaptic;Presynaptic Terminals;protein expression;receptor;recruit;repair strategy;Research;Resolution;response;Retina;Retinal Degeneration;Retinal Diseases;retinal rods;retinogenesis;Rod;Role;Sensory;sensory feedback;Shapes;Signal Transduction;Stereotyping;Stimulus;Synapses;synaptic function;synaptic inhibition;synaptogenesis;Testing;tool;Transgenic Organisms;Visual;visual information;Visual Pathways

PROJECT_TITLE: Mechanisms regulating formation and maintenance of sensory circuits

STUDY_SECTION: NTRC

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


ORG_CITY: CORAL GABLES

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

ORG_STATE: FL

PHR: PROJECT NARRATIVE Expression of neoantigens in the patient' tumor is paramount for susceptibility to immune therapy. Given the paucity of neoantigens in many patients we propose to develop novel and clinically applicable methods to induce neoantigens in the patient' disseminated tumor lesion using a novel nucleic acid-based drug and drug delivery platform. The proposed approach forms the basis for the development of preventative cancer vaccines to prevent recurrence for patients in remission, and for individuals at high risk of developing cancer, such as individuals with precancerous lesions, individuals suffering from chronic infections or individuals with genetic predisposition to cancer.

PI_NAMEs: GILBOA, ELI  (contact)

PROGRAM_OFFICER_NAME: SOMMERS, CONNIE L

PROJECT_TERMS: Ablation;antigen processing;Antigens;aptamer;Autoimmune;Binding;cancer therapy;Cancer Vaccines;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;Cells;chronic infection;clinical application;Clinical Trials;clinically relevant;combinatorial;CPG-oligonucleotide;Development;Disease;Disease remission;Down-Regulation;Drug Delivery Systems;Epitopes;Evaluation;Future;Genetic;Genetic Predisposition to Disease;Goals;Growth;high risk;Human;Immune;Immune response;Immune Targeting;Immunity;Immunotherapy;Impairment;In Situ;In Vitro;Individual;Inflammatory;Intervention;invariant chain;Lead;Lesion;Malignant Neoplasms;Measurable;Mediator;Methods;MHC Class I Genes;Modality;Modeling;mortality;Mus;Mutation;neoantigen vaccination;neoantigens;Neoplasm Metastasis;neoplastic cell;novel;Nucleic Acids;nucleolin;Oligonucleotides;Pathology;Pathway interactions;patient subsets;Patients;Peptides;Pharmaceutical Preparations;pre-clinical;Predisposition;premalignant;prevent;Procedures;programs;prototype;Reagent;Recurrence;Recurrent tumor;Risk Reduction;Small Interfering RNA;synergism;T cell response;T-Lymphocyte;T-Lymphocyte Epitopes;Testing;Time;Toxic effect;tumor;Tumor Immunity;Vaccinated;Vaccination;vaccination strategy;vaccine immunogenicity;Vaccines

PROJECT_TITLE: Vaccination against antigens induced by TAP downregulation in concurrent and future tumors

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


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

PI_NAMEs: YOKOYAMA, JENNIFER S (contact)

PROJECT_TERMS: Acceleration;Alzheimer's Disease;Amyotrophic Lateral Sclerosis;Antisense Oligonucleotides;Assessment tool;autosome;Bioinformatics;Biological;Biological Process;Biology;C9ORF72;Candidate Disease Gene;Cell Nucleus;Cell Physiology;Clinical;Collaborations;Communities;corticobasal degeneration;Data;Data Set;data sharing;Databases;Development;Diagnosis;Disease;disorder risk;Family;Frontotemporal Dementia;Frontotemporal Lobar Degenerations;frontotemporal lobar dementia amyotrophic lateral sclerosis;Gene Mutation;Genes;Genetic;Genetic Risk;genetic risk assessment;genetic risk factor;Genetic Variation;genome sequencing;Genomics;Goals;Homeostasis;Human;human disease;Human Genetics;human genomics;Inherited;insight;Knowledge;Link;Maps;MAPT gene;Metabolism;Molecular Chaperones;multidisciplinary;Mutation;Nerve Degeneration;Neurodegenerative Disorders;neuropathology;new therapeutic target;novel;older adult;Parkinson Disease;Pathogenicity;Pathologic;Pathway interactions;Patients;Peptide Hydrolases;Pick Disease of the Brain;polygenic risk score;prevent;Progressive Supranuclear Palsy;protein TDP-43;Proteins;Proteolysis;proteostasis;Recording of previous events;Research;Risk;Role;Sampling;Science;Site;success;synergism;targeted treatment;tau function;tau Proteins;Tauopathies;therapeutic development;tool;transcriptomics;Translations;Update;Variant;Visualization;whole genome

PROJECT_TITLE: Core C: Genomics and Transcriptomics


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Hematology;Human Genome;Racial and Ethnic Minority Health Research;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Transplantation

ORG_CITY: BUFFALO

ORG_NAME: ROSWELL PARK CANCER INSTITUTE CORP

ORG_STATE: NY

PHR: Project Narrative This is the first study to use both next-generation sequencing and genome-wide association study data to analyze the contribution of non-HLA genetic variants to mortality after allogeneic blood and marrow transplantation (BMT) for life-threatening hematologic cancers. Importantly, our study population includes multiple races and ethnicities which will allow us to investigate the role of genetics on BMT survival across diverse populations. The data generated by this project will be shared publicly to serve as a resource for additional research to improve survivorship after this therapy and enhance the public investment in this project.

PI_NAMEs: CLAY-GILMOUR, ALYSSA IONE;HAHN, THERESA E (contact);ZHU, QIANQIAN

PROGRAM_OFFICER_NAME: FILIPSKI, KELLY

PROJECT_TERMS: 10q21;14q32;Affect;African American population;Allogenic;American;Antigens;Asian population;Bayesian Method;Binding;Biological;Biological Assay;Blood;Bone Marrow Transplantation;Clinical;clinical practice;Code;cohort;Collaborations;Data;design;Disease;disorder risk;Donor person;Ethnic Origin;Etiology;European;exome;exome sequencing;Funding;gene network;Genes;Genetic;Genetic study;genetic variant;genome wide association study;genome-wide;Genomics;Genotype;Goals;Hematologic Neoplasms;Hematological Disease;Hispanic;Hispanic Populations;Immune response;improved;in silico;Investments;Life;Linkage Disequilibrium;Machine Learning;Major Histocompatibility Complex;Methods;Minority;Minority Groups;mortality;mortality risk;multi-ethnic;mutant;Names;next generation sequencing;novel;Pathway Analysis;Pathway interactions;Patients;Peptides;Play;polygenic risk score;Population;Population Heterogeneity;Predisposition;prognostic model;Race;rare variant;Research;Resources;Risk;Role;Sampling;Signal Transduction;study population;Surveys;survival disparity;survivorship;Technology;Testing;tool;Training;transcriptome;Translating;Transplant Recipients;Transplantation;United States National Institutes of Health;vaccine response;Validation;Variant

PROJECT_TITLE: Multi-ethnic high-throughput study to identify novel non-HLA genetic contributors to mortality after blood and marrow transplantation

STUDY_SECTION: GHD

STUDY_SECTION_NAME: Genetics of Health and Disease Study Section[GHD]


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

PROJECT_TERMS: Address;Affect;Alzheimer's Disease;Amino Acid Sequence;Animal Model;Autophagocytosis;autosome;Biology;cell type;Cells;Complex;Coupling;Databases;Degradation Pathway;Disease;DNA Sequence Alteration;Experimental Models;Focus Groups;Frontotemporal Dementia;Frontotemporal Lobar Degenerations;Gene Mutation;Genes;Genetic;genetic variant;genomic locus;Goals;Half-Life;Homeostasis;improved;Individual;Induced pluripotent stem cell derived neurons;insight;Lysosomes;Maps;Measures;Metabolic;Metabolic Pathway;Metabolism;Modeling;Molecular;Molecular Chaperones;multicatalytic endopeptidase complex;Mutation;Nerve Degeneration;Neurodegenerative Disorders;Neurons;Other Genetics;Pathway interactions;Peptide Hydrolases;Phenotype;polygenic risk score;Post-Translational Modification Site;Post-Translational Protein Processing;Prevention;protein degradation;protein metabolism;protein protein interaction;Proteolysis;proteostasis;Regulation;Research Personnel;Resolution;Resources;Signal Transduction;Site;Structure;System;tau aggregation;tau interaction;tau mutation;tau Proteins;tau-1;Tauopathies;Testing;TSC1 gene;Variant;Work

PROJECT_TITLE: Project 1: Tau metabolism: molecular chaperones, targeting and proteolysis


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Brain Cancer;Brain Disorders;Cancer;Clinical Research;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurosciences;Patient Safety;Rare Diseases

ORG_CITY: SAINT LOUIS

ORG_DEPT: NEUROSURGERY

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Project Narrative The proposed research is an academic industry partnership that will make available to neurosurgeons and neuro- oncologists a neuronavigation capability that will optimize treatment of patients with brain tumors by more efficiently and accurately localizing critical brain regions and providing prognostic information on the patient’s survival. This development is relevant to public health because it will assist clinicians to personalize patient treatment planning, including surgical strategy and subsequent oncologic care. Towards this end, we propose to create an imaging technology package that will integrate advanced machine learning techniques using resting state functional magnetic resonance imaging with an existing widely used neuro-anatomic navigation system currently used by neurosurgeons. The integrated system, which will include anatomic, functional, and prognostic information, will provide a more comprehensive patient assessment to maximize safe and effective treatment.

PI_NAMEs: LEUTHARDT, ERIC CLAUDE (contact);SHIMONY, JOSHUA S

PROGRAM_OFFICER_NAME: ZHANG, YANTIAN

PROJECT_TERMS: 3-Dimensional;Adoption;Algorithms;analysis pipeline;Anatomy;Architecture;Biological Markers;Biopsy;Brain;Brain imaging;Brain Mapping;Brain Neoplasms;Brain region;brain tumor resection;Caring;Child;Clinical;clinical decision support;clinical decision-making;Clinical Trials;clinically relevant;Cognitive;Computer software;convolutional neural network;Craniotomy;Data;Development;Devices;Diagnosis;effective therapy;Excision;experience;Failure;Functional Magnetic Resonance Imaging;functional status;Funding;Glioblastoma;Glioma;Goals;Image;Imaging technology;improved;individualized medicine;industry partner;Infrastructure;innovation;insight;Investigation;Knowledge;Lesion;Machine Learning;machine learning algorithm;Magnetic Resonance Imaging;Malignant Glioma;Maps;Methods;multilayer perceptron;Navigation System;Neuroanatomy;Neuronavigation;Neurons;Neurosurgeon;neurosurgery;next generation;operation;Operative Surgical Procedures;Outcome;Output;Pathologic;Patient Care;Patient imaging;Patient Participation;Patient-Focused Outcomes;Patients;Performance;personalized approach;Population;preservation;Procedures;Productivity;Prognosis;prognostic;prognostic algorithm;prognostic of survival;Progression-Free Survivals;prospective;Public Health;Quality Control;Quality of life;radiomics;Research;Rest;Sedation procedure;success;Surgeon;survival prediction;System;Systems Integration;Techniques;Technology;Time;tool;treatment optimization;treatment planning;tumor;United States Food and Drug Administration;Universities;Validation;Visualization;Washington;Work

PROJECT_TITLE: Advancing Neurosurgical Neuronavigation Using Resting State MRI and Machine Learning


NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Infectious Diseases;Rare Diseases;Sexually Transmitted Infections

ORG_CITY: DETROIT

ORG_NAME: WAYNE STATE UNIVERSITY

ORG_STATE: MI

PI_NAMEs: SUVAS, SUSMIT  (contact)

PROGRAM_OFFICER_NAME: MCKIE, GEORGE ANN

PROJECT_TERMS: Ablation;Adrenal Cortex Hormones;angiogenesis;Anti-viral Agents;Biological Assay;Biological Availability;Blindness;Blocking Antibodies;Blood Vessels;Cataract;Cell Aging;Cell surface;Cells;Chronic;Circulation;Clinical;conditional knockout;Confocal Microscopy;Cornea;Corneal edema;corneal epithelium;Corneal Stroma;density;Development;Disease;Enzyme-Linked Immunosorbent Assay;Epithelial Cells;Event;experimental study;Eye Infections;Glaucoma;Goals;Herpes stromal keratitis;Herpesvirus 1;Human;Hypoxia;immune modulating agents;immunopathology;Impaired wound healing;in vivo;Infection;Inflammation;Inflammatory;Insulin-Like Growth Factor Binding Protein 3;Insulin-Like Growth Factor I;Insulin-Like Growth Factor II;Insulin-Like Growth-Factor-Binding Proteins;Insulin-Like-Growth Factor I Receptor;Knock-out;Knockout Mice;Knowledge;Lesion;Leucocytic infiltrate;Leukocytes;Measures;Membrane;Molecular;mouse model;Mus;Myelogenous;Myeloid Cells;neovascularization;neutrophil;new therapeutic target;novel therapeutic intervention;Oral;Outcome;Outcome Measure;Pathogenesis;Phosphorylation;Physiologic Intraocular Pressure;Plasmids;pleiotropism;Predisposition;Protein Array;Proteins;Publishing;Receptor Signaling;Recombinant Insulin-Like Growth Factor;Recurrence;Reporting;response;Risk;Role;Sampling;senescence;Severities;Somatomedins;Stains;Steroids;Tamoxifen;Testing;Time;Topical application;Transfection;Tyrosine Kinase Inhibitor;Tyrosine Phosphorylation;United States;Vascular Endothelial Cell;Viral;Viral Load result;Virus Replication;Visual

PROJECT_TITLE: Role of insulin-like growth factor binding proteins in the pathogenesis of herpes stromal keratitis.


NIH_SPENDING_CATS: Neurosciences;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Preterm, Low Birth Weight and Health of the Newborn;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_DEPT: PATHOLOGY

PHR: NARRATIVE Germinal matrix hemorrhage (GMH) is a leading cause of neonatal death and neurodevelopmental disorders. However, the mechanism leading to GMH remains unclear. This research project brings together unparallel expertise in neuropathology, single-cell transcriptomics, in vitro disease modeling, and neural stem cell biology, to rigorously investigate the role of neuroinflammation in the pathogenesis of GMH. Results from this project will provide important insights into disease mechanism of, and therapeutic targets for, GMH.

PI_NAMEs: HUANG, ERIC J (contact)

PROGRAM_OFFICER_NAME: MORRIS, JILL A

PROJECT_TERMS: Agonist;angiogenesis;antagonist;Anti-Bacterial Agents;Bioenergetics;Bioinformatics;Biological Assay;Blood Vessels;Brain;Brain region;Cell Communication;Cell Maturation;Cell Nucleus;Cells;Cellular Stress;Cerebral cortex;Cerebral Palsy;Complex;cytotoxic;Data;Defensins;Development;Disease;disease model;Elastases;Endothelial Cells;Enzymes;Erythro;Exhibits;Fluorescence-Activated Cell Sorting;Histologic;Human;improved;In Vitro;Inflammatory;insight;Interneurons;Knowledge;Lead;Macrophage;matrigel;Mediating;Microglia;migration;Molecular;monocyte;Morphogenesis;Myeloid Progenitor Cells;Neonatal Mortality;nerve stem cell;nestin protein;neural circuit;neuroblast;Neurodevelopmental Disorder;neurogenesis;Neuroglia;Neuroimmune;neuroinflammation;neuropathology;neutrophil;Organoids;Pathogenesis;Perinatal subependymal hemorrhage;Peroxidases;Population;Pregnancy;Premature Birth;Premature Infant;prenatal;Prevalence;progenitor;Property;PTPRC gene;Radial;Research;Research Project Grants;Role;Second Pregnancy Trimester;Signal Transduction;single-cell RNA sequencing;stem cell biology;Testing;therapeutic target;transcriptomic profiling;transcriptomics

PROJECT_TITLE: Neuroinflammation and vascular development in GMH

STUDY_SECTION: NOMD

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


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: Narrative We will interrogate the developmental and genetic signature of pancreas tissue organization at unprecedented scales including spatially-resolved chromatin architecture, transcriptome, and in situ cellular function. Our results have the potential to identify key pathways including their context-specific regulatory elements, genes, and cell types, governing islet and pancreas development. If successful, these studies will provide new mechanistic insights about the functional maturation of human β cells.

PI_NAMEs: BRISSOVA, MARCELA  (contact);CAICEDO, ALEJANDRO ;LIU, JIE ;PARKER, STEPHEN CJ;POWERS, ALVIN C

PROGRAM_OFFICER_NAME: WANG, XUJING

PROJECT_TERMS: Address;Adolescent;Adult;Age;Architecture;Autoimmunity;Beta Cell;biobank;Biological Assay;Biology;Birth;Blood Vessels;Cell Communication;Cell Maturation;Cell Nucleus;Cell Physiology;cell type;Cells;Child;Childhood;Chromatin;Collaborations;Communities;Community Networks;Complement;Data;Data Analyses;Data Set;Detection;Development;diabetes mellitus therapy;diabetes pathogenesis;Diagnosis;Endocrine;endocrine pancreas development;epigenomics;Functional disorder;Gene Expression;Genes;Genetic;genetic signature;Genetic Transcription;genome wide association study;Histologic;Homeostasis;Hormone secretion;Human;Image;Immune;improved;In Situ;indexing;Individual;infancy;Infrastructure;innovation;insight;Insulin-Dependent Diabetes Mellitus;Interdisciplinary Study;islet;Knowledge;Knowledge Portal;Leadership;Life;Machine Learning;Maps;Measures;Metabolic Diseases;Molecular;Molecular Profiling;multidisciplinary;multiple omics;multiplexed imaging;Neonatal;non-diabetic;Non-Insulin-Dependent Diabetes Mellitus;novel therapeutics;Organ;Organ Donor;Pancreas;pancreas development;Pancreatic Diseases;Pathway interactions;pharmacologic;Phenotype;phenotypic data;Physiological;Physiology;Population;postnatal;postnatal development;postnatal human;postnatal period;prevent;Process;Productivity;programs;protein expression;Regulatory Element;Research;Research Personnel;Resolution;response;RNA;sex;Signal Transduction;single cell genomics;Slice;Specificity;Stimulus;Stromal Cells;Techniques;Technology;temporal measurement;Testing;Time;timeline;Tissue imaging;Tissues;tool;trait;Transcriptional Regulation;transcriptome;transcriptomics;type I and type II diabetes;vascular contributions;Visualization;XCL1 gene

PROJECT_TITLE: Integrative analysis of multi-omic signatures and cellular function in human pancreas across developmental timeline at single-cell spatial resolution


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

PI_NAMEs: KARCH, CELESTE MARIE (contact)

PROJECT_TERMS: Address;Alleles;Antisense Oligonucleotides;Binding;Biochemical;Brain;Brain region;brain tissue;Cell Nucleus;Cerebrospinal Fluid;Characteristics;Communities;corticobasal degeneration;CRISPR/Cas technology;Databases;Defect;design;Disease;disorder risk;Dominant Genes;Enzymes;Event;Exhibits;extracellular;Frontotemporal Lobar Degenerations;Gene Mutation;Genes;Genetic;Genomics;Goals;Half-Life;Haplotypes;Human;human induced pluripotent stem cells;Induced pluripotent stem cell derived neurons;Inherited;Kinetics;Lysosomes;Maps;MAPT gene;Metabolism;Methods;Modification;Molecular;Molecular Chaperones;Molecular Profiling;Molecular Structure;Monitor;mRNA Precursor;Mutagenesis;mutant;Mutation;Nerve Degeneration;Neuronal Dysfunction;Neurons;novel;novel therapeutic intervention;Pathogenesis;Pathologic;Pathway interactions;Peptide Hydrolases;polygenic risk score;Post-Translational Protein Processing;Progressive Supranuclear Palsy;Protein Isoforms;proteostasis;proteostasis loss;Regulation;Resources;Risk;RNA Splicing;Stable Isotope Labeling;Structure;tau aggregation;tau Proteins;tau-1;Tauopathies;Technology;Testing;Therapeutic;therapeutic target;Toxic effect;transcriptome;transcriptome sequencing;transcriptomics;Variant;Work

PROJECT_TITLE: Project 2: Tau metabolism: Quantifying tau half-life and secretion


ADMINISTERING_IC: AI

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Clinical Research;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Emergency Care;Emerging Infectious Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Prevention;Social Determinants of Health

ORG_CITY: CHAPEL HILL

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: NARRATIVE Jails in the United States are hot spots for spread of SARS-CoV-2 infection, resulting in a disproportionate burden of COVID-19 morbidity and mortality among incarcerated persons and correctional staff. Despite potential for high impact, limited work has investigated SARS-CoV-2 transmission dynamics in jail populations or evaluated interventions in jails to reduce COVID-19 morbidity and mortality. To address this critical need, the proposed study will examine population movement, COVID-19 testing, and COVID-19 cases in North Carolina jails, and using mathematical modeling, project incidence of SARS-CoV-2 infection and the extent to which interventions will reduce COVID-19 morbidity and mortality in jails and their surrounding communities.

PI_NAMEs: LEVINTOW, SARA NICOLE (contact)

PROGRAM_OFFICER_NAME: BOZICK, BROOKE ALLISON

PROJECT_TERMS: 2019-nCoV;Address;Admission activity;Amplifiers;Area;Black, Indigenous, People of Color;Calibration;Cessation of life;Characteristics;Communicable Diseases;Communities;comorbidity;Complex;Computer Simulation;Confined Spaces;Coupled;court;COVID-19;COVID-19 burden;COVID-19 incidence;COVID-19 morbidity;COVID-19 mortality;COVID-19 pandemic;COVID-19 prevalence;COVID-19 prevention;COVID-19 severity;COVID-19 testing;Criminal Justice;Crowding;Data;Data Sources;demographics;Development;Disease;Disease Outbreaks;disease transmission;Epidemiologist;Epidemiology;Equipment;experience;Failure;Future;General Population;Geographic Locations;Goals;Health;HIV;Hospitalization;Hot Spot;Hygiene;Immunization Programs;Imprisonment;improved;Infection;infectious disease model;Institution;Intervention;Jail;Knowledge;Law Enforcement;Lead;Link;Literature;mathematical analysis;mathematical model;Medical;Mentored Research Scientist Development Award;Mentors;Mentorship;Methodology;Modeling;Morbidity - disease rate;mortality;Movement;North Carolina;Outcome;Persons;Policies;Population;population movement;Population Sizes;prevent;Preventive;Prisons;Process;public health emergency;racial health disparity;Reporting;Research;Safety;SARS-CoV-2 infection;SARS-CoV-2 transmission;simulation;skills;Social Distance;System;Testing;therapy design;Time;Training;transmission process;United States;United States Dept. of Health and Human Services;University resources;vaccine hesitancy;Vaccines;Variant;Vulnerable Populations;Work

PROJECT_TITLE: Investigating SARS-CoV-2 transmission dynamics in jails to address the COVID-19 public health emergency

STUDY_SECTION: MID

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


NIH_SPENDING_CATS: Aging;Breast Cancer;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Colorectal Cancer;Digestive Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Lung;Lung Cancer;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Women's Health Research

ORG_CITY: WASHINGTON

ORG_NAME: GEORGETOWN UNIVERSITY

ORG_STATE: DC

PHR: Project Narrative The National Capital Area (NCA) Minority/Underserved NCORP, based at Georgetown Lombardi Comprehensive Cancer Center (LCCC) and comprises MedStar Georgetown University Hospital (MGUH) and MedStar Washington Hospital Center (MWHC), will conduct cancer clinical research towards efforts to reduce cancer-related disparities and health care outcomes. The NCA NCORP will address the needs of our catchment area via cancer prevention, control, screening as well as treatment and imaging studies.

PI_NAMEs: ADAMS-CAMPBELL, LUCILE LAUREN (contact);NOEL, MARCUS S

PROGRAM_OFFICER_NAME: HECKMAN-STODDARD, BRANDY

PROJECT_TERMS: Address;Adolescent and Young Adult;aging population;Area;arm;Awareness;base;Black Populations;Breast;Cancer Burden;cancer care;Cancer Center;cancer clinical trial;Cancer Control;cancer health disparity;Cancer Patient;cancer prevention;cancer risk;Cancer Survivor;Capital;care delivery;care outcomes;Caring;Catchment Area;Cause of Death;Clinical Research;Clinical Trials;Clinical Trials Cooperative Group;Collaborations;Colorectal Cancer;Communities;community academic partnership;community center;community collaboration;community engagement;community organizations;Community Outreach;community partners;Comprehensive Cancer Center;County;Coupled;Death Rate;design;Disparity;disparity elimination;District of Columbia;Education;ethnic diversity;experience;Faculty;Faith-based organization;Goals;Health;health assessment;Health Disparities Research;health disparity;Healthcare;Hispanic Populations;Hospitals;imaging study;improved;interest;Latino;Latino Population;Leadership;Light;Malignant Breast Neoplasm;Malignant neoplasm of cervix uteri;Malignant neoplasm of prostate;Malignant Neoplasms;Mammographic screening;Maryland;medical specialist;medically underserved;Minority;Minority Groups;minority health;minority health disparity;Neighborhoods;Nonprofit Organizations;Obesity;Oncologist;Outcome;Outpatients;outreach;Participant;Patient-Focused Outcomes;Patients;physical inactivity;Population;Prevention;Prevention trial;Primary Care Physician;programs;Quality of Care;racial diversity;Recording of previous events;recruit;Research;Research Personnel;Resources;Risk Factors;Schedule;screening;Smoking;Subgroup;Underserved Population;Uninsured;University Hospitals;Virginia;Visit;Washington;Woman


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Genetics;Hematology;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: SEATTLE

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: Project Narrative The epigenetic process safeguards cell identity during cell division through the inheritance of appropriate gene expression profiles. Little is known regarding the chromatin inheritance of a hematopoietic stem cell (HSC) state in normal human development. In this proposal, we will identify the molecular basis in constructing the heritable epigenome of HSCs and determine how chromatin dynamics confers HSC self-renewal and differentiation potential.

PI_NAMEs: ESCOBAR, THELMA  (contact)

PROGRAM_OFFICER_NAME: CHOW, CHI-WING

PROJECT_TERMS: Adult Acute Myeloblastic Leukemia;Age;Cell Cycle;Cell division;Cells;Chromatin;Complex;DNA biosynthesis;DNA replication fork;DNA Sequence Alteration;Epigenetic Process;epigenome;Gene Expression Profile;Genome engineering;Hematopoiesis;Hematopoietic;hematopoietic stem cell fate;hematopoietic stem cell self-renewal;Hematopoietic stem cells;Heritability;Histones;Human;Human Development;human induced pluripotent stem cells;human stem cells;Imaging technology;Immune system;In Vitro;Inherited;Molecular;Molecular Chaperones;Mouse Embryonic Stem Cells;NPM1 gene;nucleophosmin;Nucleosomes;Play;Polycomb;Postdoctoral Fellow;Process;Proteomics;Recycling;Repression;Role;S phase;segregation;self-renewal;Shapes;stem cell fate;System

PROJECT_TITLE: Determinants of epigenetic inheritance in human stem cell fate decisions

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CDB-L(55)R]


ADMINISTERING_IC: TW

IC_NAME: FOGARTY INTERNATIONAL CENTER

NIH_SPENDING_CATS: Neurosciences

PHR: NARRATIVE  The proposed program aims to develop and sustain capacity to conduct neurological research and impart such knowledge in Africa, by offering in-depth formal training in the design, execution, and leadership of neurological research to 24 carefully selected African scholars. The fellowship, administered through a collaboration between African and US academic institutions, as well as professional societies, will train eligible individuals in a broad range of clinical research issues, such that they can eventually populate Africa’s academic institutions as faculty, and foster enduring capacity to engage in high quality neurological research, and mentor future generations of Africans in the field.

PI_NAMEs: OVBIAGELE, BRUCE  (contact);OWOLABI, MAYOWA OJO

PROGRAM_OFFICER_NAME: LEVINTOVA, MARYA

PROJECT_TERMS: Africa;African;African ancestry;career;certificate program;Clinical;Clinical Research;Credentialing;Disease;Education;effectiveness evaluation;efficacy testing;ethnic diversity;Event;Evidence based treatment;Exposure to;Face;Faculty;Foundations;Generations;Goals;Grant;Individual;Intervention;Knowledge;Lead;Leadership;Master of Science;Medicine;member;Mentors;Morbidity - disease rate;mortality;Motivation;multidisciplinary;Nervous System Disorder;Neurologic;Neurosciences Research;Nigeria;Persons;Pharmaceutical Preparations;Population;precision medicine;Program Effectiveness;programs;Race;Research;Research Personnel;Risk Factors;Role;Safety;Scientist;skills;symposium;targeted treatment;Training;Universities

PROJECT_TITLE: Training Africans to Lead and Execute Neurological Trials & Studies (TALENTS)

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-PSE-L(55)R]


NIH_SPENDING_CATS: Aging;Eye Disease and Disorders of Vision

ORG_CITY: Aurora

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: PROJECT NARRATIVE Posterior capsule opacification or secondary cataracts is a vision impeding complication after cataract surgery and requires laser treatment to restore vision, but laser treatment can inflict damage to retina. Moreover, secondary cataracts impose a significant burden on health care costs and diminish quality of life in the elderly. The goal of our proposed studies is to understand the biochemical mechanisms of secondary cataracts to inform development of future innovative therapies for this condition.

PI_NAMEs: NAGARAJ, RAM H (contact)

PROGRAM_OFFICER_NAME: ARAJ, HOUMAM H

PROJECT_TERMS: Adherence;Adult;Advanced Glycosylation End Products;Age;aged;Aging;Amino Acids;amino group;antagonist;Anterior;Apoptosis;Aqueous Humor;Binding;Biochemical;Biochemical Pathway;capsule;carbonyl compound;Cataract;Cataract Extraction;Cell Aging;Cell Physiology;Cell secretion;cell type;Cells;clinical predictors;Complication;Country;CRISPR/Cas technology;crosslink;cytokine;Data;Development;Disease;Economic Burden;Elderly;Epithelial Cells;Epithelial Receptor Cell;epithelial to mesenchymal transition;epithelial wound;extracellular;Extracellular Matrix;Eye;fiber cell;Fibrosis;Future;glycation;Goals;Growth;Growth Factor;Health Care Costs;Human;Impairment;In Situ;in vivo;Inflammatory;Innovative Therapy;Interleukin-6;Intraocular lens implant device;knock-down;Lasers;lens;lens capsule;lens induction;Link;Mediating;Mesenchymal;Methods;migration;Modification;Molecular;novel;novel therapeutics;paracrine;Pathogenesis;Patients;Performance;Post-Translational Protein Processing;prevent;Production;Proliferating;protein structure;Proteins;Quality of life;Reaction;Reactive Oxygen Species;Receptor Down-Regulation;receptor downregulation;receptor for advanced glycation endproducts;Research;Resistance;response;retinal damage;Retinal Detachment;Role;senescence;senescence associated secretory phenotype;senescent cell;sight restoration;Testing;therapy development;time interval;Tissues;transdifferentiation;Transforming Growth Factors;Vision;Visual;Visual impairment

PROJECT_TITLE: Lens capsule and secondary cataract

STUDY_SECTION: BDE

STUDY_SECTION_NAME: Biology and Development of the Eye Study Section[BDE]


ORG_CITY: PHILADELPHIA

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: U01 Application: The role of senescent beta cells in T1D and T2D Narrative  Recent reports suggest that the elimination of senescent insulin-producing beta cells can prevent or delay the onset of type 1 and type 2 diabetes in mouse models. Here, we will test this hypothesis using advanced genetic and genomic tools in human pancreatic islets to ascertain if this approach should be pursued for clinical practice.

PI_NAMEs: KAESTNER, KLAUS H (contact)

PROJECT_TERMS: Ablation;acute stress;Age;age-related disease;Alleles;Animal Model;Autoantibodies;Autoimmunity;B-Lymphocytes;Backcrossings;Beta Cell;Biological Assay;blood glucose regulation;CDKN1A gene;CDKN2A gene;Cell Aging;Cell Cycle;Cell Cycle Arrest;cell injury;Cell Physiology;cell type;Cells;Cellular Stress;Characteristics;Chronic;clinical practice;cohort;Cre driver;Cytometry;Data;Development;Diabetes Mellitus;diabetic;diabetic patient;DNA;DNA Damage;epigenomics;Excision;Functional disorder;gain of function;Gene Expression Profile;Genes;Genetic;genetic signature;genomic tools;Genotoxic Stress;Glucose Intolerance;Histones;Human;Human Characteristics;human data;Hyperglycemia;Image;improved;Inbred NOD Mice;Inflammatory;inhibitor;Insulin;Insulin Resistance;Insulin-Dependent Diabetes Mellitus;islet;islet autoimmunity;Islet Cell;Islets of Langerhans;Knowledge;loss of function;Metabolic;Metabolism;methylome;Modality;Modeling;Molecular;Morphology;mouse model;Mus;non-diabetic;novel;Outcome;Oxidative Stress;Pancreas;Pathology;Pathway interactions;Pharmaceutical Preparations;Phenotype;Population;Prevalence;prevent;programs;Property;Recovery;Reporting;Research;response;Role;senescence;senescence associated secretory phenotype;senescent cell;senolytics;sex;Signal Transduction;single cell ATAC-seq;single-cell RNA sequencing;Stimulus;stressor;telomere;Testing;Therapeutic;TP53 gene;Transgenic Mice;Tumor Suppressor Proteins;tumorigenesis;Type 2 diabetic;type I and type II diabetes;type I diabetic;Viral Vector;Work;Xenograft Model;Xenograft procedure


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Clinical Research;Data Science;Emerging Infectious Diseases;Health Services;Infectious Diseases;Pediatric;Prevention

ORG_CITY: Ede

ORG_COUNTRY: NIGERIA

ORG_FIPS: NI

ORG_NAME: REDEEMER'S UNIVERSITY

PHR: Project Narrative Bacterial infections are highly prevalent and contribute significantly to morbidity and mortality across all age-groups but because appropriate bacterial diagnostic services are non- existent or very limited, finding the true cause of most infections and the true spread of antimicrobial resistance (AMR) is a major challenge in Africa, where data is limited. Our proposal has three goals to comparatively study bacterial isolates to inform trends in AMR and dynamics of transmission, to incorporate markers of serious bacterial infection and gene products from resistant bacteria to create a portable screening tool for clinical care and to explore the antimicrobial propers, and to explore the potential benefit of an aminoglycoside-antimicrobial peptide complex for enhanced therapeutic efficacy against multidrug resistant bacteria.

PI_NAMEs: FOUTS, DERRICK E;HAPPI, CHRISTIAN T. (contact);OBARO, STEPHEN

PROGRAM_OFFICER_NAME: NEWSOME, BRAD

PROJECT_TERMS: Acute;Address;Africa;African;age group;aged;Aminoglycosides;Ampicillin Resistance;anti-microbial peptide;Antibiotics;antimicrobial;Antimicrobial Resistance;Archives;Area;Awareness;Bacteria;Bacterial Infections;Bacterial Proteins;bacterial resistance;bactericide;Bioinformatics;Biological;Biomedical Engineering;Blood;Blood Circulation;carbapenem resistance;Caring;Case Fatality Rates;Cause of Death;Child;Chloramphenicol;Clinical;clinical care;clinical epidemiology;Collection;Communities;comparative;Comparative Study;Complex;Country;Dangerousness;Data;Data Science;Demographic and Health Surveys;Diagnostic;Diagnostic Services;Diarrhea;Disease Outbreaks;Enrollment;Enterobacteriaceae;Etiology;Evaluation;Extended-spectrum β-lactamase;Genomics;Genotype;Geography;Goals;Growth;health care service;Healthcare;High Prevalence;Human;Human Development;Human Resources;Incubators;indexing;Individual;Infection;inflammatory marker;Knowledge;Laboratories;Live Birth;Maternal Mortality;Microbe;Microbiology;Molecular;Molecular Epidemiology;Morbidity - disease rate;mortality;Multi-Drug Resistance;multidisciplinary;Multiple Bacterial Drug Resistance;Newborn Infant;Nigeria;Nigerian;novel;pathogenic bacteria;Pathway interactions;Periodicals;Pharmacy facility;Phenotype;Pneumonia;Population;portability;Prevalence;Prevention strategy;Program Development;programs;Research Proposals;resistance gene;resistant Klebsiella pneumoniae;Resource-limited setting;Rwanda;Salmonella typhi;Scientist;Screening procedure;Sentinel;Sepsis;Site;Sputum;Stream;Sulfamethoxazole;Syndrome;Tobramycin;Training;transmission process;Treatment Efficacy;trend;Trimethoprim;United Nations;Urine;Veterinarians;War;Woman

PROJECT_TITLE: Combatting AntiMicrobial Resistance in Africa Using Data Science (CAMRA)

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-BST-S(70)R]


ADMINISTERING_IC: DC

ED_INST_TYPE: ORGANIZED RESEARCH UNITS

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Autism;Behavioral and Social Science;Brain Disorders;Clinical Research;Intellectual and Developmental Disabilities (IDD);Mental Health

ORG_NAME: DREXEL UNIVERSITY

PHR: The proposed research will lay a foundation for developing innovative, individualized interventions to improve nonverbal communication (NVC) experiences for autistic adults, based on the values and first-hand experiences of our target population. Improvements in NVC are necessary for downstream improvements in a range of func- tional contexts, resulting in overall improved life outcomes associated with autism in adulthood. This project is relevant to NIDCD’s mission pertaining to intervention, and to the NIH’s Interagency Autism Coordinating Com- mittee’s dual missions related to intervention and lifespan issues. This project will produce a set of specific, stakeholder-driven recommendations for designing and prioritizing NVC intervention development, opening new horizons for how NVC is conceptualized and addressed in autism.

PI_NAMEs: DE MARCHENA, ASHLEY BROOKE (contact)

PROGRAM_OFFICER_NAME: STORKEL, HOLLY LYNN

PROJECT_TERMS: Address;Adult;adult with autism spectrum disorder;Age;Area;Autism Diagnosis;autism spectrum disorder;autistic;Behavioral;career;Child;Collaborations;Communication;Communities;community consultation;Consultations;Data;Data Collection;design;Development;disability;Education;Employment;Evidence based intervention;experience;Eye;Facial Expression;follow-up;Foundations;Future;Gestures;Goals;Grant;Guidelines;Hand;Healthcare;Heterogeneity;improved;Individual;Individual Differences;individuals with autism spectrum disorder;innovation;Intervention;Interview;Investments;Knowledge;Language;Life;life span;Machine Learning;Maps;member;Mental Health;Methods;Mission;Modeling;National Institute on Deafness and Other Communication Disorders;Nature;Nonverbal Communication;novel;Outcome;Participant;Patient Recruitments;Patient Self-Report;Pattern;preference;prospective;Quality of life;Recommendation;recruit;Research;Research Methodology;Research Personnel;Resources;response;Sampling;skills;Structure;success;Surveys;Target Populations;Testing;therapy development;Toddler;tool;trait;United States National Institutes of Health;verbal;wasting

PROJECT_TITLE: Establishing Intervention Priorities for Nonverbal Communication in Autistic Adults

STUDY_SECTION: CDRC

STUDY_SECTION_NAME: Communication Disorders Review Committee[CDRC]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;HIV/AIDS;Infectious Diseases;Lung;Rare Diseases;Tuberculosis

ORG_CITY: PITTSBURGH

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: Patients infected with both HIV and tuberculosis (TB) are at extremely high risk of death and long-term morbidity if they survive. Early treatment of both infections vastly improves long-term survival but there is a risk of TB-associated immune reconstitution syndrome (TB-IRIS) in which the symptoms of disease improve but then recur sometimes more severely than before treatment. Give that very little is currently understood about this process of TB-IRIS, this proposal identifies the basic mechanism of this poorly understood disease process and develop better strategies for prevention and treatment.

PI_NAMEs: FLYNN, JOANNE L.;LIN, PHILANA LING (contact)

PROGRAM_OFFICER_NAME: MAHON III, ROBERT N

PROJECT_TERMS: adaptive immune response;Address;Adverse effects;Aftercare;Animal Model;Animals;Anti-Retroviral Agents;antiretroviral therapy;Antitubercular Agents;Autopsy;Bacteria;Biological;biological heterogeneity;biomarker identification;Blood;CD4 Lymphocyte Count;Cells;Cessation of life;Characteristics;Clinical;clinical predictors;co-infection;Collaborations;comparison control;Complex;Country;Data;Development;Disease;disease model;Early treatment;Event;global health;Goals;Granuloma;Healthcare;Heterogeneity;high risk;HIV;HIV Infections;HIV/TB;Hospitalization;Human;human disease;human model;Image;Immune;immune function;immune reconstitution;Immune response;Immune system;Immunologics;Immunology;Improve Access;improved;in vivo imaging;Incidence;Infection;Inflammation;Inflammatory;insight;Knowledge;Lung;lymph nodes;Measures;Medical Research;Mission;Modality;Modeling;Molecular;Morbidity - disease rate;mortality;mortality risk;Mycobacterium tuberculosis;National Institute of Allergy and Infectious Disease;Nature;new technology;nonhuman primate;pathogen;Pathogenesis;Pathology;Patients;Persons;PET/CT scan;Pharmaceutical Preparations;Pharmacotherapy;Plasma;Prednisone;prevent;Prevention;Prevention strategy;Process;programs;pulmonary granuloma;radiological imaging;Recurrence;Research Infrastructure;Research Personnel;Resources;response;Risk;Signs and Symptoms;Site;SIV;Symptoms;Syndrome;synergism;Technology;Therapeutic;Time;time interval;Tissues;tool;Tuberculosis;tuberculosis drugs;tuberculosis treatment;United States National Institutes of Health;Vaccines;virtual;Virus

PROJECT_TITLE: Dissecting the pathogenesis of HIV-TB Immune reconstitution inflammatory syndrome


ORG_CITY: LA JOLLA

ORG_NAME: SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE

PHR: Project Narrative We are studying how macromolecules such as proteins and nucleic acids carry out their biological functions. A better understanding of the molecular mechanisms of how biological macromolecules work will help us to develop new drugs to fight diseases including immunodeficiencies, cancer, and neurodegeneration.

PI_NAMEs: ZHAO, JIANHUA  (contact)

PROGRAM_OFFICER_NAME: TAYLOR, VERONICA

PROJECT_TERMS: Area;Biochemical;Biological;Biological Models;Biological Process;biological systems;cell growth;Cell Line;Cell Proliferation;cell type;Cells;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;Cryoelectron Microscopy;detection of nutrient;Disease;Eligibility Determination;Environment;Epithelial Cells;fighting;FRAP1 gene;Genes;Goals;Health;Hematopoietic;Human;immunodeficiency;In Vitro;Insecta;insight;interest;Lysosomes;macromolecular assembly;Macromolecular Complexes;macromolecule;Malignant Neoplasms;Mammalian Cell;Mass Spectrum Analysis;Membrane Proteins;Metabolic Pathway;Methodological Studies;Methodology;Methods;Molecular;Molecular Chaperones;Molecular Machines;multicatalytic endopeptidase complex;Nerve Degeneration;novel therapeutics;Nucleic Acids;overexpression;particle;Pathway interactions;Preparation;Production;protein complex;protein degradation;protein function;protein purification;Proteins;Ribonucleoproteins;Sampling;Signal Transduction;structural biology;System;Techniques;Work

PROJECT_TITLE: Molecular mechanisms underlying the assembly of the human proteasome and endogenous protein complexes

STUDY_SECTION: MRAB

STUDY_SECTION_NAME: Maximizing Investigators’ Research Award B Study Section[MRAB]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Asthma;Biomedical Imaging;Biotechnology;Clinical Research;Lung;Precision Medicine;Prevention

ORG_CITY: COLUMBIA

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF MISSOURI-COLUMBIA

PHR: Project Narrative Biologic treatments of asthma are revolutionary, albeit expensive, new methods of severe asthma management; however, the current standard of care assesses individual patient response to treatment at 12 weeks following treatment initiation based on exacerbation count and patient responses to asthma questionnaires. Only an estimated 60-80% of patients treated with biologics demonstrate response. Patient- specific biomarkers of lung function which may predict response are an unmet clinical need in this patient cohort, and early detection of response to treatment could improve patient outcomes and reduce costs. In this proposal we will employ one of the most sensitive methods of assessing lung function – hyperpolarized 129Xe MRI (HPG) – to address our hypothesis that early responders to biologic treatment of severe asthma (mepolizumab in particular) can be detected by HPG.

PI_NAMEs: THOMEN, ROBERT PAUL (contact)

PROGRAM_OFFICER_NAME: HU, TOM CHIH-CHUANG

PROJECT_TERMS: Address;Affect;airway hyperresponsiveness;airway inflammation;Asthma;asthmatic;asthmatic patient;Biological;Biological Markers;Biological Products;Biological Response Modifier Therapy;Bolus Infusion;Bronchodilation;Bronchodilator Agents;Categories;Chronic Obstructive Pulmonary Disease;Clinical;Clinical assessments;Clinical Management;Clinical Trials;cohort;conventional therapy;cost;cost outcomes;Cystic Fibrosis;Data;Defect;Developed Countries;Development;Disease;Dose;Drug Targeting;Early Diagnosis;efficacy evaluation;eosinophil;eosinophilic asthma;Etiology;Evaluation;Exhibits;Extrinsic asthma;Gases;Health Care Costs;healthcare burden;Image;Imaging Techniques;Impairment;improved;improved outcome;individual patient;individual response;individualized medicine;ineffective therapies;Inhalation;inhibitor;Interleukin-5;Leukotrienes;Lung;Magnetic Resonance Imaging;Magnetism;Maps;Marketing;Measurement;Measures;mepolizumab;Methods;Molecular;new therapeutic target;Noble Gases;Nuclear;Pathway interactions;patient response;patient responsibilities;Patient-Focused Outcomes;Patients;Pharmaceutical Preparations;Physiological;Placebo Effect;Population;predicting response;primary endpoint;Process;pulmonary function;Pulmonary Function Test/Forced Expiratory Volume 1;Pulmonary function tests;Questionnaires;Refractory;Relaxation;research clinical testing;Resolution;respiratory;respiratory smooth muscle;responders and non-responders;response;Savings;Severity of illness;Signal Transduction;specific biomarkers;Sputum;standard of care;Steroids;Stimulus;Symptoms;Techniques;Time;treatment response;ventilation;Work;Xenon

PROJECT_TITLE: Hyperpolarized xenon MRI in treatment of severe asthma by mepolizumab: toward earlier detection of individual patient responses

STUDY_SECTION: CTIS

STUDY_SECTION_NAME: Clinical Translational Imaging Science Study Section[CTIS]


NIH_SPENDING_CATS: Cancer;Immunotherapy

PHR: PROJECT NARRATIVE Immune cells infiltrating cancers and chronically infected tissues acquire dysfunctional characteristics that prevent their effective reinvigoration with immunotherapy. Our lab and others have described a role for altered cellular metabolism in defining whether these immune cells become dysfunctional and short-lived or acquire long-lived characteristics associated with healthy immunity. In this proposal, we will identify precisely how the products of the mitochondria alter the course of immune differentiation to promote anti-cancer immunity, and develop strategies to metabolically manipulate this altered differentiation to improve immunotherapy.

PI_NAMEs: DELGOFFE, GREG M. (contact)

PROGRAM_OFFICER_NAME: MALLIA, CONRAD M

PROJECT_TERMS: Acetyl Coenzyme A;Acetylcysteine;Aconitate Hydratase;anti-cancer;anti-tumor immune response;Antigens;Antioxidants;Atrophic;biological adaptation to stress;Biology;Blocking Antibodies;Cell Physiology;Cells;Cellular biology;Characteristics;Chronic;Citrates;Citric Acid Cycle;conditional knockout;cytokine;Cytosol;cytotoxic;cytotoxicity;Data;design;Environment;exhaust;exhaustion;Exposure to;fatty acid oxidation;Fatty Acids;Functional disorder;Genes;Genetic;Genetic Transcription;Glucose;glucose uptake;Hypoxia;Immune;immune cell infiltrate;Immunity;Immunosuppression;Immunotherapy;improved;In Vitro;in vivo;inhibitor;Knockout Mice;lipid biosynthesis;Lipids;Lipolysis;Malignant Neoplasms;Mediating;member;Metabolic;Metabolic stress;Metabolism;Mitochondria;mitochondrial dysfunction;Modality;Modeling;Monoclonal Antibodies;neoplastic cell;novel;novel therapeutics;Nutrient;nutrient deprivation;Obesity;overexpression;Oxidative Stress;Oxygen;Pathway interactions;patient subsets;Patients;PD-1 blockade;Peroxides;pharmacologic;Phenotype;Phosphoric Monoester Hydrolases;Phosphorylation;Phosphotyrosine;Play;Predisposition;prevent;Production;progenitor;programmed cell death protein 1;programs;Protein Tyrosine Phosphatase;Proteome;Proteomics;Reactive Oxygen Species;Regulatory T-Lymphocyte;Reporting;Repression;response;Role;self-renewal;Signal Transduction;Source;Stress;success;T cell differentiation;T-Lymphocyte;Technology;Tissues;transcriptomics;tumor eradication;tumor growth;Tumor Immunity;Up-Regulation;uptake;Weight

PROJECT_TITLE: Uncovering the metabolic underpinnings of T cell exhaustion

STUDY_SECTION: CMIA

STUDY_SECTION_NAME: Cellular and Molecular Immunology - A Study Section[CMIA]


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Bioengineering

ORG_CITY: Newark

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF DELAWARE

ORG_STATE: DE

PHR: Project Narrative Tendon overuse initiates mechanical damage that leads to chronic tendinosis (degeneration) and tendinopathy (clinical presentation with pain), which are common and notoriously difficult to treat. This study will determine the mechanisms responsible for the multiscale damage in overuse tendinosis and establish these in the context of key hallmarks of human tendinosis using a preclinical in vivo model. Quantifying multiscale damage and cellular mechanisms by which loading leads to tendinosis is critical for designing and evaluating interventions to prevent and treat tendinopathy.

PI_NAMEs: ELLIOTT, DAWN M (contact)

PROGRAM_OFFICER_NAME: PINTUCCI, GIUSEPPE

PROJECT_TERMS: Ablation;achilles tendon;Actins;Acute;Animal Model;Architecture;Area;Automobile Driving;Cell Communication;Cell Density;Cell Shape;Cells;Chronic;Clinical;Clinical Research;Collagen;Collagen Fiber;Collagen Type III;Cytoskeleton;Data;depolymerization;design;Disease;Exhibits;F-Actin;Fiber;fiber cell;Foundations;Goals;Human;Image;in vivo;in vivo Model;Intervention;Knowledge;Measures;mechanical load;mechanical properties;mechanical signal;Mechanics;mechanotransduction;Modeling;Modulus;Molecular;molecular scale;Multiscale Mechanics;nanoscale;Natural regeneration;novel;Outcome;Pain;Phenotype;Physiological Processes;Physiology;polymerization;Polymers;Positioning Attribute;pre-clinical;prevent;Production;Proteins;Proteoglycan;Rattus;Rehabilitation therapy;response;Role;Signal Transduction;Slide;Study models;Tendinopathy;Tendon structure;Testing;therapy design;Time;Tissues;transmission process;Tropomyosin

PROJECT_TITLE: Multiscale tendon damage and aberrant cellular responses in an in vivo model of tendinosis

STUDY_SECTION: SBSR

STUDY_SECTION_NAME: Skeletal Biology Structure and Regeneration Study Section[SBSR]


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

ORG_CITY: Charlestown

ORG_NAME: MGH INSTITUTE OF HEALTH PROFESSIONS

ORG_STATE: MA

PHR: PROJECT NARRATIVE There is significant uncertainty in the clinical diagnosis of Alzheimer’s Disease (AD) as compared to the neuropathological-based diagnosis. The proposed research aims to identify the effect of aging and APOE genotype on speech motor control and examine the diagnostic potential of cognitively-demanding speech measures to detect early signs of dementia when early intervention and treatment against AD could be most effective. We will examine the diagnostic efficacy of speech acoustic and kinematic indices in a longitudinal paradigm by identifying whether measures of speech motor control at baseline predicts cognitive change over time and further validate this association against neuroimaging testing.

PI_NAMEs: ESHGHI, MARZIYE  (contact)

PROGRAM_OFFICER_NAME: RIVERA-RENTAS, ALBERTO L

PROJECT_TERMS: 3-Dimensional;Acoustics;Adult;Affect;Age;age effect;age related changes;age related decline;Age-associated memory impairment;Aging;Alleles;Alzheimer's Disease;Alzheimer's disease diagnosis;Alzheimer's disease pathology;Alzheimer's disease risk;Alzheimer’s disease biomarker;Amyotrophic Lateral Sclerosis;Anatomy;Apolipoprotein E;base;Biological Markers;blood oxygen level dependent;Brain;Brain region;brain tissue;Clinical;Clinical assessments;clinical diagnosis;Clinical Trials;Cognition;Cognitive;cognitive ability;cognitive change;cognitive control;cognitive function;cognitive load;cognitive process;cognitive skill;cohort;Cohort Studies;Complex;cost effective;cost efficient;Data;Dementia;Detection;detector;Diagnosis;Diagnostic;diagnostic strategy;disease prognosis;early detection biomarkers;Early Diagnosis;Early identification;Early Intervention;Early treatment;Education;Elderly;Electromagnetics;Evaluation;Frequencies;Functional disorder;functional MRI scan;Future;Genes;Genetic Predisposition to Disease;Genotype;Goals;Healthcare Industry;Human;imaging biomarker;Impaired cognition;improved;indexing;innovation;insight;Intervention;kinematics;Learning;Liquid substance;Magnetic Resonance Imaging;Measurable;Measurement;Measures;mechanical properties;Mediating;Mentored Patient-Oriented Research Career Development Award;mild cognitive impairment;Motor;motor behavior;motor control;Movement;neural correlate;Neurobehavioral Manifestations;neurobiological mechanism;Neurodegenerative Disorders;neuroimaging;neuropathology;Neuropsychological Tests;Neuropsychology;normal aging;older adult;Onset of illness;Patients;Performance;physical property;pre-clinical;Primary Progressive Aphasia;Process;Production;Research;research clinical testing;Rest;Risk;Sampling;Sensory;sex;Signal Transduction;Speech;Speech Acoustics;Structure;Techniques;Technology;Testing;Time;Trail Making Test;training opportunity;Treatment Efficacy;treatment planning;Uncertainty

PROJECT_TITLE: Early Biomarkers of Alzheimer's Disease: Using Speech Markers to Detect Mild Cognitive Impairment


PHR: Project Narrative The ability of lymphocytes (an immune cell type) to migrate, interact with other cells, and correctly localize within the body is essential to establish effective immune responses to pathogens or cancer, and plays a role in autoimmunity. We will determine if the Formin family of proteins of the lymphocyte cytoskeleton regulates how lymphocytes enter and move within tissues. This work has the potential to provide insight into novel ways to therapeutically modulate lymphocyte migration, such as in autoimmune settings and inflammatory diseases.

PI_NAMEs: JACOBELLI, JORDAN  (contact)

PROGRAM_OFFICER_NAME: JOFFE, AARON MICHAEL

PROJECT_TERMS: 3-Dimensional;Actins;Adhesions;Adhesives;Adopted;Autoimmune;Autoimmunity;Back;Biological Models;biophysical properties;Blood Vessels;cancer cell;Cell Communication;cell motility;Cell Nucleus;cell type;Cells;Characteristics;chemokine;Collagen;Complement;Complex;constriction;Cues;Cytoskeletal Proteins;Cytoskeleton;Data;Disease;Embryonic Development;Endothelial Cells;Endothelium;Environment;Environmental Risk Factor;Extracellular Matrix;Extravasation;Face;Family;FMNL1 gene;Generations;Genetic;Goals;Homologous Gene;Imaging Techniques;Immune;immune function;Immune response;Immune system;immune system function;In Vitro;in vivo;Inflammatory;insight;interstitial;Knowledge;knowledge integration;Ligands;Location;lymph nodes;Lymphocyte;Malignant Neoplasms;mechanical force;Mediating;Membrane;Methods;Microtubules;migration;Modeling;Motility;Mutation;Neoplasm Metastasis;Nonmuscle Myosin Type IIA;novel;pathogen;Pathologic;Physiological;Physiological Processes;Protein Family;Proteins;Regulation;Role;Shapes;T-Lymphocyte;Testing;Therapeutic;three-dimensional modeling;Tissues;Traction Force Microscopy;trafficking;two photon microscopy;Vascular Endothelium;Work;wound healing

PROJECT_TITLE: Mechanisms of regulation of lymphocyte migration by actin cytoskeletal effectors

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CB-H(80)S]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: BERKELEY

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: Project Narrative Clathrin-mediated endocytosis is responsible for uptake of molecules from the plasma membrane and surrounding environment, and therefore is crucial for determining how a cell will interact with its surroundings. Actin assembly near the plasma membrane generates forces that are harnessed for a variety of cellular processes including clathrin- mediated endocytosis. Mechanistic understanding of clathrin-mediated endocytosis and actin assembly are crucial to understanding normal cell physiology and a variety of pathological conditions.

PI_NAMEs: DRUBIN, DAVID G (contact)

PROGRAM_OFFICER_NAME: STOKES, KALYNDA K

PROJECT_TERMS: Actins;Address;Adhesions;Affect;Biochemical;Biochemical Reaction;Cell Line;Cell membrane;cell motility;Cell Physiology;Cell Polarity;cell type;Cells;Chimeric Proteins;Clathrin;Complement;COVID-19;Cytoskeletal Proteins;Cytoskeleton;Development Polarity;empowerment;Endocytosis;Environment;Event;Evolution;Excision;fluorescence imaging;Generations;genome editing;Human;human stem cells;human tissue;Label;Learning;Lipids;Mammals;Measures;Mediating;Membrane;Membrane Proteins;Normal Cell;Organelles;pandemic disease;Pathologic;Pathway interactions;Permeability;Play;Process;Production;Proteins;reaction rate;recruit;Regulation;Role;Route;Saccharomycetales;Site;stem cells;Structure;tissue/cell culture;uptake;Vesicle;Yeasts

PROJECT_TITLE: Actin assembly and clathrin-mediated endocytosis in yeast and mammals

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


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

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

PHR: Project Narrative/Relevance The Dot/Icm type IV secretion system is a versatile virulence nanomachine that has the amazing capacity to translocate into host cells a repertoire of over 300 different bacterial proteins during infection. The proposed work promises to provide mechanistic insights into structure and function of this fascinating nanomachine in intracellular bacterial pathogens: Legionella pneumophila and Coxiella burnetii.

PI_NAMEs: LIU, JUN  (contact);ROY, CRAIG R.

PROGRAM_OFFICER_NAME: ERNST, NANCY L

PROJECT_TERMS: Amaze;ATP Hydrolysis;ATP phosphohydrolase;Bacteria;Bacterial Proteins;Biochemical;Cell membrane;Cells;Classification;Complex;Coupling;Coxiella burnetii;Cryo-electron tomography;Cytoplasm;Cytosol;Data;Development;Electron Microscopy;fascinate;Genetic;Goals;human disease;Imaging technology;improved;In Situ;Individual;Infection;insight;Ion Channel;Ions;Legionella pneumophila;light microscopy;Location;Mediating;Membrane;Molecular;Molecular Conformation;Multiprotein Complexes;mutant;nanomachine;novel;pathogen;pathogenic bacteria;Pathway interactions;Property;protein protein interaction;Proteins;recruit;Resolution;Site;Structure;System;three dimensional structure;Time;Travel;Type IV Secretion System Pathway;Vacuole;Virulence;Visualization;Work

PROJECT_TITLE: Functional and Structural Analysis of the Dot/Icm Type IVB Secretion Machine

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


ORG_CITY: CLEVELAND

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

ORG_STATE: OH

PHR: Colorectal cancer is the second most common cause of cancer deaths in the United States, with 133,000 new cases and 50,000 deaths per year. Thus, novel therapies are urgently needed to treat this deadly disease. The goal of this project is to develop a new personalized approach to treat colorectal cancers that have specific oncogenic mutations in a gene called PIK3CA.

PI_NAMEs: WANG, ZHENGHE  (contact)

PROGRAM_OFFICER_NAME: XU, WANPING

PROJECT_TERMS: alpelisib;ATAC-seq;Automobile Driving;Breast Cancer Patient;cancer cell;Cancer Etiology;Catalytic Domain;Cell Line;Cell Nucleus;Cells;Cessation of life;Clinical Trials;colon cancer patients;colon tumorigenesis;Colonic Neoplasms;Colorectal;Colorectal Cancer;colorectal cancer treatment;Disease;Drug Combinations;effective therapy;efficacy evaluation;Enzymes;EZH2 gene;FDA approved;Foundations;Fulvestrant;Future;Genes;Genetically Engineered Mouse;Goals;Growth;Histones;Hot Spot;Human;Immunocompetent;inhibitor;innovation;IRS1 gene;knock-down;Knock-in;Malignant Neoplasms;Methylation;Modeling;mutant;Mutate;Mutation;novel;novel strategies;novel therapeutics;Nuclear;Nuclear Translocation;Oncogenes;Oncogenic;overexpression;Pathway interactions;patient derived xenograft model;Patients;personalized approach;Phosphotransferases;PIK3CA gene;PIK3CG gene;Pre-Clinical Model;Precision therapeutics;protein complex;Protein translocation;Proteins;Proto-Oncogene Proteins c-akt;Recurrence;Repression;Role;Science;Signal Transduction;single cell ATAC-seq;single-cell RNA sequencing;Solid;Specimen;Testing;tumor;tumor growth;tumor heterogeneity;tumor xenograft;tumor-immune system interactions;Tumor-infiltrating immune cells;United States

PROJECT_TITLE: Mechanisms of PIK3CA helical domain mutations driving colorectal tumorigenesis

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics - 1 Study Section[MCT1]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

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

ORG_DEPT: PSYCHIATRY

PHR: PROJECT NARRATIVE The RAW Brain - the effect of rumination, anxiety and worry on aging and dementia risk. This study will identify the pathways through which the anxiety phenotypes contribute to accelerated aging and increased dementia risk. We will follow the participants for two years and will use repeated measures of brain aging as well as measures of peripheral aging and chronic stress. The overall goal of the study is to identify neural and biological pathways leading from rumination, anxiety and worry to brain and body aging.

PI_NAMEs: ANDREESCU, CARMEN  (contact)

PROGRAM_OFFICER_NAME: LYONS, ELIZABETH ANNE

PROJECT_TERMS: Acceleration;Age;age acceleration;Aging;aging brain;aging related disease;Alzheimer's disease related dementia;Alzheimer's disease risk;Amygdaloid structure;Amyloid;Anxiety;Anxiety Disorders;anxious;arterial tortuosity;Autoimmune Diseases;Biological;Blood Vessels;Brain;Cardiovascular Diseases;carotid intima-media thickness;Cells;cerebrovascular;Chronic stress;Clinical;Cognitive;cohort;Computing Methodologies;cytokine;Data;dementia risk;Dimensions;Disease;effective intervention;excitotoxicity;follow-up;Glutamates;Goals;hippocampal atrophy;Hydrocortisone;Image;Individual;Inflammatory;inflammatory marker;late life;Length;Link;Machine Learning;Magnetic Resonance Spectroscopy;Measures;Mediating;Mental disorders;Mitochondrial DNA;Modeling;modifiable risk;Monitor;Multimodal Imaging;neural;Neuroanatomy;Neurobiology;neuromechanism;Neuropsychology;novel strategies;older adult;Participant;Pathway interactions;Peripheral;Phenotype;Plasma;Prevalence;prevent;Prevention;Proteomics;recruit;Reporting;response;Rest;Risk;Risk Factors;rumination;senescence associated secretory phenotype;Serum;Severities;Stress;symptom cluster;Symptoms;telomere;Testing;therapy design;Time;white matter

PROJECT_TITLE: The RAW Brain - The Effect of Rumination, Anxiety and Worry on Aging and Dementia Risk

STUDY_SECTION: APDA

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


NIH_SPENDING_CATS: Autoimmune Disease;Brain Disorders;Immunotherapy;Multiple Sclerosis;Neurodegenerative;Neurosciences

ORG_CITY: SALT LAKE CITY

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: NARRATIVE Suppression of the immune response would provide a potent therapy for autoimmune disease. How suppressive T cells (regulatory T cells) can optimally impact autoimmune disease is currently unknown. Our work will address this unmet need by determining at the molecular level what triggers of antigen recognition control the suppressive phenotype of regulatory T cells.

PI_NAMEs: EVAVOLD, BRIAN D (contact)

PROJECT_TERMS: Affinity;Amino Acids;Animal Model;Antigens;Autoantigens;Autoimmune Diseases;Autoimmune Responses;Binding;Biological Markers;biophysical properties;Cell Physiology;Cells;Central Nervous System;Clinical Trials;complementarity-determining region 3;Data;Demyelinating Diseases;Demyelinations;design;Diagnosis;Disease;disease model;Disease Progression;DNA;effector T cell;engineered T cells;Excision;Experimental Autoimmune Encephalomyelitis;FOXP3 gene;Functional disorder;Goals;Health;Histocompatibility Antigens Class II;HLA-DR4 Antigen;humanized mouse;Immune response;Immunosuppression;in vivo;insight;Insulin-Dependent Diabetes Mellitus;Intervention;Left;Measures;MHC antigen;MHC Class II Genes;Molecular;Multiple Sclerosis;Mutation;Myelin;novel;oligodendrocyte-myelin glycoprotein;Outcome;Peptide/MHC Complex;Peptides;Persons;Phenotype;Play;Pre-Clinical Model;Proteins;Publications;receptor binding;Regulatory T-Lymphocyte;Research Personnel;response;Rheumatoid Arthritis;Risk Factors;Role;sensor;Signal Transduction;Surrogate Markers;T cell therapy;T-Cell Activation;T-Cell Receptor;T-Lymphocyte;TCR Activation;Technology;Testing;Therapeutic;transcriptome;Transgenic Organisms;Translating;Variant;Work

PROJECT_TITLE: Defining how TCR strength of signal modulates Treg function

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IDIB-D(02)]


NIH_SPENDING_CATS: Biotechnology;Cancer;Childhood Leukemia;Clinical Research;Genetics;Hematology;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: NEW YORK

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: NARRATIVE Acute myeloid leukemia (AML) has historically been treated with chemotherapy, but patients who do not respond to treatment face a dismal prognosis. The proposed research uses genetic technologies to better understand the metabolism of leukemia cells and advance desperately needed new approaches to leukemia therapy.

PI_NAMEs: MILLMAN, SCOTT EVAN (contact)

PROGRAM_OFFICER_NAME: BIAN, YANSONG

PROJECT_TERMS: Acute Myelocytic Leukemia;acute myeloid leukemia cell;adverse outcome;alpha ketoglutarate;Biochemistry;Biological;Bone Marrow;cancer genetics;career;career development;Cell Line;Cells;Characteristics;chemotherapy;Chromatin;Chromosome abnormality;Citric Acid Cycle;Clinical;clinical practice;clinical training;Complex;CRISPR/Cas technology;cytotoxicity;Data;Development Plans;Dioxygenases;Disease;DNA Methylation;drug discovery;Drug Targeting;effective therapy;Environment;Enzyme Inhibition;Enzymes;Epigenetic Process;Face;Family;functional genomics;Funding;Gene Expression;Genetic;genetic approach;Genetic Models;genetic technology;Genetic Transcription;Genotype;Goals;Hematologic Neoplasms;histone methylation;Human;human disease;improved outcome;In Vitro;in vivo;inhibitor;instructor;International;Investigation;Isocitrate Dehydrogenase;Karyotype;Ketoglutarate Dehydrogenase Complex;leukemia;leukemia treatment;Leukemic Cell;Maintenance;Malignant Neoplasms;Mediating;Medical Oncology;Memorial Sloan-Kettering Cancer Center;Mentors;Mentorship;Metabolic;Metabolism;mimicry;Modeling;Molecular;Molecular Biology;mouse model;Mus;mutant;Mutation;Myelogenous;new therapeutic target;novel strategies;novel therapeutic intervention;Oncogenes;Oncogenic;patient derived xenograft model;Patients;Phenotype;Physicians;Positioning Attribute;Pre-Clinical Model;precursor cell;Prognosis;programs;Proliferating;Reagent;Refractory;Research;Research Personnel;Resources;Role;Sampling;Scientist;Services;skills;Solid Neoplasm;Specificity;succinyl-coenzyme A;System;Testing;Therapeutic;tool;TP53 gene;TP53-mutant acute myeloid leukemia;Training;Treatment Failure;tumor;Tumor Suppression;Tumor Suppressor Proteins;Up-Regulation;Work

PROJECT_TITLE: Exploiting alpha-ketoglutarate-dependent metabolism for therapeutic benefit in acute myeloid leukemia

STUDY_SECTION: NCI

STUDY_SECTION_NAME: Career Development Study Section (J)[NCI-J]


ORG_CITY: BOSTON

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: Project Narrative Asthmatic bronchospasm compresses the airway epithelium which, in turn, triggers aberrant airway remodeling—a cardinal feature of asthma. Here we use genomic profiling together with modern systems biology to elucidate the molecular mechanisms that underlie this pivotal mechanotransduction event.

PI_NAMEs: DE MARZIO, MARGHERITA  (contact)

PROGRAM_OFFICER_NAME: SHENOY, SIDDHARTH KAUP

PROJECT_TERMS: Affect;airway epithelium;airway goblet cell hyperplasia;airway inflammation;airway remodeling;Asthma;asthmatic;asthmatic airway;Award;Basal Cell;Binding;Biological;Biomechanics;Biometry;Biophysics;bronchial epithelium;Bronchial Spasm;Bronchoconstriction;candidate identification;career;Cell Communication;cell type;Cells;Chronic;Clinical;Clinical Data;Coagulation Process;Collagen;Complex;Computational Biology;Confusion;Data;Deposition;Development;Disease;Environment;Epithelial Cells;epithelial to mesenchymal transition;Epithelium;Event;experience;experimental study;Extracellular Matrix;Future;Genetic;Genetic Transcription;genome-wide;genomic profiling;Genomics;Goals;Goblet Cells;Grant;Heterogeneity;Human;Immune response;In Vitro;in vivo;Inflammation;Inflammatory;innovation;Link;mechanical force;Mechanical Stress;Mechanics;mechanotransduction;Mediating;Medicine;Mentors;migration;Modeling;Modernization;Molecular;molecular targeted therapies;Morphology;Muscle Contraction;Nature;network models;novel;Pathogenesis;Pathogenicity;Pathologic;Pathologic Processes;Pathway interactions;Patients;Pattern;Phenotype;Physics;Population Study;Positioning Attribute;pressure;prevent;Process;programs;Proliferating;Proteins;Pulmonology;Qualifying;repaired;Research;Research Personnel;Resources;respiratory smooth muscle;response;Role;Route;Science;Scientist;Signal Pathway;single-cell RNA sequencing;skills;Stimulus;Systems Biology;targeted treatment;Testing;Therapeutic;therapeutic biomarker;therapeutic candidate;therapeutic target;Tissues;Training;trait;transcriptome sequencing;translational impact;volunteer;wound healing

PROJECT_TITLE: Mechanogenomics of the asthmatic airway epithelium

STUDY_SECTION: MTI

STUDY_SECTION_NAME: NHLBI Mentored Transition to Independence Study Section[MTI(JA)]


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Contraception/Reproduction;Maternal Health;Maternal Morbidity and Mortality;Pregnancy;Prevention;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Urologic Diseases;Women's Health Research

ORG_DEPT: OBSTETRICS & GYNECOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

ORG_STATE: CA

PHR: PROJECT NARRATIVE Mechanical birth injury to maternal pelvic soft tissues, including pelvic skeletal muscles, is the strongest potentially preventable risk factor for long-term pelvic floor dysfunction. This project, conducted in a preclinical model validated for the studies of human pelvic muscles, will have an impact on public health by delineating the adaptive and repair mechanisms of the female pelvic muscles, with specific focus on the biological processes that regulate the functional state of endogenous muscle stem cells during pregnancy - one of the most transformative non-pathological periods along the lifespan of many women. The knowledge gained from this proposal will lead to potential new preventative strategies and therapies for enhancing pelvic skeletal muscle plasticity and improving muscle recovery following mechanical injury.

PI_NAMEs: ALPERIN, MARIANNA  (contact)

PROGRAM_OFFICER_NAME: DEYAMPERT, TARA LYNN

PROJECT_TERMS: Acute;Adult;Anatomy;Animal Model;Animals;antenatal;Architecture;Area;Biological Assay;Biological Process;Birth;Birth trauma;candidate identification;Cell Transplantation;Cells;Cesarean section;Childbirth;clinical care;Clinical Research;Cues;Data;Development;Disparity;Economic Burden;Endocrine;Environment;epigenomics;Estrogens;Exhibits;Experimental Models;experimental study;Exposure to;Female;Functional disorder;Future;Genetic Transcription;Growth;High Prevalence;Hormonal;Human;improved;In Situ;In Vitro;in vivo;Inbreeding;Injury;injury recovery;innovation;insight;interdisciplinary approach;intrapartum;Investigation;Knowledge;knowledge of results;life span;Limb structure;Link;male;Maps;Mechanics;minimally invasive;Modeling;modifiable risk;Modification;Molecular;Morbidity - disease rate;Morphology;multiple omics;Muscle;muscle progenitor cell;muscle regeneration;Muscle satellite cell;Natural regeneration;novel;novel strategies;Oxytocin;Partner in relationship;Pelvic Floor Disorders;Pelvic floor dysfunction;Pelvic Floor Muscle;Pelvic floor structure;Pelvis;Perinatal;Phenotype;Physiological;Population;postmitotic;Postpartum Period;pre-clinical;Pre-Clinical Model;Pregnancy;pregnant;Preparation;prevent;Prevention strategy;Preventive therapy;Process;Progesterone;Proliferating;Property;Protocols documentation;Public Health;Rattus;Recovery;regeneration potential;Regenerative capacity;Regulation;Relaxin;repaired;Research;response;Risk Factors;Role;Sarcomeres;Serum;Signal Pathway;Signal Transduction;Signaling Molecule;Skeletal Muscle;skeletal muscle growth;skeletal muscle plasticity;Skeletal Muscle Satellite Cells;soft tissue;Source;stem;Testing;Therapeutic;Time;Trauma;United States National Institutes of Health;Vagina;Vaginal delivery procedure;validation studies;Vision;Woman;Women's Health;women's treatment

PROJECT_TITLE: Mechanisms and Impact of Pregnancy-Induced Adaptations in Pelvic Floor Muscles

STUDY_SECTION: KUFD

STUDY_SECTION_NAME: Kidney and Urological Systems Function and Dysfunction Study Section[KUFD]


NIH_SPENDING_CATS: Infectious Diseases

ORG_NAME: CARNEGIE INSTITUTION OF WASHINGTON, D.C.

PHR: Project Narrative: The spatial organization of biological processes is fundamental to life, and lipid membranes are central to this activity. In this proposal we will examine the contributions of lipids known as hopanoids to the organization of the bacterial cell, and examine how subcellular organization is affected during bacterial infection of a eukaryotic host. This work will help determine fundamental principles of bacterial cell organization that likely can be applied to a variety of human pathogenic microbes.

PI_NAMEs: BELIN, BRITTANY JO (contact)

PROJECT_TERMS: Affect;Bacteria;Bacterial Infections;Biological Process;biophysical properties;Bradyrhizobium;Cell Cycle;Cell membrane;Cell Polarity;Cells;Cellular Membrane;Cholesterol;cholesterol analog;endosymbiont;Environment;Eukaryota;flotillin;Human;Life;Link;Lipids;Mediating;Membrane;Membrane Lipids;Membrane Microdomains;Microbe;pathogenic microbe;Regulation;Work

PROJECT_TITLE: Lipid functions in bacterial cell organization

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


ORG_CITY: SAN FRANCISCO

ORG_DEPT: UROLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE: Alterations in translation control is a “hallmark” of cancer. The PI has consistently made highly impactful contributions to our understanding of how oncogenic pathways highjack the cell’s translation apparatus to make their own tailored proteome to direct specific steps in cancer initiation and progression. The project described in this application will employ novel pharmacogenomics approaches to address major unanswered questions in the field of translation and cancer, providing the rationale and tools for a new paradigm to target human tumors.

PI_NAMEs: RUGGERO, DAVIDE  (contact)

PROGRAM_OFFICER_NAME: MAAS, STEFAN

PROJECT_TERMS: Address;Blood;cancer cell;cancer genome;cancer initiation;Cells;Development;Diet;Environment;gain of function;Gene Expression;Gene Expression Regulation;Genetic;genome-wide;Goals;Homeostasis;Human;in vivo;interest;Link;loss of function;Malignant Neoplasms;Measures;Messenger RNA;Metabolic;Methods;Mitochondria;Modernization;Molecular;mouse model;novel;novel therapeutics;Nutrient;Obesity;Oncogenes;Oncogenic;Pathway interactions;patient derived xenograft model;Pharmacogenomics;pharmacologic;Phase;Process;programs;Protein Biosynthesis;Proteome;proteostasis;Research;Ribosomes;RNA Cap-Binding Proteins;RNA Splicing;Series;Signal Transduction;Stream;synthetic lethal interaction;Therapeutic;tool;Translating;Translations;tumor;tumor progression;Tumor Suppressor Proteins;Xenograft procedure

PROJECT_TITLE: Mechanisms of regulated translation control in cancer and its therapeutic implications


NIH_SPENDING_CATS: Cystic Fibrosis;Infectious Diseases;Lung;Rare Diseases;Wound Healing and Care

ORG_CITY: PASADENA

ORG_NAME: CALIFORNIA INSTITUTE OF TECHNOLOGY

PHR: PROJECT NARRATIVE This proposal seeks to deepen our understanding of the mechanisms of efficient pyocyanin-mediated extracellular electron transfer (EET) in Pseudomonas aeruginosa biofilms and its consequences for antibiotic tolerance. We seek to test the hypothesis that modulation of EET efficiency can render biofilms more susceptible to commonly used clinical antibiotics. The work proposed here will inform the design of more effective treatment strategies for P. aeruginosa infections.

PI_NAMEs: NEWMAN, DIANNE K (contact)

PROJECT_TERMS: acute infection;Affect;Aminoglycosides;Animals;Antibiotic Therapy;antibiotic tolerance;Antibiotics;Bacteria;beta-Lactams;Bioenergetics;Biological;Burn injury;burn wound;cell type;Cells;Charge;chronic infection;Clinic;Clinical;clinically relevant;Colistin;Consumption;Cystic Fibrosis;Cystic Fibrosis sputum;Cytolysis;Defense Mechanisms;design;Development;diabetic ulcer;Diffusion;DNA;effective therapy;Electron Transport;Electrons;Equilibrium;Excision;experimental study;extracellular;Eye Infections;fitness;Fluoroquinolones;foot;Foundations;Homeostasis;improved;in vivo;Infection;insight;Knowledge;Lead;Link;Lung;Measures;Mediating;Metabolic;Methods;Microbial Biofilms;Modeling;Nutrient;opportunistic pathogen;Oxidants;Oxidation-Reduction;Oxygen;Patients;Pharmaceutical Preparations;Physiological;Pigments;Polymers;Predisposition;Property;Pseudomonas;Pseudomonas aeruginosa;Pseudomonas aeruginosa infection;Pseudomonas Infections;Pyocyanine;Reaction;response;Role;Signal Transduction;Signaling Molecule;skin wound;Specific qualifier value;System;Techniques;Technology;Testing;tool;treatment strategy;ventilator-associated pneumonia;Virulence Factors;Work;wound

PROJECT_TITLE: Biological mechanisms and consequences of efficient extracellular electron transfer in Pseudomonas aeruginosa

STUDY_SECTION: PCMB

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


NIH_SPENDING_CATS: Autoimmune Disease;Biotechnology;Clinical Research;Diabetes;Genetics;Human Genome;Immunotherapy;Pediatric

PHR: Project Narrative This genetic study focuses on type 1 diabetes mutations in the protein coding region of the human genome, which are potential biological targets for treatment. We are generating mice and human cell lines to understand how these mutations cause diabetes, as well as using these animals as preclinical models for evaluating possible precision therapies. The results from this study will enable better detection, prediction, and treatment for patients with type 1 diabetes, and may also benefit individuals with other autoimmune disorders.

PI_NAMEs: ANDERSON, MARK S (contact);GERMAN, MICHAEL S;LOWELL, CLIFFORD A

PROGRAM_OFFICER_NAME: MORRIS FEARS, MARGARET A

PROJECT_TERMS: Acceleration;Actins;Adaptor Signaling Protein;adhesion receptor;Adhesions;Adhesives;Adoptive Cell Transfers;Adoptive Transfer;Affect;Animal Model;Animals;Antigen Presentation;Antigens;Autoantibodies;Autoimmune;Autoimmune Diseases;Autoimmunity;autoreactive T cell;B-Lymphocytes;Biochemical;Biological;Breeding;Cell Adhesion;Cell Communication;Cell Line;Cell surface;Cells;Clone Cells;CRISPR/Cas technology;Critical Pathways;CTLA4 gene;Data;Defect;Dendritic Cells;Detection;Development;Diabetes Mellitus;diabetic;Disease;draining lymph node;early onset;engineered T cells;Engineering;Enrollment;Enzyme-Linked Immunosorbent Assay;Enzymes;Etiology;Event;exome sequencing;Experimental Models;experimental study;Family;Female;Frequencies;gain of function;gain of function mutation;Generations;Genes;Genetic;genetic linkage;Genetic Polymorphism;Genetic Risk;genetic risk factor;Genetic study;genome wide association study;Guanosine Triphosphate Phosphohydrolases;Histologic;Human Cell Line;Human Genome;Hyperactivity;Hyperglycemia;Image;Immune;immune activation;immune cell infiltrate;immune function;Immune Tolerance;Inbred BALB C Mice;Inbred NOD Mice;Incidence;Individual;Inflammation;Inherited;Insulin;insulin dependent diabetes mellitus onset;Insulin-Dependent Diabetes Mellitus;insulitis;Integrin Signaling Pathway;Integrins;islet;Islets of Langerhans;ITGB2 gene;Kinetics;Knock-in;Knock-in Mouse;knockin animal;leukocyte activation;Leukocytes;Life;Link;Lipid Binding;Macrophage;male;Mediating;Modeling;Mouse Cell Line;mouse model;Mouse Strains;Mus;Mutagenesis;mutant;Mutation;Myeloid Cells;neutrophil;Neutrophil Activation;Non obese;Open Reading Frames;Pathogenicity;Pathway interactions;Patients;Phenotype;Phosphatidylinositols;Phosphotransferases;Pre-Clinical Model;Precision therapeutics;prevent;Protein Region;Registries;Regulator Genes;Reporting;Risk Factors;RNA Sequence Analysis;Signal Transduction;Signaling Molecule;STAT3 gene;T-cell receptor repertoire;T-Lymphocyte;Testing;Therapeutic;Transgenic Mice;two photon microscopy;Variant

PROJECT_TITLE: Alterations of leukocyte integrin signaling leading to diabetes and autoimmunity

STUDY_SECTION: HAI

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


ED_INST_TYPE: OTHER SPECIALIZED SCHOOLS

ORG_CITY: CHAMPAIGN

ORG_DEPT: MISCELLANEOUS

ORG_NAME: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN

ORG_STATE: IL

PHR: PROJECT NARRATIVE Disorders of cell signaling cascades are known to cause developmental pathologies, inflammation, diabetes, and cancers, while the mechanisms of signaling in health and disease are not well understood. Transmembrane and juxtamembrane domains of the structurally diverse receptor tyrosine kinases are central to the signal passage into the cell and numerous point mutations of these domains are attributed to diseases, yet structures of their dimers are lacking. Our goals are to develop a versatile method that combines novel computational approaches with experimental data, and to capture long-overdue dynamic dimer structures of the wild type and the pathogenic mutated forms of representative receptor tyrosine kinase subfamilies, improving our understanding of the mechanisms of cell signaling in disease and leading to new treatments.

PI_NAMEs: POGORELOV, TARAS V. (contact)

PROGRAM_OFFICER_NAME: LEWIS, MECHELLE MAYLEBEN

PROJECT_TERMS: Binding;Biology;Cell membrane;Cell Signaling Process;Cells;Cellular Membrane;Characteristics;Chemicals;Clinical;Communities;Competence;Complex;Computer software;computer studies;Computing Methodologies;Crystallography;Cytoplasm;Data;Development;Diabetes Mellitus;dimer;Dimerization;Disease;empowerment;Entropy;Environment;experimental study;Extracellular Domain;Family;FGFR3 gene;Fluorescence Resonance Energy Transfer;Free Energy;Future;gain of function;Goals;Health;Human;Human Development;improved;Inflammation;insight;Integral Membrane Protein;Investigation;Label;Ligand Binding;Lipids;Liquid substance;Malignant Neoplasms;Measurement;Measures;Membrane;method development;Methodology;Methods;mimetics;Modeling;Molecular;Molecular Conformation;mutant;Mutate;Mutation;Nature;novel;open source;Pathogenicity;Pathology;Pathway interactions;Phosphotransferases;Play;Plug-in;Point Mutation;Positioning Attribute;prevent;Protein Family;Protocols documentation;receptor;Receptor Activation;Receptor Protein-Tyrosine Kinases;Research;Research Personnel;Resolution;response;restraint;Role;Signal Transduction;Signaling Protein;simulation;single molecule;solid state nuclear magnetic resonance;Structure;Techniques;therapy development;Time;Transmembrane Domain;transmission process;Tropomyosin;user-friendly;Validation;Vesicle;Visualization

PROJECT_TITLE: Capturing structure and dynamics of transmembrane signaling proteins

STUDY_SECTION: MSFD

STUDY_SECTION_NAME: Macromolecular Structure and Function D Study Section[MSFD]