NIH_SPENDING_CATS: Cancer;Cancer Genomics;Digestive Diseases;Esophageal Cancer;Genetics;Human Genome;Precision Medicine;Prevention;Rare Diseases

ORG_CITY: BOSTON

ORG_NAME: DANA-FARBER CANCER INST

ORG_STATE: MA

PHR: PROJECT NARRATIVE  Liquid biopsies have made significant strides in cancer medicine but substantial questions remain, such as whether cancers which shed little tumor DNA into blood could be detected with higher sensitivity methods. This proposal builds on work performed during the first cycle of this grant, aiming to develop and optimize a new technology, DS-DR-MAESTRO (minor allele enriched sequencing through recognition oligonucleotides), that affords extremely high sensitivity to detect circulating tumor DNA. The optimized DS-DR-MAESTRO technology will be applied in detecting MRD in samples collected from esophageal cancer patients, a type of cancer that is notorious for shedding low amounts of DNA in circulation.

PI_NAMEs: ADALSTEINSSON, VIKTOR ;MAKRIGIORGOS, G. MIKE (contact)

PROGRAM_OFFICER_NAME: OSSANDON, MIGUEL

PROJECT_TERMS: Address;Alleles;Biological Markers;Biological Process;Blood;Breast Cancer Patient;cancer genome;Cancer Patient;cancer type;circulating DNA;Circulation;Clinical;clinical practice;Clinical Research;Collection;Data;Detection;detection method;Detection of Minimal Residual Disease;detection sensitivity;Disease;DNA;Drug resistance;Early Diagnosis;Effectiveness;empowerment;esophageal cancer patient;Esophagus;experience;experimental study;field study;Fingerprint;Genome;genome sequencing;genome-wide;Glioma;Grant;Human;Image;improved;innovation;internal control;liquid biopsy;Malignant neoplasm of esophagus;Malignant Neoplasms;malignant stomach neoplasm;Medicine;Melanoma patient;Methods;Minor;Monitor;Mutation;Mutation Detection;Neoplasm Metastasis;neoplastic cell;new technology;Noise;novel;Oligonucleotides;Patients;precision medicine;Preparation;prevent;Primary Neoplasm;Recurrence;Renal Carcinoma;repaired;Residual Neoplasm;Sampling;Screening for cancer;Somatic Mutation;Specificity;Technology;technology development;Testing;Time;Translations;tumor;tumor DNA;tumor heterogeneity;Tumor Markers;Tumor stage;volunteer;whole genome;Work

PROJECT_TITLE: Comprehensive minimal residual disease tracking in cancer

STUDY_SECTION: GCAT

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


ADMINISTERING_IC: CA

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Clinical Research;Hematology;Orphan Drug;Rare Diseases

ORG_CITY: TAMPA

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: H. LEE MOFFITT CANCER CTR & RES INST

ORG_STATE: FL

PHR: PROJECT NARRATIVE Despite advances in our understanding of the underlying genetic abnormalities in myelofibrosis (MF) and the development of JAK2 inhibitors, MF remains an aggressive chronic myeloid malignancy due to persistence of JAK2-activating mutations in patients undergoing JAK2 inhibitor therapy, the emergence of drug resistance, and a propensity for transformation to acute myeloid leukemia (AML). Thus, there is an urgent need to devise new treatment strategies that target the molecular and genetic aberrations driving MF development and clonal expansion, particularly in triple negative MF patients who lack mutations in the JAK2 kinase pathway. This R01 research program focuses on defining the roles of a new MYC-alarmin circuit that we have shown is sufficient to provoke MF, and to preclinically assess the therapeutic potential of targeting this pathway to improve outcomes in MF.

PI_NAMEs: YUN, SEONGSEOK  (contact)

PROGRAM_OFFICER_NAME: SAYYED, ZULEKHA I

PROJECT_TERMS: Ablation;Acute Myelocytic Leukemia;antifibrotic treatment;Antiinflammatory Effect;Automobile Driving;Bone Marrow;Bone Marrow Cells;Cell Proliferation;cell type;Cells;Chronic;Clinical;Clonal Expansion;Complex;Constitutional Symptom;Curiosities;Databases;Development;Drug resistance;Dysmyelopoietic Syndromes;FDA approved;Fibrosis;Genetic;Hematologic Neoplasms;Hematopoiesis;Hematopoietic;Hematopoietic stem cells;high risk;Impairment;improved;improved outcome;in vivo;Incidence;Inferior;Inflammation;Inflammatory;inhibitor;inhibitor therapy;insight;JAK2 gene;Knock-out;Maintenance;Mediating;mesenchymal stromal cell;Metabolism;Molecular;Molecular Abnormality;Molecular Target;MPL gene;Mus;mutant;Mutation;MYC Family Protein;Myelofibrosis;Myeloproliferative disease;Myofibroblast;Natural Immunity;novel therapeutic intervention;novel therapeutics;Oncogenic;Outcome;Pathogenesis;Pathway interactions;patient derived xenograft model;patient subsets;Patients;Pattern;Persons;pharmacologic;Phenotype;Phosphotransferases;Play;pre-clinical assessment;preclinical study;programs;Proliferating;protein expression;Proteins;Research;response;Role;S100A9 gene;Sampling;SEER Program;Signal Transduction;Somatic Mutation;Splenomegaly;targeted agent;Testing;Therapeutic;therapeutic target;transcription factor;United States;Up-Regulation

PROJECT_TITLE: MYC-alarmin axis as a novel therapeutic vulnerability in myelofibrosis

STUDY_SECTION: HTBT

STUDY_SECTION_NAME: Hemostasis, Thrombosis, Blood Cells and Transfusion Study Section[HTBT]


ADMINISTERING_IC: HL

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Cardiovascular;Genetics;Heart Disease

ORG_CITY: HOUSTON

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

ORG_STATE: TX

PHR: Project Narrative Atrial fibrillation, the most prevalence arrhythmia, is a public health burden. The proposed work will elucidate the function of a newly discovered protein FK506-binding protein 5 (FKBP5) in heart and how the FKBP5-deficiency in cardiomyocytes and fibroblasts promotes the pathogenesis of atrial fibrillation.

PI_NAMEs: LI, NA  (contact)

PROGRAM_OFFICER_NAME: SHI, YANG

PROJECT_TERMS: Adenoviruses;Adipose tissue;Arrhythmia;Atrial Fibrillation;Biological Assay;Cardiac;Cardiac Electrophysiologic Techniques;Cardiac Myocytes;cell type;Central Nervous System;Chronic;Crossbreeding;Development;Echocardiography;Electric Stimulation;Event;Fibroblasts;Fibrosis;FK506 binding protein 5;Gel;Genes;Genetic Transcription;Goals;Heart;Heart Atrium;Heat-Shock Proteins 90;Histology;Human;Hypoxia Inducible Factor;Impairment;Incidence;inducible Cre;inhibitor;insight;knock-down;Knockout Mice;Left atrial structure;Left ventricular structure;Ligands;Link;LoxP-flanked allele;Maps;Mediating;Messenger RNA;Modeling;Molecular;Molecular Chaperones;mRNA Expression;Mus;Myofibroblast;novel;novel therapeutic intervention;Nuclear Translocation;Optics;Pathogenesis;Pathway interactions;Patients;Pilot Projects;Predisposition;Prevalence;prevent;promoter;Proteins;Public Health;receptor;Recurrence;Risk;Role;single nucleus RNA-sequencing;Sinus;small hairpin RNA;Stains;Tacrolimus Binding Proteins;Testing;Tissues;transcription factor;transcriptomics;Up-Regulation;Work

PROJECT_TITLE: FKBP5 AND CARDIAC ARRHYTHMOGENESIS

STUDY_SECTION: MPPB

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


ADMINISTERING_IC: VA

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: Veterans Affairs

ORG_CITY: PHILADELPHIA

ORG_NAME: PHILADELPHIA VA MEDICAL CENTER

ORG_STATE: PA

PHR: Several psychotherapies for posttraumatic stress disorder (PTSD) have a strong evidence base for their efficacy, but nonresponse rates are high, particularly among older Veterans. Accumulating evidence indicates that memory deficits and poor learning of therapy contents adversely affect psychotherapy treatment response in PTSD. However, limited research has examined methods for increasing learning of therapy contents in psychotherapy for PTSD. The proposed study aims to examine the feasibility of integrating an intervention to increase learning and memory of psychotherapy content into the provision of a widely used psychotherapy, cognitive processing therapy (CPT), for older adults with PTSD. The ultimate goal of this line of research is to develop novel rehabilitation interventions to increase functioning for individuals with PTSD.

PI_NAMEs: SCOTT, JAMES COBB (contact)

PROJECT_TERMS: acceptability and feasibility;Adherence;Affect;Aging;Behavioral;Bipolar Disorder;Case Series;Cognitive;cognitive function;Cognitive Therapy;Data;depressive symptoms;Development;education research;evidence base;executive function;experience;Feedback;functional outcomes;Future;Goals;Impaired cognition;implementation science;improved;Individual;innovation;Intervention;Knowledge;Learning;Link;Manuals;Measures;Memory;Memory impairment;Mental Depression;Mental Health Services;Methods;Neurocognitive Deficit;Neuropsychology;novel;older adult;Outcome;Patients;personalized approach;personalized medicine;Phase;Post-Traumatic Stress Disorders;Prediction of Response to Therapy;Procedures;Process;Protocols documentation;Psychotherapy;Public Health;Randomized, Controlled Trials;recruit;rehabilitation research;Rehabilitation therapy;Research;Research Project Grants;Retrieval;Risk;skills;Symptoms;Techniques;Testing;Therapeutic;therapy development;Training;treatment adherence;Treatment outcome;treatment response;user centered design;Veterans;Work

PROJECT_TITLE: Enhancing Memory in Cognitive Processing Therapy for Older Adults with PTSD

STUDY_SECTION: RRDS

STUDY_SECTION_NAME: Rehabilitation Research and Development SPiRE Program[RRDS]


NIH_SPENDING_CATS: Biotechnology;Cardiovascular;Diabetes;Genetics;Wound Healing and Care

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: Narrative: Despite current therapeutic strategies, human subjects with diabetes and peripheral artery disease (PAD) suffer from an increased risk of critical limb ischemia (CLI), a more severe condition associated with impaired growth of new blood vessels, ischemic rest pain, impaired wound healing, and a higher risk of limb amputation and cardiovascular death. We have identified a novel pro-angiogenic microRNA, termed miR-130b, in both mice and human subjects with diabetes and increasing severity of PAD. The proposed studies will provide a detailed understanding for how miR-130b promotes critical angiogenic signaling pathways and functional responses in ischemic limbs with the goal of developing novel therapies for overcoming “angiogenic resistance” in the treatment of diabetic critical limb ischemia.

PI_NAMEs: FEINBERG, MARK W (contact)

PROGRAM_OFFICER_NAME: GALIS, ZORINA S

PROJECT_TERMS: Acceleration;activin A;Acute;Amputation;angiogenesis;Angiogenesis Inhibitors;Arterial Occlusive Diseases;Biological Assay;Biopsy;Blood flow;Blood Vessels;cardiovascular risk factor;Cardiovascular system;cell growth;cell motility;Cell Proliferation;Cessation of life;Chronic;cohort;critical limb Ischemia;crosslinking and immunoprecipitation sequencing;db/db mouse;Diabetes Mellitus;diabetic;Diabetic mouse;diabetic patient;Diagnosis;Disease;Endothelial Cells;Endothelium;Event;Exhibits;experience;Exposure to;femoral artery;Foot Ulcer;Foundations;Gene Expression;gene repression;Gene set enrichment analysis;Genes;Glucose;Goals;high risk;human subject;Impaired wound healing;Impairment;improved;in vivo;inhibin B;insight;Intervention;Ischemia;ischemic injury;Isolated limb perfusion;Knockout Mice;Ligation;Light;limb amputation;limb ischemia;Limb structure;Link;loss of function;Lower Extremity;Mediating;Mediator;Medical;member;MicroRNAs;microscopic imaging;migration;miRNA expression profiling;Molecular;molecular imaging;Morbidity - disease rate;mortality;Mus;Muscle;Mutation;nanoparticle;Necrosis;new growth;new therapeutic target;non-diabetic;novel;novel therapeutics;overexpression;Pain;Pathway interactions;patient response;Patients;perfusion imaging;Peripheral arterial disease;Phenocopy;Phenotype;Plasma;posttranscriptional;prediction algorithm;Process;Proliferating;Quality of life;Regulation;Reporter Genes;Repression;Resistance;response;Rest;revascularization;Risk;Role;Severities;Signal Pathway;Signal Transduction;siRNA delivery;Skeletal Muscle;Small Interfering RNA;Stimulus;TGF Beta Signaling Pathway;Therapeutic;Tissue Sample;Tissues;Transcript;transcriptome sequencing;Transforming Growth Factor beta;translational potential;Tube;Untranslated Regions;Untranslated RNA;wound closure

PROJECT_TITLE: miR-130b, angiogenesis, and diabetic critical limb ischemia

STUDY_SECTION: IVPP

STUDY_SECTION_NAME: Integrative Vascular Physiology and Pathology Study Section[IVPP]


ORG_CITY: IOWA CITY

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: Project Narrative This project is relevant to public health because it will contribute to our understanding of the cardiac transcriptional response to stress induced hypertrophy that occurs in both human and rodent models of heart disease. The goal of this project is to determine the function of the Mediator kinase to regulate cardiac gene expression utilizing new genetic and pharmacologic tools combined with NextGen sequencing technology. This research aligns with the NHLBI's mission to promote the prevention and treatment of heart disease by advancing our understanding of the transition from the basal to hypertrophic gene programs through the Mediator kinase and the potential for developing a new therapeutic strategy to treat cardiac dysfunction.

PI_NAMEs: GRUETER, CHAD E (contact)

PROGRAM_OFFICER_NAME: TJURMINA, OLGA A

PROJECT_TERMS: Angiotensin II;Aorta;Automobile Driving;Cardiac;Cardiac Myocytes;Chromatin Remodeling Factor;Chronic;Clustered Regularly Interspaced Short Palindromic Repeats;cohort;Complex;conditional knockout;Coupling;Data;Dilated Cardiomyopathy;Disease;Enhancers;experimental study;follow-up;Functional disorder;Gene Expression;Gene Expression Regulation;gene network;Genes;Genetic;Genetic Transcription;Genome;Goals;Growth;Heart;Heart Diseases;Heart failure;Heart Hypertrophy;Histones;Human;human model;Hypertension;hypertensive;Hypertrophy;in vivo;Infusion procedures;inhibitor;Knockout Mice;Link;Measures;Mediating;Mediator;Mission;Modality;Modeling;mouse model;Mus;Myocardial dysfunction;National Heart, Lung, and Blood Institute;new therapeutic target;next generation sequencing;Nodal;novel;novel therapeutic intervention;Outcome;overexpression;Pathologic;Pathology;Patients;pharmacologic;Phosphorylation;Phosphotransferases;premature;prevent;Prevention;programs;promoter;protein expression;Proteomics;Public Health;recruit;Regulation;Research;response;Risk;Risk Factors;RNA;Rodent;Rodent Model;Signal Transduction;SIRT1 gene;small molecule;small molecule inhibitor;Stimulus;Stress;stressor;Technology;Testing;Therapeutic;therapeutic development;therapeutic target;Time;tool;transcription factor;Transcriptional Regulation;Work

PROJECT_TITLE: Mediator kinase regulation of cardiac transcription

STUDY_SECTION: MPPA

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


ORG_CITY: CHAPEL HILL

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: PROJECT NARRATIVE Thrombosis is the uncontrolled formation of a blood clot that blocks a vessel, often linked to inflammation and inflammatory disease, and is the leading cause of death and disability worldwide. The primary goal of this research program is to determine mechanisms linking fibrin(ogen) to thrombus formation and hemostasis using new tools that selectively reduce circulating fibrinogen or specifically suppress fibrin matrix formation. This research is highly relevant to public health as it will foster creative discoveries for minimizing the morbidity and mortality associated of thrombotic diseases, including inflammation-associated thrombosis, while providing critical insight into new anti-thrombotic treatments that are expected to be safer than the current options.

PI_NAMEs: FLICK, MATTHEW J. (contact);KASTRUP, CHRISTIAN

PROGRAM_OFFICER_NAME: HILL-PRYOR, CRYSTAL DARLEANE-ROBIN

PROJECT_TERMS: Acute;Address;Afibrinogenemia;Age;Blood coagulation;Blood Platelets;Carotid Artery Thrombosis;Cause of Death;Chronic;chronic inflammatory disease;clinically relevant;Coagulation Process;Coronary Arteriosclerosis;Creativeness;Data;Deep Vein Thrombosis;Development;disability;Disease;efficacy evaluation;Endotoxemia;Erythrocytes;Etiology;Fibrin;Fibrinogen;Fibrinolysis;Fostering;Fracture;Genetic;Goals;Hemorrhage;Hemostatic Agents;Hemostatic function;Heterogeneity;Impairment;Incidence;Infection;Inferior vena cava structure;Inflammation;Inflammatory;innovation;insight;knock-down;Knowledge;Link;lipid nanoparticle;Liver;Modeling;monomer;Morbidity - disease rate;mortality;mRNA delivery;Mus;mutant;Mutation;nanoparticle delivery;novel;Oral Contraceptives;Outcome;Pathogenesis;Pathologic;Pathology;Pathway interactions;pharmacologic;Plasma;polymerization;Polymers;Porosity;pre-clinical;Predisposition;Pregnancy;preservation;prevent;Process;programs;prophylactic;Proteins;Prothrombin;Public Health;Pulmonary Embolism;Research;Resistance;Risk;Risk Factors;Severities;Sickle Cell Anemia;siRNA delivery;Small Interfering RNA;Smoking;Stroke;Structure;System;targeted agent;Testing;Therapeutic;Therapeutic Uses;Thrombin;thrombogenesis;thromboinflammation;thrombolysis;Thrombosis;thrombotic;thrombotic complications;Thrombus;tool;translational potential;Trauma;Variant;Venous;venous thromboembolism;Work

PROJECT_TITLE: Novel mechanisms to limit thrombosis by decreasing fibrinogen or suppressing fibrin matrix formation


ORG_CITY: PITTSBURGH

ORG_NAME: VETERANS HEALTH ADMINISTRATION

PHR: Power systems for powered mobility devices, including power wheelchairs and scooter, have not changed significantly in decades. They have generally revolved around Lead-acid batteries, but some more recently are using Lithium-Ion batteries. Both Lead-Acid and Lithium-Ion batteries have limitations in terms of range, charging time, safety, and environmental impacts. Nickel-Zinc batteries may present many advantages to Lead- Acid and Lithium-Ion batteries, but aren’t able to directly replace them on powered mobility devices due to a small cycle life when used in low power situations. This limitation may be ameliorated if the Nickel-Zinc batteries are combined with supercapacitors. This project will develop a Nickel-Zinc and supercapacitor hybrid power system and evaluate the range of the system compared to Lead-Acid and Lithium-Ion batteries using standard range tests. The results may provide a power system that is safer, more environmentally friendly, and able to be charged faster for Veterans who use powered mobility devices.

PI_NAMEs: DUVALL, JONATHAN  (contact)

PROJECT_TERMS: Acids;Analysis of Variance;Bypass;Characteristics;Charge;Communities;density;Development;Devices;direct application;energy density;Energy Transfer;Environment;Environmental Impact;Event;Explosion;extreme temperature;Fire - disasters;Freedom;Friends;Goals;Hour;Hybrids;Ions;Laboratories;Lead;Leisure Activities;Life Cycle Stages;Lithium;Methods;mobility aid;Motor;Nickel;Performance;portability;Power Sources;Powered wheelchair;Predisposition;Reporting;Research;research facility;Running;Safety;safety testing;Speed;Sports;System;Technology;Testing;Time;Travel;Veterans;Weight;Wheelchair user;Wheelchairs;Zinc

PROJECT_TITLE: Development of Nickel-Zinc power system for powered wheelchairs


ADMINISTERING_IC: ES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Agent Orange & Dioxin;Cancer;Climate-Related Exposures and Conditions;Clinical Research;Endocrine Disruptors;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Hematology;Lymphatic Research;Lymphoma;Prevention;Rare Diseases;Social Determinants of Health;Women's Health Research

PHR: Project Narrative Multiple myeloma (MM) and non-Hodgkin lymphoma (NHL) are common immune system cancers that pose a substantial public health, personal and financial burden; treatment is expensive, and for some more aggressive subtypes, more than half of patients die within five years of diagnosis. Certain occupational exposures such as pesticides or solvents (i.e., benzene) have been shown to be risk factors for these cancers, but it is not known whether lower-dose environmental exposure to those agents also increases risk to the general population. The studies proposed in this application will make use of extensive residential histories for participants in eight large study populations, and of routine environmental monitoring for pollutants, to provide much-needed insights into the association of lower-level exposure to single and mixtures of environmental pollutants with risk of MM, NHL, and common NHL subtypes.

PI_NAMEs: BIRMANN, BRENDA M (contact)

PROGRAM_OFFICER_NAME: BOYLES, ABEE

PROJECT_TERMS: Address;Adult;Age;Air Pollutants;Area;Arsenic;Autoimmune Diseases;B-Cell Activation;Bayesian Method;Benzene;Biological Models;Biometry;black women;Body mass index;Cadmium;Calendar;California;cancer diagnosis;cancer epidemiology;cancer prevention;Cancer Prevention Study II;carcinogenicity;Cessation of life;Chlorinated Hydrocarbons;Chronic;Chronic Lymphocytic Leukemia;clinically relevant;cohort;Collaborations;Confounding Factors (Epidemiology);contextual factors;Cox Proportional Hazards Models;Data;design;Diagnosis;Dioxins;Dose;Environmental Epidemiology;Environmental Exposure;Environmental Monitoring;Environmental Pollutants;Environmental Risk Factor;Ethnic Origin;Etiology;Exposure to;Financial Hardship;follow-up;Follow-Up Studies;General Population;Geographic Information Systems;Growth Factor;Health Professional;Hematologic Neoplasms;Hematopathology;Heterogeneity;Histologic;Human;Immune;immune activation;immune function;Immune Plasma;Immune system;Immunologic Markers;immunoregulation;Incidence;indexing;Individual;Industrial Waste;Industrialization;Inflammation;Influentials;Infrastructure;insight;Knowledge;large cell Diffuse non-Hodgkin's lymphoma;Life Style;Lymphoma;Malignant lymphoid neoplasm;Malignant Neoplasms;Manuscripts;Mature Lymphocyte;Measures;Medical History;men;Metals;Methods;model organism;Modeling;Modification;molecular subtypes;Multiple Myeloma;Neighborhoods;Non-Hodgkin's Lymphoma;Non-Insulin-Dependent Diabetes Mellitus;novel;Nurses' Health Study;nutrition;obese person;Occupational;Occupational Exposure;Occupations;Participant;Pathogenesis;Pathogenicity;Patients;Persons;Pesticides;Plasma Cells;pollutant;Pollution;Polychlorinated Biphenyls;Postmenopause;Predisposition;Prevention strategy;Property;prospective;Prospective Studies;Public Health;Publishing;Qualifying;Race;Recording of previous events;Research Personnel;Residential Mobility;Resources;Risk;Risk Factors;Role;Sample Size;sex;Small-Cell Lymphoma;Smoking;sociodemographic factors;sociodemographics;Solvents;study population;Sum;teacher;Time;Tissues;tool;understudied cancer;United States;UV Radiation Exposure;Woman;Women's Health;Work

PROJECT_TITLE: Geospatially modeled environmental risk factors for lymphoid malignancies

STUDY_SECTION: CHD

STUDY_SECTION_NAME: Cancer and Hematologic Disorders Study Section[CHD]


PHR: PROJECT NARRATIVE. Cigarette smoke (CS) contributes to the development of severe influenza virus pneumonia. However, innate immune mechanisms by which CS exacerbates flu-induced lung injury are not well understood. The proposed study will introduce a novel paradigm that occlusion of lung microvasculature by neutrophil-platelet aggregates promotes CS-induced flu severity and potentially identify a new therapeutic target in the platelet-neutrophil signaling.

PI_NAMEs: NYUNOYA, TORU  (contact)

PROJECT_TERMS: Acute Lung Injury;Address;Air;Anti-viral Therapy;Antibodies;Area;Biochemical;Blood;Blood Platelets;Blood specimen;Blood Vessels;Body Weight decreased;Caspase;Cessation of life;cigarette smoke;cigarette smoke-induced;Coagulation Process;Deposition;Development;Economic Burden;effective therapy;Endosomes;Endothelial Cells;exposure to cigarette smoke;extracellular;Extravasation;Fibrin;flu;Fluorescence Microscopy;General Population;Generations;Genetic;Goals;Habits;Hemorrhage;Hemostatic function;Homologous Gene;Hour;Human;Hypoxemia;Immune;Immune response;In Vitro;in vivo;in vivo imaging;Individual;Inflammasome;Inflammation;Influenza;Influenza A virus;influenza infection;influenza virus vaccine;influenzavirus;innate immune mechanisms;Innate Immune Response;Intraperitoneal Injections;Ischemia;ischemic injury;Knockout Mice;Lung;lung imaging;lung injury;Mediating;Methods;Microcirculation;Modeling;Morbidity - disease rate;mortality;mouse model;multi-photon;Mus;Myelogenous;neutrophil;new therapeutic target;non-smoker;novel;Occlusion injury;Pathway interactions;Patients;peripheral blood;Platelet Activation;Platelet aggregation;Platelet Count measurement;Pneumonia;Predisposition;prevent;protective effect;RNA;Role;sensor;Severities;Signal Transduction;Smoke;Smoker;Smoking;smoking prevalence;Sterility;Testing;thromboinflammation;Thromboplastin;Thrombosis;Time;TLR7 gene;Up-Regulation;vascular injury;Veterans;Virus Diseases

PROJECT_TITLE: Role of smoking in severe influenza virus pneumonia

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 PULM-T (01)]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biotechnology;Clinical Research;Contraception/Reproduction;Immunization;Infectious Diseases;Infertility;Microbiome;Pelvic Inflammatory Disease;Prevention;Sexually Transmitted Infections;Vaccine Related;Women's Health Research

ORG_DEPT: PEDIATRICS

PHR: Chlamydia trachomatis is the leading bacterial cause of sexually transmitted disease worldwide. The proposed research is relevant to public health because it will lead to new diagnostic biomarkers that can identify women at increased risk of poor reproductive outcomes after infection and identifying people for targeted treatments and more frequent screening. This will reduce the burden of involuntary infertility and improve the health of young people so is well aligned with the NIH’s mission that seeks to apply knowledge to ‘enhance health, lengthen life, and reduce illness and disability’.

PI_NAMEs: DARVILLE, TONI ;O'CONNELL, CATHERINE MARY (contact)

PROGRAM_OFFICER_NAME: CHUANG, ELEANORE JENNIFER

PROJECT_TERMS: Acceleration;Automobile Driving;Bacteria;Binding;Biological Markers;biomarker development;biomarker identification;Biometry;Biopsy;candidate marker;Cell Culture Techniques;Cells;Cervical;cervicovaginal;cervicovaginal microbiome;Cervix Uteri;Chlamydia;Chlamydia Infections;Chlamydia trachomatis;chlamydia vaccine;chronic pelvic pain;Clinical;clinically relevant;co-infection;cohort;Complex;Data;data integration;Data Set;Development;Diagnosis;diagnostic biomarker;diagnostic development;disability;Disease;dysbiosis;Ectopic Pregnancy;Endocervix;Endometrial;Endometritis;Endometrium;Environment;environmental change;Environmental Risk Factor;environmental stressor;Epithelial Cell Proliferation;Epithelial Cells;Evaluation;female reproductive tract infection;fitness;Focal Infection;Funding;Gene Expression;Gene Expression Profile;Genetic Transcription;genital infection;Goals;Growth;Health;High Risk Woman;Human;Immune;Immune response;Immunity;improved;in vivo;Indoles;Infection;Infection Control;Infertility;Inflammation;Inflammatory;Inflammatory Response;innovation;insight;Integration Host Factors;Investigation;Knowledge;knowledge base;Lactobacillus;Lead;Life;Link;Mammalian Oviducts;Mediating;member;metabolome;metabolomics;metatranscriptomics;microbial;microbial community;microbiome;microbiome therapeutics;microbiota;Mission;Modeling;molecular marker;Multiomic Data;Natural History;Natural Immunity;next generation;Non-Invasive Detection;novel;novel diagnostics;novel therapeutics;Oral Contraceptives;Outcome;pathogen;Pathogenesis;Pathology;Pathway interactions;Pattern;Pelvic Inflammatory Disease;Persons;Pilot Projects;Population;predicting response;Predisposition;pressure;prevent;Primary Infection;Process;Public Health;reproductive;reproductive morbidity;reproductive outcome;reproductive tract;Research;research clinical testing;response;Risk;screening;Severities;Sexual Partners;Sexual Transmission;Sexually Transmitted Diseases;Site;Specimen;Systems Biology;Technology;Testing;Therapeutic;transcriptomics;Translating;United States National Institutes of Health;Vaccine Design;vaccine development;vaccine evaluation;Vaccines;Vagina;Woman

PROJECT_TITLE: Natural History of Chlamydia trachomatis genital tract infection in women

STUDY_SECTION: BHI

STUDY_SECTION_NAME: Bacterial-Host Interactions Study Section [BHI]


NIH_SPENDING_CATS: Biotechnology;Congenital Structural Anomalies;Genetics;Infectious Diseases;Lung;Pediatric;Rare Diseases

ORG_CITY: BALTIMORE

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

ORG_STATE: MD

PHR: PROJECT NARRATIVE Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder of cilia structure and function, characterized by chronic infections of the respiratory tract, male infertility, and disorders of organ laterality (situs inversus). In the current proposal we hypothesize that cytoglobin, a novel heme protein of yet unknown function, controls spatiotemporal nitric oxide (NO) levels in cilia in airway ciliated cells and during development, via interactions with NO synthases, necessary for normal ciliary function and left/right asymmetry of the heart. Our work aims to bridge a critical gap in knowledge about the role of NO signaling in normal ciliary function and the development of PCD and situs inversus, and has the potential to change our current paradigm for diagnosis and therapy of ciliopathies.

PI_NAMEs: CORTI, PAOLA ;GLADWIN, MARK T (contact)

PROGRAM_OFFICER_NAME: LACHOWICZ-SCROGGINS, MARRAH ELIZABETH

PROJECT_TERMS: Acute;Adult;Affect;Airway Disease;airway epithelium;airway inflammation;arm;autosome;Biochemical;Biological Assay;Biology;Bronchiectasis;Bronchitis;Cardiac;Cell Culture Techniques;Cell Line;Cell model;cell type;Cells;Chemicals;chronic infection;Chronic Sinusitis;Cilia;Ciliary epithelium;Ciliary Motility Disorders;ciliopathy;Clinical;CRISPR/Cas technology;Cystic Fibrosis;Data;Defect;Development;Diagnosis;Diagnostic tests;Disease;drug testing;Dynein ATPase;Embryo;enzyme activity;Enzymes;Epithelium;Evaluation;Exhalation;Extended Family;Fishes;Functional disorder;gain of function;Genetic;genetic variant;Genomics;Globin;Handedness;Heart;Heart Abnormalities;Heme;Hemeproteins;Hemoglobin;Hereditary Disease;Human;human model;improved;in utero;Individual;Infertility;Inflammatory;interest;knock-down;Knock-out;Knockout Mice;Knowledge;Left;Ligand Binding;Link;Lipid Peroxidation;Liquid substance;loss of function;loss of function mutation;Male Infertility;Methodology;Modeling;Motility;Motion;mouse model;Mucociliary Clearance;Mus;mutant;Mutation;Myoglobin;neuroglobin;Nitric Oxide;Nitric Oxide Donors;Nitric Oxide Synthase;Nitrites;Nose;novel;novel therapeutic intervention;Organ;overexpression;Oxidation-Reduction;Oxidative Stress;Oxidoreductase;Oxygen;Pathway interactions;Patients;Pattern;Pharmacotherapy;Phenocopy;Phenotype;Physiological;Pneumonia;Primary Ciliary Dyskinesias;Production;Protein Isoforms;Proteins;Radial;Reaction;Recombinants;Recurrence;Regulation;Reporting;Research;Respiratory Tract Infections;response;Role;sensor;Signal Pathway;Signal Transduction;Situs Inversus;small molecule;Smoking;Soluble Guanylate Cyclase;spatiotemporal;Structure;Sulfhydryl Compounds;Surface;Syndrome;Testing;Therapeutic;Variant;Vertebrates;Vesicle;Virus Diseases;Visceral;Work;Zebrafish

PROJECT_TITLE: Airway epithelial cytoglobin regulates nitric oxide synthase and development of primary ciliary dyskinesia and situs inversus

STUDY_SECTION: LCMI

STUDY_SECTION_NAME: Lung Cellular, Molecular, and Immunobiology Study Section[LCMI]


NIH_SPENDING_CATS: Breast Cancer;Cancer;Cancer Genomics;Clinical Research;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Racial and Ethnic Minority Health Research;Social Determinants of Health;Women's Health Research

ORG_CITY: CLEVELAND

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

ORG_STATE: OH

PHR: Triple-negative Breast Cancer (TNBC) is more common and exhibits higher aggressiveness in African American women as compared to their European American counterparts, with socio-economic and lifestyle factors being unable to fully account for this significant racial disparity. Our proposed studies will delineate the molecular mechanisms associated with TNBC aggressiveness with an overarching goal of identifying the etiologic factors contributing to outcome disparities in African Americans. Our proposed studies will also unravel novel surveillance and therapeutic avenues, thereby guiding and improving the clinical management of this deadly disease.

PI_NAMEs: HUANG, ALEX YEE-CHEN;SCHIEMANN, WILLIAM  (contact);ZHU, XIAOFENG

PROGRAM_OFFICER_NAME: SHARMAN, ANU

PROJECT_TERMS: Achievement;Address;African American;African American population;African American Women;African ancestry;aggressive breast cancer;American;Automobile Driving;Biological;Breast Cancer Cell;Breast Cancer Patient;breast cancer progression;CCL2 gene;chemotherapy;Clinical;Clinical Management;clinical practice;cohort;Complex;Coupled;CSF1 gene;cytokine;Data;Development;Disease;Disease-Free Survival;Disparity;Drug Targeting;Engineering;epigenomics;Etiology;European;Event;Exhibits;Functional disorder;Gene Expression;gene repression;Genetic;genetic signature;genome-wide;Genotype;Goals;Growth and Development function;Heterogeneity;immune cell infiltrate;immunoregulation;Impairment;improved;In complete remission;In Vitro;in vivo;Incidence;individualized medicine;Infiltration;innovation;insight;Investigation;Knowledge;lifestyle factors;Macrophage;Malignant Breast Neoplasm;Maps;Measures;Mediating;Medicine;Modeling;Molecular;novel;novel marker;novel therapeutic intervention;novel therapeutics;Outcome;outcome disparities;Pathologic;Patients;pre-clinical therapy;prevent;Prognosis;Race;racial disparity;racial population;Repression;Resistance;Role;Science;Signal Transduction;single-cell RNA sequencing;sociodemographic factors;socioeconomic disparity;Socioeconomic Factors;socioeconomics;survival outcome;Survival Rate;Testing;Therapeutic;therapeutic effectiveness;therapeutic target;Tissues;transcription factor;transcriptome;transcriptome sequencing;transcriptomics;treatment response;triple-negative invasive breast carcinoma;tumor;Tumor Biology;tumor-immune system interactions;tumorigenesis;tumorigenic;Tumorigenicity;United States;Variant;Woman;ZNF151 gene

PROJECT_TITLE: MIZ1 Activation in Triple-negative Breast Cancer Racial Disparities

STUDY_SECTION: BMCD

STUDY_SECTION_NAME: Basic Mechanisms of Cancer Health Disparities Study Section[BMCD]


NIH_SPENDING_CATS: Behavioral and Social Science;Cardiovascular;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Pediatric;Prevention;Social Determinants of Health;Women's Health Research

ORG_CITY: CHICAGO

ORG_NAME: LURIE CHILDREN'S HOSPITAL OF CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE This unique project will identify key timing and drivers of maternal-child cardiovascular health (CVH) starting during preconception in a diverse population. The results and products of this work will directly inform family- level and population-level strategies that address the psychosocial contexts of diverse families to promote ma- ternal and child CVH. This project aligns with the NHLBI Division of Cardiovascular Sciences’ strategic vision themes and priorities, including addressing social determinants of health and health inequities, promoting CVH across the lifespan including in infancy and early childhood, and reducing maternal cardiovascular morbidity.

PI_NAMEs: MARMA, AMANDA K (contact)

PROGRAM_OFFICER_NAME: REIS, JARED P

PROJECT_TERMS: 2 year old;Address;Affect;Age;Beginning of Life;Behavior;Birth;Cardiovascular Diseases;cardiovascular disorder risk;cardiovascular health;Cardiovascular system;Characteristics;Chicago;Child;child bearing;Child Rearing;Childhood;Clinic;Clinical;clinical care;cohort;Cohort Studies;Computerized Medical Record;Conceptions;critical period;Data;Data Collection;design;Development;digital data;Disparity;Disparity population;Dose;early childhood;Enrollment;Ethnic Origin;Event;evidence base;Family;Fathers;fetal;Future;Future Generations;Germ Cells;Gestational Age;Goals;Health behavior;health disparity;health inequalities;Health Promotion;Health Psychology;Health Resources;healthy lifestyle;Heart;improved;Individual;infancy;innovation;intergenerational;Intervention;Interview;Life;Life Cycle Stages;life span;Logic;Maps;Maternal and Child Health;Measures;Methods;Modeling;Morbidity - disease rate;Morphogenesis;Mothers;Motivation;National Heart, Lung, and Blood Institute;novel;novel strategies;offspring;Organ;Outcome;outcome prediction;Outcomes Research;Parents;peer;person centered;Persons;Population;Population Heterogeneity;Positioning Attribute;Postpartum Period;preference;Pregnancy;Premature Birth;primary outcome;Process;Psychological Factors;psychosocial;Psychosocial Factor;Public Health;Qualitative Methods;Race;recruit;Resources;Role;Science;Shapes;social;social culture;social disparities;social factors;social health determinants;Strategic vision;Stress;stress management;Surveys;Technology;Testing;theories;therapy development;Time;unintended pregnancy;Work

PROJECT_TITLE: Interpregnancy as a Critical Period for Maternal-Child Cardiovascular Health in Pediatric Clinics: Ancillary to Young Hearts

STUDY_SECTION: RPPH

STUDY_SECTION_NAME: Reproductive, Perinatal and Pediatric Health Study Section[RPPH]


ADMINISTERING_IC: DA

ED_INST_TYPE: SCHOOLS OF PHARMACY

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Cocaine;Drug Abuse (NIDA only);Neurosciences;Stimulant Use and Misuse;Substance Misuse

ORG_CITY: Chicago

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

PHR: NARRATIVE The proposed research is relevant to public health because it seeks to develop α3β4-selective nicotinic acetylcholine receptor (nAChRs) negative allosteric modulators as novel pharmacotherapies for cocaine use disorder. Because the α3β4 nAChRs have been implicated in the addictive properties of nearly all drugs of abuse, these antagonists have the potential to have a significant and far-reaching impact on the treatment of drug addictions. Thus, this research is relevant to the National Institute on Drug Abuse’s strategic goal to “develop new and improved treatments to help people with substance use disorders achieve and maintain a meaningful and sustained recovery.”

PI_NAMEs: RILEY, ANDREW  (contact)

PROGRAM_OFFICER_NAME: ANANTHAN, SUBRAMANIAM

PROJECT_TERMS: Accounting;Address;Affinity;Alcohols;Alkaloids;Allosteric Site;American;analog;Animal Model;antagonist;Attenuated;Behavior;behavioral pharmacology;Binding;Binding Sites;Biological Assay;blood-brain barrier crossing;Cause of Death;Cells;clinical development;Cocaine;Cocaine Dependence;cocaine relapse;cocaine seeking;cocaine self-administration;cocaine use;Cocaine use disorder;Collection;Complement;Data;design;Drug Addiction;Drug Kinetics;drug of abuse;drug seeking behavior;Economics;Electrophysiology (science);Emergency department visit;Evaluation;FDA approved;Goals;Healthcare Systems;improved;In Vitro;in vitro Assay;in vivo;innovation;Lead;Ligands;Locomotion;Medical;Metabolic;Methamphetamine;Methamphetamine use disorder;Modeling;Modification;multiple drug use;National Institute of Drug Abuse;Natural Products;Nature;Nicotine;Nicotinic Receptors;novel;novel therapeutics;Opioid;opioid epidemic;overdose death;Persons;Pharmaceutical Chemistry;Pharmaceutical Preparations;pharmacologic;Pharmacology;Pharmacotherapy;Physiological;Play;Pre-Clinical Model;preclinical safety;Prevalence;Property;Public Health;rational design;Rattus;Receptor Activation;Receptor Inhibition;Relapse;release of sequestered calcium ion into cytoplasm;Research;Research Project Grants;Role;safety assessment;safety study;scaffold;Self Administration;Series;Site;Site-Directed Mutagenesis;Solubility;statistics;Stimulant;stimulant use disorder;stimulant user;Structure-Activity Relationship;Substance Use Disorder;Sucrose;sustained recovery;Test Result;Testing;Therapeutic;therapeutically effective;Translating;Work

PROJECT_TITLE: Selective Targeting of Nicotinic Acetylcholine Receptor Subtypes for Cocaine Use Disorder

STUDY_SECTION: DMPB

STUDY_SECTION_NAME: Drug Discovery and Molecular Pharmacology B Study Section[DMPB]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Digestive Diseases;Emerging Infectious Diseases;Infectious Diseases;Microbiome;Prevention

ORG_CITY: NEW YORK

ORG_DEPT: GENETICS

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

ORG_STATE: NY

PHR: PROJECT NARRATIVE The variation in gut microbiota strain composition between individuals is a major determinant of the functional impact of a gut microbiota on its host. However, we know little of how our gut microbiota strains are acquired, retained, or transmitted. Using a sensitive microbial strain tracking algorithm, metagenomics, and human fecal samples from fecal microbiota transplantation (FMT) recipients as well as fecal samples from families of various size, we will test hypotheses of how gut microbial strains are transmitted therapeutically in FMT and naturally in families to establish basic science principles of gut microbiome strain transmission.

PI_NAMEs: FAITH, JEREMIAH JAMES (contact)

PROGRAM_OFFICER_NAME: LUNSFORD, DWAYNE

PROJECT_TERMS: Acute;Address;Adult;Algorithms;Awareness;Bacteria;Basic Science;biobank;Biological;Biological Response Modifier Therapy;Birth;Body Surface;Child;Clostridium difficile;colonization resistance;Communicable Diseases;Complex;Computational algorithm;computer framework;Data;Development;Disease;disorder control;disorder prevention;disorder risk;dosage;Dose;Engraftment;Familiarity;Family;Family member;family structure;fecal microbiome;fecal transplantation;Feces;Fostering;Frequencies;Funding;Genes;Genome;Grant;gut microbes;gut microbiome;gut microbiota;Health;Health Status;host microbiota;Human;human disease;Immune;immunogenicity;improved;Individual;Infection;Intestines;Knowledge;Life;member;Metagenomics;Microbe;microbial;microbial community;microbial disease;microbial products;microbiome composition;microbiota;Monitor;multi-drug resistant pathogen;nonalcoholic steatohepatitis;Parents;pathogen;Pathogenesis;pathogenic microbe;Play;Recurrence;Resources;Role;Route;Sampling;Scientist;Siblings;Skin;Societies;stool sample;Structure;Taxonomy;Testing;Therapeutic;Therapeutic Trials;Time;tool;translational study;transmission process;Transplant Recipients;trial design;Ulcerative Colitis;Variant

PROJECT_TITLE: Uncovering the rules of gut microbiome strain transmission

STUDY_SECTION: DHMI

STUDY_SECTION_NAME: Digestive System Host Defense, Microbial Interactions and Immune and Inflammatory Disease Study Section[DHMI]


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

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: Project Narrative Cilia dysfunction causes a wide range of human disorders with polycystic kidney disease (PKD) being a common manifestation. One of the central questions in PKD research is how the selective cilia import (i.e. cilia gating) of PKD proteins, particularly polycystins mutated in Autosomal Dominant PKD (ADPKD), is regulated in kidney cells. This proposal aims to combine the simple and efficient C. elegans model with disease-relevant renal cell models to uncover the novel role of Autosomal Recessive PKD (ARPKD) protein DZIP1L in establishing a functional cilia gate to promote cilia import of polycystins, reveal how dysfunctional cilia gating leads to renal disorders, and further shed light on the molecular link between the pathogenesis of ARPKD and ADPKD.

PI_NAMEs: HU, JINGHUA  (contact)

PROGRAM_OFFICER_NAME: MARIC-BILKAN, CHRISTINE

PROJECT_TERMS: Abbreviations;Acids;Ankyrin Repeat;Architecture;Area;Autosomal Dominant Polycystic Kidney;Autosomal Recessive Polycystic Kidney;base;Binding;Biology;Caenorhabditis elegans;Cell model;Cells;Characteristics;Cilia;ciliopathy;cilium biogenesis;Cilium Microtubule;Clinic;Complex;Cytoplasm;Defect;Development;Devices;Disease;Dissection;dosage;Dyes;Embryo;Embryonic Development;Environment;Etiology;Eukaryotic Cell;Event;Fiber;Functional disorder;Funding;Genetic Models;Goals;Heat shock proteins;Heat-Shock Proteins 90;Human;human disease;Impairment;Individual;inorganic phosphate;insight;interdisciplinary approach;Kidney;kidney cell;Kidney Diseases;Knock-out;Knowledge;Laboratories;Lead;Link;Maintenance;Meckel-Gruber syndrome;Mediating;Membrane;Membrane Proteins;Missense Mutation;Modeling;Molecular;Mus;Mutate;Nephronophthisis;novel;Organelles;Orthologous Gene;Pathogenesis;Pathway interactions;Phenotype;Phosphatidylinositols;Phosphoinositide Pathway;Phosphotransferases;Physiological;Physiology;PKD2 gene;PKD2 protein;Play;polycystic kidney disease 1 protein;Polycystic Kidney Diseases;Proteins;recruit;Regulation;Regulatory Pathway;renal epithelium;Research;Resources;Role;Sensory;SERPINA4 gene;Severities;Signal Transduction;Structure;Study models;Surface;Syndrome;System;Therapeutic;trafficking;Variant

PROJECT_TITLE: Molecular dissection of the ciliary gate

STUDY_SECTION: PBKD

STUDY_SECTION_NAME: Pathobiology of Kidney Disease Study Section[PBKD]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Genetics;Infectious Diseases;Lyme Disease;Tickborne Diseases;Vector-Borne Diseases

ORG_CITY: MISSOULA

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF MONTANA

ORG_STATE: MT

PHR: PROJECT NARRATIVE Lyme disease is the most common vector-borne infection in the United States, with nearly 500,000 cases per year. The bacterium Borrelia (Borreliella) burgdorferi causes Lyme disease when it is transmitted to humans by a tick vector. Bacteria, including B. burgdorferi, can themselves be infected by bacteriophages (phages), a type of virus. This application proposes to fill a knowledge gap regarding the fundamental understanding of B. burgdorferi phage biology, including the molecular basis of phage replication and the mechanisms by which phage facilitate movement of genes between bacteria, enhancing the persistence of B. burgdorferi in nature via reinfection of its hosts.

PI_NAMEs: SECOR, PATRICK R (contact)

PROGRAM_OFFICER_NAME: BOWDEN, NADINE

PROJECT_TERMS: absorption;Alleles;Antigens;Arthritis;Bacteria;Bacterial Genome;Bacteriophages;Biochemical;Biological;Biological Assay;Biology;Blood;Borrelia;Borrelia burgdorferi;Borrelia burgdorferi Group;Borrelia burgdorferi OspE protein;Coculture Techniques;Cytolysis;Data;debilitating symptom;diagnostic strategy;differential expression;experience;Experimental Models;experimental study;Family;Gene Proteins;Genes;Genetic;Genetic Materials;Genetic Transcription;Genetic Variation;Genome;Genomics;Geography;Goals;Horizontal Gene Transfer;Human;human disease;Immune;Immune Evasion;Immune response;improved;Individual;Infection;innovation;Kinetics;Knowledge;Life Cycle Stages;Link;Lyme Disease;Lyme Disease Vaccines;lyme pathogenesis;Lysogeny;Lytic;Lytic Phase;Maintenance;Measures;Mediating;Membrane Proteins;Microbial Genetics;Microbiology;Midgut;migration;Mission;Molecular;Monitor;mouse model;Movement;Mus;mutant;Myalgia;Nature;Neurologic;novel;Nutrient;Nutritional status;Order Spirochaetales;OspA protein;OspC protein;outer surface lipoprotein;packaging material;particle;Patients;Phase;Planets;plasmid DNA;Plasmids;Population;Positioning Attribute;Prevention strategy;Process;Prophages;Protein Isoforms;Recurrence;Regulation;Research;response;Role;Salivary Glands;Starvation;Stress;Testing;tick transmission;Tick-Borne Diseases;Ticks;Time;transcriptome sequencing;transcriptomics;transmission process;treatment strategy;United States;vaccine formulation;Variant;vector;vector tick;vector-borne infection;Virion;Virus;Work

PROJECT_TITLE: Phage-mediated horizontal gene transfer in Borrelia burgdorferi

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 IMII-U (01)]


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Congenital Heart Disease;Congenital Structural Anomalies;Heart Disease;Infant Mortality;Lung;Neonatal Respiratory Distress;Patient Safety;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn;Prevention;Rare Diseases

ORG_CITY: RESEARCH TRIANGLE PARK

ORG_NAME: RESEARCH TRIANGLE INSTITUTE

PHR: Project Narrative The most common cardiovascular problem observed in extremely preterm infants is patent ductus arteriosus, an extra blood vessel found in babies before or just after birth that often requires surgery. Following surgery, almost 50% of preterm infants can develop Post-ligation Cardiac Syndrome (PLCS), a condition that requires additional care and for which there are no known treatments. The proposed Milrinone for Prevention of Post- ligation Cardiac Syndrome (MIDAS) trial will aid in establishing whether milrinone (a common cardiac medication) reduces the risk of PLCS in extremely preterm infants.

PI_NAMEs: DAS, ABHIK  (contact)

PROGRAM_OFFICER_NAME: SCHWARTZ, BRYANNA NICOLE

PROJECT_TERMS: Biometry;Birth;Blood Vessels;Cardiac;Cardiac Catheterization Procedures;Cardiopulmonary;Cardiovascular Agents;Cardiovascular system;Caring;Clinical;clinical practice;Clinical Trials;Collaborations;Communication;Companions;Complex;Complication;Critical Illness;Data;Data Coordinating Center;data dissemination;Decision Making;design;Development;efficacy evaluation;electronic data capture system;Ensure;evidence base;experience;Exposure to;extreme prematurity;flexibility;follow-up;Funding;Gestational Age;Goals;Hospitals;Human Resources;improved;Incidence;Infant;Infrastructure;Institution;International;Knowledge;Leadership;Letters;Libraries;Ligation;Liquid substance;Masks;Medical;meetings;Milrinone;Monitor;Morbidity - disease rate;mortality;Multi-Institutional Clinical Trial;Multicenter Neonatal Research Network;National Heart, Lung, and Blood Institute;National Institute of Child Health and Human Development;Neonatal;neonatal outcome;neonate;Network Infrastructure;Newborn Infant;operation;Operative Surgical Procedures;organizational structure;Outcome;Patent Ductus Arteriosus;patient safety;Pharmaceutical Preparations;Population;Postoperative Period;premature;Premature Infant;preterm newborn;prevent;Prevention;Prevention approach;Procedures;Process;Productivity;programs;prophylactic;Qualifying;Randomized;Randomized Controlled Clinical Trials;randomized placebo controlled trial;randomized trial;randomized, clinical trials;Registries;Reporting;Reproducibility;Research;Research Design;Resources;Risk Reduction;Running;Safety;Specific qualifier value;Statistical Data Interpretation;Structure;success;Syndrome;System;Time;Training;trial planning;web portal

PROJECT_TITLE: 2/2 Milrinone for Prevention of Post-Patent Ductus Arteriosus Closure Syndrome in Extremely Preterm Infants (MIDAS Trial) - DCC Resubmission

STUDY_SECTION: CLTR

STUDY_SECTION_NAME: Clinical Trials Review Study Section[CLTR (OA)]


NIH_SPENDING_CATS: Biotechnology;Cystic Fibrosis;Gene Therapy;Genetics;Lung;Orphan Drug;Rare Diseases

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: Narrative: CF is an autosomal recessive disorder causing significant health problems. There are over 1000 mutations. The ultimate goal is to develop a gene therapy for CFTR based on adenoassociated viral vectors, which would ultimately help the majority of CF patients and restore the functional defect in affected organs.

PI_NAMEs: CEBOTARU, LIUDMILA  (contact)

PROJECT_TERMS: Address;adeno-associated viral vector;Affect;Animal Model;autosome;Basal Cell;beta Actin;Blood Circulation;Capsid;cell type;Cells;Characteristics;Chickens;Clinical;Clinical Trials;Cystic Fibrosis;cystic fibrosis patients;Cystic Fibrosis Transmembrane Conductance Regulator;Defect;Delta F508 mutation;design;Development;Directed Molecular Evolution;Disease;disease phenotype;Dose;effective therapy;Ferrets;functional restoration;Gene Expression;gene therapy;Gene therapy trial;Genes;Goals;Health;Human;Individual;Lung;Lung Diseases;Macaca mulatta;Measures;Modeling;Monkeys;Morbidity - disease rate;mortality;mutant;Mutation;Nature;nonhuman primate;novel;novel strategies;Organ;Pathology;Patients;Pharmacology and Toxicology;Phase I Clinical Trials;Phenotype;preclinical trial;Process;promoter;Proteins;Recombinant adeno-associated virus (rAAV);Reproducibility;Research Personnel;Safety;Serotyping;Surface;Therapeutic Agents;Therapeutic Effect;therapeutic gene;Time;Tissues;Trachea;Transduction Gene;transgene expression;Tropism;vector;Viral;Viral Vector;Virus;Work

PROJECT_TITLE: Cystic Fibrosis Gene Therapy with adeno-associated viral vectors

STUDY_SECTION: DBTD

STUDY_SECTION_NAME: Drug and Biologic Therapeutic Delivery Study Section[DBTD]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Aging;Eye Disease and Disorders of Vision;Infectious Diseases;Macular Degeneration;Neurodegenerative;Neurosciences;Pediatric

ORG_CITY: AUGUSTA

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: AUGUSTA UNIVERSITY

ORG_STATE: GA

PHR: Project Narrative Human cytomegalovirus (HCMV) infection could be a risk factor for progression of AMD as a result of viral latency in the choroid/RPE, since there is a significantly higher association of anti-HCMV IgG titers with neovascular AMD and HCMV DNA was present in choroid/RPE samples from human cadavers. Our goal is to investigate the mechanism by which latent cytomegalovirus infection in the choroid/RPE contributes to the pathogenesis of AMD, thereby potentially opening new avenues for treatment. The proposed research is relevant to public health and NIH’s mission because increasing our understanding of the pathogenesis of AMD has the potential to yield new, more efficacious and less invasive treatment options.

PI_NAMEs: ZHANG, MING  (contact)

PROGRAM_OFFICER_NAME: GORDIYENKO, NATALIYA

PROJECT_TERMS: 1 year old;Age related macular degeneration;aged;angiogenesis;Angiogenic Factor;Apical;Blindness;Blood Vessels;Bone Marrow;Cadaver;Cell secretion;Cells;Choroid;Cytomegalovirus;Cytomegalovirus Infections;Deposition;Developed Countries;Development;DNA;Etiology;Exudative age-related macular degeneration;Eye;Genes;Genetic;Genetic Transcription;Goals;Human;human old age (65+);human tissue;Immune system;Immunoglobulin G;in vivo;Inbred BALB C Mice;Individual;Infant;Inflammation;Inflammatory;innovation;Laboratories;Lesion;Life;Light;light intensity;Lighting;Location;Macrophage;Microglia;Mission;Mitochondria;mouse model;Murid herpesvirus 1;Mus;Neonatal;neonatal infection;neovascular;Nonexudative age-related macular degeneration;novel;Older Population;Organ;Outcome;Oxidative Stress;Oxidative Stress Induction;Pathogenesis;Pathologic;Pathology;Photoreceptors;Production;Public Health;Publishing;repaired;Research;Retina;Risk Factors;Role;Sampling;Site;SOD2 gene;synergism;Tamoxifen;Testing;United States National Institutes of Health;Viral;Viral Eye Infections;Virus;Virus Diseases;Virus Latency;visual dysfunction

PROJECT_TITLE: Ocular MCMV latency and AMD-like pathology

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


NIH_SPENDING_CATS: Biomedical Imaging;Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Heart Disease;Machine Learning and Artificial Intelligence

PHR: PROJECT NARRATIVE Heart failure with preserved ejection fraction (HFpEF) affects 2.5 million Americans, is rising in prevalence, and is associated with substantial morbidity and mortality. Myocardial interstitial fibrosis contributes to HFpEF, but few tools are available to diagnose or treat it. This proposal will investigate blood markers for diagnosis of myocardial fibrosis, and whether an approved heart failure drug, sacubitril/valsartan, reduces myocardial fibrosis.

PI_NAMEs: CUNNINGHAM, JONATHAN WOO (contact)

PROGRAM_OFFICER_NAME: WOO, SEUNG KYOON

PROJECT_TERMS: Address;Affect;American;Angiotensins;antifibrotic treatment;Attenuated;biobank;Biological Assay;biomarker validation;Biometry;Blood;Boston;cardiac magnetic resonance imaging;cardiovascular disorder epidemiology;career;career development;Cessation of life;circulating biomarkers;Clinical;Clinical Trials;Collagen;Collagen Fiber;Communities;coronary fibrosis;crosslink;Data;deep learning model;Deposition;design;Development;Diabetes Mellitus;Diagnosis;Diagnostic tests;effective therapy;EFRAC;Enzymes;Epidemiology;epidemiology study;extracellular;Extracellular Matrix;Fibroblasts;Fibrosis;follow-up;Foundations;Functional disorder;Funding;Future;genetic regulatory protein;Goals;Heart failure;heart imaging;high dimensionality;hospitalization rates;Hospitals;Hypertension;Immunoassay;Individual;inhibitor;innovative technologies;interstitial;Lead;Learning;Left;Machine Learning;machine learning model;Magnetic Resonance Imaging;Measurement;Measures;Mentored Patient-Oriented Research Career Development Award;Mentors;Methodology;Methods;Morbidity - disease rate;mortality;Multi-Ethnic Study of Atherosclerosis;Mus;Myocardial;Natriuretic Peptides;Neprilysin;Outcome;Participant;Patients;Pharmaceutical Preparations;Physicians;Physiological;Physiology;Pilot Projects;Plasma;precision medicine;preservation;Prevalence;prevent;primary outcome;Process;Program Development;Proteins;Proteomics;randomized trial;randomized, clinical trials;Reproducibility;Research;Research Personnel;Running;Sample Size;Scientist;skills;Specific qualifier value;Statistical Data Interpretation;statistics;systemic inflammatory response;targeted treatment;Techniques;Time;Tissue Inhibitor of Metalloproteinase-1;tool;Training;treatment effect;treatment response;valsartan;Ventricular;Woman

PROJECT_TITLE: Effect of Neprilysin Inhibition on Myocardial Interstitial Fibrosis

STUDY_SECTION: MPOR

STUDY_SECTION_NAME: NHLBI Mentored Patient-Oriented Research Study Section[MPOR (OA)]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Mental Health;Neurosciences

ORG_NAME: BOSTON UNIVERSITY MEDICAL CAMPUS

PHR: NARRATIVE The ability to regulate when and how emotions are used to guide cognition relies on the anterior cingulate cortex (ACC), a key area that provides a unique cortical integrative node for otherwise segregated cognitive, motor and limbic networks. Our previous R01 (MH116008) showed how ACC exhibited specialized inhibitory and neuromodulatory features, and diversity in its extrinsic outputs to cognitive/motor and limbic areas. Using anatomical tract-tracing, optogenetics, slice physiology, high-resolution microscopy and computational modeling in rhesus monkeys, this renewal aims to assess cellular and circuit properties of short-range intrinsic interconnections across functionally distinct rostral ‘cognitive’, ventral ‘limbic’ and dorsal ‘motor’ ACC subdivisions, which are important neural substrates for multimodal integration and are differentially affected in affective disorders.

PI_NAMEs: MEDALLA, MARIA  (contact)

PROGRAM_OFFICER_NAME: ROSSI, ANDREW F

PROJECT_TITLE: Circuit structure and dynamics in prefrontal-limbic networks

STUDY_SECTION: LMDN

STUDY_SECTION_NAME: Learning, Memory and Decision Neuroscience Study Section[LMDN]


NIH_SPENDING_CATS: Autoimmune Disease;Crohn's Disease;Digestive Diseases;Infectious Diseases;Inflammatory Bowel Disease;Wound Healing and Care

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: CLEVELAND CLINIC LERNER COM-CWRU

PHR: PROJECT NARRATIVE The cause of Crohn’s disease (CD), where inflammation attacks the intestines and other body sites, is still unknown, and treatment regimens remain inadequate for many patients with severe disease. We recently discovered Debaryomyces hansenii, a fungus present in many processed foods, in human intestinal wounds and found that it inhibits the repair of damaged tissue in murine models. We propose to determine how this fungus drives the progression of CD to gain new insights into CD and to identify new avenues for therapy.

PI_NAMEs: HOGAN, DEBORAH A;STAPPENBECK, THADDEUS S (contact)

PROGRAM_OFFICER_NAME: LOVE, DONA

PROJECT_TERMS: Animal Model;anti-fungal agents;Antifungal Therapy;Area;Bacteria;Bile Acids;cell type;Cells;chemokine;chronic infection;Clinical;clinically relevant;Colon;Critical Pathways;Crohn's disease;cytokine;Data;Deoxycholic Acid;Detection;Diet;Disease;Double-Stranded RNA;Elements;enteric infection;Environmental Risk Factor;Epithelium;experimental study;Failure;Food;food consumption;Food Industry;Functional disorder;fungus;gene product;Genome;Germination;Gnotobiotic;Goals;Growth;healing;host-microbe interactions;Human;Immune;Immune response;Immunologics;Impairment;improved;In Vitro;in vivo;Infection;Inflammation;Inflammatory;Inflammatory Bowel Diseases;Ingestion;injured;Injury;injury and repair;Innate Immune Response;insight;Interferon Type I;Interferons;Intestinal Mucosa;Intestines;Knowledge;Link;Macrophage;Macrophage Activation;Mediating;Medical center;Methods;Microbe;microbial;Morphology;mouse model;Mucositis;Mucous Membrane;Mus;mutant;mycobiome;novel;novel diagnostics;novel therapeutics;Opsin;Organism;overexpression;Partner in relationship;pathogen;Pathogenesis;Pathology;Pathway interactions;Patients;Phagocytosis;Pre-Clinical Model;prevent;Process;Production;Publishing;RANTES;Reactive Oxygen Species;Regimen;repaired;Reproduction spores;Resistance;Resolution;response;Role;Saccharomycetales;Shapes;Site;Smoking;Testing;Therapeutic;Therapeutic Intervention;Tissues;TLR3 gene;TNF gene;tool;Treatment Protocols;uptake;Viral;Virus;Work;wound;wound bed;wound healing;Yeasts

PROJECT_TITLE: Innate immune responses to tissue infection by intestinal fungi inhibit wound repair

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 KUDS-W (03)]


NIH_SPENDING_CATS: Cardiovascular;Diabetes;Heart Disease

ORG_NAME: CITY COLLEGE OF NEW YORK

PHR: PROJECT NARRATIVE Despite its clinical importance, the underlying basis of diabetic cardiomyopathy remains unclear. We have discovered a new mechanistic pathway that controls cardiac metabolic stress under diabetic conditions. This project will delineate critical molecular aspects of the pathway and its role in the pathogenesis of diabetic heart disease.

PI_NAMEs: YOSHIOKA, JUN  (contact)

PROGRAM_OFFICER_NAME: POIZAT, CORALIE ISABELLE

PROJECT_TERMS: Adaptor Signaling Protein;Address;Adult;Anabolism;Animal Model;Animals;Apoptosis;Arrestins;Binding;Carbohydrates;Cardiac;Cardiac Myocytes;Cardiomyopathies;cardioprotection;Cardiovascular system;Cell Death;Cell membrane;Cells;Cellular Stress;Cessation of life;Clinical;Clinical Research;Complication;Data;db/db mouse;Defense Mechanisms;deprivation;Development;Diabetes Mellitus;diabetic;diabetic cardiomyopathy;Diabetic mouse;Endocytosis;Endoplasmic Reticulum;endoplasmic reticulum stress;Energy Metabolism;Event;exercise capacity;exercise intolerance;Exercise Tolerance;Exhibits;Family;Future;Genes;Genetic Transcription;Glucose;glucose uptake;glycemic control;Heart;heart damage;Heart Diseases;heart function;Hexosamines;High Fat Diet;Hyperglycemia;improved;in vivo;Individual;innovation;Insulin;Insulin deficiency;Insulin-Dependent Diabetes Mellitus;Knock-out;Knockout Mice;Knowledge;knowledge of results;Left;Link;Mediating;member;metabolic phenotype;Metabolic stress;Metabolism;Modeling;Modification;Molecular;mortality;mouse model;Mus;Muscle;Myocardial;Myocardial dysfunction;Nature;Non-Insulin-Dependent Diabetes Mellitus;Nutrient;Organelles;overexpression;Pathogenesis;Pathway interactions;Peripheral;Postabsorptive Hypoglycemia;Prognosis;promoter;protein folding;Protein Glycosylation;Proteins;Proteomics;proteotoxicity;receptor;response;Response Elements;Role;Scaffolding Protein;Secondary to;Signal Transduction;Skeletal Muscle;SLC2A1 gene;Starvation;Stress;Syndrome;targeted treatment;Testing;Tissues;trafficking;transcription factor;Type 2 diabetic;Ubiquitination;Ventricular

PROJECT_TITLE: Hyperglycemia-induced regulatory mechanism of ER stress by arresting domain-containing protein 4 in diabetic cardiomyopathy

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


ADMINISTERING_IC: HD

ED_INST_TYPE: SCHOOLS OF NURSING

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

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Pediatric;Social Determinants of Health

PHR: Project Narrative Studies have found that fewer than half (48%) of children from low-income families are ready for elementary school compared to the 75% of children from moderate or high-income households. School readiness prior to entering elementary school is a critical target for intervention due to robust evidence that it may act as a protective factor for low- income students who start elementary school at a disadvantage due to lack of resources, family stress, and fewer opportunities. The proposed study has the potential to improve outcomes for these children by identifying modifiable teacher behaviors, and promoting children’s potential for learning, adaptation, and academic success.

PI_NAMEs: PROPPER, CATHI BARBRA (contact)

PROGRAM_OFFICER_NAME: MILLER, BRETT

PROJECT_TERMS: Academic skills;Address;Affect;Behavior;Behavioral;Cardiac;Characteristics;Child;Code;cognitive testing;Data;Data Collection;Disadvantaged;Education;educational atmosphere;Educational Intervention;elementary school;Emotional;Enrollment;experience;falls;Family;Funding;Goals;Head Start Program;Home;Household;improved;improved outcome;Income;Individual Differences;Instruction;Intervention;kindergarten;Knowledge;Language Development;Learning;Literature;Longitudinal Studies;Low income;lower income families;Measures;Monitor;Nervous System Physiology;Nursery Schools;Outcome;Parasympathetic Nervous System;Parents;Play;Poverty;Prevention;programs;protective factors;Psychophysiology;Readiness;recruit;Regulation;Reporting;Research Personnel;Resources;respiratory;Role;Sampling;School Teachers;Schools;Sinus Arrhythmia;skills;social;Stress;Students;success;teacher;Time;Variant;Visit;Withdrawal;Work

PROJECT_TITLE: Early Education, School Readiness, and Early School Success Among Children In Poverty: Exploring the Role of Parasympathetic Function in the Preschool Classroom

STUDY_SECTION: PDRP

STUDY_SECTION_NAME: Psychosocial Development, Risk and Prevention Study Section[PDRP]


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Chronic Liver Disease and Cirrhosis;Digestive Diseases;Genetics;Hepatitis;Liver Disease;Nutrition;Obesity;Substance Misuse

ORG_CITY: MANHASSET

ORG_NAME: FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH

PHR: NARRATIVE Alcohol-related liver disease and non-alcoholic fatty liver disease with inflammation, fat and fibrosis are risk factors for liver cancer and the two most common reasons for liver transplant in the United States. In this project, we aim to identify the molecular mechanisms that alter lipid metabolism and explore genetic variations that may lead to these conditions. This will provide a better understanding for targeted therapy aimed at liver diseases and metabolic syndromes in the future.

PI_NAMEs: MISHRA, LOPA  (contact)

PROGRAM_OFFICER_NAME: MURRAY, GARY

PROJECT_TERMS: 3-Dimensional;Acetaldehyde;Acetic Acids;Address;adduct;Affect;alcohol sensitivity;Alcoholic Liver Diseases;Alcohols;aldehyde dehydrogenases;Aldehydes;American;beta Spectrin;Binding;CASP3 gene;Caspase;Cell Line;Cell Proliferation;Cells;Characteristics;chronic liver disease;Clinical;Complex;Data;Development;Diet;Disease;DNA Repair;Embryo Deaths;endoplasmic reticulum stress;Enzymes;Ethanol Metabolism;Exposure to;Fatty acid glycerol esters;fatty liver disease;Fetal Alcohol Syndrome;Fetal Death;Fibrosis;Future;Gastrointestinal tract structure;Genes;Genetic Transcription;Genetic Variation;Genomic Instability;Glucose;Hepatocyte;Heterozygote;Human;Immune;Immune system;Impairment;improved;Inflammation;Intervention;intestinal homeostasis;knock-down;Knock-out;knockout gene;Knockout Mice;Length;lipid biosynthesis;lipid metabolism;Lipids;Liver;liver development;Liver diseases;liver injury;liver transplantation;MADH3 gene;Malignant neoplasm of liver;Mediating;Metabolic;Metabolic syndrome;Mitochondria;Modification;Molecular;mouse model;Mus;Mutant Strains Mice;non-alcoholic fatty liver disease;nonalcoholic steatohepatitis;novel;Obesity;Oncogenic;Outcome;Pathologic;Pathology;Pathway interactions;Patients;Persons;Phenotype;Play;Population;Predisposition;prevent;Primary carcinoma of the liver cells;Process;Proteins;Publishing;Reducing diet;Risk Factors;Role;Sampling;Signal Transduction;Single Nucleotide Polymorphism;Small Interfering RNA;Spectrin;SRE-1 binding protein;stem cell biomarkers;Stress;System;targeted treatment;telomere;Testing;Therapeutic;Therapeutic Intervention;Tissues;TNF gene;transcription factor;Transcriptional Activation;Transforming Growth Factor beta;tumorigenesis;United States;western diet

PROJECT_TITLE: Role of Beta Spectrin and Smad in Alcohol-Induced Liver and GI Cell Proliferation

STUDY_SECTION: HBPP

STUDY_SECTION_NAME: Hepatobiliary Pathophysiology Study Section[HBPP]


ADMINISTERING_IC: NS

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Aging;Bioengineering;Biomedical Imaging;Brain Disorders;Cerebrovascular;Clinical Research;Clinical Trials and Supportive Activities;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurosciences;Precision Medicine;Stroke

ORG_CITY: RIVERSIDE

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF CALIFORNIA RIVERSIDE

ORG_STATE: CA

PHR: PROJECT NARRATIVE The objective of this proposal is to develop a fully automatic algorithm to extract geometric features from brain vessels of stroke patients in real-time and the effects of ischemic stroke on vascular alterations. We will use these features to improve the prediction of major complications and long-term outcomes after stroke and acute reperfusion therapies.

PI_NAMEs: LAKSARI, KAVEH  (contact);TAHSILI FAHADAN, POUYA

PROGRAM_OFFICER_NAME: UTZ, URSULA

PROJECT_TERMS: Acute;Admission activity;Affect;Aftercare;algorithmic bias;Algorithms;Anatomy;Angiography;Area;Arizona;automated algorithm;Blood flow;Blood Vessels;Brain;Brain Edema;Brain hemorrhage;Brain imaging;Brain region;Bypass;Cause of Death;cerebrovascular;Cerebrovascular Circulation;Cerebrovascular Disorders;Cerebrovascular system;Cessation of life;Clinical;clinical biomarkers;Clinical Trials;cohort;Collateral Circulation;Complex;convolutional neural network;Data;data harmonization;Data Set;Databases;demographics;Development;Diagnosis;Diameter;disability;Distal;Elasticity;endovascular thrombectomy;Evaluation;Family;Functional disorder;functional outcomes;Future;Geometry;Goals;Hemorrhage;Hour;Image;imaging biomarker;improved;improved outcome;indexing;Infarction;Intravenous;Investigation;Ischemia;Ischemic Stroke;Knowledge;Lasso;Length;Longterm Follow-up;Machine Learning;machine learning algorithm;Magnetic Resonance Angiography;Malignant - descriptor;Measures;Medical;metropolitan;model generalizability;Modeling;Morphology;National Institute of Biomedical Imaging and Bioengineering;National Institute of Neurological Disorders and Stroke;neural network algorithm;Operative Surgical Procedures;Outcome;outcome prediction;Pathway interactions;Patient Selection;Patients;Pattern;Pennsylvania;Performance;Population;post stroke;predicting response;prediction algorithm;Prediction of Response to Therapy;predictive modeling;prospective;Prospective cohort;Provider;Race;radiological imaging;recruit;Recurrence;Regional Perfusion;Reperfusion Therapy;response;restoration;Risk;Role;Scanning;sex;Site;Specific qualifier value;Stroke;stroke outcome;stroke patient;stroke risk;stroke therapy;Surgical Decompression;System;Texas;thrombolysis;Time;Tissues;Training;treatment response;Validation;Variant;Vascular blood supply

PROJECT_TITLE: Dynamic cerebrovascular morphology changes in acute ischemic stroke

STUDY_SECTION: EITN

STUDY_SECTION_NAME: Emerging Imaging Technologies in Neuroscience Study Section[EITN]


NIH_SPENDING_CATS: Genetics;Neurosciences;Sleep Research

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Project Narrative Disorders of sleep regulation frequently occur in individuals with disorders of metabolism, but the relationship between the two is not understood. Our research focuses on a particular mechanism that links sleep regulation with metabolic regulation.

PI_NAMEs: RAIZEN, DAVID MENASSAH (contact);VAN DER LINDEN, ALEXANDER MARTINUS

PROGRAM_OFFICER_NAME: HE, JANET

PROJECT_TERMS: Adipocytes;Animals;Antioxidants;Automobile Driving;Caenorhabditis elegans;candidate identification;Cell Nucleus;Cells;comorbidity;Coupled;CREB1 gene;Data;Defect;Development;Enzymes;Epitopes;experimental study;Fatty acid glycerol esters;fatty acid metabolism;Fatty Acids;fly;follow-up;Funding;Future;Gene Expression;Genes;Genetic;glutamatergic signaling;Glutamates;Goals;histone deacetylase 2;Homeostasis;Immunoprecipitation;improved;Individual;Kynurenine;Link;Lipase;Literature;Measures;Mediating;Metabolic;Metabolic Diseases;Metabolism;metabolomics;Methods;Mitochondria;Mus;mutant;Mutate;neural;Neurons;Nuclear Export;Nuclear Localization Signal;overexpression;Oxidative Phosphorylation;Oxides;Phenotype;Poly(A)-Binding Proteins;Population;pressure;Proteins;Proteomics;Publishing;Reactive Oxygen Species;Regulation;Repression;Research;Resistance;Role;salt-inducible kinase;Signal Transduction;Sleep;Sleep Disorders;sleep regulation;Sleep Stages;Sleeplessness;Sorting;Supplementation;Testing;Time;Toxic effect;Transcript;Transcription Coactivator;transcriptomics;Transgenes;uptake

PROJECT_TITLE: Mechanism of Sleep Regulation by SIK3

STUDY_SECTION: BNRS

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


NIH_SPENDING_CATS: Biotechnology;Clinical Research;Genetics;Human Genome;Lung;Prevention;Pulmonary Fibrosis;Rare Diseases

ORG_CITY: BOSTON

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: 8. Project Narrative Idiopathic pulmonary fibrosis (IPF) is a disorder characterized by lung scarring and has a prognosis worse than that of most cancers. Identifying IPF at very early, but detectable, stages could lead to earlier treatment and improved outcomes for those at risk for this disease, and improving our understanding of early disease pathogenesis could lead to newer, more targeted, medical therapies. This proposal aims to improve our understanding of both early disease pathogenesis, and detection, by providing a comprehensive characterization of the proteins and genetic factors in those at risk to develop early stages of pulmonary fibrosis.

PI_NAMEs: CHO, MICHAEL H.;HUNNINGHAKE, GARY MATTHEW (contact)

PROGRAM_OFFICER_NAME: VUGA, LOUIS J

PROJECT_TERMS: Acceleration;Address;Adult;adverse outcome;Affect;Age;airway epithelium;antifibrotic treatment;Biological;Biological Assay;Biological Markers;Biological Process;Biology;biomarker identification;Blood Proteins;candidate identification;cell type;Cells;cigarette smoke;cohort;Confocal Microscopy;Data;Death Rate;Detection;Development;Disease;Disease Progression;disorder risk;drug development;Drug Targeting;Early Diagnosis;Early intervention trials;Early treatment;Environmental Risk Factor;Epithelial Cells;Exercise;exposure to cigarette smoke;fibrotic lung;First Independent Research Support and Transition Awards;Framingham Heart Study;functional decline;Future;GDF15 gene;gene discovery;Gene Expression Profile;Genetic;Genetic Risk;genetic risk factor;genetic signature;genetic variant;genome-wide;Genomics;Genotype;Goals;Grant;Guidelines;high risk;Histopathology;Hospitals;Human;human old age (65+);idiopathic pulmonary fibrosis;Image;Impairment;improved;improved outcome;in vitro Model;Individual;International;interstitial;Intervention;Intervention Trial;Link;Lung;Malignant Neoplasms;Measures;Medical;Membrane;Molecular;Morbidity - disease rate;mortality;mortality risk;MUC5B gene;Mucins;network models;novel;Participant;Pathogenesis;Pathway interactions;Patients;Pattern;peripheral blood;Persons;Physiology;Play;polygenic risk score;Prevalence;Prognosis;protein biomarkers;Protein Secretion;Proteins;proteomic signature;Proteomics;Publishing;Pulmonary Fibrosis;pulmonary function decline;Radiology Specialty;Reporting;Research;response;Risk;risk prediction;Role;Seminal;Serum Proteins;side effect;Signal Transduction;SNP genotyping;stem;Stimulus;Structure of parenchyma of lung;surfactant;transcriptomics;Treatment outcome;trial design;WFDC2 gene;Woman;Work

PROJECT_TITLE: Genetic and Genomic Characterization of the Occurrence and Progression of Interstitial Lung Abnormalities

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 EPH-C (02)]


NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Chronic Pain;Clinical Research;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Opioids;Pain Research;Palliative Care;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_NAME: DANA-FARBER CANCER INST

PHR: PROJECT NARRATIVE Pain is a common and disabling symptom of cancer, yet patients of color are half as likely as White patients to receive adequate pain management, likely because they are prescribed fewer and less potent opioids. This proposal will examine the scope and key drivers of racial and ethnic disparities in opioid management across the cancer care trajectory, using a multi-level analysis of Medicare and Medicaid claims data linked to comprehensive information about physicians, practices, systems, and neighborhoods. Findings will elucidate key mechanisms by which racism undermines equitable pain management, and will be used to design a scalable multi-level intervention to promote equitable cancer pain management.

PI_NAMEs: ENZINGER, ANDREA C (contact);WRIGHT, ALEXI A

PROGRAM_OFFICER_NAME: ETON, DAVID T

PROJECT_TERMS: active method;Address;advanced disease;advocacy organizations;Affect;Analgesics;anti-racism;Aphorisms;Asian;Attitude;beneficiary;black men;black patient;Black race;cancer care;cancer complication;cancer pain;Cancer Pain Management;Cancer Patient;Cancer Prognosis;candidate identification;care systems;Caregivers;Caring;Characteristics;Clinic;Clinical;Color;common symptom;Communities;Community Pharmacy;Conscious;Criminal Justice;Data;debilitating pain;deprivation;design;disabling symptom;Disadvantaged;Discrimination;Disparity;Distress;Dose;Drug Screening;drug testing;dual eligible;effectiveness/implementation study;end of life;Equity;ethnic disparity;Ethnic Origin;Ethnic Population;experience;falls;Family Caregiver;Feedback;Focus Groups;Future;Goals;health care quality;health inequalities;Health system;Healthcare;Hispanic;Housing;implementation strategy;Individual;Inequity;Institution;Insurance Carriers;insurance plan;Intervention;Interview;Lead;Link;Literature;Malignant Neoplasms;Mediating;Medicare;Medicare/Medicaid;Mental disorders;multilevel analysis;Neighborhoods;non-opioid analgesic;Not Hispanic or Latino;Opioid;opioid epidemic;opioid misuse;opioid use;Pain;Pain management;Palliative Care;patient engagement;Patients;Phase;Physicians;Police;policy implication;Policy Maker;Population;Population Study;Postoperative Period;Poverty;prescription opioid;prior authorization;Process;Professional Organizations;Quality of Care;Race;racial bias;racial difference;racial disparity;racial population;Racial Segregation;racism;Research;Resources;Risk;risk mitigation;Risk Reduction;Sampling;segregation;Severities;sex;Site;social;Source;Structural Racism;Survivors;survivorship;System;Testing;trial readiness;Unconscious State;urban area;Urine;Variant;Work

PROJECT_TITLE: A multi-level examination of the influences of racism on cancer pain equity

STUDY_SECTION: ODHS

STUDY_SECTION_NAME: Organization and Delivery of Health Services Study Section[ODHS]


NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Neurosciences

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: Infantile nystagmus syndrome, an involuntary oscillation of the eyes that develops in the first six months of life, is both visually and socially debilitating, but how and why it develops is poorly understood. This project aims to understand how and when development of the neural circuitry responsible for eye movements is altered in a mouse model of nystagmus. This work will both provide fundamental knowledge about neurodevelopment and identify new therapeutic targets for treatment or prevention of infantile nystagmus.

PI_NAMEs: WHITMAN, MARY CATHERINE (contact)

PROGRAM_OFFICER_NAME: ARAJ, HOUMAM H

PROJECT_TERMS: Affect;Age of Onset;Albinism;albino mouse;Area;Brain;Cell Nucleus;Child;Cholinergic Receptors;course development;Cues;Defect;density;Development;effective therapy;experimental study;Eye;Eye Movements;Functional disorder;Gene Expression Profiling;Genetic;Goals;Heterozygote;Human;Immunohistochemistry;infancy;Knowledge;Lesion;Life;Motor;motor control;Motor Neurons;mouse model;Mus;Muscle;Muscle Fibers;Mutation;Natural regeneration;Nerve;nerve supply;neural circuit;neurodevelopment;Neurologic;Neuromuscular Junction;neuronal survival;Neurons;new therapeutic target;oculomotor;Operative Surgical Procedures;optic nerve disorder;orbit muscle;Partner in relationship;Pathologic Nystagmus;Patients;Phase;Physiological;Prevention;preventive intervention;Property;Research;Retina;Role;Sampling;Secondary to;social;Social Interaction;Stroke;Synapses;Syndrome;System;Testing;therapeutic target;Trauma;tumor;Viral;Vision;Visual;Visual impairment;Work

PROJECT_TITLE: Development of Oculomotor Circuits in Nystagmus


NIH_SPENDING_CATS: Aging;Eye Disease and Disorders of Vision

PHR: PROJECT NARRATIVE As we get older, our lenses can become stiff and cloudy, which can lead to vision problems such as cataract and presbyopia (difficulty seeing things up close). This happens because of a buildup of damage caused by oxidation, which is a process that occurs naturally in the body. This study will look at the specific reasons why oxidation occurs and how it contributes to lens aging.

PI_NAMEs: FAN, XINGJUN  (contact)

PROJECT_TERMS: Address;Affect;age related;age related decline;Aging;aging related;Binding;Biological;Biology;Cataract;Cations;Cell Culture Techniques;Cell Death;Cell membrane;Cell Physiology;Cells;Cholesterol;cofactor;Colorado;Communities;Crystallins;Cytoskeleton;Data;Electron Microscopy;Embryo;Enzymes;Epithelial Cells;Foundations;Glutathione;glutathione peroxidase;Glycerophospholipids;Goals;Grant;Homeostasis;Human;Impairment;In Situ;In Vitro;in vivo;inducible Cre;insight;Integral Membrane Protein;interest;Investments;Ion Pumps;knock-down;Knock-in Mouse;Knock-out;Knockout Mice;lens;Lens development;Lens Fiber;lens induction;Link;Lipid Peroxidation;lipidomics;Lipids;liquid chromatography mass spectrometry;Mediating;Membrane;Membrane Biology;Membrane Lipids;Membrane Proteins;Membrane Structure and Function;Methods;Microphthalmos;MIP gene;Mitochondria;Modeling;mouse model;Mus;Outcome Study;oxidation;Pilot Projects;pilot test;Plasma;Play;Presbyopia;Process;Research;Risk Factors;Role;scaffold;Sphingomyelins;Structure;Suggestion;System;Tamoxifen;Testing;Universities;Vision;Wild Type Mouse

PROJECT_TITLE: Mechanisms and consequences of impaired glutathione homeostasis in the aging lens

STUDY_SECTION: BDE

STUDY_SECTION_NAME: Biology and Development of the Eye Study Section[BDE]


ED_INST_TYPE: OVERALL MEDICAL

NIH_SPENDING_CATS: Cancer;Cancer Genomics;Clinical Research;Genetics;Human Genome;Immunotherapy;Patient Safety;Prevention

ORG_CITY: HOUSTON

ORG_NAME: UNIVERSITY OF TX MD ANDERSON CAN CTR

PHR: PROJECT NARRATIVE  Identifying the risk for severe immune-related adverse events will have a major public health impact as risk assessment-based monitoring will facilitate early detection and prompt management of immune-related ad- verse events, minimizing the progression to life-threatening or fatal events. Thus, this approach will reduce treatment-induced symptom burden and mortality, while significantly improving treatment adherence and treat- ment outcome. This strategy aligns with NCI Cancer Moonshot Blue Ribbon Panel 2016 recommendations to systematically gather patient-reported outcomes and develop innovative patient-based approaches to facilitate adherence to effective therapies and improve patients’ quality of life.

PI_NAMEs: NAING, AUNG  (contact)

PROGRAM_OFFICER_NAME: FILIPSKI, KELLY

PROJECT_TERMS: Adherence;Adoption;adverse event monitoring;associated symptom;Benefits and Risks;beta Chain Antigen T Cell Receptor;Biological Markers;biomarker validation;Blood specimen;cancer care;Cancer Center;Cancer Patient;cancer therapy;Caring;Clinical;clinical practice;cohort;Collaborations;comorbidity;daily functioning;Data;Development;disability;Disease;Disease Progression;Early Diagnosis;Early treatment;effective therapy;Equipment and supply inventories;Event;experience;Frequencies;Genes;Genetic Polymorphism;Germ Lines;Haplotypes;Health Status;Hospitalization;Hospitals;immune activation;Immune checkpoint inhibitor;Immune system;immune-related adverse events;immunological intervention;Immunotherapy;improved;Incidence;innovation;Institution;interdisciplinary approach;Interruption;Intervention;Knowledge;Life;Link;Malignant Neoplasms;Measures;member;Modeling;Monitor;Morbidity - disease rate;mortality;National Cancer Institute;Nomograms;novel;Online Systems;Organ;Outcome;Outcome Measure;patient oriented;Patient Outcomes Assessments;Patient risk;Patients;peripheral blood;Physicians;Pilot Projects;Precision Health;predictive marker;predictive modeling;Prevention;Public Health;Quality of life;Recommendation;Reporting;Research Personnel;Risk;Risk Assessment;Risk Estimate;risk mitigation;risk prediction;risk prediction model;Risk Reduction;RNA;side effect;socioeconomics;surveillance strategy;Symptom Burden;Symptoms;T cell receptor repertoire sequencing;Testing;Therapeutic;tool;Translating;treatment adherence;Treatment Factor;Treatment outcome;Treatment Side Effects;tumor;tumor progression;United States National Institutes of Health;University of Texas M D Anderson Cancer Center;Visit;web app;web-based tool

PROJECT_TITLE: Integrating patient-reported outcomes and T-cell receptor sequencing to predict immune-related adverse events

STUDY_SECTION: ICSC

STUDY_SECTION_NAME: Interdisciplinary Clinical Care in Specialty Care Settings Study Section[ICSC]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Osteoporosis;Physical Injury - Accidents and Adverse Effects;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Women's Health Research

ORG_CITY: Columbus

ORG_DEPT: MISCELLANEOUS

ORG_NAME: OHIO STATE UNIVERSITY

PHR: Project Narrative Current clinical thresholds for bone mineral density (BMD) are controversial, as the conventional T-score method often classifies patients who suffer from fragility fractures as “normal”, particularly in minority women. This project aims to develop Person-specific Precision Thresholds (PPTs) for BMD in individual minority women by utilizing big data and advanced modeling techniques to account for the numerous individual-level differences. Developing next-generation PPTs can significantly improve disease diagnosis, prevention, and risk management, ultimately reducing healthcare disparities.

PI_NAMEs: WU, QING  (contact)

PROGRAM_OFFICER_NAME: JOSEPH, LYNDON

PROJECT_TERMS: Acceleration;Address;Affect;Age;Assessment tool;Big Data;Biological;bone;Bone Density;Calibration;Caucasians;Characteristics;Classification;Clinical;Clinical Data;clinical diagnosis;cohort;Communities;computerized tools;Data;design;Development;Diagnosis;Disease;disease diagnosis;disorder risk;Electronic Health Record;Environment;ethnic health disparity;ethnic minority;Ethnic Origin;feasibility testing;Fracture;fracture risk;fragility fracture;Future;Gender;Genes;Genetic;genetic variant;genomic data;Genomics;Goals;Health;health care disparity;health care quality;health equity;Healthcare;Heritability;improved;Individual;individual patient;innovation;Knowledge;Learning;learning strategy;Machine Learning;Measures;Methods;Minority;Minority Groups;Minority Women;Modeling;next generation;novel;Osteoporosis;osteoporosis with pathological fracture;Outcome;Outcomes Research;Patient-Focused Outcomes;Patients;Performance;Persons;Phenotype;Physiological;Pilot Projects;Population;Postmenopause;predictive modeling;Prevention;Public Health;Quality of life;Race;racial disparity;racial minority;Research;Research Personnel;Risk;Risk Assessment;Risk Management;Sampling;Scoring Method;sex;statistics;Techniques;Technology;Testing;Validation;Variant;White Women;Woman;Work

PROJECT_TITLE: Does Creating Person-specific Precision Thresholds Enhance the Ability of a Single Bone Density Measure to Predict Fractures in Minority Women?

STUDY_SECTION: CDMA

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


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

PHR: Dysferlinopathies are muscular dystrophies that affect thousands of Americans. They are caused by the absence of the protein dysferlin, and the subsequent failure of the muscle cell to maintain normal control of calcium signaling and to repair itself after injury. We have identified small proteins that can “fix” both of these faults. Here we proposed to optimize their activities, learn how they work, and test them in mice to learn if they provide effective therapies for these muscular dystrophies.

PI_NAMEs: BLOCH, ROBERT J (contact);WEISLEDER, NOAH

PROGRAM_OFFICER_NAME: CARIFI, EMILY FORAN

PROJECT_TERMS: Adverse effects;Affect;American;Amino Acids;Binding;Biological Assay;C-terminal;C2 Domain;Calcium Signaling;Cessation of life;Chimera organism;Clinical Treatment;Clinical Trials;Code;Collaborations;Compensation;complement C2a;Complex;Cytoplasm;Data;Defect;design;Disease;Dose;DYSF gene;dysferlinopathies;effective therapy;Engineering;Event;experimental study;Failure;Family member;Frequencies;Gene Proteins;gene repair;gene therapy;Genes;Genetic Recombination;Goals;Heterozygote;improved;In Vitro;in vitro Assay;in vivo;Individual;Injury;insight;Learning;Length;Limb-Girdle Muscular Dystrophies;Link;Measures;Mediating;Membrane;Missense Mutation;Miyoshi myopathy;Mus;Muscle;Muscle Cells;Muscular Dystrophies;mutant;Mutate;Mutation;Myopathy;N-terminal;Neuromuscular Diseases;Nonsense Codon;novel;null mutation;Open Reading Frames;Pathogenicity;Pathologic;Pathology;Patients;Phenotype;Phospholipids;Physiological;Play;Point Mutation;Preparation;PRKCA gene;Process;Property;Proteins;repaired;Reporting;RNA Splicing;Role;RyR1;Signal Transduction;skeletal;Skeletal Muscle;Specificity;Striated Muscles;Structure;Testing;Therapeutic;transduction efficiency;Variant;vector;Viral;Work

PROJECT_TITLE: C2 domain therapeutics for muscular dystrophy

STUDY_SECTION: SMEP

STUDY_SECTION_NAME: Skeletal Muscle and Exercise Physiology Study Section[SMEP]


NIH_SPENDING_CATS: Behavioral and Social Science;Chronic Pain;Clinical Research;Comparative Effectiveness Research;Pain Research;Patient Safety;Pediatric;Physical Rehabilitation;Prevention;Rehabilitation;Social Determinants of Health

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE (Public Health Relevance) In the proposed study, our aim to is develop study procedures for a randomized controlled trial to evaluate scoliosis-specific physiotherapy for adolescent idiopathic scoliosis. Over the course of the award, we will develop our protocol and manual of operating procedures, fulfill appropriate regulatory requirements, and develop and test our recruitment procedures. In so doing, we will be prepared to conduct a rigorous trial that will fundamentally add to the evidence base for non-operative management of adolescent idiopathic scoliosis, with the ultimate goal of preventing progression and the need for invasive surgery.

PI_NAMEs: SCHREIBER, SANJA ;SOMERS, EMILY CATHERINE (contact)

PROGRAM_OFFICER_NAME: WASHABAUGH, CHARLES H

PROJECT_TERMS: Acceleration;Address;Adolescent;Adult;Affect;Area;arm;Award;Caregivers;Caring;Case Report Form;Certification;Child;Child Welfare;Childhood;clinical trial protocol;Clinical Trials;common treatment;cost;Data;Deceleration;Deformity;design;Development;disability;Disproportionately impacts women;efficacy evaluation;electronic data;electronic data capture system;Etiology;Evaluation;evidence base;Exercise;Family;Female;functional improvement;Funding;Goals;Grant;Growth;Growth and Development function;Health;Health Insurance;Health Personnel;Hemorrhage;Hip region structure;human old age (65+);Idiopathic scoliosis;improved;improved outcome;Infection;Institutional Review Boards;Insurance Coverage;Intervention;intervention effect;Level of Evidence;life span;Longterm Follow-up;male;Manuals;Measurement;Mental Health;Modernization;Monitor;Morphology;Motor;motor control;motor learning;Musculoskeletal;National Institute of Arthritis, and Musculoskeletal, and Skin Diseases;Nature;neglect;Neurologic;Operative Surgical Procedures;Orthopedics;Orthotic Devices;Outcome;Pain;pain reduction;Participant;Patient observation;Patient Outcomes Assessments;Patients;Pattern;Physical therapy;Preparation;prevent;primary outcome;Procedures;Protocols documentation;Pseudarthrosis;psychosocial wellbeing;public health relevance;Publishing;Quality of life;Radiology Specialty;Randomized;Randomized, Controlled Trials;Recommendation;recruit;Repeat Surgery;Reporting;Research;Research Personnel;Respiratory physiology;rib bone structure;Risk;Risk Reduction;Roentgen Rays;Rotation;Safety;scoliosis;screening guidelines;secondary outcome;Self Perception;Shoulder;Site;Spinal;Spinal Diseases;Spinal Fusion;standard of care;Strategic Planning;Supervision;Surgeon;System;Testing;Therapeutic Intervention;Time;Traction;treatment arm;treatment guidelines;United States Preventative Services Task Force;Vertebral column;Well in self

PROJECT_TITLE: Planning grant for a randomized controlled trial of scoliosis-specific physiotherapy for adolescent idiopathic scoliosis

STUDY_SECTION: AMSC

STUDY_SECTION_NAME: Arthritis and Musculoskeletal and Skin Diseases Clinical Trials Study Section [AMSC]


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

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

ORG_CITY: DAVIS

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: Narrative Toxoplasma gondii is an obligate intracellular pathogen that can cause serious disease in immunocompromised individuals, such as AIDS patients, and fetuses, and is also a major cause of blindness in otherwise healthy individuals. In this proposal we will determine the mechanisms by which stimulated primary human cells inhibit Toxoplasma growth and how the parasite’s secreted effectors counteract these mechanisms. This will provide valuable insights into how human cells detect and destroy Toxoplasma and how Toxoplasma counteracts this, potentially leading to novel therapeutics and allowing prediction of the virulence of specific Toxoplasma strains in humans.

PI_NAMEs: SAEIJ, JEROEN  (contact)

PROGRAM_OFFICER_NAME: PESCE, JOHN T

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Affect;Antiparasitic Agents;Autophagocytosis;Binding;Binding Proteins;Biochemical;Biological Assay;Blindness;Cell Line;Cell secretion;cell type;Cells;Chemicals;Cholesterol;Compensation;Complement;CRISPR screen;CRISPR/Cas technology;cytokine;Data;Dendritic Cells;detection platform;Development;Disease;Enzyme Induction;Fetus;Fibroblasts;fitness;Fluorescence;Future;Genes;genome-wide;Goals;Growth;Guanosine Triphosphate Phosphohydrolases;guanylate;Health;Human;Immune system;immune system function;Immunity;Immunocompromised Host;immunosuppressed;Individual;Infant;infant infection;Infection;Innate Immune System;innovation;insight;Interferon Type II;Intervention;Knock-out;Knowledge;lipid metabolism;loss of function;Mediating;Membrane;Mixed Function Oxygenases;Mothers;Mus;Mutate;new therapeutic target;novel;novel therapeutics;obligate intracellular parasite;Outcome;Parasite resistance;Parasites;pathogen;Pathway interactions;Patients;Persons;Phospholipase;Play;Predisposition;prevent;Production;Proteins;Public Health;RARRES3 gene;Research;Resistance;response;Risk;Rodent;Role;Science;Susceptibility Gene;Testing;therapeutic development;Therapeutic Intervention;TNF gene;Toll-like receptor 11;Toxoplasma;Toxoplasma gondii;Toxoplasmosis;Up-Regulation;Vacuole;Virulence

PROJECT_TITLE: Restriction of Toxoplasma growth in human cells

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