NIH_SPENDING_CATS: Brain Disorders;Complementary and Integrative Health;Dietary Supplements;Genetics;Mental Health;Neurosciences;Nutrition;Pediatric

PHR: PROJECT NARRATIVE Maternal nutrition plays a vital role in the trajectory of infant brain development, and omega-3 polyunsaturated fatty acid (n-3 PUFA) deficiency during this sensitive period is linked to white matter defects and psychiatric disorders. This proposal seeks to understand whether low n-3 PUFA status culminates in the dysregulation of myelin, the axon insulator within white matter. These experiments will provide insight into a cellular mechanism by which n-3 PUFAs may contribute to cognitive function and reveal nutritional strategies for the prevention of neurodevelopmental disorders.

PI_NAMEs: RANARD, KATHERINE MARIE (contact)

PROGRAM_OFFICER_NAME: KIM, JENNY LILY

PROJECT_TERMS: Address;Affect;Anabolism;Animals;Automobile Driving;Axon;Behavioral;Biological Models;Biology;Brain;brain cell;Cell Differentiation process;Cell Lineage;Cell membrane;Cells;Childhood;Cognition Disorders;Cognitive;cognitive development;cognitive function;Color;Colorado;Consumption;Defect;Development;Developmental Biology;developmental neurobiology;dietary;dietary approach;Docosahexaenoic acid supplementation;Docosahexaenoic Acids;Elements;Exhibits;experimental study;fetal;Fishes;gene editing technology;Gene Expression;Genes;Genetic;genetic approach;Growth;Human;Image;Imaging Techniques;Immune;Immune response;In Situ Hybridization;in vivo imaging;Infant;Infant Health;Inflammatory;Inflammatory Response;insight;Intake;Knowledge;Lactation;Link;Lipids;Malnutrition;Maternal Health;Mediating;Medical;Mental disorders;Microglia;Modeling;Molecular;molecular marker;Mood Disorders;Morphology;mother nutrition;Mothers;Myelin;Myelin Sheath;myelination;N-3 polyunsaturated fatty acid;Nerve;Nervous System;Neural tube;neurobehavioral disorder;neurodevelopment;Neurodevelopmental Deficit;Neurodevelopmental Disorder;neuroinflammation;Neurons;novel;Nutrient;nutrition;Nutritional;Nutritional Requirements;Nutritional Science;offspring;oligodendrocyte lineage;oligodendrocyte progenitor;Oligodendroglia;Omega-3 Fatty Acids;Patients;Phagocytosis;Phenotype;Phospholipids;Play;precursor cell;Pregnancy;prevent;Prevention strategy;Process;Recovery;Regulation;Reporter Genes;Research;response;RNA;Role;Signal Transduction;skills;Speed;Synapses;Techniques;Testing;Therapeutic;tool;Training;transcriptome;transcriptomics;Transgenic Organisms;Universities;western diet;white matter;white matter injury;Work;Yolk Sac;Zebrafish

PROJECT_TITLE: Role of n-3 polyunsaturated fatty acids in myelinationduring development

STUDY_SECTION: NST

STUDY_SECTION_NAME: NST-2 Study Section [NST-2]


ADMINISTERING_IC: HL

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

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

ORG_CITY: STANFORD

ORG_COUNTRY: UNITED STATES

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_FIPS: US

ORG_NAME: STANFORD UNIVERSITY

ORG_STATE: CA

PHR: PROJECT NARRATIVE Coronary artery disease (CAD) is the leading cause of death worldwide, and from leveraging the power of human genetics and mechanistic discovery, we are poised to understand causal mechanisms of disease and design crucially needed therapies. In a groundbreaking discovery through complex disease genetics, RNA editing of double stranded RNA, mediated by ADAR1, has been found to powerfully influence CAD risk. In this proposal, I aim to understand the fundamental mechanisms of RNA editing and atherosclerosis, and further define the potential for targeting the dsRNA sensor MDA5 for clinical therapy — allowing me to advance my training and become an independent physician-scientist in cardiovascular medicine.

PI_NAMEs: WELDY, CHAD S (contact)

PROGRAM_OFFICER_NAME: CHEON, YEWON

PROJECT_TERMS: Acceleration;ADAR1;Address;Arteries;Atherosclerosis;autoinflammatory diseases;biobank;Bioinformatics;Breeding;calcification;Cardiovascular system;career;causal variant;Cause of Death;Cell Line;Cell Lineage;Cells;Clinical;Clonality;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;Coronary Arteriosclerosis;Coronary artery;CRISPR interference;Data;Deficiency Diseases;design;Development;Disease;disorder risk;DNA sequencing;Double-Stranded RNA;Enzymes;Epigenetic Process;epigenomic profiling;Evaluation;Foundations;Frequencies;gene discovery;Gene Expression;Gene Expression Profiling;gene network;Genes;Genetic;Genetic Diseases;Genetic Transcription;Genetic Variation;genome wide association study;Genomic approach;genomic locus;Human;Human Genetics;IFIH1;In Vitro;in vivo;Inflammation;Inflammatory Bowel Diseases;inhibitor;innovation;Interferons;knock-down;Knowledge;Lipids;loss of function;Lupus;Maps;Mediating;Medicine;Mentors;Molecular Biology;mouse model;Mus;Nature;novel;novel therapeutics;Pathogenesis;Patients;Phenotype;Physicians;Play;Process;programs;Quantitative Trait Loci;rare mendelian disorder;response;RNA;RNA Editing;Role;Scientist;sensor;Signal Transduction;single-cell RNA sequencing;skills;small molecule;Smooth Muscle Myocytes;Testing;Therapeutic;therapeutic target;Tissues;Training;transcriptome sequencing;Variant;Vascular calcification;Vascular Diseases;vascular inflammation;Vascular Smooth Muscle;whole genome;Work

PROJECT_TITLE: ADAR mediated RNA editing is a causal mechanism in coronary artery disease

STUDY_SECTION: MCBS

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


ADMINISTERING_IC: DK

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Biotechnology;Clinical Research;Clinical Trials and Supportive Activities;Diabetes;Genetics;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Patient Safety;Precision Medicine;Prevention;Racial and Ethnic Minority Health Research

ORG_CITY: HOUSTON

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

ORG_STATE: TX

PHR: PROJECT NARRATIVE This project uses both transcriptomic- and genomic-level data to identify mechanisms of individual responses to glucagon-like peptide-1 (GLP-1) in Mexican-Americans with prediabetes. The GLP-1 hormone is essential for glucose reduction, weight loss, cardiovascular risk reduction, and renal protection. Newly discovered mechanisms will illuminate causal links between disease genotype and phenotype, which may ultimately guide personalized therapeutic approaches for type 2 diabetes, prediabetes, obesity, cardiovascular disease, renal disease, and other related diseases.

PI_NAMEs: GUTIERREZ, ABSALON DENNIS (contact)

PROGRAM_OFFICER_NAME: LI, YAN

PROJECT_TERMS: Adult;Adverse effects;Affect;Aftercare;Agonist;Algorithms;American;Beta Cell;biobank;Blood;Blood Glucose;Body Weight decreased;C-Peptide;Candidate Disease Gene;Cardiovascular Diseases;cardiovascular risk factor;Cardiovascular system;Caucasians;Chemosensitization;Chronic;Chronic Disease;Clinical;Clinical Trials;cohort;Collection;Communities;comorbidity;County;Data;Databases;Diabetes Mellitus;Diabetes prevention;Disease;DNA Databases;drug efficacy;Electronic Health Record;Event;Exclusion;functional genomics;Gene Expression;gene function;Gene Targeting;Genes;Genetic;Genetic Models;Genetic study;genetic variant;genomic locus;genomic variation;Genomics;Genotype;GLP-I receptor;glucagon-like peptide 1;Glucose;Goals;Health;Hispanic;Hispanic Populations;Hormones;improved;indexing;Individual;individual response;individualized medicine;innovation;Insulin;insulin secretion;insulin sensitivity;interest;Kidney;Kidney Diseases;Knowledge;Latino Population;Link;Measurement;Measures;meetings;Metabolic;Metabolic Diseases;Methods;Mexican;Mexican Americans;Modeling;Mutation;Non-Insulin-Dependent Diabetes Mellitus;novel;Obesity;Oral;Outcome;Pathway interactions;Patients;Peripheral;peripheral blood;personalized approach;personalized therapeutic;Persons;Pharmaceutical Preparations;Pharmacogenetics;Pharmacogenomics;Pharmacologic Substance;Pharmacotherapy;phenome;Phenotype;Physiological;Plasma;Population;Populations at Risk;precision genetics;precision medicine;Precision therapeutics;Prediabetes syndrome;predicting response;predictive modeling;Prevention;Procedures;progression risk;Quantitative Trait Loci;recruit;Regimen;Regulation;Renal function;response;Risk;Risk Reduction;Role;Single Nucleotide Polymorphism;Standardization;Statistical Methods;Structure of beta Cell of islet;Study Subject;Testing;Therapeutic;Tissues;transcriptome sequencing;transcriptomics;Translating;Treatment Failure;treatment response;United States;Variant;Whole Blood

PROJECT_TITLE: Pharmacogenetics of the Response to GLP-1 in Mexican-Americans with Prediabetes

STUDY_SECTION: GHD

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


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: SAN FRANCISCO

ORG_NAME: VETERANS AFFAIRS MED CTR SAN FRANCISCO

PHR: Aortic aneurysm, a swelling of the aorta, can rupture or the layers of its wall can tear apart, namely dissect, and as such, aortic aneurysm is the 15th leading cause of death in people over age 55. Though surgery is currently performed when aneurysms of the ascending thoracic aorta reach specified size limits, unfortunately, rupture/dissection still occur in significant numbers of patients below those size guidelines with no means to predict which patients are at greater risk at this time. This proposal will investigate the role of mechanical loading on aortic aneurysm wall on the dilation and dissection of aneurysm wall among patients whose aneurysm size is below the current surgical size threshold.

PI_NAMEs: TSENG, ELAINE EVELINA (contact)

PROJECT_TERMS: 4D MRI;Age;Aneurysm;Aorta;Aortic Aneurysm;Area;Award;Biomechanics;Body Surface Area;cardiovascular emergency;Cause of Death;Cessation of life;Clinical;clinical application;clinical decision-making;Clinical Management;clinical practice;clinical risk;Development;Diameter;Dissection;Engineering;Equilibrium;Event;Failure;Finite Element Analysis;follow-up;Foundations;Geometry;Goals;Growth;Guidelines;Healthcare Systems;Height;Hospitals;improved;in vivo;indexing;Individual;Laws;Left;Length;Liquid substance;Machine Learning;Measures;mechanical load;Mechanics;Methods;mortality;Motivation;Operative Surgical Procedures;Outcome;patient stratification;patient subsets;Patients;personalized decision;Persons;Process;prospective;Publishing;repaired;Risk;Risk Marker;risk prediction;risk stratification;Role;Rupture;Services;shear stress;Specific qualifier value;Stress;Structure;Sudden Death;Swelling;Symptoms;Thoracic aorta;Thoracic Aortic Aneurysm;Time;tool;United States;Veterans;Veterans Health Administration

PROJECT_TITLE: Developing Biomechanical Predictors of Ascending Thoracic Aortic Aneurysm Growth and Dissection


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Autoimmune Disease;Cancer;Colorectal Cancer;Digestive Diseases;Inflammatory Bowel Disease

ORG_CITY: MEMPHIS

ORG_NAME: ST. JUDE CHILDREN'S RESEARCH HOSPITAL

ORG_STATE: TN

PHR: PROJECT NARRATIVE The innate immune system can impact all aspects of cancer, from tumor initiation to growth and metastasis. This research program will build on our earlier seminal discoveries related to innate immune sensors and their role in colitis-associated colorectal cancer. We will improve understanding of the role of innate immune sensors, inflammasomes, and inflammasome-mediated processes in cancer to shape future cancer treatment strategies.

PI_NAMEs: KANNEGANTI, THIRUMALA-DEVI  (contact)

PROGRAM_OFFICER_NAME: HOWCROFT, THOMAS K

PROJECT_TERMS: Area;Basic Science;Cancer Etiology;cancer therapy;Cell Death;Cessation of life;Colitis associated colorectal cancer;Colon;Colorectal Cancer;Defect;Development;Disease;Drug Targeting;Foundations;Future;Growth;Human;Immune;Immune response;Immune signaling;improved;Infection;Inflammasome;Inflammatory;innate immune pathways;Innate Immune Response;Innate Immune System;Lead;Malignant Neoplasms;Mediating;Metabolic Diseases;microbial;Natural Immunity;Neoplasm Metastasis;Nerve Degeneration;novel;novel therapeutics;Pathogenesis;Process;programs;Research;Role;Seminal;sensor;Shapes;Sterility;System;Translating;treatment strategy;tumor initiation;Tumor stage;United States

PROJECT_TITLE: Innate immune sensors, inflammasomes, and inflammasome-mediated processes in cancer


NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Genetics;Heart Disease;Pediatric;Pediatric Cardiomyopathy;Rare Diseases

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE Over 700,00 patients in the United States live with hypertrophic cardiomyopathy, a genetic heart disease. The goal of this project is to define how small changes in a gene, called missense variants, cause hypertrophic cardiomyopathy. This knowledge is critical to developing personalized treatment approaches.

PI_NAMEs: THOMPSON, ANDREA DOOLEY (contact)

PROGRAM_OFFICER_NAME: WANG, WAYNE C

PROJECT_TERMS: Acceleration;Accounting;Affect;Affinity;Affinity Chromatography;Amino Acids;Arrhythmia;Bar Codes;Binding;Binding Proteins;Biological;Biological Assay;Biological Models;Biology;Cardiac;Cardiac Myocytes;Cardiac Myosins;Cardiomyopathies;cascade genetic testing;Cell model;Cells;Chemicals;Classification;Clinical;Clinical Data;Clinical Trials;Data;Data Analyses;Development;Diagnostic;Disease;disease model;disease-causing mutation;Electrostatics;Eligibility Determination;Exhibits;experience;Experimental Genetics;Failure;Familial Hypertrophic Cardiomyopathy;Functional disorder;Future;Generations;Genes;Genetic;Genetic Diseases;Genetic Screening;Genetic Techniques;Goals;Green Fluorescent Proteins;Half-Life;Heart Atrium;Heart Diseases;Heart failure;human disease;Hypertrophic Cardiomyopathy;improved;Individual;inherited cardiomyopathy;innovation;insight;Knock-in Mouse;Knowledge;Label;Lead;Learning;Left;Left Ventricular Hypertrophy;Length;Libraries;loss of function;Mass Spectrum Analysis;Mentorship;Methods;Modeling;mouse model;mutant;Myofibrils;Myosin ATPase;myosin-binding protein C;Nature;Nonmuscle Myosin Type IIA;Nonsense Codon;novel;Outcome;Pathogenicity;Patient Care;Patients;personalized medicine;Persons;Phenotype;Physicians;Physiology;prognostication;Property;protein folding;Protein Inhibition;protein misfolding;Proteins;Relative Risks;Research Personnel;Sarcomeres;Scientist;skills;sudden cardiac death;Surface;targeted treatment;Techniques;Testing;Therapeutic;Thermodynamics;Tissues;tool;Training;Training Activity;United States;Variant;variant of unknown significance;Work

PROJECT_TITLE: Pathogenic mechanisms of myosin binding protein C missense variants within hypertrophic cardiomyopathy


NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Immunotherapy;Lung;Lung Cancer;Orphan Drug;Rare Diseases

ORG_CITY: DURHAM

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Project narrative These studies will define the role and heterogeneity of neoantigens and tumor microenvironmental immune cells in SCLC; a poorly characterized disease, due in part to its aggressiveness and challenges with presentation at a metastatic stage, which prevents tissue collection to address biological questions. Our work will generate a mechanistic rationale for more effective immunotherapies that target the diversity of SCLC, which we will leverage to design ensuing clinical trials at Moffitt Cancer Center.

PI_NAMEs: CONEJO-GARCIA, JOSE R (contact)

PROGRAM_OFFICER_NAME: LIU, YIN

PROJECT_TERMS: adaptive immune response;Address;anti-tumor immune response;Antibodies;Antibody Specificity;Antigen Targeting;Antigens;Area;Autologous;B-Lymphocytes;bench to bedside;Biological;Biopsy;butyrophilin;Cancer Center;cancer infiltrating T cells;Cancer Patient;Cell Therapy;Cells;Cessation of life;checkpoint inhibition;chemotherapy;chimeric antigen receptor T cells;Clinical;clinical development;Clinical Research Protocols;Clinical Trials;Combination immunotherapy;Cryopreservation;design;Disease;Effectiveness;Enrollment;Evolution;exosome;Functional disorder;Future;Goals;Grant;Heterogeneity;Human;human disease;Immune;immunogenicity;Immunoglobulin A;Immunoglobulin Class Switching;Immunoglobulin G;Immunotherapeutic agent;Immunotherapy;Impairment;Individual;Infiltration;Intervention;Lymphocyte;Lymphocytic Infiltrate;Malignant - descriptor;Malignant Neoplasms;Membrane;Methods;Modeling;Multiple Tumor Masses;Mutation;neoantigens;Neoplasm Circulating Cells;Neoplasm Metastasis;new therapeutic target;Newly Diagnosed;Non-Small-Cell Lung Carcinoma;novel;overexpression;participant enrollment;Patients;PD-L1 blockade;Phenotype;Pleural effusion disorder;pressure;prevent;Process;programmed cell death ligand 1;programs;Protocols documentation;Recurrence;Reporting;Research;Resected;Resistance;Resources;response;Role;Sampling;small cell lung carcinoma;Source;T-cell receptor repertoire;T-Lymphocyte;therapeutic effectiveness;therapy resistant;Tissue Banks;Tissue Donations;Tissues;tumor;tumor immunology;Tumor-Derived;Work;Xenograft procedure

PROJECT_TITLE: Inter-metastatic divergency in small cell lung cancer; implications for the design of future immunotherapies

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-TIR-W(01)Q]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Genetics;Infectious Diseases

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Project Narrative This project deals with natural killer (NK) cells which are immune cells that can control viral infections in vivo. How they do this requires further examination because they express several candidate activation receptors that have been implicated in viral control by in vitro experiments and they express inhibitory receptors that ironically also mediate viral control in vivo. Here the investigator presents recent published data using novel experimental tools that will be used in the current proposal to study how NK cells use these receptors to control viral infections in vivo.

PI_NAMEs: YOKOYAMA, WAYNE M. (contact)

PROGRAM_OFFICER_NAME: JOFFE, AARON MICHAEL

PROJECT_TERMS: Alleles;C57BL/6 Mouse;cell killing;Cells;clinically relevant;clinically significant;Complex;Coupled;CRISPR/Cas technology;Cytomegalovirus Infections;Data;Education;epidemiology study;Event;Evolution;experimental study;Family;Gene Cluster;Gene Family;Genes;Genetic;Genetic Polymorphism;genetic resistance;Genotype;Germ Lines;Haplotypes;Human;Immune;In Vitro;in vivo;insight;Investigation;killer immunoglobulin-like receptor;Knock-in Mouse;Laboratories;Lectin;Licensing;Ligands;Link;Major Histocompatibility Complex;Mediating;Memory;MHC Class I Genes;Mouse Strains;Murid herpesvirus 1;Mus;Natural Killer Cells;NK Cell Activation;Normal tissue morphology;novel;Other Genetics;Paper;Pathologic;Phenotype;Process;Publications;Publishing;Reagent;receptor;Receptor Activation;Receptor Gene;Research Personnel;response;Role;Serology;Signal Transduction;Surveys;Technology;Testing;tool;tumor;Viral;Virus Diseases

PROJECT_TITLE: Natural Killer Cell Control of Murine Cytomegalovirus Infection

STUDY_SECTION: IHD

STUDY_SECTION_NAME: Immunity and Host Defense Study Section[IHD]


NIH_SPENDING_CATS: Behavioral and Social Science;Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Cost Effectiveness Research;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Heart Disease;Mental Health;Social Determinants of Health

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: PROJECT NARRATIVE Self-care is an evidence-based strategy that can reduce the high morbidity and mortality associated with heart failure. However, little is known about how to implement self-care for heart failure in low- and middle-income country settings in ways that account for the unique needs of different cultures and contexts. Our study, which is designed to prioritize health equity throughout all phases, will compare the implementation, effectiveness, and cost effectiveness of a digital-first implementation strategy vs. a basic evidence-based package and current standard of care to improve self-care in heart failure.

PI_NAMEs: CAFAZZO, JOSEPH ANTONY;SCHWARTZ, JEREMY IAN (contact);SSINABULYA, ISAAC

PROGRAM_OFFICER_NAME: MINTZER, KEITH A

PROJECT_TERMS: Address;Adherence;Adoption;Africa South of the Sahara;Algorithms;Area;Cardiac;Caring;Cellular Phone;Center for Translational Science Activities;Cessation of life;Clinical;Clinical effectiveness;Cluster randomized trial;Collaborations;community engaged approach;cost;Cost Analysis;cost effectiveness;Cost Effectiveness Analysis;cost-effectiveness ratio;Country;dashboard;Data;Death Rate;debilitating symptom;design;Diet;digital;digital health;Effectiveness;empowerment;Ensure;Equity;evidence base;Evidence based intervention;Exercise;Goals;Government;Health;health equity;Health Priorities;health related quality of life;Healthcare;Heart failure;Hospital Referrals;Hospitalization;hybrid type 2 design;Hybrids;implementation context;implementation evaluation;implementation facilitation;implementation fidelity;implementation process;implementation science;implementation strategy;implementation/effectiveness;improved;incremental cost-effectiveness;indexing;Inequity;Infrastructure;innovation;insight;International;Internet;Interview;Knowledge;Learning;Location;low and middle-income countries;Maintenance;Mental Health;Metadata;Methods;mHealth;mobile application;Monitor;Morbidity - disease rate;mortality;National Heart, Lung, and Blood Institute;Nurses;Outcome;Outpatients;Patient Education;Patient Outcomes Assessments;patient-level barriers;Patients;Pattern;Pharmaceutical Preparations;Phase;Physicians;pilot trial;primary outcome;Process;process evaluation;Protocols documentation;Provider;provider-level barriers;Reach, Effectiveness, Adoption, Implementation, and Maintenance;Recommendation;Reporting;Research Personnel;Secure;Self Care;Service delivery model;Shapes;Site;social determinants;sociodemographic disparity;Solar Energy;standard of care;Structure;symptom management;Symptoms;Syndrome;Time;tool;treatment arm;Uganda;Universities;uptake;Work

PROJECT_TITLE: ImpleMEntation of a Digital-first care deLiverY model for heart failure in Uganda (MEDLY Uganda)

STUDY_SECTION: SIHH

STUDY_SECTION_NAME: Science of Implementation in Health and Healthcare Study Section[SIHH]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Biotechnology;Brain Cancer;Brain Disorders;Breast Cancer;Cancer;Colorectal Cancer;Digestive Diseases;Genetics;Neurosciences;Pancreatic Cancer;Prevention;Rare Diseases;Skin Cancer;Women's Health Research

ORG_DEPT: PHARMACOLOGY

PHR: Our research program uses chemical technologies and systems-level analyses to study ontogeny and oncogenesis. Our current studies focus on optogenetic regulators of developmental signaling pathways and small-molecule inhibitors of aldehyde dehydrogenases associated with stemness, cancer, and spermatogenesis.

PI_NAMEs: CHEN, JAMES K (contact)

PROGRAM_OFFICER_NAME: FABIAN, MILES

PROJECT_TERMS: Ablation;Adult;aldehyde dehydrogenase 1;aldehyde dehydrogenases;ALDH1A2 gene;Biology;Bone Morphogenetic Proteins;Cell Differentiation process;Cells;chemical synthesis;Chemicals;Chemistry;Clinical;Colorectal Cancer;contraceptive target;Cytoplasm;Development;Developmental Biology;empowerment;Enzymes;Erinaceidae;Evolution;Genes;Genetic;genetic technology;GLI gene;Glioblastoma;Growth;High-Throughput Nucleotide Sequencing;human disease;Individual;inhibitor;innovation;insight;Intestines;Knowledge;Life;Light;Male Contraceptive Agents;Malignant Breast Neoplasm;Malignant neoplasm of pancreas;Malignant Neoplasms;Medulloblastoma;Melanoma;Mitochondria;Modeling;Molecular;motor control;Motor Neurons;multipotent cell;novel;Oncogenic;optogenetics;Oxygen;Pancreas;Pathway interactions;Pattern;Photoreceptors;programs;Protein Engineering;Protein Isoforms;Reagent;Research;reverse genetics;Role;Science;Signal Pathway;Signaling Protein;small molecule;small molecule inhibitor;Specific qualifier value;Spermatogenesis;stem cells;stemness;System;Technology;Tissues;tool;transcription factor;Translating;tumor initiation;tumor progression;tumorigenesis;voltage;Zebrafish

PROJECT_TITLE: Chemical tools for developmental biology


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Gene Therapy;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Immunization;Immunotherapy;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: MINNEAPOLIS

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Project Narrative This project merges expertise in structural biology, protein engineering, T cell biology, and oncology to engineer soluble nanobody-based Notch1 activators that will transform and accelerate the development of novel T cell-based therapies to treat cancer.

PI_NAMEs: GORDON, WENDY RYAN;MURETTA, JOSEPH M. (contact)

PROGRAM_OFFICER_NAME: KYI, CINDY WIN

PROJECT_TERMS: Acceleration;Affinity;Allogenic;Antibodies;arm;Autoimmune Diseases;Back;Bacteriophages;Benchmarking;Binding;Binding Proteins;Biochemical;Biochemistry;Biological Assay;Blocking Antibodies;cancer cell;cancer therapy;Cations;Cell Differentiation Induction;cell killing;Cell Line;Cell Nucleus;Cell Surface Receptors;cell type;Cells;Cellular biology;chelation;chimeric antigen receptor;chimeric antigen receptor T cells;Clinical;Clinical Trials;Closure by clamp;Coculture Techniques;Collecting Cell;Communicable Diseases;cost;cost effective;Cultured Cells;Cyclic GMP;design;Development;Disease;Disulfides;Dose;engineered T cells;Engineering;experimental study;Exposure to;Extracellular Domain;Family;FDA approved;Freezing;Generations;Goals;graft vs host disease;health disparity;Health Services Accessibility;Hematologic Neoplasms;Homologous Gene;Immune System Diseases;immunodeficiency;Immunoglobulin Fragments;Immunotherapeutic agent;Immunotherapy;improved;individual patient;induced pluripotent stem cell;Industry Standard;innovation;Ligand Binding;Ligands;Link;Malignant Neoplasms;manufacturing process;Measures;mimetics;Minnesota;Molecular Conformation;Monitor;Mutation;nanobodies;next generation;notch protein;NOTCH3 gene;novel;Oncology;organ transplant rejection;Patients;Peptide Hydrolases;Performance;Phage Display;Physiological;Population;precursor cell;programs;Protein Engineering;protein phosphatase inhibitor-2;Proteins;Proteolysis;Reagent;receptor;Reporter;Reporting;Research;Research Personnel;Signal Transduction;Site;Source;Standardization;structural biology;Structure;Surface;surface coating;System;T cell differentiation;T cell therapy;T-Cell Activation;T-Lymphocyte;Technology;Testing;Therapeutic;therapeutic development;Time;tool;Transcription Coactivator;Transcription Initiation;Universities;Yeasts

PROJECT_TITLE: Engineering Protein Modulators of Notch Activation for T-cell immunotherapy


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Cardiovascular;Cerebrovascular;Clinical Research;Dementia;Genetics;Neurodegenerative;Neurosciences;Stroke;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: CHICAGO

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: Narrative Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a familial vascular dementia characterized by vascular failure due to degeneration of smooth muscle cells. While the cause of the disease has been attributed to mutations in NOTCH3, little is known about the cellular outcomes, vascular dysfunctions, and clinical progression. Through this application an interdisciplinary group of physicians and scientists will translate new information on the disease to improve diagnosis, prognosis and continue to explore the molecular basis of disease development.

PI_NAMEs: BOEHM, MANFRED ;IRUELA-ARISPE, M. LUISA  (contact);KOZEL, BETH A

PROGRAM_OFFICER_NAME: OLIVE, MICHELLE

PROJECT_TERMS: Address;Affect;Age;Agreement;Animal Model;Arterial Disorder;Arteries;arteriole;autosome;Biopsy Specimen;Blood specimen;Blood Vessels;Brain;Caliber;Cells;Cerebral small vessel disease;Cerebrum;Characteristics;Clinic;Clinical;clinical center;Clinical Trials;cognitive function;Collaborations;Data;Data Correlations;Dementia;deprivation;Development;Diagnosis;Disease;Disease Progression;disease-causing mutation;Endothelium;Evaluation;Evolution;Extramural Activities;Failure;gain of function;gain of function mutation;Generations;Genetic;Genotype;Goals;gray matter;Headache;Hemorrhage;human disease;Impaired cognition;Impairment;improved;induced pluripotent stem cell;Inherited;insight;Ischemia;Knowledge;Lead;Leukoencephalopathy;Life;Link;loss of function;male;Molecular;monocyte;mouse model;Mus;Mutation;Nature;Nerve Degeneration;Neurologic;Nonprofit Organizations;notch protein;NOTCH3 gene;novel;Organ;Outcome;Oxygen;Pathway interactions;Patients;Pericytes;Phenotype;Physicians;Physiological;Process;Prognosis;receptor;recruit;Research;Research Personnel;Retina;Scientist;Side;Signal Transduction;single-cell RNA sequencing;skin biopsy;Smooth Muscle Myocytes;Stroke;Subcortical Infarctions;Subcortical Leukoencephalopathy;Symptoms;targeted treatment;Testing;Therapeutic;therapy development;Tissues;transcriptome sequencing;transcriptomic profiling;Translating;Tunica Media;United States National Institutes of Health;Variant;Vascular Dementia;Vascular Diseases;Vascular Smooth Muscle;women patients

PROJECT_TITLE: Underlying Mechanisms in CADASIL


NIH_SPENDING_CATS: Ataxia Telangiectasia;Genetics;Hematology;Neurodegenerative;Pediatric;Primary Immunodeficiencies;Rare Diseases

ORG_CITY: NEW YORK

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

ORG_STATE: NY

PHR: The cell has an intricate set of pathways that sense and repair DNA damage, which is an inevitable consequence of cellular metabolism and the environment. Failure of a repair pathway, due to either overwhelming DNA damage or pathway inactivation by mutations, can lead to the propagation of genetic errors and drive the development of cancer. This proposal seeks to determine the 3-dimensional structures of protein assemblies involved in key repair pathways to better understand how they work and how they fail in cancer.

PI_NAMEs: PAVLETICH, NIKOLA P (contact)

PROGRAM_OFFICER_NAME: MACARTHUR, LINDA

PROJECT_TERMS: Acceleration;Address;Amino Acids;Ataxia Telangiectasia;ataxia telangiectasia mutated protein;ATM activation;ATP phosphohydrolase;ATR gene;Binding;Biochemical;cancer predisposition;Cell Cycle Arrest;cell growth;Cells;Chromatin;Chromosomal Instability;Closure by clamp;Complex;crosslink;Cryoelectron Microscopy;Data;design;Development;DNA;DNA Damage;DNA Double Strand Break;DNA Interstrand Crosslinking;DNA lesion;DNA Repair;DNA Repair Pathway;DNA replication fork;DNA Structure;ds-DNA;Environment;ETAA1;Failure;Family;FANCD2 protein;Fanconi Anemia pathway;Fanconi's Anemia;Genetic;Genome;Goals;homologous recombination;Hybrids;Image;Inherited;KRP protein;Lesion;Maintenance;Malignant Neoplasms;Mediating;Metabolism;Methods;Modeling;Molecular Conformation;Monoubiquitination;Mutate;Mutation;Nature;Nijmegen Breakage Syndrome;novel strategies;nuclease;Oncogenes;Orthologous Gene;Outcome;Pathway interactions;Peptides;Phosphatidylinositols;Phosphorylation;Phosphotransferases;prevent;Process;programs;protein activation;protein complex;Protein Kinase;protein purification;protein structure;Proteins;Publishing;reconstitution;recruit;repaired;replication stress;response;RNA;Role;scaffold;Signal Transduction;Single-Stranded DNA;Slide;Structure;Syndrome;Therapeutic;three dimensional structure;translocase;Tumor Suppressor Genes;ubiquitin ligase;Work;Yeasts

PROJECT_TITLE: Structural Mechanisms of DNA Damage Sensing and Activation of the ATR, Fanconi Anemia, and ATM Checkpoints

STUDY_SECTION: MSFC

STUDY_SECTION_NAME: Macromolecular Structure and Function C Study Section[MSFC]


ADMINISTERING_IC: MH

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Mental Health;Neurosciences

ORG_CITY: WASHINGTON

ORG_DEPT: NEUROSCIENCES

ORG_NAME: GEORGETOWN UNIVERSITY

ORG_STATE: DC

PHR: PROJECT NARRATIVE The goal of the research proposed in this fellowship is to determine the functional heterogeneity of neurons in the paralaminar nucleus (PL), an understudied region of the amygdala implicated in neuropsychiatric disorders. The experiments will use a mouse model to classify the diversity of mature PL neurons by linking their physiological properties, morphological features, and input/output circuitry. The results will provide crucial knowledge for understanding the role of the paralaminar nucleus in amygdala function and behavior.

PI_NAMEs: SAXON, DAVID  (contact)

PROGRAM_OFFICER_NAME: PINARD, COURTNEY ROSE

PROJECT_TERMS: Action Potentials;Adolescence;Adolescent;Adult;Age;Amygdaloid structure;Animal Model;Area;Atlases;autism spectrum disorder;base;Behavior;Behavioral;biocytin;Biological Models;Brain;Brain region;Categories;Cell Count;Cell Nucleus;Cells;Classification;Closure by clamp;Collaborations;confocal imaging;Data;Databases;density;Development;electrical property;Electrophysiology (science);Emotional;emotional behavior;entorhinal cortex;excitatory neuron;experimental study;Fellowship;gamma-Aminobutyric Acid;Goals;Growth;Heterogeneity;Hippocampus;Human;immunoreactivity;Individual;Injections;intercalation;Knowledge;Label;Lateral;Light;Link;Maps;Measures;Membrane;Mental disorders;Microscopy;Molecular;Monkeys;Morphology;mouse model;Mus;N-Methylaspartate;neuronal cell body;Neurons;neuropsychiatric disorder;optogenetics;Output;patch clamp;Pathology;Pattern;Phenotype;Physiological;Physiology;Play;Population;Post-Traumatic Stress Disorders;Pregnancy;Primates;Process;Property;reconstruction;Research;response;Role;Slice;social;Social Behavior;Source;Spike Potential;Subgroup;Synapses;Techniques;Testing;Training;Universities;Vertebral column;Viral;Virus;Work

PROJECT_TITLE: Characterizing the functional heterogeneity of the mouse paralaminar nucleus


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Biotechnology;Building Research Capacity at Institutions with Limited NIH Funding;Digestive Diseases;Genetics;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: NORTHRIDGE

ORG_DEPT: BIOLOGY

ORG_NAME: CALIFORNIA STATE UNIVERSITY NORTHRIDGE

PHR: PROJECT NARRATIVE Although decades of research have identified genetic master regulator (MR) genes that are essential for the regenerative function of stem cells, the downstream mechanisms that they regulate remain largely unknown. This project seeks to characterize the function of a small set of validated MR targets in the regulation of intestinal stem cells, using the fruit fly Drosophila melanogaster as an experimental model system. The research proposed is dually relevant to the NIH mission, for it will contribute to our basic understanding of how stem cells can be used safely and effectively in regenerative medicine, while specifically expanding the repertoire of therapeutic targets for the treatment of gastrointestinal disease.

PI_NAMEs: LOZA COLL, MARIANO A (contact)

PROGRAM_OFFICER_NAME: PEI, WUHONG

PROJECT_TERMS: Address;adult stem cell;Affect;automated image analysis;Automobile Driving;Behavior;Binding;Biological Assay;Biological Models;Biomedical Research;Body System;cell behavior;Cell Count;Cell Differentiation process;Cell Therapy;cell type;Chemical Injury;combinatorial;Combined Modality Therapy;Complement;Complex;Critical Pathways;design;Development;DNA;Drosophila genus;Drosophila melanogaster;educational atmosphere;Enterocytes;Enteroendocrine Cell;Epidermal Growth Factor Receptor;Experimental Models;Family;Fostering;Future Generations;Gastrointestinal Diseases;gene conservation;Gene Targeting;Genetic;Genetic Transcription;genome-wide;Goals;Hormone secretion;Image;Immunofluorescence Microscopy;improved;improved outcome;in vivo;Individual;Infection;Injury;innovation;Intervention;intestinal barrier;intestinal homeostasis;Intestines;Investments;Knowledge;life span;MAPK8 gene;Maps;Midgut;Minority;Mission;Mitotic;model organism;Molecular;Morphology;notch protein;novel strategies;Organ;Outcome;Pathogenicity;Pathway interactions;Phenotype;premature;prevent;public trust;regeneration function;regeneration potential;Regenerative capacity;Regenerative Medicine;Regulation;Regulator Genes;Regulatory Pathway;Reporter;Research;Research Personnel;Research Project Grants;Science;self-renewal;side effect;Signal Pathway;Signal Transduction;Signal Transduction Pathway;Sister;Snails;Stains;STAT protein;Statistical Data Interpretation;stem cell function;stem cell proliferation;stem cell therapy;stem cells;Students;System;Testing;Therapeutic;therapeutic candidate;therapeutic target;therapy development;tissue stem cells;Tissues;Toxic effect;training opportunity;transcription factor;undergraduate student;Underrepresented Students;United States National Institutes of Health;Universities

PROJECT_TITLE: Genetic interactions among targets of master regulator genes as drivers of complex behavior in Drosophila intestinal stem cells


ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

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

ORG_CITY: SEATTLE

ORG_NAME: FRED HUTCHINSON CANCER CENTER

ORG_STATE: WA

PHR: PROJECT NARRATIVE Simultaneous profiling of the transcriptomic and epigenomic readouts along the one-dimensional (1D) genome and high-throughput three-dimensional (3D) chromatin conformation assays have both advanced to single-cell resolution. This project will propose statistical and machine learning-based models with accompanying software for jointly modeling 3D chromatin structure, transcriptomics, and epigenomics data while deciphering the distal gene regulatory networks in an individual cell. These studies will enhance our understanding of the function of non-coding regions as regulators of cell fate and infer how the cis-regulatory changes lead to different cell types during development and impact immunotherapeutic treatment.

PI_NAMEs: ZHENG, YE  (contact)

PROGRAM_OFFICER_NAME: GILCHRIST, DANIEL A

PROJECT_TERMS: 3-Dimensional;Acceleration;Acute;Acute Lymphocytic Leukemia;Address;Agreement;Architecture;Award;Benchmarking;Biological;Biological Assay;Blood Component Removal;brain cell;brain tissue;CAR T cell therapy;career;career development;Cell Line;cell type;Cells;Cellular Indexing of Transcriptomes and Epitopes by Sequencing;chimeric antigen receptor T cells;Chromatin;Chromatin Structure;CISH gene;collaborative environment;computer framework;Computer software;computerized tools;Data;Development;Distal;DNA;Educational Status;Elements;Enhancers;epigenome;epigenomic profiling;epigenomics;Foundations;Fred Hutchinson Cancer Research Center;Frequencies;Gene Expression;Gene Expression Regulation;gene regulatory network;Genes;Genome;genome-wide;genomic data;Genomics;Goals;Hi-C;histone modification;Histones;Human;Immunology;Immunotherapeutic agent;Immunotherapy;Individual;insight;Investigation;Joints;leukemia/lymphoma;Machine Learning;machine learning framework;machine learning model;Maps;Membrane Proteins;Mentors;Methods;Modality;Modeling;Molecular Conformation;multimodality;Multiomic Data;multiple omics;Mus;Neighborhoods;novel;Organ;patient response;Patients;Peripheral Blood Mononuclear Cell;Polycomb;programs;promoter;Regulation;Regulatory Element;Repression;research facility;Resolution;Role;Sampling;Signal Transduction;Signaling Protein;single cell technology;single-cell RNA sequencing;Specific qualifier value;statistical and machine learning;statistical learning;Statistical Models;statistics;Structure;System;Technology;Three-dimensional analysis;three-dimensional modeling;Tissues;tool;Training;transcriptome;transcriptomic profiling;transcriptomics;treatment response;Turtles;unsupervised clustering;Untranslated RNA;Variant

PROJECT_TITLE: Bridging the gap: joint modeling of single-cell 1D and 3D genomics

STUDY_SECTION: GNOM

STUDY_SECTION_NAME: Genome Research Study Section[GNOM-G]


FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

NIH_SPENDING_CATS: Obesity

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: Obesity is now among the leading causes of medical morbidity and health care costs in the U.S. The regulation of body weight - and the impact of excess weight on clinical phenotypes such as diabetes, cardiovascular disease and cancer - is extremely complex necessitating special training in centers with broad basic and translational research portfolios for the scientists who will help to break this nexus of disease. The objective of this longstanding training program is to increase the young investigator pool working on the biology of obesity and its co-morbidities through academic course work and sophisticated research experiences, enabling them to become independent investigators who can assume leadership positions in this field. This program has important national implications by virtue of its provision of a critical group of bioscientists.

PI_NAMEs: GALLAGHER, DYMPNA  (contact)

PROGRAM_OFFICER_NAME: KAMARA, FANTA

PROJECT_TERMS: Grant;Obesity;Research;Training

PROJECT_TITLE: Obesity Research Center Training Grant


NIH_SPENDING_CATS: Cancer;Immunotherapy

ORG_CITY: CHAPEL HILL

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: PROJECT NARRATIVE T cells are a part of the immune system able to control tumor growth, but are ineffective in most cancer patients. Our lab has made the groundbreaking discovery that T cells entering tumors experience chronic stress that can exhaust T cell function in tumors. Our proposal will formally prove that targeting the chronic stress response holds the power to restore essential T cell functions and invigorate control of tumors to allow immunotherapy to work better in sarcomas with global implications for all cancer patients.

PI_NAMEs: THAXTON, JESSICA E (contact)

PROGRAM_OFFICER_NAME: ZAMISCH, MONICA

PROJECT_TERMS: activating transcription factor 4;Acute;acute stress;Acute-Phase Reaction;Affect;Animals;anti-PD1 therapy;Apoptotic;arm;attenuation;biological adaptation to stress;cancer immunotherapy;Cancer Patient;CAR T cell therapy;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Death;Cell Death Induction;Cell Physiology;Cells;Cellular biology;Cessation of life;checkpoint therapy;Chronic;Chronic stress;Cytoprotection;Data;Development;drug development;effector T cell;Endoplasmic Reticulum;endoplasmic reticulum stress;Enzymes;Eukaryotic Initiation Factor-2;exhaust;exhaustion;Exhibits;experience;Generations;Genetic;Genetic Transcription;Human;humanized mouse;Immune system;immunogenic;Immunotherapy;Impairment;improved;in vivo;Inflammatory;innovation;interest;kinase inhibitor;Measures;Memory;Memory impairment;Metabolic;Metabolic Diseases;Metabolic dysfunction;metabolomics;Molecular;Molecular Target;mouse model;Mus;Mutant Strains Mice;overexpression;Oxidoreductase;Patients;PF4 Gene;Phase;Phenotype;Phosphorylation;Phosphotransferases;Process;programmed cell death protein 1;programs;Protein Kinase;protein kinase R;Proteins;Reactive Oxygen Species;Research;response;Role;Sarcoma;sensor;Shapes;Solid Neoplasm;Stress;success;T memory cell;T-Lymphocyte;targeted treatment;Testing;Toxic effect;trait;Translational Repression;Translations;tumor;Tumor Antigens;tumor growth;tumor microenvironment;Tumor Promotion;Tumor-Infiltrating Lymphocytes;Work

PROJECT_TITLE: Targeting Chronic ER Stress in T Cells to Improve Cancer Immunotherapy

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-OTC-M(08)F]


NIH_SPENDING_CATS: Genetics;Human Genome

ORG_CITY: WORCESTER

ORG_DEPT: GENETICS

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

ORG_STATE: MA

PHR: The biogenesis of mRNA is a complex and highly regulated process, requiring coordination between transcrip- tional and RNA processing machinery that each comprise of hundreds of regulatory RNAs and proteins, resulting in many possible alternative isoforms expressed from a single gene. While we can now extensively catalog the abundance and variability of mRNA isoforms across cellular states, we are still limited in our abilities to predict coordination between the molecular steps that give rise to cellular diversity and the rates at which each of these mechanisms occurs. Here, we propose to generate checkpointed time-series RNA-sequencing data and robust statistical models to quantify RNA processing rates, fully characterize the kinetic competition underlying alterna- tive isoform expression, and identify genetic variants associated with variabilty in RNA processing rates across human cell lines.

PI_NAMEs: ENGELHARDT, BARBARA ;PAI, ATHMA A (contact)

PROJECT_TERMS: Address;Affect;Alleles;Alternative Splicing;Biogenesis;blind;Calibration;Catalogs;cell type;Cells;Chromosome Mapping;Complex;Computer software;Data;Dependence;Disease;disease mechanisms study;Disparate;DNA;Event;Exons;Experimental Designs;Genes;Genetic;Genetic Determinism;genetic element;Genetic Transcription;genetic variant;genome wide association study;Genomics;Genotype;Goals;Human;Human Cell Line;human disease;Individual;insight;Instruction;Joints;kinetic model;Kinetics;Measurement;Messenger RNA;Methods;Modeling;Molecular;Outcome;Polyadenylation;Population;Probability;Process;Protein Isoforms;Proteins;Protocols documentation;Quantitative Trait Loci;Regulation;Resources;RNA;RNA Polymerase II;RNA Processing;RNA Splicing;Series;Site;Space Models;spatiotemporal;Specific qualifier value;Statistical Methods;Statistical Models;Time;training data;trait;Transcription Initiation;transcriptome sequencing;Translating;Uncertainty;user-friendly;Validation;Variant;Work

PROJECT_TITLE: A kinetic framework to map the genetic determinants of alternative RNA isoform expression

STUDY_SECTION: GCAT

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


NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Neurosciences;Nutrition;Obesity;Physical Activity;Prevention;Sleep Research

ORG_CITY: BOSTON

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: Narrative Breakthrough animal experimental evidence and preliminary human data suggest that high fat-dietary intake may disrupt circadian organization and that circadian disruption increases the risk for obesity. This project will determine whether a high-fat diet, vs. a low-fat diet, will alter the circadian system and thereby circadian rhythms in energy intake and expenditure in humans. This research will provide novel mechanistic insights into the link between macronutrient intake and the circadian system, and may help in the design of evidence-based dietary intervention incorporating “timing” to combat the obesity epidemic.

PI_NAMEs: SCHEER, FRANK A (contact)

PROGRAM_OFFICER_NAME: DONZE, LAURIE FRIEDMAN

PROJECT_TERMS: Animal Experiments;Award;Behavior;Biological;Body Weight Changes;Body Weight decreased;Carbohydrates;Chronic;circadian;Circadian desynchrony;Circadian Dysregulation;circadian pacemaker;Circadian Rhythms;combat;Consensus;Crossover Design;Data;design;Desire for food;Diet;dietary;Dietary Fats;Dietary intake;Dietary Intervention;Disease;Eating;energy balance;Energy Intake;Energy Metabolism;Epidemic;Epidemiology;evidence base;Exposure to;Fat-Restricted Diet;Fatty acid glycerol esters;Feeding behaviors;Goals;Health;High Fat Diet;Hormones;Human;human data;Hunger;improved;Individual;insight;Intake;Jet Lag Syndrome;ketogentic;Knowledge;Laboratories;Length;Life Style;Life Style Modification;Light;Link;Macronutrients Nutrition;Measures;Medicine;Metabolic;Metabolic Diseases;Metabolism;Motor Activity;Nobel Prize;novel;Obesity;Obesity Epidemic;obesity risk;obesity treatment;Organ;Pathogenicity;Peripheral;Phase;Physical activity;Physiology;Play;Prevalence;Prevention;preventive intervention;Protocols documentation;Public Health;Randomized;Regulation;Research;Risk;Risk Factors;Role;shift work;Sleep;social;System;Testing;Therapeutic;Therapeutic Intervention;Tissues;Visit;Weight maintenance regimen;Work

PROJECT_TITLE: Effect of high fat diet on the circadian system and on circadian rhythms in energy intake and expenditure

STUDY_SECTION: BNRS

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


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Drug Abuse (NIDA only);Estrogen;Neurosciences;Opioid Misuse and Addiction;Opioids;Substance Misuse;Women's Health Research

ORG_CITY: CHARLESTON

ORG_NAME: MEDICAL UNIVERSITY OF SOUTH CAROLINA

ORG_STATE: SC

PHR: PROJECT NARRATIVE In recent years, rapid increases in the prevalence of opioid use disorder have uncovered sex differences in opioid use, such as a predisposition to opioid use in females that can negatively impact treatment outcomes. This is particularly concerning, as females have often been excluded from research studies on reward processing and addiction. This proposal aims to address this research gap by describing the mechanisms by which estrogen impacts heroin seeking, knowledge that could help tailor sex-specific interventions for opioid use disorder.

PI_NAMEs: CARTER, JORDAN SCOTT (contact)

PROGRAM_OFFICER_NAME: LIN, YU

PROJECT_TERMS: Abstinence;addiction;Address;Agonist;Agreement;Amygdaloid structure;antagonist;Behavioral;Biological;Brain;Brain region;Cannulas;career;cell type;Chronic Disease;conditioning;cost;Cues;Data;Disease;Disparity;Down-Regulation;drug reward;drug seeking behavior;Economic Burden;Epidemic;ESR1 gene;Estradiol;Estrogen Receptor 2;Estrogen Receptors;Estrogens;Evaluation;Exclusion;expression vector;Extinction;Fellowship;Female;follow-up;FOS gene;Fright;genetic approach;Goals;Government;Heroin;Impairment;Infusion procedures;Intervention;Investigation;Knowledge;male;Measures;Memory;memory recall;Mental Health;Mentorship;Messenger RNA;Molecular;mRNA Expression;Neurons;neurosteroids;Opioid;opioid use;opioid use disorder;Overdose;overexpression;Pathologic;Pathology;Pathway interactions;Persons;Pharmaceutical Preparations;pharmacologic;Pharmacotherapy;Predisposition;prescription opioid misuse;Prevalence;prevent;Process;Property;Protocols documentation;Rattus;receptor;Regulation;Relapse;Research;research study;Resistance;response;reward processing;Rewards;Risk;Rodent;Role;Self Administration;Sensory;sex;Sex Differences;Signal Transduction;skills;small hairpin RNA;social determinants;Substance Use Disorder;Synaptic plasticity;Testing;Therapeutic;Tissues;Training;Treatment outcome;Validation;Visual

PROJECT_TITLE: Establishing sex-specific mechanisms for estrogen receptor beta in heroin extinction memory recall


NIH_SPENDING_CATS: Genetics;Nutrition;Obesity

ORG_CITY: DALLAS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: Project Narrative The circadian clock in mammals coordinates many aspects of normal physiology and behavior and when these clocks are disrupted, many health problems, including several types of mental illness, cancer and metabolic problems can occur. This project will investigate how the molecular mechanism of the clock works to keep proper time and drive rhythms in cellular function. This information will be critical for future manipulation of the circadian timing system as a treatment modality for humans suffering from circadian-related health problems.

PI_NAMEs: GREEN, CARLA B. (contact)

PROGRAM_OFFICER_NAME: AKACEM, LAMEESE DANA

PROJECT_TERMS: ARNTL gene;Behavior;Binding;Biochemistry;Cardiovascular Diseases;Cell Physiology;Cells;Cholesterol Homeostasis;circadian;Circadian Dysregulation;circadian pacemaker;circadian regulation;Clock protein;Complex;cryptochrome 1;cryptochrome 2;Data;Diabetes Mellitus;diet-induced obesity;experimental study;Family;Feedback;Funding;Future;Genes;Genetic;Genetic Transcription;Health;high throughput screening;Human;Inflammatory;insight;Intracellular Membranes;Jet Lag Syndrome;Laboratories;Link;Malignant Neoplasms;Mammals;member;Mental disorders;Metabolic;Metabolic Pathway;Metabolism;metabolomics;Mitochondria;Modality;Modeling;Molecular;mouse model;Mus;NADP;nocturnin;Nutrient availability;Obesity;Output;Periodicity;Phosphoric Monoester Hydrolases;Physiology;Protein Isoforms;Proteins;Repression;Resistance;Ribonucleases;Role;shift work;small molecule;Structure;System;Time;Tissues;transcription factor;Triglyceride Metabolism;Work

PROJECT_TITLE: Molecular mechanisms of mammalian circadian clock function - Renewal - 1


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Clinical Research;Data Science;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurosciences;Physical Injury - Accidents and Adverse Effects;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury

ORG_CITY: UNIVERSITY PARK

ORG_DEPT: PSYCHOLOGY

ORG_NAME: PENNSYLVANIA STATE UNIVERSITY, THE

ORG_STATE: PA

PHR: Project Narrative Traumatic brain injury (TBI) can cause widespread alteration in brain structure and function, but sample size in imaging studies is often limited, and differences in data acquisition and variables can create obstacles to data sharing. We propose to develop an open-source workflow for utilizing behavioral and MRI data that addresses these concerns and allows for harmonization across sites, supporting “big data” analyses that can identify clinically-meaningful patient subgroups in TBI, a goal that is not feasible with small datasets. Achieving the proposed Aims will make a curated and harmonized dataset available to the TBI community as well as procedures and data processing pipelines adaptable to other disorders in the clinical neurosciences.

PI_NAMEs: DENNIS, EMILY LARSEN;HILLARY, FRANK GERARD (contact);TATE, DAVID F;WILDE, ELISABETH A

PROGRAM_OFFICER_NAME: UMOH, NSINI ALEASE

PROJECT_TERMS: Acceleration;Address;Age;Attenuated;behavior test;Behavioral;behavioral construct;Big Data;Biological Markers;Brain;Brain Diseases;Brain Injuries;Calibration;Clinical;clinical heterogeneity;Code;Cognitive;cohort;Collaborations;collaborative environment;combat;Communities;computerized data processing;cost;Darkness;Data;data acquisition;Data Aggregation;Data Analyses;data analysis pipeline;Data Collection;data curation;data harmonization;data ingestion;data pipeline;data quality;Data Set;data sharing;Decentralization;Decision Trees;design;Development;Disease;Environment;Epilepsy;flexibility;Functional Imaging;Functional Magnetic Resonance Imaging;Genetic;Goals;Guidelines;Heterogeneity;heterogenous data;Image;image processing;imaging study;Informatics;Injury;insight;International;Machine Learning;machine learning framework;Magnetic Resonance Imaging;Measures;Memory;Mental Depression;Meta-Analysis;Methods;Modeling;multimodal data;neuroimaging;Neuronal Plasticity;Neuropsychology;Neurosciences;novel;open data;open source;Outcome;patient population;Patient Self-Report;patient subsets;Patient-Focused Outcomes;Patients;Pattern;Performance;Phase;Phenotype;Population Study;portability;Post-Traumatic Stress Disorders;Procedures;Process;prognostic value;Protocols documentation;Public Health;Quality Control;Research;Research Personnel;response;Rest;Sample Size;Sampling;satisfaction;Science;Severities;sharing platform;Site;Socioeconomic Status;Standardization;Stream;stroke recovery;structural imaging;Structure;success;TBI Patients;Techniques;Testing;Time;tool;Traumatic Brain Injury;Validation;virtual;virtual environment;working group

PROJECT_TITLE: Advancing Secondary Data Analysis: the ENIGMA Brain Injury Data Harmonization Initiative


ADMINISTERING_IC: AT

IC_NAME: NATIONAL CENTER FOR COMPLEMENTARY & INTEGRATIVE HEALTH

NIH_SPENDING_CATS: Aging;Complementary and Integrative Health;Dietary Supplements;Genetics;Microbiome;Nutrition;Prevention

PHR: PROJECT NARRATIVE Kombucha, a fermented tea that contains probiotic microbes, has seen a surge in popularity in the United States since the turn of the century. Kombucha is purported to have many health benefits, however, none have been rigorously tested and the molecular relationship between the microbial components of Kombucha and the consumer remains unexplored. The impact of individual probiotic microbes on human health is difficult to deconvolute, therefore, I will use C. elegans as a model to elucidate the molecular mechanisms by which Kombucha-associated microbes may promote health and longevity.

PI_NAMEs: DUMEZ, RACHEL NELL (contact)

PROGRAM_OFFICER_NAME: KIM, HYE-SOOK

PROJECT_TERMS: 16S ribosomal RNA sequencing;Address;Adenosine Monophosphate;Aging;aging process;Animal Model;Animals;Beverages;Binding Sites;Biochemical;Biological;Biological Assay;Biological Models;Biological Process;Caenorhabditis elegans;Carbon;Cells;commensal microbes;Communities;Complementary Health;Complex;Consumption;Data;detection of nutrient;Diet;dietary control;differential expression;Environmental Risk Factor;Escherichia coli;Etiology;experimental study;extend lifespan;Fatty acid glycerol esters;Fatty Acids;Fermentation;Food;FRAP1 gene;Gastrointestinal tract structure;Gene Expression;Genes;Genetic;genetic approach;genetic regulatory protein;Genetic Transcription;Genomic approach;gut microbes;gut microbiome;Health;Health Benefit;Health Promotion;HNF4A gene;Homeostasis;host-microbe interactions;Human;human subject;Immune response;in vivo;Individual;Ingestion;insight;Insulin;Integrative Medicine;Investigation;Laboratories;life span;lipid metabolism;Lipids;Lipolysis;Longevity;longevity gene;Marketing;Measures;Metabolic;metabolic abnormality assessment;Metabolic Pathway;Metabolism;Methods;Microbe;microbial;microbial community;microbiome;microorganism;Modeling;Molecular;mRNA sequencing;mutant;Mutation;Nematoda;Nuclear;Ontology;oxidation;Oxidoreductase;Pathway interactions;Persons;Phenotype;Physiological;Physiological Processes;Physiology;Play;Population;Preventive care;Probiotics;promoter;Protein Kinase;Reporter;resident commensals;response;Role;Safety;Shapes;Signal Pathway;Signal Transduction;Source;Stains;Standardization;System;Tea;Testing;Thinness;transcription factor;Transcriptional Regulation;transcriptome;transcriptomics;United States;Volatile Fatty Acids

PROJECT_TITLE: Elucidating the Host Metabolic Response to Consumption of Kombucha-associated Microorganisms


ORG_CITY: BRONX

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

PHR: NARRATIVE Evasion of apoptosis is a hallmark of cancer development, maintenance and chemoresistance. Pro-apoptotic BAX functions as gateway to apoptosis induction and our previous work has highlighted direct BAX activation as a promising therapeutic strategy. The goal of this proposal is to investigate small-molecule BAX activators in different type of tumors and investigate novel mechanisms and biomarkers that will facilitate the application of BAX activators to cancer patients.

PI_NAMEs: GAVATHIOTIS, EVRIPIDIS  (contact)

PROGRAM_OFFICER_NAME: KONDAPAKA, SUDHIR B

PROJECT_TERMS: Acute Myelocytic Leukemia;analog;Apoptosis;Apoptotic;BAX gene;Bax protein;BCL-2 Protein;BCL1 Oncogene;BCL2L1 gene;Binding;Biochemical;Biological Assay;Biological Availability;Biological Markers;cancer cell;Cancer Model;Cancer Patient;cancer therapy;Cell Death;Cell Line;Cell Membrane Permeability;Cell Survival;Chemicals;Chemoresistance;Clinical;clinical application;clinical candidate;Combined Modality Therapy;comparative efficacy;Development;Drug Kinetics;efficacy evaluation;Ensure;Family;Family member;FDA approved;Fluorescence Polarization;Funding;Generations;Goals;Growth;Hematologic Neoplasms;improved;In Vitro;in vivo;Induction of Apoptosis;inhibitor;innovation;insight;Investigational New Drug Application;Laboratories;leukemia;Liposomes;Maintenance;Malignant neoplasm of pancreas;Malignant Neoplasms;Maximum Tolerated Dose;MCL1 gene;Metabolic;Mitochondria;mitochondrial dysfunction;Molecular;Molecular Conformation;neoplastic cell;Non-Small-Cell Lung Carcinoma;novel;novel marker;novel therapeutic intervention;Oral;patient derived xenograft model;Patients;Permeability;Pharmaceutical Chemistry;pharmacologic;Pharmacology;Property;protein E;Protein Family;Proteins;Regulation;Resistance;Safety;Site;small molecule;Solid Neoplasm;Solubility;Therapeutic;therapeutic target;Toxicology;translational approach;Treatment Efficacy;tumor;tumor growth;Work

PROJECT_TITLE: Small Molecule Activators of Pro-apoptotic BAX for Cancer Therapy

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics - 2 Study Section[MCT2]


NIH_SPENDING_CATS: Diabetes;Nutrition

ORG_CITY: OKLAHOMA CITY

ORG_NAME: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR

ORG_STATE: OK

PHR: Project narrative: It is estimated that there are over three hundred million of diabetes patients globally. Proinsulin misfolding/ER stress-associated beta cell dysfunction and death play an important role in the onset and progression of diabetes. The proposed research is directly relevant to public health because our work on chemicals that protect function and survival of insulin-producing pancreatic beta cell has the potential to develop them into drugs to treat diabetes.

PI_NAMEs: WANG, WEIDONG  (contact)

PROGRAM_OFFICER_NAME: LI, YAN

PROJECT_TERMS: absorption;analog;Animal Model;Animals;Area;ATF6 gene;Beta Cell;Binding Proteins;Biochemical;Biological Assay;Biological Availability;Cell Physiology;Cell Survival;Cells;Cellular Assay;Cessation of life;Chemical Structure;Chemicals;Cytoprotection;Data;db/db mouse;Development;Diabetes Mellitus;diabetic;Diabetic mouse;Drug Kinetics;Drug or chemical Tissue Distribution;Eating;Endoplasmic Reticulum;endoplasmic reticulum stress;Ensure;Event;Excretory function;Failure;Foundations;Functional disorder;Half-Life;high throughput screening;Hyperglycemia;improved;In Vitro;in vivo;in vivo evaluation;inhibitor;Insulin;insulin sensitivity;Intervention;Lead;Metabolic;Metabolism;misfolded protein;Modeling;Mus;Names;novel;novel therapeutics;Organ;Pathologic;Pathway interactions;Patients;Peripheral;Permeability;Pharmaceutical Chemistry;Pharmaceutical Preparations;pharmacologic;Plasma;Play;prevent;Process;Production;Proinsulin;Property;protein misfolding;Proteins;Public Health;Research;response;Role;Safety;small molecule;small molecule inhibitor;Solubility;Standardization;Streptozocin;Stress;Structure;Structure of beta Cell of islet;Structure-Activity Relationship;systemic toxicity;Testing;Therapeutic;time use;Toxic effect;Treatment Efficacy;Weight Gain;Work

PROJECT_TITLE: Developing proinsulin misfolding inhibitors for beta cell protection and diabetes treatment


NIH_SPENDING_CATS: Biotechnology;Clinical Research;Genetics;HIV/AIDS;Human Genome;Infectious Diseases;Neurosciences;Prevention

PHR: Public Health Relevance Cryptococcal meningitis (CM), a fungal infection around the brain, causes 15-20% of AIDS-related deaths in Africa and is the most common cause of neurologic infection in Africa. This research seeks to determine genetic and immunological risk factors during CM, how these factors influence clinical outcomes such as death and neurologic impairment, and will develop diagnostic tests for biomarkers of disease that can be used to identify patients at high risk death.

PI_NAMEs: BAZIRA, JOEL ;MEYA, DAVID BISAGAYA;NIELSEN, KIRSTEN  (contact)

PROGRAM_OFFICER_NAME: SRINIVASAN, SUDHA

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Acute;Adult;Affect;Africa;African;AIDS-Related Opportunistic Infections;Alleles;Basic Science;Biological Assay;Biological Markers;Biology;Brain;Caring;Cause of Death;CD4 Positive T Lymphocytes;Cerebrospinal Fluid;Cessation of life;chemokine;Chromosomes;Clinical;clinical infrastructure;clinical practice;Clinical Research;clinical sequencing;Collaborations;Communicable Diseases;Complex;Cryptococcal Meningitis;Cryptococcosis;Cryptococcus;cytokine;Death Rate;Development;Diagnostic;Diagnostic tests;Disease;Exhibits;Failure;Foundations;Funding;fungal genetics;Genes;Genetic;Genetic Variation;genome wide association study;genomic biomarker;Genomics;Genotype;Goals;Helper-Inducer T-Lymphocyte;high risk;high risk population;Hospitalization;Human;Immune;Immune response;Immunity;Immunologic Markers;Immunologics;Immunology;Impairment;in silico;Infection;Inflammatory;Infrastructure;Interleukin-2;knowledge base;Laboratories;Mediating;Medical;Meningitis;Minnesota;Molecular;monocyte;Morbidity - disease rate;mortality;mortality risk;mouse model;Mycoses;Nervous System Disorder;Neurocognitive Deficit;Neurologic;Neurological outcome;neutrophil;novel;Outcome;Patient Isolation;Patient-Focused Outcomes;Patients;Phenotype;Plasma;polarized cell;Process;programs;public health relevance;Research;Research Personnel;research study;response;Risk Factors;routine care;Science;Serum;Single Nucleotide Polymorphism;Technology;Th1 Cells;trait;Translating;Translational Research;translational study;treatment strategy;Tuberculosis;Uganda;United States National Institutes of Health;Universities;Variant;Virulence

PROJECT_TITLE: Genomic Research Capacity Building for Cryptococcosis Translational Studies


NIH_SPENDING_CATS: Breast Cancer;Cancer;Genetics;Women's Health Research

ORG_NAME: GEORGE WASHINGTON UNIVERSITY

PHR: Project Narrative Lactate is a newly identified substrate of cancer cells, yet its regulatory mechanism is not fully understood. The overall goal of this proposal is to understand a previously unappreciated mechanisms by focusing on BACH1 involved in lactate catabolism of triple negative breast tumors. Our research team will identify whether blockade of BACH1 promotes shift of cancer cell populations toward lactate catabolic pathways, making cancer cells more sensitive to the therapy targeting lactate metabolism.

PI_NAMEs: LEE, JIYOUNG  (contact)

PROGRAM_OFFICER_NAME: WILLIS, KRISTINE AMALEE

PROJECT_TERMS: Acute Intermittent Porphyria;Animal Model;anti-cancer;anti-cancer therapeutic;Antineoplastic Agents;BACH1 gene;Binding;Biochemical Pathway;biochemical tools;Biological Assay;Breast Cancer Cell;Breast Cancer Model;Breast Cancer Patient;Breast Cancer Treatment;cancer cell;Cancer Cell Growth;cancer therapy;Carbon;Catabolism;Cells;Cellular biology;Clinical Data;Clinical Research;clinically significant;Combined Modality Therapy;Consumption;Data;Dependence;Development;Drug Design;Drug Targeting;Enzymes;FDA approved;Gene Expression;gene repression;Genes;Genetic;Genetic Transcription;Goals;heme a;Hemin;Heterogeneity;improved;In Vitro;in vivo;Individual;inhibitor;innovation;insight;Label;Lactate Dehydrogenase;Lactate Transporter;Link;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary Neoplasms;Messenger RNA;Metabolic;Metabolic Pathway;metabolic phenotype;Metabolism;metabolomics;Mitochondria;mitochondrial metabolism;Molecular;Molecular Biology;mouse model;mRNA Expression;multidisciplinary;Mus;Nature;Neoplasm Metastasis;neoplastic cell;novel;novel strategies;oxidation;Pathway interactions;patient derived xenograft model;Patient-Focused Outcomes;Patients;Pharmaceutical Preparations;pharmacologic;Play;Population;Predisposition;programs;Publishing;pyruvate carrier;Regulation;Repression;Research;Research Personnel;Research Proposals;Respiration;response;Role;single-cell RNA sequencing;skills;small hairpin RNA;Source;targeted treatment;Testing;Therapeutic;Therapeutic Intervention;therapeutic target;therapeutically effective;tool;Transcript;transcription factor;Transcription Repressor;Transcriptional Regulation;transcriptomics;triple-negative invasive breast carcinoma;tumor;tumor heterogeneity;tumor metabolism;Work

PROJECT_TITLE: Understanding lactate catabolism by BACH1 in triple negative breast cancer

STUDY_SECTION: TCB

STUDY_SECTION_NAME: Tumor Cell Biology Study Section[TCB]


ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

ORG_CITY: SALT LAKE CITY

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: Project Narrative Flux through oxidative phosphorylation is regulated by mechanisms that are not completely understood. The proposed research will address fundamental questions on how the lipid composition of mitochondrial membrane regulates bioenergetics. Findings from these studies have implications for health and disease across multiple organ systems.

PI_NAMEs: FUNAI, KATSUHIKO  (contact)

PROGRAM_OFFICER_NAME: ANSONG, CHARLES KWAKU

PROJECT_TERMS: Adenocarcinoma;Affect;Affinity;Architecture;ATP Synthesis Pathway;Binding;Bioenergetics;Body System;Carnitine;cell type;Chemicals;Complex;Cone;Consumption;Crista ampullaris;diagnostic platform;Disease;electron donor;electron energy;Electron Transport;Electrons;Electrophysiology (science);energy efficiency;Exercise;exercise training;fatty liver disease;Fluorometry;Health;Impairment;improved;Inner mitochondrial membrane;Intervention;Intestines;Lipids;Liver Mitochondria;Membrane;Membrane Potentials;Microscopy;Mitochondria;mitochondrial membrane;Modeling;Mus;Muscle Mitochondria;oligomycin sensitivity-conferring protein;Outer Mitochondrial Membrane;Oxidation-Reduction;Oxidative Phosphorylation;Oxidative Stress;Oxidative Stress Induction;Phosphatidylethanolamine;Play;Process;Prognosis;Proton-Motive Force;Protons;Pyruvate;pyruvate carrier;Reaction;Regulation;Research;Resolution;Respiration;respiratory;Role;Series;Shapes;Skeletal Muscle;Spirometry;Steatohepatitis;stem cells;Surface;Testing;Transferase;tumorigenesis;Warburg Effect

PROJECT_TITLE: PE in modulation of energy flux through OXPHOS

STUDY_SECTION: BBM

STUDY_SECTION_NAME: Biochemistry and Biophysics of Membranes Study Section[BBM]


NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Cancer Genomics;Clinical Research;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Human Genome;Precision Medicine;Rural Health;Social Determinants of Health

ORG_CITY: KANSAS CITY

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF KANSAS MEDICAL CENTER

ORG_STATE: KS

PHR: PUBLIC HEALTH SIGNIFICANCE Each year >500,000 Americans diagnosed with cancer have tumors that could be targeted with an FDA- approved drug to treat their disease more effectively. However, there is wide variation in use of these treatments in clinical practice. Rural patients, who are more likely to die from cancer than their non-rural counterparts, are less likely to receive targeted cancer therapies and could benefit greatly from interventions to address this quality gap.

PI_NAMEs: ELLIS, SHELLIE DAWN (contact);GODWIN, ANDREW K.

PROGRAM_OFFICER_NAME: WEAVER, SALLIE JAYNE

PROJECT_TERMS: Address;Adherence;Administrator;Adopted;Adoption;Advanced Malignant Neoplasm;American;cancer care;cancer health disparity;Cancer Patient;cancer therapy;care delivery;care providers;Caring;clinical practice;Cognition;Communication;Communities;community advisory board;Community Clinical Oncology Program;community engagement;community setting;Community Surveys;comparison group;Diagnosis;Diagnostic;Disease;Disparity;Early treatment;Effectiveness of Interventions;effectiveness testing;Elements;Eligibility Determination;Ensure;evidence base;experience;Failure;FDA approved;feasibility testing;Feedback;Focus Groups;Fostering;Future;genomic profiling;Genomics;geographic disparity;Geography;Goals;Guideline Adherence;Guidelines;Harm Reduction;Health;implementation facilitation;improved;improved outcome;Infrastructure;Institution;Interruption;Intervention;Job Satisfaction;Knowledge;Malignant Neoplasms;Measurement;Measures;Medical Oncologist;Medical Records;Molecular;molecular marker;Monitor;mortality;multidisciplinary;novel;Oncologist;Oncology;oncology program;Outcome;Pathologist;Pathology;Patient Care;Patient-Focused Outcomes;Patients;Pharmaceutical Preparations;Positioning Attribute;precision medicine;precision oncology;Problem Solving;Process;Professional Organizations;programs;Protocols documentation;Provider;Public Health;Quality of Care;Quasi-experiment;randomized trial;Readiness;Recommendation;Reflex action;Reporting;Research;Role;Rural;rural disparities;rural patients;rural setting;Sampling;Science;Scientific Advances and Accomplishments;Scientist;Series;Somatic Mutation;Specialist;Standardization;Surveys;System;targeted cancer therapy;targeted delivery;targeted treatment;Team Process;Technology;Testing;Time;time use;tumor;unnecessary treatment;uptake;Variant;Work

PROJECT_TITLE: TEAMSPORT to Community TEAMSPORT: Validating and Adapting a Precision Oncology Reflex Testing Team Intervention to Reduce Rural Disparities in Cancer Care Delivery

STUDY_SECTION: HSQE

STUDY_SECTION_NAME: Health Services: Quality and Effectiveness Study Section[HSQE]


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Immunization;Immunotherapy;Nanotechnology;Orphan Drug;Ovarian Cancer;Prevention;Rare Diseases;Vaccine Related;Women's Health Research

ORG_CITY: LA JOLLA

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

ORG_STATE: CA

PHR: Narrative A plant virus-based therapeutic is proposed for treatment and relapse prevention of ovarian cancer. This pro- posal is based on our data demonstrating that the plant virus-based therapeutic stimulates potent anti-tumor responses, suppresses metastatic development and recurrence. We will develop a 3D printed biopolymer im- plant containing the plant virus and irradiated cancer cells to prime tumor specific immunity post-surgery to pro- tect women from relapse and therefore increase survival.

PI_NAMEs: CHEN, SHAOCHEN ;FIERING, STEVEN ;STEINMETZ, NICOLE FRANZISKA (contact)

PROGRAM_OFFICER_NAME: HARRIS, RAYMOND D

PROJECT_TERMS: 3-Dimensional;3D Print;adaptive immune response;Adjuvant;Antigens;Antitumor Response;Biocompatible Materials;Biological Testing;Biopolymers;bioprinting;C57BL/6 Mouse;cancer cell;cancer immunotherapy;Cancer Vaccines;Cells;Cessation of life;chemotherapy;Clinical Trials;clinically significant;Complex;Data;design;Development;Devices;Disease;Disease remission;Dose;efficacy evaluation;electron energy;engineering design;Formulation;Future;Geometry;Hour;Image;Immune;immune activation;Immunity;Immunologics;Immunooncology;Immunosuppression;Immunotherapy;Implant;in situ vaccination;innovation;insight;intraperitoneal;Investigation;Irradiated tumor;Left;Location;Malignant neoplasm of ovary;Mechanics;Medicine;Memory;meter;Methods;Modeling;Modification;mouse model;nano;nanoparticle;Nature;neoantigens;neoplastic cell;novel;Operative Surgical Procedures;Optics;ovarian cancer prevention;Patients;Pattern recognition receptor;Peptides;photopolymerization;Plant Viruses;Plants;Printing;Process;Prognosis;prophylactic;Proteins;Publishing;Quality Control;recruit;Recurrence;Relapse;relapse prevention;Reproducibility;Resolution;scaffold;Scanning Electron Microscopy;Serous;Source;Stimulus;subcutaneous;Surrogate Markers;System;Techniques;Testing;Therapeutic;translational approach;Treatment Efficacy;tumor;Tumor Antigens;Tumor Debulking;Tumor Immunity;tumor microenvironment;vaccination schedule;Vaccines;Virus-like particle;Woman;X ray spectroscopy

PROJECT_TITLE: Bioprinting Plant Virus Nanoparticles for Immunotherapy and Relapse Prevention of Ovarian Cancer


ADMINISTERING_IC: MD

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

NIH_SPENDING_CATS: Behavioral and Social Science;HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Women's Health Research

ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE Women constitute 18% of new HIV infections in 2020, and 71% of these were among Black/African American and Hispanic women and yet only 7.4% of PrEP users are women. To understand PrEP equity for women overall, it is essential to evaluate better methods to identify women with PrEP indications, to stratify them by race and ethnicity, and to determine how characteristics of women with PrEP indications vary geographically. We propose to conduct analyses on existing datasets to 1) to better understand the characteristics of women with indications for PrEP, particularly those indications unrecognized by women and their healthcare providers, and re-estimate the number of heterosexual women with PrEP indications, 2) to determine the current racial/ethnic distribution of women PrEP users including creating imputation models for missing data, and 3) to determine spatio-temporal patterns of PrEP uptake among women in the US.

PI_NAMEs: BENNETT, BRADY W (contact)

PROGRAM_OFFICER_NAME: OLADEINDE, YEWANDE A

PROJECT_TERMS: Affect;African American;AIDS prevention;Behavior;Behavioral;Black race;black women;career;Categories;Characteristics;comparative;Data;data imputation;data quality;Data Set;Databases;Disparate;Disparity;Eligibility Determination;Epidemic;Epidemiology;Equation;Equity;Ethnic Origin;Evaluable Disease;Family;Geography;Goals;Government;Growth;Guidelines;health equity;Health Personnel;Heterosexuals;Hispanic;Hispanic Women;HIV;HIV diagnosis;HIV Infections;HIV risk;Inequity;Infection;Knowledge;Latinx population;Logistic Regressions;low socioeconomic status;male;men;men who have sex with men;Methodology;Methods;Modeling;Oral;Pattern;Performance;Pharmacologic Substance;Pharmacy facility;Policies;pre-exposure prophylaxis;Public Health;Race;Records;Research;Risk;Risk Factors;sex;Sexual Partners;sociodemographic factors;Socioeconomic Status;Spatial Distribution;spatiotemporal;statistics;Surveys;Training;United States;United States Dept. of Health and Human Services;uptake;validation studies;Woman;women's diagnosis;Work

PROJECT_TITLE: Gaps and Determinants in PrEP Uptake and Need: Understanding Disparities in PrEP Among Women in the United States


ED_INST_TYPE: SCHOOLS OF NURSING

NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Health Services;Heart Disease;Heart Disease - Coronary Heart Disease;Patient Safety

PHR: PROJECT NARRATIVE The primary objective of this study is to identify degrees of change in patient reported outcome measures that matter for guiding changes in clinical management of cardiac conditions. We are evaluating changes in patient reported outcome measures for patients with heart failure and coronary heart disease that are associated with improvements in their condition. The results of this study will build evidence for clinically meaningful changes in patient outcome measures and will include a framework to integrate patient reported outcome information into shared decision making and communication between healthcare professionals and patients.

PI_NAMEs: MASTERSON CREBER, RUTH MARIE (contact)

PROGRAM_OFFICER_NAME: SIDDIQUI, AYESHA SAEED

PROJECT_TERMS: Acute;Adult;Affect;Cardiac;Cardiovascular Diseases;Cardiovascular system;Caregivers;Caring;Clinical;clinical decision-making;clinical encounter;Clinical Management;clinical practice;Code;cohort;Communication;communication behavior;Computer software;Coronary Artery Bypass;Coronary heart disease;Country;Cues;Data;Decision Making;Disease;Disease Management;Early Intervention;effectiveness evaluation;EFRAC;Ethnography;Event;experience;follow-up;frailty;Gait speed;Goals;Habits;Health;Health Professional;Healthcare Systems;Heart;Heart failure;Hospitalization;improved;Individual;insight;Interview;Logistic Regressions;Measures;medical specialties;Methods;Monitor;Morbidity - disease rate;mortality;New York;non-verbal;novel;Operative Surgical Procedures;Outcome;Outcome Measure;patient engagement;Patient Outcomes Assessments;Patient-Focused Outcomes;Patients;Persons;Population;preservation;pro-brain natriuretic peptide (1-76);Process;Quality of life;Receiver Operating Characteristics;Recovery;Reporting;Research;Research Personnel;Scheme;shared decision making;Societies;Symptoms;Testing;theories;verbal;Walking;Work

PROJECT_TITLE: Improve the Meaning of Patient Reported Outcomes to Evaluate Effectiveness for Cardiac Care" (IMPROVE-Cardiac Care)

STUDY_SECTION: CDMA

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


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Hearing Loss;Neurosciences;Pediatric

ORG_NAME: NEW YORK UNIVERSITY

PHR: PROJECT NARRATIVE Up to 80% of children suffer at least one bout of impaired hearing during a time when the brain is especially vulnerable to deprivation, often causing lasting deficits in speech comprehension which are correlated with impaired perception of changes in the spectral content of sounds. This proposal seeks to 1) establish an animal model to assess perception of spectral modulation, 2) assess the impact of developmental hearing loss on perception and neural coding of spectral modulation and 3) test a novel gene therapy approach to rescue these deficits. This work will address an important lack of understanding of behavioral deficits following hearing loss and help direct future research towards therapeutic interventions.

PI_NAMEs: MASRI, SAMER  (contact)

PROGRAM_OFFICER_NAME: SCHURMAN, JACLYN REBECCA

PROJECT_TERMS: Abbreviations;Acoustics;Address;adeno-associated viral vector;Adolescent;Affect;Animal Model;Animals;Auditory area;Auditory Perception;aversive conditioning;awake;Behavior;behavior test;Behavioral;Behavioral Paradigm;Bilateral;Brain;calmodulin-dependent protein kinase II;Child;Code;comparison control;Comprehension;Control Groups;critical period;Custom;deprivation;Detection;Development;Discrimination;drug action;Ear;Earplug;Education;Electrodes;Excision;gene therapy;Genetic;Genome;Gerbils;Goals;hearing impairment;Hearing Tests;hippocampal pyramidal neuron;Impairment;Implant;Inhibitory Synapse;Language Development;Link;Measures;Mediating;Methods;neural;neuromechanism;Neurons;Noise;normal hearing;novel;novel therapeutics;Perception;Perceptual learning;Performance;pharmacologic;Pharmacologic Substance;Population;postsynaptic;Preparation;Procedures;Process;promoter;Protein Isoforms;receptor;Reporter;Research;response;Role;Signal Transduction;sound;Speech;speech in noise;Speech Perception;Stimulus;support vector machine;synaptic inhibition;Task Performances;Testing;Therapeutic Intervention;Time;Training;transmission process;Variant;vector;Viral;Virus;With laterality;Work

PROJECT_TITLE: Genetic rescue of a developmental hearing loss-induced spectral processing deficit


ADMINISTERING_IC: HS

IC_NAME: AGENCY FOR HEALTHCARE RESEARCH AND QUALITY

ORG_NAME: UNIVERSITY OF WASHINGTON

PHR: NARRATIVE The transition from hospital to a skilled nursing facility is a vulnerable point in the continuum of care, and medication-related errors during transitions are a major driver of avoidable harm and healthcare utilization. Using a cluster-randomized design with a network of four hospitals and 16 skilled nursing facilities, we will compare clinical outcomes of integrating pharmacists into the care transition process, targeting key gaps that contribute to medication errors, and evaluate its impact on medication-related problems and patient and caregiver-reported measures of transition quality.

PI_NAMEs: DAVIDSON, GIANA  (contact)

PROGRAM_OFFICER_NAME: CHANEY, KEVIN

PROJECT_TITLE: Preventing Medication-Related Problems in Care Transitions to Skilled Nursing Facilities

STUDY_SECTION: HEOR

STUDY_SECTION_NAME: Healthcare Effectiveness and Outcomes Research[HEOR]


ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: PROJECT NARRATIVE  Home dialysis is a preferred treatment for end-stage renal disease but is substantially underutilized, particularly among socially disadvantaged populations. This project leverages a national, randomized alternative payment model that incentivizes home dialysis to identify the structures and processes of care that are associated with higher home dialysis uptake. It also evaluates whether the alternative payment model led to reductions in socioeconomic and racial/ethnic disparities in home dialysis uptake.

PI_NAMEs: TUMMALAPALLI, SRI LEKHA  (contact)

PROGRAM_OFFICER_NAME: WILLIS, TAMARA

PROJECT_TITLE: Impact of the ESRD Treatment Choices Model on Home Dialysis Uptake and Disparities

STUDY_SECTION: HCRT

STUDY_SECTION_NAME: Healthcare Research Training [HCRT]


ADMINISTERING_IC: AG

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: NATIONAL INSTITUTE ON AGING

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

PHR: Narrative Alzheimer's disease and related dementias (ADRD) are one of the most important medical problems of our time. The University of Washington Alzheimer's Disease Research Center is dedicated to understanding the different disease processes underlying dementia and resistance to dementia. It supports a wide variety of research studies of ADRD from the perspectives of genetics, cognition, imaging, and neuropathology.

PI_NAMEs: GRABOWSKI, THOMAS J. (contact)

PROGRAM_OFFICER_NAME: SILVERBERG, NINA B

PROJECT_TERMS: Abbreviations;Acceleration;Alaska Native;Alzheimer's Disease;Alzheimer's disease related dementia;American Indians;Anatomy;Automobile Driving;Autopsy;Biological;biological heterogeneity;Biological Markers;Brain;cell repository;Cellular biology;Cerebral cortex;Cerebrum;Clinical;Cognition;Cognitive;Collection;Communities;Data;data management;Data Set;data sharing;Dedications;Dementia;Discipline;Disease;education research;Educational workshop;effective therapy;Etiology;Fostering;Frontotemporal Dementia;Functional disorder;Genetic;genetic information;Goals;Heterogeneity;human subject;Image;improved;Informatics;innovation;interest;Investigation;lens;Letters;Liquid substance;Location;Medical;Medical center;medical schools;Memory;Methods;Modeling;multidisciplinary;National Institute on Aging;Nerve Degeneration;neuropathology;Neurosciences;new technology;next generation;Outcome;outreach;Participant;Pathology;Pathway interactions;Phenotype;Philosophy;Population;precision medicine;Preventive treatment;Process;programs;Psychometrics;Quality Control;Readiness;recruit;Research;Research Personnel;research study;resilience;Resistance;Resources;statistics;stem cells;Stratification;Techniques;Time;Training;Tribes;Universities;Washington;Wellness Center;Work

PROJECT_TITLE: Biological heterogeneity in ADRD


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);American Indian or Alaska Native;Brain Disorders;Dementia;Health Disparities and Racial or Ethnic Minority Health Research;Neurodegenerative;Neurosciences;Racial and Ethnic Minority Health Research

PROJECT_TERMS: Abbreviations;Advocate;Alaska Native;Alzheimer's Disease;Alzheimer's disease related dementia;American Indians;biological heterogeneity;Biological Markers;Brain;cell repository;Clinical Research;Collaborations;Communities;data management;Data Set;Dementia;Development;education research;Ensure;Fostering;Goals;Grant;Health;Human;Image;Infrastructure;Institution;International;Leadership;Letters;Link;medical schools;Memory;National Institute on Aging;neuropathology;operation;outreach;Participant;Phenotype;Philosophy;Program Research Project Grants;programs;Quality Control;recruit;Research;Research Personnel;Resources;Running;statistics;synergism;Time;Universities;Vision;Washington;Wellness Center;Work

PROJECT_TITLE: Administrative Core


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

PI_NAMEs: JAYADEV, SUMAN  (contact)

PROJECT_TERMS: Abbreviations;Address;adjudication;Adult;Affect;Age;Alaska Native;Alaska Native population;Algorithms;Alzheimer's Disease;Alzheimer's disease related dementia;American Indian Population;American Indians;Anatomy;Automobile Driving;Autopsy;Biodiversity;Biological;biological heterogeneity;Biological Markers;Biology;Blood;Brain;Calibration;Cerebrospinal Fluid;Cerebrovascular Disorders;Clinical;clinical center;Clinical Data;Clinical Protocols;Cognitive;cognitive enhancement;cohort;Cohort Studies;Collaborations;Communities;community based participatory research;comorbidity;Consensus;Data;data management;Data Set;Dementia;demographics;Detection;diagnostic algorithm;Disease;disease heterogeneity;Education;education research;effective intervention;Enrollment;Equitable healthcare;Evaluation;Faculty;Frontotemporal Dementia;Genetic;Genetic Risk;genome wide association study;Genomics;Health;Heterogeneity;Human Genetics;Image;Imaging technology;improved;innovation;Institution;interoperability;Investigation;Justice;Knowledge;Liquid substance;Longitudinal cohort;Measures;Medical center;Memory;Methods;mild cognitive impairment;Modernization;multimodal neuroimaging;multimodality;Nerve Degeneration;neuropathology;Neuropsychological Tests;Neuropsychology;normal aging;outreach;Participant;Pathologic;pathological aging;Pathology;Pattern;Persons;Phenotype;Population;Process;programs;prospective;Protocols documentation;Psychometrics;Quality Control;Race;recruit;Research;research clinical testing;Research Personnel;resilience;Resistance;Resources;Risk;rural Americans;Science;Skin;socioeconomics;Standardization;statistics;Testing;translational study;Underrepresented Populations;Universities;Variant;Washington;Wellness Center;Work

PROJECT_TITLE: Clinical Core


NIH_SPENDING_CATS: Cancer;Digestive Diseases;Hematology;Pancreatic Cancer;Prevention;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: Narrative The primary focus of my work has been to understand the mechanisms by which cancers subvert normal developmental and stem cell signals to grow, spread and evade therapy. Over the last decade our work has ranged from discovery of new signals involved in cancer growth and progression to preclinical work that has formed the basis of clinical trials testing new agents for drug-resistant leukemias – leading to the recent approval of Glasdegib to treat aggressive leukemia – and pancreatic cancer. In the coming years, we will continue to strive to make important contributions that will have a meaningful impact on the many lives that deeply depend on the discoveries we make as a community.

PI_NAMEs: REYA, TANNISHTHA  (contact)

PROGRAM_OFFICER_NAME: HILDESHEIM, JEFFREY

PROJECT_TERMS: Benign;Cancer Biology;Cancer Control;cancer heterogeneity;cancer initiation;Cancer Relapse;cancer therapy;Cells;Clinical Trials;Communities;Development;Drug resistance;Early Diagnosis;Evolution;Growth;Hematologic Neoplasms;Image;improved;Lesion;leukemia;Malignant neoplasm of pancreas;Malignant Neoplasms;Molecular;New Agents;Patient-Focused Outcomes;pre-clinical;programs;Recurrent disease;Regulation;Research;Role;Signal Transduction;stem cells;Testing;therapy resistant;tumor progression;Undifferentiated;Work

PROJECT_TITLE: Molecular strategies for early detection and targeting of cancer


NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Digestive Diseases;Genetics;HIV/AIDS;Hepatitis;Hepatitis - B;Infectious Diseases;Liver Disease

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Hepatitis B virus (HBV) chronically infects 4% of the global population and up to 30% of people living with HIV as current treatments rarely lead to cure. Protein coding HBV RNAs which have been modified by human proteins are associated with treatment resistance and increased disease in a manner similar to HIV co- infection. We will quantify these modified viral RNAs in HIV-HBV co-infection and HBV monoinfection, a current unknown, and search for novel targets for drug development.

PI_NAMEs: GRUDDA, TANNER  (contact)

PROGRAM_OFFICER_NAME: RADKE, JOSHUA BRYAN

PROJECT_TERMS: Acceleration;Address;Affect;alternative treatment;analog;Ancillary Study;antagonist;Anti-viral Therapy;Archives;Biological Assay;Biological Markers;Blood;Cause of Death;Cell Line;Cell Nucleus;Cells;Chronic;Chronic Hepatitis B;Circular DNA;co-infection;Code;Cohort Studies;comparative;Death Rate;deep sequencing;Development;differential expression;digital;Disease;Disease Progression;drug development;Excision;Frequencies;Gene Expression;Gene Silencing;Genes;Genetic Transcription;Genomics;Goals;Hepatitis;Hepatitis B;Hepatitis B Infection;Hepatitis B Surface Antigens;Hepatitis B Virus;Hepatocyte;HepG2;HIV;Human;Immune response;In Vitro;Individual;Interferons;Interruption;knock-down;Lead;Link;Liver;Liver diseases;liver injury;Measures;Messenger RNA;Metabolic Clearance Rate;Methods;Modeling;Molecular;Mus;N-terminal;new therapeutic target;novel;overexpression;Participant;Pathway interactions;Pegylated Interferon Alfa;Persons;Polymerase;Population;Primary carcinoma of the liver cells;Protein Splicing;Proteins;Reporting;Research;Resistance;response;Reverse Transcription;Risk;RNA;RNA Interference;RNA Splicing;Role;Sampling;Serum;side effect;Signal Transduction;Small Interfering RNA;Surface Antigens;Techniques;therapy resistant;Tissues;tool;Transcript;Up-Regulation;Validation;Viral;viral DNA;Viral hepatitis;Viral Proteins;viral RNA;Viremia;Virus Diseases;Virus Replication

PROJECT_TITLE: Quantifying the frequency and diversity of spliced HBV mRNAs in HIV-HBV co-infection and their role in modulating viral transcription and host immune responses


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Dementia;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences

PI_NAMEs: SHOJAIE, ALI  (contact)

PROJECT_TERMS: Alzheimer's Disease;Alzheimer's disease diagnosis;Alzheimer's disease related dementia;Architecture;biological heterogeneity;Biological Markers;Clinical;Code;Collaborations;Computer Security;Computer software;computerized data processing;Computers;Consultations;Data;data access;Data Analyses;Data Collection;data management;data quality;Data Reporting;data sharing;data submission;Databases;design;Development;electronic data;Ensure;Environment;Genotype;Goals;Image;Individual;Laboratories;Maintenance;Manuscripts;Methodology;Mission;Monitor;neuropathology;Preparation;Prevention;Procedures;quality assurance;Quality Control;query tools;Reporting;Research;Research Personnel;Resources;Sampling;Site;Source;Specialist;Statistical Data Interpretation;statistics;tool;Translations;Universities;Washington;Writing

PROJECT_TITLE: Data Management and Statistical Core


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Biomedical Imaging;Brain Disorders;Dementia;Neurodegenerative;Neurosciences;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

PI_NAMEs: KEENE, CHRISTOPHER DIRK (contact)

PROJECT_TERMS: Abbreviations;Acceleration;Adult;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease related dementia;Autopsy;biobank;Biological;Biological Assay;biological heterogeneity;Biological Markers;Body Fluids;Brain;Brain imaging;Brain region;brain research;brain tissue;cell type;Cells;Cellular Structures;Clinical;Cognitive;cohort;Consensus;Data;data management;data quality;data sharing;Dementia;Development;Diagnostic;education research;Ensure;Equipment and supply inventories;Evaluation;Experimental Models;Family;Fostering;Functional Imaging;Funding;Future;Genetic;Goals;Guidelines;Heterogeneity;Human;Image;image reconstruction;Immunoassay;improved;in silico;Individual;Infrastructure;innovation;Investments;Knowledge;Leadership;Liquid substance;Longitudinal Studies;Magnetic Resonance Imaging;Measures;Medicine;Methods;Microscopic;Molecular;Molecular Profiling;Names;Nerve Degeneration;neuroimaging;neuroinflammation;neuropathology;neurotoxicity;next generation;non-demented;novel;outreach;Pathologic;Pathologic Processes;Pathology;Peptides;Phase;Policies;Positioning Attribute;Process;Productivity;Psychometrics;Publications;radiological imaging;Recording of previous events;recruit;Reporting;repository;Research;Research Activity;Research Personnel;Research Subjects;Research Support;Resources;Sampling;screening;Specimen;statistics;Stem Cell Research;stem cells;structural imaging;Supporting Cell;Therapeutic;Three-Dimensional Image;Tissues;Training;United States National Institutes of Health;virtual;Vision

PROJECT_TITLE: Precision Neuropathology Core