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

ORG_CITY: GALVESTON

ORG_NAME: UNIVERSITY OF TEXAS MED BR GALVESTON

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because it focuses on identifying previously unappreciated molecular/cellular mechanisms promoting synapse resilience to the detrimental impact of toxic tau oligomers in Alzheimer's disease (AD). This is ultimately expected to drive the development of a novel, effective preventive/curative therapy for AD, thus improving these patients' health while driving down the societal cost for their care, which is expected to increase to unbearable proportions by the year 2050. Thus, the proposed research is relevant to the part of NIH's mission concerned with fostering creative discoveries and their application to advance the Nation's capacity to protect and improve health.

PI_NAMEs: LIMON, AGENOR ;TAGLIALATELA, GIULIO  (contact)

PROJECT_TERMS: Affect;Alzheimer's Disease;Alzheimer's disease patient;Alzheimer's disease related dementia;Alzheimer's disease therapy;American;Autologous;Automobile Driving;Binding;Biochemistry;Brain;Caring;Clinical;Clinical Treatment;conformer;Consensus;Creativeness;curative treatments;Data;Dementia;Development;Disease;Effectiveness;Event;Fluorescence;Fostering;Foundations;Functional disorder;glutamatergic signaling;Goals;Health;Health Care Costs;Human;improved;Individual;innovation;Knowledge;LDL-Receptor Related Protein 1;Lipoprotein Receptor;Literature;Long-Term Potentiation;Mediating;Mission;Molecular;Molecular Neurobiology;neuron loss;neuropathology;non-demented;novel;Pathologic;Pathology;Patients;Physiology;Preventive;protein complex;Proteins;Public Health;Publishing;Qualifying;receptor mediated endocytosis;Research;resilience;Resistance;response;Role;Severities;societal costs;sound;Specimen;Staging;Standardization;Synapses;synaptic function;Synaptic Receptors;tau aggregation;tau Proteins;Tauopathies;Testing;Therapeutic;Toxic effect;United States National Institutes of Health;uptake;Work

PROJECT_TITLE: Tau oligomer conformers and synaptic vulnerability/resilience in AD and related disorders

STUDY_SECTION: CNN

STUDY_SECTION_NAME: Clinical Neuroscience and Neurodegeneration Study Section[CNN]


ADMINISTERING_IC: TW

ARRA_FUNDED: N

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: FOGARTY INTERNATIONAL CENTER

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

ORG_CITY: PARKTOWN

ORG_COUNTRY: SOUTH AFRICA

ORG_FIPS: SF

ORG_NAME: WITS HEALTH CONSORTIUM (PTY), LTD

PHR: The MADIVA Research Hub will develop data science techniques and solutions to tackle the problem of multimorbidity in Africa – the problem of multiple co-occurring diseases significantly adding to the health burden in Africa. Our primary research sites in rural Bushbuckridge, South Africa and urban Nairobi, Kenya each have rich data sets from longitudinal studies collected by the health and demographic surveillance systems based there, together with a nascent set of clinical health records and genomic data. We will develop and apply data science techniques to link the different data sets, build dashboards for different stakeholders and apply new machine learning techniques to automatically stratify populations for risk profiles to different diseases, including the use of polygenic risk scores.

PI_NAMEs: HAZELHURST, SCOTT  (contact);KYOBUTUNGI, CATHERINE ;RAMSAY, MICHELE MICHELE;TOLLMAN, STEPHEN

PROGRAM_OFFICER_NAME: NEWSOME, BRAD

PROJECT_TERMS: Academic Medical Centers;Address;Africa;African;Area;Behavioral;Black Box;career;Clinic;Clinical;clinical risk;Cohort Studies;Collaborations;Communities;Complex;Computer software;cost;dashboard;Data;Data Analyses;data infrastructure;data integration;data management;data quality;Data Science;Data Set;data sharing;data standards;data visualization;design;Development;digital;Disease;epidemiologic data;Epidemiology;Ethics;Evaluation;gene environment interaction;genomic data;Grant;Health;health record;Health Status;Health system;Healthcare;heterogenous data;high risk;high risk population;improved;Incubated;Individual;innovation;insight;Intervention;Kenya;Laboratories;Leadership;Link;longitudinal dataset;Longitudinal Studies;Machine Learning;machine learning model;Mentors;metadata standards;Methods;model building;Modeling;Monitor;multidimensional data;multiple chronic conditions;Network Infrastructure;novel;Outcome;Persons;Pharmaceutical Preparations;Pharmacogenomics;Pilot Projects;Play;Policies;polygenic risk score;Population Research;population stratification;Precision Health;Prevalence;Procedures;Process;programs;Protocols documentation;Public Health;public health intervention;Quality Control;Records;Research;Research Personnel;Research Project Grants;Risk;risk prediction model;Role;Running;Rural;Scientist;Site;social;social interventions;software development;South Africa;South African;Stratification;Structure;Subgroup;System;Techniques;Technology;tool;Training;Trauma;Universities;Urban Population;Visualization;Work

PROJECT_TITLE: MADIVA  (Multimorbidity in Africa: Digital innovation, visualisation and application)

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


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Biotechnology;Infectious Diseases;Lung;Pneumonia;Pneumonia and Influenza;Rare Diseases

ORG_CITY: COLUMBIA

ORG_COUNTRY: UNITED STATES

ORG_DEPT: BIOCHEMISTRY

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF MISSOURI-COLUMBIA

ORG_STATE: MO

PHR: Narrative / Public Health Relevance Integrated biophysical analyses of the Dot/Icm secretion system, an essential virulence factor for Legionella pneumophila, will provide the basis for the design of (1) anti-virulence drugs and (2) targeted delivery of gene and protein therapeutics. In order to exploit this bacterial system which evolved to deliver macromolecules to eukaryotic cells, we must understand how the Dot/Icm system selects and engages the cargo it transports across membrane barriers. The development of in vitro thermodynamics and kinetics assays to define the key steps in this process, testing mechanistic hypotheses derived from high-resolution cryoEM structures, will pave the way for new technologies to prevent infection and develop therapeutics.

PI_NAMEs: DURIE, CLARISSA LYNN (contact)

PROGRAM_OFFICER_NAME: WAIRKAR, YOGESH PRABHAKAR

PROJECT_TERMS: Antibiotic Resistance;Bacteria;Bacterial Infections;Binding;Biochemical;Biological;Biological Assay;Biological Models;biophysical analysis;Biophysics;Carrier Proteins;Cell secretion;Cells;Complement;Complex;Coupled;Cryoelectron Microscopy;Defect;design;Development;Disease;Engineering;Environment;Enzyme Kinetics;Eukaryotic Cell;experimental study;extracellular;Family;fighting;Foundations;Gene Delivery;Genetic;genetic approach;Hydrolysis;Immune system;In Vitro;Infection;Infection prevention;insight;Kinetics;Label;Legionella pneumophila;Legionnaires' Disease;macromolecule;Membrane;Molecular;Motor;new technology;next generation;Nucleic Acids;Nutrient;Organelles;Pathogenesis;pathogenic bacteria;Peptide Signal Sequences;Pharmaceutical Preparations;Process;Protein translocation;protein transport;Proteins;public health relevance;Reaction;Research Project Summaries;resistance gene;Resolution;response;Scientist;Structure;System;targeted delivery;Testing;Therapeutic;therapeutic protein;Thermodynamics;tool;trafficking;Type IV Secretion System Pathway;Virulence;Virulence Factors;Work

PROJECT_TITLE: Protein Transport Across Membrane by Bacterial Pathogens


ADMINISTERING_IC: NS

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Neurosciences

ORG_CITY: PHILADELPHIA

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: The majority of neurological and psychiatric disorders remain without effective preventions, treatments, or cures. One contributing factor may be the lack of individuals who have a deep understanding of both the clinical conditions, and of how to conduct laboratory research into the causes of disease and the development of treatments. This grant supports an education program for physicians who want to develop laboratory research skills so that they can be a bridge between doctors and scientists, helping to translate the results of basic innovative scientific research into new, effective preventions, treatments, or cures for persons with neurological, psychiatric, and neurodegenerative disorders.

PI_NAMEs: AGUIRRE, GEOFFREY KARL;JENSEN, FRANCES E (contact)

PROGRAM_OFFICER_NAME: REZAIZADEH, KAVON PAUL

PROJECT_TITLE: Remapping Clinical Neuroscience through Translation and Innovation Training (ReCoNnecT-IT)


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Coronaviruses;Coronaviruses Therapeutics and Interventions;Emerging Infectious Diseases;Genetics;Infectious Diseases

ORG_CITY: LA JOLLA

ORG_NAME: LA JOLLA INSTITUTE FOR IMMUNOLOGY

ORG_STATE: CA

PHR: The molecular mechanisms by which SARS-CoV-2 assembles and encapsidates its RNA genome are unknown. This project will determine the structure of the essential nucleocapsid protein and how it orchestrates assembly of the SARS-CoV-2 capsid. Findings from this study will provide a basis for rational design of pan-coronavirus medicines.

PI_NAMEs: SAPHIRE, ERICA OLLMANN (contact)

PROGRAM_OFFICER_NAME: PLIMACK, MARY KATHERINE BRADFORD

PROJECT_TERMS: 2019-nCoV;Address;Affinity;Antibodies;antiviral drug development;Bacterial RNA;Biochemical;Biological Assay;Capsid;Cells;Complement;Complex;Coronavirus;coronavirus antiviral;crosslink;Cryoelectron Microscopy;Data;density;Diameter;dimer;Dimerization;Disease;Electron Microscopy;Electrophoretic Mobility Shift Assay;Exclusion;Family;flexibility;Genetic Transcription;Genome;Goals;Hand;Histones;In Vitro;Individual;innovation;Label;Length;Maps;Mass Spectrum Analysis;Mediating;Medicine;Modeling;Molecular;Molecular Conformation;Molecular Machines;Nucleocapsid;Nucleocapsid Proteins;pandemic disease;particle;Play;polymerization;Polymers;Positioning Attribute;Process;Proteins;rational design;reconstitution;Resolution;RNA;RNA Binding;RNA chemical synthesis;RNA Recognition Motif;RNA Viruses;RNA-Protein Interaction;Role;SARS-CoV-2 genome;SARS-CoV-2 inhibitor;SARS-CoV-2 variant;screening;self organization;Site;stem;stoichiometry;structural biology;Structural Protein;Structure;System;variants of concern;Viral;viral RNA;Viral Structural Proteins;Virion;Virus;Virus Assembly;Visualization;Work

PROJECT_TITLE: Structure of the SARS-CoV-2 Nucleocapsid: building block to viral capsid

STUDY_SECTION: MCV

STUDY_SECTION_NAME: Molecular and Cellular Biology of Virus Infection Study Section[MCV]


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Cancer

ORG_CITY: BATON ROUGE

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: LOUISIANA STATE UNIV A&M COL BATON ROUGE

ORG_STATE: LA

PHR: Project Narrative The resistance of cancer cells to therapeutic drugs is a significant barrier to successful cancer treatment and the primary factor in cancer recurrence. The proposed study investigates lipid-driven cell death in drug- resistant cancer by manipulating ferroptosis, an alternate cell death mechanism, utilizing the spatial lipidomics technique. 1

PI_NAMEs: GARTIA, MANAS RANJAN  (contact)

PROGRAM_OFFICER_NAME: MASKERI, BAISHALI

PROJECT_TERMS: cancer cell;cancer recurrence;cancer therapy;Cardiovascular Diseases;Cell Culture Techniques;Cell Death;Cell Line;Cells;Chemicals;Chemistry;chemotherapy;Diabetes Mellitus;Disease;disease phenotype;Disease Progression;Drug resistance;Drug Sensitization;Goals;Heterogeneity;Image;improved;In Vitro;in vivo;in vivo Model;insight;Iron;iron metabolism;lipid metabolism;Lipid Peroxidation;lipidomics;Lipids;liquid chromatography mass spectrometry;Malignant Neoplasms;Maps;metabolomics;Methods;Modification;Molecular;multiple omics;Neurodegenerative Disorders;novel;Onset of illness;Outcome;Pathology;Pathway interactions;peroxidation;Pharmaceutical Preparations;Physiological Processes;Pre-Eclampsia;Raman Spectrum Analysis;refractory cancer;Resistance;Resolution;Role;Sepsis;success;Techniques;Therapeutic;therapeutic target;three dimensional cell culture;Tissues

PROJECT_TITLE: Spatial metabolomics with subcellular resolution to identify therapeutic targets


ADMINISTERING_IC: DE

ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Dental, Oral, and Craniofacial Disease;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Infectious Diseases;Pediatric;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: BOSTON

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: UNIVERSITY OF MASSACHUSETTS BOSTON

ORG_STATE: MA

PHR: PROJECT NARRATIVE The proposed research is important given that Brazilians are fast growing, and understudied ethnic minority immigrant population currently underrepresented in oral health (OH) and early childhood caries (ECC) research. This proposed community-based research will gather baseline data on Brazilian immigrant parents’ OH and ECC knowledge, attitudes, behaviors, and experiences with OH/dental health care access and utilization for their young children (< 6 years of age), therefore, building the knowledge base of oral and dental health among Brazilians in the US. The information gathered will be essential for designing effective, contextually grounded, culturally tailored interventions to meet the specific OH needs of Brazilian parents and children living in the United States.

PI_NAMEs: LINDSAY, ANA CRISTINA TERRA DE SOUZA (contact)

PROGRAM_OFFICER_NAME: ELWOOD, WILLIAM N

PROJECT_TERMS: 2 year old;20 year old;6 year old;Acculturation;Affect;American Indians;Back;Basic Science;Behavioral;Biological;Brazil;care systems;Caries prevention;Characteristics;Child;Childhood;Chronic;Chronic stress;Communicable Diseases;Communities;community based research;community engaged research;Control Locus;culturally appropriate intervention;Data;Dental Care;Dental caries;Dental Hygiene;Dental Insurance;design;Disease;early childhood;early experience;Environment;ethnic minority;Ethnic Population;experience;Face;Family;Fathers;Focus Groups;Foundations;Future;Health;Health behavior;health belief;health care availability;health care service utilization;health knowledge;Health Knowledge Attitudes Practice;Health Promotion;health related quality of life;Health Status;Healthcare;Healthcare Systems;High Prevalence;High-dimensional Modeling;Hispanic;Immigrant;Immigrant family;Immigration;improved;Individual;information gathering;innovation;Intervention;Intervention Trial;knowledge base;Language;Latin American;Latinx;Latinx population;Length;Low income;low socioeconomic status;Minority;Modeling;Mothers;Native-Born;Oral health;Outcome;Outcomes Research;Parents;Patient Self-Report;Phase;Physical environment;pilot test;Play;Population;Portuguese;prevent;preventive intervention;Psychosocial Assessment and Care;Psychosocial Factor;Qualitative Research;Questionnaires;racial minority;racial population;Research;Research Methodology;Residencies;Risk;Role;Science;Self Efficacy;social capital;Social Environment;Social support;sociodemographics;socioeconomics;Spanish;Stress;Surveys;Time;Translating;Underrepresented Populations;United States

PROJECT_TITLE: SORRIA! Assessing Brazilian Immigrant Parents' Oral Health Knowledge, Attitudes, and Behaviors for their Young Children

STUDY_SECTION: SPIP

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


NIH_SPENDING_CATS: Brain Disorders;Genetics;Huntington's Disease;Neurodegenerative;Neurosciences;Rare Diseases

ORG_CITY: NEW YORK

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

ORG_STATE: NY

PHR: We propose to elucidate molecular mechanism for neuroprotective autophagy in Huntington's disease (HD) and determine therapeutic potential for selective autophagy in treating the disease.

PI_NAMEs: YUE, ZHENYU  (contact)

PROGRAM_OFFICER_NAME: MILLER, DANIEL L

PROJECT_TERMS: Acceleration;Age;Agonist;Amino Acid Sequence;Animal Model;Antisense Oligonucleotides;Autophagocytosis;Axon;Biological Availability;Biological Markers;Body Weight;Brain;CAG repeat;Cell model;Cells;Clinical Trials;Complex;CRISPR/Cas technology;Data;Disease;disease model;Disease Progression;DNA;Drug Targeting;excitotoxicity;Functional disorder;gain of function;Genes;Genetic;Genetic Transcription;Goals;GTF2H1 gene;Huntington Disease;Huntington gene;Impairment;improved;injured;Knock-in;Knockout Mice;Lysosomes;Mediating;Mendelian disorder;Methods;Mitochondria;Molecular;mouse model;Mus;mutant;neuroprotection;neurotoxicity;novel;Nuclear Inclusion;Nuclear Pore Complex;Oral;Organelles;overexpression;oxidative damage;Pathogenicity;Pathway interactions;pharmacologic;Phenotype;Phosphotransferases;Physiological;polyglutamine;Post-Translational Protein Processing;postnatal;prevent;Process;protein aggregation;Proteins;Proteomics;proteostasis;proteotoxicity;Quality Control;Refractory;Regulation;Reporting;Research;Resistance;response;RNA;RNA Interference;RNA Splicing;Role;Scaffolding Protein;Signal Transduction;small molecule;Stress;success;Symptoms;Synapses;System;Techniques;Testing;Therapeutic;therapeutic development;therapeutic target;Toxic effect;Toxicity Tests;trafficking

PROJECT_TITLE: Determining Selective Autophagy Kinase in Modulating Neurotoxicity in Huntington's Disease Model

STUDY_SECTION: CMND

STUDY_SECTION_NAME: Cellular and Molecular Biology of Neurodegeneration Study Section[CMND]


ED_INST_TYPE: UNIVERSITY-WIDE

NIH_SPENDING_CATS: Building Research Capacity at Institutions with Limited NIH Funding;Cardiovascular;Heart Disease;Kidney Disease;Neurosciences;Opioids

ORG_CITY: SAN ANTONIO

ORG_NAME: UNIVERSITY OF THE INCARNATE WORD

ORG_STATE: TX

PHR: Relevance  Heart failure is characterized by increases in sympathetic nerve activity, plasma angiotensin II,  and chronic extracellular fluid accumulation. Therefore, further understanding of different  mechanisms and novel drugs that can either contribute to or oppose this disease is crucial from  the perspective of disease diagnostics and the development of new therapeutic strategies.

PI_NAMEs: GOTTLIEB, HELMUT B (contact)

PROGRAM_OFFICER_NAME: FRINCU, CRINA

PROJECT_TERMS: Adrenergic beta-Antagonists;Adult;Affect;Affinity;Agonist;Angiotensin II;Angiotensin-Converting Enzyme Inhibitors;Animals;Antioxidants;Area;beta-Endorphin;Blood;Blood Pressure;Bradycardia;Brain;Brain region;Cardiovascular Physiology;Cardiovascular system;Categories;Cell Nucleus;Central Nervous System;Chronic;Collaborations;Conscious;Coronary artery;cost;cytokine;Data;Development;Diagnosis;Dimensions;Disease;disease diagnostic;Diuresis;Diuretics;Dose;Dynorphins;Edema;Electrolytes;endogenous opioids;Enkephalins;Ensure;Excretory function;Experimental Designs;Extracellular Fluid;Family;FDA approved;Female;Functional disorder;Generations;Heart;Heart failure;Heart Rate;hindbrain;Homeostasis;Hormonal;Hormone secretion;Human;Hypotension;Immunoassay;Immunohistochemistry;improved;in vivo;Individual;Inflammation;Inflammation Mediators;Inflammatory;Inflammatory Response;innovation;Institution;Investigation;kappa opioid receptors;Kidney;Knowledge;Laboratories;Left ventricular structure;Ligands;Ligation;Liquid substance;male;Measures;Mediating;Microinjections;Modality;Modeling;Molecular Biology;Morbidity - disease rate;mortality;Myocardial Infarction;Nerve;neural;Neural Pathways;Neuroanatomy;nociceptin;novel;novel strategies;novel therapeutic intervention;novel therapeutics;Opioid;Opioid Peptide;Opioid Receptor;ORL1 receptor;paraventricular nucleus;Pathway interactions;Patients;Peptides;Peripheral;Pharmaceutical Preparations;pharmacologic;Pharmacology;Physiological;Physiology;Plasma;Play;Potassium;Process;Productivity;Rattus;Reactive Oxygen Species;receptor;Receptor Activation;Regimen;Regulation;Renal function;Renin-Angiotensin-Aldosterone System;response;Role;side effect;Signal Transduction;Site;Sodium;standard of care;Sympathetic Nervous System;Symptoms;System;Testing;Therapeutic;Third ventricle structure;Urine;Vasopressins;Water;Western Blotting;Workload

PROJECT_TITLE: CNS sites involved in the cardiovascular and renal effects of nociceptin in rats with heart failure


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Clinical Research;Coronaviruses;Emerging Infectious Diseases;Genetics;Human Genome;Infectious Diseases;Post-Acute Sequelae of SARS-CoV-2 infection (PASC) including Long COVID

ORG_CITY: ALBANY

ORG_DEPT: PHYSIOLOGY

ORG_NAME: ALBANY MEDICAL COLLEGE

PHR: Project Narrative: Given the strong impact of COVID-19 infection in the Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), the proposed research is relevant to public health because the elucidation of the mechanisms regulating persistent DNA methylation in inflammatory cells are ultimately expected to lead to better understanding of the process’ pathophysiology. Moreover, the identification of a novel phenotype as proposed here could facilitate early targeting of a subgroup of vulnerable patients, which represents a top priority of the NHLBI mission.

PI_NAMEs: ALISCH, REID SPENCER;JAITOVICH, ADOLFO ARIEL (contact)

PROGRAM_OFFICER_NAME: BREEN, JOSEPH J

PROJECT_TERMS: 2019-nCoV;Acute;acute COVID-19;acute infection;Acute respiratory failure;Age Factors;Blood;Blood specimen;Cell Separation;Cells;Cessation of life;Chemicals;chromatin modification;Classification;Clinical;clinical phenotype;Cognitive;COVID-19;COVID-19 burden;COVID-19 impact;COVID-19 patient;COVID-19 severity;COVID-19 survivors;Critical Illness;Data;Development;Dimensions;disorder control;DNA;DNA Maintenance;DNA Methylation;DNA methylation profiling;DNA sequencing;Dyspnea;Environmental Risk Factor;Epigenetic Process;epigenetic regulation;Exhibits;Functional disorder;Future;Gene Expression;Gene Expression Profile;Gene Expression Regulation;genome-wide;Genomics;histone modification;Hospitalization;Hospitals;Immune;Individual;individual response;Inflammatory;inorganic phosphate;instrument;Integration Host Factors;Leukocytes;Long COVID;long-term sequelae;longitudinal analysis;Lymphoid;Lymphoid Cell;machine learning classification;Magnetism;Measures;Methylation;methylation biomarker;methylome;Mission;Modification;Molecular;multiple omics;Muscle Weakness;Myelogenous;Myeloid Cells;National Heart, Lung, and Blood Institute;Nature;novel;Outcome;Participant;Patients;Pattern;Phenotype;Population;Positioning Attribute;post SARS-CoV-2 infection;Post-Acute Sequelae of SARS-CoV-2 Infection;post-COVID-19;Predisposition;Process;Public Health;Publishing;Recovery;Regulation;Reporting;Research;Resolution;RNA;RNA Sequences;Sampling;SARS-CoV-2 infection;Sensitivity and Specificity;Severity of illness;Sleep Disorders;Subgroup;Testing;Time;Tissues;Transcript;transcriptome;transcriptome sequencing;United States National Institutes of Health;Untranslated RNA;whole genome

PROJECT_TITLE: Blood DNA Methylation Biomarkers of Post Acute Sequelae of SARS CoV 2 Infection (PASC)

STUDY_SECTION: PRID

STUDY_SECTION_NAME: Population based Research in Infectious Disease Study Section[PRID]


NIH_SPENDING_CATS: Biotechnology;Genetics;Neurosciences

ORG_CITY: SAINT LOUIS

ORG_DEPT: PSYCHIATRY

ORG_NAME: WASHINGTON UNIVERSITY

PHR: NARRATIVE Astrocytes are a key support cell in the brain, with each astrocyte making close contact with thousands of neuronal synapses to support their function and viability. This proposal focuses on understanding the biological processes allowing each such contact to be fine-tuned to support the demands of an individual synapse. Dysregulation of these astrocyte processes is thought to occur in neurodegenerative diseases.

PI_NAMEs: DOUGHERTY, JOSEPH D (contact)

PROGRAM_OFFICER_NAME: TYLER, WILLIAM A

PROJECT_TERMS: Astrocytes;Award;Belief;Binding;Binding Sites;Biological Assay;Biological Phenomena;Biological Process;Brain;Cell Nucleus;cell type;Cells;Complex;Coupling;Cues;Databases;Dendritic Spines;density;design;Elements;experimental study;Face;Family;fascinate;Fluorescent in Situ Hybridization;Gene Expression;Genes;Image;in vivo;Individual;inhibitor;Learning;Machine Learning;Mediating;Memory;Messenger RNA;Methods;MicroRNAs;Minority;Modeling;Molecular;Morphology;mRNA Translation;Mutation;Neurodegenerative Disorders;Neuroglia;Neurons;overexpression;Pathway interactions;Peripheral;pharmacologic;Phosphorylation;Phosphotransferases;Physiological;Post-Translational Protein Processing;Process;Proteins;Proteome;Regulation;Reporter;response;Response Elements;Ribosomes;RNA;RNA-Binding Proteins;Role;Signal Transduction;Site;Slice;Specificity;Structure;Supporting Cell;Synapses;Synaptosomes;Testing;tool;Trans-Activators;Transcript;Transcriptional Regulation;Translating;Translation Process;Translational Regulation;Translational Repression;Translations;translatome;Untranslated Regions;Validation;Work

PROJECT_TITLE: Regulation of local translation in glia

STUDY_SECTION: CMBG

STUDY_SECTION_NAME: Cellular and Molecular Biology of Glia Study Section[CMBG]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Cardiovascular;Congenital Heart Disease;Heart Disease;Pediatric;Rare Diseases

ORG_CITY: MADISON

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: NARRATIVE Genetic mutations in the cardiac ryanodine receptor gene (RYR2) may lead to RyR2 channel dysfunction and lethal arrhythmogenic syndromes, such as catecholaminergic polymorphyc ventricular tachycardia (CPVT), a congenital disease affecting children and young adults with an apparently normal heart, and arrhythmogenic right ventricular cardiomyopathy (ARVC), a structural cardiac disease of right ventricular predominance. RyR2 dysfunction also plays a pivotal role in other major cardiomyopathies such as atrial fibrillation and heart failure; however, there is not yet a single drug in the market specifically designed to control RyR2 dysfunction. In this study, we use cryo-electron microscopy and other cutting-edge techniques to develop a rationalized and novel paradigm for the treatment of CPVT and other RyR2 dysfunction-linked cardiomyopathies, based on calcins, a group of cell permeable peptides that target RyRs with high affinity and specificity.

PI_NAMEs: VALDIVIA, HECTOR H (contact);VAN PETEGEM, FILIP

PROGRAM_OFFICER_NAME: TJURMINA, OLGA A

PROJECT_TERMS: Adrenergic Agents;Affect;Affinity;Agonist;Amino Acids;analog;Animal Model;Animals;Area;Arrhythmia;Arrhythmogenic Right Ventricular Dysplasia;Atrial Fibrillation;Binding;Biological Assay;Biology;Cardiac;Cardiac Myocytes;Cardiomyopathies;Catecholaminergic Polymorphic Ventricular Tachycardia;Cells;Child;Complex;Coupling;Cryoelectron Microscopy;design;Development;Diastole;Disease;DNA Sequence Alteration;effective therapy;Family;Functional disorder;gain of function mutation;Genetic Transcription;Goals;Heart;Heart Diseases;Heart failure;Hyperactivity;Hypertrophic Cardiomyopathy;Individual;insight;Ions;Knock-in;Label;Ligands;Link;Marketing;Mediating;member;Membrane;Modeling;Molecular;Mus;Muscle Cells;Muscle Fibers;mutant;Mutation;nanomolar;novel;Oryctolagus cuniculus;Pathologic;Penetration;Peptides;Perfusion;Permeability;Pharmaceutical Preparations;pharmacologic;Pharmacotherapy;Phase;Play;prevent;Process;programs;Property;rational design;Rationalization;Receptor Gene;Role;Ryanodine Receptor Calcium Release Channel;RyR2;Sarcoplasmic Reticulum;Scorpions;Series;Site;Specificity;stem;Structure;Sudden Death;Syndrome;Techniques;Testing;Therapeutic;transcription factor;Transmembrane Domain;Venoms;Ventricular;Ventricular Tachycardia;Vestibule;young adult

PROJECT_TITLE: Rational Design from Cryo-EM Structures of High-Affinity Ryanodine Receptor Ligands Based on Natural Peptides

STUDY_SECTION: MPPB

STUDY_SECTION_NAME: Integrative Myocardial Physiology/Pathophysiology B Study Section[MPPB]


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Cancer;Genetics;Human Genome

ORG_DEPT: ANATOMY/CELL BIOLOGY

PHR: Project Narrative Relevance to Public Health: This study investigates the fundamental mechanisms of self-assembly and liquid-liquid phase separation of tumor suppressors (53BP1 and BRCA1) and of chromatin organization in DNA damage responses. Mutations in 53BP1/BRCA1 or dysregulated chromatin architectures result in DNA damage accumulation and genome instability, which are strongly linked to cancer development as well as a myriad of other disorders of tissue physiology. Further, loss of 53BP1 function in BRCA1 mutant cells is associated with treatment resistance to PARP inhibitors, a major anti-cancer therapy.

PI_NAMEs: GARABEDIAN, MIKAEL  (contact)

PROGRAM_OFFICER_NAME: STOKES, KALYNDA K

PROJECT_TERMS: Address;Amino Acid Sequence;Aneuploidy;Architecture;Automobile Driving;Binding Proteins;Biochemical;Biochemical Reaction;Biological Assay;BRCA1 gene;cancer therapy;Cell Cycle;Cell Nucleus;cell transformation;Cells;Cellular biology;Chromatin;Chromatin Loop;chromatin modification;chromosome fusion;Chromosomes;Complex;Data;Defect;Development;Disease;DNA;DNA Damage;DNA lesion;DNA Repair;DNA Repair Pathway;Epigenetic Process;Equipment;Exons;Foundations;Functional disorder;genome integrity;Genomic Instability;Genotoxic Stress;Goals;Heterochromatin;Homeostasis;homologous recombination;Human;Image;In Vitro;insight;interdisciplinary approach;Knowledge;Lead;Link;Liquid substance;Maintenance;Malignant Neoplasms;Measures;Mediating;Modification;mutant;Mutation;Nonhomologous DNA End Joining;Nucleosomes;Organizational Change;p53-binding protein 1;Pathway interactions;Pennsylvania;Phase;Physical condensation;Physiological;Physiology;Play;Point Mutation;Poly(ADP-ribose) Polymerase Inhibitor;Positioning Attribute;programs;Proteins;Public Health;reconstitution;recruit;repaired;Research;Resistance;response;Role;self assembly;Stretching;superresolution microscopy;System;Testing;therapy resistant;Tissues;tool;TP53 gene;Training;Tumor Suppressor Proteins;Universities;Visualization;Work

PROJECT_TITLE: Characterizing the role of tumor suppressor phase separation and chromatin organization in maintaining genomic integrity


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

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: PROJECT NARRATIVE Astrocytes, microglia and monocytes play important roles in multiple sclerosis (MS) and other neurologic diseases, but the mechanisms that control them and their interactions in the central nervous system (CNS) are still largely unknown. This project studies a novel subset of disease-promoting astrocytes, their regulation by microglia and monocytes, and a candidate therapeutic approach for astrocyte modulation in MS.

PI_NAMEs: QUINTANA, FRANCISCO J. (contact)

PROGRAM_OFFICER_NAME: UTZ, URSULA

PROJECT_TERMS: adaptive immunity;antagonist;Astrocytes;Cell Communication;Cells;Central Nervous System;Central Nervous System Diseases;Clinical;CNS autoimmune disease;Coupled;CRISPR/Cas technology;Cytometry;Data;Data Set;digital;Disease;Disease Progression;Disease remission;drug candidate;Drug Modulation;Event;Experimental Autoimmune Encephalomyelitis;Fluorescent in Situ Hybridization;Generations;glial activation;Goals;gray matter;Health;Human;Immune;In Situ Hybridization;In Vitro;Inflammation;Inflammatory;Inflammatory Response;interest;Investigation;knock-down;Ligands;Link;Maps;Messenger RNA;Methods;Microfluidics;Microglia;Modeling;Molecular;Molecular Chaperones;monocyte;Multiple Sclerosis;Multiple Sclerosis Lesions;Nerve Degeneration;Nervous System Disorder;Nervous System Physiology;Neuroglia;Neurological disability;novel;nucleic acid detection;Nucleic Acids;Pathogenesis;Pathogenicity;Pathology;Pathway interactions;Patients;Peripheral;pharmacologic;Phase;Play;Population;Primary Progressive Multiple Sclerosis;Process;Progressive Disease;recruit;Regulation;Relapse;Reporter;Reporting;response;RNA Splicing;Role;Signal Transduction;single nucleus RNA-sequencing;single-cell RNA sequencing;spatiotemporal;Surface;Techniques;Testing;Therapeutic;therapeutic candidate;therapeutic target;therapy development;Tissues;transcription factor;two photon microscopy;Vascular Endothelial Growth Factor B;white matter;XBP1 gene;young adult

PROJECT_TITLE: Pathogenic Astrocyte Populations in EAE and MS


ADMINISTERING_IC: CA

ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biomedical Imaging;Biotechnology;Cancer;Cancer Genomics;Genetic Testing;Genetics;Human Genome;Lung;Lung Cancer;Precision Medicine;Prevention

ORG_CITY: LOS ANGELES

ORG_DEPT: DENTISTRY

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PROJECT NARRATIVE Lung cancer is the leading cause of cancer death in the U.S. and worldwide. This application seeks to develop novel blood-based lung cancer-associated molecular markers to distinguish between patients with benign or malignant nodules detected on computed tomography. It can provide a ground-breaking improvement in sensitivity and specificity as required to reliably detect lung cancer at an early stage.

PI_NAMEs: LI, FENG  (contact);WONG, DAVID T

PROGRAM_OFFICER_NAME: MARQUEZ, GUILLERMO

PROJECT_TERMS: actionable mutation;Apoptotic;Benign;Bioinformatics;Biologic Characteristic;Biological;Biological Assay;Biological Markers;Biological Process;Blood;Cancer Detection;Cancer Etiology;Cancer Patient;cell free DNA;Cells;Cessation of life;Chest;Clinical;clinical application;cohort;computed tomography screening;Data;Death Rate;Development;Diagnosis;diagnostic strategy;direct application;Disease;DNA;DNA Library;DNA Markers;DNA sequencing;Drug resistance;early detection biomarkers;Early Diagnosis;Early Intervention;effective therapy;Elements;Epidermal Growth Factor Receptor;Face;Frequencies;Generations;genome-wide;Hematopoiesis;high risk population;improved;Individual;Libraries;liquid biopsy;low dose computed tomography;lung basal segment;lung cancer screening;Lung Neoplasms;Lung nodule;Malignant - descriptor;Malignant neoplasm of lung;Malignant Neoplasms;Medical center;Methods;Modeling;molecular diagnostics;molecular marker;Molecular Profiling;Monitor;Morbidity - disease rate;mortality;Mutation;Names;Necrosis;neoplastic cell;new technology;Nodule;Non-Invasive Detection;Non-Small-Cell Lung Carcinoma;novel;novel marker;Nucleic Acids;Patients;Pattern;Performance;Plasma;Population;predictive modeling;Preparation;Procedures;Publications;Research;response;screening program;Sensitivity and Specificity;Single-Stranded DNA;Solid Neoplasm;Somatic Mutation;Source;Statistical Data Interpretation;Testing;Therapeutic;Thoracic Radiography;tumor;tumor DNA;Validation;Variant;Work;X-Ray Computed Tomography

PROJECT_TITLE: Novel ultra-short cell free DNA biomarkers for early detection of non-small cell lung cancer.


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

ORG_NAME: DANA-FARBER CANCER INST

PHR: Project Narrative The PGC1a pathway is critical for the regulation of mitochondrial biogenesis and oxidative metabolism. In this proposal we suggest experiments exploring the translation of the PGC1a mRNA and the development of new methods for the identification of secreted factors regulated by PGC1a. Together, these studies may provide the means for therapeutic intervention in obesity, diabetes, neuromuscular diseases and other important human disorders.

PI_NAMEs: SPIEGELMAN, BRUCE M. (contact)

PROGRAM_OFFICER_NAME: LYNCH, CHRISTOPHER

PROJECT_TERMS: Ablation;adeno-associated viral vector;Adipocytes;adipokines;adiponectin;Adipose tissue;Affect;angiogenesis;Architecture;Binding;Biochemical;Biogenesis;Biological;Biology;Body Composition;Brain region;Cell Respiration;Cells;cold temperature;crosslink;Data;Development;Diabetes Mellitus;Disease;Distant;drug development;Energy Metabolism;Enterobacteria phage P1 Cre recombinase;experimental study;extracellular;Fatty acid glycerol esters;Fiber;gain of function;Gene Expression;Genes;Genetic;genome wide association study;glucose tolerance;Grant;Health;High Fat Diet;Homeostasis;Human;Individual;Inflammation;Injections;insight;Insulin Resistance;Intercellular Fluid;interest;Knock-out;Knockout Mice;Link;Liquid substance;Liver;loss of function;Luciferases;Maps;Mass Spectrum Analysis;Mediating;Mediator;Messenger RNA;Metabolic;Metabolic Diseases;Methods;Mitochondria;Molecular;Mus;Muscle;Muscular Atrophy;Muscular Dystrophies;Mutation;nerve supply;Nervous System Disorder;Neuromuscular Diseases;Neuromuscular Junction;neurotrophic factor;novel;Nuclear Protein;Obesity;Oxidative Regulation;Parkinson Disease;Pathologic;Pathway Analysis;Pathway interactions;Peripheral;PGC1a Regulation Pathway;Pharmaceutical Preparations;Physical activity;Physical Exercise;Physiological;Physiology;Play;polypeptide;Polyribosomes;Process;promoter;Proteins;Recombinants;reduce symptoms;Regulation;Reporter;Reporting;Research;ribosome profiling;Ribosomes;RNA;RNA Binding;RNA Sequences;RNA-Binding Proteins;Rodent;Role;Site;Skeletal Muscle;Small Interfering RNA;Specificity;Spirometry;Structure;System;targeted treatment;Tertiary Protein Structure;Therapeutic;Therapeutic Intervention;Thermogenesis;Tissues;Titrations;Transcription Coactivator;transcription factor;transcriptome sequencing;Transgenic Mice;Translations;Weight Gain;Work

PROJECT_TITLE: PGC1alpha Pathway: Novel Intracellular and Extracellular Mediators

STUDY_SECTION: CSME

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


NIH_SPENDING_CATS: Infectious Diseases;Nutrition

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: NARRATIVE In this application we report our discovery of the Zng1 vertebrate zinc metallochaperone that insert zinc cofactors into methionine aminopeptidase 1 (Metap1) and the zinc finger homeobox 3 (Zfhx3), and we demonstrate that zinc cofactor insertion is required for the function of these proteins. Defective Metap and Zfhx3 activity is linked to increased susceptibility to infection and consistent with this, loss of Zng1 function leads to aberrant cellular physiology and a defective immune response. These discoveries establish ZNG1 as a new factor involved in protecting against infection through regulated zinc insertion into zinc requiring host defense proteins.

PI_NAMEs: GIEDROC, DAVID P.;SKAAR, ERIC P (contact)

PROGRAM_OFFICER_NAME: SINGLETON, KENTNER L

PROJECT_TERMS: Ablation;Affect;Animals;Binding;Biochemical;Biological;Biology;Cell Physiology;Cells;cellular development;Chemicals;Client;Clinical;cofactor;combat;Communicable Diseases;Complex;Cytosol;Data;Defect;defined contribution;Developing Countries;Development;Dietary Intervention;Dietary Zinc;Enzymes;Etiology;Exhibits;experimental study;Family;Gene Expression;Genetic Transcription;Growth;Guanosine Triphosphate Phosphohydrolases;Homeostasis;Host Defense;Human;human disease;immune function;Immune response;in vivo;Incidence;Infection;infection risk;insight;Life;Ligands;Link;Maintenance;Malignant Neoplasms;Mediating;metalloenzyme;Metalloproteins;Metals;methionyl aminopeptidase;Micronutrients;Modeling;Molecular;Molecular Chaperones;mortality;Mus;N-terminal;Names;Nature;Nervous System Disorder;Nucleotides;nutrition;Outcome;Peptide Hydrolases;Persons;Physiological;Physiology;Play;Population;Predisposition;Process;protein function;Proteins;Proteome;proteostasis;Public Health;Regulation;Reporting;response;Risk Factors;Role;Single Nucleotide Polymorphism;Starvation;Structure;Testing;Therapeutic;Tissues;transcription factor;Transition Elements;Translation Process;Zebrafish;ZFHX3 gene;Zinc;Zinc deficiency;Zinc Fingers

PROJECT_TITLE: The role of the ZNG1 metallochaperone in the host response to infection


ADMINISTERING_IC: TR

IC_NAME: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES

NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: TUFTS UNIVERSITY BOSTON

PHR: Project Narrative To improve health, we need to train researchers to be innovators in research, who can work with other investigators within and outside of their fields, who are excellent communicators to all audiences. The Tufts K12 Program has successfully trained early career investigators who remain active in research and leadership positions. In the next grant period, we will provide a career development plan that will support Scholars in gaining the skills necessary to become independently funded investigators who are leaders in their fields and advance interdisciplinary translational science.

PI_NAMEs: FREUND, KAREN  (contact);INKER, LESLEY ANN

PROGRAM_OFFICER_NAME: CURE, PABLO

PROJECT_TERMS: Appointment;career;career development;clinical translation;Communication;Complex;Development Plans;Discipline;early-career faculty;Faculty;Funding;Future;Goals;Health;improved;Individual;innovation;Institution;investigator training;Leadership;Mentored Clinical Scientist Development Program;Mentors;multidisciplinary;next generation;Outcome;Process;programs;Research;Research Methodology;Research Personnel;Research Project Grants;Science;self-directed learning;skill acquisition;skills;success;System;Training;Translational Research;translational scientist;Universities

PROJECT_TITLE: CTSA K12 Program at Tufts University


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

ORG_CITY: INDIANAPOLIS

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: Public Health Relevance Statement This Workshop is relevant to public health concerns because it brings a multi-disciplinary group of senior and junior scientists together to discuss recent advances in musculoskeletal biology related to bone disease. The Workshop will serve the junior scientist community and provide developmental activities and sessions, while addressing pertinent questions and scientific advancement in our understanding of musculoskeletal disease. The workshop provides vertically-oriented information, from basic science to clinical practice, to physicians, scientists, and engineers who may not be completely familiar with all aspects of these diseases of public health concern.

PI_NAMEs: ROBLING, ALEXANDER G (contact)

PROGRAM_OFFICER_NAME: WASHABAUGH, CHARLES H

PROJECT_TERMS: Address;Area;Award;Basic Science;Biology;Biomechanics;bone;Bone Diseases;career development;Cartilage Diseases;Cells;Cities;Clinical;Clinical Investigator;clinical practice;Clinical Sciences;Collaborations;Communities;Data;Degenerative polyarthritis;design;Development;Disease;Educational workshop;Electronic Mail;Engineering;experimental study;Faculty;Feedback;follow-up;Future;Goals;Idaho;Image;improved;innovation;insight;interdisciplinary collaboration;Interdisciplinary Communication;interest;investigator training;Knowledge;Link;Location;meetings;Molecular;Molecular Target;multidisciplinary;Musculoskeletal;Musculoskeletal Diseases;Myopathy;Orthopedics;Osteoclasts;Participant;Pathogenesis;Physicians;Play;posters;Prevention;Problem Solving;Process;programs;Public Health;public health relevance;Request for Applications;Research;Research Personnel;Resort;response;Role;Scientific Advances and Accomplishments;Scientist;Senior Scientist;skeletal disorder;skeletal stem cell;Slide;Societies;Sodium Chloride;student training;Students;Surveys;symposium;Therapeutic;Time;Tissues;tool;Utah;Visit;web site;Work

PROJECT_TITLE: ORS Musculoskeletal Biology Workshop at Zermatt

STUDY_SECTION: AMS

STUDY_SECTION_NAME: Arthritis and Musculoskeletal and Skin Diseases Special Grants Study Section[AMS]


NIH_SPENDING_CATS: Biotechnology;Cancer;Digestive Diseases;Orphan Drug;Pancreatic Cancer;Rare Diseases

ORG_CITY: OMAHA

ORG_NAME: UNIVERSITY OF NEBRASKA MEDICAL CENTER

ORG_STATE: NE

PHR: Project Narrative  MAP3K1 is an emerging therapeutic target. Through an iterative synthesis and screening we identified 50-008 that targets MAP3K1 and exhibits broad anticancer activities. We expect to define the mechanism of action and optimize 50-008 to identify a lead compound suitable for IND-enabling toxicity studies.

PI_NAMEs: NATARAJAN, AMARNATH (AMAR)  (contact)

PROGRAM_OFFICER_NAME: KONDAPAKA, SUDHIR B

PROJECT_TERMS: Acceleration;analog;anticancer activity;Apoptosis;Binding;Biological Availability;Body Weight;BRAF gene;Breast;Cancer cell line;Cell Cycle;Cell Line;Cell Membrane Permeability;Clinical Data;Clinical Trials;Collaborations;Colonic Neoplasms;Complication;Cullin Proteins;Development;Dose;Dose Limiting;drug discovery;Drug Kinetics;early onset;efficacy evaluation;Evaluation;Exhibits;FDA approved;flexibility;Foundations;Growth;Head;improved;Inflammation;Inhibition of Cancer Cell Growth;inhibitor;Interleukin-6;intraperitoneal;Invaded;Investigation;Lead;lead candidate;lead optimization;Ligase;Lung;Mainstreaming;Malignant neoplasm of pancreas;Malignant Neoplasms;MAP3K1 gene;Mass Spectrum Analysis;MEKs;Metabolic;migration;Modeling;Modification;Molecular Conformation;mouse model;Mus;Mutation;Nature;Neoplasm Metastasis;novel therapeutics;Oncogenes;Oral;Organoids;Pancreas;pancreatic cancer model;pancreatic cancer patients;pancreatic neoplasm;Paper;Peripheral;Permeability;Pharmacodynamics;Phosphorylation;Positioning Attribute;predictive modeling;Protac;Proteome;Publishing;Quinoxalines;Reporting;Resistance;Safety;screening;Signal Transduction;small molecule inhibitor;Solubility;Structure;Study models;Surface;T47D;Testing;Thalidomide;therapeutic target;Toxic effect;transcriptome sequencing;tumor;tumor growth;Tumor Suppressor Genes;tumorigenesis;United States National Institutes of Health;upstream kinase;Western Blotting;Xenograft procedure

PROJECT_TITLE: Development of Quinoxaline Based IKKbeta Inhibitors for Kras Driven Cancers

STUDY_SECTION: DMPC

STUDY_SECTION_NAME: Drug Discovery and Molecular Pharmacology C Study Section[DMPC]


ADMINISTERING_IC: MD

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

NIH_SPENDING_CATS: Building Research Capacity at Institutions with Limited NIH Funding;Cardiovascular;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Social Determinants of Health

ORG_DEPT: NEUROSCIENCES

ORG_NAME: MEHARRY MEDICAL COLLEGE

PHR: Project Narrative The long-term objective of the Endowment for Cardiometabolic Health Disparities Research is to expand the capacity of Meharry Medical College (MMC) to enhance research and research training in minority health. The program will address health disparities in cardiometabolic health disproportionately prevalent in the African Americans in Nashville and Davidson County, the catchment areas of MMC. This will be accomplished by recruiting and developing new research faculty, establishing a new PhD program in cardiometabolic health disparities, and promoting research infrastructure.

PI_NAMEs: HILDRETH, JAMES E;SHANKER, ANIL  (contact)

PROGRAM_OFFICER_NAME: MARSHALL, VANESSA J

PROJECT_TERMS: Address;African American;African American population;Area;Behavioral;Big Data Methods;Biological;Biology;Black race;Cardiometabolic Disease;cardiometabolism;cardiovascular health;Cardiovascular system;Catchment Area;Cessation of life;Communities;comorbidity;Complement;Computational Science;Computer software;Coronary heart disease;County;Data Collection;Dedications;Development;Diabetes Mellitus;Disease;Disparity;Doctor of Philosophy;doctoral student;Economic Burden;Educational Curriculum;Educational process of instructing;Endowment;Enrollment;Environment;Faculty;Funding;Goals;graduate school;graduate student;Health;health care delivery;Health Disparities Research;health disparity;Health Professional;Health Sciences;Historically Black Colleges and Universities;Income;inner city;Institution;instructor;instrumentation;Interdisciplinary Study;Investments;Leadership;medical schools;Medicine;Mentors;Minority;Minority Groups;minority health;minority health disparity;minority investigator;Outcome;Pathway interactions;Population;Postdoctoral Fellow;premature;Primary Health Care;Program Sustainability;programs;Public Health;Qualifying;Recording of previous events;recruit;Research;research faculty;Research Infrastructure;Research Personnel;Research Project Grants;Research Training;Schools;Science;Scientist;Secure;skills;socioeconomics;Stroke;Students;synergism;Teacher Professional Development;technological innovation;Tennessee;tenure track;Training;training opportunity;Training Programs;Translational Research;undergraduate student;Underrepresented Students;Universities;Vulnerable Populations


ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Project Narrative The principal goal of this project is to understand how nerve terminals in the brain precisely control and modulate the release of neurotransmitters in response to calcium signals. Neurotransmitter release forms the basis for the information transfer in neuronal networks and, thus, vital to understanding how the brain functions both in health and disease. By harnessing the strengths of the individual applicants, we aim to build a mechanistic molecular model of calcium-triggered neurotransmitter release, thus closing the gap between the intrinsic behaviour of the vesicular release machinery components and the complex dynamics of vesicular release at functionally distinct types of synapses.

PI_NAMEs: KRISHNAKUMAR, SHYAM S (contact);VOLYNSKI, KIRILL

PROGRAM_OFFICER_NAME: MATOS GALICIA, HEIDI YANICE

PROJECT_TERMS: Affect;Affinity;Behavior;Binding;Biochemical;Biochemistry;Biological Assay;Brain;Calcium;Calcium ion;Calcium Signaling;Cells;Closure by clamp;Communication;Complex;controlled release;Coupling;crosslink;Disease;Docking;Dyes;experience;Genetic;Glutamates;Goals;Health;Image;In Vitro;in vivo;Individual;insight;Kinetics;Learning;loss of function;Measurement;Measures;Mediating;Memory;Mental disorders;millisecond;Modeling;Molecular;molecular modeling;Mutation;Nerve;Nervous System Disorder;neural;Neurons;neurotransmission;neurotransmitter release;novel;Pattern;Physiological;Physiology;presynaptic;Presynaptic Terminals;Process;Property;Protein Isoforms;Proteins;Protocols documentation;reconstitution;Regulation;Research;response;Role;sensor;Shapes;Signal Transduction;single-molecule FRET;Site;Synapses;Synaptic Membranes;Synaptic Vesicles;synaptotagmin;synaptotagmin I;System;temporal measurement;Testing;Time;Titrations;tool;Vesicle;vesicular release;Work

PROJECT_TITLE: Calcium control of Neurotransmitter Release

STUDY_SECTION: NC

STUDY_SECTION_NAME: Neuronal Communications Study Section[NC]


ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: University of Pennsylvania PDX Development and Trial Centers Project Narrative – Human malignancies, particularly AML and ovarian, continue to have a high mortality. We will optimize human patient derived xenotransplantation models for AML, ovarian cancer and other malignancies and use these models to test new therapies for these diseases.

PI_NAMEs: CARROLL, MARTIN  (contact)

PROGRAM_OFFICER_NAME: HENDERSON, LORI A

PROJECT_TERMS: 15 year old;Acute Myelocytic Leukemia;animal facility;Bioinformatics;bioinformatics infrastructure;Biology;burden of illness;Cancer cell line;cancer type;Characteristics;Clear cell renal cell carcinoma;Clinical;clinical implementation;Clinical Trials;Collection;Combined Modality Therapy;Communities;Core Facility;Dedications;Development;Disease;experience;Glioblastoma;Goals;Human;Human Resources;Infection;Infection Control;Link;Malignant - descriptor;Malignant Breast Neoplasm;Malignant neoplasm of ovary;Malignant Neoplasms;MDM2 gene;Measures;member;Menin;Modeling;Molecular;mortality;Multiple Myeloma;Mus;NCI Center for Cancer Research;Non-Malignant;novel therapeutic intervention;novel therapeutics;Ovarian;Ovarian Clear Cell Tumor;Ovarian Serous Adenocarcinoma;patient derived xenograft model;Patients;Pennsylvania;Phase;phase 2 study;Phase I Clinical Trials;Phase I/II Clinical Trial;Pilot Projects;pre-clinical;precision oncology;Primary carcinoma of the liver cells;rare cancer;Recording of previous events;Reproducibility;Research;Research Personnel;response;Sampling;skills;stem cells;targeted treatment;Testing;Therapeutic;Tissue Banks;TP53 gene;translational potential;treatment response;tumor;Universities;University resources;Work;Xenograft Model;Xenograft procedure

PROJECT_TITLE: University of Pennsylvania Patient-derived Xenograft Development and Trials Center


NIH_SPENDING_CATS: Biotechnology;Cancer;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research

PROJECT_TERMS: Acceleration;Advocate;Award;Awareness;Biostatistics Core;Cancer Patient;Clinic;Clinical Trials;Collaborations;Communication;Communities;community engagement;Community Outreach;Data Commons;Development;Disabled Persons;Ensure;equity, diversity, and inclusion;Goals;Human Resources;Individual;innovation;Institution;Leadership;lecturer;Malignant Neoplasms;Manuscripts;meetings;Minority Groups;Outcomes Research;patient derived xenograft model;Patients;Pennsylvania;Pilot Projects;preclinical development;programs;Progress Reports;Publications;recruit;Research;Research Personnel;Resources;Schedule;Services;success;Tissue Banks;Tissues;training opportunity;Translational Research;Underrepresented Minority;Universities;Update;Visit;Woman;Work;Writing


NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Nonembryonic - Non-Human

PI_NAMEs: SKULI, NICOLAS  (contact)

PROJECT_TERMS: Academic Detailing;Address;Adoption;Affect;animal care;Animal Husbandry;Animals;Behavior;BLT mice;Bone Marrow;Caring;Cell Physiology;Center for Translational Science Activities;Complex;Consultations;Core Facility;cost;cytokine;Decontamination;Development;education research;Engraftment;Equipment;experimental study;fetal;Growth;Growth Factor;Guidelines;Human;human model;Human Resources;human tissue;IL6 gene;Immunocompromised Host;Infection;laboratory experiment;leukemia;leukemia tissue bank;Liver;Maintenance;Malignant Neoplasms;Methods;model development;Modeling;mouse model;Mouse Strains;Mus;Natural Killer Cells;novel;Operative Surgical Procedures;Outcomes Research;patient derived xenograft model;Pennsylvania;Pilot Projects;Procedures;Productivity;programs;Publications;Reproducibility;Research;Research Personnel;Running;skills;stem cells;Sterility;success;Thymus Gland;Tissue Banks;Tissue Harvesting;Tissues;Training;Transgenes;Transgenic Organisms;Transplantation;Universities;Xenograft procedure

PROJECT_TITLE: PDX Core


NIH_SPENDING_CATS: Brain Disorders;Epilepsy;Genetics;Human Genome;Intellectual and Developmental Disabilities (IDD);Neurodegenerative;Neurosciences;Pediatric

ORG_CITY: CHICAGO

ORG_DEPT: PHARMACOLOGY

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE Developmental and epileptic encephalopathies are particularly severe infant-onset epilepsies that are difficult to treat and pose a significant lifetime burden for patients, families, and society. Varying severity of epilepsy in KCNB1-associated encephalopathy in humans and mouse models suggests a contribution of genetic modifiers. Identifying modifier loci that influence severity of epilepsy will support the development of better treatments to improve the lives of individuals with developmental and epileptic encephalopathy.

PI_NAMEs: KEARNEY, JENNIFER A (contact)

PROGRAM_OFFICER_NAME: WHITTEMORE, VICKY R

PROJECT_TERMS: Address;Affect;American;autism symptoms;Behavioral;Brain region;Candidate Disease Gene;Case Study;Catalogs;Cessation of life;Characteristics;Child;Chromosome Mapping;Clinical;clinical phenotype;Code;Complex;Copy Number Polymorphism;Data;Data Set;Development;Developmental Delay Disorders;Disease;disease-causing mutation;DNA;Dominant-Negative Mutation;effective therapy;Electroencephalography;Encephalopathies;Epilepsy;epileptic encephalopathies;Etiology;Exhibits;Family;Foundations;Functional disorder;Future;Gene Expression;gene function;gene network;Genes;Genetic;Genetic Predisposition to Disease;genetic variant;Health;Heritability;Hippocampus;Human;human model;Hybrids;improved;improved outcome;Inbred Mouse;Inbred Strains Mice;Inbreeding;Incidence;Individual;Infant;Intellectual functioning disability;Knowledge;life span;Live Birth;Maps;Medical;Modeling;mortality risk;mouse model;Mus;Nervous System Disorder;network architecture;neurobehavior;Neurodevelopmental Disorder;Neurosciences;novel therapeutic intervention;Pathogenicity;Pathway interactions;patient population;Patients;Penetrance;Pharmaceutical Preparations;Phenotype;Population;Predisposition;Public Health;Quantitative Trait Loci;Recombinant Inbred Strain;Recombinants;Recurrence;Refractory;Reporting;resistant strain;response;Risk;risk variant;Seizures;Severities;Single Nucleotide Polymorphism;Societies;targeted treatment;Testing;Therapeutic Intervention;trait;Transcript;transcriptome;transcriptome sequencing;Validation;Variant;Voltage-Gated Potassium Channel;Work

PROJECT_TITLE: Genetic Mapping of Modifier Loci in a Mouse Model KCNB1 Encephalopathy

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


PI_NAMEs: LONG, QI  (contact)

PROJECT_TERMS: Address;arm;Artificial Intelligence;Bioinformatics;Biological Markers;biomedical informatics;Biometry;Cancer Center;Clinical;Clinical Trials;clinically relevant;Collaborations;Consensus;Consultations;Data;Data Analyses;data management;Data Storage and Retrieval;design;Development;Ensure;Epidemiology;Evolution;experience;Faculty;Genomics;high standard;Home;Human;Human Resources;in vivo;Informatics;Leukemic Cell;Measurement;medical schools;Mentors;Methodology;multiple omics;next generation sequence data;next generation sequencing;novel;novel strategies;patient derived xenograft model;Patients;Pennsylvania;phase II trial;Phenotype;Pilot Projects;potential biomarker;preclinical study;Productivity;professor;Proteomics;Reporting;Research;Research Design;Research Personnel;response;Role;Students;Techniques;Time;transcriptome sequencing;Transplantation;tumor;tumor growth;Tumor Volume;Universities;Variant;Work;Xenograft procedure

PROJECT_TITLE: Bioinformatics Core


NIH_SPENDING_CATS: Autoimmune Disease;Genetics;Immunotherapy;Kidney Disease;Lupus;Lymphatic Research;Psoriasis

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: Project Narrative The major long-term goal of our study is to determine the biological relevance of a novel metabolite (3HKA) of the tryptophan metabolism, in immunological tolerance. Our data indicate that this metabolite has immunosuppressive capability in animal models of Psoriasis and SLE reducing the clinical, biochemical, and immunological signatures of the disease. As such, we propose to therapeutically develop 3HKA as an additional drug to treat autoimmune diseases.

PI_NAMEs: SANTAMBROGIO, LAURA  (contact)

PROGRAM_OFFICER_NAME: VAZQUEZ-MALDONADO, NANCY

PROJECT_TERMS: adaptive immune response;Adenylate Cyclase;Amines;analog;Animal Model;Anti-Inflammatory Agents;Antigen-Presenting Cells;Antiinflammatory Effect;Autoimmune Diseases;Binding;Biochemical;Biogenic Amines;Biological;Biological Assay;Biological Response Modifiers;biophysical analysis;Biophysics;Biotinylation;Catabolism;CD8-Positive T-Lymphocytes;Cell secretion;Cells;chemokine;Clinical;Complex;CRISPR library;Cyclic AMP;cytokine;Data;Dendritic Cells;Disease;Drug Kinetics;Endowment;Enzymes;Erythema;Essential Amino Acids;Exhibits;Experimental Models;experimental study;Forskolin;G-Protein-Coupled Receptors;Generations;Genetic;Genetic Transcription;Glomerulonephritis;Goals;Human;IL17 gene;Immune;Immune Tolerance;Immunologics;Immunophenotyping;Immunoprecipitation;immunoregulation;Immunosuppression;improved;In Vitro;in vitro testing;in vivo;Incubated;Inflammatory;Interferon Type II;Interleukin-1 beta;Interleukin-6;kidney dysfunction;knock-down;Knowledge;Kynurenine;Lateral;Libraries;Ligands;Lupus;Lymphatic Endothelial Cells;Mammalian Cell;Maps;Mass Spectrum Analysis;Mediating;Melatonin;Memory;Metabolic Pathway;Modeling;mouse model;Mus;Nephritis;nephrotoxicity;novel;Nuclear;Nuclear Translocation;Orphan;Pathologic;Pathway interactions;Pharmaceutical Preparations;Pharmacodynamics;Phenotype;phosphoproteomics;Phosphotransferases;Physiological;Process;Production;protective effect;Proteinuria;Psoriasis;receptor;Regulation;Reporting;screening;Series;Serotonin;Serum;Signal Transduction;Signal Transduction Pathway;Skin;STAT1 gene;stem;Stimulus;Systemic Lupus Erythematosus;T memory cell;T-Cell Activation;Testing;Therapeutic;Thick;Titrations;TNF gene;Toxic effect;Tryptophan;Tryptophan Metabolism Pathway;Urea Nitrogen

PROJECT_TITLE: Biochemical and functional characterization of a novel anti-inflammatory biogenic amine


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

PROJECT_TERMS: Acute Myelocytic Leukemia;Address;advanced disease;Biology;Chimeric Proteins;Classification;Clinical;cohort;Collection;Combined Modality Therapy;Communities;Complex;Data;Development;Disease;disorder subtype;DNMT3a;Documentation;Drug Combinations;drug development;drug testing;Engraftment;Epigenetic Process;Failure;FLT3 gene;FLT3 inhibitor;Genetic;Human;in vivo;inhibitor;leukemia;leukemic stem cell;Malignant Neoplasms;Menin;Mixed-Lineage Leukemia;MLL gene;Modeling;Molecular;molecular modeling;molecular targeted therapies;Mouse Strains;Mus;mutant;Mutate;Mutation;new therapeutic target;next generation sequencing;novel;novel therapeutics;nucleophosmin;Oncogenes;Pathogenesis;patient derived xenograft model;Pennsylvania;Performance;Pharmaceutical Preparations;Phase;phase II trial;Phenotype;Pre-Clinical Model;Proteins;Relapse;Research Project Grants;response;Sampling;Subgroup;Survival Rate;targeted treatment;Therapeutic;therapy development;Tissue Transplantation;TP53 gene;transcriptome sequencing;Transplant-Related Disorder;Transplantation;treatment response;United States National Institutes of Health;Universities;Xenograft procedure

PROJECT_TITLE: Acute myeloid leukemia (AML) Research Project


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Cardiovascular

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: PROJECT NARRATIVE Cardiovascular disease (CVD) remains a leading cause of death in the United States and is linked to inflammatory signaling that promotes endothelial barrier dysfunction, a hallmark of inflammatory responses. Thrombin is generated during vascular injury and inflammation and promotes endothelial barrier disruption through p38 MAPK signaling. However, the pathways that regulate p38 MAPK signaling following thrombin stimulation is not known and important to understand to develop new strategies for the treatment of CVD.

PI_NAMEs: CHENG, NORTON  (contact)

PROGRAM_OFFICER_NAME: MEADOWS, TAWANNA

PROJECT_TERMS: Actins;Adaptor Signaling Protein;Adherens Junction;Automobile Driving;Binding;Binding Proteins;Biochemical;Biological Assay;Blood Vessels;Cardiovascular Diseases;Cause of Death;Cell membrane;Cells;Centers for Disease Control and Prevention (U.S.);Complex;Cytoskeleton;Deubiquitination;Development;Early Endosome;Endosomes;Endothelial Cells;endothelial dysfunction;Endothelium;Enzymes;Extravasation;Functional disorder;G Protein-Coupled Receptor Signaling;G-Protein-Coupled Receptors;Generations;genome-wide;Goals;GPR3 gene;Human;In Vitro;in vivo;Inflammation;Inflammation Mediators;Inflammatory;Inflammatory Response;Knowledge;Libraries;Link;MAP3K7 gene;MAP3K7IP1 gene;Mediating;Methods;Microscopic;Microscopy;Mitogen-Activated Protein Kinases;Molecular;mouse model;Mus;Myosin Light Chains;novel therapeutic intervention;p38 Mitogen Activated Protein Kinase;PAR-1 Receptor;Pathway interactions;Permeability;Phosphotransferases;Process;protein complex;recruit;Regulation;Research;response;RNA interference screen;Role;Signal Pathway;Signal Transduction;Small Interfering RNA;Testing;therapeutic development;Thrombin;Time;Ubiquitin;ubiquitin isopeptidase;ubiquitin-protein ligase;Ubiquitination;United States;vascular inflammation;vascular injury;Work

PROJECT_TITLE: Regulation of thrombin-induced p38 MAPK pro-inflammatory signaling by deubiquitinases


NIH_SPENDING_CATS: Biotechnology;Cancer;Genetics;Orphan Drug;Ovarian Cancer;Precision Medicine;Rare Diseases;Uterine Cancer;Women's Health Research

PI_NAMEs: SIMPKINS, FIONA  (contact)

PROJECT_TERMS: Address;Affect;American Society of Clinical Oncology;Apoptosis;Apoptotic;Behavior;Black Populations;black women;Cancer Etiology;Cancer Model;Cancer Patient;cancer subtypes;Cancer Therapy Evaluation Program;Carcinoma;Carcinosarcoma;Cell Cycle Arrest;Cell Nucleus;Characteristics;Chemoresistance;chemotherapy;Clinic;Clinical;Clinical Trials;Combined Modality Therapy;Communities;Data;Development;Disease;Disease Resistance;disorder subtype;DNA Repair;Dose;Drug Combinations;drug development;Drug resistance;Drug Synergism;effective therapy;Evaluation;fimbria;Future;Gene Expression;Genetic Predisposition to Disease;Genomics;Goals;Gynecologic;Histologic;Horns;In Vitro;in vivo;in vivo Model;ineffective therapies;Laboratories;Lead;leiomyosarcoma;Libraries;Malignant Epithelial Cell;Malignant Female Reproductive System Neoplasm;Malignant neoplasm of ovary;Malignant Neoplasms;MDM2 gene;Mediating;Modeling;Molecular;Molecular Profiling;mortality;Mus;mutant;Mutation;mutational status;new combination therapies;novel;novel drug combination;novel therapeutics;Oncology;Organoids;Ovarian Clear Cell Tumor;Ovarian Serous Adenocarcinoma;Ovary;Papillary;Parents;patient derived xenograft model;Patients;Pennsylvania;Phase;Platinum;Poly(ADP-ribose) Polymerase Inhibitor;potential biomarker;pre-clinical;Pre-Clinical Model;Preclinical Drug Development;prevent;Primary Neoplasm;Process;Proteomics;Recurrence;Research;Resistance;response;response biomarker;Serous;standard of care;synergism;targeted treatment;Techniques;Therapeutic;TP53 gene;Transplant Recipients;Transplantation;tumor;Tumor Suppressor Proteins;Universities;Uterine Cancer;Uterine Leiomyosarcoma;Uterus;White Women;Women's mortality

PROJECT_TITLE: Platform to develop targeted therapies for aggressive less common gynecological cancers


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Mental Health;Pediatric

ORG_CITY: CAMBRIDGE

ORG_DEPT: PSYCHOLOGY

ORG_NAME: HARVARD UNIVERSITY

PHR: Project Narrative Identifying how infants learn words is crucial for understanding language development in the first years of life, which has downstream effects on other aspects of lifelong success and achievement. Establishing normative baselines for the skills underlying early word learning has immediate and direct applicability to several populations: children with hearing loss, children with an Autism Spectrum Disorder (ASD), and children with Developmental Language Delays, all of whom previous work has demonstrated show delayed or impaired language abilities, on average, relative to typically-developing children. This program of research will be especially informative for tailoring more accurate assessment and support at younger ages for these populations, by uncovering which aspects of infants’ social and linguistic abilities link up with their early word learning, and the roles that experience and maturation play in this process.

PI_NAMEs: BERGELSON, ELIKA  (contact)

PROGRAM_OFFICER_NAME: SALO, VIRGINIA CHARLOTTE

PROJECT_TERMS: Achievement;Address;Affect;Age;Attention;autism spectrum disorder;autistic children;Behavior;behavioral outcome;Books;Child;Child Support;clinical application;Cognitive;Comprehension;comprehension test;Cues;Data;design;Development;Diagnosis;early childhood;Early Diagnosis;Early Intervention;Educational process of instructing;Ensure;evidence base;experience;Exposure to;Foundations;Future;Grain;Hearing;hearing impairment;Heart;improved;Infant;innovation;insight;Intervention;joint attention;Knowledge;Language;language comprehension;Language Delays;Language Development;Language Disorders;language impairment;Learning;lens;Life;life span;Linguistics;Link;Measures;multitask;novel;Play;Population;Prevalence;Process;Production;programs;Regulation;Research;Role;Sampling;Schools;skills;social;Social outcome;social skills;sound;success;Testing;theories;Time;Vocabulary;word learning;Word Processing;Work

PROJECT_TITLE: Linguistic, Social, and Cognitive Determinants of Early Word Learning

STUDY_SECTION: LCOM

STUDY_SECTION_NAME: Language and Communication Study Section[LCOM]


NIH_SPENDING_CATS: Neurosciences

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Project Narrative This program prepares a diverse group of junior investigators for research careers across the translational continuum of neuroscience. We offer training experiences designed to educate basic scientists about neurologic disease and to provide clinician-scientists pursuing laboratory-based research or clinical research the opportunity to develop and enhance their research skills. Training is a combination of mentored research, formal education, and a Core Program focused on enhancing specific research, quantitative, biostatistical and career development skills.

PI_NAMEs: KLEINDORFER, DAWN O;PAULSON, HENRY L (contact)

PROGRAM_OFFICER_NAME: WEIGAND, LETITIA ALEXIS

PROJECT_TERMS: Clinical;Neurosciences;Training

PROJECT_TITLE: Training in Clinical and Basic Neuroscience


ORG_CITY: PHILADELPHIA

PROJECT_TERMS: Address;Basic Science;Budgets;Cancer Center;cancer health disparity;Clinic;Clinical;Collaborations;Common Neoplasm;Communities;Complement;Data;Development;Disabled Persons;Ensure;Equity;Evaluation;Faculty;Financial Support;Fostering;Funding;Goals;Grant;health care disparity;high risk;Human Resources;innovation;Intervention;Methodology;Monitor;novel;novel strategies;patient derived xenograft model;Pennsylvania;Pilot Projects;Process;programs;Progress Reports;Racial Equity;recruit;Research;research and development;Research Personnel;Resources;success;Technology;Testing;Tissue Banks;Tissue Expansion;tissue resource;tool;translational potential;Translational Research;Underrepresented Minority;Universities;Woman;Work

PROJECT_TITLE: Pilot Projects-Tran-Network


NIH_SPENDING_CATS: Breast Cancer;Cancer;Clinical Research;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Precision Medicine;Prevention;Women's Health Research

ORG_NAME: UNIVERSITY OF CHICAGO

PHR: Project Narrative Nearly one in eight women will develop a diagnosis of breast cancer over the course of their lifetime, and selection of treatment is often based off a gene expression assay such as OncotypeDX. Deep learning can integrate readily available clinical, pathologic, and immune features to predict recurrence and chemotherapy benefit, resulting in more accurate, faster, and cost-effective treatment decisions.

PI_NAMEs: HOWARD, FREDERICK MATTHEW (contact)

PROGRAM_OFFICER_NAME: BOULANGER-ESPEUT, CORINNE A

PROJECT_TERMS: American Cancer Society;Anti-estrogen Therapy;Artificial Intelligence;biobank;Biological Assay;Biological Markers;biomarker validation;Biopsy;breast cancer diagnosis;cancer diagnosis;Cancer Etiology;cancer prevention;Cancer Prognosis;cancer recurrence;cancer survival;career;Cell Density;Cells;Cessation of life;chemotherapy;Chicago;Clinical;Clinical Data;clinical implementation;clinical practice;clinical predictors;Clinical Research;clinically relevant;cohort;combat;cost effective;cost effective treatment;Data;data streams;Databases;deep learning;deep learning model;design;Diagnosis;digital;digital pathology;Disease;Disparity;ERBB2 gene;experience;Gene Expression;Gene Expression Profile;Gene Expression Profiling;genomic biomarker;Goals;Guidelines;health care disparity;Hematoxylin and Eosin Staining Method;Histology;Hormone Receptor;hormone receptor-positive;hormone therapy;Image;Image Analysis;Immune;Immunofluorescence Immunologic;Immunological Models;Immunology;implementation science;improved;individualized medicine;Institution;Malignant Breast Neoplasm;Malignant Neoplasms;model development;Modeling;mortality;novel;participant enrollment;Pathologic;Pathologist;Pathology;Patient Care;Patient Selection;patient subsets;Patients;Performance;personalized medicine;Positioning Attribute;predictive marker;Prognosis;prognostic;prognostic model;quantitative imaging;receptor expression;Recommendation;Recurrence;Research Personnel;Resource-limited setting;Retrospective cohort;Risk;Sampling;Selection for Treatments;Stains;Techniques;Test Result;Testing;Time;Training;treatment response;Tumor-Infiltrating Lymphocytes;United States;Universities;Validation;Woman;Women's mortality;Work

PROJECT_TITLE: Integrating Clinical, Pathologic, and Immune Features to Predict Breast Cancer Recurrence and Chemotherapy Benefit

STUDY_SECTION: NCI

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


ORG_CITY: ATLANTA

ORG_DEPT: PATHOLOGY

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: Project Narrative Antiretroviral therapy (ART) has reduced HIV-related morbidity and mortality for most of the infected individuals. However, the maintenance of the HIV as reservoirs, mainly in tissues, poses a major obstacle for HIV cure. The understanding of how these reservoirs are formed and maintained over time in tissues, even during ART, will enlighten HIV cure strategies, aiming at eradicating HIV tissue sanctuaries. These mechanisms will be addressed in this proposal.

PI_NAMEs: PEREIRA RIBEIRO, SUSAN  (contact)

PROGRAM_OFFICER_NAME: NOVAK, LEIA KAYE

PROJECT_TERMS: Address;Aftercare;Animals;Anti-Inflammatory Agents;Antibodies;antiretroviral therapy;BCL1 Oncogene;biobank;Biology;CD4 Positive T Lymphocytes;Cells;Chromatin;Chronic;chronic infection;Clustered Regularly Interspaced Short Palindromic Repeats;cohort;confocal imaging;cytokine;Data;Data Analyses;differentiation in vitro;Fine needle aspiration biopsy;Frequencies;Gene Targeting;Genes;Genetic Transcription;Helper-Inducer T-Lymphocyte;HIV;HIV Infections;Human;immunoregulation;In Vitro;in vitro Model;in vivo;Individual;Infection;innovation;interdisciplinary approach;interest;Interleukin-10;interleukin-21;Interleukin-6;Interruption;Intervention;knockout gene;Lead;Lymph Node Tissue;lymph nodes;Lymphoid Tissue;Macaca;Macaca mulatta;Maintenance;Methods;Modeling;Molecular;Morbidity - disease rate;mortality;multiple omics;novel;Oligonucleotides;Pathogenesis;Pathway interactions;Pattern;PD-1 blockade;PD-1 pathway;Peripheral Blood Mononuclear Cell;Plasma;Play;Predisposition;Productivity;programmed cell death protein 1;Protein Isoforms;Provirus Integration;Proviruses;Research Personnel;Retrospective Studies;RNA;Role;Sampling;Series;Signal Pathway;Signal Transduction;single cell analysis;Site;SIV;Specimen;STAT3 gene;Suspensions;synergism;Testing;TGF Beta Signaling Pathway;Time;Tissue imaging;Tissues;Tonsil;tool;transcription factor;transcriptomics;Transforming Growth Factor beta;Viral;viral DNA;Viral Genes;viral rebound;Viral reservoir;viral RNA;Viremia;Virion;virology;Work

PROJECT_TITLE: Defining molecular pathways triggered by IL-10 and TGFb that drive HIV integration and persistence in Tfh cells in lymph nodes

STUDY_SECTION: HIVD

STUDY_SECTION_NAME: HIV Immunopathogenesis and Vaccine Development Study Section[HIVD]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Hematology;Immunotherapy;Infectious Diseases;Orphan Drug;Primary Immunodeficiencies;Rare Diseases

ORG_CITY: MEMPHIS

ORG_NAME: ST. JUDE CHILDREN'S RESEARCH HOSPITAL

PHR: PROJECT NARRATIVE We are interested in understanding the causes and developing new and better treatments for primary hemophagocytic lymphohistiocytosis (pHLH), an expanding spectrum of inherited disorders of the immune system associated with severe hyperinflammation. This R21 Exploratory/Developmental Research Grant will examine whether and how pharmacologic inhibition of the immunoproteasome, a protein complex that plays a critical role in the immune system by degrading proteins into small peptides for presentation on the surface of antigen presenting cells, lessens inflammation in a mouse model of pHLH. These studies are relevant to public health and immunodeficiency because they will provide insights into the role of the immunoproteasome in the pathogenesis of pHLH and elucidate whether targeting this protein complex lessens disease manifestations and improves survival, thus setting the stage for future clinical trials in humans.

PI_NAMEs: NICHOLS, KIM ERIKA (contact)

PROGRAM_OFFICER_NAME: MORRIS FEARS, MARGARET A

PROJECT_TERMS: Address;Allogenic;Anemia;Animals;Antigen Presentation;Antigen-Presenting Cells;Antigens;Automobile Driving;B-Lymphocytes;Blood;Body Weight decreased;CD8-Positive T-Lymphocytes;Cells;chemotherapeutic agent;Clinical;Clinical Trials;clinically significant;Coculture Techniques;congenital immunodeficiency;cytokine;cytotoxic;Defect;Development;Dexamethasone;Disease;effective therapy;Epitopes;Etoposide;Exposure to;familial hemophagocytic lymphohistiocytosis;Feedback;Ferritin;Flare;Flow Cytometry;Future;Glucocorticoids;Harvest;Height;Hematopoietic;Hematopoietic Stem Cell Transplantation;Hemophagocytic Lymphohistiocytoses;Hereditary Disease;Histology;Homeostasis;Human;Immune;immune activation;Immune response;Immune system;Immune System Diseases;immunodeficiency;immunopathology;improved;In Vitro;in vitro Assay;in vitro Model;in vivo;Individual;Infection;Infiltration;Inflammation;Inflammatory;inhibitor;insight;interest;Interferon Type II;Investigation;ITGAX gene;Jordan;Label;Laboratories;Learning;Lymphocytic choriomeningitis virus;Macrophage;Major Histocompatibility Complex;Measures;Modeling;mouse model;Mus;Natural Killer Cells;novel;novel therapeutic intervention;Organ;Outcome;OVA-8;Pathogenesis;Patients;Peptides;perforin;peripheral blood;Pharmaceutical Preparations;pharmacologic;Play;Process;Production;Proliferating;protein complex;Proteins;Public Health;Regimen;Research Project Grants;response;Role;Schedule;Serum;Signs and Symptoms;Sorting;Splenocyte;Splenomegaly;Surface Antigens;T-Cell Activation;T-Cell Proliferation;T-Lymphocyte;targeted agent;Testing;Therapeutic;Therapeutic Effect;therapeutic target;Thrombocytopenia;Tissues;TNF gene;Toxic effect;VDAC1 gene;Viral;Viral Load result;Viral Proteins;Virus;Virus Diseases;Visceromegaly

PROJECT_TITLE: Targeting the immunoproteasome as a novel therapeutic strategy for hemophagocytic lymphohistiocytosis

STUDY_SECTION: III

STUDY_SECTION_NAME: Innate Immunity and Inflammation Study Section[III]


NIH_SPENDING_CATS: Infectious Diseases;Lung;Pneumonia;Pneumonia and Influenza;Rare Diseases

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

PHR: Project Narrative: These studies will define mechanisms underlying how TNF promotes effector-triggered immunity in DCs to restrict the bacterial pathogen Legionella pneumophila. These studies will provide fundamental insight into host defense mechanisms that may enable the development of novel therapeutics for treating bacterial infection.

PI_NAMEs: SHIN, SUNNY  (contact)

PROGRAM_OFFICER_NAME: ERNST, NANCY L

PROJECT_TERMS: Ablation;Anti-Bacterial Agents;Antibiotic Resistance;antimicrobial;Apoptosis;Autoimmune Diseases;Bacterial Infections;BCL2 gene;Biochemical;burden of illness;CASP3 gene;CASP8 gene;Cell Death;Cells;community acquired pneumonia;contaminated water;Crohn's disease;Data;defined contribution;Dendritic Cells;Development;Disease;Family member;gain of function;Genetic;Goals;Hospitals;Host Defense;Host Defense Mechanism;Humira;Immune;Immune response;Immunity;Immunocompromised Host;immunosuppressed;Immunosuppressive Agents;improved;In Vitro;in vivo;Individual;Induction of Apoptosis;Infection;Infection Control;infection risk;infliximab;Inhalation;Inhibition of Apoptosis;inhibitor;Innate Immune Response;insight;Integration Host Factors;Legionella;Legionella pneumophila;Legionnaires' Disease;Licensing;loss of function;Lung;Lung infections;Macrophage;Mediating;Medical;Molecular;Mus;mutant;Mycobacterium tuberculosis;Natural Immunity;novel;novel therapeutics;opportunistic pathogen;pathogen;pathogenic bacteria;Patients;permissiveness;pharmacologic;Play;Protein Biosynthesis;Protein Family;Psoriasis;Public Health;response;Rheumatoid Arthritis;Risk;Role;Salmonella;Signal Transduction;targeted treatment;Testing;Therapeutic;therapeutic development;Time;TNF gene;Translations;Type IV Secretion System Pathway;Ulcerative Colitis;United States

PROJECT_TITLE: Effector-triggered immunity against Legionella pneumophila in dendritic cells


NIH_SPENDING_CATS: Clinical Research;Genetics;Pediatric;Primary Immunodeficiencies;Rare Diseases

PHR: PROJECT NARRATIVE  We showed that human SERPINB1 deficiency leads to impaired T cell activation and causes a primary immunodeficiency characterized by susceptibility to severe mycobacterial infections. We will investigate the previously unknown role of SERPINB1 in T cell immunity and identify the pathways it orchestrates. Finally, we will perform phenome-wide association studies (pheWAS) to investigate the connection of genetic variants in the SERPINB1 pathway with more common human diseases.

PI_NAMEs: MARTINEZ BARRICARTE, RUBEN  (contact)

PROJECT_TERMS: Abnormal Neutrophil;Affect;Alleles;Antimycobacterial Agents;Apoptosis;Autoimmunity;Basic Science;biobank;Biochemistry;Biological;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;cell injury;Cell Line;Cell Physiology;Cells;Cellular biology;Cessation of life;Chemicals;Clinical;congenital immunodeficiency;CRISPR/Cas technology;Critical Pathways;Cytometry;Data;Disease;Electronic Health Record;exome sequencing;experimental study;follow-up;Frequencies;Future;Genes;Genetic;genetic approach;Genetic Databases;genetic disorder diagnosis;Genetic Polymorphism;Genetic Predisposition to Disease;Genetic Transcription;genetic variant;Human;human disease;Immunity;immunodeficiency;Immunologics;Immunophenotyping;immunoregulation;Impairment;Infection;inhibitor;interleukin-23;Knowledge;Learning;Left;Malignant Neoplasms;Mediating;memory CD4 T lymphocyte;Mendelian disorder;Methods;Molecular Biology;Mus;Mutation;mycobacterial;Mycobacterium Infections;Nature;Neutropenia;neutrophil;Nonsense Mutation;Pathway interactions;Patients;Peptide Hydrolases;Persons;phenome;Population Genetics;Predisposition;prevent;Proteins;Rare Diseases;Research;response;reverse genetics;Risk;Role;Sampling;Serine Protease;single-cell RNA sequencing;STAT3 gene;suicide inhibitor;T cell differentiation;T memory cell;T-Cell Activation;T-Lymphocyte;Testing;Therapeutic;Variant;Work

PROJECT_TITLE: The role of SERPINB1 in T cell function and its contribution to human diseases

STUDY_SECTION: IHD

STUDY_SECTION_NAME: Immunity and Host Defense Study Section[IHD]


NIH_SPENDING_CATS: Bioengineering;Neurosciences

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PROJECT NARRATIVE The mammalian hypothalamus plays a critical role in the control of functions that are essential for an animals’ survival individually and at the species level, including ingestive, reproductive, and defensive behaviors, as well as maintaining homeostasis. The goal of this project is to construct a multimodal, multiscale, 3D anatomic atlas of the male and female mouse hypothalamus that reflects the functional diversity of the structure, providing a more accurate template upon which hypotheses can be generated and tested. Understanding the detailed architecture of the hypothalamus alongside functional data is critical foundation for understanding dysfunction and disease states associated with this key brain region.

PI_NAMEs: DONG, HONG-WEI  (contact)

PROGRAM_OFFICER_NAME: HE, JANET

PROJECT_TERMS: 3-Dimensional;Aggressive behavior;Algorithms;Anatomy;Androgen Receptor;Animals;Antibodies;Architecture;Arousal;Atlases;Axon;Behavior;Behavioral;Brain;Brain region;calbindin;Catalogs;cell type;Circadian Rhythms;Classification;cloud based;computational platform;computer infrastructure;Data;data exchange;data portal;Dendrites;design;Disease;Estrogen Receptors;excitatory neuron;Feeding behaviors;Female;Foundations;Functional disorder;Genetic;Genetic Markers;Glutamates;Goals;Heterogeneity;Histologic;Homeostasis;Human;hypocretin;Hypothalamic structure;Immunohistochemistry;Individual;Informatics;inhibitory neuron;innovation;Internal Ribosome Entry Site;Investigation;Knock-in Mouse;Label;Lateral Hypothalamic Area;Light;male;Manuals;Maps;Metabolism;Methods;Microscope;microscopic imaging;Microscopy;Modeling;Molecular;Morphology;multimodality;Mus;network architecture;neural;Neural Pathways;Neurons;Neuropeptides;novel;Organizational Productivity;Pathway interactions;Physiologic Thermoregulation;Play;Process;Property;Publishing;Rabies;reconstruction;Reporter;reproductive;Reproductive Behavior;Resolution;Role;sex;sexual dimorphism;Social Behavior;Specificity;Structure;Synapses;Taxonomy;Techniques;Testing;Tracer;Undifferentiated;Viral;Visualization

PROJECT_TITLE: A three dimensional multimodal cellular connectivity atlas of the mouse hypothalamus

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-NV-P(81)S]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Machine Learning and Artificial Intelligence;Prevention;Racial and Ethnic Minority Health Research;Rural Health;Social Determinants of Health

ORG_CITY: MILWAUKEE

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

PHR: Project Narrative This study seeks to use novel methods and data to address the following aims: 1) Examine the relationship between regional exposure to structural racism and the propensity of hospital and clinic closures; 2) examine the relationship between hospital and clinic closures and community assets (pertaining to employment, income, and education) and community health outcomes (across mortality, disability, and chronic disease burden); 3) predict risk of closure among urban hospitals and clinics that are disproportionately serving racial/ethnic minorities from neighborhoods with exposure to structural racism (defined as historic redlining); 4) undertake stakeholder engagement to address prevention of future closures and/or examine ways to decrease the potential adverse community impact of hospital and clinic closures.

PI_NAMEs: EGEDE, LEONARD E. (contact);LINDE, SEBASTIAN

PROGRAM_OFFICER_NAME: STINSON, NATHANIEL

PROJECT_TERMS: Acute;Address;Affect;Area;Attention;burden of chronic illness;Caring;Clinic;Clinics and Hospitals;Code;Communities;Community Health;COVID-19 pandemic;Crows;Data;Diabetes Mellitus;differences in access;disability;Discrimination;disparity gap;econometrics;Economics;Education;Employment;ethnic health disparity;ethnic minority;ethnic minority population;Ethnic Origin;Event;explainable machine learning;Exposure to;Fostering;Future;gaps in access;Goals;Health;health care availability;health disparity;Hospital Closures;Hospitals;Housing;Income;Individual;Inequity;inner city;innovation;Insurance;intergenerational;Investments;Knowledge;Laws;Legal;Link;Literature;machine learning method;Measures;Methodology;Methods;mortality;Myocardial;Neighborhoods;novel;Outcome;Pathway interactions;Policies;poor health outcome;Prevention;Primary Care;Quality of Care;Race;racial health disparity;racial minority;racial minority population;Resources;Risk;Risk Factors;risk prediction;Rural;Rural Hospitals;Schools;segregation;Services;Shock;social;Societies;Structural Racism;System;trend;United States Agency for Healthcare Research and Quality;Urban Community;Urban Hospitals;urban setting;Work

PROJECT_TITLE: Impact of structural racism on hospital/clinic closures, community assets, and health outcomes in urban communities

STUDY_SECTION: HHD

STUDY_SECTION_NAME: Healthcare and Health Disparities Study Section[HHD]


NIH_SPENDING_CATS: Atherosclerosis;Cardiovascular;Cerebrovascular;Clinical Research;Congenital Structural Anomalies;Genetics;Heart Disease;Heart Disease - Coronary Heart Disease;Pediatric

PHR: PROJECT NARRATIVE The hypothesis that drives this proposal is dysregulation of the fluid shear stress (FSS) mechanotransduction pathways that drive physiological flow-dependent remodeling can lead to pathological remodeling in vascular malformations in hereditary hemorrhagic telangiectasia (HHT) or to failed remodeling in coronary and peripheral artery disease in patients. Elucidating this regulatory network will allow its effective manipulation to either decrease or increase vascular lumen diameter, thereby improving outcomes in HHT patients who suffer from excessive pathological remodeling, and from patients with coronary and peripheral artery disease where physiological remodeling is impaired.

PI_NAMEs: EICHMANN, ANNE CHRISTINE (contact);SCHWARTZ, MARTIN A

PROGRAM_OFFICER_NAME: GAO, YUNLING

PROJECT_TERMS: Address;Adult;Arteries;Arteriovenous malformation;Binding;Biological;Blood flow;Blood Vessels;Cell Cycle Arrest;Cell Surface Receptors;Complex;Coronary;Coronary Arteriosclerosis;CRISPR screen;Data;Development;Diameter;Disease;Embryo;Embryonic Development;Endoglin;Endothelial Cells;Failure;Gene Expression;Genes;Genetic;hemodynamics;Hemorrhage;Hereditary hemorrhagic telangiectasia;Homeostasis;Human;Impairment;improved;improved outcome;in vivo;Inflammatory;inhibitor;insight;KDR gene;Knowledge;Life;Ligands;Link;Liquid substance;loss of function;malformation;mechanotransduction;Mediating;Mediator;mitochondrial metabolism;Molecular;mouse model;Mus;mutant;novel;Pathologic;Pathway interactions;Patients;Perfusion;Pericytes;Peripheral arterial disease;Physiological;Piezo 1 ion channel;PIK3CG gene;Prevention;programs;receptor;recruit;Regulation;Reporting;response;Role;Sampling;shear stress;Signal Pathway;Signal Transduction;single-cell RNA sequencing;Telangiectasis;Testing;therapeutic evaluation;therapeutic target;Tissues;Vascular Endothelial Cell;Vascular remodeling;whole genome;Zebrafish

PROJECT_TITLE: Flow regulation of the Alk1/Eng pathway in vascular homeostasis and disease

STUDY_SECTION: CDD

STUDY_SECTION_NAME: Cardiovascular Differentiation and Development Study Section[CDD]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

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);Biotechnology;Brain Disorders;Cerebrovascular;Dementia;Neurodegenerative;Neurosciences;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

PHR: PROJECT NARRATIVE Aging is the number one risk factor for most neurodegenerative disorders; however, currently zero therapeutics are capable of reversing aging-associated cognitive decline. The aim of this proposal is to understand the contribution of protein homeostasis (proteostasis) and stress response machinery to the functional restoration observed in heterochronic parabiosis, a model in which the circulatory systems of young and old mice are surgically fused and bloodborne factors are shared between them. The experiments outlined herein will identify proteins which misfold during aging as well as their impact on downstream stress response pathways of aging brain endothelial cells of the blood-brain barrier.

PI_NAMEs: GIADONE, RICHARD  (contact)

PROGRAM_OFFICER_NAME: SARE, RACHEL

PROJECT_TERMS: abeta accumulation;adeno-associated viral vector;Age;age related neurodegeneration;Aging;aging brain;aging mechanism;aging related;aging related disease;aging reversal;Alzheimer's Disease;Alzheimer's disease related dementia;Animals;Biochemical;biological adaptation to stress;Biological Assay;Blood - brain barrier anatomy;Blood Cells;Brain;brain cell;brain endothelial cell;Cardiovascular system;Cell Culture Techniques;Cell Physiology;cell type;Cells;Cerebrovascular system;Cognitive;Complement;cytokine;Dementia;differential expression;Disease;Electrical Resistance;Endothelium;Exhibits;experimental study;Exposure to;functional decline;Functional disorder;functional improvement;functional restoration;Gene Expression Profiling;Genes;hallmarks of aging;healthy aging;Heat shock proteins;Heat-Shock Response;Hippocampus;Homeostasis;Human;human induced pluripotent stem cells;Impaired cognition;Impairment;improved;In Vitro;in vitro Model;in vivo;Incidence;induced pluripotent stem cell;juvenile animal;knock-down;Link;Mass Spectrum Analysis;Measures;misfolded protein;Modeling;Molecular;Molecular Chaperones;Mus;Mutation;Neurodegenerative Disorders;normal aging;novel;novel therapeutics;old mice;Operative Surgical Procedures;Outcome;overexpression;Parabiosis;Pathogenesis;Pathologic;Pathway interactions;Patients;Permeability;Phenotype;Physiological;protein aggregation;Protein Biosynthesis;protein expression;Proteins;Proteomics;proteostasis;restoration;Risk Factors;Role;Sampling;Serotyping;Stress;System;Techniques;Therapeutic;Viral;Work

PROJECT_TITLE: Understanding Roles for Protein Homeostasis Machinery in Aging Brain Vasculature


NIH_SPENDING_CATS: Biotechnology;Duchenne/ Becker Muscular Dystrophy;Gene Therapy;Genetics;Immunotherapy;Muscular Dystrophy;Neurosciences;Pediatric;Rare Diseases

ORG_CITY: COLUMBIA

ORG_NAME: UNIVERSITY OF MISSOURI-COLUMBIA

PHR: Public Health Relevance AAV-mediated CRISPR/Cas9 gene-editing therapy is a promising approach to treat Duchenne muscular dystrophy (DMD). We recently found that the cytotoxic T cell response to Cas9 is a major hurdle to achieving persistent CRISPR therapy in the canine DMD model. In this study, we will explore novel strategies to overcome Cas9 immunity and achieve long-lasting CRISPR editing in dystrophic canines.

PI_NAMEs: DUAN, DONGSHENG  (contact)

PROGRAM_OFFICER_NAME: NUCKOLLS, GLEN H

PROJECT_TERMS: Abbreviations;adeno-associated viral vector;Affect;Alanine;Animal Model;Antigen-Presenting Cells;Attenuated;Bacterial Proteins;Biological Models;canine model;Canis familiaris;CD8-Positive T-Lymphocytes;CD8B1 gene;Cells;cellular transduction;clinically relevant;Clustered Regularly Interspaced Short Palindromic Repeats;CRISPR/Cas technology;Cytokeratin-8 Staining Method;cytokine;cytotoxic;Cytotoxic T-Lymphocytes;Data;Dependovirus;Development;Digestion;Disease;DNA cassette;Duchenne muscular dystrophy;Dystrophin;effective therapy;effector T cell;Engineering;Epitopes;Epstein-Barr Virus Nuclear Antigens;Equilibrium;Frameshift Mutation;Future;gene therapy;Generations;Genes;Genetic;Genetic Transcription;genome editing;Genome engineering;Glycine;Granzyme;Guide RNA;Histologic;Human;human disease;Immune;Immune response;Immunity;Immunologics;Immunosuppression;improved;Innate Immune Response;Maps;mdx mouse;Mediating;MicroRNAs;Modeling;Monitor;mouse model;multicatalytic endopeptidase complex;Mus;Muscle;Muscle Cells;Myopathy;novel strategies;null mutation;Oligonucleotides;Outcome;Pathology;Patients;Peptides;Pharmaceutical Preparations;Physiological;prednisolone;prevent;promoter;protein degradation;Proteins;Protocols documentation;public health relevance;response;restoration;RNA;Site;System;T cell infiltration;T cell response;T-Lymphocyte Epitopes;Testing;Therapeutic;therapeutic genome editing;TLR9 gene;transgene expression;Translating;Translations;vector;vector genome;vector induced;Work

PROJECT_TITLE: CRISPR editing therapy for Duchenne muscular dystrophy

STUDY_SECTION: TAG

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


ADMINISTERING_IC: DA

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: American Indian or Alaska Native;Behavioral and Social Science;Clinical Research;Drug Abuse (NIDA only);Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Pediatric;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Substance Misuse

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: PROJECT NARRATIVE This research addresses critical public health inequities related to alcohol and drug use within American Indian and First Nations (Indigenous) communities. We will identify diverse patterns and social determinants of substance use and recovery across 3 generations of Indigenous families with special attention to processes of recovery and resilience. Results will include precise targets for substance use prevention, intervention and policy to be shared with community stakeholders across the 8-participating reservation/reserves with an ultimate goal of reducing health inequities.

PI_NAMEs: SITTNER, KELLEY ;WALLS, MELISSA L. (contact)

PROGRAM_OFFICER_NAME: VIDAL, SARAH

PROJECT_TERMS: Abstinence;Address;Adolescent;Adult;alcohol and other drug;alcohol consequences;Alcohol consumption;American Indians;Attention;Awareness;Caregivers;Child;Child Rearing;Childhood;Communities;community based participatory research;Computer Assisted;Data;data access;Development;Developmental Course;Discrimination;Drug usage;Early identification;emerging adult;Enrollment;epidemiologic data;Epidemiologic Factors;Epidemiology;epidemiology study;Etiology;evidence base;experience;Exposure to;Extended Family;Family;family influence;Family member;family support;Generations;Genetic;Goals;Grant;healing;Health;health inequalities;Heterogeneity;Indigenous;indigenous community;Individual;Inequity;innovation;intergenerational;Intervention;intervention program;Interview;Knowledge;Learning;Life;Life Cycle Stages;Measures;Mediator;Methamphetamine;Nature;neglect;novel;Opioid;Outcome;Output;Participant;Pathology;Pathway interactions;Pattern;peer;Persons;Policies;polysubstance use;population health;Premature Mortality;Prevention;Prevention program;Process;protective factors;Public Health;public health intervention;racism;Recovery;Research;Reservations;resilience;Risk;Risk Factors;social determinants;social health determinants;social influence;sociocultural determinant;Stress;Structure;Substance abuse problem;substance abuse treatment;substance use;Substance Use Disorder;substance use prevention;Surveys;theories;transmission process;Trauma;tribal community;Tribes;Visit;Work

PROJECT_TITLE: Indigenous Pathways of Substance Use Risk and Resilience across Three Generations

STUDY_SECTION: BGES

STUDY_SECTION_NAME: Behavioral Genetics and Epidemiology Study Section[BGES]