ORG_CITY: IOWA CITY

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: Project Narrative MPNSTs lack effective therapies, highlighting a critical need to develop novel treatment strategies. I hypothesize that MEK-CDK4/6 inhibition causes MPNST regression and increased response to immune checkpoint blockade therapy through a plasma cell-dependent modulation of tumor infiltrating immune cells. These studies will define, for the first time in any tumor type, the biological significance of intratumoral plasma cells in therapy-induced antitumor immunity.

PI_NAMEs: LINGO, JOSHUA J (contact)

PROGRAM_OFFICER_NAME: ADAMS, GREGORY

PROJECT_TERMS: Acute;adaptive immunity;anti-tumor immune response;Antibodies;Antitumor Response;Automobile Driving;B-Lymphocytes;Biological;CD8-Positive T-Lymphocytes;CDK4 gene;CDKN2A gene;Cells;chemokine;Chemotactic Factors;Clustered Regularly Interspaced Short Palindromic Repeats;cytokine;Data;Dendritic Cells;Diagnosis;Drug resistance;effective therapy;Excision;experimental study;Flow Cytometry;Goals;Human;human disease;Immune;immune cell infiltrate;immune checkpoint blockade;Immune response;Immunity;Immunocompetent;Immunotherapy;Impairment;improved;Infiltration;interest;kinase inhibitor;Laboratory Finding;Leucocytic infiltrate;Location;Malignant Neoplasms;Measures;Mediating;MEK inhibition;MEKs;Modeling;mouse model;Mus;Natural Immunity;Nerve;Neurofibrosarcoma;NF1 gene;NF1 mutation;novel;Oncogenic;Operative Surgical Procedures;Patients;Pharmaceutical Preparations;Plasma Cells;programmed cell death ligand 1;Radiation therapy;RAS driven tumor;response;Role;Sarcoma;standard of care;T-Lymphocyte;targeted treatment;tertiary lymphoid organ;Testing;Time;transcriptome;transcriptome sequencing;Treatment Efficacy;treatment strategy;tumor;Tumor Immunity;Tumor-infiltrating immune cells;Up-Regulation;Wild Type Mouse

PROJECT_TITLE: Intratumoral plasma cells in MPNST response to CDK4/6 targeted therapy and sensitization to immune checkpoint blockade


ADMINISTERING_IC: AI

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

ORG_CITY: SAINT LOUIS

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PI_NAMEs: KRUPNICK, ALEXANDER S. (contact)

PROJECT_TERMS: Acute;allograft rejection;Allograft Tolerance;Animals;Antigen Presentation;Antigen-Presenting Cells;Antigens;Autologous;Bispecific Antibodies;CD8-Positive T-Lymphocytes;Cells;chemokine;Chronic;Clinical;Complement;Cross Presentation;cytokine;Data;Development;Down-Regulation;eosinophil;experience;Family;Feedback;Foundations;FOXP3 gene;Funding;Graft Rejection;Graft Survival;Graft Tolerance;Grant;Health;Hematopoietic;Human;Immune response;immunoregulation;Immunosuppression;improved;in vivo;Inflammation Mediators;Inflammatory;Interferon Type II;Interferons;Interleukin-1;Interleukin-1 beta;Lung;lung allograft;lung development;Lung Transplantation;Lymphoid Tissue;Maintenance;Mediating;member;Methods;migration;mouse model;Nitric Oxide;NOS2A gene;novel;Organ;Organ Transplantation;Pathway interactions;PD-1/PD-L1;Play;Population;Post-Translational Protein Processing;prevent;Production;programmed cell death ligand 1;Protocols documentation;receptor;Regulatory T-Lymphocyte;response;Role;Shapes;Signal Transduction;Solid;Specificity;Surface;synaptogenesis;T cell differentiation;T-Cell Receptor;T-Lymphocyte;Testing;TNF gene;translational potential;Transplantation Tolerance;Work

PROJECT_TITLE: Inflammatory Cellular Mechanisms for Establishing and Maintaining Lung Allograft Tolerance


NIH_SPENDING_CATS: Immunotherapy;Infectious Diseases;Lung;Organ Transplantation;Prevention;Rare Diseases;Transplantation

PI_NAMEs: GELMAN, ANDREW ERIC (contact)

PROJECT_TERMS: Ablation;adaptive immune response;Adoptive Transfer;airway epithelium;airway repair;Allograft Tolerance;Allografting;Alveolar Macrophages;Autoantigens;Autoimmune Diseases;autoreactivity;Bone Marrow Transplantation;Bronchiolitis;Bronchiolitis Obliterans;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Proliferation;cell regeneration;Cell Survival;Cells;Chromatin;Chronic;Clinical;Communication;Coupled;CSF3 gene;cytotoxic CD8 T cells;Data;Dendritic Cells;Development;Disease;donor-specific antibody;effector T cell;epithelial injury;epithelial stem cell;Exposure to;extracellular;Foundations;Functional disorder;functional loss;Gastroesophageal reflux disease;Gene Targeting;Generations;Genes;Graft Rejection;Granulocyte-Macrophage Colony-Stimulating Factor;Immune;Immunologics;Impairment;improved;Infection;Infiltration;Inflammatory;Injury;Innate Immune Response;innovation;Interferon Type I;ITGAX gene;Joints;Laboratories;Left;Lesion;Life;Lung;lung allograft;Lung Diseases;Lung Transplantation;Macrophage;Maintenance;Mediating;Mediator;Methods;MHC Class I Genes;Modeling;monocyte;Mus;Natural Killer Cells;neutrophil;novel;novel strategies;novel therapeutic intervention;Operative Surgical Procedures;Organ;Organ Transplantation;Outcome Study;pathogen;Pathogenesis;Pathologic;Pathway interactions;Patients;Play;prevent;Prevention;Process;progenitor;Regimen;Regulation;Reperfusion Injury;Reporting;response;retransplantation;Rheumatoid Arthritis;Risk;Risk Factors;Role;Shapes;Solid;Stress;Syndrome;synergism;T cell response;T-Lymphocyte Subsets;Techniques;Toxic Environmental Substances;trafficking;Transforming Growth Factor beta;transplant model;Transplant Recipients;Transplantation Tolerance

PROJECT_TITLE: Mechanisms that Promote Chronic Lung Transplant Rejection


ADMINISTERING_IC: HD

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

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

NIH_SPENDING_CATS: Brain Disorders;Cerebral Palsy;Neurosciences;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Physical Rehabilitation;Rehabilitation

ORG_CITY: BLACKSBURG

ORG_NAME: VIRGINIA POLYTECHNIC INST AND ST UNIV

ORG_STATE: VA

PI_NAMEs: DARRAGH, AMY R (contact)

PROJECT_TERMS: Academy;Agreement;American;Area;Award;Cerebral Palsy;Childhood;Clinical;Collaborations;Common Data Element;Communities;community setting;Data;Data Analyses;Development;efficacious treatment;Ensure;Feedback;Foundations;Funding;Funding Agency;Goals;Grant;Guidelines;implementation science;improved;Incentives;Individual;innovation;Interdisciplinary Study;Investments;Leadership;Letters;Medicine;member;Mentors;method development;Methods;Mission;Monitor;multidisciplinary;Outcome Study;Pathway interactions;peer;Peer Review;Persons;Pilot Projects;Population;Preparation;Privatization;Problem Solving;Process;programs;rehabilitation research;Rehabilitation therapy;Reporting;Research;Research Activity;research and development;Research Personnel;research study;Resources;Role;Strategic Planning;Suggestion;technique development;Time;United States National Institutes of Health;volunteer;Work

PROJECT_TITLE: National Pediatric Rehabilitation Resource Center: Pilot Studies


PI_NAMEs: RAMEY, CRAIG T (contact)

PROJECT_TERMS: Advertisements;Advocacy;Affect;Awareness;Child;Childhood;Clinic;Clinical;design;disability;effectiveness evaluation;Family;Funding;Goals;improved;Infrastructure;Journals;Medical center;Monitor;outreach;Pamphlets;Philosophy;posters;Productivity;Professional Organizations;Registries;rehabilitation research;Rehabilitation therapy;Research;Research Personnel;Resources;Site;social media;special interest group;United States National Institutes of Health;Update;web site;Work;working group

PROJECT_TITLE: National Pediatric Rehabilitation Resource Center: Promoting Center Expertise


ADMINISTERING_IC: AA

ED_INST_TYPE: SCHOOLS OF PHARMACY

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Substance Misuse

ORG_CITY: AUSTIN

ORG_NAME: UNIVERSITY OF TEXAS AT AUSTIN

ORG_STATE: TX

PHR: PROJECT NARRATIVE This training program directly addresses the great need for highly trained scientists in an area of public health urgency – alcoholism, the consequences of which are devastating to the individual or developing fetus as in the case of fetal alcohol spectrum disorders. Trainees will learn cutting edge research techniques and will perform research on alcohol related problems to provide new information that may guide treatments or further our understanding of the causes and consequences of the disease of alcoholism.

PI_NAMEs: NIXON, KIMBERLY  (contact)

PROGRAM_OFFICER_NAME: POWELL, ELIZABETH

PROJECT_TERMS: Behavioral;Ethanol;neurochemistry

PROJECT_TITLE: Neurochemical & Behavioral Correlates of ETOH Effects


NIH_SPENDING_CATS: Behavioral and Social Science;Neurosciences;Pediatric;Physical Rehabilitation;Rehabilitation

PI_NAMEs: RAMEY, SHARON LANDESMAN (contact)

PROJECT_TERMS: Advocacy;Area;Budgets;Childhood;Clinical;Clinical Trials;Communication;Communities;Consensus;Data;Decision Making;Funding;Goals;improved;Information Systems;Infrastructure;interdisciplinary collaboration;Investments;Joints;Lateral;Lead;Leadership;Medical center;member;Mentors;Modeling;multidisciplinary;National Institute of Child Health and Human Development;Network Infrastructure;operation;Parents;Pilot Projects;Productivity;programs;Recording of previous events;rehabilitation research;Rehabilitation therapy;Research;Resources;Rewards;Role;Scientist;Targeted Research;technique development;United States National Institutes of Health

PROJECT_TITLE: National Pediatric Rehabilitation Resource Center: Administrative Oversight


PROJECT_TERMS: Appointment;base;Biomedical Research;Childhood;Clinic;Clinical;Clinical Research;Collaborations;cost;Dedications;Education;Educational process of instructing;experience;Faculty;Funding;Home;Individual;Infrastructure;Institution;Joints;Laboratories;Lead;Location;Mentors;Monitor;Ohio;operation;outreach;Pediatric Hospitals;Phase;Pilot Projects;Postdoctoral Fellow;Qualifying;rehabilitation research;Rehabilitation therapy;Research;Research Activity;Research Institute;Resources;Role;Scientist;Senior Scientist;technique development;Time;Travel;United States National Institutes of Health;Universities;Virginia;Work

PROJECT_TITLE: National Pediatric Rehabilitation Resource Center: Center Collaborations with Other Institutions


ED_INST_TYPE: SCHOOLS OF MEDICINE

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

ORG_CITY: HERSHEY

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: PENNSYLVANIA STATE UNIV HERSHEY MED CTR

ORG_STATE: PA

PI_NAMEs: HU, JIANMING  (contact)

PROGRAM_OFFICER_NAME: FLORES, AMANDA CHRISTINE

PROJECT_TERMS: Anti-viral Agents;Autophagosome;Award;Biological Assay;Capsid;Capsid Proteins;Cell Extracts;Cell Fractionation;Cell Line;Cell Nucleus;Cell-Free System;Cells;Chronic Hepatitis B;chronic liver disease;Chronic viral hepatitis;Circular DNA;Cirrhosis;Complement;Complex;cytokine;Cytoplasm;Data;Deoxyribonucleases;Development;differential expression;Disease;DNA;DNA amplification;DNA Repair;end stage liver disease;Endosomes;Episome;Event;Failure;Gene Expression;gene induction;Genes;Genetic Transcription;Goals;Green Fluorescent Proteins;Hepadnaviridae;Hepatitis B Virus;Hepatocyte;Human;Image;Immune response;Immunocompetent;In Vitro;Infection;Inflammation;Inflammatory;inhibitor;Innate Immune Response;insight;Instruction;Integration Host Factors;Interruption;knock-down;knockout gene;late endosome;Liver Cirrhosis;Malignant neoplasm of liver;Measurement;Monitor;mouse model;multicatalytic endopeptidase complex;Mus;mutant;Mutation;Natural Immunity;novel;Nuclear;Nuclear Extract;nuclease;Nucleocapsid;permissiveness;Phosphorylation;Physiological;Play;Predisposition;Process;Protein Kinase;Protein phosphatase;Relaxation;repaired;Reporter;response;Risk;Role;small molecule inhibitor;Stimulator of Interferon Genes;System;targeted agent;Testing;trafficking;transcriptome sequencing;Tropism;Variant;Viral;Virion;Virus;Virus Diseases;Virus Receptors;Virus Replication;Work

PROJECT_TITLE: Mechanisms of Hepadnavirus Assembly and Replication

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Autoimmune Disease;Diabetes;Eye Disease and Disorders of Vision;Neurodegenerative;Neurosciences

ORG_CITY: CHARLOTTESVILLE

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: UNIVERSITY OF VIRGINIA

PHR: Project Narrative Multiple lines of evidence suggest that NLRP3 inflammasome may contribute to the pathogenesis of diabetic retinopathy, a prevalent and blinding complication that arises due to diabetes. We will investigate this inflammasome in diabetic retinopathy with the goal that understanding the role of this pathway in retinal disease could provide new medically relevant knowledge for this blinding condition.

PI_NAMEs: AMBATI, JAYAKRISHNA  (contact);GELFAND, BRADLEY DAVID

PROGRAM_OFFICER_NAME: GORDIYENKO, NATALIYA

PROJECT_TERMS: Ablation;Acute;Address;Affect;Age related macular degeneration;Alzheimer's Disease;Animal Model;Apoptosis;Atherosclerosis;Blindness;Blood Vessels;Blood-Retinal Barrier;CASP1 gene;Cell Death;Cell model;cell type;Cells;Chronic;Clinical;Complex;Complication;cytokine;Defect;diabetes management;Diabetes Mellitus;diabetic;Diabetic mouse;Diabetic Retinopathy;Dimensions;Disease;Dose;efficacy evaluation;efficacy testing;endothelial dysfunction;Exhibits;Eye diseases;Functional disorder;Genetic;Genetic Recombination;Glucose;Goals;Hemorrhage;Human;Immune;Immune signaling;In Situ;Individual;Inflammasome;Inflammatory;inhibitor;insight;Insulin-Dependent Diabetes Mellitus;Intervention;islet amyloid polypeptide;Knock-out;Knowledge;Leukostasis;Lytic;Measures;Medical;Methods;Microvascular Dysfunction;Mitochondria;Modeling;Molecular Biology Techniques;mouse model;Mus;Myeloid Cells;Nerve Degeneration;neural;neural model;Neuroglia;Neurons;neurovascular;Nonesterified Fatty Acids;pathogen;Pathogenesis;Pathologic;Pathologic Processes;Pathology;Pathway interactions;Patients;Peptide Hydrolases;Persons;pharmacologic;Phenotype;pre-clinical;Pre-Clinical Model;prevent;Process;Production;promoter;Reactive Oxygen Species;recruit;Reporter Genes;Research;response;Retina;Retinal Diseases;Rheumatoid Arthritis;Risk;Role;Sampling;Signal Transduction;Source;Streptozocin;Streptozocin Diabetes;stressor;Testing;Therapeutic;Transgenic Organisms;Vision

PROJECT_TITLE: Nlrp3 inflammasome activation in early diabetic retinopathy

STUDY_SECTION: DPVS

STUDY_SECTION_NAME: Diseases and Pathophysiology of the Visual System Study Section[DPVS]


ADMINISTERING_IC: CA

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Breast Cancer;Cancer;Cancer Genomics;Genetics;Human Genome;Precision Medicine;Women's Health Research

ORG_CITY: IRVINE

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

ORG_STATE: CA

PHR: Narrative The vast majority of breast cancer related deaths are caused by the metastatic spread of cancer from the breast to other organs in the body. This project would help to understand which types of cells from the tumor are capable of colonizing the major organs in the body. In the long term, this information should point to ways of preventing metastasis and more effective ways to treat patients who already have metastatic breast cancer.

PI_NAMEs: LEV, TATYANA  (contact)

PROJECT_TERMS: advanced breast cancer;Animals;Antibodies;Bioinformatics;bioinformatics tool;Biological Assay;Brain;BRCA1 gene;BRCA1 Mutation;breast cancer metastasis;Cancer Biology;cancer cell;cancer genomics;Cause of Death;Cell Differentiation process;cell type;Cells;Cessation of life;Chromatin;Clonal Evolution;Complex;Computer Analysis;Custom;Data;data integration;design;Development;Disease;Disseminated Malignant Neoplasm;DNA;DNA copy number;DNA Repair;DNA sequencing;Duct (organ) structure;Educational process of instructing;Epigenetic Process;epigenomics;Epithelial Cells;Evolution;exome;exome sequencing;experimental study;Faculty;Gene Expression;Gene Expression Profile;Genetic;Genetic Transcription;Genomic Instability;genomic tools;Genomics;Genotype;Goals;Harvest;Heterogeneity;Human Resources;Impairment;improved;Injections;innovation;insight;Investigation;Laboratories;Laboratory Animals;Learning;Liver;Localized Malignant Neoplasm;Lung;Malignant - descriptor;Malignant Breast Neoplasm;Malignant Neoplasms;mammary epithelium;Mammary Neoplasms;Mentors;Metastatic breast cancer;metastatic process;Methodology;Milk;Mission;Modeling;molecular marker;molecular oncology;molecular pathology;mouse model;Mouse Strains;Multiomic Data;multiple omics;Mus;mutant;Mutant Strains Mice;Mutate;Mutation;Mutation Analysis;Myoepithelial cell;Neoplasm Metastasis;neoplastic cell;Organ;Patients;Pattern;personalized medicine;Phenotype;Pilot Projects;Population;Positioning Attribute;Postdoctoral Fellow;prevent;Primary Neoplasm;progenitor;Property;Resistance;Resolution;RNA;single cell genomics;stem cells;Students;Surveys;symposium;Systems Biology;Techniques;Technology;Testing;TP53 gene;Training;transcriptomics;Trees;tumor;tumor heterogeneity;undergraduate student;Variant;Woman;Work;XCL1 gene

PROJECT_TITLE: Intratumor heterogeneity in BRCA1-mutated breast cancer metastasis


ADMINISTERING_IC: EB

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Neurosciences

ORG_CITY: CAMBRIDGE

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

ORG_STATE: MA

PHR: NARRATIVE The mission of the NBETP is to train early-mid stage graduate students to become future leaders at the interface between neurobiology and engineering, a frontier highlighted by the Federal BRAIN Initiative and critical in the ongoing quest to understand the brain and its diseases. Training in neurobiological engineering is accomplished via a blend of course requirements in neuroscience and engineering, as well as associated activities that encourage student participation, leadership, and career development.

PI_NAMEs: JASANOFF, ALAN  (contact)

PROGRAM_OFFICER_NAME: GATLIN, TINA L

PROJECT_TITLE: Neurobiological Engineering Training Program


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Biomedical Imaging;Clinical Research;Mental Health;Neurosciences;Psychosis;Serious Mental Illness

ORG_CITY: NEW YORK

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: Project Narrative: Hallucinations are widespread and debilitating but current treatments often fail to improve symptoms and cause severe side effects that limit treatment adherence. We will use a novel fMRI-compatible auditory task, computational modeling, and a validated proxy measure for midbrain dopamine function to identify the neurocognitive mechanisms and circuitry underlying hallucination proneness in the general population. This approach will allow us measure circuit-specific alterations driving false perceptions and could prompt individualized treatment strategies that may not only be more effective but could also limit problematic side effects and improve quality of life.

PI_NAMEs: BUCK, JUSTIN  (contact)

PROGRAM_OFFICER_NAME: AVENILLA, FRANK R

PROJECT_TERMS: Adherence;Arbitration;Auditory;Automobile Driving;Basal Ganglia;Behavior;behavior prediction;Brain Diseases;Brain region;Clinical;Cognitive;cognitive process;comorbidity;Computer Models;Corpus striatum structure;Data;design;Detection;Development;Dissociation;Dopamine;dopaminergic neuron;Dorsal;effective therapy;expectation;experience;Fostering;Functional Magnetic Resonance Imaging;General Population;Hallucinations;Hearing;improved;Incentives;indexing;individualized medicine;interest;Learning;Link;Literature;Magnetic Resonance Imaging;Mathematics;Measures;Midbrain structure;Modeling;neural;neural circuit;neural correlate;neurochemistry;Neurocognitive;neuroimaging;neuromelanin;Neurosciences;novel;Participant;Patients;Perception;Perceptual disturbance;Perceptual learning;pharmacologic;phenomenological models;predictive modeling;Process;Proxy;Psychiatry;Quality of life;Reporting;Research Personnel;Rewards;role model;Sampling;Schizophrenia;sensory stimulus;Severities;side effect;Signal Transduction;Specificity;Stimulus;Substantia nigra structure;symptomatic improvement;Testing;theories;Training;transmission process;treatment adherence;treatment strategy;Update;Ventral Striatum;Ventral Tegmental Area

PROJECT_TITLE: Testing competing models of the computational role of dopamine in hallucinations


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Aging;Atherosclerosis;Cardiovascular;Clinical Research;Genetics;Heart Disease;Heart Disease - Coronary Heart Disease;Human Genome;Precision Medicine;Prevention

ORG_CITY: BOSTON

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: Project Narrative Recurrent myocardial infarctions (MI) represent one-third of all MIs and carry a markedly higher risk of morbidity and mortality. While much work has been done to identify common genetic variation for incident coronary artery disease, there is a large gap in the literature as to what variants contribute to recurrent MI. This proposal aims to discover new germline and somatic mutations associated with recurrent MI and then apply them to guide therapeutic decisions in secondary prevention of ischemic heart disease.

PI_NAMEs: MARSTON, NICHOLAS  (contact)

PROGRAM_OFFICER_NAME: WOO, SEUNG KYOON

PROJECT_TERMS: Adult;Applied Genetics;Atherosclerosis;Award;Biological;Birth;Cardiology;Cardiovascular Diseases;Cardiovascular system;Caring;Chairperson;Circulation;Clinical;clinical application;Clinical Trials;Clinical Trials Design;Collaborations;Computational Biology;Coronary Arteriosclerosis;Coronary heart disease;Data;data curation;data management;Data Set;Death Rate;Decision Making;Dedications;design;Development;Disease;Educational workshop;Epidemiologist;Event;exome sequencing;experience;Faculty;Foundations;Funding;Genes;Genetic;Genetic Databases;genetic predictors;Genetic Predisposition to Disease;Genetic Risk;genetic variant;Genetic Variation;genome wide association study;genome-wide;Genotype;Germ-Line Mutation;Goals;Hematopoiesis;high risk;Hospitals;Hypertension;improved;Individual;individualized medicine;Inflammation;insight;Large-Scale Sequencing;Lead;Learning;Lipids;Literature;Manuscripts;medical schools;Medicine;Mentorship;Morbidity - disease rate;mortality;Myocardial Infarction;Myocardial Ischemia;National Research Service Awards;novel;Oral;Pathway interactions;Patient Selection;Patients;personalized medicine;Play;polygenic risk score;Population;prevent;Prevention;Prevention therapy;Primary Prevention;Public Health Schools;Publishing;randomized, clinical trials;Recurrence;Recurrence Score;Research;Research Personnel;Risk Marker;risk prediction;Role;Rupture;Science;Secondary Prevention;Somatic Mutation;symposium;Teaching Hospitals;Testing;Therapeutic;Thrombosis;Thrombus;Time;Training;Variant;Vascular remodeling;Woman;Work

PROJECT_TITLE: Discovery and Application of Germline and Somatic Mutations for Risk Prediction and Personalized Therapy to Prevent Recurrent Myocardial Infarction

STUDY_SECTION: MCBS

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


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Dementia;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Neurodegenerative;Neurosciences;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: Project Narrative As the US population becomes older and more diverse, there is urgent need to cultivate a pool of health disparities researchers who can advance translational research in aging and Alzheimer's Disease and Related Dementias (ADRD) disparities and promote evidence-based interventions in both clinical practices and community-based settings. With this grant, I propose to: 1) establish a research training program to build academic capacity and leadership to advance the science of aging and ADRD health disparities; 2) advance innovative participatory, systems science, and implementation science frameworks and methods for aging and ADRD research in minority and health disparity populations; and 3) mentor junior scientists in applying multi- level, community-engaged frameworks and rigorous methods to advance the science of aging and ADRD health disparities research.

PI_NAMEs: TRINH-SHEVRIN, CHAU  (contact)

PROGRAM_OFFICER_NAME: LUO, YUAN

PROJECT_TERMS: Academic/Teacher Award;Acceleration;Address;Aging;aging population;Alzheimer's Disease;Alzheimer's disease related dementia;Applied Research;Asian Americans;Award;Behavior Therapy;career;career development;Chronic Disease;Clinical;clinical investigation;clinical practice;Clinical Sciences;Communities;community clinical linkage;community partners;Community Practice;curriculum development;Development;Development Plans;disease disparity;Disparity;disparity reduction;Dissemination and Implementation;Educational Curriculum;Educational workshop;Ensure;Environment;ethnic minority population;evidence base;Evidence based intervention;experience;Faculty;Foundations;Funding;Grant;Health;Health Disparities Research;health disparity;health disparity populations;implementation framework;implementation science;Individual;Infrastructure;innovation;Institutionalization;interest;Intervention;Laboratories;large datasets;Leadership;Link;Longevity;Medicine;Mentors;Mentorship;Methods;middle age;minority disparity;minority health;minority health disparity;minority health professional;Minority Health Research;Modeling;National Institute on Minority Health and Health Disparities;next generation;older adult;Older Population;Pilot Projects;Population;population health;Postdoctoral Fellow;prevent;Prevention Research;Program Development;Program Sustainability;programs;racial disparity;racial minority population;Recording of previous events;recruit;Research;Research Activity;Research Methodology;Research Personnel;Research Training;Science;Scientist;Secure;Senior Scientist;Series;simulation;socioeconomic disparity;Structure;System;Time;Training;training opportunity;Training Programs;Translational Research;Translations;Underrepresented Minority;United States Agency for Healthcare Research and Quality;United States National Institutes of Health

PROJECT_TITLE: Academic Leadership Award in Alzheimer's Disease and Aging Research for Chau Trinh-Shevrin, DrPH

STUDY_SECTION: NIA

STUDY_SECTION_NAME: Behavior and Social Science of Aging Study Section[NIA-S]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Genetics;Infectious Diseases;Lung;Pneumonia;Pneumonia and Influenza

ORG_CITY: SAN FRANCISCO

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: Project Narrative Ribosome-associated quality control (RQC) is a protein surveillance pathway in cells that is activated after the detection of stalled ribosomes and helps maintain the homeostasis and fidelity of protein synthesis. The adaptive mechanisms cells utilize to cope with ribosome stalling stress remain poorly defined. It is understood that the bacterial pathogen Legionella pneumophila (L.p.) secretes specific toxins into cells that cause translational pausing and global ribosome stalling. We take advantage of L.p. derived toxins to challenge the RQC pathway and identify a putative stress response pathway that helps cells cope with ribosome stalling insults.

PI_NAMEs: MUKHERJEE, SHAERI  (contact)

PROGRAM_OFFICER_NAME: REDDY, MICHAEL K

PROJECT_TERMS: 3' Untranslated Regions;activating transcription factor;activating transcription factor 3;anti-toxin;Apoptosis;Bacteria;Biochemical;Biological;biological adaptation to stress;Cell Death;Cell Nucleus;Cell Survival;Cells;Cellular biology;Chemicals;ChIP-seq;Clustered Regularly Interspaced Short Palindromic Repeats;Collaborations;coping;CREB1 gene;Data;Dedications;Detection;Disease;Dose;Endoplasmic Reticulum;Ensure;experimental study;Family;Genetic;Genetic Transcription;Goals;Gram-Negative Bacteria;Health;Homeostasis;Human;Infection;inhibitor;insight;Internal Ribosome Entry Site;Lead;Legionella;Legionella pneumophila;Legionnaires' Disease;Light;Link;Maintenance;Mammalian Cell;Mammals;MAPK8 gene;Maps;Mass Spectrum Analysis;Mediating;member;Messenger RNA;Metabolic;Modeling;Molecular;multicatalytic endopeptidase complex;novel;p38 Mitogen Activated Protein Kinase;pathogen;pathogenic bacteria;Pathway interactions;Phosphotransferases;polypeptide;Positioning Attribute;Process;Production;programs;Protein Biosynthesis;Protein Synthesis Inhibition;Proteins;proteostasis;Quality Control;recruit;Regulation;Reporter;Resolution;response;Ribosomes;RNA;Role;Signal Pathway;Signal Transduction;single molecule;Stimulus;Stress;Techniques;Testing;tool;Toxin;Transcript;transcription factor;transcriptional reprogramming;Translating;Translations;Transmembrane Transport;Type IV Secretion System Pathway;Ubiquitination;Up-Regulation;Vacuole;Work;Yeasts

PROJECT_TITLE: Legionella effectors reveal novel signaling function for the ribosome quality control (RQC) pathway

STUDY_SECTION: MBPP

STUDY_SECTION_NAME: Membrane Biology and Protein Processing Study Section[MBPP]


NIH_SPENDING_CATS: Clinical Research;Genetics

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Narrative: One of the principle cells involved in allergic reactions is the basophil. This application proposes to study one of the reasons that this cell type is more or less sensitive to stimulation. These studies will investigate how the cell controls expression of a critically important protein involved in cell activation.

PI_NAMEs: MACGLASHAN, DONALD W (contact)

PROGRAM_OFFICER_NAME: DONG, GANG

PROJECT_TERMS: Affect;Allergic Reaction;anti-IgE;Antibodies;B-Lymphocytes;Basophils;Behavior;Binding;Biological Response Modifier Therapy;Blood;Blood specimen;CD34 gene;cell type;Cells;Clinic;Clinical;clinical efficacy;Consent;cytokine;Data;Elements;Event;Exclusion;Family;Feedback;Gene Expression;Generations;Genetic;Genetic Polymorphism;Genetic Transcription;Genotype;Heterogeneity;Histamine Release;Human;Hypersensitivity;IgE;IgE Receptors;Immediate hypersensitivity;Individual;International;Laboratories;Leukocytes;Link;Linkage Disequilibrium;mast cell;Mediating;Modeling;mRNA Differential Displays;Observational Study;omalizumab;Organ;Pathway interactions;Patients;peripheral blood;Phosphotransferases;Pilot Projects;Population;programs;promoter;Promoter Regions;Protein Tyrosine Kinase;Proteins;Reaction;receptor;Regulation;Regulatory Pathway;Reporting;response;Rodent;Sampling;Signal Pathway;Signal Transduction;SNP genotyping;SYK gene;Testing;Tissues;transcription factor;transcriptome

PROJECT_TITLE: Regulation of Syk Expression in Human Basophils

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IDIB-E(57)]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging

ORG_DEPT: CHEMISTRY

PHR: Project Narrative In this project, we design, fabricate and validate a new type of microscope objective, namely a non-concentric reflective objective. This objective overcomes all limitations of commercial reflective objectives, which are invariably based on the Schwarzschild-Cassegrain design. The new lens features perfect color correction from the ultraviolet to the mid-infrared, a wide field of view, unparalleled throughput and a well-behaved pointspread function, thus enabling new and advanced nonlinear optical technologies that have so far been stifled by the lack of a high performance objective lens.

PI_NAMEs: POTMA, ERIC OLAF (contact)

PROGRAM_OFFICER_NAME: ANDERSON, AFROUZ AZARI

PROJECT_TITLE: BROADBAND FOCUSING FOR EXTREME MULTIMODAL MICROSCOPY

STUDY_SECTION: ISD

STUDY_SECTION_NAME: Instrumentation and Systems Development Study Section[ISD]


ORG_CITY: SEATTLE

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: Recent sequencing efforts have identified hundreds of millions of single nucleotide variants in human genomes that contribute to complex traits and diseases by interacting with one another and with genetic variation in repetitive DNA elements. The challenge of functionally interpreting this vast amount of variation is formidable: even considering only gene deletions, >108 and >1012 combinations for all 2-and 3-way interactions in the human genome would need to be tested. To reduce the complexity of variant combinations, we use genetically tractable model organisms and cutting-edge technologies to rigorously assess the various types of genetic interactions and to identify those with the most impact on phenotype, thereby generating both testable hypotheses for human genetics and novel technologies for testing them.

PI_NAMEs: QUEITSCH, CHRISTINE  (contact)

PROGRAM_OFFICER_NAME: MASKERI, BAISHALI

PROJECT_TERMS: Affect;Caenorhabditis elegans;Complex;Copy Number Polymorphism;Data;Disease;DNA;DNA biosynthesis;DNA Repair Gene;Dominant-Negative Mutation;Elements;Fertility;fitness;Gene Deletion;Gene Expression;Genes;Genetic;Genetic Epistasis;genetic technology;Genetic Variation;Genome Stability;genome-wide;genomic locus;Genomics;Genotype;healthspan;high throughput analysis;Human;Human Genetics;Human Genome;life span;Maps;Measurement;Mitochondria;model organism;Molecular;Mutation;new technology;Partner in relationship;Pathway interactions;Pharmaceutical Preparations;Phenotype;polypeptide;Population;protein folding;Proteins;Resistance;Ribosomal DNA;Robotics;Saccharomyces cerevisiae;Single Nucleotide Polymorphism;Stress;Surface;Technology;Testing;tool;trait;Variant;Yeasts

PROJECT_TITLE: Toward a mechanistic understanding of genetic interactions

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


ED_INST_TYPE: SCHOOL OF MEDICINE & DENTISTRY

NIH_SPENDING_CATS: Aging;Assistive Technology;Bioengineering;Clinical Research;Eye Disease and Disorders of Vision;Neurosciences

ORG_CITY: ROCHESTER

ORG_NAME: UNIVERSITY OF ROCHESTER

PHR: NARRATIVE Myopia or near sightedness affects not only visual acuity, but even when corrected it is linked to a higher risk of retinal detachment, glaucoma, and cataract. We propose studies to better understand how multifocal contact lenses can help slow down myopia progression, focusing on the interaction with crystalline lens accommodation. This will have direct implications for the optimization and personalization strategies for contact lens designs that provide uncompromised visual quality at all distances and effective accommodative response.

PI_NAMEs: MARCOS, SUSANA  (contact)

PROGRAM_OFFICER_NAME: WIGGS, CHERI

PROJECT_TITLE: Interplay between multifocal optics and accommodation: implications for myopia progression

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


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Cannabinoid Research;Dementia;Natural Products;Neurodegenerative;Neurosciences

ORG_CITY: GAINESVILLE

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: Project Narrative: Older adults represent the fastest growing group of cannabis users, as well as the age group at greatest risk for cognitive decline and Alzheimer's disease, but little is known about how cannabis affects age-related cognitive impairments and Alzheimer's disease pathology. The proposed project will use aged rats to determine the effects of cannabis (beneficial, detrimental, or neutral) on cognitive decline in aging and Alzheimer's disease-like neuropathology.

PI_NAMEs: BIZON, JENNIFER LYNN;SETLOW, BARRY  (contact)

PROGRAM_OFFICER_NAME: WAGSTER, MOLLY V

PROJECT_TERMS: Acute;Address;adverse outcome;Affect;Age;age group;age related;age related neurodegeneration;Age-associated memory impairment;aged;Aging;aging related;Agitation;Alzheimer like pathology;Alzheimer's Disease;Alzheimer's disease pathology;Anorexia;Anxiety;Attenuated;Behavioral;Behavioral Symptoms;Biochemical;Brain;Cannabinoids;Cannabis;cannabis administration;Chronic;Cognition;Cognitive deficits;Cognitive remediation;Consumption;Data;Electrophysiology (science);executive function;experimental study;Exposure to;Functional disorder;Goals;Hippocampus;Human;Impaired cognition;Impairment;Individual;Inflammation;inflammatory marker;Knowledge;Link;male;marijuana smoke;marijuana use;marijuana user;medial temporal lobe;Mediating;Memory;middle age;Modeling;Mus;Nerve Degeneration;neural;Neurobiology;neuroinflammation;neuropathology;novel;old mice;older adult;Oral;Pain;Pathology;Performance;Persons;pre-clinical research;Prefrontal Cortex;programs;Rattus;Recreation;remediation;Research;Risk;Route;sex;Shapes;Short-Term Memory;Signal Transduction;Sleeplessness;Smoking;spatial memory;Structure;Synapses;tau aggregation;tau expression;tau Proteins;Testing;Tetrahydrocannabinol;young adult

PROJECT_TITLE: Effects of cannabis on age-related cognitive decline and Alzheimers disease pathology

STUDY_SECTION: BRLE

STUDY_SECTION_NAME: Biobehavioral Regulation, Learning and Ethology Study Section[BRLE]


NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Hematology;Infectious Diseases;Lung;Microbiome;Pediatric;Sepsis

ORG_CITY: PHILADELPHIA

ORG_NAME: CHILDREN'S HOSP OF PHILADELPHIA

PHR: PROJECT NARRATIVE Children with sepsis and multi-organ dysfunction syndrome (MODS) demonstrate high morbidity and mortality. Successful treatment requires timely delivery of effective antibiotic concentrations to the site of infection, but in sepsis this is often impaired by an over- or under-active host immune response to infection. Within the context of two ongoing randomized trials being conducted within the Collaborative Pediatric Critical Care Research Network (CPCCRN), which will examine how modifying the host immune response to infection in children with sepsis and MODS impacts outcomes, our proposed research will study how the host immune response and organ dysfunction in sepsis influence antibiotic concentrations over time, and how both antibiotic concentrations and the host immune response impact clinical and microbiological outcomes.

PI_NAMEs: DOWNES, KEVIN JAMES (contact)

PROGRAM_OFFICER_NAME: JENKINS, TAMMARA L

PROJECT_TERMS: adverse outcome;Age;anakinra;Anti-Inflammatory Agents;Antibiotics;Biological;Blood;Blood capillaries;Blood specimen;Child;Childhood;Clinical;Critical Care;Critical Illness;Critically ill children;Development;Dose;Double-Blind Method;Drug Kinetics;Enrollment;Ensure;Fever;Functional disorder;Granulocyte-Macrophage Colony-Stimulating Factor;high risk;Immune;Immune response;Immune System Diseases;Immunophenotyping;immunoregulation;Impairment;individualized medicine;Infection;Inflammation;Inflammation Mediators;Inflammatory Response;Knowledge;Leukocytes;Lower Respiratory Tract Infection;Maintenance;Measurement;Measures;Metagenomics;microbiome;microbiome composition;Morbidity - disease rate;mortality;Multicenter Trials;Names;Network Infrastructure;next generation sequencing;Organ;Outcome;pathogenic bacteria;pediatric sepsis;Perfusion;Pharmaceutical Preparations;pharmacokinetic model;Phenotype;Placebo Control;Population;primary outcome;Production;randomized trial;Recovery of Function;Renal function;Research;Respiratory Failure;respiratory microbiome;respiratory pathogen;Respiratory System;response;Risk;Sampling;secondary analysis;Sepsis;septic;simulation;Site;Source;Survivors;Syndrome;Testing;Therapeutic;Time;Tissues;treatment optimization;Treatment outcome;treatment strategy;Weight

PROJECT_TITLE: PediatRic sEpsiS induCed MODS: Relationship of Immune-phenotypes and antiBiotic Exposures (PRESCRIBE) study

STUDY_SECTION: SAT

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


ADMINISTERING_IC: VA

FUNDING_MECHANISM: OTHERS

IC_NAME: Veterans Affairs

ORG_CITY: SALT LAKE CITY

ORG_NAME: VA SALT LAKE CITY HEALTHCARE SYSTEM

ORG_STATE: UT

PHR: The proposed research is relevant to Veteran health because it focuses on identifying therapeutic targets to improve functional capacity, exercise tolerance, and quality of life in Veterans with peripheral artery disease (PAD). Physical activity is the most beneficial and cost-effective treatment for Veterans with PAD, however, issues with oxygen delivery and utilization dramatically impair exercise compliance. The cause of these oxygen delivery and utilization impairments is likely increased oxidative stress and inflammation. The proposed project will comprehensively examine the novel strategy of Nuclear Factor Erythroid-2-like 2 (Nrf2) activation using PB125, aimed at diminishing oxidative stress and inflammation, and thereby abating the negative impacts of the disease. This therapeutic will be evaluated in isolation and in combination with exercise rehabilitation to determine if there is a synergistic benefit. The ultimate goal is to provide insight into a potential novel therapeutic treatment for this disease, therefore, improving exercise tolerance and quality of life in this growing population.

PI_NAMEs: CRAIG, JESSE CHARLES (contact)

PROJECT_TERMS: Abate;Acceleration;Activities of Daily Living;Address;Adherence;antioxidant enzyme;Antioxidants;Arteries;Atherosclerosis;Behavioral;Blood flow;Blood Pressure;Blood Vessels;cardiovascular risk factor;Cardiovascular system;Clinical;clinical practice;Clinical Trials;cognitive function;cost effective treatment;Death Rate;Development;Diabetes Mellitus;Diagnosis;Disease;Effectiveness;Event;evidence base;Exercise;exercise capacity;exercise intolerance;exercise rehabilitation;Exercise Tolerance;functional decline;Functional disorder;functional improvement;Future;General Population;Goals;Health;Healthcare Systems;hemodynamics;Hypertension;Impairment;improved;in vivo;Inflammation;Inflammatory;insight;Insurance Coverage;Knowledge;Lower Extremity;Medicine;Metabolic;Metabolic dysfunction;Mitochondria;mitochondrial dysfunction;Morbidity - disease rate;mortality;Motivation;Muscle;novel strategies;novel therapeutics;nuclear factor-erythroid 2;Obesity;Operative Surgical Procedures;Outcome;Oxidative Stress;Oxygen;Pain;pain reduction;Pathology;Pathway interactions;Patients;Peripheral;Peripheral arterial disease;pharmacologic;Phase;Physical activity;physical inactivity;Placebos;Play;Population;Prevalence;psychosocial;Quality of life;Randomized;readmission rates;Regulation;Rehabilitation therapy;Research;Respiration;response;Risk;Risk Factors;Role;Safety;Site;Skeletal Muscle;Smoking;Supplementation;Symptoms;Testing;Therapeutic;therapeutic target;Treatment Effectiveness;Vascular Diseases;Veterans

PROJECT_TITLE: Improving exercise rehabilitation efficacy and outcomes in Veterans with peripheral artery disease: Targeting oxidative stress and inflammation

STUDY_SECTION_NAME: Career Development Program - Panel II[RRD9]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Bioengineering;Biotechnology;Brain Disorders;Dementia;Genetics;Lewy Body Dementia;Neurodegenerative;Neurosciences;Parkinson's Disease

ORG_CITY: STANFORD

ORG_DEPT: NEUROLOGY

ORG_NAME: STANFORD UNIVERSITY

PHR: An exciting new area in neurodegenerative disease research is the emerging phenomenon of prion-like spreading of neurodegenerative disease proteins. Our experiments will provide fundamental mechanistic insight into how the proteins spread, how the spread impacts functional decline, and how the spread can be altered for therapy. The tools we apply and the lessons we learn will likely be broadly applicable to other neurodegenerative diseases including Alzheimer’s disease and related dementia.

PI_NAMEs: GITLER, AARON D.;LEE, JIN HYUNG  (contact)

PROGRAM_OFFICER_NAME: MARIC, MAJA

PROJECT_TERMS: 3-Dimensional;Address;Affect;alpha synuclein;Alzheimer's Disease;Alzheimer's disease related dementia;Amygdaloid structure;Animals;Area;Brain;brain circuitry;Brain region;cell type;cingulate cortex;Computer Models;Corpus striatum structure;Data;Dementia;Dementia with Lewy Bodies;density;Development;Diffusion;Disease;Distal;empowerment;Encephalopathies;Engineering;experimental study;fascinate;functional decline;Functional Magnetic Resonance Imaging;Gene Expression;Gene Expression Profile;Genes;Genetic;genetic manipulation;Genetic Predisposition to Disease;Goals;high resolution imaging;Image;imaging approach;Infectious Agent;Injections;innovation;insight;interest;Investigation;Laboratories;Learning;Lewy body pathology;Location;LRRK2 gene;Maps;Measures;Methods;Monitor;Mus;Nerve Degeneration;Nervous System;neural;Neurodegenerative Disorders;Neurons;novel;olfactory bulb;optogenetics;Parkinson Disease;Pathologic;Pathology;pathology imaging;Pathway interactions;Pattern;Predisposition;Prion Diseases;prion-like;Prions;Process;protein aggregation;Proteins;Research;Resolution;Rodent;Role;Route;Substantia nigra structure;Synapses;tau Proteins;Technology;Testing;Therapeutic;therapeutic development;Time;tool;Visualization

PROJECT_TITLE: Innovating high-resolution novel imaging approaches to elucidate mechanisms of prion-like spreadingof neurodegenerative disease

STUDY_SECTION: CMND

STUDY_SECTION_NAME: Cellular and Molecular Biology of Neurodegeneration Study Section[CMND]


NIH_SPENDING_CATS: Cardiovascular;Heart Disease

ORG_CITY: HOUSTON

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

PHR: Project Narrative Loss of cardiomyocytes by necrotic cell death is the direct mechanistic basis for mortality due to myocardial infarction injury, as well as ensuing heart failure associated with an array of cardiomyopathies. This proposal will explore novel mechanisms in regards to the composition and regulation of the mitochondria permeability transition pore and its opening, which is the critical event that is responsible for regulated necrotic cell death. Further definition and molecular composition of the permeability transition pore is critical for designing new therapeutic strategies.

PI_NAMEs: KARCH, JASON MICHAEL (contact)

PROGRAM_OFFICER_NAME: WONG, RENEE P

PROJECT_TERMS: Adenine Nucleotides;Affect;Ants;Binding;Calcium;candidate identification;Cardiac Myocytes;Cardiomyopathies;Cause of Death;Cell Culture System;Cell Death;Cells;Cessation of life;Characteristics;Communities;Compensation;Crista ampullaris;Cyclophilin A;cyclophilin D;Cyclosporine;Data;desensitization;design;Enterobacteria phage P1 Cre recombinase;Event;Excision;Family;Family member;Genetic;Heart;Heart failure;In Vitro;in vivo;inhibitor;Injury;Inner mitochondrial membrane;insight;Ischemia;ischemic injury;Isomerism;Knockout Mice;Laboratories;Liver;Liver Mitochondria;Masks;Measures;Membrane;Membrane Potentials;Membrane Proteins;mimetics;Mitochondria;mitochondrial dysfunction;mitochondrial permeability transition pore;Molecular;mortality;Mus;Mutate;Myocardial Infarction;Myocardial Ischemia;Necrosis;novel;novel therapeutic intervention;Organelles;Outer Mitochondrial Membrane;Oxygen;Peptidylprolyl Isomerase;Permeability;Probability;Production;protective effect;Protein Isoforms;Proteins;Regulation;Reperfusion Injury;Resistance;Role;Rupture;SLC25A4 gene;SLC25A5 gene;Swelling;Therapeutic;therapeutic target;Tissues;Work

PROJECT_TITLE: Molecular Regulation of Mitochondrial Permeability Transition and its Role in Regulated Necrosis

STUDY_SECTION: MIM

STUDY_SECTION_NAME: Myocardial Ischemia and Metabolism Study Section[MIM]


ED_INST_TYPE: HOSPITALS

NIH_SPENDING_CATS: Cancer;Genetics

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF TX MD ANDERSON CAN CTR

PHR: PROJECT NARRATIVE Many types of endogenous DNA lesions or damage induced by radiation and chemotherapy lead to replication stress and activate the replication checkpoint pathway. While the integrity of the replication checkpoint pathway is critically important for cell survival, the mechanisms underlying replication checkpoint control and cell viability are not fully understood. In this project, we will determine the mechanisms underlying replication and cell cycle checkpoint control with the long-term goal of exploiting this checkpoint pathway for cancer therapy.

PI_NAMEs: CHEN, JUNJIE  (contact)

PROGRAM_OFFICER_NAME: WEINREICH, MICHAEL DALE

PROJECT_TERMS: Address;Antineoplastic Agents;Binding;cancer therapy;Cell Cycle;Cell Cycle Checkpoint;Cell Cycle Progression;Cell Cycle Regulation;Cell Line;Cell Proliferation;Cell Survival;Cells;CHEK1 gene;chemotherapeutic agent;Chemotherapy and/or radiation;Clinical Trials;Defect;DNA;DNA biosynthesis;DNA Damage;DNA lesion;DNA Repair;DNA replication fork;Ensure;established cell line;ETAA1;Event;Genetically Engineered Mouse;Genome;genome integrity;Goals;helicase;Immune checkpoint inhibitor;inhibitor;Lead;Lesion;Maintenance;MCM2 gene;Mediating;Mitosis;Molecular;Monitor;Oncogenes;Pathway interactions;Phosphorylation;Phosphotransferases;Play;Polymerase;prevent;Process;Proliferating;protein degradation;protein function;Protein Kinase;Proteins;Radiation;Radiation Induced DNA Damage;recruit;Regulation;Replication Initiation;replication stress;response;Role;S phase;Signal Transduction;Single-Stranded DNA;SS DNA BP;Structure;System;Testing;TOPBP1 Gene;upstream kinase;Work

PROJECT_TITLE: Elucidating mechanisms underlying replication checkpoint control

STUDY_SECTION: RTB

STUDY_SECTION_NAME: Radiation Therapeutics and Biology Study Section[RTB]


NIH_SPENDING_CATS: Brain Disorders;Cardiovascular;Clinical Research;Complementary and Integrative Health;Congenital Heart Disease;Congenital Structural Anomalies;Depression;Heart Disease;Maternal Health;Mental Health;Mental Illness;Pediatric;Rare Diseases;Serious Mental Illness;Women's Health Research

ORG_CITY: IOWA CITY

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF IOWA

PHR: RELEVANCE Depressions during pregnancy affects nearly 20% of women, and 10% of pregnant women are taking selective serotonin reuptake inhibitors (SSRIs). SSRIs impact serotonin signaling and animal models of SSRI exposure show reduced ventricular size and function. This translational study seeks to define if maternal depression and/or its treatment impacts ventricular development in infants.

PI_NAMEs: HASKELL, SARAH ELIZABETH (contact)

PROGRAM_OFFICER_NAME: EGERSON, D'ANDREA R

PROJECT_TERMS: 1 year old;Address;Adult;Affect;Animal Model;Animals;antepartum depression;anti-depressive agents;bench to bedside;Birth;Cardiac;Cardiac Myocytes;cardiogenesis;Cardiology;Cardiovascular Diseases;cardiovascular health;Cardiovascular system;Childhood;clinically relevant;Congenital Heart Defects;Critical Care;Data;Depressed mood;detection sensitivity;Development;Dimensions;Disease;Echocardiography;Epidemiology;expectation;Exposure to;fetal;Fetal Development;Fetus;Frequencies;Future;Genetic;Gestational Age;Growth;Health;health of the mother;heart dimension/size;heart function;hemodynamics;Human;Imaging Techniques;Impairment;indexing;Individual;infancy;Infant;inhibitor therapy;innovation;insight;interpersonal therapy;intrauterine environment;Investigation;Knowledge;Left;Long-Term Effects;maternal depression;Measurement;Measures;Medical;Mental Depression;Monitor;Mothers;Mus;Myocardial;Neonatal;Newborn Infant;Nonpharmacologic Therapy;offspring;Outcome;outcome prediction;Pediatrics;Performance;perinatal mental health;peripartum depression;persistent pulmonary hypertension;pharmacologic;Pharmacological Treatment;Physiological;Pilot Projects;policy implication;Population;postnatal;Pre-Clinical Model;Predictive Value;Pregnant Women;prenatal exposure;Prospective Studies;Psychiatry;Public Health;Recommendation;recruit;Reporting;Research;Research Design;Risk;risk prediction;Selective Serotonin Reuptake Inhibitor;Serotonin;Sertraline;Signal Transduction;Structure;Techniques;Time;Translating;translational goal;translational study;treatment risk;United States;Ventricular;Ventricular Function;Woman;Work;Zebrafish

PROJECT_TITLE: SSRI Exposure and Ventricular Development from Bench to Bedside: A Prospective Study to Determine if Maternal Depression Treatment Impacts Offspring Cardiac Development


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Autoimmune Disease;Brain Disorders;Multiple Sclerosis;Neurodegenerative;Neurosciences

ORG_CITY: MADISON

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: Multiple sclerosis (MS) is the major cause of non-traumatic neurological disability in young adults in the US. Using a rodent model (Shiverer) for late phase MS, we discovered a major cause of grey matter damage for this disease phase. This damage is caused by inappropriate intrusion of an axonal mitochondrial anchor, Syntaphilin (SNPH), into dendrites. SNPH immobilizes mitochondria in dendrites and causes neurons to be excited to death. We will explore which glutamate receptors are involved in this toxicity, and how synaptic activity causes harmful migration of SNPH to dendrites. Preventing toxic SNPH migration into dendrites is a potential treatment strategy for MS.

PI_NAMEs: CHIU, SHING YAN (contact)

PROGRAM_OFFICER_NAME: UTZ, URSULA

PROJECT_TERMS: Address;Affect;Agonist;Animal Model;antagonist;Axon;axonal degeneration;Basic Science;Behavior;Cells;Cerebellum;Cessation of life;Clinical;Cloning;Coupled;Demyelinations;Dendrites;design;Disease;disease model;dysmyelination;excitotoxicity;Exclusion;Fiber;follow-up;Functional disorder;Genetic;Glutamate Receptor;Glutamate Transporter;glutamatergic signaling;Glutamates;gray matter;Health;Immobilization;Injections;insight;Kinesin;Mediating;Methods;migration;Mitochondria;Mitochondrial Proteins;Modeling;Movement;Multiple Sclerosis;multiple sclerosis treatment;Mus;N-Methyl-D-Aspartate Receptors;N-Methylaspartate;Nerve Degeneration;Neurological disability;Neurons;novel;Nuclear;oligodendrocyte progenitor;Pathologic;Pathology;Pathway interactions;Phase;precursor cell;preemptive intervention;prevent;Proteins;Purkinje Cells;receptor;Receptor Activation;recruit;remyelination;Reporting;Rodent Model;Secondary to;Signal Transduction;Surface;Synapses;syntaphilin;Testing;Therapeutic;Toxic effect;treatment strategy;uptake;white matter;young adult

PROJECT_TITLE: Novel Pathways to Excitotoxicity in Multiple Sclerosis Caused by Inappropriate Intrusion of an Axonal Mitochondrial Anchor Syntaphilin into Dendrites

STUDY_SECTION: NOMD

STUDY_SECTION_NAME: Neural Oxidative Metabolism and Death Study Section[NOMD]


PHR: MSTP Project Narrative Progress towards solving major health problems will require a steady source of well-trained new investigators who have the clinical background to appreciate major medical issues and the research skills to tackle them. Over the years, MD-PhD programs have proven to be a highly effective way to train such investigators. We seek funding to continue our highly successful MD-PhD Program at The Johns Hopkins University School of Medicine.

PI_NAMEs: COX, ANDREA L (contact)

PROGRAM_OFFICER_NAME: AIYEGBO, MOHAMMED S

PROJECT_TERMS: Medical;Scientist;Training Programs

PROJECT_TITLE: Medical Scientist Training Program

STUDY_SECTION: TWD

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


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Facioscapulohumeral Muscular Dystrophy;Genetics;Muscular Dystrophy;Rare Diseases

ORG_CITY: RENO

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF NEVADA RENO

ORG_STATE: NV

PHR: PROJECT NARRATIVE: Among the most common muscle disorders, Facioscapulohumeral Muscular Dystrophy (FSHD) is caused by misexpression of the DUX4 gene in skeletal muscles. CRISPR inhibition technology provides an avenue for targeting and reducing such pathogenic gene expression, with long-term or permanent beneficial effects. Here we will test the efficacy, specificity, and stability of CRISPR inhibition in two complementary mouse models of FSHD, including a xenograft model that will allow us to study the effects of this approach in human muscle derived from FSHD patient cells.

PI_NAMEs: JONES, PETER L (contact)

PROGRAM_OFFICER_NAME: CARIFI, EMILY FORAN

PROJECT_TERMS: 4q35;Address;adeno-associated viral vector;adenovirus mediated delivery;Affect;Alleles;Animal Model;Cells;Chromatin;Chromosomes;Clinical Data;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;CRISPR/Cas technology;D4Z4;design;Disease;Distal;effective therapy;efficacy testing;efficacy validation;Engineering;Epigenetic Process;Exons;Facioscapulohumeral Muscular Dystrophy;Gene Expression;gene repression;Genes;Genetic;Genetic Transcription;Genome;Genomic Segment;Human;improved;in vivo;in vivo evaluation;inhibitor;Mammals;Mediating;Messenger RNA;Methyl-CpG-Binding Protein 2;Modeling;mouse model;Mus;Muscle;Muscle Cells;muscular dystrophy mouse model;Myopathy;novel;Orthologous Gene;Pathogenesis;Pathogenicity;Pathology;Pathway interactions;Patients;permissiveness;Phenotype;pre-clinical;pre-clinical assessment;Primates;promoter;Relaxation;Repetitive Sequence;Repression;SET Domain;Skeletal Muscle;Specificity;Staphylococcus aureus;Technology;Testing;Therapeutic;transcriptome;Transgenic Mice;Validation;vector;Viral Load result;virulence gene;Xenograft Model;Xenograft procedure

PROJECT_TITLE: CRISPR-inhibition for FSHD


ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

ORG_CITY: KANSAS CITY

ORG_NAME: CHILDREN'S MERCY HOSP (KANSAS CITY, MO)

PHR: Project Narrative Next generation sequencing (NGS) has transformed the field of genomics, bringing it to the forefront of healthcare, however the rapid pace of technological developments in the field challenges even field experts to remain current. The successful implementation of genomics into clinical practice requires much more than a superficial understanding of the technology. The proposed course, "An Immersive Experience in Medical Genomics" is designed for a broad audience of clinicians seeking a strong foundation in genomics, and will be structured to facilitate collaboration and crosstalk across disciplines.

PI_NAMEs: FARROW, EMILY  (contact)

PROGRAM_OFFICER_NAME: RIDER, RENEE ANNE

PROJECT_TERMS: Applications Grants;Area;Attention;bridge program;career;case-based;Child;Childhood;Clinical;clinical care;clinical practice;Clinical Research;clinical translation;Collaborations;Complex;Consultations;Course Content;Data;data sharing;Dedications;design;Discipline;E-learning;Education;Educational Curriculum;Educational process of instructing;Educational workshop;effectiveness evaluation;ethical, legal, and social implication;Ethics;exome sequencing;experience;Exposure to;flexibility;Foundations;Funding;Genome;genome sequencing;Genomic medicine;Genomics;Goals;Growth and Development function;Healthcare;Hospitals;Human Resources;Impact evaluation;implementation facilitation;Informed Consent;innovation;interest;Knowledge;Learning Module;lectures;Medical;Modeling;Modification;multimodality;next generation sequencing;Outcome;Participant;patient engagement;Patients;personalized genomics;pragmatic implementation;precision medicine;programs;Publications;Research;research clinical testing;Research Personnel;Spottings;Structure;Technology;technology development;Testing;Time;tool;Training;translational genomics;translational research program;Underrepresented Minority;underserved community;Vulnerable Populations;web site

STUDY_SECTION: GNOM

STUDY_SECTION_NAME: Genome Research Study Section[GNOM-G]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Diabetes;Neurosciences;Nutrition

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Project Narrative Stress-induced hyperglycemia is an important survival response that fuels the metabolic activity needed to fight and escape threats; however severe or chronic activation of this response can lead to diabetes. This project aims to define the neural circuits and metabolic mechanisms that regulate stress-induced glucose mobilization and differentiate these from the circuits that mediate stress-induced behaviors. Once these mechanisms have been identified, we will be able to develop therapeutics that can target metabolic outcomes of stress-induced hyperglycemia without affecting behavioral responses.

PI_NAMEs: AFFINATI, ALISON HOLLEY (contact)

PROGRAM_OFFICER_NAME: COOKE, BRAD

PROJECT_TERMS: Acute;Adipose tissue;Affect;Anatomy;Automobile Driving;Behavior;Behavioral;behavioral genomics;behavioral phenotyping;behavioral response;Bioinformatics;biological adaptation to stress;blood glucose regulation;Brain;Brain region;career;Cell Nucleus;Cells;Central Nervous System;Cholecystokinin B Receptor;Chronic;Chronic stress;Critical Illness;Development;Diabetes Mellitus;Dorsal;Energy Metabolism;experimental study;fighting;Foundations;Freezing;Functional disorder;Genetic Transcription;Glucocorticoids;Gluconeogenesis;Glucose;glucose disposal;glucose production;Glycerol;Goals;Hepatic;Homeostasis;Hormonal;Hyperglycemia;Hypoglycemia;Hypothalamic structure;Impairment;improved;Insulin;Intervention;Ketones;Lead;Link;Lipid Mobilization;Lipids;Liver;Location;Maps;Medial;Mediating;Metabolic;Metabolism;midbrain central gray substance;neural circuit;Neural Pathways;Neuroanatomy;Neurons;Norepinephrine;Nutrient;optogenetics;Organ;Outcome;Output;Pattern;Peripheral;Physicians;Physiology;Play;Population;Postabsorptive Hypoglycemia;preference;Preoptic Areas;programs;receptor expression;Regulation;response;restraint;Role;Scientist;single nucleus RNA-sequencing;Site;stable isotope;Stimulus;Stress;stressor;Sympathetic Nervous System;System;Testing;Therapeutic;Tissues;tool;Training;Work

PROJECT_TITLE: Identifying functional and anatomic mechanisms of glucose mobilization by cholecystokinin b receptor containing neurons in the ventromedial nucleus of the hypothalamus

STUDY_SECTION: DDK

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


ADMINISTERING_IC: DA

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Chronic Pain;Clinical Research;Drug Abuse (NIDA only);Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Opioid Misuse and Addiction;Opioids;Pain Research;Physical Injury - Accidents and Adverse Effects;Prescription Drug Misuse;Prevention;Rural Health;Social Determinants of Health;Substance Misuse

ORG_CITY: Newark

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: PROJECT NARRATIVE: The proposed project will apply novel methods to identify a comprehensive set of individual sociodemographic and clinical characteristics that define longitudinal patterns of prescription opioid use for chronic pain and predict transitions to fatal and non-fatal overdose in vulnerable groups. This project will also examine linkages between prescription opioid treatment trajectories and broader social and structural characteristics to understand how population-level sociodemographic and socioeconomic factors, the distribution of health care resources, and state policies influence risk of opioid overdose and fatality at the individual level. The research will contribute fundamental knowledge about the patterns and risks associated with opioid prescribing practices for pain management and identify areas where programs and policies are needed to improve health care access and quality to ultimately reduce the risk of opioid overdose and death.

PI_NAMEs: SAMPLES, HILLARY  (contact)

PROGRAM_OFFICER_NAME: PARKER, ERIN MARGARET

PROJECT_TERMS: abuse liability;Accidental Injury;Accounting;Address;Admission activity;Adult;Age;American;Area;beneficiary;career;career development;Cause of Death;Cessation of life;Characteristics;chronic pain;Clinical;clinical care;clinical epidemiology;clinical pain;comorbidity;contextual factors;County;Data;Data Files;Data Sources;Death Rate;Development;Development Plans;disability;disabled;Disparity population;dosage;Dose;Early Intervention;Education;effective intervention;Eligibility Determination;Enrollment;Ethics;Ethnic Origin;Formulation;Funding;geographic difference;Geography;Goals;Guidelines;Health;health care availability;Health Resources;Health Services Accessibility;Health Services Research;Health system;Healthcare;Healthcare Systems;high risk population;Hospitals;Improve Access;improved;Income;indexing;Individual;Individual Adjustment;innovation;Intervention;Knowledge;Life Expectancy;Link;Longitudinal Studies;Measures;Medicaid;Medical;Mental disorders;Mentorship;Methodology;Methods;Minority;Monitor;Morbidity - disease rate;mortality;National Institute of Drug Abuse;non-cancer chronic pain;novel;Opioid;opioid epidemic;opioid mortality;opioid overdose;opioid use;opioid use disorder;Outcome;Overdose;overdose death;Overdose reduction;overdose risk;Pain;Pain management;Pathway interactions;patient population;Pattern;Patterns of Care;personalized approach;Pharmaceutical Preparations;Pharmacy facility;Policies;Policy Research;Population;population based;Population Characteristics;Poverty;Practice Guidelines;prescription monitoring program;prescription opioid;Prescription opioid overdose;prevent;programs;Public Health;Race;Reporting;Research;Research Methodology;Research Personnel;Resources;response;Risk;Risk Factors;Risk Reduction;rural counties;Secure;Services;sex;social;social epidemiology;sociodemographics;Socioeconomic Factors;spatial epidemiology;statistics;stem;Strategic Planning;substance use;System;tertiary prevention;theories;Time;Training;Training Support;treatment pattern;trend;Unemployment;Universities;Vulnerable Populations;Work

PROJECT_TITLE: Multi-level associations between opioid use and overdose: Individual, clinical, and population-based risk factors for fatality

STUDY_SECTION: HSOD

STUDY_SECTION_NAME: Health Services Organization and Delivery Study Section[HSOD]


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

ORG_CITY: DURHAM

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: PROJECT NARRATIVE Heart failure (HF) is the leading cause of hospitalization in older adults and represents an enormous public health burden. Despite the contributions of countless studies, national campaigns, and financial incentives, high rates of rehospitalization continue to put enormous strain on the U.S. healthcare system and on those suffering from the disease. We propose to integrate the strengths of life course theory, data, and methods to examine the longitudinal patterns and predictors of hospitalization in older adults diagnosed with HF.

PI_NAMEs: DUPRE, MATTHEW E. (contact)

PROGRAM_OFFICER_NAME: SERRA, MONICA CHRISTINE

PROJECT_TERMS: Address;Admission activity;Adult;Aging;Attention;Behavioral;burden of illness;Caring;Characteristics;Classification;Clinical;clinical practice;Clinical Research;cohort;cost;critical period;Data;design;Diagnosis;Disease;Electronic Health Record;experience;Face;financial incentive;Goals;Health;Health and Retirement Study;Healthcare Systems;Heart failure;hospital admission rate;Hospitalization;hospitalization rates;Hospitals;human old age (65+);improved;indexing;Intervention;Investments;Knowledge;Length of Stay;Life Cycle Stages;longitudinal dataset;Longitudinal Studies;Medicare;Medicare claim;Methods;Mission;Modeling;older adult;Patient risk;Patients;Pattern;Persons;Population;Predictive Factor;prevent;Probability;prospective;psychosocial;Public Health;Quality of Care;Recurrence;Reproducibility;Research Personnel;response;Risk;Sampling;socioeconomics;theories;Time;tool;Treatment Failure;United States National Institutes of Health

PROJECT_TITLE: A Life Course Approach to Identify Risks of Hospitalization in Older Adults with Heart Failure

STUDY_SECTION: HSQE

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


ORG_CITY: NEW YORK

ORG_DEPT: PATHOLOGY

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: We do not understand how melanocytes de-differentiate into transcriptionally heterogeneous melanoma cell states that define poor outcome in patients. Screening for changes in DNA methylation, we discovered de- repression of NR2F2-isoform2 in patients where melanoma had spread from skin to other body parts, and now propose to determine whether and how NR2F2-isoform2 affects melanoma heterogeneity and metastatic potential. By understanding NR2F2-isoform2 function, we expect to identify the cell state responsible for metastatic progression, and factors we can harness to predict, prevent, or inhibit metastasis in melanoma patients.

PI_NAMEs: HERNANDO, EVA  (contact);SCHOBER, MARKUS

PROGRAM_OFFICER_NAME: GRIL, BRUNILDE M

PROJECT_TERMS: Adjuvant Therapy;Affect;apoAI regulatory protein-1;Biological;biomarker panel;Body part;cancer cell;Candidate Disease Gene;Cell Differentiation process;Cells;Cessation of life;clinical decision-making;cofactor;cost;CpG dinucleotide;Cutaneous Melanoma;Data;demethylation;derepression;Dermis;Development;Diagnosis;Dimerization;Disease;Distant;DNA analysis;DNA Binding Domain;DNA Methylation;Endowment;Epidermis;Epigenetic Process;epithelial to mesenchymal transition;Excision;gain of function;Genes;genetic signature;Genetic Transcription;Growth;Heterogeneity;Human;human model;Hypermethylation;Immunohistochemistry;improved;In Situ Hybridization;In Vitro;in vivo Model;insight;Intervention;Invaded;loss of function;Malignant Neoplasms;Measures;melanocyte;Melanoma;Melanoma Cell;Melanoma patient;Metastatic Melanoma;Metastatic/Recurrent;Methylation;Modeling;Molecular;molecular marker;Morbidity - disease rate;mortality;mouse model;Mus;Neoplasm Metastasis;Neural Crest;Neural Crest Cell;Newly Diagnosed;novel;Nuclear Receptors;Organ;Outcome;patient derived xenograft model;Patient Selection;Patient-Focused Outcomes;Patients;Phenotype;prevent;primary outcome;Prognosis;Prognostic Marker;promoter;Prospective cohort;Protein Isoforms;Recurrence;Regulation;Resected;Risk;Role;Sampling;screening;side effect;single molecule;Site;Skin;Testing;therapeutic target;transcription factor;Transcription Initiation Site;Treatment outcome;tumor;tumor heterogeneity;tumor progression;Tumor stage;Work;Xenograft procedure

PROJECT_TITLE: Defining epigenetic regulators of tumor heterogeneity and metastasis in melanoma

STUDY_SECTION: TPM

STUDY_SECTION_NAME: Tumor Progression and Metastasis Study Section[TPM]


FUNDING_MECHANISM: RESEARCH CENTERS

ORG_CITY: BIRMINGHAM

ORG_NAME: BIRMINGHAM VA MEDICAL CENTER

ORG_STATE: AL

PHR: Black adults in the US have the highest prevalence rate of hypertension and heart failure in the world. Blacks have higher xanthine oxidase activity than Whites. This grant will measure left ventricular function with cardiac magnetic resonance imaging after blockade of xanthine oxidase with allopurinol in Black Veterans.

PI_NAMEs: DELL'ITALIA, LOUIS J. (contact)

PROJECT_TERMS: Adult;African American;African American population;Allopurinol;Bioenergetics;Black Populations;Black race;Blood Pressure;Calcium;Cardiac;cardiac magnetic resonance imaging;Cardiac Myocytes;Cities;Clinical Trials;Consensus;cytokine;Death Rate;depressive symptoms;Diastolic blood pressure;Diuretics;EFRAC;exercise capacity;Functional disorder;Generations;Goals;Grant;Health;Health Care Costs;Heart failure;High Prevalence;high risk population;Hydrogen Peroxide;Hypertension;hypertensive;Hypoxanthines;Impairment;improved;Incidence;indexing;Inflammatory;Innate Immune Response;Kansas;Left;Left Ventricular Dysfunction;Left Ventricular Function;Left Ventricular Hypertrophy;Left Ventricular Mass;Left Ventricular Remodeling;Left ventricular structure;Link;Magnetic Resonance;Measures;Mitochondria;Mitochondrial DNA;Molecular;Morbidity - disease rate;mortality;Myofibrils;Oxidants;Oxidative Stress;Pathway interactions;Patients;Persons;Pharmaceutical Preparations;Physiologic intraventricular pressure;Plasma;Population;preservation;Prevalence;Preventive;Production;Quality of life;Questionnaires;Radial;Reporting;Resistant Hypertension;Risk Factors;Severities;Shortening Fraction;Spironolactone;Superoxides;Symptoms;Testing;Therapeutic;Thick;Toll-like receptors;Ventricular;Veterans;Walking;Work;Xanthine Oxidase;Xanthines

PROJECT_TITLE: Allopurinol Improves Diastolic Function in African Americans with Resistant Hypertension

STUDY_SECTION: RRDS

STUDY_SECTION_NAME: Rehabilitation Research and Development SPiRE Program[RRDS]


NIH_SPENDING_CATS: Clinical Research;Digestive Diseases;HIV/AIDS;Hepatitis;Hepatitis - B;Immunotherapy;Infectious Diseases;Liver Disease

ORG_CITY: LONDON

ORG_COUNTRY: UNITED KINGDOM

ORG_FIPS: UK

ORG_NAME: UNIVERSITY COLLEGE LONDON

ORG_ZIPCODE: WC1E 6BT

PHR: Project Narrative In depth immunological studies of clinical material (blood and liver) to evaluate immune pathways/interplay between key immune cell populations in co-infected vs. HBV mono- infected patients and selective harnessing of adaptive NK cells to effect a functional cure.

PI_NAMEs: PEPPA, DIMITRA  (contact)

PROGRAM_OFFICER_NAME: RADKE, JOSHUA BRYAN

PROJECT_TERMS: Antibodies;antiretroviral therapy;Autologous;Blood;CD8-Positive T-Lymphocytes;Cell Physiology;Cells;Chronic;Clinical;clinical material;Clinical Trials;co-infection;cohort;cytokine;Development;effective therapy;efficacy evaluation;Endosomes;Endowment;env Gene Products;Exclusion;exhaustion;Exhibits;Fine needle aspiration biopsy;Genetic Transcription;Goals;Hepatic;Hepatitis B Infection;Hepatitis B Virus;high risk;HIV;HIV Infections;Human;Immune;immune activation;Immune response;Immunologics;immunoregulation;Immunotherapeutic agent;innovation;Knowledge;Liver;Malignant Neoplasms;Mediating;Memory;Metabolic;Molecular;Natural Killer Cell Immunotherapy;Natural Killer Cells;neutralizing antibody;novel;Outcome;Pathogenicity;Pathway interactions;Patients;Peripheral;peripheral blood;Phenotype;Population;Process;Production;Property;Proteomics;receptor;Recovery;Reporting;Residual state;Resolution;response;restraint;Role;single cell analysis;single-cell RNA sequencing;Site;T-Cell Activation;T-Lymphocyte;Testing;Therapeutic;Tissues;Toxic effect;transcriptomics;Vaccination;Vaccine Therapy;Viral;Virus;Virus Diseases;Virus Replication;Work

PROJECT_TITLE: Exploiting Natural Killer cells in HIV/HBV co-infection to achieve eradication

STUDY_SECTION: HIVD

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


NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Infectious Diseases;Mental Health;Networking and Information Technology R&D (NITRD);Prevention;Social Determinants of Health;Telehealth

ORG_CITY: SAN DIEGO

ORG_DEPT: PSYCHOLOGY

ORG_NAME: SAN DIEGO STATE UNIVERSITY

PHR: We propose here a theoretically-grounded (in the IMB model), accessible and sustainable mHealth PrEP care continuum intervention for gay, bisexual, and other men who have sex with men (GBMSM) and transgender women (TW), called eSTEP (Electronic Support To Engage with PrEP). The eSTEP WebApp will be tailored by sexuality and gender status and include a set of interactive components delivered before in-person HIV testing (e.g., PrEP information on the benefits of PrEP) and after the participant tests HIV-negative and agrees to start PrEP (e.g., adherence self-monitoring). If feasible and acceptable, eSTEP will be the first scalable mHealth intervention that addresses the full PrEP continuum of care for GBMSM and TW to help reach the End the HIV Epidemic goal of substantially reducing new HIV infections in the US.

PI_NAMEs: HORVATH, KEITH JOSEPH (contact);LITTLE, SUSAN JANET

PROGRAM_OFFICER_NAME: STIRRATT, MICHAEL JAMES

PROJECT_TERMS: acceptability and feasibility;Address;Adherence;Agreement;AIDS prevention;Appointment;Awareness;Behavioral;Biological;Bisexual;Black race;Blood;care outcomes;Caring;Clinic;Clinical;Communities;community advisory board;Continuity of Patient Care;Data;Databases;Development;Devices;Dose;Dryness;eHealth;Electronics;Eligibility Determination;eligible participant;Epidemic;ethnic minority;Feedback;flexibility;Focus Groups;Follow-Up Studies;Gays;Gender;Goals;Health;Hearing;high risk;high risk population;HIV;HIV Infections;HIV Seronegativity;human centered design;Human immunodeficiency virus test;improved;Individual;innovation;Internet;Intervention;Interview;Latinx;meetings;member;men;men who have sex with men;mHealth;mhealth interventions;Minority;Modeling;Monitor;Motivation;Outcome;Participant;Patient Self-Report;Persons;pre-exposure prophylaxis;Preparation;prevent;primary outcome;Procedures;Process;programs;Provider;Publishing;Qualifying;racial minority;Randomized;Randomized, Controlled Trials;Recommendation;Reporting;Resources;Risk Factors;Risk Reduction;Running;scale up;secondary outcome;Series;Services;Sexual Health;Sexuality;Site;skills;social stigma;Spottings;Stigmatization;Surveys;Testing;therapy development;Time;transgender women;treatment arm;Universities;uptake;usability;Visit;web site;willingness

PROJECT_TITLE: eSTEP: An integrated mHealth intervention to engage high-risk individuals along the full PrEP care continuum


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Clinical Research;Emerging Infectious Diseases;Genetics;Infectious Diseases;Prevention

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: PROJECT NARRATIVE Staphylococcus aureus, including MRSA, is among the most common causes of human bacterial infections, and it is thought that it spreads in hospitals before causing new infections. By examining the whole genomes (that is, all DNA gene sequences) of S. aureus strains carried asymptomatically on admission and those causing infections in patients on two hospital units, we will investigate how genetic characteristics of the bacteria influence the likelihood of their spread from person to person in the hospital. We will also determine if healthcare workers or inanimate objects serve as carriers of bacteria later found to spread to new patients, and with this information, improved, targeted preventive interventions can later be introduced to decrease the risk of S. aureus infections in hospitals.

PI_NAMEs: DAVID, MICHAEL ZDENEK (contact)

PROGRAM_OFFICER_NAME: HUNTLEY, CLAYTON C

PROJECT_TERMS: acquired drug resistance;acquired factor;Admission activity;Affect;Antibiotic Resistance;Antimicrobial Resistance;Area;Bacteria;Bacterial Infections;Bacteriophages;beta-Lactams;Characteristics;clinical risk;Code;cohort;Collection;Communities;Data;Data Collection;Detection;discrete data;Disease Outbreaks;Distant;DNA;Environment;Evolution;Frequencies;Future;Genes;Genetic;genetic discrimination;Genetic Markers;genome sequencing;genomic data;Goals;Hand;health care settings;Health Personnel;Healthcare;high risk;hospital bed;Hospital Units;Hospitalization;Hospitals;Human;Human body;improved;Individual;Infection;Infection Control;Infectious Skin Diseases;Inpatients;Investigation;Link;Lung infections;methicillin resistant Staphylococcus aureus;methicillin susceptible Staphylococcus aureus;microbial;Mobile Genetic Elements;Mucous Membrane;neonate;Nose;Nosocomial Infections;Obesity;Organ;pathogen;Pathogenicity;Pathway interactions;Patients;Patients' Rooms;Pennsylvania;Persons;Plasmids;Population;Prevalence Study;prevent;preventive intervention;Preventive measure;Process;Resistance;resistance factors;resistant strain;Resolution;Risk;Risk Factors;Route;Sampling;Sepsis;Site;Skin;Staphylococcus aureus;Staphylococcus aureus infection;Testing;trait;transmission process;University Hospitals;Variant;Virulence;Virulence Factors;whole genome

PROJECT_TITLE: Staphylococcus aureus SPREAD (S. aureus Study of Prevalence Resistance and Environmental Dissemination)

STUDY_SECTION: CRFS

STUDY_SECTION_NAME: Clinical Research and Field Studies of Infectious Diseases Study Section[CRFS]


NIH_SPENDING_CATS: Cardiovascular;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Lung;Racial and Ethnic Minority Health Research

ORG_CITY: DALLAS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: Project Narrative There is a shortage of M.D.-scientists despite the growing need in research. We propose a research training program to train a diverse group of M.D. residents who will conduct laboratory-based, translational, clinical, and population research to detect, treat, and prognosticate diseases affecting the heart, lungs, and blood throughout the human lifespan.

PI_NAMEs: ROHATGI, ANAND KUMAR (contact)

PROGRAM_OFFICER_NAME: SCHOPFER, DAVID WESLEY

PROJECT_TERMS: Address;Adult;Affect;Asian;Asian Indian;Biomedical Research;Black race;Blood;Breeding;Bronchopulmonary Dysplasia;Cardiovascular Diseases;career;Cessation of life;Childhood;Chronic Disease;Clinical;Clinical Research;Communities;Conceptions;Congenital Heart Defects;Cystic Fibrosis;design;Detection;Development;Diagnostic;disability;Disease;disease prognosis;Doctor of Medicine;Ensure;Environment;Equilibrium;Evaluation;experience;Faculty;faculty mentor;Foundations;Funding;Future;Hawaiian;Health;health disparity;Heart;Heart Diseases;Hemophilia A;Hispanic;Hospitalization;Hospitals;Human;human disease;improved;Individual;innovation;Institution;interest;Internal Medicine;Intervention;Investigation;Laboratories;life span;Lung;Lung Diseases;Maintenance;medical schools;Medical Students;member;Mentors;Minority;Monitor;multidisciplinary;next generation;Outcome;patient population;Patient Recruitments;Patients;Pediatrics;personalized medicine;Physicians;Population;population health;Population Heterogeneity;Population Research;Prevention;programs;Race;recruit;Research;Research Personnel;Research Priority;Research Training;Residencies;Risk;Scientist;skills;strength training;Teaching Hospitals;Texas;Training;Training Programs;Translational Research;Underrepresented Populations;United States National Institutes of Health;Universities;Woman

PROJECT_TITLE: University of Texas Southwestern - Stimulating Access to Research in Residency (UT-StARR) Program


NIH_SPENDING_CATS: Clinical Research;Genetics;Hematology;Human Genome;Infectious Diseases;Sepsis

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: PROJECT NARRATIVE Sepsis is the most frequent cause of death in United States hospitals, and the number one cause of death worldwide, responsible for 11 million deaths in 2017. Primary drivers of sepsis morbidity and mortality are immune exhaustion leading to deadly secondary infection, and organ tissue damage leading to multi-organ failure. Here we seek to develop a deeper understanding of these processes through cell-free DNA epigenomics to track the kinetics and dynamics of dysfunctional/exhausted T cells as well as organ damage during sepsis, which should stimulate future research efforts to ameliorate these primary drivers of sepsis-mediated morbidity and mortality.

PI_NAMEs: CHAUDHURI, AADEL  (contact)

PROGRAM_OFFICER_NAME: ZHAO, XIAOLI

PROJECT_TERMS: Bioinformatics;Blood;Blood specimen;Cause of Death;cell free DNA;Cells;Cessation of life;Data;Disease;DNA analysis;DNA methylation profiling;epigenomics;exhaust;exhaustion;genome wide methylation;Immune;improved;innovation;Intensive Care Units;Kinetics;Literature;Mediating;Methodology;Methods;Morbidity - disease rate;mortality;Multiple Organ Failure;Organ;Outcome;Patient Admission;Patients;Plasma Cells;Process;programs;Research;secondary infection;Sepsis;Source;State Hospitals;T-Lymphocyte;Tissues;United States;Work

PROJECT_TITLE: Cell-free DNA epigenomics to track the dynamics of organ damage and immune exhaustion during sepsis

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


ORG_CITY: HANOVER

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: DARTMOUTH COLLEGE

ORG_STATE: NH

PHR: Project Narrative Inhibition of the Wnt Receptor Complex by the Tumor Suppressor Adenomatous Polyposis Coli Colorectal cancer is the second leading cause of cancer-related death in the United States, with limited options for therapy. The goal of this proposed study is to determine how the one critical protein that prevents the initiation step of colorectal cancer normally functions, to elucidate what happens in colorectal cells when this protein is lost, and to devise and test new strategies to block the growth of colorectal cancer cells based on these discoveries. The knowledge gained from this proposed study will provide new approaches for the treatment for colorectal cancer.

PI_NAMEs: AHMED, YASMATH  (contact);LEE, ETHAN ;ROBBINS, DAVID J

PROGRAM_OFFICER_NAME: MAAS, STEFAN

PROJECT_TERMS: Antibodies;APC gene;APC mutation;APC2 gene;Apoptosis;Attenuated;beta catenin;Binding;Biochemistry;cancer cell;Cancer Etiology;cancer initiation;Cancer Model;Cell Maintenance;cell motility;Cell Proliferation;cell type;Cells;Cessation of life;Clathrin;Clinical;Colon;colon cancer patients;colon carcinogenesis;Colorectal;Colorectal Cancer;colorectal cancer treatment;Complex;cost effective;Critical Pathways;density;Development;driver mutation;Drosophila genus;druggable target;efficacy testing;Endocytosis;enhancer-binding protein AP-2;Genes;Genetic;Genetic Engineering;Goals;Growth;Human;Human Engineering;In Vitro;in vivo;inhibitor;Intestines;Knowledge;LDL-Receptor Related Protein 1;Left;Ligands;lipoprotein receptor-related protein 6;Maintenance;Malignant Neoplasms;MAP Kinase Gene;Mediating;Modeling;Molecular;Molecular Weight;multidisciplinary;Mus;mutant;Mutation;Neoplasm Metastasis;novel;novel therapeutic intervention;Organoids;paralogous gene;Pathway interactions;patient derived xenograft model;Physiological;PIK3CG gene;Predisposition;prevent;Proliferating;Proteins;Proteolysis;Proteomics;Publishing;receptor;Receptor Activation;Role;Screening procedure;Series;Signal Transduction;Signal Transduction Pathway;stem cells;Sucrose;Testing;Therapeutic;TP53 gene;Transcription Coactivator;Transcriptional Activation;Transforming Growth Factor beta;Translating;tumor;tumor progression;Tumor Suppressor Proteins;Tumorigenicity;United States;WNT Signaling Pathway;Xenograft procedure

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


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Clinical Research;Diabetes;Emerging Infectious Diseases;HIV/AIDS;Infectious Diseases;Maternal Health;Maternal Morbidity and Mortality;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Prevention;Rare Diseases;Tuberculosis;Women's Health Research

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: PROJECT NARRATIVE Diabetes weakens the immune response to tuberculosis (TB) and triples the risk of developing active TB, but we do not yet know whether gestational diabetes has the same effect. The proposed research addresses a significant research gap that threatens the health of pregnant women worldwide: gestational diabetes affects 16% of pregnancies globally and up to 40% in India, where TB is a major cause of maternal mortality, especially for women with HIV. We propose to determine how HIV causes gestational diabetes and how gestational diabetes leads to increased active TB, which responds to the NIH priority of pursuing novel treatment strategies for HIV, diabetes and TB in pregnant women, a historically underrepresented group in clinical research.

PI_NAMEs: MATHAD, JYOTI S (contact)

PROGRAM_OFFICER_NAME: LOMBO RODRIGUEZ, TANIA

PROJECT_TERMS: Address;Adverse effects;Affect;antenatal;antiretroviral therapy;base;BCG Vaccine;Blood;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Physiology;Cells;Cellular Immunity;Child;Chronic;Clinic;Clinical;Clinical Research;Clinical Trials;cohort;Country;cytokine;Data;Detection;diabetes management;Diabetes Mellitus;Diabetes prevention;diabetes risk;Disease;Enrollment;experience;Flow Cytometry;Foundations;Functional disorder;Funding;Gestational Diabetes;glucose metabolism;glucose receptor;GLUT 4 protein;Goals;Government;Growth;Health;Health Priorities;high risk;high risk population;High Risk Woman;HIV;HIV/TB;Home;Immune;Immune response;Immunity;Impairment;improved;Incidence;India;Infant;infection risk;Inflammation;Inflammatory;Influenza;Insulin Resistance;insulin signaling;Intervention;Knowledge;Link;Longitudinal cohort study;Longitudinal Studies;Macrophage;Maternal and Child Health;Maternal Mortality;Mediating;medical schools;Memory;Mother-to-child HIV transmission;Mycobacterium tuberculosis;Mycobacterium tuberculosis antigens;Neonatal Mortality;Non-Insulin-Dependent Diabetes Mellitus;novel;novel strategies;OGTT;Persons;Placenta;Plasma;Population;Postpartum Period;Pregnancy;Pregnant Women;Prevalence;prevent;preventable death;Prevention;Prevention approach;Research;Risk;Role;Sampling;screening;Second Pregnancy Trimester;T cell response;T memory cell;T-Cell Activation;T-Lymphocyte;Third Pregnancy Trimester;TNF gene;treatment strategy;Tuberculosis;Underrepresented Populations;United States National Institutes of Health;vaccine response;Visit;Woman;women's diagnosis;Work

PROJECT_TITLE: HIV, gestational diabetes and TB in pregnancy

STUDY_SECTION: HCAC

STUDY_SECTION_NAME: HIV Coinfections and HIV Associated Cancers Study Section[HCAC]


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Assistive Technology;Behavioral and Social Science;Bioengineering;Clinical Research;Clinical Trials and Supportive Activities;Disability Research;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurosciences;Rehabilitation

ORG_CITY: PORTLAND

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: PROJECT NARRATIVE The populations of US citizens with severe speech and physical impairments secondary to neurodevelopmental and neurodegenerative diseases are increasing as medical technologies advance and successfully support life. These individuals with limited to no movement could potentially contribute to their medical decision making, informed consent, and daily caregiving if they had faster, more reliable means that adapt to their best access methods in communication technologies, as proposed in BCI-FIT. This project implements the translation of basic computer science and engineering into clinical care, supporting the proposed NIH Roadmap and public health initiatives.

PI_NAMEs: FRIED-OKEN, MELANIE  (contact)

PROGRAM_OFFICER_NAME: MILLER, ROGER

PROJECT_TERMS: acronyms;Adult;alternative communication;Attention;Behavioral;Brain;brain computer interface;Calibration;caregiving;Clinical;Clinical assessments;clinical care;Clinical Data;clinical implementation;Clinical Sciences;Cognition;Cognitive;cognitive ability;Collaborations;Communication;Communities;community based participatory research;computer science;Computers;Data;Decision Making;disability;Disease;Drowsiness;Electroencephalography;Engineering;Environment;EP300 gene;experience;Experimental Designs;experimental study;Eye Movements;Fatigue;Feedback;Goals;Guidelines;Head Movements;improved;Individual;Informed Consent;innovation;Knowledge;Language;Learning;learning strategy;Letters;Life;Locked-In Syndrome;Machine Learning;Measures;Medical;Medical Technology;Methods;Modality;Modeling;motor disorder;Motor Skills;Movement;multidisciplinary;multimodal fusion;multimodality;Muscle;Natural Language Processing;Neurodegenerative Disorders;Neurodevelopmental Disorder;neurophysiology;Participant;Partner Communications;Pattern;Performance;Persons;Pharmaceutical Preparations;phrases;physical impairment;Policies;Population;Protocols documentation;Psychological reinforcement;Public Health;Questionnaires;Recommendation;Rehabilitation therapy;Research;Research Design;residence;response;Role;satisfaction;Science;Secondary to;Self-Help Devices;sensor;Sensory;signal processing;Signal Transduction;simulation;Solid;Source;Speech;Speed;spelling;Supplementation;System;Techniques;Technology;Testing;theories;Time;Training;transfer learning;Translational Research;Translations;United States National Institutes of Health;verbal;visual tracking;Vocabulary;Workload;Writing

PROJECT_TITLE: Optimizing BCI-FIT: Brain Computer Interface - Functional Implementation Toolkit


NIH_SPENDING_CATS: Autoimmune Disease;Biotechnology;Clinical Research;Clinical Trials and Supportive Activities;Gene Therapy;Genetics;Lung;Pediatric;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Transplantation

ORG_CITY: CINCINNATI

ORG_NAME: CINCINNATI CHILDRENS HOSP MED CTR

ORG_STATE: OH

PHR: NARRATIVE The proposed research is relevant to public health because it is expected to establish the feasibility of the first specific therapy for hPAP in children and introduces a novel approach for treating lung diseases, pulmonary macrophage transplantation. This approach will represent a major improvement over the current therapy, whole lung lavage, which is inefficient, highly invasive, and unavailable at most clinical centers particularly for use in children, some of whom require it as frequently as every one to two months. Thus, the proposed re- search is relevant to the part of NIH’s mission that pertains to developing fundamental knowledge that will help to reduce the burden of human illness, and will also inform mechanisms by which GM-CSF contributes to alve- olar macrophage development, surfactant homeostasis, and lung function in health and disease.

PI_NAMEs: KRISCHER, JEFFREY P;TRAPNELL, BRUCE C (contact)

PROGRAM_OFFICER_NAME: VUGA, LOUIS J

PROJECT_TERMS: Ablation;Address;Adopted;Adult;Adverse event;Advisory Committees;Age Months;Alveolar;Alveolar Macrophages;Alveolus;Animal Model;Autologous;Autologous Transplantation;Biological;Biological Markers;Bone Marrow;Bone Marrow Purging;Bronchoalveolar Lavage;CD34 gene;Cell Proliferation;Cell Therapy;Cell Transplantation;Cells;Child;Childhood;Clinical;clinical center;clinical development;clinical outcome measures;Clinical Protocols;Clinical Research;Clinical Trials;Clinical Trials Data Monitoring Committees;cohort;Complement;CSF2RA gene;design;Development;Diagnosis;Diagnostic;Disease;Dose;driving force;Drug Kinetics;efficacy clinical trial;efficacy study;efficacy trial;Engraftment;Excision;Feedback;first-in-human;Formulation;Functional disorder;Future;gene complementation;gene correction;Gene Transfer;Genes;Goals;Good Manufacturing Process;Granulocyte-Macrophage Colony-Stimulating Factor;Granulocyte-Macrophage Colony-Stimulating Factor Receptors;Growth;Health;Health Status;Homeostasis;Human;human study;improved;in vivo;Informed Consent;Inherited;innovation;Institution;institutional biosafety committee;Institutional Review Boards;Intervention;Investigational Drugs;Investigational New Drug Application;Knowledge;Lentivirus Vector;Lung;Lung Diseases;Macrophage;manufacture;Measures;Mediating;Medical;Medical center;Mission;Morbidity - disease rate;mouse model;Mus;Mutation;Myeloid Cells;nonhuman primate;novel strategies;Outcome;Outcome Measure;Pamphlets;Pathogenesis;Patients;pediatric patients;Pharmacodynamics;pharmacokinetics and pharmacodynamics;Pharmacotherapy;Phase;phase 2 study;phase I trial;Phenotype;Physiological;Population;Preparation;Procedures;programs;Public Health;Pulmonary Alveolar Proteinosis;pulmonary function;Pulmonary Surfactants;Quality of life;Radiology Specialty;Receptor Signaling;Reporting;Research;Research Personnel;Resources;Respiratory Failure;response;Safety;safety assessment;self-renewal;Serious Adverse Event;Severities;Signal Transduction;stability testing;supplemental oxygen;surfactant;Therapeutic;therapeutic development;Time;Toxicology;Transplantation;transplantation therapy;United States National Institutes of Health;Writing

PROJECT_TITLE: Human gene transfer & macrophage cell transplantation therapy of hereditary PAP (hPAP)


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Bioengineering;Coronaviruses;Emerging Infectious Diseases;HIV/AIDS;Infectious Diseases

ORG_CITY: SEATTLE

ORG_NAME: UNIVERSITY OF WASHINGTON

PHR: NARRATIVE Protein-mediated membrane fusion is a fundamental process that is essential for biological functions as wide ranging as gamete fertilization, formation of placenta, synaptic vesicle trafficking, tissue development, mitochondrial function, and enveloped virus infection. Despite its significance, relatively little is understood at a mechanistic and structural level regarding how specialized fusion protein machinery and membranes interact in order to go from a prefusion to activated fusogenic to the final formation of a fusion pore. Here cryo-electron microscopy and structural mass spectrometry will be used to study membrane fusion in two biomedically important enveloped viruses, thus providing new insights into how very different protein machines accomplish similar physical functions of merging two distinct membranes into one.

PI_NAMEs: LEE, KELLY KEISEN (contact)

PROGRAM_OFFICER_NAME: SHANKAR, UDAY K

PROJECT_TERMS: 2019-nCoV;ACE2;Acute;Address;Adopted;Alpha Virus;Architecture;Binding;Biological;Biological Process;CD4 Antigens;Cell fusion;Cells;Chikungunya virus;Chimeric Proteins;Coronavirus;Coupled;Cryo-electron tomography;Cryoelectron Microscopy;density;Deuterium;Development;dimer;Disease;Engineering;Event;Evolution;experimental study;Fertilization;Freezing;Germ Cells;global health;Goals;HIV;Hydrogen;Image;Individual;Influenza Hemagglutinin;influenzavirus;inhibitor;insight;Invaded;Investigation;Knowledge;Length;Lipid Bilayers;Maintenance;Mass Spectrum Analysis;Mediating;Membrane;Membrane Fusion;Membrane Lipids;Membrane Proteins;Methods;Mitochondria;Molecular;Molecular Conformation;molecular imaging;Monitor;Mutation;nanometer resolution;neutralizing antibody;novel;pandemic impact;Pathway interactions;Peptide Hydrolases;Physical Function;Placenta;prevent;Process;programs;protein structure;Proteins;Reaction;receptor;receptor binding;Research;Resolution;Sampling;SARS-CoV-2 spike protein;Signal Transduction;Societies;Structure;Synapses;Synaptic Vesicles;System;targeted treatment;Testing;Time;Tissues;TMPRSS2 gene;trafficking;Vertebral column;Vesicle;Viral;Virion;Virus;Virus Diseases;Virus-like particle;Visualization;Work

PROJECT_TITLE: Lipid Bilayer Remodeling and Protein Intermediates During Membrane Fusion

STUDY_SECTION: BBM

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