NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Digestive Diseases;Food Allergies;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Nutrition;Pediatric;Prevention;Social Determinants of Health

ORG_CITY: WASHINGTON

ORG_NAME: CHILDREN'S RESEARCH INSTITUTE

ORG_STATE: DC

PHR: PROJECT NARRATIVE Daily adherence to food allergen avoidance and emergency preparedness is challenging particularly during early adolescence. The Food Allergy Mastery (FAM) Program is a novel behavioral intervention that is developed to equip youth with food allergy knowledge and self-management skills, bolster their food allergy-related problem- solving, social skills, and social support, and attenuate food allergy anxiety. We expect this program will increase the likelihood that youth will engage in appropriate food allergy self-management, improve quality of life, and ultimately, reduce risk for anaphylaxis.

PI_NAMEs: HERBERT, LINDA JONES (contact)

PROGRAM_OFFICER_NAME: SUBRAMANIAN, HARIHARAN

PROJECT_TERMS: acceptability and feasibility;Accidents;Address;Adherence;Adolescence;Adolescent;Affect;Age;Allergens;Allergic Reaction;Anaphylaxis;Anxiety;anxiety management;arm;Assertiveness;Asthma;Attenuated;Award;Baltimore;Behavior;Behavior Therapy;bullying;care systems;Caregivers;Child Health;Chronic Disease;Clinical;Communication;comorbidity;critical developmental period;Development;early adolescence;Early Intervention;Eating;Education;Emergency Care;emergency preparedness;Emergency Situation;Emergency treatment;Epinephrine;Ethnic Origin;Evaluation;evidence base;executive function;experience;Exposure to;Focus Groups;follow-up;Food;food allergen;Food Hypersensitivity;Food Safety;Fright;group intervention;Health behavior;health care service utilization;health disparity;Health Professional;high risk;high risk population;Home;improved;Ingestion;Intervention;Knowledge;Knowledge Management;Life;mental training;Minor;National Institute of Allergy and Infectious Disease;novel;Outcome;Parents;Participant;Patients;peer;peer support;Pilot Projects;Population;prevent;primary caregiver;Probability;Problem Solving;programs;psychosocial;Quality of life;Race;Randomized;Reporting;Research;Research Project Grants;Risk;Risk Reduction;Self Efficacy;Self Management;self-management program;skills;social skills;Social support;socioeconomics;Stress;Training;treatment as usual;treatment response;United States;Variant;Visit;Work;young adult;Youth

PROJECT_TITLE: Evaluation of a Behavioral Intervention to Promote Food Allergy Self-Management Among Early Adolescents

STUDY_SECTION: LCBH

STUDY_SECTION_NAME: Lifestyle Change and Behavioral Health Study Section[LCBH]


ADMINISTERING_IC: DC

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Assistive Technology;Bioengineering;Clinical Research;Clinical Trials and Supportive Activities;Hearing Loss;Neurosciences;Pediatric;Rehabilitation

ORG_CITY: NASHVILLE

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: NARRATIVE There is a rapidly growing population of adult and pediatric cochlear implant (CI) recipients with acoustic hearing preservation in the implanted ear(s) allowing for combined Electric and binaural Acoustic Stimulation (EAS). Despite the rapid technological and surgical advancements that have led to this increased prevalence, there is limited research on EAS outcomes—particularly for pediatric EAS listeners—including the expected trajectory of benefit following EAS fitting and underlying mechanisms driving benefit in EAS users of all ages. The purpose of this project is to provide a comprehensive description of behavioral and electrophysiologic measures of binaural hearing in adults and children both with normal hearing and EAS users.

PI_NAMEs: GIFFORD, RENE H (contact)

PROGRAM_OFFICER_NAME: KING, KELLY ANNE

PROJECT_TERMS: Acceleration;Acoustic Stimulation;Acoustics;Acute;Adolescence;Adult;Age;Audiology;Auditory;Auditory area;Auditory Evoked Potentials;Auditory system;Automobile Driving;Behavioral;Benchmarking;Bilateral;Binaural;binaural hearing;Brain Stem;Child;Childhood;Chronic;Chronology;Clinical;clinical application;Clinical Management;clinical translation;Clinical Trials;Cochlear implant procedure;Cochlear Implants;Complex;Contralateral;Cues;Data;deaf;Development;Devices;Diffuse;Ear;Electric Stimulation;Electrodes;Electrophysiology (science);Environment;evidence based guidelines;Exhibits;Frequencies;Hearing;Hearing Aids;hearing impairment;hearing preservation;Implant;improved;Inherited;innovation;insight;Intervention;Intervention Studies;Investigation;Knowledge;longitudinal design;Low Frequency Deafness;Measures;Mediating;Mediation;Modality;neural;Noise;normal hearing;novel;Operative Surgical Procedures;Outcome;Performance;Phase;Population;Positioning Attribute;Prevalence;Process;Recommendation;Research;Research Activity;Resolution;response;Scientist;Sensorineural Hearing Loss;Space Perception;Speech;Speech Discrimination;speech recognition;System;Techniques;Technology;Time;Weight;With laterality

PROJECT_TITLE: Binaural cue sensitivity in children and adults with combined electric and acoustic stimulation


ADMINISTERING_IC: ES

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

ORG_CITY: NEW YORK

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

ORG_STATE: NY

PHR: PROJECT NARRATIVE Replication stress is a fundamental step and an early driver of tumorigenesis and has been associated with many activated oncogenes. The goal of this study is to define the molecular events that govern the early changes to DNA replication initiation and termination across the genome during oncogene activation. Deciphering the mechanisms that contribute to oncogene-induced replication stress may provide new avenues for targeted cancer treatment.

PI_NAMEs: HUANG, TONY TUNG (contact)

PROGRAM_OFFICER_NAME: SHAUGHNESSY, DANIEL

PROJECT_TERMS: Acceleration;Address;Affect;Biological;biological adaptation to stress;Cancer cell line;cancer therapy;carcinogenesis;Carcinogens;CCNE1 gene;Cell Physiology;Cells;Characteristics;Chromosome Breakage;Codon Nucleotides;Deceleration;deprivation;Development;DNA;DNA biosynthesis;DNA Damage;DNA replication fork;DNA-Directed DNA Polymerase;Ensure;Environment;Event;Future;Gene Amplification;Genes;Genetic Transcription;Genome;genome integrity;genome-wide;Genomic Instability;Genomics;genotoxicity;Goals;Head;Human;In Vitro;in vitro Model;innovation;Investigation;Knowledge;Malignant Neoplasms;Modeling;Molecular;Mutagens;nucleotide metabolism;Nucleotides;Oncogene Activation;Oncogenes;Oncogenic;Ovarian Serous Adenocarcinoma;overexpression;Pathway interactions;Physiological;Play;Point Mutation;Polyadenylation;premalignant;Premalignant Cell;prevent;Probability;Process;programs;Proto-Oncogenes;recruit;Regulation;Replication Initiation;replication stress;Reporting;Research;response;restraint;RNA Polymerase II;Role;Shapes;Site;Source;Speed;Techniques;Testing;Time;Transcription Initiation Site;Translating;Tumor Suppressor Genes;tumorigenesis

PROJECT_TITLE: Defining the molecular basis of oncogene-induced replication stress

STUDY_SECTION: CE

STUDY_SECTION_NAME: Cancer Etiology Study Section[CE]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: IRVINE

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

ORG_STATE: CA

PHR: Radiation therapy is one of the most common treatments for cancer. Upon conclusion, we will translate a new in vivo dosimeter prototype into a workable tool for radiation therapy dose monitoring based on an academic-Industrial partnership between University of Oklahoma (OU) and PhotoSound Technologies Inc. The technological advances in using dual modal X-ray-induced Acoustic Computed tomography (XACT) and ultrasound imaging for in vivo dosimetry will decrease radiation treatment toxicity and improve clinical outcomes for cancer patients.

PI_NAMEs: CHEN, YONG ;IVANOV, VASSILI ;XIANG, LIANGZHONG SHAWN (contact)

PROGRAM_OFFICER_NAME: TATA, DARAYASH B

PROJECT_TERMS: 3-Dimensional;absorption;Acoustics;Award;California;Cancer Patient;cancer therapy;Cause of Death;Clinic;Clinical;clinical implementation;clinical translation;common treatment;Computed Tomography Scanners;Computer Simulation;Dedications;design and construction;Detection;detector;Dose;dose information;dosimetry;Electrical Engineering;Elements;Ensure;experience;Feedback;Frequencies;Goals;Health Sciences;Image;imaging capabilities;Imaging Device;imaging system;Imaging Techniques;improved;in vivo;industry partner;innovation;Inpatients;instrumentation;Intellectual Property;Intensity-Modulated Radiotherapy;Intervention;Investigation;Ions;Linear Accelerator Radiotherapy Systems;Location;Malignant Neoplasms;Maps;Measurement;Medical;Modality;Monitor;new technology;novel;Oklahoma;Outcome;Patients;Performance;Photons;Physiologic pulse;Positioning Attribute;product development;Prostate;prototype;Public Health;Radiation;Radiation Dose Unit;Radiation Oncologist;Radiation therapy;Radiometry;real time monitoring;real-time images;Recording of previous events;Research;Resolution;Roentgen Rays;Safety;Shapes;Signal Transduction;simulation;soft tissue;Speed;success;System;Techniques;Technology;temporal measurement;Testing;Time;Tissues;tool;Transducers;Translating;Translations;Treatment-related toxicity;tumor;Ultrasonography;ultrasound;United States National Institutes of Health;Universities;Visualization;Water;Work;X-Ray Computed Tomography

PROJECT_TITLE: Academic-Industry Partnership for the Translation of a 4D in vivo Dosimetry Approach for Radiation Therapy


ED_INST_TYPE: UNIVERSITY-WIDE

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE: OVERALL The Great Lakes Center for Fresh Waters and Human Health at the University of Michigan (UM) is building on five years of successful interdisciplinary collaboration and community engagement to better understand the increasing risks that cyanobacterial harmful algal blooms (cHAB) pose to freshwater ecosystems and human health. This Center, led by a multi-institutional team of biomedical scientists, limnologists and community engagement experts, seeks to advance their work in Lake Erie by characterizing how climate change affects cHAB growth, production and transport of toxins through water and the atmosphere, and impacts public health outcomes, especially for vulnerable populations.

PI_NAMEs: DICK, GREGORY JAMES (contact);KENNEDY, DAVID JOSEPH

PROGRAM_OFFICER_NAME: DZIERLENGA, ANIKA LIN

PROJECT_TERMS: Address;aerosolized;Affect;Ally;Atmosphere;atmospheric modeling;biomedical scientist;Boat;Businesses;Cells;Chronic;climate change;climate impact;Coast Guard;Collaborations;Communication;Communities;community engagement;Community Networks;community science;Complex Mixtures;Core Facility;Coupling;Cyanotoxin;Data;Data Science;design;Development;drinking water;Ecosystem;Enhancement Technology;Ensure;Environment;Event;experience;experimental study;exposed human population;exposure pathway;First Independent Research Support and Transition Awards;Fostering;Fresh Water;Goals;Grant;Great Lakes Region;Growth;harmful algal blooms;Health;Human;Human Resources;hydrodynamic model;innovation;Institution;inter-institutional;interdisciplinary collaboration;Investments;Laboratories;Letters;Light;Methods;Michigan;Modeling;Monitor;multidisciplinary;Multiomic Data;Mus;National Oceanic and Atmospheric Administration;new technology;next generation;Nutrient;Oceans;Ohio;Organ;Outcome;Outcomes Research;Planets;Precipitation;predicting response;Process;Production;programs;Proliferating;Public Health;Public Policy;Recording of previous events;recruit;Research;Research Design;Research Project Grants;Resource Sharing;response;Retirement;Risk;Risk Assessment;Sampling;Science;Scientist;Sea;Structure;Students;synergism;System;Technology;Temperature;Tissues;Toxic effect;Toxin;Training;Translating;Universities;Variant;Vulnerable Populations;Water;Water Supply;waterborne;Work

STUDY_SECTION_NAME: Special Emphasis Panel[ZES1 LKB-K (P)]


NIH_SPENDING_CATS: Climate-Related Exposures and Conditions

PI_NAMEs: DICK, GREGORY JAMES (contact)

PROJECT_TERMS: Advisory Committees;Area;Benchmarking;Budgets;career;Climate;climate change;Collaborations;Communication;Communities;community engagement;Community Outreach;Comparative Study;Core Facility;Data;data dissemination;data management;data sharing;data submission;Databases;design;Dissemination and Implementation;Doctor of Philosophy;Education;Ensure;equity, diversity, and inclusion;Evaluation;Event;experience;Fostering;Fresh Water;fundamental research;Goals;harmful algal blooms;Head;Health;high school;Human;Institution;Interdisciplinary Study;Investigation;Justice;Leadership;Letters;member;Mentors;Metadata;Michigan;Modeling;multidimensional data;multidisciplinary;multiple omics;National Institute of Environmental Health Sciences;next generation;Outcome;outreach;patient engagement;Performance;Policies;Policy Maker;Process;Productivity;Progress Reports;Public Policy;public repository;recruit;Research;Research Activity;Research Infrastructure;Research Personnel;Research Project Grants;Resource Sharing;Resources;Retirement;Risk;Role;Science;Scientist;service coordination;skills;social media;stakeholder perspectives;Students;symposium;Training;Translating;undergraduate student;Universities;Water Supply;web site;Work

PROJECT_TITLE: Admin Core


NIH_SPENDING_CATS: Behavioral and Social Science;Climate-Related Exposures and Conditions;Foodborne Illness;Pediatric;Prevention;Social Determinants of Health

PI_NAMEs: KENNEDY, DAVID JOSEPH (contact)

PROJECT_TERMS: Address;Ally;Area;Award;behavior change;Boat;Businesses;Client;climate change;Clinical Research;Coast Guard;Collaborations;Communication;Communities;community center;community engagement;Community Medicine;community science;Data;Dedications;design;Development;Disparity;Doctor of Philosophy;Economics;Ecosystem;Education;Ensure;Environmental Health;Environmental Medicine;Environmental Risk Factor;Event;experience;Exposure to;Faculty;Fellowship Program;First Generation College Students;Fishes;Fresh Water;Funding;Future;General Population;Goals;Grant;Great Lakes Region;harmful algal blooms;hazard;Health;health equity;health literacy;Health Personnel;Health Professional;high risk population;high school;High School Student;Human;Human Resources;Ice;Ice Cover;Individual;Institution;instrument;interest;Joints;Journalism;Leadership;Learning;learning engagement;literacy;marginalization;marginalized population;Medicine;member;Mentors;Michigan;Minority;Monitor;next generation;Occupational Medicine;Ohio;outreach;patient engagement;Planet Earth;Policies;poor health outcome;prevent;Prevention;Printing;programs;Public Health;recruit;Research;Research Personnel;Research Project Grants;resilience;Resources;Risk;Role;Sampling;Scholarship;Science;Scientist;Sea;service member;social health determinants;sociocultural determinant;STEM field;structural determinants;Students;Surveys;tool;Training;Training Programs;Translational Research;United States National Institutes of Health;Universities;verbal;Veterans;Vulnerable Populations;Water;water testing;Woman;Work;Workforce Development;Writing

PROJECT_TITLE: Community Engagement Core


NIH_SPENDING_CATS: Biotechnology;Climate-Related Exposures and Conditions;Foodborne Illness;Genetics;Human Genome;Lung;Natural Products

PI_NAMEs: WESTRICK, JUDY A (contact)

PROJECT_TERMS: Aerosols;Agriculture;Air;airway inflammation;Anatoxins;Animal Feed;Animals;Area;Award;Carbon;Cell Physiology;Cells;climate change;college;community engagement;Community Health;Core Facility;cost;Cyanotoxin;cylindrospermopsin;Data;data integration;data integrity;Data Scientist;Databases;Dedications;DNA sequencing;Ecosystem;Emerging Technologies;Ensure;Environmental Health;Environmental Science;environmental stressor;experience;Experimental Designs;experimental study;Exposure to;Forestry;Frequencies;Fresh Water;Functional disorder;Genetic;Genomics;harmful algal blooms;Health;Hepatotoxicity;high throughput analysis;high throughput technology;Human;Image;In Vitro;in vivo;Individual;Inhalation;innovation;instrumentation;Laboratories;laboratory experiment;Longevity;Mass Chromatography;Mass Fragmentography;mass spectrometer;mass spectrometric imaging;Mass Spectrum Analysis;Measures;member;metabolomics;Metagenomics;Methodology;Michigan;microcystin;Modeling;Monitor;Mus;Nasal cavity;novel;Nutrient;Ohio;operation;Outcome;Paralysed;Peptides;Pigments;Play;Poisoning;Privatization;Production;Productivity;Research;Research Personnel;Role;sample collection;Sampling;Saxitoxin;secondary metabolite;Services;Shellfish;Source;Structure of parenchyma of lung;Subgroup;Techniques;Technology;Temperature;Tissues;Toxic effect;Toxin;Trachea;Training;transcriptome sequencing;transcriptomics;Universities;Variant;volatile organic compound;Water;water quality;water testing;Work

PROJECT_TITLE: Facility Core


NIH_SPENDING_CATS: Climate-Related Exposures and Conditions;Infectious Diseases;Natural Products;Nutrition

PI_NAMEs: BULLERJAHN, GEORGE S (contact)

PROJECT_TERMS: Address;Aeromonas;Affect;Algae;Algal Blooms;Anatoxins;Attention;bacterial community;benthos;Biology;Biomass;Cell model;Characteristics;Chemicals;Chlorophyll;climate change;climate impact;Communities;Complex;Core Facility;Cyanobacterium;Cyanotoxin;Data;Development;Diatoms;Diffusion;drinking;drinking water;Ecosystem;environmental change;Event;experimental study;extreme weather;Frequencies;Fresh Water;Funding;Gene Expression;Gene Expression Regulation;Great Lakes Region;Green Algae;Growth;Health;Human;In Situ;Inhalation;Irrigation;Klebsiella;Knowledge;lens;Light;Link;Maintenance;Measures;Mediating;Metagenomics;metatranscriptomics;Methods;microbiome;microcystin;Molecular;Monitor;Nutrient;Odors;Oxidative Stress;pathogen;pathogenic bacteria;Penetration;Perception;Personal Satisfaction;Physiologic pulse;Phytoplankton;Plankton;predictive modeling;Process;Production;programs;Recreation;Research;residence;response;Role;sample collection;Sampling;Saxitoxin;secondary metabolite;Severities;Shotguns;Site;stable isotope;Stimulus;Surveys;System;Taste Perception;Techniques;Temperature;Testing;Time;water quality;Water Supply;welfare;Wood material

PROJECT_TITLE: The impact of climate change-driven episodic events on cHAB growth and secondary metabolite production


NIH_SPENDING_CATS: Asthma;Climate-Related Exposures and Conditions;Clinical Research;Lung

PI_NAMEs: HALLER, STEVEN T (contact)

PROJECT_TERMS: 3-Dimensional;absorption;Address;aerosolized;Aerosols;Affect;Airway Disease;airway epithelium;airway inflammation;Alanine;Alveolar;Animals;Apoptosis;Arginine;Asthma;asthma model;asthmatic;Biological;Biological Assay;Blood;Body System;cardiovascular disorder risk;cell growth;Cell Line;Cells;clinically significant;Communities;community engagement;Complex Mixtures;Core Facility;Coughing;Cyanobacterium;Cyanotoxin;Data;Disease;Dose;Dyspnea;Environment;Epithelial Cells;Evaluation;Exhalation;exposed human population;exposure route;Exposure to;Fresh Water;Funding;Gene Expression;General Population;granulocyte;harmful algal blooms;Health;Health Professional;Human;Hypersensitivity;Image;immunotoxicity;In Vitro;Individual;Inflammation;Inflammatory;Inhalation Exposure;Investigation;Kidney;Knowledge;Leucine;Literature;Liver;Lung;lung health;lung injury;Measures;Metabolism;microcystin;Microcystis;Modeling;Molecular;mouse model;Mus;neutrophil;Nitric Oxide;novel;novel strategies;Oceans;Oral;organ injury;particle;Pathway interactions;Patients;Persons;Phenotype;Physical condensation;Physiological;Policies;Population;Populations at Risk;Predisposition;primary outcome;programs;Proliferating;Prospective, cohort study;pulmonary function;Pulmonary Inflammation;Questionnaires;Reporting;Research;respiratory;Respiratory System;response;Risk;Route;Seasons;secondary metabolite;Source;Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization;Spirometry;Stroke;System;Testing;Tissues;tool;Toxic effect;Toxic Environmental Substances;Toxin;Travel;Urine;Water;waterborne;Work

PROJECT_TITLE: Adverse Health Effects Following Exposure to Aerosolized Cyanotoxins


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Chronic Pain;Clinical Research;Clinical Trials and Supportive Activities;Neurosciences;Pain Research;Rehabilitation

ORG_CITY: HOUSTON

ORG_DEPT: NEUROSURGERY

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

ORG_STATE: TX

PHR: Project Narrative Spinal cord stimulation (SCS) is a promising nonpharmacological intervention for the treatment of chronic pain. Current technology for SCS is based on time-invariant pulses (TIP) which can constrain the location and quality of paresthesia coverage, and contribute to the development of tolerance to the therapy. To overcome these challenges, we propose to develop and clinically test a device capable of delivering novel stimulation time variant pulse (TVPs) patterns, in which a stimulation parameter changes according to a modulatory time- varying function, a strategy which may lead to improved long-term pain outcomes with SCS.

PI_NAMEs: ESTELLER, ROSANA ;VISWANATHAN, ASHWIN  (contact)

PROGRAM_OFFICER_NAME: HUDAK, ERIC MICHAEL

PROJECT_TERMS: Action Potentials;Acute;Adoption;allodynia;behavioral response;Biometry;chronic pain;chronic pain management;chronic pain patient;Clinical;Clinical effectiveness;clinical pain;Clinical Research;Computer software;Data;Data Collection;design;Development;Devices;digital data;disability;dorsal column;Double-Blind Method;Effectiveness;Elements;Esthesia;Evaluation;Feasibility Studies;Fiber;first-in-human;Frequencies;habituation;Home;human study;Hyperalgesia;Implant;implantable device;implantation;improved;improved outcome;Incidence;innovation;Institutional Review Boards;Investigation;Location;Longevity;Longterm Follow-up;Measurement;Medical;Modality;Morphology;Nature;Neurons;Neurostimulation procedures of spinal cord tissue;Nonpharmacologic Therapy;novel;Numeric Rating Scale;Opioid;opioid misuse;opioid use;Outcome;Outcome Measure;Pain;Pain Measurement;pain model;pain outcome;pain patient;pain reduction;pain relief;Paresthesia;Patients;Pattern;Phase;Physiologic pulse;Physiological;porcine model;pre-clinical;preclinical study;Randomized;randomized controlled design;Randomized, Controlled Trials;Recovery;recruit;Refractory;Reporting;Research;research clinical testing;response;Risk;Rodent;Role;Sensory;Software Design;Software Validation;Stimulus;Systems Development;Technology;Testing;Time;time use;Training;treatment effect;Treatment Efficacy;Treatment Failure;treatment responders;Variant;Width

PROJECT_TITLE: Novel Stimulation Patterns to Improve the Effectiveness of Spinal Cord Stimulation

STUDY_SECTION: NSD

STUDY_SECTION_NAME: Neurological Sciences and Disorders C Study Section[NSD-C]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Digestive Diseases;Emerging Infectious Diseases;Foodborne Illness;Genetics;Infectious Diseases;Rare Diseases

ORG_CITY: BOSTON

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: HARVARD MEDICAL SCHOOL

ORG_STATE: MA

PHR: RELEVANCE (See instructions): Bacterial viruses called phage play a major role in controlling the transmission of Vibrio cholerae, the  infectious agent of the lethal disease cholera. The proposed studies seek to define the mechanism of  bacterial systems that defend against phages because many of these have been shown to have  counterparts in human cells that defend against viruses including Covid-19.Thus, discoveries made through  our work may lead to new strategies to control or eradicate human viruses that impact public health.

PI_NAMEs: MEKALANOS, JOHN JOSEPH (contact)

PROGRAM_OFFICER_NAME: ZEITUNI, AMIR E

PROJECT_TERMS: Acetylmuramyl-Alanyl-Isoglutamine;Address;Aeromonas;Amplifiers;Anabolism;Animals;Bacteria;Bacteriophages;Biochemical;Biochemistry;Biological;Biology;biotypes;Cell Death;Cell Density;cell preparation;Cell Survival;Cell Wall;Cells;Cessation of life;Cholera;Chromosomes;Complex;computational pipelines;COVID-19;CRISPR interference;Cryoelectron Microscopy;cytokine;Cytolysis;Cytosol;Disease;Disease Outbreaks;DNA;DNA Binding;DNA biosynthesis;Enzymes;Escherichia coli;Essential Genes;experimental study;Exposure to;Genes;Genetic Transcription;Genome;genome analysis;genome sequencing;genome-wide;Human;Immune;In Vitro;in vivo;Infection;Infectious Agent;innate immune pathways;Instruction;Island;knock-down;Knock-out;Liquid substance;Monitor;Mucous Membrane;Natural Products;nuclease;pandemic disease;Pathogenesis;Pathway interactions;Permeability;Phenazines;Phenotype;Play;protein purification;Proteins;Public Health;quorum sensing;reconstitution;Regulation;Resistance;resistance mechanism;response;Role;Signal Transduction;Structure;System;Testing;transmission process;uptake;Vibrio;Vibrio cholerae;Vibrio cholerae infection;Virulence;Virus;Work

PROJECT_TITLE: Coordinate Regulation of Virulence in Vibrio Cholerae

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


ED_INST_TYPE: SCHOOL OF MEDICINE & DENTISTRY

ORG_CITY: ROCHESTER

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF ROCHESTER

PHR: OVERALL NARRATIVE The Lake Ontario Center for Microplastics and Human Health in a Changing Environment aims to prevent negative health impacts of microplastics in the context of climate change in the Great Lakes region. Our multidisciplinary systems research integrates assessment of sources, transport, fate, and impact of anthropogenic debris into Lake Ontario, with experimental investigation of biological activity of real-world mixtures of microplastics, associated biofilms, and other chemical contaminants utilizing novel nanomembrane technology. Multidirectional engagement with diverse partners will support community science, environmental health literacy, and capacity to promote multilevel solutions.

PI_NAMEs: KORFMACHER, KATRINA S (contact);TYLER, ANNA CHRISTINA

PROJECT_TERMS: Address;Affect;Amphibia;anthropogenesis;antiviral immunity;Area;Biodistribution;Biological;Biological Markers;Biological Models;biological systems;Cells;Characteristics;Chemicals;climate change;climate impact;Communication;Communities;Community Actions;community engagement;community partners;community science;Complex;cytotoxicity;Dermal;Development;drinking water;Dust;Ecosystem;Environment;environmental change;Environmental Health;Epithelium;exposed human population;Exposure to;fitness;Food;Food Chain;Foundations;Frequencies;Fresh Water;Future;Goals;Great Lakes Region;Habitats;Health;health literacy;Homeostasis;Human;Ice Cover;Immune;Immune response;improved;Inflammation;Ingestion;Inhalation;innovation;Institution;interest;Investigation;Knowledge;Lung;Mediating;member;Metals;Methods;metrology;Microbial Biofilms;microorganism;Modeling;multidisciplinary;nanomembrane;novel;novel strategies;Ontario;Outcome;Outcome Study;particle;Pathogenicity;Pattern;persistent organic pollutants;Persons;Physiology;Planet Earth;Plastics;Play;Policies;Policy Maker;Pollution;Polymers;Precipitation;prevent;Research;Research Personnel;Research Project Grants;Resources;response;Risk;Role;Sampling;Science;Source;Standardization;Surface;System;systems research;Technology;Temperature;Time;Translations;Uncertainty;Universities;Variant;vector;Water;Water Pollutants;Whole Organism;Work;Xenopus


PHR: Core A – Administration – Project Narrative The inherent complexity of microplastics (MP) and human health requires coordination, evaluation, adaptation, and facilitation of multidirectional communication both internally and externally. The Administrative Team will support these efforts through: 1) administrative, fiscal and scientific oversight; 2) communication about the Center to maximize its research, engagement, and translation impacts; 3) evaluation activities that provide ongoing feedback on Center goals, including the Plan to Enhance Diverse Perspectives. Our intentionally collaborative administrative structures will support convergent multidisciplinary, engaged, systems science that informs effective solutions.

PI_NAMEs: KORFMACHER, KATRINA S (contact)

PROJECT_TITLE: Administrative Core


NIH_SPENDING_CATS: Bioengineering;Nanotechnology

PHR: Narrative The Materials and Metrology Core (MMC) will serve as a resource for the center that: 1) maintains and distributes standard materials; 2) develops, documents and teaches consensus protocols; 3) facilitates access to instruments and other resources useful in microplastic research. The MMC will also facilitate public access to the products of the Center.

PI_NAMEs: MCGRATH, JAMES L (contact)

PROJECT_TERMS: Address;Adopted;Aging;analytical method;Area;Biological;Chemicals;Classification;Communities;Consensus;Core Facility;Dedications;Detection;Development;Devices;Digestion;Educational process of instructing;Electron Microscope;Electron Microscopy;Environment;Equipment and supply inventories;Fiber;Filtration;Food;Generations;Health;Human;human tissue;Image;In Situ;Ingestion;Inhalation;instrument;Laboratories;laboratory facility;Learning;Literature;Location;Machine Learning;Maintenance;Manuals;manufacture;Mass Spectrum Analysis;member;Membrane;meter;Methods;metrology;mimetics;nanomembrane;Nature;novel;online resource;Ontario;Optics;Pattern;Permeability;Plastics;pollutant;Privatization;Process;Production;professor;Property;Protocols documentation;Publishing;Quality Control;Reproducibility;Research;Research Personnel;Research Project Grants;Resistance;Resource Development;Resources;risk minimization;Sampling;Side;Silicon;Source;Spectroscopy, Fourier Transform Infrared;Standardization;Teaching Method;Techniques;Technology;Time;Tissues;tool;Training;Trust;Universities;Water;web-accessible;Work

PROJECT_TITLE: Materials and Metrology Core (MMC)


NIH_SPENDING_CATS: Climate-Related Exposures and Conditions;Endocrine Disruptors

PHR: Narrative – Project 2 The objectives of Project #2 are to improve our understanding of human exposure to environmental microplastics in Lake Ontario near shore water and air. We will learn about the human health impacts associated with this exposure. Studies will also reveal how microplastic particles interact with pollutants to modify bioactivity.

PI_NAMEs: DELOUISE, LISA A (contact)

PROJECT_TERMS: Accidents;Adsorption;Affect;Air;air sampling;aquatic organism;Aryl Hydrocarbon Receptor;Biological;Cells;Chemicals;Chronic;climate change;Colon;Color;Consumption;cytotoxicity;design;Diameter;Ecosystem;Endocrine disruption;Environment;Environmental Pollutants;Environmental Wind;Epithelial Cells;Epithelium;Exhibits;exposed human population;Exposure to;Fiber;fine particles;Future;Health;High Pressure Liquid Chromatography;Human;improved;in vivo;Inductively Coupled Plasma Mass Spectrometry;Ingestion;Ions;Knowledge;Learning;Light;Literature;Measures;Mechanics;Metabolism;Metals;meter;metrology;Microspheres;Monitor;Municipalities;nanomembrane;nile red;Oceans;Ontario;Oxygen;particle;persistent organic pollutants;Plankton;Plastics;pollutant;pollutant interaction;Polymers;Polystyrenes;Property;Receptor Activation;Risk;Role;Sampling;Seasonal Variations;Seasons;Shapes;Site;Skin;Source;Spectrum Analysis;Stains;Study models;System;Techniques;Technology;Temperature;Testing;Time;Toxic effect;Toxicology;uptake;UV induced;Water;water sampling;Work

PROJECT_TITLE: Investigating Environmental Microplastic Particles and Pollutant Interactions in a Changing Environment


NIH_SPENDING_CATS: Climate-Related Exposures and Conditions;Endocrine Disruptors;Foodborne Illness;Infectious Diseases

PHR: Project 3 – Project Narrative Although increasing exposure to plastic debris such as microplastics have become a major concern for human health, little is still known about their specific long-term biological impacts and how climate changes affect these effects. The goal of this project is to leverage a sensitive and reliable experimental platform in the amphibian Xenopus laevis to rigorously assess the biodistribution of microplastics and resulting impacts on development, fitness, immune homeostasis and antimicrobial immunity, under varied conditions of temperature. Given the high degree of evolutionary conservation of vertebrate physiology, the outcomes from this study are relevant to human health.

PI_NAMEs: ROBERT, JACQUES  (contact)

PROJECT_TERMS: Acute;adaptive immune response;Address;Adult;Affect;aged;Amphibia;Animals;anthropogenesis;antimicrobial;antiviral immunity;Atrazine;Bacteria;Binding;Biodistribution;Biological;Biological Markers;Biomedical Research;Carbaryl;Cells;Chemicals;Chronic;Cities;Climate;climate change;climate impact;Collaborations;Communicable Diseases;Comparative Biology;cost effective;Cryoultramicrotomy;Cytolysis;Data;Defect;density;design;Detection;Development;developmental plasticity;Dose;drinking water;Ecology;Ecosystem;Embryonic Development;Endocrine Disruptors;Environment;Exposure to;Filtration;Fishes;fitness;Flow Cytometry;Fluorescence Microscopy;Fresh Water;future climate scenario;Gastrointestinal tract structure;Genus Mycobacterium;Gills;Goals;Health;High temperature of physical object;Homeostasis;Host resistance;Human;human model;Immune;immune function;immune resistance;Immune response;Immune system;immune system function;Immunity;Immunologics;Incubated;Infection;Inflammation;Ingestion;Innate Immune Response;innovation;Intestines;Invertebrates;Laboratories;Laboratory Organism;Life;Liver;Long-Term Effects;Lymphocyte;Macrophage;marine;Mechanics;meter;Methodology;metrology;Monitor;nanomembrane;New York;nile red;Ontario;Organism;Outcome Study;particle;pathogen;Pathogenesis;pathogenic microbe;Perinatal;Physiology;Plastics;Poikilotherms;poikilothermy;pollutant;Polyethylene Terephthalates;Polyethylenes;Polystyrenes;Postembryonic;Poxviridae;Rana;Ranavirus;Research Proposals;Resistance;Risk;Sampling;Silicon;Spleen;Stains;Standardization;success;System;Tadpoles;Temperature;Testing;Thymus Gland;Time;Tissues;transcriptomics;Vaccinia;virtual;Visualization;Water;Water Pollutants;Xenopus;Xenopus laevis;young adult

PROJECT_TITLE: Biodistribution and biological impact assessment of micro-plastics water contaminants using a sensitive and reliable Xenopus experimental platform


NIH_SPENDING_CATS: Amyotrophic Lateral Sclerosis (ALS);Biotechnology;Brain Disorders;Genetics;Neurodegenerative;Neurosciences;Orphan Drug;Rare Diseases

ORG_CITY: SALT LAKE CITY

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: Project Narrative Neurodegenerative diseases are imposing an increasing health and financial burden given the rapid increase of the aging segment of the population. Currently, no therapeutics exist that significantly modify sporadic amyotrophic lateral sclerosis (ALS). This grant will use proven methods for developing a potent antisense oligonucleotide therapeutic that normalizes pathologically high STAU1 expression. Because other neurodegenerative diseases are also characterized by STAU1 overabundance, this therapeutic may be effective for other neurological diseases as well.

PI_NAMEs: PULST, STEFAN M.;SCOLES, DANIEL R (contact)

PROGRAM_OFFICER_NAME: ROOF, REBECCA

PROJECT_TERMS: acute toxicity;Age;Aging;ALS patients;Amyotrophic Lateral Sclerosis;Antisense Oligonucleotide Therapy;Antisense Oligonucleotides;Autophagocytosis;Bacterial Artificial Chromosomes;Biological Assay;Cells;Chemicals;Chemistry;Data;Development;Disease;disease model;Dose;efficacy evaluation;efficacy study;efficacy testing;experience;Fibroblasts;Financial Hardship;Frequencies;Future;Genes;Genetic;Grant;Health;High Pressure Liquid Chromatography;Histologic;Human;improved;In Vitro;in vivo;in vivo Model;Injections;Investigation;knock-down;Lead;LY6E gene;Measures;Methods;Modeling;Modification;Molecular;molecular phenotype;Motor;motor behavior;Motor Cortex;Motor Neurons;mouse model;Mus;Nerve Degeneration;Nervous System Disorder;Neurodegenerative Disorders;neurodegenerative phenotype;Pathologic;Patients;Phase;phase I trial;Phenotype;phosphorothioate;Population;Preparation;protein aggregation;protein biomarkers;protein TDP-43;Proteins;PrP;Purkinje Cells;screening;Solubility;Spinal Cord;sporadic amyotrophic lateral sclerosis;Structure-Activity Relationship;success;Synapses;Therapeutic;therapeutic target;Toxic effect;Transgenic Mice;United States National Institutes of Health;uptake;Validation;Vertebral column;Work

PROJECT_TITLE: Targeting STAU1 for TDP-43 proteinopathies

STUDY_SECTION_NAME: Neurological Sciences and Disorders B Study Section[NSD-B]


NIH_SPENDING_CATS: Cancer;Clinical Research;Comparative Effectiveness Research;Dissemination and Implementation Research;HPV and/or Cervical Cancer Vaccines;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Immunization;Infectious Diseases;Prevention;Primary Health Care;Sexually Transmitted Infections;Social Determinants of Health;Vaccine Related

ORG_CITY: Los Angeles

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: PROJECT NARRATIVE There are multiple evidence-based strategies (EBS) for increasing HPV vaccination among target adolescent populations, but few of these programs are routinely used in practice, including in safety-net clinics serving communities at higher risk for HPV-associated cancers. This R37 extension project aims to evaluate longer-term sustainability, maintenance, and equity requirements for use of EBS and identify factors that impact broader system-level adoption and scale-up within health care settings for underserved populations to inform practice change for HPV vaccine improvement relevant to real-world clinical settings.

PI_NAMEs: TSUI, JENNIFER  (contact)

PROGRAM_OFFICER_NAME: KOBRIN, SARAH

PROJECT_TERMS: Acceleration;Address;Adolescent;Adoption;Advocate;Area;Award;Cancer Burden;Clinic;Clinical;Communities;Complex;concept mapping;County;COVID-19 pandemic;Data;design;Disparity;Ensure;Equity;Ethnography;evidence base;Funding;health care settings;Health Services;Health system;Healthcare;Healthcare Systems;Hospitals;HPV vaccine acceptance;HPV-High Risk;Human Papilloma Virus Vaccination;Human Papilloma Virus Vaccine;Human Papilloma Virus-Related Malignant Neoplasm;Hybrids;implementation context;implementation process;implementation science;implementation strategy;improved;Intervention;Knowledge;Leadership;Los Angeles;Low income;Maintenance;marginalized community;Measures;member;Methods;Modeling;multidisciplinary;New Jersey;Outcome;parent project;Parents;personalized approach;Physicians;Policies;Population;practice setting;pragmatic trial;Primary Care;primary care setting;Procedures;Process;programs;Provider;provider communication;Qualifying;Reach, Effectiveness, Adoption, Implementation, and Maintenance;Recording of previous events;Research;research study;Resources;safety net;Sampling;scale up;Science;Signal Transduction;Site;System;Time;Training;Translating;Underinsured;Underserved Population;United States;uptake;vaccine access;Work

PROJECT_TITLE: Advancing the implementation of evidence-based strategies for HPV vaccination in safety-net primary care settings


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cachexia;Cancer;Digestive Diseases;Gene Therapy;Genetics;Liver Disease;Lung;Lung Cancer;Nanotechnology;Nutrition;Orphan Drug;Pancreatic Cancer;Rare Diseases

ORG_CITY: CORVALLIS

ORG_NAME: OREGON STATE UNIVERSITY

ORG_STATE: OR

PHR: PROJECT NARRATIVE Cachexia is a debilitating metabolic disorder characterized by an involuntary loss of lean body mass, systemic inflammation, and negative protein and energy balance. It is the primary cause of death for up to 30% of cancer patients and there are currently no effective therapies to manage cachexia. The proposed project will provide novel nanomedicine-based therapeutic strategies that stimulate appetite and attenuate cachexia-associated muscle wasting and systemic inflammation in cancer patients.

PI_NAMEs: TARATULA, OLEH  (contact)

PROGRAM_OFFICER_NAME: HECKMAN-STODDARD, BRANDY

PROJECT_TERMS: activin A;Activins;Acyltransferase;Affect;antagonist;Anti-Inflammatory Agents;appetite loss;Applications Grants;Attenuated;Behavior;Behavioral;Binding;Body Composition;Body Weight decreased;Cachexia;Cancer Cachexia;cancer cell;Cancer Model;Cancer Patient;cancer therapy;Cause of Death;Cells;chemotherapy;Circulation;Cisplatin;Clinical Trials;Code;Consumption;Data;design;Desire for food;Differentiation and Growth;Disease;Eating;effective therapy;efficacy evaluation;Endothelial Cells;energy balance;Ensure;Exhibits;Fatty acid glycerol esters;Follistatin;Gene Delivery;ghrelin;Glycoproteins;Goals;Head and Neck Cancer;Health;Hepatocyte;Hormone secretion;Hormones;Human;Hypothalamic structure;improved;increased appetite;Inflammation;Inflammatory;inhibitor;intraperitoneal;Intravenous;intravenous administration;intravenous injection;IRAK4 gene;Kupffer Cells;lean body mass;lipid nanoparticle;Literature;Liver;Lung;malignant ascites;Malignant neoplasm of lung;Malignant neoplasm of ovary;Malignant Neoplasms;Mediating;Messenger RNA;Metabolic;Metabolic Diseases;Metastatic Neoplasm to the Lung;Modeling;morphogens;mouse model;mRNA delivery;Mus;muscle form;Muscular Atrophy;Myoblasts;nanomedicine;nanoparticle;nanoparticle delivery;nanopolymer;nanotechnology platform;Neoplasm Metastasis;novel;Nutritional Support;overexpression;Pancreas;pancreatic cancer model;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma model;parent grant;Patients;Peptides;Persons;Pharmaceutical Preparations;pharmacologic;Phenotype;physical impairment;Play;Pre-Clinical Model;preclinical study;preservation;prevent;Production;Proliferating;Proteins;Quality of life;receptor;Reporting;Research;Research Personnel;Role;Route;Serum;Site;Skeletal Muscle;skeletal muscle wasting;skeletal preservation;Solid Neoplasm;Stomach;subcutaneous;Subcutaneous Injections;Syndrome;System;systemic inflammatory response;Technology;Testing;Therapeutic;Therapeutic Agents;therapeutic RNA;Thinness;Toxic effect;translational potential;translational therapeutics;Treatment Efficacy;Treatment outcome;tumor;tumor progression;validation studies;Vascular Cell Adhesion Molecule-1;Wild Type Mouse

PROJECT_TITLE: Novel Nanomedicine-Based Therapeutic Approach For Treatment of Cancer Cachexia


FUNDING_MECHANISM: SBIR-STTR RPGS

NIH_SPENDING_CATS: Biotechnology;Facioscapulohumeral Muscular Dystrophy;Gene Therapy;Genetics;Muscular Dystrophy;Neurosciences;Orphan Drug;Rare Diseases

ORG_CITY: Gaithersburg

ORG_NAME: MIRECULE, INC.

ORG_STATE: MD

PHR: Project Narrative  Over 50 inherited neuromuscular disorders including myopathies, muscular dystrophies, and metabolic muscle disorders have been identified with a monogenic underpinning. These neuromuscular disorders are characterized by progressive weakness and degeneration of muscle tissue. In this Fast-track SBIR proposal miRecule will develop a muscle-specific platform (Muscle- NAVTM) for the delivery of therapeutic oligonucleotide to treat inherited muscle disorders. Facioscapulohumeral muscular dystrophy (FSHD) is the third most common form of MD with roughly 20,000 patients presenting with symptoms in the US. FSHD results in progressive weakness in the muscles of the face, shoulders, arms, abdomen, and legs. To validate our Muscle-NAV platform we propose to deliver our (ASO) targeting DUX4 (miRecule candidate MC- DX4) for the treatment of FSHD.

PI_NAMEs: SALEH, ANTHONY D (contact)

PROGRAM_OFFICER_NAME: CAPORELLO, EMILY LAURA

PROJECT_TERMS: Abdomen;ACTA1 gene;Address;Affect;Affinity;Animal Model;Antibodies;antibody conjugate;antigen binding;Antisense Oligonucleotide Therapy;Antisense Oligonucleotides;Apoptosis;arm;Binding;Biodistribution;Biological Response Modifier Therapy;Blood;Cells;cellular targeting;Chemicals;Chemistry;comparative efficacy;Contracts;cytokine;Cytoplasm;Data;design;Development;Disease;Dose;Duchenne muscular dystrophy;Dyes;effective therapy;Elements;Endocytosis;Endocytosis Induction;Endosomes;Engineering;Exercise;Face;Facioscapulohumeral Muscular Dystrophy;Genes;Half-Life;Hand Strength;HepG2;Histopathology;Homeobox;Human;hydrophilicity;improved;In Vitro;in vivo;Inflammatory;Inherited;Injections;innovation;knock-down;Label;Lead;lead candidate;Leg;Legal patent;Libraries;Licensing;manufacture;manufacturing scale-up;Marketing;Maximum Tolerated Dose;Measures;Membrane;Metabolic;Modeling;Monitor;mouse model;Mus;Muscle;Muscle Cells;muscle degeneration;Muscle function;Muscular Dystrophies;muscular dystrophy mouse model;Mutate;Mutation;Myoblasts;Myopathy;Neuromuscular Diseases;nonhuman primate;novel;oligonucleotide delivery;oligonucleotide therapeutics;Oligonucleotides;Orphan;Outcome;Oxidative Stress;Pathology;Patients;Peripheral Blood Mononuclear Cell;Phage Display;pharmacokinetics and pharmacodynamics;Phase;Pre-Clinical Model;pre-Investigational New Drug meeting;Process;Proteins;Rare Diseases;Rattus;receptor;receptor mediated endocytosis;Repression;Risk;RNA delivery;RNA Stability;Rodent;Running;Safety;scale up;screening;Serum;Shoulder;Small Business Innovation Research Grant;small molecule;Sum;Symptoms;synergism;targeted delivery;Technology;technology platform;technology validation;Testing;Therapeutic;therapeutic development;therapeutic RNA;therapeutically effective;Tissues;Toxic effect;Toxicology;Transcript;transcription factor;Treatment Efficacy;uptake;Xenograft procedure

PROJECT_TITLE: A Novel RNA Therapeutics Platform to Treat Facioscapulohumeral Muscular Dystrophy  and other Neuromuscular Disorders

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-BST-R(10)B]


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Biotechnology;Cancer

ORG_CITY: BERKELEY

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: Project Narrative (Public Health Relevance Statement) Reversible oxidation and reduction of protein methionines is an emerging mechanism for maintaining cellular homeostasis, contributing to regulation of protein function, cell signaling, and antioxidant defense. Indeed, increased oxidative stress and/or decreased capacity for reduction of methionine sulfoxide to methionine is linked to life-span regulation, neurodegeneration, vascular diseases and thrombosis, and cancer cell proliferation. We are developing new chemical tools to probe methionine with high specificity in protein and proteome settings to identify, biochemically characterize, and provide new imaging reagents for redox- responsive methionine sites important to physiology and disease, particularly in metabolic and oncogenic proteins.

PI_NAMEs: CHANG, CHRISTOPHER J. (contact)

PROGRAM_OFFICER_NAME: ANSONG, CHARLES KWAKU

PROJECT_TERMS: activity-based protein profiling;adduct;Amino Acids;Antioxidants;Biochemical;Biology;Biomimetics;cancer cell;Cancer cell line;Cell Fractionation;Cell Line;Cell model;Cell Proliferation;Cells;Cellular Metabolic Process;Chemicals;Chemistry;chemoproteomics;collaborative environment;Complex;Cysteine;Data;Data Set;design;desthiobiotin;Development;Disease;Drug Metabolic Detoxication;Ectopic Expression;Endowment;Engineering;Enzymes;Free Energy;Glucose;Glycolysis;Health;Homeostasis;Hydrogen Peroxide;Image;improved;innovation;inorganic phosphate;Isotopes;Knock-out;Label;life span;Link;liquid chromatography mass spectrometry;lung cancer cell;Malignant Neoplasms;Maps;Mass Spectrum Analysis;Metabolic;Metabolism;Methionine;methionine sulfoxide;methionine sulfoxide reductase;Methods;model design;Modeling;multiple omics;mutant;Mutation;NADP;Neoplasm Metastasis;Nerve Degeneration;Neurodegenerative Disorders;Nitrogen;NMR Spectroscopy;novel;Oncogenic;oxaziridine;Oxidants;oxidation;Oxidation-Reduction;Oxidative Stress;Oxidative Stress Induction;pancreatic cancer model;Pathologic;Pathology;Pathway interactions;Pentosephosphate Pathway;Phase;Physiological;Physiological Processes;Physiology;Post-Translational Protein Processing;predictive modeling;Property;protein function;protein purification;Proteins;Proteome;Proteomics;public health relevance;Pyruvate Kinase;Reagent;Regulation;Research Personnel;Resistance;Respiration;response;Shunt Device;Signal Transduction;Site;Specificity;Sulfoxide;Sulfur;Surface;Techniques;Testing;Thrombosis;Time;Tissues;tool;Training;Vascular Diseases

PROJECT_TITLE: Chemical Probes to Study Methionine Redox Biology

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


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Endocrine Disruptors;Genetics;Human Genome;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: STONY BROOK

ORG_DEPT: PATHOLOGY

ORG_NAME: STATE UNIVERSITY NEW YORK STONY BROOK

PHR: Project Narrative  Environmental exposure to carcinogenic metal (metalloid) arsenic, especially the trivalent form, As3+(iAs), has long been a major public health concern. The research proposed in this application is aimed at increasing our understanding of mechanisms by which iAs induces generation of the cancer stem-like cells (CSCs). Main efforts will be on the role of iAs-induced Nrf2-HIF1a signaling linked to glycolysis and the formation of CSCs.

PI_NAMEs: CHEN, FEI  (contact)

PROJECT_TERMS: Address;Affect;Arsenic;arsenic carcinogenesis;Biochemical;Biological Assay;Bladder;bronchial epithelium;cancer type;carcinogenicity;Carcinogens;Cells;Characteristics;ChIP-seq;chromatin remodeling;Citric Acid Cycle;Consumption;Country;CRISPR/Cas technology;Data;Deposition;Environmental Carcinogens;Environmental Exposure;epigenetic marker;Epigenetic Process;Epithelial Cells;Exhibits;Exposure to;Food;Fruit;Generations;Genes;Genetic Transcription;Glucose;Glycolysis;Grain;ground water;Hematopoietic System;HIF1A gene;Histone H3;histone methylation;Human;In Vitro;in vivo;Industrialization;inhibitor;Irrigation;Kidney;Link;Liver;Lung;Lysine;Maintenance;Malignant - descriptor;Malignant neoplasm of lung;Malignant Neoplasms;MAPK8 gene;Metabolic;Metabolism;metabolomics;Metals;Methylation;Minerals;Mitochondria;mitochondrial metabolism;Organ;Oxidative Phosphorylation;Pathway interactions;Pattern;Persons;Planet Earth;Play;Proteomics;Public Health;Research;response;Rice;Role;self-renewal;Signal Transduction;Skin;Soil;stem-like cell;stemness;targeted cancer therapy;Testing;transcription factor;transcriptome sequencing;transcriptomics;Translating;Ubiquitination;United States;Vegetables;Water;Workplace

PROJECT_TITLE: Dissecting Nrf2-dependent HIF1a activation mechanism in arsenic-induced cancer stem-like cells

STUDY_SECTION: SIEE

STUDY_SECTION_NAME: Systemic Injury by Environmental Exposure[SIEE]


NIH_SPENDING_CATS: Genetics;Lung

PHR: Project Narrative Nickel (Ni) compounds are environmental toxicants, prevalent in the atmosphere due to their widespread use in several industrial processes, as well as extensive consumption of Ni containing products. Although Ni- compounds have been conclusively shown to be associated with a multitude of human health risks including allergic contact dermatitis, bronchitis, pulmonary fibrosis, pulmonary edema and lung and nasal cancers, the molecular basis of Ni-induced diseases remain poorly understood. This study will investigate the mechanisms underlying Ni-induced diseases by examining the long-term changes to the transcriptome and epigenome that occur due to Ni exposure.

PI_NAMEs: COSTA, MAX ;CUDDAPAH, SURESH  (contact)

PROGRAM_OFFICER_NAME: TYSON, FREDERICK L

PROJECT_TERMS: Agar;Allergic Contact Dermatitis;Asthma;Atmosphere;Atopic Dermatitis;Binding;Binding Sites;bronchial epithelium;Bronchitis;Cell-Cell Adhesion;Cells;Characteristics;Chromatin;Chromatin Structure;Consumption;Coupled;CRISPR/Cas technology;Development;differential expression;Disease;DNA Binding;Environment;epidemiology study;Epigenetic Process;epigenome;Epithelial Cells;Epithelium;Etiology;Exposure to;Fibrosis;Fossil Fuels;functional outcomes;Gene Activation;Gene Expression;Gene Expression Alteration;Gene Silencing;Generations;Genes;Genetic Transcription;genome-wide;Goals;Grant;Health;Health Hazards;histone modification;Histones;Human;human disease;Industrialization;insight;knock-down;Long-Term Effects;Lung;Malignant Neoplasms;Maps;Mediating;Medical Device;medical implant;Mesenchymal;Methyltransferase;Molecular;Mus;Neoplasm Metastasis;Neoplastic Cell Transformation;Nickel;Nose;novel;Nude Mice;Outcome;overexpression;Pathogenicity;Phenotype;Physical condensation;Predisposing Factor;Predisposition;prevent;Prevention;Process;promoter;Property;Proteins;Pulmonary Edema;Pulmonary Fibrosis;Regulation;Risk;Role;Source;Stainless Steel;Structure;System;Testing;Toxic Environmental Substances;Transcription Alteration;transcription factor;transcriptome;tumor;Up-Regulation;Zinc Fingers

PROJECT_TITLE: Persistent transcriptional changes induced by nickel through epigenetic alterations

STUDY_SECTION: XNDA

STUDY_SECTION_NAME: Xenobiotic and Nutrient Disposition and Action Study Section[XNDA]


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Foodborne Illness;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Prevention;Rural Health;Social Determinants of Health

ORG_CITY: LEXINGTON

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: UNIVERSITY OF KENTUCKY

ORG_STATE: KY

PHR: PROJECT NARRATIVE Appalachian Kentuckians in Martin and Letcher Counties are grappling with a health-threatening drinking water crisis arising from exposures to disinfection by-products (DBPs). DBPs include compounds that have been associated with a variety of adverse health effects, including increased risk of bladder cancer and cardiovascular birth defects. This study, which builds on findings from two community-engaged NIEHS P30-funded pilot studies and one P30-funded community grant, uses a multi-method approach, stakeholder-engaged approach to reduce DBP exposures and improve public health in target counties.

PI_NAMEs: HOOVER, ANNA GOODMAN;UNRINE, JASON  (contact)

PROGRAM_OFFICER_NAME: O'FALLON, LIAM

PROJECT_TERMS: Acids;Address;Appalachian Region;Businesses;Cardiovascular system;Characteristics;Chemicals;Chemistry;Chloramines;Chlorates;Chlorine;citizen science;Coal;Collaborations;Communication;Communities;community academic partnership;community partners;Congenital Abnormality;Consultations;County;Data;Disinfectants;Disinfection;drinking water;Economics;Environmental Health;exposure route;Exposure to;Funding;Goals;Grant;ground water;Halogens;Health;health communication;health literacy;Home;Human;improved;indoor air;Infrastructure;Intervention;Kentucky;Knowledge;Laws;Location;Malignant neoplasm of urinary bladder;Methods;Modeling;National Institute of Environmental Health Sciences;Ozone;Participant;Persons;Pilot Projects;Population;predictive modeling;Process;public drinking;Public Health;Reaction;Regulation;Research;Research Personnel;Resources;Risk;Risk Reduction;Route;rural America;Rural Community;rural dwellers;Sampling;Scientist;social;Source;Surface;System;Testing;Training and Infrastructure;Trihalomethanes;Trust;Ultraviolet Rays;United States;United States Environmental Protection Agency;Universities;Variant;Virginia;Water;water quality;West Virginia

PROJECT_TITLE: A university-community partnership to reduce exposure to disinfection byproducts in Appalachia


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Amyotrophic Lateral Sclerosis (ALS);Biotechnology;Brain Disorders;Neurodegenerative;Neurosciences;Prevention;Rare Diseases

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PI_NAMEs: RE, DIANE BERENGERE (contact)

PROGRAM_OFFICER_NAME: HOLLANDER, JONATHAN

PROJECT_TERMS: ALS patients;Amyotrophic Lateral Sclerosis;Autopsy;Binding;biobank;Biogenesis;Biological Markers;Blood;Blood Circulation;Brain;capsule;Cells;Central Nervous System;Cerebrospinal Fluid;Clinical;cohort;Collection;Communication;Disease;Disease Progression;Dose;effective therapy;Elements;Environmental Exposure;Enzyme-Linked Immunosorbent Assay;Etiology;Evaluation;Exposure to;extracellular vesicles;GLAST Protein;Hair;Human;improved;In Vitro;Lead levels;Link;Measures;Mediating;Membrane;Metal exposure;Metals;MicroRNAs;minimally invasive;Molecular Profiling;motor neuron degeneration;Motor Neurons;Nervous System Disorder;Neural Cell Adhesion Molecule L1;Neuroglia;Neurons;neurotoxic;novel;novel marker;Nucleic Acids;Organ;Paralysed;Pathogenicity;Pathway interactions;Patients;Peripheral;Phenotype;protein TDP-43;Proteins;Reporting;Research;Role;Sampling;Signal Transduction;Source;Surface;System;Testing;Time;Tissues;toxic metal;transcriptome sequencing;Travel;Treatment Efficacy;Tube;Veterans;Visit

PROJECT_TITLE: Brain-derived extracellular vesicles as a novel source of biomarkers for disease progression and environmental exposure in ALS

STUDY_SECTION: NAME

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


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Digestive Diseases;Emerging Infectious Diseases;Foodborne Illness;Infectious Diseases;Malaria;Orphan Drug;Pediatric;Rare Diseases;Vector-Borne Diseases

ORG_CITY: SEATTLE

ORG_NAME: SEATTLE CHILDREN'S HOSPITAL

ORG_STATE: WA

PHR: PROJECT NARRATIVE The investigators have identified a new lead series of compounds that are effective at curing mice of a parasitic infection. The project will conduct lead optimization and characterization studies using in vitro and in vivo assays. Synthetic chemistry will be guided by structure-based rational design and final compounds will be tested in an animal model.

PI_NAMEs: STAKER, BART LEE (contact)

PROGRAM_OFFICER_NAME: JOY, DEIRDRE A

PROJECT_TERMS: Affinity;Aftercare;Age;Animal Model;Animals;Antiparasitic Agents;Binding;Biological Assay;Carbon;Case Study;Characteristics;Chemicals;Child;Childhood;Communicable Diseases;Cryptosporidiosis;Cryptosporidium;Cryptosporidium parvum;Data;design;Diarrhea;Drug Design;drug discovery;Drug Kinetics;drug synthesis;Drug Targeting;druggable target;effective therapy;efficacy study;Enzymes;Fatty Acids;Glycine;Goals;gut colonization;high throughput screening;Human;improved;In Vitro;in vivo;Incidence;Infection;inhibitor;Insect Vectors;Lead;lead optimization;lead series;Leishmaniasis;Libraries;Malaria;Malnutrition;Measures;Membrane;Methods;Modeling;mouse model;Mus;Mutate;Myristates;N-myristoyltransferase;N-terminal;Oral;Parasites;Parasitic Diseases;Parasitic infection;Peptides;Pharmaceutical Preparations;Pharmacology and Toxicology;Plasmodium;Plasmodium falciparum;pre-clinical;preclinical development;Preclinical Drug Development;Preparation;programs;Proteins;rational design;Reporting;Research Personnel;Resistance;Roentgen Rays;Route;scaffold;screening;Screening Result;Series;Solubility;Structure;Synthesis Chemistry;Testing;Time;Toxoplasma;Translating;Work

PROJECT_TITLE: Structural Analysis and Inhibitor Optimization of Cryptosporidium n-myristoyltransferase for Drug Discovery

STUDY_SECTION: DDR

STUDY_SECTION_NAME: Drug Discovery and Mechanisms of Antimicrobial Resistance Study Section[DDR]


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

NIH_SPENDING_CATS: Bioengineering;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD)

ORG_NAME: ADVANCED SCIENCE RESEARCH CENTER

PHR: Knowing the structure, dynamics and ligand binding specificity of proteins and nucleic acids is essential to understanding the mechanisms of human disease and to the optimal design of molecules that can intervene therapeutically in disease processes. Nuclear Magnetic Resonance (NMR) Spectroscopy is one of the most versatile techniques for obtaining this molecular information. This research will further develop and extend an integrated, software application for processing, analyzing, and using NMR data, and thereby make the use of these techniques faster and more accessible to a wider population of researchers.

PI_NAMEs: JOHNSON, BRUCE A (contact)

PROGRAM_OFFICER_NAME: BARNES, CHARLES ASHLEY

PROJECT_TERMS: Acceleration;Algorithms;Architecture;Area;biological research;Chemicals;cloud based;cloud platform;Collection;Computer Analysis;Computer software;computerized data processing;computerized tools;computing resources;Cryoelectron Microscopy;Data;Data Analyses;data exchange;data standards;deep learning;deep learning algorithm;design;Development;Disease;Documentation;experience;Goals;graphical user interface;Harvest;Health;Human;human disease;insight;interest;Java;Knowledge;Libraries;Ligand Binding;Linux;Machine Learning;magnetic field;Methods;Modernization;Molecular;molecular dynamics;Molecular Structure;Names;new technology;NMR Spectroscopy;Noise;novel strategies;Nuclear Magnetic Resonance;Nucleic Acids;open source;Performance;Population;Positioning Attribute;Principal Investigator;Process;Programming Languages;programs;Protein Analysis;Proteins;Protocols documentation;rapid technique;Research;Research Personnel;Running;Scheme;Science;Scientist;signal processing;Source Code;Specificity;Speed;structural biology;Structure;symposium;Techniques;Therapeutic;Time;time use;tool;Translating;usability;virtual machine;Visualization;X-Ray Crystallography

PROJECT_TITLE: NMRFx: An Integrated software suite for macromolecular NMR analysis

STUDY_SECTION: MSFD

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


NIH_SPENDING_CATS: Assistive Technology;Bioengineering;Clinical Research;Hearing Loss;Neurosciences;Rehabilitation

ORG_DEPT: BIOMEDICAL ENGINEERING

PHR: Hearing loss typically involves difficulty understanding sounds, especially in backgrounds of noise. We are developing and testing a new framework for describing the way that sounds are represented in the responses of neurons. Knowledge of how the healthy brain copes with difficult listening environments will provide new and important insights for aiding listeners with hearing loss. The Public Health Relevance of this project is to develop a better understanding of the difficulties in noisy situations for listeners with hearing loss.

PI_NAMEs: CARNEY, LAUREL H. (contact)

PROGRAM_OFFICER_NAME: MILLER, ROGER

PROJECT_TERMS: Acoustic Nerve;Acoustics;Address;Affect;Anatomy;Auditory;auditory pathway;Auditory system;Automobile Driving;awake;Brain;Cells;cellular transduction;Central Nervous System;Characteristics;Cochlea;Cochlear Implants;Code;Collection;Complex;Computer Models;coping;Cues;Data;Data Set;density;design;Detection;Discrimination;Environment;experimental analysis;experimental study;Feedback;Foundations;Frequencies;Goals;Hearing;Hearing Aids;hearing impairment;Human;improved;Inferior Colliculus;Inner Hair Cells;innovation;insight;interest;Knowledge;Loudness;Masks;Medial;Midbrain structure;Modeling;Nerve Fibers;neural;Neurons;Noise;normal hearing;novel strategies;Oryctolagus cuniculus;Pattern;Perception;Performance;Peripheral;Phase;Physiological;Physiology;Play;predictive modeling;Property;Psychoacoustics;Psychophysics;public health relevance;receptive field;Research Design;Resolution;response;Role;Science;Sensorineural Hearing Loss;Shapes;Signal Detection Analysis;sound;Stimulus;Structure;System;task analysis;Testing;Textbooks;theories;Time

PROJECT_TITLE: Developing and Testing Models of the Auditory System With and Without Hearing Loss

STUDY_SECTION: AUD

STUDY_SECTION_NAME: Auditory System Study Section[AUD]


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

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: PROJECT NARRATIVE The cellular degradative process of autophagy is a major host defense pathway. Thus, gene variants and pharmacological interventions that affect autophagy are predicted to modulate susceptibility to bacterial pathogens. In this proposal, we will investigate the physiological mechanisms by which autophagy alters defense against two significant bacterial pathogens, Salmonella enterica Typhimurium and Staphylococcus aureus.

PI_NAMEs: CADWELL, KEN HASHIGIWA (contact)

PROGRAM_OFFICER_NAME: ALEXANDER, WILLIAM A

PROJECT_TERMS: Address;Adverse effects;Affect;Alleles;Amino Acid Substitution;antimicrobial;Attention;Autophagocytosis;Autophagosome;Bacteria;Bacterial DNA;Bacterial Infections;Binding;Biogenesis;Biological;Cell Culture Techniques;Cell Death;Cell Physiology;cell type;Cells;Cellular biology;Citrobacter rodentium;Communicable Diseases;Complex;CRISPR/Cas technology;Cues;cytokine;Cytokine Suppression;Cytosol;Data;design;Disease;Dominant-Negative Mutation;Drug Targeting;Epithelial Cells;Event;exosome;experimental study;extracellular;extracellular vesicles;Frequencies;Funding;Genetic Screening;genetic variant;Goals;Heterozygote;Host Defense;host-microbe interactions;Human;Immune response;Immunity;improved outcome;Infection;Infectious Agent;Inflammation Mediators;Inflammatory;inhibitor;Innate Immune Response;Intervention;intestinal epithelium;Knowledge;loss of function;Lysosomes;Mammalian Cell;Mediating;Mediator;Membrane;Microbe;Microscopy;Mitochondria;Modeling;Molecular;monocyte;mouse model;Mus;Natural Immunity;Necrosis;Norovirus;novel;pathogen;Pathogen detection;pathogenic bacteria;Pathway interactions;pharmacologic;Physiological;Play;Population;Predisposition;prevent;Process;Production;programs;Proteins;Proteomics;receptor;recruit;Recycling;response;Role;Salmonella;Salmonella typhimurium;Staphylococcus aureus;Staphylococcus aureus infection;Techniques;Testing;therapeutic target;Toxin;trafficking;Variant;Vesicle;Virulence

PROJECT_TITLE: Redefining the role of autophagy in bacterial disease

STUDY_SECTION: IHD

STUDY_SECTION_NAME: Immunity and Host Defense Study Section[IHD]


NIH_SPENDING_CATS: Natural Products

ORG_CITY: GAINESVILLE

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: Project Narrative Many nematode (roundworm) species are parasites of humans, livestock, and crops, infecting one-third of humans world-wide and causing billions of dollars in agricultural losses. An understanding of the chemical signals used by nematodes to control their development will provide new strategies and chemical treatments to interfere with the life cycles of parasitic species and reduce their survival.

PI_NAMEs: BUTCHER, REBECCA A (contact)

PROGRAM_OFFICER_NAME: ASLAN, KADIR

PROJECT_TITLE: Small-molecule signals controlling nematode development

STUDY_SECTION: MRAB

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


NIH_SPENDING_CATS: Bioengineering;Genetics

ORG_CITY: Chicago

ORG_NAME: NORTHWESTERN UNIVERSITY

ORG_STATE: IL

PHR: Narrative All genetic processes are ultimately controlled by protein-DNA interactions. Incorrect processing of DNA in humans lead to a wide range of genetic disorders, while induction of changes in DNA processing provides a strategy to control pathogenic organisms. The proposed project seeks to obtain mechanistic understanding of proteins that interact with DNA and thereby to advance our ability to control genetic processes.

PI_NAMEs: MARKO, JOHN F (contact)

PROGRAM_OFFICER_NAME: SAKALIAN, MICHAEL

PROJECT_TERMS: Affect;Architecture;Binding Proteins;Cell division;Cell Nucleus;Cells;Chromatin Loop;Chromatin Structure;chromosome replication;Chromosome Structures;Chromosomes;cofactor;cohesin;Complex;condensin;Data;Dependence;Dissociation;DNA;DNA analysis;DNA Folding;DNA Repair;DNA-Binding Proteins;DNA-Protein Interaction;Environment;Eukaryota;Excision;experimental study;fighting;Fluorescence;Genes;Genetic;Genetic Diseases;Genetic Processes;Genome;Health;Histones;HMGB1 gene;Human;hydrodynamic flow;Impairment;in vivo;Kinetics;Label;Lead;Length;Magnetism;Maintenance;Measurement;Mechanics;Mediating;Metaphase;Micromanipulation;Microscopy;Motor;Multienzyme Complexes;novel;Nucleoproteins;Organism;Pathogenicity;Pathology;Phase;Play;preservation;Process;Prokaryotic Cells;protein complex;protein degradation;protein function;Proteins;Quantum Dots;Reaction;Side;single molecule;Single-Stranded DNA;Sodium Chloride;Structural Protein;Structure;Testing;Time;Torque;transcription factor;Visualization;Yeasts

PROJECT_TITLE: Activities of nucleoprotein complexes visualized in single-molecule experiments

STUDY_SECTION: MSFC

STUDY_SECTION_NAME: Macromolecular Structure and Function C Study Section[MSFC]


NIH_SPENDING_CATS: Clinical Research;Contraception/Reproduction;Endocrine Disruptors;Infertility;Women's Health Research

ORG_DEPT: OBSTETRICS & GYNECOLOGY

PHR: PROJECT NARRATIVE Exposure to phthalates, a class of chemicals that humans are unavoidably exposed to on a daily basis, is increasingly being recognized as contributing to the prevalence of infertility, in which defects in ovulation are the leading cause of infertility in women. The proposed research will address this public health concern by providing a more complete understanding of how phthalates inhibit prostaglandins and angiogenesis, which are essential for ovulation and fertility in women. Because infertility in women seeking to conceive leads to impairments in their physical and mental health, the overarching goal of this proposal is to establish novel rescue approaches to alleviate phthalate-induced reproductive dysfunction and infertility.

PI_NAMEs: HANNON, PATRICK RYAN (contact)

PROGRAM_OFFICER_NAME: SCHUG, THADDEUS

PROJECT_TERMS: Agonist;angiogenesis;Angiogenesis Inhibition;Angiogenic Factor;Animal Model;Award;Biological Assay;Blood capillaries;Cell model;Cell Proliferation;Cells;Chemicals;cost;Couples;critical period;Cyclic AMP;Cyclooxygenase Inhibitors;Data;Defect;Dose;Endocrine Disruptors;Endothelial Cells;Ensure;Environment;Environmental Health;Exhibits;exposed human population;Exposure to;Failure;Female infertility;Fertility;Fertility Rates;FGF2 gene;Foundations;Functional disorder;Goals;granulosa cell;Healthcare;Housing;Human;human model;Impairment;In Vitro;in vivo;Infertility;Link;Literature;Mediator;Medical;Mental Health;Metabolism;migration;Modeling;mouse model;Mus;Nature;Non-Steroidal Anti-Inflammatory Agents;novel;Oocytes;Outcome;Ovarian;Ovarian Follicle;Ovarian Granulosa Cell;Ovary;Ovulation;Ovulation Inhibition;Parents;Pathway interactions;personal care products;phthalates;physical conditioning;Pregnant Women;Prevalence;prevent;Process;Production;Proliferating;Prostaglandin Inhibition;Prostaglandin Production;Prostaglandin-Endoperoxide Synthase;Prostaglandins;PTGS2 gene;Public Health;Quality of life;receptor;reproductive;Reproductive Health;Research;Rodent Model;Sampling;Signal Transduction;Signaling Molecule;Social Functioning;Societies;Stress;Supplementation;Testing;Time;Toxic effect;translational approach;urinary;VEGFA gene;Woman;Women's Health;Women's prevalence;Work

PROJECT_TITLE: Phthalate-Induced Dysregulation of Prostaglandin and Angiogenic Function During Ovulation in Women


NIH_SPENDING_CATS: Genetics;Hearing Loss;Neurosciences

ORG_CITY: BALTIMORE

ORG_DEPT: NEUROSCIENCES

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: PROJECT NARRATIVE Hearing loss is a major health problem that significantly affects the life quality of affected individuals. Many forms or hearing loss are caused by defects in auditory hair cells and the neurons that innervate them. We propose here to study the mechanisms that regulate the connectivity of spiral ganglion neurons that innervate hair cells, and how they are affected in a genetic form of hearing loss with the anticipation that our studies will ultimately lead to a better treatment of the disease.

PI_NAMEs: MUELLER, ULRICH  (contact)

PROGRAM_OFFICER_NAME: CYR, JANET

PROJECT_TERMS: Affect;Afferent Neurons;aging population;Anatomy;Auditory;Auditory Perception;Cell Communication;Child;Data;deafness;Defect;Development;Disease;Electrophysiology (science);Felis catus;Fluorescence;Gene Modified;Genes;Genetic;genetic manipulation;genomic tools;Genomics;Goals;Hair Cells;Health;Hearing;hearing impairment;Hearing Tests;Histology;Human;Image;Individual;inducible Cre;Inner Hair Cells;insight;Laboratories;Link;Maps;Measures;Molecular;Molecular Profiling;Mus;Mutation;nerve supply;Neuronal Differentiation;Neurons;Outer Hair Cells;Pattern;Play;postnatal;Presbycusis;Property;Publications;Publishing;Quality of life;Regulation;Reporter;Sense Organs;Signal Transduction;single-cell RNA sequencing;sound;spiral ganglion;Tamoxifen;Testing;Tinnitus;Wild Type Mouse;Work

PROJECT_TITLE: Mechanisms of Auditory Circuit Development


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

ORG_CITY: NEW YORK

ORG_DEPT: PEDIATRICS

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: Human health and disease are shaped by a range of life-long exposures, and our biological response to them, underscoring the need for a systematic plan to integrate environmental health/exposomics into precision medicine initiatives. Clinician-scientists are a critical bridge for translating basic and clinical research into new paradigms of clinical care. The Mount Sinai K12 program will develop healthcare professionals poised to integrate environmental science with evolving precision medicine and clinical care efforts and catalyze the development of the next generation of versatile children's environmental health leaders to address emerging complexities of pediatric and reproductive environmental health.

PI_NAMEs: WRIGHT, ROSALIND J (contact)

PROJECT_TERMS: Address;Caring;Child;Child Health;Child health care;Childhood;Chronic Disease;Clinical;clinical center;Country;Development;Discipline;Disease;disorder prevention;disorder risk;early childhood;Ecosystem;Environment;Environmental Health;Environmental Science;Fellowship Program;fetal;Genetic;Health;Health Professional;Healthcare;Human;Individual;Infrastructure;Institution;Investments;Lead;Learning;Life;Life Cycle Stages;Medical;medical specialties;Mentored Clinical Scientist Development Program;Methods;microbial;Molecular;next generation;novel strategies;Outcome;Pediatrics;Perinatal;Physicians;Physiological;precision medicine;Precision Medicine Initiative;programs;reproductive;Reproductive Health;Research;research and development;Role;Running;Scholars Program;Science;Scientist;Shapes;social;System;Toxin;Training;Translating;Translations;Vision;Workforce Development;workforce needs

PROJECT_TITLE: Scholars in Environmental Pediatrics, Reproductive Health, and Life Course Science


NIH_SPENDING_CATS: Contraception/Reproduction;Genetics

ORG_CITY: DALLAS

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: PROJECT NARRATIVE Cytoskeletal proteins play fundamental roles in many biological processes in all eukaryotes. Given their essentiality, they are traditionally thought to be highly conserved. However, many cytoskeletal proteins, especially those that are expressed in the male germline, are subject to accelerated diversification in the form of gene duplications and rapid evolution in multiple animal lineages. This proposal investigates how cytoskeletal proteins undergo adaptation for novel functions during spermatogenesis and impact male reproductive fitness.

PI_NAMEs: SCHROEDER, COURTNEY MEGAN (contact)

PROGRAM_OFFICER_NAME: ADKINS, RONALD

PROJECT_TERMS: Acceleration;Actin-Binding Protein;Actins;Amino Acid Substitution;Animals;Antibodies;Automobile Driving;Biochemistry;Biological Assay;Biological Process;Candidate Disease Gene;Cell division;cell motility;comparative genomics;cost;Cytoskeletal Proteins;Cytoskeleton;Defect;design;Drosophila genome;Drosophila genus;Drosophila inturned protein;Eukaryota;Event;Evolution;Exhibits;Family;Family member;Fertility;fitness;fitness test;fly;Future;Gene Duplication;Gene Family;Gene Proteins;Generations;Genes;Genetic;genetic signature;Germ Lines;Histologic;Histology;Infertility;innovation;Insecta;Interdisciplinary Study;Knock-out;Knockout Mice;male;male fertility;Male Infertility;mammalian genome;Mammals;member;Men's Role;Microscopy;Microtubules;Modeling;Molecular;Mus;novel;Nuclear;Orthologous Gene;paralogous gene;Phenotype;Play;Postdoctoral Fellow;pressure;programs;Protein Biochemistry;Protein Family;Proteins;Recording of previous events;recruit;Recurrence;Reproduction;reproductive;reproductive fitness;Research;Role;skills;sperm cell;Spermatogenesis;Structure;Surveys;System;Testing;Testis;tool;Training;Work

PROJECT_TITLE: Genetic Innovation of Cytoskeletal Proteins for Specialized Functions in the Male Germline


ORG_CITY: IRVINE

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: PROJECT NARRATIVE Using combined genetic, biochemical, spectroscopic and structural approaches, we propose to investigate how M-cluster, the unique metallocofactor of molybdenum nitrogenase, is assembled into a functional unit. Through our proposed studies, we expect to refine the biosynthetic mechanism of this catalytically important and chemically unprecedented metallocluster, which will provide crucial insights into the structural-functional relationship of nitrogenase and reveal some general principles of the assembly of complex metalloclusters in biological systems.

PI_NAMEs: RIBBE, MARKUS W (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TITLE: Nitrogenase assembly mechanism


NIH_SPENDING_CATS: Cancer;Childhood Leukemia;Hematology;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: PORTLAND

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

PHR: Hematologic malignancies that carry an activating mutation in the tyrosine phosphatase PTPN11 continue to carry a poor prognosis. Targeting this pathway to improve treatment of these diseases has remained difficult. We have recently shown that PTPN11 activity is dependent on activation by a tyrosine kinase, TNK2 that can be readily chemically targeted. Interrogation of these findings will lead to a better understanding of the activation and dependence of this pathway to improve treatment.

PI_NAMEs: CHANG, BILL H (contact);TYNER, JEFFREY WALLACE

PROGRAM_OFFICER_NAME: CHEN, WEIWEI

PROJECT_TERMS: Acute Myelocytic Leukemia;acute myeloid leukemia cell;Adaptor Signaling Protein;Address;Animal Model;Biochemical;Biochemical Pathway;Biological Assay;Biological Models;Bone Marrow Cells;cell killing;Cell Line;Cell model;Cell Survival;Cells;Chemicals;Chemoresistance;Clinical;clinical development;Combined Modality Therapy;Complex;CRISPR/Cas technology;Data;Dependence;Development;Disease;Drug Combinations;effective therapy;Evaluation;experience;Foundations;Goals;Hematologic Neoplasms;Hematology;Hematopoietic;Immunodeficient Mouse;improved;In Vitro;in vivo;inhibitor;Juvenile Myelomonocytic Leukemia;Knowledge;leukemia;Leukemic Cell;Malignant Neoplasms;MAP Kinase Gene;MAPK Signaling Pathway Pathway;MEKs;Modeling;Molecular;mouse model;Mus;mutant;Mutation;neoplastic cell;novel;Pathogenesis;Pathway interactions;Patients;Phosphorylation;Phosphotransferases;Play;pre-clinical;Prognosis;Proliferating;protein complex;Protein Dephosphorylation;protein phosphatase inhibitor-2;Protein Tyrosine Kinase;Protein Tyrosine Phosphatase;Proteins;PTPN11 gene;response;RNA Interference;Role;Sampling;Signal Transduction;small molecule inhibitor;Solid Neoplasm;targeted treatment;Tertiary Protein Structure;Testing;Therapeutic;therapeutic target;Transduction Gene;Transgenic Organisms;Treatment Protocols;Validation;Xenograft procedure

PROJECT_TITLE: Targeting PTPN11 dependent Hematologic Malignancies

STUDY_SECTION: DT

STUDY_SECTION_NAME: Developmental Therapeutics Study Section[DT]


NIH_SPENDING_CATS: Aging;Biodefense and Related Countermeasures;Biotechnology;Emerging Infectious Diseases;Immunization;Infectious Diseases;Influenza;Lung;Natural Products;Pneumonia and Influenza;Prevention;Vaccine Related

ORG_CITY: FARMINGTON

ORG_NAME: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT

ORG_STATE: CT

PHR: PROJECT NARRATIVE Older adults have reduced immune responses to vaccination that leave them more vulnerable to infectious diseases, such as influenza. The overall hypothesis in this proposal is that the age-associated accumulation of senescent cells and the senescence associated secretory phenotype (SASP) are the main drivers of diminished vaccine responses with aging. To assess this we will 1) pharmacologically eliminate senescent cells in mice via senolytic drugs prior to influenza vaccination and determine immunomodulatory effects on cell- mediated and humoral responses to vaccination and influenza infection challenge; and 2) determine translational impact via in vitro analyses of human T and B cell responses when exposed to senescent media.

PI_NAMEs: BARTLEY, JENNA  (contact)

PROGRAM_OFFICER_NAME: LEITNER, WOLFGANG W

PROJECT_TERMS: Adjuvant;Age;age related;age-related disease;aged;Aging;aging population;Antibodies;Antibody titer measurement;B-Lymphocytes;Biology of Aging;Cause of Death;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;Cell Aging;Cell Cycle Arrest;cell type;Cells;Cessation of life;chemokine;Clinical;Clinical Trials;Coin;Communicable Diseases;Complex;COVID-19 pandemic;COVID-19 vaccine;cytokine;Dasatinib;draining lymph node;Drug Combinations;Exposure to;extend lifespan;FDA approved;Flow Cytometry;flu;Functional disorder;Gene Expression;Genus Hippocampus;Geroscience;hallmarks of aging;healthspan;Helper-Inducer T-Lymphocyte;Human;Immune response;Immune system;Immunity;Immunohistochemistry;immunoregulation;Impairment;improved;In Vitro;Individual;Infection;Inflammatory;inflammatory milieu;Influenza;influenza infection;Influenza vaccination;influenza virus vaccine;Lung;Mediating;Memory;Metabolic;Metabolism;Methods;Morbidity - disease rate;mortality;Mus;neutralizing antibody;Nucleoproteins;old mice;older adult;Older Population;Pathology;Pathway interactions;Pharmaceutical Preparations;pharmacologic;Phenotype;Pilot Projects;Play;Predisposition;prevent;programs;Pulmonary Inflammation;Quercetin;Recombinants;response;Risk;Role;Safety;senescence;senescence associated secretory phenotype;senescent cell;senolytics;Serum;Severities;Severity of illness;Spleen;Structure of germinal center of lymph node;systemic inflammatory response;T cell response;T-Cell Proliferation;T-Lymphocyte;Testing;Tissues;tool;translational impact;Vaccinated;Vaccination;vaccine access;vaccine efficacy;vaccine immunogenicity;vaccine response;Vaccines;Viral;Viral Load result;young adult

PROJECT_TITLE: Impact of Senolytics on Aged Vaccine Responses

STUDY_SECTION: CMAD

STUDY_SECTION_NAME: Cellular Mechanisms in Aging and Development Study Section[CMAD]


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: SAN DIEGO

ORG_NAME: VA SAN DIEGO HEALTHCARE SYSTEM

PHR: Lung cancer is the leading cause of cancer death in the country, surpassing deaths caused by colorectal, prostate and breast cancers combined. Veterans are at higher risk of lung cancer due to the higher rate of smoking and environmental toxin exposures. The lack of effective therapy provides the impetus to search for alternative, safe, and efficacious anticancer agents to improve treatment strategy against lung cancer, enhance the probability of a cure and reduce recurrence. Based on encouraging preclinical and clinical findings in a lung cancer chemoprevention pilot study, the purpose of this new CSR&D Merit Review proposal is to evaluate the feasibility of a standardized grape seed procyanidin extract with enhanced bioavailabilities, leucoselect phytosome, for neoadjuvant treatment of resectable stage I and II lung cancer in a phase IIa clinical trial, to establish safety, feasibility, define and validate mechanisms of action, identify suitable surrogate endpoint biomarkers and set the stage for larger, confirmatory trials in the near future.

PI_NAMEs: MAO, JENNY T (contact)

PROJECT_TERMS: A549;Adverse reactions;Aftercare;anti-cancer;Antineoplastic Agents;Apoptosis;Arachidonate 15-Lipoxygenase;arm;aspirate;Biological Availability;Biological Markers;Biological Monitoring;biological specimen archives;Biopsy;Blood;Bronchoalveolar Lavage;Bronchoalveolar Lavage Fluid;Bronchoscopy;C-reactive protein;cancer chemoprevention;Cancer Etiology;Cancer Patient;cancer therapy;capsule;carcinogenicity;cardiovascular health;CASP3 gene;Cause of Death;Cells;Cessation of life;Chest;Clinic;Clinical;Clinical Research;Clinical Trials;Colorectal Cancer;Common Terminology Criteria for Adverse Events;Complex;confirmatory clinical trial;confirmatory trial;Consent;Country;Data;Development;Diagnosis;Diagnostic Procedure;Dinoprostone;Down-Regulation;Drug Kinetics;Early treatment;effective therapy;Eicosanoids;Enrollment;Epigenetic Process;Epoprostenol;Excision;follow-up;Food Supplements;former smoker;Future;Gene Expression Profile;grape seed;Growth;Health Food;high risk;Human;Hydroxyeicosatetraenoic Acids;IGF Type 2 Receptor;improved;indexing;inflammatory marker;insight;Interleukin-10;Interleukin-12;Interleukin-6;Label;Lesion;Lung;Lung Neoplasms;lymph nodes;Malignant Breast Neoplasm;Malignant neoplasm of lung;Malignant neoplasm of prostate;Malignant Neoplasms;Measures;Mediating;MicroRNAs;Monitor;Needles;Neoadjuvant Therapy;neoplastic cell;Newly Diagnosed;Non-Small-Cell Lung Carcinoma;Nude Mice;oncoprotein p21;Operative Surgical Procedures;Oral;Oral Administration;Outcome;Participant;Pathologic;Pathway interactions;Patients;Pharmacodynamics;pharmacokinetics and pharmacodynamics;Phase;Phospholipids;Phosphorylation;Physiological;Pilot Projects;Plasma;pre-clinical;predicting response;Probability;Procyanidins;Production;Proliferation Marker;Property;Prostaglandins I;Proto-Oncogene Proteins c-akt;PTEN gene;Qualifying;Questionnaires;recruit;Recurrence;Resectable;response;RNA;Role;Safety;Sampling;Serum;Smoking;soy;Specimen;Standardization;Structure of parenchyma of lung;Surrogate Endpoint;Telephone;Testing;Therapeutic;Time;Tissues;Toxic Environmental Substances;treatment strategy;tumor;Tumor Immunity;Tumor Suppressor Proteins;tumor xenograft;Up-Regulation;Urine;Veterans;Visit;Xenograft procedure

PROJECT_TITLE: Leucoselect Phytosome for Neoadjuvant Treatment of Early Stage Lung Cancer


NIH_SPENDING_CATS: Biomedical Imaging;Biotechnology;Cancer;Lung;Lung Cancer;Prevention;Rare Diseases

ORG_NAME: FRED HUTCHINSON CANCER CENTER

PHR: PROJECT NARRATIVE Small cell lung cancer (SCLC) accounts for >30,000 American lives each year and portends five-year survival rates of just ~7%. Detection of SCLC at early stage drastically improves these survival metrics. We propose to leverage molecular features unique to SCLC, such as the development of autoantibody-antigen complexes, to validate a plasma biomarker panel capable of SCLC early detection to allow for early initiation of potentially curative chemotherapy.

PI_NAMEs: HOUGHTON, A MCGARRY (contact);LAMPE, PAUL D.

PROGRAM_OFFICER_NAME: MARQUEZ, GUILLERMO

PROJECT_TERMS: Accounting;American;Antibodies;Antigens;Autoantibodies;Autoantigens;Biological Assay;biomarker panel;Breast;Cancer Center;Cancer Etiology;Cancer Patient;candidate marker;cardiovascular health;case control;Central Nervous System;Cessation of life;chemotherapy;Clinic;Clinical;clinical diagnosis;clinical practice;cohort;Colon Carcinoma;Complex;computed tomography screening;Data Set;Detection;detection method;detection platform;Development;Diagnosis;Diagnostic;Disease;early detection biomarkers;Early Diagnosis;Extensive Stage;Generations;Goals;high dimensionality;Human;Hybrids;Image;implementation strategy;improved;Length;Lesion;Limited Stage;Lung;lung cancer screening;Malignant neoplasm of lung;Malignant Neoplasms;Methodology;Minority;Modality;Modeling;Molecular;Nodule;Non-Small-Cell Lung Carcinoma;novel;Outcome;Ovarian;Pancreas;Paraneoplastic Syndromes;Patients;Plasma;Prevention;Process;Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial;Proteins;Proteomics;Reproducibility;Sampling;screening;Screening for cancer;small cell lung carcinoma;Specimen;statistics;Survival Rate;Testing;Time;Translating;tumor;Validation;Variant;Women's Health;X-Ray Computed Tomography

PROJECT_TITLE: Tumor-specific autoantibodies for SCLC early detection

STUDY_SECTION: CBSS

STUDY_SECTION_NAME: Cancer Biomarkers Study Section[CBSS]


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

ORG_CITY: CINCINNATI

ORG_NAME: CINCINNATI CHILDRENS HOSP MED CTR

ORG_STATE: OH

PHR: Project Narrative While silencers (cis-regulatory elements) are known to be highly cell type specific, their contribution to CD4 T cell homeostasis is unknown. This proposal seeks to identify functional silencer elements in CD4 cells, and provide a mechanism for silencer activation through PRC2 binding and H3K27me3 formation. This proposal aims to provide a catalogue of T cell specific silencer elements, the defining histone marks, and transcription factor regulation of silencers in T cells.

PI_NAMEs: STEFAN, KURTIS  (contact)

PROGRAM_OFFICER_NAME: GONDRE-LEWIS, TIMOTHY A

PROJECT_TERMS: Acetylation;Atlases;Award;Binding;Binding Sites;Bioinformatics;Biological;Biological Assay;Biological Process;Biomedical Research;career;Catalogs;CD4 Positive T Lymphocytes;cell type;Cells;Cellular biology;Cessation of life;Characteristics;ChIP-seq;Chromatin;Clinical Oncology;Clinical Skills;cohort;Communication;Complex;cytokine;Data;Deposition;Disease;doctoral student;Elements;Enhancers;experience;EZH2 gene;Fellowship;Future;Gene Expression;Gene Expression Profile;Gene Expression Regulation;gene repression;Generations;Genes;Genetic Transcription;genome wide screen;genome-wide;Genomics;Goals;Health;Heterochromatin;Hi-C;histone modification;Histones;Homeostasis;Human;Human Genome;insight;Jurkat Cells;Laboratories;Libraries;Location;Lysine;Maintenance;Malignant Neoplasms;Mediating;Mentorship;Methods;Methylation;Molecular Biology;Molecular Biology Techniques;novel;Patient-Focused Outcomes;Pattern;Peripheral;pharmacologic;Plasmids;Polycomb;Production;programs;Publishing;recruit;Regulation;Regulatory Element;Reporting;Repression;Research;Research Personnel;Rest;Role;Site;T-Cell Activation;T-Lymphocyte;Testing;Training;Training Programs;transcription factor;Transcription Repressor;Transcriptional Regulation;Transcriptional Silencer Elements;transcriptome;Transfection;Tumor Promotion;Universities;Untranslated RNA;Validation;vector;Work;XCL1 gene

PROJECT_TITLE: Silencer Control of T cell Homeostasis

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


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

NIH_SPENDING_CATS: Biotechnology;Clinical Research;Immunization;Infectious Diseases;Lung;Pneumonia;Pneumonia and Influenza;Prevention;Vaccine Related

ORG_CITY: ATHENS

ORG_NAME: UNIVERSITY OF GEORGIA

ORG_STATE: GA

PHR: Streptococcus pneumoniae remains a leading cause of bacterial pneumonia and death due to infectious diseases worldwide despite the use of two approved vaccines targeting the serotypically diverse capsular polysaccharide. The infection rate remains high, especially in older adults, primarily due to infection with serotypes not included in current vaccines, and treatment options can be limited as there has been a rise in antibiotic resistance among non-vaccine serotypes. The research described in this R01 proposal will determine the protective efficacy and underlying structural and mechanistic correlates of protection of human monoclonal antibodies to highly conserved pneumococcal surface proteins.

PI_NAMEs: MOUSA, JARROD  (contact)

PROGRAM_OFFICER_NAME: UPADHYAY, MEENU MISHRA

PROJECT_TERMS: Acute;Address;Adhesions;Agglutination;Antibiotic Resistance;Antibodies;Antigen Targeting;Antigens;Asthma;B-Lymphocytes;Bacteremia;Bacteria;Bacterial Pneumonia;Binding;Cardiovascular Diseases;Cells;Cessation of life;Chronic Obstructive Pulmonary Disease;Clinical Trials;Communicable Diseases;Complement;Coupled;Cryoelectron Microscopy;Data;Death Rate;Deposition;Development;Diabetes Mellitus;Disease Management;Encapsulated;Epitopes;Exhibits;Failure;Frequencies;Growth;high risk population;HIV;Human;human monoclonal antibodies;Immunologics;improved;In Vitro;in vivo;Incidence;Individual;Infection;infection rate;infectious disease treatment;influenza infection;innovation;Interferometry;Invaded;Lung;Macrophage;Mediating;Membrane Proteins;Meningitis;Microbial Biofilms;Modeling;Monoclonal Antibodies;mouse model;Mus;Mutation;Nasopharynx;National Institute of Allergy and Infectious Disease;neutrophil;novel therapeutics;older adult;Otitis Media;pandemic influenza;pathogen;pathogenic bacteria;Pathway interactions;Pharmaceutical Preparations;Pneumococcal Colonization;Pneumococcal Infections;Pneumococcal Pneumonia;Pneumococcal vaccine;Pneumonia;Polysaccharides;prevent;Prevention;prophylactic;protective efficacy;Proteins;Protocols documentation;Readiness;Research;Role;Serotyping;Specificity;Streptococcus pneumoniae;structural determinants;synergism;Techniques;Therapeutic;United States National Institutes of Health;vaccine efficacy;Vaccines;Work;X-Ray Crystallography

PROJECT_TITLE: Epitope and mechanistic correlates of broadly protective human antibodies for pneumococcal infection

STUDY_SECTION: CMIA

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


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Digestive Diseases;Emerging Infectious Diseases;Foodborne Illness;Health Effects of Indoor Air Pollution;Infectious Diseases;Microbiome;Vector-Borne Diseases

ORG_CITY: VERMILLION

ORG_NAME: UNIVERSITY OF SOUTH DAKOTA

ORG_STATE: SD

PHR: STATEMENT OF PUBLIC HEALTH SIGNIFICANCE Enteric infectious diseases are among the most common illnesses in the world and the bacterium Salmonella enterica serovar Typhimurium is both a NIAID category B priority pathogen and a leading cause of morbidity and mortality from diarrhea globally. Colonization of cockroaches by S. Typhimurium not only enhances the potential for vector-borne transmission relative to mechanical mechanisms, but also creates an interphase for the evolution of antibiotic resistance and virulence traits that could influence the severity of cockroach-borne human infections. By illuminating the active role of cockroaches as vectors, our work will improve appreciation of cockroach control among the scientific and public health fields, which may lead to more concerted efforts to use existing cockroach control tools or develop novel tools for infection prevention in high-risk areas.

PI_NAMEs: PIETRI, JOSE ENRIQUE (contact)

PROJECT_TERMS: Address;Adhesions;Adult;anti-microbial peptide;Antibiotic Resistance;antimicrobial;Area;Bacteria;Bacterial Genes;Biological;Biological Assay;Biological Phenomena;Biological Process;Biology;Category B pathogen;Cells;colonization resistance;Communicable Diseases;Complex;Data;Development;Diarrhea;diarrheal disease;Dictyoptera;Disease;Disease Outbreaks;Enteral;Environment;Escherichia coli;Event;Evolution;Exhibits;Feces;Fluorescence Microscopy;Functional disorder;Gastrointestinal tract structure;Gene Expression;Genes;German population;Gnotobiotic;gut colonization;gut microbiota;high risk;Human;Image;improved;Infection;Infection prevention;Ingestion;Insecta;insight;Intake;Integration Host Factors;interest;Interphase;Invaded;knock-down;Laboratories;life span;Life Style;Link;Location;Mechanics;Membrane;Microbial Biofilms;Microscopy;Modeling;Monitor;Morbidity - disease rate;mortality;mutant;National Institute of Allergy and Infectious Disease;Nature;novel;Nymph;pathogen;pathogenic bacteria;Population;Process;Protocols documentation;Public Health;Quantitative Reverse Transcriptase PCR;Research Project Grants;RNA Interference;Role;Salmonella;Salmonella typhimurium;Severities;Shapes;Site;spatiotemporal;System;Testing;Tissues;tool;trait;transmission process;Up-Regulation;vector;vector-borne;Virulence;Vomiting;Work

PROJECT_TITLE: Biological vector borne transmission of Salmonella by cockroaches

STUDY_SECTION: VB

STUDY_SECTION_NAME: Vector Biology Study Section[VB]


NIH_SPENDING_CATS: Genetics;Human Genome

ORG_CITY: BOSTON

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: RELEVANCE (See instructions): Our proposed studies will further elucidate the mechanism of chromatin loop extrusion-mediated lgH CSR, test the role of loop extrusion in SHM and also address the function of recurrent BCR clonotypes expressed in chronic intestinal Peyer's Patch germinal cente rs. To address these questions, we are applying a host of powerful new technologies developed by our lab. The proposed work should advance our understanding of key antibody maturation mechanisms and may provide insights into potential roles of Peyer's Patch germinal center antibodies with respect to involvement in normal physiology or disease.

PI_NAMEs: ALT, FREDERICK W. (contact)

PROGRAM_OFFICER_NAME: CASTLEMAN, MORIAH JOVITA

PROJECT_TERMS: Address;Alleles;Antibodies;Antigens;Autoantigens;B cell repertoire;B-Cell Activation;B-Lymphocytes;Binding;Biological Assay;Biological Models;blastocyst;Cell Cycle;Cell Line;Cell Lineage;Cells;Chromatin;Chromatin Loop;Chronic;cohesin;Complex;Development;dextran sulfate sodium induced colitis;dietary;Disease;Downstream Enhancer;Elements;embryonic stem cell;Engineering;Enhancers;Exons;Frequencies;G1 Phase;Generations;Genetic Complementation Test;Genetic Transcription;Genomic Segment;Germ Lines;global run on sequencing;Goals;Grant;Guide RNA;Human;Image;Immunoglobulin Class Switching;Immunoglobulin Constant Region;Immunoglobulin Somatic Hypermutation;Immunoglobulin Switch Recombination;in vivo;in vivo Model;insight;Instruction;Intestines;Knock-in;Label;Location;Maps;Mediating;microbial;microbiome;microbiota composition;Modeling;mouse model;Mus;new technology;news;pandemic disease;Pattern;Peyer's Patches;Physiological;Physiology;Play;Positron-Emission Tomography;Predisposition;Probability;Productivity;Progress Reports;protein complex;Publications;Published Comment;Recurrence;Regulation;repaired;Repetitive Sequence;Reporting;Research;response;Role;single-cell RNA sequencing;Site;Structure of germinal center of lymph node;Study models;System;Testing;Textbooks;V(D)J Recombination;Work

PROJECT_TITLE: Mechanisms that Regulate Antibody Class Switch Recombination and Somatic Hypermutation

STUDY_SECTION_NAME: NSS