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

ORG_CITY: WALTHAM

ORG_NAME: BRANDEIS UNIVERSITY

ORG_STATE: MA

PHR: Project Narrative The proposed research contributes to public health by investigating the ways in which culture impacts memory and brain activity. Cross-cultural comparisons are needed to have accurate understanding of how memory works and whether strategies are equally effective across groups. Understanding cultural differences in the use of memory strategies can inform the development of effective interventions to maintain memory function with aging and Alzheimer's disease, to improve cognition in diverse populations.

PI_NAMEs: DUARTE, AUDREY ;GUTCHESS, ANGELA  (contact)

PROGRAM_OFFICER_NAME: TREVINO, MELISSA

PROJECT_TERMS: Address;Affect;Aging;Alzheimer's Disease;Attention;behavior measurement;Brain;Brain Injuries;Chinese;Chinese American;Cities;Cognition;Cognitive;cognitive neuroscience;Cognitive Science;Collection;Cross-Cultural Comparison;demographics;Development;East Asian;effective intervention;Effectiveness;Electroencephalography;Emotional;Episodic memory;episodic memory impairment;ethnic minority population;Ethnic Origin;Event;Familiarity;Future;Generations;Goals;Heterogeneity;Hydrocortisone;implementation strategy;improved;Individual;Individual Differences;Intervention;Language;Latino;Learning;life span;Literature;Measures;Memory;Memory impairment;Mexican Americans;Nerve Degeneration;neural;neural correlate;normal aging;Not Hispanic or Latino;Outcome;Patient Self-Report;Performance;Persons;Population Heterogeneity;Positioning Attribute;Process;Public Health;Race;racial minority population;Research;response;Retrieval;Role;Sampling;Shapes;Societal Factors;Stress;study population;success;Testing;theories;Thinking;Update;Work

PROJECT_TITLE: How culture shapes memory strategies

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 BP-Y (02)]


ADMINISTERING_IC: NS

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Cancer Genomics;Genetics;Human Genome;Neurosciences;Orphan Drug;Rare Diseases

ORG_CITY: NEW HAVEN

ORG_COUNTRY: UNITED STATES

ORG_DEPT: NEUROSURGERY

ORG_FIPS: US

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Glioblastoma (GBM) is the most aggressive type of malignant primary brain tumor and accounts for the majority of deaths among brain tumor patients due to its highly invasive nature and lack of therapeutics that efficiently target invasion. This proposed study will use recently developed spatial single cell RNA-sequencing and spatial Assay for Transposase-Accessible Chromatin (ATAC)-sequencing on GBM tumor samples to provide a comprehensive understanding of the genetic and epigenetic regulators of driving GBM invasion, that will serve as novel targets to evaluate the potential of invasion-targeting therapy. Findings from this study will elucidate a comprehensive analysis of genetic and epigenetic regulators of GBM invasion, mechanistic insight through chromatin accessibility and interactions with the tumor microenvironment, and evaluate the therapeutic potential and mechanistic impact of invasion therapy which ultimately may inform future therapeutic modalities and improve clinical outcome for patients with glioblastoma.

PI_NAMEs: LONG, GRETCHEN IRELLA (contact)

PROGRAM_OFFICER_NAME: MATTHEWS, MARGUERITE

PROJECT_TERMS: Astrocytes;ATAC-seq;Automobile Driving;Biomedical Engineering;Blood Vessels;Brain Neoplasms;Candidate Disease Gene;candidate identification;Cell Communication;cell type;Cells;Central Nervous System Neoplasms;Cessation of life;Characteristics;Chromatin;Classification;Clinical;Collaborations;contrast enhanced;CRISPR/Cas technology;Crystallins;Data;Data Set;design;Diagnosis;differential expression;Epigenetic Process;epigenetic regulation;Excision;experimental study;Extracellular Matrix;Future;Genes;Genetic;genetic analysis;Genetic Materials;genome-wide;Glioblastoma;Glioma;Goals;histological specimens;Histology;Human;Implant;improved;In Vitro;in vivo;insight;Invaded;Investigation;knock-down;Knock-out;Knowledge;Macrophage;Malignant - descriptor;Microglia;migration;Modality;Molecular;Mus;nanoparticle;Nature;neoplastic cell;Neurons;Neurosurgeon;Normal Cell;novel;Operative Surgical Procedures;Organoids;Outcome;overexpression;overexpression analysis;Pathology;patient derived xenograft model;Patient-Focused Outcomes;Patients;Peripheral;Phenotype;Postoperative Period;Primary Brain Neoplasms;prognostic;Prognostic Marker;Recurrent tumor;Relapse;Research;Role;Sampling;single-cell RNA sequencing;Stains;Survival Rate;targeted treatment;Therapeutic;therapeutic candidate;therapeutic target;Time;transcriptomics;Transposase;Treatment Failure;tumor;tumor microenvironment

PROJECT_TITLE: Genetic and epigenetic mechanisms of glioblastoma invasion and their therapeutic implication

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F09B-Z (20)]


ADMINISTERING_IC: DC

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Neurosciences

ORG_CITY: BOSTON

ORG_DEPT: BIOLOGY

ORG_NAME: HARVARD MEDICAL SCHOOL

PHR: Project Narrative We will elucidate the most fundamental event in hearing: the conversion of a sound-induced mechanical stimulus into an electrical signal by the receptor cells of the inner ear. We will use a combination of biochemical, physiological and computational methods to understand how the mechanical stimulus is transferred from linking proteins, PCDH15 or LHFPL5, to an ion channel protein, TMC1, and to understand how the stimulus opens the ion channel in order to generate the electrical signal. This work will produce a fundamental understanding of one form of mechanosensation which can be applied to others such as touch, and will reveal mechanisms of pathophysiology caused by deafness-causing mutations.

PI_NAMEs: COREY, DAVID P (contact);SOTOMAYOR, MARCOS

PROGRAM_OFFICER_NAME: FREEMAN, NANCY

PROJECT_TERMS: Affinity;Auditory;Binding;Biochemical;Biochemistry;Cell Physiology;Cells;cellular transduction;Co-Immunoprecipitations;Complex;Computer software;Computing Methodologies;Cross-Linking Reagents;Cryoelectron Microscopy;Cysteine;Data;deafness;Electron Microscopy;Electrophysiology (science);Event;flexibility;Functional disorder;genetic deafness;Hair Cells;Hearing;Heavy Metals;In Vitro;insight;Interferometry;Ion Channel;Ion Channel Gating;Ion Channel Protein;Ions;Knowledge;Laboratories;Labyrinth;Link;link protein;Location;mechanical stimulus;mechanotransduction;Membrane;Methods;Modeling;Molecular;Molecular Conformation;molecular dynamics;Movement;Mutagenesis;mutant;Mutation;PCDH15 gene;Physiological;protein aminoacid sequence;Protein Biochemistry;protein structure prediction;Proteins;Reagent;Receptor Cell;Receptor Signaling;Signal Transduction;Site-Directed Mutagenesis;sound;Stimulus;Structural Models;Structure;Testing;Touch sensation;Transmembrane Domain;Work

PROJECT_TITLE: Molecular Mechanisms of Auditory Transduction

STUDY_SECTION: AUD

STUDY_SECTION_NAME: Auditory System Study Section[AUD]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Bioengineering;Biomedical Imaging;Clinical Research;Clinical Trials and Supportive Activities;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Nutrition;Obesity;Osteoporosis;Prevention

ORG_CITY: WINSTON-SALEM

ORG_DEPT: NEUROSCIENCES

ORG_NAME: WAKE FOREST UNIVERSITY HEALTH SCIENCES

ORG_STATE: NC

PHR: PROJECT NARRATIVE Despite the associated improvements in cardiometabolic and physiological health, intentional weight loss for obese older adults can exacerbate age-related declines in musculoskeletal health and increase fracture risk, leading many to consider alternative therapeutic approaches. This F31 Independent Predoctoral Fellowship Award will develop an automated computational pipeline to assess muscle health in older adults undergoing weight loss via caloric restriction and randomized to perform no additional lifestyle intervention, participate in supervised resistance training, or wear an incrementally-weighted vest. The results of this study will improve our understanding of muscle-bone interactions and elucidate the mechanism by which weight loss increases age- related declines, providing evidence to support and guide clinical therapeutics for weight loss that can preserve musculoskeletal health.

PI_NAMEs: LYNCH, DELANIE  (contact)

PROGRAM_OFFICER_NAME: TSAP, LEONID V

PROJECT_TERMS: Address;Adherence;Age;age related decline;age-related muscle loss;Aging;Algorithms;Area;Attenuated;automated image analysis;automated segmentation;Award;Beavers;Biomechanics;Biomedical Engineering;Biometry;Body fat;Body Weight decreased;bone;Bone Density;bone health;bone loss;bone mass;bone strength;Caloric Restriction;cardiometabolism;career;Clinical;clinical care;Clinical Management;Clinical Research;Clinical Trials;clinically relevant;collaborative environment;combat;comorbidity;computational pipelines;Consumption;convolutional neural network;cost;Data;data management;density;design;Development;Elements;Engineering;Epidemiology;Exercise;exercise training;experience;Fellowship;Fracture;fracture risk;Funding;Future;Goals;Guidelines;Health;Heterogeneity;Hip region structure;Image Analysis;image processing;imaging informatics;improved;independency;interdisciplinary collaboration;Intervention;intervention effect;Investigation;investigator training;lifestyle intervention;Machine Learning;Manuals;Measures;mechanical stimulus;Mechanical Stress;Mediating;Mentors;Mentorship;Modeling;Morphology;Muscle;muscle form;Muscular Atrophy;Musculoskeletal;Network-based;Obesity;obesity management;older adult;open source;Osteoporosis;Outcome;Parents;Participant;Patients;Physiological;Physiology;pre-doctoral;preservation;primary outcome;Principal Investigator;Process;Radiology Specialty;radiomics;Randomized;Research;Research Personnel;Research Project Grants;resistance exercise;Resources;response;Safety;sarcopenia;Scanning;Science;screening;skills;Structure;success;Techniques;Texture;Therapeutic;Thick;Thigh structure;Time;tool;Training;training data;Training Programs;Universities;uptake;Vertebral column;Visual;weight loss intervention;Work;X-Ray Computed Tomography

PROJECT_TITLE: INVESTigations of Muscle and Bone Health: Developing Automated Approaches for CT-Based Analyses

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F10B-C (20)]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Clinical Research;Genetics;Hematology;Human Genome;Immunotherapy;Orphan Drug;Prevention;Rare Diseases

ORG_CITY: NEW YORK

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

ORG_STATE: NY

PHR: Project Narrative Splicing factor gene mutations are prevalent in blood disorders and induce widespread, recurrent alternative splicing events. We propose a novel approach of targeting these mutations via antigen-based immunotherapies, based on the hypothesis that mis-spliced mRNAs give rise to meaningful tumor antigens. The proposed research will (1) contribute to the understanding of mis-spliced mRNAs as immunotherapeutic targets and (2) inspire T-cell receptor therapies for myelodysplastic syndromes and immunoprevention strategies for clonal hematopoiesis with spliceosomal mutations.

PI_NAMEs: KIM, WON JUN  (contact)

PROGRAM_OFFICER_NAME: PHILP, DEBORAH

PROJECT_TERMS: Acute Myelocytic Leukemia;adaptive immunity;Affinity;Alleles;Alternative Splicing;Animals;Antigens;Bar Codes;Binding;Biological Assay;Bone Marrow;candidate validation;Career Choice;CD8-Positive T-Lymphocytes;Cell Line;Cells;cellular transduction;clinical implementation;Clustered Regularly Interspaced Short Palindromic Repeats;Coculture Techniques;Data Set;Disease;DNA;Doctor of Philosophy;doctoral student;Dysmyelopoietic Syndromes;engineered T cells;Engineering;Engraftment;Ensure;erythroleukemic cell;Event;Exons;FDA approved;Future;Gene Expression Profile;Gene Mutation;Genes;Genomic approach;Genomics;Genotype;Goals;Hematological Disease;Hematopoiesis;high risk;HLA-A gene;HLA-A2 Antigen;Human;Immune;immunogenic;immunogenicity;Immunologic Surveillance;immunological intervention;Immunoprecipitation;Immunoprevention;Immunotherapeutic agent;Immunotherapy;improved;in silico;In Vitro;in vivo;Institution;Intravenous;Introns;Jurkat Cells;K-562;K562 Cells;Laboratories;Lead;loss of function mutation;Luciferases;Malignant Neoplasms;Mass Spectrum Analysis;Medicine;Mentors;Mentorship;Messenger RNA;MHC Class I Genes;Minor;Modality;multiple omics;Mus;mutant;Mutation;Myeloid Leukemia;novel;novel strategies;nuclear factors of activated T-cells;Oncogenic;overexpression;Pathogenesis;Patients;Peptides;peripheral blood;Peripheral Blood Mononuclear Cell;Pharmaceutical Preparations;polypeptide;predictive tools;Prevention strategy;programs;progression risk;Protein Isoforms;Proteins;Recurrence;Reporter;Research;Research Personnel;RNA Splicing;Sampling;Scientist;single-cell RNA sequencing;Solid;Somatic Mutation;Source;Specificity;Spliceosomes;SRSF2 gene;Stains;T cell receptor repertoire sequencing;T cell response;T-Cell Antigen Receptor Specificity;T-Cell Receptor;T-Cell Receptor Therapy;T-Lymphocyte;targeted treatment;Therapeutic;Tissues;Training;transcriptome sequencing;Translating;Transplantation;tumor;Tumor Antigens;Tumor Burden;vaccination strategy;Vaccines;Work

PROJECT_TITLE: Identifying mis-splicing-derived antigens in spliceosomal mutant myelodysplasia and targeting via T-cell receptor therapeutics

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F10C-D (20)]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

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

ORG_CITY: CHARLOTTESVILLE

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: PROJECT NARRATIVE Multiple sclerosis (MS) is driven by an autoimmune attack against myelin in the Central Nervous System, though the etiology of this disease remains unclear. Enteric Glial Cells (EGCs) are potential autoimmune targets in MS as they express several myelin proteins which are known targets in MS patients. In this proposal, I aim to characterize T cell responses targeting EGCs in an animal model of MS and investigate how depleting EGCs impacts disease severity, providing insights into how the Enteric Nervous System may be implicated in MS etiology and pathology.

PI_NAMEs: BROWN, RYAN  (contact)

PROGRAM_OFFICER_NAME: MOITRA, KAROBI

PROJECT_TERMS: Ablation;Adoptive Transfer;Animal Model;Antigen Presentation;Antigen-Presenting Cells;Antigens;Astrocytes;Autoimmune;autoimmune pathogenesis;Autoimmune Responses;Autoimmunity;autoreactive T cell;Biological Assay;Biological Models;Bone Marrow;brain cell;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Communication;cell type;Cells;Central Nervous System;Chronic;Coculture Techniques;Complex;Cues;cytokine;Data;Dendritic Cells;Diagnosis;Diphtheria Toxin;diphtheria toxin receptor;Disease;Disease remission;draining lymph node;Dyes;Enteral;Enteric Nervous System;Environment;enzyme linked immunospot assay;Etiology;Event;experience;Experimental Autoimmune Encephalomyelitis;experimental study;Flow Cytometry;Functional Gastrointestinal Disorders;gastrointestinal;gastrointestinal symptom;Gastrointestinal tract structure;Glial Fibrillary Acidic Protein;Goals;gut inflammation;Harvest;Hybrids;IL17 gene;Immune;Immune response;Immune system;Immune Targeting;Immunity;Immunize;Immunologic Receptors;inducible gene expression;Infiltration;Inflammation;Inflammatory;Inflammatory Bowel Diseases;insight;Intestines;Label;Link;Lymphoid Tissue;Mediating;Mesentery;Modeling;Monitor;mouse model;Multiple Sclerosis;multiple sclerosis patient;Mus;Myelin;Myelin Basic Proteins;Myelin Proteins;Nervous System Disorder;Neurodegenerative Disorders;Neuroglia;Neuroimmune;Neurons;new therapeutic target;Onset of illness;Pathology;Patients;Peptides;Peripheral;Peyer's Patches;Phase;Phenotype;Physiologic pulse;Play;Production;Proliferating;promoter;Proteins;Proteolipids;Regulation;Relapse;response;Risk;Role;Severities;Severity of illness;SJL/J Mouse;Spinal Cord;T cell response;T-Cell Activation;T-Lymphocyte;Tamoxifen;Testing;transcriptomics;Work

PROJECT_TITLE: Investigating a Role for Antigen Presentation by Enteric Glial Cells in Experimental Autoimmune Encephalomyelitis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F07B-G (20)]


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Genetics

ORG_DEPT: DERMATOLOGY

PHR: PROJECT NARRATIVE Comedones are an exceedingly common dermatologic problem across the lifespan. Rare comedonal diseases such as nevus comedonicus and common comedonal diseases such as epidermal inclusion cysts have been connected via mutations in the same gene, NEK9, a gene associated with ciliary dysfunction. This project serves to relate the NEK9 gene, ciliary function, and comedogenesis together to better understand the formation of comedones during development and adulthood and use our findings to inform better treatment of both rare and common comedonal diseases.

PI_NAMEs: ELLIS, KATHARINE TAYLOR (contact)

PROGRAM_OFFICER_NAME: VINCENT, ISAAH S

PROJECT_TERMS: Acne Vulgaris;Adult;Affect;base;Biological;Biological Assay;Biology;Birth;Cell Cycle Progression;cell fate specification;Cells;Cellular biology;Characteristics;Cilia;ciliopathy;Clinical;Clinical Data;Comedo;Confocal Microscopy;Cyst;Data;Defect;Dermatologic;design;Detection;Development;Disease;DNA Sequence Alteration;Epithelial cyst;Exhibits;exome;exome sequencing;experience;Fingers;Functional disorder;gene induction;Genes;Genetic;Genetic Predisposition to Disease;Genetic Transcription;GLI gene;Hair follicle structure;Hair shaft structure;Histology;Human;Image;Immunofluorescence Immunologic;in utero;In Vitro;in vivo;in vivo Model;Individual;Inflammatory;insight;Institution;Keratin;keratinization;keratinocyte;Lead;Learning;Lesion;life span;Literature;Maintenance;Methods;Microscopy;Mitosis;Modeling;Molecular;Morphogenesis;Morphology;mosaic;mouse model;mutant;Mutation;Nevus;notch protein;novel;NUP98 gene;Organelles;Pain;Pathogenesis;Pathology;Pathway Analysis;Pathway interactions;Phenotype;Physicians;Play;postnatal;Primary Lesion;Production;promoter;protein transport;Proteins;Rare Diseases;rare genetic disorder;Reporting;Research;Role;Scientist;Sequence Analysis;SHH gene;Signal Pathway;Signal Transduction;Signaling Protein;Skin;skin disorder;smoothened signaling pathway;Somatic Mutation;Sonic Hedgehog Pathway;Specific qualifier value;Structure;Structure of retinal pigment epithelium;Tamoxifen;Techniques;Testing;Therapeutic;therapeutic target;Time;Tissues;tool;Training;Transgenes;Transgenic Mice;Variant;Western Blotting

PROJECT_TITLE: Leveraging mosaic genodermatoses to discover genetic and molecular mechanisms of comedogenesis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F05-Q (20)]


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

ORG_DEPT: GENETICS

PHR: PROJECT NARRATIVE Alzheimer’s disease (AD) is an age-related neurodegenerative disease affecting millions of people worldwide for which limited therapeutics are currently available to slow or halt disease onset or progression. The studies outlined in this proposal will elucidate the role of microglial protein quality control in the context of AD pathogenesis. This will both advance our understanding of the mechanisms underlying the progression of diverse neurodegenerative proteinopathies, and identify potential targets for future therapeutic development.

PI_NAMEs: SANDERS, BENJAMIN EDWARD (contact)

PROGRAM_OFFICER_NAME: SARE, RACHEL

PROJECT_TERMS: abeta accumulation;abeta oligomer;Ablation;Acceleration;Adult;Affect;age related neurodegeneration;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Amyloid beta-Protein;Appearance;Behavioral;Behavioral Paradigm;Biochemical;Cause of Death;Characteristics;Cognition;Communication;Data;Dementia;Disease;Disease associated microglia;Disease Marker;disease phenotype;Disease Progression;Down-Regulation;Embryo;Environment;equity, diversity, and inclusion;Etiology;experimental study;extracellular;familial Alzheimer disease;Fellowship;Foundations;Future;Gene Expression Regulation;Gene Mutation;Genes;Genetic;Genetic Transcription;Gliosis;Goals;Heterogeneity;Histocompatibility Antigens Class II;Histologic;holistic approach;Immunohistochemistry;Immunotherapy;Impaired cognition;improved;Inflammatory Response;Interferons;Knock-out;Lysosomes;Measures;Memory impairment;Memory Loss;Mentors;Microglia;Modeling;monomer;morris water maze;mouse model;Mus;nemo-like kinase;Nerve Degeneration;Nervous System;Neurodegenerative Disorders;Neurofibrillary Tangles;Neuroglia;Neuroimmune;neuron development;Neurons;Neurosciences;Onset of illness;Pathogenesis;Pathologic;Pathology;Pathway interactions;Persons;Phagocytes;Phagocytosis;Phagocytosis Induction;Phenotype;Physiological;programs;Proliferating;protein aggregation;protein TDP-43;Protein-Serine-Threonine Kinases;Proteins;Quality Control;Regulation;Research Personnel;response;Role;Senile Plaques;Short-Term Memory;Signal Transduction;single-cell RNA sequencing;skills;success;Symptoms;Synapses;tau Proteins;Testing;Therapeutic;therapeutic development;therapeutic target;Tissues;Training;transcriptomics;Transgenic Mice;United States;Universities;Up-Regulation;Western Blotting

PROJECT_TITLE: Nemo-like kinase regulation of microglial function and heterogeneity in Alzheimer's disease

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


NIH_SPENDING_CATS: Aging;Bioengineering;Biotechnology;Immunotherapy;Infectious Diseases;Regenerative Medicine;Wound Healing and Care

ORG_CITY: BALTIMORE

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Project Narrative Traumatic events can lead to major muscle loss that exceeds the body’s natural ability to heal. While materials derived from biological tissues can engage the immune system to promote regeneration of muscle in these traumatic wounds, aging causes dysregulation of these responses. Our strategy utilizes pre-existing T-cell immunity generated by past infections as the basis of a strategy to enhance the material-induced immune response and promote greater muscle recovery in the elderly.

PI_NAMEs: KELLY, SEAN  (contact)

PROGRAM_OFFICER_NAME: BOYCE, AMANDA T

PROJECT_TERMS: Activities of Daily Living;Adaptive Immune System;adaptive immunity;Address;age effect;age related;aged;Aging;animal old age;Antibodies;Antibody Therapy;Antigen-Presenting Cells;antigen-specific T cells;Antigens;Area;Biocompatible Materials;Biological;Blood group antigen S;career;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;CD8B1 gene;Cells;Clinical;Combination immunotherapy;cytokine;Cytomegalovirus;Defect;design;Elderly;Encapsulated;eosinophil;Epitopes;Equilibrium;experience;Extracellular Matrix;Fibrosis;Flow Cytometry;Frequencies;Future;Gel;Gene Expression;Genes;Goals;healing;Histology;Human;human data;Human Herpesvirus 4;IL17 gene;Immune response;Immune system;Immunity;Immunologics;immunomodulatory therapies;immunoregulation;Immunotherapy;Implant;implantation;improved;Infection;Inflammation;Inflammatory;Influenza;Innate Immune System;innovation;insight;Interleukin-4;juvenile animal;Lead;Life;lipid biosynthesis;Measures;Mediating;Methods;Modeling;mouse model;Mus;Muscle;muscle regeneration;Muscular Atrophy;Natural regeneration;old mice;Operative Surgical Procedures;Ovalbumin;Patients;Peptides;Phenotype;Physiological;Population;pre-clinical;Process;Proteins;quadriceps muscle;Recording of previous events;Recovery;regenerative;Regenerative capacity;regenerative repair;repaired;Research;response;Role;scaffold;single-cell RNA sequencing;Sorting;Source;Specificity;Stains;synergism;T cell response;T-Cell Immunologic Specificity;T-Lymphocyte;Tissues;Training;traumatic event;traumatic wound;Vaccinia virus;Viral;Virus;volumetric muscle loss;Work;wound;wound healing

PROJECT_TITLE: Leveraging pre-existing immunity to enhance pro-regenerative T-cell responses in aged mice


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

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

PHR: Project Narrative Malaria is a deadly disease with the majority of these deaths attributable to Plasmodium falciparum infection, complicated by a lack of natural sterilizing immunity in humans and current vaccines with modest and strain- specific efficacy. Using samples from a cohort in a low transmission setting in Senegal, we will seek to understand the kinetics and dynamics of functional immune responses to merozoite antigens that provide broad protection against multiple strains. The proposed project will aid current vaccine efforts by identifying broadly functionally protective immune responses with consideration to antibody characteristics and natural parasite diversity.

PI_NAMEs: HAGADORN, KELLY  (contact)

PROJECT_TERMS: Affect;Affinity;Africa South of the Sahara;Age;Alleles;Antibodies;Antibody titer measurement;antibody-dependent cell cytotoxicity;Antigen Targeting;Antigenic Diversity;Antigens;asexual;attributable mortality;Avidity;Biophysics;Blood;Cause of Death;Cessation of life;Characteristics;chemotherapy;Child;Clinical;Clinical Trials;cohort;Complement Activation;Cross Reactions;Development;Disease;Distant;Dominant Genetic Conditions;Drug resistance;Epitopes;Erythrocytes;Exposure to;Fc Receptor;functional decline;Genetic;Genetic Polymorphism;Genetic Variation;Genomics;Genotype;global health;Goals;Health Priorities;Human;Immune;Immune response;Immune System Diseases;Immunity;Individual;Infection;Invaded;Kinetics;Learning;Malaria;malaria infection;Malaria Vaccines;Measures;Mediating;Modification;Parasites;Phagocytosis;Plasmodium;Plasmodium falciparum;Play;Polysaccharides;Population;Recommendation;Research;Respiratory Burst;response;Role;Sampling;Senegal;Serum;Severity of illness;Specificity;tool;Transcend;Transgenic Organisms;transmission process;vaccine candidate;vaccine development;Vaccines

PROJECT_TITLE: The Kinetics and Dynamics of Functional Immune Responses to Plasmodium falciparum Strains


ED_INST_TYPE: UNIVERSITY-WIDE

NIH_SPENDING_CATS: Neurosciences;Physical Injury - Accidents and Adverse Effects;Rehabilitation;Spinal Cord Injury;Traumatic Head and Spine Injury

ORG_CITY: PHILADELPHIA

ORG_NAME: DREXEL UNIVERSITY

ORG_STATE: PA

PHR: Narrative Spasticity is a condition that manifests after spinal cord injury and causes severe difficulties in the daily lives of patients. While there are pharmacological treatments available to treat spasticity, they have significant side effects, including a decrease in spinal excitability, which further diminish motor recovery. This project will investigate if epidural stimulation can be used as a treatment to alleviate spasticity.

PI_NAMEs: WEINBERGER, JEREMY  (contact)

PROGRAM_OFFICER_NAME: BAMBRICK, LINDA LOUISE

PROJECT_TERMS: Adult;Affect;Animal Model;Animals;Body Weight;Chlorides;Chronic;Contusions;Development;disability;Dizziness;Down-Regulation;Electrodes;Electromyography;Evoked Potentials;experimental study;Fostering;Frequencies;functional improvement;GABA Agonists;gamma-Aminobutyric Acid;H-Reflex;Homeostasis;Human;Hyperreflexia;Immunohistochemistry;improved;Individual;individualized medicine;injured;Injury;insight;Intervention;Knowledge;Lesion;Locomotion;Locomotor Recovery;Locomotor training;Maintenance;Maps;Measures;Mediating;Membrane;Mental Depression;Motor;Motor Neurons;Motor output;motor recovery;Movement;Muscle;Muscle Contraction;Neurons;optimal treatments;Outcome;Outcome Measure;Pathway interactions;Patients;pharmacologic;Pharmacological Treatment;Physiologic pulse;Protocols documentation;Randomized;Rattus;Recovery;Reflex action;Regimen;Reporting;Resources;restoration;Seizures;Sensory;Severities;side effect;Site;Sleep;Smooth Muscle;spasticity;Spinal;Spinal Cord;Spinal cord injury;Spinal cord injury patients;spinal reflex;Sprague-Dawley Rats;stem;Symptoms;Synapses;therapy design;Training;treatment optimization;United States

PROJECT_TITLE: Multisite Electrode Arrays to Optimize Epidural Stimulation for Spasticity Following Spinal Cord Injury

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


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

PHR: PROJECT NARRATIVE Alzheimer’s Disease is the most prevalent form of late-onset dementia, but patients with presenilin-1 mutations can develop early-onset dementia in their 40s. A patient with a mutation in APOE3 (APOE3cc) didn’t develop dementia until her 70s, despite having a presenilin-1 mutation. This project will dissect the cell type-specific molecular mechanisms governing the neuroprotective effect regulated by the APOE3cc mutation.

PI_NAMEs: NAGUIB, SARAH  (contact)

PROGRAM_OFFICER_NAME: CHAKROBORTY, SHREAYA

PROJECT_TERMS: Affect;Age;Aging;Alzheimer's Disease;Alzheimer's disease patient;Alzheimer's disease risk;Antioxidants;Apolipoprotein E;apolipoprotein E-3;Astrocytes;Autopsy;autosomal dominant Alzheimer's disease;Behavior assessment;behavioral response;Biological Assay;brain cell;Brain region;cell type;Cells;Central Nervous System;Coculture Techniques;Cognition;Cognitive deficits;Colombia;Data;Dementia;early onset;experimental study;Functional disorder;Gene Expression Profile;Genes;genetic analysis;Genetic Transcription;Genus Hippocampus;Health;Hippocampus;human model;hyperphosphorylated tau;Impaired cognition;In Vitro;in vivo;inhibitor;Interferon Activation;Interferon Suppression;Interferon Type I;Interferons;kindred;Link;lipid metabolism;Lipids;Measures;Mediating;Memory impairment;Metabolic;metabolic profile;metabolomics;Microglia;mild cognitive impairment;Mitochondria;Molecular;morris water maze;mouse model;Mus;Mutation;Nerve Degeneration;Neurites;Neurofibrillary Tangles;Neuroglia;Neurons;neuroprotection;neutralizing antibody;Oxidative Stress;Pathology;Pathway interactions;Patients;Phagocytes;Plasma;presenilin-1;Protein Isoforms;pup;Reactive Oxygen Species;Regulation;resilience;response;Role;Senile Plaques;Signal Transduction;single nucleus RNA-sequencing;Symptoms;Synapses;tau aggregation;tau Proteins;Tauopathies;Testing;therapeutic target;transcriptome sequencing;type I interferon receptor;Variant;β-amyloid burden

PROJECT_TITLE: Elucidating the Cell-Type Specific Neuroprotective Mechanisms in the APOE3 Christchurch Mutation in Alzheimer's Disease


ADMINISTERING_IC: MH

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Pediatric;Social Determinants of Health;Women's Health Research

ORG_CITY: Princeton

ORG_DEPT: PSYCHOLOGY

ORG_NAME: PRINCETON UNIVERSITY

ORG_STATE: NJ

PHR: Project Narrative Gender disparities in mental health are stark—relative to men, women consistently report higher rates of anxiety and depression, as well as lower levels of self-esteem—and emerge by adolescence. To date, research on these gender differences has focused largely on the role of biological factors linked to sex (e.g., hormonal differences). The current research will pursue a more complete understanding of how gender disparities in mental health emerge by examining adolescents who vary both in assigned sex and gender identity (i.e., cisgender and transgender youth): in doing so, this project will clarify the role of gender identity in predicting gender disparities in mental health and reveal the psychological variables related to gender (e.g., attributes, behaviors, and experiences common in men vs. women) that account for such disparities.

PI_NAMEs: LESHIN, RACHEL A (contact)

PROGRAM_OFFICER_NAME: CORNELL, ASHLEY ROSE

PROJECT_TERMS: Accounting;Address;Adolescence;Adolescent;adolescent mental health;Age;Anxiety;Behavior;Biological;Biological Factors;Biology;Birth;boys;brain circuitry;Categories;Characteristics;cisgender;Complex;Cross-Sectional Studies;Data Collection;Development;Disparity;Exhibits;experience;Female;Feminine;Gender;gender difference;gender disparity;gender diverse;gender equity;Gender Identity;Genetic;girls;Hormonal;Hormones;innovation;insight;Investigation;Link;longitudinal analysis;Longitudinal Studies;male;man;Masculine;Measures;Mediating;Mediation;men;Mental Depression;Mental Health;nonbinary;North America;novel;Outcome;Pathway interactions;Population Heterogeneity;Positioning Attribute;Principal Investigator;Process;psychologic;psychological distress;Reporting;Research;Role;Sampling;self esteem;Series;sex;sex assigned;Sexism;sexual identity;social;Subgroup;transgender;Woman;Youth

PROJECT_TITLE: The psychological underpinnings of gender disparities in adolescent mental health

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


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Neurosciences

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: PROJECT NARRATIVE During developmental refinement of synaptic connections in the visual thalamus, astrocytes wrap around clusters of synapses. In this pilot proposal, we will examine the role of this astrocytic wrapping in the process of synapse elimination and strengthening. Additionally, we will test whether the astrocytic wrapping acts to increase the concentration of neurotransmitters around the synaptic clusters.

PI_NAMEs: CHEN, CHINFEI  (contact);UMEMORI, HISASHI

PROGRAM_OFFICER_NAME: FLANDERS, MARTHA C

PROJECT_TERMS: Address;Affect;Area;Astrocytes;Axon;Binding;Brain;Brain Stem;Central Nervous System;Cognition;Cognition Disorders;confocal imaging;Data;Defect;Dendrites;Development;Dorsal;Electron Microscopy;Endowment;Environment;Exhibits;experimental study;Family member;Fibroblast Growth Factor Receptor 2;Fibroblast Growth Factor Receptors;gamma-Aminobutyric Acid;Genetic;Glutamates;Impairment;In Vitro;insight;Interneurons;Kinetics;Knowledge;Lateral Geniculate Body;Mediating;Modeling;Molecular;Morphology;mouse model;Mus;Mutant Strains Mice;Mutation;Nature;Neuroglia;Neuromodulator;Neurons;neuroregulation;Neurosciences;Neurotransmitters;Phenotype;Physiological;Play;presynaptic;Presynaptic Terminals;Process;receptor;response;Retina;retinal axon;Retinal Ganglion Cells;retinogeniculate;Role;sensor;Sensory;Signal Transduction;Structure;Synapses;System;Testing;Thalamic Nuclei;Thalamic structure;tool;transmission process;two-photon;Visual

PROJECT_TITLE: Elucidating synaptic motifs in the visual thalamus

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 ICN-Y (02)]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Behavioral and Social Science;Neurosciences;Nutrition;Obesity;Prevention

ORG_CITY: HOUSTON

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

ORG_STATE: TX

PHR: Through hypothalamic and extrahypothalamic nodes, stress imparts flexibility to an organism's ability to maintain long-term weight homeostasis (WH). This application will explore the role of the neurons expressing Corticotrophin Releasing Factor Receptor 1 (CRFR1) neurons in the Bed Nucleus of Stria Terminalis (BNSTCRFR1) in modifying WH. These studies will mechanistically explore the neural basis through which stress alters WH, and in the long-term, spur development of novel therapeutics that prevent or mollify stress-related disturbances in WH.

PI_NAMEs: ROMERO, JUAN MANUEL (contact)

PROGRAM_OFFICER_NAME: RIVERS, ROBERT C

PROJECT_TERMS: American;Amygdaloid structure;Area;Behavior;Behavioral;Binding;Biological Assay;Body Composition;Body Weight;Body Weight decreased;Brain;Catalogs;Cells;Central Nervous System;Cessation of life;Chronic;Chronic stress;Collaborations;college;Communication;conditional knockout;Control Animal;Corticotropin-Releasing Hormone;Corticotropin-Releasing Hormone Receptors;CRF receptor type 1;Data;Development;Disease;Electrophysiology (science);Energy Intake;Energy Metabolism;Epidemic;experimental study;Face;Fatty acid glycerol esters;Feeding behaviors;flexibility;food consumption;Generations;Genetic;Goals;Health Care Costs;Homeostasis;House mice;Human;Hypothalamic structure;Image;Immunohistochemistry;innovation;insight;interest;Investigation;Laboratory Animals;Lead;Lesion;loss of function;LoxP-flanked allele;Maintenance;Maps;Measurement;Measures;Mediating;Medicine;Mentorship;Metabolic;Metabolism;Methodology;Methods;Modeling;Molecular;Monitor;mouse model;Mus;Nervous System;neural;Neurologic;neuromechanism;Neurons;novel;novel therapeutics;Organism;Overweight;Patients;Peptides;perceived stress;Peripheral;Phenotype;Physicians;Physiological;Population;presynaptic;prevent;Process;Quality of life;rabies viral tracing;receptor;Regulation;Research Institute;Resources;Role;Scientist;Signal Transduction;Site;skills;Stress;Structure;Structure of terminal stria nuclei of preoptic region;System;Testing;Tetanus Toxin;Therapeutic;therapy development;Translations;United States;Viral;Virus;Weight;weight maintenance;Weight maintenance regimen

PROJECT_TITLE: THE ROLE OF CORTICOTROPHIN RELEASING FACTOR RECEPTOR 1 NEURONS IN THE BED NUCLEUS OF THE STRIA TERMINALIS IN MODULATING WEIGHT HOMEOSTASIS

STUDY_SECTION_NAME: Special Emphasis Panel[ZDK1 GRB-2 (O1)]


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF PHARMACY

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: Chicago

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

ORG_STATE: IL

PHR: NARRATIVE Natural product-based drugs are the cornerstone of drugs available on the market today. Genome mining and microbial engineering have consistently been efficacious tools for natural product dug discovery and development. Current advances in molecular genetics, such as fast, accurate, and affordable sequencing technologies, enable us to further tap into the potential of microbial natural products for drug discovery. These technological advances leave room for significant advancement in microbial production and engineering. Currently, there is a bottleneck in natural product drug discovery brought on by a shortage of well-studied bacterial hosts available for heterologous expression of unexplored gene clusters. The lack of diverse and well- studied host strains results in minimal yield production platforms, which limit the ability to utilize microbes for natural product drug discovery and development. The research outlined in this proposal aims to test and develop a Burkholderia bacterial host from strain FERM BP-3421, a strain proven capable of producing medicinally relevant compounds in gram per liter scale. Development of this Burkholderia strain increases the diversity of well-studied host strains available to the scientific community. Furthermore, the proposed testing of the Burkholderia host will result in the immediate production of natural products that have potential as drug leads.

PI_NAMEs: FERNANDEZ, HANNAH NAOMI (contact)

PROGRAM_OFFICER_NAME: STAMM, JOYCE CHIN-CHIN NG

PROJECT_TERMS: Affect;Affinity;Anabolism;Anti-Bacterial Agents;Antibiotics;Biodiversity;Bioinformatics;Biological;Biological Process;Burkholderia;Burkholderiaceae;chemical synthesis;Collaborations;Communities;Development;DNA;DNA biosynthesis;DNA Methylation;DNA Sequence Alteration;drug development;drug discovery;drug modification;endosymbiont;Engineering;epigenetic marker;Epigenetic Process;Epitopes;Escherichia coli;Evaluation;experimental study;Family;follow-up;Future;Gene Cluster;Genes;Genetic Transcription;Genome;genome sequencing;improved;Industrialization;Investigation;Lasso;Libraries;Literature;Marketing;Medicine;Methods;Microbe;microbial;microbial host;Microbial natural product;Mining;Modeling;Modification;Molecular;Molecular Genetics;Mutation;nanopore;Natural product discovery;Natural Product Drug;Natural Products;novel;Orphan;Peptides;Pharmaceutical Preparations;Phase;Phenotype;Plasmids;Polymerase Chain Reaction;Positioning Attribute;Production;Publishing;Regulation;Reporting;Reproducibility;Research;Resistance;Reverse engineering;Ribosomes;Techniques;Technology;Testing;Therapeutic;tool;transcriptome sequencing;transcriptomics;vector

PROJECT_TITLE: Reverse Engineering High Yield Lasso Peptide Production by a Burkholderia Heterologous Host

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F04-S (20)]


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Emerging Infectious Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Mental Health;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: MINNEAPOLIS

ORG_DEPT: FAMILY MEDICINE

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Project Narrative This project adds four additional waves of survey and two waves of time diary data to the NICHD-supported National Couples’ Health and Time Study (NCHAT), which is the only population-representative, multi-method study of American couples that includes fully-powered samples of racially and ethnically diverse and sexual and gender diverse individuals collected during the COVID-19 pandemic and the co-occurring period of intense racial trauma. These longitudinal data, which will be made publicly available, and the current and future analyses are essential to identify the risk and resilience factors associated with the long-term impacts of discrimination and COVID stress on mental health and family functioning among the most marginalized Americans. This project will identify mental health adaptations to the pandemic and racial injustice and produce policy-relevant recommendations to promote improved well-being during periods of uncertainty and stress.

PI_NAMEs: KAMP DUSH, CLAIRE M (contact);MANNING, WENDY D.

PROGRAM_OFFICER_NAME: POPKIN, RONNA

PROJECT_TERMS: Acute;Adult;Age;American;anti-Asian;anti-racism;Articulation;Black race;Climate;cohort;Communities;County;Coupled;Couples;COVID-19;COVID-19 pandemic;COVID-19 stress;Data;Data Collection;data infrastructure;Deterioration;diaries;Discipline;Discrimination;Disparity;ethnic diversity;Event;experience;Family;flexibility;Florida;follow-up;Future;Gays;gender diverse;Hate;Health;health disparity;health equity;Health equity research;health inequalities;Healthcare;Immigrant;Impairment;improved;Individual;Inequity;innovation;insight;Institution;Interview;Investments;Knowledge;Laws;lens;Lesbian Gay Bisexual Transgender Queer;Long COVID;marginalization;Measurement;Measures;Mediator;Mental Health;Methods;multidisciplinary;Murder;National Institute of Child Health and Human Development;novel;pandemic disease;perceived discrimination;Personal Satisfaction;Persons;Policies;Population;Population Heterogeneity;Positioning Attribute;pressure;Race;racial diversity;racial health disparity;racial identity;Racial injustice;Recommendation;Recovery;Reporting;Research;Research Personnel;resilience factor;Resources;Respondent;Rights;Risk Factors;Same-sex;Sampling;Sampling Studies;Sexism;sexual identity;Shock;social;social determinants;Social support;Socialization;Stress;stressor;Structural Racism;Surveys;System;Tennessee;Testing;Time;Time Study;time use;Trauma;Uncertainty;United States;United States National Academy of Sciences;Violence;Vulnerable Populations

PROJECT_TITLE: A Longitudinal Examination of Mechanisms Underlying Intersectional Health Disparities in the United States

STUDY_SECTION: SSPA

STUDY_SECTION_NAME: Social Sciences and Population Studies A Study Section[SSPA]


NIH_SPENDING_CATS: Biotechnology;Gene Therapy;Genetics;Neurodegenerative;Neurosciences;Orphan Drug;Rare Diseases

ORG_CITY: GAINESVILLE

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: The proposed research is relevant to public health as it develops and establishes alternative splicing as a powerful and viable method to control regulation of gene therapies. Current gene therapies do not take advantage of this ubiquitous regulatory mechanism, and we propose to use it to achieve tissue-specific and self-regulatory control over AAV-delivered cargoes. Findings from this study will constitute new compositions and guiding principles for the development of gene therapy cargoes.

PI_NAMEs: WANG, ERIC T (contact)

PROGRAM_OFFICER_NAME: MORRIS, JILL A

PROJECT_TERMS: 3' Untranslated Regions;adenovirus mediated delivery;Alternative Splicing;Behavior;Binding Sites;Bioinformatics;Calpain;Capsid;Cell Culture Techniques;cell type;Central Nervous System;Clinic;Code;design;Development;direct application;Disease;disease model;DNA biosynthesis;DNA cassette;DNA sequencing;Dose;Elements;Engineering;Exons;FDA approved;Focus Groups;frataxin;Friedreich Ataxia;Gene Expression;Gene Expression Regulation;gene replacement;gene therapy;Genetic Diseases;Genetic Transcription;Genome;Heart;hnRNP A1;improved;in vivo;Individual;induced pluripotent stem cell;Introns;knock-down;Leber's amaurosis;Limb-Girdle Muscular Dystrophies;Liver;Measures;Mediating;Medicine;Methods;Methyl-CpG-Binding Protein 2;MicroRNAs;miniaturize;Modality;Modeling;Motor Neuron Disease;Muscle;Mutate;Mutation;Nuclear Export;Output;overexpression;Pattern;Phenotype;Physiological;Pre-Clinical Model;preference;preservation;promoter;protein TDP-43;Proteins;prototype;Public Health;rational design;Regulation;Reporter;Research;Rett Syndrome;RNA Processing;RNA Splicing;RNA-Binding Proteins;Site;Skeletal Muscle;Spinal Ganglia;Spinal Muscular Atrophy;Testing;Therapeutic;therapeutic gene;Tissue-Specific Gene Expression;Tissue-Specific Splicing;Tissues;Toxic effect;Tracer;transcriptome;transcriptome sequencing;transduction efficiency;Translations;Tropism;Variant;Viral Load result;Work

PROJECT_TITLE: Smarter gene therapies: alternative splicing cassettes for tissue-and self-regulated cargo expression

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 MGG-A (02)]


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Digestive Diseases;Microbiome;Nutrition

ORG_CITY: TROY

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: RENSSELAER POLYTECHNIC INSTITUTE

PHR: PROJECT NARRATIVE Bacteroides species are prevalent and abundant in the human intestinal microbiota providing the host with numerous properties essential for health. In this proposal, we will examine new pathways and factors that these bacteria use to generate energy and their contribution to human health and disease prevention. These studies will ultimately support the design of better probiotic formulations and inform about factors important in the restoration of a healthy gut community to various patient populations.

PI_NAMEs: BARQUERA, BLANCA  (contact);COMSTOCK, LAURIE E

PROGRAM_OFFICER_NAME: RANALLO, RYAN

PROJECT_TERMS: Address;Affect;antiporter;Bacteria;bacterial fitness;Bacteroides;Bacteroides fragilis;Bile Acids;Biochemical;Biochemistry;Cell Physiology;Cell Respiration;Code;Color;Communities;Complex;Consumption;Cytoplasm;Data;Dependence;design;Developmental Process;dietary;Dietary Polysaccharide;Digestion;disorder prevention;electron donor;Electron Transport;Electrons;Enzymatic Biochemistry;Enzymes;experience;experimental study;Fermentation;fitness;Food;Formulation;Generations;Genes;Genetic;Gnotobiotic;Growth;gut bacteria;gut inflammation;gut microbiome;gut microbiota;Health;Health Benefit;Human;Hydrophobicity;immunoregulation;In Vitro;in vivo;Industrialization;Inflammation;Ion Pumps;isoprenoid;member;men;Metabolism;metabolomics;microbial;microbiota;microbiota composition;Monosaccharides;mouse model;Multienzyme Complexes;NADH;Nitric Oxide;nitric oxide reductase;Nitrites;Nitrogen Dioxide;Nutrient;Operon;Oxidants;Pathway interactions;patient population;Physiology;Polysaccharides;Population;Probiotics;Process;Production;Property;protective effect;Protons;Quinones;Regulation;Respiration;respiratory;Respiratory Chain;respiratory enzyme;restoration;Role;Side;Source;Support System;Toxic effect;transcriptomics;Translating;Variant;Vitamin K 2;Volatile Fatty Acids;Work

PROJECT_TITLE: Respiration and fitness in Bacteroides


ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: TEMPLE UNIV OF THE COMMONWEALTH

PHR: Current therapeutics for atherosclerosis fail to consider the role of inflammation and lymphatic system function, both of which have the potential to promote plaque stability. Through preliminary in vitro and in vivo models, we found that IL-19, an endogenous anti-inflammatory cytokine, induces the formation of functional lymphatic vessels by modifying their permeability, which has the potential to increase both white blood cell egression and reverse cholesterol transport. This grant will explore the mechanism of action behind IL-19’s effect on lymphatic system function in the setting of hypercholesterolemia.

PI_NAMEs: PELUZZO, AMANDA  (contact)

PROGRAM_OFFICER_NAME: CHEON, YEWON

PROJECT_TERMS: Anti-Inflammatory Agents;Aorta;Area;Arterial Fatty Streak;atherogenesis;Atherogenic Diet;Atherosclerosis;Attenuated;Automobile Driving;Biological Assay;Blood Vessels;cadherin 5;Cardiovascular Diseases;Cause of Death;Cell Proliferation;Cell Separation;cell transformation;Cells;Cessation of life;chemokine;Cholesterol;combat;cytokine;Data;Dermal;Disease;Disease Progression;draining lymph node;Dyes;Ear;electric impedance;Endothelial Cells;Environment;Enzyme-Linked Immunosorbent Assay;Evans blue stain;Excision;experience;fluorescein isothiocyanate dextran;Foam Cells;Gene Expression;Genes;Grant;Health;High Density Lipoproteins;Human;hypercholesterolemia;Hyperlipidemia;Immune;immunocytochemistry;immunoregulation;improved;In Vitro;in vivo;in vivo Model;Inflammation;Inflammatory;interleukin-19;knock-down;Knowledge;Leukocytes;lipid transport;Lipids;Liquid substance;Lymphangiogenesis;Lymphatic;Lymphatic Endothelial Cells;Lymphatic function;Lymphatic System;lymphatic vessel;Maintenance;migration;Modeling;Molecular;Morphology;Mus;Myocardial Infarction;novel;Oils;Outcome;oxidized low density lipoprotein;Pathogenesis;Pathway interactions;Patients;Permeability;Phosphorylation;prevent;Process;Proliferating;Property;Regulation;Reporting;Resolution;reverse cholesterol transport;Role;Serum;Signal Transduction;Small Interfering RNA;Stains;STAT3 gene;Stroke;Surface;Therapeutic;trafficking;transcription factor;transcriptome sequencing;Tube;Tunica Adventitia;Up-Regulation;uptake;Vascular Diseases;Western Blotting

PROJECT_TITLE: IL-19 Modifies Lymphatic Flux During Hyperlipidemia

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


ORG_DEPT: NEUROLOGY

PHR: PROJECT NARRATIVE A robust immune response to intracerebral hemorrhage (ICH) is well documented but the B cell response in the post-ICH brain remains poorly understood. This grant proposes a thorough characterization of the B cell response to ICH over time, with particular emphasis on understanding the phenotype and function of brain- infiltrating IgA+ B cells. This work will therefore have important implications for our understanding of the adaptive immune response to brain injury and may guide therapeutics targeting post-ICH inflammation-induced damage.

PI_NAMEs: OHASHI, SARAH  (contact)

PROGRAM_OFFICER_NAME: HEWETT, SANDRA JEANNE

PROJECT_TERMS: Accounting;adaptive immune response;Antibodies;antibody-dependent cell cytotoxicity;antibody-dependent cellular phagocytosis;Autoantibodies;B-Cell Antigen Receptor;B-Lymphocytes;Binding;Biological Assay;Blood;Blood Vessels;Brain;Brain hemorrhage;Brain region;brain tissue;Cause of Death;Cell Aggregation;Cell Physiology;Cells;Cellular biology;Central Nervous System;Central Nervous System Infections;Cerebral hemisphere hemorrhage;Characteristics;Chronic;Clonal Expansion;Cognitive;Collaborations;collagenase;Complement;Demyelinations;disability;Disease;Exhibits;Experimental Autoimmune Encephalomyelitis;experimental study;Family;Goals;Grant;Hemorrhage;Histology;Human;Immune response;Immunoglobulin A;Immunoglobulin-Secreting Cells;Immunoglobulins;Impaired cognition;Infiltration;Inflammation;Injections;Injury;insight;Interleukin-10;Ipsilateral;Ischemic Stroke;Knowledge;Light;Link;Long-Term Effects;Measures;Mediating;Meningeal;Meninges;migration;Modeling;Monoclonal Antibodies;Moods;mortality;Motor;mouse model;Mucous Membrane;Multiple Sclerosis;multiple sclerosis patient;Mus;N-Methyl-D-Aspartate Receptors;Nature;neurogenesis;neuroinflammation;neuroprotection;neurotrophic factor;novel;Oligoclonal Bands;oligodendrocyte-myelin glycoprotein;overexpression;Pathology;Patients;peripheral blood;Phenotype;Plasma Cells;Play;Population;Positioning Attribute;post stroke;Proliferating;Proteins;Recombinants;Recovery;Recovery of Function;recruit;repaired;Reporting;Research;response;response to brain injury;Role;Shapes;single-cell RNA sequencing;Site;Small Intestines;Spinal Cord;Stroke;stroke model;stroke recovery;Survivors;tertiary lymphoid organ;Testing;Therapeutic;therapeutic target;Time;Tissues;Transgenic Mice;Work

PROJECT_TITLE: Investigating the origin and role of the IgA+ B cell response to intracerebral hemorrhage


NIH_SPENDING_CATS: Bioengineering

ORG_CITY: PITTSBURGH

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: CARNEGIE-MELLON UNIVERSITY

PHR: Sensing of the mechanical stiffness of embryos and similarly small tissues is extremely important in fields such as developmental biology and cancer biology. However, many important questions are unanswered due to the fact that the available instrumentation for measuring at such small scales is table-mounted and is very limited in its range and direction of motion, such that it can only perform sensing on tissue of a certain regular shape or on flat, horizontal surfaces. This project will develop a new type of stiffness-sensing instrument that combines the large range of motion of the human hand with the accuracy of microrobotics in order to produce an instrument that shares the strengths of both, and therefore is capable of sensing in ways that other instruments cannot.

PI_NAMEs: RIVIERE, CAMERON N (contact)

PROGRAM_OFFICER_NAME: BARNES, CHARLES ASHLEY

PROJECT_TERMS: 3-Dimensional;Address;Animals;Area;Articular Range of Motion;Atomic Force Microscopy;Biochemical;Biological Models;Biomechanics;Cancer Biology;Cell Differentiation process;Cells;Compensation;Complex;Data Analyses;Development;Developmental Biology;Devices;Disease;Dorsal;Elasticity;Embryo;Embryonic Development;Ensure;Epithelial Cells;experience;experimental study;Extracellular Matrix;Frequencies;Gene Expression;Geometry;Growth;Hand;Hour;Human;Image;In Situ;in vivo;inhibitor;instrument;instrumentation;interest;Intuition;kinematics;knockout gene;Knowledge;Laboratories;Location;longitudinal analysis;Maintenance;Measurement;Measures;mechanical properties;Mechanics;Mesenchymal;Methods;micromanipulator;microrobot;Microscope;Modulus;Motion;mutant;Natural regeneration;Optics;Organ;Organoids;Performance;Photography;Physical shape;Physiological;Play;Property;Proteins;prototype;Research Personnel;Residual state;Robotics;Role;Sample Size;Sampling;Scanning;Scientist;Shapes;Solid;Sorting;Surface;System;Techniques;Technology;Testing;Tissue Sample;Tissues;tool;Tremor;visual tracking;Xenopus

PROJECT_TITLE: A handheld tissue force microscope

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 BBBT-M (82)]


NIH_SPENDING_CATS: Autism;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Intellectual and Developmental Disabilities (IDD);Machine Learning and Artificial Intelligence;Mental Health;Networking and Information Technology R&D (NITRD);Neurosciences;Pediatric

ORG_CITY: SEATTLE

ORG_NAME: SEATTLE CHILDREN'S HOSPITAL

ORG_STATE: WA

PHR: PROJECT NARRATIVE This study builds and deploys a tablet-based system for collecting information about infant and toddler attention patterns associated with autism. We use this system in two groups of 2-year-old toddlers with and without autism who we follow up with at 3-years (one group in lab, the other remote), and also collect data from a large community sample of 3- to 36-months old infants to help establish developmental baselines. The goals of this study are to: (1) accelerate research methods for large scale collection of mobile device eye-tracking data; (2) use these methods to better understand unique qualities of autistic attention; and (3) to use that understanding to better characterize individual attention profiles with the goal of advancing personalized medicine in toddlers with ASD.

PI_NAMEs: SHIC, FREDERICK  (contact)

PROGRAM_OFFICER_NAME: GILOTTY, LISA

PROJECT_TERMS: 2 year old;Acceleration;Age;Age Months;algorithm development;Algorithms;Animals;Attention;autism spectrum disorder;autistic;autistic children;automated assessment;Behavior assessment;Behavioral;Biological Markers;Biology;Caregivers;Child;Clinic;Clinical;Clinical assessments;clinical phenotype;Cognition;Cognitive;Collection;Communities;comparison group;Computer software;Computer Vision Systems;cost;Data;Data Collection;data infrastructure;data quality;data standards;design;Development;Diagnosis;Diagnostic;early childhood;Emotional;Equation;Evaluation;Face;Facial Expression;Family;Feedback;First Degree Relative;follow-up;Friends;gaze;General Population;Geography;Goals;handheld mobile device;Heterogeneity;Home;improved;Individual;Infant;information gathering;Infrastructure;infrastructure development;Interview;Knowledge;Laboratories;machine learning model;Measures;Methods;Modeling;Monitor;Motivation;Movement;Nature;neural network;Neurodevelopmental Disorder;novel;optimal treatments;Outcome;Parents;Participant;Pattern;Performance;personalized medicine;personalized strategies;Persons;predictive modeling;preference;Procedures;Process;prognostic;Questionnaires;recruit;Reflex action;Research;Research Methodology;Resources;Risk;Route;Sampling;sex;showing emotion;skills;social;Social Network;Standardization;Structure;Surveys;System;Tablet Computer;Tablets;Task Performances;Technology;Telephone;Testing;Toddler;tool;Translating;treatment response;treatment strategy;usability;Visible Radiation;Visual attention;visual information;visual tracking

PROJECT_TITLE: Atypical Development in Infants and Toddlers: Computational Attentional Signatures through Mobile Eye Tracking

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 BP-P (02)]


ORG_CITY: ATLANTA

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE Circuit dysfunction is a phenotype in early-stage Alzheimer’s disease (AD), yet the interaction between circuit dysfunction and the emergence of classic AD pathology remains unclear. This proposal will investigate how the emergence of pathological tau is related to cell-type-specific mechanisms of circuit dysfunction in a model of early AD. Ultimately, this proposal aims to address neuron- and circuit-level excitability changes in early AD, and establish a cell-type-specific mechanism causally linked to pathological tau progression.

PI_NAMEs: BANKS, EMMIE  (contact)

PROGRAM_OFFICER_NAME: HAAKENSON, CHELSEA MARIE

PROJECT_TERMS: abeta accumulation;Acceleration;Acute;Address;Affect;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease patient;Amyloid beta-Protein;beta amyloid pathology;Brain region;cell type;Cognition;Data;Dementia;Dependovirus;Disease;disease model;Dissection;Electrophysiology (science);Enhancers;entorhinal cortex;Equilibrium;Event;excitatory neuron;Functional disorder;Gene Expression;Genes;Genetic;Genetic Enhancement;genetic inhibitor;Human;Human Amyloid Precursor Protein;human model;hyperphosphorylated tau;Immunohistochemistry;Impaired cognition;in vivo;insight;Interneurons;Intervention;Investigation;Investigational Therapies;Lateral;Link;Measures;Memory;Modeling;Molecular Conformation;mouse model;Mus;mutant;Nerve Degeneration;Neurofibrillary Tangles;neuronal excitability;Neurons;Parvalbumins;patch clamp;Pathologic;Pathology;Phenotype;Physiology;Predisposition;preservation;Process;Property;protein aggregation;response;Role;Senile Plaques;Slice;System;targeted treatment;tau aggregation;tau mutation;tau Proteins;Time;Transgenic Organisms;Viral;Wild Type Mouse;Work

PROJECT_TITLE: Interneuron dysfunction and the emergence of tau pathology in early Alzheimer’s disease


NIH_SPENDING_CATS: Cardiovascular;Prevention;Rare Diseases

ORG_CITY: CINCINNATI

ORG_NAME: UNIVERSITY OF CINCINNATI

ORG_STATE: OH

PHR: PROJECT NARRATIVE: RELEVANCE TO PUBLIC HEALTH Abdominal aortic aneurysm (AAA) is characterized by progressive deterioration of the aortic wall and catastrophic aortic failure resulting in sudden death in >80% of acute ruptures leading to the death of ~30,000 Americans and ~500,000 people worldwide. Unfortunately, there are no pharmacological treatments available for the prevention of AAA progression and rupture and the only option for these patients is surgical intervention. Our proposal seeks to investigate the mechanisms by which trimethylamine N-oxide (TMAO) activation of its putative binding target protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) contributes to vascular smooth muscle cell (VSMC) dysfunction and subsequent initiation and progression of AAA to elucidate novel therapeutic targets for this lethal disease.

PI_NAMEs: BENSON, TYLER WENDORF (contact)

PROGRAM_OFFICER_NAME: NEILSON, KAREN MARY

PROJECT_TERMS: Abdominal Aortic Aneurysm;Acute;Advisory Committees;Affect;Age;American;Amines;Aneurysm;Angiotensin-Converting Enzyme Inhibitors;Aorta;Apoptosis;Apoptotic;Atlases;Attenuated;Autophagocytosis;Binding;Calcium;Cardiometabolic Disease;Cardiovascular Diseases;Cardiovascular system;CASP3 gene;Categories;Cause of Death;Cessation of life;Choline;Chronic;cohort;Communities;Cyclic AMP-Dependent Protein Kinases;Data;Death Rate;Deterioration;Diameter;Diet;dietary;Disease;druggable target;Endocrine;endoplasm;Endoplasmic Reticulum;endoplasmic reticulum stress;experience;experimental study;Failure;Fatty acid glycerol esters;feeding;Functional disorder;Gender;Goals;gut microbes;gut microbiome;Human;Hypertension;In Vitro;in vivo;Incidence;Inflammatory;Intervention;Intestines;Link;LoxP-flanked allele;male;Matrix Metalloproteinases;Medial;Mediating;men;Mentorship;Metabolic;Mitochondria;mitochondrial dysfunction;mouse model;Mus;new therapeutic target;novel;Operative Surgical Procedures;Organ;Organism;Oxides;Pathogenesis;Pathology;Pathway interactions;Patient Care;Patients;Persons;pharmacologic;Pharmacologic Substance;Pharmacological Treatment;Phenotype;Phosphotransferases;Plasma;prevent;Prevention;Process;protein kinase R;Proteins;Public Health;Publishing;Reactive Oxygen Species;receptor;Research Personnel;Research Proposals;response;Risk;Risk Factors;Role;Rupture;Ruptured Aneurysm;Signal Transduction;single-cell RNA sequencing;Site;Smooth Muscle Myocytes;Source;success;Sudden Death;surgical risk;Testing;Tobacco use;United States;Universities;vascular inflammation;Vascular Smooth Muscle;Woman;Work

PROJECT_TITLE: The role of VSMC-specific PERK in TMAO-induced abdominal aortic aneurysm


NIH_SPENDING_CATS: Genetics;Hematology;Rare Diseases

ORG_CITY: DETROIT

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: WAYNE STATE UNIVERSITY

ORG_STATE: MI

PHR: PROJECT NARRATIVE Langerhans cell histiocytosis (LCH) is an often-lethal inflammatory myeloid neoplasia that arises due to mutations (most commonly in the protein BRAF) that persistently activate the mitogen-activated protein kinase (MAPK) signaling pathway in myeloid lineage cells, which alters their physiology leading to accumulation of LCH cells in tissues and reshaping of the tissue microenvironment. Current treatment strategies, which include chemotherapy or inhibitors of MAPK signaling have significant toxic side-effects and do not eliminate LCH cell precursors leading to recurrent disease and deleterious life-long complications. Recent studies from our lab have identified that the epigenetic protein HDAC3 modulates many facets of myeloid cell biology, including development, making it a promising therapeutic target that may provide persistent disease remission for patients with LCH.

PI_NAMEs: DIMITRION, PETER  (contact)

PROGRAM_OFFICER_NAME: MCINTYRE, JEREMY COLIN

PROJECT_TERMS: Ablation;Address;Adult;Alveolar Macrophages;Anti-Inflammatory Agents;Apoptosis;Attenuated;Biology;Biopsy;Bone Development;Bone Marrow;BRAF gene;Cancer Biology;career;Cell Communication;cell community;Cell Lineage;Cells;Cellular biology;Characteristics;chemotherapy;Child;Childhood Hodgkin's Lymphoma;Clinical;clinical training;cytokine;Cytometry;Data;Dedications;Development;Disease;Disease Progression;Disease remission;Drug Targeting;Emigrations;Endowment;Environment;Eosinophilic Granuloma;Epigenetic Process;epigenetic regulation;epigenomics;Evolution;Flow Cytometry;Frequencies;Functional disorder;Gene Expression;Genes;Genetic;Goals;Granuloma;HDAC3 gene;Health system;Hematology;Hematopoietic stem cells;Heterogeneity;high risk;histiocyte;Histone Deacetylase Inhibitor;Homeostasis;Image;Immune;Immunology;Incidence;Infiltration;Inflammatory;inhibitor;insight;Institution;Invaded;Lesion;Life;Liver;Lung;lymph nodes;Malignant Neoplasms;Matrix Metalloproteinases;medical schools;MEKs;Mentors;migration;Mitogen-Activated Protein Kinase Inhibitor;Mitogen-Activated Protein Kinases;Modeling;Mononuclear;mouse model;Mus;Mutation;Myelogenous;myeloid cell development;Myeloid Cells;Myeloid Progenitor Cells;Myeloproliferative disease;Neoplasms;neoplastic;novel;novel therapeutics;Organ;Pathogenesis;Pathogenicity;Pathologic;Patients;personalized medicine;Phagocytes;Pharmaceutical Preparations;pharmacologic;Phenotype;Physicians;Physiology;Population;pre-clinical;precursor cell;prevent;Procedures;progenitor;prognostic value;programs;Property;Proteins;recruit;Recurrence;Recurrent disease;Research Training;Resistance;Role;Scientist;senescence associated secretory phenotype;Severities;Shapes;side effect;Signal Pathway;Signal Transduction;single-cell RNA sequencing;standard of care;Testing;Therapeutic;therapeutic target;Time;Tissues;Toxic effect;Training;transcriptome sequencing;Transforming Growth Factor beta;Translating;treatment strategy;Universities

PROJECT_TITLE: Epigenetic Regulation of Langerhans Cell Histiocytosis Pathophysiology and Microenvironment by HDAC3


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Neurosciences

ORG_CITY: BOSTON

ORG_NAME: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)

PHR: PROJECT NARRATIVE This project will provide fundamental insight into how decision-making emerges from various cell types and different subregions of the dorsolateral prefrontal cortex, a brain area that is frequently impaired in psychiatric and neurological disorders. Our results will be invaluable for better understanding how neural activity in this clinically relevant brain region leads to cognition. These insights, when combined with precise techniques to perturb neurons and networks are essential for the development of circuit level therapeutics for psychiatric and movement disorders, and the next generation of brain machine interfaces used for recovery of function following brain injury.

PI_NAMEs: LEE, ERIC KENJI (contact)

PROGRAM_OFFICER_NAME: OSBORNE, LESLIE CAROL

PROJECT_TERMS: Address;adjudication;Anatomy;Arbitration;Area;Behavioral;Biological Assay;Brain;Brain Injuries;brain machine interface;Brain region;candidate identification;cell type;Cells;clinically relevant;Cognition;Cognitive deficits;Complex;Computer Models;Cues;Data;Decision Making;Development;dimension reduction;discrimination task;Disease;Dorsal;Electrodes;Electrophysiology (science);excitatory neuron;Exhibits;experimental study;Functional Magnetic Resonance Imaging;Future;Goals;Human;Impairment;in vivo;inhibitory neuron;insight;Interneurons;Location;Macaca;Mental disorders;Modality;Modeling;models and simulation;Monkeys;Motor Cortex;Movement Disorders;Mus;Nature;Nervous System Disorder;neural;neural circuit;Neurons;neurophysiology;next generation;novel;Output;Parvalbumins;Pattern;Physiological;Population;Population Analysis;Population Heterogeneity;Prefrontal Cortex;Primates;Principal Component Analysis;Process;Property;Publishing;Reaction Time;Recovery;Recovery of Function;Research;response;Role;Schizophrenia;Sensory;sensory stimulus;Shapes;Short-Term Memory;Signal Transduction;Somatostatin;spatiotemporal;Stimulus;Stroke;Structure;Study models;Techniques;Testing;theories;Therapeutic;Time;Training;transcriptomics;Variant

PROJECT_TITLE: Neural Circuit Dynamics Underlying Perceptual Decision Making in the Macaque Dorsolateral Prefrontal Cortex

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F01B-M (20)]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_DEPT: SURGERY

PHR: PROJECT NARRATIVE Adoptive T cell transfer therapy is a promising approach to treat aggressive solid tumors; however, many patients still do not respond. We discovered that a CD4+ T helper subset, termed Th17 cells, regresses large melanoma tumors when infused into mice and this immunity is partially dependent upon host B cells. Our mechanistic studies, aimed to understand the relationship between infused Th17 cells and host B cells, will allow us to harness these pathways to elicit robust anti-tumor immune responses in patients in future clinical trials.

PI_NAMEs: COLE, ANNA CAMILLE ELYSE (contact)

PROGRAM_OFFICER_NAME: PURI, ANU

PROJECT_TERMS: Ablation;activation-induced cytidine deaminase;Address;Adoptive Transfer;Animals;anti-tumor immune response;Antibodies;antibody transfer;Antigen Presentation;Antigens;Antitumor Response;B cell differentiation;B Cell Proliferation;B-Lymphocytes;Biological Assay;Biological Markers;Blinking;cancer cell;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;Cell Maturation;Cell secretion;Cell Survival;Cell Therapy;Cells;clinical application;Clinical Trials;Coculture Techniques;Cues;cytokine;cytotoxicity;Development;draining lymph node;empowerment;Engraftment;Event;experience;Exposure to;Fostering;Future;gene induction;IL17 gene;immune checkpoint blockade;Immunity;Immunoglobulin Class Switching;Impairment;improved;In Vitro;Individual;Inflammatory;insight;Interferon Type II;interleukin-21;interleukin-21 receptor;Investigation;Malignant Neoplasms;Mediating;Melanoma;Melanoma Tumor;Metastatic Neoplasm to the Lung;Mus;nano-string;novel therapeutics;Paper;Pathway interactions;Patients;Play;Production;Proliferating;Relapse;Reporting;response;Role;self-renewal;Signal Transduction;Solid Neoplasm;synergism;T cell therapy;T-Lymphocyte;Testing;Time;TNFSF5 gene;transcription factor;Treatment Failure;tumor;Tumor Escape;tumor growth;Tumor Immunity;unpublished works;Work

PROJECT_TITLE: Mechanism underlying how host B cells empower adoptively transferred Th17 cells with durable tumor immunity

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F09C-Z (20)]


NIH_SPENDING_CATS: Autoimmune Disease;Cancer;Digestive Diseases;Immunotherapy;Inflammatory Bowel Disease

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

PHR: Project Narrative Immune checkpoint inhibitor (ICI) induced diarrhea and colitis represents a significant clinical problem, affects up to 40% of immunotherapy patients. Our proposal aims to characterize immune subsets driving ICI-induced colon inflammation and target these populations using drugs that may be advanced to human trials after evaluation in a novel model of concurrent colitis and malignancy. We expect our research to identify and advance rational targeted therapies modulating immune cells in ICI-colitis, ultimately leading to improved treatment regimens to mitigate ICI-colitis while preserving ICI-mediated anti-tumor immunity.

PI_NAMEs: MANN, JACQUELINE  (contact)

PROGRAM_OFFICER_NAME: JAKOWLEW, SONIA B

PROJECT_TERMS: Address;Affect;Aftercare;Animal Model;anti-CTLA-4 therapy;anti-PD-1;Antigens;Antitumor Response;Autologous;Automobile Driving;Biopsy;Blood;Blood specimen;cancer care;Cancer Patient;CD8B1 gene;Cell Communication;Cell Physiology;cell type;Cells;checkpoint therapy;Circulation;Clinical;Clone Cells;Coculture Techniques;cohort;Colitis;Colon;Colonic inflammation;Colonic Neoplasms;CTLA4 gene;Cytotoxic T-Lymphocytes;Data;design;Development;Diarrhea;Disease;Drug Targeting;Drug usage;effector T cell;Epithelium;Evaluation;experience;Gene Expression;Goals;Homing;Human;Immune;Immune checkpoint inhibitor;Immune response;immune-related adverse events;immunomodulatory therapies;immunoregulation;Immunosuppression;Immunosuppressive Agents;Immunotherapy;improved;Infiltration;Inflammation;Inflammatory Bowel Diseases;infliximab;insight;Intervention;Malignant Neoplasms;Mediating;Modeling;Molecular;mouse model;Mucous Membrane;Mus;neoplastic cell;novel;Organoids;Pathogenesis;Patients;Pharmaceutical Preparations;Phenotype;Population;Portraits;pre-clinical;Pre-Clinical Model;Preclinical Drug Evaluation;preservation;Prevention;programmed cell death protein 1;prospective;Quality of life;rational design;recruit;Regimen;Reporting;Research;Resolution;response;Role;Sampling;secondary lymphoid organ;Selection for Treatments;Site;Specificity;survival outcome;Symptoms;T cell infiltration;T-cell receptor repertoire;T-Lymphocyte;T-Lymphocyte Subsets;Target Populations;targeted treatment;Testing;Therapeutic;Tissues;Toxic effect;trafficking;transcriptome;translational potential;Treatment Protocols;treatment response;tumor;Tumor Cell Line;Tumor Immunity;tumor progression;Validation;Withdrawal

PROJECT_TITLE: Investigating mechanisms of pathogenesis and treatment response in immune checkpoint inhibitor induced colitis


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

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: NARRATIVE We previously discovered that a large insertion in intron 32 of TAF1 is functionally associated with intron retention and alternative splicing in the disease X-linked dystonia parkinsonism (XDP) and that there are protein aggregates in XDP postmortem brain. In this renewal, we will determine whether these signatures can be ameliorated by treating with antisense oligonucleotides, including if the treatment has an impact on the clearance of protein aggregates from cultures of neurons and glia. This endeavor will clarify the disease mechanism and inform future genetic therapy for XDP and many other neurodegenerative diseases with which XDP has commonalities, such as Alzheimer’s Disease, Parkinson’s Disease, and Huntington’s Disease.

PI_NAMEs: BRAGG, DAVID CRISTOPHER;LAGIER-TOURENNE, CLOTILDE ;TALKOWSKI, MICHAEL E (contact)

PROGRAM_OFFICER_NAME: SIEBER, BETH-ANNE

PROJECT_TERMS: Affect;Age;Alternative Splicing;Alzheimer's Disease;Animals;Antisense Oligonucleotide Therapy;Antisense Oligonucleotides;Atrophic;Autopsy;Basal Ganglia;Basal Ganglia Diseases;Biochemical;Biological Assay;Brain;Brain imaging;Brain region;brain tissue;causal variant;Cell model;Cell Survival;cell type;Cells;Characteristics;Clustered Regularly Interspaced Short Palindromic Repeats;Coculture Techniques;Corpus striatum structure;Coupled;CRISPR-mediated transcriptional activation;cytokine;Data;Defect;Disease;Dystonia;Electron Microscopy;Excision;Functional disorder;functional genomics;Funding;Future;Gene Expression Profile;gene therapy;Genes;Genetic;genetic architecture;Genetic Transcription;Genome;genome editing;Genomics;Global Change;Grant;Haplotypes;Huntington Disease;Image;Immunofluorescence Immunologic;In Situ Hybridization;Induced Neurons;induced pluripotent stem cell;Induced pluripotent stem cell derived neurons;Inflammation;Inflammatory;innovation;insight;Introns;Iron;Lead;Length;male;Maps;Mass Spectrum Analysis;Mediating;Mediator;Mendelian disorder;Methods;Microglia;Minisatellite Repeats;Modeling;Molecular;molecular pathology;Molecular Profiling;Monitor;Mutation;Nerve Degeneration;nerve stem cell;Nervous System;Neurodegenerative Disorders;Neuroglia;neuroinflammation;neuron loss;Neurons;neuropathology;new technology;Onset of illness;Parkinson Disease;Parkinsonian Disorders;Pathogenesis;Pathogenicity;Pathologic;Pathology;Pathway interactions;Patients;Pattern;Phagocytosis;Phenotype;Philippines;Post-Translational Protein Processing;potential biomarker;programs;protein aggregation;proteostasis;Reporter;Repression;Research Personnel;Resources;response;Retroelements;Retrotransposon;RNA Splicing;Role;Sampling;Series;single-cell RNA sequencing;Specificity;Stimulus;Structure;superresolution imaging;Surveys;Symptoms;TAF1 gene;targeted treatment;tau aggregation;tau Proteins;Tauopathies;Technology;Testing;Therapeutic;Tissues;Titrations;Toxic effect;Transcript;transcriptome;transcriptomics;treatment effect;Ubiquitin;X-linked dystonia parkinsonism

PROJECT_TITLE: Assembling the Genetic Architecture of X-linked Dystonia Parkinsonism

STUDY_SECTION: TAG

STUDY_SECTION_NAME: Therapeutic Approaches to Genetic Diseases Study Section[TAG]


NIH_SPENDING_CATS: Breast Cancer;Cancer;Eye Disease and Disorders of Vision;Genetics;Neurosciences;Pediatric;Pediatric Cancer;Rare Diseases;Women's Health Research

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: Project Narrative The retinoblastoma (Rb) tumor suppressor is a negative regulator of cellular proliferation that is inactivated through phosphorylation by the cyclin-dependent kinases 4 and 6 (Cdk4/6). Very little is known about additional mechanisms that inactivate Rb and therefore dictate its functional properties. This project will investigate how the ubiquitin-mediated degradation of Rb controls normal cell cycle progression and therapeutic response to Cdk4/6 inhibitors in the context of breast cancer, and my findings will broaden our overall understanding of how Rb’s tumor suppressive functions are regulated.

PI_NAMEs: APONTE, AMY  (contact)

PROGRAM_OFFICER_NAME: ADAMS, GREGORY

PROJECT_TERMS: Address;Affect;Binding;Biochemical;Biological;Biological Assay;Breast Cancer Cell;Cancer Biology;Carcinoma;CDK4 gene;Cell Culture Techniques;Cell Cycle;Cell Cycle Arrest;Cell Cycle Progression;Cell Cycle Regulation;Cell Line;Cell Proliferation;Cells;Cellular biology;Clinical;clinically relevant;Co-Immunoprecipitations;CRISPR/Cas technology;Cyclin-Dependent Kinases;Data;design;DNA;DNA biosynthesis;DNA Tumor Viruses;Engineering;ERBB2 gene;experience;Family;FDA approved;Flow Cytometry;fluorescence imaging;Fluorescence-Activated Cell Sorting;G1 Phase;Gene Activation;gene repression;Genes;Genetic;Goals;hormone receptor-positive;hormone therapy;Human;imaging approach;improved;In Vitro;in vivo;inhibitor;Link;live cell imaging;Malignant Breast Neoplasm;Malignant Neoplasms;Mass Spectrum Analysis;Mediating;Metastatic breast cancer;Modeling;multicatalytic endopeptidase complex;mutant;Normal Cell;novel;Oncoproteins;Pathway interactions;patient subsets;Patients;Pattern;Pharmaceutical Preparations;Pharmacotherapy;Phosphorylation;Physiology;Play;prevent;Proliferating;Property;protein degradation;protein expression;protein purification;Proteins;Recurrence;Regulation;Resistance;response;Retinoblastoma;retinoblastoma pathway;Retinoblastoma Protein;retinoblastoma tumor suppressor;Role;Signal Transduction;Stains;success;System;Systems Biology;Testing;therapy resistant;tool;Training;transcription factor;Transcriptional Activation;treatment response;tumor;Tumor Suppressor Proteins;Ubiquitin;ubiquitin ligase;Ubiquitination

PROJECT_TITLE: Regulation of the retinoblastoma (Rb) tumor suppressor by the ubiquitin-proteasome system

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F05-D (21)]


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Orphan Drug;Rare Diseases;Tuberculosis

ORG_CITY: Newark

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

PHR: PROJECT NARRATIVE Novel drugs for the treatment of tuberculosis that are capable of shortening treatment duration, treating drug- resistant infection, and preventing the rise of further resistance are urgently needed. Our proposed research will harness Mycobacterium tuberculosis amidases to activate amide prodrugs, thereby identifying prodrugs that are activated by several amidases and yielding novel, pyrazinoic acid-releasing amides that can restore pyrazinamide-like activity in pyrazinamide-resistant strains. In doing so, this work will demonstrate a novel approach to drug discovery that enables the design of prodrugs that can treat drug-resistant disease and have extremely high barriers to resistance.

PI_NAMEs: KODALI, SWETHA  (contact)

PROGRAM_OFFICER_NAME: MENDEZ, SUSANA

PROJECT_TERMS: amidase;Amides;Amines;Antitubercular Agents;Bacteria;bacterial metabolism;Carboxylic Acids;Cause of Death;cell envelope;Cells;chemical genetics;Clinical;Communicable Diseases;design;Development;Disease;Disease Resistance;Drug Compounding;drug development;drug discovery;Drug resistance;Drug resistant Mycobacteria Tuberculosis;Drug usage;Environment;Enzyme Kinetics;Enzymes;experience;Expression Library;Future;Generations;Genes;global health;Hydrolysis;hydrophilicity;Hydrophobicity;Individual;Infection;Infectious Agent;Knowledge;Libraries;Link;Lipids;Mediating;medical schools;Metabolism;Mutation;Mycobacterium tuberculosis;New Jersey;novel;novel strategies;novel therapeutics;overexpression;Parents;Pathway interactions;Penetration;Pharmaceutical Preparations;Physicians;Prevalence;prevent;Prodrugs;programs;Proteins;public health research;Pyrazinamide;Pyrazinamide resistance;pyrazinoic acid;Regimen;Research;Research Institute;Research Personnel;Resistance;Resistance development;resistant strain;Scientist;small molecule;small molecule libraries;Specificity;Techniques;Training;treatment duration;Tuberculosis;tuberculosis drugs;tuberculosis treatment;Work

PROJECT_TITLE: Harnessing Amide Linkers for Antitubercular Drug Development


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

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

PHR: Project Narrative Although Clostridioides difficile is an important human pathogen, relatively little is known about how basic transcription processes regulate virulence and pathogenesis. This research will determine how Rho and Nus factors dependent termination regulates C. difficile virulence, sporulation, and pathogenesis. The results will expand our understanding of the diverse functions of these well-conserved bacterial transcription elongation and termination factors and potentially reveal new avenues for the development of C. difficile treatment strategies.

PI_NAMEs: PLASKON, DYLAN  (contact)

PROJECT_TERMS: 5' Untranslated Regions;Amino Acids;Anaerobic Bacteria;Antibiotic Resistance;Antibiotics;antitermination;ATP phosphohydrolase;Attenuated;Bacteria;Base Sequence;Binding Sites;Biochemical;Biological Assay;Biology;C-terminal;career development;Cell Wall;Cessation of life;Charge;Clostridium difficile;combat;comparative;comparison control;Consensus;Consensus Sequence;CRISPR interference;Data;Defect;Deletion Mutation;Development;Diarrhea;DNA-Directed RNA Polymerase;Elongation Factor;Environment;environmental change;functional restoration;Gene Expression;Gene Expression Regulation;gene repression;Genes;Genetic;genetic approach;Genetic Complementation Test;genetic element;genetic manipulation;Genetic Transcription;Genome;Goals;Growth;Guanine + Cytosine Composition;Heterogeneity;Hospitals;human pathogen;Immunology;improved;In Vitro;Infection;Investigation;knock-down;Laboratories;Maps;Mediating;Methods;Microbiology;Modeling;Motility;mouse model;mutant;Mutation;N-terminal;North Carolina;Operon;opportunistic pathogen;Organism;Outcome;pathogen;Pathogenesis;pathogenic bacteria;Phenotype;Physiology;Play;Population;prevent;Process;Productivity;Pseudomembranous Colitis;Publishing;recombinase;Regulation;Reporting;Repression;Reproduction spores;Research;rho;Rho Factor;RNA Recognition Motif;Role;Sigma Factor;Site;Symptoms;Techniques;termination factor;Therapeutic;Thick;Toxin;Training;Transcript;Transcription Process;transcription termination;Transcriptional Elongation Factors;transcriptome;transcriptome sequencing;treatment strategy;Universities;Virulence;Virulence Factors;virulence gene

PROJECT_TITLE: Rho dependent regulation of Clostridioides difficile virulence

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F07A-B (20)]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Orphan Drug;Rare Diseases

ORG_CITY: WORCESTER

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

PI_NAMEs: AZZOLINO, VINCENT  (contact)

PROGRAM_OFFICER_NAME: DAVIS, MINDY I

PROJECT_TERMS: 3-Dimensional;Active Sites;acute flaccid myelitis;Affect;Affinity;Anti-viral Agents;Binding;Biological Assay;Case Study;Caspase;Cessation of life;Child;Clinical;Cocrystallography;Common Cold;Complex;Computational Technique;Consensus;Crystallization;Data;Defect;design;Development;Disease Outbreaks;Drug Design;Drug resistance;Drug Targeting;emerging pathogen;Encephalitis;Enterovirus;Enterovirus 68;Enzyme Inhibition;Enzyme Interaction;enzyme substrate;Enzymes;experience;Family;Family Picornaviridae;fitness;Fluorescence;Fluorescence Resonance Energy Transfer;functional group;Future;global health;Goals;Hand, Foot and Mouth Disease;Healthcare Systems;Hepatitis;Incidence;Infection;inhibitor;insight;Molecular;Mutation;Myocarditis;nanomolar;Neurologic;Neurologic Deficit;novel;Paralysed;Patients;Peptide Hydrolases;Pharmaceutical Preparations;Physicians;Poliomyelitis;Polyproteins;Predisposition;promote resilience;Protease Inhibitor;Public Health;Research;resilience;Resistance;resistance mutation;respiratory;Respiratory Disease;RNA Viruses;scaffold;Scientist;Severities;Site;small molecule;small molecule inhibitor;Spinal cord grey matter structure;structural biology;Structure;Substrate Specificity;Testing;Training;trend;United States;United States Food and Drug Administration;Viral;Virus;Virus Inhibitors;Visualization;Work

PROJECT_TITLE: Characterization of Enterovirus 68 3C Protease For the Development of Robust and Potent Direct-Acting Antiviral Inhibitors

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


NIH_SPENDING_CATS: Bioengineering;Contraception/Reproduction;Infertility;Pregnancy;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Embryonic - Human

PHR: Project Narrative: Early pregnancy loss can be a devastating outcome for people with the ability to become pregnant, and nearly two-thirds of all losses occur prior to and around the time of implantation. Extrapolation of data from animal models of implantation is challenging at this stage owing to the lack of knowledge regarding conservation or divergence of these mechanisms across key mammalian species. Through understanding how morphogen and mechanical cues via WNT/β-catenin signaling orchestrate correct embryo development at this period across species, we will be able to confidently extrapolate data from animal models towards human health applications to better understand the root causes of pregnancy loss.

PI_NAMEs: ABEL, ASHLEY  (contact)

PROGRAM_OFFICER_NAME: JOHNSTON, DANIEL STEPHEN

PROJECT_TERMS: 3-Dimensional;Actins;Address;Affect;animal data;Animal Model;Animals;Apical;Architecture;Automobile Driving;beta catenin;Biological Assay;Biomechanics;Biomedical Engineering;Cell Aggregation;Cell Communication;Cell surface;Cells;clinically relevant;Comprehension;Conceptions;Coupled;Cues;Data;Development;Dimensions;Disease;Drops;early pregnancy;early pregnancy loss;Embryo;Embryo Research;embryo tissue;Embryonic Development;Epiblast;Epithelium;experimental study;ezrin;Fertilization;Fetus;Fibrosis;fluorescence lifetime imaging;Future;gene network;Goals;Health;health application;Heterogeneity;high resolution imaging;Human;Human Development;human embryonic development;Image;Image Analysis;imaging software;Immunofluorescence Immunologic;implantation;In Vitro;in vivo;insight;interest;Investigation;knock-down;Knowledge;Lead;Ligands;Link;live cell imaging;loss of function;Malignant Neoplasms;Mammals;mechanical signal;Mechanics;Membrane;model development;Modeling;moesin;Molecular;Morphogenesis;morphogens;Morphology;Mus;nonhuman primate;novel;Nuclear;Osmosis;Outcome;Pathologic;Persons;Phosphorylation;Pluripotent Stem Cells;Pregnancy loss;pregnant;Process;Proteins;Proxy;radixin protein;receptor;Regulation;Reporter;Reproducibility;Research;Rodent;Role;self organization;Shapes;Signal Transduction;Species Specificity;spheroids;Spontaneous abortion;stem cell model;Surface Tension;Suspensions;Techniques;Testing;Time;Tissues;transcriptomics;Translating;Western Blotting;Work

PROJECT_TITLE: Multispecies investigation of early pregnancy loss mechanisms using bioengineered stem cell models


ADMINISTERING_IC: MD

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Prevention;Primary Health Care;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: DURHAM

ORG_NAME: DUKE UNIVERSITY

PHR: Relevance to Public Health: Black patients receive lower quality healthcare than their White counterparts. This study will develop a measure to identify structures and processes within primary care practices that may either contribute to these disparities or improve equitable care for Black patients.

PI_NAMEs: JOHNSON, KIMBERLY S. (contact)

PROGRAM_OFFICER_NAME: WHITE, DOLLY PENN

PROJECT_TERMS: Accounting;Address;Adherence;Adult;Affect;Area;black patient;Black Populations;Black race;black/white disparity;blood pressure control;care providers;Caring;Centers for Disease Control and Prevention (U.S.);Chronic Disease;Clinic;clinical practice;cognitive interview;Collaborations;colon cancer screening;Communication;cost;cultural competence;Data;design;diabetes control;Discrimination;Disease;Disparity;disparity reduction;Education;Effectiveness;Electronic Health Record;Equity;evidence base;Glycosylated hemoglobin A;Goals;Health;Health behavior;health belief;health care disparity;health care quality;health care settings;health data;health determinants;Health Disparities Research;health disparity;health equity;health equity promotion;health inequalities;health outcome disparity;Health Personnel;Health Services Accessibility;Health system;Healthcare;Healthcare Systems;implicit bias;improved;Income;Inequity;Infrastructure;Institutional Racism;Insurance;Intervention;Interview;Intuition;Measures;Methods;minority health;minority health disparity;Minority Health Research;minority patient;Not Hispanic or Latino;Outcome;Patients;Policies;poor health outcome;practice setting;practice-based research network;Prevention;Primary Care;primary care clinic;primary care practice;primary care setting;Process;Property;Provider;provider factors;Psychometrics;Public Health;Qualitative Methods;racial disparity;racial diversity;Racial Equity;racism;Research;residential segregation;response;Review Literature;Role;screening;Screening for cancer;social health determinants;Standardization;Structural Racism;Structure;Surveys;Testing;Variant

PROJECT_TITLE: Measuring Racial Equity and Institutional Racism in Primary Care (EQUIP)

STUDY_SECTION: HHD

STUDY_SECTION_NAME: Healthcare and Health Disparities Study Section[HHD]


NIH_SPENDING_CATS: Cancer;Colorectal Cancer;Digestive Diseases;Genetics;Immunotherapy;Prevention;Sleep Research

ORG_CITY: IRVINE

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

ORG_STATE: CA

PHR: PROJECT NARRATIVE The incidence of early-onset CRC has been increasing at an alarming rate. Concurrently, younger populations experience circadian clock disruption through exposure to light-at-night and erratic sleep/wake and feeding/fasting patterns. The goal of this proposal is to define the complex connection between circadian clock disruption, immunity and CRC pathogenesis which will provide critical evidence for CRC prevention and treatment.

PI_NAMEs: FORTIN, BRIDGET  (contact)

PROJECT_TERMS: Acceleration;Address;Affect;Age;aged;ARNTL gene;Beds;Biological Assay;Blood Circulation;c-myc Genes;cancer diagnosis;cancer initiation;cancer prevention;cancer risk;cancer therapy;Carcinogens;Cell Line;Cell Physiology;Cells;chemokine;ChIP-seq;Circadian Dysregulation;circadian pacemaker;circadian regulation;Circadian Rhythms;Colon Carcinoma;Colorectal Cancer;colorectal cancer prevention;Complex;cytokine;cytotoxic CD8 T cells;Data;Devices;Disease;disorder prevention;early onset colorectal cancer;Eating;Environment;Environmental Risk Factor;Enzyme-Linked Immunosorbent Assay;epidemiologic data;Epithelium;experience;Exposure to;Fasting;feeding;Flow Cytometry;Genes;Genetic;Genetic Models;Genetic Predisposition to Disease;Genetic Transcription;Goals;high risk;Homeostasis;Hour;Human;Immune;Immune response;Immune system;Immunity;Immunosuppression;Impairment;improved;in vivo;Incidence;Individual;Infection;Inflammation;Inflammatory;Inflammatory Response;International Agency for Research on Cancer;intestinal epithelium;intestinal homeostasis;intestinal tumorigenesis;Intestines;knock-down;Knowledge;Life Style;Light;Link;Lymphoid Cell;Malignant Neoplasms;Mediating;Melatonin;Modeling;Modernization;Molecular;Monoclonal Antibodies;monocyte;Myeloid Cells;Myeloid-derived suppressor cells;Names;Older Population;Organoids;Outcome;Pathogenesis;Pathway interactions;Patients;Pattern;Periodicity;permissiveness;pharmacologic;Phenotype;Population;Prevention strategy;Probability;Rectal Cancer;Reporting;Research;Risk Factors;Role;screening;shift work;Signal Pathway;single-cell RNA sequencing;Sleep;Sleep disturbances;sleep quality;Societies;Sorting;systemic inflammatory response;T-Lymphocyte;Technology;Time;Tissues;trafficking;trend;Tumor Immunity;tumor progression;tumor-immune system interactions;tumorigenesis;United States;WNT Signaling Pathway;Work;young adult

PROJECT_TITLE: Clock Disruption Accelerates Colorectal Cancer and Promotes Immunosuppression


NIH_SPENDING_CATS: Cardiovascular;Congenital Heart Disease;Congenital Structural Anomalies;Heart Disease;Neurodegenerative;Pediatric;Rare Diseases

ORG_DEPT: PEDIATRICS

PHR: Project Narrative Congenital heart disease is a major cause of illness in newborns and children. While studying a gene that may cause congenital heart disease, we discovered how cells use energy could affect the type of cell that forms. Our work seeks to understand how a cell uses energy and changes its behavior and fate.

PI_NAMEs: JONAS, ELIZABETH ANN;KHOKHA, MUSTAFA K (contact)

PROGRAM_OFFICER_NAME: MUKHOPADHYAY, MAHUA

PROJECT_TERMS: Affect;Amphibia;antagonist;ATP phosphohydrolase;Behavior;beta catenin;blastocyst;Bone Morphogenetic Proteins;Cardiac;Cell Communication;cell type;Cells;Child;Citric Acid Cycle;congenital heart abnormality;Consumption;Data;Defect;Disease;Dorsal;Electron Transport;Embryo;Embryonic Development;Enzymes;experimental study;Gene Expression;Genes;Genetic Transcription;Growth Factor;HIF1A gene;Hypoxia;Inner mitochondrial membrane;Investigation;Left;Leigh Disease;loss of function mutation;Measures;Membrane;Mesoderm Cell;Metabolic;Metabolic Pathway;Metabolism;Mitochondria;Mitochondrial Diseases;mitochondrial metabolism;Modeling;Neurons;Newborn Infant;overexpression;Oxygen;Oxygen Consumption;Patients;Pattern;permissiveness;Process;Production;Protons;Rana;Reactive Oxygen Species;Role;Running;sensor;Side;Signal Pathway;Signal Transduction;Site;Situs Inversus;Specific qualifier value;Spemann's Organizer;Succinates;Testing;Time;Tissues;Traction;Translations;Visit;WNT Signaling Pathway;Work;Xenopus

PROJECT_TITLE: Regional specific metabolism regulates specification of the Spemann Organizer

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 CDB-B (02)]


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

PHR: PROJECT NARRATIVE APOBEC3 enzymes play a crucial role in several biological events in relation to innate and adaptive immune responses. The upregulation of APOBEC3A and APOBEC3B in urothelial carcinoma warrants further investigation and a direct comparison to determine the source of APOBEC3 induced somatic mutations in this cancer type. The studies outlined in this proposal will identify the source of APOBEC3 induced mutagenesis in urothelial carcinoma.

PI_NAMEs: STURDIVANT, MICHAEL SEAN (contact)

PROJECT_TERMS: Accounting;adaptive immune response;Address;amino group;anti-PD1 therapy;Automobile Driving;Bar Codes;Biological;Cancer cell line;cancer type;CD8-Positive T-Lymphocytes;Cell Death;Cell Line;Cells;Cessation of life;checkpoint inhibition;Clonal Evolution;Clonality;Combined Modality Therapy;Cytidine Deaminase;Cytosine deaminase;Cytosine Nucleotides;Deaminase;Dimethyl Sulfoxide;Disease Progression;DNA;Doxycycline;Enzymes;Epitopes;Event;Evolution;Excision;exhaustion;exome sequencing;Experimental Models;experimental study;Family;Genomic Instability;Genomics;Homologous Gene;Human;immune checkpoint blockade;Immunocompetent;Immunotherapy;improved;in vitro Assay;in vivo;inducible gene expression;Innate Immune Response;Investigation;Malignant neoplasm of urinary bladder;Malignant Neoplasms;member;men;Modality;Modeling;Monitor;Mus;Muscle;muscle invasive bladder cancer;Mutagenesis;Mutation;neoplastic cell;overexpression;Patients;Play;Point Mutation;Population;Prevalence;Proliferating;Protein Inhibition;Proteins;Refractory;Resistance;resistance mechanism;response;Role;Somatic Mutation;Source;Survival Rate;System;Technology;therapeutic target;therapy resistant;Time;Transitional Cell Carcinoma;treatment response;tumor;tumor exome;tumor heterogeneity;tumor microenvironment;tumor-immune system interactions;United States;Up-Regulation;Uracil;Urinary tract;Woman;Work

PROJECT_TITLE: The Mutagenic Effects of APOBEC3A and APOBEC3B in Urothelial Carcinoma

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F09A-R (20)]