ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Depression;Dissemination and Implementation Research;Health Services;Mental Health;Mental Illness;Pediatric;Prevention;Primary Health Care

ORG_CITY: Chicago

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

PHR: Prevention of depressive disorders has become a key priority for the NIMH, but we have no widely available public health strategy to reduce morbidity and mortality. To address this need, we developed and evaluated the primary care based-technology “behavioral vaccine,” Competent Adulthood Transition with Cognitive-Behavioral Humanistic and Interpersonal Therapy (CATCH- IT). We will engage N=4 health systems representative of the United States health care system, and conduct a factorial design study to optimize the intervention in preparation for an implementation study and eventual dissemination.

PI_NAMEs: GLADSTONE, TRACY G;VAN VOORHEES, BENJAMIN W (contact)

PROGRAM_OFFICER_NAME: ROONEY, MARY

PROJECT_TERMS: 18 year old;Address;Adolescence;Adolescent;Affect;associated symptom;Behavioral;Cells;Characteristics;China;Clinical Trials;Clinical Trials Design;Cognitive;Cognitive Therapy;collaboratory;Communities;Complex;cost;depression prevention;Depressive disorder;depressive symptoms;design;Developed Countries;Diagnosis;Disease;Dose;Dropout;efficacy trial;experience;Family;follow-up;functional status;Geographic state;Health Status;Health system;Healthcare;Healthcare Systems;high risk;high risk population;High School Student;implementation determinants;implementation study;implementation trial;improved outcome;indicated prevention;interpersonal therapy;Intervention;Mediating;Mediator;Mental Depression;mental disorder prevention;Minor;model design;Modeling;Mood Disorders;Morbidity - disease rate;mortality;multiphase optimization strategy;National Institute of Mental Health;Outcome;parenting intervention;Parents;Participant;peer;PF4 Gene;Phase;Population;population based;Preparation;preservation;prevent;Prevention;Preventive;preventive intervention;Primary Care;primary care practice;protective factors;psychologic;Public Health;Randomized;randomized, clinical trials;Recommendation;recruit;Research Design;resilience;resilience factor;Resources;Risk;rumination;Rural;satisfaction;Selection for Treatments;single episode major depressive disorder;Site;suburb;Symptoms;Technology;technology intervention;Testing;Time;transition to adulthood;Trauma;United States;United States Preventative Services Task Force;Vaccines;Work;Youth

PROJECT_TITLE: Primary Care Based Depression Prevention in Adolescents: Intervention Optimization in Preparation for Implementation Study


ADMINISTERING_IC: HD

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

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

NIH_SPENDING_CATS: Genetics

ORG_CITY: NEW YORK

ORG_COUNTRY: UNITED STATES

ORG_DEPT: BIOCHEMISTRY

ORG_FIPS: US

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: PROJECT NARRATIVE: As cells differentiate, they activate signaling cascades that are precisely controlled in time to achieve the fully committed phenotype. However, current technologies are limited in their ability to characterize these precise temporal changes. To address this, we are developing a programmable platform that can reveal the impact of important mRNA players on cellular differentiation with unprecedented time resolution.

PI_NAMEs: ZACCARA, SARA  (contact)

PROGRAM_OFFICER_NAME: STEIN, KATHRYN K

PROJECT_TERMS: Address;Biological Process;Cell Differentiation process;chromatin remodeling;Complex;Development;essays;Event;flexibility;Gene Expression;gene regulatory network;Genetic Transcription;Heterogeneity;Hour;imaging system;innovation;Messenger RNA;mRNA Decay;mRNA Transcript Degradation;Pattern;Phenotype;Process;programs;Proteins;Regulation;Resolution;RNA Degradation;Role;Signal Transduction;stem cells;Technology;Testing;Time;Transcription Regulation Pathway;Transcriptional Regulation

PROJECT_TITLE: Programmable depletion and rescue platform to screen dynamic regulatory events during cellular differentiation.

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 RCCS-L (70)]


ADMINISTERING_IC: CA

FUNDING_MECHANISM: SBIR-STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: WOODINVILLE

ORG_NAME: CANCER TARGETED TECHNOLOGY, LLC

ORG_STATE: WA

PHR: PROJECT NARRATIVE This project will develop an innovative prostate-specific membrane antigen-targeted drug that delivers a highly potent chemotherapeutic, monomethyl auristatin E, directly to the prostate cancer cell and not to healthy tissues using a novel pH-sensitive drug delivery system. The goal is to protect patients from the negative side effects of the chemotherapy, with the added benefit of greater efficacy of the therapeutic drug.

PI_NAMEs: LANGTON-WEBSTER, BEATRICE  (contact)

PROGRAM_OFFICER_NAME: DJEMIL, SARRA

PROJECT_TERMS: Ablation;Acute;advanced prostate cancer;Affinity;American;androgen deprivation therapy;androgen independent prostate cancer;Animal Model;animal safety;Animals;Antibody-drug conjugates;antigen binding;Antigen Targeting;Area Under Curve;Binding;Biological Markers;Blood;Bone Diseases;cancer cell;cancer diagnosis;Cancer Etiology;Cells;Cessation of life;chemical synthesis;chemotherapy;Chlorides;Chronic;Clinical;Clinical Protocols;Clinical Trials;clinically relevant;cost;cytotoxicity;design;Development;Diagnostic;docetaxel;Dose;Dose Limiting;Drug Delivery Systems;drug efficacy;Drug Kinetics;Drug Targeting;Engineering;FDA approved;FOLH1 gene;Future;Goals;good laboratory practice;Grant;Half-Life;Hormones;Image;Immunotherapy;improved;ineffective therapies;innovation;liquid chromatography mass spectrometry;Lymphoma;Lysosomes;Malignant neoplasm of cervix uteri;Malignant neoplasm of prostate;Malignant Neoplasms;men;Metastatic Neoplasm to the Bone;Monitor;Mus;neoplastic cell;new technology;Normal Cell;Normal tissue morphology;novel;novel therapeutics;Outcome;overexpression;patient derived xenograft model;Patients;Pharmaceutical Preparations;Phase;Phase I Clinical Trials;Positron-Emission Tomography;Preparation;Procedures;Process;Prodrugs;prostate cancer cell;prostate cancer model;Prostate Cancer therapy;Proteins;protocol development;Provenge;Quality of life;Radiation therapy;radiotracer;Radium;Rattus;Regimen;Resistance;Safety;safety study;scaffold;Schedule;side effect;Small Business Innovation Research Grant;small molecule;specific biomarkers;Specific qualifier value;stability testing;standard of care;success;System;targeted delivery;taxane;Technology;Testing;Therapeutic;Therapeutic Effect;Therapeutic Index;Tissues;Toxic effect;Treatment Efficacy;Tubulin;tumor;Tumor Antigens;tumor growth;Urea;Urothelium;Vertebral column;Visualization;Work

PROJECT_TITLE: Development of an Innovative PSMA-Targeted Small Molecule Prodrug for Prostate Cancer

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 CTH-T (10)]


ORG_CITY: DURHAM

ORG_DEPT: NEUROSURGERY

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: PROJECT NARRATIVE To date scientists have lacked methods for studying the human brain at a cellular level. Using novel techniques for investigating specific cell types in live human brain tissues, here we will investigate how inhibitory nerve cells shape human brain functions. Our findings will advance our understanding of the human brain and accelerate new therapies for brain disorders.

PI_NAMEs: SOUTHWELL, DEREK G. (contact)

PROGRAM_OFFICER_NAME: KIM, DOUGLAS SUN-IL

PROJECT_TERMS: Acceleration;Alzheimer's Disease;Anatomy;autism spectrum disorder;Biological Models;Brain;Brain Diseases;brain disorder therapy;brain tissue;Catalogs;Cell Shape;cell type;Cerebral cortex;design;Disease;Elements;Epilepsy;Functional disorder;Genetic;grasp;Human;innovation;Interneurons;Knowledge;Laboratories;Laboratory mice;Left;Methods;multimodality;Nervous System Disorder;neural circuit;Neurons;Neurosciences;Neurosurgical Procedures;novel;novel therapeutics;Phenotype;Physiological;Population;Process;Property;Research;Role;Scientist;Specimen;targeted treatment;Techniques;tool;transcriptomics

PROJECT_TITLE: Exploring cortical inhibitory circuit design in the human brain

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 RCCS-A (70)]


ED_INST_TYPE: GRADUATE SCHOOLS

ORG_CITY: Princeton

ORG_DEPT: NEUROSCIENCES

ORG_NAME: PRINCETON UNIVERSITY

ORG_STATE: NJ

PHR: Project Narrative: Primate neocortex has expanded in evolution and has acquired novel connectivity motifs to support advanced functions such as cognition. Understanding developmental bases of these innovations will shed light into how they are perturbed in neurodevelopmental disorders. This proposal uses innovative molecular approaches based on barcoded viruses to reveal lineage and connectivity relationships within and between the expanded portions of the primate neocortex.

PI_NAMEs: KRIENEN, FENNA MARIE (contact)

PROGRAM_OFFICER_NAME: LEINWAND, SARAH GOLDBERG

PROJECT_TERMS: Address;Affect;Area;Bar Codes;base;Brain;Callithrix;Callithrix jacchus jacchus;cell type;Cells;Characteristics;Cognition;Cognitive;cognitive function;demographics;Development;Developmental Process;Disease;DNA sequencing;Emerging Technologies;Evolution;Gene Expression;Genetic Models;Genome;Genomics;Homologous Gene;Improve Access;in utero;Individual;innovation;Knowledge;Light;Mammals;Measurement;Methods;Modeling;Modernization;Modification;Molecular;Mus;Neocortex;neocortical;Neurodevelopmental Disorder;novel;Pre-Clinical Model;Primates;Process;programs;Property;Recording of previous events;Research;Rodent;Sensory;Sensory Process;single-cell RNA sequencing;statistics;stem cell population;Synapses;System;Technology;tool;Virus;Work

PROJECT_TITLE: Genomic recording systems to reveal evolutionary modifications in primate neocortex


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: WORCESTER

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

ORG_STATE: MA

PHR: Project Narrative Nucleic acids, such as DNA and RNA, exist in cells as highly complex molecular structures subject to numerous modifications and vulnerable to damage, either of which can change their function and impact cellular states; however current sequencing technology can only analyze their base sequence, ignoring much of this information. Here, I present preliminary data and propose a path to expand a technique developed by my lab to directly sequence modified or damaged DNA or RNA, using an innovative approach to modify novel sequencing technology. With these tools, we hope to understand the processes that converge on DNA and RNA, such as chemotherapy in cancer or natural damage that occurs during aging or neurodegeneration, to better learn how cells modify, repair, and interpret their genomes.

PI_NAMEs: FLAVAHAN, WILLIAM ALEXANDER (contact)

PROGRAM_OFFICER_NAME: SAKALIAN, MICHAEL

PROJECT_TERMS: Aging;Alkylation;Bar Codes;base;Base Pairing;Base Sequence;cancer therapy;Cells;Chemical Structure;chemotherapy;Chromatin;Complex;Cytosine;Data;Detection;Development;Devices;Dimensions;DNA;DNA Damage;Engineering;experimental study;Generations;genetic regulatory protein;Genome;genotoxicity;innovation;Learning;Libraries;Malignant Neoplasms;Measures;Messenger RNA;Methods;Methylation;Modification;Molecular;Molecular Structure;nanopore;Nerve Degeneration;next generation sequencing;novel sequencing technology;Nucleic Acids;oxidation;Process;Proliferating;Property;Reading;Reference Values;Regulation;repaired;RNA;Shapes;Structure;Techniques;Technology;Third Generation Sequencing;tool;Training;transcriptome;Untranslated RNA;Work

PROJECT_TITLE: Expanding the capabilities of third-generation sequencing for multi-dimensional genome and transcriptome analysis.


ADMINISTERING_IC: ES

ED_INST_TYPE: SCHOOLS OF PHARMACY

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Nanotechnology;Social Determinants of Health

ORG_CITY: SALT LAKE CITY

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: PROJECT NARRATIVE Extracellular vesicles (EVs) are shed into the bloodstream by all cells in the body, providing a unique opportunity to monitor the health impact of environmental exposures through liquid biopsies. Here we propose a technology framework integrating bulk and single EV omics, nanotechnologies, and microtechnologies to extract the blood fingerprints of organ-specific biological responses to life course experiences. The proposed methodologies, technologies, as well as data sets, will be of high value to both basic and translational research communities.

PI_NAMEs: LU, YUE  (contact)

PROGRAM_OFFICER_NAME: CUI, YUXIA

PROJECT_TERMS: Back;Basic Science;Bioinformatics;Biological;Biology;Blood;Blood Circulation;Body System;Cells;climate change;Communicable Diseases;Communities;Computer software;Data Set;Development;Diagnostic;Diameter;digital;ds-DNA;Environment;Environmental Exposure;Environmental Impact;Epitopes;experience;extracellular vesicles;Fingerprint;Foundations;Goals;Health;Health Status;Heterogeneity;Human;Immunoassay;Individual;Infrastructure;innovation;insight;Interdisciplinary Study;Life Cycle Stages;liquid biopsy;Lung;Malignant neoplasm of lung;Measurement;Membrane;Messenger RNA;Methodology;Methods;Microfluidics;MicroRNAs;minimally invasive;Molecular;Molecular Epidemiology;Monitor;nanoparticle;Nanotechnology;Organ;Organ Specificity;Play;Population;programs;Proteins;Reporting;Research;Resolution;Resources;response;RNA;Role;social disparities;Sorting;Source;Statistical Models;System;Technology;Tissues;tool;trafficking;Transcript;Translational Research;Vesicle;Work

PROJECT_TITLE: Monitoring Human Exposome with Extracellular Vesicle Tricorder


ORG_DEPT: PATHOLOGY

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: PROJECT NARRATIVE Immunotherapies have revolutionized the treatment of cancer, but only a small fraction of patients benefit from these therapies. In my recent work, I pioneered a new class of chimeric antigen receptor (CAR) T cells, peptide- centric (PC)-CARs, paving the way for a clinical trial slated to open in 2024 and offering a roadmap for developing immunotherapies for the lethal cancers that don't benefit from first-generation CAR T cells. Here I introduce a multi-pronged approach to build on these methods, offering innovative new strategies for developing safer and more effective therapeutic strategies that can to lead to new therapies for the most challenging cancers.

PI_NAMEs: YARMARKOVICH, MARK  (contact)

PROGRAM_OFFICER_NAME: LIU, YIN

PROJECT_TERMS: adaptive immunity;Address;Antigens;Award;cancer cell;Cancer Patient;cancer therapy;Cells;chimeric antigen receptor;chimeric antigen receptor T cells;Clinical Trials;clinically relevant;Complex;Computing Methodologies;cross reactivity;Dangerousness;Derivation procedure;Development;Eligibility Determination;Engineering;experience;Generations;high reward;high risk;Human Biology;Immune;Immune checkpoint inhibitor;Immune Evasion;Immune response;immunoengineering;Immunotherapy;in silico;innovation;leukemia;Libraries;Logic;Malignant Neoplasms;Methods;Mutation;Nature;new technology;novel;novel strategies;novel therapeutics;Organism;patient population;patient response;Patients;Peptides;Population;Pre-Clinical Model;Process;process improvement;receptor;refractory cancer;Research;Reverse engineering;screening;Solid Neoplasm;success;System;therapeutically effective;tool;tumor;Tumor Antigens;United States National Institutes of Health;Work

PROJECT_TITLE: Expanding CAR T cell applications through high-throughput forward- and reverse immune engineering


ORG_CITY: SAN ANTONIO

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER

ORG_STATE: TX

PHR: PROJECT NARRATIVE FOR FUNDED GRANT (MOSAIC K99/R00) The androgen receptor is a type I nuclear hormone receptor and master transcription factor responsible for differentiation and development of the male phenotype. Its hyperactivation is associated with multiple diseases, including metastatic prostate cancer, androgenetic alopecia, androgen insensitivity syndrome, and Kennedy’s disease. This proposal seeks to understand the mechanism of androgen receptor regulation and determinants of its aberrant activity using biochemical, structural, and cellular methods, which can facilitate the development of novel androgen receptor inhibitors and lend mechanistic insight towards other related nuclear hormone receptors.

PI_NAMEs: WASMUTH, ELIZABETH VICTORINA (contact)

PROJECT_TERMS: Acceleration;Administrative Supplement;Affinity;Androgen Antagonists;androgen independent prostate cancer;Androgen Receptor;Androgen-Insensitivity Syndrome;Androgens;Atomic Force Microscopy;Binding;Biochemical;Biological;Biology;Cancer Biology;career;cell growth;Cell Line;Cells;Cellular Morphology;ChIP-seq;Chromatin;cofactor;Communication;Complement;Complex;Consensus;Cryoelectron Microscopy;Dedications;design;Development;Dimerization;Disease;Dissection;DNA;DNA Binding;DNA Binding Domain;Drug Targeting;Electron Microscopy;Electrons;enzalutamide;Etiology;Exhibits;experience;flexibility;functional outcomes;Funding;Generations;genetic corepressor;Genetic Transcription;Glucocorticoid Receptor;Goals;Grant;Growth;Health;human disease;improved;In Vitro;in vivo;inhibitor;innovation;insight;Joints;Kennedy Syndrome;Knowledge;Laboratories;Leadership;Ligand Binding Domain;Maintenance;male;Male Pattern Baldness;Malignant neoplasm of prostate;Mediating;Memorial Sloan-Kettering Cancer Center;Metastatic Prostate Cancer;Methods;Mineralocorticoid Receptor;Modeling;Molecular;mosaic;Mutation;N-terminal;National Institute of General Medical Sciences;novel;Nuclear Hormone Receptors;Nucleoproteins;Output;Parents;particle;Phase;Phenotype;Phenotypic Sex;post-doctoral training;Process;Progesterone Receptors;Prostate;prostate cancer cell;protein protein interaction;protein purification;Proteins;Receptor Activation;receptor binding;Receptor Inhibition;Receptor Signaling;Recombinants;Regulation;Reporting;Research;Research Personnel;Research Support;Resolution;Running;Sex Differentiation;Sexual Development;Site;skills;Stanolone;structural biology;structural determinants;Structure;Surface;System;Technology;Testing;Testosterone;Training;Transactivation;transcription factor;Transcriptional Regulation;transcriptome;transcriptome sequencing;Universities;Validation;Variant;Visualization;Work;X-Ray Crystallography

PROJECT_TITLE: Biochemical, structural and molecular dissection of androgen receptor transcriptional activity.


ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Congenital Structural Anomalies;Data Science;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Pediatric

ORG_CITY: STANFORD

ORG_DEPT: GENETICS

ORG_NAME: STANFORD UNIVERSITY

ORG_STATE: CA

PHR: PROJECT NARRATIVE Capitalizing on recent technological strides and the amassed big data, we can now envision in silico models of mammalian organogenesis at the embryo level, offering profound predictive insights into human development and relevant diseases. This proposal seeks to pioneer such a venture by constructing the first-ever foundational in silico model of mouse embryogenesis, using Ultima's revolutionary cost-effective “mostly natural sequencing- by-synthesis” chemistry and ultra-high field of view (300, 000 mm2) spatially barcoded wafer disc platform for 3D single-cell spatial multi-omics across E6.5 to E16.5, coupled with cutting-edge machine learning methods like Fourier neural operator learning, graph neural network and the Generative Pre-trained Transformer (as employed in ChatGPT). This proposal will thus set the stage for groundbreaking predictions, including discerning the regulatory mechanisms behind, e.g., the heart's chamber formation and congenital heart disorders.

PI_NAMEs: QIU, XIAOJIE  (contact)

PROGRAM_OFFICER_NAME: FLETCHER, COLIN F

PROJECT_TERMS: 3-Dimensional;Accounting;Atlases;Bar Codes;Big Data;Biological Process;Caenorhabditis elegans;Cell model;cell motility;Cells;ChatGPT;complex data;Computational Biology;Computer Vision Systems;congenital heart abnormality;cost effective;cost efficient;Coupled;CRISPR/Cas technology;Data;Data Set;data-driven model;Developmental Biology;Differential Equation;differential geometry;Dimensions;Disease;Embryo;Embryonic Development;Genomics;Goals;graph neural network;Heart;Human Development;human pathogen;in silico;innovation;insight;Label;Learning;Machine Learning;machine learning method;mathematical methods;Metabolic;Methods;Modeling;mouse model;multidimensional data;multimodality;Multiomic Data;multiple omics;Mus;Mycoplasma genitalium;Nature;neural;next generation sequencing;Organogenesis;pre-trained transformer;Process;protein expression;Reporting;RNA;Signal Transduction;Slice;Synthesis Chemistry;Techniques;Technology;temporal measurement;Therapeutic Intervention;transcriptomics;vector;zygote

PROJECT_TITLE: Towards Foundational 3D In Silico Models of Whole Mouse Embryogenesis


ORG_CITY: LA JOLLA

ORG_NAME: SCRIPPS RESEARCH INSTITUTE, THE

PHR: Developing a CRISPR-free mammalian recombineering system Project Narrative The ability to manipulate large segments of DNA in mammalian cells is essential for research and therapeutics, but we lack genome editing techniques capable of making kilobase-scale DNA changes without cytotoxic double-strand breaks. In this proposal, I describe the development and use of a mammalian recombineering platform, a CRISPR-free genome editing system that enables large DNA insertions, deletions, and substitutions on the human genome without the introduction of double-strand breaks or DNA scars. Our compact recombineering machinery can enable “all-in-one” single-AAV correction of multi-allelic diseases, thus impacting fields from basic research to therapeutics.

PI_NAMEs: MILLER, SHANNON MARIE (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TERMS: Address;Alleles;Bacteria;Basic Science;Cell Line;Cell model;Cicatrix;Clinic;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;cytotoxic;Data;detection method;Development;Directed Molecular Evolution;Disease;DNA;Engineering;Enterococcus faecium;Gaucher Disease;Genes;Genome;genome editing;Genomics;Human Genome;improved;inhibitor;Laboratories;Mammalian Cell;Methods;Mutation;Organism;Proteins;Recombinant adeno-associated virus (rAAV);recombinase;repaired;Research;synthetic biology;System;Techniques;Therapeutic


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Antimicrobial Resistance;Biotechnology;Cancer;Genetics;Infectious Diseases;Malaria;Orphan Drug;Rare Diseases;Vector-Borne Diseases

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

PHR: PROJECT NARRATIVE The emergence of artemisinin-resistant Plasmodium falciparum (Pf) parasites imperils global malaria treatment and control. Quiescence plays a central role in artemisinin-resistant parasite survival, as well as in the parasite starvation response, but drivers of entry into and exit from this cellular state remain unknown. The proposed research will employ transcriptomics, mass spectrometry and genetic knockdowns to identify and characterize novel epigenetic mechanisms that regulate drug-resistant parasite entry into and exit from quiescence, thereby fundamentally altering how we understand parasite gene regulation and allowing for the development of novel antimalarials to combat one of the deadliest global diseases.

PI_NAMEs: SMALL-SAUNDERS, JENNIFER L. (contact)

PROGRAM_OFFICER_NAME: MCGUGAN, GLEN C

PROJECT_TERMS: 5 year old;Africa;Amino Acyl Transfer RNA;Anti-malarials;Artemisinins;Asia;biological adaptation to stress;Biological Assay;Biology;Biotinylation;Blood;Cell Separation;Cells;Cessation of life;Child;Codon Nucleotides;combat;CRISPR/Cas technology;Culicidae;Development;Disease;Drug resistance;Endocytosis;Epigenetic Process;epitranscriptomics;Eukaryota;Exposure to;Falciparum Malaria;Gene Expression Regulation;Genetic;Genetic Transcription;global health;Growth;Hemoglobin;In Vitro;Isoleucine;knock-down;Life Cycle Stages;Liver;Malaria;Mass Spectrum Analysis;Mediating;Modification;Molecular;mosquito-borne;Mutation;neoplastic cell;new therapeutic target;novel;Parasite resistance;Parasites;Parasitic Diseases;pathogen;persistent bacteria;Pharmaceutical Preparations;Physiologic pulse;Plasmodium falciparum;Play;Population;Predisposition;Proteins;Proteome;Reporter;Reproducibility;Research;Resistance;resistant Plasmodium falciparum;response;RNA-Binding Proteins;Role;Starvation;Stress;System;Techniques;Testing;Time;tool;transcriptomics;Transfer RNA;Translations;Tumor Biology;Untranslated RNA

PROJECT_TITLE: Epigenetic drivers of quiescence in artemisinin-resistant Plasmodium falciparum malaria


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

ORG_CITY: AUGUSTA

ORG_NAME: AUGUSTA UNIVERSITY

ORG_STATE: GA

PHR: Parkinson’s disease is a devastating neurodegenerative disorder for which there is currently no cure. Extensive evidence suggests that the disease may originate in the gastrointestinal tract; however, there is an urgent need for animal models that allow for rapid, large-scale testing to uncover novel gut-to-brain mechanisms of disease. In the proposed study, we will generate a suite of new gut-to-brain disease models using the small nematode worm, C. elegans, and with a combination of high-throughput screening and single cell RNA-sequencing analyses, we will provide the most comprehensive investigation to date of the mechanisms underlying neurotoxic disease spread from the gut, with our results bearing significant implications for early therapeutic interventions in Parkinson’s disease.

PI_NAMEs: MOR, DANIELLE EMILLE (contact)

PROGRAM_OFFICER_NAME: SIEBER, BETH-ANNE

PROJECT_TERMS: Acceleration;Address;age related neurodegeneration;Aging;alpha synuclein;Animal Model;Behavioral;Biological Models;Brain;Brain Diseases;Caenorhabditis elegans;Cell Surface Proteins;cell type;Cells;Central Nervous System;Dietary Intervention;Disease;disease model;Disease Progression;Event;Functional disorder;Gastrointestinal tract structure;Genetic Transcription;high throughput screening;Human;Inclusion Bodies;insight;Invaded;Investigation;Lewy Bodies;Link;Maps;model organism;Modeling;Molecular;Nature;Nematoda;Nerve Degeneration;Nervous System;Neurodegenerative Disorders;Neurons;neurotoxic;novel;Parkinson Disease;Pathologic;Pathology;pharmacologic;Predisposition;prevent;prion-like;Proteins;receptor;resilience;Resolution;Rodent Model;Role;single-cell RNA sequencing;Testing;Therapeutic;Therapeutic Intervention;transmission process;Whole Organism;Work

PROJECT_TITLE: Towards a comprehensive understanding of the neurotoxic spread of α-synuclein from gut to brain in Parkinson's disease


NIH_SPENDING_CATS: Cancer;Lung;Lung Cancer;Rare Diseases

PHR: PROJECT NARRATIVE Cancer metastasis accounts for more than 8 million deaths worldwide annually, however, our understanding of the mechanisms underlying metastasis remains incomplete. This proposal aims to develop a comprehensive, spatiotemporally-resolved roadmap of small cell lung cancer metastasis by developing and applying new technologies that integrate single-cell lineage tracing, spatial transcriptomics, and transcriptional recording. A comprehensive understanding of these mechanisms will reveal key molecular changes underlying each step of metastatic progression, and could potentially inform rational therapeutic approaches.

PI_NAMEs: YANG, DIAN  (contact)

PROGRAM_OFFICER_NAME: LI, JERRY

PROJECT_TERMS: Biological;cancer type;Cell Lineage;Cells;Cessation of life;Circulation;Clinical;Dissection;Disseminated Malignant Neoplasm;Distant;Environment;Event;Evolution;Future;Gene Expression;Generations;Genes;Genetic Transcription;Genetically Engineered Mouse;Goals;insight;Malignant neoplasm of lung;Maps;Molecular;mouse model;Nature;Neoplasm Metastasis;Neurosecretory Systems;new technology;novel;Phase;Primary Neoplasm;Process;Resolution;Sampling;Signal Transduction;Site;small cell lung carcinoma;spatiotemporal;Technology;Therapeutic;therapeutic development;therapeutically effective;Time;transcriptomics;tumor;Work

PROJECT_TITLE: Towards a Comprehensive, Spatiotemporal Roadmap of Cancer Metastasis


ADMINISTERING_IC: TW

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: FOGARTY INTERNATIONAL CENTER

NIH_SPENDING_CATS: Clinical Research;HIV/AIDS

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: NARRATIVE Mozambique (a country in Africa with the fourth highest HIV prevalence globally) has made good progress in HIV pandemic control, but significant gaps remain. Leveraging proven leadership and expertise as Mozambique’s lead HIV Strategic Information partner and a history of highly successful partnerships between the University of Eduardo Mondlane (UEM) and Vanderbilt University Medical Center (VUMC), the Vanderbilt- Mozambique Biomedical Informatics (VM-BMI) Training and Research program will increase biomedical informatics (BMI) capacity for HIV research at UEM. Over the course of the five-year project, VM-BMI will train 6 UEM faculty fellows, 10 master’s-level UEM students, and 200 Mozambican workshop and bootcamp participants with an eye towards long-term sustainability.

PI_NAMEs: CHILUNDO, BALTAZAR ;MOSSE, EMILIO LUIS;WERE, MARTIN CHIENG (contact);WESTER, C. WILLIAM

PROGRAM_OFFICER_NAME: BANSAL, GEETHA PARTHASARATHY

PROJECT_TERMS: Academic Medical Centers;Address;Africa;Biology;biomedical informatics;Caring;Clinical;Computational Science;Country;Data;design;Discipline;Disease;Educational workshop;Enrollment;Epidemic;epidemic response;experience;Faculty;Genetic;Genomics;Goals;Health;HIV;Individual;Infection;Informatics;informatics training;Information Sciences;Lead;Leadership;Molecular Epidemiology;Mozambique;personalized approach;Persons;Portuguese;programs;Proteomics;Public Health;Research;Research Training;response;Scientist;skills;Students;Training;Training Programs;Viral Load result

PROJECT_TITLE: Vanderbilt-Mozambique Biomedical Informatics (VM-BMI) Training and Research Program

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 DCAI-S (55)]


ADMINISTERING_IC: EB

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

ORG_CITY: IRVINE

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: Project narrative Fluorescence imaging is a crucial tool for monitoring biomolecular processes at high spatial resolutions and in real time but has limited utility for deep tissue imaging because the few available fluorophores in the NIR-II tissue transparency window (1,000 to 1,700 nm) suffer from challenges such as low brightness, large size, and toxicity. This proposed work pioneers a new approach to develop small, bright, tunable, and biocompatible NIR-II emitters for targeted in vivo molecular imaging, by exploiting a new class of NIR-emissive DNA-stabilized silver nanoclusters. We envision that these new NIR-II fluorescent probes will transform the field of deep tissue fluorescence imaging, with applications ranging from cancer research to vascular imaging.

PI_NAMEs: COPP, STACY MARLA (contact)

PROGRAM_OFFICER_NAME: ATANASIJEVIC, TATJANA

PROJECT_TERMS: anti-cancer research;Antibodies;aptamer;Biological;biomaterial compatibility;biomedical imaging;Blood Vessels;cancer imaging;Chemicals;Chemistry;Color;deep field survey;DNA;Dyes;experimental study;Fluorescence;fluorescence imaging;Fluorescent Probes;fluorophore;Hybrids;Image;in vivo;in vivo evaluation;in vivo imaging;interest;Liquid substance;Machine Learning;Malignant Breast Neoplasm;Molecular;molecular imaging;Molecular Target;Monitor;mouse model;nanocluster;nanoparticle;novel;novel strategies;Nucleic Acids;Organ;peer;Peptides;Physiological Processes;Process;programs;quantum;Research;research and development;Research Personnel;Resolution;screening;Silver;Solubility;Stains;Therapeutic;therapeutic development;Time;Tissue imaging;Tissue Model;Tissues;tool;Toxic effect;Work

PROJECT_TITLE: Deep-tissue targeted molecular imaging with a palette of NIR-II emissive DNA-stabilized nanoclusters


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

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

ORG_CITY: HOUSTON

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

PHR: PROJECT NARRATIVE Aging is driven by accumulated damage in cells over time that disrupts normal tissue function. Often, this process is exacerbated by repeated injuries that stimulate proliferation and wound-induced inflammation. This proposal leverages a highly aging-resistant organism that reproduces solely through asexual reproduction and whole-body regeneration to uncover the cellular and molecular basis for whole-organism rejuvenation and anti-aging.

PI_NAMEs: BENHAM-PYLE, BLAIR WHITNEY (contact)

PROGRAM_OFFICER_NAME: WANG, FEI

PROJECT_TERMS: Address;adult stem cell;age acceleration;age related;age-related disease;aged;Aging;aging mechanism;aging related;Animals;anti aging;anti-cancer;asexual;Asexual Reproduction;Biological Assay;Cell Aging;cell type;Cells;Clonal Expansion;Detection;Disease Outcome;disorder risk;fly;Foundations;gene discovery;Generations;Genes;Genomic Instability;Genomics;Goals;Growth;hallmarks of aging;Human;improved;Inflammation;injured;Injury;Intervention;Knowledge;Life Cycle Stages;life span;Malignant Neoplasms;Methods;Modeling;Molecular;Mus;Mutation;Natural regeneration;Nematoda;Normal tissue morphology;Organism;Planarians;Platyhelminths;Process;Proliferating;regenerative;Regenerative capacity;Rejuvenation;Research;Research Personnel;Resistance;RNA Interference;Signal Pathway;Signal Transduction;stem cell exhaustion;Time;Tissues;transcriptomics;Whole Organism;Work;wound;Yeasts

PROJECT_TITLE: Uncovering cellular and molecular adaptations for whole-organism rejuvenation


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Bioengineering;Biotechnology

ORG_CITY: BERKELEY

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: PROEJCT NARRATIVE Cells are the fundamental unit of life. All cellular functions ultimately result from the structure, interactions, and organization of their component macromolecules. I will develop new methods using cryo-EM to visualize macromolecular structure within cells. This will provide previously inaccessible insight into the molecular mechanisms of cellular processes in health and disease.

PI_NAMEs: LUCAS, BRONWYN AYLA (contact)

PROGRAM_OFFICER_NAME: FLICKER, PAULA F

PROJECT_TERMS: 3-Dimensional;Address;Biological;Biology;Cell Physiology;Cells;cellular imaging;Complex;Cryoelectron Microscopy;Development;Disease;Health;Heterogeneity;Image;Imaging technology;Individual;insight;Life;Macromolecular Complexes;macromolecule;Methods;Molecular;Molecular Structure;new technology;Postdoctoral Fellow;programs;Radiation induced damage;reconstruction;Research;Resolution;Ribosomes;single molecule;Structure;Technology;United States National Institutes of Health;Visualization

PROJECT_TITLE: New cryo-EM methods to visualize ribosome heterogeneity at single molecule resolution in cells


ADMINISTERING_IC: IP

IC_NAME: NATIONAL CENTER FOR IMMUNIZATION AND RESPIRATORY DISEASES

ORG_CITY: DALLAS

ORG_NAME: BAYLOR RESEARCH INSTITUTE

PHR: COMPONENT A – PROJECT NARRATIVE: The planned research is relevant to public health because accurately estimating influenza and COVID-19 vaccine effectiveness (VE) to prevent mild to moderate illness treated in ambulatory settings is a critical component in evaluating the protection provided by nationwide vaccination programs and for the CDC Advisory Committee on Immunization Practices (ACIP) to modify recommendations regarding use of vaccines and antiviral medications as needed. Our Component A project, “Credible Effectiveness Measures of Seasonal Influenza, COVID-19, and Other Respiratory Virus Vaccines against Ambulatory Care for Acute Illness in Texas”, will assess VE against laboratory-confirmed infection with vaccine-preventable respiratory viruses (seasonal/pandemic influenza, COVID-19, and other respiratory viruses such as Respiratory Syncytial Virus for which vaccines may become available) among children and adults needing ambulatory care for acute illness, monitor ongoing viral evolution of influenza and SARS-CoV-2 viruses through genomic sequencing, and conduct potentially year-round surveillance of COVID-19 for respective VE and incidence estimation. This research will generate new knowledge towards the long-term goal of advancing understanding of the epidemiology of viral respiratory infections while measuring the public health impact of immunization of children and adults on reducing the overall burden of illness and improving the health of the population.

PI_NAMEs: GAGLANI, MANJUSHA  (contact)

PROJECT_TITLE: RFA-IP-22-004, Component A _ Credible Effectiveness Measures of Seasonal Influenza, COVID-19 and Other Respiratory Virus Vaccines against Ambulatory Care for Acute Illness in Texas (and Component D).


ORG_CITY: SEATTLE

ORG_NAME: KAISER FOUNDATION HEALTH PLAN OF WASHINGTON

PHR: NARRATIVE Annual review of how well vaccines work is needed in the United Statis to inform public health policy. We will collect data from people of all ages from 2022-2027 to understand how well vaccines work by collecting patient data, electronic health record data, nose and throat specimens with results for flu and COVID-19 testing, and blood draw. We will work with all collaborators for success of the research.

PI_NAMEs: WERNLI, KAREN J (contact)

PROJECT_TITLE: RFA-IP-22-004, Evaluating influenza, SARS-CoV-2, and other respiratory virus vaccine effectiveness in prevention of acute illness in Washington state 2022-2027


NIH_SPENDING_CATS: Cancer;Clinical Research;Clinical Trials and Supportive Activities;Digestive Diseases;Microbiome;Patient Safety

ORG_CITY: SAN CARLOS

ORG_NAME: ENVIVO BIO INC

PHR: Project Narrative Envivo Bio Inc. will develop the CapScan intestinal sampling capsule in order to generate a comprehensive and quantitative overview of metabolites and microbes in the human gut. Metabolite and gut bacteria analyses will be conducted in healthy volunteers and also in patients with common digestive problems to explore the extent of changes before and after treatment, ultimately setting the stage for CapScan to be used to study a broad range of gut disorders.

PI_NAMEs: SHALON, TIDHAR DARI (contact)

PROGRAM_OFFICER_NAME: KUMAR, AMIT

PROJECT_TERMS: Aftercare;Amendment;Antibiotic Therapy;Ascending colon;Blood Tests;capsule;Cecum;Clinical;Clinical Research;Collaborations;Collection;Deglutition;design;Development;Devices;Dimensions;Disease;DNA sequencing;Duodenum;Elements;experimental study;feasibility testing;Feces;Food;Gastric Emptying;Gastroenterologist;gastrointestinal;Gastrointestinal Diseases;Gastrointestinal tract structure;Generations;Goals;Growth;gut bacteria;gut microbes;gut microbiota;Health;healthy volunteer;Hour;Human;human subject;Human Volunteers;ileum;inhibitor;Intestines;jejunum;Length;Liquid substance;Measures;Medicine;Metabolic;Metabolic Pathway;metabolome;metabolomics;Metagenomics;Microbe;microbial;microbial genomics;microbiome;milliliter;Modeling;Molecular Weight;Monitor;novel;Patients;Persons;Polyvinyl Alcohol;Protocols documentation;Proton Pump Inhibitors;prototype;Pump;Recovery;regional difference;Reproducibility;research clinical testing;Research Personnel;rifaximin;Rod;safety assessment;Sampling;Serious Adverse Event;Shapes;Small Intestines;Specific qualifier value;Specificity;Stomach;Technology;Testing;Time;Tube;Universities

PROJECT_TITLE: Development and clinical evaluation of the CapScan gastrointestinal sampling device for metabolomics monitoring


ADMINISTERING_IC: HL

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Cardiovascular;Heart Disease;Prevention

PHR: Project Narrative This grant will provide funding for a training program in cardiovascular and other chronic disease prevention. The program’s objective is to mentor doctoral level scientists in interdisciplinary and translational research aimed at preventing chronic diseases, with a strong emphasis on behavioral interventions that can advance health equity.

PI_NAMEs: GARDNER, CHRISTOPHER D (contact)

PROGRAM_OFFICER_NAME: COADY, SEAN

PROJECT_TERMS: Cardiovascular Diseases;Chronic Disease;disorder prevention;Training Programs

PROJECT_TITLE: Cardiovascular and Chronic Disease Prevention Training Program

STUDY_SECTION: NITM

STUDY_SECTION_NAME: NHLBI Institutional Training Mechanism Study Section[NITM(OA)]


ADMINISTERING_IC: OD

IC_NAME: OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH

NIH_SPENDING_CATS: Building Research Capacity at Institutions with Limited NIH Funding;Clinical Research;Clinical Trials and Supportive Activities;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Patient Safety;Pediatric;Primary Health Care;Rural Health;Social Determinants of Health

ORG_CITY: BURLINGTON

ORG_NAME: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE

ORG_STATE: VT

PHR: NARRATIVE Despite being a large segment of the population, rural, minority, and underserved children are traditionally underrepresented in clinical trials, often due to decreased access. Failure to represent these children in pediatric studies overlooks the needs of an important segment of the population, limits the scientific evidence base, and leads to unequal distribution of the opportunity to benefit from medicine and research. Our program, IMproving Pediatric Access to Clinical Trials in Vermont (IMPACT VT) will continue to collaborate as an ECHO IDeA States Pediatric Clinical Trials Network Site to improve clinical trials access, develop and implement clinical trials pertinent to our populations, train a pipeline of pediatric investigators committed to clinical trials research for rural and underserved children, and in the long-term decrease disparities with the goal of improving health for all children.

PI_NAMEs: COWAN, KELLY JEAN (contact);YOUNG, LESLIE W

PROGRAM_OFFICER_NAME: RAJU, TONSE N

PROJECT_TERMS: Adherence;American;Area;base;burden of illness;Caring;Certification;Child;Child Health;Childhood;Clinical;clinical development;Clinical Protocols;Clinical Research;clinical research site;clinical translation;Clinical Trials;Clinical Trials Network;Collaborations;Communities;Conduct Clinical Trials;Data Collection;Dedications;Development;disparity reduction;Ensure;evidence base;Failure;Family;Family Practice;Goals;Health;Health Personnel;improved;Incentives;Infrastructure;Institutional Review Boards;interest;Leadership;Learning;Maintenance;Measures;Medical center;medical specialties;Medicine;Mentors;Minority;minority children;Monitor;Multi-Institutional Clinical Trial;New England;Outcome;outreach;outreach program;Pediatric Hospitals;Pediatric Research;Pediatrics;Population;Primary Care;primary medical care;programs;protocol development;Provider;Research;Research Personnel;Research Training;Resource Sharing;Resources;Rural;rural area;Rural Community;Rural Health;rural health network;Site;success;Training;Translational Research;underserved area;underserved community;United States National Institutes of Health;Universities;Vermont;Work


ORG_CITY: CHICAGO

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: NARRATIVE OVERALL Recovery from viral pneumonia is a clinically important yet understudied process. Despite advances in supportive care and treatment with anti-viral medications, viral pneumonia-induced ARDS carries a mortality rate approaching 40%. By linking causal mechanistic studies in cell and murine models with bronchoalveolar samples from patients with severe viral pneumonia, this PPG seeks to identify mechanisms that promote the successful transition from the initial deleterious phases of acute lung injury to the later phases of resolution and lung repair in the virus-injured lung.

PI_NAMEs: RIDGE, KAREN M (contact)

PROGRAM_OFFICER_NAME: MONGODIN, EMMANUEL FRANCK

PROJECT_TERMS: 2019-nCoV;Acute Lung Injury;Acute Respiratory Distress Syndrome;Address;Aging;Alveolar;Alveolar Macrophages;Anti-viral Agents;Bronchoalveolar Lavage;Bronchoalveolar Lavage Fluid;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;Cell model;Cells;Cessation of life;Clinical;Complex;COVID-19 pandemic;Data Set;Death Rate;Development;Disease;Distal;DNA;DNA Modification Methylases;Electron Transport;Epithelial Cells;Epithelium;experimental study;Failure;Functional disorder;Genetic;Human;Hypermethylation;Immune;Immune response;Immunologics;Impairment;Individual;individualized medicine;Infection;Inflammasome;Inflammation;Inflammatory;Inflammatory Response;Influenza A virus;Infrastructure;innovation;Intervention;Knowledge;Link;Lower respiratory tract structure;Lung;lung injury;lung repair;Lymphocyte;Macrophage Activation;Mechanical ventilation;Mediating;Mitochondria;monocyte;Morbidity - disease rate;mortality;mouse model;multiple omics;Mutant Strains Mice;neutrophil;NF-kappa B;Organ;Outcome;participant enrollment;pathogen;pathological aging;Pathway interactions;Patients;pharmacologic;Phase;Phenotype;Play;Pneumonia;Population;Preparation;prevent;Primary Infection;Process;Production;Productivity;prospective;Pulmonary Inflammation;Recovery;recruit;Regulatory T-Lymphocyte;repair function;repaired;Research Personnel;resilience;Resolution;respiratory;Respiratory Failure;response;Risk;Role;Sampling;Science;Scientist;seasonal influenza;Secondary to;Signal Transduction;Structure of parenchyma of lung;Supportive care;Technology;Testing;Tidal Volume;Time;tissue repair;Tissues;ventilation;Vimentin;Viral;Viral Pneumonia;Virus;Work

PROJECT_TITLE: Mechanisms of Recovery from Viral Pneumonia

STUDY_SECTION: HLBP

STUDY_SECTION_NAME: Heart, Lung, and Blood Program Project Study Section[HLBP(MA)]


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

PHR: PROJECT NARRATIVE The studies proposed in this application will examine the role of myosteatosis as a determinant of cardiometabolic syndrome (CMS) in obesity. Using a mouse model of obesity individually crossed with models of Galectin 3 (GAL3), NADPH Oxidase 1 (NOX1), and stearoyl-CoA desaturase-1 (SCD1) deletion, we will test the hypothesis that obesity-driven ectopic fat accumulation in SKM drives vascular dysfunction and impaired angiogenesis in a GAL-3 and NOX1 dependent manner and is the underlying cause of CMS, which is ameliorated by the reversal of myosteatosis, improving cardiovascular health by restoring insulin sensitivity. This proposal seeks to explore a novel and poorly understood risk factor in metabolic syndrome and will, through the targeting of the GAL3, NOX1, and SCD1 genes, shed new insight into the mechanisms by which skeletal muscle is protective of vascular health, as well as provide potential therapeutic targets for the treatment of cardiovascular disease.

PI_NAMEs: SPEESE, ANDREW  (contact)

PROGRAM_OFFICER_NAME: NEILSON, KAREN MARY

PROJECT_TERMS: Acute;Aging;American;angiogenesis;Angiopoietin-2;Aorta;artery occlusion;Automobile Driving;Biology;Blood flow;Blood Glucose;Blood Vessels;Body Composition;Body Weight decreased;Cardiometabolic Disease;cardiometabolism;Cardiovascular Diseases;cardiovascular health;Cardiovascular system;Cause of Death;Cell Separation;Chemistry;Chronic;Data;db/db mouse;density;Deposition;design;Development;Distal;Down-Regulation;Endothelial Cells;endothelial dysfunction;Endothelium;Enzymes;Exercise;Fatty acid glycerol esters;femoral artery;Funding;Galectin 3;GDF8 gene;Gene Expression;Genes;Genetic;Genetic Models;glucose disposal;glucose tolerance;glycation;Goals;Health;Hindlimb;Impairment;improved;In Vitro;in vivo;Infiltration;insight;Insulin Resistance;insulin sensitivity;insulin signaling;Intervention;Intracellular Accumulation of Lipids;Ischemia;knockout gene;Knockout Mice;Laboratories;Link;Lipids;Liver;Measurement;Measures;Mediating;medical schools;Mentorship;Metabolic;Metabolic syndrome;Metabolism;Modeling;mortality;mouse model;mRNA Expression;Mus;muscle form;muscle hypertrophy;Muscular Atrophy;Myography;NADPH Oxidase 1;neovascularization;new growth;novel;Obese Mice;obese patients;obese person;Obesity;Operative Surgical Procedures;Organ;Outcome;overexpression;oxidant stress;Patient Compliance;Perfusion;Peripheral;pharmacologic;Phenocopy;Phenotype;Physiological;Physiology;Plasma;post-doctoral training;pre-doctoral;preservation;pressure;protein expression;receptor for advanced glycation endproducts;Recording of previous events;Recovery;Resolution;response;restraint;Risk;Risk Factors;Role;sarcopenia;Site;Skeletal Muscle;skeletal muscle growth;skeletal muscle wasting;Source;Stearoyl-CoA Desaturase;Syndrome;Testing;Therapeutic;therapeutic target;Training;Triglycerides;United States;Universities;Vascular Diseases;Vascular Endothelial Growth Factors;Western Blotting

PROJECT_TITLE: Increasing muscle mass resolves vascular dysfunction in obesity


NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Lung;Pneumonia;Pneumonia and Influenza;Rare Diseases

PHR: PROJECT NARRATIVE It is not required per instructions stated on the Funding Opportunity Announcement PAR-18-405, Section IV. Application and Submission Information, Administrative Core, Research & Related Other Project Information (Administrative Core), “Project Narrative: Do not complete.”

PROJECT_TERMS: 2019-nCoV;acute hypoxemic respiratory failure;Acute Lung Injury;Acute Respiratory Distress Syndrome;Advisory Committees;Alveolar;Alveolar Macrophages;Animals;burden of illness;Cause of Death;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;Cell model;Cells;Cessation of life;Clinical;Collaborations;collaborative environment;Committee Members;Communication;community acquired pneumonia;COVID-19;Cytoprotection;Development;Disease;Distal;economic cost;Economics;Epithelial Cells;Etiology;experimental study;Failure;Feedback;Fostering;Functional disorder;Funding Opportunities;Hospitalization;Human Resources;Hypoxemia;Immune;Immune response;Immunologics;individualized medicine;Infection;Inflammation;Inflammatory;Influenza A virus;Information Dissemination;innovation;Institution;Instruction;Interdisciplinary Study;Link;Lower Respiratory Tract Infection;Lower respiratory tract structure;Lung;lung development;lung injury;lung repair;Lymphocyte;monocyte;mouse model;neutrophil;novel therapeutic intervention;Organ;Outcome;participant enrollment;Pathogenesis;Pathogenicity;Pathway interactions;Patients;Phase;Play;Pneumonia;Population;Postdoctoral Fellow;Process;programs;Publications;Pulmonary Inflammation;Reagent;Recovery;recruit;repaired;Research;Research Personnel;resilience;Resolution;Resource Sharing;Resources;Respiratory Failure;Role;Sampling;Services;Structure;student mentoring;Supportive care;Techniques;Testing;Tidal Volume;tissue repair;Tissues;United States;ventilation;Viral Load result;Viral Pneumonia;Virus;Work

PROJECT_TITLE: Administrative Core

STUDY_SECTION_NAME: Heart, Lung, and Blood Program Project Study Section[HLBP]


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Breast Cancer;Cancer;Cancer Genomics;Clinical Research;Clinical Trials and Supportive Activities;Genetics;Human Genome;Precision Medicine;Women's Health Research

ORG_NAME: UNIVERSITY OF WASHINGTON

PHR: PAR-19-363, Integration of Imaging and Fluid-Based Tumor Monitoring in Cancer Therapy (R01 Clinical Trial Optional) Project Narrative: Assessing response to therapy in patients with bone-only (BO) or bone- dominant (BD) metastatic breast cancer (MBC) is hampered by absence of easily measurable disease by standard imaging criteria and by lack of effective blood biomarkers (i.e., tumor markers). This proposal will integrate fluid-based tumor monitoring (by serial collection of circulating tumor DNA, ctDNA) and FDG-PET/CT imaging to determine if these biomarkers, separately or combined, can predict a response to therapy for in patients with BO or BD MBC in the context of a multi-center, prospective clinical trial, EA1183 (FEATURE).

PI_NAMEs: SPECHT, JENNIFER MARIE (contact)

PROGRAM_OFFICER_NAME: ZHANG, YANTIAN

PROJECT_TERMS: American College of Radiology Imaging Network;Biological Assay;Biological Markers;Blood;blood-based biomarker;bone;burden of illness;cancer therapy;Categories;circulating biomarkers;Classification;Clinical;clinical practice;clinical predictors;Clinical Trials;Collection;Data Set;design;Disease;Disease Progression;Eastern Cooperative Oncology Group;Enrollment;Exclusion;experience;fluorodeoxyglucose positron emission tomography;Future;Generations;genome sequencing;Genomics;glucose metabolism;Goals;Guidelines;Image;imaging biomarker;improved;Lesion;liquid biopsy;Liquid substance;Malignant Bone Neoplasm;Malignant Breast Neoplasm;Measurable Disease;Measurement;Measures;Metabolic;Metastatic breast cancer;Metastatic Neoplasm to the Bone;Methods;Modality;Monitor;Multi-Institutional Clinical Trial;Outcome;Outcome Study;patient population;patient response;Patients;PET/CT scan;predicting response;Prediction of Response to Therapy;Progression-Free Survivals;prospective;Residual Neoplasm;Resistance;response;Role;Scanning;Site;skeletal-related events;Systemic Therapy;Testing;Time;tool;Tracer;treatment response;tumor;Tumor Biology;tumor DNA;Tumor Markers;tumor metabolism;uptake;whole genome;X-Ray Computed Tomography

PROJECT_TITLE: Role of ctDNA change as a response measure in the EA1183 patient population and how ctDNA changes correlate with metabolic response by serial FDG PET/CT


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

NIH_SPENDING_CATS: Attention Deficit Hyperactivity Disorder (ADHD);Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Mental Health;Neurosciences;Pediatric

ORG_CITY: EUGENE

ORG_NAME: UNIVERSITY OF OREGON

ORG_STATE: OR

PHR: PROJECT NARRATIVE Inhibitory control is an essential brain function that is disrupted in people with attention deficit hyperactivity disorder (ADHD). Despite significant progress in illuminating mechanisms and key neural substrates underlying inhibitory control, physiological distinctions between processes related to termination of movement and the cognitive control processes that initiate inhibition are still unclear. This project will address this gap in knowledge by disentangling cortical signatures of the cognitive and motoric aspects of inhibitory control, which will ultimately pave the way for objective diagnostic tools and targeted treatments for ADHD.

PI_NAMEs: SCHULTZ, KELSEY E (contact)

PROGRAM_OFFICER_NAME: KIM, JENNY LILY

PROJECT_TERMS: Acceleration;Address;Adult;American;Anatomy;Area;Attention deficit hyperactivity disorder;Basal Ganglia;Behavioral;Brain;Child;Cognitive;cognitive control;Communication;Data;Development;Diagnosis;diagnostic tool;Disease;Dissociation;Electroencephalography;Electrophysiology (science);Epilepsy;Frequencies;Functional disorder;Hyperactivity;inattention;Inferior frontal gyrus;innovation;Knowledge;Methods;Modeling;Monitor;Motor;Motor Cortex;Motor output;Movement;neural;Neurologic;neurophysiology;neurosurgery;novel;Participant;Patient Monitoring;Performance;Persons;pharmacologic;Physiological;Physiological Processes;Prefrontal Cortex;Prevalence;Process;Reaction;Research;Resistance;Resolution;Sampling;Scalp structure;Signal Transduction;Stimulant;support network;System;Testing;Time;Treatment Protocols;treatment response;trial comparing

PROJECT_TITLE: Characterizing cortical signatures of inhibitory control


ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: Project Narrative The ability to develop a high resolution non-invasive prenatal screen (hrNIPS) that comprehensively surveys all coding variation for pathogenic variants would decrease morbidity associated with invasive testing and has the potential to transform maternal fetal medicine. The optimization and implementation of methods to call the spectrum of variation (SNV, indel, CNV) with hrNIPS and integration of systematic phenotyping will bring this approach closer to clinical use, contribute to the repertoire of variation associated with anomalies in pregnancy, and develop an infrastructure that can be applied to other projects.

PI_NAMEs: DUYZEND, MICHAEL H (contact)

PROGRAM_OFFICER_NAME: PARISI, MELISSA

PROJECT_TERMS: Acceleration;Advisory Committees;Algorithms;Amniocentesis;analytical method;Aneuploidy;Automobile Driving;Awareness;biobank;Blood;Blood specimen;Calibration;career;carrier testing;cell free DNA;cell free fetal DNA;Chorionic Villi Sampling;Clinical;clinical application;clinical diagnosis;Clinical Management;clinically relevant;cloud based;Code;Counseling;Data;database structure;Detection;Development;Diagnosis;diagnostic screening;Discipline;DNA;early pregnancy;exome;exome sequencing;Family;Fellowship;fetal;gene discovery;Genes;Genetic;Genetic Code;Genetic Diseases;genetic testing;Genetic Variation;Genomics;Genotype;Goals;hands on research;Human;improved;Incidental Findings;Infrastructure;innovation;insertion/deletion mutation;insight;Institution;International;Karyotype;laboratory experience;Maternal-fetal medicine;Medicine;member;Mendelian disorder;Mentors;Methods;Modeling;Molecular Diagnosis;Morbidity - disease rate;Mothers;neonatal outcome;novel;Ontology;Pathogenicity;Patients;Performance;Phenotype;phenotypic data;Physicians;Plasma;population based;Pregnancy;Pregnancy Outcome;prenatal;Prenatal care;Prenatal Diagnosis;prenatal testing;Preventive measure;Preventive treatment;Research;Research Support;Resolution;Sampling;Scientist;screening;Sensitivity and Specificity;Signs and Symptoms;Site;skills;standard of care;Standardization;Statistical Models;Structure;Surveys;targeted sequencing;Techniques;Technology;Testing;Time;tool;Training;training opportunity;Umbilical Cord Blood;Variant;Work

PROJECT_TITLE: Comprehensive and non-invasive prenatal screening of coding variation

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


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: PHILADELPHIA

ORG_NAME: PHILADELPHIA VA MEDICAL CENTER

ORG_STATE: PA

PHR: The VA’s Maintaining Internal Systems and Strengthening Integrated Outside Networks (MISSION) Act of 2018 greatly expanded opportunities for Veterans to be referred outside of the VA for complex cardiac procedures. However the VA is a national leader in quality of care for advanced cardiac procedures, thus increased referrals outside of the VA may lower the quality of cardiac care, worsen clinical outcomes, and increase VA’s costs for Veterans receiving cardiac procedures. Our multi-disciplinary research team will use VA’s extensive national data resources on cardiovascular procedural care to examine the MISSION Act’s effect on health care access, quality, outcomes, and costs among Veterans receiving major cardiac procedures. The project’s overarching goals are to inform Veterans’ decisions regarding where they receive advanced cardiac care, improve care coordination, optimize clinical outcomes, and reduce costs.

PI_NAMEs: GROENEVELD, PETER W. (contact)

PROJECT_TERMS: Accounting;Address;Administrator;Affect;aortic valve replacement;Cardiac;Cardiac Surgery procedures;Cardiology;cardiology service;Cardiovascular Diseases;Cardiovascular system;care coordination;care costs;care outcomes;care providers;Caring;Catheterization;Clinical;Clinical assessments;Clinical Data;Colorado;Community Healthcare;Community Hospitals;Complex;Coronary Artery Bypass;cost;Cost Analysis;Data;Data Analyses;data registry;data resource;Data Set;data warehouse;Databases;Decision Making;Diagnosis;Dimensions;Eligibility Determination;Enrollment;Event;experience;Fees;Funding;Future;Goals;health care availability;Health Care Costs;health care quality;health care service;health care service utilization;health economics;Health Personnel;Health Services Accessibility;Health system;Healthcare;Healthcare Systems;Heart Diseases;Hospitals;improved;Information Resources;innovation;insight;Interdisciplinary Study;Intervention;intervention cost;Joints;Laboratories;Leadership;Measures;Medical;Medical center;Medicare claim;Methodology;Morbidity - disease rate;mortality;mortality risk;multidisciplinary;novel;Office Surgery;operation;Operative Surgical Procedures;Outcome;Outcomes Research;Pathway interactions;Patient Care;patient registry;Patients;percutaneous coronary intervention;Performance;Philadelphia;Policy Maker;Probability;procedure cost;Procedures;Process;programs;Provider;Quality of Care;readmission rates;Registries;Reporting;Research;Research Personnel;Resources;Risk Adjustment;Services;Shapes;Surgical Valves;System;Time;tool;Travel;valve replacement;Veterans;Veterans Health Administration;Work

PROJECT_TITLE: Impact of the MISSION Act on Quality and Outcomes of Interventional Cardiology and Cardiac Surgery among Veterans

STUDY_SECTION_NAME: HSR-5 Health Care System Organization and Delivery and Women's Health[HSR5]


NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Biodefense and Related Countermeasures;Clinical Research;Coronaviruses;Coronaviruses Therapeutics and Interventions;Emerging Infectious Diseases;Infectious Diseases;Influenza;Lung;Pneumonia;Pneumonia and Influenza;Rare Diseases

PHR: PROJECT NARRATIVE It is not required per instructions stated on the Funding Opportunity Announcement PAR-18-405, Section IV. Application and Submission Information, Scientific Core, Research & Related Other Project Information (Scientific Core), “Project Narrative: Do not complete.”

PI_NAMEs: WUNDERINK, RICHARD G (contact)

PROJECT_TERMS: 2019-nCoV;Acute Renal Failure with Renal Papillary Necrosis;Acute Respiratory Distress Syndrome;Address;Affect;Alveolar;Animal Model;Animals;Antibiotics;antimicrobial;Biological;Biological Markers;Bronchoalveolar Lavage;Bronchoalveolar Lavage Fluid;Catabolism;Cause of Death;Cell model;Cells;Cessation of life;chemokine;chronic infection;Clinical;clinical phenotype;clinically relevant;co-infection;Communicable Diseases;community acquired pneumonia;Country;COVID-19;COVID-19 pandemic;COVID-19 pneumonia;Critical Care;Data;Death Certificates;Death Rate;Discrimination;Encephalopathies;epigenomics;Failure;Flow Cytometry;Functional disorder;Funding Opportunities;Goals;Grant;Human;Immune;Immune system;Infection;Inflammation;Inflammatory;Influenza;Influenza A virus;influenza pneumonia;Infrastructure;Injury;Instruction;International;Intubation;Knowledge;Liquid substance;Liver Dysfunction;Lower Respiratory Tract Infection;Lung;lung failure;lung injury;lung repair;Mechanical ventilation;metabolomics;microbiome alteration;Modeling;Modernization;mortality;mouse model;Mus;Muscle;National Institute of Allergy and Infectious Disease;Nosocomial pneumonia;Organ;Organ failure;Oseltamivir;Outcome;pathogen;pathogenic bacteria;pathogenic virus;Pathway interactions;Patients;Pattern;Phenotype;Pneumonia;pneumonia treatment;Population;Population Study;programs;Protein Analysis;Protocols documentation;Publishing;Recovery;remdesivir;repaired;Research;Research Personnel;Resolution;Resources;Respiratory Tract Infections;respiratory virus;response;Sampling;Sepsis;sepsis induced ARDS;severe COVID-19;Sorting;Streptococcus pneumoniae;superinfection;Systems Biology;Therapeutic Intervention;Time;transcriptomics;United States;Universities;Vasoconstrictor Agents;Viral;Viral Pneumonia;Virus

PROJECT_TITLE: Clinical Phenotyping and Human Core


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

ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

PHR: Project Narrative: Centrosome aberrations disrupt mitosis and lead to genome instability: a hallmark of cancer. This study aims to understand how Orb2, a conserved RNA-binding protein implicated in RNA localization and translational regulation, regulates neural stem cell centrosome dynamics and mitotic spindle organization required for mitotic fidelity. Successful completion of this study will illuminate drivers of disease progression and liabilities opportune for intervention.

PI_NAMEs: BUEHLER, JOSEPH  (contact)

PROGRAM_OFFICER_NAME: MATTHEWS, MARGUERITE

PROJECT_TERMS: Apical;Auras;aurora kinase A;Binding;Biological Models;Brain;cancer cell;Cell Cycle;Cell division;Cells;Cellular biology;Centrioles;Centrosome;Centrosome Pathway;Chromosome Segregation;CPE-binding protein;crosslinking and immunoprecipitation sequencing;Cytokinesis;Data;daughter cell;Defect;Disease;Disease Progression;Drosophila genus;Exhibits;Failure;Genomic Instability;Goals;Human;Image;insight;Interphase;Intervention;Lead;Malignant neoplasm of brain;Malignant Neoplasms;Mediating;Membrane;Messenger RNA;Metaphase;Microtubule-Organizing Center;Microtubules;Mitosis;Mitotic;Mitotic spindle;Modeling;Natural regeneration;nerve stem cell;neuroregulation;Organelles;Orthologous Gene;Post-Transcriptional Regulation;Prognosis;Proteins;recruit;Regulation;Reporting;Repression;RNA;RNA Binding;RNA-Binding Proteins;Role;segregation;self-renewal;stem cell model;stem cells;Testing;trafficking;Transcript;Translational Regulation;Translational Repression;Translations;tumor progression;tumorigenesis

PROJECT_TITLE: Elucidating the mechanisms of Orb2 mediated neural stem cell asymmetry and division

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


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Project Narrative Tendon hierarchical structure dictates its ability to effectively transmit loads from muscle to bone and formation of tendon during tendon development and healing is reliant on coordination of multiscale regulatory governing processes such as formation of fibrils from collagen molecules, assembly of fibril bundles to form fibers, and recruitment of fibers to form fascicles. The objective of this proposal is to establish the mechanisms involving collagen XII regulation of tendon hierarchical structure, mechanical function and composition throughout postnatal development and healing. Utilizing our innovative mouse models, we will define tendon-specific regulatory mechanisms involving collagen XII to provide a fundamental understanding of the acquisition of tendon structure and function and its re-establishment during healing.

PI_NAMEs: DISTEFANO, MICHAEL STEVEN (contact)

PROGRAM_OFFICER_NAME: PINTUCCI, GIUSEPPE

PROJECT_TERMS: achilles tendon;Biological;Biological Assay;bone;Cell surface;clinical phenotype;cohesion;Collagen;Collagen Fibril;Communication;Data;Development;Discrimination;Extracellular Matrix;Fascicle;Fiber;Fibril-Associated Collagens;fibrillogenesis;flexibility;Foundations;healing;human disease;Impairment;Inferior;Injury;innovation;Investigation;knock-down;Knock-out;Knockout Mice;mechanical properties;Mechanics;Mediating;Modeling;mouse model;multidisciplinary;Mus;Muscle;nanoscale;novel;postnatal development;prenatal;Process;Property;recruit;Regenerative response;Regulation;repaired;Research Personnel;response;response to injury;restoration;Role;Scientific Inquiry;scleraxis;Structure;tendon development;Tendon Injuries;Tendon structure;Testing;tissue regeneration;Tissues;transmission process;wound

PROJECT_TITLE: Regulatory Mechanisms of Collagen XII in Establishing Achilles Tendon Hierarchical Structure and Function in Postnatal Development and Healing


ADMINISTERING_IC: MD

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Depression;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Mental Illness;Pediatric;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: RICHMOND

ORG_DEPT: PSYCHOLOGY

ORG_NAME: VIRGINIA COMMONWEALTH UNIVERSITY

ORG_STATE: VA

PHR: PROJECT NARRATIVE  Racial discrimination has been identified as the primary social stressor for Black youth1 where 90% of Black youth (age 8-16) reportedly experienced at least one racial discriminatory encounter.2 The proposed study will utilize physiological data to assess the physical effects of in-the-moment racial coping paired with self-report of racial coping and mental health outcomes among Black adolescents. The proposed research will 1) provide a person-centered approach to understanding racial coping and its effects on depression, stress, and anxiety, as well as the moderating effects of cultural familial processes on racial coping, and 2) inform theory and efforts to promote positive youth development in the face of racial discrimination.

PI_NAMEs: DAVIS, RACHEL J (contact)

PROGRAM_OFFICER_NAME: GARRIDO, CARLOS OSWALDO

PROJECT_TERMS: Address;Adolescence;Adolescent;Adolescent Development;adolescent mental health;Adverse effects;Affect;African American;Age;allostatic load;Anxiety;anxiety symptoms;Arousal;Award;Behavioral;Biological;Black Populations;Black race;cardiovascular risk factor;Child Rearing;Chronic;Cognitive;cognitive function;coping;Coping Skills;Data;Decision Making;depressive symptoms;Development;Discrimination;emotion regulation;Emotional;Emotions;Environment;Equilibrium;experience;flexibility;Future;Galvanic Skin Response;Goals;Health;high risk sexual behavior;Hormonal;Individual;Individual Differences;Injury;Intervention;Investigation;junior high school;Link;Literature;Logistic Regressions;Longitudinal Studies;Measurement;Measures;Mental Depression;Mental Health;Methods;microaggression;Modeling;National Institute of Mental Health;National Institute on Minority Health and Health Disparities;National Research Service Awards;Nature;neglect;novel;Outcome;outcome prediction;Parents;Pathway interactions;Patient Self-Report;perceived discrimination;person centered;Personal Satisfaction;Physical assessment;physical conditioning;Physiological;Physiological Processes;Population;positive youth development;Prevalence;Process;psychological distress;Psychopathology;psychosocial development;Public Health;Race;racial difference;racial discrimination;racial population;racism;Regulation;Reporting;Research;research and development;Resolution;respiratory;Risk;Role;Sinus Arrhythmia;skills;social stressor;Socialization;Stimulus;Stress;stress symptom;Structure;Subgroup;Substance abuse problem;System;Taxes;Testing;theories;Virginia;Youth

PROJECT_TITLE: A Physiological Approach to Examining the Role of Racial Coping on Mental Health Among Black Adolescents

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


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

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: PROJECT NARRATIVE Missense mutations directly cause or exacerbate human diseases by introducing changes to the amino acid sequence of a protein that disrupt its native biophysical properties. Attempts to predict these functional effects from sequence variation have leveraged recent advancements in sequence-based machine learning, but have suffered from a lack of large, biochemical datasets connecting sequence variance to descriptive measurements of in vitro effects. Here, I will develop a cutting-edge experimental strategy to make quantitative biophysical measurements for thousands of mutations in a major class of human proteins and establish a framework for leveraging this data to enhance sequence-based predictive models for variant effects prediction.

PI_NAMEs: OLIVAS, MICAH  (contact)

PROGRAM_OFFICER_NAME: FUFA, TEMESGEN D

PROJECT_TERMS: Address;Adoption;Affect;Affinity;Agreement;Alanine;Algorithms;Amino Acid Sequence;Amino Acid Substitution;Base Sequence;Binding;Biochemical;Biological Assay;biophysical properties;Biophysics;blind;Catalysis;Cells;Clinical;ClinVar;Cloning;Code;cofactor;Collaborations;Complex;computer framework;Computer Models;computerized tools;cost;Coupled;Data;data integration;Data Set;Databases;deep learning;deep learning model;design;Development;Disease;disease phenotype;DNA sequencing;Engineering;Enzymes;experimental study;Explosion;Family;Fellowship;Fluorescence;Foundations;Free Energy;functional outcomes;Funding;Gene Expression Regulation;Genome;genomic data;Genomic medicine;Glycine;Goals;Human;human disease;Human Genome;improved;In Vitro;in vitro testing;in vivo;insight;Kinetics;Laboratories;Learning;Libraries;Machine Learning;machine learning model;Maps;Measurement;Measures;MEKs;Metabolism;Methods;microfluidic technology;Microfluidics;Missense Mutation;Modeling;Molecular Conformation;molecular sequence database;Mutagenesis;mutant;Mutation;Nature;novel;Orthologous Gene;Output;Pathogenicity;Performance;Phenotype;Positioning Attribute;Postdoctoral Fellow;precision medicine;predictive modeling;Property;Protein Biochemistry;protein expression;protein folding;protein function;protein structure prediction;Proteins;Publishing;Reaction;Recombinants;Research;Research Design;Resources;Role;Scanning;Sequence Analysis;Series;skills;Structure;success;supervised learning;Techniques;Testing;Thermodynamics;Training;Translating;United States National Institutes of Health;Universities;Valine;Variant;Vertebral column;Work

PROJECT_TITLE: High-throughput thermodynamic and kinetic measurements for variant effects prediction in a major protein superfamily


NIH_SPENDING_CATS: Cardiovascular;Congenital Heart Disease;Congenital Structural Anomalies;Genetics;Heart Disease;Human Genome;Infant Mortality;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Rare Diseases

PHR: Project Narrative A protein traffic control system that regulates left-right patterning and heart development The development of the heart and its correct connection to major blood vessels depends on complex and poorly understood systems that control left-right asymmetry of our internal organs. By advancing the understanding of cell-cell communication mechanisms that establish the identity of the left and right sides of the heart, we hope to build the foundation for new diagnostic, preventative and therapeutic strategies for the ~7000 babies born in the United States each year with severe congenital heart disease.

PI_NAMEs: GUNN, TERESA M;LO, CECILIA W.;ROHATGI, RAJAT  (contact)

PROGRAM_OFFICER_NAME: SCHRAMM, CHARLENE A

PROJECT_TERMS: 3-Dimensional;Affect;Alleles;Anatomy;Attenuated;Biochemical;Biological Assay;Birth;Blood Vessels;cardiogenesis;Cell Communication;Cell surface;Cells;Characteristics;Clustered Regularly Interspaced Short Palindromic Repeats;Code;cohort;Complex;Congenital Abnormality;congenital heart abnormality;Congenital Heart Defects;CRISPR screen;critical developmental period;critical period;Data;Defect;Development;Diagnostic;Double Outlet Right Ventricle;Embryo;Erinaceidae;exome sequencing;Face;Foundations;Functional disorder;Genes;Genetic;genetic architecture;Genetic Predisposition to Disease;genetic testing;genome-wide;Heart;heart defect;Human;Human Genetics;in vitro Assay;Infant Mortality;Inheritance Patterns;Integral Membrane Protein;Left;Life;Ligands;Limb structure;Link;Live Birth;Membrane;Membrane Proteins;Modeling;Molecular;Morbidity - disease rate;Morphogenesis;mortality;mouse development;mouse genetics;mouse model;Mus;mutant;Mutation;novel;novel diagnostics;Operative Surgical Procedures;Organ;Outcome;Pathogenicity;Pathway interactions;Patients;Pattern;Penetrance;pharmacologic;Phenocopy;Play;Procedures;Proteins;Proteomics;receptor;Receptor Signaling;reconstruction;Registries;Research Personnel;Role;Side;Signal Transduction;Situs Inversus;Skeleton;smoothened signaling pathway;stillbirth;Structural Congenital Anomalies;Syndrome;System;Testing;Therapeutic;Tissues;trafficking;Transducers;Transposition of Great Vessels;ubiquitin ligase;ubiquitin-protein ligase;Ubiquitination;United States;Variant;Visceral

STUDY_SECTION: CDD

STUDY_SECTION_NAME: Cardiovascular Differentiation and Development Study Section[CDD]


ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Hypertension;Neurosciences;Women's Health Research

ORG_CITY: Newark

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: UNIVERSITY OF DELAWARE

ORG_STATE: DE

PHR: PROJECT NARRATIVE Sodium sensing in the brain is critical in mediating neurohormonal responses to acute hypernatremia. The goal of this proposal is to use BOLD fMRI to determine whether there are sex differences in central neural activation of sodium sensing brain regions and brain regions involved in regulating sympathetic outflow during acute hypernatremia elicited via hypertonic saline infusion. Identification of sex differences in brain activation could have important implications for understanding sex differences in fluid balance and blood pressure responses to sodium.

PI_NAMEs: ROMBERGER, NATHAN  (contact)

PROJECT_TERMS: Acute;Adult;Age;Androgen Receptor;Animals;Blood;Blood - brain barrier anatomy;blood oxygen level dependent;Blood Pressure;blood pressure control;blood pressure regulation;Brain;Brain region;Cardiac Output;cardioprotection;Cardiovascular system;Catecholamines;Cell Nucleus;Data;Dehydration;Development;Dietary Sodium;Disease;Estrogen Receptors;Event;Exercise;female sex hormone;Fluid Balance;Functional Magnetic Resonance Imaging;Goals;Gonadal Steroid Hormones;Head;health disparity;High Prevalence;Hormonal;Human;Hypernatremia;Hypertension;Hypothalamic structure;Incidence;Infusion procedures;insight;Instruction;Insula of Reil;Intake;Ischemia;Isometric Exercise;Lower Body Negative Pressure;male;Measures;Mediating;men;Menstrual cycle;Muscle;Nerve;neural;neuroimaging;Neurons;neuroregulation;Norepinephrine;Organ;organum vasculosum of the lamina terminalis;Peripheral Resistance;Phase;Plasma;Prevalence;Productivity;Prosencephalon;Public Health;Research;response;Rest;Rodent;Rodent Model;Saline;salt intake;salt sensitive;Scientist;sex;Sex Differences;Signal Transduction;Sodium;Sodium Chloride;stressor;Subfornical Organ;technical writing;Thirst;Training;Vasopressins;Woman;Women's Role;young woman

PROJECT_TITLE: Sex Differences in Central Neural Activation During Acute Hypernatremia


NIH_SPENDING_CATS: Complementary and Integrative Health;Dietary Supplements;Nutrition;Prevention;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: SALT LAKE CITY

ORG_NAME: UNIVERSITY OF UTAH

PHR: PROJECT NARRATIVE Folate-mediated one-carbon metabolism regulates biological processes critical to hematopoietic stem cell (HSC) establishment and function, however how folate supplementation affects the developing hematopoietic system is unknown. We hypothesize that varying prenatal folate status will affects alter HSC function across adulthood by perturbing HSC metabolism during development. The objective of this grant is to identify the effect of varying prenatal folate status on HSC function and development across the lifespan.

PI_NAMEs: KRUM, BRIAN  (contact)

PROGRAM_OFFICER_NAME: BAI, C BRIAN

PROJECT_TERMS: Address;Adult;Adult Children;Affect;Automobile Driving;Bioinformatics;Biological Process;Blood;Carbon;career development;Cell Compartmentation;Cell Lineage;Cell Nucleus;Cell Physiology;Cell Proliferation;Cells;Cellular Metabolic Process;Chronic;Chronic Disease;Complex;Cytoplasm;Data;Data Set;Development;Developmental Process;Disease;disorder risk;early-life nutrition;Ensure;Epigenetic Process;epigenetic regulation;Event;Exposure to;Failure;fetal;Fetal Development;Folic Acid;Folic Acid Deficiency;Folic acid fortification;folic acid supplementation;Formates;Gene Expression;Genome Stability;Glycolysis;Goals;Grant;Growth;Health;Hematopoiesis;Hematopoietic;hematopoietic stem cell self-renewal;Hematopoietic stem cells;Hematopoietic System;Heterogeneity;Immune;immune function;Immune System Diseases;Inflammation;interest;Intervention;Life;life span;Link;Lymphoid;Maps;Measures;Mediating;Membrane Potentials;Mentorship;Metabolic;Metabolism;Methylation;Mitochondria;mitochondrial membrane;mitochondrial metabolism;Modeling;Molecular;mother nutrition;Multipotent Stem Cells;Neural Tube Closure;Neural Tube Defects;nutrition;Nutritional;Onset of illness;Outcome;Output;Oxidative Phosphorylation;Pathogenesis;Pattern;perinatal development;Population;postnatal period;Predisposition;prenatal;prenatal testing;prevent;Prevention;Process;Production;programs;Proliferating;Public Health;Purines;Reactive Oxygen Species;Regulation;Research;Respiratory Chain;Risk;S-Adenosylhomocysteine;S-Adenosylmethionine;self-renewal;Shapes;skill acquisition;skills;Source;Stem Cell Development;stem cell function;stem cells;success;Testing;thymidylate;Time;tool;Toxicant exposure;Training;Translations;Universities;Utah;Work;Writing

PROJECT_TITLE: Metabolic Programming of Hematopoietic Stem Cell Function by Prenatal Folate


NIH_SPENDING_CATS: Autoimmune Disease;Biotechnology;Genetics;Human Genome;Lupus;Women's Health Research

ORG_CITY: HERSHEY

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: PENNSYLVANIA STATE UNIV HERSHEY MED CTR

PHR: PROJECT NARRATIVE The genetic architecture of X chromosome and X-chromosome inactivation (XCI) escape and their links to sex- biased phenotypes remains poorly understood, presumably due to unique analytic challenges. In this research we propose two methods that accurately model the unique biology of X chromosome to genetically identify relevant tissue/cell types and X-linked genes in which aberrant regulation of XCI plays a significant role in the etiology of complex diseases and traits. We will apply our methods to some of the largest datasets across various tissue/cell types and a variety of complex traits including lupus, diabetes, and addiction to not only improve functional genomics and disease association analysis of the X chromosome but also highlight the unappreciated role escape from XCI plays in shaping human health.

PI_NAMEs: MARKUS, HAVELL  (contact)

PROGRAM_OFFICER_NAME: MCINTYRE, JEREMY COLIN

PROJECT_TERMS: addiction;Address;Alleles;Allelic Imbalance;Autoimmune Diseases;Biological Assay;Biology;Cell Fraction;Cell Line;cell type;Cells;Clinical;clinically relevant;Complex;computational suite;Data;Data Set;Development;Diabetes Mellitus;Disease;Disproportionately impacts women;Dosage Compensation (Genetics);Etiology;Female;functional genomics;Gene Dosage;Gene Expression Regulation;Gene Silencing;Genes;Genetic;genetic architecture;genetic association;Genetic Transcription;genetic variant;genome wide association study;Genomics;Genotype;Haplotypes;Health;Heritability;Heterozygote;Human;human tissue;Human X Chromosome;improved;Individual;individual variation;Knowledge;Link;Lupus;lymphoblast;male;Maps;Mendelian randomization;Methods;Modeling;Mosaicism;Non-Insulin-Dependent Diabetes Mellitus;novel;Phase;Phenotype;Play;Population;Quantitative Trait Loci;Regulation;Research;Role;Sampling;Series;sex;Sex Bias;Shapes;Statistical Methods;Time;Tissue-Specific Gene Expression;Tissues;tool;trait;transcriptome sequencing;Variant;Work;X Chromosome;X Inactivation

PROJECT_TITLE: Genetic regulation of genes on active and inactive X chromosome and their contribution to sex-biased diseases

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


NIH_SPENDING_CATS: Biotechnology;Endocrine Disruptors;Genetics;Human Genome;Social Determinants of Health

ORG_CITY: DURHAM

ORG_DEPT: BIOLOGY

ORG_NAME: DUKE UNIVERSITY

PHR: The proposed research is relevant to public health because it will harness innovative genomics approaches to identify causal gene variants and regulatory pathways involved in response to poly- and perfluoroalkyl substance (PFAS) exposure to reveal specific structure-activity signatures of toxicity. This knowledge will potentially advance risk assessment for the thousands of PFAS pollutants of unknown toxicity. The proposed research is relevant to the parts of the mission of National Institutes of Environmental Health Sciences to identify variation in sensitivity and response to exposures, advance predictive toxicology, and ultimately contribute to the reduction of negative health outcomes associated with environmental pollution.

PI_NAMEs: LEUTHNER, TESS CATHERINE (contact)

PROGRAM_OFFICER_NAME: HUMBLE, MICHAEL C

PROJECT_TERMS: Acceleration;Affect;ATAC-seq;bioaccumulation;Caenorhabditis elegans;Candidate Disease Gene;causal variant;Cessation of life;chemical safety;Chemicals;Chromatin;Chromatin Structure;consumer product;contaminated drinking water;cooking;Data;Development;Dimensions;Disease;drinking;Environmental Health;Environmental Pollution;Epidemiology;Etiology;Exhibits;Exposure to;Frequencies;Functional disorder;functional genomics;functional group;Gene Expression;Gene Expression Regulation;Genes;Genetic;genetic architecture;genetic variant;Genetic Variation;genome editing;genome resource;genome wide association study;Genomic approach;genomic variation;Goals;Half-Life;Health;Health protection;Hour;Immune;improved;Individual;Industrialization;innovation;insulin signaling;Kidney Diseases;Knowledge;Laboratories;Length;lipid metabolism;Liver diseases;Malignant Neoplasms;Mediating;Methodology;Mission;Molecular;mRNA sequencing;multiple omics;National Institute of Environmental Health Sciences;novel;novel strategies;Outcome;Pattern;Phenotype;pollutant;Pollution;Poly-fluoroalkyl substances;Population;Population Growth;Positioning Attribute;premature;Process;Production;Property;Public Health;Quantitative Trait Loci;Regulation;Regulatory Pathway;Reproduction;Research;Research Proposals;Resistance;Resources;response;Risk Assessment;safety testing;Site;Structure;Structure-Activity Relationship;Technology;Testing;Thyroid Gland;Toxic effect;Toxicity Tests;Toxicology;transcriptome sequencing;Transposase;Variant

PROJECT_TITLE: Natural variation in C. elegans responses to environmental pollution


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Bioengineering;Biotechnology;Emerging Infectious Diseases;Genetics;Human Genome;Infectious Diseases;Influenza;Lung;Pneumonia;Pneumonia and Influenza;Regenerative Medicine

PI_NAMEs: MISHARIN, ALEXANDER  (contact)

PROJECT_TERMS: Acceleration;aged;Alveolar;alveolar epithelium;Alveolar Macrophages;Animal Experiments;Animal Model;Animals;Attention;B-Lymphocytes;Blinded;Blood Vessels;Bone Marrow;Breeding;Cell Separation;cell type;Cells;central database;Chest;Chimera organism;Collagen;conditional knockout;cost;Cre driver;cytokine;Dendritic Cells;Deposition;DNA;Endothelial Cells;Enterobacteria phage P1 Cre recombinase;Environment;eosinophil;epigenomics;Epithelial Cells;Epithelium;experience;experimental study;Fibroblasts;Flow Cytometry;Funding Opportunities;Generations;Genes;Genetically Engineered Mouse;Genotype;Histologic;Human Resources;Immune;indexing;Individual;inducible Cre;Infection;Inflammatory;Influenza;influenza A pneumonia;Influenza A virus;Influenza A Virus, H1N1 Subtype;Instruction;interest;interstitial;Intervention;Knock-out;Knockout Mice;Libraries;Liquid substance;Lung;Lung Compliance;lung injury;lung repair;lymphoid organ;Macrophage;mast cell;Measurement;Measures;Mechanics;metabolomics;Modeling;Molecular;monocyte;Morbidity - disease rate;mortality;mouse model;Mus;Natural Killer Cells;neutrophil;non-invasive imaging;Outcome Measure;overexpression;Pathway interactions;Phenotype;Pneumonia;Population;Procedures;programs;Proteins;Pulmonary Inflammation;Recovery;recruit;repaired;Reporter;Reproducibility;Research;Research Personnel;Resistance;Resources;response;RNA;second harmonic;single-cell RNA sequencing;Sorting;Standardization;Strategic Planning;Structure;synergism;System;T-Lymphocyte;T-Lymphocyte Subsets;Techniques;Testing;Tissues;Titrations;tool;transcriptome sequencing;transcriptomics;Transgenic Organisms;Type II Epithelial Receptor Cell;Viral;Viral Pneumonia;Virus

PROJECT_TITLE: The Cell Phenotyping and Mouse Core


NIH_SPENDING_CATS: Cardiovascular;Congenital Heart Disease;Congenital Structural Anomalies;Heart Disease;Pediatric;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: PROJECT NARRATIVE Abnormalities in right ventricle (RV) development are associated with congenital heart disease (CHD), however lack of appropriate animal models has hindered studies of the molecular basis of RV development following chamber formation. Our analysis of mice with cardiomyocyte (CM)-specific knockout (cKO) of NEDD4 (Neural precursor cell expressed developmentally downregulated protein 4), a HECT E3 ubiquitin ligase, revealed a unique RV-specific phenotype. Proposed studies are aimed to elucidate the role of NEDD4 in RV development, as well as the impact of congenital RV defects on cardiac performance, by histological, physiological, biochemical, and molecular analyses of constitutive Nedd4 cKO mice, and to determine the critical window during which NEDD4 is required for RV development by analysis of tamoxifen-inducible Nedd4 knockout mice.

PI_NAMEs: FANG, XI  (contact)

PROJECT_TERMS: Ablation;Adult;Agreement;Animal Model;Anterior;Binding;Biochemical;C2 Domain;Cardiac;Cardiac Myocytes;cardiogenesis;Cellular Membrane;comparison control;congenital heart abnormality;Critical Pathways;Data;Defect;Development;differential expression;early embryonic stage;Embryo;Endoplasmic Reticulum;Family;Growth;Heart;Heart Atrium;heart function;Histologic;Human;Knock-out;Knockout Mice;Left ventricular structure;malformation;Mediating;member;Membrane;Mesoderm;Modeling;Molecular;Molecular Analysis;Morphology;mouse model;Mus;mutant;N-terminal;nerve stem cell;novel;Nuclear;Pathway interactions;Performance;Perinatal;Phenotype;Phospholipids;Physiological;Play;postnatal;Proline;Proteins;Proteomics;Pulmonary vessels;Right Ventricular Dysfunction;Right ventricular structure;Role;Specific qualifier value;Tamoxifen;Testing;Time;Tissues;Transmission Electron Microscopy;Tube;UBE3A gene;ubiquitin-protein ligase;Vacuole;Ventricular;Vesicle

PROJECT_TITLE: NEDD4 in right ventricular development


NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Lung;Lung Cancer;Palliative Care;Precision Medicine;Prevention

PHR: PROJECT NARRATIVE Advances in precision oncology have led to extended survival for patients with metastatic oncogene-driven non-small cell lung cancer (NSCLC), yet metastatic NSCLC remains incurable and patients live with uncertainty regarding their prognosis that leads to distress. This clinical research and career development proposal will support an early stage investigator to refine and pilot test a palliative care intervention that integrates elements of survivorship care for patients with metastatic oncogene-driven NSCLC. The intervention aims to decrease distress related to uncertainty, increase self-efficacy for management of chronic disease, improve prognostic understanding and increase communication about goals and values to inform future decision making among this novel population of cancer survivors living with incurable cancer.

PI_NAMEs: PETRILLO, LAURA ANNE (contact)

PROGRAM_OFFICER_NAME: RADAEV, SERGEY

PROJECT_TERMS: acceptability and feasibility;Active Learning;Address;Adenocarcinoma;Advanced Malignant Neoplasm;Advisory Committees;Advocate;Area;Award;Awareness;Behavior Therapy;Behavioral;Behavioral Research;Cancer Etiology;Cancer Survivor;Cancer Survivorship;care delivery;care preference;career;career development;Caring;Cessation of life;Chronic;Chronic Disease;Clinical Research;Clinical Trials;Clinical Trials Design;Collaborations;Communication;coping;Data Analyses;Decision Making;Disseminated Malignant Neoplasm;Distress;Documentation;driver mutation;Elements;Eligibility Determination;end of life care;end-of-life communication;Enrollment;Epidermal Growth Factor;Exclusion;experience;Feedback;Five-Year Plans;follow-up;Foundations;Funding;Future;Goals;Grant;Health;improved;innovation;Intervention;intervention effect;Interview;Knowledge;life-limiting cancer;Lived experience;Malignant neoplasm of lung;Malignant Neoplasms;Medical;medical specialties;Mentors;Mentorship;Modeling;Mutation;Non-Small-Cell Lung Carcinoma;novel;novel therapeutics;Oncogenes;Oncogenic;Oncologist;Oncology;Palliative Care;participant enrollment;Patient Care;patient oriented;patient population;patient subsets;Patients;Physicians;Pilot Projects;pilot test;Population;Population Intervention;Positioning Attribute;precision medicine;precision oncology;preference;Prognosis;prognostic;programs;Protocols documentation;Psychology;Public Health Schools;Quality of life;randomized, clinical trials;Randomized, Controlled Trials;Research;research and development;Research Methodology;Research Personnel;response;Self Efficacy;side effect;skills;Specialist;Supportive care;Surveys;Survivors;survivorship;symposium;Symptom Burden;targeted treatment;therapy development;Training;treatment as usual;treatment trial;Treatment/Psychosocial Effects;trial comparing;Uncertainty;United States;United States National Institutes of Health

PROJECT_TITLE: Optimizing Supportive Care for Patients with Metastatic Lung Cancer in the Era of Precision Oncology

STUDY_SECTION: NCI

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


NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Influenza;Lung;Pneumonia;Pneumonia and Influenza;Rare Diseases;Regenerative Medicine

PHR: PROJECT NARRATIVE It is not required per instructions stated on the Funding Opportunity Announcement PAR-18-405, Section IV. Application and Submission Information, Project, Research & Related Other Project Information (Project), “Project Narrative: Do not complete.”

PI_NAMEs: RIDGE, KAREN M (contact)

PROJECT_TERMS: 2019-nCoV;Acute;Acute Respiratory Distress Syndrome;Adenosine;Alveolar Macrophages;Amphiregulin;Antibodies;Automobile Driving;Cells;chemokine;Clinical;clinically relevant;community acquired pneumonia;conditional knockout;COVID-19;COVID-19 patient;COVID-19 pneumonia;Credentialing;cytokine;Data;depolymerization;Epidermal Growth Factor;Epithelium;Etiology;Exhibits;experimental study;extracellular;Failure;Flow Cytometry;Funding;Funding Opportunities;Gene Expression;Gene Expression Profile;Genes;IL18 gene;Immune response;Impairment;improved;Infection;Inflammasome;Inflammation;Inflammatory;Inflammatory Response;Influenza A virus;influenza infection;injury and repair;Instruction;Interleukin-1 beta;Intermediate Filaments;Knockout Mice;Lower respiratory tract structure;Lung;lung injury;lung repair;Macrophage;Mediating;Metabolic;Monoclonal Antibodies;monocyte;Morbidity - disease rate;mortality;mouse model;Mus;National Institute of Allergy and Infectious Disease;novel;Outcome;participant enrollment;pathogen;Patients;Phenotype;placebo controlled trial;Play;Pneumonia;prevent;Process;Production;Proliferating;Pulmonary Inflammation;Recovery;recruit;Regulatory T-Lymphocyte;repair function;repaired;Reporting;Research;Resolution;Respiratory Failure;Role;Signal Transduction;Structure of parenchyma of lung;targeted treatment;Techniques;Testing;tissue repair;Tissues;Vimentin;Viral;Viral Pneumonia;Virus;Virus Diseases

PROJECT_TITLE: Project 1: Vimentin regulates host response and repair mechanisms to influenza A viral pneumonia


NIH_SPENDING_CATS: Clinical Research;Physical Injury - Accidents and Adverse Effects;Prevention

ORG_CITY: KUMASI

ORG_COUNTRY: GHANA

ORG_FIPS: GH

ORG_NAME: KWAME NKRUMAH UNIVERSITY/SCIENCE/TECH

PHR: NARRATIVE In stark contrast to the reduction in injury deaths among industrial nations, low and middle-income countries have experienced growing rates of injury, especially in sub-Saharan Africa. This proposal builds upon long- standing collaborations developed among the Kwame Nkrumah University of Science and Technology (KNUST), other Ghanaian institutions involved with injury control, and the University of Washington, in order to (i) develop a cadre of trained injury research leaders, and (ii) engage junior researchers in innovative, mentored injury related health research to reduce the burden of injury and strengthen the practice of injury control; and (iii) build capacity for injury control in Ghanaian and other West African institutions. We will develop, expand and consolidate existing collaborative research and training networks by integrating researchers from Ghana, other West African nations, the UW and other institutions with a shared commitment to preventing and treating injury.

PI_NAMEs: DONKOR, PETER  (contact);MOCK, CHARLES N.

PROGRAM_OFFICER_NAME: LEVINTOVA, MARYA

PROJECT_TITLE: Strengthening Injury Control Research in Ghana and West Africa


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Complementary and Integrative Health;Data Science;Machine Learning and Artificial Intelligence;Natural Products;Networking and Information Technology R&D (NITRD)

ORG_CITY: Nashville

ORG_DEPT: CHEMISTRY

ORG_NAME: VANDERBILT UNIVERSITY

PHR: Project Narrative Natural products from bacteria, fungi, and plants have long been a rich source of therapeutically relevant molecules, but the relationship between natural product structure and activity is not fully understood, hindering our ability to further optimize natural products for therapeutic use. Machine learning can be used to develop models that explain trends in data and make predictions for new data points. In this work we will apply machine learning to understand structure-activity relationships in natural products, design biosynthetic gene clusters to improve our ability to biosynthesize natural product analogs, and repurpose natural products as protein- protein interaction inhibitors.

PI_NAMEs: WALKER, ALLISON SARA (contact)

PROGRAM_OFFICER_NAME: NGUYEN, HAN

PROJECT_TERMS: Anabolism;analog;Attention;Bacterial natural products;Behavior;Biochemical;Biological;Chemical Structure;Chemicals;Complex;Computational Technique;computerized tools;Computers;Coupling;Data;design;Directed Molecular Evolution;drug discovery;Enzymes;experimental study;fungus;Gene Cluster;gene product;Genes;genetic approach;Genetic Structures;graph neural network;high throughput screening;improved;inhibitor;interest;Machine Learning;machine learning algorithm;machine learning method;machine learning model;method development;Methods;Modeling;Molecular Machines;molecular modeling;natural product inspired;Natural Products;novel;Pathway interactions;Peptide Leader Sequences;peptide synthase;Peptides;Plants;polyketide synthase;Property;protein aminoacid sequence;protein protein interaction;Ribosomes;Source;Structure;Structure-Activity Relationship;System;Therapeutic;Therapeutic Uses;training data;trend;Work

PROJECT_TITLE: Machine learning approaches for the discovery, repurposing, and optimization of natural products with therapeutic potential