ORG_DEPT: BIOLOGY

ORG_NAME: CLARK ATLANTA UNIVERSITY

PHR: Chemoresistant prostate cancer (PCa) is lethal with no cure. This R01 project will develop a novel class of EED inhibitors that interrupt EED-EZH2 interaction and block noncanonical EZH2 survival signaling in chemoresistant PCa cells. We anticipate to identify several patentable, highly potent and efficacious EED inhibitors with optimized pharmacological profiles and drug-like properties, which can be promptly moved to the next stages of drug development. This project is original, innovative and has high impact on both translational research and patient care.

PI_NAMEs: WU, DAQING  (contact)

PROGRAM_OFFICER_NAME: AGYIN, JOSEPH KOFI

PROJECT_TERMS: ABCB1 gene;absorption;advanced prostate cancer;analog;androgen independent prostate cancer;anticancer activity;Basic Science;Binding;Biological;Biology;Cancer Patient;Characteristics;Chemicals;Chemoresistance;chemotherapy;Clinical;clinical development;Complex;Death Rate;design;Development;Disease Progression;docetaxel;Dose;Drug Design;drug development;drug discovery;Drug Kinetics;drug synthesis;Ectoderm;Embryo;Enhancers;Epigenetic Process;Excretory function;Goals;good laboratory practice;Growth;Homologous Gene;improved;In Vitro;in vivo;in vivo evaluation;inhibitor;innovation;Interruption;Intervention;Knowledge;Lead;lead optimization;Malignant neoplasm of prostate;Medical;Metabolism;mortality;Mus;NCI Center for Cancer Research;new chemical entity;novel;novel strategies;Oncogenic;Outcome;Pathway interactions;Patient Care;Patients;Pharmaceutical Preparations;pharmacologic;Pharmacology;Phenotype;Polycomb;pre-clinical;Pre-Clinical Model;preclinical development;preclinical efficacy;preclinical safety;Property;prostate cancer cell;prostate cancer model;Prostate Cancer therapy;Protein Kinase;Qualifying;rational design;Reader;Research;research and development;Resistance;S phase;Safety;screening;Signal Transduction;small molecule;Specificity;standard of care;Stat2 protein;Stat3 protein;survivin;Testing;Texas;theranostics;Therapeutic;therapeutic development;Toxic effect;Toxicology;Translating;Translational Research;Universities;Work;Xenograft Model

PROJECT_TITLE: Targeting chemoresistant prostate cancer with novel EED inhibitors

STUDY_SECTION: DT

STUDY_SECTION_NAME: Developmental Therapeutics Study Section[DT]


ADMINISTERING_IC: AI

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

ORG_CITY: ROCKVILLE

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: ABVACC, INC.

ORG_STATE: MD

PHR: Staphylococcus aureus (SA) and in particular methicillin resistant SA (MRSA) is a major human pathogen that causes a wide range of infections from skin infections to life threatening bloodstream infections with high mortality rate. Currently nearly as many people die in the US from SA as from AIDS. The efforts towards development of vaccines have been unsuccessful. The recent clinical study on Merck V710 vaccine for SA in patients undergoing cardiac surgeries led to increased mortality in people who were vaccinated and got infected after operation. Studies indicate that there is a detrimental immune response in some patients that leads to vaccine failure. The goal of this proposal is to delineate the underlying mechanisms of the deleterious and protective immune responses to SA vaccines. These studies will help us develop more effective vaccines in future.

PI_NAMEs: AMAN, M JAVAD (contact);ARCHER, NATHAN K.

PROGRAM_OFFICER_NAME: RITCHIE, ALEC

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Adjuvant;Affect;Antibiotic Resistance;Antibiotics;Antigens;Bacteremia;Cardiac Surgery procedures;CD4 Positive T Lymphocytes;cell injury;cell mediated immune response;Cessation of life;Clinical;clinical care;Clinical Research;Clinical Trials;Cutaneous;cytokine;Death Rate;Development;Disease;efficacy testing;Endothelial Cells;Epithelial Cells;Exposure to;Future;Generations;Goals;HLA-DR4 Antigen;Human;human pathogen;humanized mouse;IL17 gene;Immune;Immune Evasion;Immune response;Immunity;Immunization;Immunize;Immunologics;immunopathology;Immunotherapy;improved;Incidence;Individual;Infection;Infectious Skin Diseases;insight;Interferon Type II;Interleukin-2;Iron;Life;Macaca fascicularis;Mediating;methicillin resistant Staphylococcus aureus;Modeling;Morbidity - disease rate;mortality;Multiple Organ Failure;Mus;mutant;nonhuman primate;novel;operation;Operative Surgical Procedures;Outcome;Parents;Pathogenicity;Patient-Focused Outcomes;Patients;Persons;Phenotype;Pilot Projects;Placebo Control;Placebos;Pre-Clinical Model;premature;Prevalence;prevent;Proteins;Public Health;Recurrence;response;Role;Sepsis;Serum;Staphylococcal Vaccines;Staphylococcus aureus;Staphylococcus aureus infection;Stromal Cells;Superantigens;Surface;Surface Antigens;Systemic infection;T cell anergy;T cell response;T-Lymphocyte;Testing;Time;Toxin;Toxoids;Transgenic Mice;Transgenic Organisms;Treatment Failure;Vaccinated;Vaccination;vaccination outcome;Vaccine Adjuvant;vaccine development;vaccine efficacy;vaccine failure;vaccine immunogenicity;vaccine platform;vaccine-induced immunity;Vaccinee;Vaccines;Virulence;Virulence Factors;Whole Cell Vaccine;Wild Type Mouse

PROJECT_TITLE: Protective versus deleterious immune responses that impact vaccine efficacy against Staphylococcus aureus bloodstream infection

STUDY_SECTION: VMD

STUDY_SECTION_NAME: Vaccines Against Microbial Diseases Study Section[VMD]


ED_INST_TYPE: SCHOOLS OF MEDICINE

ORG_CITY: NEW YORK

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

ORG_STATE: NY

PHR: NARRATIVE Tuberculosis remains a leading cause of death from infection because the causative agent, Mycobacterium tuberculosis (Mtb), is highly successful at moving in airborne micro-droplets from the damaged lungs of one coughing, talking or sneezing person to the healthy lungs of several others. To succeed in this journey, Mtb must survive drastic, rapid, sequential changes in the composition of the surrounding fluid; the concentrations of oxygen, carbon dioxide, water and hydrogen ions; and the ambient temperature. This Program Project brings new technologies and animal models to bear to characterize Mtb's transmission biology at genomic, metabolomic and lipidomic levels; to use the physics of respirable aerosols to guide the development and use of a mouse model for testing genetic hypotheses; and to improve on the historic guinea pig model of natural transmission through new molecular knowledge of how Mtb makes an infected host cough.

PI_NAMEs: NATHAN, CARL FRANCIS;RHEE, KYU Y (contact)

PROGRAM_OFFICER_NAME: LACOURCIERE, KAREN A

PROJECT_TERMS: aerosolized;Aerosols;Air;Animal Model;Animals;Area;Basic Science;Biochemical;Biology;Biophysics;Burn injury;Candidate Disease Gene;Carbon Dioxide;Cause of Death;Cavia;Cessation of life;Characteristics;chemotherapy;clinical phenotype;Communicable Diseases;Communities;Coughing;COVID-19;Development;Devices;Discipline;Disease;Drug Targeting;Ensure;Environmental Risk Factor;Event;experimental study;Foundations;Gases;gene function;Generations;Genes;Genetic;genetic testing;genome wide screen;Genomics;Goals;grasp;guinea pig model;Human;Human Resources;Humidity;improved;In Vitro;Incidence;Infection;innovation;Integration Host Factors;Intervention;Knowledge;Life Cycle Stages;lipidomics;Lipids;Liquid substance;Lung;lung injury;Mechanics;Metabolic;Metabolic Pathway;metabolomics;Methods;Microbiology;Modeling;Modification;Molecular;mortality;mouse model;Mycobacterium tuberculosis;new technology;novel;novel strategies;Outcome;Oxygen;pandemic disease;pathogen;Persons;Physics;Physiological;Physiology;pre-clinical;pressure;programs;Property;Protons;reproductive;Research;Research Personnel;respiratory;response;Route;Sneezing;Source;Stress;Technology;Temperature;Testing;tool;Translating;transmission blocking;transmission process;Travel;Tuberculosis;tuberculosis treatment;Virulence Factors;Water

PROJECT_TITLE: Transmission Aerobiology of M. tuberculosis: Genes and Metabolic Pathways That Sustain Mtb Across an Evolutionary Bottleneck


ADMINISTERING_IC: CA

ED_INST_TYPE: SCHOOLS OF PHARMACY

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: PITTSBURGH

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: NARRATIVE This PITT-CAL ETCTN PK Resource Laboratory will serve as a consolidated, integrated resource providing PK analyses to the NCI Experimental Therapeutics Clinical Trials Network (ETCTN). By characterizating absorption, disposition, metabolism, and excretion (ADME), and integration of this knowledge with biomarker and clinical findings through application of our pharmacology expertise, we will rapidly and efficiently advance CTEP agents through the various phases of clinical development, ultimately enhancing the quality of care of cancer patients.

PI_NAMEs: BEUMER, JAN HENDRIK (contact);SYNOLD, TIMOTHY W

PROGRAM_OFFICER_NAME: IVY, S PERCY

PROJECT_TERMS: absorption;Adopted;Antineoplastic Agents;Area Under Curve;Award;Biological;Biological Assay;Biological Markers;Cancer Center;Cancer Patient;Cancer Therapy Evaluation Program;Capital;Cell Therapy;Cities;Clinical;clinical development;Clinical Research;Clinical Trials;Clinical Trials Network;Comprehensive Cancer Center;Consultations;Core Facility;Correlative Study;Data;Data Analyses;data integration;Data Reporting;design;Development;Dose;drug development;Drug Interactions;Drug Kinetics;Early Therapeutic-Clinical Trials Network;Ensure;Evaluation;Excretory function;experience;Food;Funding;Future;Goals;good laboratory practice;Half-Life;Infrastructure;instrumentation;International;Investigation;Investigational Therapies;Investments;knowledge integration;Laboratories;laboratory experience;Laboratory Personnel;Lead;Leadership;Life Cycle Stages;Malignant Neoplasms;Measures;member;Metabolic;Metabolism;multidisciplinary;National Cancer Institute;Pharmaceutical Preparations;Pharmacodynamics;pharmacokinetics and pharmacodynamics;pharmacologic;Pharmacology;Phase;Philosophy;Plasma;Population;pre-clinical;Procedures;Process;Protocols documentation;Quality Control;Quality of Care;Reagent;Reporting;Research;research clinical testing;Research Design;Research Infrastructure;Research Personnel;Resources;response;sample collection;Sampling;Science;small molecule;Specimen;statistics;Testing;Tissues;Toxic effect;Training;U-Series Cooperative Agreements;Writing

PROJECT_TITLE: PITT-CAL ETCTN PK Resource Laboratory


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

PI_NAMEs: RHEE, KYU Y (contact)

PROJECT_TERMS: Address;aerosolized;Animal Model;Biology;Budgets;Businesses;Characteristics;clinical phenotype;Communication;conflict resolution;data exchange;data sharing;Development;Discipline;Drug Targeting;Ensure;Epidemiology;Equipment;Funding;gene function;Genes;Genetic;Goals;In Vitro;Intervention;Liquid substance;material transfer agreement;meetings;Metabolic;Metabolic Pathway;Microbiology;Modification;Mycobacterium tuberculosis;National Institute of Allergy and Infectious Disease;Needs Assessment;novel strategies;programs;Property;Protocols documentation;Research;Research Personnel;Resolution;respiratory;response;Role;Route;Supervision;synergism;Testing;Translating;transmission blocking;transmission process;Travel;tuberculosis treatment;Work

PROJECT_TITLE: Administrative Core


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Clinical Research;Emerging Infectious Diseases;Genetics;Infectious Diseases;Orphan Drug;Rare Diseases;Tuberculosis

PI_NAMEs: DARTOIS, VERONIQUE  (contact)

PROJECT_TERMS: Address;aerosolized;Aerosols;Affect;Animal Model;Animals;Automobile Driving;Bacillus;Bacteria;Bacterial Genes;bacterial genetics;bactericide;Bacteriology;Bar Codes;Biological;Biophysics;biosafety level 3 facility;Candidate Disease Gene;candidate validation;Cavia;Clinical;clinically relevant;Cone;Coughing;Data Set;deep sequencing;Desiccation;Devices;Disease;Dose;Doxycycline;experimental study;Exposure to;fitness;fly;Foamy Macrophage;Generations;Genes;Genetic;Genetic study;Genomic DNA;Histologic;Human;immunopathology;Impairment;In Vitro;in vivo;Infection;knock-down;Liquid substance;Lung;man;Measures;Metabolic;Metabolic Pathway;Modeling;mouse model;Mus;mutant;Mycobacterium tuberculosis;Nose;Oryctolagus cuniculus;Outcome;Output;Pathway interactions;Pharmaceutical Preparations;Physiology;Program Research Project Grants;programs;Publishing;Reproducibility;Resource Sharing;respiratory;response;Stress;Testing;Time;tool;transmission process;treatment response;tuberculosis drugs;Validation;Variant;Viscosity;Work

PROJECT_TITLE: Core B: Animal Model Core


NIH_SPENDING_CATS: Biotechnology;Cancer;Genetics;Immunotherapy;Lung;Lung Cancer;Orphan Drug;Rare Diseases

ORG_CITY: TAMPA

ORG_NAME: H. LEE MOFFITT CANCER CTR & RES INST

ORG_STATE: FL

PHR: The transcriptional co-activator YAP1 is the oncogenic component of the Hippo signaling cascade and contributes to the genesis and metastasis of a variety of cancers, by modulating a variety of oncogenic events including proliferation, epithelial-mesenchymal transition, angiogenesis and metastasis. Here we find that YAP1 is regulated by a novel set of signaling events. Our ongoing studies show that the tank binding kinase TBK1 binds to and phosphorylates YAP1; depletion of TBK1 significantly elevated YAP1 levels selectively in K- Ras mutant lung cancers, through arginine methylation mediated by CARM1. We hypothesize that these regulatory mechanisms facilitate the growth of K-Ras mutant lung cancers and can be targeted for therapy.

PI_NAMEs: KISSIL, JOSEPH  (contact)

PROGRAM_OFFICER_NAME: WATSON, JOANNA M

PROJECT_TERMS: Adenocarcinoma Cell;Affect;amlexanox;angiogenesis;anti-cancer;anticancer activity;Arginine;Binding;Blood Vessels;Cancer Etiology;Cancer Patient;cell transformation;chemotherapeutic agent;ChIP-seq;Clinical Trials;coactivator-associated arginine methyltransferase 1;Coculture Techniques;combat;Communication;Complex;Cytoplasm;Cytotoxic T-Lymphocytes;Dimensions;Disease;Down-Regulation;driver mutation;Drug resistance;Epidermal Growth Factor Receptor;Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor;Epithelium;Erlotinib;Event;experimental study;F-Box Proteins;gemcitabine;Gene Expression Regulation;Gene Targeting;Genetic;Genetic Transcription;Growth;Hematologic Neoplasms;HIF1A gene;Human;Hydroxylation;Hypoxia;Immune checkpoint inhibitor;Immunosuppression;Immunotherapy;improved;In Vitro;in vivo evaluation;inhibitor;Isogenic transplantation;KRAS2 gene;Lung;Lung Adenocarcinoma;lung cancer cell;Malignant neoplasm of lung;Malignant neoplasm of pancreas;Malignant Neoplasms;Mediating;Mediation;MEKs;Mesenchymal;Methylation;mimicry;Modality;Molecular;mortality;mouse model;multicatalytic endopeptidase complex;Mus;mutant;Mutation;Nature;Neoplasm Metastasis;Neurofibromin 2;Non-Small-Cell Lung Carcinoma;non-smoker;Normal tissue morphology;novel;novel strategies;Nuclear Hormone Receptors;Oncogenic;Operative Surgical Procedures;Organ Size;overexpression;Pancreas;Pathway interactions;patient subsets;Patients;Phosphorylation;Phosphotransferases;Platinum Compounds;PLK1 gene;Primary Neoplasm;Proliferating;Proteins;Recurrence;Recurrent tumor;Regulation;Reporting;Resistance development;response;RNA Processing;Role;Sampling;self-renewal;Signal Pathway;Signal Transduction;Smoker;stem-like cell;Survival Rate;T-Lymphocyte;TANK-binding kinase 1;targeted treatment;taxane;Testing;Therapeutic;therapeutic target;Time;Transcription Coactivator;Transcription Factor AP-1;transcriptome sequencing;Transferase;transplant model;tumor;tumor progression;tumor xenograft;United States;Xenograft Model

PROJECT_TITLE: CARM1-mediated regulation of YAP1 as a therapeutic target in lung cancer

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


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Mental Health;Mental Illness;Neurosciences;Precision Medicine;Psychosis;Schizophrenia;Serious Mental Illness

ORG_CITY: BOSTON

ORG_NAME: BETH ISRAEL DEACONESS MEDICAL CENTER

ORG_STATE: MA

PHR: Project Narrative Treatment advances in psychosis are limited by the use of phenomenology-defined diagnoses based on symptomatic outcomes, rather than by neurobiological constructs monitored by quantitative characteristics. The Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) uses biomarkers to define psychosis subgroups with the goal of testing the advantages of B-SNIP biomarkers for diagnostic and therapeutic decisions, consistent with principles in the NIMH Strategic Plan. We propose to test Biotype1 psychosis subgroup with clozapine, and predict a differential clinical response to clozapine compared with Biotype2, marked by normalization of IEA, cortical attractor network activity and an advantage over usual antipsychotic drugs, establishing low IEA in Biotype1 as a predictive biomarker for clozapine efficacy.

PI_NAMEs: KESHAVAN, MATCHERI S. (contact)

PROGRAM_OFFICER_NAME: RUDORFER, MATTHEW V

PROJECT_TERMS: anti-depressive agents;Antipsychotic Agents;Bacterial Artificial Chromosomes;Biological Markers;biotypes;blind;Blinded;Blood;Characteristics;Chemistry;Clinical;Clinical assessments;clinical efficacy;Clinical Trials;Clinical Trials Cooperative Group;Clinical Trials Design;Clozapine;Cognition;Communities;Complex;Consent;deviant;Diagnosis;Diagnostic;Dose;Double-Blind Method;Dropout;Drug Monitoring;Electrocardiogram;Electroencephalography;forging;Future;Goals;Grant;improved;Individual;Libraries;Measures;Monitor;Myocarditis;National Institute of Mental Health;neural;Neurobiology;Neutropenia;Outcome;Participant;Patients;Pharmaceutical Preparations;Pharmacotherapy;phenomenological models;Phenotype;phenotypic biomarker;Physicians;Physiological;Plasma;predictive marker;Preparation;proband;Prognosis;Psychoses;Randomized;recruit;Regimen;research clinical testing;Resistance;response;Risperidone;Saccades;Safety;Sampling;Schedule;Schizophrenia;Seizures;side effect;Site;Specific qualifier value;stimulus processing;Strategic Planning;Subgroup;symptomatic improvement;Symptoms;Testing;Therapeutic;Time;Titrations;treatment duration;volunteer;Work

PROJECT_TITLE: 4/5: Antipsychotic Response to Clozapine in B-SNIP Biotype-1 (CLOZAPINE)


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Clinical Research;Emerging Infectious Diseases;Genetics;Infectious Diseases;Lung;Orphan Drug;Rare Diseases;Tuberculosis

PI_NAMEs: NATHAN, CARL FRANCIS (contact)

PROJECT_TERMS: aerosolized;Air;Alleles;Alveolar;Animal Model;Antioxidants;assay development;bactericide;Bicarbonates;Biological Assay;Biology;Buffers;Candidate Disease Gene;Carbon;Cavia;Clinical;Collaborations;Communicable Diseases;Complex;CRISPR interference;Desiccation;Development;disease transmission;DNA Repair;Dose;drug candidate;Drug Combinations;Drug Targeting;drug testing;epidemic response;Ethambutol;evaporation;Gene Expression;gene function;gene product;Genes;genome-wide;Goals;Hydration status;Hypoxia;In Vitro;Individual;Inhalation;innovation;isoniazid;knock-down;Knock-out;Lesion;Leukocytes;Libraries;Linezolid;Lipids;Liquid substance;Lung;lung lesion;Measles;Mechanics;Metabolic Pathway;Metabolism;metabolomics;meter;Modeling;Mus;mutant;Mycobacterium tuberculosis;Necrosis;Necrotic Lesion;neutrophil;new therapeutic target;novel strategies;Oryctolagus cuniculus;Persons;Pharmaceutical Preparations;Phenotype;Physiological;Population;Preclinical Testing;programs;prophylactic;proteostasis;Pulmonary alveolar structure;Pyrazinamide;Regimen;Reproduction;Research;Research Personnel;Resuscitation;Rifampin;Stress;surfactant;Surveys;Testing;Therapeutic;tool;transmission blocking;transmission process;Tuberculosis;tuberculosis drugs;Validation;Virulence

PROJECT_TITLE: Project 1: Transmission Biology of M. tuberculosis: Genes Required to Survive Stressful Transitions


ADMINISTERING_IC: DK

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Digestive Diseases

ORG_CITY: SEATTLE

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: NARRATIVE Surgeons need formalized, rigorous training programs to prepare them to conduct the type of research that is needed for a more effective and efficient healthcare delivery system. This T32 training program prepares surgeons for successful careers in research and in leading the learning healthcare systems of the future, with a focus on gastrointestinal conditions that are some of the most common reasons for surgery. With rigorous training in research methods, practical skills for leading research centers, statewide and national platforms for community-based research, and structured mentorship, these trainees will become independently funded scientists and leaders in high-impact surgical research.

PI_NAMEs: FLUM, DAVID R (contact)

PROGRAM_OFFICER_NAME: SERRANO, KATRINA JANE

PROJECT_TERMS: Fellowship;Gastrointestinal Surgical Procedures;Outcomes Research

PROJECT_TITLE: Gastrointestinal Surgery Outcomes Research Fellowship


ADMINISTERING_IC: AG

ED_INST_TYPE: ORGANIZED RESEARCH UNITS

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Clinical Research

ORG_CITY: ANN ARBOR

ORG_DEPT: MISCELLANEOUS

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE  We propose to form a research network of internationally-renowned methodological and substantive experts who are actively researching the benefits of new data collection methodologies for longitudinal studies of aging in response to recent societal developments. The proposed network will meet regularly to shape methodological innovations specifically for the measurement of aging populations and design studies that will produce evidence-based best practices for this type of longitudinal measurement. Via a coordinated international program of training, consulting, thematic working group meetings, and pilot research projects, we aim to set the agenda for methodological research on longitudinal studies of aging and protect NIA investments in population-representative longitudinal studies by maximizing their methodological quality.

PI_NAMEs: LEE, SUNG-HEE ;WEST, BRADY T (contact)

PROGRAM_OFFICER_NAME: KARRAKER, AMELIA WILKES

PROJECT_TERMS: Acceleration;Aging;aging demography;aging population;Appointment;Asian Americans;Behavioral;Biological Markers;Biosocial;Collaborations;Communication;Complement;Complex;Consent;Consult;COVID-19 pandemic;Data;Data Collection;data collection methodology;design;Development;Devices;Educational workshop;Electronics;Ensure;Environment;Ethnic Origin;evidence base;experience;Faculty;Funding;Future;Goals;Group Meetings;Health;Health and Retirement Study;Hispanic Americans;Hispanic Populations;Home;improved;Influentials;innovation;International;Interview;Investigation;Investments;Lead;Life Cycle Stages;Linguistics;Link;Longitudinal Studies;Measurement;Measures;meetings;member;Methodology;Methods;Michigan;mid-career faculty;Minority;Minority Groups;Modernization;new technology;Online Systems;Paper;Participant;Patient Self-Report;Pilot Projects;Play;Population;population based;Population Study;Postdoctoral Fellow;programs;Race;Records;recruit;Research;Research Activity;research and development;Research Design;Research Methodology;Research Personnel;Research Project Grants;response;Retirement;Role;Running;Series;Shapes;social;Social Interaction;Subgroup;Survey Methodology;Surveys;synergism;Techniques;Technology;Time;Training;Training Activity;Training Programs;trend;Universities;virtual;web portal;web site;Work;working group

PROJECT_TITLE: Network for Advancing Methodological Research in Longitudinal Studies of Aging


PROJECT_TERMS: aerosolized;Aerosols;Air;Alleles;Anabolism;Animal Model;Antimicrobial Resistance;Area;Arginine;Atmosphere;atmospheric carbon dioxide;Attention;Biological Assay;Buffers;Carbamyl Phosphate;Carbon Dioxide;carbonate dehydratase;Cause of Death;Clinic;Clinical;clinically relevant;Collaborations;Communicable Diseases;comparative;Complex;CRISPR interference;Culture Media;Data;Desiccation;Diagnostic tests;Disease;Ensure;Environment;Enzymes;Epidemiology;Event;Face;Gases;Genes;genetic approach;genome sequencing;Goals;Human;Hydration status;Hypoxia;Immunity;Impairment;In Vitro;Infection;Interruption;Intervention;Life;Life Cycle Stages;lipidome;lipidomics;Lipids;Liquid substance;Location;Measurable;Mediating;Metabolic;Metabolic Pathway;Metabolism;microbial products;Modality;Modeling;Mus;Mycobacterium tuberculosis;Nature;novel;Nucleotide Biosynthesis;Oryctolagus cuniculus;pandemic disease;pandemic response;Pathogenicity;Phase;Phenotype;physiologic model;Physiological;Physiology;pressure;prevent;programs;Purines;Pyrimidine;Recording of previous events;Reporting;response;Saline;Series;Source;Stress;Testing;transcriptome;transcriptomics;transmission blocking;transmission process;Tuberculosis;Vaccines;whole genome

PROJECT_TITLE: Project 2: Essential metabolic objectives of M. tuberculosis aerobiology


ADMINISTERING_IC: DC

ED_INST_TYPE: SCHOOLS OF EDUCATION

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Cerebrovascular;Clinical Research;Clinical Trials and Supportive Activities;Neurosciences;Physical Rehabilitation;Rehabilitation;Stroke

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: NEW YORK UNIVERSITY

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because it focuses on combining theoretically-guided behavioral intervention with neuromodulation to optimize treatment for acquired speech deficits subsequent to stroke, which pose a significant barrier to effective communication, and limit participation in professional, social, and family environments. While current treatments can promote some limited recovery, residual disability remains a problem, and understanding the mechanism of recovery will create the potential for significantly improved individualized outcomes. Thus, the proposed research is relevant to the part of the NIH's mission that pertains to reducing illness and disability.

PI_NAMEs: BUCHWALD, ADAM  (contact)

PROGRAM_OFFICER_NAME: KOPF, LISA MARIE

PROJECT_TERMS: Address;Affect;Anatomy;Anodes;Anterior;Apraxia;Association Learning;Behavior;Behavior Therapy;Behavioral;behavioral outcome;chronic stroke;Clinical;Combined Modality Therapy;Communication;Data;design;direct application;disability;Effectiveness;Electrodes;Environment;experimental study;Family;Functional Magnetic Resonance Imaging;Goals;Impairment;improved;indexing;Individual;innovation;Insula of Reil;Intervention;Learning;learning outcome;Left;Lesion;Life;Light;Location;Measures;Methodology;Mission;Modeling;Motor;Motor Cortex;motor learning;motor recovery;neural;Neurobiology;neuroimaging;Neurologic;neuromechanism;neuroregulation;novel;Outcome;Participant;Pathway Analysis;Phase;Population;Positioning Attribute;Production;Protocols documentation;Public Health;Quality of life;Recovery;Research;Residual state;Rest;Role;skills;social;sound;Speech;Speech Sound;Stroke;stroke recovery;stroke survivor;Techniques;Testing;Time Series Analysis;Training;transcranial direct current stimulation;treatment effect;treatment optimization;Treatment outcome;United States;United States National Institutes of Health;Validation;Work

PROJECT_TITLE: Optimizing speech motor learning with neuromodulation: Behavioral outcomes and neural mechanisms

STUDY_SECTION: MFSR

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


NIH_SPENDING_CATS: Adolescent Sexual Activity;Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Dissemination and Implementation Research;HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Mental Health;Pediatric;Pediatric - AIDS;Prevention;Primary Health Care;Social Determinants of Health

ORG_CITY: PROVIDENCE

ORG_NAME: RHODE ISLAND HOSPITAL

ORG_STATE: RI

PHR: PROJECT NARRATIVE Adolescent sexual minority males are at higher risk than other groups for HIV infection in the United States; yet, there are few interventions focused on HIV prevention in this group, including those involving pre-exposure prophylaxis (PrEP) uptake. Importantly, parents are a main source of support for adolescents yet rarely included in research or interventions. Dr. Rusley will work with his mentor team to develop a family-based HIV prevention intervention that includes PrEP for adolescent sexual minority males, with the goal to decrease HIV transmission in this key population.

PI_NAMEs: RUSLEY, JACK  (contact)

PROGRAM_OFFICER_NAME: KAMATH, SUSANNAH M A

PROJECT_TERMS: acceptability and feasibility;Address;Adolescence;Adolescent;Adolescent and Young Adult;Adolescent Medicine;Adult;Age;AIDS prevention;Area;attentional control;Behavior;behavior change;Behavior Therapy;Behavioral Sciences;Bisexual;career;Child;Childhood;Clinical Research;Communication;Counseling;critical developmental period;Data;Disclosure;Disparity;Education;Effectiveness;Effectiveness of Interventions;emtricitabine;Environment;Ethical Issues;evaluation/testing;evidence base;experience;Family;first sexual experience;follow-up;formative assessment;Foundations;Friends;Fumarates;Funding;Gays;Goals;group intervention;health disparity;high risk;high risk population;HIV;HIV Infections;HIV risk;Hospitals;implementation design;implementation science;improved;Incidence;Individual;Interdisciplinary Study;interest;Intervention;intervention effect;intervention mapping;Intervention Trial;Interview;Knowledge;Learning Module;male;male health;men;men who have sex with men;Mentored Patient-Oriented Research Career Development Award;Mentors;Methods;Motivation;motivational enhancement therapy;Outcome Assessment;parental involvement;Parents;Participant;pilot test;Play;Population;Populations at Risk;pre-exposure prophylaxis;prevent;Prevention;Prevention Research;Prevention strategy;preventive intervention;Primary Care;primary care clinician;primary care provider;primary care setting;primary outcome;Process;Public Health;Randomized;randomized trial;recruit;Research;Research Personnel;Rhode Island;Risk;Risk Behaviors;risk perception;Risk Reduction;Role;Sampling;Scientist;secondary outcome;sexual debut;Sexual Health;sexual minority male;sexual minority youth;Sexuality;skills;Source;success;Tenofovir;Testing;therapy development;Time;tool;Training;transmission process;Trust;United States;United States National Institutes of Health;Universities;uptake;Work;young man;Youth

PROJECT_TITLE: A family-based intervention to improve HIV pre-exposure prophylaxis uptake for adolescent sexual minority males


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Biotechnology;Genetics;Human Genome;Lung;Networking and Information Technology R&D (NITRD);Precision Medicine;Prevention;Rare Diseases

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: PROJECT NARRATIVE Genetic differences between individuals can influence gene expression levels across different tissues and cell types, and it is unknown if this tissue-specific regulation of gene expression affects risk of developing the acute respiratory distress syndrome (ARDS) during critical illness. In this proposal, we will apply an advanced computational framework to existing genetic data to predict the gene expression levels of lung tissue and immune cells in patients at high risk for developing ARDS. This research will advance practitioners’ ability to incorporate genetic information to bring more personalized care to critically ill patients.

PI_NAMEs: KERCHBERGER, VERN ERIC (contact)

PROGRAM_OFFICER_NAME: KALANTARI, ROYA

PROJECT_TERMS: Academic Medical Centers;Acute;Acute Lung Injury;Acute Respiratory Distress Syndrome;Address;Adult;Advisory Committees;Affect;biobank;Biology;biomedical informatics;Biopsy;career;cell type;Cells;Chronic Disease;classifier algorithm;Clinical;clinical translation;cohort;Cohort Studies;computer framework;Critical Care;Critical Illness;Data;Data Scientist;Databases;design;Diagnosis;differential expression;Disease;Disease Outcome;Disease susceptibility;disorder risk;disorder subtype;DNA;Doctor of Philosophy;Electronic Health Record;Electronic Medical Records and Genomics Network;Enrollment;Foundations;functional genomics;Future;Gene Expression;Gene Expression Regulation;gene function;Genes;Genetic;genetic analysis;genetic information;Genetic Predisposition to Disease;Genetic Risk;Genetic study;genetic variant;genome wide association study;Genotype;Goals;Healthcare Systems;Heterogeneity;high risk;human tissue;Immune;improved;Individual;Inflammation;innovation;Investigation;Knowledge;Lead;Lung;Lymphocyte;Measures;Mentors;Mentorship;Methods;Modeling;mortality risk;National Heart, Lung, and Blood Institute;new therapeutic target;novel;Outcome;Pathogenesis;patient oriented;Patient-Focused Outcomes;Patients;Performance;personalized care;Phenotype;population based;precision medicine;Predisposition;prospective;Qi;Research;Research Personnel;Research Project Grants;Resources;Risk;risk prediction;Sampling;Single Nucleotide Polymorphism;skills;Source;Strategic vision;Structure;Structure of parenchyma of lung;Syndrome;Testing;Tissue Sample;Tissue-Specific Gene Expression;Tissues;Training;transcriptome;United States;United States National Institutes of Health;Variant;Whole Blood

PROJECT_TITLE: Tissue-specific functional genomics in the acute respiratory distress syndrome

STUDY_SECTION: MCBS

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


NIH_SPENDING_CATS: Biotechnology;Brain Cancer;Brain Disorders;Cancer;Genetics;Neurosciences;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: SAN FRANCISCO

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: Project narrative This proposal focuses on mechanisms of Hedgehog signaling through the tumor microenvironment in glioblastoma, an incurable cancer of the central nervous system and the most common primary malignant brain tumor. Our objective is to understand why pharmacologic inhibition of Hedgehog signaling unexpectedly accelerates invasion and tumorigenesis of glioblastoma cells. Using a novel human astrocyte organoid model of glioblastoma and patient derived xenografts, this work will provide fundamental insights into how the Hedgehog pathway functions in cancer, and establish the preclinical basis for new clinical trials in glioblastoma patients.

PI_NAMEs: RALEIGH, DAVID R (contact)

PROGRAM_OFFICER_NAME: WOODHOUSE, ELIZABETH

PROJECT_TERMS: Acceleration;Adult;adult stem cell;Agonist;antagonist;Astrocytes;Biology;BMP5 gene;BMP7 gene;Bone Morphogenetic Proteins;Brain;cancer cell;Cancer Etiology;cancer stem cell;Cell Communication;Cell membrane;cell motility;cell type;Cells;Cerebrum;Cilia;Clinical Data;Clinical Trials;clinically relevant;Coculture Techniques;Communication;CRISPR interference;Data;Defect;Development;DIF factor;Erinaceidae;experimental study;Extracellular Matrix;flexibility;Gene Activation;Gene Expression;Gene Targeting;Genes;Genetic Transcription;Glioblastoma;Goals;Growth;hedgehog signal transduction;Human;human pluripotent stem cell;improved;in vivo;innovation;insight;Invaded;Ligands;live cell imaging;Malignant - descriptor;Malignant neoplasm of brain;Malignant neoplasm of central nervous system;Malignant neoplasm of urinary bladder;Malignant Neoplasms;migration;Modeling;molecular scale;morphogens;Mus;novel;Organoids;Pathway interactions;patient derived xenograft model;Patients;pharmacologic;Pharmacology;pre-clinical;Process;programs;Research;restraint;Role;SHH gene;Signaling Protein;single-cell RNA sequencing;smoothened signaling pathway;stem cell division;stem cell homeostasis;stem cells;Structure;Surface;System;targeted treatment;Testing;Tissue Differentiation;transcriptome sequencing;tumor;tumor growth;tumor microenvironment;tumor progression;tumorigenesis;Vertebrates;Work

PROJECT_TITLE: Mechanisms of Hedgehog signaling in glioblastoma

STUDY_SECTION: TME

STUDY_SECTION_NAME: Tumor Microenvironment Study Section[TME]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Genetics;Infectious Diseases;Neurosciences;Pain Research;Rare Diseases;Tuberculosis

PI_NAMEs: SHILOH, MICHAEL  (contact)

PROJECT_TERMS: aerosolized;Animal Experiments;Animal Model;Animals;Bacteria;Binding;Biochemical;Biochemistry;Biological Assay;Biological Models;Carbon Dioxide;Cavia;Cholera Toxin;Collaborations;Complex;Coughing;CRISPR/Cas technology;Data;Desiccation;Diarrhea;Disease;disease transmission;Electrophysiology (science);epidemiology study;experimental study;Foundations;Future;G-Protein-Coupled Receptors;Genes;Genetic;genetic approach;Genus Mycobacterium;glycolipid receptor;Glycolipids;Goals;Human;human disease;Immunohistochemistry;in vivo;in vivo evaluation;Individual;Infection;inhibitor;insight;Knock-out;Laboratories;Lipids;Liquid substance;Measures;Mediating;Mediation;Metabolic Pathway;Modeling;Molecular;Molecular Biology;mutant;mycobacterial;Mycobacterium tuberculosis;Nebulizer;Neurons;Neurosciences;Nociception;Nociceptors;novel;novel strategies;Orphan;Pain;particle;Particle Size;pathogen;pathogenic bacteria;Persons;polyketide synthase;Population;Predictive Factor;Prevalence;Production;programs;protein complex;Proteins;receptor;Recording of previous events;Research;Resistance;response;Resuscitation;Route;screening;Stress;success;sulfolipids;sulfotransferase;Symptoms;System;Testing;Tissues;transmission process;Tuberculosis;Vibrio cholerae;Virulence;Virulent;Work;World Health

PROJECT_TITLE: Project 3: Mechanisms of cough in M. tuberculosis transmission


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Drug Abuse (NIDA only);HIV/AIDS;Infectious Diseases;Opioid Misuse and Addiction;Opioids;Prevention;Substance Misuse

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: PAR-20-221: NIDA Avant-Garde Alex K. Shalek NARRATIVE People who inject drugs (PWID) with opioid use disorder (OUD) or polysubstance used disorder (PSUD) have a substantial risk for developing and incidence of HIV-1 and other infection. To develop effective prophylactics and therapeutics against HIV-1 and other infections for individuals with OUD or PSUD, we must first understand how opioids and the lived experiences of OUD/PSUD impact the immune system at a cellular and molecular level. The goal of our NIDA Avant-Garde DP1 proposal is to define, at unprecedented resolution, how OUD and PSUD influence immune function and responses to HIV-1 and other pathogens by developing and applying innovative single-cell and bulk profiling and perturbation tools, helping to inform the design of novel cure and prevention strategies for those with OUD or PSUD, as well as others.

PI_NAMEs: SHALEK, ALEX K (contact)

PROGRAM_OFFICER_NAME: VEMURI, KIRAN R V

PROJECT_TERMS: Biological;Biopsy;Boston;Cells;Chemicals;Clinical;Communities;design;Development;Disease;drug metabolism;Drug usage;Environmental Risk Factor;Equipment Contamination;Exposure to;fitness;Gastrointestinal tract structure;General Population;genomic profiling;Goals;Health;HIV-1;Human;immune function;Immune response;Immune system;Immunity;Immunologics;immunoregulation;improved;Incidence;Individual;Infection;Injecting drug user;innovation;insight;Investigation;Knowledge;Lived experience;Liver;Methods;Molecular;Mucous Membrane;National Institute of Drug Abuse;novel;Opioid;opioid use disorder;pathogen;Peripheral Blood Mononuclear Cell;Physiology;polysubstance use;Positioning Attribute;Prevention;Prevention strategy;programs;prophylactic;Resolution;Risk;Sampling;screening;social;Technology;Test Result;Testing;Therapeutic;Tissues;tool;Treatment Efficacy;Work

PROJECT_TITLE: Defining the impact of drug use on immune function and fitness against HIV-1


NIH_SPENDING_CATS: Autoimmune Disease;Lupus

ORG_CITY: STONY BROOK

ORG_DEPT: PHYSIOLOGY

ORG_NAME: STATE UNIVERSITY NEW YORK STONY BROOK

PHR: W. Todd Miller Project Narrative This project examines a novel series of mutations in cellular enzymes that are found in patients with severe lupus. The proposed work will shed light on the activity and substrate specificity of these enzymes in normal physiology, and may provide new strategies to modulate these pathways in human disease.

PI_NAMEs: MILLER, W TODD (contact)

PROGRAM_OFFICER_NAME: RICE, JEFFREY S

PROJECT_TERMS: Active Sites;Apoptosis;Apoptotic;Autoimmune Diseases;BCAR1 gene;Binding;Binding Sites;Biological Assay;Cell model;Cell Surface Receptors;Cells;cohort;Collaborations;Coupled;Coupling;Crystallization;Disease;Environmental Risk Factor;Enzyme Kinetics;Enzymes;Eukaryotic Cell;Excision;experimental study;Fluorescence;Genetic;Growth;Human;human disease;induced pluripotent stem cell;Inflammatory;Insecta;insight;Laboratories;Link;loss of function mutation;Lupus;Macrophage;Malignant Neoplasms;Mammalian Cell;Mammary Neoplasms;Measures;mutant;Mutation;new therapeutic target;Normal Cell;novel;novel therapeutic intervention;Pathology;Pathway interactions;patient derived induced pluripotent stem cells;Patients;Phagocytes;Phagocytosis;Phosphatidylserines;Phosphotransferases;Physiological;Physiology;Protein Tyrosine Kinase;Proteins;PTK6 gene;Receptor Protein-Tyrosine Kinases;Regulation;Role;Series;Signal Pathway;Signal Transduction;Structure;Substrate Specificity;Systemic Lupus Erythematosus;Testing;three dimensional structure;Work

PROJECT_TITLE: Nonreceptor tyrosine kinases in Systemic Lupus Erythematosus

STUDY_SECTION: MIST

STUDY_SECTION_NAME: Molecular and Integrative Signal Transduction Study Section[MIST]


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Genetics;Human Genome;Precision Medicine

ORG_DEPT: PATHOLOGY

PHR: PROJECT NARRATIVE The University of Michigan Center for Translational Cancer Proteogenomics (UM-CTCP) will perform advanced proteogenomics analyses a part of the Clinical Proteomic Tumor Analysis Consortium (CPTAC) initiative. Working in collaboration with other members of the CPTAC, UM-CTCP will apply its advanced computational infrastructure for comprehensive and global characterization of genomics, transcriptomics, and proteomics data, collected from several cohorts of human tumors using NCI-provided biospecimens. UM- CTCP will conduct integrative analyses of data across these different data types with a goal to identify potentially cancer-related molecular alterations and to elucidate how distinct changes at the protein level are related to abnormalities in cancer genomes. A second priority of UM-CTCP is to assist with the selection of cancer-specific protein candidates for subsequent functional studies and validation using targeted assays.

PI_NAMEs: DHANASEKARAN, SARAVANA MOHAN ;NESVIZHSKII, ALEXEY I (contact)

PROGRAM_OFFICER_NAME: HILTKE, TARA

PROJECT_TERMS: Acceleration;Address;Adoption;Algorithms;Area;Benchmarking;bioinformatics tool;Biological;Biological Assay;Biological Markers;biomarker discovery;biomarker signature;Cancer Biology;cancer genetics;cancer genome;cancer genomics;cancer subtypes;cancer type;candidate selection;Cell Communication;Cells;Cellularity;Clinical;clinical implementation;clinically actionable;clinically relevant;Clonal Expansion;Code;cohort;Collaborations;Communities;computer infrastructure;computerized tools;computing resources;Copy Number Polymorphism;Data;Data Analyses;data modeling;Data Reporting;data visualization;Development;Disease;Early Detection Research Network;Ensure;Epigenetic Process;Event;experience;Foundations;Future;Gene Fusion;Generations;Genes;Genetic;genetic signature;Genome;genomic aberrations;Genomics;Goals;Histologic;Human;improved;Individual;individual patient;innovation;insight;inter-institutional;Investigation;Knowledge;Malignant Neoplasms;Measures;member;Methods;Michigan;Mission;Modeling;Molecular;molecular subtypes;multidisciplinary;multiple omics;Mutation;new technology;novel;novel strategies;Oncogenic;Oncology;oncology program;Pathologist;Pathology;Pathway Analysis;Patients;Peptides;Phenotype;Ploidies;Positioning Attribute;Post-Translational Protein Processing;precision oncology;Prognostic Marker;protein biomarkers;Proteins;proteogenomics;Proteome;Proteomics;Quality Control;Recording of previous events;Renaissance;Research;Research Personnel;Resources;SAGA;search engine;specific biomarkers;Speed;success;Systems Biology;technology development;therapeutic target;Time;Tissues;tool;transcriptome;transcriptomics;translational impact;Translations;tumor;Tumor Biology;tumor microenvironment;United States National Institutes of Health;Universities;Untranslated RNA;Validation;whole genome;Work;working group


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Tickborne Diseases;Vector-Borne Diseases

ORG_CITY: TOLEDO

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS

ORG_STATE: OH

PHR: Our research is focused on understanding how a cellular antiviral factor is used by some viruses to grow and cause disease. We will determine how to treat or prevent tick-borne flavivirus infections by targeting the cellular factor.

PI_NAMEs: TAYLOR, ROGER TRAVIS (contact)

PROGRAM_OFFICER_NAME: ALARCON, RODOLFO M

PROJECT_TERMS: Affect;Anti-viral Response;Attenuated;Attenuated Vaccines;attenuation;Binding;Biochemical;Cell Line;cell type;Cells;Cellular biology;cellular targeting;Complex;Data;Dendritic Cells;Disease;drug development;Environment;Enzymes;Equilibrium;Flavivirus;Flavivirus Infections;Genetic;genetic approach;genetic manipulation;Immune response;improved;In Vitro;in vivo;Infection;inhibitor;Innate Immune Response;insight;Knock-out;Link;Mediating;Mediator;Methods;Modification;mosquito-borne;mouse model;Mutagenesis;mutant;Mutate;Mutation;Neurons;Nonstructural Protein;Outcome;pathogen;Pathogenesis;Peptide Hydrolases;prevent;Process;Productivity;protein expression;Proteins;recruit;Regulation;Reporting;Research;response;Role;Signal Transduction Pathway;Site-Directed Mutagenesis;Structure;Testing;Therapeutic;Therapeutic Uses;tick-borne flavivirus;TNF Receptor-Associated Factors;Ubiquitin;ubiquitin-protein ligase;Ubiquitination;vaccine development;vector;Viral;Viral Physiology;Viral Proteins;Virulent;Virus;Virus Diseases;Virus Replication

PROJECT_TITLE: Understanding the proviral role for TRAF6 interaction with the viral protease in flavivirus replication and pathogenesis

STUDY_SECTION: VIRA

STUDY_SECTION_NAME: Virology - A Study Section[VIRA]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Bioengineering;Emerging Infectious Diseases;Infectious Diseases;Lung;Rare Diseases;Tuberculosis

PI_NAMEs: BOUROUIBA, LYDIA  (contact)

PROJECT_TERMS: Address;Aerobic;aerosolized;Air;Animal Model;Animals;Back;BCG Live;Behavior;Biological;Biology;Biophysics;Carbon Dioxide;Collaborations;Communicable Diseases;Controlled Study;Coughing;Desiccation;Development;disease transmission;Dose;Encapsulated;Environment;evaporation;Evolution;Exercise;Experimental Animal Model;experimental study;Fluids and Secretions;Formulation;Generations;Genes;Genus Mycobacterium;Humidity;Hydration status;improved;In Vitro;Inhalation;insight;interfacial;Intervention;Knowledge;Light;Liquid substance;Mathematics;Metabolic Pathway;Modeling;mutant;mycobacterial;Mycobacterium bovis;Mycobacterium tuberculosis;new technology;novel;Organism;Persons;phase change;physical process;physical property;Physics;Physiological;Physiology;Property;Resolution;Respiration;respiratory;Respiratory Disease;Rest;Rheology;Shapes;Sneezing;Solid;Surface Tension;Suspensions;Technology;technology platform;Temperature;Testing;transmission blocking;transmission process;Tuberculosis;Vaccines;Variant;viscoelasticity;Work

PROJECT_TITLE: Project 4: Biophysics of Mtb droplets and fluid spray technology to elucidate Mtb transmission


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Drug Abuse (NIDA only);Neurosciences;Opioid Misuse and Addiction;Opioids;Substance Misuse

ORG_CITY: IOWA CITY

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: Narrative The US is facing a crisis of opioid overdoses and addiction. Current therapies consist largely of alternative opioids (i.e. maintenance with methadone or buprenorphine) and do not correct neurobiological factors underlying addiction, including the long-lasting changes in the neural plasticity thought to contribute to drug cravings that cause relapse, and perpetuate the illness. This proposal focuses on a recently identified pH- dependent signaling pathway at synapses in the nucleus accumbens that may be targeted to reverse the neurobiology underlying craving with non-opioid medications already used in humans for other illnesses.

PI_NAMEs: WEMMIE, JOHN A (contact)

PROGRAM_OFFICER_NAME: TSAI, SHANG-YI ANNE

PROJECT_TERMS: Acetazolamide;addiction;Altitude Sickness;ASIC channel;Behavior;Behavioral;Brain;Buprenorphine;carbonate dehydratase;Carbonic Anhydrase Inhibitors;Carbonic Anhydrase IV;Chronic;Clinical;Cocaine;conditioned place preference;craving;Dendritic Spines;Dose;drug craving;drug of abuse;drug relapse;drug seeking behavior;Drug usage;drug withdrawal;Epilepsy;experimental study;Foundations;Glutamates;Goals;Human;improved;Incubated;inhibitor;Injections;innovation;Knowledge;Maintenance;Measures;Mediating;Methadone;Molecular;Molecular Target;Morphine;Mus;Nature;Neurobiology;Neuronal Plasticity;Neurons;Neurotransmitters;non-opioid analgesic;novel;Nucleus Accumbens;Opiate Addiction;Opioid;opioid abuse;opioid epidemic;opioid mortality;opioid overdose;opioid use disorder;opioid withdrawal;Pathway interactions;Persons;Pharmaceutical Preparations;pharmacologic;Physiology;Pilot Projects;Play;postsynaptic;prevent;Protons;Relapse;Role;Self Administration;Signal Pathway;Synapses;Synaptic Cleft;Synaptic Transmission;Testing;Vesicle;Withdrawal

PROJECT_TITLE: Novel mechanisms for correcting opioid-induced synaptic abnormalities

STUDY_SECTION: MNPS

STUDY_SECTION_NAME: Molecular Neuropharmacology and Signaling Study Section[MNPS]


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

ORG_DEPT: NEUROLOGY

PHR: PROJECT NARRATIVE Alterations in emotion, empathy, and social behavior are early features of Alzheimer's disease that are often overlooked. A more sophisticated understanding of how neurodegeneration, neural network aberrations, and neuropathological changes relate to emotion physiology, behavior, and experience across the Alzheimer's disease spectrum will be critical for improving early diagnosis, broadening current conceptualizations of disease progression, and advancing biological models of affective symptoms.

PI_NAMEs: STURM, VIRGINIA EMILY (contact)

PROGRAM_OFFICER_NAME: STOECKEL, LUKE

PROJECT_TERMS: abeta accumulation;abeta deposition;Affect;Affective Symptoms;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Amyloid beta-Protein;Anxiety;Atrophic;Autonomic nervous system;Behavior;Behavioral;Biological Markers;Biological Models;Brain;cerebral atrophy;Clinical;Clinical Data;Cognitive deficits;Color;Data;Deposition;Diagnosis;Disease;Disease Progression;Disinhibition;Early Diagnosis;Emotional;Emotions;Empathy;Episodic memory;experience;Face;Facial Expression;forging;Functional disorder;Generations;Impaired cognition;improved;Interoception;Laboratories;Language;Link;Measures;medial temporal lobe;Memory Loss;men;Molecular;Moods;Nerve Degeneration;network dysfunction;neural circuit;neural network;Neuroanatomy;Neurobehavioral Manifestations;neuroimaging;neuropathology;Participant;Pathologic Processes;Pathology;Pattern;Persons;Phase;Physiology;Positron-Emission Tomography;pre-clinical;Primary Progressive Aphasia;Reaction;Reporting;Research;Severity of illness;Social Behavior;Social Environment;Specificity;Structure;Support System;Syndrome;System;tau mutation;tau Proteins;Testing;Tracer;uptake;Variant;Visuospatial;Woman

PROJECT_TITLE: Emotion alterations across the Alzheimer's disease spectrum

STUDY_SECTION: APDA

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


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

ORG_CITY: GRAND RAPIDS

ORG_NAME: VAN ANDEL RESEARCH INSTITUTE

PHR: PROJECT NARRATIVE Over 6.5 million people in the United States currently live with progressive neurodegenerative Alzheimer’s disease and related dementias, yet no disease-modifying treatments are available. The proposed research is aimed at understanding network and cell-level vulnerability to pathological protein progression with a focus on the impact that multiple pathologies have on disease progression. Understanding how dementia progresses is critical to assess therapeutic efficacy and improve disease prognosis and therefore relevant to the missions of the NIA and the NIH.

PI_NAMEs: HENDERSON, MICHAEL  (contact)

PROGRAM_OFFICER_NAME: GRAY, ERIN EMILY

PROJECT_TERMS: Affect;Aging;alpha synuclein;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease patient;Alzheimer's disease related dementia;Amyloid beta-Protein;Anatomy;Animal Model;Atlases;Behavior assessment;beta amyloid pathology;Binding;Brain;Brain Pathology;Brain region;Cells;cerebral atrophy;Clinical;Complex;Computer Models;connectome;Data;Dementia;Dementia with Lewy Bodies;Development;Diffusion;Disease;disease prognosis;Disease Progression;efficacy evaluation;Evaluation;extracellular;Gene Expression;Hippocampus;Human;human model;Immunofluorescence Immunologic;improved;In Situ Hybridization;Individual;Injections;insight;Knock-in Mouse;Lewy Body Disease;Maps;Mission;Modeling;Molecular;molecular marker;Molecular Profiling;Mus;Nature;Nerve Degeneration;network models;Neurites;Neuroanatomy;Neurodegenerative Disorders;Neurons;novel;novel therapeutic intervention;Pathogenicity;Pathologic;Pathology;Pathway Analysis;Patients;Persons;phosphoneuroprotein 14;Physiology;Population;protein aggregation;Proteins;Research;resilience;Resolution;Resources;Senile Plaques;spatiotemporal;tau aggregation;tau mutation;tau Proteins;Testing;Time;tool;transcriptomics;Treatment Efficacy;United States;United States National Institutes of Health;Wild Type Mouse;Work

PROJECT_TITLE: Network and cellular vulnerability to pathological protein progression


NIH_SPENDING_CATS: Biotechnology;HIV/AIDS;Immunization;Infectious Diseases;Prevention;Vaccine Related;Vaccine Related - AIDS

ORG_CITY: BALTIMORE

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

PHR: Narrative This project address the major challenge of improving the quality of vaccine-elicited responses against the neutralizing antibody targets on the virus pathogen by novel immunogen design. This study proposes to modify vaccine candidates derived from HIV-1 envelope glycoproteins for efficiently activating, selectively expanding, and precisely shepherding HIV-1 broadly neutralizing antibody (bNAb) germline precursor to achieve bNAb response elicitation and to develop new vaccination regimens to optimize the vaccination efficacy. The outcomes of this study will contribute to the development of a broadly effective HIV-1 vaccine as well as increase understanding of host/pathogen interactions.

PI_NAMEs: LI, YUXING  (contact)

PROGRAM_OFFICER_NAME: MALASPINA, ANGELA

PROJECT_TERMS: Address;Affinity;Alleles;Animals;Antibodies;Antibody Affinity;Antibody Response;Antigens;B cell repertoire;B-Cell Antigen Receptor;B-Lymphocytes;Binding Sites;Cavia;CD4 Antigens;Clinical Research;clinical translation;Clone Cells;Complex;cross reactivity;design;Development;donor-specific antibody;Elements;emerging pathogen;Epitopes;experimental study;Frequencies;Funding;Generations;Genes;Genetic;Germ Lines;Glycoproteins;guinea pig model;HIV;HIV Antibodies;HIV vaccine;HIV-1;HIV-1 vaccine;Human;Immune response;Immunization;Immunize;immunogenicity;Immunoglobulin Somatic Hypermutation;improved;Individual;Infection;innovation;Knock-in Mouse;Light;Modeling;Modification;Monoclonal Antibodies;mouse model;neutralizing antibody;novel;novel vaccines;Outcome Study;pathogen;pathogenic virus;Pathway interactions;Patients;Play;preclinical study;Process;programs;receptor binding;Regimen;Resolution;response;Role;Serum;Specificity;Structure of germinal center of lymph node;success;Testing;Vaccination;vaccine candidate;vaccine development;Vaccines;Virus

PROJECT_TITLE: High-resolution definition of B cell responses to HIV Env for immunogen design


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Clinical Research;Congenital Structural Anomalies;Genetic Testing;Genetics;Human Genome;Nanotechnology;Pediatric

ORG_NAME: PACIFIC NORTHWEST RESEARCH INSTITUTE

PHR: PROJECT NARRATIVE Public health relevance: Inversions are mostly unnoticed in the genome even with pathogenic consequences for its carriers. This project will uncover the origins of inversions, their contribution to human genomic architecture and disease diagnosis with high impact to chromosome structure, gene regulation and the genetic basis of human biology.

PI_NAMEs: FONSECA, CLAUDIA CARVALHO (contact)

PROGRAM_OFFICER_NAME: MASKERI, BAISHALI

PROJECT_TERMS: Affect;Architecture;Biological;Biological Process;Candidate Disease Gene;candidate identification;Chromosomal Instability;Chromosome Structures;Chromosomes;Classification;clinical phenotype;comparative genomic hybridization;Complex;Congenital Abnormality;congenital anomaly;Copy Number Polymorphism;Cytogenetics;Data;Defect;Detection;Diagnosis;Disease;disease diagnosis;DNA;DNA Repair;DNA Sequence;DNA Sequence Alteration;DNA Sequence Rearrangement;ds-DNA;Etiology;Event;Evolution;Frequencies;Gene Expression Regulation;Generations;Genetic;Genetic Diseases;genetic disorder diagnosis;Genetic Recombination;Genome;Genome Mappings;genome sequencing;Genomic Segment;genomic signature;genomic tools;Genomics;Goals;Haplotypes;high risk;Human;Human Biology;Human Development;Human Genome;Individual;Infertility;Inherited;Malignant Neoplasms;Maps;Mediating;Meiosis;Methodology;Mitosis;Mitotic;Molecular;Molecular Abnormality;nanopore;next generation sequencing;offspring;Optics;Pathogenicity;Patients;Pattern;Phase;Phenotype;Population Genetics;Predisposition;Prevalence;Primates;proband;Procedures;Production;public health relevance;reference genome;repaired;reproductive;Role;Sampling;Series;SNP array;Structure;Subgroup;Techniques;Testing;tool;trait;Validation;Variant;whole genome;Work

PROJECT_TITLE: Uncovering inversion formation in the human genome and its impact to disease.

STUDY_SECTION: GHD

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


ED_INST_TYPE: GRADUATE SCHOOLS

ORG_CITY: MADISON

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: Project Narrative This research will refine and test an automated tool for measuring speech sound development in children. This tool will identify if a child has speech sounds that are not developing in a normal or typical way, will reveal which specific sounds are not developing typically, and will indicate which speech sounds make the largest contribution to speech intelligibility for children at different ages. This information can be used to develop speech therapies that maximize speech intelligibly. The research will benefit all children, but has special application to children with cerebral palsy.

PI_NAMEs: BERISHA, VISAR ;HUSTAD, KATHERINE C (contact)

PROJECT_TITLE: Quantifying articulatory performance in children with dysarthria:  Development of an automated metric for clinical use


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Depression;Major Depressive Disorder;Mental Health;Mental Illness;Neurosciences;Serious Mental Illness

ORG_CITY: TULSA

ORG_NAME: LAUREATE INSTITUTE FOR BRAIN RESEARCH

ORG_STATE: OK

PHR: Project Narrative Inflammation is hypothesized to contribute to the pathogenesis of major depressive disorder (MDD) but the precise inflammatory mechanisms and how these processes influence neural systems to generate depressive symptoms are still poorly understood. This project seeks to elucidate the neural circuitry underlying a maladaptive homeostatic response to inflammation in MDD by using a placebo-controlled lipopolysaccharide challenge that will cause a transient inflammatory response. The proposed research is highly pertinent to public health because it will identify brain targets relevant to inflammation-induced depression, which is a necessary step in the development of immune-based interventions for mood disorders.

PI_NAMEs: SAVITZ, JONATHAN  (contact)

PROGRAM_OFFICER_NAME: LAWHORN, COLLENE

PROJECT_TERMS: Acute;Affect;Anhedonia;Attention;Behavior;Biological;Blood;Brain;Characteristics;Chronic;cingulate cortex;Clinical;Clinical assessments;clinical predictors;Color;Communication;cytokine;Data;Depressed mood;depressed patient;depressive behavior;depressive symptoms;Development;Diagnosis;Double-Blind Method;early life stress;Emotions;experimental study;Failure;follow-up;Functional Magnetic Resonance Imaging;Heart;hemodynamics;Homeostasis;Hour;Human;Immune;Immune system;Immunologics;Immunotherapy;In Vitro;in vivo;Individual;Inflammation;Inflammation Mediators;Inflammatory;inflammatory marker;Inflammatory Response;Infusion procedures;innovation;Insula of Reil;Interleukin-6;Interoception;Intervention;Knowledge;Lipopolysaccharides;Major Depressive Disorder;Measures;Mediating;Medicine;Mental Depression;monocyte;Mood Disorders;Moods;MRI Scans;neural;neural circuit;Outcome;Participant;Pathogenesis;Pathway interactions;patient population;patient subsets;Patients;Pattern;Persons;Placebo Control;placebo controlled study;Placebos;pleasure;primary outcome;Process;programs;psychologic;Psychometrics;Public Health;Randomized;Recovery;Recurrence;recurrent depression;Research;response;Rest;Risk;Role;safety assessment;Saline;sex;Sex Differences;Signal Transduction;Sleep;Stimulus;Stomach;Subgroup;symptomatology;Symptoms;System;Testing;Time;Treatment Failure;Visit

PROJECT_TITLE: Neural response to inflammatory challenge in major depressive disorder

STUDY_SECTION: MESH

STUDY_SECTION_NAME: Biobehavioral Mechanisms of Emotion, Stress and Health Study Section[MESH]


NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Immunotherapy;Skin Cancer

ORG_CITY: LEXINGTON

ORG_NAME: UNIVERSITY OF KENTUCKY

ORG_STATE: KY

PHR: PROJECT NARRATIVE Metastatic melanoma is one of the deadliest cancers, and although immunotherapy and targeted agents extend survival, some melanomas do not respond to the treatments or develop resistance; thus, the 5-year survival rate remains dismal. This proposal examines the mechanism by which ABL family proteins contribute to BRAF/MEK inhibitor resistance and includes a clinical trial to test the safety and initial efficacy of an ABL1/2 inhibitor in combination with BRAF/MEK inhibitors for treating refractory melanomas.

PI_NAMEs: KOLESAR, JILL MARIE;PLATTNER, RINA  (contact);WILSON, MELISSA A

PROGRAM_OFFICER_NAME: SONG, MIN-KYUNG H

PROJECT_TERMS: ABL1 gene;advanced disease;Animal Model;Animals;antileukemic agent;arm;Basic Science;Biochemical;Biological;biomarker development;BRAF gene;Cell Line;Cells;Cessation of life;chemokine;Clinical;Clinical Trials;Coculture Techniques;Collaborations;Conditioned Culture Media;Coupling;cytokine;Data;Dose;Dose Limiting;Drug Kinetics;Drug resistance;drug-sensitive;early phase clinical trial;effective therapy;ERBB2 gene;ERBB3 gene;Experimental Designs;experimental study;Family;FDA approved;Flow Cytometry;gain of function;Genetically Engineered Mouse;Goals;Growth Factor;Hematologic Neoplasms;human tissue;Immune;immune cell infiltrate;immunoregulation;Immunotherapeutic agent;Immunotherapy;improved;In Vitro;in vivo;in vivo Model;Incidence;inhibitor;innovation;interdisciplinary approach;Intervention;Invaded;Kentucky;Link;loss of function;Maintenance;Malignant Neoplasms;Manuscripts;MAP3K1 gene;Mass Spectrum Analysis;Mediating;MEKs;Melanoma;Melanoma Cell;Metastatic Melanoma;Modeling;Molecular;Monitor;mutant;Mutation;Neoplasm Metastasis;next generation sequencing;novel;Oncologist;open label;Pathway interactions;patient subsets;Patients;Pharmaceutical Preparations;Pharmacodynamics;pharmacokinetics and pharmacodynamics;pharmacologic;Phase;phase 2 study;Phase I/II Clinical Trial;Phase I/II Trial;Phosphotransferases;PI3K/AKT;prevent;primary endpoint;Protein Family;Protein Secretion;Protein Tyrosine Kinase;Proteomics;Proto-Oncogene Proteins c-akt;Publishing;Qualifying;randomized, clinical trials;Recommendation;Records;Refractory;Regimen;RELA gene;Relapse;Research;Research Personnel;Resistance;Resistance development;resistance mechanism;response;RNA Interference;Role;Safety;safety testing;Sampling;secondary endpoint;Series;Serum;Serum Proteins;single-cell RNA sequencing;Site;Survival Rate;targeted agent;Testing;therapy resistant;Toxic effect;transcriptome sequencing;translational goal;Translational Research;Treatment Protocols;tumor;Tumor Burden;tumor-immune system interactions;Xenograft procedure

PROJECT_TITLE: Combating melanoma resistance by targeting ABL1/2

STUDY_SECTION: CONC

STUDY_SECTION_NAME: Clinical Oncology Study Section[CONC]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Anxiety Disorders;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Mental Health;Mental Illness;Neurosciences

ORG_CITY: TALLAHASSEE

ORG_DEPT: PSYCHOLOGY

ORG_NAME: FLORIDA STATE UNIVERSITY

PHR: Project Narrative The proposed basic science research project will reveal the neural circuit connectivity and behavioral function of chemically-identified brainstem neurons that signal to the limbic forebrain to increase threat-induced emotional responses, akin to symptoms of anxiety in humans. For this, a new transgenic rat model will be used to target two specific groups of hindbrain neurons that express glucagon-like peptide 1 (GLP1) and project to the limbic forebrain. Given evidence that brainstem GLP1 neurons and limbic GLP1 receptors are similar in rats and humans, results from this basic science project have potential translational relevance for understanding the neurobiological bases of normal threat responses and pathological anxiety in humans.

PI_NAMEs: RINAMAN, LINDA M (contact)

PROGRAM_OFFICER_NAME: BREEDEN, ANDREW LEE

PROJECT_TERMS: Acute;Affective;Amygdaloid structure;Animal Model;Anterolateral;Anxiety;Anxiety Disorders;anxiety symptoms;Arousal;Axon;base;Basic Science;behavior test;Behavioral;Behavioral Assay;Behavioral inhibition;Behavioral Model;behavioral response;Brain;Brain region;Brain Stem;Cell Nucleus;Cells;Central Lateral Nucleus;Chemicals;Chronic;Clinical Research;Clozapine;Cognitive;comparative;Coupled;Cytoplasm;Dependovirus;designer receptors exclusively activated by designer drugs;Dimensions;Documentation;Dorsal;Emotional;Exposure to;Fasting;Feedback;Female;Fluorescent in Situ Hybridization;fluorophore;Future;Genes;Genetic;GLP-I receptor;Glucagon;glucagon-like peptide 1;Glutamates;high resolution imaging;hindbrain;Human;Ipsilateral;Label;male;Maps;Mental disorders;model organism;Modeling;Molecular Target;mRNA Expression;neural;neural circuit;neurobiological mechanism;Neurobiology;Neurons;neurotransmission;nonhuman primate;novel;Nucleus solitarius;Oxides;Pathologic;Pathological anxiety;Pathway interactions;Phenotype;Physiological;Physiological Processes;Population;Pre-Clinical Model;presynaptic;Prosencephalon;rabies viral tracing;Rat Transgene;Rattus;Receptor Signaling;Research;Research Project Grants;response;Reticular Formation;Rodent;Role;selective expression;Sensory;sensory feedback;Series;Sex Differences;Signal Pathway;Signal Transduction;Source;Spinal;Sprague-Dawley Rats;Structure;Structure of terminal stria nuclei of preoptic region;Synapses;Testing;tool;Transgenic Organisms;translational potential;United States;vigilance;Viral;Visceral

PROJECT_TITLE: Central GLP1 Signaling Pathways and Anxiety

STUDY_SECTION: NNRS

STUDY_SECTION_NAME: Neuroendocrinology, Neuroimmunology, Rhythms and Sleep Study Section[NNRS]


NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Clinical Research;Hematology;Infectious Diseases;Lung;Pneumonia;Pneumonia and Influenza;Rare Diseases;Sepsis

PHR: PROJECT NARRATIVE Every year nearly 25 million people survive sepsis worldwide. One in ten will be readmitted with pneumonia, aspiration pneumonitis and/or respiratory failure within 90 days of discharge. The goal of this project is to understand the biological mechanisms predisposing to these complications in order to prevent and treat them.

PI_NAMEs: DENSTAEDT, SCOTT JOHN (contact)

PROJECT_TERMS: Alveolar;alveolar epithelium;Apoptosis;aspirate;Biological;Biological Assay;Brain;brain dysfunction;Calgranulin A;career;career development;Career Mobility;cecal ligation puncture;Cell Death;Cell Separation;Cells;Cessation of life;chemokine;Chronic;Coculture Techniques;Critical Care;cytokine;Data;design;Development;Development Plans;Dextrans;Epigenetic Process;epigenomics;Epithelial Cells;Exhibits;experience;Flow Cytometry;Foundations;Functional disorder;Gene Expression;Goals;healthy volunteer;hospital readmission;Hospitalization;Human;Immune;Immune response;Immunofluorescence Immunologic;Immunology;In Vitro;in vivo;Incubated;Inflammation;Inflammation Mediators;Inflammatory;inflammatory marker;Injury;Innate Immune Response;insight;Intranasal Administration;Klebsiella pneumoniae;Knockout Mice;Knowledge;Ligands;Link;Lipopolysaccharides;Lung;lung injury;Lung Lavage Fluid;Measures;Medicine;Mentors;Mentorship;Microscopy;Modeling;Modernization;monocyte;mouse model;Mus;Neurocognitive;neutrophil;Neutrophil Infiltration;novel;operation;Pathway interactions;Patients;Permeability;Persons;Phenotype;Physicians;Plasma;Pneumonia;Predisposition;prevent;Production;Pulmonary Inflammation;Recovery;recruit;Research;Respiratory Failure;response;response to injury;Risk;Role;S100A8 gene;Scientist;Secondary to;Sepsis;septic patients;Signal Transduction;Signaling Protein;Sterility;Stimulus;Supportive care;Survivors;targeted treatment;Techniques;TLR4 gene;TNF gene;Training;transcriptomics;Transgenic Mice;translational approach;translational study;Work

PROJECT_TITLE: Predisposition for Lung Injury in Sepsis Survival


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

ORG_CITY: NEW YORK

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: PROJECT NARRATIVE  Preclinical studies in rodent models and in vitro show that subtle decreases in body and brain temperature increase tau protein pathology, which is a central cause of Alzheimer’s disease; however, it’s not yet known whether body and brain temperature influences tau pathology in human, or, whether the known decrease in body temperature with ageing could contribute to increasing tau pathology with older age. In our preliminary study, we showed for the first time that lower body temperature naturalistically measured over 2 days in cognitively normal older adults strongly predicted increased tau pathology measured with tau position emission tomography. In the current study, we propose to build on this preliminary work using similar methods in a larger study of one hundred older adults who are cognitively normal or have mild cognitive impairment; results have the potential to identify a novel pathway underlying tau pathology in Alzheimer’s Disease, and, because lower body temperature may be a modifiable risk factor, to support future clinical studies to prevent the progress of tau pathology.

PI_NAMEs: BLESSING, ESTHER MARIAN (contact)

PROGRAM_OFFICER_NAME: MACKIEWICZ, MIROSLAW

PROJECT_TERMS: abeta accumulation;actigraphy;Age;age acceleration;age related;Aging;aging brain;aging population;Algorithm Design;Alzheimer disease prevention;Alzheimer's Disease;Alzheimer's disease risk;Amyloid;Amyloid beta-Protein;apolipoprotein E-4;Area;awake;blood-based biomarker;Body measure procedure;Body Temperature;Brain;burden of illness;Clinical Research;Cognition;Cognitive;Cross-Sectional Studies;Data;Dependence;Evaluation;Female;Foundations;Functional disorder;Future;glymphatic clearance;Home;Hour;Human;human old age (65+);hyperphosphorylated tau;Impaired cognition;Impairment;In Vitro;insight;inter-individual variation;Intervention;Kinetics;Knowledge;Lead;Link;Magnetic Resonance Imaging;male;Measurement;Measures;Mediating;Medical;Methods;mild cognitive impairment;Modeling;modifiable risk;Molecular;Neurodegenerative Disorders;neurofibrillary tangle formation;Neurofibrillary Tangles;neuron loss;Neurons;Neuropsychology;Non-Insulin-Dependent Diabetes Mellitus;novel;older adult;Participant;Pathologic;Pathology;Pathway interactions;Phase;Phosphoric Monoester Hydrolases;Phosphotransferases;Physiologic Thermoregulation;Plasma;Polysomnography;Population;Positioning Attribute;Positron-Emission Tomography;pre-clinical;preclinical study;Prevalence;prevent;Process;Property;Prospective Studies;Recording of previous events;Risk Factors;risk selection;Rodent;Rodent Model;Sampling;Scanning;screening;Seasons;Senile Plaques;sex;Sleep;sleep quality;Sleep Wake Cycle;Slow-Wave Sleep;Smoking;Symptoms;Synapses;System;tau aggregation;tau Proteins;tau-1;Telemetry;Temperature;Testing;Thermometry;Time;tomography;Tracer;Translating;Translations;uptake;Visit;Work;β-amyloid burden

PROJECT_TITLE: Investigating the Temperature Dependence of Age-related Tau Pathology Relevant to Early Alzheimer's Disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-BDCN-W(02)]


ADMINISTERING_IC: NS

ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Brain Disorders;Clinical Research;Epilepsy;Neurodegenerative;Neurosciences;Precision Medicine;Prevention

ORG_CITY: HOUSTON

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

ORG_STATE: TX

PHR: PROJECT NARRATIVE The main goal of this project is to develop an informatics approach for automated extraction of SUDEP risk markers from multimodal clinical data to enable individualized SUDEP risk assessment. Success of this study will enable systematic SUDEP risk assessment based on known and putative factors and communication of such risk factors to patients with epilepsy. Ultimately, this study can lead to evidence-based SUDEP risk assessment tools that help clinicians and patients manage potentially modifiable risks, leading to overall reduced SUDEP mortality and improved epilepsy patient care.

PI_NAMEs: CUI, LICONG  (contact)

PROGRAM_OFFICER_NAME: WHITTEMORE, VICKY R

PROJECT_TERMS: 15 year old;Academy;Acceleration;Adult;Affect;Algorithms;American;Apnea;Assessment tool;automated algorithm;Autopsy;Basic Science;Biological;Biological Markers;biomarker identification;Brain;Brain Injuries;Caring;Categories;Cause of Death;Cessation of life;Clinical;Clinical Data;cohort;Collaborations;Communication;Computational algorithm;computerized tools;Controlled Vocabulary;Data;Data Element;data repository;Data Set;Dedications;Development;Disparate;early onset;Electrocardiogram;Electroencephalography;Electrophysiology (science);Epilepsy;Equipment and supply inventories;Europe;evidence base;Exclusion;Functional disorder;Funding;Future;Generations;Goals;Guidelines;imaging biomarker;improved;Incidence;Individual;Informatics;Information Systems;innovation;Institution;Intervention;Medical center;Methods;Modeling;modifiable risk;Monitor;mortality;multimodal data;multimodality;National Institute of Neurological Disorders and Stroke;Neurology;Ontology;participant enrollment;Patient Care;Patients;Persons;Phenotype;Physiological;post stroke;predictive marker;preventable death;Readability;Recommendation;Reporting;Research;Risk;Risk Assessment;Risk Factors;Risk Marker;Safety;Seizures;Semantics;Signal Transduction;Standardization;Status Epilepticus;Structure;success;sudden unexpected death in epilepsy;System;Techniques;Terminology;Text;Tonic - clonic seizures;tool;Unified Medical Language System;United States;United States National Institutes of Health;Vocabulary;years of life lost

PROJECT_TITLE: An informatics framework for SUDEP Risk Marker Identification and Risk Assessment


NIH_SPENDING_CATS: Clinical Research;Drug Abuse (NIDA only);Fentanyl Misuse and Addiction;Harm Reduction for Substance Misuse;Opioid Misuse and Addiction;Opioids;Prevention;Substance Misuse;Substance Misuse Prevention

ORG_CITY: PHILADELPHIA

ORG_DEPT: EMERGENCY MEDICINE

ORG_NAME: THOMAS JEFFERSON UNIVERSITY

PHR: PROJECT NARRATIVE Fentanyl test strips (FTS) are increasingly being used by people who use drugs, including those who use drugs other than heroin, to detect the presence of fentanyl in the unregulated drug supply as a strategy to prevent unintentional fentanyl overdose. Recent work based in Philadelphia found alarmingly high rates of FTS positivity in non-heroin drugs, suggesting that people who use drugs are incorrectly using FTS, incorrectly interpreting results, the non-heroin drug supply is much more contaminated than prior estimates have suggested, or a combination of the three. This project will fill important evidence gaps by assessing the real- world accuracy of FTS use by people who use drugs and current presence of fentanyl in non-heroin drugs in Philadelphia, Pennsylvania.

PI_NAMEs: REED, MEGAN  (contact)

PROGRAM_OFFICER_NAME: ZUR, JULIA BETH

PROJECT_TERMS: Acetaminophen;Address;Anticonvulsants;Benzodiazepines;Case Study;Cities;community organizations;community partnership;Consensus;Data;drug market;drug testing;Drug usage;Drug user;Education Gap;evidence base;Fentanyl;fentanyl contamination;fentanyl overdose;fentanyl test;fentanyl use;Goals;Harm Reduction;Heroin;Illicit Drugs;Interview;Knowledge;Laboratories;Law Enforcement;Length;Location;Low Prevalence;Methods;Municipalities;non-opioid analgesic;Outcome;Overdose;overdose prevention;overdose risk;Patient Self-Report;Pennsylvania;Pharmaceutical Preparations;Philadelphia;Preparation;prescription opioid;Prevalence;prevent;Prevention Measures;Prevention strategy;Process;recruit;Reporting;Research;Research Personnel;Sampling;Side;simulation;Stimulant;sugar;Syncope;synthetic cannabinoid;Tablets;Technology;test strip;Testing;Time;tool;Training;Water;Work

PROJECT_TITLE: Assessing fentanyl test strip use accuracy and fentanyl presence in the non-heroin drug supply

STUDY_SECTION: CIHB

STUDY_SECTION_NAME: Community Influences on Health Behavior Study Section[CIHB]


ADMINISTERING_IC: ES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Aging;Cardiovascular;Clinical Research;Contraception/Reproduction;Endocrine Disruptors;Health Effects of Indoor Air Pollution;Heart Disease;Infertility;Maternal Health;Nutrition;Obesity;Pregnancy;Prevention;Social Determinants of Health;Women's Health Research

ORG_CITY: BOSTON

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: NARRATIVE There is very limited knowledge on the impact of environmental exposures during pregnancy and long-term maternal health. We will evaluate the associations of urinary phthalate and organophosphate flame retardant metabolite concentrations during three window of exposure (preconception, pregnancy and midlife) with cardiovascular and metabolic health in midlife. Results will inform clinical care for women from the reproductive years through midlife and cardiovascular guidelines.

PI_NAMEs: MINGUEZ ALARCON, LIDIA  (contact)

PROGRAM_OFFICER_NAME: BOYLES, ABEE

PROJECT_TERMS: Accounting;Adherence;Age;Anthropometry;Archives;Attention;Binding;Biological Markers;Birth;Birth Rate;Blood Pressure;Body mass index;cardiometabolism;Cardiovascular Diseases;cardiovascular disorder prevention;cardiovascular disorder risk;cardiovascular health;cardiovascular risk factor;Cardiovascular system;Cause of Death;Chemicals;Chronic Disease;Clinic;clinical care;cohort;Collection;Conceptions;consumer product;Couples;Databases;Diabetes Mellitus;Diet;Disease;disorder risk;Eating;Enrollment;Environment;environmental chemical;Environmental Exposure;Environmental Impact;Etiology;experimental study;Exposure to;Female;Fertility;Flame Retardants;Future;General Population;Gestational Diabetes;gestational weight gain;Glucose;glucose metabolism;Guidelines;Health;Health Status;healthy lifestyle;high risk;Human;Hypertension;Impairment;Individual;Inflammatory;Investigation;Joints;Knowledge;Length;Life Style;Link;lipid metabolism;Lipids;Live Birth;Longterm Follow-up;Maternal Health;Measures;Medical Device;men;Menopause;Metabolic;middle age;Modification;Nuclear Receptors;Obesity;offspring;Organophosphates;Outcome;Outcome Measure;Participant;Peroxisome Proliferator-Activated Receptors;personal care products;phthalates;Physical activity;Placenta;Pregnancy;Pregnancy Complications;Pregnancy loss;Pregnancy Outcome;Premature Birth;preventive intervention;Recommendation;recruit;Regulation;reproductive;Reproductive Health;Research Priority;Risk Factors;Sampling;screening;Series;Smoke;Smoking;Symptoms;Syndrome;Testing;Time;urinary;Urine;Weight;Woman;Women's mortality

PROJECT_TITLE: Exposure to phthalates and OP flame retardants and long-term maternal cardiovascular and metabolic health

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-PSE-N(91)S]


ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

PHR: Project Narrative In the first years of its existence this Center for Synthetic Regulatory Genomics has generated about 40 “Big DNA” molecules, most of which are more than 50,000 base pairs long and many of which are 100,000-200,000 long, as well as the technology to deliver these DNAs to stem cells, and ultimately to make mouse models. These resources have been used to dissect how genes are turned on and off in real human or mouse chromosomes and have also produced powerful models of human disease.

PI_NAMEs: BOEKE, JEF D (contact)

PROGRAM_OFFICER_NAME: GILCHRIST, DANIEL A

PROJECT_TERMS: Affect;Animal Model;Animals;Base Pairing;Behavior;Binding;Biochemical;Bioethics;Biotechnology;Brain;Cell Lineage;Cells;Chromatin;Chromosomes;Clustered Regularly Interspaced Short Palindromic Repeats;Code;Collection;combinatorial;Communities;Complex;Coupling;Cultured Cells;dark matter;design;Development;Disease;disease model;Elements;Embryonic Development;Engineering;Enhancers;Ensure;Exposure to;Failure;Fostering;functional genomics;Gene Expression Profile;Gene Library;Genes;Genetically Engineered Mouse;Genome;Genome engineering;genome wide association study;genomic locus;genomic predictors;Genomics;Genus Vanilla;Haplotypes;Human;human disease;Human Genetics;Human Genome;human model;humanized mouse;Image;Imaging technology;improved;innovation;Investigation;Length;Libraries;Light;machine learning prediction;Mammalian Cell;mammalian genome;Maps;member;Methodology;Minority;model organism;Modeling;Modification;Molecular Conformation;mouse model;Mus;new technology;Nuclear;outreach;outreach program;personalized medicine;Phase;Phenotype;Play;portability;Positioning Attribute;Production;programs;promoter;Reagent;Regulatory Element;Research;Research Personnel;Resolution;Resources;Role;Services;Spottings;stem cells;Students;System;Technology;tool;trait;translational applications;undergraduate student;Untranslated RNA;Validation;Variant;variant of interest;vector;Visualization;Work;Writing;Yeasts;Zinc Fingers

PROJECT_TITLE: CEGS: Center for Synthetic Regulatory Genomics - Renewal

STUDY_SECTION: GNOM

STUDY_SECTION_NAME: Genome Research Study Section[GNOM-G]


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

ORG_CITY: STANFORD

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: STANFORD UNIVERSITY

PHR: Among all organs in the body, we understand the brain least--we still do not know how the brain controls movement. This work seeks to uncover explanations on how the brain controls voluntary movement in free behavior like walking and running. This new insight will be critical to developing better recovery treatments for people with movement disabilities.

PI_NAMEs: LINDERMAN, SCOTT WARREN;NUYUJUKIAN, PAUL  (contact)

PROGRAM_OFFICER_NAME: OSBORNE, LESLIE CAROL

PROJECT_TITLE: CRCNS: Deconstructing dynamics of motor cortex in freely moving behavior


NIH_SPENDING_CATS: Biotechnology;Cancer;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

ORG_NAME: DANA-FARBER CANCER INST

PHR: Project Narrative We propose to develop a new strategy to develop small molecule degrader drugs, a new therapeutic regiment for cancer treatment that greatly expands the range of drug targets beyond what is accessible to more traditional inhibitors. We expect this to have a profound impact on cancer drug discovery and human health.

PI_NAMEs: FISCHER, ERIC SEBASTIAN (contact)

PROGRAM_OFFICER_NAME: FORRY, SUZANNE L

PROJECT_TERMS: Address;Antineoplastic Agents;assay development;Back;Binding Proteins;Biological;Biological Assay;Biology;cancer therapy;Cell Death;cell killing;Cell Line;Chemical Structure;Chemicals;chemoproteomics;clinical development;Communities;Complex;CUL2 gene;Data;Dependence;design;Development;Docking;dosage;drug development;drug discovery;Drug Targeting;Drug toxicity;Enzymes;Evaluation;Ewings sarcoma;Exhibits;Family;Family member;Feeds;Genetic;Goals;HDAC4 gene;HDAC6 gene;HDAC8 gene;Health;Histone Deacetylase;Histone Deacetylase Inhibitor;Human;human disease;In Vitro;in vivo;Inflammasome;inhibitor;inhibitor therapy;interest;Lead;lead optimization;Leukemic Cell;Libraries;Ligands;Ligase;Malignant Childhood Neoplasm;Malignant Neoplasms;Mediating;member;Methods;Modality;mutant;Nature;novel;novel therapeutics;Nuclear Hormone Receptors;Outcome;Pathway interactions;Pharmaceutical Chemistry;Pharmaceutical Preparations;pharmacologic;Phosphotransferases;Play;Process;Property;protein degradation;Protein Degradation Induction;Protein Family;Proteins;Proteome;Proteomics;RBX1 gene;recruit;Research;Role;Route;Scaffolding Protein;screening;small molecule;small molecule libraries;Structure;success;synergism;Testing;Therapeutic;therapeutic candidate;therapeutic target;tool;transcription factor;translational potential;ubiquitin-protein ligase;Ubiquitination;Work;young adult

PROJECT_TITLE: Development of a generalizable chemo-proteomics screening platform for small molecule degraders applied to HDACs

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


NIH_SPENDING_CATS: Genetics;Human Genome;Nutrition

ORG_CITY: COLLEGE STATION

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR

PHR: Project Narrative: The ability to endure bouts of starvation and infection is a primitive challenge in animals, and in order to combat these ancient stressors animals, from insects to humans, have developed highly integrated metabolic and innate immune stress responses. Unfortunately, over-nutrition associated with modern high-calorie diets and poor eating habits often leads to mis-regulation of these same primitive responses and the development of metabolic diseases. The goal of our research is to use the fruit fly, Drosophila melanogaster, as a simple model system to uncover the origins of diet-metabolic-innate immune interactions in order to advance our knowledge of diet- mediated metabolic dysfunction in humans.

PI_NAMEs: KARPAC, JASON S (contact)

PROGRAM_OFFICER_NAME: BASU, RAJATAVA

PROJECT_TERMS: Acute;Address;Animals;antagonist;Architecture;Attenuated;attenuation;Binding;biological adaptation to stress;Biological Models;Calories;Catabolism;cell type;Cells;Chromatin;chromatin modification;chromatin remodeling;Chromatin Remodeling Factor;Chronic;combat;Complex;Coupled;Development;Diabetes Mellitus;Diet;Diet and Nutrition;Diet Habits;dietary;dietary control;DNA-Directed RNA Polymerase;Drosophila genus;Drosophila melanogaster;energy balance;Equilibrium;Etiology;functional genomics;Gene Expression;gene induction;gene regulatory network;Genes;Genetic;Genetic Models;Genetic Screening;Genetic Transcription;genome-wide;genomic locus;Genomics;Goals;Histone Deacetylase;Homeostasis;Human;Immune;Immune signaling;Immune Targeting;In Vitro;in vivo;Infection;innate immune function;Innate Immune Response;Insecta;insight;Insulin;Invertebrates;Knowledge;Link;lipid metabolism;Lipids;Macronutrients Nutrition;Mammals;Mediating;Metabolic;Metabolic Diseases;Metabolic dysfunction;Metabolism;Modeling;Modernization;Molecular;Molecular Biology;Natural Immunity;NF-kappa B;novel;Nucleic Acid Regulatory Sequences;Nutrient;nutrition;Obesity;Organism;Overnutrition;pathogen;Pathology;Physiology;recruit;Regulation;Research;response;Role;screening;Sense Organs;Shapes;Signal Pathway;Signal Transduction;Starvation;Sterility;stressor;System;Testing;Tissues;transcription factor;Transcriptional Activation

PROJECT_TITLE: Genetic Modeling of Diet, NFkB, and Metabolic Interactions

STUDY_SECTION: CSME

STUDY_SECTION_NAME: Cell Signaling and Molecular Endocrinology Study Section[CSME]


NIH_SPENDING_CATS: Microbiome;Neurosciences

ORG_CITY: EAST LANSING

ORG_DEPT: ZOOLOGY

ORG_NAME: MICHIGAN STATE UNIVERSITY

PHR: NARRATIVE The vertebrate gut contains millions of bacteria, called the microbiome, that can have wide-ranging effects on host biology; in fact, recent studies have shown that the gut microbiome can drastically affect development and function of the brain and the nervous system of the gut. However, the large numbers of bacterial species in the gut and complexity of the vertebrate nervous system means that in order to understand how the microbiome interacts with the nervous system we need to find simple, manipulable systems in which to study these phenomena. We propose to use the association between the Hawaiian bobtail squid and its glowing bacterial symbiont as a simple, accessible, and manipulable model system in which to study interactions between beneficial microbes and animal nervous systems, focusing on the role of neurotransmitters in relaying signals between bacteria and their hosts.

PI_NAMEs: HEATH-HECKMAN, ELIZABETH A. (contact)

PROGRAM_OFFICER_NAME: RIDDLE, ROBERT D

PROJECT_TERMS: Activities of Daily Living;Address;Adolescent;Affect;Animals;Apoptosis;appendage;Bacteria;beneficial microorganism;Biological Models;Biology;Brain;Central Nervous System;Characteristics;Communities;Complex;connectome;Data;Development;Embryonic Development;Enteral;Enteric Nervous System;Epithelium;Euprymna scolopes;FMRFamide;Foundations;gene product;Genes;Genetic;Goals;gut microbiome;hatching;Hawaiian;Hindgut;Image;Imaging Techniques;immunocytochemistry;In Situ Hybridization;Individual;innovation;insight;interest;Knowledge;Label;Light;Lipopolysaccharides;Location;Mediating;Methods;Microbe;microbial;microbiome;Modeling;mutant;mutualism;Nervous System;Neurobiology;neurodevelopment;neuron development;Neuronal Plasticity;Neurons;Neuropeptides;Neurotransmitters;Nitric Oxide;Optics;Organ;Outcome;Pathway interactions;Peptidoglycan;Peripheral Nervous System;pharmacologic;Phenotype;Physiology;Positioning Attribute;Postembryonic;Process;Production;Proteins;Reaction;receptor;Resources;response;RNA;Role;Signal Transduction;Source;Squid;Structure;Study models;Surface;symbiont;Symbiosis;System;Techniques;Testing;Time;Tissues;transcriptome sequencing;V. fischeri-squid system;Vibrio;Vibrio fischeri;Visualization;Whole Organism;Work

PROJECT_TITLE: Determining the Role of Bacterial Products on Neuronal Localization and Function in a Symbiotic Organ

STUDY_SECTION: NDPR

STUDY_SECTION_NAME: Neurodifferentiation, Plasticity, Regeneration and Rhythmicity Study Section[NDPR]


NIH_SPENDING_CATS: Cardiovascular;Clinical Research

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

PHR: PROJECT NARRATIVE With the rise in the impact of cardiovascular disease on US and world health, it is critical to train the next generation of physician-scientists in translational cardiovascular research. Participation in mentored research provides valuable training and increases the likelihood that medical students will continue to pursue research as part of their careers. This multidisciplinary Stanford Cardiovascular Summer Research Training Program for Medical Students is designed to train a diverse cohort of medical students in basic, clinical, translational and population level cardiovascular science, to provide them with a strong foundation of medical ethics, and to foster their development into investigators dedicated to identifying innovative solutions and capable of translating research into clinical success to combat cardiovascular disease.

PI_NAMEs: DAVIS, JAMAINE S;FACUNDO, AMERICA ;WU, JOSEPH C. (contact)

PROGRAM_OFFICER_NAME: MEADOWS, TAWANNA

PROJECT_TERMS: Address;Cardiovascular system;career;career development;Clinical;Clinical Trials;cohort;Country;Dedications;Educational Curriculum;Evaluation;Event;experience;Exposure to;Faculty;faculty mentor;Familiarity;Foundations;Future;Goals;improved;Industry Collaboration;innovation;Institution;Longevity;medical schools;Medical Students;Medicine;Mentors;Monitor;Philosophy;Physicians;Population;precision medicine;programs;Puerto Rico;recruit;Reproducibility;Research;Research Ethics;Research Project Grants;Research Training;Resources;responsible research conduct;Science;Scientist;social;Students;success;summer research;Time;Training;Training Programs;translational medicine;Underrepresented Minority;Underrepresented Students;Universities;Work


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

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: PROJECT NARRATIVE This project is relevant to public health because it examines if cognitive outcomes are worsening in middle age and if environmental exposures and genetic risk predict cognitive outcomes in this age group. The study's findings will help elucidate the burden and mechanisms of cognitive decline in middle age and inform policy planning to mitigate the projected burden of dementia.

PI_NAMEs: BROWN, REBECCA TYLER (contact)

PROGRAM_OFFICER_NAME: BANDIERA, FRANK

PROJECT_TERMS: Address;Adult;Age;age group;Age of Onset;Aging;aging related;Alcohol consumption;Alzheimer's disease related dementia;Alzheimer's disease risk;American;Chronic;Cognition;Cognitive;cognitive impairment no dementia;Coupled;Crime;Data;Data Analyses;Data Set;Dementia;dementia burden;dementia risk;Disease;Engineering;Enrollment;Environment;Environmental Exposure;Environmental Risk Factor;Epidemiology;ethnic minority;Exposure to;food insecurity;Funding;Genetic;Genetic Risk;genetic risk factor;Health;Health and Retirement Study;Health behavior;Health behavior change;Health Status;high risk;Hypertension;Impaired cognition;improved;Incidence;Individual;Intercept;interest;Intervention;Knowledge;Life Cycle Stages;Link;Longitudinal Studies;low socioeconomic status;Measures;Medical;Medicine;middle age;modifiable risk;Neighborhoods;novel;Obesity;older adult;Outcome;Participant;Physical environment;Play;Policies;Pollution;Population;Predictive Factor;premature;Prevalence;prevent;Prevention;Prevention strategy;Public Health;racial minority;Risk;Risk Factors;risk prediction;Role;Social Environment;Social support;Study models;Subgroup;Surveys;Testing;Time;trend;United States National Academy of Sciences

PROJECT_TITLE: Trajectories of Cognition in Middle Age: Implications for Alzheimer's Disease and Related Dementias in the U.S.

STUDY_SECTION: SPIP

STUDY_SECTION_NAME: Social Psychology, Personality and Interpersonal Processes Study Section[SPIP]


ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: Narrative The overall objective is to evaluate a newly discovered inhibitor of 12/15-lipoxygenase as novel treatment for ischemic stroke. To this end, the inhibitor will be tested in rodent models of transient focal ischemia within the multi-center SPAN network.

PI_NAMEs: VAN LEYEN, KLAUS  (contact)

PROGRAM_OFFICER_NAME: JANIS, SCOTT

PROJECT_TERMS: Acute;Advocate;aged;Alteplase;Animal Experimentation;apoptosis inducing factor;Apoptotic;Arachidonate 15-Lipoxygenase;Area;behavior test;Behavioral;Blinded;Blood - brain barrier anatomy;Cells;Cerebral Ischemia;Clinic;Clinical Treatment;Clinical Trials;clinically relevant;Coagulation Process;comorbidity;db/db mouse;Death Rate;design;Dose;Edema;efficacy testing;Enzymes;experience;Female;Filament;Functional disorder;Genes;Goals;Hemorrhage;High Pressure Liquid Chromatography;Human;Hypertension;improved;improved outcome;In Vitro;Inbred SHR Rats;indexing;Infarction;inhibitor;Injury;Intervention;Intravenous;Ischemia;Ischemic Stroke;Knock-out;Knockout Mice;Laboratories;Laboratory Research;Lead;Lipoxygenase Inhibitors;Magnetic Resonance Imaging;male;Mass Spectrum Analysis;Measures;Meta-Analysis;Middle Cerebral Artery Occlusion;Mitochondria;Modality;Modeling;mouse model;Mus;Neurologic;neuron loss;Neurons;neuroprotection;Non-Insulin-Dependent Diabetes Mellitus;novel;Nuclear Translocation;Outcome;Outcome Study;Oxidative Stress;Patients;pharmacokinetics and pharmacodynamics;pharmacologic;Phase;pre-clinical;Pre-Clinical Model;Preclinical Testing;preclinical trial;programs;Property;Quality Control;Rattus;Reperfusion Therapy;Rodent;Rodent Model;Safety;safety testing;Sample Size;Scientist;Sensorimotor functions;sex;side effect;Site;Specificity;Stroke;stroke therapy;Subgroup;success;support network;Swelling;systematic review;Testing;Therapeutic;treatment optimization;Treatment Protocols;United States National Institutes of Health;Work

PROJECT_TITLE: Testing the Lipoxygenase Inhibitor BPN-27332 as Acute Phase Stroke Treatment in the SPAN Network