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

ORG_CITY: CLEVELAND

ORG_DEPT: NUTRITION

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

PHR: PROJECT NARRATIVE Tumor differences between patients can hinder the prediction of therapeutic response in cancer, as patients with seemingly similar tumors often display varying levels of chemo-sensitivity or -resistance. This work aims to abandon the “one-drug-ﬁts-all” approach and produce a novel method for discovering biomarkers of therapeutic sensitivity and resistance in cancer. Our results will assist clinicians in choosing the best available treatment for each individual patient.

PI_NAMEs: SCARBOROUGH, JESSICA ANNE (contact)

PROGRAM_OFFICER_NAME: PURI, ANU

PROJECT_TERMS: bcr-abl Fusion Proteins;Biological Markers;Biological Models;cancer cell;Cancer cell line;cancer gene expression;cancer subtypes;cancer type;Cell Line;chemotherapy;Chronic Myeloid Leukemia;Clinical;Clinical Treatment;Collection;Data;Data Set;Databases;design;differential expression;Disease Progression;Drug resistance;drug sensitivity;effective therapy;Epidermal Growth Factor Receptor;Evolution;experimental study;Gene Expression;Gene Expression Profile;Gene Expression Profiling;gene product;Genes;Genomics;Genotype;Grouping;Imatinib;improved;Individual;individual patient;Inter-tumoral heterogeneity;interest;machine learning model;Malignant Neoplasms;Methods;Molecular;Molecular Profiling;Mutation;Network-based;Non-Small-Cell Lung Carcinoma;novel;novel strategies;Oncology;open data;Outcome;Patients;personalized approach;personalized care;personalized medicine;Pharmaceutical Preparations;Phenotype;Philadelphia Chromosome;precision medicine;Prediction of Response to Therapy;predictive tools;pressure;Process;Research;Research Personnel;Resistance;responders and non-responders;response;Sampling;Shapes;Somatic Mutation;Stochastic Processes;success;targeted treatment;Testing;The Cancer Genome Atlas;Therapeutic;therapy resistant;Time;Tissue-Specific Gene Expression;tool;treatment planning;treatment response;tumor;Work

PROJECT_TITLE: Exploiting convergent evolution to design biomarker extraction tools for the prediction of therapeutic response in cancer


ADMINISTERING_IC: CA

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

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

ORG_CITY: BOSTON

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: DANA-FARBER CANCER INST

ORG_STATE: MA

PHR: Project Narrative – Project 1 CHU-Toulouse / DFCI This project will help develop minimal residual disease (MRD)-based therapeutics and will investigate whether sustained MRD negativity will be of therapeutic importance. It will redefine, using genomic and epigenomic data, a new risk stratification model.

PI_NAMEs: AVET LOISEAU, HERVE  (contact)

PROJECT_TERMS: 17p;Address;Antibodies;arm;Biochemical;Bortezomib;cancer genomics;Categories;Chemicals;Clinical;Clinical Research;Clonality;cohort;Combined Modality Therapy;conventional dosing;Cox Models;Data;Dexamethasone;Diagnosis;Disease remission;Dose;epigenomics;follow-up;France;Frequencies;Funding;Genomics;Goals;Immune;immune modulating agents;Immunotherapy;improved;improved outcome;inhibitor therapy;lenalidomide;Maintenance;Maintenance Therapy;Measures;Melphalan;Modeling;Modernization;Multiple Myeloma;Mutation;Neoadjuvant Therapy;new therapeutic target;Newly Diagnosed;novel;Outcome;Patient-Focused Outcomes;Patients;Prognosis;Prognostic Factor;Prognostic Marker;Progression-Free Survivals;Proteasome Inhibitor;Quadruplet Multiple Birth;Randomized;relapse patients;Residual Neoplasm;Residual state;response;Risk;risk stratification;Role;standard of care;Therapeutic;transcriptome;Transplantation;treatment arm;Tumor Burden;Untranslated RNA;Vertebral column

PROJECT_TITLE: Project 1: Developing MRD-based therapeutic strategy in newly diagnosed multiple myeloma


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

PHR: Project Narrative – Project 2 Whitehead Institute at MIT Transcription is a fundamental cellular process whose proper regulation is essential to establishment and maintenance of healthy cell states. Recent discoveries suggest that this process involves dynamic formation and dissolution of biomolecular condensates, and how they are dysregulated in tumor cells. This project aims to provide new insights into dysregulation of transcriptional condensates in multiple myeloma cells, with the goal of enabling development of novel therapeutic molecules with improved efficacy and reduced toxicity.

PI_NAMEs: YOUNG, RICHARD  (contact)

PROJECT_TERMS: Antineoplastic Agents;Behavior;Binding;Biochemical;cancer genomics;Cell Physiology;Cells;chemical property;Chemicals;Chemistry;Chromosome Mapping;Cisplatin;cofactor;Development;DNA Binding Domain;DNA Repair;DNA-Directed RNA Polymerase;Drug Targeting;Enhancers;Environment;Epigenetic Process;epigenetic regulation;Feedback;Funding;Gene Expression;Gene Expression Regulation;Genes;Genetic Transcription;Goals;improved;insight;Maintenance;Mediating;Membrane;Modeling;Multiple Myeloma;neoplastic cell;novel therapeutics;Nucleic Acids;Oncogenes;Oncogenic;Organelles;Pharmaceutical Preparations;pharmacologic;Physical condensation;Physiological Processes;Process;programs;promoter;Property;Proteins;Regulation;RNA;RNA Binding;RNA Recognition Motif;Role;Site;small molecule;Specificity;Tamoxifen;Testing;Therapeutic;therapeutic development;Toxic effect;transcription factor;Transcriptional Activation Domain;Transcriptional Regulation;YY1 Transcription Factor

PROJECT_TITLE: Project 2: Investigating regulation of transcriptional condensates in multiple myeloma


PHR: Project Narrative – Project 3 Dana-Farber Cancer Institute This project will validate biologically relevant and clinically applicable lncRNAs in myeloma and investigate therapeutic agents directed at these targets, both alone and in combination, in vitro and in vivo for potential clinical consideration.

PI_NAMEs: ANDERSON, KENNETH C. (contact)

PROJECT_TERMS: Animal Model;Area;Automobile Driving;Back;Behavior;bench to bedside;Biological;Biological Models;Bone Marrow;c-myc Genes;cancer genomics;Cell Communication;cell growth;Cell Line;Cell Survival;Cells;Chromatin;Classification;Clinical;clinical application;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;Combined Modality Therapy;Complex;Dana-Farber Cancer Institute;Data;Data Set;Dependence;Development;differential expression;Disease;DNA-Protein Interaction;Drug resistance;Enzymes;Epigenetic Process;epigenomics;flexibility;Frequencies;Funding;gain of function;gene regulatory network;Genes;Genetic;Genetic Transcription;Genomics;Human;Human Genome;improved;In Vitro;in vivo;in vivo Model;inhibitor;Left;lipid biosynthesis;loss of function;Mediating;Metabolic;Modeling;Molecular;Molecular Target;Multiple Myeloma;neoplastic cell;next generation;novel;novel therapeutics;Oligonucleotides;Outcome;outcome prediction;Pathway interactions;Patient-Focused Outcomes;Patients;Play;pre-clinical;predict clinical outcome;Probability;Process;prognostic significance;Proliferating;protein B;Proteins;Reporting;Research;response;Ribonucleoproteins;Risk;Risk Marker;RNA;Role;scaffold;small molecule;small molecule inhibitor;Span 80;Specificity;Stromal Cells;targeted agent;Techniques;Therapeutic;Therapeutic Agents;therapeutic target;transcription factor;Transcriptional Regulation;transcriptome sequencing;transcriptomics;translational therapeutics;Translations;Untranslated RNA;Validation

PROJECT_TITLE: Project 3: Defining the biologic role and therapeutic implications of lncRNA in multiple myeloma


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Genetics;Hematology;Human Genome;Rare Diseases

PHR: Project Narrative – Project 4 Dana-Farber Cancer Institute The proposed studies will investigate key features of clonal complexity and evolution for their role in MM progression and elucidate mechanisms driving these processes. We will also investigate the role of PBK on clonal evolution and growth of MM cells and evaluate PBK inhibitor for impact on MM cell growth and survival and the mechanisms driving clonal evolution.

PI_NAMEs: MUNSHI, NIKHIL C. (contact)

PROJECT_TERMS: Architecture;Automobile Driving;cancer cell;cancer genomics;cell behavior;cell growth;Cell Survival;cell type;Cells;Characteristics;chemotherapy;Clonal Evolution;Code;Color;Complex;Dana-Farber Cancer Institute;Data;Diagnosis;Disease;Disease Progression;Disease-Free Survival;DNA Damage;DNA Repair;DNA Repair Gene;DNA Repair Pathway;Dose;drug resistance development;drug standard;epigenomics;Evolution;FOXM1 gene;Frequencies;Functional disorder;Funding;Genes;Genetic;genetic signature;Genome;Genome Stability;genome-wide;Genomic approach;Genomic Instability;Genomics;Goals;Growth;Heterogeneity;high risk;homologous recombination;improved;In Vitro;in vivo;kinase inhibitor;Left;loss of function;Malignant Neoplasms;Mediating;member;Modeling;mouse model;Multiple Myeloma;Mutation;Newly Diagnosed;Normal Cell;novel;Outcome;Pathway interactions;Patients;PDZ-binding kinase;Pharmaceutical Preparations;Phase;Phosphorylation;Phosphotransferases;premalignant;prevent;Process;Relapse;repaired;Reporting;Role;Sampling;Single base substitution;Subgroup;Therapeutic;Time;timeline;transcription factor;transcriptomics

PROJECT_TITLE: Project 4: Targeting genomic instability and evolution in myeloma


ADMINISTERING_IC: HL

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Atherosclerosis;Biotechnology;Cardiovascular;Genetics;Heart Disease;Heart Disease - Coronary Heart Disease;Human Genome;Prevention

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: PROJECT NARRATIVE An increased understanding of the molecular mechanisms underlying vascular calcification is fundamental in identifying novel therapeutic targets to treat a broad range of cardiovascular diseases. This proposal aims to elucidate the role of novel genes associated with coronary artery and aortic calcification in order to provide mechanistic insights on vascular disease. Defining the molecular underpinnings associated with vascular calcification will have important implications for the prevention and treatment of highly morbid vascular diseases.

PI_NAMEs: LEE, SUJIN  (contact)

PROGRAM_OFFICER_NAME: MEADOWS, TAWANNA

PROJECT_TERMS: abdominal aorta;adenoviral mediated;Aorta;Arylsulfatases;Atherosclerosis;Automobile Driving;Bioinformatics;Biological Assay;Biology;Blood Vessels;Bone Development;Bone Morphogenetic Proteins;calcification;Cardiovascular Diseases;cardiovascular risk factor;career;cartilage development;Cell Physiology;Cells;Cellular Assay;Code;Cohort Studies;Communication;Coronary;Coronary Arteriosclerosis;Coronary artery;coronary artery calcification;Cultured Cells;Cytosol;Data;Disease;Esters;Event;Experimental Models;experimental study;Family;Fellowship;Focal Adhesion Kinase 1;Funding;Genes;genome wide association study;genome-wide;Genomics;Goals;HDAC4 gene;HDAC5 gene;HDAC9 gene;Histone Deacetylase;In Vitro;in vivo;Individual;inhibitor;insight;kinase inhibitor;knock-down;Knockout Mice;Laboratories;Leadership;Mediating;member;Mentorship;Methods;Modeling;Molecular;Morbidity - disease rate;mortality;mouse model;mRNA Expression;Myocardial Infarction;new therapeutic target;novel;Nuclear;Osteogenesis;osteogenic;overexpression;Pathogenesis;Pathology;Peripheral arterial disease;pharmacologic;Phenotype;Phosphorylation;Play;prevent;Prevention;Process;programs;Protein Family;Proteins;Regulation;Research;Risk Factors;Role;Scientist;Signal Pathway;Signaling Protein;Single Nucleotide Polymorphism;skills;Small Interfering RNA;Smooth Muscle Myocytes;Stroke;Sulfatases;Sulfate;Surgeon;targeted treatment;Testing;transcription factor;United States National Institutes of Health;Variant;Vascular calcification;Vascular Diseases;Vascular Smooth Muscle;X Chromosome

PROJECT_TITLE: Novel Molecular Regulators of Vascular Calcification


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Genetics;Hematology;Human Genome;Orphan Drug;Precision Medicine;Rare Diseases

PHR: Project Narrative – Core 1 – Administrative Core Dana-Farber Cancer Institute The core will provide a central integrative function, monitoring conduct of international clinical trial and sample collection and processing, providing effective communication between investigators.

PROJECT_TERMS: Address;Advisory Committees;Algorithms;Autologous Stem Cell Transplantation;Basic Science;Behavior;Cancer Center;cancer genomics;Clinical;Clinical Research;Clinical Trials;Collaborations;collaborative trial;Communication;Dana-Farber Cancer Institute;data exchange;Dependence;Disease;Dose;epigenomics;France;Genetic Transcription;Genomic Instability;Genomics;Goals;Grant;Innovative Therapy;Institution;International;Laboratories;Link;Massachusetts;meetings;Melphalan;Molecular;Molecular Abnormality;molecular targeted therapies;Monitor;Multiple Myeloma;new therapeutic target;next generation;Oncogenic;Outcome;Patients;Physical condensation;pre-clinical;programs;Regulation;Research;Research Personnel;Research Project Grants;Resources;RNA;Role;sample collection;Sampling;Science;Site;survival outcome;Technology;Therapeutic;Tissue Banks;transcription factor;translational medicine;Translational Research;Travel;Untranslated RNA

PROJECT_TITLE: Core 1: Administrative Core


ADMINISTERING_IC: NS

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Cancer;Immunotherapy;Neuroblastoma;Neurosciences;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: LA JOLLA

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

ORG_STATE: CA

PHR: Project Narrative Neuroblastoma is a pediatric extra-cranial solid tumor and despite extensive multimodal treatments, most of the high-risk pediatric patients develop progressive disease. Hence, there is critical need to develop novel therapies for neuroblastoma. The goal of this proposal is to study the mechanistic roles of Syk in the regulation of tumor growth and immunosuppression and to evaluate the potential of Syk inhibitors in combination with immunotherapy and radiotherapy for the treatment of high-risk neuroblastoma.

PI_NAMEs: JOSHI, SHWETA  (contact)

PROGRAM_OFFICER_NAME: KOTLIAROVA, SVETLANA

PROJECT_TERMS: adaptive immune response;adaptive immunity;anti-PD-1;anti-PD-L1;anti-tumor immune response;arginase;Bone Marrow;CD8-Positive T-Lymphocytes;Cell Line;Cells;Cephalic;checkpoint therapy;Child;Childhood Extracranial Solid Tumor;Clinical;combinatorial;Combined Modality Therapy;cytotoxic;cytotoxic CD8 T cells;Data;Disease;driving force;enhancer binding protein;Failure;Genetic;Genetic Transcription;Goals;high risk;high risk population;Histology;Hypoxia Inducible Factor;hypoxia inducible factor 1;Immune;immune cell infiltrate;immune checkpoint blockade;Immune checkpoint inhibitor;Immunologic Memory;Immunologic Stimulation;Immunologics;Immunooncology;Immunosuppression;Immunotherapy;Implant;improved;improved outcome;In Vitro;Infiltration;Inflammatory;Innate Immune Response;Interleukin-10;Knockout Mice;Knowledge;Laboratories;Macrophage;Malignant Childhood Neoplasm;Mediating;Molecular;Monoclonal Antibodies;mouse model;Mus;Mutation;MYCN gene;Myelogenous;Neoplasm Metastasis;neoplastic cell;Neuroblastoma;novel;novel therapeutic intervention;novel therapeutics;Oncogenes;patient stratification;Patient-Focused Outcomes;Patients;pediatric patients;pharmacologic;Phenotype;Phosphotransferases;Ploidies;Population;predicting response;Prognosis;Progressive Disease;Radiation therapy;recruit;Regulation;Research;Resistance;Role;Signal Pathway;Signal Transduction;standard care;standard of care;SYK gene;synergism;T cell response;T-Lymphocyte;Testing;transcriptomics;Transforming Growth Factor beta;Treatment Failure;tumor;tumor growth;tumor microenvironment;tumor progression;Tumor Promotion;Tumor-associated macrophages;tumor-immune system interactions;Tyrosine Kinase Inhibitor

PROJECT_TITLE: Targeting Syk to enhance anti-tumor immune responses in neuroblastoma

STUDY_SECTION: CII

STUDY_SECTION_NAME: Cancer Immunopathology and Immunotherapy Study Section[CII]


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Radiation Oncology

ORG_CITY: Aurora

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: PROJECT NARRATIVE Cone beam computed tomography (CBCT) is the most commonly used volumetric image guidance modality in radiation therapy. A major drawback of CBCT is its poor image quality, which prevents its use in treatment monitoring and adaptations to personalize radiation therapy. In this project, we propose a novel solution, two- dimensional antiscatter grid, to improve CBCT image quality to levels that has not been achieved previously. Successful completion of our project can open the path to CBCT-based treatment monitoring and adaptations, and therefore, can enable personalized radiation therapy for large patient populations.

PI_NAMEs: ALTUNBAS, CEM  (contact)

PROGRAM_OFFICER_NAME: OBCEMEA, CEFERINO H

PROJECT_TERMS: Address;Affect;Algorithms;Anatomy;Architecture;Area;Belgium;Cancer Patient;Clinical;clinical decision-making;Clinical Trials;Collaborations;Colorado;computerized data processing;cone-beam computed tomography;Data;design;Development;Devices;Disease;Dose;Evaluation;experimental study;fabrication;Florida;Geometry;Health;Image;image guided;image registration;Image-Guided Surgery;improved;individualized medicine;Intervention;Interventional radiology;Investigation;Ions;Limb structure;Manufacturer;maxillofacial;Measures;medical schools;Methods;Modality;Modification;Monitor;Noise;Normal tissue morphology;novel;Orthopedics;patient population;Patients;Performance;Photons;Play;Prediction of Response to Therapy;prevent;prospective;proton therapy;prototype;Radiation Dose Unit;radiation response;Radiation Scattering;Radiation therapy;radiomics;Regimen;Reporting;Role;Scanning;Site;soft tissue;Software Tools;Spiral Computed Tomography;Structure;System;Technology;Testing;Texture;Tissues;tool;Toxic effect;transmission process;Treatment Protocols;Treatment-related toxicity;tumor;Tumor Tissue;two-dimensional;Universities;Variant;Visualization;Work

PROJECT_TITLE: Improving quantitative accuracy and tissue visualization in CBCT guided radiation therapy

STUDY_SECTION: RTB

STUDY_SECTION_NAME: Radiation Therapeutics and Biology Study Section[RTB]


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Genetics;Hematology;Human Genome;Networking and Information Technology R&D (NITRD);Rare Diseases

PHR: Project Narrative – Core 2 – Clinical and Tissue Core CHU-Toulouse / DFCI This core will help collect data, procure, process and store tissue samples and develop a integrated database to collect and store data from various sources.

PROJECT_TERMS: Acceleration;Age;Architecture;Biological;Biological Specimen Banks;Biomedical Research;Blood specimen;Bortezomib;cancer genomics;Cells;central database;Clinical;Clinical Data;clinical database;clinical practice;Clinical Protocols;Clinical Research;Clinical Trials;Clinical Trials Database;clinically relevant;Collection;comparative effectiveness;Complex;complex data;Computerized Medical Record;Confidential Information;Dana-Farber Cancer Institute;Data;Data Analyses;data integration;data modeling;data repository;Data Sources;Databases;Dexamethasone;DNA;DNA sequencing;Dose;Epidemiology;Floods;Funding;Future;Genetic;genomic data;Genomics;Goals;graphical user interface;Health;Human Characteristics;human disease;Institution;Intuition;lenalidomide;Link;Modernization;Molecular Genetics;Monoclonal gammopathy of uncertain significance;Multiple Myeloma;next generation;Online Systems;Patients;Plasma;preservation;Procedures;Process;programs;Public Domains;Publications;Quality Control;Research;Research Personnel;Research Support;Resources;response;RNA;Sampling;Secure;Serum;Site;Source;Standardization;Structure;System;Technology;Thalidomide;Tissue Banks;Tissue Sample;Tissues;Training;transcriptome sequencing;Transplantation;Treatment Protocols;tumor;web portal;Work

PROJECT_TITLE: Core 2 - Clinical and Tissue Core


ADMINISTERING_IC: AI

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Maternal Health;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Vector-Borne Diseases;Women's Health Research

ORG_CITY: PITTSBURGH

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: PROJECT NARRATIVE Bunyaviruses, such as Rift Valley fever (RVFV), Cache Valley (CVV), and Schmallenberg viruses (SBV), cause significant fetal death and abnormalities in ruminants. RVFV infection in humans is associated with late term miscarriage and still births, however it is unclear whether CVV, SBV and a related bunyavirus, La Crosse virus (LACV), can undergo vertical transmission in humans. This proposal will utilize human, sheep, and rat placenta ex plants and human trophoblast organoid models to identify host and virus factors that influence tropism and pathologies associated with congenital bunyavirus infection.

PI_NAMEs: MCMILLEN, CYNTHIA  (contact)

PROGRAM_OFFICER_NAME: ALARCON, RODOLFO M

PROJECT_TERMS: Affect;Agriculture;animal facility;Anti-viral Response;Apoptosis;Apoptotic;Arboviruses;Autophagocytosis;Biological Models;Biological Response Modifiers;Birth;Bunyavirus Infections;Cache Valley virus;career;career development;Cell Death;Cells;Cellular Tropism;Communities;congenital infection;Containment;COVID-19 pandemic;Culicidae;Data;Development;Development Plans;Disease;Economics;Emerging Communicable Diseases;Environment;Event;experience;fetal;Fetal Death;Gene Expression;Generations;Genetic;Goals;Health;high risk;Human;Immune response;Immunology;In Vitro;Infection;Inhibition of Apoptosis;Innate Immune Response;Integration Host Factors;Interferon Type I;Interferons;Investigation;Knock-out;La Crosse virus;Laboratories;laboratory facility;Life;Livestock;Maternal-Fetal Exchange;Mediating;Mediator;Medical;Mentors;Mentorship;Modeling;multiple myeloma M Protein;Natural Immunity;Nature;Nonstructural Protein;novel;Organoids;Orthobunyavirus;Pathogenesis;Pathology;Pathway interactions;permissiveness;Placenta;Placental Biology;placental infection;Plants;Predisposition;pregnant;Pregnant Women;prevent;Process;Productivity;programs;Proteins;prototype;Rattus;Research;responsible research conduct;Rift Valley Fever;Rift Valley fever virus;Ruminants;Scientist;Severities;Sheep;Spontaneous abortion;Syncytiotrophoblast;System;Teratogens;tissue tropism;Tissues;Training;training opportunity;transmission process;trophoblast;Tropism;Universities;Vertical Transmission;Viral;Viral Pathogenesis;Virulence Factors;Virus;Virus Diseases;Virus Replication;zoonotic spillover

PROJECT_TITLE: Host and Viral Determinants of Orthobunyavirus Vertical Transmission: Novel Model Systems to Understand the Mechanisms of Congenital Disease in Humans and Ruminants

STUDY_SECTION: MID

STUDY_SECTION_NAME: Microbiology and Infectious Diseases B Research Study Section[MID-B]


ORG_NAME: BOSTON UNIVERSITY MEDICAL CAMPUS

PHR: Project Narrative Vitamin A deficiency (VAD) results in epithelial injury and an increased risk and severity of lung infections in mammals, yet the mechanisms associated with microbe-microbe, host-microbe, and microbe-diet interactions involved in the observed VAD lung pathology remains unknown. We propose to investigate the role of dietary vitamin A and its derivatives on the microbial composition, biofilm formation, and metabolic changes in differentially expressed microbes in VAD lungs compared to controls. The proposed study aims to identify and characterize novel host-microbe and microbe-microbe interactions critical for lung health that are dysregulated in vitamin A deficient lungs.

PI_NAMEs: QUILES, KILONI  (contact)

PROGRAM_OFFICER_NAME: ESPINOZA-PINTUCCI, MARISOL

PROJECT_TERMS: Adult;Affect;airway epithelium;airway immune response;antimicrobial;Asthma;Biology;Bronchoalveolar Lavage Fluid;Cell Culture Techniques;Cells;Chronic Obstructive Pulmonary Disease;Collection;Communities;comparison control;Complex;Core Facility;Data;design;Diet;dietary;differential expression;Disease;Distal;dysbiosis;Ecosystem;Environment;epithelial injury;Epithelium;Event;Exhibits;Exposure to;fluorescence imaging;Functional disorder;Future;Gene Expression;Genes;germ free condition;gut dysbiosis;gut microbiome;Health;Homeostasis;host-microbe interactions;Human;Immune;immune function;Impairment;in silico;In Vitro;in vivo;Injections;interest;Knowledge;Laboratories;Link;Lower respiratory tract structure;Lung;Lung Diseases;lung health;Lung infections;lung injury;lung microbiome;machine learning algorithm;Maintenance;Malnutrition;Mammals;Measures;Mediating;Metabolic;Metabolic Pathway;Metabolism;metatranscriptomics;Microbe;microbial;Microbial Biofilms;microbial colonization;microbial composition;microbial homeostasis;microbiome;Microscope;Microscopy;Modeling;Motility;Mucociliary Clearance;Mucous Membrane;Mus;Natural regeneration;next generation sequencing;novel;Outcome;Paraffin Embedding;Pathogenesis;Pathology;Pathway interactions;Patients;Pattern;Peer Review;permissiveness;Phenotype;Physiological Processes;programs;protein expression;protein structure;Protocols documentation;Publishing;pulmonary function;Pulmonary Pathology;Quantitative Reverse Transcriptase PCR;repaired;Respiratory Disease;Respiratory Tract Infections;Risk;RNA;Role;SARS-CoV-2 infection;Severities;Sterility;Structure of parenchyma of lung;System;Systems Biology;Techniques;Technology;Testing;Time;Tissue Stains;Tissues;Trachea;Tracheal Epithelium;Transcript;Tretinoin;Tuberculosis;Viral;Vitamin A;Vitamin A Deficiency;Work

PROJECT_TITLE: Microbial Dysbiosis and Epithelial Dysfunction in Vitamin A-deficient Lungs


PHR: Project Narrative – Core 3 – Epigenomics Core Broad Institute The mission of this Core is to provide data on epigenomic profile in clinical and preclinical samples using a standardized approach.

PI_NAMEs: EPSTEIN, CHARLES B (contact)

PROJECT_TERMS: Adopted;Algorithms;ATAC-seq;Bar Codes;cancer genomics;Cell Count;Cells;ChIP-seq;Chromatin;Chromatin Structure;Clinical;Clinical Trials;Code;cofactor;Data;Development;Diagnosis;Distal;Enhancers;Epigenetic Process;epigenomics;Gene Expression;Gene Expression Regulation;Genetic Enhancer Element;Genomics;Goals;histone modification;improved;indexing;innovation;Maps;Methods;Mission;Modification;Molecular;multimodal data;Multiple Myeloma;multiple omics;neoplastic cell;new therapeutic target;Oncogenic;participant enrollment;Physical condensation;pre-clinical;Procedures;programs;Regulatory Element;Relapse;RNA;Sampling;Standardization;Therapeutic;Time;Transcript;transcription factor;transcriptomics;tumor;Untranslated RNA;Variant;Work;XCL1 gene

PROJECT_TITLE: Core 3 - Epigenomics Core


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Cancer

ORG_CITY: NEW YORK

ORG_DEPT: PATHOLOGY

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because dysregulation of cell cycle initiation results in human diseases, such as cancer and degenerative disorders. Outcomes from this research will provide new insights into alternate mechanisms of cell cycle entry that will pinpoint novel targets for therapeutic interventions for cancer and degenerative diseases. Thus, this proposal is relevant to NIGMS’s mission to drive and foster innovative research and strategies to ultimately protect human health.

PI_NAMEs: YANG, HEE WON  (contact)

PROGRAM_OFFICER_NAME: WAIRKAR, YOGESH PRABHAKAR

PROJECT_TERMS: Abnormal Cell;Binding;Biochemical;Bypass;c-myc Genes;cancer cell;Cancer Intervention;cancer type;cdc Genes;CDK2 gene;CDK4 gene;Cell Cycle;Cell Cycle Regulation;Cell Line;Cell Physiology;Cell Proliferation;Cells;cellular imaging;Classification;Clinical;Data;Degenerative Disorder;Deubiquitinating Enzyme;Development;developmental disease;E2F transcription factors;Event;Fostering;Foundations;Gene Expression;Genetic;genetic approach;Genetic Transcription;Goals;Health;Heterogeneity;Human;human disease;Imaging technology;In Vitro;in vivo;inhibitor;inhibitor therapy;innovation;insight;Investigation;Left;Maintenance;Malignant Neoplasms;Mammalian Cell;Mediating;Methodology;Mission;Molecular;multicatalytic endopeptidase complex;Mutation;National Institute of General Medical Sciences;new therapeutic target;novel;novel therapeutic intervention;Organism;Outcome;Outcomes Research;Pathway interactions;pharmacologic;Phosphorylation;Phosphotransferases;Play;Population;Post-Translational Protein Processing;Process;programs;protein activation;protein degradation;protein expression;Protein Family;Proteins;Public Health;Regulation;Reporter;Reporting;Research;Resistance;response;Retinoblastoma Protein;Role;sensor;Signal Transduction;single cell technology;Stress;success;Testing;Tissues;Tumor Suppressor Genes;Ubiquitin;ubiquitin isopeptidase;ubiquitin-protein ligase

PROJECT_TITLE: Deciphering the mechanism of non-canonical cell cycle entry

STUDY_SECTION: CSRS

STUDY_SECTION_NAME: Cellular Signaling and Regulatory Systems Study Section[CSRS]


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

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

ORG_CITY: AUSTIN

ORG_DEPT: MISCELLANEOUS

ORG_NAME: UNIVERSITY OF TEXAS AT AUSTIN

ORG_STATE: TX

PHR: PROJECT NARRATIVE Patients with the congenital defect of bicuspid aortic valve (BAV) develop aortic stenosis (AS) earlier and more often than patients with normal tricuspid aortic valves (TAV), which adversely affects BAV patients’ length and quality of life. The goal of this study is to understand changes in biochemical signaling that occur in the major cell type of valves, valve interstitial cells, due to abnormal deformation patterns present in BAVs. Two-photon microscopy of excised valves, proteomics-based steady state biochemical modeling, and 3D biaxial oscillatory stretch screens will be employed to determine the relationships between micromechanical environments and biochemical signaling cascades so that novel pharmacological targets for AS can be identified.

PI_NAMEs: WEST, TONI MCCLISH (contact)

PROGRAM_OFFICER_NAME: CHEON, YEWON

PROJECT_TERMS: 3-Dimensional;Actins;Address;Affect;Age;Anatomy;aortic valve;aortic valve disorder;aortic valve replacement;Aortic Valve Stenosis;Architecture;Basal Cell;bicuspid aortic valve;biobank;Biochemical;biochemical model;biomechanical model;Body System;Cell Physiology;Cell Shape;cell type;Cells;Cellular Morphology;Clinical;Commissure;conditioning;Congenital Abnormality;Cytoskeleton;Data;Development;Disease;Disease Progression;Early Diagnosis;Early identification;Echocardiography;effective therapy;Environment;Ethylenes;Event;experience;experimental study;Exposure to;Extracellular Matrix;Fellowship;Gel;Glycols;Goals;Heart Valves;Human;Image;In Situ;interstitial cell;Investigation;Lead;Legal patent;Length;Link;malformation;mathematical model;Measures;mechanical signal;Mechanics;Mediating;metaplastic cell transformation;Microscopy;Modeling;Morbidity - disease rate;Morphology;mortality;Myofibroblast;novel;Nuclear;Organ;Pathway interactions;Patients;Pattern;Periodicity;Persons;pharmacologic;Pharmacological Treatment;Phenotype;Procedures;Process;Proteins;Proteomics;Quality of life;Research;Research Personnel;response;Risk;Role;Running;Sampling;Series;Sex Differences;Signal Transduction;Smooth Muscle;Stimulus;Stretching;System;Texas;therapeutic target;Tissues;Training;transcription factor;Transforming Growth Factor beta;Travel;treatment strategy;two photon microscopy;Universities;valve replacement;Work

PROJECT_TITLE: Cyclic stretch of bicuspid aortic valves: elucidating its implications for cell signaling and tissue mechanics.


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Genetics;Hematology;Human Genome;Rare Diseases

PHR: Project Narrative – Core 4 – Genome Sequencing Core Dana-Farber Cancer Institute The core will perform high output whole genome bulk and single cell sequencing, uniformly analyze clinical sample both to investigate for genomic changes in MM at the time of diagnosis and at relapse and correlate changes in MM with various clinical groups as well as identify clonal complexity and variations and mutational signatures operative in myeloma.

PI_NAMEs: LOHR, JENS G (contact)

PROJECT_TERMS: analysis pipeline;Base Pairing;Bioinformatics;Cancer Center;cancer genome;cancer genomics;Cell Count;cell free DNA;Cells;Clinical;Code;cost effective;Dana-Farber Cancer Institute;Data;Data Analyses;data modalities;Diagnosis;DNA;DNA methylation profiling;DNA sequencing;DNA Sequencing Facility;Evolution;flexibility;Future;Genes;genome sequencing;genome-wide;Genomic Segment;Genomics;Goals;improved;Individual;Informatics;innovation;instrument;Laboratories;Methylation;Multiple Myeloma;Mutation;Newly Diagnosed;next generation sequencing;novel sequencing technology;Output;Patients;Process;Relapse;Resolution;Running;Sampling;Sampling Studies;Science;Sequence Analysis;sequencing platform;single cell genomics;single cell sequencing;Standardization;Subgroup;targeted sequencing;Technology;Testing;Time;Untranslated RNA;Variant;whole genome

PROJECT_TITLE: Core 4 - Genome Sequencing Core


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Autoimmune Disease;Bioengineering;Clinical Research;Crohn's Disease;Digestive Diseases;Genetics;Infectious Diseases;Inflammatory Bowel Disease;Nutrition

ORG_CITY: CAMBRIDGE

ORG_NAME: BROAD INSTITUTE, INC.

PHR: PROJECT NARRATIVE Intestinal inflammatory diseases, such as ulcerative colitis and Crohn’s disease are a substantial public health burden. This proposal will identify the cellular and tissue dynamics underlying homeostasis in the small intestine and colon and how these dynamics are disrupted due to inflammation. Through generation of spatial maps allowing for comparison across many intestinal inflammatory diseases and validation of these high-resolution maps in model systems, this research is designed to inform treatment of these inflammatory diseases, including the development of therapeutics.

PI_NAMEs: UHLER, CAROLINE ;XAVIER, RAMNIK J (contact)

PROGRAM_OFFICER_NAME: RAVICHANDRAN, VEERASAMY

PROJECT_TERMS: Anatomy;Atlases;Biological Models;Biology;Celiac Disease;Cell Communication;Cell model;Cell Physiology;cell type;Cells;Clinical Pathology;clinically significant;Coculture Techniques;Colon;Complex;Complication;Computer Analysis;computerized tools;Computing Methodologies;Crohn's disease;Cues;design;Development;Diet;dietary;Dietary Component;Dietary Factors;Disease;Dissection;Enteric Nervous System;enteric pathogen;Environment;eosinophilic gastroenteritis;Epithelial Cells;Equilibrium;Extracellular Matrix;Fibroblasts;Fibrosis;Gastrointestinal Diseases;Gene Expression;Gene Expression Profile;Gene Expression Profiling;Generations;genetic risk factor;Genetic Transcription;Goals;Gut Mucosa;Health;Helminths;Homeostasis;Human;human disease;Immune;Immunity;In Situ;Infection;Inflammation;Inflammatory;Inflammatory Bowel Diseases;Inflammatory Response;innovation;intercellular communication;Intestinal Mucosa;Intestines;Knowledge;Location;Maps;Metabolism;Methods;Microbe;microbiome;Modeling;Molecular;mouse model;Mucosal Immunity;Mucous Membrane;Mus;Neurons;novel;Nuclear RNA;Organoids;pathogen;Pathology;Pathway interactions;Physiological;Physiology;Portraits;Process;programs;protein expression;Public Health;Recovery;Refractory Disease;Research;resident commensals;Resolution;response;Sampling;Sensory;Signal Transduction;Small Intestines;spatial integration;spatiotemporal;Stimulus;Stress;System;Technology;temporal measurement;therapeutic development;Tissues;transcriptome sequencing;Translating;Ulcerative Colitis;Validation;Xenobiotics

PROJECT_TITLE: Spatial and temporal resolution to dissect cellular circuits controlling intestinal physiology, immunity, and inflammatory pathologies


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Genetics;Hematology;Human Genome;Orphan Drug;Precision Medicine;Rare Diseases

PHR: Project Narrative – Core 5 – Biostatistics and Bioinformatics Core Dana-Farber Cancer Institute This core will help analyze a large, randomized phase III study comparing two consolidation treatment schedules for MRD negative patients to determine the role of HDT and role of single versus tandem HDT for MRD positive patients to inform therapeutic approaches. The core will provide bioinformatic support to unravel and integrate the genomic changes to better understand disease biology, features predictive of progression and define those changes able to predict outcome and inform the development of novel therapeutics.

PI_NAMEs: PARMIGIANI, GIOVANNI LUIGI (contact)

PROJECT_TERMS: Address;Autologous Stem Cell Transplantation;Basic Science;Behavior;Bioinformatics;Biology;Biometry;cancer genomics;Cells;Clinical;Clinical Research;Clinical Trials;clinically relevant;Collaborations;Color;Dana-Farber Cancer Institute;Data;Data Analyses;data exchange;data warehouse;Databases;Dependence;design;Development;Diagnosis;Disease;Disease remission;DNA Sequence Alteration;epigenomics;Evaluation;Funding;Genetic Transcription;Genomics;Goals;Grant;Heterogeneity;High Dose Chemotherapy;high throughput analysis;Immunotherapy;Individual;International;Maintenance;Maintenance Therapy;Mediating;member;Methods;Multiple Myeloma;Neoadjuvant Therapy;next generation;next generation sequencing;novel strategies;novel therapeutics;Oncogenic;outcome prediction;Patients;phase 3 study;Phase III Clinical Trials;Physical condensation;pre-clinical;Procedures;Process;programs;Quality Control;Randomized;Regulation;Research;Research Personnel;Resistance;Resolution;response;Risk;RNA;RNA Binding;Role;Sampling;Site;Specimen;Stratification;success;survival outcome;Therapeutic;Tissue Banks;transcriptomics;Treatment Protocols;Work;Writing

PROJECT_TITLE: Core 5 - Biostatistics and Bioinformatics Core


NIH_SPENDING_CATS: Biotechnology;Breast Cancer;Cancer;Cancer Genomics;Clinical Research;Genetics;Human Genome;Immunotherapy;Women's Health Research

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: PROJECT NARRATIVE Breast cancer is the leading cause of death due to cancer in women and triple negative breast cancer has the worst prognosis of all major types of breast cancer. A patient's own immune system plays an important role in the efficacy of certain cancer treatments, such as immunotherapy. A better understanding of the role of B-cells (a major component of the immune system) in triple negative breast cancer may lay the foundation for improved immunotherapies or prognostic tools.

PI_NAMEs: DOWNS-CANNER, STEPHANIE M (contact)

PROGRAM_OFFICER_NAME: BIAN, YANSONG

PROJECT_TERMS: Active Learning;Affinity;anti-tumor immune response;Antibodies;Antibody Affinity;Antibody Formation;Antibody Response;Antigen Presentation;Antigen Targeting;Antigens;Antitumor Response;Award;B-Cell Activation;B-Cell Antigen Receptor;B-Lymphocyte Subsets;B-Lymphocytes;Bioinformatics;Biological Markers;Biology;Breast Cancer cell line;Breast Cancer Model;breast surgery;Cancer Etiology;cancer therapy;cancer type;career development;Caring;Cause of Death;Cell Physiology;Cell Therapy;Cells;Cellular biology;Cellular Immunology;Cessation of life;checkpoint inhibition;checkpoint therapy;chemotherapy;Clinical;Clonal Expansion;Clone Cells;Cloning;Complex;cytokine;Data;Data Set;Development;Development Plans;diagnostic strategy;Environment;Epitopes;Experimental Designs;Face;Foundations;Funding;Generations;genetic signature;Goals;Human;Immune;Immune system;Immunoglobulin Somatic Hypermutation;Immunotherapy;improved;improved outcome;Infiltration;insight;Invaded;Knowledge;Light;Malignant Breast Neoplasm;Malignant Neoplasms;Mass Spectrum Analysis;Mediating;meetings;Mentors;Monoclonal Antibodies;Mus;neoantigens;neoplasm immunotherapy;novel;overexpression;pathogenic microbe;Patients;Persons;Phenotype;Physicians;Plasmablast;Play;pre-clinical;Principal Investigator;Production;Prognosis;prognostic tool;programs;Proliferating;Protein Fragment;Reaction;Records;Research;response;Role;Sampling;Scientific Advances and Accomplishments;Scientist;side effect;single cell sequencing;single-cell RNA sequencing;standard care;Structure;Structure of germinal center of lymph node;success;Surgeon;Surgical Oncologist;symposium;T cell response;T-Lymphocyte;Techniques;Testing;The Cancer Genome Atlas;Therapeutic;Training;transcriptome sequencing;triple-negative invasive breast carcinoma;tumor;Tumor Antigens;Tumor Immunity;tumor microenvironment;Tumor-Infiltrating Lymphocytes;Woman;Women's mortality;Work

PROJECT_TITLE: The role of B-cells in the anti-tumor immune response in triple negative breast cancer

STUDY_SECTION: NCI

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


ADMINISTERING_IC: MH

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Biotechnology;Clinical Research;Clinical Trials and Supportive Activities;Drug Abuse (NIDA only);Emerging Infectious Diseases;HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Immunization;Infectious Diseases;Mental Health;Prevention;Social Determinants of Health;Substance Misuse;Vaccine Related

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: PROJECT NARRATIVE This project will investigate the influence of vaccine characteristics, information in the community, vaccination norms, and public health policies on the intention to receive an HIV vaccine should it be approved. It will inform vaccination policy and communications more generally with respect to other adolescent and adult vaccines.

PI_NAMEs: ALBARRACIN, DOLORES  (contact)

PROGRAM_OFFICER_NAME: STIRRATT, MICHAEL JAMES

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Adolescent;Adult;Affect;Area;Attitude;Basic Science;Behavior Control;behavior measurement;Behavioral;Belief;Caring;Characteristics;cohort;Communication;Communities;County;COVID-19;COVID-19 vaccination;Data;Data Sources;design;Disease;Ecology;Economics;Education;Enrollment;ethnic minority;evidence base;Evolution;experience;experimental study;Family;Friends;Funding;Future;Goals;health communication;Health Policy;Health system;Hepatitis A;HIV;HIV prevention trial;HIV vaccine;HIV Vaccine Trials Network;Homophobia;Impairment;Individual;Infection;Influenza;innovation;Institutional Racism;Intention;Knowledge;Lesbian Gay Bisexual Transgender;Link;Longitudinal Surveys;Measures;Mediating;Mediator;Medicine;men;men who have sex with men;Misinformation;Modeling;novel vaccines;Outcome;Participant;Pattern;peer;Pennsylvania;Pharmaceutical Preparations;Phase;Policies;Politics;Population;Positioning Attribute;pre-exposure prophylaxis;Prevalence;Privacy;Process;Psychology;Public Health;Public Policy;Randomized;Recommendation;recruit;regional difference;Registries;Religion;Research;Risk;Sampling;Science;seropositive;Services;Severities;Shapes;social media;social stigma;Source;stem;Surveys;Testing;Time;Trust;University resources;uptake;Vaccinated;Vaccination;vaccine development;vaccine hesitancy;vaccine platform;vaccine safety;vaccine trial;Vaccines;young man

PROJECT_TITLE: Understanding the Regional Ecology of a Future HIV Vaccine


NIH_SPENDING_CATS: Aging

ORG_CITY: SAN DIEGO

ORG_NAME: SCINTILLON INSTITUTE FOR PHOTOBIOLOGY

PHR: Narrative We propose to develop novel methodologies to enable modulation of the cellular redox environment with spatiotemporal precision. The methodology will be based on native or engineered enzymes that will be amendable to targeting to different cellular compartments. Our tools will lead to a better understanding of the role of redox imbalance in disease processes and hold therapeutic promise for reversing metabolic imbalances.

PI_NAMEs: CRACAN, VALENTIN  (contact)

PROGRAM_OFFICER_NAME: ANSONG, CHARLES KWAKU

PROJECT_TITLE: Expanding the set of genetically encoded tools for compartment-specific manipulation of redox metabolism in living cells

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CB-H(55)R]


NIH_SPENDING_CATS: Cancer;Cervical Cancer;Genetics;Infectious Diseases;Prevention;Sexually Transmitted Infections;Women's Health Research

ORG_CITY: MANHATTAN

ORG_DEPT: BIOLOGY

ORG_NAME: KANSAS STATE UNIVERSITY

ORG_STATE: KS

PHR: The proposed research is relevant to public health because it is a necessary step towards improving cervical cancer care and prevention by understanding fundamental aspects of the HPV oncogenes that cause cervical cancer, by testing the hypothesis that HPV oncogenes make DNA damage more mutagenic. The project is relevant to the mission of the National Cancer Institute and the R21 mechanism as it will provide preliminary data for an R01 proposal.

PI_NAMEs: WALLACE, NICHOLAS A (contact)

PROJECT_TERMS: Address;Alu Elements;bioinformatics pipeline;cancer care;cancer prevention;cell fixing;Cells;Cervical;Cisplatin;Confocal Microscopy;Data;deep sequencing;Development;digital;DNA;DNA Damage;DNA Repair;Double Strand Break Repair;Exploratory/Developmental Grant;Frequencies;Genetic Recombination;Genome;genotoxicity;Goals;homologous recombination;HPV E7;HPV-High Risk;Human papilloma virus infection;human papilloma virus oncogene;Human Papillomavirus;improved;inhibitor;innovation;insertion/deletion mutation;Intervention;Knowledge;Lesion;Life Cycle Stages;Malignant neoplasm of cervix uteri;Malignant Neoplasms;Mediating;Methods;Microscopy;Mission;Molecular;Mutagenesis;Mutagens;Mutation;National Cancer Institute;Normal tissue morphology;novel;Oncogenes;Papillomavirus Transforming Protein E6;Pathway interactions;Pharmaceutical Preparations;Play;premalignant;prevent;Process;Property;Proteins;Public Health;Publishing;Radiation therapy;Radiation Toxicity;recruit;repaired;Reporter;Research;Role;Signal Transduction;Site;small molecule inhibitor;Testing;therapeutic target;Time;TP53 gene;tumor;Tumor Suppressor Proteins;tumorigenesis;Viral;Virus Replication;Woman;Work

PROJECT_TITLE: Defining the ability of HPV oncogenes to promote mutagenesis

STUDY_SECTION: CE

STUDY_SECTION_NAME: Cancer Etiology Study Section[CE]


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Genetics;Neurosciences

ORG_CITY: EUGENE

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF OREGON

ORG_STATE: OR

PHR: PROJECT NARRATIVE Neural circuits generate sensation, movement and cognition, and aberrant neural circuits are implicated in many neurodevelopmental and psychiatric disorders. Thus, is it important to identify the developmental mechanisms that establish neuronal connectivity, including transcription factors, and determine whether they also maintain neural circuits into adulthood. Drosophila is a simple and powerful system to address these questions, with the goal of identifying mechanisms conserved from fly to mammals.

PI_NAMEs: LEE, KRISTEN M (contact)

PROGRAM_OFFICER_NAME: KOSTER, MARANKE IRENE

PROJECT_TERMS: Address;Adult;Affect;Aging;Attention deficit hyperactivity disorder;autism spectrum disorder;Axon;behavioral phenotyping;Biological Assay;Biological Metamorphosis;Brain;Caenorhabditis elegans;Cell surface;Central Nervous System;Cognition;Complex;Coupled;Data;Defect;Dendrites;Development;Developmental Process;Drosophila genus;Drug abuse;Embryo;Esthesia;Event;experimental study;fascinate;fly;Foundations;Gene Expression;Gilles de la Tourette syndrome;Goals;homeodomain;Hormones;Individual;interest;Interneurons;Larva;Learning;Life;Link;Locomotion;Maintenance;Mammals;Membrane;Mental disorders;Modeling;Molecular;molecular marker;Molecular Profiling;Morphology;Motor;Movement;neural;neural circuit;neural patterning;Neurites;Neurodevelopmental Disorder;neurogenesis;neuromechanism;Neuronal Plasticity;Neurons;Neurotransmitters;optogenetics;Outcome;Phenotype;Property;Puberty;response;Risk;RNA interference screen;Role;Schizophrenia;Shapes;Sleep;Specific qualifier value;Synapses;System;Testing;Therapeutic;transcription factor;Walking;Work

PROJECT_TITLE: Linking neuronal identity transcription factors to neural circuit establishment and maintenance


FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

ORG_CITY: RICHMOND

ORG_NAME: VIRGINIA COMMONWEALTH UNIVERSITY

ORG_STATE: VA

PHR: The MD-PhD dual degree program at Virginia Commonwealth University has been training diverse physician- scientists to make discoveries that advance human health since 1986. Our trainee-centered program provides outstanding integrated clinical and research instruction, promotes research reproducibility, transparency, and responsible conduct in mentors and trainees, and fosters wellness. We seek funding to train a greater number of diverse future physician-scientists and better meet the pressing need for innovation in biomedical research and medicine.

PI_NAMEs: DONNENBERG, MICHAEL S (contact)

PROGRAM_OFFICER_NAME: AKACEM, LAMEESE DANA

PROJECT_TERMS: Medical;Scientist;Training Programs

PROJECT_TITLE: VCU Medical Scientist Training Program

STUDY_SECTION: TWD

STUDY_SECTION_NAME: Training and Workforce Development Study Section - A[TWD-A]


ORG_CITY: SALT LAKE CITY

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: Project Narrative The enzyme p97 is an abundant and conserved molecular machine that unfolds proteins prior to their degradation. p97 is regulated by many binding partners through unknown mechanisms. The proposed research will investigate how binding partners regulate p97, which will inform how p97 complexes function in maintaining cellular health and how mutations cause imbalance in protein homeostasis.

PI_NAMEs: MACK, DEIRDRE  (contact)

PROGRAM_OFFICER_NAME: MCINTYRE, JEREMY COLIN

PROJECT_TITLE: Mechanism of Substrate Unfolding by the AAA+ ATPase p97 and Binding Partners


NIH_SPENDING_CATS: Cardiovascular;Congenital Heart Disease;Heart Disease;Heart Disease - Coronary Heart Disease;Orphan Drug;Pediatric;Prevention;Rare Diseases

ORG_CITY: Nashville

ORG_NAME: VANDERBILT UNIVERSITY

ORG_STATE: TN

PHR: PROJECT NARRATIVE Sudden cardiac death (SCD) accounts for 15% of all mortality in the United States. Patients at the greatest risk for SCD – those with existing heart disease – live without effective drugs to prevent this devastating outcome. This project entails development of a new potential drug targeting pathologic intracellular calcium release and testing its therapeutic efficacy in mice with chronic heart disease.

PI_NAMEs: GOCHMAN, AARON  (contact)

PROJECT_TERMS: Address;analog;Anti-Arrhythmia Agents;Arrhythmia;Binding;Biological Assay;Calcium;Calcium Oscillations;Calcium-Sensing Receptors;Cardiac;Cardiac Myocytes;Catecholaminergic Polymorphic Ventricular Tachycardia;Cell membrane;Cells;Chronic;Closure by clamp;Collaborations;Complement;Congestive Heart Failure;Coupling;Data;Development;Diastole;Docking;drug candidate;Drug Kinetics;Drug Targeting;Electrophysiology (science);embolic stroke;Failure;Flecainide;Future;Genetic;Heart;Heart Atrium;Heart Diseases;high risk;Hyperactivity;Image;in silico;In Vitro;inhibitor;Ion Channel;lead candidate;Libraries;Measurement;Measures;Mechanics;Mediating;Membrane;Membrane Potentials;Mentors;Modeling;Morbidity - disease rate;mortality;mouse model;Mus;Muscle Contraction;Mutation;Myocardial Contraction;Myocardial Infarction;novel therapeutics;Outcome;oxidation;patch clamp;Pathologic;patient population;Patient risk;Patients;Permeability;Pharmaceutical Preparations;Phosphorylation;Physiological;Post-Translational Protein Processing;preclinical study;prevent;Process;Property;Receptor Inhibition;Research;Risk;Risk Reduction;Ryanodine Receptor Calcium Release Channel;Sarcoplasmic Reticulum;Signal Transduction;Sodium;structural heart disease;sudden cardiac death;Syndrome;Synthesis Chemistry;Systole;Testing;Therapeutic;therapeutic candidate;therapeutic evaluation;tool;Treatment Efficacy;United States;Ventricular Arrhythmia;voltage;voltage sensitive dye

PROJECT_TITLE: Targeting pathologic intracellular calcium release to prevent lethal arrhythmias


ADMINISTERING_IC: DE

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Clinical Research;Dental, Oral, and Craniofacial Disease;Infectious Diseases;Microbiome;Pediatric;Prevention;Social Determinants of Health

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: PROJECT NARRATIVE The oral microbiome is a major determinant of caries risk and its assembly and evolution is susceptible to environmental exposures. The proposed research is relevant to the NIDCR's mission to improve dental and oral health as it will identify the environmental exposures, and the critical time points, that influence the microbiome and modify caries risk. This can be translated into actionable interventions to reduce caries prevalence, and with further research building upon these findings, other oral diseases.

PI_NAMEs: ADLER, CHRISTINA JANE;PETRICK, LAUREN  (contact)

PROGRAM_OFFICER_NAME: CHOU, ALICIA YESIU

PROJECT_TERMS: 1 year old;8 year old;Affect;Age;Biological;Biological Assay;Biological Markers;Birth;Calibration;Chemical Exposure;Chemicals;Childhood;Clinical;Clinical Data;cohort;Conceptions;cost effective;Data;deciduous tooth;Dental;Dental caries;Development;Developmental Biology;dimension reduction;Disease;dysbiosis;early childhood;early life exposure;Elements;Endocrine;Environment;environmental chemical;Environmental Exposure;Environmental Risk Factor;Evolution;experience;Exposure to;fetal;Fetal Development;Foundations;Future;Genes;Genetic Risk;Goals;gut microbiome;Health;health data;high dimensionality;Histologic;Hour;Human;Human Microbiome;Immune;improved;innovation;Intervention;Joints;Life;Linear Models;Link;Measurement;Measures;Mediating;Metabolic;metabolome;metabolomics;Metagenomics;Methods;microbial;microbiome;Mission;Mixed Dentition;Mouth Diseases;multidimensional data;National Institute of Dental and Craniofacial Research;Non-linear Models;novel;novel marker;Nutrient;Nutritional;Odontogenesis;Oral health;oral microbiome;Outcome;Participant;Pathway interactions;Periodontal Diseases;permanent tooth;Placenta;Poison;population based;postnatal;Predisposition;prenatal;Prevalence;prevent;Prospective cohort;Recording of previous events;repository;Research;Research Design;Research Support;Resources;response;Risk;Sampling;Second Pregnancy Trimester;Statistical Data Interpretation;Statistical Methods;Sum;synergism;System;Techniques;Technology;temporal measurement;Testing;Third Pregnancy Trimester;Time;Tooth Diseases;Tooth structure;toxic metal;Toxicant exposure;Translating;Twin Multiple Birth;Twin Studies

PROJECT_TITLE: Reconstructing early life environmental exposures using tooth biomarkers and their influence on the trajectory of the oral microbiome and oral health in childhood

STUDY_SECTION: ODCS

STUDY_SECTION_NAME: Oral, Dental and Craniofacial Sciences Study Section[ODCS]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Bioengineering;Biotechnology;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Coronaviruses Vaccines;Emerging Infectious Diseases;HIV/AIDS;Immunization;Immunotherapy;Infectious Diseases;Nanotechnology;Prevention;Vaccine Related

ORG_CITY: SEATTLE

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: PROJECT NARRATIVE This project will investigate the impact of HIV-related immune dysfunction on the immunogenicity and durability of a second-generation replicating RNA COVID-19 vaccine. Data generated from this project will support further development and evaluation of a COVID-19 vaccine that is more amenable for worldwide distribution, especially is resource limited settings, and for use in people living with HIV and in immunosuppressed individuals.

PI_NAMEs: O'CONNOR, MEGAN A (contact)

PROGRAM_OFFICER_NAME: LAWRENCE, DIANE M

PROJECT_TERMS: 2019-nCoV;Alpha Virus;Anabolism;Animals;Antigens;antiretroviral therapy;Automobile Driving;B-Lymphocytes;breakthrough infection;CAR T cell therapy;cardiovascular disorder risk;CD4 Lymphocyte Count;Cells;Cessation of life;comorbidity;Country;COVID-19;COVID-19 risk;COVID-19 vaccination;COVID-19 vaccine;cytokine;Data;Development;Diabetes Mellitus;Disease;Dose;Evaluation;Exclusion;exhaustion;Formulation;Frequencies;Generations;Goals;Helper-Inducer T-Lymphocyte;HIV;HIV Infections;HIV/AIDS;Hospitalization;Human;humoral immunity deficiency;immune activation;Immune response;Immune System Diseases;Immunity;Immunization;Immunocompromised Host;immunogenic;immunogenicity;Immunologic Factors;Immunologic Memory;immunosuppressed;Immunosuppression;impaired driving performance;Impairment;improved;Individual;Infection;Influenza Hemagglutinin;lipid nanoparticle;Lipids;Macaca;Macaca nemestrina;Malignant Neoplasms;Measures;Memory;Messenger RNA;Methods;Modeling;mortality;mRNA lipid nano particle vaccine;MS4A1 gene;Mus;nanoemulsion;nanoparticle;neutralizing antibody;nonhuman primate;novel;Persons;Phase I Clinical Trials;Population;pre-clinical;Prevalence;Proteins;Public Health;receptor binding;Regulatory T-Lymphocyte;Replicon;Resource-limited setting;response;RNA;RNA replication;RNA vaccine;Role;SARS-CoV-2 B.1.1.529;SARS-CoV-2 immunity;SARS-CoV-2 infection;SARS-CoV-2 spike protein;SARS-CoV-2 variant;Secondary Immunization;severe COVID-19;SIV;Structure of germinal center of lymph node;T-Lymphocyte;Testing;treatment strategy;vaccine access;vaccine candidate;vaccine delivery;vaccine immunogenicity;vaccine platform;vaccine strategy;vaccine trial;Vaccines;variants of concern;Viral;Virus Replication;Work

PROJECT_TITLE: SARS-CoV-2 vaccine durability during SIV infection

STUDY_SECTION: HIVD

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


ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

PHR: The MIT Department of Biology trains some of the world’s most talented young scientists to unravel cellular and molecular complexities fundamental to human health and disease. Our program provides training in the foundational approaches to biological research and a deep research experience in a student’s chosen area. We also educate students about the basis of ethical and humane decision-making and prepare diverse individuals for leadership positions in a range of biomedical careers.

PI_NAMEs: GEHRING, MARY  (contact);LAUB, MICHAEL

PROGRAM_OFFICER_NAME: JONES, LATAISIA CHERIE

PROJECT_TITLE: Pre-doctoral Training in Fundamental Approaches to Biochemistry and Cell and Molecular Biology


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Neurosciences;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_DEPT: BIOMEDICAL ENGINEERING

PHR: Project Narrative This study characterizes the tissue response and safety limits of electrical micro-stimulation in multiple non- neuronal brain cells over time. Electrical stimulation is being used to probe brain activity and also treat a wide- range of diseases (e.g. Parkinson’s disease). A state-of-the-art imaging approach is proposed to guide the use of stimulation to induce changes in brain activity, including progenitor proliferation and differentiation.

PI_NAMEs: KOZAI, TAKASHI DANIEL YOSHIDA (contact)

PROGRAM_OFFICER_NAME: HWANG, GRACE MEI-HUA

PROJECT_TERMS: 2',3'-Cyclic-Nucleotide Phosphodiesterases;angiogenesis;Astrocytes;Automobile Driving;Basic Science;Behavior;Biology;Biophysics;Blood flow;Blood Vessels;Brain;brain cell;brain tissue;Calcium;Cell Lineage;Cells;Charge;Chemicals;Chronic;Clinical;clinical application;clinical implementation;Coupled;Databases;Degenerative Disorder;design;Development;Device Designs;Disease;DsRed;electric impedance;Electric Stimulation;electrical microstimulation;Electrodes;Electrophysiology (science);Event;excitotoxicity;Foreign Bodies;Frequencies;Future;Health;Health Status;Image;imaging approach;imaging platform;Imaging Techniques;Imaging technology;Immune;Immunohistochemistry;implantable device;implantation;improved;in vivo;in vivo imaging;Injury;Intervention;Investigation;Mental Depression;Microelectrodes;Microglia;microstimulation;Molecular;Monitor;Morphology;multiphoton imaging;Mus;myelination;Myelogenous;Nerve Regeneration;neural network;Neuroglia;neuronal excitability;Neurons;neuroregulation;Neurosciences;Neurosciences Research;neurovascular coupling;oligodendrocyte progenitor;Oligodendroglia;Optics;Parkinson Disease;Patients;Pericytes;Periodicity;Personal Satisfaction;Phase;Photic Stimulation;Physiological;predictive modeling;Prevalence;Proliferating;Property;Protein Analysis;ratiometric;Recommendation;Regenerative Medicine;Research;response;RNA analysis;Safety;sensor;Sensory;Signal Transduction;Smooth Muscle Myocytes;spatiotemporal;Spectrum Analysis;stem cell differentiation;stem cell proliferation;stem cells;Stimulus;Supporting Cell;Techniques;Therapeutic;Time;tissue repair;Tissues;Transgenic Animals;Vascular Smooth Muscle;vasoconstriction;Vasodilation;Visual Cortex;voltage;Work

PROJECT_TITLE: Elucidating electrical stimulation induced non-neuronal activity using emerging in vivo imaging technology and electrophysiology


ED_INST_TYPE: UNIVERSITY-WIDE

NIH_SPENDING_CATS: Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Transplantation

PHR: NARRATIVE Endogenous thymic regeneration is an important process enabling restoration of immune competence; however, this regenerative capacity diminishes with age such that severe damage (i.e., the pre-conditioning for hematopoietic stem cell transplants) leads to prolonged periods of immunodeficiency that detrimentally impact patient outcomes. In this proposal, we seek to understand how the thymus responds to injurious stimuli and how its endogenous regeneration is regulated. Better understanding these mechanisms may inform therapeutic strategies that boost thymic function after acute or chronic forms of insult, which could benefit patients whose thymus has been decimated due to age, infection, or common cancer treatments.

PI_NAMEs: GRANADIER, DAVID WILLIAM (contact)

PROGRAM_OFFICER_NAME: WELNIAK, LISBETH A

PROJECT_TERMS: Acute;Adolescent;Adult;Age;age related;aged;Aging;aging population;Apoptotic;Attention;attenuation;Biological;cancer therapy;CASP1 gene;Cell Death;Cells;Chronic;Clinical;clinically relevant;conditioning;constriction;cytokine;Data;Detection;Exposure to;Hematopoietic Stem Cell Transplantation;IL18 gene;Immune;immune function;immune reconstitution;Immune response;Immunocompetence;immunodeficiency;immunogenic cell death;improved;Incidence;Infection;Inflammatory;Injury;innovation;insight;interleukin-23;Ionizing radiation;irradiation;Lymphoid Cell;Lymphopenia;Lytic;Malignant - descriptor;Malignant Neoplasms;Mediator;Modeling;Molecular;Monoclonal Antibodies;mortality;Natural regeneration;novel therapeutic intervention;Opportunistic Infections;Organ;Pathway interactions;Patient-Focused Outcomes;Patients;Pattern;Peripheral;Population;preclinical study;preconditioning;Process;Production;Productivity;Recovery;regenerative;Regenerative capacity;Relapse;repaired;Reporting;restoration;Risk;Risk Factors;Role;Signal Transduction;Source;Stem cell transplant;Stimulus;Stress;T cell reconstitution;T-Cell Development;T-Cell Receptor;T-Lymphocyte;Therapeutic;therapeutic target;Thymic epithelial cell;thymic regeneration;thymocyte;Thymus Gland;tissue injury;tissue regeneration;tissue repair;Tissues;transplant model;Transplant Recipients;Transplantation;vaccine response;Whole-Body Irradiation

PROJECT_TITLE: Targeting IL-18 in Thymic Regeneration

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


ORG_CITY: CHAMPAIGN

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN

ORG_STATE: IL

PHR: Paragons of Conformational Control in Metalloenzyme Reactivity Lisa Olshansky Project Narrative. From transport to respiration to biosynthesis, metalloenzyme function relies on the precise interplay between conformational dynamics and active site modulation. However, defining the specific structure-function correlations operative in complex redox machines can be extremely challenging. By creating simplified paragons of conformational control in metalloenzyme reactivity we capture the essence of this interplay, dissecting the energetic costs and consequences associated with regulation of function in the maintenance of human health.

PI_NAMEs: OLSHANSKY, LISA  (contact)

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CB-P(55)R]


NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Heart Disease;Kidney Disease;Organ Transplantation;Patient Safety;Prevention;Social Determinants of Health;Transplantation

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: PROJECT NARRATIVE The proposed research seeks to leverage a novel health records platform to build a comprehensive and transportable cardiovascular risk-prediction model specific to kidney transplant patients. The study will engineer a data visualization tool that allows patients and providers to engage in shared decision-making and identify targets of clinical and structural intervention. The results will be critical for informing individualized risk management of cardiovascular disease, improving long-term outcomes, and reducing health disparities with implications for dissemination across multiple institutions.

PI_NAMEs: BOWRING, MARY GRACE (contact)

PROGRAM_OFFICER_NAME: MEADOWS, TAWANNA

PROJECT_TERMS: Accounting;Acute;Address;Allografting;Area;Biological Markers;burden of illness;Calibration;Cardiovascular Diseases;cardiovascular disorder risk;Cardiovascular Models;cardiovascular risk factor;Cardiovascular system;Cause of Death;Cessation of life;Chronic;Chronic Kidney Failure;Clinical;clinical biomarkers;clinical decision-making;clinical implementation;cohort;Complex;Computer software;Confusion;Consensus;Data;Data Set;data visualization;Development;Discrimination;Disease;Disease Outcome;Disparate;Electronic Health Record;Engineering;Equilibrium;Evaluation;Event;evidence based guidelines;Exclusion;experience;Face;Frequencies;General Population;Goals;hazard;Health;health record;high risk;Hospitals;Housing;Immunosuppression;improved;improved outcome;Incidence;Income;Inflammation;Institution;interactive visualization;Intervention;Interview;Kidney Diseases;Kidney Transplantation;Knowledge;Manuals;Mentors;Metabolic;model building;Modeling;Modification;Morbidity - disease rate;mortality;Myocardial Infarction;novel;Outcome;Pathway interactions;patient oriented;patient population;Patients;Pharmaceutical Preparations;Physicians;pilot test;Population;predictive modeling;predictive tools;prevent;primary endpoint;Provider;Recording of previous events;Reduce health disparities;Research;Risk;Risk Estimate;Risk Factors;Risk Management;risk prediction;risk prediction model;ROC Curve;Severities;shared decision making;side effect;Socioeconomic Factors;standard of care;Structure;System;Testing;Time;time use;tool;Transplant Recipients;transplant registry;Transplantation;usability;Validation;Visualization software;Work

PROJECT_TITLE: Leveraging a novel health records platform to predict the development of cardiovascular disease following kidney transplantation

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


NIH_SPENDING_CATS: Biotechnology;Chronic Liver Disease and Cirrhosis;Digestive Diseases;Hepatitis;Hepatitis - C;Infectious Diseases;Liver Disease;Organ Transplantation;Transplantation

ORG_CITY: SAINT LOUIS

ORG_NAME: SAINT LOUIS UNIVERSITY

ORG_STATE: MO

PHR: Project Narrative In the United States, chronic liver diseases rank 11th and 5th cause for deaths in all ages and in age 44~65- year group, respectively (National Vital Statistics Report 2019), yet up to 30% of patients with chronic liver diseases have no clear etiology. With the identification of a candidate virus in our preliminary studies, the current application aims to characterize this novel human virus and its link with liver disease. The etiological understanding is central to the prevention and management of life-threatening liver diseases.

PI_NAMEs: FAN, XIAOFENG  (contact)

PROGRAM_OFFICER_NAME: PARK, EUN-CHUNG

PROJECT_TERMS: Acute Hepatitis;Acute Liver Failure;Adult;Age;Antibodies;Antibody Response;Autoimmunity;Blood donor;Capsid Proteins;Cause of Death;Chronic Hepatitis;chronic liver disease;Cirrhosis;Classification;Clinical;clinical phenotype;Clinical Trials;Cloning;Cohort Studies;Data;design;Dideoxy Chain Termination DNA Sequencing;Digestion;DNA;Double Stranded DNA Virus;drug induced liver injury;ds-DNA;Enzyme-Linked Immunosorbent Assay;Etiology;Exclusion;experimental study;GB virus C;Genbank;Genes;Genetic Diseases;Genome;Grant;Hepatitis;Hepatitis A;Hepatitis C;Hepatitis C virus;Hepatitis Viruses;Human;human virome;hydropathy;Immunoglobulin G;Immunoglobulin M;in silico;Individual;Knowledge;Lead;Life;Ligation;Link;Liver;Liver diseases;liver transplantation;Living Donor Liver Transplantation;Machine Learning;Malignant neoplasm of liver;Measurement;Mediating;Membrane;Methods;Morphologic artifacts;Names;Nature;next generation sequencing;nonalcoholic steatohepatitis;novel;Nucleic Acids;Patients;Peptides;Prevention;Primer Extension;Probability;problem drinker;Reagent;Reporting;Research;response;Scanning;Sensitivity and Specificity;sequencing platform;Series;Serology test;Serum;Single-Stranded DNA;Specimen;Structure;Surface;Testing;Tissues;Transfusion-Transmitted Virus;Transplant Recipients;Tropism;United States;United States National Institutes of Health;Venous blood sampling;Viral;Viral Genome;virome;Virus;Vital Statistics;Walking;whole genome

PROJECT_TITLE: A Novel Human Virus in Patients with Cryptogenic Liver Disease

STUDY_SECTION: EDIT

STUDY_SECTION_NAME: Etiology, Diagnostic, Intervention and Treatment of Infectious Diseases Study Section[EDIT]


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

ORG_CITY: OMAHA

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF NEBRASKA MEDICAL CENTER

ORG_STATE: NE

PHR: PROJECT NARRATIVE EWS-FLI1 oncogenic transcription factor regulates the expression of USP1 in Ewing sarcoma, an aggressive pediatric bone cancer. USP1 deubiquitinase regulates HELLS and is required for stem cell maintenance, genome stability and promotes cell proliferation bypassing oncogene-induced replication stress.

PI_NAMEs: GHOSAL, GARGI  (contact)

PROGRAM_OFFICER_NAME: LUO, RUIBAI

PROJECT_TERMS: Apoptosis;Basic Science;biological adaptation to stress;bone;Bypass;cancer cell;Cell Aging;Cell Cycle;Cell Cycle Arrest;Cell Cycle Progression;Cell Death;cell growth;Cell Line;Cell Maintenance;Cell Physiology;Cell Proliferation;Cells;chemotherapy;Childhood;ChIP-seq;Chromatin;chromatin remodeling;Chromosomal translocation;Chromosome 11;Chromosome 22;comparative;Data;Deubiquitination;Development;Disease Progression;DNA;DNA biosynthesis;DNA Damage;DNA fiber assay;DNA Methylation;DNA Repair;DNA-protein crosslink;E2F transcription factors;Epigenetic Process;epigenetic regulation;Ewings sarcoma;EWSR1 gene;Family;FLI1 gene;Gene Expression;Gene Fusion;Generations;Genes;Genetic Transcription;Genome;Genome Stability;genome wide methylation;genome-wide analysis;Genomic Instability;Growth;HELLS gene;Histones;improved;In Vitro;in vivo;inhibitor;insight;knock-down;Lysine;Malignant Bone Neoplasm;Malignant Neoplasms;Maps;Mediating;Mesenchymal Stem Cells;methylation pattern;Molecular;mutant;new therapeutic target;Normal Cell;novel;Oncogenes;Oncogenic;overexpression;Pathogenesis;Pathway interactions;Patients;Pharmaceutical Preparations;Phenocopy;Proteins;Regulation;repaired;replication stress;response;Role;S phase;Sarcoma;senescence;Site;small molecule;standard of care;stem cells;t(11;22)(q24;q12);targeted treatment;Testing;Therapeutic;transcription factor;transcriptome sequencing;Treatment Efficacy;treatment strategy;tumor;tumor growth;tumorigenesis;Ubiquitin;ubiquitin isopeptidase;ubiquitin-protein ligase;ubiquitin-specific protease;Ubiquitination;Xenograft Model

PROJECT_TITLE: Mechanisms underlying USP1-mediated bypass of EWS-FLI1 oncogene-induced replication stress in Ewing sarcoma


ED_INST_TYPE: SCHOOLS OF SOCIAL WELFARE/WORK

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Eating Disorders;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Mental Illness;Nutrition;Obesity;Prevention;Primary Health Care;Racial and Ethnic Minority Health Research;Telehealth

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: PROJECT NARRATIVE Behavioral treatment of obesity is the most efficacious non-surgical intervention for obesity. Certain eating behaviors (e.g., binge eating) that remain untreated have the potential to worsen weight outcomes. This project will develop and pilot a digital health intervention to reduce binge eating and prevent weight gain among Black women in primary care.

PI_NAMEs: GOODE, RACHEL W. (contact)

PROGRAM_OFFICER_NAME: SERRANO, KATRINA JANE

PROJECT_TERMS: Address;Adult;Applications Grants;attentional control;Award;Awareness;Behavior Therapy;Behavioral;Binge Eating;Binge eating disorder;black women;Body mass index;Body Weight Changes;Body Weight decreased;career;clinical trial implementation;Clinical Trials;clinically significant;Cognitive Therapy;Communities;Conduct Clinical Trials;Control Groups;cost;Coupled;Data;design;Desire for food;Development;Dietary Intervention;digital delivery;digital health;digital treatment;Disparate;Doctor of Philosophy;Drops;E-learning;Eating;Eating Behavior;Eating Disorders;effective therapy;efficacy testing;Evaluation;Exercise;Face;Feedback;Focus Groups;Foundations;Future;Goals;health disparity;implementation science;improved;Informal Social Control;Intervention;Intervention Studies;Investigator-Initiated Research;Knowledge;medical specialties;Mental Health;Mentored Patient-Oriented Research Career Development Award;Mentors;Metabolic syndrome;Methods;Morbid Obesity;Multi-Institutional Clinical Trial;Multimedia;National Institute of Diabetes and Digestive and Kidney Diseases;Non-Insulin-Dependent Diabetes Mellitus;Obesity;obesity prevention;obesity treatment;Outcome;patient engagement;Persons;Physicians;poor health outcome;Population;Population Heterogeneity;Pragmatic clinical trial;pragmatic trial;preference;prevent;Primary Care;primary outcome;programs;Randomized;randomized, clinical trials;recruit;Reporting;Research;Research Personnel;Research Project Grants;Risk;Risk Reduction;satisfaction;Scientist;secondary outcome;skills;technology intervention;Testing;theories;Therapeutic Intervention;Time;tool;Training;Treatment outcome;treatment trial;United States;United States National Institutes of Health;usability;Weight;Weight Gain;weight gain prevention;weight loss intervention;Weight maintenance regimen;White Women;Work

PROJECT_TITLE: Developing a Culturally-Relevant Digital Health Intervention to Treat Binge Eating and Obesity

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Digestive Diseases and Nutrition C Study Section[DDK-C]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Diabetes;Eye Disease and Disorders of Vision;Genetics;Neurosciences

ORG_CITY: DETROIT

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: WAYNE STATE UNIVERSITY

ORG_STATE: MI

PHR: In the pathogenesis of diabetic retinopathy, retinal mitochondria are damaged and the electron transport chain system is compromised, fueling into a vicious cycle of free radicals. Diabetes also alters expression of many long noncoding RNAs (LncRNA), and these RNAs with > 200 nucleotides lack an open reading frame for translation. Mitochondrial DNA encodes three LncRNAs, but their role in regulating mitochondrial homeostasis in diabetic retinopathy is not clear. This proposal is focused on understanding the role of mtDNA-encoded LncRNA Cytochrome B, important in the functioning of complex III, in maintaining mitochondrial homeostasis in diabetic retinopathy. These studies carry a significant translational impact as they are expected to identify novel therapeutic targets to prevent the development and progression of diabetic retinopathy, offering patients additional means to prevent/halt this sight-threatening complication of diabetes.

PI_NAMEs: KOWLURU, RENU A. (contact)

PROGRAM_OFFICER_NAME: SHEN, GRACE L

PROJECT_TERMS: Acceleration;Aging;Apoptosis;Attenuated;Binding;Biochemical;Biogenesis;Biological;Blindness;Blood capillaries;Cells;Characteristics;Chronic Disease;Code;Complex;Complications of Diabetes Mellitus;cytochrome c;Cytochromes b;Cytosol;Data;Defect;Development;Diabetes Mellitus;Diabetic mouse;Diabetic Retinopathy;Digestion;Disease;DNA;Down-Regulation;Electron Transport;Electron Transport Complex III;Endothelial Cells;Free Radicals;Fright;Gene Expression;Generations;Genes;Genetic Transcription;Glycine decarboxylase;Goals;helicase;Histones;Histopathology;Homeostasis;Human;Human Genome;Hyperglycemia;Impairment;In Vitro;in vivo;in vivo Model;innovation;Lead;member;Messenger RNA;Metabolic;MicroRNAs;Mitochondria;Mitochondrial DNA;Modeling;Molecular;mtTF1 transcription factor;new therapeutic target;novel;Nuclear;nuclease;Nucleotides;Open Reading Frames;Pathogenesis;Patients;Play;Porifera;prevent;Proteins;Regulation;Retina;Retinal Diseases;RNA;RNA Processing;RNA Sequences;RNase P;Rodent;Role;scaffold;Superoxides;System;Testing;Therapeutic;therapeutic target;Transcript;transcription factor;translational impact;Translations;Untranslated RNA;Vision

PROJECT_TITLE: Diabetic Retinopathy, Mitochondria Damage and Long Non-coding RNAs

STUDY_SECTION_NAME: Pathophysiology of Eye Disease - 2 Study Section[PED2]


ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Data Science;Genetics;Human Genome;Networking and Information Technology R&D (NITRD)

ORG_CITY: COLUMBUS

ORG_NAME: RESEARCH INST NATIONWIDE CHILDREN'S HOSP

ORG_STATE: OH

PHR: Project Narrative Currently, it is very time-consuming and costly to search multiple resources to clinically evaluate genomic variants. This project will create the computational concepts and tools needed to quickly and precisely search across many resources, dramatically reducing the time and cost of clinical variant evaluation while improving our ability to find relevant clinical evidence.

PI_NAMEs: WAGNER, ALEX HANDLER (contact)

PROGRAM_OFFICER_NAME: KULCHAK RAHM, ALANNA LEE

PROJECT_TERMS: Clinical;clinical care;clinical decision support;clinically relevant;clinically significant;Collection;combinatorial;computable knowledge;Consumption;cost;Data;data ecosystem;data harmonization;Data Sources;Decision Making;design;Development;Diagnosis;Discipline;Education;Evaluation;genetic variant;Genome;genomic data;Genomic medicine;Genomics;Growth;Health;improved;Individual;innovation;interoperability;Intuition;Knowledge;knowledge network;knowledgebase;Left;Literature;Malignant Neoplasms;Modernization;novel;Patients;Privatization;Prognosis;Reporting;Research;Research Activity;research clinical testing;Resources;Risk;Role;Services;Standardization;support tools;System;Therapeutic;Time;tool;tool development;Validation;Variant;Work

PROJECT_TITLE: Development and validation of a computable knowledge framework for genomic medicine


NIH_SPENDING_CATS: Bioengineering;Cancer;Digestive Diseases;Liver Cancer;Liver Disease;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: LA JOLLA

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

ORG_STATE: CA

PHR: Narrative: The overall goal of our research is to provide a better understanding of how cancer cells misinterpret or ignore signals that normally tell cells to stop dividing or begin suicide, leading to uncontrolled tumor growth. We will also develop novel assays to facilitate the development of new cancer therapeutics.

PI_NAMEs: ZHANG, JIN  (contact)

PROGRAM_OFFICER_NAME: COUCH, JENNIFER A

PROJECT_TERMS: anti-cancer research;Apoptosis;Architecture;Automobile Driving;awake;Biochemical;Biochemistry;Biological Assay;Biosensor;Buffers;cancer cell;cell growth;cell growth regulation;Cell Proliferation;cell transformation;Cells;Cessation of life;Cyclic AMP;Cyclic AMP-Dependent Protein Kinases;Development;Fibrolamellar Hepatocellular Carcinoma;Goals;high resolution imaging;Image;Imaging technology;innovative technologies;Laboratories;Length;Liquid substance;Malignant neoplasm of pancreas;Malignant Neoplasms;Measures;Molecular;Mus;novel;novel therapeutics;Oncogenic;Pathway interactions;Peer Review;Phase;Phosphotransferases;Physical condensation;Physiological;programs;protein protein interaction;Protein Subunits;Publishing;Ras Inhibitor;Regulation;Research;Research Support;Second Messenger Systems;Signal Transduction;Signaling Molecule;spatiotemporal;Suicide;Technology;Therapeutic;tumor growth;tumorigenesis;ultra high resolution;uncontrolled cell growth

PROJECT_TITLE: Live-cell Activity Architecture in Cancer


ADMINISTERING_IC: ES

FUNDING_MECHANISM: OTHERS

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

ORG_CITY: SILVER SPRING

ORG_NAME: CENTER FOR CONSTRUCTION RES AND TRAINING

PHR: Project Narrative The relevance of this proposal, which is national in scope, is to prevent work-related fatalities, injuries and illnesses by training construction workers on DOE sites how best to protect themselves, their workplaces and their communities from exposure to radiation and other hazardous materials encountered during hazardous waste operations, facility decommissioning, decontamination and demolition, hazardous materials transportation, environmental restoration of contaminated facilities or chemical emergency response. A well trained construction workforce enables DOE, its contractors and subcontractors, and other stakeholders, such as trade unions and Native American tribes, protect not only the workers themselves but communities surrounding DOE sites.

PI_NAMEs: CAIN, CHRISTINA TRAHAN (contact)

PROGRAM_OFFICER_NAME: BEARD, SHARON

PROJECT_TERMS: Air;Ally;apprenticeship;arm;Canada;Cementation;chemical disaster;Collaborations;Communities;Complex;Containment;Continuing Education;Contractor;Decontamination;Department of Energy;Educational Curriculum;Educational process of instructing;Emergency response;Engineering;Evaluation;Excision;experience;Exposure to;Funding Opportunities;Generations;Hazardous Substances;Hazardous Waste;Health;Industry;Injury;instructor;International;Iron;Knowledge;Letters;Measures;meetings;Metals;model development;National Institute of Environmental Health Sciences;Native American Tribe;Nonprofit Organizations;North America;Nuclear Weapon;operation;Outcome;Plumbing;prevent;programs;Qualifying;Radiation;Research;response;restoration;Safety;Site;Students;Surveys;Trade Unions;Trainers Training;Training;Training and Education;Training Programs;Transportation;U-Series Cooperative Agreements;United States;Veterans;Work;Workplace

PROJECT_TITLE: HAZMAT Training at DOE Nuclear Weapons Complex


NIH_SPENDING_CATS: Genetics

ORG_CITY: KANSAS CITY

ORG_NAME: UNIVERSITY OF KANSAS MEDICAL CENTER

PHR: Project Narrative Ribonucleotides are the most common lesion in the genome and have been linked to human disease. The goal of this project is to determine the structural and biological effects of ribonucleotides on telomere integrity, as well as characterizing the repair of ribonucleotides at telomeres. This project will provide technical and professional training by using a unique combination of biophysical, structural, and cellular assays to address the project goal.

PI_NAMEs: CORTEZ, LUIS MANUEL (contact)

PROJECT_TERMS: Address;Affect;Antibodies;Apoptosis;Biochemical;Biological;Biological Assay;Biophysics;Biotin;Cancer Biology;career;Cell Culture Techniques;Cell Line;Cells;Cellular Assay;Chromosomes;Circular Dichroism;Circular Dichroism Spectroscopy;Complement;Critical Thinking;Data;DNA;DNA annealing;DNA biosynthesis;DNA Damage;DNA Folding;Doctor of Philosophy;Ensure;Enzymes;Excision Repair;experimental study;G-Quartets;Genome;genome integrity;Genomic Instability;Goals;Higher Order Chromatin Structure;human disease;In Vitro;innovation;Left;Length;Lesion;Link;Malignant Neoplasms;Mechanics;Molecular Conformation;Monitor;mutant;Nucleotides;Oligonucleotides;Pathway interactions;Physicians;Proteins;reconstitution;repaired;Repetitive Sequence;Research;Ribonucleotides;RNA;RNA-Directed DNA Polymerase;Scientist;senescence;skills;Spectrophotometry;Structure;System;Telomerase;telomere;Telomere Maintenance;Testing;Tissues;Training;Transfection;Untranslated RNA

PROJECT_TITLE: Structural and Biological Effects of Ribonucleotide Insertion into Telomeres

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F08-A(20)L]


NIH_SPENDING_CATS: Cardiovascular;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Heart Disease - Coronary Heart Disease;Human Genome;Networking and Information Technology R&D (NITRD);Precision Medicine;Prevention

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: PROJECT NARRATIVE The goal of our project is to use genotype and phenotype data from a variety of sources, to generate polygenic risk scores (PRSs) for individuals belonging to diverse ancestries. Our focus will be on developing PRSs for coronary heart disease (CHD) and its major risk factors (hypertension, diabetes, obesity, hypercholesterolemia), collectively an enormous public health burden world-wide. We will develop methods to account for diverse genetic ancestry in models of polygenic risk and integrate PRSs into existing clinical risk prediction equations to estimate absolute risk of CHD for use in clinical decision making.

PI_NAMEs: KULLO, IFTIKHAR J (contact);SCHAID, DANIEL J.

PROGRAM_OFFICER_NAME: ROWLEY, ROBB KENNETH

PROJECT_TERMS: Address;Admixture;Adult;All of Us Research Program;biobank;Categories;Classification;clinic ready;Clinical;clinical decision-making;clinical practice;clinical risk;cloud platform;cohort;Collaborations;Complex;Computing Methodologies;Coronary heart disease;Data;Data Element;data harmonization;data integration;data modeling;Data Set;data standards;database of Genotypes and Phenotypes;Development;Diabetes Mellitus;Disease;disorder risk;East Asian;Electronic Health Record;Electronic Medical Records and Genomics Network;Ensure;Equation;Equity;European ancestry;Gene Frequency;Generations;Genetic;Genetic Diseases;Genetic Variation;genome wide association study;genomic data;Genomic medicine;Genotype;Goals;Grant;Health;health disparity;heart disease risk;Heritability;hypercholesterolemia;Hypertension;improved;Individual;innovation;International;large datasets;Linkage Disequilibrium;Metadata;Methods;Middle Eastern;Modeling;novel;Obesity;Ontology;Outcome;Pattern;Performance;Phase;Phenotype;phenotypic data;polygenic risk score;Population;Population Genetics;Population Heterogeneity;precision medicine;Prevention;programs;Public Health;randomized, clinical trials;Risk;Risk Estimate;Risk Factors;risk prediction;risk stratification;risk variant;Sample Size;Site;Source;South Asian;Statistical Methods;statistics;Testing;Therapeutic;Variant;Veterans;Weight;Work;working group

PROJECT_TITLE: Polygenic Risk of Disease in Populations of Diverse Ancestry


NIH_SPENDING_CATS: Contraception/Reproduction;Genetics;Human Genome;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: DURHAM

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: DUKE UNIVERSITY

PHR: PROJECT NARRATIVE Reproductive health is dependent upon the formation of spermatogonial stem cells (SSCs) from its precursor cells, male germ cells (MGCs), and mechanisms governing this vital period of development are largely unknown. The primary aim of this study is to elucidate how an RNA binding protein (RBP), DND1, can post-transcriptionally regulate its target transcripts, thereby ensuring MGC-to-SSC development. Results obtained from this study can provide insight into why post-transcriptional regulation by RBPs play a critical role in MGC development across species and contribute to reproductive health.

PI_NAMEs: HATKEVICH, TALIA LEE (contact)

PROGRAM_OFFICER_NAME: KENT, TRAVIS JOHN

PROJECT_TERMS: Binding;Birth;Cell Reprogramming;Chromatin;Complex;Confocal Microscopy;Cytoplasm;Cytoplasmic Granules;Data;Data Set;design;Development;Diffuse;DNMT3a;Embryo;Ensure;Epigenetic Process;Exhibits;experimental study;Fellowship;Fertility;fetal;Genetic Transcription;Genome;Germ;Goals;HDAC6 gene;histone modification;Human;improved;Infertility;insight;KDM5B gene;Knowledge;Laboratories;Lead;Life;life span;liquid chromatography mass spectrometry;Locales;male;Mediating;Mediator;Messenger RNA;Metabolism;Methylation;Methyltransferase;Microscopy;Modification;Molecular Profiling;Mus;novel;Phase;Play;Post-Transcriptional Regulation;postnatal;posttranscriptional;precursor cell;programs;Proteins;Proteome;Regulation;Repression;reproductive;Reproductive Health;Research;Research Personnel;Resolution;RNA immunoprecipitation sequencing;RNA-Binding Proteins;Role;Scientific Advances and Accomplishments;self-renewal;SETDB1 gene;Site;skills;SMARCA4 gene;SMARCA5 gene;sperm cell;Spermatocytes;Stem Cell Development;stem cell population;stem cells;Testing;Time;tool;Training;Transcript;transcriptomics;Translating;Translation Initiation;Translational Derepression;Translational Regulation;Translational Repression;Translations;translatome;Universities;Work

PROJECT_TITLE: Regulation of Male Germ Cell Development through DND1-Mediated Translation of Epigenetic Factors

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F06-L(20)L]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Lung;Neurosciences

ORG_DEPT: PSYCHOLOGY

PHR: PROJECT NARRATIVE Understanding communication between the lung and brain is critical in order to understand how respiratory viral infections ultimately impact the central nervous system. This proposal examines lung-brain communication in the onset of influenza A in a mouse model, testing the hypothesis that the lung and brain exert bidirectional influence to influence altering each organ’s immune state. In Aim 1 the role of pulmonary neuroendocrine cells in infection onset is studied by ablating these cells prior to infection, and in Aim 2 the role of neuronal activity in infection onset is studied by chemogenetic reactivation of relevant neuronal populations.

PI_NAMEs: MONROE, SARAH KATHERINE (contact)

PROGRAM_OFFICER_NAME: MATTHEWS, MARGUERITE

PROJECT_TERMS: 3-Dimensional;Ablation;adenovirus mediated delivery;analysis pipeline;Attenuated;Automobile Driving;Brain;brain health;brain tissue;Cell Count;Cells;Central Nervous System;Central Nervous System Infections;cognitive function;Communication;Computer software;COVID-19 pandemic;cytokine;Data;Designer Drugs;designer receptors exclusively activated by designer drugs;Epithelial Cells;Epithelium;experience;Face;Focal Infection;Gene Expression;Genes;Genetic;Genetic Recombination;Goals;Health;Hippocampus;Image;Immune;immune cell infiltrate;immune function;Immune response;Immune signaling;Immunologic Memory;Impairment;indexing;Infection;Inflammation;Inflammatory;Inflammatory Response;Influenza A virus;influenza infection;Invaded;Knowledge;Label;Link;Lung;lung health;Lung infections;Machine Learning;Maps;Measures;Microglia;Modeling;Molecular;Morphology;mouse model;Mus;nerve supply;neural;Neuroendocrine Cell;Neuroimmune;Neurons;Neuropeptides;neurotransmission;Organ;Outcome;Peripheral;Phagocytes;Population;Proteomics;Recovery;respiratory;respiratory challenge;Respiratory Tract Infections;response;Role;Sensory;Signal Pathway;Signal Transduction;Societies;Structure of parenchyma of lung;Testing;Tissues;Up-Regulation;Vagus nerve structure;Viral Respiratory Tract Infection;Virus;Virus Diseases

PROJECT_TITLE: Lung-brain communication in the onset of respiratory viral infection.


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

PHR: Project Narrative Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a genetic disorder characterized by the growth of numerous cysts in the kidneys. The mechanism underlying ADPKD is obscure with two major theories, haploinsufficiency (where a simple decrease in protein level is enough to cause disease) and the `two hit' hypotheses (where an individual is born with a defective gene then acquires another mutation on the normal gene causing the disease). This application will use NanoView technology to measure the level of polycystin-1 on exosomes to distinguish these two ideas.

PI_NAMEs: WARD, CHRISTOPHER J (contact)

PROGRAM_OFFICER_NAME: MARIC-BILKAN, CHRISTINE

PROJECT_TERMS: Affect;Age;Aging;Alleles;Alternative Splicing;Attenuated;Autosomal Dominant Polycystic Kidney;Clinical;Clone Cells;Cyst;design;Disease;dosage;End stage renal failure;Epithelium;Exons;exosome;experimental study;extracellular vesicles;Functional disorder;Gene Dosage;Genes;Genetic Diseases;Genome;Growth;Height;Human;Individual;Inherited;Introns;Kidney;Legal patent;Length;Lipids;Measures;Membrane;Messenger RNA;misfolded protein;Modality;Modeling;Modification;Mus;mutant;Mutation;nanopore;Nephrons;new technology;Nonsense Codon;Normal Statistical Distribution;novel;Null Lymphocytes;Pathogenesis;Persons;PKD1 gene;PKD2 protein;polycystic kidney disease 1 protein;Population;premature;Prevalence;Process;prominin;promoter;Proteins;Research Personnel;Reverse Transcriptase Polymerase Chain Reaction;RNA Splicing;Severity of illness;Signal Transduction;Site;Somatic Mutation;Surface;Technology;Terminator Codon;theories;Time;Transcript;Tubular formation;urinary;Urine;Variant;Vesicle;Visualization;Western Blotting;Work

PROJECT_TITLE: Human-specific Abnormal Alternative Splicing of the Wild-type PKD1 Gene Induces Premature Termination of Polycystin-1

STUDY_SECTION: KMBD

STUDY_SECTION_NAME: Kidney Molecular Biology and Genitourinary Organ Development[KMBD]


ORG_DEPT: SURGERY

PHR: PROJECT NARRATIVE_Overall Infection with HIV-1, the virus that causes AIDS, is a significant public health problem world-wide. An improved understanding of the specific functional and qualitative features of how the human immune system fights HIV-1 infection and how these features contribute to protection against infection is needed. This Program focuses on the role of what is known as the “Fc receptor” of antibodies and their interactions and cooperation with a variety of immune cells. This work will reveal how to maximize the body’s immune response against HIV-1 to yield more effective prevention, vaccine, and cure approaches, with potential for significant benefits to public health.

PI_NAMEs: TOMARAS, GEORGIA DORIS (contact)

PROGRAM_OFFICER_NAME: BOGGIANO, CESAR AUGUSTO

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Animal Model;Antibodies;Antibody Specificity;antiviral immunity;Autologous;Biological Models;Biophysics;Cells;Cellular biology;Clinical;Clinical Research;cohort;Collaborations;Communicable Diseases;COVID-19;defined contribution;Educational process of instructing;Effector Cell;efficacy trial;Elements;Environment;Epitopes;experimental study;Fc domain;Fc Receptor;fighting;Genetic Determinism;Genotype;global health;Goals;Heterogeneity;HIV Infections;HIV-1;Human;human model;humanized mouse;Immune;Immune response;Immune system;Immunity;Immunoglobulin Allotypes;immunoprophylaxis;improved;In Situ;In Vitro;in vivo;Infection;Joints;Knowledge;Learning;Macaca mulatta;Mediating;Methods;Modeling;Monoclonal Antibodies;mouse model;neutralizing antibody;new pandemic;Outcome;pandemic disease;pathogen;Phagocytes;polyclonal antibody;Population;Positioning Attribute;Pre-Clinical Model;preclinical study;prevent;Prevention;Productivity;programs;Property;prophylactic;protective efficacy;Public Health;rational design;Receptor Cell;Recording of previous events;Resources;response;Role;Sampling;Serum;Source;Specimen;Structure;Testing;Therapeutic;treatment planning;vaccine efficacy;vaccine strategy;Vaccines;Viral;Viral Antibodies;Viral Physiology;Virus;Virus Replication;Work

PROJECT_TITLE: Impact of Antibody Effector Function Diversity on Antiviral Activity In Situ


NIH_SPENDING_CATS: Cancer;Digestive Diseases;Eye Disease and Disorders of Vision;Genetics;Human Genome;Liver Disease;Rare Diseases

ORG_CITY: TAMPA

ORG_NAME: H. LEE MOFFITT CANCER CTR & RES INST

ORG_STATE: FL

PHR: Uveal melanoma (UM) is a highly aggressive and frequently fatal cancer of the eye that metastasizes to the liver. The goal of this proposed study is to define the mechanisms underlying UM liver metastasis development and progression and to develop novel therapeutic strategies for the treatment of established UM liver metastases.

PI_NAMEs: HARBOUR, JAMES WILLIAM;LICHT, JONATHAN D.;SMALLEY, KEIRAN  (contact)

PROGRAM_OFFICER_NAME: BENAVIDEZ, JUSTIN MICHAEL

PROJECT_TERMS: Adjuvant Therapy;Adoption;Alleles;angiogenesis;Animal Model;ATAC-seq;Automobile Driving;Binding Sites;Cells;Chromatin;Clinical;Clinical Trials;combinatorial;CRISPR screen;Data;Data Set;Dependence;Development;Diagnosis;Disease;Drug resistance;Environment;Epigenetic Process;epigenomics;FGF2 gene;Fostering;GDF15 gene;Gene Expression;Gene Expression Profiling;Genes;Genetic;Genetic Predisposition to Disease;Genetic Transcription;GNAQ gene;Goals;Grant;Growth;HDAC1 gene;Hepatic Stellate Cell;high risk;Histone Deacetylase;IL8 gene;innovation;jun Oncogene;knock-down;Knowledge;Liver;Maintenance;malignant neoplasm of eye;MAP Kinase Gene;Mediating;MEK inhibition;melanocyte;Melanoma Cell;Metastatic Neoplasm to the Liver;Modeling;Molecular;multiple omics;Mus;mutant;Mutation;Neoplasm Metastasis;novel;novel strategies;novel therapeutic intervention;Oncogenic;Output;Pathway interactions;Patients;Phenotype;prevent;Program Sustainability;programs;Proteomics;Risk;Role;senescence;Signal Induction;Signal Pathway;Signal Transduction;Signaling Molecule;small molecule inhibitor;Specimen;Subgroup;targeted treatment;Testing;Therapeutic;therapy resistant;Time;TP53 gene;transcription factor;treatment strategy;tumor progression;Up-Regulation;Uveal Melanoma;Vascular Endothelial Growth Factors;Xenograft Model

PROJECT_TITLE: Characterization and targeting of the epigenetic state underlying uveal melanoma liver metastasis

STUDY_SECTION: TPM

STUDY_SECTION_NAME: Tumor Progression and Metastasis Study Section[TPM]