NIH_SPENDING_CATS: Genetics;Human Genome;Neurosciences;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Nonembryonic - Human

PHR: NARRATIVE The molecular mechanisms that govern the development of the human nervous system are incompletely understood. We recently discovered that expression of a transcription factor critical for neural development, SOX2, is regulated via dynamic reorganization of the three-dimensional architecture of the genome. Our research will elucidate the mechanisms underlying this previously unrecognized process and will allow us to harness the dynamics of 3D genome organization toward understanding and treating neurodevelopmental disorders.

PI_NAMEs: PLACANTONAKIS, DIMITRIS G. (contact)

PROGRAM_OFFICER_NAME: LAVAUTE, TIMOTHY M

PROJECT_TERMS: 3-Dimensional;Affect;Architecture;ATAC-seq;Attenuated;Binding;Biological;Biological Assay;bisulfite sequencing;cell fate specification;cell type;Cells;Chromatin;chromatin immunoprecipitation;Chromatin Loop;chromatin modification;chromosome conformation capture;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;CRISPR-mediated transcriptional activation;Data;Development;Disease;Distal;Distant;DNA Binding;Embryonic Development;embryonic stem cell;Enhancers;epigenetic silencing;Etiology;Excision;Genes;Genetic Enhancer Element;Genetic Transcription;Genome;genomic locus;Genomics;Health;Hi-C;Human;human embryonic stem cell;Impairment;In Vitro;in vivo;interest;Mediating;Methylation;Microscopic;Molecular;multidisciplinary;Neighborhoods;nerve stem cell;Nervous System;neural;neurodevelopment;Neurodevelopmental Disorder;Neuroectoderm;neurogenesis;novel;Nuclear;pluripotency;Process;progenitor;programs;promoter;Property;protein protein interaction;Proteins;Regenerative Medicine;Regulation;Repression;Research;self-renewal;single-cell RNA sequencing;spatiotemporal;Specific qualifier value;stem cell biology;stem cell differentiation;Teratoma;Testing;Transcript;transcription factor;translational potential;Untranslated RNA

PROJECT_TITLE: Developmentally Regulated Enhancers and Chromatin Architecture in Human Neurogenesis

STUDY_SECTION: NCF

STUDY_SECTION_NAME: Neurogenesis and Cell Fate Study Section[NCF]


ADMINISTERING_IC: AI

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Autoimmune Disease;Kidney Disease;Lung

ORG_CITY: PHILADELPHIA

ORG_COUNTRY: UNITED STATES

ORG_DEPT: PHARMACOLOGY

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: This project will use an innovative mouse model of human ANCA-associated vasculitis (AAV) to understand how the potentially fatal disease in humans is caused and what newer and safer treatment options can be developed. AAV is an autoimmune disease characterized by patient’s own immune system attacking their vital organs such as the kidney and lung. If untreated, patients can die from kidney failure and lung bleeding. The current treatments are consisted with immunosuppressive drugs that carry high toxicity from long-term use and are not always efficacious to prevent relapses. In this project, we will test the hypothesis that complement, a series of proteins in the blood which are normally involved in protecting us from infection, may misdirect its attack on the kidney and lung to cause the pathological symptoms seen in AAV. We will also test several inhibitors of complement in our model to see if they can prevent or reduce kidney and lung injury. These studies may lead to the development of novel therapeutics that are more effective and safer than nonspecific immunosuppressive drugs (e.g. steroids) currently used in human AAV patients with significant side effects.

PI_NAMEs: SONG, WENCHAO  (contact)

PROGRAM_OFFICER_NAME: HUDSPETH, KELLY

PROJECT_TERMS: Adaptive Immune System;Affect;Alternative Complement Pathway;ANCA vasculitis;Antibodies;Antigens;Antineutrophil Cytoplasmic Antibodies;Autoantibodies;Autoimmune;Autoimmune Diseases;Blood;Cellular Immunity;Clinical;Complement;Complement 5a;Complement Activation;Complement Inactivators;Complement Membrane Attack Complex;complement system;Crescentic Glomerulonephritis;Cytoplasm;Development;Disease;disease model;disease phenotype;Hemorrhage;Human;human disease;human model;Immune;Immune system;Immunosuppression;Immunosuppressive Agents;Infection;Inflammation;Injury to Kidney;Innate Immune System;innovation;Investigational Therapies;Kidney;Kidney Failure;Lung;lung injury;Mediating;Modeling;mouse model;Mus;neutrophil;novel therapeutics;Organ;organ injury;Pathogenesis;Pathogenicity;Pathologic;Pathology;Patients;Peroxidases;Play;prevent;Properdin;Proteinase 3;Proteins;relapse prevention;Respiratory System;Role;Series;side effect;Specificity;Steroids;Symptoms;systemic autoimmune disease;T-Lymphocyte;Testing;Therapeutic;Toxic effect;Treatment Efficacy;Treatment Protocols;Vasculitis

PROJECT_TITLE: Complement in Pathogenesis and Experimental Therapy of ANCA Disease

STUDY_SECTION: III

STUDY_SECTION_NAME: Innate Immunity and Inflammation Study Section[III]


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Behavioral and Social Science;Bioengineering;Brain Disorders;Clinical Research;Data Science;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Opioid Misuse and Addiction;Opioids;Substance Misuse

ORG_CITY: WORCESTER

ORG_DEPT: EMERGENCY MEDICINE

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

ORG_STATE: MA

PHR: NARRATIVE STATEMENT Medications for opioid use disorder such as buprenorphine provide an effective treatment option that significantly improves outcomes; however impact is limited by adherence challenges. We propose to develop a novel wearable sensor system, MINDER, which will continuously monitor physiologic changes to detect buprenorphine use and will use machine learning algorithms to accurately identify adherence to buprenorphine use in laboratory and field settings. The results of this study will form the foundation for a wearable, sensor- based, real-time monitoring system for individuals being treated with MOUD, and to develop precision medicine interventions for OUD.

PI_NAMEs: CARREIRO, STEPHANIE P (contact)

PROGRAM_OFFICER_NAME: LASH, TIFFANI BAILEY

PROJECT_TERMS: Accelerometer;addiction;Adherence;Agonist;Algorithms;Artificial Intelligence;Behavior Therapy;Biometry;Buprenorphine;buprenorphine treatment;Clinical;clinical practice;Communities;Companions;computer human interaction;Custom;Data;data communication;data ingestion;Data Set;design;Detection;Development;Device or Instrument Development;Digital biomarker;Drug Screening;effective therapy;Event;experience;Foundations;Health Personnel;Health Technology;Heart Rate;Human;improved;improved outcome;Individual;Infrastructure;Ingestion;innovation;Intervention;iterative design;Laboratories;Lived experience;Machine Learning;machine learning algorithm;machine learning model;Measures;Medical Device;medication for opioid use disorder;Medicine;Methodology;Methods;mHealth;mobile application;Modeling;Monitor;Morbidity - disease rate;mortality;Motion;Nature;novel;open source;Opioid;Opioid agonist;opioid misuse;opioid mortality;opioid use;opioid use disorder;Optics;Outcome;overdose death;Overdose reduction;Patient Self-Report;Patients;Persons;Physiologic Monitoring;Physiological;precision medicine;preference;prevent;Process;prototype;Public Health;real time monitoring;Records;Recovery;Research;Research Personnel;Risk;sensor;Skin Temperature;success;Support System;System;Systems Development;Testing;Time;Toxicology;Upper arm;Urine;usability;wearable device;wearable sensor technology

PROJECT_TITLE: MINDER: Wearable sensor-based detection of digital biomarkers of adherence to medications for opioid use disorder

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-HSS-B(90)S]


ADMINISTERING_IC: DK

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Kidney Disease;Prevention

ORG_CITY: DURHAM

ORG_DEPT: PEDIATRICS

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: NARRATIVE/RELEVANCE STATEMENT Innovations in medicine, particularly for diseases that disparately affect minority and underserved populations, are at risk because those entering the biomedical research career path continue to underrepresent certain historically excluded populations. The Duke Paired Undergraduate Mentoring Program (PUMP) in Uronephrology is a sustainable program that will develop a diverse pipeline and enhance success in academic careers by providing mentorship and skills-building, thereby preparing the next generation of scientists to advance urology and nephrology-related disease prevention, treatment, and cure. This program will serve as a model for expanding across disciplines to develop the biomedical workforce and meet the nation’s needs for innovation in medicine.

PI_NAMEs: GBADEGESIN, RASHEED ADEBAYO (contact)

PROGRAM_OFFICER_NAME: MARIC-BILKAN, CHRISTINE

PROJECT_TERMS: Acute Renal Failure with Renal Papillary Necrosis;Address;Admission activity;Adult;Affect;African American population;Area;Biomedical Research;biomedical scientist;career;Career Choice;career development;Caring;Childhood;Chronic Kidney Failure;cohort;Collaborations;cost;cost estimate;Critical Thinking;Development;Discipline;Disease;disease disparity;disorder prevention;Diverse Workforce;E-learning;Economic Burden;educational atmosphere;Educational Curriculum;Educational workshop;End stage renal failure;Environmental Risk Factor;equity, diversity, and inclusion;Evaluation;evidence base;Exclusion;experience;Face;Faculty;falls;Funding;Future;Future Generations;Genetic;Goals;graduate school;graduate student;Health;Health system;Hospitalization;Individual;innovation;Institution;interest;Internet;Interview;Journals;Kidney Diseases;laboratory experience;Laboratory Research;Leadership;Link;Medical;medical schools;Medical Students;Medicine;meetings;Mentors;Mentorship;Minority Groups;Minority-Serving Institution;model development;Modeling;Nephrology;next generation;Occupations;Outcome;outcome disparities;Participant;Pathway interactions;Persons;Physicians' Offices;Population;Positioning Attribute;Postbaccalaureate;Postdoctoral Fellow;Prevention;Process;Program Sustainability;programs;recruit;Renal Replacement Therapy;Research;Research Personnel;Research Project Grants;Research Training;Resources;Risk;Science;Scientist;skill acquisition;skills;Southeastern United States;STEM field;Structure;student mentoring;Students;success;summer program;summer research;symposium;Talents;Training;Twitter;undergraduate student;Underserved Population;Universities;Urology;virtual

PROJECT_TITLE: The Paired Undergraduate Mentoring Program (PUMP) in Uronephrology

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Kidney, Urologic and Hematologic Diseases D Study Section[DDK-D]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Dental, Oral, and Craniofacial Disease;Digestive Diseases;Genetics;Immunotherapy;Prevention;Rare Diseases

ORG_CITY: TUCSON

ORG_DEPT: OTOLARYNGOLOGY

ORG_NAME: UNIVERSITY OF ARIZONA

ORG_STATE: AZ

PHR: PROJECT NARRATIVE These studies will determine the role of TP53 and CDKN2A mutations in promoting malignant progression of oral premalignant lesions and in the response to oral cancer prevention with antibodies that reinvigorate the immune system. We will also investigate novel strategies, based on reactivation of TP53 functions, to sensitize oral premalignant lesions to immunoprevention. Molecular and cellular analyses of the oral lesions that evade immunoprevention will identify mechanisms that promote resistance and will help refine future prevention interventions. 1

PI_NAMEs: CAULIN, CARLOS  (contact)

PROGRAM_OFFICER_NAME: GUNASEKHARAN, VIGNESH KUMAR

PROJECT_TERMS: Affect;Alleles;anti-PD-1;anti-PD1 antibodies;Antibodies;Appearance;Carcinogens;Carcinoma;CDKN2A gene;cell type;Cells;checkpoint inhibition;Chemopreventive Agent;Clinical Trials;Combined Modality Therapy;Cre lox recombination system;design;Development;DNA Sequence Alteration;Epithelial Cells;Epithelium;Future;gain of function mutation;Genes;Genetic;Genetically Engineered Mouse;Goals;high risk;Histologic;Human;Immune;immune checkpoint blockade;Immune system;Immunoprevention;Immunosuppression;improved;in vivo;Lead;Lesion;Malignant - descriptor;malignant mouth neoplasm;Malignant Neoplasms;Mediating;Molecular;Monitor;mouse model;Mouth Neoplasms;mouth squamous cell carcinoma;Mus;mutant;Mutate;Mutation;novel strategies;Oral;oral cancer prevention;oral carcinogenesis;oral cavity epithelium;oral lesion;oral status;oral tissue;Outcome;Patients;premalignant;prevent;Prevention;Prevention strategy;Preventive;preventive intervention;Primary Neoplasm;Process;programmed cell death protein 1;progression risk;Relapse;Resistance;response;Risk Assessment;Role;Survival Rate;Testing;Tobacco;tobacco exposure;TP53 gene;transcriptome;tumor;Tumor Immunity;Tumor Promotion;tumor-immune system interactions

PROJECT_TITLE: Genetic Alterations That Confer High Risk to Oral Premalignant Lesions

STUDY_SECTION: CPSS

STUDY_SECTION_NAME: Cancer Prevention Study Section[CPSS]


NIH_SPENDING_CATS: Congenital Structural Anomalies;Kidney Disease;Pediatric;Polycystic Kidney Disease

ORG_CITY: OKLAHOMA CITY

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR

ORG_STATE: OK

PHR: Project Narrative Our lab demonstrated that KRM accelerate cyst growth in multiple animal models of cystic kidney disease and are also present in patients with accelerated rates of renal function decline making KRM- targeted therapeutics highly desirable; however, it is not feasible to give patients resident macrophage targeted inhibitors for long periods as these inhibitors deplete resident macrophages in other tissues where they are needed for basic biological functions. In this application, we seek to identify a tissue specific approach for long- term KRM depletion by studying the mechanism of KRM niche filling after depletion in wild type and cystic mice. If successful, these data would provide a novel approach to target KRM in patients with cystic kidney disease or any other disease that involves KRM including acute kidney injury.

PI_NAMEs: ZIMMERMAN, KURT A (contact)

PROJECT_TERMS: Acceleration;Acute Renal Failure with Renal Papillary Necrosis;Affect;Animal Model;Biological Process;Bone Marrow;Brain;Candidate Disease Gene;Cardiac;Cells;Chronic;Chronic Kidney Failure;Clinical;Communities;Cyst;Cystic Kidney Diseases;Data;Development;Disease;Disease Progression;Engraftment;Erythrocytes;experience;fighting;Genes;Genetic Transcription;Goals;Growth;healthcare burden;Human;Immunology;Infection;Infection prevention;inhibitor;interest;Intervention;Kidney;Knockout Mice;Knowledge;Liver;Macrophage;Maps;monocyte;mouse model;Mus;novel strategies;Patients;Persons;pharmacologic;Pharmacologic Substance;Population;Process;Proliferating;recruit;Recycling;Renal function;Severities;Source;Synapses;targeted treatment;Testing;Therapeutic;Tissues;Wild Type Mouse

PROJECT_TITLE: Targeting kidney resident macrophage niche filling to slow cystic kidney disease

STUDY_SECTION: PBKD

STUDY_SECTION_NAME: Pathobiology of Kidney Disease Study Section[PBKD]


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

ORG_CITY: MADISON

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: Project Narrative The goal of this project is to investigate how different members of the microbiota, as well as different microbiota compositions affect the virulence of enteric pathogens. This work has fundamental implications for how differential compositions of microbiota may affect disease outcome and susceptibility to pathogens. Defining the mechanisms by which the microbiota affects the regulation and activity of virulence factors expressed by intestinal pathogens would represent a significant step forward in the field of microbiota-pathogen interactions.

PI_NAMEs: MARESSO, ANTHONY W;SPERANDIO, VANESSA  (contact)

PROGRAM_OFFICER_NAME: BAQAR, SHAHIDA

PROJECT_TERMS: Acceleration;Address;Affect;Applications Grants;Bacterial Adhesins;Bacteroides;Bacteroidetes;Biological Models;Carbon;Citrobacter rodentium;Clostridium difficile;Colon;Communities;Complex;Cues;Data;design;Disease;Disease Outcome;Disease susceptibility;Enteral;enteric infection;enteric pathogen;Enterococcus faecalis;Enterocytes;Environment;Epithelium;Escherichia coli;Escherichia coli EHEC;Escherichia coli Infections;Escherichia coli O157:H7;experimental study;Fingerprint;Firmicutes;Fucose;gastrointestinal;Gastrointestinal tract structure;Gene Expression;Genetic Transcription;Goals;Growth;gut colonization;gut microbiota;Harvest;Health;holistic approach;host microbiota;Human;In Vitro;Individual;Infection;Infectious colitis;Lesion;Mediating;member;Metabolic;Metabolism;microbiota;microbiota composition;model building;mouse model;mucinase;Mucous body substance;Mus;Nutrient;organic acid;pathogen;Pathogenicity Island;Play;programs;Proteobacteria;receptor;Regulation;Resistance;response;Role;Salmonella enterica;Signal Transduction;Source;Succinates;sugar;System;Virulence;Virulence Factors;virulence gene;Work

PROJECT_TITLE: Sugar regulation of EHEC virulance

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


ED_INST_TYPE: SCHOOLS OF NURSING

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Cancer;Caregiving Research;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Cost Effectiveness Research;Depression;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Mental Health;Palliative Care;Prevention;Racial and Ethnic Minority Health Research;Rural Health;Social Determinants of Health;Telehealth

ORG_CITY: BIRMINGHAM

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: The burden placed on family caregivers and the toll on their mental and physical health have never been greater and will continue to rise; by 2026 the number of individuals with cancer is expected to swell to over 20 million and in 2019, the number in the their last year of life was over 600,000. Healthcare clinicians should be concerned with the health of family caregivers for their own sake (e.g. preventing future family caregiver morbidity), but also because these caregivers deliver 80% of the home care to community-dwelling patients with advanced illness. Replacing these services with paid professional help would be economically unfeasible as caregiving services have been valued at $450 billion; thus it is imperative that interventions be developed that keep caregivers healthy and functioning, not only for their own sake, but also so they can provide the best care possible to patients with cancer.

PI_NAMEs: ODOM, JAMES N. (contact)

PROGRAM_OFFICER_NAME: ADAMS, LYNN S

PROJECT_TERMS: Academy;acceptability and feasibility;Address;Adult;Advance Care Planning;advanced disease;Advanced Malignant Neoplasm;African American;African American population;Anxiety;Attention;Awareness;Behavioral;Bereavement;Cancer Center;Cancer Patient;Care given by nurses;care recipients;care systems;Caregiver Burden;caregiver interventions;Caregiver support;Caregivers;caregiving;Caring;Collaborations;Communities;Complex;coping;cost;Cost Analysis;cost effectiveness;Decision Making;Diagnosis;Dissemination and Implementation;Distress;Effectiveness;effectiveness testing;effectiveness-implementation randomized trial;end of life;experience;Family Caregiver;Family health status;Family member;feasibility testing;follow-up;Formal caregiver;formative assessment;Friends;Future;global health;Health;health care service utilization;Healthcare;Hospitals;Hybrids;implementation cost;implementation evaluation;implementation trial;improved;indexing;Individual;innovation;Interdisciplinary Study;Intervention;Knowledge;Life;Malignant Neoplasms;Measures;Mediator;Medicine;Mental Depression;Mental Health;Minority;Modeling;Morbidity - disease rate;multi-component intervention;Newly Diagnosed;Nurses;Outcome;Outpatients;Palliative Care;Participant;patient home care;Patient-Focused Outcomes;Patients;Persons;physical conditioning;pilot test;Play;Population;prevent;Process;Professional Practice;psychoeducation;Psychologist;Public Health;Quality of life;Readiness;recruit;Reporting;Reproducibility;Research;Research Design;response;Role;Rural;rural Americans;rural dwellers;rural residence;rural underserved;Sampling;screening;service delivery;Services;Site;skills;Social support;Standardization;Stress;Stress and Coping;stress management;Swelling;symposium;systematic review;Techniques;telehealth;telephone session;Testing;theories;therapy design;Training;treatment as usual;Underserved Population;Work

PROJECT_TITLE: Lay Coach-led Early Palliative Care for Underserved Advanced Cancer Caregivers

STUDY_SECTION: DIRH

STUDY_SECTION_NAME: Dissemination and Implementation Research in Health Study Section[DIRH]


ADMINISTERING_IC: HD

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

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

NIH_SPENDING_CATS: Congenital Structural Anomalies;Neurosciences;Pediatric;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: SEATTLE

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: PROJECT NARRATIVE Our skin functions as a finely tuned sensory organ that allows us to detect an array of sensory stimuli. The axon endings of somatosensory neurons densely innervate skin where they detect touch, pressure and pain. Specialized skin cells develop during skin organogenesis and influence axon growth, function and repair. To better understand how the skin sensory system develops, this proposal uses zebrafish as an accessible model for studying how specialized sensory cells arise during skin organogenesis, interact with axons and differentiate from stem cell progenitors.

PI_NAMEs: RASMUSSEN, JEFFREY PHILIP (contact)

PROGRAM_OFFICER_NAME: TOYAMA, REIKO

PROJECT_TERMS: Ablation;Address;Adolescent;Adult;Affect;Anatomy;appendage;Axon;axon growth;Basal Cell;Cell Communication;Cell Lineage;cell type;Cells;Chronic;Complex;Cre driver;Cutaneous;Data;Development;Disease;Embryo;Epidermis;Epithelium;Etiology;Event;experimental study;Fishes;Genetic;genetic manipulation;Goals;Growth;Homeostasis;Homologous Gene;human disease;Image;in utero;in vivo;Individual;insight;Knowledge;Link;Maps;Merkel Cells;Molecular;Morphogenesis;Multipotent Stem Cells;mutant;Nerve;Nervous System;neuron development;Neurons;novel;Organ;organ growth;Organogenesis;Pain;Pattern;Peripheral;Population;Preparation;pressure;repaired;Reporter;Resolution;response;Rodent;Sensory;Sensory Process;sensory stimulus;sensory system;serial imaging;Signal Pathway;Signal Transduction;single-cell RNA sequencing;Skin;skin organogenesis;somatosensory;spatiotemporal;Specific qualifier value;Spinal Ganglia;stem cell differentiation;stem cell population;stem cells;Stimulus;Structure;Study models;Supporting Cell;System;Systems Development;Tactile;Techniques;Testing;Tissues;tool;Touch sensation;Transgenic Organisms;Work;Zebrafish

PROJECT_TITLE: Dynamics of skin sensory specialization during vertebrate organogenesis

STUDY_SECTION_NAME: Development - 1 Study Section[DEV1]


NIH_SPENDING_CATS: Clinical Research;Cystic Fibrosis;Infectious Diseases;Lung;Rare Diseases

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: PROJECT NARRATIVE Our proposed studies will investigate how ezrin, an actin-binding protein, regulates the macrophage immunomodulatory and bactericidal functions during lung infections. The relevance of this study is based on our recent finding that ezrin levels are low in macrophages from individuals with cystic fibrosis, a disease characterized by lung infection and hyper-inflammation. These studies will deepen understanding of MΦ biology and identify potential targets for therapies against lung diseases.

PI_NAMEs: BRUSCIA, EMANUELA MARINA (contact)

PROGRAM_OFFICER_NAME: SUBRAMANIAN, HARIHARAN

PROJECT_TERMS: Actin-Binding Protein;Actins;Adhesions;Affect;Alveolar Macrophages;Asthma;Bacteria;Bacterial Infections;bactericide;Binding;Biology;Blood Cells;Calpain;Cell Adhesion;cell cortex;Cell membrane;Cell Physiology;Cells;chronic inflammatory lung disease;Chronic Obstructive Pulmonary Disease;Cystic Fibrosis;cystic fibrosis mouse;cystic fibrosis patients;Cystic Fibrosis Transmembrane Conductance Regulator;Cytoskeleton;Data;Disease;Event;Extracellular Matrix;ezrin;Failure;fighting;Functional disorder;Gatekeeping;Goals;Health;Host Defense;IgG Receptors;immune function;Immune response;Immune signaling;Immune System Diseases;immunoregulation;Impairment;improved;in vivo Model;Individual;Infection;Inflammation;Inflammatory;Inflammatory Response;innovation;Integrins;interstitial;Knock-out;Knockout Mice;Lipopolysaccharides;Lung;Lung Diseases;Lung immune response;Lung infections;Macrophage;Macrophage Activation;member;Membrane Proteins;microorganism;Modeling;moesin;Molecular;monocyte;Morbidity - disease rate;mortality;mouse model;Mucous body substance;Obstruction;particle;pathogen;Pathologic;Pathway interactions;Phagocytes;Phagocytosis;PI3K/AKT;PIK3CG gene;Population;Proliferating;Protein Family;Pseudomonas aeruginosa;Publishing;Pulmonary Cystic Fibrosis;Pulmonary Inflammation;radixin protein;recruit;Reporting;Research;Research Personnel;Resolution;Respiratory Tract Infections;response;Role;Severity of illness;Shapes;Signal Transduction;Staphylococcus aureus;Stimulus;Structure of parenchyma of lung;targeted treatment;Testing;therapeutic target;Tissues;Work

PROJECT_TITLE: Role of Ezrin in Macrophages


NIH_SPENDING_CATS: Bioengineering;Cancer;Clinical Research;Machine Learning and Artificial Intelligence;Nanotechnology;Ovarian Cancer;Prevention;Rare Diseases;Women's Health Research

ORG_CITY: NEW YORK

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

ORG_STATE: NY

PHR: NARRATIVE Serum biomarker measurements have been widely used as diagnostic indicators, but many markers are not sufficiently sensitive or specific assessments of disease state. This work builds a platform technology to detect whole disease fingerprints from patient biofluids to improve diagnosis, screening, and biomarker discovery processes. We will initially focus this effort on the outstanding need for improved detection of high-grade serous ovarian cancer.

PI_NAMEs: HELLER, DANIEL ALAN (contact)

PROGRAM_OFFICER_NAME: MULVANEY, SHAWN PATRICK

PROJECT_TERMS: Acceleration;Adsorption;Binding;Binding Proteins;Biological;Biological Markers;biomarker discovery;biomarker identification;biomarker validation;Blinded;burden of illness;CA-125 Antigen;Cancer Patient;cancer recurrence;Carbon Nanotubes;Chemicals;Clinical;clinically relevant;Collection;Color;Data Set;design;Detection;Diagnosis;Diagnostic;Disease;disease classification;Disease remission;DNA;DNA Library;DNA Sequence;Early Diagnosis;Elements;Event;Excision;Exhibits;experimental study;FDA approved;Fingerprint;improved;innovation;large datasets;Libraries;Machine Learning;machine learning algorithm;machine learning classification;machine learning model;Malignant neoplasm of ovary;Measurement;Modeling;Molecular;molecular marker;nanosensors;novel marker;Operative Surgical Procedures;Optics;Outcome;Patients;Pattern;Perception;Pharmaceutical Preparations;predictive modeling;prevent;Principal Component Analysis;Process;Property;Protein Analysis;protein biomarkers;Proteins;Proteomics;Recurrence;response;Salts;Sampling;screening;Screening for Ovarian Cancer;sensor;Serous;Serum;Source;Specificity;Survival Rate;technology platform;Testing;Training;Validation;Variant;Work

PROJECT_TITLE: Nanosensor Array Platform to Capture Whole Disease Fingerprints

STUDY_SECTION: ISD

STUDY_SECTION_NAME: Instrumentation and Systems Development Study Section[ISD]


FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

NIH_SPENDING_CATS: Pediatric

ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: The most common cause of death in infants and children admitted to a pediatric intensive care unit (PICU) is neurological system failure and the survivors suffer life-long neuro-morbidities. Our unique program trains MDs, PhDs, and MD/PhDs in basic, translational, or clinical research, from seven departments that treat infants and children who require neurocritical care across the continuum of care, from the field to the emergency department, the PICU, and to rehabilitation and recovery. The goal of our program is that our graduates ultimately develop into independent investigators who are fully equipped to bring their expertise to rigorously and ethically study and successfully develop novel neuroprotective, resuscitative, and regenerative therapies, and improve neuro-outcomes across all of pediatric neurocritical care.

PI_NAMEs: CLARK, ROBERT S B;KOCHANEK, PATRICK M (contact)

PROGRAM_OFFICER_NAME: JENKINS, TAMMARA L

PROJECT_TERMS: Caring;Childhood;Research;Resuscitation

PROJECT_TITLE: Pediatric Neurointensive Care and Resuscitation Research


ED_INST_TYPE: HOSPITALS

NIH_SPENDING_CATS: Cancer;Cancer Genomics;Genetics;Human Genome;Prostate Cancer;Urologic Diseases

ORG_CITY: HOUSTON

ORG_NAME: UNIVERSITY OF TX MD ANDERSON CAN CTR

ORG_STATE: TX

PHR: Project Narrative The proposed research is highly relevant to public health, as the identification of fundamental pathways and novel molecular drivers for treatment-emergent lineage plasticity of prostate cancer and the development of new strategies to combat antiandrogen therapy resistance are expected to unlock the secrets in cancer drug resistance mechanisms, and will therefore yield important opportunities to advance therapeutic options and improve outcomes for the cancer victims. Thus, the proposed research is relevant to the NIH’s mission to develop fundamental knowledge that will help improve the quality of the life and medical outcomes of patients.

PI_NAMEs: SONG, MIN SUP  (contact)

PROGRAM_OFFICER_NAME: MAAS, STEFAN

PROJECT_TERMS: Adenocarcinoma;Androgen Antagonists;androgen independent prostate cancer;Androgen Receptor;Androgens;Anti-androgen Therapy;ASCL1 gene;Biology;bioprocess;cancer cell;cancer drug resistance;cancer therapy;cancer type;Cell Fate Control;Cell Lineage;Cells;Clinical;clinical application;Clinical Management;combat;Complex;Cyclic AMP-Dependent Protein Kinases;Data;Development;Drug resistance;Enzymes;Epigenetic Process;Epithelium;epitranscriptome;Eukaryota;Excess Mortality;Genetic;genetic analysis;Goals;Heterogeneity;Histologic;improved;improved outcome;In Vitro;in vivo Model;inhibitor;Knowledge;Laboratories;Link;Malignant neoplasm of prostate;Malignant Neoplasms;Mediating;Medical;Messenger RNA;Methyltransferase;Mission;Modification;Molecular;Mus;Neoplasm Metastasis;neural;neuroendocrine differentiation;Neuroendocrine Prostate Cancer;Neurosecretory Systems;novel;Outcome;Pathologic;Pathway interactions;Patient Care;Patient Selection;Patient-Focused Outcomes;Patients;pharmacologic;Phenotype;Post-Transcriptional Regulation;prevent;Process;programs;prostate cancer cell;prostate cancer progression;Prostate Cancer therapy;Protein Kinase A Inhibitor;protein kinase inhibitor;Public Health;Quality of life;receptor expression;receptor function;Receptor Signaling;Recurrence;Research;Resistance;resistance mechanism;response;ribosome profiling;RNA;Role;targeted treatment;Testing;Therapeutic;Therapeutic Intervention;therapeutic target;therapy resistant;Tissues;transcription factor;transcriptomic profiling;transdifferentiation;Translating;Translations;tumor;United States National Institutes of Health;Variant;Work

PROJECT_TITLE: Targeting m6A RNA epigenetics in treatment-emergent neuroendocrine prostate cancer


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Clinical Research

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Project Narrative The goal of the proposed studies is to study the molecular and cellular mechanisms whereby extracellular ERp57 and PDI in concert with their oxidase ERO1α regulate neutrophil adhesive function cooperatively and distinctly, contributing to neutrophil recruitment and tissue damage under inflammatory conditions. This project will provide important evidence that extracellular ERO1α-thiol isomerase redox-relay signaling occurs outside activated neutrophils and targeting the signaling pathway will effectively block excessive neutrophil recruitment to sites of thromboinflammation.

PI_NAMEs: CHO, JAEHYUNG  (contact)

PROGRAM_OFFICER_NAME: CHARETTE, MARC F

PROJECT_TERMS: Acute;Adhesions;Adhesives;Affect;Binding;Binding Proteins;Biochemical;Biological;Blocking Antibodies;Blood Platelets;Blood Vessels;Cell Communication;Cell Physiology;Cell Surface Receptors;Cells;Complex;conditional knockout;Data;design;Disease;disulfide bond;Endoplasmic Reticulum;Endothelial Cells;ERp57;extracellular;Extracellular Protein;Family member;Glycoproteins;Goals;Imaging Techniques;Immune response;in vivo;Inflammation;Inflammatory;inflammatory milieu;Innate Immune Response;insight;Integrins;Ischemic Stroke;Isomerase;Knockout Mice;Knowledge;Leukocytes;Ligand Binding;Ligands;lung ischemia;Macrophage-1 Antigen;Mediating;Modeling;Modification;Molecular;mouse model;NADPH Oxidase;Natural Immunity;neutrophil;Neutrophil Infiltration;novel;novel therapeutic intervention;Oxidases;Oxidation-Reduction;Oxidative Stress;Pathologic;Peptides;Peroxidases;Process;Protein Disulfide Isomerase;Proteins;Pulmonary Inflammation;Reactive Oxygen Species;receptor;recruit;Role;role model;Signal Pathway;Signal Transduction;Site;Sulfhydryl Compounds;Surface;targeted treatment;Testing;thromboinflammation;Thrombus;Tissues;vascular inflammation

PROJECT_TITLE: Thiol isomerases in neutrophil recruitment and thromboinflammatory disease

STUDY_SECTION: AICS

STUDY_SECTION_NAME: Atherosclerosis and Inflammation of the Cardiovascular System Study Section[AICS]


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

ORG_CITY: WASHINGTON

ORG_NAME: GEORGETOWN UNIVERSITY

ORG_STATE: DC

PHR: New targeted therapies are needed for cancer patients that improve survival and decrease side- effects of therapy by improving recognition of tumor as distinct from host. We show novel data that supports EWS-FLI1 as having a significant role is splicing from cell lines to patient tumors. The modeling of splicing from normal tissue to ES tumor will both inform the process of oncogenic splicing and potentially provide novel therapeutic targets.

PI_NAMEs: TORETSKY, JEFFREY A (contact)

PROGRAM_OFFICER_NAME: WITKIN, KEREN L

PROJECT_TERMS: Alternative Splicing;analog;anti-cancer;Apoptosis;ARID1A gene;Binding;Bioinformatics;Biophysics;Cancer Patient;Carcinoma;Cell Line;Cells;Cessation of life;Chimeric Proteins;Chromosomal translocation;Clinical Trials;Collection;Complex;CRISPR screen;Data;Development;Dissection;Dysmyelopoietic Syndromes;Enhancers;Ewings sarcoma;EWS-FLI1 fusion protein;Exhibits;Exons;Generations;Genes;Genetic;Genetic Transcription;Global Change;Guide RNA;Heterogeneous-Nuclear Ribonucleoprotein K;Human;improved;inhibitor;innovation;Investigation;Knowledge;Lead;Length;leukemia;Ligation;Malignant Neoplasms;Mesenchymal Stem Cells;Messenger RNA;Modeling;multidisciplinary;mutant;Mutation;Names;new therapeutic target;Normal tissue morphology;novel;Oncogenic;Outcome;overexpression;Pathogenesis;Pathway interactions;Patients;Pattern;Pediatric Neoplasm;personalized medicine;Phase I Clinical Trials;Process;Protein Isoforms;Proteins;Recurrence;Regulation;Reporting;RNA;RNA Binding;RNA Helicase;RNA helicase A;RNA Interference;RNA Sequences;RNA Splicing;RNA-Binding Proteins;Role;Sarcoma;senescence;Series;side effect;single molecule;single molecule real time sequencing;Site;small molecule;Spliceosomes;Stratification;Technology;Testing;therapeutic target;Time;Transcriptional Regulation;tumor;tumorigenesis;Untranslated RNA;Variant

PROJECT_TITLE: Dissection of EWS-FLI1 oncogenic mechanisms and small molecule targeting

STUDY_SECTION: CAMP

STUDY_SECTION_NAME: Cancer Molecular Pathobiology Study Section[CAMP]


NIH_SPENDING_CATS: Autoimmune Disease;Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Diabetes;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Pediatric;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: BOSTON

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: PROJECT NARRATIVE The use of personal medical devices (e.g. continuous glucose monitors) by youth with type 1 diabetes as well as their potential to aid children and their caregivers to manage the daily demands of type 1 diabetes and optimize blood sugar control have rapidly expanded over the past twenty years. However, demographic (e.g. race/ethnicity) and socioeconomic (e.g. household income, parental education, and insurance) factors impact access to and continued use of such technology. The goals of this project are to better describe and analyze the interplay of such factors in sustained utilization of CGM in different clinical settings and to characterize their impact on a national level to enable the development and implementation of a pilot study designed to achieve improved equity in continuous glucose monitoring use for pediatric patients with type 1 diabetes.

PI_NAMEs: TREMBLAY, ELISE SCHLISSEL (contact)

PROGRAM_OFFICER_NAME: THORNTON, PAMELA L

PROJECT_TERMS: acceptability and feasibility;acute care;Address;Adherence;Adolescent;Automobile Driving;biomedical referral center;Black race;Blood Glucose;Boston;burnout;care delivery;career;caregiver stress;Caregivers;Caring;Child;Childhood;Childhood diabetes;Climacteric;Clinic;Clinical;clinical research site;Clinical Trials;cohort;Continuous Glucose Monitor;Coupled;Data;Data Collection;Databases;Demographic Analyses;Development;Devices;Diabetes Mellitus;Diabetic Ketoacidosis;Disease;Disparate;Disparity;disparity gap;disparity reduction;Education;Endocrinologist;Endocrinology;Enrollment;Ensure;Environment;Equity;ethnic disparity;Ethnic Origin;Ethnic Population;Evaluation;Event;experience;Family;Foundations;Future;glucose monitor;glycemic control;Glycosylated hemoglobin A;Goals;Grant;health care disparity;health equity;Health Insurance;Health Services Research;Hispanic;hospital care;Hospitals;Household;Hybrids;Hypoglycemia;improved;improved outcome;Income;Individual;inner city;Insulin;Insulin-Dependent Diabetes Mellitus;Insurance;Intervention;Low income;low socioeconomic status;marginalization;Measures;Medical center;Medical Device;Medicine;Mentored Patient-Oriented Research Career Development Award;Mentorship;Metabolic Control;Methods;Modernization;Morbidity - disease rate;mortality;National Health Insurance;novel;Outcome;outcome disparities;patient navigation;patient oriented;patient population;Patients;Pattern;Pediatric Hospitals;pediatric patients;Physicians;Pilot Projects;Population;Positioning Attribute;programs;psychoeducational intervention;Public Health;Public Health Education;public health insurance;Race;racial disparity;racial population;Research;Research Design;Research Methodology;Resources;Risk;safety net;Sampling;Scientist;Site;skills;Socioeconomic Status;socioeconomics;Source;Statistical Data Interpretation;Subgroup;System;technological innovation;Technology;therapy design;Time;Training;uptake;Youth

PROJECT_TITLE: Optimizing Use of Continuous Glucose Monitoring (CGM) to Advance Health Equity Among Youth with Type 1 Diabetes (T1D)

STUDY_SECTION_NAME: Diabetes, Endocrinology and Metabolic Diseases B Study Section[DDK-B]


NIH_SPENDING_CATS: Biotechnology;Cardiovascular;Genetics;Heart Disease;Heart Disease - Coronary Heart Disease;Human Genome;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Transplantation

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: Project Narrative The human heart shows little regenerative capacity following an injury such as a heart attack, resulting in decreased cardiac function and increased incidence of heart failure. The proposed work is expected to reveal key regulatory mechanisms by which epicardial cells guide successful heart regeneration in zebrafish. This study will provide novel insights into the natural regenerative capacity of the zebrafish heart and will inform new approaches to promote cardiac repair in heart attack victims.

PI_NAMEs: CAO, JINGLI  (contact)

PROGRAM_OFFICER_NAME: SHI, YANG

PROJECT_TERMS: Ablation;Address;Adult;Alleles;angiogenesis;ATAC-seq;attack victim;Bacterial Artificial Chromosomes;Binding Sites;Biological Assay;Biology;Candidate Disease Gene;Cardiac Myocytes;cardiac regeneration;cardiac repair;Cell Proliferation;Cell Separation;Cell Transplantation;cell type;Cells;Chromatin;Cicatrix;Clinical;Collagen;Coronary;Environment;Epicardium;Gene Expression Regulation;Genes;Genetic;genetic manipulation;genetic signature;genome-wide;Heart;Heart Block;heart damage;Heart failure;heart function;Heart Injuries;Human;human stem cell-derived;Impairment;in vivo;Incidence;inhibitor;Injury;insight;Knock-in;Knowledge;Label;Mammals;Maps;Mediating;Mesothelial Cell;Mitogens;Modeling;Molecular;multipotent cell;muscle regeneration;mutant;Mutate;Myocardial Infarction;Myocardium;Natural regeneration;new therapeutic target;novel;novel strategies;Nucleic Acid Regulatory Sequences;Outcome;paracrine;Paracrine Communication;Pathway interactions;Patients;Pericytes;pharmacologic;progenitor;Proliferating;receptor;regenerative;Regenerative capacity;Regenerative response;regenerative therapy;Regulatory Element;Reporter;response;response to injury;revascularization;Role;Signal Transduction;single-cell RNA sequencing;Source;stem cell expansion;stem cell proliferation;stem cells;Supporting Cell;Surface;Testing;therapy development;Transcriptional Regulation;transcriptome;transcriptomic profiling;Transducers;Transgenic Organisms;Transplantation;Up-Regulation;Work;Zebrafish

PROJECT_TITLE: Mechanisms controlling epicardial-dependent promotion of heart regeneration in zebrafish.

STUDY_SECTION: CDD

STUDY_SECTION_NAME: Cardiovascular Differentiation and Development Study Section[CDD]


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

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

ORG_CITY: STANFORD

ORG_DEPT: MISCELLANEOUS

ORG_NAME: STANFORD UNIVERSITY

ORG_STATE: CA

PHR: Project Narrative Viral proteins interact with human proteins to hijack human cells and replicate transmissible viral particles. To learn more about how this process works, this project will screen for protein-protein interactions between viral proteins and human proteins and between viral proteins and other viral proteins. To potentially identify new antiviral drugs, this project will also screen for small molecules that modulate the new protein-protein interactions that are identified.

PI_NAMEs: SHERLOCK, GAVIN J (contact)

PROGRAM_OFFICER_NAME: SASTALLA, INKA I

PROJECT_TERMS: Animals;Anti-viral Agents;Bar Codes;Biological Assay;Cell Culture Techniques;Cell Physiology;Cells;Communication;Communities;Complement;Cowpox;Data;Data Set;DHFR gene;Dihydrofolate Reductase;dimer;Drug Screening;Drug Targeting;drug testing;Epidemic;Funding;gene synthesis;Genes;genetic analysis;genetic variant;genome-wide;Grant;Health;Hepatitis E;Herpesviridae;high throughput screening;Human;human coronavirus;human population genetics;Infection;Influenza B Virus;Influenza C Virus;Learning;Libraries;Maps;Measures;Molecular;Mutagenesis;Natural regeneration;Open Reading Frames;Output;particle;pathogenic virus;Pathway interactions;Pharmaceutical Preparations;Process;Protein Fragment;protein protein interaction;Protein-Protein Interaction Map;Proteins;Rabies;Readiness;Research;Resources;Scanning;screening;sequencing platform;small molecule;small molecule libraries;System;Technology;Variant;Viral;Viral Proteins;Virulence;Virus;virus testing;Work;Yeasts;Zoonoses;zoonotic spillover

PROJECT_TITLE: PPiSeq: High-Throughput Protein-Protein Interaction Sequencing

STUDY_SECTION: GCAT

STUDY_SECTION_NAME: Genomics, Computational Biology and Technology Study Section[GCAT]


ORG_CITY: BALTIMORE

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

ORG_STATE: MD

PHR: PROJECT NARRATIVE  The overall goal of the Inter-collaborative Radiation Countermeasures (INTERACT) Consortium, a newly formed University of Maryland School of Medicine (UMSOM)-based Center for Medical Countermeasures against Radiation (CMCR), is to develop safe, effective, and practical medical countermeasures (MCM) to mitigate and/or treat acute radiation syndrome (ARS) and the delayed effects of acute radiation exposure (DEARE). INTERACT is a partnership of internationally-recognized investigators from four U.S.-based universities who possess a broad depth of expertise in MCM development, a unique set of animal model platforms, and a common goal of sharing ideas and quality practices to advance the cutting-edge scientific discovery and translational development of MCMs. This will be accomplished through partnering with the nation- wide consortium to bring multidisciplinary expertise, advanced capabilities, and wide-ranging resources necessary to strengthen the National Institute of Allergy and Infectious Diseases (NIAID)/National Institute of Health (NIH)’s mission to provide safe and effective medical management to victims of a radiological or nuclear incident. !

PI_NAMEs: CARRIER, FRANCE  (contact);JACKSON, ISABEL LAUREN

PROGRAM_OFFICER_NAME: TALIAFERRO, LANYN P

PROJECT_TERMS: Acceleration;Acute;Adolescent;Adult;Advanced Development;age acceleration;aging process;Animal Model;animal rule;Biological;Biological Markers;Biological Process;Blood;Cell Aging;Clinical;Clinical Trials;Communication;Cutaneous;Data;data sharing;design;Development;Dose;Drug Kinetics;Elderly;Ensure;Event;Exposure to;Failure;Fostering;Funding;Funding Opportunities;gastrointestinal;Generations;Genomic Instability;Goals;Government Agencies;Hematopoietic;Hour;improved;industry partner;Inflammation;Injury;interdisciplinary approach;international partnership;Investigation;Knowledge;Laboratory Research;Life;Maryland;Medical;Medical center;medical countermeasure;medical schools;member;Miniature Swine;Mission;Mitochondria;Modeling;Molecular;Morbidity - disease rate;mortality;multidisciplinary;multiorgan injury;National Institute of Allergy and Infectious Disease;new therapeutic target;nonhuman primate;Nuclear;Nuclear Accidents;Organ;Organ failure;Oryctolagus cuniculus;Pharmaceutical Preparations;Pharmacodynamics;Pharmacologic Substance;pharmacometrics;Pilot Projects;Population;pre-clinical;programs;public health emergency;Quality of life;Radiation;Radiation Accidents;radiation countermeasure;Radiation exposure;Radiation Injuries;Radiation Sicknesses;Radiation Syndromes;Radiation Toxicity;Radiology Specialty;Readiness;Recording of previous events;Recovery;Regulatory Pathway;research and development;Research Personnel;Resource Sharing;Resources;Safety;Services;Site;synergism;System;Technology Transfer;Testing;Therapeutic Intervention;tissue regeneration;Tissues;Treatment Efficacy;United States Food and Drug Administration;United States National Institutes of Health;Universities;Whole-Body Irradiation

PROJECT_TITLE: Intercollaborative Radiation Countermeasure (INTERACT) Consortium for Advanced Development of Medical Countermeasures to Mitigate/Treat Acute and Delayed Radiation Syndromes


NIH_SPENDING_CATS: Biodefense and Related Countermeasures

PI_NAMEs: JACKSON, ISABEL LAUREN (contact)

PROJECT_TERMS: Accounting;Achievement;Acute;Address;Administrative Coordination;Administrator;Advanced Development;Advisory Committees;Biological;Biometry;Budgets;career;Cell Line;Chemicals;Collaborations;Communication;conflict resolution;Control Groups;cost effective;Data;data sharing;Development;dosimetry;Ensure;Evaluation;experimental study;Fostering;Goals;Government;Human Resources;Individual;Industry;Infrastructure;Institution;Intellectual Property;interest;Leadership;Maryland;Measures;Medical center;medical countermeasure;meetings;member;Modeling;Monitor;National Institute of Allergy and Infectious Disease;operation;Peer Review;Performance;Preparation;Procedures;Productivity;programs;Publications;Radiation;radiation countermeasure;Radiation Physics;Radiation Syndromes;Randomized;Reagent;Reporting;Research;Research Project Grants;Resource Allocation;Resource Sharing;Resources;Science;Services;sex;Site;sound;Strategic Planning;Strategic vision;Structure;student training;success;symposium;synergism;System;Testing;Time;Training and Education;Travel;United States National Institutes of Health;Universities;web site

PROJECT_TITLE: Administrative Core


PI_NAMEs: TERRIN, MICHAEL L (contact)

PROJECT_TERMS: Acute;Advanced Development;Animal Model;Animals;Archives;Basic Science;Biocompatible Materials;Bioinformatics;Biological Markers;Biometry;Businesses;Calendar;Collaborations;Communication;Communities;Computer software;Data;Data Coordinating Center;data exchange;data sharing;Documentation;Educational Activities;Educational Materials;Equipment;Event;experience;Funding;General Population;Information Dissemination;Infrastructure;innovation;interest;Link;Medical center;medical countermeasure;meetings;Methods;Modeling;Monitor;National Heart, Lung, and Blood Institute;National Institute of Allergy and Infectious Disease;Nature;Pilot Projects;Procedures;programs;Protocols documentation;Publications;Radiation;radiation countermeasure;Radiation Syndromes;Radiobiology;Reagent;Research;Research Personnel;Resources;response;Running;Schedule;social media;Specimen;stem cell biology;stem cells;symposium;System;Training and Education;Translational Research;U-Series Cooperative Agreements;United States National Institutes of Health;Update;web page;web site

PROJECT_TITLE: Consortium-Wide Coordinating Core


NIH_SPENDING_CATS: Infectious Diseases;Lung;Orphan Drug;Rare Diseases

ORG_CITY: HACKENSACK

ORG_NAME: HACKENSACK UNIVERSITY MEDICAL CENTER

ORG_STATE: NJ

PHR: NARRATIVE A deadly lung disease caused by nontuberculous mycobacteria (NTM), cousins of the bacterium that causes tuberculosis, is becoming more prevalent worldwide, particularly in aging and immunocompromised individuals, and cystic fibrosis patients. Currently available therapies often fail to achieve cure due to the natural resistance of NTMs to most antibiotics, including rifamycins which show excellent activity against many other bacterial infections. Here we propose to generate new rifamycins that are specifically active against important NTM species to improve the treatment NTM disease.

PI_NAMEs: ALDRICH, COURTNEY C;DICK, THOMAS  (contact)

PROGRAM_OFFICER_NAME: BOYCE, JIM P

PROJECT_TERMS: Acceleration;Acute;ADP ribosylation;Aging;analog;Antibiotics;Automobile Driving;Bacteria;Bacterial Infections;bacterial resistance;bactericide;Binding Proteins;Biological Assay;Chemicals;Chronic;Clinical;clinically relevant;Combined Antibiotics;comorbidity;Complement;Complex;CYP3A4 gene;cystic fibrosis patients;Cytochrome P450;Data;Development;Diagnostic;Disease;DNA-Directed RNA Polymerase;Dose;Drug Interactions;Drug Kinetics;efficacy study;Ensure;Environment;Enzymes;Exhibits;Future;Genetic Polymorphism;Genomics;global health;Goals;Immunity;Immunocompromised Host;improved;In Vitro;in vivo;Individual;Industry Standard;Infection;Knock-out;Knowledge;Lead;Lung;Lung Diseases;lung injury;lung lesion;Measures;Metabolic;Metabolism;Mixed Function Oxygenases;mortality;mouse model;mutant;Mutation;mycobacterial;Mycobacterium abscessus;Mycobacterium avium Complex;Mycobacterium chelonae;Mycobacterium fortuitum;Mycobacterium Infections;Mycobacterium kansasii;Mycobacterium tuberculosis;Mycobacterium xenopi;Naphthoquinones;Natural Resistance;Nodule;non-tuberculosis mycobacteria;novel;opportunistic pathogen;Oral;Outcome;oxidation;pathogen;Patients;Penetration;Pharmaceutical Chemistry;Pharmaceutical Preparations;Pharmacodynamics;Phosphorylases;Plasma Proteins;Play;pre-clinical;preclinical development;Predisposition;prevent;programs;Property;Publishing;Pulmonary Pathology;Pulmonary Tuberculosis;Recommendation;Refractory;Regimen;Resistance;resistome;response;Rifabutin;Rifampin;Rifamycins;Role;Site;Sputum;Testing;Therapeutic;treatment duration;Tuberculosis;tuberculosis treatment

PROJECT_TITLE: Optimization of rifamycins to overcome intrinsic resistance of nontuberculous mycobacteria to improve treatment of NTM lung disease

STUDY_SECTION: DMPA

STUDY_SECTION_NAME: Drug Discovery and Molecular Pharmacology A Study Section [DMPA]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Hematology;Physical Injury - Accidents and Adverse Effects

PROJECT_TERMS: Acute;Advanced Development;animal efficacy;Animal Model;animal rule;Animals;archive data;assay development;biodosimetry;Biological Markers;Biological Products;biomarker identification;Blinded;Blood;Blood Coagulation Factor;Blood specimen;Bone Marrow;Breeding;Chemistry;Chinese;Collaborations;Controlled Study;Cutaneous;Data;data archive;data framework;data quality/integrity;data standards;Databases;Development;Doctor of Philosophy;Dose;drug development;Drug Kinetics;efficacy evaluation;efficacy study;Ensure;Ethics;experience;Fibroblast Growth Factor;flexibility;Future;good laboratory practice;Hematology;Human;Investigational New Drug Application;irradiation;Laboratories;Macaca mulatta;Marketing;Maryland;medical countermeasure;member;mid-career faculty;Miniature Swine;Modeling;models and simulation;Monitor;nanoparticle;National Institute of Allergy and Infectious Disease;nonhuman primate;Nuclear;Nuclear Accidents;Oryctolagus cuniculus;Pharmaceutical Preparations;Pharmacodynamics;pharmacokinetics and pharmacodynamics;Pharmacology;pharmacometrics;porcine model;preclinical trial;Qualifying;quality assurance;Radiation Accidents;radiation countermeasure;Radiation exposure;Radiation Injuries;Radiation Sicknesses;Radiation Syndromes;Randomized;Recommendation;Regimen;Regulation;Regulatory Affairs;Regulatory Pathway;Resources;Rodent;Safety;screening;Secure;Serum;Services;Skin;Standardization;stem;System;Technology;Testing;Therapeutic;Thromboplastin;Tissue Banks;Tissue Sample;Toxic effect;translational medicine;Treatment Protocols;trial design;United States Food and Drug Administration;United States National Institutes of Health;Validation;Whole-Body Irradiation

PROJECT_TITLE: Animal Efficacy and Pharmacometric Modeling Core


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Hematology;Physical Injury - Accidents and Adverse Effects

PI_NAMEs: ORSCHELL, CHRISTIE M (contact)

PROJECT_TERMS: Acute;Advanced Development;Affect;Age;aging reversal;Agonist;Animal Model;animal rule;Animals;BCL2L1 gene;Benign;Biology;Blood;Body System;Bone Marrow;Cardiac;Cells;Cessation of life;Childhood;Chronic Disease;Collaborations;combinatorial;CSF3 gene;Data;Depressed mood;Development;Dinoprostone;Dose;Edg4 Protein;efficacy study;Eicosanoids;Elderly;Environment;Etiology;Event;Exposure to;FDA approved;Filgrastim;General Population;Genetic Transcription;Goals;Grant;Granulocyte Colony-Stimulating Factor;Granulocyte-Macrophage Colony-Stimulating Factor;Hematologist;Hematopoiesis;Hematopoietic;hematopoietic stem cell fate;Hematopoietic stem cells;Hematopoietic System;Hemorrhage;Human;Human Resources;Inbreeding;Individual;Infection;irradiation;Joints;Kidney;Licensing;Life;lung injury;Lymphoid;medical countermeasure;Medical Research;Modeling;Molecular;mouse model;Mus;National Institute of Allergy and Infectious Disease;Natural regeneration;nonhuman primate;novel;Nuclear Accidents;Organ;Pegfilgrastim;Polypharmacy;Population;Populations at Risk;Primates;Productivity;programs;Qualifying;Radiation;Radiation Accidents;radiation countermeasure;Radiation Dose Unit;Radiation exposure;Radiation induced damage;Radiation Injuries;radiation mitigator;Radiation Protection;Radiation Syndromes;Radiation Toxicity;Radiology Specialty;radioprotected;Recovery;Regimen;repaired;Research Personnel;Residual state;response;sargramostim;Schedule;senescence;senescent cell;senolytics;stem cell biology;Stress;survival outcome;Survivors;System;Testing;Time;Tissues;Toxic effect;treatment effect;warfighter;young adult

PROJECT_TITLE: Development of dmPGE2 and Bcl-xl-targeting senolytics as medical countermeasures for H-ARS and DEARE


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Bioengineering;Digestive Diseases;Genetics;Nanotechnology;Physical Injury - Accidents and Adverse Effects;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

PI_NAMEs: TIGYI, GABOR J (contact)

PROJECT_TERMS: Acceleration;Acute;Advanced Development;Affect;Agonist;analog;Animal Model;animal rule;Apoptotic;Benzoic Acids;Biological Assay;Bone Marrow;Cell Death;cell injury;cell killing;cell regeneration;Cell Survival;Cells;cellular targeting;Cessation of life;Clinical Trials;Collaborations;college;Colon;Communities;Complex;Data;Development;Devices;DNA;DNA Integration;DNA Repair;DNA-dependent protein kinase;Dose;drug candidate;drug development;drug discovery;Drug Formulations;Drug Kinetics;Drug Targeting;efficacy study;Enzymes;Evaluation;experience;Explosion;FDA approved;first responder;Formulation;Funding;G-Protein-Coupled Receptors;gamma irradiation;gastrointestinal;gastrointestinal epithelium;gene product;Generations;Genes;Genotoxic Stress;Goals;Growth Factor;Hematopoietic;Hematopoietic stem cells;Human;in vivo;Induction of Apoptosis;Inhibition of Apoptosis;Injury;Intestines;Investigational Drugs;Ionizing radiation;irradiation;Knowledge;Laboratories;Lethal Dose 50;Leucine-Rich Repeat;LGR5 gene;lipid mediator;lysophosphatidic acid;Lysophosphatidic Acid Receptors;Macaca mulatta;MAPK3 gene;Mediating;Medical;medical countermeasure;Military Personnel;Mitotic;Modeling;Molecular;Molecular Mechanisms of Action;mortality;Mus;nanoparticle;nanoparticle drug;National Institute of Allergy and Infectious Disease;Natural regeneration;NF-kappa B;nonhuman primate;Nuclear;Nuclear Reactor Accidents;Organ;Outcome;Pathology;Pathway interactions;Patients;Pharmaceutical Preparations;Pharmacy facility;Population;pre-Investigational New Drug meeting;prevent;programs;Property;Protein phosphatase;Proteins;Proto-Oncogene Proteins c-akt;Radiation;radiation countermeasure;Radiation Dose Unit;Radiation exposure;Radiation induced damage;Radiation Induced DNA Damage;Radiation Injuries;radiation mitigation;radiation mitigator;Radiation Protection;radiation risk;Radiation Syndromes;Radiation Toxicity;radiation-induced injury;receptor;recruit;regenerative;repaired;Research;Research Proposals;response;Role;Safety;senescence;Signal Transduction;small molecule;stem cell survival;stem cells;Terrorism;Testing;Therapeutic;Toxicokinetics;Transgenic Mice

PROJECT_TITLE: IND-enabling development of Radioprotectin 1: a dual GI/HE radiation mitigator


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Hematology;Physical Injury - Accidents and Adverse Effects;Regenerative Medicine;Wound Healing and Care

PI_NAMEs: OKUNIEFF, PAUL  (contact)

PROJECT_TERMS: Accidents;Acute;Advanced Development;Affect;animal rule;Biological Markers;Biology;Blood Platelets;Bone Growth;Bone Marrow;bone preservation;Brain Diseases;Bulla;Burn injury;cell type;Cessation of life;Clinical;Complex;cost;CSF3 gene;Cutaneous;cytokine;Data;design;Dose;Drug Kinetics;efficacy study;Endothelial Cells;Epithelium;Event;experience;Family suidae;FGF2 gene;Fibroblast Growth Factor;Fibroblast Growth Factor Receptors;Follow-Up Studies;Functional disorder;Funding;gastrointestinal;good laboratory practice;graft vs host disease;healing;Heart Diseases;Hematologic Agents;Hematology;Hematopoietic;Hemorrhage;Human;improved;Individual;Inflammation;Injury;Intervention;Investigational Drugs;Investigational New Drug Application;irradiation;Ischemia;Knowledge;Length;Life;Light;Lung;Macaca;Macaca mulatta;Maintenance;mass casualty;Maximum Tolerated Dose;medical countermeasure;meetings;Mesenchymal;Miniature Swine;model design;Modeling;Monkeys;mouse model;multiorgan damage;Mus;Myocardial Ischemia;National Institute of Allergy and Infectious Disease;Nerve Regeneration;nonhuman primate;Nuclear;Nutrient;Oral mucous membrane structure;Organ;organ injury;Oxygen;peptidomimetics;Perfusion;Pharmaceutical Preparations;Pharmacodynamics;pharmacokinetics and pharmacodynamics;platelet function;Play;preclinical study;preservation;pressure;prevent;Process;Production;Proteins;public health emergency;Radiation;Radiation Accidents;radiation burn;radiation countermeasure;Radiation exposure;Radiation Injuries;radiation mitigation;Radiation Syndromes;Radiation Toxicity;Radiodermatitis;Radiology Specialty;Rattus;Readiness;receptor binding;Recombinant Fibroblast Growth Factor;Recommendation;Research Project Grants;response;response biomarker;Role;Safety;Schedule;senescence;Site;Skin;stem cell proliferation;Strontium;Strontium-90;Supportive care;Syndrome;telomere;Testing;Therapeutic;Time;Tissues;Toxic effect;Toxicity Tests;Trauma;United States National Institutes of Health;Vascular regeneration;Whole-Body Irradiation;Wistar Rats;Work;wound;wound healing

PROJECT_TITLE: FGF-2 mimetic peptides as pleuripotent mitigators of ARS and DEARE


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Lung;Physical Injury - Accidents and Adverse Effects;Pulmonary Fibrosis

PROJECT_TERMS: Acute;Address;Advanced Development;Agreement;Anatomy;animal efficacy;Animal Model;animal rule;Animals;Area;BCL2L1 gene;Biological Process;Blinded;Blood specimen;Bone Marrow;C57L/J Mouse;Cancer Patient;candidate validation;Cell Aging;Cell Death;Cell Separation;Cell Survival;Clinical;Clinical Data;Collaborations;Combined Modality Therapy;Competitive Binding;Complex;Data;design;Development;Disease Progression;DNA Damage;Dose;Drug Exposure;Drug Kinetics;efficacy study;Enzyme-Linked Immunosorbent Assay;Estrogen Receptor 2;Evaluation;experience;experimental study;Exposure to;Fibrosis;functional outcomes;Goals;good laboratory practice;Hour;Human;improved;In Vitro;indexing;Individual;Inflammation;Inflammatory Response;Intramuscular;Intramuscular Injections;Knowledge;Life;Lung;lung injury;Mediating;medical countermeasure;Medical Imaging;member;Methods;Modeling;Morbidity - disease rate;mouse model;Mus;nano;Natural History;NF-kappa B;nonhuman primate;novel;Nuclear Accidents;Oral;Oral Administration;Outcome;Outcome Measure;Oxidative Stress;Pathogenesis;Patients;Peripheral Blood Mononuclear Cell;pharmacodynamic biomarker;pharmacologic;pharmacometrics;Plasma;Play;Protac;Publishing;Pulmonary Inflammation;Radiation Accidents;radiation countermeasure;Radiation Dose Unit;Radiation exposure;Radiation Fibrosis;Radiation induced damage;Radiation Injuries;Radiation Pneumonitis;Radiation Sicknesses;Radiation Syndromes;Radiation therapy;Radiation Toxicity;Randomized;Readiness;Recovery;Recovery of Function;Regimen;Regulatory Pathway;repaired;Research;Rodent;Role;Safety;senescence;senescent cell;senolytics;Signal Transduction;standard of care;Statistical Data Interpretation;Structure of parenchyma of lung;Supportive care;survival outcome;Suspensions;Syndrome;Systems Biology;Technology;Testing;Therapeutic;tissue biomarkers;tissue injury;Tissues;transcriptome sequencing;Treatment Efficacy;United States Food and Drug Administration;Whole-Body Irradiation

PROJECT_TITLE: Development of BIO 300 for mitigation and/or treatment of radiation pneumonitis and fibrosis


ADMINISTERING_IC: ES

ED_INST_TYPE: EARTH SCIENCES/RESOURCES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

ORG_CITY: ITHACA

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: CORNELL UNIVERSITY

PHR: This project will elucidate the molecular organization and function of proteins that regulate yeast genomes. Such organization has direct parallels in human systems, both normal and diseased cell states, and thus will help create better diagnostics and treatments for diseases.

PI_NAMEs: PUGH, B FRANKLIN (contact)

PROGRAM_OFFICER_NAME: TYSON, FREDERICK L

PROJECT_TERMS: Acute;acute stress;Architecture;Binding;biological adaptation to stress;Biological Assay;Budgets;Cell model;Cells;Chromatin;Chronic stress;cofactor;Collection;Complex;computational pipelines;cost;Data;Data Set;Development;Diagnostic;Disease;DNA;DNA Polymerase II;Enhancers;epigenome;epigenomics;Event;extracellular;Funding;Gene Activation;gene environment interaction;Gene Expression Regulation;gene function;gene induction;gene synthesis;Genes;genetic manipulation;genetic regulatory protein;Genetic Transcription;Genome;genome-wide;Genomics;Goals;Grant;Heat-Shock Response;histone modification;Hour;Human;insight;Life;Maps;Measurable;Measures;Mediator;Molecular;Nature;novel;Oxidative Stress;Pathway interactions;Peptide Initiation Factors;Peroxides;Process;promoter;protein function;Proteins;Publishing;Regulation;Regulator Genes;Repression;Research Project Grants;Resolution;response;Role;Saccharomyces;Saccharomycetales;SAGA;Signal Transduction;Starvation;Stress;Structure;System;Testing;Tissues;Transcription Elongation;transcription factor;Transcription Initiation;United States National Institutes of Health;Work;Yeasts

PROJECT_TITLE: HIGH RESOLUTION EPIGENOMIC MAPS OF YEAST IN RESPONSE TO ENVIRONMENTAL STRESS


ADMINISTERING_IC: GM

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

PHR: A major signaling molecule for the innate immune system and target of the last-resort antibiotic colistin, lipopolysaccharide is an essential, ubiquitous component of the gram-negative bacterial cell envelope. Despite being implicated in processes ranging from cell envelope permeability to division, the precise contribution of lipopolysaccharide to gram-negative physiology is poorly understood. Applying genetic and cytological approaches, I propose to fill this gap in our understanding of this essential molecule.

PI_NAMEs: VALDEZ, RYAN ADAM (contact)

PROGRAM_OFFICER_NAME: MCINTYRE, JEREMY COLIN

PROJECT_TERMS: Acinetobacter baumannii;Address;Animals;Antibiotics;Applied Genetics;Atomic Force Microscopy;Bacteria;Biology;Bypass;career;Cell division;cell envelope;cell growth;Cell Physiology;Cell Separation;Cell Survival;Cell Wall;Cells;Cellular Morphology;Charge;Clinical;Colistin;colistin resistance;Collection;Compensation;conditional mutant;crosslink;Cytology;Data;Defect;Divalent Cations;Drug Targeting;Escherichia coli;experimental study;Fellowship;Filament;gain of function;genetic approach;Gram-Negative Bacteria;Gram-Negative Bacterial Infections;Grant;Growth;Immune system;Immune Targeting;Infection;Innate Immune System;insight;interest;knock-down;Lead;Lipopolysaccharides;Mediator;Membrane;Mentors;Microscopy;Modeling;Morphology;mutant;Mutation;Nature;Organism;Osmolar Concentration;Osmotic Shocks;pathogen;Peptidoglycan;Permeability;Phenotype;Phospholipids;Physiology;pressure;Process;professor;Protein Biochemistry;Research Personnel;Role;Signal Transduction;Signaling Molecule;single cell analysis;skills;stem;Structure;Testing;Time;Work

PROJECT_TITLE: Illuminating the essential role of the outer membrane component and drug target, lipopolysaccharide

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


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Cardiovascular;Clinical Research;Coronaviruses;Emerging Infectious Diseases;Heart Disease;Infectious Diseases;Lung;Post-Acute Sequelae of SARS-CoV-2 infection (PASC) including Long COVID

ORG_CITY: MINNEAPOLIS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: NARRATIVE Coronavirus Disease 2019 (COVID-19) has become a widespread global pandemic. While the primary clinical manifestation of severe COVID-19 is lung failure, complications following acute illness can involve long-term manifestations that are not fully understood. Our work will help expand our understanding of the long-term cardiac effects from severe COVID-19 and their underlying mechanisms, which could help enhance health, lengthen life, and reduce illness and disability in survivors.

PI_NAMEs: BAKER, JASON V;SHENOY, CHETAN N (contact)

PROGRAM_OFFICER_NAME: DESVIGNE-NICKENS, PATRICE

PROJECT_TERMS: 2019-nCoV;ACE2;Acute;acute COVID-19;adaptive immune response;Admission activity;Award;Biological Markers;Blood specimen;Cardiac;cardiac magnetic resonance imaging;Cardiology;Cardiomyopathies;Cardiopulmonary;cardiovascular effects;cardiovascular injury;Cardiovascular system;CD4 Positive T Lymphocytes;Cells;Chronic;Clinical;clinically relevant;cohort;Communicable Diseases;coronary fibrosis;COVID-19;COVID-19 patient;COVID-19 survivors;cytokine;Diffuse;disability;Endothelial Cells;Epidemic;Epidemiology;experience;Fibroblasts;Fibrosis;Frequencies;Functional disorder;Goals;Health;Heart Abnormalities;heart damage;Heart Diseases;Heart Injuries;Hospitalization;Immune;immune activation;Immune response;Immunofluorescence Immunologic;Immunologics;Immunology;improved;In Vitro;Infection;Inflammation;Inflammatory;Influenza;influenza infection;injured airway;Injury;Intervention;Knowledge;Late Effects;Life;Long COVID;Low Prevalence;lung failure;Lymphopenia;Macrophage;Magnetic Resonance;Measures;Mediating;Microcirculation;monocyte;Mononuclear;Muscle Cells;Myocardial;Myocardial dysfunction;myocardial injury;Myocarditis;Natural Immunity;neutrophil;novel;Organ;pandemic disease;Participant;participant enrollment;particle;Pathology;Patients;Peptides;Pericytes;persistent symptom;Phenotype;Post-Acute Sequelae of SARS-CoV-2 Infection;Proteins;Protocols documentation;receptor;Recovery;Reporting;Research;Respiratory Disease;Respiratory Failure;response;risk stratification;SARS-CoV-2 infection;Science;severe COVID-19;spatial relationship;Specialist;Specimen;study population;Survivors;Symptoms;systemic inflammatory response;T cell response;T-Lymphocyte;Testing;thrombotic complications;Tissues;Troponin;Viral;Virus Diseases;Work;wound healing

PROJECT_TITLE: Immunologic basis of cardiac disease after severe COVID-19

STUDY_SECTION: CCHS

STUDY_SECTION_NAME: Clinical Integrative Cardiovascular and Hematological Sciences Study Section[CCHS]


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

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

PHR: Project Narrative A common type of childhood cancer, acute myelogenous leukemia (AML), affects approximately 500 U.S. children annually, and only about half survive. This project will examine how to target the metabolic dependencies of pediatric AML. Additionally, we will test a well-tolerated drug for incorporation into treatment for pediatric AML.

PI_NAMEs: STEVENS, ALEXANDRA  (contact)

PROGRAM_OFFICER_NAME: BIAN, YANSONG

PROJECT_TERMS: Acute Myelocytic Leukemia;acute myeloid leukemia cell;Adult Acute Myeloblastic Leukemia;Affect;Anti-malarials;Apoptosis;atovaquone;Award;biological adaptation to stress;Biological Assay;Bone Marrow;Bone Marrow Cells;career;career development;Cell Death;Cell Survival;Characteristics;Chemoresistance;chemotherapeutic agent;chemotherapy;Child;Childhood;Childhood Acute Myeloid Leukemia;Clinical;cohort;college;Complex;CRISPR/Cas technology;Cytotoxic Chemotherapy;Data;Death Rate;Dependence;design;Development Plans;Diagnostic;Disease;Disease remission;Drug Combinations;Drug resistance;Electron Transport;Electron Transport Complex III;Elements;Environment;Evaluation;experimental study;FDA approved;FLT3 gene;Foundations;Funding;Future;Gene Expression Profile;Genes;Goals;Hematologic Neoplasms;Human;immunodeficient mouse model;improved;In Vitro;Induction of Apoptosis;Inhibition of Apoptosis;Institution;Kinetics;Knowledge;Laboratories;Laboratory Finding;Learning;leukemia;leukemia treatment;Leukemic Cell;Literature;Malignant Childhood Neoplasm;Mass Spectrum Analysis;Measures;Medical center;Medicine;Mentors;Mentorship;Metabolic;Metabolic Pathway;Metabolism;metabolomics;Mitochondria;MLL gene;mouse model;Myeloproliferative disease;Newly Diagnosed;Outcome;Oxidative Phosphorylation;Pathway interactions;patient derived xenograft model;Patients;Pediatric Oncology Group;Pharmaceutical Preparations;phase III trial;Phosphorylation Inhibition;Physicians;Pneumonia;Positioning Attribute;preclinical evaluation;prevent;programs;Publishing;Recurrent disease;Relapse;relapse prevention;Research;Research Personnel;Resistance;Resources;respiratory;Sampling;Scholarship;Scientist;Shapes;standard care;stem cell survival;Stress;targeted agent;Techniques;Testing;Texas;Therapeutic;Time;transcriptome;transcriptome sequencing;Treatment Protocols;Treatment-related toxicity;Work

PROJECT_TITLE: Exploiting the Metabolic Dependencies of Pediatric AML

STUDY_SECTION: NCI

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


NIH_SPENDING_CATS: Complementary and Integrative Health;Congenital Structural Anomalies;Dietary Supplements;Kidney Disease;Nutrition;Pediatric;Polycystic Kidney Disease;Prevention;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_DEPT: PATHOLOGY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease and the fourth most common cause of end stage renal failure. Tolvaptan, the only FDA-approved drug that is proven to delay the progression of ADPKD, is expensive and is associated with some side effects that may limit its use in some patients. Our overall goal is to understand the metabolic derangement and the underlying molecular mechanism in ADPKD, in order to develop novel therapeutics targeting metabolic pathways to ameliorate ADPKD.

PI_NAMEs: DAI, DAO-FU  (contact)

PROGRAM_OFFICER_NAME: MARIC-BILKAN, CHRISTINE

PROJECT_TERMS: Ablation;absorption;Acetyl Coenzyme A;Acyl Coenzyme A;Adenosine Triphosphate;aerobic glycolysis;Animal Model;Apoptotic;Attenuated;Autosomal Dominant Polycystic Kidney;beta-Hydroxybutyrate;Branched-Chain Amino Acids;carboxylation;Cell Line;Citric Acid Cycle;clinical application;clinical development;clinical translation;Cyst;Cystic kidney;Defect;Depressed mood;design;Development;Diet;Dietary Intervention;dietary restriction;dietary supplements;Disease Progression;Dropout;End stage renal failure;Epithelial Cells;experimental study;Fasting;fatty acid oxidation;Fatty Acids;FDA approved;fibroblast growth factor 21;Fibroblast Growth Factor Receptors;food restriction;FRAP1 gene;Genetic;Genus Hippocampus;Glucose;glucose metabolism;Goals;Growth;Health;Human;Human Cell Line;human induced pluripotent stem cells;Impairment;In Vitro;in vivo;induced pluripotent stem cell;Inflammatory;inhibitor;insulin sensitivity;Intervention;Isoleucine;ketogenesis;ketogenic diet;Ketone Bodies;Ketones;Ketosis;Kidney;kidney cell;Kidney Diseases;Kidney Failure;Knowledge;Link;Malonyl Coenzyme A;Measures;Mediating;Mediator;Metabolic;Metabolic Diseases;Metabolic Pathway;Metabolism;metabolomics;Mitochondria;Modeling;Molecular;mouse model;Mus;Mutation;Neurodegenerative Disorders;new therapeutic target;non-compliance;novel;Organ;Organoids;Outcome;oxidation;Oxygen Consumption;Palmitates;Pathology;Pathway interactions;Patients;Pharmaceutical Preparations;Physiology;PKD1 gene;PKD2 gene;Polycystic Kidney Diseases;Proteins;Proteomics;pyruvate carrier;Renal function;Renal tubule structure;Reporting;Research;response;Role;Serum;side effect;Signal Transduction;SIRT1 gene;solute;Testing;Time-restricted feeding;tolvaptan;Tubular formation;Urine;Warburg Effect;Water

PROJECT_TITLE: Metabolic reprogramming and FGF21 signaling in kidney health and polycystic kidney diseases


NIH_SPENDING_CATS: Cardiovascular;Genetics;Heart Disease;Heart Disease - Coronary Heart Disease

ORG_CITY: Columbus

ORG_DEPT: PHYSIOLOGY

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: Project Narrative Individuals who survive a heart attack are at risk for developing heart failure, which affects 6 Million Americans and has a 5 year mortality rate over 40%. Fibroblasts, a type of cell found in the heart, become activated after a heart attack and long-term activation of these cells contributes to heart failure progression. Preventing prolonged fibroblast activation may enable us to develop new therapies to treat heart failure.

PI_NAMEs: STRATTON, MATTHEW  (contact)

PROGRAM_OFFICER_NAME: ADHIKARI, BISHOW B

PROJECT_TERMS: Acceleration;Affect;American;Angiotensin II;antifibrotic treatment;Biology;Blood Vessels;Cardiac;Cardiac Myocytes;Cause of Death;cell type;Cells;Cicatrix;Clinic;Clinical;clinically relevant;coronary fibrosis;Data;Death Rate;Deposition;digital;effective therapy;Essential Genes;Extracellular Matrix;Fibroblasts;Fibrosis;Flow Cytometry;Functional disorder;Gene Expression;Genes;Genetic Transcription;Heart;Heart failure;heart function;heart preservation;Human;Hypertrophy;Immune;immunoregulation;In Vitro;in vivo;Individual;Inflammation;Injury;innovation;interstitial;Intervention;Investigation;Knock-out;Knockout Mice;Knowledge;LacZ Genes;Macrophage;Macrophage Activation;MADH2 gene;Mediating;Modeling;Molecular;multicatalytic endopeptidase complex;Mus;Myocardial dysfunction;Myocardial Infarction;Myocardial Ischemia;Myocarditis;Myofibroblast;nano-string;neutrophil;Neutrophil Infiltration;novel;novel therapeutics;Nuclear Protein;Organ;p38 Mitogen Activated Protein Kinase;Pathologic;Pathology;Pathway interactions;Patients;Physiological;Physiology;Population;preclinical development;preservation;prevent;Process;professor;programs;Proliferating;Property;Proteasome Inhibition;protein degradation;protein expression;Proteins;prototype;Public Health;recruit;Reporter;Research Personnel;response;Risk;Rodent;Rodent Model;Role;Sampling;selective expression;single nucleus RNA-sequencing;Site;SMAD2 protein;Stress;targeted treatment;Testing;TGFB1 gene;Therapeutic;tool;Toxic effect;Transcription Coactivator;transcription factor;transcriptome sequencing;Transforming Growth Factor beta;Ubiquitination;Ventricular;Western Blotting;Work

PROJECT_TITLE: The role of Sertad4 in pathologic cardiac remodeling.

STUDY_SECTION: MPPA

STUDY_SECTION_NAME: Integrative Myocardial Physiology/Pathophysiology A Study Section [MPPA]


ORG_CITY: WILMINGTON

ORG_NAME: NEMOURS CHILDREN'S HOSPITAL, DELAWARE

ORG_STATE: DE

PHR: PROJECT NARRATIVE Sepsis is the most common cause of multiple organ dysfunction syndrome (MODS), and sepsis-induced MODS is a leading cause of prolonged hospitalization and death for children. We previously found that children with prolonged MODS also have persistent immune cell mitochondrial dysfunction. Through the proposed study, we will now determine if mechanisms that normally restore and maintain mitochondrial health are abnormal in children with prolonged sepsis-induced MODS, leading to persistent mitochondrial dysfunction that then sustains inflammation and increases severity and duration of organ dysfunction.

PI_NAMEs: WEISS, SCOTT L (contact)

PROJECT_TERMS: Address;Animal Model;Antibiotics;Biogenesis;Body System;Caring;Cause of Death;Cell Physiology;Cell Respiration;Cells;Cessation of life;Child;Clinical;cytokine;Cytosol;Data;Enrollment;Etiology;Event;experimental study;Functional disorder;Future;Genetic Transcription;Goals;Health;high risk;Hospitalization;Human;Human Herpesvirus 4;Immune;Immune response;improved;In Vitro;in vitro Model;Infection;Inflammasome;Inflammation;Inflammatory;Injury;interest;Investigation;Life;Link;Lipopolysaccharides;lipoteichoic acid;lymphoblast;Lymphocyte Activation;Measures;Medical emergency;Metabolic;Mitochondria;Mitochondrial Diseases;Mitochondrial DNA;mitochondrial dysfunction;Multiple Organ Failure;National Institute of Child Health and Human Development;Organ;Oxidation-Reduction;Pathologic;Pathway interactions;Patients;Pattern;pediatric sepsis;Peripheral Blood Mononuclear Cell;Persons;Plasma;Prevention;Process;protein expression;Proteins;Protocols documentation;Quality Control;Recovery;Refractory;Regulation;Respiration;Resuscitation;RNA;Sampling;Sepsis;septic;Septic Shock;Severities;Shock;Speed;Stimulator of Interferon Genes;Suggestion;systemic inflammatory response;Testing;Therapeutic;therapeutic target;Therapeutically Targetable;TLR9 gene;translational potential;United States;Work

PROJECT_TITLE: Effect of Mitochondrial Quality Control on Systemic Inflammation and Organ Dysfunction in Pediatric Sepsis

STUDY_SECTION: SAT

STUDY_SECTION_NAME: Surgery, Anesthesiology and Trauma Study Section[SAT]


ADMINISTERING_IC: AT

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL CENTER FOR COMPLEMENTARY & INTEGRATIVE HEALTH

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Complementary and Integrative Health;Dietary Supplements;Genetics;Natural Products

ORG_CITY: LOS ANGELES

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: Project Narrative Plant natural products and plant natural product-derived drugs have been indispensible towards the treatment of different diseases and the prophylactic maintenance of healthy lifestyle. In this proposal, we aim to use synthetic biology strategies for yeast-based, high-titer production of monoterpene indole alkaloids, a family of plant compounds of which many are therapeutically important.

PI_NAMEs: DI CARLO, DINO ;TANG, YI  (contact)

PROGRAM_OFFICER_NAME: KIM, HYE-SOOK

PROJECT_TERMS: Achievement;addiction;Anabolism;Behavior;Biological;Biological Models;Cell Separation;Cells;Chemicals;Chemistry;Cloning;Clustered Regularly Interspaced Short Palindromic Repeats;Collaborations;Collection;Complex;CRISPR interference;CRISPR-mediated transcriptional activation;Data;Derivation procedure;Directed Molecular Evolution;Disease;Encapsulated;Engineering;Enzymatic Biochemistry;Enzymes;Evaluation;Family;Fluorescence;Genes;Genetic Screening;Genome;genome wide screen;genome-wide;glucosidase;Grant;Growth;healthy lifestyle;high throughput screening;Hydrogels;Ibogaine;improved;Indole Alkaloids;interest;Investigation;Letters;Liquid substance;Maintenance;Metabolic;Metabolic Biotransformation;Methods;microbial;microbial host;Microfluidic Microchips;Microfluidics;Monoterpenes;Mutagenesis;mutant;nanobiotechnology;Natural Products;novel strategies;Opiate Addiction;Opioid;Organism;particle;Pathway interactions;Pharmaceutical Preparations;pharmacologic;Pharmacologic Substance;Phytochemical;Plant alkaloid;plant metabolites;Plant natural product;Plants;Positioning Attribute;Process;Production;promoter;prophylactic;Psychotropic Drugs;reconstitution;reconstruction;Reporter;Reporting;Research Project Grants;Saccharomyces cerevisiae;screening;Signaling Molecule;small molecule;Sorting;Source;strictosidine;success;synthetic biology;System;Technology;Therapeutic;tool;Vinblastine;Yeasts

PROJECT_TITLE: Engineering Yeast towards High Titer Production of Monoterpene Indole Alkaloid Natural Products

STUDY_SECTION: CSB

STUDY_SECTION_NAME: Chemical Synthesis and Biosynthesis Study Section[CSB]


NIH_SPENDING_CATS: Cardiovascular;Heart Disease;Heart Disease - Coronary Heart Disease

ORG_CITY: Aurora

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: PROJECT NARRATIVE Heart failure remains the foremost barrier to human health and wellness, contributing to more deaths and morbidity than almost any other disease. This debilitating and progressive disease is worsened by chronic inflammation and fibrosis of the heart but the underlying mechanisms are poorly understood, preventing development of new therapies. Our proposal seeks to elucidate a new mechanism of how cardiac macrophages expressing the receptor CX3CR1 can resolve chronic inflammation and limit fibrosis, thus preventing heart failure and potentially improving outcomes for patients with many types of cardiovascular disease.

PI_NAMEs: VAGNOZZI, RONALD JOSEPH (contact)

PROJECT_TERMS: Ablation;Acceleration;Acute;Acute myocardial infarction;Address;Anti-Inflammatory Agents;Atomic Force Microscopy;Automobile Driving;Biological Assay;Biophysics;Bone Marrow;Bone Marrow Transplantation;Cardiac;cardiogenesis;Cardiovascular Diseases;CCL2 gene;Cells;Cessation of life;chemokine receptor;Chronic;Cicatrix;Complex;coronary fibrosis;Cues;cytokine;Data;Development;Disease;Embryo;Equilibrium;Extracellular Matrix;Fibroblasts;Fibrosis;G-Protein-Coupled Receptors;Gene Delivery;Genetic;genome-wide;global health;Goals;healing;Health;Heart;Heart failure;heart function;Heart Injuries;Human;Immune;immune function;Immune response;Immunologic Stimulation;Impairment;improved;improved outcome;Infarction;Inflammation;Inflammatory;Inflammatory Response;Injury;Innate Immune Response;innovation;insight;Knockout Mice;Knowledge;Ligands;Macrophage;macrophage-derived chemokine;Maintenance;Mass Spectrum Analysis;Mediating;Modeling;Molecular;monocyte;Morbidity - disease rate;mortality;mouse model;multiple omics;Mus;Myocardial;Myocardial dysfunction;Myocardial Infarction;Myocardial Ischemia;Myocarditis;neutrophil;novel;novel therapeutics;Organ;Outcome;Pathologic;Pathology;Pathway interactions;Patient-Focused Outcomes;Patients;Peripheral;Phenotype;Postdoctoral Fellow;prevent;Process;Progressive Disease;Proliferating;Property;Proteomics;receptor;recruit;repaired;Resolution;response;response to injury;Role;Rupture;Severities;Signal Pathway;Signal Transduction;Signaling Molecule;Spleen;Structure;Surface;Surgical Models;T-Lymphocyte;Techniques;Testing;Therapeutic;therapy development;tissue injury;Tissues;transcriptomics;transplant model;Viral;virtual;Work;wound healing

PROJECT_TITLE: Mechanisms of Cardiac Injury Resolution by CX3CR1+ Macrophages

STUDY_SECTION: MPPB

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


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: PORTLAND

ORG_NAME: PORTLAND VA MEDICAL CENTER

ORG_STATE: OR

PHR: This prospective cohort study aims to characterize Veterans’ experiences with, and outcomes following, discontinuation of long-term opioid therapy. Results from this study will provide VA operations administrators, hospital executives, and clinicians with information that characterizes opioid discontinuation from patients’ perspectives. These perspectives can inform best practices for discontinuing opioid therapy, when clinically indicated, while simultaneously mitigating negative consequences of discontinuation and engaging and empowering patients to manage chronic pain with evidence-based non-opioid treatment modalities available within VA and in the community. Such approaches are highly consistent with patient-centered care paradigms.

PI_NAMEs: LOVEJOY, TRAVIS IAN (contact)

PROJECT_TERMS: Accounting;Acute;Address;Administrator;Attention;Caring;Cessation of life;Characteristics;chronic pain management;chronic pain patient;Clinical;cohort;Communities;Community Networks;Data;Data Analyses;design;Dose;Electronic Health Record;empowerment;Enrollment;ethnic minority;Ethnic Origin;evidence base;experience;Feeling suicidal;Female;follow up assessment;Gender;Goals;Guidelines;health care service utilization;health disparity;Heroin;Hospitals;improved;Intervention;Interview;Mental Health;Methodology;Methods;Modality;non-cancer chronic pain;non-opioid analgesic;operation;Opioid;opioid epidemic;opioid therapy;Outcome;Overdose;Pain;Pain Clinics;Pain intensity;Pain interference;Pain management;pain outcome;pain patient;Patient Monitoring;Patient-Centered Care;Patient-Focused Outcomes;Patients;Pharmaceutical Preparations;Pharmacy facility;Population;prescription opioid;Primary Care;Process;Prospective, cohort study;Qualitative Methods;Quality of life;Quality of Life Assessment;Race;racial minority;Random Allocation;Reporting;Resources;risk mitigation;Safety;Sampling;Secondary pain;Severities;Structure;substance use;Suicide attempt;Surveys;Symptoms;systematic review;Telephone;Testing;trend;Veterans;Volition

PROJECT_TITLE: Chronic Pain Management and Patient-Centered Outcomes Following Discontinuation of Long-Term Opioid Therapy

STUDY_SECTION_NAME: HSR-1 Health Care and Clinical Management[HSR1]


NIH_SPENDING_CATS: Biotechnology;Chronic Liver Disease and Cirrhosis;Clinical Research;Congenital Structural Anomalies;Digestive Diseases;Genetics;Liver Disease;Pediatric;Rare Diseases

ORG_CITY: PHILADELPHIA

ORG_NAME: CHILDREN'S HOSP OF PHILADELPHIA

ORG_STATE: PA

PHR: Genomic diagnostics relies on the accurate interpretation of genetic variation to disease causation, which can be hampered by the large predominance of Variants of Uncertain Significance (VOUS) identified in many disease genes as well as variable expressivity, a hallmark feature of many genetic diseases. We will work to resolve both types of uncertainty for the autosomal dominant disorder, Alagille syndrome, which is caused by mutations in JAG1 and NOTCH2. We have developed an innovative, high-throughput assay to resolve missense variant classification, and we will utilize transcriptomics to better understand genotype- phenotype relationships that will ultimately provide guidance to clinicians and geneticists and develop tools and techniques that we can apply to other disease genes.

PI_NAMEs: SPINNER, NANCY BETTINA (contact)

PROGRAM_OFFICER_NAME: PAWLIKOWSKA, LUDMILA SYLWIA

PROJECT_TERMS: Accounting;Affect;Alagille Syndrome;Atlases;autosome;Benign;Biological Assay;Calibration;Cell Line;Cells;Childhood;Classification;Clinical;clinical diagnostics;ClinVar;Complex;Data;design;Detection;Development;Diagnosis;Diagnostic;Disease;disease-causing mutation;disorder control;DNA;Etiology;Evaluation;Exons;experimental study;Eye;Face;Facies;Formalin;Future;Gene Expression;Gene Expression Profile;Gene Expression Profiling;Genes;Genetic;Genetic Diseases;Genetic Variation;Genomic medicine;Genomics;Genotype;glycosylation;Heart;High Prevalence;high throughput screening;improved;Individual;innovation;Kidney;Knowledge;Libraries;Ligands;Liver;Liver diseases;liver transplantation;loss of function;Managed Care;Measures;Membrane;Mendelian disorder;Methodology;Methods;Missense Mutation;Modeling;Molecular;multiplex assay;mutant;Mutation;notch protein;Notch Signaling Pathway;Nucleotides;Paraffin Embedding;Pathogenicity;Patient Care;Patients;Persons;Phenotype;Positioning Attribute;Property;protein function;Protein Truncation;Proteins;Proteomics;receptor;Receptor Signaling;Reporter;Reporting;Resolution;sample fixation;Sampling;Series;Severity of illness;Signal Transduction;Site;spine bone structure;System;Techniques;Testing;Therapeutic;Tissue Sample;tool;transcriptomics;Uncertainty;Validation;Variant;variant of unknown significance;Work

PROJECT_TITLE: Resolving Uncertainty in Alagille Syndrome Diagnostics

STUDY_SECTION: GHD

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


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

ORG_CITY: TALLAHASSEE

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: FLORIDA STATE UNIVERSITY

ORG_STATE: FL

PHR: Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are two closely related viruses that cause thousands of deaths and hundreds of thousands of hospitalizations worldwide each year. There are no approved vaccines for either virus, although pre-fusion-stabilized RSV fusion (F) proteins have shown great promise in clinical trials. This proposal will determine if a chimeric F protein bearing immunodominant epitopes of both RSV and hMPV F proteins is protective in several animal infection models of RSV and hMPV.

PI_NAMEs: MOUSA, JARROD  (contact)

PROGRAM_OFFICER_NAME: KIM, SONNIE

PROJECT_TERMS: Acute;Advanced Development;African Green Monkey;Animal Model;Animals;Antibodies;Antigens;Cell surface;Cessation of life;Child;Childhood;Chimeric Proteins;Clinical Trials;Complex;Cotton Rats;COVID-19 pandemic;design;Development;Dose;Ensure;Enzyme-Linked Immunosorbent Assay;Epitope Mapping;Epitopes;evidence base;Glycoproteins;Goals;Hospitalization;Human Metapneumovirus;Immune;Immune response;Immunity;Immunodominant Epitopes;immunogenicity;Immunologics;improved;in vivo;Individual;Infection;innovation;Interferometry;Lower Respiratory Tract Infection;manufacture;Messenger RNA;Modeling;Monkeys;Monoclonal Antibodies;mouse model;mRNA lipid nano particle vaccine;mRNA Stability;Mus;neutralizing antibody;nonhuman primate;novel vaccines;permissiveness;Pneumovirus;pre-clinical;Pre-Clinical Model;protective efficacy;protein structure;Protein Subunits;Proteins;Rapid screening;Recombinant Proteins;Research;Research Personnel;Research Project Grants;respiratory pathogen;Respiratory syncytial virus;Respiratory syncytial virus RSV proteins;Rodent;Safety;SARS-CoV-2 spike protein;screening;Serology;Structure;success;synergism;Technology;Testing;Vaccinated;Vaccination;vaccine candidate;vaccine development;Vaccines;Viral;Viral Respiratory Tract Infection;Virus

PROJECT_TITLE: An immunodominance-based Pan-Pneumovirus vaccine for protection against RSV and hMPV

STUDY_SECTION: VID

STUDY_SECTION_NAME: Vaccines Against Infectious Diseases Study Section[VID]


NIH_SPENDING_CATS: Bioengineering;Data Science;Emerging Infectious Diseases;Infectious Diseases;Kidney Disease;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Organ Transplantation;Precision Medicine;Transplantation

ORG_CITY: DURHAM

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: BK virus is a common infection of immune-suppressed kidney transplant patients, leading in some cases to loss of the transplanted kidney. There is no effective anti-viral against BK virus and the standard practice is to reduce immunosuppression, which can itself lead to kidney rejection; hence the management of immunosuppression of these patients is very challenging. We propose to use existing data sets from NIH- funded transplantation clinical trials to develop mathematical models and optimal control algorithms of the dynamic interactions between the virus, the immune systems, and the transplanted kidney and to build a software tool for personalized immunosuppression in these patients.

PI_NAMEs: MCCARTHY, JANICE MARIE (contact);TRAN, HIEN T

PROGRAM_OFFICER_NAME: ROBIEN, MARK ANDREW

PROJECT_TERMS: Address;Adult;Affect;Algorithms;allograft rejection;Anti-viral Agents;BK Virus;Calibration;Characteristics;Childhood;Clinical;Clinical Data;Clinical Management;clinical practice;Clinical Treatment;Clinical Trials;Collaborations;Communicable Diseases;Complex;Consensus;control theory;cost;Coupled;Creatinine;Cytotoxic T-Lymphocytes;Data;Data Analyses;Data Science;Data Set;Data Sources;design;Development;Differential Equation;dosage;Dose;dynamic system;Effectiveness;Ensure;Equation;experience;flexibility;Funding;Goals;graft function;Graft Rejection;Human;Immune;Immune response;Immunologics;Immunology;immunoregulation;Immunosuppression;Immunosuppressive Agents;improved;Incidence;individual patient;Infection;innovation;Intervention;Kidney;kidney cell;Kidney Cell Infection;Kidney Diseases;Kidney Transplantation;Knowledge;Laboratories;Lead;Learning;Literature;Machine Learning;mathematical model;Mathematics;Measurement;Measures;Mediating;model development;Modeling;Modernization;Monitor;Morbidity - disease rate;National Institute of Allergy and Infectious Disease;neural network;novel;Opportunistic Infections;optimal control theory;Organ;Organ Transplantation;Outcome;Output;Patient Care;Patient-Focused Outcomes;Patients;personalized management;personalized medicine;Pharmaceutical Preparations;Physicians;post-transplant;predictive modeling;Proliferating;Publishing;Regimen;renal damage;Research;Risk;Sample Size;Schedule;software development;Software Tools;Solid;Specific qualifier value;standard of care;Statistical Methods;System;Testing;Therapeutic immunosuppression;Time;tool;Translating;transplant centers;Transplant Recipients;Transplantation;Transplantation and Immune System;United States National Institutes of Health;Validation;Viral;Viral Load result;Viremia;Virus;Virus Diseases;Withdrawal;Work

PROJECT_TITLE: Mathematical modeling for optimal control of BK virus infection in kidney transplant recipients

STUDY_SECTION: CDMA

STUDY_SECTION_NAME: Clinical Data Management and Analysis Study Section[CDMA]