NIH_SPENDING_CATS: Anxiety Disorders;Attention Deficit Hyperactivity Disorder (ADHD);Autism;Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Depression;Genetics;Human Genome;Intellectual and Developmental Disabilities (IDD);Major Depressive Disorder;Mental Health;Mental Illness;Neurosciences;Pediatric;Serious Mental Illness;Tourette Syndrome

ORG_CITY: WEST LAFAYETTE

ORG_NAME: PURDUE UNIVERSITY

ORG_STATE: IN

PHR: PROJECT NARRATIVE Tourette Syndrome (TS) is a complex disorder, for which there is no cure and efforts to develop novel treatments are hampered by our limited understanding of the neurobiology and brain structural and functional deficits that underlie the disorder. TS is also highly heterogeneous and often comorbid with Obsessive Compulsive Disorder (OCD), Attention Deficit and Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), Major Depressive Disorder (MDD), and Anxiety Disorder (AXD), further complicating our efforts. Leveraging ties to ENIGMA and an international network of collaborators, we will pursue the largest neuroimaging and genetics studies for TS to date, pooling, harmonizing and jointly analyzing worldwide datasets for TS and highly comorbid disorders shedding light into TS neurobiology and identifying biomarkers that could help tailor individualized management approaches.

PI_NAMEs: PASCHOU, PERISTERA  (contact)

PROGRAM_OFFICER_NAME: PEVSNER, JONATHAN ABRAM

PROJECT_TERMS: Address;Affect;Agreement;analysis pipeline;Anxiety Disorders;Attention deficit hyperactivity disorder;autism spectrum disorder;Behavioral;biobank;Biological Markers;biomarker identification;biomarker validation;Black race;Brain;Brain imaging;Brain region;Categories;Child;Clinical;Clinical Data;cohort;Collaborations;comorbidity;Complex;Country;Data;Data Analyses;Data Set;Databases;Development;Diagnostic;Disease;Environmental Risk Factor;Etiology;Functional disorder;Functional Magnetic Resonance Imaging;Future;gene interaction;Generations;Genetic;genetic association;genetic information;Genetic Risk;Genetic study;genome wide association study;genomic locus;Genomics;Gilles de la Tourette syndrome;Goals;Heterogeneity;Hispanic;Impairment;improved;Individual;individual patient;individualized medicine;Infrastructure;International;Lead;Light;Magnetic Resonance Imaging;Maintenance;Major Depressive Disorder;Maps;Mental disorders;Meta-Analysis;Motor Tics;Neurobiology;neuroimaging;neuropsychiatric disorder;novel;Obsessive-Compulsive Disorder;outcome prediction;Participant;Pathway interactions;Patients;personalized management;Phenotype;Play;population based;Population Heterogeneity;portability;psychiatric genomics;Publishing;Quality Control;Quality of life;recruit;Reproducibility;Research Personnel;Resources;risk variant;Role;Sample Size;Sampling;Site;Standardization;structural imaging;Structure;success;Testing;Vocal Tics;working group

PROJECT_TITLE: Tourette Syndrome genetics and neuroimaging international collaborative study

STUDY_SECTION: NAME

STUDY_SECTION_NAME: Neurological, Aging and Musculoskeletal Epidemiology Study Section[NAME]


ADMINISTERING_IC: AG

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE ON AGING

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);Behavioral and Social Science;Brain Disorders;Cardiovascular;Cerebrovascular;Clinical Research;Dementia;Eye Disease and Disorders of Vision;Heart Disease;Hypertension;Neurodegenerative;Neurosciences;Prevention;Social Determinants of Health;Vascular Contributions to Cognitive Impairment and Dementia (VCID);Women's Health Research

ORG_CITY: Columbus

ORG_COUNTRY: UNITED STATES

ORG_DEPT: OPHTHALMOLOGY

ORG_FIPS: US

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: PROJECT NARRATIVE Remodeling of microvessels in the retina from hypertension may be a clue to vascular risk factors of cognitive decline during aging. Our proposal will begin to advance understanding of the retinal microvessels as a biomarker of hypertensive effects on cognitive function. Results from our proposed studies will contribute new knowledge about the hypertension-related mechanisms of dementia, one of public health and social care priorities worldwide with a rapid aging population.

PI_NAMEs: KARVONEN-GUTIERREZ, CARRIE ANNE;MOROI, SAYOKO E (contact)

PROGRAM_OFFICER_NAME: ROBERTS, LUCI

PROJECT_TERMS: Activities of Daily Living;Age;Aging;aging population;Alzheimer's Disease;Alzheimer's disease risk;Behavior;Biological Aging;Biological Factors;Biological Markers;Blood Chemical Analysis;Blood Pressure;blood pressure control;blood pressure reduction;Blood Vessels;Boston;Brain;brain health;Cardiovascular system;care providers;Caring;Central Nervous System;Clinical;Clinical assessments;clinical examination;Cognitive aging;cognitive function;cognitive testing;cohort;Cohort Studies;Data;Data Set;Dementia;demographics;design;Digit structure;digital;Drug Side Effects;Evaluation;Event;Eye;Fundus;Future;Genetic Risk;Goals;Growth;Health;healthy aging;Heart;Heart Diseases;human old age (65+);Hypertension;hypertensive;Hypertensive Retinopathy;Image;Impaired cognition;improved;Individual;Inflammation;Inflammatory;Intervention;Kidney;Knowledge;late life;Lesion;Life Style;Longitudinal Studies;meetings;Memory;menopausal aging;Mental disorders;Michigan;middle age;mild cognitive impairment;Modality;Modeling;Myocardial Infarction;Nervous System Disorder;older adult;ophthalmic examination;Optical Coherence Tomography;Optics;Organ;Pharmaceutical Preparations;Population;Prevalence;prevent;Prevention;Public Health;public health priorities;Publications;Race;Recording of previous events;response;Retina;Retinal Diseases;retinal imaging;retinal ischemia;Risk;secondary analysis;Sensitivity and Specificity;social;social factors;social health determinants;Standardization;Stroke;Study of Women's Health Across the Nation;Surveys;teleophthalmology;Testing;Thick;Thinking;tomography;translational impact;Treatment outcome;Vascular remodeling;vascular risk factor;Visit;Woman;Women's Health;Women's study;World Health Organization Disability Assessment Schedule

PROJECT_TITLE: Evaluation of retinal imaging as a biomarker of hypertensive effects on cognitive function

STUDY_SECTION: ASG

STUDY_SECTION_NAME: Aging Systems and Geriatrics Study Section[ASG]


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

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

ORG_CITY: UNIVERSITY PARK

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: PENNSYLVANIA STATE UNIVERSITY, THE

ORG_STATE: PA

PHR: PROJECT NARRATIVE  This project examines the role of domestic and international migration in determining area-level mortality rates and geographic inequality in mortality across counties, metropolitan areas, states, and regions of the United States between 1990 and present, as well as cross-national inequalities in mortality among 18 high- income countries. In addition to investigating how low-mortality migrants may decrease average mortality rates of specific areas, we assess how migrants impact the mortality rates of non-migrants by making areas where they settle better places to live. The findings inform our understanding of how policies relating to migration may have short- and long-term effects on place-based health and health inequalities.

PI_NAMEs: HENDI, ARUN ;HO, JESSICA YU (contact)

PROGRAM_OFFICER_NAME: BANDIERA, FRANK

PROJECT_TERMS: Adult;Affect;Age;Alcohol abuse;American;Area;Automobile Driving;built environment;Cardiometabolic Disease;cardiometabolic risk;Censuses;Characteristics;cigarette smoking;Communities;Country;County;Data;Death Rate;Deterioration;Dimensions;Drug abuse;Economic Conditions;Economics;Education;Employment;experience;follow-up;geographic disparity;Geographic Locations;geographic population;Geography;Health;health care availability;health inequalities;Health Promotion;Heterogeneity;Immigration;improved;Income;Individual;Inequality;Infrastructure;insight;International;International Migrations;Investments;Knowledge;Life Expectancy;life span;Life Tables;Link;Long-Term Effects;Measures;Methodology;Methods;metropolitan;middle age;Migrant;migration;Modeling;mortality;Mortality Decline;mortality disparity;Native-Born;Nonmigrant;Nurses;Occupations;Out-Migrations;Personal Satisfaction;Persons;Physicians;Policies;Population;prescription monitoring program;Process;Property;public database;Quality of life;Quasi-experiment;Research Design;Research Personnel;Resources;response;Role;Safety;Shapes;Social Conditions;socioeconomics;Stream;Suicide;trend;Unemployment;United States;Variant;Vital Statistics;Work

PROJECT_TITLE: Migration and Geographic Inequality in Mid-Life Mortality


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Cardiovascular;Clinical Research;Genetics;Heart Disease;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: BOSTON

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

ORG_STATE: MA

PHR: NARRATIVE  Desmosomes connect heart muscle cells and function as signaling centers, and desmosome mutations cause arrhythmogenic cardiomyopathy. However, the mechanisms by which perturbation of desmosomes leads to abnormal heart rhythm and contraction is not known. We will study the function of desmosomes and how desmosome mutations cause cardiomyopathy.

PI_NAMEs: PU, WILLIAM TSWENCHING (contact)

PROGRAM_OFFICER_NAME: BALIJEPALLI, RAVI C

PROJECT_TERMS: Ablation;Acceleration;Adhesives;Adipose tissue;Adult;Arrhythmia;arrhythmogenic cardiomyopathy;ATAC-seq;Biomedical Engineering;candidate identification;candidate selection;Cardiac;Cardiac Myocytes;Cardiomyopathies;Cell Nucleus;Cells;Chemicals;Complex;Data;defined contribution;desmoplakin;Desmosomes;Development;DISC components;Disease;Dissection;Elements;Experimental Models;Fluorescent in Situ Hybridization;follow-up;Functional disorder;gain of function;Gene Expression;Gene Expression Regulation;Genes;Genetic;genetic approach;Genetic Transcription;Goals;Heart Abnormalities;Heart failure;heart rhythm;Homeostasis;Human;human induced pluripotent stem cells;improved;In Situ Hybridization;in vivo;induced pluripotent stem cell;inhibitor;innovation;insight;Intercalated disc;Knowledge;Lead;Life;Link;loss of function;Metabolism;Methods;Modeling;Molecular;mosaic;multiple omics;Mus;Muscle function;mutant;Mutation;Myocardial Contraction;Myocardial dysfunction;Myocardium;N-Cadherin;novel;Pathogenesis;Pathway interactions;Patients;Periodicity;Phenotype;Plasma;preservation;protein function;Proteins;Proteomics;Regulatory Element;Relaxation;Resolution;Role;Sarcomeres;Signal Transduction;single molecule;single nucleus RNA-sequencing;Testing;transcriptome;transcriptomics;Ventricular Arrhythmia;WNT Signaling Pathway

PROJECT_TITLE: Desmosomes in cardiomyocyte homeostasis and disease

STUDY_SECTION: MPPB

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


NIH_SPENDING_CATS: Cardiovascular;Heart Disease;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: NEW YORK

ORG_DEPT: PHARMACOLOGY

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

ORG_STATE: NY

PHR: PROJECT NARRATIVE Although all drugs must be tested for their potential to cause ventricular arrhythmia as an adverse event, the probability of an arrhythmia depends on both the drug and the characteristics of the particular patient. This research will advance the use of mathematical models to predict the risk of drug-induced arrhythmia, particularly by developing a platform to assess how patient demographics and comorbidities interact with drugs to increase or decrease personalized risk.

PI_NAMEs: SOBIE, ERIC A (contact)

PROJECT_TERMS: Action Potentials;Address;Adverse event;Affect;Algorithmic Software;Area;Arrhythmia;associated symptom;Calcium;Calibration;Cardiac;Cardiac Electrophysiologic Techniques;Cardiac Myocytes;Characteristics;Chronic;Classification;Communities;comorbidity;computational pipelines;computerized tools;COVID-19 pandemic;Dangerousness;Data;demographics;Disease;drug candidate;drug classification;Drug Combinations;drug development;Drug Modelings;Drug Screening;drug testing;Drug usage;Electrophysiology (science);Event;experimental study;Fever;heart cell;Heart Diseases;Heart failure;Heterogeneity;Hypokalemia;improved;In Vitro;Individual;induced pluripotent stem cell;Inflammation;innovation;Ion Channel;Laboratories;Machine Learning;machine learning algorithm;machine learning classifier;machine learning model;machine learning prediction;mathematical model;Measures;medication safety;Minority;Modeling;Muscle Cells;novel;novel therapeutics;Patients;Pharmaceutical Preparations;Pharmacology;Phenotype;Physiology;Play;Population;Population Heterogeneity;Predisposition;Probability;Reaction;Research;Research Personnel;response;Risk;risk prediction;Role;Safety;sex;Sex Differences;simulation;skills;stem cells;success;System;Testing;Torsades de Pointes;Ventricular;Ventricular Arrhythmia;virtual;Work

PROJECT_TITLE: Predicting determinants of susceptibility to drug-induced arrhythmias

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CVRS-Q(02)]


ADMINISTERING_IC: VA

FUNDING_MECHANISM: OTHERS

IC_NAME: Veterans Affairs

ORG_NAME: VA BOSTON HEALTH CARE SYSTEM

PHR: Memory impairment has a significant impact on a Veteran's ability to lead a productive and fulfilling life, affecting an array of cognitive functions, including the ability to make well-informed healthcare decisions, and directly influencing quality of life. I study the cognitive and neural bases of memory impairment in patients with severe global amnesia as a result of lesions to the medial temporal lobes. Although global amnesia is rare, disruption of the medial temporal lobe memory system occurs in many neurological and psychiatric disorders that affect the Veteran population. Thus, insights gained from the study of amnesia can be applied to the study of other clinical populations. I have examined the impact of memory impairment in Veterans with traumatic brain injury, and currently study how memory impairment may contribute to the development and maintenance of symptoms associated with posttraumatic stress disorder. My work promises to guide clinical assessment of Veterans with memory impairment and may offer new targets for theoretically informed interventions.

PI_NAMEs: VERFAELLIE, MIEKE H. (contact)

PROJECT_TERMS: Address;Affect;Aging;Amnesia;associated symptom;Autobiography;Award;base;Behavior;Behavioral;behavioral outcome;Binding;Blast Injuries;career;Characteristics;Chronic Phase;Clinical;Clinical assessments;Cognition;Cognitive;cognitive control;Cognitive deficits;cognitive function;cognitive neuroscience;comorbidity;Compensation;Corpus striatum structure;Decision Making;Development;discounting;Disease;Elements;Encephalitis;Event;experience;Food;Functional Magnetic Resonance Imaging;Funding;Future;Global Amnesias;Goals;Grant;Healthcare;Heterogeneity;Hippocampus;Human;Impairment;Individual;information processing;Injury;insight;Intervention;Laboratories;Language;language comprehension;language processing;Learning;Lesion;Life;Maintenance;Measures;medial temporal lobe;Memory;Memory Disorders;Memory impairment;Mental disorders;mild traumatic brain injury;military veteran;Mission;Morals;Nervous System Disorder;neural;neuroimaging;neuromechanism;Neuropsychology;Outcome;Pathology;Patients;Performance;physical symptom;Play;Population;Post-Traumatic Stress Disorders;Poverty;preference;Process;Productivity;psychiatric comorbidity;Quality of life;Race;Research;Rest;Retrieval;Rewards;Role;Scientist;Secondary to;Semantic memory;Semantics;Short-Term Memory;simulation;Stroke;Syndrome;System;Thinking;Traumatic Brain Injury;Unconscious State;Update;Veins;Veterans;white matter;Work

PROJECT_TITLE: CSRD Research Career Scientist Award Application


ORG_CITY: DETROIT

ORG_NAME: JOHN D DINGELL VA MEDICAL CENTER

ORG_STATE: MI

PHR: Sleep apnea (SA) is increased in intact and spinal cord injured Veterans and is linked to autonomic, cardiovascular, metabolic and neurocognitive dysfunction. Thus, the development of novel treatments to mitigate associated co-morbidities is imperative. We are exploring the role that serotonin has in exacerbating SA in spinal cord injury, using a non‐anesthetized spontaneously breathing mouse model with or without genetic depletion of central nervous system serotonin. We are also exploring in Veterans if repeated daily exposure to mild intermittent hypoxia (MIH) mitigates co-morbidities linked to SA. We propose MIH targets numerous co- morbidities and initiates respiratory plasticity that enhances upper airway stability. Increased stability could reduce the therapeutic pressure required to treat SA and improve treatment compliance resulting in a secondary pathway to mitigate co-morbidities linked to SA.

PI_NAMEs: MATEIKA, JASON H. (contact)

PROJECT_TERMS: Adenosine;airway muscle;Animals;Apnea;Arousal;Award;Breathing;Cardiovascular system;career;Caring;Central Nervous System;Chest wall structure;comorbidity;Continuous Positive Airway Pressure;Coupled;Development;Diabetes Mellitus;Exposure to;Fatigue;Frequencies;Functional disorder;Genetic;Health;Human;Hypercapnia;Hypertension;Hypoxia;improved;improved outcome;improvement on sleep;Incidence;Individual;Innovative Therapy;Knockout Mice;Laboratories;Legal patent;Limb structure;Link;Metabolic;Metabolic dysfunction;military veteran;Modification;Motor;mouse model;Mus;neural;Neurocognitive;Neuromodulator;Neurons;Norepinephrine;novel;Obstructive Sleep Apnea;Outcome;Outcome Measure;Pathway interactions;Patients;Population;pressure;Prevalence;Publishing;receptor;Recovery;Reflex action;Research;respiratory;Respiratory Diaphragm;response;Role;Scientist;Serotonergic System;Serotonin;Severities;Sleep;Sleep Apnea Syndromes;Spinal Cord;Spinal cord injury;Spinal cord injury patients;Stroke;Therapeutic;trait;treatment adherence;Tryptophan 5-monooxygenase;United States;United States Department of Veterans Affairs;ventilation;Veterans;Work


ADMINISTERING_IC: GM

ED_INST_TYPE: ORGANIZED RESEARCH UNITS

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: TEMPE

ORG_DEPT: PHYSIOLOGY

ORG_NAME: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS

ORG_STATE: AZ

PHR: PROJECT NARRATIVE Attachment of bacteria to tissue surfaces is often the first step in an infection, but how bacteria sense surfaces is poorly understood. The bacterial flagellar motor, which propels bacteria through fluids, is now believed to be a mechanosensor responsible for sensing surfaces. This project will investigate how the motor senses and transduces mechanical forces and will aid in developing preventive or therapeutic strategies against harmful bacterial biofilms.

PI_NAMEs: WADHWA, NAVISH  (contact)

PROGRAM_OFFICER_NAME: AINSZTEIN, ALEXANDRA M

PROJECT_TERMS: Affect;Bacteria;bacterial genetics;Bacterial Infections;Behavior;Binding;Biochemical;Biology;biophysical techniques;Biophysics;Cell Wall;Complex;Data;diguanylate cyclase;extracellular;Filament;Genetic;genomic tools;Goals;Image;improved;individual response;Infection;K-Series Research Career Programs;Link;Liquid substance;Measures;mechanical force;mechanical load;Mechanical Stimulation;Mechanics;mechanotransduction;Mediating;Membrane Potentials;Mentored Clinical Scientist Development Award (K08);Mentors;Microbial Biofilms;Molecular;molecular imaging;Motility;Motor;novel;novel therapeutic intervention;Optics;Osmosis;Outcome;Output;Pathway interactions;Peptidoglycan;Periodicity;Polymers;Positioning Attribute;prevent;Preventive;Process;Proton-Motive Force;Regulation;Research;response;Rotation;Second Messenger Systems;self assembly;sensor;Side;Signal Pathway;Signal Transduction;single molecule;skills;Statistical Models;stoichiometry;Surface;Swimming;Testing;Therapeutic;Tissues;tool;Torque;Training;transmission process;transposon sequencing;Virulence Factors;Work

PROJECT_TITLE: Identifying the mechanisms of mechanosensing by the bacterial flagellar motor

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


ORG_CITY: BLOOMINGTON

ORG_NAME: TRUSTEES OF INDIANA UNIVERSITY

PHR: PROJECT NARRATIVE Hypertension is an important cause of cardiovascular disease morbidity and mortality and affects 46% of Americans. Inflammation and associated immunopathogenesis are key contributors to the development of hypertension. Our studies aim to determine the mechanisms by which PGI2 restrains immune cell function in hypertension, thereby identifying PGI2 as a potential therapeutic for the treatment of hypertension and its associated end-organ damage.

PI_NAMEs: NORLANDER, ALLISON ELIZABETH (contact)

PROGRAM_OFFICER_NAME: OH, YOUNGSUK

PROJECT_TERMS: Adaptive Immune System;Address;Adult;Affect;Allergic inflammation;American;analog;Angiotensin II;Anti-Inflammatory Agents;Antigen Presentation;Aorta;Arachidonic Acids;Award;Biological Availability;Blood Pressure;blood pressure control;blood pressure elevation;Blood Vessels;Cardiovascular Diseases;Cardiovascular system;career;career development;Cell Physiology;cell type;Cells;clinical investigation;clinical translation;clinically significant;Coxibs;cyclooxygenase 2;Cyclooxygenase Inhibitors;cytokine;Data;Dendritic Cells;Development;Development Plans;Disease;disease model;Disease Progression;eicosanoid metabolism;Environment;Enzymes;Epoprostenol;Etiology;Experimental Models;FDA approved;Foundations;Gene Expression Profile;high salt diet;Human;Hypertension;hypertension control;hypertension treatment;hypertensive;Immune;Immune response;Immune system;immunoregulation;Impairment;Individual;Inflammation;Inflammatory;Inflammatory Response;Infusion procedures;Innate Immune System;Invaded;Journals;Kidney;Knockout Mice;Laboratories;Lead;Lipids;Macrophage;Maps;Mentors;Metabolic Pathway;Modeling;monocyte;Morbidity - disease rate;mortality;mouse model;Mus;normotensive;novel;novel therapeutics;Organ;Pathogenesis;Pathway interactions;Patients;Pharmaceutical Preparations;Phase;Phenotype;Play;prevent;Production;programs;Property;Prostaglandin Receptor;Prostaglandins;Publications;Pulmonary Hypertension;receptor;Regulatory T-Lymphocyte;Research;Research Personnel;response;restraint;Role;Signal Pathway;Signal Transduction;Site;Stimulus;T cell infiltration;T-Lymphocyte;T-Lymphocyte Subsets;Testing;Th1 Cells;Th2 Cells;Therapeutic;Thromboxanes;Training;transcriptome sequencing;Treprostinil;United States;Vascular Diseases;vascular inflammation;Vasoconstrictor Agents;Wild Type Mouse

PROJECT_TITLE: PGI2 restrains immunopathogenesis in hypertension


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Cancer;Digestive Diseases;Genetics;Orphan Drug;Pancreatic Cancer;Rare Diseases

ORG_CITY: SAINT LOUIS

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Project Narrative The RAS genes are mutated in a third of human cancers in the USA, including in some of the most intractable cancers like pancreatic. Despite this prominence the encoded oncoproteins are extremely difficult to pharmacologically target. I therefore propose to identify the proteins RAS oncoproteins interact with to drive tumorigenesis as a way to unveil potential new drug targets to treat a huge proportion of human cancers.

PI_NAMEs: ADHIKARI, HEMA  (contact)

PROGRAM_OFFICER_NAME: XU, WANPING

PROJECT_TERMS: Ablation;Antineoplastic Agents;Automobile Driving;Binding;Biochemical;Biological Assay;cancer cell;Cell Fractionation;cell growth;cell transformation;Clinical;CRISPR/Cas technology;Cultured Cells;Data;Data Set;Dependence;Disease;Drug Targeting;Enhancers;experimental study;Future;Genes;Genetic;Genetically Engineered Mouse;Genotype;Goals;Grant;Homeostasis;Human;Immunotherapy;inhibitor;inorganic phosphate;K-ras mouse model;KRAS oncogenesis;KRAS2 gene;Label;Libraries;Lipids;Malignant Neoplasms;MAP Kinase Gene;Mediating;Mediator;Membrane;Mining;mouse model;mutant;Mutate;Mutation;Nature;new therapeutic target;novel;novel therapeutics;Oncogenes;Oncogenic;Oncoproteins;Oxidation-Reduction;Oxidative Stress;Oxidative Stress Induction;Pancreas;pancreatic cancer model;Pathway interactions;Pentosephosphate Pathway;Pharmaceutical Preparations;pharmacologic;Phase;Phosphatidylinositol Phosphates;Phosphatidylinositols;phosphoproteomics;Phosphotransferases;Prevalence;Process;Protein Isoforms;Proteins;RAS driven cancer;RAS genes;RAS inhibition;Ras Inhibitor;ras Oncogene;ras Proteins;Research;Research Personnel;response;Role;Signal Transduction;Signaling Protein;small molecule inhibitor;Stress;Systems Biology;Techniques;Testing;Therapeutic;therapeutic target;Training;tumor growth;tumor xenograft;tumorigenesis;tumorigenic;Validation;Xenograft procedure

PROJECT_TITLE: Interrogating the RAS interactome for therapeutic vulnerabilities

STUDY_SECTION: NCI

STUDY_SECTION_NAME: Transition to Independence Study Section (I)[NCI-I]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Coronaviruses;Coronaviruses Therapeutics and Interventions;Emerging Infectious Diseases;Infectious Diseases;Prevention

ORG_CITY: INDIANAPOLIS

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

PHR: PROJECT NARRATIVE We will develop technology that enables the rapid discovery of new bicyclic peptides—molecules with diagnostic and therapeutic applications against a range of diseases. We will apply this technology towards the discovery of bicyclic peptides with broad-spectrum antiviral properties against coronaviruses that cause severe respiratory disease in humans.

PI_NAMEs: THARP, JEFFERY MICHEAL (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TERMS: 2019-nCoV;Acceleration;Address;Adoption;Affinity;Amines;Amino Acids;Amino Acyl-tRNA Synthetases;Anti-viral Agents;Antibodies;Bacteriophage M13;Bacteriophages;Binding;career;career development;Cells;Chemicals;combinatorial;Communicable Diseases;Coronavirus;Coronavirus Infections;Coupled;Cyclic Peptides;Cyclization;Cysteine;Development;Development Plans;Diagnosis;Diagnostic;Directed Molecular Evolution;Disease;Drug Targeting;Engineering;Evolution;functional group;future pandemic;Genetic Code;glycosylation;Goals;Human;human coronavirus;In Vitro;in vivo;inhibitor;Laboratories;Learning Skill;Libraries;Ligands;Mediating;Membrane Fusion;Mentors;Methods;Middle East Respiratory Syndrome Coronavirus;Modeling;Molecular Conformation;novel;novel coronavirus;novel therapeutics;Peptide Conformation;peptide drug;Peptide Library;Peptides;Periodicity;Phage Display;Phase;prevent;Prevention;programs;Property;protein protein interaction;Proteins;Reaction;Research;Respiratory Disease;Ribosomes;Route;SARS coronavirus;scaffold;screening;Side;small molecule;Surface;System;Techniques;Technology;technology development;Therapeutic;thioether;tool;Training;Transfer RNA;Translations;Tyrosine-tRNA Ligase;Viral;Viral Physiology;Virus;Work

PROJECT_TITLE: Genetically encoded bicyclic peptide libraries for the discoveryof novel antiviral agents


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Autoimmune Disease;Biodefense and Related Countermeasures;Clinical Research;Digestive Diseases;Emerging Infectious Diseases;Foodborne Illness;Genetics;Human Genome;Infectious Diseases;Inflammatory Bowel Disease;Microbiome;Rare Diseases

ORG_CITY: CHARLOTTESVILLE

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PI_NAMEs: PETRI, WILLIAM A (contact)

PROGRAM_OFFICER_NAME: PESCE, JOHN T

PROJECT_TERMS: Adult;Affect;Amebiasis;Amebic colitis;American;Bacteria;Bangladesh;Bile Acids;Birth;Bone Marrow;Candidate Disease Gene;cell type;Cells;Child;cohort;Colitis;Collaborations;Communication;conditional knockout;CREM protein;Cryptosporidiosis;CUL2 gene;Cyclic AMP;Cyclic AMP Response Element;Data;deoxycholate;Development;Diarrhea;diarrheal disease;Disease;DNA Sequence Alteration;Entamoeba histolytica;Enterobacteria phage P1 Cre recombinase;eosinophil;Epithelium;exome sequencing;Gene Expression;Gene Expression Profile;Genes;Genetic;genetic epidemiology;Genetic Transcription;genetic variant;Genetic Variation;genome wide association study;genome-wide;Genotype;Genotype-Tissue Expression Project;Goals;Goblet Cells;gut microbiome;Human;Human Genetics;Immune;Immunity;In Vitro;in vivo;Infection;Inflammatory Bowel Diseases;Injury;Innate Immune Response;innovation;Instruction;intestinal epithelium;Intestines;Investigation;Knock-out;Knockout Mice;Life;Link;Lymphoid Cell;Macrophage;Maps;Mediating;Mediator;microbiome;mouse model;Mus;Names;Natural Immunity;novel strategies;Parasites;Parasitology;Pathway interactions;Patients;pediatric patients;pleiotropism;Predisposition;Principal Investigator;professional atmosphere;programs;promoter;PTPRC gene;Publications;Quantitative Trait Loci;Reporting;Resistance;response;Risk Factors;RNA interference screen;Role;Screening Result;Shigella Infections;Signal Transduction;single cell sequencing;Subgroup;Susceptibility Gene;Tamoxifen;targeted sequencing;Testing;Tissue-Specific Gene Expression;Tissues;trait;transcription factor;Variant;villin;whole genome;Work

PROJECT_TITLE: Role of CREM in Amebic Colitis and Inflammatory Bowel Disease


ORG_CITY: KANSAS CITY

ORG_NAME: KANSAS CITY VA MEDICAL CENTER

PHR: Frailty is defined as a greater susceptibility to stressors resulting from age-related impairments in adaptive biological systems. Frailty leads to poorer physical performance and functional capacity and higher risk of adverse outcomes including falls, hospitalization, and mortality. Resilience, defined as the capacity to recover from disruptions to homeostasis, is critical to successful aging because it precedes frailty and enhances adults’ ability to maintain optimal health and function well into older age. Evidence-based therapies to help older adults enhance resilience are limited and the biological underpinnings contributing to improved resilience have not yet been fully characterized. To address this important need, we will conduct a clinical trial to examine the benefits of center- and home-based high intensity interval training (HIIT) on functional capacity, frailty, and resilience, and also to identify novel biomarkers of resilience in older Veterans.

PI_NAMEs: TROEN, BRUCE R. (contact)

PROJECT_TERMS: Activities of Daily Living;Address;Adult;adverse outcome;Affect;Age;age group;Age Years;age-related disease;Aging;aging related;attentional control;Award;Bioenergetics;Biological;Biological Markers;biological systems;Blood;Blood Cells;C-reactive protein;cardiorespiratory fitness;Clinical Trials;Cognition;Cognitive;cognitive function;cognitive performance;cognitive recovery;cognitive testing;comorbidity;Complex;Control Groups;disability;Enrollment;Equilibrium;evidence base;executive function;Exercise;Exhibits;falls;feasibility trial;Female;frailty;Genus Hippocampus;Goals;Health;health care service utilization;healthspan;Heart Rate;high risk;Home;Homeostasis;Hospitalization;Human;human old age (65+);improved;Individual;Inflammation;Inflammatory;inflammatory marker;innovation;Interleukin-10;Interleukin-6;Interval training;late life;male;Measures;metabolic profile;Methods;MicroRNAs;miRNA expression profiling;Mission;Mitochondria;mitochondrial metabolism;Molecular;monocyte;mortality;Motor;Mus;Muscle;muscle form;next generation sequencing;novel marker;novel strategies;older adult;Participant;peripheral blood;Physical assessment;Physical Function;Physical Performance;Physiological;Predisposition;Prevalence;prevent;promote resilience;Quality of life;Randomized;Randomized, Controlled Trials;Recovery;Regimen;resilience;resilience biomarker;response;Response to stimulus physiology;Series;Serum;Stress;stressor;Stretching;success;Testing;Therapeutic;Training Programs;United States;Veterans;Walking

PROJECT_TITLE: High Intensity Interval Training (HIIT) to Reduce Frailty and Enhance Resilience in Older Veterans

STUDY_SECTION_NAME: Chronic Medical Conditions & Aging[RRD6]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

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

ORG_CITY: POCATELLO

ORG_DEPT: BIOLOGY

ORG_NAME: IDAHO STATE UNIVERSITY

ORG_STATE: ID

PHR: In the human malaria parasite, Plasmodium falciparum, the lack of knowledge regarding most essential processes and regulatory pathways, particularly in the mitochondria, is a critical barrier to identifying and developing new drug targets. Ideally these targets are highly conserved and should be resistant to mutation or have limited ability to change in order to evolve resistance. This proposal outlines methods to identify and define previously unknown and uncharacterized aspects of parasite mitochondrial biology, with the goal of advancing rational drug design against this deadly parasite.

PI_NAMEs: LANE, KRISTIN D (contact)

PROGRAM_OFFICER_NAME: MCGUGAN, GLEN C

PROJECT_TERMS: Address;Alleles;Biochemistry;Biological Assay;Biology;Biotin;Cell Physiology;Circular DNA;Complex;Crista ampullaris;Data;Development;DNA;DNA Repair Pathway;DNA-Directed RNA Polymerase;Drug Design;drug development;Drug resistance;Drug Targeting;Electron Transport;Engineering;Enzymes;Eukaryota;Evolution;Exonuclease;Exposure to;falls;Gene Expression;Gene Expression Profile;Gene Expression Regulation;gene repression;Genes;Genetic Recombination;Genetic Transcription;Genome;genome sequencing;Goals;Histones;Human;In Vitro;in vivo;inhibitor;Knowledge;Label;Laboratories;Life;Life Cycle Stages;Link;Malaria;member;Metabolic;Methods;Mitochondria;Mitochondrial DNA;mitochondrial genome;Mitochondrial Proteins;Mitochondrial RNA;Modeling;Molecular Analysis;mutant;Mutate;Mutation;new therapeutic target;novel;novel strategies;novel therapeutic intervention;novel therapeutics;Organelles;Parasites;Pathway interactions;Peptide Initiation Factors;Plasmodium falciparum;Preparation;pressure;Process;protein complex;Proteome;reconstitution;Regulation;Regulatory Pathway;Repression;Resistance;Sequence Analysis;Sigma Factor;Source;System;targeted treatment;Techniques;transcriptome;Translational Repression;Translations;whole genome

PROJECT_TITLE: MOLECULAR ANALYSIS OF MALARIA MITOCHONDRIAL GENE REGULATION


FUNDING_MECHANISM: SBIR-STTR RPGS

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Immunization;Infectious Diseases;Lung;Nanotechnology;Pediatric;Pneumonia;Pneumonia and Influenza;Prevention;Vaccine Related

ORG_CITY: ANN ARBOR

ORG_NAME: BLUEWILLOW BIOLOGICS, INC.

PHR: Project Narrative Respiratory Syncytial Virus (RSV) is a common cause of upper and lower respiratory tract infections and immunocompromised individuals (e.g. infants, young children and elderly) are at particularly high risk of severe infection and disease.  There is no FDA-approved vaccine currently available to treat RSV and other therapies have either limited efficacy and/or are plagued by adverse side-effects.  In this proposal, we will apply our proprietary NanoVaxTM nanoemulsion adjuvant technology to enable future manufacturing of a potent RSV vaccine that is safe, and facilitates intranasal delivery to confer protective, mucosal immunity against the virus.

PI_NAMEs: TRABBIC, KEVIN  (contact)

PROGRAM_OFFICER_NAME: KIM, SONNIE

PROJECT_TERMS: Acute;Address;Adjuvant;Adolescence;Adult;Age;Agreement;Airway Disease;Antigens;Asthma;Biological Assay;Biological Products;Bronchiolitis;Bronchitis;cell bank;Cell Line;Cessation of life;Child;Childhood;Chronic Obstructive Pulmonary Disease;clinical development;clinical material;Clinical Trials;Coenzyme A;Common Cold;Congestive Heart Failure;cost;Cotton Rats;Croup;Cyclic GMP;Death Rate;Development;Disease;Effectiveness;Elderly;Exhibits;FDA approved;Financial Hardship;Focal Infection;Formulation;Foundations;Future;global health;Health;Healthcare Systems;high risk;Hospitals;Human;Immune response;Immunization;Immunocompromised Host;immunogenicity;improved;Individual;Infant;infant infection;Infection;innovation;International;Intramuscular;Licensing;Lower Respiratory Tract Infection;Lung;manufacture;manufacturing process;Marketing;Medical;Molecular Conformation;Mucosal Immune Responses;Mucosal Immunity;Mucous Membrane;nanoemulsion;novel;pathogen;Patient-Focused Outcomes;Phase;Pneumonia;Population;preservation;prevent;Process;Production;protein expression;Proteins;Recombinants;recurrent infection;Research;respiratory;Respiratory Mucosa;Respiratory syncytial virus;Respiratory Syncytial Virus Infections;Respiratory syncytial virus RSV F proteins;Respiratory Syncytial Virus Vaccines;Risk;Route;Running;Sexual Transmission;side effect;Small Business Innovation Research Grant;success;Technology;Technology Transfer;Therapeutic;United States;United States National Institutes of Health;Upper respiratory tract;Vaccination;vaccine access;Vaccine Design;Vaccines;Vial device;Viral;Viral Antigens;Viral Pathogenesis;Virus;Virus Diseases;Visit;Work

PROJECT_TITLE: Development of a Mucosal Nanoemulsion-Adjuvanted RSV Vaccine using Recombinant Pre-Fusion F Protein

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IMM-R(12)]


ADMINISTERING_IC: AA

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Cannabinoid Research;Clinical Research;Depression;Digestive Diseases;Endocannabinoid System Research;Mental Health;Mental Illness;Microbiome;Neurosciences;Prevention;Substance Misuse;Substance Misuse Prevention

ORG_CITY: FORT COLLINS

ORG_DEPT: PSYCHOLOGY

ORG_NAME: COLORADO STATE UNIVERSITY

ORG_STATE: CO

PHR: Project Narrative Heavy and persistent alcohol use has clear harmful effects on the gut and its microbiome, such as leaky gut and inflammatory bowel disease, while recent research suggests cannabis may have systemic effects that are opposite to those of alcohol, such as reducing or preventing alcohol-induced liver, bowel and systemic inflammation. Furthermore, psychological processes such as emotion regulation have a bidirectional relationship with the gut microbiome through the gut-brain axis and are heavily associated with inflammation as well. This proposal aims to examine these relationships through the modulation of signaling within the endocannabinoid system, which interacts with the brain, gut microbiome and immune system, and could be the basis for a proposed endocannabinoid-microbiota-gut-brain axis.

PI_NAMEs: DRENNAN, MEGGAN L (contact)

PROGRAM_OFFICER_NAME: PERRUCCIO, ELIZABETH M

PROJECT_TERMS: 16S ribosomal RNA sequencing;Affect;Age;Alcohol consumption;alcohol effect;alcohol exposure;alcohol misuse;alcohol prevention;alcohol use disorder;Alcohol withdrawal syndrome;Alcohols;Animals;Anxiety;anxiety reduction;anxiety symptoms;Applications Grants;Bacteria;Behavior;Bifidobacterium;Binding;Biological;Biometry;Blood specimen;Brain;cannabinoid receptor;Cannabinoids;Cannabis;Central Nervous System;Chronic;Clinical Treatment;Cognitive;Collection;comorbidity;Competence;Data;depressive symptoms;design;Diagnosis;Drug usage;dysbiosis;emotion regulation;Emotional;Endocannabinoids;endogenous cannabinoid system;Enzymes;Equation;Equipment and supply inventories;Event;exogenous cannabinoid;experience;Goals;gut health;gut inflammation;gut microbiome;gut-brain axis;Health;Heavy Drinking;Human;Immune system;improved;indexing;Individual;Inflammation;Inflammatory Bowel Diseases;Inflammatory Response;innovation;insight;intestinal barrier;Intestinal permeability;Intestines;Investigation;Knowledge;Leaky Gut;Link;Literature;liver inflammation;marijuana use;marijuana user;Mental Depression;Mental disorders;Mental Health;Methodology;Methods;microbial;microbiome;microbiome analysis;microbiome research;microbiota-gut-brain axis;Modeling;Mood Disorders;mood regulation;novel;Outcome;Patient Self-Report;Pattern;Permeability;Physiological;Physiological Processes;Plasma;Population;Process;protective effect;Proteobacteria;psychologic;Psychological Factors;psychological symptom;Psychopathology;Psychophysiology;Questionnaires;receptor binding;receptor expression;Receptor Signaling;Research;Research Personnel;response;Role;Scientist;Signal Transduction;Signaling Molecule;skills;Social Anxiety Disorder;statistics;stem;stool sample;substance use;substance use treatment;systemic inflammatory response;systems research;Testing;Tetrahydrocannabinol;Tight Junctions;Time;Training;trait;Up-Regulation;zonulin

PROJECT_TITLE: Exploring differential biological and psychological effects of regular alcohol and cannabis use in humans


ORG_CITY: ATLANTA

ORG_DEPT: SURGERY

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: As the third most common cause of death in the United States following heart disease and cancer, sepsis represents a prevalent and deadly public health issue, but alarmingly, there are no approved therapeutics available for sepsis once antibiotics and supportive therapy fail. Current mouse models used to study sepsis make use of laboratory animals that are relatively devoid of memory T cells—immune cells which are generated in humans as a result of exposure to microbial pathogens. Here, we interrogate a critical pathway (CD28) that regulates the function of memory T cells during sepsis; therapeutic targeting of this pathway will lead to improvements in sepsis-induced immune dysregulation and mortality.

PI_NAMEs: FORD, MANDY L (contact)

PROGRAM_OFFICER_NAME: LEITNER, WOLFGANG W

PROJECT_TERMS: Acute;Adult;Animals;Antibiotic Therapy;Antigens;Bacteria;Bacterial Infections;Biological Markers;Cause of Death;CD28 gene;CD8-Positive T-Lymphocytes;CD8B1 gene;cecal ligation puncture;Cell Compartmentation;cell type;Cells;Cessation of life;chronic infection;clinically relevant;Critical Pathways;Data;Dependence;Development;differential expression;Down-Regulation;Equilibrium;Exhibits;experience;Exposure to;FOXP3 gene;Frequencies;Functional disorder;Funding;Heart Diseases;Human;Immune;Immune system;Immunologic Memory;immunomodulatory strategy;Immunosuppression;improved;in vivo;Infection;insight;Interleukin-10;Investigation;Knowledge;Laboratory Animals;Laboratory mice;Malignant Neoplasms;Mediating;Memory;Modeling;mortality;mortality risk;mouse model;Mus;Natural Killer Cells;Outcome;Pathogenesis;pathogenic microbe;Pathway interactions;Patients;Persons;Phenotype;Physiological;prevent;protective effect;Public Health;Publishing;receptor;Regulatory T-Lymphocyte;Reporting;Resolution;risk stratification;Role;Sepsis;septic;septic patients;Signal Transduction;Supportive care;T memory cell;T-Cell Activation;T-Lymphocyte;Testing;Therapeutic;therapeutic target;Time;United States;Virus;Virus Diseases;Work

PROJECT_TITLE: Memory T Cell Cosigning Pathways in Sepsis-Induced Immune  Dysregulation

STUDY_SECTION: SAT

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


NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_CITY: PISCATAWAY

ORG_DEPT: GENETICS

ORG_NAME: RUTGERS, THE STATE UNIV OF N.J.

ORG_STATE: NJ

PHR: PROJECT NARRATIVE This project seeks to understand how selfish genetic elements known as transposons are able to remain active in the genomes of most organisms despite the existence of highly specialized pathways used by host genomes to identify them and suppress their activity. The research proposed here is relevant to human health because mutations created by transposons are responsible for over one hundred mendelian diseases in humans. Understanding how transposons are able to avoid being silenced by their host could lead to novel interventions to reduce transposon activity, thereby supporting the NIH’s mission to enhance health and reduce illness.

PI_NAMEs: ELLISON, CHRISTOPHER EUGENE (contact)

PROGRAM_OFFICER_NAME: MACARTHUR, LINDA

PROJECT_TERMS: Address;Affect;Agreement;arms race;Biological Assay;Candidate Disease Gene;Clustered Regularly Interspaced Short Palindromic Repeats;Codon Nucleotides;comparative genomics;Conflict (Psychology);Data;DNA;DNA Insertion Elements;DNA Transposable Elements;Drosophila genus;Drosophila melanogaster;Elements;Equation;Eukaryota;Event;fitness;Gene Expression;Gene Expression Regulation;Gene Silencing;Gene Targeting;Genes;Genetic;Genome;genome editing;Goals;Health;histone acetyltransferase;Homologous Gene;Host Defense;Human;innovation;insight;Intervention;knock-down;Knowledge;Laboratories;Measures;Mediating;Mendelian disorder;Mission;Modeling;mutant;Mutation;novel;Organism;Outcome;Ovary;Pathway interactions;Phenotype;piRNA;Repression;Research;RNA Interference;Selfish Genes;Side;Small RNA;Sterility;telomere;Testing;theories;Transcriptional Silencer Elements;transcriptome sequencing;United States National Institutes of Health;Untranslated RNA;Up-Regulation

PROJECT_TITLE: Mechanisms and evolutionary consequences of transposon strategies to counteract host silencing

STUDY_SECTION: GVE

STUDY_SECTION_NAME: Genetic Variation and Evolution Study Section[GVE]


NIH_SPENDING_CATS: Bioengineering

ORG_CITY: NEW HAVEN

ORG_DEPT: CHEMISTRY

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Project Narrative This MIRA project will use theoretical methods, closely coupled with experimental data, to elucidate the basic factors that control the movement of electrons and protons in biological systems, providing fundamental insights into a wide range of biochemical processes essential to living systems. In particular, this project will enhance understanding of the radical translocation mechanism of ribonucleotide reductase, which plays a critical role in DNA synthesis, replication, and repair. The general insights about controlling electrons and protons provided by this work may also have broader implications for protein engineering, drug design, and optogenetics.

PI_NAMEs: HAMMES-SCHIFFER, SHARON  (contact)

PROGRAM_OFFICER_NAME: GERSHENSON, ANNE

PROJECT_TERMS: alpha helix;Biochemical;Biochemical Process;Biological;Biological Models;Biological Process;biological systems;Biomimetics;Cell Respiration;Complex;Coupled;Cryoelectron Microscopy;Data;DNA biosynthesis;Drug Design;Electron Transport;Electronics;Electrons;Electrostatics;Environment;Enzymes;Equilibrium;Goals;Hydrogen;Individual;insight;kinetic model;Kinetics;Length;Measurement;Methods;Molecular Conformation;molecular dynamics;Motion;Movement;multi-scale modeling;Nuclear;Nucleotides;optogenetics;Organism;Pathway interactions;Play;Process;protein complex;Protein Conformation;Protein Engineering;Proteins;Protons;prototype;quantum;quantum chemistry;Reaction;repaired;Ribonucleotide Reductase;Role;Series;Solvents;Structure;Theoretical Studies;theories;Thermodynamics;Time;Tryptophan;Tyrosine;Work

PROJECT_TITLE: Coupled Protons and Electrons in Biological Systems

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


NIH_SPENDING_CATS: Clinical Research;Genetics;Lung;Pulmonary Fibrosis;Rare Diseases

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: NARRATIVE Idiopathic Pulmonary fibrosis (IPF), a devastating form of interstitial lung disease in adults, is marked by progressive scarring of lung tissue, respiratory failure, and death for which there is a significant unmet need for effective medical therapies. To overcome one of the current barriers in IPF research (a dearth of preclinical models) and to facilitate a better understanding of the fibrotic processes for the identification of new therapeutic targets, we developed two novel mouse models expressing mutations in the Surfactant Protein C (SP-C) gene that are associated with an IPF like syndrome in humans. These highly relevant preclinical models used in conjunction with human IPF lung and serum samples will serve as a comprehensive preclinical platform to identify cell populations, signaling pathways, biomarkers, and the contributions of age and sex on IPF development towards the goal of accelerating the discovery of new IPF treatments.

PI_NAMEs: BEERS, MICHAEL FRANCIS (contact)

PROGRAM_OFFICER_NAME: GOMEZ, CHRISTIAN RENE

PROJECT_TERMS: Acceleration;Address;Adult;Age;aged;Aging;Alleles;Alveolar;alveolar epithelium;Anabolism;Apoptosis;Architecture;Automobile Driving;Autophagocytosis;biobank;Biological Markers;biomarker identification;Bronchoalveolar Lavage Fluid;candidate marker;Cells;Cellular biology;Cellular Stress;Cessation of life;Characteristics;Chronic;Cicatrix;Clinical;cohort;Communities;Complication;Coupled;Data;Dependence;Development;Disease;Disease Progression;Distal;Elements;endoplasmic reticulum stress;Epithelium;Evolution;fibrogenesis;Fibrosis;fibrotic lung;Foundations;Functional disorder;Gases;Gene Expression Profile;Gene Mutation;Generations;Genes;genetic variant;Goals;Hand;High Resolution Computed Tomography;high resolution imaging;Histology;Human;idiopathic pulmonary fibrosis;Impairment;in vivo;inhibition of autophagy;Injury;injury and repair;insight;Interstitial Lung Diseases;Investigation;Knock-in;Knock-in Mouse;Ligands;Lung;lung repair;Lung Transplantation;Maps;Medical;Medicine;Mesenchymal;Modeling;Morbidity - disease rate;mortality;mouse model;Mus;mutant;Mutant Strains Mice;Mutation;new therapeutic target;nintedanib;non-Native;novel;novel therapeutics;older adult;Organelles;Organoids;Outcome;Pathogenesis;Pathway interactions;patient subsets;Patients;Pattern;Peripheral;Phenotype;Physiological;Physiology;Pirfenidone;Population;pre-clinical;Pre-Clinical Model;primary endpoint;Process;programs;Protein Isoforms;Proteomics;Published Comment;Publishing;Pulmonary Fibrosis;Pulmonary Surfactant-Associated Protein C;Quality Control;radiological imaging;receptor;Refractory;Reporting;Research;Resources;Respiratory Failure;response;Sampling;secondary endpoint;segregation;Serum;sex;Signal Pathway;single-cell RNA sequencing;Stress;Structure of parenchyma of lung;Syndrome;Testing;Therapeutic;therapeutic development;therapy outcome;Time;trafficking;transcriptomics;Transplantation;Usual Interstitial Pneumonia;Validation;validation studies;Work;wound healing

PROJECT_TITLE: Surfactant Protein C Mouse Models: A Fit For Purpose Preclinical Platform For Advancing Discovery In And Treatment Of Idiopathic Pulmonary Fibrosis


ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: Project Narrative Colorectal cancer (CRC) is the third most common cancer in men and the second in women with a worldwide total of over 1.8 million new cases per year. Dietary factors play an important role in CRC because these tumors develop adjacent to the intestinal lumen and receive direct exposure to ingested nutrients, chemicals, and microbiota throughout the day. Fructose consumption is associated with CRC risk and CRC-specific mortality so this proposal will test how the major fructose metabolite, fructose 1-phosphate, alters cellular metabolism to promote tumor cell survival.

PI_NAMEs: GONCALVES, MARCUS DASILVA (contact)

PROGRAM_OFFICER_NAME: KUMAR, AMIT

PROJECT_TERMS: Adult;Binding;Biochemical;Biological Assay;cancer cell;Cell Count;Cell Density;Cell Hypoxia;Cell Survival;Cells;Cellular Metabolic Process;Chemicals;clinical development;Clinical Research;Colon;colon cancer cell line;Colorectal Cancer;colorectal cancer progression;colorectal cancer risk;combat;Consumption;cost;Data;Development;dietary;Dietary Factors;Dose;Drug Design;Drug Targeting;Eating;Ensure;Enzyme Kinetics;Enzymes;experimental study;Exposure to;Food;Fructose;fructose-1-phosphate;Future;Gene Activation;Generations;Genes;Genetic;Genetic Models;Glucose;Goals;Growth;Human;Hypoxia;hypoxia inducible factor 1;improved;Incidence;Ingestion;inhibitor;Intake;intestinal adenoma;Intestines;Isoenzymes;Isotopes;Ketohexokinase;Kinetics;Link;Malignant Neoplasms;Mass Spectrum Analysis;Measures;Mediator;men;Metabolic;Metabolic syndrome;Metabolism;metabolomics;microbiota;middle age;Modality;Modeling;Molecular;mortality;mouse model;Mus;mutant;Mutation;new therapeutic target;novel therapeutics;Nutrient;Obesity;Oral;Organ;Organoids;Oxygen;Patients;pharmacologic;Physiology;Placebos;Play;pre-clinical;Process;programs;Prospective, cohort study;Protein Biochemistry;Protein Isoforms;Proteins;Public Health;Publications;Pyruvate Kinase;Recombinant Proteins;Recombinants;Role;Science;small molecule;Structure;Sucrose;sugar;Testing;Time;Tracer;Transactivation;tumor;tumor growth;tumor metabolism;Tumor Promotion;Variant;Woman

PROJECT_TITLE: Molecular Mechanisms of Fructose-induced Colorectal Cancer Cell Survival

STUDY_SECTION: CPSS

STUDY_SECTION_NAME: Cancer Prevention Study Section[CPSS]


NIH_SPENDING_CATS: Clinical Research;Genetics;Hematology;Human Genome;Prevention;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Transplantation

ORG_CITY: ITHACA

ORG_NAME: CORNELL UNIVERSITY

PHR: Allogeneic Hematopoietic Cell Transplantation (HCT) is a life-saving therapy for the treatment of blood cancers and immune disorders, but complications due to graft-versus-host disease (GVHD), an immune response that can affect any organ, limit the long-term benefits of HCT. This proposal explores the highly translational concept that a measurement of the tissues-of-origin of cell-free DNA in the blood circulation enables to detect GVHD and its organ involvement and can predict long-term outcomes of HCT. Successful implementation of these studies will lead to a blood test for the monitoring of GVHD after HCT, which will represent a critical advance in HCT that can lead to better strategies to prevent GVHD and better treatments.

PI_NAMEs: DE VLAMINCK, IWIJN  (contact);RITZ, JEROME

PROGRAM_OFFICER_NAME: NABAVI, NASRIN N

PROJECT_TERMS: accurate diagnosis;Acute;Acute Graft Versus Host Disease;Address;Affect;Allogenic;Bacterial Infections;Behavior Therapy;biobank;Bioinformatics;Biological Assay;biomarker panel;Biopsy;bisulfite sequencing;Blood;Blood Circulation;Blood Tests;blood treatment;Caring;Cell Death;cell free DNA;cell type;Cells;Cessation of life;classification algorithm;Clinical;clinical practice;cohort;Collaborations;Colonoscopy;Control Groups;Data;Detection;Diagnosis;Diagnostic;diagnostic strategy;diagnostic tool;DNA sequencing;Early Diagnosis;early onset;Endoscopy;Engraftment;epigenetic profiling;Etiology;Future;Genetic Fingerprintings;genome-wide;Goals;graft vs host disease;Hematological Disease;Hematopoietic Neoplasms;Hematopoietic Stem Cell Transplantation;Immune;Immune response;Immune System Diseases;improved;Injury;innovation;Life;Liver;liver biopsy;Malignant - descriptor;Maps;Measurement;Medical;Metagenomics;Methods;Methylation;Modality;Monitor;mortality;Non-Invasive Detection;non-invasive monitor;Non-Malignant;noninvasive diagnosis;Organ;organ injury;Outcome;outcome prediction;Patient Monitoring;Patient-Focused Outcomes;Patients;Performance;Pilot Projects;Plasma;prevent;Procedures;prognostic performance;prophylactic;Prospective cohort;Prospective Studies;protein biomarkers;Proteins;Public Health;recruit;Retrospective Studies;Risk;Sampling;Severities;Skin;skin biopsy;Symptoms;Testing;Therapeutic immunosuppression;Time;Tissues;tool;translational study;Translations;Transplant Recipients;Transplantation;treatment strategy;Virus Diseases

PROJECT_TITLE: Epigenetic Profiling of circulating cell-free DNA for the Monitoring of Graft-Versus-Host Disease after Hematopoietic Cell Transplantation

STUDY_SECTION: TTT

STUDY_SECTION_NAME: Transplantation, Tolerance, and Tumor Immunology Study Section[TTT]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Autoimmune Disease;Bioengineering;Biomedical Imaging;Brain Disorders;Machine Learning and Artificial Intelligence;Multiple Sclerosis;Neurodegenerative;Neurosciences

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

PHR: PROJECT NARRATIVE Multiple sclerosis (MS) is common, affecting over 700,000 people in the US. It is an inflammatory demyelinating disease of the central nervous system with pronounced axon damage inflicting long-term neurological disability. Accurate assessment of axonal injury early especially in normal appearing white matter is crucially important in therapeutic intervention. For example, we cannot expect remyelination to work on absent or critically injured axons. Thus, the proposed diffusion basis spectrum imaging to model intra-axonal diffusion for improving the sensitivity of detecting axonal injury is of great importance in treating and curing MS.

PI_NAMEs: SONG, SHENG-KWEI  (contact)

PROGRAM_OFFICER_NAME: UTZ, URSULA

PROJECT_TERMS: Affect;Area;Autopsy;Axon;axon injury;Biological Markers;Brain;Cellularity;central nervous system demyelinating disorder;central nervous system injury;Classification;Clinical;code development;cohort;Contrast Media;Coupled;Data;data-driven model;deep learning algorithm;deep neural network;Demyelinating Diseases;Demyelinations;density;detection sensitivity;Diffuse Axonal Injury;Diffusion;Diffusion Magnetic Resonance Imaging;Disease Progression;Edema;Electrophysiology (science);Experimental Autoimmune Encephalomyelitis;Experimental Designs;Fast Blue;Fiber;Gadolinium DTPA;Gadopentetate Dimeglumine;Germany;Glucose;Histologic;Histology;Human;Image;imaging approach;Immunohistochemistry;improved;in vivo;Inflammation;Inflammatory;Injury;Magnetic Resonance Imaging;manganese chloride;Measurement;Minor;Modeling;Morphology;Multiple Sclerosis;multiple sclerosis patient;Mus;Myelin;Nerve;Neurological disability;neurotransmission;novel;Optic Nerve;Pathology;Perfusion;Periodic acid Schiff stain method;Persons;preservation;prevent;programs;Protocols documentation;Rana;remyelination;Reporting;Ringer's solution;Sampling;sciatic nerve;Sensitivity and Specificity;severe injury;Signal Transduction;Silver;Specificity;Specimen;spectrograph;Spinal cord injury;Stains;Structure;support vector machine;Temperature;Therapeutic Intervention;Time;Tissues;Tolonium chloride;Translating;Treatment Efficacy;Uncertainty;Validation;vasogenic edema;virtual;Water;white matter;Work

PROJECT_TITLE: Virtual Histology for Assessing MS Pathologies

STUDY_SECTION: EITN

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


ORG_CITY: BLACKSBURG

ORG_NAME: VIRGINIA POLYTECHNIC INST AND ST UNIV

PHR: Project Narrative Tetraploidization (doubling of the genome) has been proposed to promote tumorigenesis due to the concomitant acquisition of extra centrosomes (key organelles for cell division) during the tetraploidization process. However, this is inconsistent with recent evidence that newly formed tetraploid cells rapidly lose their extra centrosomes, suggesting that the evolution of tetraploid cells may be influenced by specific conditions present in the native tissue and/or in the tumor microenvironment. This project will investigate this possibility by integrating experimental approaches and mathematical modeling to determine which events, cellular processes, and microenvironmental factors are important for the evolution and tumorigenic potential of tetraploid cells.

PI_NAMEs: CIMINI, DANIELA  (contact);SCHMELZ, EVA M.

PROGRAM_OFFICER_NAME: MILLER, RITA K

PROJECT_TERMS: 3-Dimensional;Affect;Aneuploidy;Animal Model;Automobile Driving;Breast Epithelial Cells;Buffers;cancer cell;cancer therapy;Cell division;Cell Physiology;Cells;Centrosome;Chemicals;Chromosomal Instability;chromosome missegregation;Chromosomes;Clonal Evolution;Collagen;collagen scaffold;Colorectal Cancer;Communication;dynamical evolution;Environment;environmental stressor;Epithelial Cells;Event;Evolution;experimental study;Exposure to;Future;Genome;Goals;Human;in vivo;interdisciplinary approach;intestinal epithelium;Knowledge;Lead;mathematical model;Mitosis;Modeling;Molecular Target;mouse model;multidisciplinary;Mus;neoplastic cell;novel;Nude Mice;Nutrient;Organelles;Outcome;Ovarian;Oxygen;Pattern;Physiological;Ploidies;Population;Population Dynamics;predictive modeling;pressure;Process;Proliferating;Property;Reporting;Research;Role;Shapes;Side;Signaling Molecule;Stromal Cells;subcutaneous;Surface;System;Testing;Tetraploidy;Time;tissue culture;Tissues;tumor;tumor microenvironment;Tumor-Derived;tumorigenesis;tumorigenic;Variant;whole genome

PROJECT_TITLE: Combining modeling and experiments to study the evolution of cells with altered ploidy

STUDY_SECTION: NCSD

STUDY_SECTION_NAME: Nuclear and Cytoplasmic Structure/Function and Dynamics Study Section[NCSD]


NIH_SPENDING_CATS: Genetics

ORG_CITY: SEATTLE

ORG_NAME: FRED HUTCHINSON CANCER CENTER

ORG_STATE: WA

PHR: Narrative Proper chromatin regulation is essential for all DNA-dependent processes. How chromatin can be regulated in a genome-wide scale is not well understood. We will use yeast quiescence as a model to elucidate molecular mechanisms and functions of global chromatin reprogramming.

PI_NAMEs: TSUKIYAMA, TOSHIO  (contact)

PROGRAM_OFFICER_NAME: CHOW, CHI-WING

PROJECT_TERMS: Affect;Biochemistry;Cell Cycle Regulation;Cells;Chromatin;Chromatin Remodeling Factor;Development;DNA;DNA biosynthesis;DNA Damage;DNA Repair;driver mutation;Eukaryotic Cell;Funding;Gene Expression;Genetic Recombination;Genetic Transcription;genome-wide;Genomics;Goals;in vivo;Malignant Neoplasms;Mitotic Cell Cycle;model organism;Modeling;Molecular;Molecular Genetics;Mutation;novel;Nucleosomes;Physical condensation;posttranscriptional;Process;programs;Regulation;Research Personnel;response;S phase;Saccharomycetales;Time;Work;Yeasts

PROJECT_TITLE: Molecular mechanisms and functions of global chromatin control

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


ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Biotechnology;Chronic Pain;Genetics;Neurodegenerative;Neurosciences;Pain Research;Peripheral Neuropathy

ORG_CITY: RICHARDSON

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF TEXAS DALLAS

ORG_STATE: TX

PHR: PROJECT NARRATIVE  Chronic pain is one of the major public health concerns in the US; there is a pressing need to discover and evaluate novel therapeutic targets for pain treatment. Previous studies and preliminary data show that sigma 2/transmembrane protein 97 (σ2/TMEM97) receptor may be a such a novel target. This proposal combines in vivo and in vitro approaches to determine cell-type specific differences in σ2/TMEM97-driven peripheral nociception at the cellular, molecular, and behavioral level.

PI_NAMEs: HONG, VERONICA MINSU (contact)

PROGRAM_OFFICER_NAME: MOHAPATRA, DURGA PRASANNA

PROJECT_TERMS: abuse liability;Acute Pain;Affect;Affinity Chromatography;Agonist;Anatomy;Animal Behavior;antagonist;Behavior;Behavioral;behavioral pharmacology;Biological;Biological Process;Calcium;Calcium Signaling;career;Cell membrane;Cell Physiology;cell type;Cells;Cholesterol Homeostasis;Chronic inflammatory pain;chronic pain;Clinic;clinical translation;Crossbreeding;Data;Data Analyses;differential expression;Down-Regulation;Economic Burden;effective therapy;efficacy evaluation;Endoplasmic Reticulum;Experimental Designs;experimental study;Future;ganglion cell;Gene Expression;Genes;Genetic Transcription;Genomic approach;Goals;Homeostasis;human induced pluripotent stem cells;Hypersensitivity;In Situ Hybridization;In Vitro;in vivo;Individual;Inflammation;Inflammatory;inflammatory modulation;inflammatory pain;Injury;insight;Integral Membrane Protein;interdisciplinary approach;Interleukin-6;Investigation;Knock-out;Knockout Mice;Knowledge;Learning;Ligands;Link;Literature;Location;loss of function;LoxP-flanked allele;Mechanics;Mediating;Molecular;Molecular Biology;Molecular Profiling;Molecular Target;multi-electrode arrays;Mus;Neurons;Neuropathy;neuroregulation;Neurosciences;new therapeutic target;Nociception;Nociceptors;Non-Steroidal Anti-Inflammatory Agents;novel;Opioid;Pain;Pain management;pain model;Peripheral;Peripheral Nervous System;Pharmaceutical Preparations;pharmacologic;Pharmacology;Pharmacology Study;Play;Population;Property;Public Health;Publications;receptor;Recovery;response;Ribosomes;Rodent;Role;side effect;sigma-2 receptor;Signal Transduction;Site;Spinal Ganglia;System;Techniques;Testing;Therapeutic;therapeutic target;Training;training opportunity;transcriptome sequencing;transcriptomic profiling;Transgenic Animals;Transgenic Mice;Transgenic Organisms;Translating;Up-Regulation;Wild Type Mouse

PROJECT_TITLE: Sigma 2 Receptor (TMEM97): Investigating the Peripheral Role of this Novel Therapeutic Target for Pain


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Clinical Research;Cost Effectiveness Research;Emerging Infectious Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Infectious Diseases;Lung;Prevention;Rare Diseases;Tuberculosis

ORG_CITY: BOSTON

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: BOSTON UNIVERSITY MEDICAL CAMPUS

PHR: Project Narrative. Increasing tuberculosis case detection, especially in high-risk groups, is critical to meet the World Health Organization’s End TB Strategy to reduce tuberculosis incidence by 90% globally by 2035. A significant barrier to achieving this goal is that a large proportion of patients are unable to produce sputum and are therefore are not evaluated with commonly used and recommended diagnostics such as GeneXpert, culture, and smear testing. The overall goal of this proposal is to identify and quantify the burden of undiagnosed tuberculosis in Brazilian prisoners, evaluate the feasibility and value of non-sputum-based diagnostics to improve case detection in this setting, and to identify cost-effective algorithms for tuberculosis screening in prisons.

PI_NAMEs: MARTINEZ, LEONARDO  (contact)

PROGRAM_OFFICER_NAME: MENDEZ, SUSANA

PROJECT_TERMS: Adult;Aerosols;Algorithms;Brazil;burden of illness;career;career development;case finding;Characteristics;Chest;Child;Childhood;clinical epidemiology;Collaborations;Communicable Diseases;Contracts;cost effective;cost effectiveness;Cost Effectiveness Analysis;Data;Data Collection;Decision Trees;design;Detection;Development Plans;Diagnosis;Diagnostic;diagnostic algorithm;Diagnostic tests;diagnostic tool;Early Diagnosis;Enrollment;Environment;Epidemiologist;Epidemiology;Exhalation;experience;Extramural Activities;Fostering;Funding;Future;General Population;Goals;Grant;Health Policy;high risk;high risk population;HIV;Imprisonment;improved;Incidence;Individual;Infectious Disease Epidemiology;Intervention;Journals;K-Series Research Career Programs;Masks;Mass Screening;mathematical model;Measures;meetings;Mentors;Mentorship;Methodology;Methods;Mycobacterium tuberculosis;Natural History;novel;novel diagnostics;Patients;Peer Review;point of care;Population;Prevalence;Prisoner;Prisons;Program Development;programs;Publishing;Recommendation;Research;Research Personnel;routine screening;Sampling;screening;skills;Specificity;Sputum;Statistical Methods;Symptoms;System;systematic review;Testing;tool;Training;transmission process;Triage;Tuberculosis;Tuberculosis diagnosis;tuberculosis diagnostics;United States National Institutes of Health;Visit;Work;World Health Organization;Writing

PROJECT_TITLE: Identifying effective and efficient approaches to tuberculosis screening in Brazilianprisons

STUDY_SECTION: MID

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


NIH_SPENDING_CATS: Genetics;Human Genome

ORG_NAME: HARVARD MEDICAL SCHOOL

PHR: PROJECT NARRATIVE All organisms must regulate the expression of their genetic information for normal growth and development. This application proposes to study this regulation by the analysis of proteins that are essential for normal gene expression. The information learned from these studies will improve our understanding of human biology.

PI_NAMEs: WINSTON, FRED M. (contact)

PROGRAM_OFFICER_NAME: WAIRKAR, YOGESH PRABHAKAR

PROJECT_TERMS: Address;Alanine;Amino Acids;Binding;Binding Sites;Biochemical;Biological Assay;Biological Models;Cancer Etiology;Cells;ChIP-seq;Chromatin;Chromatin Structure;Compensation;Complex;Defect;Development;Disease;DNA;DNA biosynthesis;DNA Damage;DNA Double Strand Break;Double Strand Break Repair;Elongation Factor;experimental study;Gene Expression;genetic information;Genetic Transcription;genome integrity;Genome Stability;Genomic approach;Genomic Instability;Genomics;Goals;Growth;Growth and Development function;Health;histone modification;Histones;Human;Human Biology;human disease;Hybrids;improved;In Vitro;in vivo;insight;Knowledge;Learning;Malignant Neoplasms;Mammalian Cell;Modeling;Molecular Chaperones;mutant;Mutation;mutation screening;N-terminal;Nature;Nucleosomes;Organism;Phenotype;physical impairment;Play;Positioning Attribute;Process;Protein Analysis;Protein Dynamics;Proteins;Publishing;Regulation;repaired;RNA;RNA Polymerase II;Role;Saccharomyces cerevisiae;Series;Suppressor Genes;Suppressor Mutations;Surface;Testing;Transcription Alteration;Transcription Elongation;Transcriptional Elongation Factors;Transcriptional Regulation;Yeasts

PROJECT_TITLE: Analysis of conserved eukaryotic transcription elongation factors

STUDY_SECTION: MGB

STUDY_SECTION_NAME: Molecular Genetics B Study Section[MGB]


NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Brain Disorders;Cerebrovascular;Clinical Research;Neurosciences;Stroke

ORG_CITY: IOWA CITY

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: Public Health Relevance We propose to map specific domains of cognitive impairment that occur following focal brain injury, such as deficits in language, memory and attention, to specific brain regions. We will evaluate whether these symptom- specific ‘maps’ can be used with other sources of predictive information to advance stroke management by predicting personalized cognitive outcomes.

PI_NAMEs: BOES, AARON D (contact)

PROGRAM_OFFICER_NAME: BABCOCK, DEBRA J

PROJECT_TERMS: Acute;Address;Adult;Age;Anxiety;Attention;Brain;Brain Mapping;Brain region;Chronic;Clinical;clinical care;Cognitive;Cognitive deficits;cognitive performance;cognitive testing;cohort;common symptom;connectome;connectome data;Data;data integration;Databases;Decision Making;demographics;design;Diagnosis;disability;disabling symptom;Education;experience;Factor Analysis;Focal Brain Injuries;Foundations;Gender;Handedness;Human;human data;Impaired cognition;improved;Individual;innovation;insight;International;Iowa;Ischemic Stroke;Language;Lesion;Life;Link;Location;long term recovery;Longitudinal cohort;loved ones;Magnetic Resonance Imaging;Manuals;Maps;Masks;Medical;Memory;Methods;MRI Scans;multiple data sources;Neuroanatomy;neuroimaging;Neurologist;Neuropsychological Tests;Neurosciences Research;Outcome;Outcome Assessment;Outcome Measure;outcome prediction;Patients;performance tests;personalized predictions;Phase;Positioning Attribute;post stroke;Prognosis;prospective;Provider;public health relevance;Recovery;Registries;Rehabilitation therapy;Resources;Risk;Scanning;screening;Site;Source;Specialist;Statistical Models;Stroke;stroke cognitive outcome;stroke outcome;stroke patient;Structure;Structure-Activity Relationship;Symptoms;Testing;tool;Translating;Universities;vascular risk factor;Work

PROJECT_TITLE: Predicting Cognitive Outcomes from Stroke Based on Lesion Location

STUDY_SECTION: CP

STUDY_SECTION_NAME: Cognition and Perception Study Section[CP]


ORG_CITY: SAN FRANCISCO

ORG_NAME: VETERANS AFFAIRS MED CTR SAN FRANCISCO

ORG_STATE: CA

PHR: Veterans must often wait and travel significant distances to receive care from a VA dermatologist. Emerging innovative technologies promise to allow VA to deliver expert skin care to Veterans wherever and whenever they need it. By moving Veterans’ images and histories instead of people, skin concerns can be more rapidly diagnosed and managed remotely by a dermatologist or eventually by a computer trained by artificial intelligence methods. This project will implement a VA-developed teledermatology mobile application at three VA facilities and measure its ability to deliver dermatologic care directly to Veterans in a timely and travel- minimizing manner, and patient and VA staff satisfaction with the process. In parallel, the project will use the data that Veteran patients submit to train and refine artificial intelligence-powered computer vision models whose performance will be tested against dermatologists. The readiness of Veterans and VA to implement these technologies will also be evaluated.

PI_NAMEs: OH, DENNIS H (contact);WEINSTOCK, MARTIN A.

PROJECT_TERMS: Address;Appointment;Area;Artificial Intelligence;artificial intelligence method;Benchmarking;Caring;Categories;Client satisfaction;Clinic;Collaborations;Community Healthcare;Computer Assisted;Computer Vision Systems;Computer-Assisted Diagnosis;Computers;connected care;Consult;Consultations;coronavirus pandemic;Data;data warehouse;Dermatologic;Dermatologist;Dermatology;Diagnosis;Diagnostic;digital imaging;Eligibility Determination;Evaluation;experience;follow-up;Foundations;Future;Geography;Goals;health care service organization;Health Personnel;Health system;Home;Hybrids;Image;Improve Access;improved;innovation;innovative technologies;Intervention;Interview;Leadership;Link;Measures;Mediating;Medical;medical specialties;Methodology;mHealth;mobile application;Modeling;Nevi and Melanomas;novel coronavirus;organizational readiness;Outcome;pandemic disease;Pathway interactions;Patient Care;Patients;Performance;Persons;Population;Positioning Attribute;pragmatic study;primary care clinic;Process;programs;prospective;Quality of Care;rapid diagnosis;Readiness;Recommendation;Recording of previous events;remote health care;Remote management;Research Design;Role;satisfaction;Secure;Self Direction;Site;Skin;Skin Care;skin disorder;Surveys;System;Technology;teledermatology;telehealth;Testing;Time;tool;Training;Travel;treatment as usual;Triage;United States Department of Veterans Affairs;Veterans;Vision;Wait Time;willingness

PROJECT_TITLE: Improving dermatology access by direct-to-patient teledermatology and computer-assisted diagnosis

STUDY_SECTION_NAME: HSN-1 Health Services Research Innovation[HSN1]


ED_INST_TYPE: OVERALL MEDICAL

ORG_CITY: PORTLAND

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: PROJECT NARRATIVE Although lifelong suppression of HIV replication with antiretroviral therapy (ART) seems possible, side effects, need for strict adherence, resistance, stigma and cost all contribute to the necessity of finding an ‘HIV cure’. As a model for HIV infection, and to better understand viral reservoirs in different organs and cell types, we propose to integrate several novel multi-omic in situ approaches to monkeys infected with the simian immunodeficiency virus (SIV), allowing an in-depth single-cell characterization of viral reservoirs with various levels of residual activity in terms of the expression of viral transcripts. Our ‘panomic’ approach and longitudinal high-density data sets will allow us to develop a comprehensive “atlas” of persistent VR and the cellular immune neighborhoods in which they reside within key organ systems and tissue compartments, and will help identify and characterize novel cellular pathways and factors, phenotypic characteristics and inflammatory immune pathways involved in viral persistence.

PI_NAMEs: ESTES, JACOB D (contact)

PROGRAM_OFFICER_NAME: REFSLAND, ERIC WILLIAM

PROJECT_TERMS: Adherence;adverse outcome;Anatomy;Anti-Inflammatory Agents;antiretroviral therapy;Atlases;Autopsy;Binding;Biochemistry;Blood;Body System;cell type;Cells;Characteristics;Chronic;Clinical;Communities;cost;Cues;Data;Data Set;density;Dissociation;Event;Gastrointestinal tract structure;Genetic Transcription;Goals;HIV;HIV Infections;Immune;immune activation;Immunology;improved;In Situ;In Situ Hybridization;in situ sequencing;Individual;Infection;Inflammation;Inflammatory;innovation;insight;Interdisciplinary Study;Interruption;laser capture microdissection;Lymphoid Tissue;Maps;Mass Spectrum Analysis;memory CD4 T lymphocyte;mesenteric lymph node;Modeling;Molecular;Molecular Analysis;Monkeys;multiple omics;Multiplexed Ion Beam Imaging;Neighborhoods;next generation;nonhuman primate;novel;novel strategies;Organ;Pathology;Pathway interactions;Peripheral;peripheral blood;Pharmaceutical Preparations;Phenotype;Proteins;Proteomics;Research Proposals;Residual state;Resistance;Resolution;response;Rest;RNA;Sampling;Scientist;side effect;SIV;social stigma;Sorting;Source;spatiotemporal;Spleen;Testing;Time;tissue mapping;Tissues;Transcript;transcriptome sequencing;transcriptomic profiling;Viral;Viral Genome;Viral reservoir;viral RNA;Virion;Virus;Virus Diseases;Virus Latency;Virus Replication

PROJECT_TITLE: Defining Mechanisms of Viral Persistence in Situ at the Single-Cell Level


ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: Project Narrative This study will determine how the location and movement of a subset of white blood cells associated with ‘allergic immunity’ controls their function, ultimately regulating organ damage and repair. We will determine how these cells move from their homes in resting organs to new sites during inflammation, and how this ‘niche spread’ can be limited to impact organ physiology and pathology.

PI_NAMEs: MOLOFSKY, ARI B (contact)

PROGRAM_OFFICER_NAME: SUBRAMANIAN, HARIHARAN

PROJECT_TERMS: Allergic;Allergic Disease;Alveolus;Area;Asthma;atopy;Bacterial Infections;Benefits and Risks;Blood;Blood Vessels;CD4 Positive T Lymphocytes;Cells;cellular targeting;cytokine;Data;Diagnostic;Duct (organ) structure;Equilibrium;Fibroblasts;Fibrosis;Future;Genetic;Genetic Transcription;Goals;Helminths;Helper-Inducer T-Lymphocyte;Hematopoietic;Hepatocyte;Home;Hyperactivity;Hypersensitivity;Immune;Immune response;Immunity;Immunophenotyping;Impairment;in vivo;Inflammation;Inflammatory;Inflammatory Response;Influenza A virus;Interferon Type II;Interleukin-13;Interleukin-5;Kinetics;Leukocytes;Liver;Location;Lung;Lymphocyte;Lymphocyte Subset;Lymphoid Cell;Mediating;Modeling;mortality;Movement;multimodality;Mus;Organ;Organ Transplantation;Outcome;Papain;Parabiosis;Pathologic;Pathology;Pathway interactions;Physiological;Physiology;Production;Protozoa;repaired;Repression;Residencies;response;Rest;Route;Shapes;Signal Transduction;Site;Source;Stimulus;Stromal Cells;T-Lymphocyte;Testing;Therapeutic;Three-Dimensional Imaging;Time;Tissues;tool;trafficking;TSLP gene;virtual;Virus Diseases;Work

PROJECT_TITLE: Localization and function of tissue type 2 lymphocytes during mixed inflammation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IDIA-D(90)]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

ORG_CITY: NEW YORK

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: PROJECT NARRATIVE HIV-infected patients in the United States now live longer, owing to the effective antiretroviral therapy, but the prevalence of chronic kidney disease continues to increase in this HIV-infected population due to comorbidities with diabetes, hypertension, and HCV. This study will unravel the molecular mechanisms of how chronic HIV infection contributes to the progression of age-related kidney disease, specifically diabetic kidney disease. The knowledge gained will enable the development of effective targeted and personalized therapies.

PI_NAMEs: HE, JOHN CIJIANG (contact);MA'AYAN, AVI

PROGRAM_OFFICER_NAME: NIHALANI, DEEPAK

PROJECT_TERMS: Acceleration;age related;Aging;Animal Model;antiretroviral therapy;Archives;Automobile Driving;Biopsy;Cells;Chronic;Chronic Kidney Failure;Clinical Data;cohort;Collaborations;comorbidity;comparison control;Complement;Data;data integration;Data Set;Development;Diabetes Mellitus;diabetic;Diabetic mouse;Diabetic Nephropathy;diabetic patient;Disease Progression;Dose;Doxycycline;efficacy validation;End stage renal failure;Epithelial Cells;Exposure to;Formalin;Gene Expression;Gene Expression Profile;Genes;genetic signature;Goals;Hepatitis C virus;HIV;HIV Infections;HIV Seropositivity;HIV therapy;HIV-1;Human;Hypertension;Immune;In Situ Hybridization;Inflammation;Injury;Injury to Kidney;Kidney;kidney biopsy;kidney cell;Kidney Diseases;Kidney Transplantation;Knowledge;Leukocytes;Longitudinal Studies;Maps;Mediating;Modeling;Molecular;mouse model;Mus;new therapeutic target;non-diabetic;novel therapeutics;Organ;Paraffin Embedding;Pathway interactions;Patients;personalized medicine;Pharmaceutical Preparations;Pharmacology;Pharmacotherapy;Plasma;podocyte;Population;Prevalence;Process;PTPRC gene;Publishing;Regimen;Reporting;response;RNA;Sample Size;Scientist;single-cell RNA sequencing;Slide;small molecule;Streptozocin;System;T-Lymphocyte;targeted treatment;Therapeutic;Tissues;transcriptomic profiling;transcriptomics;Transgenic Mice;Transgenic Organisms;Tubular formation;United States;Veterans;Viral Load result;Viremia;web platform;web portal

PROJECT_TITLE: Elucidating the Molecular Mechanisms that Mediate DKD Progression in Patients Living with HIV


NIH_SPENDING_CATS: Chronic Pain;Natural Products;Neurosciences;Nutrition;Pain Research

PHR: This project is focused on elucidating mechanisms that underlie our sense of touch (somatosensation). Results from these studies will expand our understanding of molecular and cellular mechanisms that contribute to acute and persistent pain. As such, our work will aid in the development of therapeutic strategies (such as novel drugs) for treating chronic pain syndromes and other clinical disorders.

PI_NAMEs: JULIUS, DAVID  (contact)

PROJECT_TERMS: Acute;Acute Pain;Acute pain management;Afferent Neurons;Analgesics;Anatomy;Binding;Biochemical;Biophysics;Brain;Capsaicin;Cells;Chemicals;Chili Pepper;Chronic;chronic pain;chronic pain management;Chronic pain syndrome;Clinical;Complex;Detection;Development;Disease;environmental change;environmental disparity;Family;Genetic;Genus Mentha;Goals;Hypersensitivity;imaging modality;in vivo imaging;Inflammatory;Injury;insight;interest;Ion Channel;Irritants;Mechanics;Medication Management;member;Menthol;Modality;Molecular;Morphine;Mus;Natural Products;Nature;Nerve Fibers;Nociception;Nociceptors;novel;novel therapeutics;Opioid Receptor;Opium;Pain;Papaver;Pathologic;Pathway interactions;Persistent pain;Pharmaceutical Preparations;pharmacologic;Pharmacology;Physiological;Plant natural product;Play;Population;pressure;Process;receptor;response;Role;Salicylic Acids;Signal Transduction;somatosensory;Spinal Cord;Stimulus;Syndrome;Temperature;therapeutic development;tool;Touch sensation;transmission process;TRP channel;Willow;Work

PROJECT_TITLE: Natural products as probes of the pain pathway


NIH_SPENDING_CATS: Cardiovascular;Heart Disease

PHR: NARRATIVE Cardiac fibrosis and heart failure have profound clinical impact on morbidity and mortality in the United States and worldwide. This project will take a multi-faceted approach to study a novel target of cardiac fibrosis by employing structural biology, chemical biology and genetic strategies. These findings will lead to new ways in which pharmacological intervention can be used as a treatment against heart failure.

PI_NAMEs: BENNETT, ANTON M (contact);LOLIS, ELIAS

PROGRAM_OFFICER_NAME: SHI, YANG

PROJECT_TERMS: Adopted;Allosteric Site;Binding;Binding Sites;Biology;biophysical techniques;Catalysis;Catalytic Domain;Cells;Cellular biology;Chemicals;Clinical;Complex;coronary fibrosis;Coupled;CRISPR/Cas technology;Data;Development;Disease;druggable target;Effectiveness;Experimental Models;fibrogenesis;Fingerprint;Generations;Genetic;genetic approach;Goals;Heart;Heart failure;in vivo;inhibitor;insight;Intervention;Kinetics;Knock-in;Knock-in Mouse;MAPK8 gene;Mediating;Mitogen-Activated Protein Kinases;Modeling;Molecular;Morbidity - disease rate;mortality;mouse genetics;Mus;mutant;novel;operation;Outcome;p38 Mitogen Activated Protein Kinase;Pathway interactions;pharmacologic;phosphatase inhibitor;phosphoproteomics;Phosphoric Monoester Hydrolases;Physiological;Play;pressure;Protein Dephosphorylation;Protein Kinase Interaction;Proteomics;Regulation;Resolution;Role;Signal Transduction;Site;small molecule;Specificity;structural biology;structural determinants;Structure;Therapeutic;therapeutic target;Tissues;transcriptomics;Transforming Growth Factor beta;United States;Work

PROJECT_TITLE: MKP5 allostery in MAPK regulation and signaling in the heart

STUDY_SECTION: MIST

STUDY_SECTION_NAME: Molecular and Integrative Signal Transduction Study Section[MIST]


ED_INST_TYPE: SCHOOL OF MEDICINE & DENTISTRY

NIH_SPENDING_CATS: Neurosciences

ORG_CITY: ROCHESTER

ORG_NAME: UNIVERSITY OF ROCHESTER

PHR: Project Narrative Changes in the way neurons communicate are crucial to brain function, including development, learning and aging. Defects in this neuronal plasticity underlie many neurological disorders, such as autism, epilepsy and Alzheimer’s disease. Recently it has become clear that microglia, which are immune cells, are an integral part of brain circuitry and contribute critically to normal brain function and plasticity. Here we will investigate microglial mechanisms that govern changes in neuronal networks. This will yield information with broad implications for understanding and treating a large spectrum of human neurological disorders.

PI_NAMEs: MAJEWSKA, ANNA K (contact)

PROGRAM_OFFICER_NAME: LEENDERS, MIRIAM

PROJECT_TERMS: Adrenergic Agents;Adrenergic Receptor;Affect;Aging;Alzheimer's Disease;Anesthesia procedures;Animals;Arousal;autism spectrum disorder;awake;Behavior;beta-2 Adrenergic Receptors;Biological Assay;Brain;brain circuitry;Cells;Communication;conditional knockout;critical period;Defect;Development;Disease;Epilepsy;experience;experimental study;Human;Immune;in vivo;in vivo two-photon imaging;insight;Intervention;Knock-out;Learning;Mediating;Microglia;Modeling;Molecular;Monitor;Morphology;Motility;Nervous System Disorder;Neurodevelopmental Disorder;neuroinflammation;Neuromodulator;Neuronal Plasticity;Neurons;new therapeutic target;Norepinephrine;Ocular Dominance;optogenetics;Pathologic;Pathway interactions;Phagocytes;pharmacologic;Physiological;Process;reduce symptoms;response;response to injury;Role;Signal Pathway;Signal Transduction;Site;Sleep;Specificity;Structure;Synapses;Synaptic Cleft;Synaptic plasticity;Testing;Visual;Visual Cortex;Wakefulness;Work

PROJECT_TITLE: Mechanisms that Regulate Microglial Dynamics in the Context of Plasticity

STUDY_SECTION: CMBG

STUDY_SECTION_NAME: Cellular and Molecular Biology of Glia Study Section[CMBG]


NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome;Stem Cell Research;Stem Cell Research - Embryonic - Human

ORG_CITY: UNIVERSITY PARK

ORG_NAME: PENNSYLVANIA STATE UNIVERSITY, THE

ORG_STATE: PA

PHR: Project Narrative Mis-regulation of gene expression are highly linked to various types of human diseases. Chromatin accessibility and 3D chromosome organization play essential roles in gene regulation. By studying these phenomena, we will contribute to our understanding of disease mechanisms, as well as providing potential treatment targets.

PI_NAMEs: BAI, LU  (contact)

PROGRAM_OFFICER_NAME: VATAKIS, DIMITRIOS NIKOLAOS

PROJECT_TERMS: 3-Dimensional;Address;Alleles;Binding;Binding Sites;Biological Assay;Cells;Chromatin;Chromatin Structure;chromosome conformation capture;Chromosome Structures;Chromosomes;cofactor;developmental disease;Disease;Drosophila genus;Event;Foundations;Gene Cluster;Gene Expression;Gene Expression Regulation;Genes;Genetic;Genetic Screening;Genome;Goals;Grant;Health;Human Cell Line;human disease;Image;innovation;insight;Invaded;Kinetics;Link;Liquid substance;Malignant Neoplasms;Mediating;Methods;National Institute of General Medical Sciences;novel;Nucleosomes;Oligonucleotides;Phase;Play;Pluripotent Stem Cells;programs;Research;Role;System;Testing;Yeasts

PROJECT_TITLE: Mechanism of chromatin accessibility, 3D chromosome organization, and their functions in gene regulation


NIH_SPENDING_CATS: Women's Health Research

ORG_CITY: CAMBRIDGE

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

ORG_STATE: MA

PHR: Project Narrative Reducing the incidence of devastating birth defects requires a mechanistic understanding of cell signaling and force transmission in developing tissues. My lab uses Drosophila to investigate force generation by the actomyosin cytoskeleton and its regulation within cells and across tissues. These studies will provide insight into the interplay between contractile signaling and force generation, providing a framework for understanding emergent tissue shapes.

PI_NAMEs: MARTIN, ADAM CHRISTOPHER (contact)

PROGRAM_OFFICER_NAME: WELLS, MELISSA LYNN

PROJECT_TERMS: Actomyosin;Affect;Behavior;Biological;cell behavior;Cells;Complex;Congenital Abnormality;Cytoplasm;Cytoskeleton;Development;Drosophila genus;Engineering;Epithelium;Exhibits;gastrulation;Generations;Germ Lines;Goals;Guanosine Triphosphate Phosphohydrolases;Incidence;insight;Link;Mathematics;Mechanics;member;Molecular;Morphogenesis;Movement;multidisciplinary;Oocytes;Oogenesis;Pattern;Physiologic pulse;Regulation;Research;response;rho GTP-Binding Proteins;rho GTPase-activating protein;Role;Shapes;Signal Pathway;Signal Transduction;Supporting Cell;Tissues;transmission process;Visualization;Work

PROJECT_TITLE: Tissue morphogenesis: From signals to forces

STUDY_SECTION: MRAC

STUDY_SECTION_NAME: Maximizing Investigators' Research Award C Study Section[MRAC]


NIH_SPENDING_CATS: Biotechnology;Brain Cancer;Brain Disorders;Cancer;Cancer Genomics;Genetics;Human Genome;Neurosciences;Orphan Drug;Precision Medicine;Rare Diseases

ORG_CITY: BIRMINGHAM

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: PROJECT NARRATIVE Gliomas, the most common primary brain tumor in humans, are genetically heterogeneous tumors. Our goal is to credential novel genetically engineered human models of gliomas against patient-derived models using comprehensive biological, molecular, drug therapy profiling. Models will be designed to genetically match their human counterparts and used to develop rational combination therapies that combat drug resistance mechanisms.

PI_NAMEs: FURNARI, FRANK ;MILLER, CHRISTOPHER RYAN (contact);O'ROURKE, DONALD M

PROGRAM_OFFICER_NAME: WATSON, JOANNA M

PROJECT_TERMS: Address;Affect;Alabama;Biological;Biological Models;Biology;Blood - brain barrier anatomy;Brain;Brain Neoplasms;CDKN2A gene;Cells;Chemicals;Clinic;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;combat;combinatorial;Combined Modality Therapy;Complex;Coupled;Credentialing;Data;Deletion Mutation;design;Development;Disease;driver mutation;Drug resistance;drug sensitivity;Drug Targeting;Engineering;Engraftment;Ensure;Epidermal Growth Factor Receptor;Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor;epidermal growth factor receptor VIII;epigenomics;established cell line;experience;experimental study;Extracellular Domain;Failure;Foundations;Future;Generations;Genetic;Genetic Engineering;Genetic Heterogeneity;genome editing;Genomics;Genotype;Glioblastoma;Glioma;Goals;Growth;Heterogeneity;Human;human disease;human induced pluripotent stem cells;human model;Human Pathology;Inflammatory;inhibitor;inhibitor therapy;Investigational Therapies;Malignant neoplasm of brain;Malignant neoplasm of lung;Malignant Neoplasms;Mass Spectrum Analysis;Methods;Missense Mutation;Modeling;Molecular;Molecular and Cellular Biology;Molecular Conformation;mouse model;mutant;Mutation;neoplastic cell;nerve stem cell;neuro-oncology;next generation;next generation sequencing;novel;Operative Surgical Procedures;Organoids;overexpression;Pathway interactions;patient derived xenograft model;Patient Selection;Patients;Penetrance;Pharmaceutical Preparations;Pharmacotherapy;Phenotype;Phosphotransferases;PIK3CG gene;Pre-Clinical Model;Precision therapeutics;preclinical development;Preclinical Drug Development;preservation;Primary Brain Neoplasms;Proteomics;PTEN gene;Publishing;Receptor Protein-Tyrosine Kinases;resistance mechanism;response;Signal Transduction;small molecule;success;Symbiosis;Testing;Therapeutic;Therapeutic Uses;transcriptomics;tumor;tumor heterogeneity;tumorigenesis;Tyrosine Kinase Inhibitor;Universities;Work;Xenograft procedure

PROJECT_TITLE: Credentialing next-generation human glioma models for precision therapeutics


NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Diabetes;Dissemination and Implementation Research;Health Services;Networking and Information Technology R&D (NITRD);Patient Safety

ORG_CITY: HERSHEY

ORG_NAME: PENNSYLVANIA STATE UNIV HERSHEY MED CTR

PHR: Project Narrative This research will compare the effectiveness of alert-clinical decision support (CDS) for the management of abnormal glucose in the hospital on clinical, economic and practice performance outcomes in patients admitted to an academic and a community hospital. Anticipating an impactful project, this tool will optimize hospital glucose control and improve patients’ outcomes providing an evidence-based resource to improve patient care. As a subsequent advancement of this alert-CDS, it can be adapted into an electronic medical agnostic tool using standards of interoperability within health informatics to widely benefit many patient across hospitals.

PI_NAMEs: PICHARDO-LOWDEN, ARIANA RAQUEL (contact)

PROGRAM_OFFICER_NAME: BURCH, HENRY B

PROJECT_TERMS: Acute;Address;Admission activity;Algorithms;blood glucose regulation;care delivery;Caring;case finding;Cessation of life;Clinical;clinical decision support;Clinical Decision Support Systems;Clinical Management;Collaborations;Community Hospitals;compare effectiveness;Competence;computerized;Computerized Medical Record;Consultations;cost;Counseling;Data;Data Collection;data management;Decision Making;design;Diabetes Mellitus;Discipline;Dose;economic outcome;Economics;Eligibility Determination;evidence base;experience;Exposure to;Frequencies;Glucose;glycemic control;Health;Health Care Costs;Health Services;hospital care;hospital readmission;Hospital Units;hospital utilization;Hospitalization;Hospitals;Hour;Hyperglycemia;Hypoglycemia;implementation tool;improved;improved outcome;Infection;Information Technology;innovation;Inpatients;Institution;instrument;Insulin;Intensive Care;Intensive Care Units;interoperability;Interruption;Intervention;Intravenous;Judgment;Knowledge;Leadership;Length of Stay;Long-Term Care;medical complication;Medical Electronics;Mentored Patient-Oriented Research Career Development Award;Modality;mortality;mortality risk;multidisciplinary;National Institute of Diabetes and Digestive and Kidney Diseases;Nosocomial Infections;novel;Outcome;Outcome Study;Patient Admission;Patient Care;Patient-Focused Outcomes;Patients;Performance;Persons;Pilot Projects;Population;primary endpoint;Process;process improvement;programs;Protocols documentation;Provider;Public Health Informatics;Recommendation;Recurrence;Relative Risks;Research;Research Personnel;Resources;Risk;Sample Size;Sampling;skills;standard care;statistics;Stress;subcutaneous;success;support tools;Surgical complication;System;systematic review;Testing;Time;Time Series Analysis;tool;treatment as usual;virtual;Work

PROJECT_TITLE: Glucose Management Clinical Decision Support to Improve Outcomes in Academic and Community Hospitals

STUDY_SECTION: ICSC

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


FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: Narrative  There is excitement that combining engineering and computational disciplines with the life sciences may enable major breakthroughs in the cardiovascular (CV) sciences, yet few training programs exist at this intersection. This new T32 at Stanford provides cutting-edge training for post-PhD, -MD or -MD/PhD fellows combining engineering, CV physiology and medicine that is focused on mentored research, didactics, professional growth, training in diversity, ethics and other key topics. The T32 is well positioned for success due to an excellent pool of applicants, dedicated interdisciplinary faculty, and co-location of top-tier schools of Engineering, Medicine and Humanities and Sciences on a single campus in Silicon Valley.

PI_NAMEs: MARSDEN, ALISON L;NARAYAN, SANJIV M (contact)

PROGRAM_OFFICER_NAME: CHEON, YEWON

PROJECT_TERMS: Heart;Medicine;Training Programs

PROJECT_TITLE: Computational Medicine in the Heart, Integrated Training Program

STUDY_SECTION: NITM

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


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

ORG_CITY: CHAPEL HILL

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: Project Narrative:  Multiple sclerosis (MS) is a debilitating autoimmune neuroinflammation disease inflicting millions of people worldwide. CD4 T cells, especially Th17 cells, are central to autoimmune neuroinflammation. Our recent findings revealed a novel role for TGF-β superfamily and related signaling to regulate T cell function and the development of autoimmune neuroinflammation. This study aims to reveal previous unappreciated cellular and molecular mechanisms underlying TGF-β superfamily signaling in controlling Th17 cell differentiation and function for autoimmunity. The success of this study will gain critical mechanistic insights into T cell mediated autoimmune neuroinflammation and shed new light on how to mitigate related disease by targeting TGF-β superfamily signaling pathways.

PI_NAMEs: WAN, YISONG  (contact)

PROGRAM_OFFICER_NAME: GUERAU, MIREIA

PROJECT_TERMS: activin A;adaptive immunity;Address;Adopted;Autoimmune;Autoimmunity;CD4 Positive T Lymphocytes;Cell Differentiation process;Cell Physiology;Cells;Critical Pathways;cytokine;Development;differentiation in vitro;Disease;effective therapy;Etiology;Experimental Autoimmune Encephalomyelitis;Generations;Genes;Genetic;genetic signature;Goals;Granulocyte-Macrophage Colony-Stimulating Factor;Homeostasis;Human;IL17 gene;IL6 gene;Immune;Immune Tolerance;in vivo;Inflammatory;insight;interest;Interleukin-10;Mediating;member;Molecular;Molecular Target;Multiple Sclerosis;multiple sclerosis treatment;Mus;Natural Immunity;neuroinflammation;novel;Pathogenicity;Pathology;Pathway interactions;Persons;Phenotype;programs;Proteins;receptor;Regulator Genes;Research;Role;Signal Pathway;Signal Transduction;SKI gene;success;T-Cell Activation;T-Lymphocyte;TGF-beta type I receptor;Tissues;Transforming Growth Factor beta

PROJECT_TITLE: TGF-b superfamily signaling in controlling Th17 cell function in autoimmune neuroinflammation

STUDY_SECTION: CNBT

STUDY_SECTION_NAME: Clinical Neuroimmunology and Brain Tumors Study Section[CNBT]